@article {1082, title = {Use of sonography to evaluate carotid atherosclerosis in the elderly. The Cardiovascular Health Study. CHS Collaborative Research Group.}, journal = {Stroke}, volume = {22}, year = {1991}, month = {1991 Sep}, pages = {1155-63}, abstract = {

Carotid sonography is being performed on more than 5,000 participants in the Cardiovascular Health Study, a prospective, multicenter study of cardiovascular disease in men and women aged 65 years and older. The sonographic methods used to examine and measure the extracranial carotid arteries are described. Initial validation studies were performed on 61 subjects with a mean age of 68.6 years. Analysis of within- and between-sonographer differences and between-reader differences were performed for selected variables. In general, the mean absolute differences for within- and between-sonographer comparisons were small, with even less variability between readers. Variability was less for the common carotid artery than for the internal carotid artery. These data suggest that carotid sonography is a reliable and reproducible method for use in the study of carotid atherosclerosis in population studies.

}, keywords = {Age Factors, Aged, Arteriosclerosis, Carotid Arteries, Carotid Artery Diseases, Carotid Artery, Internal, Female, Humans, Image Interpretation, Computer-Assisted, Image Processing, Computer-Assisted, Male, Prospective Studies, Ultrasonography}, issn = {0039-2499}, doi = {10.1161/01.str.22.9.1155}, author = {O{\textquoteright}Leary, D H and Polak, J F and Wolfson, S K and Bond, M G and Bommer, W and Sheth, S and Psaty, B M and Sharrett, A R and Manolio, T A} } @article {749, title = {Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. The CHS Collaborative Research Group.}, journal = {Stroke}, volume = {23}, year = {1992}, month = {1992 Dec}, pages = {1752-60}, abstract = {

BACKGROUND AND PURPOSE: This article describes the prevalence of extracranial carotid atherosclerosis assessed by ultrasonography, its association with risk factors, and its relation to symptomatic coronary disease and stroke in men and women aged > or = 65 years.

METHODS: Maximum percent stenosis, maximum common carotid artery wall thickness, and maximum internal carotid artery wall thickness were assessed using duplex ultrasound in 5,201 men and women aged > or = 65 years in the Cardiovascular Health Study, a study of the risk factors and natural history of cardiovascular disease in the elderly. Existing coronary disease and stroke were assessed by physical examination and participant history.

RESULTS: Detectable carotid stenosis was present in 75\% of men and 62\% of women, although the prevalence of > or = 50\% stenosis was low, 7\% in men and 5\% in women. Maximum stenosis and maximum wall thickness measurements increased with age and were uniformly greater at all ages in men than in women (p < 0.00001). Established risk factors for atherosclerosis (hypertension, smoking, diabetes) and indications of vascular disease (left ventricular hypertrophy, major electrocardiographic abnormality, bruits, and history of heart disease or stroke) related to all three carotid artery measures in the elderly. Of the three ultrasound measures, the best correlate for a history of coronary disease was maximum internal carotid artery wall thickness. For stroke the best correlate was common carotid artery wall thickness. Multiple logistic regression models of prevalent coronary heart disease and stroke that included the ultrasound findings indicated, after adjustment for age and sex, that maximum internal wall thickness and maximum common carotid wall thickness were significant correlates of both. Maximum stenosis did not add significantly to the correlation.

CONCLUSIONS: In the elderly the incidence of carotid atherosclerosis was high, although the frequency of severe disease was low. The prevalence and severity of carotid atherosclerosis continued to increase with age even in the late decades of life, and more disease was found in men than in women at all ages. Known risk factors for atherosclerosis continued to relate to carotid abnormalities in the later decades of life, both in symptomatic and asymptomatic subjects.

}, keywords = {Aged, Arteriosclerosis, Cardiomegaly, Carotid Artery Diseases, Cerebrovascular Disorders, Coronary Disease, Female, Humans, Male, Medical Records, Prevalence, Regression Analysis, Risk Factors, Ultrasonography}, issn = {0039-2499}, doi = {10.1161/01.str.23.12.1752}, author = {O{\textquoteright}Leary, D H and Polak, J F and Kronmal, R A and Kittner, S J and Bond, M G and Wolfson, S K and Bommer, W and Price, T R and Gardin, J M and Savage, P J} } @article {748, title = {Isolated systolic hypertension and subclinical cardiovascular disease in the elderly. Initial findings from the Cardiovascular Health Study.}, journal = {JAMA}, volume = {268}, year = {1992}, month = {1992 Sep 09}, pages = {1287-91}, abstract = {

OBJECTIVE: To assess the association between isolated systolic hypertension (ISH) and subclinical disease in adults aged 65 years and above.

DESIGN: Medicare eligibility lists were used to obtain a representative sample of 5201 community-dwelling elderly persons for the Cardiovascular Health Study, a National Heart, Lung, and Blood Institute--sponsored cohort study of risk factors for coronary heart disease and stroke. In this cross-sectional analysis of baseline data, we excluded 3012 participants who were receiving antihypertensive medications, had clinical cardiovascular disease, or had a diastolic blood pressure of at least 90 mm Hg.

