@article {1428, title = {Prevalence and correlates of respiratory symptoms and disease in the elderly. Cardiovascular Health Study.}, journal = {Chest}, volume = {106}, year = {1994}, month = {1994 Sep}, pages = {827-34}, abstract = {

Spirometry was performed by 5,201 elderly participants of the Cardiovascular Health Study during their baseline examination and a subset of the ATS/DLD-78 respiratory questionnaire was administered by trained interviewers. In never smokers (46 percent of the cohort), the overall prevalence of chronic cough was 9 percent, chronic phlegm was 13 percent, attacks of wheezing with dyspnea were 8 percent, and grade 3 dyspnea on exertion was 10 percent. The prevalence of lung disease in current smokers (12 percent of the cohort) was 8/7 percent (men/women) with chronic bronchitis and 14/5 percent with emphysema. Overall, 6 percent reported asthma (a physician-confirmed history) and 12 percent reported hay fever. Using a logistic regression model, attacks of wheezing with dyspnea were strongly associated with a lower FEV1, coronary heart disease, heart failure, and a large waist size (in participants without a diagnosis of asthma, chronic bronchitis, or emphysema). Undiagnosed airways obstruction was twice as likely in women and those with lower income, and was associated with current and former smoking, pack-years of smoking, and chronic cough. Dyspnea on exertion (DOE) was three times or more likely if a participant reported heart failure, coronary heart disease, or emphysema; and much more likely if their FEV1 or FVC was substantially reduced. Dyspnea on exertion was also positively associated with older age, chronic bronchitis or asthma, a larger waist or hip size, pack-years of smoking, and less education. We conclude that DOE and attacks of wheezing with dyspnea are commonly associated with cardiovascular disease and a low FEV1 in those over 65 years and that airways obstruction frequently remains undiagnosed in the elderly.

}, keywords = {Aged, Aged, 80 and over, California, Cohort Studies, Female, Humans, Lung Diseases, Male, Maryland, Multivariate Analysis, North Carolina, Pennsylvania, Prevalence, Prognosis, Respiratory Tract Diseases, Spirometry, Surveys and Questionnaires}, issn = {0012-3692}, author = {Enright, P L and Kronmal, R A and Higgins, M W and Schenker, M B and Haponik, E F} } @article {1452, title = {Picture-sort method for administering a food frequency questionnaire to older adults.}, journal = {J Am Diet Assoc}, volume = {96}, year = {1996}, month = {1996 Feb}, pages = {137-44}, abstract = {

OBJECTIVE: To assess the validity of a picture-sort approach to administering the National Cancer Institute food frequency questionnaire to older adults.

DESIGN: A picture-sort interview was conducted in each respondent{\textquoteright}s home. After the picture sort, a 24-hour recall interview was administered on the same occasion. Five additional in-home recall interviews were subsequently conducted at approximately 1-month intervals.

SUBJECTS/SETTING: Forty-seven female and 49 male volunteers aged 66 to 100 years were recruited from among Cardiovascular Health Study participants from Maryland and North Carolina.

MAIN OUTCOME MEASURES: Estimates from the picture sort and the recall for intakes of macronutrients, cholesterol, fiber, and selected vitamins and minerals exclusive of supplements.

STATISTICAL ANALYSES: Comparison of means estimated by the two methods and correlation analyses were used. Correlations were adjusted under varied assumptions about the nature of the information contained in the six 24-hour recalls relative to respondents{\textquoteright} usual intakes.

RESULTS: After correction for attenuation, Pearson correlation coefficients for macronutrients ranged from .41 for protein to .74 for saturated fat and cholesterol. For vitamins and minerals, correlations ranged from .26 for beta carotene to .62 for calcium.

APPLICATIONS: Picture-sort estimates of mean nutrient intakes were comparable with estimates based on 24-hour recalls, and correlations with reference data were similar to those reported in the literature for conventionally administered food frequency questionnaires. This dietary assessment method may, therefore, offer a way to simplify or structure responses to improve ease of administration and increase respondents{\textquoteright} liking for the interview without loss of data quality.

}, keywords = {Aged, Aged, 80 and over, Audiovisual Aids, Data Interpretation, Statistical, Diet Records, Eating, Female, Humans, Interviews as Topic, Male, Mental Recall, Surveys and Questionnaires}, issn = {0002-8223}, doi = {10.1016/S0002-8223(96)00042-9}, author = {Kumanyika, S and Tell, G S and Fried, L and Martel, J K and Chinchilli, V M} } @article {1478, title = {Dietary assessment using a picture-sort approach.}, journal = {Am J Clin Nutr}, volume = {65}, year = {1997}, month = {1997 Apr}, pages = {1123S-1129S}, abstract = {

Food-frequency questionnaires are usually administered as a list of foods to be checked off by the respondent or interviewer. Techniques in which participants sort into categories cards on which names or pictures of foods are printed can also be used to assess food intake. Food-frequency scores were obtained from a five-category picture sort administered to 4643 men and women aged > or = 65 y in the Cardiovascular Health Study (CHS). This one-step (qualitative) assessment yielded significant associations in expected directions between frequency scores and sex, age, race or ethnicity, body mass index, and use of a special diet. In the two-step (semiquantitative) version of this instrument, an interviewer documented specific frequencies and portion-size information for the foods in each sorting category. A substudy of the two-step version with 96 CHS participants indicated relative validity similar to that of conventionally administered food-frequency questionnaires. The one-step version may be broadly applicable to situations in which general food-pattern data can be informative and cost and time limitations are great. When it is feasible, the two-step picture sort may offer certain methodologic advantages because respondents have a chance to change their responses and the format may simplify the cognitive-response task. Sorting or picture-sort procedures deserve systematic attention in research on dietary assessment methods.

}, keywords = {Aged, Audiovisual Aids, Diet, Female, Food, Humans, Male, Nutrition Assessment, Surveys and Questionnaires}, issn = {0002-9165}, author = {Kumanyika, S K and Tell, G S and Shemanski, L and Martel, J and Chinchilli, V M} } @article {1473, title = {Sleep disturbance, psychosocial correlates, and cardiovascular disease in 5201 older adults: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {45}, year = {1997}, month = {1997 Jan}, pages = {1-7}, abstract = {

OBJECTIVES: To describe the prevalence of self reported sleep disturbances in older men and women and to describe their relationships with health status and cardiovascular disease (CVD).

DESIGN: Cross-sectional study of sleep disturbance, CVD, general health, psychosocial factors, physical function, and use of psychotropic medications.

SETTING: Participants of the Cardiovascular Health Study, 5201 adults aged 65 and older recruited from a random sample of noninstitutionalized Medicare enrollees in four US communities.

MEASURES: Self-reported sleep disturbances and standardized questionnaires for cardiopulmonary symptoms and diseases, depression, social support, activities of daily living, physical activity, cognitive function, and current medications, spirometry, ECG, echocardiography, and carotid ultrasound.

RESULTS: Women were twice as likely as men to report difficulty falling asleep (30\% vs 14\%). Daytime sleepiness, difficulty falling asleep, and frequent awakenings increased in prevalence with age. All symptoms were related strongly to depression. Symptoms of daytime sleepiness were also related strongly to poor health and limitations in activities of daily living in men and women. In multivariate analysis, men taking benzodiazepines were likely to report difficulty falling asleep and daytime sleepiness, whereas women taking benzodiazepines reported difficulty falling asleep and waking up too early. After accounting for these factors, the only cardiovascular disease independently associated with sleep disturbances was angina. Men and women with confirmed angina were 1.6 times more likely to report trouble falling asleep. Independent relationships between sleep disturbances and cardiovascular risk factors such as obesity, hypertension, smoking, and diabetes were relatively weak and inconsistent, though smokers were less likely to report frequent awakenings.

CONCLUSIONS: Sleep disturbances are relatively common in older men and women and are associated with poor health, depression, angina, limitations in activities of daily living, and the use of benzodiazepines.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cross-Sectional Studies, Depression, Female, Geriatric Assessment, Health Surveys, Humans, Male, Prevalence, Psychotropic Drugs, Random Allocation, Risk Factors, Sex Factors, Sleep Wake Disorders, Social Support, Surveys and Questionnaires, United States}, issn = {0002-8614}, author = {Newman, A B and Enright, P L and Manolio, T A and Haponik, E F and Wahl, P W} } @article {1516, title = {Utilities for major stroke: results from a survey of preferences among persons at increased risk for stroke.}, journal = {Am Heart J}, volume = {136}, year = {1998}, month = {1998 Oct}, pages = {703-13}, abstract = {

BACKGROUND: Patient beliefs, values, and preferences are crucial to decisions involving health care. In a large sample of persons at increased risk for stroke, we examined attitudes toward hypothetical major stroke.

METHODS AND RESULTS: Respondents were obtained from the Academic Medical Center Consortium (n = 621), the Cardiovascular Health Study (n = 321 ), and United Health Care (n = 319). Preferences were primarily assessed by using the time trade off (TTO). Although major stroke is generally considered an undesirable event (mean TTO = 0.30), responses were varied: although 45\% of respondents considered major stroke to be a worse outcome than death, 15\% were willing to trade off little or no survival to avoid a major stroke.

CONCLUSIONS: Providers should speak directly with patients about beliefs, values, and preferences. Stroke-related interventions, even those with a high price or less than dramatic clinical benefits, are likely to be cost-effective if they prevent an outcome (major stroke) that is so undesirable.

}, keywords = {Adult, Age Distribution, Aged, Aged, 80 and over, Attitude to Health, Female, Health Status, Humans, Intracranial Embolism and Thrombosis, Male, Middle Aged, Quality of Life, Sex Distribution, Surveys and Questionnaires, United States}, issn = {0002-8703}, author = {Samsa, G P and Matchar, D B and Goldstein, L and Bonito, A and Duncan, P W and Lipscomb, J and Enarson, C and Witter, D and Venus, P and Paul, J E and Weinberger, M} } @article {1523, title = {Relation of sleepiness to respiratory disturbance index: the Sleep Heart Health Study.}, journal = {Am J Respir Crit Care Med}, volume = {159}, year = {1999}, month = {1999 Feb}, pages = {502-7}, abstract = {

Obstructive sleep apnea syndrome is a well recognized cause of excessive sleepiness; however, the relation of sleepiness to mild sleep-disordered breathing (SDB), which affects as much as half the adult population, is uncertain. In order to explore this relation, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study, a longitudinal study of the cardiovascular consequences of SDB. The study sample comprises 886 men and 938 women, with a mean age of 65 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Sleep-disordered breathing was quantified by the respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, measured during in-home polysomnography. When RDI was categorized into four groups (< 5, 5 to < 15, 15 to < 30, >/= 30), a significantly progressive increase in mean ESS score was seen across all four levels of SDB, from 7.2 (4.3) in subjects with RDI < 5 to 9.3 (4.9) in subjects with RDI >/= 30 (p < 0.001). There was no significant modification of this effect by age, sex, body mass index, or evidence of chronic restriction of sleep time or periodic limb movement disorder. The percentage of subjects with excessive sleepiness, defined as an ESS score >/= 11, increased from 21\% in subjects with RDI < 5 to 35\% in those with RDI >/= 30 (p < 0. 001). We conclude that SDB is associated with excess sleepiness in community-dwelling, middle-aged and older adults, not limited to those with clinically apparent sleep apnea.

}, keywords = {Aged, Cardiovascular Diseases, Cross-Sectional Studies, Disorders of Excessive Somnolence, Female, Humans, Male, Middle Aged, Polysomnography, Respiration, Retrospective Studies, Severity of Illness Index, Sleep Apnea Syndromes, Surveys and Questionnaires}, issn = {1073-449X}, doi = {10.1164/ajrccm.159.2.9804051}, author = {Gottlieb, D J and Whitney, C W and Bonekat, W H and Iber, C and James, G D and Lebowitz, M and Nieto, F J and Rosenberg, C E} } @article {603, title = {Stability and change in older adults{\textquoteright} social contact and social support: the Cardiovascular Health Study.}, journal = {J Gerontol B Psychol Sci Soc Sci}, volume = {54}, year = {1999}, month = {1999 Sep}, pages = {S302-11}, abstract = {

OBJECTIVES: The aim of this study was to examine the degree of individual change in structural indicators of social support (family network contact and close friend network contact) and functional indicators of social support (belonging, appraisal, and tangible support) during late life.

METHODS: Using a large population-based sample of older adults, hierarchical linear modeling was applied to examine the extent of change in social contact and support as well as sociodemographic characteristics (age, race, gender, and education) that might explain individual variability in contact and support at baseline and over time.

RESULTS: Consistent with predictions, small yet significant increases were observed in belonging support and tangible support. Contrary to predictions, no evidence was found for significant individual change in family network contact, close friend network contact, or appraisal support. Sociodemographic characteristics were more consistent predictors of variability in contact and support at baseline than variability over time.

DISCUSSION: The findings of this study add to a growing literature suggesting that late life is not typically characterized by a decline in important social resources.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cross-Sectional Studies, Educational Status, Family, Female, Health Status, Humans, Interpersonal Relations, Linear Models, Longitudinal Studies, Male, Predictive Value of Tests, Sex Factors, Social Support, Socioeconomic Factors, Surveys and Questionnaires, Time Factors, United States}, issn = {1079-5014}, doi = {10.1093/geronb/54b.5.s302}, author = {Martire, L M and Schulz, R and Mittelmark, M B and Newsom, J T} } @article {610, title = {Daytime sleepiness predicts mortality and cardiovascular disease in older adults. The Cardiovascular Health Study Research Group.}, journal = {J Am Geriatr Soc}, volume = {48}, year = {2000}, month = {2000 Feb}, pages = {115-23}, abstract = {

INTRODUCTION: As part of the baseline examination in the Cardiovascular Health Study, sleep disturbance symptoms including snoring and daytime sleepiness, were assessed as potential risk factors or precipitants of cardiovascular disease (CVD). Because of the association of sleep disturbance with poorer health and the possible associations of sleep apnea with CVD, we hypothesized that those with poorer sleep or daytime sleepiness may be at increased risk of mortality or incident CVD.

SETTING: Participants (n = 5888) were recruited in 1989, with an additional minority cohort recruited in 1993, in four US communities for a cohort study designed to evaluate risk factors for cardiovascular disease.

METHODS: An interview-administered questionnaire regarding health and sleep habits with ongoing ascertainment of total mortality and cardiovascular disease morbidity and mortality, including total CVD morbidity and mortality, incident myocardial infarction, and congestive heart failure.

