@article {873, title = {Cystatin C and incident peripheral arterial disease events in the elderly: results from the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Dec 12-26}, pages = {2666-70}, abstract = {

BACKGROUND: The association of cystatin C, a novel marker of renal function, with risk for developing complications related to peripheral arterial disease (PAD) has not been examined.

METHODS: We evaluated the hypothesis that a high cystatin C concentration is independently associated with future PAD events among 4025 participants in the Cardiovascular Health Study who underwent serum cystatin C measurement at the 1992-1993 visit and who did not have PAD at baseline. The association of cystatin C quintiles with time to first lower-extremity PAD procedure (bypass surgery, angioplasty, or amputation) was evaluated using multivariable proportional hazards models. Secondary analyses were conducted using quintiles of serum creatinine level and estimated glomerular filtration rate (eGFR).

RESULTS: The annualized risk of undergoing a procedure for PAD was 0.43\% per year among participants in the highest cystatin C quintile (>1.27 mg/L) compared with 0.21\% per year or less in all other quintiles. After multivariable adjustment for known risk factors for PAD, elevated cystatin C levels remained associated with the outcome (hazard ratio, 2.5 for highest vs lowest quintile of cystatin C, 95\% confidence interval, 1.2-5.1). The highest quintiles of serum creatinine level and eGFR were not associated with future PAD events in either unadjusted or adjusted analyses.

CONCLUSION: Elevated concentrations of cystatin C were independently predictive of incident PAD events among community-dwelling elderly patients.

}, keywords = {Aged, Cohort Studies, Cystatin C, Cystatins, Female, Health Surveys, Humans, Longitudinal Studies, Male, Peripheral Vascular Diseases, Predictive Value of Tests, Risk Factors, ROC Curve, United States}, issn = {0003-9926}, doi = {10.1001/archinte.165.22.2666}, author = {O{\textquoteright}Hare, Ann M and Newman, Anne B and Katz, Ronit and Fried, Linda F and Stehman-Breen, Catherine O and Seliger, Stephen L and Siscovick, David S and Shlipak, Michael G} } @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 {865, title = {Kidney function as a predictor of noncardiovascular mortality.}, journal = {J Am Soc Nephrol}, volume = {16}, year = {2005}, month = {2005 Dec}, pages = {3728-35}, abstract = {

Chronic kidney disease is associated with a higher risk for cardiovascular mortality, as well as all-cause mortality. Whether chronic kidney disease is a predictor of noncardiovascular mortality is less clear. To further explore the latter, the association of kidney function with total noncardiovascular mortality and cause-specific mortality was assessed in the Cardiovascular Health Study, a community-based cohort of older individuals. Kidney disease was assessed using cystatin C and estimated GFR in 4637 participants in 1992 to 1993. Participants were followed until June 30, 2001. Deaths were adjudicated as cardiovascular or noncardiovascular disease by committee, and an underlying cause of death was assigned. The associations of kidney function with total noncardiovascular mortality and cause-specific mortality were analyzed by proportional hazards regression. Noncardiovascular mortality rates increased with higher cystatin C quartiles (16.8, 17.1, 21.6, and 50.0 per 1000 person-years). The association of cystatin C with noncardiovascular mortality persisted after adjustment for demographic factors; the presence of diabetes, C-reactive protein, hemoglobin, and prevalent cardiovascular disease; and measures of atherosclerosis (hazard ratio 1.69; 95\% confidence interval 1.33 to 2.15, for the fourth quartile versus the first quartile). Results for estimated GFR were similar. The risk for noncardiac deaths attributed to pulmonary disease, infection, cancer, and other causes was similarly associated with cystatin C levels. Kidney function predicts noncardiovascular mortality from multiple causes in the elderly. Further research is needed to understand the mechanisms and evaluate interventions to reduce the high mortality rate in chronic kidney disease.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases, Cause of Death, Cohort Studies, Confidence Intervals, Creatinine, Cystatin C, Cystatins, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Kidney Function Tests, Longitudinal Studies, Male, Probability, Proportional Hazards Models, Risk Assessment, Severity of Illness Index, Survival Analysis, United States}, issn = {1046-6673}, doi = {10.1681/ASN.2005040384}, author = {Fried, Linda F and Katz, Ronit and Sarnak, Mark J and Shlipak, Michael G and Chaves, Paulo H M and Jenny, Nancy Swords and Stehman-Breen, Catherine and Gillen, Dan and Bleyer, Anthony J and Hirsch, Calvin and Siscovick, David and Newman, Anne B} } @article {918, title = {Metabolic syndrome and cardiovascular disease in older people: The cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {54}, year = {2006}, month = {2006 Sep}, pages = {1317-24}, abstract = {

OBJECTIVES: To assess the prospective association between metabolic syndrome (MetS) and cardiovascular disease (CVD) in older people and to evaluate the effect of lowering the threshold for impaired fasting glucose (IFG) on the prevalence of IFG and MetS and the risk of CVD.

DESIGN: Prospective cohort study.

SETTING: Four field centers in U.S. communities.

PARTICIPANTS: Three thousand five hundred eighty-five subjects in the Cardiovascular Health Study free of diabetes mellitus and CVD at baseline (mean age 72, 62\% female, 14\% black).

MEASUREMENTS: Baseline measures of MetS components and adjudicated incident CVD events. MetS (2001) was defined first using the original criteria from the Third Adult Treatment Panel Report of the National Cholesterol Education Program (> or =3 of the following: large waist circumference (women >88 cm, men >102 cm), elevated triglycerides (> or =1.70 mmol/L), low high-density lipoprotein cholesterol (men <1.04 mmol/L, women <1.30 mmol/L), elevated fasting glucose (6.1-6.9 mmol/L), and high blood pressure (> or =130/85 mmHg or self-reported use of medications for hypertension). Subjects were also classified according to the revised definition of the MetS (2005) that applies the lower threshold for fasting glucose (5.6-6.9 mmol/L).

RESULTS: During follow-up (median 11 years), 818 coronary heart disease (CHD), 401 stroke, and 554 congestive heart failure (CHF) events occurred. Age- and race-adjusted hazard ratios (HRs) for CHD, stroke, and CHF were 1.30 (95\% confidence interval (CI) = 1.07-1.57), 0.94 (95\% CI = 0.73-1.21), and 1.40 (95\% CI = 1.12-1.76) for women and 1.35 (95\% CI = 1.10-1.66), 1.51 (95\% CI = 1.08-2.12), and 1.47 (95\% CI = 1.14-1.90) for men, respectively. Overall, women and men with MetS (2005) were 20\% to 30\% more likely to experience any CVD event than subjects without MetS (2005). Using the lower cut-point for IFG resulted in a near tripling in IFG prevalence (16\% to 46\%) and an additional 9\% classified with MetS (2005) but HRs similar to those estimated from the original MetS (2001) criteria. High blood pressure was the component most strongly associated with incident CHD.

CONCLUSION: Results from this study of an elderly, population-based cohort provide support for earlier investigations in primarily middle-aged populations that link the presence of MetS with the development of CVD and further underscore the importance of recognizing and treating its individual components, particularly high blood pressure.