MAIN OUTCOME MEASURES: For electrocardiogram: myocardial infarction, left ventricular hypertrophy, and left ventricular mass as measures of myocardial damage and strain; for echocardiography: left ventricular mass, fractional shortening, and Doppler flow velocities as measures of cardiac systolic and diastolic function; and for carotid sonography: carotid arterial intima-media thickness as a measure of atherosclerosis.

RESULTS: Among the 2189 men and women in this analysis, 195 (9\%) had ISH (systolic blood pressure, greater than or equal to 160 mm Hg) and 596 (23\%) had borderline ISH (systolic blood pressure, 140 to 159 mm Hg). Systolic blood pressure was associated with myocardial infarction by electrocardiogram (P = .02). Borderline and definite ISH were strongly associated with left ventricular mass (P less than .001). While there was little association with cardiac systolic function, borderline and definite ISH were associated with cardiac diastolic function (P less than .001). Isolated systolic hypertension was also strongly associated with increased intima-media thickness of the carotid artery (P less than .001).

CONCLUSIONS: While cohort analyses of future repeated measures will provide a better assessment of risk, both borderline and definite ISH were strongly related to a variety of measures of subclinical disease in elderly men and women.

}, keywords = {Aged, Aged, 80 and over, Cardiomegaly, Cardiovascular Diseases, Carotid Artery Diseases, Cerebrovascular Disorders, Coronary Disease, Cross-Sectional Studies, Echocardiography, Electrocardiography, Female, Humans, Hypertension, Male, Myocardial Infarction, Prospective Studies, Risk Factors, Systole}, issn = {0098-7484}, author = {Psaty, B M and Furberg, C D and Kuller, L H and Borhani, N O and Rautaharju, P M and O{\textquoteright}Leary, D H and Bild, D E and Robbins, J and Fried, L P and Reid, C} } @article {1440, title = {Sonographic evaluation of carotid artery atherosclerosis in the elderly: relationship of disease severity to stroke and transient ischemic attack.}, journal = {Radiology}, volume = {188}, year = {1993}, month = {1993 Aug}, pages = {363-70}, abstract = {

Doppler and real-time ultrasound (US) were performed to evaluate the extent of atherosclerotic changes in the carotid artery and to assess their relationship to prevalent cerebrovascular disease. Real-time US scans and Doppler measurements of the carotid arteries were analyzed in 5,201 subjects aged 65 years or older. Severity of atherosclerotic lesions was associated with increased frequencies of hyperechoic, irregular, and heterogeneous textured lesions (P < .0001). The severity of internal carotid artery stenosis was associated with thickening of the intima-media layer of the common carotid artery wall (r = .37, P < .0001). A history of stroke and transient ischemic attack (TIA) was more likely when hyperechoic, heterogeneous, and irregular lesions were seen in the carotid artery. Internal carotid artery stenosis correlated better with prevalent stroke and TIA than did sonographic descriptions of plaque texture. However, the prevalence of hyperechoic, heterogeneous, and irregular lesions increased as the degree of internal carotid stenosis increased. On real-time images alone, the average of the internal carotid artery maximal wall thickness is the sonographic measure of atherosclerosis that enables the best prediction of prevalent stroke and TIA.

}, keywords = {Aged, Arteriosclerosis, Carotid Artery Diseases, Carotid Artery, Internal, Carotid Stenosis, Cerebrovascular Disorders, Female, Humans, Ischemic Attack, Transient, Male, Ultrasonography}, issn = {0033-8419}, doi = {10.1148/radiology.188.2.8327679}, author = {Polak, J F and O{\textquoteright}Leary, D H and Kronmal, R A and Wolfson, S K and Bond, M G and Tracy, R P and Gardin, J M and Kittner, S J and Price, T R and Savage, P J} } @article {1525, title = {Relationships of cerebral MRI findings to ultrasonographic carotid atherosclerosis in older adults : the Cardiovascular Health Study. CHS Collaborative Research Group.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {19}, year = {1999}, month = {1999 Feb}, pages = {356-65}, abstract = {

Cerebral magnetic resonance imaging (MRI) has demonstrated a high prevalence of infarct-like lesions, white matter hyperintensities, and evidence of cerebral atrophy in older adults. While these findings are generally believed to be related to ischemia and atherosclerosis, their relationship to atherosclerosis in the carotid arteries remains to be explored. Study subjects were part of the multicenter Cardiovascular Health Study, a cross-sectional study of 3502 women and men >/=65 years of age undergoing cranial MRI and carotid ultrasonography. MRI infarcts were detected in 1068 participants (29.3\%) and measurable carotid plaque in 2745 (75.3\%). MRI infarcts, ventricular and sulcal widening, and white matter score were strongly associated with carotid intimal-medial thickness (IMT) and stenosis degree after adjustment for age and sex (all P<0. 01). Associations with plaque characteristics were less strong and less consistent; MRI infarcts were weakly associated only with surface irregularity, and ventricular size was weakly associated only with lesion density (both P<0.04). In contrast, sulcal widening was strongly related to plaque characteristics, with scores being higher in those with heterogeneous and irregular plaque (both P<0. 009). Adjustment for other risk factors, and for carotid IMT/stenosis, removed associations of MRI findings with plaque characteristics except for weak relationships remaining between MRI infarcts and surface irregularity and between sulcal score and heterogeneous plaque (both P<0.03). MRI abnormalities show strong and consistent relationships with increasing carotid IMT and stenosis degree but less strong associations with plaque characteristics, especially after adjusting for IMT and stenosis.