RESULTS: Daytime sleepiness was the only sleep symptom that was significantly associated with mortality in both men and women. The unadjusted hazard ratio was 2.12 (1.66, 2.72) in women and 1.40 (1.12, 1.73) in men. Men who reported difficulty falling asleep also had an increased mortality rate (HR = 1.43 (1.14, 1.80)) which was not seen in women. The risks were attenuated with adjustment for age but remained significant for daytime sleepiness in women (HR = 1.82 (1.42, 2.34)) and for difficulty falling asleep in men. (HR = 1.29 (1.03, 1.63)). Frequent awakenings, early morning awakening, and snoring were not associated with a significantly increased risk of mortality in these older men and women. Crude event rates were evaluated for total incident cardiovascular morbidity and mortality, incident myocardial infarction, and incident congestive heart failure (CHF). Incident CVD rates were higher in both men and women with daytime sleepiness. The aged adjusted HR was 1.35 (95\% CI = 1.03, 1.76) in men and was 1.66 (95\% CI = 1.28, 2.16) in women. Incident CVD was not higher in those with any other sleep disturbance including snoring. The risk of CVD events associated with daytime sleepiness was attenuated but remained significant in women after adjustment for age. Incident myocardial infarction (MI) rates were also higher in women with daytime sleepiness but were not significantly higher in men. Incident CHF rates were increased in both men and women with daytime sleepiness. In men, the age adjusted HR was 1.49 (95\% CI, 1.12- 1.98) and in women, was 2.21 (95\% CI, 1.64-2.98). Women reporting both daytime sleepiness and frequent awakening had a hazard ratio of 2.34 (95\% CI, 1.66-3.29) for incident CHF compared with those with daytime sleepiness but without frequent awakening. This interaction was not found in men.

CONCLUSIONS: In this study, daytime sleepiness was the only sleep disturbance symptom that was associated with mortality, incident CVD morbidity and mortality, MI, and CHF. These findings were stronger in women than men, i.e., the associations persisted for mortality, CVD, and CHF in women after adjustment for age and other factors. Thus, a report of daytime sleepiness identifies older adults at increased risk for total and cardiovascular mortality, and is an independent risk factor in women.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases, Cohort Studies, Female, Health Status, Heart Failure, Humans, Incidence, Male, Multivariate Analysis, Myocardial Infarction, Odds Ratio, Risk Factors, Sex Factors, Sleep Apnea Syndromes, Sleep Stages, Sleep Wake Disorders, Snoring, Surveys and Questionnaires, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2000.tb03901.x}, author = {Newman, A B and Spiekerman, C F and Enright, P and Lefkowitz, D and Manolio, T and Reynolds, C F and Robbins, J} } @article {632, title = {Importance of heart failure with preserved systolic function in patients > or = 65 years of age. CHS Research Group. Cardiovascular Health Study.}, journal = {Am J Cardiol}, volume = {87}, year = {2001}, month = {2001 Feb 15}, pages = {413-9}, abstract = {

Although congestive heart failure (CHF) is a common syndrome among the elderly, there is a relative paucity of population-based data, particularly regarding CHF with normal systolic left ventricular function. A total of 4,842 independent living, community-dwelling subjects aged 66 to 103 years received questionnaires on medical history, family history, personal habits, physical activity, and socioeconomic status, confirmation of pre-existing cardiovascular and cerebrovascular disease, anthropometric measurements, casual seated random-zero blood pressure, forced vital capacity and expiratory volume in 1 second, 12-lead supine electrocardiogram, fasting glucose, creatinine, plasma lipids, carotid artery wall thickness by ultrasonography, and echocardiography-Doppler examinations. Participants with at least 1 confirmed episode of CHF by Cardiovascular Health Study criteria were considered prevalent for CHF. The prevalence of CHF was 8.8\% and was associated with increased age, particularly for women, in whom it increased more than twofold from age 65 to 69 years (6.6\%) to age > or = 85 years (14\%). In multivariate analysis, subjects with CHF were more likely to be older (odds ratio [OR] 1.2 for 5-year difference, men OR 1.1), and more often had a history of myocardial infarction (OR 7.3), atrial fibrillation (OR 3.0), diabetes mellitus (OR 2.1), renal dysfunction (OR 2.0 for creatinine < or = 1.5 mg/ dl), and chronic pulmonary disease (OR 1.8; women only). The echocardiographic correlates of CHF were increased left atrial and ventricular dimensions. Importantly, 55\% of subjects with CHF had normal left ventricular systolic function and 80\% had either normal or only mildly reduced systolic function. Among subjects with CHF, women had normal systolic function more frequently than men (67\% vs 42\%; p < 0.001). Thus, CHF is common among community-dwelling elderly. It increases with age and is usually associated with normal systolic LV function, particularly among women. The finding that a large proportion of elderly with CHF have preserved LV systolic function is important because there is a paucity of data to guide management in this dominant subset.

}, keywords = {Aged, Aged, 80 and over, Analysis of Variance, Chi-Square Distribution, Echocardiography, Doppler, Female, Health Status, Heart Failure, Humans, Logistic Models, Longitudinal Studies, Male, Prevalence, Risk Factors, Surveys and Questionnaires, United States, Ventricular Function, Left}, issn = {0002-9149}, doi = {10.1016/s0002-9149(00)01393-x}, author = {Kitzman, D W and Gardin, J M and Gottdiener, J S and Arnold, A and Boineau, R and Aurigemma, G and Marino, E K and Lyles, M and Cushman, M and Enright, P L} } @article {638, title = {The role of comorbidity in the assessment of intermittent claudication in older adults.}, journal = {J Clin Epidemiol}, volume = {54}, year = {2001}, month = {2001 Mar}, pages = {294-300}, abstract = {

The prevalence of intermittent claudication (IC) in older adults by questionnaire is less than 5\% while the prevalence of peripheral arterial disease (PAD) by non-invasive testing is 2-4-fold higher. Comorbid conditions may result in under-reporting intermittent claudication (IC) as assessed by the Rose Questionnaire. We examined characteristics of those who report leg pain in relationship to other comorbid conditions and disability in 5888 participants of the Cardiovascular Health Study (CHS). Older adults with exertional leg pain, not meeting criteria for IC, had a higher prevalence of PAD on non-invasive testing with the ankle-arm index than those without pain, as well as a higher prevalence of arthritis. The pattern of responses suggested that pain for both conditions was reported together. The Rose Questionnaire for IC is specific for PAD, but a negative questionnaire does not indicate a lack of symptoms, rather the presence of PAD along with other conditions that can cause pain.

}, keywords = {Aged, Angina Pectoris, Arterial Occlusive Diseases, Cerebrovascular Disorders, Cohort Studies, Comorbidity, Diabetes Mellitus, Female, Humans, Intermittent Claudication, Leg, Male, Prevalence, Sensitivity and Specificity, Surveys and Questionnaires}, issn = {0895-4356}, doi = {10.1016/s0895-4356(00)00308-5}, author = {Newman, A B and Naydeck, B L and Sutton-Tyrrell, K and Polak, J F and Kuller, L H} } @article {658, title = {Transforming self-rated health and the SF-36 scales to include death and improve interpretability.}, journal = {Med Care}, volume = {39}, year = {2001}, month = {2001 Jul}, pages = {670-80}, abstract = {

BACKGROUND: Most measures of health-related quality of life are undefined for people who die. Longitudinal analyses are often limited to a healthier cohort (survivors) that cannot be identified prospectively, and that may have had little change in health.

OBJECTIVE: To develop and evaluate methods to transform a single self-rated health item (excellent to poor; EVGGFP) and the physical component score of the SF-36 (PCS) to new variables that include a defensible value for death.

METHODS: Using longitudinal data from two large studies of older adults, health variables were transformed to the probability of being healthy in the future, conditional on the current observed value; death then has the value of 0. For EVGGFP, the new transformations were compared with some that were published earlier, based on different data. For the PCS, how well three different transformations, based on different definitions of being healthy, discriminated among groups of patients, and detected change in time were assessed.

RESULTS: The new transformation for EVGGFP was similar to that published previously. Coding the 5 categories as 95, 90, 80, 30, and 15, and coding dead as 0 is recommended. The three transformations of the PCS detected group differences and change at least as well as the standard PCS.

CONCLUSION: These easily interpretable transformed variables permit keeping persons who die in the analyses. Using the transformed variables for longitudinal analyses of health when deaths occur, either for secondary or primary analysis, is recommended. This approach can be applied to other measures of health.

}, keywords = {Aged, Data Interpretation, Statistical, Death, Decision Making, Female, Health Status, Humans, Logistic Models, Longitudinal Studies, Male, Models, Statistical, Quality of Life, ROC Curve, Surveys and Questionnaires}, issn = {0025-7079}, doi = {10.1097/00005650-200107000-00004}, author = {Diehr, P and Patrick, D L and Spertus, J and Kiefe, C I and McDonell, M and Fihn, S D} } @article {736, title = {Recruitment of healthy adults into a study of overnight sleep monitoring in the home: experience of the Sleep Heart Health Study.}, journal = {Sleep Breath}, volume = {7}, year = {2003}, month = {2003 Mar}, pages = {13-24}, abstract = {

The Sleep Heart Health Study (SHHS) is a prospective cohort study using participants from several ongoing cardiovascular and respiratory disease research projects to investigate the relationship between sleep-disordered breathing and cardiovascular disease. This study design required unusual and different recruiting techniques to meet the study{\textquoteright}s enrollment goal of between 6000 and 6600 participants. Individuals were recruited to undergo an overnight home polysomnogram, completion of several questionnaires, and collection of a small amount of physical examination data. This article describes the methods used to recruit these participants and how these procedures influenced the final participation rate and the representativeness of SHHS to its parent cohorts. Of 30,773 people eligible for recruitment into SHHS, attempts were made to enroll 11,145 (36\%). Of those contacted, 6441 ultimately agreed to participate (58\%). Recruitment rates (38 to 91\%) varied among sites. SHHS participants were slightly younger (63.0 vs. 65.0 years, p < 0.001), had more years of education (14.1 vs. 13.7, p < 0.001), more likely to snore (34\% vs. 23\%, p < 0.001), had higher Epworth sleepiness scores (7.7 vs. 6.5, p < 0.001), slightly higher higher systolic and diastolic blood pressures (127.6/73.9 vs. 127.2/72.1, p < 0.001 for diastolic only), and a slightly higher body mass index (BMI) (28.5 vs. 27.5, p < 0.001). We conclude that it is feasible to recruit existing participants from one large-scale epidemiologic study into another with a high degree of success. However, the characteristics of the new cohort may vary in several respects from their original cohorts and therefore interpretation of study results will have to consider these differences.

}, keywords = {Adult, Body Mass Index, Cardiovascular Diseases, Catchment Area, Health, Circadian Rhythm, Cohort Studies, Disorders of Excessive Somnolence, Health Status, Home Care Services, Humans, Hypertension, Patient Selection, Polysomnography, Prospective Studies, Severity of Illness Index, Sleep Apnea Syndromes, Surveys and Questionnaires, United States}, issn = {1520-9512}, doi = {10.1007/s11325-003-0013-z}, author = {Lind, Bonnie K and Goodwin, James L and Hill, Joel G and Ali, Tauqeer and Redline, Susan and Quan, Stuart F} } @article {728, title = {Variation in symptoms of sleep-disordered breathing with race and ethnicity: the Sleep Heart Health Study.}, journal = {Sleep}, volume = {26}, year = {2003}, month = {2003 Feb 01}, pages = {74-9}, abstract = {

STUDY OBJECTIVES: To examine the relation of sleep-related symptoms to race and ethnicity in a diverse sample of middle-aged and older men and women.

DESIGN: Cross-sectional questionnaire survey.

SETTING: In the initial phase of the Sleep Heart Health Study, men and women enrolled in participating epidemiologic cohort studies were surveyed.

PARTICIPANTS: 13,194 men and women 40 years of age and older, including 11,517 non-Hispanic white, 648 black, 643 American Indian, 296 Hispanic, and 90 Asian-Pacific Islander.

INTERVENTIONS: Not applicable.

MEASUREMENTS AND RESULTS: After adjustment for BMI and other factors, frequent snoring was more common among Hispanic women (odds ratio (OR) = 2.25, 95\% confidence interval (CI) = 1.48, 3.42) and black women (OR = 1.55, 95\% Ci = 1.13, 2.13) than among non-Hispanic white women. Hispanic men were significantly more likely to report frequent snoring than non-Hispanic white men (OR = 2.30, 95\% CI = 1.43, 3.69). Black, American Indian, and Asian men did not differ significantly from white men in snoring prevalence. American Indian women were significantly more likely to report breathing pauses during sleep than their white, non-Hispanic counterparts (OR = 1.52, 95\% CI 1.03, 2.24), although polysomnography data on a subset of the sample suggested that the association between this symptom reported on questionnaire and objective evidence of sleep-disordered breathing may be weaker among American Indians than among other groups. Mean Epworth Sleepiness Scale scores were slightly higher in black men and women than in their white, non-hispanic counterparts.

CONCLUSIONS: Frequent snoring was more common among black and Hispanic women and Hispanic men than among their white non-Hispanic counterparts, even after adjusting for BMI and other factors. Further research including polysomnography and objective measurements of sleepiness is needed to assess the physiologic and clinical significance of these findings.

}, keywords = {Adult, Cross-Sectional Studies, Electroencephalography, Electrooculography, Ethnic Groups, Female, Heart Rate, Humans, Male, Polysomnography, Severity of Illness Index, Sleep Apnea Syndromes, Snoring, Surveys and Questionnaires}, issn = {0161-8105}, author = {O{\textquoteright}Connor, George T and Lind, Bonnie K and Lee, Elisa T and Nieto, F Javier and Redline, Susan and Samet, Jonathan M and Boland, Lori L and Walsleben, Joyce A and Foster, Gregory L} } @article {799, title = {The association of personal and neighborhood socioeconomic indicators with subclinical cardiovascular disease in an elderly cohort. The cardiovascular health study.}, journal = {Soc Sci Med}, volume = {59}, year = {2004}, month = {2004 Nov}, pages = {2139-47}, abstract = {

There has been recent interest in determining whether neighborhood characteristics are related to the cardiovascular health of residents. However, there are no data regarding the relationship between neighborhood socioeconomic status (SES) and prevalence of subclinical cardiovascular disease (CVD) in the elderly. We related personal SES (education, income, and occupation type) and neighborhood socioeconomic characteristics (a block-group score summing six variables reflecting neighborhood income and wealth, education, and occupation) to the prevalence of subclinical CVD (asymptomatic peripheral vascular disease or carotid atherosclerosis, electrocardiogram or echocardiogram abnormalities, and/or positive responses to Rose Questionnaire claudication or angina pectoris) among 3545 persons aged 65 and over, without prevalent CVD, in the Cardiovascular Health Study. Sixty percent of participants had at least one indicator of subclinical disease. Compared to those without, those with subclinical disease had significantly lower education, income, and neighborhood scores and were more likely to have blue-collar jobs. After adjustment for age, gender, and race, those in the lowest SES groups had increased prevalence of subclinical disease compared with those in the highest SES groups (OR = 1.50; 95\% CI 1.21, 1.86 for income; OR = 1.41; 95\% CI 1.18, 1.69 for education; OR = 1.39; 95\% CI 1.16, 1.67 for block-group score). Those reporting a blue-collar lifetime occupation had greater prevalence of subclinical disease relative to those reporting a white-collar occupation (OR = 1.29; 95\% CI 1.02-1.59). After adjustment for behavioral and biomedical risk factors, all of these associations were reduced. Neighborhood score tended to remain inversely associated with subclinical disease after adjustment for personal socioeconomic indicators but associations were not statistically significant. Personal income and blue-collar occupation remained significantly associated with subclinical disease after simultaneous adjustment for neighborhood score and education. Personal and neighborhood socioeconomic indicators were associated with subclinical disease prevalence in this elderly cohort. These relationships were reduced after controlling for traditional CVD risk factors.