}, keywords = {African Americans, Age Factors, Aged, Aged, 80 and over, Blood Glucose, Cardiovascular Diseases, Cohort Studies, European Continental Ancestry Group, Fasting, Female, Humans, Incidence, Male, Metabolic Syndrome, Risk Factors, Sex Factors}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2006.00862.x}, author = {McNeill, Ann Marie and Katz, Ronit and Girman, Cynthia J and Rosamond, Wayne D and Wagenknecht, Lynne E and Barzilay, Joshua I and Tracy, Russell P and Savage, Peter J and Jackson, Sharon A} } @article {997, title = {Clinical factors, but not C-reactive protein, predict progression of calcific aortic-valve disease: the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {50}, year = {2007}, month = {2007 Nov 13}, pages = {1992-8}, abstract = {

OBJECTIVES: The purpose of this study was to examine the relationship between C-reactive protein (CRP) and calcific aortic valve disease in a large, randomly selected, population-based cohort.

BACKGROUND: The pathobiology of calcific aortic stenosis involves an active inflammatory, atheromatous, osteogenic process. Elevations in CRP, a measure of systemic inflammation, have been associated with aortic stenosis.

METHODS: Two-dimensional and Doppler echocardiography and CRP measurement were performed at baseline in 5,621 participants in the Cardiovascular Health Study. Multivariable analysis was used to identify CRP as a predictor of baseline and incident aortic stenosis.

RESULTS: At a mean echocardiographic follow-up of 5 years, 9\% of subjects with aortic sclerosis progressed to some degree of aortic stenosis. Increasing age (odds ratio [OR] 1.13, 95\% confidence interval [CI] 1.09 to 1.16; p < 0.001) and male gender (OR 3.05, 95\% CI 1.76 to 5.27; p < 0.001) were related to risk of incident aortic stenosis, whereas increasing height (OR 0.96, 95\% CI 0.94 to 0.99; p = 0.013) and African-American ethnicity conveyed a lower risk (OR 0.49, 95\% CI 0.25 to 0.95; p = 0.035). C-reactive protein, treated as a continuous variable, was not associated with baseline aortic stenosis, progression to aortic sclerosis (adjusted OR 0.93, 95\% CI 0.85 to 1.02; p = 0.107), or progression to aortic stenosis (adjusted OR 0.85, 95\% CI 0.70 to 1.03; p = 0.092).

CONCLUSIONS: In this large population-based cohort, approximately 9\% of subjects with aortic sclerosis progressed to aortic stenosis over a 5-year follow-up period. There was no association between CRP levels and the presence of calcific aortic-valve disease or incident aortic stenosis. C-reactive protein appears to be a poor predictor of subclinical calcific aortic-valve disease.

}, keywords = {Aged, Aged, 80 and over, Aortic Valve, Aortic Valve Stenosis, C-Reactive Protein, Calcinosis, Cardiovascular Diseases, Cohort Studies, Disease Progression, Female, Follow-Up Studies, Heart Valve Diseases, Humans, Male, Risk Factors}, issn = {1558-3597}, doi = {10.1016/j.jacc.2007.07.064}, author = {Novaro, Gian M and Katz, Ronit and Aviles, Ronnier J and Gottdiener, John S and Cushman, Mary and Psaty, Bruce M and Otto, Catherine M and Griffin, Brian P} } @article {972, title = {Relationship of uric acid with progression of kidney disease.}, journal = {Am J Kidney Dis}, volume = {50}, year = {2007}, month = {2007 Aug}, pages = {239-47}, abstract = {

BACKGROUND: Uric acid levels are increased in patients with kidney dysfunction. We tested the hypothesis that uric acid may be associated with kidney disease progression.

STUDY DESIGN: Cohort study.

SETTING \& PARTICIPANTS: 5,808 participants of the Cardiovascular Health Study.

PREDICTOR: Uric acid levels.

OUTCOMES \& MEASUREMENTS: Kidney disease progression was defined as a decrease in estimated glomerular filtration rate (GFR) of 3 mL/min/1.73 m(2) per year or greater (>or=0.05 mL/s) and as incident chronic kidney disease (CKD). Measures of kidney function were estimated GFR using the Modification of Diet in Renal Disease Study equation.

RESULTS: Higher quintiles of uric acid levels were associated with greater prevalences of estimated GFR less than 60 mL/min/1.73 m(2) (<1.00 mL/s) of 7\%, 14\%, 12\%, 25\%, and 42\% for quintiles 1 (6.90 mg/dL [>410 micromol/L]), respectively. In comparison, there was only a modest, but significant, association between quintiles of uric acid levels and progression of kidney function decrease, with adjusted odds ratios of 1.0, 0.88 (95\% confidence interval [CI], 0.64 to 1.21), 1.23 (95\% CI, 0.87 to 1.75), 1.47 (95\% CI, 1.04 to 2.07), and 1.49 (95\% CI, 1.00 to 2.22) for quintiles 1 through 5, respectively. No significant association was found between uric acid level and incident CKD (adjusted odds ratio, 1.00; 95\% CI, 0.89 to 1.14).

LIMITATIONS: Measurements of albuminuria were not available.

CONCLUSIONS: Uric acid levels are associated strongly with prevalent CKD. In comparison, greater uric acid levels had a significant, but much weaker, association with progression of kidney disease.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Cross-Sectional Studies, Disease Progression, Female, Glomerular Filtration Rate, Humans, Kidney Diseases, Male, Prospective Studies, Uric Acid}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2007.05.013}, author = {Chonchol, Michel and Shlipak, Michael G and Katz, Ronit and Sarnak, Mark J and Newman, Anne B and Siscovick, David S and Kestenbaum, Bryan and Carney, Jan Kirk and Fried, Linda F} } @article {1049, title = {Association between lower digit symbol substitution test score and slower gait and greater risk of mortality and of developing incident disability in well-functioning older adults.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Sep}, pages = {1618-25}, abstract = {

OBJECTIVES: To determine whether, in well-functioning older adults, a lower score on the Digit Symbol Substitution Test (DSST) and slower gait are associated with greater risk of mortality and of developing incident disability independent of other risk factors, including brain structural abnormalities (white matter hyperintensities, brain infarcts, ventricular enlargement) and whether the combination of varying levels of DSST score and gait speed are associated with a greater risk of mortality and disability than low DSST or slow gait alone.

DESIGN: Observational cohort study.

SETTING: Community.

PARTICIPANTS: Three thousand one hundred fifty-six (43\% men, 29\% black, mean age 70.4) participants in the Cardiovascular Health Study (CHS), free from stroke and physical disability and with a modified Mini-Mental State Examination (3MS) score of 80 or higher.

MEASUREMENTS: Total mortality and incident disability (self-report of any difficulty performing one or more of the six activities of daily living) ascertained over a median follow-up time of 8.4 years.

RESULTS: By the end of follow-up, 704 participants had died and 1,096 had incident disability. In Cox proportional hazards models adjusted for age, sex, race, education, cardiovascular disease, and brain magnetic resonance imaging abnormalities, lower DSST score and slower gait remained significantly associated with greater risk of mortality and of incident disability. Mortality rates were higher in those who had both low DSST score (<27 points) and slow gait (speed <1.0 m/s) than in those who had only low DSST score, only slow gait, or neither (rates per 1,000 person years (p-y): 61.2, 42.8, 20.8, and 16.3, respectively). A similar risk gradient was observed for incident disability (82.0, 57.9, 47.9, and 36.0/1,000 p-y, respectively).