}, keywords = {Aged, Arteriosclerosis, Brain, Cardiovascular System, Carotid Artery Diseases, Cerebral Infarction, Cohort Studies, Cross-Sectional Studies, Echoencephalography, Female, Health Status, Humans, Magnetic Resonance Imaging, Male, Prevalence}, issn = {1079-5642}, author = {Manolio, T A and Burke, G L and O{\textquoteright}Leary, D H and Evans, G and Beauchamp, N and Knepper, L and Ward, B} } @article {640, title = {Associations of subclinical cardiovascular disease with frailty.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {56}, year = {2001}, month = {2001 Mar}, pages = {M158-66}, abstract = {

BACKGROUND: Frail health in old age has been conceptualized as a loss of physiologic reserve associated with loss of lean mass, neuroendocrine dysregulation, and immune dysfunction. Little work has been done to define frailty and describe the underlying pathophysiology.

METHODS: Frailty status was defined in participants of the Cardiovascular Health Study (CHS), a cohort of 5,201 community-dwelling older adults, based on the presence of three out of five clinical criteria. The five criteria included self-reported weight loss, low grip strength, low energy, slow gait speed, and low physical activity. We examined the spectrum of clinical and subclinical cardiovascular disease in those who were frail (3/5 criteria) or of intermediate frailty status (1 or 2/5 criteria), compared to those who were not frail (0/5). We hypothesized that the severity of frailty would be related to a higher prevalence of reported cardiovascular disease (CVD), as well as to a greater extent of CVD, measured by noninvasive testing.

RESULTS: Of 4,735 eligible participants, 2,289 (48\%) were not frail, 299 (6\%) were frail, and 2.147 (45\%) were of intermediate frailty status. Those who were frail were older (77.2 yrs) compared to those who were not frail (71.5 yrs) or intermediate (73.4 yrs) (p < .001). Frailty status was associated with clinical CVD and most strongly with congestive heart failure (odds ratio [OR] = 7.51 (95\% confidence interval [CI] = 4.66-12.12). In those without a history of a CVD event (n = 1.259), frailty was associated with many noninvasive measures of CVD. Those with carotid stenosis >75\% (adjusted OR = 3.41), ankle-arm index <0.8 (adjusted OR = 3.17) or 0.8-0.9 (adjusted OR = 2.01), major electrocardiography (ECG) abnormalities (adjusted OR = 1.58), greater left ventricular (LV) mass by echocardiography (adjusted OR = 1.16), and higher degree of infarct-like lesions in the brain (adjusted OR = 1.71), were more likely to be frail compared to those who were not frail. The overall associations of each of these noninvasive measures of CVD with frailty level were significant (all p < .05).

CONCLUSIONS: Cardiovascular disease was associated with an increased likelihood of frail health. In those with no history of CVD, the extent of underlying cardiovascular disease measured by carotid ultrasound and ankle-arm index, LV hypertrophy by ECG and echocardiography, was related to frailty. Infarct-like lesions in the brain on magnet resonance imaging were related to frailty as well.

}, keywords = {Aged, Ankle, Arm, Black or African American, Blood Pressure, Brain, Cardiovascular Diseases, Carotid Artery Diseases, Cerebral Infarction, Cerebrovascular Disorders, Cohort Studies, Echocardiography, Electrocardiography, Frail Elderly, Health Status, Heart Failure, Humans, Magnetic Resonance Imaging, United States, Vascular Diseases}, issn = {1079-5006}, doi = {10.1093/gerona/56.3.m158}, author = {Newman, A B and Gottdiener, J S and McBurnie, M A and Hirsch, C H and Kop, W J and Tracy, R and Walston, J D and Fried, L P} } @article {753, title = {Alcohol consumption and carotid atherosclerosis in older adults: the Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {23}, year = {2003}, month = {2003 Dec}, pages = {2252-9}, abstract = {

OBJECTIVE: The association of alcohol use with atherosclerosis is inconsistent in previous studies.

METHODS AND RESULTS: For the Cardiovascular Health Study, 5888 adults aged 65 years and older underwent a standardized interview and examination. They reported beer, wine, and liquor use individually and underwent B-mode ultrasonography to determine internal and common carotid intima-media thickness (IMT). We compared composite carotid IMT values cross-sectionally using linear regression to adjust for demographic and clinical characteristics. Among 4247 participants free of cardiovascular disease, consumers of 1 to 6 drinks per week had 0.07+/-0.04-mm lower composite IMT and consumers of 14 or more drinks per week had 0.07+/-0.05-mm higher IMT than abstainers (P quadratic trend=0.02). We found similar relationships using internal and common carotid thickness measures and among men and women. The higher IMT associated with heavier alcohol use was particularly strong among 1592 participants with confirmed cardiovascular disease (0.24+/-0.09 mm greater than abstainers). Controlling for HDL cholesterol levels reduced the effect on composite IMT among consumers of 1 to 6 drinks per week by 22\%.

