@article {933, title = {Association of kidney function with incident hip fracture in older adults.}, journal = {J Am Soc Nephrol}, volume = {18}, year = {2007}, month = {2007 Jan}, pages = {282-6}, abstract = {

Kidney dysfunction is associated with bone loss, and patients with ESRD have an increased risk for hip fracture. However, the association of mild to moderate kidney disease with hip fracture has not been studied previously. The association of kidney function with incident hip fracture was examined among participants in the Cardiovascular Health Study, a community-based cohort of older individuals. The primary measure of kidney function was serum cystatin C, a measure that does not depend on lean mass. Hip fractures were identified using International Classification of Diseases, Ninth Revision codes for hospitalizations. A total of 4699 individuals had cystatin C measured in 1992 to 1993 and did not have a hip fracture before cystatin C measurement. The association of kidney function with hip fracture was analyzed with Cox proportional hazards models. Analyses were conducted separately for men and women. After a mean follow-up of 7.1 yr, 195 incident hip fractures occurred in women and 79 occurred in men. Higher cystatin C levels were associated with a higher risk for fracture in women (hazard ratio [HR] 1.26; 95\% confidence interval [CI] 1.14 to 1.38 per SD) and in men (HR 1.27; 95\% CI 1.11 to 1.46). After multivariable adjustment, higher cystatin C levels were significantly associated with hip fracture in women (HR 1.16; 95\% CI 1.01, 1.33) but not in men (HR 1.14; 95\% CI 0.86 to 1.52), although the magnitude of the association was similar. Kidney dysfunction, as assessed by cystatin C, is associated with an increased risk for hip fracture. Further studies are needed to evaluate potential mediators of this relationship and to assess whether interventions can decrease this risk.

}, keywords = {Aged, Aged, 80 and over, Cystatin C, Cystatins, Female, Hip Fractures, Humans, Kidney, Kidney Failure, Chronic, Longitudinal Studies, Male, Osteoporosis, Prospective Studies, Risk Factors, Sex Factors}, issn = {1046-6673}, doi = {10.1681/ASN.2006050546}, author = {Fried, Linda F and Biggs, Mary Louise and Shlipak, Michael G and Seliger, Stephen and Kestenbaum, Bryan and Stehman-Breen, Catherine and Sarnak, Mark and Siscovick, David and Harris, Tamara and Cauley, Jane and Newman, Anne B and Robbins, John} } @article {928, title = {Determinants of serum total and free testosterone levels in women over the age of 65 years.}, journal = {J Clin Endocrinol Metab}, volume = {92}, year = {2007}, month = {2007 Feb}, pages = {509-16}, abstract = {

CONTEXT: Little is known about testosterone (T) levels and their determinants in women of late postmenopausal age.

OBJECTIVE: We describe levels of total and free T and selected factors that influence these levels in a random sample of older women.

DESIGN: Levels of serum total T and free T by microdialysis were measured using ultrasensitive assays in 347 community-dwelling women aged 65-98 yr enrolled in the Cardiovascular Health Study. Cross-sectional analyses were performed to define factors associated with total and free T levels.

RESULTS: In adjusted models: 1) total T levels declined with age until 80, whereas free T levels did not vary by age; 2) women with bilateral oophorectomy had 23\% lower total T and 16\% lower free T levels than those with at least one intact ovary; 3) oral estrogen users had total and free T levels that were 47\% lower than never users; 4) obese women had 47\% higher total T and 20\% higher free T levels, and overweight women had 24\% higher total T and 14\% higher free T levels, than normal weight women; and 5) free T levels were 51\% higher in black women. Corticosteroid users had 75\% lower total T and 43\% lower free T levels than nonusers.