CONCLUSION: In well-functioning older adults, low DSST score and slow gait, alone or in combination, could be risk factors for mortality and for developing disability, independent of other risk factors, including measures of brain integrity.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Analysis of Variance, Atrophy, Brain, Brain Diseases, Cause of Death, Cohort Studies, Disability Evaluation, Discrimination Learning, Female, Gait, Humans, Male, Memory, Short-Term, Mobility Limitation, Neuropsychological Tests, Pattern Recognition, Visual, Psychometrics, Psychomotor Performance, Risk Factors}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2008.01856.x}, author = {Rosano, Caterina and Newman, Anne B and Katz, Ronit and Hirsch, Calvin H and Kuller, Lewis H} } @article {1012, title = {Cystatin C concentration as a predictor of systolic and diastolic heart failure.}, journal = {J Card Fail}, volume = {14}, year = {2008}, month = {2008 Feb}, pages = {19-26}, abstract = {

BACKGROUND: Risk factors for heart failure (HF) may differ according to ejection fraction (EF). Higher cystatin C, a marker of kidney dysfunction, is associated with incident HF, but previous studies did not determine EF at diagnosis. We hypothesized that kidney dysfunction would predict diastolic HF (DHF) better than systolic HF (SHF) in the Cardiovascular Health Study.

METHODS AND RESULTS: Cystatin C was measured in 4453 participants without HF at baseline. Incident HF was categorized as DHF (EF > or = 50\%) or SHF (EF < 50\%). We compared the association of cystatin C with the risk for DHF and SHF, after adjustment for age, sex, race, medications, and HF risk factors. During 8 years of follow-up, 167 participants developed DHF and 206 participants developed SHF. After adjustment, sequentially higher quartiles of cystatin C were associated with risk for SHF (competing risks hazard ratios 1.0 [reference], 1.99 [95\% confidence interval 1.14-3.48], 2.32 [1.32-4.07], 3.17 [1.82-5.50], P for trend < .001). The risk for DHF was apparent only at the highest cystatin C quartile (hazard ratios 1.0 [reference], 1.09 [0.62-1.89], 1.08 [0.61-1.93], and 1.83 [1.07-3.11]).

CONCLUSIONS: Cystatin C levels are linearly associated with the incidence of systolic HF, whereas only the highest concentrations of cystatin C predict diastolic HF.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Cohort Studies, Confidence Intervals, Cystatin C, Cystatins, Echocardiography, Female, Heart Failure, Diastolic, Heart Failure, Systolic, Humans, Longitudinal Studies, Male, Predictive Value of Tests, Probability, Proportional Hazards Models, Risk Assessment, Sensitivity and Specificity, Stroke Volume, Survival Analysis}, issn = {1532-8414}, doi = {10.1016/j.cardfail.2007.09.002}, author = {Moran, Andrew and Katz, Ronit and Smith, Nicolas L and Fried, Linda F and Sarnak, Mark J and Seliger, Stephen L and Psaty, Bruce and Siscovick, David S and Gottdiener, John S and Shlipak, Michael G} } @article {1130, title = {Association of chronic kidney disease with the spectrum of ankle brachial index the CHS (Cardiovascular Health Study).}, journal = {J Am Coll Cardiol}, volume = {54}, year = {2009}, month = {2009 Sep 22}, pages = {1176-84}, abstract = {

OBJECTIVES: This study sought to determine the association of chronic kidney disease (CKD) with high ankle brachial index (ABI) measurement and to compare its strength with that of CKD with a low ABI.

BACKGROUND: CKD is an important risk factor for cardiovascular disease (CVD) events. A high ABI, a marker of lower extremity arterial stiffness, is associated with CVD events and mortality. The association between CKD and high ABI is unknown.

METHODS: The CHS (Cardiovascular Health Study) enrolled community-living people >65 years of age and measured kidney function and ABI. Glomerular filtration rate (GFR) was estimated using equations that incorporated either cystatin C or creatinine, and CKD was defined by estimated GFR <60 ml/min/1.73 m(2). The ABI was categorized as low (<0.90), low-normal (0.90 to 1.09), normal (1.10 to 1.40), and high (>1.40 or incompressible). Multinomial logistic regression was used to evaluate the associations of CKD with ABI categories.

RESULTS: Among 4,513 participants, 23\% had CKD, 13\% had a low ABI, and 3\% had a high ABI. In models adjusted for age, sex, race, hypertension, diabetes, smoking, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and C-reactive protein, cystatin C-based CKD was associated with both low ABI (relative risk [RR]: 2.0; 95\% confidence interval [CI]: 1.6 to 2.5; p <0.001) and high ABI (RR: 1.6; 95\% CI: 1.0 to 2.3; p = 0.03). Results were similar when CKD was defined by creatinine.

CONCLUSIONS: CKD is associated with both the high and the low extremes of ABI in community-living older people. Future studies should evaluate whether arterial stiffness is an important mechanism leading to CVD in people with CKD.

}, keywords = {Aged, Aged, 80 and over, Ankle Brachial Index, C-Reactive Protein, Cardiovascular Diseases, Chronic Disease, Cohort Studies, Cross-Sectional Studies, Female, Glomerular Filtration Rate, Humans, Kidney Diseases, Lipids, Male, Risk Factors}, issn = {1558-3597}, doi = {10.1016/j.jacc.2009.06.017}, author = {Ix, Joachim H and Katz, Ronit and de Boer, Ian H and Kestenbaum, Brian R and Allison, Matthew A and Siscovick, David S and Newman, Anne B and Sarnak, Mark J and Shlipak, Michael G and Criqui, Michael H} } @article {1056, title = {Association of renal function with cardiac calcifications in older adults: the cardiovascular health study.}, journal = {Nephrol Dial Transplant}, volume = {24}, year = {2009}, month = {2009 Mar}, pages = {834-40}, abstract = {

BACKGROUND: Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are highly prevalent in patients with end-stage renal disease. It is less well established whether milder kidney disease is associated with cardiac calcifications. We evaluated the relationships between renal function and MAC, aortic annular calcification (AAC) and AVS in the elderly.

METHODS: From the Cardiovascular Health Study, a community-based cohort of ambulatory adults >or= age 65, a total of 3929 individuals (mean +/- SD age 74 +/- 5 years, 60\% women) were evaluated with two-dimensional echocardiography. Renal function was assessed by means of creatinine-based estimated glomerular filtration rate (eGFR) and cystatin C.

RESULTS: The prevalences of MAC and AAC were significantly higher in individuals with an eGFR < 45 mL/ min/1.73 m(2) (P < 0.01 for each), and cystatin C levels were significantly higher in individuals with MAC or AAC compared to individuals without these cardiac calcifications (P < 0.001 for each). After multivariate-adjustment, an eGFR <45 mL/min/1.73 m(2) was significantly associated with MAC [odds ratio 1.54 (95\% CI 1.16-2.06), P = 0.003] and not associated with AAC [1.30 (0.97-1.74), P = 0.085] and AVS [1.15 (0.86-1.53), P = 0.355]. In addition, cystatin C levels were independently associated with MAC [odds ratio per SD 1.12 (1.05-1.21), P = 0.001] and not associated with AAC [1.07 (1.00-1.15), P = 0.054] and AVS [0.99 (0.93-1.06), P = 0.82]. Furthermore, the prevalence of multiple cardiac calcifications was higher in subjects with an eGFR < 45 mL/ min/1.73 m(2) and increased per quartile of cystatin C (P-values < 0.001). In addition, a significant trend was observed between an eGFR < 45 mL/min/1.73 m(2), increasing levels of cystatin C and the number of cardiac calcifications (P < 0.05).

CONCLUSIONS: In a community-based cohort of the elderly, moderate kidney disease as defined by an eGFR <45 mL/min/1.73m(2) and elevated levels of cystatin C was associated with prevalent MAC. In addition, a significant trend was observed between an eGFR <45 mL/min/1.73m(2), increasing levels of cystatin C and the number of cardiac calcifications. No associations were found between renal function and AAC or AVS.