CONCLUSIONS: Relative to older adults who abstain from alcohol, consumption of 1 to 6 drinks per week had an inverse association with carotid atherosclerosis whereas consumption of 14 or more drinks had a positive association.

}, keywords = {Aged, Alcohol Drinking, Cardiovascular Diseases, Carotid Artery Diseases, Cross-Sectional Studies, Female, Health Surveys, Humans, Longitudinal Studies, Male, Prospective Studies}, issn = {1524-4636}, doi = {10.1161/01.ATV.0000101183.58453.39}, author = {Mukamal, Kenneth J and Kronmal, Richard A and Mittleman, Murray A and O{\textquoteright}Leary, Daniel H and Polak, Joseph F and Cushman, Mary and Siscovick, David S} } @article {967, title = {Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {116}, year = {2007}, month = {2007 Jul 03}, pages = {32-8}, abstract = {

BACKGROUND: Carotid atherosclerosis, measured as carotid intima-media thickness or as characteristics of plaques, has been linked to cardiovascular disease (CVD) and to C-reactive protein (CRP) levels. We investigated the relationship between carotid atherosclerosis and CRP and their joint roles in CVD prediction.

METHODS AND RESULTS: Of 5888 participants in the Cardiovascular Health Study, an observational study of adults aged > or = 65 years, 5020 without baseline CVD were included in the analysis. They were followed up for as long as 12 years for CVD incidence and all-cause mortality after baseline ultrasound and CRP measurement. When CRP was elevated (> 3 mg/L) among those with detectable atherosclerosis on ultrasound, there was a 72\% (95\% CI, 1.46 to 2.01) increased risk for CVD death and a 52\% (95\% CI, 1.37 to 1.68) increased risk for all-cause mortality. Elevated CRP in the absence of atherosclerosis did not increase CVD or all-cause mortality risk. The proportion of excess risk attributable to the interaction of high CRP and atherosclerosis was 54\% for CVD death and 79\% for all-cause mortality. Addition of CRP or carotid atherosclerosis to conventional risk factors modestly increased in the ability to predict CVD, as measured by the c statistic.

CONCLUSIONS: In older adults, elevated CRP was associated with increased risk for CVD and all-cause mortality only in those with detectable atherosclerosis based on carotid ultrasound. Despite the significant associations of CRP and carotid atherosclerosis with CVD, these measures modestly improve the prediction of CVD outcomes after one accounts for the conventional risk factors.

}, keywords = {African Americans, Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Carotid Artery Diseases, Cohort Studies, Comorbidity, Diabetes Mellitus, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Hyperlipidemias, Hypertension, Incidence, Inflammation, Kaplan-Meier Estimate, Male, Mass Screening, Mortality, Myocardial Infarction, Obesity, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, ROC Curve, Smoking, Stroke, Survival Analysis, Tunica Intima, Tunica Media, Ultrasonography, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.106.645606}, author = {Cao, Jie J and Arnold, Alice M and Manolio, Teri A and Polak, Joseph F and Psaty, Bruce M and Hirsch, Calvin H and Kuller, Lewis H and Cushman, Mary} } @article {1019, title = {Associations between common fibrinogen gene polymorphisms and cardiovascular disease in older adults. The Cardiovascular Health Study.}, journal = {Thromb Haemost}, volume = {99}, year = {2008}, month = {2008 Feb}, pages = {388-95}, abstract = {

Elevated plasma fibrinogen is a risk factor for cardiovascular disease (CVD), but associations between fibrinogen single nucleotide polymorphisms (SNPs) and disease risk are inconsistent. We investigated whether common (> or = 5\% minor allele frequency) variation in the fibrinogen genes (FGA, FGB, FGG) is associated with fibrinogen concentration, carotid artery intima-medial thickness (IMT) and risk of incident myocardial infarction (MI), ischemic stroke and CVD mortality in European- (EA) and African-descent (AA) adults (> or = 65 years) from the Cardiovascular Health Study. TagSNPs were genotyped in 3,969 EA and 719 AA free of MI or stroke at baseline. Race-specific models included multiple testing correction and adjustment for sex, age and site. Among EA, minor alleles of FGA3807, FGB1437 and FGG902 were associated with higher fibrinogen levels; whereas FGA251, FGA2224, FGA6534 and FGG10034 were associated with lower levels, p<0.004 for each. Strongest associations were seen for FGB1437; each additional copy of the minor allele was associated with 13 mg/dl (95\%CI: 9-16) higher fibrinogen level. Similar trends in AA were not significant. Fibrinogen haplotypes were not significantly associated with internal or common carotid IMT. No associations with MI or CVD mortality were seen in EA, though FGB1038 and FGG902 were significantly associated with increased and decreased risk of stroke in men, respectively, as were related haplotypes. FGB1038 was also associated with CVD mortality in AA, HR = 1.9 (95\%CI: 1.3-2.7). In conclusion, while fibrinogen genetic variation was strongly associated with fibrinogen levels, there was less evidence of association with the more complex outcomes of IMT and CVD events.