}, keywords = {Aged, California, Cardiovascular Diseases, Cohort Studies, Female, Geography, Humans, Male, Maryland, Medicare, North Carolina, Pennsylvania, Residence Characteristics, Risk Factors, Social Class, Socioeconomic Factors, Surveys and Questionnaires}, issn = {0277-9536}, doi = {10.1016/j.socscimed.2004.03.017}, author = {Nordstrom, Cheryl K and Diez Roux, Ana V and Jackson, Sharon A and Gardin, Julius M} } @article {805, title = {Barriers to health care access among the elderly and who perceives them.}, journal = {Am J Public Health}, volume = {94}, year = {2004}, month = {2004 Oct}, pages = {1788-94}, abstract = {

OBJECTIVES: We evaluated self-perceived access to health care in a cohort of Medicare beneficiaries.

METHODS: We identified patterns of use and barriers to health care from self-administered questionnaires collected during the 1993-1994 annual examination of the Cardiovascular Health Study.

RESULTS: The questionnaires were completed by 4889 (91.1\%) participants, with a mean age of 76.0 years. The most common barriers to seeing a physician were the doctor{\textquoteright}s lack of responsiveness to patient concerns, medical bills, transportation, and street safety. Low income, no supplemental insurance, older age, and female gender were independently related to perceptions of barriers. Race was not significant after adjustment for other factors.

CONCLUSIONS: Psychological and physical barriers affect access to care among the elderly; these may be influenced by poverty more than by race.

}, keywords = {Aged, Aged, 80 and over, Chi-Square Distribution, Female, Health Behavior, Health Services Accessibility, Humans, Logistic Models, Male, Medicare, Patients, Surveys and Questionnaires, United States}, issn = {0090-0036}, doi = {10.2105/ajph.94.10.1788}, author = {Fitzpatrick, Annette L and Powe, Neil R and Cooper, Lawton S and Ives, Diane G and Robbins, John A} } @article {776, title = {Sleep and reported daytime sleepiness in normal subjects: the Sleep Heart Health Study.}, journal = {Sleep}, volume = {27}, year = {2004}, month = {2004 Mar 15}, pages = {293-8}, abstract = {

STUDY OBJECTIVES: To describe the distribution of nocturnal sleep characteristics and reports of daytime sleepiness in a large well-defined group of healthy adults.

DESIGN: The Sleep Heart Health Study is a multicenter study examining sleep and cardiopulmonary parameters through nocturnal polysomnography in adults enrolled in geographically distinct cardiovascular cohorts.

SETTING: Community setting.

PARTICIPANTS: 470 subjects enrolled in the Sleep Heart Health Study (n = 6440) were selected as a {\textquoteright}normative{\textquoteright} group based on screening of health conditions and daily habits that could interfere with sleep.

MEASUREMENTS AND RESULTS: Home-based nocturnal polysomnography was obtained on all participants and centrally scored for sleep and respiratory parameters. Demographic and health-related data were obtained and updated at the time of the home visit. Sleep efficiency decreased by 1.6\% for each 10 years of increased age. Sleep time decreased by 0.1 hours (6.0 minutes) for each 10-year age increase and was longer in women. The arousal index increased by 0.8 for each 10-year increase in age and was lower by 1.4 in women. Women had a lower mean percentage of stage 1 and stage 2 sleep. Mean percentage of slow-wave sleep was higher in women (by 6.7\%). Percentage of slow-wave sleep decreased with increased age for men only (by 1.9\% for each 10-year age change).

CONCLUSIONS: Data suggest a clear lessening in the quantity and quality of sleep with age that appears to be more rapid in males compared to females.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Circadian Rhythm, Cohort Studies, Disorders of Excessive Somnolence, Female, Health Status, Humans, Male, Middle Aged, Polysomnography, Sleep, Sleep Stages, Surveys and Questionnaires}, issn = {0161-8105}, doi = {10.1093/sleep/27.2.293}, author = {Walsleben, Joyce A and Kapur, Vishesh K and Newman, Anne B and Shahar, Eyal and Bootzin, Richard R and Rosenberg, Carl E and O{\textquoteright}Connor, George and Nieto, F Javier} } @article {834, title = {Association of sleep time with diabetes mellitus and impaired glucose tolerance.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Apr 25}, pages = {863-7}, abstract = {

BACKGROUND: Experimental sleep restriction causes impaired glucose tolerance (IGT); however, little is known about the metabolic effects of habitual sleep restriction. We assessed the cross-sectional relation of usual sleep time to diabetes mellitus (DM) and IGT among participants in the Sleep Heart Health Study, a community-based prospective study of the cardiovascular consequences of sleep-disordered breathing.

METHODS: Participants were 722 men and 764 women, aged 53 to 93 years. Usual sleep time was obtained by standardized questionnaire. Diabetes mellitus was defined as a serum glucose level of 126 mg/dL or more (> or =7.0 mmol/L) fasting or 200 mg/dL or more (> or =11.1 mmol/L) 2 hours following standard oral glucose challenge or medication use for DM. Impaired glucose tolerance was defined as a 2-hour postchallenge glucose level of 140 mg/dL or more (> or =7.8 mmol/L) and less than 200 mg/dL. The relation of sleep time to DM and IGT was examined using categorical logistic regression with adjustment for age, sex, race, body habitus, and apnea-hypopnea index.

RESULTS: The median sleep time was 7 hours per night, with 27.1\% of subjects sleeping 6 hours or less per night. Compared with those sleeping 7 to 8 hours per night, subjects sleeping 5 hours or less and 6 hours per night had adjusted odds ratios for DM of 2.51 (95\% confidence interval, 1.57-4.02) and 1.66 (95\% confidence interval, 1.15-2.39), respectively. Adjusted odds ratios for IGT were 1.33 (95\% confidence interval, 0.83-2.15) and 1.58 (95\% confidence interval, 1.15-2.18), respectively. Subjects sleeping 9 hours or more per night also had increased odds ratios for DM and IGT. These associations persisted when subjects with insomnia symptoms were excluded.

CONCLUSIONS: A sleep duration of 6 hours or less or 9 hours or more is associated with increased prevalence of DM and IGT. Because this effect was present in subjects without insomnia, voluntary sleep restriction may contribute to the large public health burden of DM.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Blood Glucose, Diabetes Mellitus, Disease Progression, Female, Glucose Intolerance, Humans, Male, Middle Aged, Odds Ratio, Prevalence, Prospective Studies, Sleep, Surveys and Questionnaires, Time Factors, United States}, issn = {0003-9926}, doi = {10.1001/archinte.165.8.863}, author = {Gottlieb, Daniel J and Punjabi, Naresh M and Newman, Ann B and Resnick, Helaine E and Redline, Susan and Baldwin, Carol M and Nieto, F Javier} } @article {870, title = {Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4.}, journal = {Neurology}, volume = {65}, year = {2005}, month = {2005 Nov 08}, pages = {1409-14}, abstract = {

OBJECTIVE: To compare associations of lean fish vs fatty fish (tuna or other fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD) and in relation to APOE epsilon4 status in the Cardiovascular Health Cognition Study (CHCS).

METHODS: Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician{\textquoteright}s assessment, and committee consensus. We used Cox proportional hazards regression to calculate hazard ratios of dementia, AD, and VaD with lean fried fish, fatty fish, or total fish intake, which were then stratified by the presence of APOE epsilon4.

RESULTS: Although consumption of lean fried fish had no protective effect, consumption of fatty fish more than twice per week was associated with a reduction in risk of dementia by 28\% (95\% CI: 0.51 to 1.02), and AD by 41\% (95\% CI: 0.36 to 0.95) in comparison to those who ate fish less than once per month. Stratification by APOE epsilon4 showed this effect to be selective to those without the epsilon4 allele. Adjustment by education and income attenuated the effect.

CONCLUSION: In the Cardiovascular Health Cognition Study, consumption of fatty fish was associated with a reduced risk of dementia and Alzheimer disease for those without the APOE epsilon4 allele.

}, keywords = {Aged, Alzheimer Disease, Apolipoprotein E4, Apolipoproteins E, Cohort Studies, Dementia, Dietary Fats, Unsaturated, Fatty Acids, Omega-3, Feeding Behavior, Female, Fish Oils, Fish Products, Food, Formulated, Genetic Predisposition to Disease, Humans, Incidence, Male, Risk Factors, Socioeconomic Factors, Surveys and Questionnaires}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000183148.34197.2e}, author = {Huang, T L and Zandi, P P and Tucker, K L and Fitzpatrick, A L and Kuller, L H and Fried, L P and Burke, G L and Carlson, M C} } @article {833, title = {Factors associated with incidence and persistence of symptoms of disturbed sleep in an elderly cohort: the Cardiovascular Health Study.}, journal = {Am J Med Sci}, volume = {329}, year = {2005}, month = {2005 Apr}, pages = {163-72}, abstract = {

BACKGROUND: There are limited data pertaining to the factors influencing the incidence and persistence of sleep symptoms in the elderly. The purpose of this study was to determine the incidence and nonremission rates of the following sleep symptoms: trouble falling asleep (TFA), frequent awakenings (FA), and excessive daytime sleepiness (EDS) in the Cardiovascular Health Study (CHS), a prospective multicenter study of cardiovascular disease in a large cohort of elderly adults. Factors influencing these rates were assessed as well.

METHODS: 4467 participants in CHS were surveyed for the presence of TFA, FA, and EDS as well as other health problems at their baseline examination and at a follow-up examination 1 to 4 years later.

RESULTS: Annualized incidence and nonremission rates were the following: TFA (2.8\% and 15.4\%), FA (12.3\% and 22.7\%), and EDS (4.4\% and 13.4\%). Women were more likely to have incident and persistent TFA. Depression was the primary factor predicting the incidence of all three sleep symptoms. However, other health conditions, including respiratory symptoms and cardiovascular disease, and limitation in activities of daily living were important as well. Depression also was the most important factor associated with persistence of these sleep symptoms. The role of other health conditions in determining nonremission was much more limited.

CONCLUSIONS: Incidence of sleep disturbances in the elderly is related to depression, health conditions, and physical functioning. However, persistence of sleep disturbances is best predicted by the presence of depression.

}, keywords = {Aged, Cardiovascular Diseases, Cohort Studies, Depression, Female, Health Status, Humans, Incidence, Logistic Models, Male, Odds Ratio, Prevalence, Risk Factors, Sex Factors, Sleep Initiation and Maintenance Disorders, Surveys and Questionnaires}, issn = {0002-9629}, doi = {10.1097/00000441-200504000-00001}, author = {Quan, Stuart F and Katz, Ronit and Olson, Jean and Bonekat, William and Enright, Paul L and Young, Terry and Newman, Anne} } @article {818, title = {Fish consumption and stroke risk in elderly individuals: the cardiovascular health study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Jan 24}, pages = {200-6}, abstract = {

BACKGROUND: Associations between fish consumption and stroke risk have been inconsistent, possibly because of the differences in types of fish meals consumed. Additionally, such relationships have not been specifically evaluated in the elderly, in whom disease burden may be high and diet less influential.

METHODS: Among 4775 adults 65 years or older (range, 65-98 years) and free of known cerebrovascular disease at baseline in 1989-1990, usual dietary intake was assessed using a food frequency questionnaire. In a subset, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches (fish burgers), correlated with plasma phospholipid long-chain n-3 fatty acid levels. Incident strokes were prospectively ascertained.

RESULTS: During 12 years of follow-up, participants experienced 626 incident strokes, including 529 ischemic strokes. In multivariate analyses, tuna/other fish consumption was inversely associated with total stroke (P = .04) and ischemic stroke (P = .02), with 27\% lower risk of ischemic stroke with an intake of 1 to 4 times per week (hazard ratio [HR], 0.73; 95\% confidence interval [CI], 0.55-0.98) and 30\% lower risk with intake of 5 or more times per week (HR, 0.70; 95\% CI, 0.50-0.99) compared with an intake of less than once per month. In contrast, fried fish/fish sandwich consumption was positively associated with total stroke (P = .006) and ischemic stroke (P = .003), with a 44\% higher risk of ischemic stroke with consumption of more than once per week (HR, 1.44; 95\% CI, 1.12-1.85) compared with consumption of less than once per month. Fish consumption was not associated with hemorrhagic stroke.

CONCLUSIONS: Among elderly individuals, consumption of tuna or other broiled or baked fish is associated with lower risk of ischemic stroke, while intake of fried fish or fish sandwiches is associated with higher risk. These results suggest that fish consumption may influence stroke risk late in life; potential mechanisms and alternate explanations warrant further study.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Animals, Cohort Studies, Confidence Intervals, Diet, Fatty Acids, Omega-3, Female, Fish Oils, Fishes, Humans, Incidence, Male, Multivariate Analysis, Probability, Proportional Hazards Models, Risk Assessment, Seafood, Sensitivity and Specificity, Sex Distribution, Stroke, Surveys and Questionnaires, Survival Rate, United States}, issn = {0003-9926}, doi = {10.1001/archinte.165.2.200}, author = {Mozaffarian, Dariush and Longstreth, W T and Lemaitre, Rozenn N and Manolio, Teri A and Kuller, Lewis H and Burke, Gregory L and Siscovick, David S} } @article {839, title = {Predictors of heartburn during sleep in a large prospective cohort study.}, journal = {Chest}, volume = {127}, year = {2005}, month = {2005 May}, pages = {1658-66}, abstract = {

BACKGROUND AND AIMS: Nocturnal gastroesophageal reflux, which may result in nocturnal heartburn, has been demonstrated to be associated with a more severe form of gastroesophageal reflux disease (GERD). The aim of this study was to determine the clinical predictors of heartburn during sleep in a large prospective cohort study.

METHODS: Study subjects were members of the parent cohorts from which the Sleep Heart Health Study (SHHS) recruited participants. SHHS is a multicenter, longitudinal, cohort study of the cardiovascular consequences of sleep-disordered breathing. As part of the recruitment process, parent cohort members completed a questionnaire that permitted an assessment of the relationships between heartburn during sleep, and patient demographics, sleep abnormalities, medical history, and social habits in nine community-based parent cohorts across the United States. All variables, significant at the p < 0.05 level, were included as independent variables in multivariate logistic regression models with heartburn during sleep status included as the dependent variable

RESULTS: A total of 15,314 subjects completed the questions about heartburn during sleep, and of these, 3,806 subjects (24.9\%) reported having this symptom. In four increasingly comprehensive multivariate models, increased body mass index (BMI), carbonated soft drink consumption, snoring and daytime sleepiness (Epworth sleepiness scale score), insomnia, hypertension, asthma, and usage of benzodiazepines were strong predictors of heartburn during sleep. In contrast, college education decreased the risk of reporting heartburn during sleep.

CONCLUSIONS: Heartburn during sleep is very common in the general population. Reports of this type of symptom of GERD are strongly associated with increased BMI, carbonated soft drink consumption, snoring and daytime sleepiness, insomnia, hypertension, asthma, and usage of benzodiazepines. Overall, heartburn during sleep may be associated with sleep complaints and excessive daytime sleepiness.