}, keywords = {Aged, Aortic Valve, Calcinosis, Case-Control Studies, Cohort Studies, Creatinine, Cystatin C, Female, Glomerular Filtration Rate, Heart Valve Diseases, Humans, Kidney Diseases, Male, Mitral Valve, Risk Factors}, issn = {1460-2385}, doi = {10.1093/ndt/gfn544}, author = {Asselbergs, Folkert W and Mozaffarian, Dariush and Katz, Ronit and Kestenbaum, Bryan and Fried, Linda F and Gottdiener, John S and Shlipak, Michael G and Siscovick, David S} } @article {1099, title = {Multiple loci associated with indices of renal function and chronic kidney disease.}, journal = {Nat Genet}, volume = {41}, year = {2009}, month = {2009 Jun}, pages = {712-7}, abstract = {

Chronic kidney disease (CKD) has a heritable component and is an important global public health problem because of its high prevalence and morbidity. We conducted genome-wide association studies (GWAS) to identify susceptibility loci for glomerular filtration rate, estimated by serum creatinine (eGFRcrea) and cystatin C (eGFRcys), and CKD (eGFRcrea < 60 ml/min/1.73 m(2)) in European-ancestry participants of four population-based cohorts (ARIC, CHS, FHS, RS; n = 19,877; 2,388 CKD cases), and tested for replication in 21,466 participants (1,932 CKD cases). We identified significant SNP associations (P < 5 {\texttimes} 10(-8)) with CKD at the UMOD locus, with eGFRcrea at UMOD, SHROOM3 and GATM-SPATA5L1, and with eGFRcys at CST and STC1. UMOD encodes the most common protein in human urine, Tamm-Horsfall protein, and rare mutations in UMOD cause mendelian forms of kidney disease. Our findings provide new insights into CKD pathogenesis and underscore the importance of common genetic variants influencing renal function and disease.

}, keywords = {Chromosome Mapping, Cohort Studies, Genetic Variation, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Kidney, Kidney Failure, Chronic, Meta-Analysis as Topic, Mucoproteins, Netherlands, Polymorphism, Single Nucleotide, Prevalence, Uromodulin}, issn = {1546-1718}, doi = {10.1038/ng.377}, author = {K{\"o}ttgen, Anna and Glazer, Nicole L and Dehghan, Abbas and Hwang, Shih-Jen and Katz, Ronit and Li, Man and Yang, Qiong and Gudnason, Vilmundur and Launer, Lenore J and Harris, Tamara B and Smith, Albert V and Arking, Dan E and Astor, Brad C and Boerwinkle, Eric and Ehret, Georg B and Ruczinski, Ingo and Scharpf, Robert B and Chen, Yii-Der Ida and de Boer, Ian H and Haritunians, Talin and Lumley, Thomas and Sarnak, Mark and Siscovick, David and Benjamin, Emelia J and Levy, Daniel and Upadhyay, Ashish and Aulchenko, Yurii S and Hofman, Albert and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and van Duijn, Cornelia M and Chasman, Daniel I and Par{\'e}, Guillaume and Ridker, Paul M and Kao, W H Linda and Witteman, Jacqueline C and Coresh, Josef and Shlipak, Michael G and Fox, Caroline S} } @article {1131, title = {Obesity and change in estimated GFR among older adults.}, journal = {Am J Kidney Dis}, volume = {54}, year = {2009}, month = {2009 Dec}, pages = {1043-51}, abstract = {

BACKGROUND: The prevalence of chronic kidney disease is growing most rapidly among older adults; however, determinants of impaired kidney function in this population are not well understood. Obesity assessed in midlife has been associated with chronic kidney disease.

STUDY DESIGN: Cohort study.

SETTING \& PARTICIPANTS: 4,295 participants in the community-based Cardiovascular Health Study, aged >or= 65 years.

PREDICTORS: Body mass index, waist circumference, and fat mass measured using bioelectrical impedance.

OUTCOME: Change in glomerular filtration rate (GFR) during 7 years of follow-up.

MEASUREMENTS: Longitudinal estimates of GFR calculated using the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation.

RESULTS: Estimated GFR decreased by an average of 0.4 +/- 3.6 mL/min/1.73 m(2)/y, and rapid GFR loss (>3 mL/min/1.73 m(2)/y) occurred in 693 participants (16\%). Baseline body mass index, waist circumference, and fat mass were each associated with increased risk of rapid GFR loss: ORs, 1.19 (95\% CI, 1.09-1.30) per 5 kg/m(2), 1.25 (95\% CI, 1.16-1.36) per 12 cm, and 1.14 (95\% CI, 1.05-1.24) per 10 kg after adjustment for age, sex, race, and smoking. The magnitude of increased risk was larger for participants with estimated GFR < 60 mL/min/1.73 m(2) at baseline (P for interaction < 0.05). Associations were substantially attenuated by further adjustment for diabetes, hypertension, and C-reactive protein level. Obesity measurements were not associated with change in GFR estimated using serum cystatin C level.

LIMITATIONS: Few participants with advanced chronic kidney disease at baseline, no direct GFR measurements.

CONCLUSION: Obesity may be a modifiable risk factor for the development and progression of kidney disease in older adults.

}, keywords = {Aged, Aging, Body Composition, Body Mass Index, Chronic Disease, Cohort Studies, Creatinine, Cystatin C, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Longitudinal Studies, Male, Obesity, Risk Factors}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2009.07.018}, author = {de Boer, Ian H and Katz, Ronit and Fried, Linda F and Ix, Joachim H and Luchsinger, Jose and Sarnak, Mark J and Shlipak, Michael G and Siscovick, David S and Kestenbaum, Bryan} } @article {1090, title = {Race, gender, and mortality in adults > or =65 years of age with incident heart failure (from the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {103}, year = {2009}, month = {2009 Apr 15}, pages = {1120-7}, abstract = {

In patients with heart failure (HF), mortality is lower in women versus men. However, it is unknown whether the survival advantage in women compared with men is present in both whites and African Americans with HF. The inception cohort consisted of adults > or =65 years with incident HF after enrollment in the CHS, a prospective population-based study of cardiovascular disease. Of 5,888 CHS subjects, 1,264 developed new HF and were followed up for 3 years. Subjects were categorized into 4 race-gender groups, and Cox proportional hazard regression models were used to examine whether 3-year total and cardiovascular mortality differed among the 4 groups after adjusting for sociodemographic factors, co-morbidities, and treatment. A gender-race interaction was also tested for each outcome. In subjects with incident HF, African Americans had more hypertension and diabetes than whites, and white men had more coronary heart disease than other gender-race groups. Receipt of cardiovascular treatments among the 4 groups was similar. Mortality rates after HF were lower in women compared with men (for white women, African-American women, African-American men, and white men, total mortality was 35.5, 33.6, 44.4, and 40.5/100 person-years, and cardiovascular mortality was 18.4, 19.5, 20.2, and 22.7/100 person-years, respectively). After adjusting for covariates, women had a 15\% to 20\% lower risk of total and cardiovascular mortality compared with men, but there was no significant difference in outcome by race. The gender-race interaction for either outcome was not significant. In conclusion, in older adults with HF, women had significantly better survival than men irrespective of race, suggesting that gender-based survival differences may be more important than race-based differences.