CONCLUSIONS: Bilateral oophorectomy, estrogen use, corticosteroid use, and low body mass index are independent risk factors for lower T levels in women aged 65 yr and over. Although highly prevalent in women of this age, the physiological significance of low T levels in late postmenopausal women requires further investigation.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Aging, Body Mass Index, Cross-Sectional Studies, Estrogen Replacement Therapy, Female, Humans, Hypogonadism, Multivariate Analysis, Nonlinear Dynamics, Obesity, Ovariectomy, Ovary, Postmenopause, Predictive Value of Tests, Prevalence, Risk Factors, Testosterone}, issn = {0021-972X}, doi = {10.1210/jc.2006-1399}, author = {Cappola, Anne R and Ratcliffe, Sarah J and Bhasin, Shalender and Blackman, Marc R and Cauley, Jane and Robbins, John and Zmuda, Joseph M and Harris, Tamara and Fried, Linda P} } @article {1128, title = {Age and cystatin C in healthy adults: a collaborative study.}, journal = {Nephrol Dial Transplant}, volume = {25}, year = {2010}, month = {2010 Feb}, pages = {463-9}, abstract = {

BACKGROUND: Kidney function declines with age, but a substantial portion of this decline has been attributed to the higher prevalence of risk factors for kidney disease at older ages. The effect of age on kidney function has not been well described in a healthy population across a wide age spectrum.

METHODS: The authors pooled individual-level cross-sectional data from 18 253 persons aged 28-100 years in four studies: the Cardiovascular Health Study; the Health, Aging and Body Composition Study; the Multi-Ethnic Study of Atherosclerosis and the Prevention of Renal and Vascular End-Stage Disease cohort. Kidney function was measured by cystatin C. Clinical risk factors for kidney disease included diabetes, hypertension, obesity, smoking, coronary heart disease, cerebrovascular disease, peripheral arterial disease and heart failure.

RESULTS: Across the age range, there was a strong, non-linear association of age with cystatin C concentration. This association was substantial, even among participants free of clinical risk factors for kidney disease; mean cystatin C levels were 46\% higher in participants 80 and older compared with those <40 years (1.06 versus 0.72 mg/L, P < 0.001). Participants with one or more risk factors had higher cystatin C concentrations for a given age, and the age association was slightly stronger (P < 0.001 for age and risk factor interaction).

CONCLUSIONS: There is a strong, non-linear association of age with kidney function, even in healthy individuals. An important area for research will be to investigate the mechanisms that lead to deterioration of kidney function in apparently healthy persons.

}, keywords = {Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Cystatin C, Humans, Kidney, Middle Aged, Reference Values}, issn = {1460-2385}, doi = {10.1093/ndt/gfp474}, author = {Odden, Michelle C and Tager, Ira B and Gansevoort, Ron T and Bakker, Stephan J L and Katz, Ronit and Fried, Linda F and Newman, Anne B and Canada, Robert B and Harris, Tamara and Sarnak, Mark J and Siscovick, David and Shlipak, Michael G} } @article {1222, title = {Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.}, journal = {Diabetes Care}, volume = {33}, year = {2010}, month = {2010 Dec}, pages = {2684-91}, abstract = {

OBJECTIVE: Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin.

RESEARCH DESIGN AND METHODS: Via meta-analysis of data from 14 cohorts comprising \~{} 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value <0.0028 (0.05 of 18 tests) as statistically significant.

RESULTS: Greater whole-grain food intake was associated with lower fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95\% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P < 0.0001 and -0.011 pmol/l [ln] insulin [-0.015 to -0.007], P = 0.0003). No interactions met our multiple testing-adjusted statistical significance threshold. The strongest SNP interaction with whole-grain intake was rs780094 (GCKR) for fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele.