}, keywords = {Aged, Body Mass Index, Carbonated Beverages, Cohort Studies, Educational Status, Female, Gastroesophageal Reflux, Heartburn, Humans, Male, Middle Aged, Multivariate Analysis, Prospective Studies, Sleep, Surveys and Questionnaires}, issn = {0012-3692}, doi = {10.1378/chest.127.5.1658}, author = {Fass, Ronnie and Quan, Stuart F and O{\textquoteright}Connor, George T and Ervin, Ann and Iber, Conrad} } @article {858, title = {Sleepiness in patients with moderate to severe sleep-disordered breathing.}, journal = {Sleep}, volume = {28}, year = {2005}, month = {2005 Apr}, pages = {472-7}, abstract = {

BACKGROUND: Population-based studies suggest that complaints of sleepiness are absent in many individuals with sleep-disordered breathing. We investigated the prevalence of sleepiness as well as factors associated with sleepiness in individuals with moderate to severe sleep-disordered breathing (apnea-hypopnea index > or = 15).

DESIGN: Cross-sectional study.

SETTING: The Sleep Heart Health Study.

PARTICIPANTS: Sleep Heart Health Study participants (N = 6440).

MEASUREMENTS AND RESULTS: Sleepiness was defined as an Epworth Sleepiness Scale score >10 or a report of at least frequently feeling unrested or sleepy. Forty-six percent of participants with moderate to severe sleep-disordered breathing (n = 1149) reported sleepiness. Characteristics associated with sleepiness after adjustment for confounders included presence of respiratory disease, shorter self-reported weekday and weekend sleep, sleep durations, complaints of insufficient sleep, complaints of sleep maintenance insomnia, early morning awakening, habitual snoring, and complaints of awakening with leg cramps or leg jerks. Some respiratory polysomnography measures were associated with sleepiness, but sleep-stage percentages and measures of sleep disruption were not.

CONCLUSIONS: In this community-based cohort, subjective sleepiness is absent in many individuals with significant sleep-disordered breathing. Comorbid conditions, including respiratory disease, sleep restriction, insomnia, and nocturnal leg complaints, are important risk factors for sleepiness in individuals with moderate to severe sleep-disordered breathing.

}, keywords = {Aged, Body Mass Index, Cohort Studies, Cross-Sectional Studies, Disorders of Excessive Somnolence, Female, Humans, Male, Middle Aged, Oxygen, Polysomnography, Prevalence, Risk Factors, Severity of Illness Index, Sleep Apnea Syndromes, Sleep Arousal Disorders, Sleep Stages, Surveys and Questionnaires}, issn = {0161-8105}, doi = {10.1093/sleep/28.4.472}, author = {Kapur, Vishesh K and Baldwin, Carol M and Resnick, Helaine E and Gottlieb, Daniel J and Nieto, F Javier} } @article {924, title = {Clinical course of mesenteric artery stenosis in elderly americans.}, journal = {Arch Intern Med}, volume = {166}, year = {2006}, month = {2006 Oct 23}, pages = {2095-100}, abstract = {

BACKGROUND: To examine prospectively the relationship between stenosis or occlusion of the celiac and superior mesenteric arteries and symptoms of chronic intestinal ischemia in free-living elderly patients in the United States.

METHODS: As part of an ancillary study to the Cardiovascular Health Study, participants in the Forsyth County (North Carolina) cohort underwent visceral duplex ultrasonography of the celiac and superior mesenteric arteries. Critical mesenteric artery stenosis (MAS) or occlusion was defined by Doppler flow ultrasound-derived criteria. Clinical outcomes were assessed at annual follow-up examinations and review of death certificates. Multivariate associations between the presence of MAS and all-cause mortality and adverse cardiovascular events were analyzed. Participants with MAS were contacted to determine the presence of symptoms consistent with chronic intestinal ischemia.

RESULTS: Of 553 participants who underwent visceral duplex ultrasonography, 97 (17.5\%) had disease of the celiac or superior mesenteric artery. At a mean follow-up of 6(1/2) years, 20 participants with MAS (20.6\%) and 93 without MAS (20.4\%) had died (relative risk, 1.01; 95\% confidence interval, 0.66-1.55). No deaths were attributed to intestinal infarction. No association existed between the presence of MAS and prevalent cardiovascular disease, all-cause mortality, or adverse cardiovascular events. A questionnaire was completed by 71\% of the surviving participants with MAS. No participant reported symptoms or weight loss consistent with chronic intestinal ischemia.

CONCLUSIONS: Mesenteric artery stenosis was a common finding in free-living elderly patients. At long-term follow-up, the presence of asymptomatic MAS was not associated with death or adverse cardiovascular events. Participants with asymptomatic MAS by duplex ultrasonographic criteria did not experience intestinal infarction or develop chronic intestinal ischemia.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Comorbidity, Female, Humans, Male, Mesenteric Arteries, Mesenteric Vascular Occlusion, Proportional Hazards Models, Prospective Studies, Radiography, Risk Factors, Surveys and Questionnaires, Ultrasonography}, issn = {0003-9926}, doi = {10.1001/archinte.166.19.2095}, author = {Wilson, David B and Mostafavi, Kian and Craven, Timothy E and Ayerdi, Juan and Edwards, Matthew S and Hansen, Kimberley J} } @article {888, title = {A cross-sectional study of vitamin C and cognitive function in older adults: the differential effects of gender.}, journal = {J Nutr Health Aging}, volume = {10}, year = {2006}, month = {2006 Jan-Feb}, pages = {37-44}, abstract = {

Previous studies have suggested that vitamin C status may be associated with cognitive function in community-dwelling populations. However, this has not been consistent across all studies due to methodological differences. This cross-sectional study assessed the association between vitamin C and cognitive function in 544 community-dwelling older adults aged 65 or older who participated in both the Cardiovascular Health Study (CHS) and the CLUE II study in 1989. Three percent of the subjects had low plasma vitamin C concentrations (< 40 mg/dL) and 15\% had low total vitamin C intake (< 60 mg/day). Most participants (96.7 percent) had normal cognitive function. In the unadjusted analyses, the highest fifth of plasma vitamin C concentration was associated with better Digit Symbol Substitution Test (DSST) scores and marginally associated with Mini-Mental State Examination (MMSE) compared to the lowest fifth. Total vitamin C intake, measured by Block{\textquoteright}s food frequency questionnaire, was generally associated with higher MMSE scores, though it was not significant. Adjusting for numerous factors did not substantially change results. In a stratified analysis by gender, higher plasma concentrations or intake were associated with higher MMSE scores for men but not for women. These mixed results do not provide strong evidence of an association between vitamin C concentrations or intake and cognitive function.

}, keywords = {Aged, Aging, Ascorbic Acid, Cognition, Cross-Sectional Studies, Diet, Female, Health Surveys, Humans, Male, Mental Status Schedule, Nutrition Surveys, Nutritional Requirements, Sex Factors, Surveys and Questionnaires}, issn = {1279-7707}, author = {Sato, R and Helzlsouer, K J and Comstock, G W and Hoffman, S C and Norkus, E P and Fried, L P} } @article {902, title = {Obstructive sleep apnea-hypopnea and neurocognitive functioning in the Sleep Heart Health Study.}, journal = {Sleep Med}, volume = {7}, year = {2006}, month = {2006 Sep}, pages = {498-507}, abstract = {

BACKGROUND AND PURPOSE: Obstructive sleep apnea-hypopnea (OSAH) is associated with sleep fragmentation and nocturnal hypoxemia. In clinical samples, patients with OSAH frequently are found to have deficits in neuropsychological function. However, the nature and severity of these abnormalities in non-clinical populations is less well defined.

PATIENTS AND METHODS: One hundred and forty-one participants from the Tucson, AZ and New York, NY field centers of the Sleep Heart Health Study completed a battery of neuropsychological tests for 9-40 months (mean=24 months, SD=7 months) after an unattended home polysomnogram. Sixty-seven participants had OSAH (AHI>10) and 74 did not have OSAH (control (CTL), apnea-hypopnea index (AHI)<5). In addition to the individual tests, composite variables representing attention, executive function, MotorSpeed and processing speed were constructed from the neuropsychological test battery.

RESULTS: There were no significant differences in any individual neuropsychological test or composite variable between the OSAH and CTL groups. However, when time spent with O(2) saturations less than 85\% was dichotomized into those participants in the top quartile of the distribution and those in the lower three quartiles, motor speed was significantly impaired in those who were more hypoxemic. In addition, poorer motor speed (model adjusted R(2)=0.242, P<0.001) and processing speed performance (model adjusted R(2)=0.122, P<0.001) were associated with more severe oxygen desaturation even after controlling for degree of daytime sleepiness, age, gender and educational level.

CONCLUSIONS: Mild to moderate OSAH has little impact on the selected measures of attention, executive function, motor speed and processing speed. However, hypoxemia adversely affects both motor and processing speed. These results suggest that in middle-aged to elderly adults the neuropsychological effects of clinically unrecognized mild to moderate OSAH are neither global nor large.

}, keywords = {Brain, Cognition Disorders, Continuous Positive Airway Pressure, Demography, Disorders of Excessive Somnolence, Electromyography, Electrooculography, Female, Health Status, Humans, Hypoxia, Male, Middle Aged, Neuropsychological Tests, Oxygen, Polysomnography, Severity of Illness Index, Sleep Apnea, Obstructive, Surveys and Questionnaires}, issn = {1389-9457}, doi = {10.1016/j.sleep.2006.02.005}, author = {Quan, Stuart F and Wright, Ron and Baldwin, Carol M and Kaemingk, Kristine L and Goodwin, James L and Kuo, Tracy F and Kaszniak, Alfred and Boland, Lori L and Caccappolo, Elise and Bootzin, Richard R} } @article {989, title = {Genome-wide association of sleep and circadian phenotypes.}, journal = {BMC Med Genet}, volume = {8 Suppl 1}, year = {2007}, month = {2007 Sep 19}, pages = {S9}, abstract = {

BACKGROUND: Numerous studies suggest genetic influences on sleepiness and circadian rhythms. The Sleep Heart Health Study collected questionnaire data on sleep habits and sleepiness from 2848 Framingham Heart Study Offspring Cohort participants. More than 700 participants were genotyped using the Affymetrix 100K SNP GeneChip, providing a unique opportunity to assess genetic linkage and association of these traits.

METHODS: Sleepiness (defined as the Epworth Sleepiness Scale score), usual bedtime and usual sleep duration were assessed by self-completion questionnaire. Standardized residual measures adjusted for age, sex and BMI were analyzed. Multipoint variance components linkage analysis was performed. Association of SNPs to sleep phenotypes was analyzed with both population-based and family-based association tests, with analysis limited to 70,987 autosomal SNPs with minor allele frequency > or =10\%, call rate > or =80\%, and no significant deviation from Hardy-Weinberg equilibrium (p > or = 0.001).

RESULTS: Heritability of sleepiness was 0.29, bedtime 0.22, and sleep duration 0.17. Both genotype and sleep phenotype data were available for 749 subjects. Linkage analysis revealed five linkage peaks of LOD >2: four to usual bedtime, one to sleep duration. These peaks include several candidate sleep-related genes, including CSNK2A2, encoding a known component of the circadian molecular clock, and PROK2, encoding a putative transmitter of the behavioral circadian rhythm from the suprachiasmatic nucleus. Association tests identified an association of usual bedtime with a non-synonymous coding SNP in NPSR1 that has been shown to encode a gain of function mutation of the neuropeptide S receptor, whose endogenous ligand is a potent promoter of wakefulness. Each copy of the minor allele of this SNP was associated with a 15 minute later mean bedtime. The lowest p value was for association of sleepiness with a SNP located in an intron of PDE4D, which encodes a cAMP-specific phosphodiesterase widely expressed in human brain. Full association results are posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite.

CONCLUSION: This analysis confirms prior reports of significant heritability of sleepiness, usual bedtime, and usual sleep duration. Several genetic loci with suggestive linkage to these traits are identified, including linkage peaks containing circadian clock-related genes. Association tests identify NPSR1 and PDE4D as possible mediators of bedtime and sleepiness.

}, keywords = {Adult, Alleles, Cardiovascular Diseases, Circadian Rhythm, Cohort Studies, Female, Gene Frequency, Genetic Linkage, Genome, Human, Genotype, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Sleep, Surveys and Questionnaires}, issn = {1471-2350}, doi = {10.1186/1471-2350-8-S1-S9}, author = {Gottlieb, Daniel J and O{\textquoteright}Connor, George T and Wilk, Jemma B} } @article {996, title = {Relationship between reported and measured sleep times: the sleep heart health study (SHHS).}, journal = {J Clin Sleep Med}, volume = {3}, year = {2007}, month = {2007 Oct 15}, pages = {622-30}, abstract = {

STUDY OBJECTIVE: Subjective and objective assessments of sleep may be discrepant due to sleep misperception and measurement effects, the latter of which may change the quality and quantity of a person{\textquoteright}s usual sleep. This study compared sleep times from polysomnography (PSG) with self-reports of habitual sleep and sleep estimated on the morning after a PSG in adults.

DESIGN: Total sleep time and sleep onset latency obtained from unattended home PSGs were compared to sleep times obtained from a questionnaire completed before the PSG and a Morning Survey completed the morning after the PSG.

PARTICIPANTS: A total of 2,113 subjects who were > or = 40 years of age were included in this analysis.

MEASURES AND RESULTS: Subjects were 53\% female, 75\% Caucasian, and 38\% obese. The mean habitual sleep time (HABTST), morning estimated sleep time (AMTST), and PSG total sleep times (PSGTST) were 422 min, 379 min, and 363 min, respectively. The mean habitual sleep onset latency, morning estimated sleep onset latency, and PSG sleep onset latency were 17.0 min, 21.8 min, and 16.9 min, respectively. Models adjusting for related demographic factors showed that HABTST and AMTST differ significantly from PSGTST by 61 and 18 minutes, respectively. Obese and higher educated people reported less sleep time than their counterparts. Similarly, small but significant differences were seen for sleep latency.

CONCLUSIONS: In a community population, self-reported total sleep times and sleep latencies are overestimated even on the morning following overnight PSG.

