@article {864, title = {A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Oct 24}, pages = {2214-20}, abstract = {

BACKGROUND: Anemia is viewed as a negative prognostic factor in the elderly population; its independent impact on survival is unclear.

METHODS: Baseline hemoglobin quintiles and anemia, as defined by the World Health Organization criteria, were assessed in relation to mortality in the Cardiovascular Health Study, a prospective cohort study with 11.2 years of follow-up of 5888 community-dwelling men and women 65 years or older, enrolled in 1989-1990 or 1992-1993 in 4 US communities.

RESULTS: A total of 1205 participants were in the lowest hemoglobin quintile (<13.7 g/dL for men; <12.6 g/dL for women), and 498 (8.5\%) were anemic (<13 g/dL for men; <12 g/dL for women). A reverse J-shaped relationship with mortality was observed; age-, sex-, and race-adjusted hazard ratios (95\% confidence interval [CI]) in the first and fifth quintiles, compared with the fourth quintile, were 1.42 (95\% CI, 1.25-1.62) and 1.24 (95\% CI, 1.09-1.42). After multivariate adjustment, these hazard ratios were 1.33 (95\% CI, 1.15-1.54) and 1.17 (95\% CI, 1.01-1.36). The demographic- and fully-adjusted hazard ratios of anemia for mortality were 1.57 (95\% CI, 1.38-1.78) and 1.38 (95\% CI, 1.19-1.54). Adjustment for causes and consequences of anemia (renal function, inflammation, or frailty) did not reduce associations.

CONCLUSIONS: Lower and higher hemoglobin concentrations and anemia by World Health Organization criteria were independently associated with increased mortality. The World Health Organization criteria did not identify risk as well as a lower hemoglobin value. Additional study is needed on the clinically valid definition for and causes of anemia in the elderly and on the increased mortality at the extremes of hemoglobin concentrations.

}, keywords = {Age Factors, Aged, Anemia, California, Female, Follow-Up Studies, Health Status, Hemoglobins, Humans, Male, Maryland, Multivariate Analysis, North Carolina, Observation, Pennsylvania, Prospective Studies, Risk Factors, Severity of Illness Index, Survival Rate}, issn = {0003-9926}, doi = {10.1001/archinte.165.19.2214}, author = {Zakai, Neil A and Katz, Ronit and Hirsch, Calvin and Shlipak, Michael G and Chaves, Paulo H M and Newman, Anne B and Cushman, Mary} } @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 {6398, title = {Systolic and diastolic blood pressure, incident cardiovascular events, and death in elderly persons: the role of functional limitation in the Cardiovascular Health Study.}, journal = {Hypertension}, volume = {64}, year = {2014}, month = {2014 Sep}, pages = {472-80}, abstract = {

Whether limitation in the ability to perform activities of daily living (ADL) or gait speed can identify elders in whom the association of systolic and diastolic blood pressure (DBP) with cardiovascular events (CVDs) and death differs is unclear. We evaluated whether limitation in ADL or gait speed modifies the association of systolic blood pressure or DBP with incident CVD (n=2358) and death (n=3547) in the Cardiovascular Health Study. Mean age was 78{\textpm}5 and 21\% reported limitation in >=1 ADL. There were 778 CVD and 1289 deaths over 9 years. Among persons without and those with ADL limitation, systolic blood pressure was associated with incident CVD: hazard ratio [HR] (per 10-mm Hg increase) 1.08 (95\% confidence interval, 1.03, 1.13) and 1.06 (0.97, 1.17), respectively. ADL modified the association of DBP with incident CVD. Among those without ADL limitation, DBP was weakly associated with incident CVD, HR 1.04 (0.79, 1.37) for DBP >80, compared with <65 mm Hg. Among those with ADL limitation, DBP was inversely associated with CVD: HR 0.65 (0.44, 0.96) for DBP 66 to 80 mm Hg and HR 0.49 (0.25, 0.94) for DBP >80, compared with DBP <=65. Among people with ADL limitation, a DBP of 66 to 80 had the lowest risk of death, HR 0.72 (0.57, 0.91), compared with a DBP of <=65. Associations did not vary by 15-feet walking speed. ADL can identify elders in whom diastolic hypotension is associated with higher cardiovascular risk and death. Functional status, rather than chronologic age alone, should inform design of hypertension trials in elders.

}, keywords = {Activities of Daily Living, African Continental Ancestry Group, Aged, Aged, 80 and over, Blood Pressure, Cardiovascular Diseases, Diastole, European Continental Ancestry Group, Female, Follow-Up Studies, Gait, Heart Rate, Humans, Incidence, Longitudinal Studies, Male, Risk Factors, Survival Rate, Systole}, issn = {1524-4563}, doi = {10.1161/HYPERTENSIONAHA.114.03831}, author = {Peralta, Carmen A and Katz, Ronit and Newman, Anne B and Psaty, Bruce M and Odden, Michelle C} }