}, keywords = {African Americans, Age Factors, Aged, Brain Ischemia, Cardiovascular Diseases, Carotid Artery Diseases, European Continental Ancestry Group, Female, Fibrinogen, Gene Frequency, Genetic Predisposition to Disease, Haplotypes, Humans, Male, Myocardial Infarction, Polymorphism, Single Nucleotide, Population Surveillance, Proportional Hazards Models, Prospective Studies, Reproducibility of Results, Risk Assessment, Risk Factors, Sex Factors, Stroke, United States}, issn = {0340-6245}, doi = {10.1160/TH07-08-0523}, author = {Carty, Cara L and Cushman, Mary and Jones, Daniel and Lange, Leslie A and Hindorff, Lucia A and Rice, Kenneth and Jenny, Nancy S and Durda, J Peter and Walston, Jeremy and Carlson, Christopher S and Nickerson, Debbie and Tracy, Russell P and Reiner, Alex P} } @article {1006, title = {Coronary artery calcium, carotid artery wall thickness, and cardiovascular disease outcomes in adults 70 to 99 years old.}, journal = {Am J Cardiol}, volume = {101}, year = {2008}, month = {2008 Jan 15}, pages = {186-92}, abstract = {

Few population studies have evaluated the associations of both coronary artery calcium (CAC) and carotid ultrasound with cardiovascular events, especially in adults >70 years of age. At the Pittsburgh Field Center of the Cardiovascular Health Study, 559 men and women, mean age 80.2 (SD 4.1) years had CAC score assessed by electron beam computerized tomographic scan and common and internal carotid artery intimal medial wall thickness (CCA-IMT and ICA-IMT) by carotid ultrasound between 1998 and 2000 and were followed for total and incident cardiovascular disease events through June 2003. Crude rates and hazard ratios for total and incident events were examined with and without adjustment for cardiovascular risk factors. After 5 years, there were 127 cardiovascular disease events, 48 myocardial infarctions or cardiovascular disease deaths, and 28 strokes or stroke deaths. Total and incident cardiovascular disease event rates were higher in each quartile of CAC and CCA-IMT, but not of ICA-IMT. For total cardiovascular disease, the adjusted hazard ratio for the fourth versus first quartile of CAC was 2.1 (95\% confidence interval 1.2 to 3.9) and for CCA-IMT was 2.3 (95\% confidence interval 1.3 to 4.1). The CCA-IMT was more strongly related to stroke risk than was CAC, although CAC was also an important predictor of stroke. No significant gender differences were found, although relative risks appeared to be stronger in women, especially for stroke. In conclusion, in adults >70 years of age, CAC and CCA-IMT had similar hazard ratios for total cardiovascular disease and coronary heart disease. The CCA-IMT was more strongly related to stroke than CAC, but CAC was also a predictor of stroke.

}, keywords = {Aged, Aged, 80 and over, Carotid Artery Diseases, Carotid Artery, Common, Carotid Artery, Internal, Coronary Artery Disease, Coronary Vessels, Female, Humans, Male, ROC Curve, Severity of Illness Index, Survival Analysis, Ultrasonography, United States}, issn = {0002-9149}, doi = {10.1016/j.amjcard.2007.07.075}, author = {Newman, Anne B and Naydeck, Barbara L and Ives, Diane G and Boudreau, Robert M and Sutton-Tyrrell, Kim and O{\textquoteright}Leary, Daniel H and Kuller, Lewis H} } @article {957, title = {Relation of sleep-disordered breathing to carotid plaque and intima-media thickness.}, journal = {Atherosclerosis}, volume = {197}, year = {2008}, month = {2008 Mar}, pages = {125-31}, abstract = {

BACKGROUND: Sleep-disordered breathing (SDB) is associated with clinical cardiovascular disease (CVD), but its relation to subclinical atherosclerosis remains to be determined.

METHODS: We analyzed the cross-sectional associations of SDB, measured by the respiratory disturbance index (RDI), a hypoxemia index, and an arousal index, with carotid plaque and carotid intima-media thickness (IMT), measured by ultrasound. The sample included 985 participants in the Sleep Heart Health Study (mean age-62, median RDI-8.7) with no history of coronary heart disease and stroke, of whom 396 had evidence of a carotid plaque.

RESULTS: As compared with the first quartile of the RDI (0-1.2), the crude odds ratio for carotid plaque was 1.14, 1.27, and 1.48 for the second (1.3-4.1), third (4.2-10.7), and fourth (>10.7) quartile, respectively. After adjustment for CVD risk factors, the corresponding odds ratios were reduced (1.00, 1.04, 1.07, and 1.25). Similarly, the unadjusted mean carotid IMT increased with RDI, but adjusted means (mm) were similar (0.84, 0.85, 0.84, 0.85). Spline regression models did not show monotonicity of the dose-response functions at the right end of the RDI distribution. Neither the hypoxemia index nor the arousal index was associated with carotid plaque or carotid IMT.

CONCLUSION: The results of this study suggest that crude, positive associations between SDB and subclinical atherosclerosis can be attributed to confounding by CVD risk factors.