}, keywords = {Adult, Attitude to Health, Female, Health Status, Humans, Male, Middle Aged, Polysomnography, Psychometrics, Sleep Initiation and Maintenance Disorders, Sleep Stages, Surveys and Questionnaires, Time Factors, Wakefulness}, issn = {1550-9389}, author = {Silva, Graciela E and Goodwin, James L and Sherrill, Duane L and Arnold, Jean L and Bootzin, Richard R and Smith, Terry and Walsleben, Joyce A and Baldwin, Carol M and Quan, Stuart F} } @article {994, title = {Alcohol consumption and lower extremity arterial disease among older adults: the cardiovascular health study.}, journal = {Am J Epidemiol}, volume = {167}, year = {2008}, month = {2008 Jan 01}, pages = {34-41}, abstract = {

Few studies of the relation of alcohol intake to lower-extremity arterial disease (LEAD) have included clinical events and objective measurements repeated longitudinally. As part of the Cardiovascular Health Study, a study of older adults from four US communities, 5,635 participants reported their use of beer, wine, and spirits yearly. Incident LEAD was identified by hospitalization surveillance. Technicians measured ankle-brachial index 6 years apart in 2,298 participants. A total of 172 cases of LEAD were documented during a mean of 7.5 years of follow-up between 1989 and 1999. Compared with abstention, the multivariable-adjusted hazard ratios were 1.10 (95\% confidence interval (CI): 0.71, 1.71) for <1 alcoholic drink per week, 0.56 (95\% CI: 0.33, 0.95) for 1-13 drinks per week, and 1.02 (95\% CI: 0.53, 1.97) for > or =14 drinks per week (p for quadratic trend = 0.04). These relations were consistent within strata of sex, age, and apolipoprotein E genotype, and neither lipids nor inflammatory markers appeared to be important intermediates. Change in ankle-brachial index showed a similar relation (p for quadratic trend = 0.01). Alcohol consumption of 1-13 drinks per week in older adults may be associated with lower risk of LEAD, but heavier drinking is not associated with lower risk.

}, keywords = {Aged, Alcohol Drinking, Female, Follow-Up Studies, Health Surveys, Humans, Intermittent Claudication, Male, Prevalence, Prospective Studies, Risk Factors, Surveys and Questionnaires, Time Factors, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwm274}, author = {Mukamal, Kenneth J and Kennedy, Margaret and Cushman, Mary and Kuller, Lewis H and Newman, Anne B and Polak, Joseph and Criqui, Michael H and Siscovick, David S} } @article {1004, title = {Association of restless legs syndrome and cardiovascular disease in the Sleep Heart Health Study.}, journal = {Neurology}, volume = {70}, year = {2008}, month = {2008 Jan 01}, pages = {35-42}, abstract = {

OBJECTIVE: We evaluated the cross-sectional association between restless legs syndrome (RLS) and prevalent cardiovascular disease (CVD) in a large community-based sample of middle-aged and elderly subjects.

METHODS: This is a cross-sectional observational study of 1,559 men and 1,874 women (mean age of 67.9 years) who were enrolled in the Sleep Heart Health Study, a community-based study of the cardiovascular consequences of sleep-disordered breathing. RLS was defined by positive responses on a self-administered questionnaire to the four diagnostic criteria, with symptoms occurring at least five times per month and associated with at least moderate distress. Coronary artery disease (CAD) was determined by self-report of doctor-diagnosed angina, myocardial infarction, or coronary revascularization procedure. Total CVD included CAD or history of physician-diagnosed stroke or heart failure. The relation of RLS to prevalent CAD and CVD was examined by multivariable logistic regression models

RESULTS: RLS was present in 6.8\% of women (n = 128) and 3.3\% of men (n = 51). After adjustment for age, sex, race, body mass index, diabetes mellitus, systolic blood pressure, antihypertensive medication use, total:high-density lipoprotein cholesterol ratio, and smoking history, the ORs for CAD were 2.05 (95\% CI 1.38 to 3.04) and for CVD were 2.07 (1.43 to 3.00) for subjects with RLS compared to those without RLS. The associations of RLS with CAD and CVD were stronger in those with RLS symptoms at least 16 times per month and were stronger in those with severe than in those with moderately bothersome symptoms.

CONCLUSIONS: Restless legs syndrome (RLS) is associated with prevalent coronary artery disease and cardiovascular disease. This association appears stronger in those with greater frequency or severity of RLS symptoms.

}, keywords = {Aged, Body Mass Index, Cardiovascular Diseases, Cross-Sectional Studies, Evaluation Studies as Topic, Female, Health Surveys, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Prevalence, Restless Legs Syndrome, Surveys and Questionnaires}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000287072.93277.c9}, author = {Winkelman, John W and Shahar, Eyal and Sharief, Imran and Gottlieb, Daniel J} } @article {1041, title = {Subjective and objective sleep quality in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the sleep heart health study.}, journal = {Am J Kidney Dis}, volume = {52}, year = {2008}, month = {2008 Aug}, pages = {305-13}, abstract = {

BACKGROUND: Studies examining sleep in the hemodialysis (HD) population have largely lacked an adequate comparison group. It therefore is uncertain whether poor sleep quality in the HD population reflects age, chronic health conditions, or effects of conventional HD therapy.

STUDY DESIGN: Cross-sectional matched-group study.

SETTING \& PARTICIPANTS: Forty-six in-center HD patients were compared with 137 community participants participating in the Sleep Heart Health Study matched for age, sex, body mass index, and race.

PREDICTOR: HD patients compared with community-dwelling non-HD participants.

OUTCOMES \& MEASUREMENTS: Home unattended polysomnography was performed and scored by using similar protocols. Sleep habits and sleepiness were assessed by using the Sleep Habits Questionnaire and Epworth Sleepiness Scale.

RESULTS: Average age of study samples was 63 years, 72\% were white, and average body mass index was 28 +/- 5 kg/m(2). HD patients were significantly more likely than community participants to have short sleep (odds ratio, 3.27; 95\% confidence interval, 1.16 to 9.25) and decreased sleep efficiency (odds ratio, 5.5; 95\% confidence interval, 1.5 to 19.6). HD patients reported more difficulty getting back to sleep (odds ratio, 2.25; 95\% confidence interval, 1.11 to 4.60) and waking up too early (odds ratio, 2.39; 95\% confidence interval, 1.01 to 5.66). There was no association between polysomnography sleep time and self-reported sleep time (r = 0.09; P = 0.6) or between the Epworth Sleepiness Scale and severity of sleep apnea (r = 0.10; P = 0.5) in the HD population.

LIMITATIONS: The study was limited to participants older than 45 years.

CONCLUSIONS: Kidney failure treated with thrice-weekly HD is significantly associated with poor subjective and objective sleep quality.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cross-Sectional Studies, Disease Progression, Female, Follow-Up Studies, Heart Rate, Humans, Incidence, Kidney Failure, Chronic, Male, Middle Aged, Odds Ratio, Pennsylvania, Polysomnography, Prognosis, Renal Dialysis, Retrospective Studies, Risk Factors, Severity of Illness Index, Sleep, Sleep Apnea Syndromes, Surveys and Questionnaires}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2008.04.019}, author = {Unruh, Mark L and Sanders, Mark H and Redline, Susan and Piraino, Beth M and Umans, Jason G and Chami, Hassan and Budhiraja, Rohit and Punjabi, Naresh M and Buysse, Daniel and Newman, Anne B} } @article {1102, title = {Spousal suffering and partner{\textquoteright}s depression and cardiovascular disease: the Cardiovascular Health Study.}, journal = {Am J Geriatr Psychiatry}, volume = {17}, year = {2009}, month = {2009 Mar}, pages = {246-54}, abstract = {

OBJECTIVES: To assess the effects of suffering in a spouse on prevalent and incident psychiatric (depression) and physical morbidity (cardiovascular disease [CVD]) in their partner, controlling for known risk factors for depression and CVD.

DESIGN: Descriptive longitudinal study.

PARTICIPANTS: A total of 1,330 older married couples enrolled in the Cardiovascular Health Study, a large epidemiologic study of the elderly.

MEASUREMENTS: Predictor variables were physical, psychological, and existential/spiritual indicators of suffering. Primary outcomes were prevalent and incident depression and CVD.

RESULTS: Controlling for known risk factors for depression, the authors found a dose-response relationship between suffering in a spouse and concurrent depression in their partner as well as a relationship between suffering and the partner{\textquoteright}s future risk for depression. With respect to CVD, and controlling for subclinical CVD at baseline, husbands whose wives reported high levels of suffering also had higher rates of prevalent CVD, but there were no significant associations between wives suffering and husbands incident CVD. There were no associations between husbands{\textquoteright} suffering and wives{\textquoteright} prevalent or incident CVD.

CONCLUSION: Exposure to spousal suffering is an independent and unique source of distress in married couples that contributes to psychiatric and physical morbidity. More attention should be paid to the interpersonal effects of suffering in married couples and to its role in contributing to morbidity.

}, keywords = {Activities of Daily Living, Aged, Cardiovascular Diseases, Caregivers, Depression, Female, Follow-Up Studies, Humans, Incidence, Logistic Models, Longitudinal Studies, Male, Prevalence, Risk Factors, Socioeconomic Factors, Spouses, Stress, Psychological, Surveys and Questionnaires}, issn = {1545-7214}, doi = {10.1097/JGP.0b013e318198775b}, author = {Schulz, Richard and Beach, Scott R and Hebert, Randy S and Martire, Lynn M and Monin, Joan K and Tompkins, Connie A and Albert, Steven M} } @article {1212, title = {Cognition and the risk of hospitalization for serious falls in the elderly: results from the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {65}, year = {2010}, month = {2010 Nov}, pages = {1242-9}, abstract = {

BACKGROUND: Many elderly adults fall every year, sometimes resulting in serious injury and hospitalization. Although impaired cognition is a risk factor for injurious falls, little is known about cognitive decline above the threshold of impairment and risk of serious falls in community-dwelling seniors.

METHODS: In total, 702 of 5,356 older adults participating in the Cardiovascular Health Study experienced an injurious fall between 1990 and 2005, as indicated by hospitalization records. General cognition was measured annually with the Modified Mini-Mental State Examination and processing speed with the Digit Symbol Substitution Test. The Cox regression model was used to calculate hazard ratio and 95\% confidence interval with and without time-dependent covariates and adjusted for known risk factors.

RESULTS: Participants with slightly decreased Digit Symbol Substitution Test scores were at increased risk for a serious fall (hazard ratio = 1.58, 95\% confidence interval = 1.15-2.17). The risk continued to increase with each quartile decrease in Digit Symbol Substitution Test score. Participants without prevalent cardiovascular disease at baseline and decreased Modified Mini-Mental State Examination scores (80-89) had a 45\% increased risk for a serious fall and those at high risk for dementia (<80) were at twice the risk as participants scoring above 90 (hazard ratio = 2.16, 95\% confidence interval = 1.60-2.91).

CONCLUSIONS: Both decreased general cognition and decreased processing speed appear to be potential risk factors for serious falls in the elderly. When assessing the risk of serious falls in elderly patients, clinicians should consider usual factors like gait instability and sensory impairment as well as less obvious ones such as cardiovascular disease and cognitive function in nondemented adults.

}, keywords = {Accidental Falls, Aged, Aged, 80 and over, Chi-Square Distribution, Cognition Disorders, Female, Follow-Up Studies, Geriatric Assessment, Hospitalization, Humans, Male, Mental Status Schedule, Physical Examination, Proportional Hazards Models, Risk Assessment, Risk Factors, Surveys and Questionnaires}, issn = {1758-535X}, doi = {10.1093/gerona/glq115}, author = {Welmerink, Diana B and Longstreth, W T and Lyles, Mary F and Fitzpatrick, Annette L} } @article {1203, title = {Egg consumption and risk of type 2 diabetes in older adults.}, journal = {Am J Clin Nutr}, volume = {92}, year = {2010}, month = {2010 Aug}, pages = {422-7}, abstract = {

BACKGROUND: Type 2 diabetes (T2D) remains an important public health issue in the United States. There are limited and inconsistent data on the association between egg consumption and fasting glucose or incident diabetes.

OBJECTIVES: We assessed the association between egg intake and incident diabetes in older adults.

DESIGN: In this prospective study of 3898 men and women from the Cardiovascular Health Study (1989-2007), we assessed egg consumption by using a picture-sorted food questionnaire and ascertained incident T2D annually by using information on hypoglycemic agents and plasma glucose. We used Cox proportional hazards models to estimate adjusted relative risks.

RESULTS: During a mean follow-up of 11.3 y, 313 new cases of T2D occurred. Crude incidence rates of T2D were 7.39, 6.83, 7.00, 6.72, and 12.20 per 1000 person-years in people who reported egg consumption of never, <1 egg/mo, 1-3 eggs/mo, 1-4 eggs/wk, and almost daily, respectively. In multivariable-adjusted models, there was no association between egg consumption and increased risk of T2D in either sex and overall. In a secondary analysis, dietary cholesterol was not associated with incident diabetes (P for trend = 0.47). In addition, egg consumption was not associated with clinically meaningful differences in fasting glucose, fasting insulin, or measures of insulin resistance despite small absolute analytic differences that were significant.

CONCLUSION: In this cohort of older adults with limited egg intake, there was no association between egg consumption or dietary cholesterol and increased risk of incident T2D.

}, keywords = {Aged, Blood Glucose, Cholesterol, Dietary, Diabetes Mellitus, Type 2, Diet, Diet Surveys, Eggs, Feeding Behavior, Female, Humans, Insulin, Insulin Resistance, Male, Proportional Hazards Models, Prospective Studies, Risk Factors, Surveys and Questionnaires}, issn = {1938-3207}, doi = {10.3945/ajcn.2010.29406}, author = {Djouss{\'e}, Luc and Kamineni, Aruna and Nelson, Tracy L and Carnethon, Mercedes and Mozaffarian, Dariush and Siscovick, David and Mukamal, Kenneth J} } @article {1211, title = {Fish consumption, bone mineral density, and risk of hip fracture among older adults: the cardiovascular health study.}, journal = {J Bone Miner Res}, volume = {25}, year = {2010}, month = {2010 Sep}, pages = {1972-9}, abstract = {

Marine n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be beneficial for bone health, but few studies have investigated the association with fish consumption. Our aim was to study associations of fish and EPA + DHA consumption with bone mineral density (BMD) and hip fracture risk and determine whether high linoleic acid (LA) intake, the major dietary n-6 PUFA, modifies the associations. The study population consisted of 5045 participants aged 65 years and older from the Cardiovascular Health Study. Data on BMD were available for 1305 participants. Food-frequency questionnaire was used to assess dietary intake, and hip fracture incidence was assessed prospectively by review of hospitalization records. After multivariable adjustment, femoral neck BMD was 0.01 g/cm(2) lower in the highest versus lowest tuna/other-fish intake category (p = .05 for trend). EPA + DHA intake (higher versus lower median of 0.32 g/day) was associated with lower femoral neck BMD (0.66 versus 0.71 g/cm(2), p < .001) among those with LA intake greater than the median 12.1 g/day (p = .03 for interaction). No significant associations were found with total-hip BMD. During mean follow-up of 11.1 years, 505 hip fractures occurred. Fish or EPA + DHA consumption was not significantly associated with fracture incidence [hazard ratio (HR) for extreme categories: HR = 1.23, 95\% confidence interval (CI) 0.83-1.84 for tuna/other fish; HR = 1.16, 95\% CI 0.91-1.49 for fried fish; and HR = 0.98, 95\% CI 0.71-1.36 for EPA + DHA]. High LA intake did not modify these associations. In this large prospective cohort of older adults, fish consumption was associated with very small differences in BMD and had no association with hip fracture risk.