}, keywords = {African Americans, Age Factors, Aged, Aged, 80 and over, Cohort Studies, Continental Population Groups, European Continental Ancestry Group, Female, Heart Failure, Humans, Incidence, Male, Proportional Hazards Models, Sex Factors, United States}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2008.12.043}, author = {Parashar, Susmita and Katz, Ronit and Smith, Nicholas L and Arnold, Alice M and Vaccarino, Viola and Wenger, Nanette K and Gottdiener, John S} } @article {1186, title = {Alcohol consumption and kidney function decline in the elderly: alcohol and kidney disease.}, journal = {Nephrol Dial Transplant}, volume = {25}, year = {2010}, month = {2010 Oct}, pages = {3301-7}, abstract = {

BACKGROUND: Alcohol consumption appears to be protective for cardiovascular disease; however, its relationship with kidney disease is unclear.

METHODS: This prospective cohort study included 4343 subjects from the Cardiovascular Health Study, a longitudinal, community-based cohort of persons aged >=65 from four US communities. We used previously defined categories based on weekly alcohol consumption: none, former, <1 drink, 1-6 drinks, 7-13 drinks and >=14 drinks. Cystatin C was measured at baseline, year 3 and year 7; eligible subjects had at least two measures. Estimated GFR(cys) was calculated from cystatin C. The primary outcome was rapid kidney function as an annual estimated GFR (eGFR(cys)) loss >3 mL/min/1.73 m(2)/year.

RESULTS: Eight percent of the cohort reported former alcohol use and 52\% reported current alcohol consumption. During a mean follow-up of 5.6 years, 1075 (25\%) participants had rapid kidney function decline. In adjusted logistic regression models, there was no association between alcohol use and kidney function decline (odds ratio, 95\% confidence interval: none = reference; former = 1.18, 0.89-1.56; <1 drink = 1.20, 0.99-1.47; 1-6 = 1.18, 0.95-1.45; 7-13 = 1.10, 0.80-1.53; >14 = 0.89, 0.61-1.13). Results were similar with kidney function decline as a continuous outcome.

CONCLUSIONS: Our results suggest that moderate alcohol consumption has neither adverse nor beneficial effects on kidney function. Although clinicians will need to consider the potential deleterious effects associated with alcohol consumption, there does not appear to be a basis for recommending that older adults discontinue or initiate light to moderate alcohol consumption to protect against kidney disease.

}, keywords = {Aged, Aging, Alcohol Drinking, Cohort Studies, Cystatin C, Female, Glomerular Filtration Rate, Humans, Kidney, Kidney Diseases, Male, Prospective Studies}, issn = {1460-2385}, doi = {10.1093/ndt/gfq188}, author = {Menon, Vandana and Katz, Ronit and Mukamal, Kenneth and Kestenbaum, Bryan and de Boer, Ian H and Siscovick, David S and Sarnak, Mark J and Shlipak, Michael G} } @article {1190, title = {Association between baseline kidney function and change in CRP: an analysis of the cardiovascular health study.}, journal = {Nephron Clin Pract}, volume = {115}, year = {2010}, month = {2010}, pages = {c114-21}, abstract = {

BACKGROUND: In cross-sectional analyses, C-reactive protein (CRP) levels are inversely related to levels of kidney function. The relationship between kidney function and subsequent changes in CRP is unknown.

METHODS: We studied 4,364 individuals from the Cardiovascular Health Study, a longitudinal cohort of community-dwelling older adults. Baseline eGFRcys was estimated using cystatin C. CRP was measured at baseline and after 3 and 7 years of follow-up; slopes of change in CRP were calculated.

RESULTS: The mean (SD) age of the cohort was 72 (5.2) years; mean (SD) eGFRcys was 78.9 (18.4) ml/min/1.73 m(2). The median (interquartile range IQR) baseline CRP was 2.39 (1.22, 4.33) mg/l; the median (IQR) yearly change in CRP was -0.0051 (-0.020 to 0.27) mg/l/year. After adjustment for demographic characteristics and the initial level of CRP, each standard deviation lower baseline eGFR was associated with a small and non-significant yearly increase in CRP (0.032 mg/l/year; 95\% CI: -0.005 to 0.070, p = 0.094).

CONCLUSIONS: We did not find a relationship between eGFR and subsequent changes in CRP. The association between kidney function and CRP in cross-sectional analyses may reflect unmeasured confounding by atherosclerosis; alternatively, the burden of comorbidity and interval mortality in this population may have masked a stronger longitudinal association between kidney function and change in CRP. Further study in younger populations may clarify whether impaired kidney function leads to change in inflammation over time.

}, keywords = {Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Cohort Studies, Cross-Sectional Studies, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Function Tests, Longitudinal Studies, Male, Residence Characteristics}, issn = {1660-2110}, doi = {10.1159/000312874}, author = {Rifkin, Dena E and Katz, Ronit and Fried, Linda F and Kestenbaum, Bryan and Jenny, Nancy Swords and Newman, Anne B and Siscovick, David S and Shlipak, Michael G and Sarnak, Mark J} } @article {1166, title = {Impaired kidney function and atrial fibrillation in elderly subjects.}, journal = {J Card Fail}, volume = {16}, year = {2010}, month = {2010 Jan}, pages = {55-60}, abstract = {

BACKGROUND: Impaired kidney function is associated with increased risk for cardiovascular events. We evaluated whether kidney function is associated with atrial fibrillation (AF) risk in elderly persons.

METHODS AND RESULTS: Subjects were participants in the Cardiovascular Health Study (CHS), a population-based cohort of ambulatory elderly. Measures of kidney function were cystatin C and creatinine-based estimated glomerular filtration rate (eGFR). Among the 4663 participants, 342 (7\%) had AF at baseline and 579 (13\%) developed incident AF during follow-up (mean 7.4 years). In unadjusted analyses, cystatin C quartiles were strongly associated with prevalent AF with a nearly 3-fold odds in the highest quartile compared with the lowest (HR=1.19, 95\% CI [0.80-1.76] in quartile 2; HR=2.00, 95\% CI [1.38-2.88] in quartile 3; and HR=2.87, 95\% CI [2.03-4.07] in quartile 4). This increased risk for prevalent AF remained significant after multivariate adjustment. The risk for incident AF increased across cystatin C quartiles in the unadjusted analysis (HR=1.37, 95\% CI [1.07-1.75] in quartile 2; HR=1.43, 95\% CI [1.11-1.84] in quartile 3; and HR=1.88, 95\% CI [1.47-2.41] in quartile 4); however, after multivariate adjustment, these findings were no longer significant. An estimated GFR <60 mL.min.1.73m(2) was associated with prevalent and incident AF in unadjusted, but not multivariate analyses.

CONCLUSIONS: Impaired kidney function, as measured by cystatin C, is an independent marker of prevalent AF; however, neither cystatin C nor eGFR are predictors of incident AF.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Atrial Fibrillation, Cohort Studies, Cross-Sectional Studies, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Diseases, Kidney Function Tests, Male}, issn = {1532-8414}, doi = {10.1016/j.cardfail.2009.07.002}, author = {Deo, Rajat and Katz, Ronit and Kestenbaum, Bryan and Fried, Linda and Sarnak, Mark J and Psaty, Bruce M and Siscovick, David S and Shlipak, Michael G} } @article {1127, title = {Inflammatory biomarkers and decline in kidney function in the elderly: the Cardiovascular Health Study.}, journal = {Nephrol Dial Transplant}, volume = {25}, year = {2010}, month = {2010 Jan}, pages = {119-24}, abstract = {

BACKGROUND: Cross-sectional studies have demonstrated a consistent and linear association between circulating inflammatory markers and kidney function. The objective of this study was to determine whether elevated markers of inflammation are independently associated with longitudinal kidney function decline.