}, keywords = {Aged, Carotid Arteries, Carotid Artery Diseases, Female, Humans, Male, Middle Aged, Odds Ratio, Risk Factors, Sleep Apnea Syndromes, Tunica Intima, Tunica Media, Ultrasonography}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2007.02.029}, author = {Wattanakit, Keattiyoat and Boland, Lori and Punjabi, Naresh M and Shahar, Eyal} } @article {980, title = {Relationship between brachial flow-mediated dilation and carotid intima-media thickness in an elderly cohort: the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {197}, year = {2008}, month = {2008 Apr}, pages = {840-5}, abstract = {

OBJECTIVE: The aim of this study was to determine the relationship between brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) in a large multi-ethnic elderly cohort.

BACKGROUND: Brachial flow-mediated dilation (FMD) is a physiologic measure and carotid IMT is an anatomic structural measure of subclinical atherosclerosis. Both brachial FMD and carotid IMT have been associated with cardiovascular risk factors and cardiovascular events. The relationship between brachial FMD and carotid IMT is less clear especially in older adults.

METHODS: Brachial FMD, carotid IMT and traditional cardiovascular risk factors were measured in 2338 adults, age 72-98 years who were participants in the Cardiovascular Health Study. The relationship between FMD and IMT was assessed both unadjusted and also after adjusting for age, gender and race/ethnicity, BMI, HDL, LDL, systolic and diastolic blood pressure, serum creatinine, current smoking, diabetes mellitus, hormone therapy and prior CVD.

RESULTS: Both brachial FMD and carotid IMT correlated significantly with age, HDL levels, waist/hip ratio, serum cholesterol and number of CV risk factors. Brachial FMD was not associated with CCA IMT in this elderly cohort (Pearson partial correlation coefficient=-0.0252, p=0.222). In the adjusted linear regression model with CCA IMT as the dependent variable, brachial FMD was also not associated with CCA IMT (beta coefficient=-0.006, p=0.470).

CONCLUSION: Brachial FMD and CCA IMT are not related in population-based older adults. Brachial FMD and CCA IMT may be distinct and independent stages in the complex atherosclerotic process.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Brachial Artery, Carotid Arteries, Carotid Artery Diseases, Cohort Studies, Female, Hemorheology, Humans, Male, Tunica Intima, Tunica Media, Ultrasonography, Vasodilation}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2007.07.032}, author = {Yeboah, Joseph and Burke, Gregory L and Crouse, John R and Herrington, David M} } @article {1351, title = {Retinal microvascular signs and disability in the Cardiovascular Health Study.}, journal = {Arch Ophthalmol}, volume = {130}, year = {2012}, month = {2012 Mar}, pages = {350-6}, abstract = {

OBJECTIVE: To study the associations of retinal microvascular changes, which are associated with systemic conditions and cognitive decline, with disability in performing activities of daily living (ADL).

DESIGN: Prospective cohort study of 1487 community-dwelling participants in the Cardiovascular Health Study (mean age, 78 years) who were free of ADL disability and had available data on retinal signs and carotid intima-media thickness at the 1998-1999 visit. Main outcome measures were incident ADL disability, defined as self-reported difficulty in performing any ADL, by the presence of retinal signs and advanced carotid atherosclerosis, defined by carotid intima-media thickness in the 80th percentile or more or 25\% or more stenosis, and potential mediation by cerebral microvascular disease on brain imaging or by executive dysfunction, slow gait, and depressive mood, which are symptoms of frontal subcortical dysfunction.

RESULTS: During the median follow-up of 3.1 years (maximum, 7.8 years), participants with 2 or more retinal signs had a higher rate of disability than those with fewer than 2 retinal signs (10.1\% vs 7.1\%; adjusted hazard ratio, 1.45; 95\% confidence interval, 1.24-1.69; P~<~.001). There was no evidence of interaction by advanced carotid atherosclerosis (P~>~.10). The association seemed to be partially mediated by executive dysfunction, slow gait, and depressive symptoms but not by cerebral microvascular disease on brain imaging.

CONCLUSIONS: These results provide further support for the pathophysiologic and prognostic significance of microvascular disease in age-related disability. However, it remains to be determined how to best use retinal photography in clinical risk prediction.

}, keywords = {Activities of Daily Living, Aged, Carotid Artery Diseases, Cognition Disorders, Diagnostic Techniques, Ophthalmological, Disability Evaluation, Follow-Up Studies, Humans, Hypertension, Incidence, Kaplan-Meier Estimate, Microcirculation, Predictive Value of Tests, Prevalence, Prognosis, Prospective Studies, Retinal Diseases, Risk Factors, Smoking}, issn = {1538-3601}, doi = {10.1001/archophthalmol.2011.360}, author = {Kim, Dae Hyun and Chaves, Paulo H M and Newman, Anne B and Klein, Ronald and Sarnak, Mark J and Newton, Elizabeth and Strotmeyer, Elsa S and Burke, Gregory L and Lipsitz, Lewis A} } @article {6094, title = {Lack of associations of ten candidate coronary heart disease risk genetic variants and subclinical atherosclerosis in four US populations: the Population Architecture using Genomics and Epidemiology (PAGE) study.}, journal = {Atherosclerosis}, volume = {228}, year = {2013}, month = {2013 Jun}, pages = {390-9}, abstract = {

BACKGROUND: A number of genetic variants have been discovered by recent genome-wide association studies for their associations with clinical coronary heart disease (CHD). However, it is unclear whether these variants are also associated with the development of CHD as measured by subclinical atherosclerosis phenotypes, ankle brachial index (ABI), carotid artery intima-media thickness (cIMT) and carotid plaque.