}, keywords = {Aged, Aged, 80 and over, Animals, Bone Density, Diet, Female, Fishes, Hip Fractures, Humans, Male, Risk Factors, Surveys and Questionnaires}, issn = {1523-4681}, doi = {10.1002/jbmr.87}, author = {Virtanen, Jyrki K and Mozaffarian, Dariush and Cauley, Jane A and Mukamal, Kenneth J and Robbins, John and Siscovick, David S} } @article {1172, title = {Food sources of individual plasma phospholipid trans fatty acid isomers: the Cardiovascular Health Study.}, journal = {Am J Clin Nutr}, volume = {91}, year = {2010}, month = {2010 Apr}, pages = {883-93}, abstract = {

BACKGROUND: The overall consumption of trans fatty acids (TFAs) increases the risk of coronary artery disease. However, multiple TFA isomers exist, each with potentially different health effects. Different food sources of these specific TFA isomers are not well established.

OBJECTIVE: Our objective was to determine the major independent food sources of specific TFA isomers.

DESIGN: We investigated relations of major potential food sources of TFAs, as assessed by serial food-frequency questionnaires, with 10 plasma phospholipid TFA isomers [5 trans (t-) 18:1, 3 t-18:2, and 2 t-16:1] in 3330 older adults in the Cardiovascular Health Study, a community-based multicenter cohort. Stepwise regression was used to identify independent major food sources of individual plasma phospholipid TFA isomers, which were adjusted for demographic, lifestyle, and dietary factors.

RESULTS: All 5 t-18:1 isomers were similarly associated with foods commonly made with partially hydrogenated vegetable oils (PHVOs), including biscuits (0.51 higher SD of total 18:1 fatty acid concentrations per serving/d, P < 0.01), chips and/or popcorn (0.33 higher SD per serving/d, P = 0.02), margarine (0.32 higher SD per serving/d, P < 0.001), fried foods (0.32 higher SD per serving/d, P = 0.04), and bakery foods (0.23 higher SD per serving/d, P = 0.02). Each of the t-18:2 isomers were associated only with bakery foods (0.50 higher SD of total 18:2 fatty acid concentrations per serving/d, P < 0.001). Ruminant foods were major correlates of t-16:1n-7, including red meats (0.72 higher SD per serving/d, P < 0.001), butter (0.43 higher SD per serving/d, P < 0.001), and higher-fat dairy (0.37 higher SD per serving/d, P < 0.001). In contrast, t-16:1n-9 were derived mainly from margarine (0.31 higher SD per serving/d, P < 0.001).

CONCLUSIONS: t-18:1 Isomers are similarly derived from multiple PHVO-containing foods. In contrast, t-18:2 and t-16:1n-9 isomers are derived from more-specific types of PHVO-containing foods. Ruminant foods are major sources of t-16:1n-7. Different TFA isomers and dietary sources should be considered when investigating health effects and interventions to lower TFAs.

}, keywords = {Aged, Cardiovascular System, Diet, Diet Surveys, Dietary Fats, Female, Food Analysis, Health, Humans, Hydrogenation, Isomerism, Male, Phospholipids, Plant Oils, Regression Analysis, Surveys and Questionnaires, Trans Fatty Acids}, issn = {1938-3207}, doi = {10.3945/ajcn.2009.28877}, author = {Micha, Renata and King, Irena B and Lemaitre, Rozenn N and Rimm, Eric B and Sacks, Frank and Song, Xiaoling and Siscovick, David S and Mozaffarian, Dariush} } @article {1239, title = {Physical activity predicts gray matter volume in late adulthood: the Cardiovascular Health Study.}, journal = {Neurology}, volume = {75}, year = {2010}, month = {2010 Oct 19}, pages = {1415-22}, abstract = {

OBJECTIVES: Physical activity (PA) has been hypothesized to spare gray matter volume in late adulthood, but longitudinal data testing an association has been lacking. Here we tested whether PA would be associated with greater gray matter volume after a 9-year follow-up, a threshold could be identified for the amount of walking necessary to spare gray matter volume, and greater gray matter volume associated with PA would be associated with a reduced risk for cognitive impairment 13 years after the PA evaluation.

METHODS: In 299 adults (mean age 78 years) from the Cardiovascular Health Cognition Study, we examined the association between gray matter volume, PA, and cognitive impairment. Physical activity was quantified as the number of blocks walked over 1 week. High-resolution brain scans were acquired 9 years after the PA assessment on cognitively normal adults. White matter hyperintensities, ventricular grade, and other health variables at baseline were used as covariates. Clinical adjudication for cognitive impairment occurred 13 years after baseline.

RESULTS: Walking amounts ranged from 0 to 300 blocks (mean 56.3; SD 69.7). Greater PA predicted greater volumes of frontal, occipital, entorhinal, and hippocampal regions 9 years later. Walking 72 blocks was necessary to detect increased gray matter volume but walking more than 72 blocks did not spare additional volume. Greater gray matter volume with PA reduced the risk for cognitive impairment 2-fold.

CONCLUSION: Greater amounts of walking are associated with greater gray matter volume, which is in turn associated with a reduced risk of cognitive impairment.

}, keywords = {Aged, Aged, 80 and over, Brain, Brain Mapping, Cardiovascular Diseases, Cognition Disorders, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mental Status Schedule, Motor Activity, Neuropsychological Tests, Odds Ratio, Predictive Value of Tests, Surveys and Questionnaires}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e3181f88359}, author = {Erickson, K I and Raji, C A and Lopez, O L and Becker, J T and Rosano, C and Newman, A B and Gach, H M and Thompson, P M and Ho, A J and Kuller, L H} } @article {1233, title = {Post hoc Parkinson{\textquoteright}s disease: identifying an uncommon disease in the Cardiovascular Health Study.}, journal = {Neuroepidemiology}, volume = {35}, year = {2010}, month = {2010}, pages = {241-9}, abstract = {

BACKGROUND: Although ongoing cohort studies offer a unique opportunity to apply existing information collected prospectively to further the scientific understanding of Parkinson{\textquoteright}s disease (PD), they typically have limited information for clinical diagnosis.

METHODS: We used combinations of self-report, International Classification of Diseases - 9th edition codes and antiparkinsonian medications to identify PD in the Cardiovascular Health Study. To determine whether the expected inverse association between smoking and PD is evident using our outcome definitions, we assessed baseline smoking characteristics for various definitions of PD.

RESULTS: We identified 60 cases with prevalent PD (1.0\%; 95\% confidence interval, CI = 0.8-1.3\%) and 154 with incident PD by year 14. Clear associations were observed for current smokers (odds ratio, OR = 0.50; 95\% CI = 0.26-0.95) and for those who smoked >=50 pack-years (OR = 0.53; 95\% CI = 0.29-0.96). Estimates for smoking were similar when >=2 data sources were required. Estimates for self-report alone were attenuated towards null.

CONCLUSIONS: Using multiple data sources to identify PD represents an alternative method of outcome identification in a cohort that would otherwise not be possible for PD research. Ongoing cohort studies can provide settings in which rapid replication and explorations of new hypotheses for PD are possible.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular System, Cohort Studies, Female, Health Status, Humans, Incidence, Male, Odds Ratio, Parkinson Disease, Prevalence, Prospective Studies, Risk Factors, Smoking, Surveys and Questionnaires, United States}, issn = {1423-0208}, doi = {10.1159/000319895}, author = {Ton, T G and Jain, S and Boudreau, R and Thacker, E L and Strotmeyer, E S and Newman, A B and Longstreth, W T and Checkoway, H} } @article {1180, title = {Prevalence, incidence, and persistence of major depressive symptoms in the Cardiovascular Health Study.}, journal = {Aging Ment Health}, volume = {14}, year = {2010}, month = {2010 Mar}, pages = {168-76}, abstract = {

PURPOSE: To explore the association of major depressive symptoms with advancing age, sex, and self-rated health among older adults.

DESIGN AND METHODS: We analyzed 10 years of annual assessments in a longitudinal cohort of 5888 Medicare recipients in the Cardiovascular Health Study. Self-rated health was assessed with a single question, and subjects categorized as healthy or sick. Major depressive symptoms were assessed using the Center for Epidemiologic Studies Short Depression Scale, with subjects categorized as nondepressed (score < 10) or depressed (> or =10). Age-, sex-, and health-specific prevalence of depression and the probabilities of transition between depressed and nondepressed states were estimated.

RESULTS: The prevalence of a major depressive state was higher in women, and increased with advancing age. The probability of becoming depressed increased with advancing age among the healthy but not the sick. Women showed a greater probability than men of becoming depressed, regardless of health status. Major depressive symptoms persisted over one-year intervals in about 60\% of the healthy and 75\% of the sick, with little difference between men and women.

IMPLICATIONS: Clinically significant depressive symptoms occur commonly in older adults, especially women, increase with advancing age, are associated with poor self-rated health, and are largely intransigent. In order to limit the deleterious consequences of depression among older adults, increased attention to prevention, screening, and treatment is warranted. A self-rated health item could be used in clinical settings to refine the prognosis of late-life depression.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Cohort Studies, Depression, Depressive Disorder, Major, Female, Geriatric Assessment, Health Status, Humans, Incidence, Longitudinal Studies, Male, Personality Assessment, Prevalence, Psychiatric Status Rating Scales, Quality of Life, Sex Factors, Surveys and Questionnaires}, issn = {1364-6915}, doi = {10.1080/13607860903046537}, author = {Thielke, Stephen M and Diehr, Paula and Unutzer, Jurgen} } @article {1189, title = {Sleep disturbances, quality of life, and ethnicity: the Sleep Heart Health Study.}, journal = {J Clin Sleep Med}, volume = {6}, year = {2010}, month = {2010 Apr 15}, pages = {176-83}, abstract = {

STUDY OBJECTIVES: To compare health-related quality of life (HR-QOL) across subgroups defined by sleep disturbances and ethnicity.

METHODS: Men (47\%) and women (53\%) Sleep Heart Health Study participants age 40 and older (N = 5237) underwent overnight polysomnography and completed self-report questionnaires on symptoms of sleep disturbances. The physical and mental composite scales (PCS and MCS) of the Medical Outcomes Study 36-item short form survey assessed HR-QOL and were compared to sleep data.

RESULTS: Participants self-identified as Caucasian/White (n = 4482, 86\%), African American/Black (n = 490, 9\%), or Hispanic/Mexican American (n = 265, 5\%). The prevalence of obstructive sleep apnea (OSA) was 17\%, frequent snoring was 34\%, difficulty initiating or maintaining sleep (DIMS; insomnia symptoms) was 30\%, and excessive daytime sleepiness (EDS) was 25\%. African American participants with frequent snoring, insomnia symptoms, or EDS had significantly poorer physical health compared to Caucasians (p < 0.001). Hispanics with frequent snoring, insomnia symptoms, or EDS had significantly poorer mental health than Caucasian participants (p <0.001). Neither PCS nor MCS scores differed significantly across ethnic subgroups for participants with moderate to severe OSA (respiratory disturbance index > 15, 4\% desaturation).

CONCLUSIONS: Across ethnic/racial subgroups, sleep disturbances are associated with worse physical and better mental HR-QOL than the U.S. norm, but this relationship may be moderated by comorbid health conditions. This study replicates and extends prior research indicating differences among minority and non-minority participants and highlights the need for future studies of sleep disturbances with larger samples of minorities that control for comorbid health conditions.

}, keywords = {African Americans, Cohort Studies, Ethnic Groups, European Continental Ancestry Group, Female, Health Status, Heart Diseases, Hispanic Americans, Humans, Longitudinal Studies, Male, Mental Health, Middle Aged, Polysomnography, Prevalence, Quality of Life, Sleep Apnea, Obstructive, Sleep Initiation and Maintenance Disorders, Sleep Wake Disorders, Snoring, Surveys and Questionnaires, United States}, issn = {1550-9389}, author = {Baldwin, Carol M and Ervin, Ann-Margret and Mays, Mary Z and Robbins, John and Shafazand, Shirin and Walsleben, Joyce and Weaver, Terri} } @article {1342, title = {Identification of patients with sleep disordered breathing: comparing the four-variable screening tool, STOP, STOP-Bang, and Epworth Sleepiness Scales.}, journal = {J Clin Sleep Med}, volume = {7}, year = {2011}, month = {2011 Oct 15}, pages = {467-72}, abstract = {

STUDY OBJECTIVE: The Epworth Sleepiness Scale (ESS) has been used to detect patients with potential sleep disordered breathing (SDB). Recently, a 4-Variable screening tool was proposed to identify patients with SDB, in addition to the STOP and STOP-Bang questionnaires. This study evaluated the abilities of the 4-Variable screening tool, STOP, STOP-Bang, and ESS questionnaires in identifying subjects at risk for SDB.

METHODS: A total of 4,770 participants who completed polysomnograms in the baseline evaluation of the Sleep Heart Health Study (SHHS) were included. Subjects with RDIs >= 15 and >= 30 were considered to have moderate-to-severe or severe SDB, respectively. Variables were constructed to approximate those in the questionnaires. The risk of SDB was calculated by the 4-Variable screening tool according to Takegami et al. The STOP and STOP-Bang questionnaires were evaluated including variables for snoring, tiredness/sleepiness, observed apnea, blood pressure, body mass index, age, neck circumference, and gender. Sleepiness was evaluated using the ESS questionnaire and scores were dichotomized into < 11 and >= 11.

RESULTS: The STOP-Bang questionnaire had higher sensitivity to predict moderate-to-severe (87.0\%) and severe (70.4\%) SDB, while the 4-Variable screening tool had higher specificity to predict moderate-to-severe and severe SDB (93.2\% for both).

CONCLUSIONS: In community populations such as the SHHS, high specificities may be more useful in excluding low-risk patients, while avoiding false positives. However, sleep clinicians may prefer to use screening tools with high sensitivities, like the STOP-Bang, in order to avoid missing cases that may lead to adverse health consequences and increased healthcare costs.

}, keywords = {Blood Pressure, Body Mass Index, Cohort Studies, Female, Humans, Male, Mass Screening, Middle Aged, Polysomnography, Predictive Value of Tests, Prospective Studies, Risk, ROC Curve, Sensitivity and Specificity, Severity of Illness Index, Sleep Apnea Syndromes, Snoring, Surveys and Questionnaires}, issn = {1550-9397}, doi = {10.5664/JCSM.1308}, author = {Silva, Graciela E and Vana, Kimberly D and Goodwin, James L and Sherrill, Duane L and Quan, Stuart F} } @article {1338, title = {Surrogate screening models for the low physical activity criterion of frailty.}, journal = {Aging Clin Exp Res}, volume = {23}, year = {2011}, month = {2011 Jun}, pages = {209-16}, abstract = {

BACKGROUND AND AIMS: Low physical activity, one of five criteria in a validated clinical phenotype of frailty, is assessed by a standardized, semiquantitative questionnaire on up to 20 leisure time activities. Because of the time demanded to collect the interview data, it has been challenging to translate to studies other than the Cardiovascular Health Study (CHS), for which it was developed. Considering subsets of activities, we identified and evaluated streamlined surrogate assessment methods and compared them to one implemented in the Women{\textquoteright}s Health and Aging Study (WHAS).

