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Hemoglobin decline, function, and mortality in the elderly: the cardiovascular health study.

ABSTRACT: While anemia is associated with poor functional and mortality outcomes in the elderly, the impact of hemoglobin decline is less studied. We evaluated the determinants and consequences of hemoglobin decline in 3,758 non-anemic participants from the Cardiovascular Health Study, a prospective cohort of community-dwelling elderly ?65 years old at baseline and followed for up to 16 years. Hemoglobin was measured at baseline and 3 years later and anemia defined by World Health Organization (WHO) criteria. We modeled hemoglobin decline in two ways: (1) per each 1 g/dL decrease in hemoglobin and (2) development of anemia by the WHO criteria. Among participants without baseline anemia, hemoglobin decreased by 0.4 g/dL and 9% developed anemia over 3 years. Baseline increasing age, female sex, diabetes, and kidney disease predicted hemoglobin decline over 3 years. Baseline increasing age, being African-American, and kidney disease predicted anemia development over 3 years. Hemoglobin decline was associated with subsequent worse cognitive function in men and anemia development with subsequent worse cognitive function in women. Both anemia development (HR 1.39, 95% CI 1.15, 1.69) and hemoglobin decline (HR 1.11, 95% CI 1.04, 1.18 per 1 g/dL decrease) predicted subsequent mortality in men and women. Hemoglobin decreases identified a large group of elderly individuals at risk for subsequent adverse outcomes who would not be identified using the WHO anemia criteria. These data may allow clinicians to identify at-risk elderly individuals for early intervention to improve the quality and quantity of life.

SUBMITTER: Zakai NA

PROVIDER: S-EPMC3860593 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Hemoglobin decline, function, and mortality in the elderly: the cardiovascular health study.

Zakai Neil A NA French Benjamin B Arnold Alice M AM Newman Anne B AB Fried Linda F LF Robbins John J Chaves Paulo P Cushman Mary M

American journal of hematology 20121009 1

While anemia is associated with poor functional and mortality outcomes in the elderly, the impact of hemoglobin decline is less studied. We evaluated the determinants and consequences of hemoglobin decline in 3,758 non-anemic participants from the Cardiovascular Health Study, a prospective cohort of community-dwelling elderly ≥65 years old at baseline and followed for up to 16 years. Hemoglobin was measured at baseline and 3 years later and anemia defined by World Health Organization (WHO) crite ...[more]

PMID: 23044913

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Project description:Rationale & objectiveUromodulin is released by tubular epithelial cells into the serum and lower levels are associated with more severe interstitial fibrosis and tubular atrophy. Low serum uromodulin (sUMOD) levels are associated with mortality and cardiovascular disease. However, little is known about the association of sUMOD levels with long-term kidney outcomes in older adults, a population with a high prevalence of interstitial fibrosis and tubular atrophy.Study designCase-cohort study and case-control study.Setting & participantsRandom subcohort (n=933) and additional cases of end-stage kidney disease (ESKD) and kidney function decline (≥30% decline in estimated glomerular filtration rate [eGFR]) during follow-up of the Cardiovascular Health Study (CHS).PredictorsUMOD level.OutcomesESKD (n=14) from the random subcohort and all additional ESKD cases from outside the random subcohort (n=39) during follow-up (10 years, case-cohort study); kidney function decline of≥30% eGFR at 9 years of follow-up in individuals with repeated eGFR assessments from the random subcohort (n=56) and additional cases (n=123). 224 participants from the random subcohort served as controls (case-control study).Analytical approachModified multivariable Cox regression for ESKD and multivariable logistic regression for kidney function decline. Both analyses adjusted for demographics, eGFR, urinary albumin-creatinine ratio, and other kidney disease progression risk factors.ResultsMean age of the random subcohort was 78 years, 40% were men, 15% were black. Mean sUMOD level was 127±64ng/mL and eGFR was 63±19mL/min/1.73m2. In multivariable analysis, each 1-SD higher sUMOD level was associated with 63% lower risk for ESKD (HR, 0.37; 95% CI, 0.14-0.95). In demographic-adjusted analyses of kidney function decline, each 1-SD higher sUMOD level was associated with 25% lower odds of kidney function decline (OR, 0.75; 95% CI, 0.60-0.95); after multivariable adjustment, the association was attenuated and no longer significant (OR, 0.88; 95% CI, 0.68-1.14).LimitationsPossibility of survival bias in the kidney function decline analysis.ConclusionsHigher sUMOD levels may identify elderly persons at reduced risk for ESKD.