METHODS: This study included 4128 subjects from the Cardiovascular Health Study. Cystatin C was measured at baseline, 3 years later and 7 years later; eligible subjects had at least two measures. Cystatin C-based estimated glomerular filtration rate (eGFR(cysC)) was estimated, and rapid kidney function decline was defined as an annual loss of eGFR(cysC) >3 mL/min/1.73 m(2). Predictors included ten inflammatory and procoagulant biomarkers: C-reactive protein, interleukin-6, intercellular adhesion molecule-1, white blood cell count, fibrinogen, factor VII, factor VIII, D-dimer, plasmin-antiplasmin complex and serum albumin.

RESULTS: During the study, 1059 subjects (26\%) had a rapid decline in kidney function. In contrast to the other nine inflammatory or procoagulant biomarkers, serum albumin had a consistent and inverse association with rapid kidney function decline [final adjusted logistic regression model: 1.14-fold increased odds (95\% CI 1.06-1.23) of rapid decline per standard deviation lower albumin]. The lowest quartile of albumin had an odds ratio of 1.55 (95\% CI 1.23-1.96) for rapid decline compared with the highest quartile. These associations persisted after adjusting the albumin models for CRP, IL-6 and fibrinogen.

CONCLUSIONS: In contrast to nine other inflammatory and procoagulant markers, only lower baseline levels of serum albumin were consistently associated with a rapid decline in kidney function, as measured by cystatin C-based eGFR.

}, keywords = {Aged, Biomarkers, C-Reactive Protein, Cohort Studies, Cystatin C, Female, Glomerular Filtration Rate, Humans, Inflammation, Intercellular Adhesion Molecule-1, Interleukin-6, Kidney, Logistic Models, Longitudinal Studies, Male, Prospective Studies, Serum Albumin}, issn = {1460-2385}, doi = {10.1093/ndt/gfp429}, author = {Keller, Christopher and Katz, Ronit and Sarnak, Mark J and Fried, Linda F and Kestenbaum, Bryan and Cushman, Mary and Shlipak, Michael G} } @article {1230, title = {Chronic kidney disease and the risk of end-stage renal disease versus death.}, journal = {J Gen Intern Med}, volume = {26}, year = {2011}, month = {2011 Apr}, pages = {379-85}, abstract = {

BACKGROUND: Among older adults with chronic kidney disease (CKD), the comparative event rates of end-stage renal disease (ESRD) and cause-specific death are unknown.

OBJECTIVE: To compare the rates of ESRD, cardiovascular and non-cardiovascular death and examine risk factors for ESRD and all-cause mortality in Cardiovascular Health Study (CHS) participants.

DESIGN: The CHS is a longitudinal cohort study of community-dwelling adults aged 65 years and older.

PARTICIPANTS: 1,268 participants with an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m(2) were followed until the time of first event (ESRD, cardiovascular or non-cardiovascular death) or until March 31, 2003.

MAIN MEASURES: The outcomes were ESRD, cardiovascular- and non-cardiovascular death. Rates of each event were calculated, and a Cox Proportional Hazards Model with a competing risk framework was used to examine risk factors for ESRD as compared with death. Predictors included age, gender, race, BMI, hypertension, diabetes, cardiovascular disease, heart failure, tobacco use, eGFR, and total cholesterol.

KEY RESULTS: During 9.7 years of follow-up, 5\% of the cohort progressed to ESRD, and 61\% of the cohort died. The rate (per 100 person-years) was 0.5 for ESRD and 6.8 for all-cause mortality (3.0 for cardiovascular and 3.8 for non-cardiovascular mortality). In the competing risk framework, lower eGFR, male gender, African-American race, and higher BMI were associated with an increased risk of ESRD.

CONCLUSIONS: Older adults with CKD are 13-fold more likely to die from any cause than progress to ESRD and are 6-fold more likely to die from cardiovascular causes than develop ESRD.

}, keywords = {Aged, Aged, 80 and over, Cause of Death, Cohort Studies, Female, Follow-Up Studies, Humans, Kidney Failure, Chronic, Longitudinal Studies, Male, Prospective Studies, Renal Insufficiency, Chronic, Risk Factors, Treatment Outcome}, issn = {1525-1497}, doi = {10.1007/s11606-010-1511-x}, author = {Dalrymple, Lorien S and Katz, Ronit and Kestenbaum, Bryan and Shlipak, Michael G and Sarnak, Mark J and Stehman-Breen, Catherine and Seliger, Stephen and Siscovick, David and Newman, Anne B and Fried, Linda} } @article {1277, title = {Longitudinal association of depressive symptoms with rapid kidney function decline and adverse clinical renal disease outcomes.}, journal = {Clin J Am Soc Nephrol}, volume = {6}, year = {2011}, month = {2011 Apr}, pages = {834-44}, abstract = {

BACKGROUND AND OBJECTIVES: Depression is a risk indicator for adverse outcomes in dialysis patients, but its prognostic impact in individuals who are not yet on dialysis is unknown. This study examines whether depressive symptoms are longitudinally associated with renal function decline, new-onset chronic kidney disease (CKD), ESRD, or hospitalization with acute kidney injury (AKI).

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: Depressive symptoms were measured in a longitudinal cohort study with the 10-item Centers for Epidemiologic Studies Depression scale using a previously validated cut-off value (>=8). CKD at study entry and during follow-up was defined as an estimated GFR (eGFR) < 60 ml/min per m(2). Outcomes were rapid decline in eGFR (>3 ml/min per m(2) per year), new-onset CKD, ESRD (U.S. Renal Data System-based), and AKI (based on adjudicated medical record review). The median follow-up duration was 10.5 years.

RESULTS: Depressed participants (21.2\%) showed a higher prevalence of CKD at baseline compared with nondepressed participants in multivariable analysis. Depression was associated with a subsequent risk of rapid decline in eGFR, incident ESRD, and AKI, but not incident CKD in unadjusted models. In multivariable analyses, only associations of depressive symptoms with AKI remained significant.

CONCLUSIONS: Elevated depressive symptoms are associated with subsequent adverse renal disease outcomes. The depression-related elevated risk of AKI was independent of traditional renal disease risk factors and may in part be explained by the predictive value of depression for acute coronary syndromes and heart failure hospitalizations that can be complicated by AKI.

}, keywords = {Acute Kidney Injury, Aged, Chronic Disease, Cohort Studies, Comorbidity, Depression, Female, Follow-Up Studies, Glomerular Filtration Rate, Humans, Kidney Diseases, Longitudinal Studies, Male}, issn = {1555-905X}, doi = {10.2215/CJN.03840510}, author = {Kop, Willem J and Seliger, Stephen L and Fink, Jeffrey C and Katz, Ronit and Odden, Michelle C and Fried, Linda F and Rifkin, Dena E and Sarnak, Mark J and Gottdiener, John S} } @article {1329, title = {Vitamin D, parathyroid hormone, and cardiovascular events among older adults.}, journal = {J Am Coll Cardiol}, volume = {58}, year = {2011}, month = {2011 Sep 27}, pages = {1433-41}, abstract = {

OBJECTIVES: The aim of this study was to evaluate associations of 25-hydroxyvitamin D (25-OHD) and parathyroid hormone (PTH) concentrations separately and in combination with incident cardiovascular events and mortality during 14 years of follow-up in the CHS (Cardiovascular Health Study).

BACKGROUND: Vitamin D deficiency and PTH excess are common in older adults and may adversely affect cardiovascular health.

METHODS: A total of 2,312 participants who were free of cardiovascular disease at baseline were studied. Vitamin D and intact PTH were measured from previously frozen serum using mass spectrometry and a 2-site immunoassay. Outcomes were adjudicated cases of myocardial infarction, heart failure, cardiovascular death, and all-cause mortality.