METHODS: Ten CHD risk single nucleotide polymorphisms (SNPs) were genotyped in individuals of European American (EA), African American (AA), American Indian (AI), and Mexican American (MA) ancestry in the Population Architecture using Genomics and Epidemiology (PAGE) study. In each individual study, we performed linear or logistic regression to examine population-specific associations between SNPs and ABI, common and internal cIMT, and plaque. The results from individual studies were meta-analyzed using a fixed effect inverse variance weighted model.

RESULTS: None of the ten SNPs was significantly associated with ABI and common or internal cIMT, after Bonferroni correction. In the sample of 13,337 EA, 3809 AA, and 5353 AI individuals with carotid plaque measurement, the GCKR SNP rs780094 was significantly associated with the presence of plaque in AI only (OR~=~1.32, 95\% confidence interval: 1.17, 1.49, P~=~1.08~{\texttimes}~10(-5)), but not in the other populations (P~=~0.90 in EA and P~=~0.99 in AA). A 9p21 region SNP, rs1333049, was nominally associated with plaque in EA (OR~=~1.07, P~=~0.02) and in AI (OR~=~1.10, P~=~0.05).

CONCLUSIONS: We identified a significant association between rs780094 and plaque in AI populations, which needs to be replicated in future studies. There was little evidence that the index CHD risk variants identified through genome-wide association studies in EA influence the development of CHD through subclinical atherosclerosis as assessed by cIMT and ABI across ancestries.

}, keywords = {African Americans, Aged, Ankle Brachial Index, Asymptomatic Diseases, Carotid Artery Diseases, Carotid Intima-Media Thickness, Coronary Disease, European Continental Ancestry Group, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Indians, North American, Linear Models, Logistic Models, Male, Mexican Americans, Middle Aged, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Predictive Value of Tests, Risk Assessment, Risk Factors, United States}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2013.02.038}, author = {Zhang, Lili and B{\r u}zkov{\'a}, Petra and Wassel, Christina L and Roman, Mary J and North, Kari E and Crawford, Dana C and Boston, Jonathan and Brown-Gentry, Kristin D and Cole, Shelley A and Deelman, Ewa and Goodloe, Robert and Wilson, Sarah and Heiss, Gerardo and Jenny, Nancy S and Jorgensen, Neal W and Matise, Tara C and McClellan, Bob E and Nato, Alejandro Q and Ritchie, Marylyn D and Franceschini, Nora and Kao, W H Linda} } @article {6665, title = {Fibrosis-related biomarkers and large and small vessel disease: the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {239}, year = {2015}, month = {2015 Apr}, pages = {539-46}, abstract = {

OBJECTIVE: Fibrosis has been implicated in a number of pathological, organ-based conditions of the liver, kidney, heart, and lungs. The objective of this study was to determine whether biomarkers of fibrosis are associated with vascular disease in the large and/or small vessels.

METHODS: We evaluated the associations of two circulating biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with incident peripheral artery disease (PAD) and subclinical macrovascular (carotid intima-media thickness, flow-mediated vasodilation, ankle-brachial index, retinal vein diameter), and microvascular (retinal artery diameter and retinopathy) disease among older adults in the Cardiovascular Health Study. We measured TGF-β and PIIINP from samples collected in 1996 and ascertained clinical PAD through 2011. Measurements of large and small vessels were collected between 1996 and 1998.

RESULTS: After adjustment for sociodemographic, clinical, and biochemical risk factors, TGF-β was associated with incident PAD (hazard ratio [HR]~=~1.36 per doubling of TGF-β, 95\% confidence interval [CI]~=~1.04, 1.78) and retinal venular diameter (1.63~μm per doubling of TGF-β, CI~=~0.23, 3.02). PIIINP was not associated with incident PAD, but was associated with carotid intima-media thickness (0.102~mm per doubling of PIIINP, CI~=~0.029, 0.174) and impaired brachial artery reactivity (-0.20\% change per doubling of PIIINP, CI~=~-0.39,~-0.02). Neither TGF-β nor PIIINP were associated with retinal arteriolar diameter or retinopathy.

CONCLUSIONS: Serum concentrations of fibrosis-related biomarkers were associated with several measures of large vessel disease, including incident PAD, but not with small vessel disease. Fibrosis may contribute to large vessel atherosclerosis in older adults.