Project description:BackgroundImpaired pulmonary function (IPF) and left ventricular systolic dysfunction (LVSD) are prevalent in the elderly and are associated with significant morbidity and mortality. The main objectives of this study were to examine the relative impact and joint association of IPF and LVSD with heart failure, cardiovascular mortality and all-cause mortality, and their impact on risk classification using a continuous net reclassification index.Methods and resultsWe followed 2342 adults without prevalent cardiovascular disease (mean age, 76 years) from the Cardiovascular Health Study for a median of 12.6 years. LVSD was defined as LV ejection fraction <55%. IPF was defined as: forced expiratory volume in 1 second:forced vital capacity <70%, and predicted forced expiratory volume in 1 second <80%. Outcomes included heart failure hospitalization, cardiovascular mortality, all-cause mortality, and composite outcome. LVSD was detected in 128 subjects (6%), IPF in 441 (19%) and both in 38 (2%). Compared to those without LVSD or IPF, there was a significantly increased cardiovascular risk for groups of LVSD only, IPF only, and LVSD plus IPF, adjusted hazard ratio (95% CI) 2.1 (1.5-3.0), 1.7 (1.4-2.1), and 3.2 (2.0-5.1) for HF; 1.8 (1.2-2.6), 1.4 (1.1-1.8), and 2.8 (1.7-4.7) for cardiovascular mortality; 1.3 (1.0-1.8), 1.7 (1.4-1.9), and 2.1 (1.5-3.0) for all-cause mortality, and 1.6 (1.3-2.1), 1.7 (1.5-1.9), and 2.4 (1.7-3.3) for composite outcome, respectively. Risk classification improved significantly for all outcomes when IPF was added to the adjusted model with LVSD or LVSD to IPF.ConclusionsWhile risk of cardiovascular outcomes was the highest among elderly with both LVSD and IPF, risk was comparable between subjects with IPF alone and those with LVSD alone. This observation, combined with improved risk classification by adding IPF to LVSD or LVSD to IPF, underscore the importance of comprehensive heart and lung evaluation in cardiovascular outcome assessment.

Project description:ObjectivesThis study aimed to investigate the relationship between cardiovascular mortality in elderly Asians and decline in renal function.DesignA retrospective cohort study.SettingCommunity-based health examination database from Taipei city.ParticipantsAt the beginning, the database included 315 045 health check-up visits of 97 803 elderly persons aged ≥65 years old from 2005 to 2012. After excluding missing values and outliers, there were 64 732 elderly persons with at least two visits retained for further analyses.Primary outcome measuresKidney function indicators include estimated glomerular filtration rate (eGFR) and urine protein, and rapid decline in eGFR was defined as slope ≤ -5 mL/min/1.73 m2 per year. The endpoint outcome was defined as the cardiovascular deaths registered in the death registry encoded by the International Classification of Diseases. We applied a Cox proportional hazards model to analyse the association between renal function and cardiovascular mortality.ResultsIn this study, we found 1264 elderly persons died from cardiovascular diseases, for whom the data included 4055 previous health check-up visits. We observed significant and independent associations of eGFR <60 mL/min/1.73 m2 (HR (95% CI) of 60>eGFR≥45 and eGFR<45 in males: 2.85 (1.33 to 6.09) and 3.98 (1.84 to 8.61); in females: 3.66 (1.32 to 10.15) and 6.77 (2.41 to 18.99)), positive proteinuria (HR (95% CI) of +/-, +,++ and +++, ++++ in males: 1.51 (1.29 to 1.78) and 2.31 (1.51 to 3.53); in females: 1.93 (1.54 to 2.42) and 4.23 (2.34 to 7.65)) and rapid decline in eGFR (HR (95% CI) in males: 3.24 (2.73 to 3.85); in females: 2.83 (2.20 to 3.64) with higher risk of cardiovascular mortality. The joint effect of increased concentration of urine protein and reduced eGFR was associated with a higher risk of cardiovascular mortality.ConclusionsRenal function and rapid decline in renal function are independent risk factors for cardiovascular mortality in the elderly.