RESULTS: There were 384 participants (17\%) with serum 25-OHD concentrations <15 ng/ml and 570 (25\%) with serum PTH concentrations >= 65 pg/ml. After adjustment, each 10 ng/ml lower 25-OHD concentration was associated with a 9\% greater (95\% confidence interval [CI]: 2\% to 17\% greater) relative hazard of mortality and a 25\% greater (95\% CI: 8\% to 44\% greater) relative hazard of myocardial infarction. Serum 25-OHD concentrations <15 ng/ml were associated with a 29\% greater (95\% CI: 5\% to 55\% greater) risk for mortality. Serum PTH concentrations >= 65 pg/ml were associated with a 30\% greater risk for heart failure (95\% CI: 6\% to 61\% greater) but not other outcomes. There was no evidence of an interaction between serum 25-OHD and PTH concentrations and cardiovascular events.

CONCLUSIONS: Among older adults, 25-OHD deficiency is associated with myocardial infarction and mortality; PTH excess is associated with heart failure. Vitamin D and PTH might influence cardiovascular risk through divergent pathways.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Cohort Studies, Female, Follow-Up Studies, Humans, Male, Parathyroid Hormone, Prospective Studies, Vitamin D}, issn = {1558-3597}, doi = {10.1016/j.jacc.2011.03.069}, author = {Kestenbaum, Bryan and Katz, Ronit and de Boer, Ian and Hoofnagle, Andy and Sarnak, Mark J and Shlipak, Michael G and Jenny, Nancy S and Siscovick, David S} } @article {1372, title = {Insulin resistance, cystatin C, and mortality among older adults.}, journal = {Diabetes Care}, volume = {35}, year = {2012}, month = {2012 Jun}, pages = {1355-60}, abstract = {

OBJECTIVE: Insulin resistance is a risk factor for cardiovascular and noncardiovascular diseases. Impaired kidney function is linked with insulin resistance and may affect relationships of insulin resistance with health outcomes.

RESEARCH DESIGN AND METHODS: We performed a cohort study of 3,138 Cardiovascular Health Study participants (age >= 65 years) without diabetes. Insulin sensitivity index (ISI) was calculated from fasting and 2-h postload insulin and glucose concentrations. Associations of ISI and fasting insulin concentration with all-cause mortality were tested using Cox proportional hazards models, adjusting for demographic variables, prevalent cardiovascular disease, lifestyle variables, waist circumference, and LDL cholesterol. Subsequent models were additionally adjusted for or stratified by glomerular filtration rate estimated using serum cystatin C (eGFR).

RESULTS: A total of 1,810 participants died during the 14.7-year median follow-up. Compared with the highest quartile of ISI, the lowest quartile (most insulin resistant) was associated with 21\% (95\% CI 6-41) and 11\% (-3 to 29) higher risks of death without and with adjustment for eGFR, respectively. Compared with the lowest quartile of fasting insulin concentration, the highest quartile was associated with 22\% (4-43) and 4\% (-12 to 22) higher risks of death without and with adjustment for eGFR, respectively. Similar attenuation by eGFR was observed when blood pressure, triglycerides, HDL cholesterol, and C-reactive protein were included in models.

CONCLUSIONS: Insulin resistance measured as ISI or fasting insulin concentration is associated with increased risk of death among older adults, adjusting for conventional confounding characteristics. Impaired kidney function may mediate or confound this relationship.

}, keywords = {Aged, Aged, 80 and over, Blood Glucose, Blood Pressure, C-Reactive Protein, Cardiovascular Diseases, Cholesterol, HDL, Cholesterol, LDL, Cohort Studies, Cystatin C, Fasting, Female, Glomerular Filtration Rate, Humans, Insulin Resistance, Life Style, Male, Mortality, Predictive Value of Tests, Proportional Hazards Models, Renal Insufficiency, Risk Factors, Triglycerides, Waist Circumference}, issn = {1935-5548}, doi = {10.2337/dc11-1657}, author = {de Boer, Ian H and Katz, Ronit and Chonchol, Michel B and Fried, Linda F and Ix, Joachim H and Kestenbaum, Bryan and Mukamal, Kenneth J and Peralta, Carmen A and Siscovick, David S} } @article {1322, title = {The risk of infection-related hospitalization with decreased kidney function.}, journal = {Am J Kidney Dis}, volume = {59}, year = {2012}, month = {2012 Mar}, pages = {356-63}, abstract = {

BACKGROUND: Moderate kidney disease may predispose to infection. We sought to determine whether decreased kidney function, estimated by serum cystatin C level, was associated with the risk of infection-related hospitalization in older individuals.

STUDY DESIGN: Cohort study.

SETTING \& PARTICIPANTS: 5,142 Cardiovascular Health Study (CHS) participants with measured serum creatinine and cystatin C and without estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m(2) at enrollment.

PREDICTOR: The primary exposure of interest was eGFR using serum cystatin C level (eGFR(SCysC)).

OUTCOME: Infection-related hospitalizations during a median follow-up of 11.5 years.

RESULTS: In adjusted analyses, eGFR(SCysC) categories of 60-89, 45-59, and 15-44 mL/min/1.73 m(2) were associated with 16\%, 37\%, and 64\% greater risk of all-cause infection-related hospitalization, respectively, compared with eGFR(SCysC) >=90 mL/min/1.73 m(2). When cause-specific infection was examined, eGFR(SCysC) of 15-44 mL/min/1.73 m(2) was associated with an 80\% greater risk of pulmonary and 160\% greater risk of genitourinary infection compared with eGFR(SCysC) >=90 mL/min/1.73 m(2).

LIMITATIONS: No measures of urinary protein, study limited to principal discharge diagnosis.

CONCLUSIONS: Lower kidney function, estimated using cystatin C level, was associated with a linear and graded risk of infection-related hospitalization. These findings highlight that even moderate degrees of decreased kidney function are associated with clinically significant higher risks of serious infection in older individuals.

}, keywords = {Aged, Cohort Studies, Female, Glomerular Filtration Rate, Hospitalization, Humans, Infection, Kidney, Male, Risk Factors}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2011.07.012}, author = {Dalrymple, Lorien S and Katz, Ronit and Kestenbaum, Bryan and de Boer, Ian H and Fried, Linda and Sarnak, Mark J and Shlipak, Michael G} } @article {5999, title = {Blood pressure components and decline in kidney function in community-living older adults: the Cardiovascular Health Study.}, journal = {Am J Hypertens}, volume = {26}, year = {2013}, month = {2013 Aug}, pages = {1037-44}, abstract = {

BACKGROUND: Although hypertension contributes to kidney dysfunction in the general population, the contributions of elevated systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) to kidney function decline in community-dwelling older adults are unknown.

METHODS: We used linear and logistic regression to examine the separate and combined associations of SBP, DBP, and PP at baseline with kidney function decline among 4,365 older adults in the Cardiovascular Health Study. We used cystatin C to estimate glomerular filtration rate on 3 occasions over 7 years of follow-up. We defined rapid decline >= 3ml/min/year.