METHODS: Using data on men and women ages 65 and older from the CHS, we applied logistic regression models to rank activities by "relative influence" in predicting low physical activity.We considered subsets of the most influential activities as inputs to potential surrogate models (logistic regressions). We evaluated predictive accuracy and predictive validity using the area under receiver operating characteristic curves and assessed criterion validity using proportional hazards models relating frailty status (defined using the surrogate) to mortality.

RESULTS: Walking for exercise and moderately strenuous household chores were highly influential for both genders. Women required fewer activities than men for accurate classification. The WHAS model (8 CHS activities) was an effective surrogate, but a surrogate using 6 activities (walking, chores, gardening, general exercise, mowing and golfing) was also highly predictive.

CONCLUSIONS: We recommend a 6 activity questionnaire to assess physical activity for men and women. If efficiency is essential and the study involves only women, fewer activities can be included.

}, keywords = {Activities of Daily Living, Aged, Cohort Studies, Exercise, Female, Follow-Up Studies, Frail Elderly, Geriatric Assessment, Humans, Leisure Activities, Logistic Models, Male, Motor Activity, Prospective Studies, Surveys and Questionnaires, Women{\textquoteright}s Health}, issn = {1594-0667}, author = {Eckel, Sandrah P and Bandeen-Roche, Karen and Chaves, Paulo H M and Fried, Linda P and Louis, Thomas A} } @article {1396, title = {Circulating and dietary α-linolenic acid and incidence of congestive heart failure in older adults: the Cardiovascular Health Study.}, journal = {Am J Clin Nutr}, volume = {96}, year = {2012}, month = {2012 Aug}, pages = {269-74}, abstract = {

BACKGROUND: Few studies have evaluated the association between the n-3 fatty acid α-linolenic acid (ALA) and the incidence of congestive heart failure (CHF).

OBJECTIVE: We investigated whether plasma phospholipid concentrations and estimated dietary consumption of ALA are associated with incident CHF.

DESIGN: We used data from the Cardiovascular Health Study, a prospective cohort study of cardiovascular diseases among adults aged >=65 y, from 4 US communities. A total of 2957 participants free of prevalent heart disease and with available fatty acid measurements were included in biomarker analyses (30,722 person-years and 686 incident CHF events). A total of 4432 participants free of prevalent heart disease were included in dietary analyses (52,609 person-years and 1072 events). We investigated the association of ALA with incident CHF by using Cox regression.

RESULTS: After adjustment for age, sex, race, education, smoking status, BMI, waist circumference, and alcohol consumption, plasma phospholipid ALA was not associated with incident CHF (HR for the highest compared with the lowest quartile: 0.97; 95\% CI: 0.79, 1.21; P-trend = 0.85). Likewise, dietary ALA was not associated with incident CHF (adjusted HR for the highest compared with the lowest quartile: 0.96; 95\% CI: 0.82, 1.20; P-trend = 0.97). We observed no association of biomarker or dietary ALA with nonvalvular CHF subtype. We also found little evidence of an association between ALA and CHF in subgroups based on age, sex, diabetes, fish consumption, BMI, or FADS2 genotype (rs1535).

CONCLUSION: ALA intake is not associated with incident CHF in older adults. This trial was registered at clinicaltrials.gov as NCT00005133.

}, keywords = {Aged, Alcohol Drinking, alpha-Linolenic Acid, Biomarkers, Body Mass Index, Cardiovascular Diseases, Diet, Fatty Acid Desaturases, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Polymorphism, Single Nucleotide, Prevalence, Prospective Studies, Risk Factors, Smoking, Surveys and Questionnaires, United States}, issn = {1938-3207}, doi = {10.3945/ajcn.112.037960}, author = {Lemaitre, Rozenn N and Sitlani, Colleen and Song, Xiaoling and King, Irena B and McKnight, Barbara and Spiegelman, Donna and Sacks, Frank M and Djouss{\'e}, Luc and Rimm, Eric B and Siscovick, David S and Mozaffarian, Dariush} } @article {1397, title = {Trans-fatty acid consumption and heart rate variability in 2 separate cohorts of older and younger adults.}, journal = {Circ Arrhythm Electrophysiol}, volume = {5}, year = {2012}, month = {2012 Aug 01}, pages = {728-38}, abstract = {

BACKGROUND: Trans-fatty acid (TFA) consumption is associated with risk of coronary heart disease, and trans-18:2, but not trans-18:1, in red blood cell membranes has been associated with sudden cardiac arrest. Abnormal heart rate variability (HRV) reflects autonomic dysfunction and predicts cardiac death. Relationships between TFA consumption and HRV remain understudied. We determined whether total TFA consumption, as well as trans-18:1 and trans-18:2 TFA consumption, was independently associated with HRV in 2 independent cohorts in the United States and Portugal.

METHODS AND RESULTS: In 2 independent cohorts of older US adults (Cardiovascular Health Study [CHS], age 72{\textpm}5 years, 1989/1995) and young Portuguese adults (Porto, age 19{\textpm}2 years, 2008/2010), we assessed habitual TFA intake by food frequency questionnaires in CHS (separately estimating trans-18:1 and trans-18:2) and multiple 24-hour recalls in Porto (estimating total TFA only, which in a subset correlated with circulating trans-18:2 but not trans-18:1, suggesting that we captured the former). HRV was assessed using 24-hour Holters in CHS (n=1076) and repeated short-term (5-minute) ECGs in Porto (n=160). We used multivariate-adjusted linear regression to relate TFA consumption to HRV cross-sectionally (CHS, Porto) and longitudinally (CHS). In CHS, higher trans-18:2 consumption was associated with lower 24-hour SD of all normal-to-normal intervals both cross-sectionally (-12\%; 95\% CI, -19\% to -6\%; P=0.001) and longitudinally (-15\%; 95\% CI, -25\% to -4\%; P= 0.009) and lower 24-hour SD of 5-minute average N-N intervals and mean of the 5-minute SD of N-N intervals calculated over 24 hours (P<0.05 each). Higher trans-18:1 consumption in CHS was associated with more favorable 24-hour HRV in particular time-domain indices (24-hour SD of all normal-to-normal intervals, SD of 5-minute average N-N intervals, mean of the 5-minute SD of N-N intervals calculated over 24 hours; P<0.05 each). In Porto, each higher SD TFA consumption was associated with 4\% lower 5-minute 24-hour SD of all normal-to-normal intervals (95\% CI, -8\% to -1\%; P=0.04) and 7\% lower 5-minute square root of the mean of the squares of successive N-N differences (95\% CI, -13\% to -1\%; P=0.04).

CONCLUSIONS: Trans-18:2 consumption is associated with specific, less favorable indices of HRV in both older and young adults. Trans-18:1 consumption is associated with more favorable HRV indices in older adults. Our results support the need to investigate potential HRV-related mechanisms, whereby trans-18:2 may increase arrhythmic risk.

}, keywords = {Adolescent, Age Factors, Aged, Aging, Arrhythmias, Cardiac, Cohort Studies, Cross-Sectional Studies, Dietary Fats, Electrocardiography, Ambulatory, Feeding Behavior, Female, Heart Rate, Humans, Linear Models, Longitudinal Studies, Male, Multivariate Analysis, Portugal, Predictive Value of Tests, Prospective Studies, Risk Assessment, Risk Factors, Surveys and Questionnaires, Trans Fatty Acids, United States, Young Adult}, issn = {1941-3084}, doi = {10.1161/CIRCEP.111.966259}, author = {Soares-Miranda, Luisa and Stein, Phyllis K and Imamura, Fumiaki and Sattelmair, Jacob and Lemaitre, Rozenn N and Siscovick, David S and Mota, Jorge and Mozaffarian, Dariush} } @article {6062, title = {Circulating 25-hydroxyvitamin D is associated with insulin resistance cross-sectionally but not longitudinally in older adults: The Cardiovascular Health Study.}, journal = {Metabolism}, volume = {62}, year = {2013}, month = {2013 Dec}, pages = {1788-94}, abstract = {

BACKGROUND: Despite extensive study, the role of vitamin D in insulin resistance and secretion remains unclear.

OBJECTIVE: To examine the cross-sectional and longitudinal relationships between 25-hydroxyvitamin D (25(OH)D) concentrations and indices of insulin resistance and secretion in older adults.

METHODS AND RESULTS: Among 2134 participants of the Cardiovascular Health Study who were free from cardiovascular disease, we measured serum 25(OH)D concentrations in samples collected in 1992-1993. We examined insulin resistance and secretion using Homeostasis Model Assessment (HOMA) estimates cross-sectionally and among 1469 participants who had repeated HOMA measures four years later (1996-1997). In cross-sectional analysis, each 10 ng/mL increment in 25(OH)D concentration was associated with a 0.09 lower adjusted HOMA-IR [95\% CI (-0.17, -0.02), p=0.01]. However, baseline 25(OH)D concentrations were not associated with change in HOMA-IR over 4 years of follow up (p=0.48). 25(OH)D concentrations were not associated with insulin secretion, as determined by HOMA-β, in either cross-sectional or longitudinal analysis.

CONCLUSIONS: Circulating 25(OH)D concentrations are associated with lower insulin resistance in cross-sectional but not longitudinal analyses. Whether this reflects residual confounding in cross-sectional analyses or the short-term nature of the relationship between vitamin D and insulin sensitivity will require trials with repeated measures of these factors.

}, keywords = {Adiposity, Aged, Anthropometry, Cardiovascular Diseases, Cross-Sectional Studies, Exercise, Female, Humans, Hydroxycholecalciferols, Inflammation, Insulin, Insulin Resistance, Longitudinal Studies, Male, Middle Aged, Obesity, Risk Factors, Surveys and Questionnaires}, issn = {1532-8600}, doi = {10.1016/j.metabol.2013.07.008}, author = {Danziger, John and Biggs, Mary L and Niemi, Matt and Ix, Joachim H and Kizer, Jorge R and Djouss{\'e}, Luc and de Boer, Ian H and Siscovick, David S and Kestenbaum, Bryan and Mukamal, Kenneth J} } @article {6163, title = {Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake.}, journal = {Am J Clin Nutr}, volume = {97}, year = {2013}, month = {2013 Jun}, pages = {1395-402}, abstract = {

BACKGROUND: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants.

OBJECTIVE: The objective of the study was to identify common genetic variants that are associated with macronutrient intake.

DESIGN: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 {\texttimes} 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n = 7724) provided additional replication data.

RESULTS: A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (β {\textpm} SE: 0.25 {\textpm} 0.04\%; P = 1.68 {\texttimes} 10(-8)) and lower fat (β {\textpm} SE: -0.21 {\textpm} 0.04\%; P = 1.57 {\texttimes} 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI)-increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (β {\textpm} SE: 0.10 {\textpm} 0.02\%; P = 9.96 {\texttimes} 10(-10)), independent of BMI (after adjustment for BMI, β {\textpm} SE: 0.08 {\textpm} 0.02\%; P = 3.15 {\texttimes} 10(-7)).

CONCLUSION: Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at clinicaltrials.gov as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).

}, keywords = {Alleles, Atherosclerosis, Body Mass Index, Dietary Carbohydrates, Dietary Fats, Dietary Proteins, Energy Intake, European Continental Ancestry Group, Fibroblast Growth Factors, Follow-Up Studies, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Life Style, Obesity, Polymorphism, Single Nucleotide, Prospective Studies, Quantitative Trait Loci, Surveys and Questionnaires}, issn = {1938-3207}, doi = {10.3945/ajcn.112.052183}, author = {Tanaka, Toshiko and Ngwa, Julius S and van Rooij, Frank J A and Zillikens, M Carola and Wojczynski, Mary K and Frazier-Wood, Alexis C and Houston, Denise K and Kanoni, Stavroula and Lemaitre, Rozenn N and Luan, Jian{\textquoteright}an and Mikkil{\"a}, Vera and Renstrom, Frida and Sonestedt, Emily and Zhao, Jing Hua and Chu, Audrey Y and Qi, Lu and Chasman, Daniel I and de Oliveira Otto, Marcia C and Dhurandhar, Emily J and Feitosa, Mary F and Johansson, Ingegerd and Khaw, Kay-Tee and Lohman, Kurt K and Manichaikul, Ani and McKeown, Nicola M and Mozaffarian, Dariush and Singleton, Andrew and Stirrups, Kathleen and Viikari, Jorma and Ye, Zheng and Bandinelli, Stefania and Barroso, In{\^e}s and Deloukas, Panos and Forouhi, Nita G and Hofman, Albert and Liu, Yongmei and Lyytik{\"a}inen, Leo-Pekka and North, Kari E and Dimitriou, Maria and Hallmans, G{\"o}ran and K{\"a}h{\"o}nen, Mika and Langenberg, Claudia and Ordovas, Jose M and Uitterlinden, Andr{\'e} G and Hu, Frank B and Kalafati, Ioanna-Panagiota and Raitakari, Olli and Franco, Oscar H and Johnson, Andrew and Emilsson, Valur and Schrack, Jennifer A and Semba, Richard D and Siscovick, David S and Arnett, Donna K and Borecki, Ingrid B and Franks, Paul W and Kritchevsky, Stephen B and Lehtim{\"a}ki, Terho and Loos, Ruth J F and Orho-Melander, Marju and Rotter, Jerome I and Wareham, Nicholas J and Witteman, Jacqueline C M and Ferrucci, Luigi and Dedoussis, George and Cupples, L Adrienne and Nettleton, Jennifer A} } @article {6546, title = {Dietary protein intake and change in estimated GFR in the Cardiovascular Health Study.}, journal = {Nutrition}, volume = {30}, year = {2014}, month = {2014 Jul-Aug}, pages = {794-9}, abstract = {

OBJECTIVE: With aging, kidney function declines, as evidenced by reduced glomerular filtration rate. It is controversial whether or not high protein intake accelerates this decline. The aim of this study was to determine whether high protein intake was associated with declines in kidney function among older patients.

METHODS: We examined whether dietary protein is associated with change in kidney function (mean follow-up 6.4 y [SD = 1.4, range = 2.5-7.9] in the Cardiovascular Health Study (N = 3623). We estimated protein intake using a food frequency questionnaire and estimated glomerular filtration rate from cystatin C. Associations between protein intake and kidney function were determined by linear and logistic regression models.

RESULTS: Average protein intake was 19\% of energy intake (SD = 5\%). Twenty-seven percent (n = 963) of study participants had rapid decline in kidney function, as defined by (ΔeGFRcysC > 3 mL{\textbullet}min{\textbullet}1.73 m(2)). Protein intake (characterized as g/d and \% energy/d), was not associated with change in estimated glomerular filtration rate (P > 0.05 for all comparisons). There were also no significant associations when protein intake was separated by source (animal and vegetable).

CONCLUSION: These data suggest that higher protein intake does not have a major effect on kidney function decline among elderly men and women.