CONCLUSIONS: Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

}, keywords = {Adult, Aged, Blood Glucose, Edible Grain, European Continental Ancestry Group, Fasting, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Humans, Insulin, Male, Middle Aged, Polymorphism, Single Nucleotide}, issn = {1935-5548}, doi = {10.2337/dc10-1150}, author = {Nettleton, Jennifer A and McKeown, Nicola M and Kanoni, Stavroula and Lemaitre, Rozenn N and Hivert, Marie-France and Ngwa, Julius and van Rooij, Frank J A and Sonestedt, Emily and Wojczynski, Mary K and Ye, Zheng and Tanaka, Tosh and Garcia, Melissa and Anderson, Jennifer S and Follis, Jack L and Djouss{\'e}, Luc and Mukamal, Kenneth and Papoutsakis, Constantina and Mozaffarian, Dariush and Zillikens, M Carola and Bandinelli, Stefania and Bennett, Amanda J and Borecki, Ingrid B and Feitosa, Mary F and Ferrucci, Luigi and Forouhi, Nita G and Groves, Christopher J and Hallmans, G{\"o}ran and Harris, Tamara and Hofman, Albert and Houston, Denise K and Hu, Frank B and Johansson, Ingegerd and Kritchevsky, Stephen B and Langenberg, Claudia and Launer, Lenore and Liu, Yongmei and Loos, Ruth J and Nalls, Michael and Orho-Melander, Marju and Renstrom, Frida and Rice, Kenneth and Riserus, Ulf and Rolandsson, Olov and Rotter, Jerome I and Saylor, Georgia and Sijbrands, Eric J G and Sjogren, Per and Smith, Albert and Steingr{\'\i}msd{\'o}ttir, Laufey and Uitterlinden, Andr{\'e} G and Wareham, Nicholas J and Prokopenko, Inga and Pankow, James S and van Duijn, Cornelia M and Florez, Jose C and Witteman, Jacqueline C M and Dupuis, Jos{\'e}e and Dedoussis, George V and Ordovas, Jose M and Ingelsson, Erik and Cupples, L Adrienne and Siscovick, David S and Franks, Paul W and Meigs, James B} } @article {1259, title = {Gait speed and survival in older adults.}, journal = {JAMA}, volume = {305}, year = {2011}, month = {2011 Jan 05}, pages = {50-8}, abstract = {

CONTEXT: Survival estimates help individualize goals of care for geriatric patients, but life tables fail to account for the great variability in survival. Physical performance measures, such as gait speed, might help account for variability, allowing clinicians to make more individualized estimates.

OBJECTIVE: To evaluate the relationship between gait speed and survival.

DESIGN, SETTING, AND PARTICIPANTS: Pooled analysis of 9 cohort studies (collected between 1986 and 2000), using individual data from 34,485 community-dwelling older adults aged 65 years or older with baseline gait speed data, followed up for 6 to 21 years. Participants were a mean (SD) age of 73.5 (5.9) years; 59.6\%, women; and 79.8\%, white; and had a mean (SD) gait speed of 0.92 (0.27) m/s.

MAIN OUTCOME MEASURES: Survival rates and life expectancy.

RESULTS: There were 17,528 deaths; the overall 5-year survival rate was 84.8\% (confidence interval [CI], 79.6\%-88.8\%) and 10-year survival rate was 59.7\% (95\% CI, 46.5\%-70.6\%). Gait speed was associated with survival in all studies (pooled hazard ratio per 0.1 m/s, 0.88; 95\% CI, 0.87-0.90; P < .001). Survival increased across the full range of gait speeds, with significant increments per 0.1 m/s. At age 75, predicted 10-year survival across the range of gait speeds ranged from 19\% to 87\% in men and from 35\% to 91\% in women. Predicted survival based on age, sex, and gait speed was as accurate as predicted based on age, sex, use of mobility aids, and self-reported function or as age, sex, chronic conditions, smoking history, blood pressure, body mass index, and hospitalization.

CONCLUSION: In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults.

}, keywords = {Aged, Cohort Studies, Female, Gait, Geriatric Assessment, Humans, Life Expectancy, Male, Survival Analysis, United States}, issn = {1538-3598}, doi = {10.1001/jama.2010.1923}, author = {Studenski, Stephanie and Perera, Subashan and Patel, Kushang and Rosano, Caterina and Faulkner, Kimberly and Inzitari, Marco and Brach, Jennifer and Chandler, Julie and Cawthon, Peggy and Connor, Elizabeth Barrett and Nevitt, Michael and Visser, Marjolein and Kritchevsky, Stephen and Badinelli, Stefania and Harris, Tamara and Newman, Anne B and Cauley, Jane and Ferrucci, Luigi and Guralnik, Jack} } @article {6070, title = {A genome-wide association study of depressive symptoms.}, journal = {Biol Psychiatry}, volume = {73}, year = {2013}, month = {2013 Apr 01}, pages = {667-78}, abstract = {

BACKGROUND: Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms.

METHODS: In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p<1{\texttimes}10(-5)) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies.

RESULTS: The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05{\texttimes}10(-7)). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19{\texttimes}10(-3)). This 5q21 region reached genome-wide significance (p = 4.78{\texttimes}10(-8)) in the overall meta-analysis combining discovery and replication studies (n = 51,258).