RESULTS: Average age was 72.2 and mean (standard deviation) SBP, DBP, and PP were 135 (21), 71 (11), and 65 (18) mm Hg, respectively. SBP and PP, rather than DBP, were most significantly associated with kidney function decline. In adjusted linear models, each 10-mm Hg increment in SBP and PP was associated with 0.13ml/min/year (-0.19, -0.08, P < 0.001) and 0.15-ml/min/year faster decline (-0.21, -0.09, P < 0.001), respectively. Each 10-mm Hg increment in DBP was associated with a nonsignificant 0.10-ml/min/year faster decline (95\% confidence interval, -0.20, 0.01). In adjusted logistic models, SBP had the strongest associations with rapid decline, with 14\% increased hazard of rapid decline (95\% confidence interval, 10\% to 17\%, P < 0.01) per 10mm Hg. In models combining BP components, only SBP consistently had independent associations with rapid decline.

CONCLUSIONS: Our findings suggest that elevated BP, particularly SBP, contributes to declining kidney function in older adults.

}, keywords = {Aged, Blood Pressure, Cohort Studies, Cystatin C, Diastole, Disease Progression, Female, Glomerular Filtration Rate, Humans, Hypertension, Logistic Models, Longitudinal Studies, Male, Pulse, Renal Insufficiency, Chronic, Systole}, issn = {1941-7225}, doi = {10.1093/ajh/hpt067}, author = {Rifkin, Dena E and Katz, Ronit and Chonchol, Michel and Shlipak, Michael G and Sarnak, Mark J and Fried, Linda F and Newman, Anne B and Siscovick, David S and Peralta, Carmen A} } @article {5854, title = {Hypertension and low HDL cholesterol were associated with reduced kidney function across the age spectrum: a collaborative study.}, journal = {Ann Epidemiol}, volume = {23}, year = {2013}, month = {2013 Mar}, pages = {106-11}, abstract = {

PURPOSE: To determine if the associations among established risk factors and reduced kidney function vary by age.

METHODS: We pooled cross-sectional data from 14,788 nondiabetics aged 40 to 100 years in 4 studies: Cardiovascular Health Study, Health, Aging, and Body Composition Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-Stage Disease cohort.

RESULTS: Hypertension and low high-density lipoprotein (HDL) cholesterol were associated with reduced cystatin C-based estimated glomerular filtration rate (eGFR) across the age spectrum. In adjusted analyses, hypertension was associated with a 2.3 (95\% confidence interval [CI], 0.1, 4.4), 5.1 (95\% CI, 4.1, 6.1), and 6.9 (95\%~CI, 3.0, 10.4) mL/min/1.73 m(2) lower eGFR in participants 40 to 59, 60 to 79, and at least 80~years, respectively (P for interaction < .001). The association of low HDL cholesterol with reduced kidney function was also greater in the older age groups: 4.9 (95\% CI, 3.5, 6.3), 7.1 (95\% CI, 6.0, 8.3), 8.9 (95\% CI, 5.4, 11.9) mL/min/1.73 m(2) (P for interaction < .001). Smoking and obesity were associated with reduced kidney function in participants under 80 years. All estimates of the potential population impact of the risk factors were modest.

CONCLUSIONS: Hypertension, obesity, smoking, and low HDL cholesterol are modestly associated with reduced kidney function in nondiabetics. The associations of hypertension and HDL cholesterol with reduced kidney function seem to be stronger in older adults.

}, keywords = {Adult, Age Factors, Aged, Aged, 80 and over, Aging, Causality, Cholesterol, LDL, Cohort Studies, Comorbidity, Cross-Sectional Studies, Cystatin C, Female, Humans, Hypertension, Kidney Function Tests, Male, Netherlands, Obesity, Prevalence, Renal Insufficiency, Chronic, Risk Factors, Smoking, United States}, issn = {1873-2585}, doi = {10.1016/j.annepidem.2012.12.004}, author = {Odden, Michelle C and Tager, Ira B and Gansevoort, Ron T and Bakker, Stephan J L and Fried, Linda F and Newman, Anne B and Katz, Ronit and Satterfield, Suzanne and Harris, Tamara B and Sarnak, Mark J and Siscovick, David and Shlipak, Michael G} } @article {6295, title = {Relative risks of chronic kidney disease for mortality and end-stage renal disease across races are similar.}, journal = {Kidney Int}, volume = {86}, year = {2014}, month = {2014 Oct}, pages = {819-27}, abstract = {

Some suggest race-specific cutpoints for kidney measures to define and stage chronic kidney disease (CKD), but evidence for race-specific clinical impact is limited. To address this issue, we compared hazard ratios of estimated glomerular filtration rates (eGFR) and albuminuria across races using meta-regression in 1.1 million adults (75\% Asians, 21\% Whites, and 4\% Blacks) from 45 cohorts. Results came mainly from 25 general population cohorts comprising 0.9 million individuals. The associations of lower eGFR and higher albuminuria with mortality and end-stage renal disease (ESRD) were largely similar across races. For example, in Asians, Whites, and Blacks, the adjusted hazard ratios (95\% confidence interval) for eGFR 45-59 versus 90-104 ml/min per 1.73 m(2) were 1.3 (1.2-1.3), 1.1 (1.0-1.2), and 1.3 (1.1-1.7) for all-cause mortality, 1.6 (1.5-1.7), 1.4 (1.2-1.7), and 1.4 (0.7-2.9) for cardiovascular mortality, and 27.6 (11.1-68.7), 11.2 (6.0-20.9), and 4.1 (2.2-7.5) for ESRD, respectively. The corresponding hazard ratios for urine albumin-to-creatinine ratio 30-299 mg/g or dipstick 1+ versus an albumin-to-creatinine ratio under 10 or dipstick negative were 1.6 (1.4-1.8), 1.7 (1.5-1.9), and 1.8 (1.7-2.1) for all-cause mortality, 1.7 (1.4-2.0), 1.8 (1.5-2.1), and 2.8 (2.2-3.6) for cardiovascular mortality, and 7.4 (2.0-27.6), 4.0 (2.8-5.9), and 5.6 (3.4-9.2) for ESRD, respectively. Thus, the relative mortality or ESRD risks of lower eGFR and higher albuminuria were largely similar among three major races, supporting similar clinical approach to CKD definition and staging, across races.

}, keywords = {Adult, African Continental Ancestry Group, Aged, Aged, 80 and over, Albuminuria, Asian Continental Ancestry Group, Cardiovascular Diseases, Cohort Studies, Creatinine, European Continental Ancestry Group, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Male, Middle Aged, Odds Ratio, Renal Insufficiency, Chronic, Risk Factors}, issn = {1523-1755}, doi = {10.1038/ki.2013.553}, author = {Wen, Chi Pang and Matsushita, Kunihiro and Coresh, Josef and Iseki, Kunitoshi and Islam, Muhammad and Katz, Ronit and McClellan, William and Peralta, Carmen A and Wang, Haiyan and de Zeeuw, Dick and Astor, Brad C and Gansevoort, Ron T and Levey, Andrew S and Levin, Adeera} } @article {8095, title = {Galectin-3 and Soluble ST2 and Kidney Function Decline in Older Adults: The Cardiovascular Health Study (CHS).}, journal = {Am J Kidney Dis}, volume = {67}, year = {2016}, month = {2016 06}, pages = {994-6}, keywords = {Aged, Cohort Studies, Creatinine, Cystatin C, Female, Galectin 3, Glomerular Filtration Rate, Humans, Interleukin-1 Receptor-Like 1 Protein, Logistic Models, Longitudinal Studies, Male, Prognosis, Renal Insufficiency, Chronic}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2015.12.022}, author = {Bansal, Nisha and Katz, Ronit and Seliger, Stephen and DeFilippi, Christopher and Sarnak, Mark J and Delaney, Joseph A and Christenson, Robert and de Boer, Ian H and Kestenbaum, Bryan and Robinson-Cohen, Cassianne and Ix, Joachim H and Shlipak, Michael G} }