}, keywords = {Aged, Ankle Brachial Index, Biomarkers, Brachial Artery, Carotid Artery Diseases, Carotid Intima-Media Thickness, Cross-Sectional Studies, Female, Fibrosis, Humans, Incidence, Male, Peptide Fragments, Peripheral Arterial Disease, Predictive Value of Tests, Procollagen, Prognosis, Prospective Studies, Retinal Diseases, Risk Factors, Transforming Growth Factor beta, United States, Vasodilation}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2015.02.020}, author = {Agarwal, Isha and Arnold, Alice and Glazer, Nicole L and Barasch, Eddy and Djouss{\'e}, Luc and Fitzpatrick, Annette L and Gottdiener, John S and Ix, Joachim H and Jensen, Richard A and Kizer, Jorge R and Rimm, Eric B and Siscovick, David S and Tracy, Russell P and Wong, Tien Y and Mukamal, Kenneth J} } @article {6876, title = {Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0132321}, abstract = {

BACKGROUND: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events.

METHODS: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity.

RESULTS: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites.

CONCLUSION: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.

}, keywords = {Adult, Age Distribution, Aged, Carotid Artery Diseases, Carotid Intima-Media Thickness, Cholesterol, HDL, Cholesterol, LDL, Comorbidity, Continental Population Groups, Diabetes Mellitus, Dyslipidemias, Ethnic Groups, Female, Follow-Up Studies, Global Health, Humans, Hypertension, Incidence, Linear Models, Male, Middle Aged, Myocardial Infarction, Prevalence, Proportional Hazards Models, Risk Factors, Smoking, Stroke}, issn = {1932-6203}, doi = {10.1371/journal.pone.0132321}, author = {Gijsberts, Crystel M and Groenewegen, Karlijn A and Hoefer, Imo E and Eijkemans, Marinus J C and Asselbergs, Folkert W and Anderson, Todd J and Britton, Annie R and Dekker, Jacqueline M and Engstr{\"o}m, Gunnar and Evans, Greg W and de Graaf, Jacqueline and Grobbee, Diederick E and Hedblad, Bo and Holewijn, Suzanne and Ikeda, Ai and Kitagawa, Kazuo and Kitamura, Akihiko and de Kleijn, Dominique P V and Lonn, Eva M and Lorenz, Matthias W and Mathiesen, Ellisiv B and Nijpels, Giel and Okazaki, Shuhei and O{\textquoteright}Leary, Daniel H and Pasterkamp, Gerard and Peters, Sanne A E and Polak, Joseph F and Price, Jacqueline F and Robertson, Christine and Rembold, Christopher M and Rosvall, Maria and Rundek, Tatjana and Salonen, Jukka T and Sitzer, Matthias and Stehouwer, Coen D A and Bots, Michiel L and den Ruijter, Hester M} } @article {9383, title = {High-risk carotid plaques and incident ischemic stroke in patients with atrial fibrillation in the Cardiovascular Health Study.}, journal = {Eur J Neurol}, volume = {30}, year = {2023}, month = {2023 Jul}, pages = {2042-2050}, abstract = {

BACKGROUND AND PURPOSE: Whether carotid artery disease could improve stroke risk stratification tools in patients with atrial fibrillation (AF) remains uncertain. This study was undertaken to investigate the risk of ischemic stroke associated with occlusive and nonocclusive carotid atherosclerotic~disease in patients with AF in the prospective population-based Cardiovascular Health Study.

METHODS: We included participants aged >=65 years with AF. We used multivariable Cox regression analysis to explore the risk of ischemic stroke associated with the percentage of carotid stenosis, plaque irregularity, echogenicity, and vulnerability (markedly irregular, ulcerated, or hypoechoic plaques).

RESULTS: A total of 1398 participants were included (55.2\% female, 61.7\% aged 65-74 years). The maximum carotid stenosis was <50\%, 50\%-99\%, and 100\% in 94.5\%, 5\%, and 0.5\% of participants, respectively. High-risk plaques based on echogenicity and plaque irregularity were found in 25.6\% and 8.9\% of participants, respectively. After a median follow-up of 10.9 years (interquartile range = 7.5-15.6), 298 ischemic strokes were recorded. There was no difference in the incidence of ischemic stroke according to the degree of carotid artery stenosis (p = 0.44), plaque echogenicity (low vs. high risk, p = 0.68), plaque irregularity (low vs. high risk, p = 0.55), and plaque vulnerability (p = 0.86). The CHA$_{2}$DS$_{2}$-VASc score was associated with an increased risk of ischemic stroke (adjusted hazard ratio = 1.28, 95\% confidence interval = 1.18-1.40, p < 0.001). Both maximum grade of stenosis and plaque vulnerability were not associated with incident ischemic stroke (all p > 0.05).

CONCLUSIONS: Neither the degree of carotid stenosis nor the presence of vulnerable plaques was associated with incident ischemic stroke in this cohort~of individuals with AF. This suggests that carotid disease was probably not a significant contributor to ischemic stroke in this population.

}, keywords = {Atrial Fibrillation, Carotid Artery Diseases, Carotid Stenosis, Female, Humans, Ischemic Stroke, Male, Plaque, Atherosclerotic, Prospective Studies, Risk Factors, Stroke}, issn = {1468-1331}, doi = {10.1111/ene.15817}, author = {Noubiap, Jean Jacques and Thomas, Gijo and Kamtchum-Tatuene, Joseph and Middeldorp, Melissa E and Sanders, Prashanthan} }