Project description:BackgroundUromodulin (UMOD) is released by renal tubular cells into the serum (sUMOD) and urine. Lower urine UMOD has been linked to mortality and cardiovascular disease but much less is known about sUMOD. We evaluated the association of sUMOD with these outcomes in community-dwelling older adults.MethodsWe measured sUMOD in a random subcohort of 933 participants enrolled in the Cardiovascular Health Study. The associations of sUMOD with all-cause mortality, incident heart failure (HF) and incident cardiovascular disease (CVD; myocardial infarction, stroke and mortality due to coronary disease or stroke) were evaluated using multivariable Cox regression, adjusting for study participants' demographics, estimated glomerular filtration rate (eGFR), albuminuria and CVD risk factors. Generalized additive models with splines were used to address the functional form of sUMOD with outcomes. Due to nonlinear associations of sUMOD with all outcomes, 2.5% of the values on either end of the sUMOD distribution were excluded from the analyses, limiting the range of sUMOD to 34.3-267.1 ng/mL.ResultsThe mean age was 78 ± 5 years, 40% were male, sUMOD level was 127 ± 64 ng/mL, eGFR was 63 mL/min/1.73 m2 and 42% had CKD defined as eGFR <60 mL/min/1.73 m2. Patients in the lower sUMOD quartiles had lower eGFR and higher albuminuria (P < 0.01, respectively). During a median follow-up of 9.9 years, 805 patients died, 283 developed HF and 274 developed CVD. In multivariable analysis, higher sUMOD was significantly associated with a lower hazard for mortality {hazard ratio [HR] 0.89 [95% confidence interval (CI) 0.80-0.99] per 1 standard deviation (SD) higher sUMOD}, CVD [HR 0.80 (95% CI 0.67-0.96)] and the composite endpoint [HR 0.88 (95% CI 0.78-0.99)]; the association with HF was not statistically significant [HR 0.84 (95% CI 0.70-1.01)].ConclusionHigher sUMOD is independently associated with a lower risk for mortality and CVD in older adults.

Project description:RATIONALE & OBJECTIVES:Lower 25-hydroxyvitamin D concentrations have been associated with risk for kidney function decline, heart failure, and mortality. However, 25-hydroxyvitamin D requires conversion to its active metabolite, calcitriol, for most biological effects. The associations of calcitriol concentrations with clinical events have not been well explored. STUDY DESIGN:Case-cohort study. SETTING & PARTICIPANTS:Well-functioning community-living older adults aged 70 to 79 years at inception who participated in the Health, Aging, and Body Composition (Health ABC) Study. PREDICTOR:Serum calcitriol measured using positive ion electrospray ionization-tandem mass spectrometry. OUTCOMES:Major kidney function decline (?30% decline in estimated glomerular filtration rate from baseline), incident heart failure (HF), and all-cause mortality during 10 years of follow-up. ANALYTIC APPROACH:Baseline calcitriol concentrations were measured in a random subcohort of 479 participants and also in cases with major kidney function decline [n=397]) and incident HF (n=207) during 10 years of follow-up. Associations of serum calcitriol concentrations with these end points were evaluated using weighted Cox regression to account for the case-cohort design, while associations with mortality were assessed in the subcohort alone using unweighted Cox regression. RESULTS:During 8.6 years of mean follow-up, 212 (44%) subcohort participants died. In fully adjusted models, each 1-standard deviation lower calcitriol concentration was associated with 30% higher risk for major kidney function decline (95% CI, 1.03-1.65; P=0.03). Calcitriol was not significantly associated with incident HF (HR, 1.16; 95% CI, 0.94-1.47) or mortality (HR, 1.01; 95% CI, 0.81-1.26). We observed no significant interactions between calcitriol concentrations and chronic kidney disease status, baseline intact parathyroid or fibroblast factor 23 concentrations. LIMITATIONS:Observational study design, calcitriol measurements at a single time point, selective study population of older adults only of white or black race. CONCLUSIONS:Lower calcitriol concentrations are independently associated with kidney function decline in community-living older adults. Future studies will be needed to clarify whether these associations reflect lower calcitriol concentrations resulting from abnormal kidney tubule dysfunction or direct mechanisms relating lower calcitriol concentrations to more rapid loss of kidney function.

Dataset Information

Hemoglobin decline, function, and mortality in the elderly: the cardiovascular health study.

Publications

Hemoglobin decline, function, and mortality in the elderly: the cardiovascular health study.

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