CONCLUSIONS: The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms.

}, keywords = {Aged, Aged, 80 and over, Chromosomes, Human, Pair 5, Depression, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide}, issn = {1873-2402}, doi = {10.1016/j.biopsych.2012.09.033}, author = {Hek, Karin and Demirkan, Ayse and Lahti, Jari and Terracciano, Antonio and Teumer, Alexander and Cornelis, Marilyn C and Amin, Najaf and Bakshis, Erin and Baumert, Jens and Ding, Jingzhong and Liu, Yongmei and Marciante, Kristin and Meirelles, Osorio and Nalls, Michael A and Sun, Yan V and Vogelzangs, Nicole and Yu, Lei and Bandinelli, Stefania and Benjamin, Emelia J and Bennett, David A and Boomsma, Dorret and Cannas, Alessandra and Coker, Laura H and de Geus, Eco and De Jager, Philip L and Diez-Roux, Ana V and Purcell, Shaun and Hu, Frank B and Rimma, Eric B and Hunter, David J and Jensen, Majken K and Curhan, Gary and Rice, Kenneth and Penman, Alan D and Rotter, Jerome I and Sotoodehnia, Nona and Emeny, Rebecca and Eriksson, Johan G and Evans, Denis A and Ferrucci, Luigi and Fornage, Myriam and Gudnason, Vilmundur and Hofman, Albert and Illig, Thomas and Kardia, Sharon and Kelly-Hayes, Margaret and Koenen, Karestan and Kraft, Peter and Kuningas, Maris and Massaro, Joseph M and Melzer, David and Mulas, Antonella and Mulder, Cornelis L and Murray, Anna and Oostra, Ben A and Palotie, Aarno and Penninx, Brenda and Petersmann, Astrid and Pilling, Luke C and Psaty, Bruce and Rawal, Rajesh and Reiman, Eric M and Schulz, Andrea and Shulman, Joshua M and Singleton, Andrew B and Smith, Albert V and Sutin, Angelina R and Uitterlinden, Andr{\'e} G and V{\"o}lzke, Henry and Widen, Elisabeth and Yaffe, Kristine and Zonderman, Alan B and Cucca, Francesco and Harris, Tamara and Ladwig, Karl-Heinz and Llewellyn, David J and R{\"a}ikk{\"o}nen, Katri and Tanaka, Toshiko and van Duijn, Cornelia M and Grabe, Hans J and Launer, Lenore J and Lunetta, Kathryn L and Mosley, Thomas H and Newman, Anne B and Tiemeier, Henning and Murabito, Joanne} } @article {6587, title = {Association of a cystatin C gene variant with cystatin C levels, CKD, and risk of incident cardiovascular disease and mortality.}, journal = {Am J Kidney Dis}, volume = {63}, year = {2014}, month = {2014 Jan}, pages = {16-22}, abstract = {

BACKGROUND: Carriers of the T allele of the single-nucleotide polymorphism rs13038305 tend to have lower cystatin C levels and higher cystatin C-based estimated glomerular filtration rate (eGFRcys). Adjusting for this genetic effect on cystatin C concentrations may improve GFR estimation, reclassify cases of chronic kidney disease (CKD), and strengthen risk estimates for cardiovascular disease (CVD) and mortality.

STUDY DESIGN: Observational.

SETTING \& POPULATION: 4 population-based cohorts: Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health (CHS), Framingham Heart (FHS), and Health, Aging, and Body Composition (Health ABC) studies.

PREDICTORS: We estimated the association of rs13038305 with eGFRcys and serum creatinine-based eGFR (eGFRcr) and performed longitudinal analyses of the associations of eGFRcys with mortality and cardiovascular events following adjustment for rs13038305.

OUTCOMES: We assessed reclassification by genotype-adjusted eGFRcys across CKD categories: <45, 45-59, 60-89, and >= 90 mL/min/1.73 m(2). We compared mortality and CVD outcomes in those reclassified to a worse eGFRcys category with those unaffected. Results were combined using fixed-effect inverse-variance meta-analysis.