}, keywords = {Aged, Aging, Diet, Dietary Proteins, Feeding Behavior, Female, Glomerular Filtration Rate, Health, Humans, Kidney, Male, Regression Analysis, Surveys and Questionnaires}, issn = {1873-1244}, doi = {10.1016/j.nut.2013.12.006}, author = {Beasley, Jeannette M and Katz, Ronit and Shlipak, Michael and Rifkin, Dena E and Siscovick, David and Kaplan, Robert} } @article {6365, title = {Physical activity, inflammation, and volume of the aging brain.}, journal = {Neuroscience}, volume = {273}, year = {2014}, month = {2014 Jul 25}, pages = {199-209}, abstract = {

Physical activity influences inflammation, and both affect brain structure and Alzheimer{\textquoteright}s disease (AD) risk. We hypothesized that older adults with greater reported physical activity intensity and lower serum levels of the inflammatory marker tumor necrosis factor α (TNFα) would have larger regional brain volumes on subsequent magnetic resonance imaging (MRI) scans. In 43 cognitively intact older adults (79.3{\textpm}4.8 years) and 39 patients with AD (81.9{\textpm}5.1 years at the time of MRI) participating in the Cardiovascular Health Study, we examined year-1 reported physical activity intensity, year-5 blood serum TNFα measures, and year-9 volumetric brain MRI scans. We examined how prior physical activity intensity and TNFα related to subsequent total and regional brain volumes. Physical activity intensity was measured using the modified Minnesota Leisure Time Physical Activities questionnaire at year 1 of the study, when all subjects included here were cognitively intact. Stability of measures was established for exercise intensity over 9 years and TNFα over 3 years in a subset of subjects who had these measurements at multiple time points. When considered together, more intense physical activity intensity and lower serum TNFα were both associated with greater total brain volume on follow-up MRI scans. TNFα, but not physical activity, was associated with regional volumes of the inferior parietal lobule, a region previously associated with inflammation in AD patients. Physical activity and TNFα may independently influence brain structure in older adults.

}, keywords = {Aged, Aged, 80 and over, Aging, Alzheimer Disease, Apolipoproteins E, Brain, Female, Humans, Inflammation, Longitudinal Studies, Magnetic Resonance Imaging, Male, Motor Activity, Neuroimmunomodulation, Neuropsychological Tests, Organ Size, Parietal Lobe, Surveys and Questionnaires, Tumor Necrosis Factor-alpha}, issn = {1873-7544}, doi = {10.1016/j.neuroscience.2014.05.005}, author = {Braskie, M N and Boyle, C P and Rajagopalan, P and Gutman, B A and Toga, A W and Raji, C A and Tracy, R P and Kuller, L H and Becker, J T and Lopez, O L and Thompson, P M} } @article {6592, title = {Regular fish consumption and age-related brain gray matter loss.}, journal = {Am J Prev Med}, volume = {47}, year = {2014}, month = {2014 Oct}, pages = {444-51}, abstract = {

BACKGROUND: Brain health may be affected by modifiable lifestyle factors; consuming fish and antioxidative omega-3 fatty acids may reduce brain structural abnormality risk.

PURPOSE: To determine whether dietary fish consumption is related to brain structural integrity among cognitively normal elders.

METHODS: Data were analyzed from 260 cognitively normal individuals from the Cardiovascular Health Study with information on fish consumption from the National Cancer Institute Food Frequency Questionnaire and brain magnetic resonance imaging (MRI). The relationship between fish consumption data collected in 1989-1990 and brain structural MRI obtained in 1998-1999 was assessed using voxel-based morphometry in multiple regression analyses in 2012. Covariates were age, gender, race, education, white matter lesions, MRI-identified infarcts, waist-hip ratio, and physical activity as assessed by the number of city blocks walked in 1 week. Volumetric changes were further modeled with omega-3 fatty acid estimates to better understand the mechanistic link between fish consumption, brain health, and Alzheimer disease.

RESULTS: Weekly consumption of baked or broiled fish was positively associated with gray matter volumes in the hippocampus, precuneus, posterior cingulate, and orbital frontal cortex even after adjusting for covariates. These results did not change when including omega-3 fatty acid estimates in the analysis.

CONCLUSIONS: Dietary consumption of baked or broiled fish is related to larger gray matter volumes independent of omega-3 fatty acid content. These findings suggest that a confluence of lifestyle factors influence brain health, adding to the growing body of evidence that prevention strategies for late-life brain health need to begin decades earlier.

}, keywords = {Aged, Aged, 80 and over, Animals, Brain, Cross-Sectional Studies, Diet, Fatty Acids, Omega-3, Female, Fishes, Gray Matter, Humans, Life Style, Magnetic Resonance Imaging, Male, Regression Analysis, Surveys and Questionnaires}, issn = {1873-2607}, doi = {10.1016/j.amepre.2014.05.037}, author = {Raji, Cyrus A and Erickson, Kirk I and Lopez, Oscar L and Kuller, Lewis H and Gach, H Michael and Thompson, Paul M and Riverol, Mario and Becker, James T} } @article {6270, title = {Sleep duration does not mediate or modify association of common genetic variants with type 2 diabetes.}, journal = {Diabetologia}, volume = {57}, year = {2014}, month = {2014 Feb}, pages = {339-46}, abstract = {

AIMS/HYPOTHESIS: Short and long sleep duration are associated with increased risk of type 2 diabetes. We aimed to investigate whether genetic variants for fasting glucose or type 2 diabetes associate with short or long sleep duration and whether sleep duration modifies the association of genetic variants with these traits.

METHODS: We examined the cross-sectional relationship between self-reported habitual sleep duration and prevalence of type 2 diabetes in individuals of European descent participating in five studies included in the Candidate Gene Association Resource (CARe), totalling 1,474 cases and 8,323 controls. We tested for association of 16 fasting glucose-associated variants, 27 type 2 diabetes-associated variants and aggregate genetic risk scores with continuous and dichotomised (<=5~h or >=9~h) sleep duration using regression models adjusted for age, sex and BMI. Finally, we tested whether a gene {\texttimes} behaviour interaction of variants with sleep duration had an impact on fasting glucose or type 2 diabetes risk.

RESULTS: Short sleep duration was significantly associated with type 2 diabetes in CARe (OR 1.32; 95\% CI 1.08, 1.61; p = 0.008). Variants previously associated with fasting glucose or type 2 diabetes and genetic risk scores were not associated with sleep duration. Furthermore, no study-wide significant interaction was observed between sleep duration and these variants on glycaemic traits. Nominal interactions were observed for sleep duration and PPARG rs1801282, CRY2 rs7943320 and HNF1B rs4430796 in influencing risk of type 2 diabetes (p < 0.05).

CONCLUSIONS/INTERPRETATION: Our findings suggest that differences in habitual sleep duration do not mediate or modify the relationship between common variants underlying glycaemic traits (including in circadian rhythm genes) and diabetes.

}, keywords = {Blood Glucose, Body Composition, Body Mass Index, Cross-Sectional Studies, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Fasting, Female, Genetic Predisposition to Disease, Genetic Variation, Genotype, Glucose Intolerance, Glycated Hemoglobin A, Humans, Insulin Resistance, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Sleep, Surveys and Questionnaires, Time Factors, United States}, issn = {1432-0428}, doi = {10.1007/s00125-013-3110-y}, author = {Tare, Archana and Lane, Jacqueline M and Cade, Brian E and Grant, Struan F A and Chen, Ting-Hsu and Punjabi, Naresh M and Lauderdale, Diane S and Zee, Phyllis C and Gharib, Sina A and Gottlieb, Daniel J and Scheer, Frank A J L and Redline, Susan and Saxena, Richa} } @article {6545, title = {Association of mitochondrial DNA levels with frailty and all-cause mortality.}, journal = {J Mol Med (Berl)}, volume = {93}, year = {2015}, month = {2015 Feb}, pages = {177-186}, abstract = {

Mitochondrial function is altered with age and variants in mitochondrial DNA (mtDNA) modulate risk for several age-related disease states. However, the association of mtDNA copy number, a readily available marker which reflects mitochondrial depletion, energy reserves, and oxidative stress, on aging and mortality in the general population has not been addressed. To assess the association between mtDNA copy number and two primary outcomes--prevalent frailty and all-cause mortality--we utilize data from participants who were from two multicenter, multiethnic, community-based, prospective studies--the Cardiovascular Health Study (CHS) (1989-2006) and the Atherosclerosis Risk in Communities (ARIC) study (1987-2013). A total of 4892 participants (43.3\% men) from CHS and 11,509 participants (44.9\% men) from ARIC self-identifying as white or black were included in the analysis. mtDNA copy number, the trait of interest, was measured using a qPCR-based method in CHS and an array-based method in ARIC from DNA isolated from whole blood in participants from both cohorts. In race-stratified meta-analyses, we observe a significant inverse association of mtDNA copy number with age and higher mtDNA copy number in women relative to men. Lower mtDNA copy number was also significantly associated with prevalent frailty in white participants from CHS (OR 0.91, 95\% CI 0.85-0.97). Additionally, mtDNA copy number was a strong independent predictor of all-cause mortality in an age- and sex-adjusted, race-stratified analysis of 16,401 participants from both cohorts with a pooled hazard ratio of 1.47 (95\% CI 1.33-1.62) for the lowest quintile of mtDNA copy number relative to the highest quintile. Key messages: Mitochondrial DNA (mtDNA) copy number is associated with age and sex. Lower mtDNA copy number is also associated with prevalent frailty. mtDNA copy number is a significant predictor of all-cause mortality in a multiethnic population.

}, keywords = {African Americans, Aged, Aged, 80 and over, Aging, DNA, Mitochondrial, European Continental Ancestry Group, Female, Follow-Up Studies, Gene Dosage, Geriatric Assessment, Humans, Kaplan-Meier Estimate, Male, Mortality, Odds Ratio, Population Surveillance, Prospective Studies, Surveys and Questionnaires, United States}, issn = {1432-1440}, doi = {10.1007/s00109-014-1233-3}, author = {Ashar, Foram N and Moes, Anna and Moore, Ann Z and Grove, Megan L and Chaves, Paulo H M and Coresh, Josef and Newman, Anne B and Matteini, Amy M and Bandeen-Roche, Karen and Boerwinkle, Eric and Walston, Jeremy D and Arking, Dan E} } @article {6823, title = {Positive association of tomato consumption with serum urate: support for tomato consumption as an anecdotal trigger of gout flares.}, journal = {BMC Musculoskelet Disord}, volume = {16}, year = {2015}, month = {2015}, pages = {196}, abstract = {

BACKGROUND: Gout is a consequence of an innate immune reaction to monosodium urate crystals deposited in joints. Acute gout attacks can be triggered by dietary factors that are themselves associated with serum urate levels. Tomato consumption is an anecdotal trigger of gout flares. This study aimed to measure the frequency of tomato consumption as a self-reported trigger of gout attacks in a large New Zealand sample set, and to test the hypothesis that tomato consumption is associated with serum urate levels.

METHODS: Two thousand fifty one New Zealanders (of M{\={a}}ori, Pacific Island, European or other ancestry) with clinically-ascertained gout were asked about gout trigger foods. European individuals from the Atherosclerosis Risk In Communities (ARIC; n = 7517) Study, Cardiovascular Health Study (CHS; n = 2151) and Framingham Heart Study (FHS; n = 3052) were used to test, in multivariate-adjusted analyses, for association between serum urate and tomato intake.

RESULTS: Seventy one percent of people with gout reported having >=1 gout trigger food. Of these 20\% specifically mentioned tomatoes, the 4(th) most commonly reported trigger food. There was association between tomato intake and serum urate levels in the ARIC, CHS and FHS combined cohort (β = 0.66 μmolL(-1) increase in serum urate per additional serve per week; P = 0.006) - evident in both sexes (men: β = 0.84 μmolL(-1), P = 0.035; women: β = 0.59 μmolL (-1), P = 0.041).

CONCLUSIONS: While our descriptive and observational data are unable to support the claim that tomato consumption is a trigger of gout attacks, the positive association between tomato consumption and serum urate levels suggests that the self-reporting of tomatoes as a dietary trigger by people with gout has a biological basis.

}, keywords = {Adolescent, Adult, Aged, European Continental Ancestry Group, Female, Gout, Humans, Hyperuricemia, Lycopersicon esculentum, Male, Middle Aged, New Zealand, Oceanic Ancestry Group, Surveys and Questionnaires, Uric Acid, Young Adult}, issn = {1471-2474}, doi = {10.1186/s12891-015-0661-8}, author = {Flynn, Tanya J and Cadzow, Murray and Dalbeth, Nicola and Jones, Peter B and Stamp, Lisa K and Hindmarsh, Jennie Harr{\'e} and Todd, Alwyn S and Walker, Robert J and Topless, Ruth and Merriman, Tony R} } @article {6990, title = {Fibroblast Growth Factor-23 and Frailty in Elderly Community-Dwelling Individuals: The Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {64}, year = {2016}, month = {2016 Feb}, pages = {270-6}, abstract = {

OBJECTIVES: To evaluate whether fibroblast growth factor 23 (FGF-23) is related to frailty and to characterize the nature of their joint association with mortality.

DESIGN: Cross-sectional analysis for frailty and longitudinal cohort analysis for mortality.

SETTING: Cardiovascular Health Study.

PARTICIPANTS: Community-dwelling individuals (N = 2,977; mean age 77.9 {\textpm} 4.7, 40\% male, 83\% white).

MEASUREMENTS: The predictor was serum FGF-23 concentration (C-terminal enzyme-linked immunosorbent assay), and the outcomes were frailty status (determined according to frailty phenotype criteria of weight loss, weakness, exhaustion, slowness, and low physical activity) and mortality. Multinomial logistic regression was used to assess the cross-sectional association between FGF-23 and frailty and prefrailty, adjusting for demographic characteristics, cardiovascular disease and risk factors, and kidney markers. Proportional hazards Cox proportional hazards regression was used to assess the association between FGF-23, frailty, and all-cause mortality.

RESULTS: Mean estimated glomerular filtration rate (eGFR) was 64 {\textpm} 17 mL/min per 1.73 m(2) . Median FGF-23 was 70.3 RU/mL (interquartile range 53.4-99.2); 52\% were prefrail, and 13\% were frail. After multivariate adjustment, each doubling in FGF-23 concentration was associated with 38\% (95\% confidence interval (CI) = 17-62\%) higher odds of frailty than of nonfrailty and 16\% (95\% CI = 3-30\%) higher odds of prefrailty. FGF-23 (hazard ratio (HR) = 1.16, 95\% CI = 1.10-1.23) and frailty (HR = 1.82, 95\% CI = 1.57-2.12) were independently associated with mortality, but neither association was meaningfully attenuated when adjusted for the other.

CONCLUSION: In a large cohort of older adults, higher FGF-23 was independently associated with prevalent frailty and prefrailty. FGF-23 and frailty were independent and additive risk factors for mortality. FGF-23 may be a marker for functional outcomes.

}, keywords = {Aged, Anthropometry, Biomarkers, Cardiovascular Diseases, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Fibroblast Growth Factors, Frail Elderly, Glomerular Filtration Rate, Humans, Independent Living, Longitudinal Studies, Male, Phenotype, Risk Factors, Surveys and Questionnaires}, issn = {1532-5415}, doi = {10.1111/jgs.13951}, author = {Beben, Tomasz and Ix, Joachim H and Shlipak, Michael G and Sarnak, Mark J and Fried, Linda F and Hoofnagle, Andrew N and Chonchol, Michel and Kestenbaum, Bryan R and de Boer, Ian H and Rifkin, Dena E} }