RESULTS: In 14,645 participants, each copy of the T allele of rs13038305 (frequency, 21\%) was associated with a 6.4\% lower cystatin C concentration, 5.5-mL/min/1.73 m(2) higher eGFRcys, and 36\% [95\% CI, 29\%-41\%] lower odds of CKD. Associations with CVD (HR, 1.17; 95\% CI, 1.14-1.20) and mortality (HR, 1.22; 95\% CI, 1.19-1.24) per 10-mL/min/1.73 m(2) lower eGFRcys were similar with or without rs13038305 adjustment. 1,134 (7.7\%) participants were reclassified to a worse CKD category following rs13038305 adjustment, and rates of CVD and mortality were higher in individuals who were reclassified. However, the overall net reclassification index was not significant for either outcome, at 0.009 (95\% CI, -0.003 to 0.022) for mortality and 0.014 (95\% CI, 0.0 to 0.028) for CVD.

LIMITATIONS: rs13038305 explains only a small proportion of cystatin C variation.

CONCLUSIONS: Statistical adjustment can correct a genetic bias in GFR estimates based on cystatin C in carriers of the T allele of rs13038305 and result in changes in disease classification. However, on a population level, the effects on overall reclassification of CKD status are modest.

}, keywords = {Aged, Bias, Biomarkers, Cardiovascular Diseases, Creatinine, Cystatin C, Female, Genetic Variation, Glomerular Filtration Rate, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Renal Insufficiency, Chronic, Risk Assessment, Risk Factors, Severity of Illness Index, Statistics as Topic, Survival Rate}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2013.06.015}, author = {O{\textquoteright}Seaghdha, Conall M and Tin, Adrienne and Yang, Qiong and Katz, Ronit and Liu, Yongmei and Harris, Tamara and Astor, Brad and Coresh, Josef and Fox, Caroline S and Kao, W H Linda and Shlipak, Michael G} } @article {7161, title = {Gait Speed Predicts Incident Disability: A Pooled Analysis.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {71}, year = {2016}, month = {2016 Jan}, pages = {63-71}, abstract = {

BACKGROUND: Functional independence with aging is an important goal for individuals and society. Simple prognostic indicators can inform health promotion and care planning, but evidence is limited by heterogeneity in measures of function.

METHODS: We performed a pooled analysis of data from seven studies of 27,220 community-dwelling older adults aged 65 or older with baseline gait speed, followed for disability and mortality. Outcomes were incident inability or dependence on another person in bathing or dressing; and difficulty walking {\textonequarter} - {\textonehalf} mile or climbing 10 steps within 3 years.

RESULTS: Participants with faster baseline gait had lower rates of incident disability. In subgroups (defined by 0.2 m/s-wide intervals from <0.4 to >= 1.4 m/s) with increasingly greater gait speed, 3-year rates of bathing or dressing dependence trended from 10\% to 1\% in men, and from 15\% to 1\% in women, while mobility difficulty trended from 47\% to 4\% in men and 40\% to 6\% in women. The age-adjusted relative risk ratio per 0.1 m/s greater speed for bathing or dressing dependence in men was 0.68 (0.57-0.81) and in women: 0.74 (0.66-0.82); for mobility difficulty, men: 0.75 (0.68-0.82), women: 0.73 (0.67-0.80). Results were similar for combined disability and mortality. Effects were largely consistent across subgroups based on age, gender, race, body mass index, prior hospitalization, and selected chronic conditions. In the presence of multiple other risk factors for disability, gait speed significantly increased the area under the receiver operator characteristic curve.

CONCLUSION: In older adults, gait speed predicts 3 year incidence of bathing or dressing dependence, mobility difficulty, and a composite outcome of disability and mortality.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Aging, Cohort Studies, Disability Evaluation, Disabled Persons, Female, Gait, Geriatric Assessment, Humans, Independent Living, Male, Mobility Limitation, Predictive Value of Tests, Prognosis, Psychomotor Performance, Risk Assessment, Risk Factors, ROC Curve, Survival Analysis, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glv126}, author = {Perera, Subashan and Patel, Kushang V and Rosano, Caterina and Rubin, Susan M and Satterfield, Suzanne and Harris, Tamara and Ensrud, Kristine and Orwoll, Eric and Lee, Christine G and Chandler, Julie M and Newman, Anne B and Cauley, Jane A and Guralnik, Jack M and Ferrucci, Luigi and Studenski, Stephanie A} }