Lipids and Morality in the Elderly
Lipids and Morality in the Elderly
Objectives: To investigate the relationship between plasma lipids and risk of death from all causes in nondemented elderly.
Design: Prospective cohort study.
Setting: Community-based sample of Medicare recipients, aged 65 years and older, residing in northern Manhattan.
Participants: Two thousand two hundred seventy-seven nondemented elderly, aged 65 to 98; 672 (29.5%) white/non-Hispanic, 699 (30.7%) black/non-Hispanic, 876 (38.5%) Hispanic, and 30 (1.3%) other.
Measurements: Anthropometric measures: fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-HDL-C, body mass index, and apolipoprotein E (APOE) genotype. Clinical measures: neuropsychological, neurological, medical, and functional assessments; medical history of diabetes mellitus, heart disease, hypertension, stroke, and treatment with lipid-lowering drugs. Vital status measure: National Death Index date of death. Survival methods were used to examine the relationship between plasma lipids and subsequent mortality in younger and older nondemented elderly, adjusting for potential confounders.
Results: Nondemented elderly with levels of total cholesterol, non-HDL-C, and LDL-C in the lowest quartile were approximately twice as likely to die as those in the highest quartile (rate ratio (RR)=1.8, 95% confidence interval (CI)=1.3–2.4). These results did not vary when analyses were adjusted for body mass index, APOE genotype, diabetes mellitus, heart disease, hypertension, stroke, diagnosis of cancer, current smoking status, or demographic variables. The association between lipid levels and risk of death was attenuated when subjects with less than 1 year of follow-up were excluded (RR=1.4, 95% CI=1.0–2.1). The relationship between total cholesterol, non-HDL-C, HDL-C, and triglycerides and risk of death did not differ for older (≥75) and younger participants (>75), whereas the relationship between LDL-C and risk of death was stronger in younger than older participants (RR=2.4, 95% CI=1.2–4.9 vs RR=1.6, 95% CI=1.02–2.6, respectively). Overall, women had higher mean lipid levels than men and lower mortality risk, but the risk of death was comparable for men and women with comparable low lipid levels.
Conclusion: Low cholesterol level is a robust predictor of mortality in the nondemented elderly and may be a surrogate of frailty or subclinical disease. More research is needed to understand these associations.
High levels of cholesterol and low-density lipoprotein cholesterol (LDL-C) are associated with greater cardiovascular and all-cause mortality in middle-aged populations. Trials of lipid-lowering agents have demonstrated a reduction in cardiovascular outcomes in these populations, but there are conflicting data exploring these associations in elderly subjects. A persistent association between high cholesterol and LDL-C and mortality remains, particularly in the youngest old, but studies have also found that lower high-density lipoprotein cholesterol (HDL-C) levels are a stronger predictor of mortality than total cholesterol in the elderly. There is increasing evidence of an inverse association between total cholesterol levels and risk of cardiovascular and all-cause mortality. A U-shaped or J-shaped relationship between total cholesterol and mortality has also been found. No relationship was found between cholesterol levels and mortality risk in the elderly in Framingham Study or in the Established Populations for Epidemiologic Studies in the Elderly.
Cholesterol levels decline with age and with chronic disease, inflammation, malnutrition, or poor health status in elderly persons. Thus, lower cholesterol levels in the elderly may represent a surrogate for comorbidity, frailty, or subclinical disease. Although elevated total cholesterol levels have been related to mortality from coronary heart disease after adjustment for frailty or comorbidity and cardiovascular risk factors such as stroke, serum albumin, and iron, other studies have found that low cholesterol is related to mortality even with adjustment for health status and indicators of frailty.
No study, to the authors' knowledge, has taken dementia status into account in the relationship between cholesterol and mortality. Weight loss and greater mortality in patients with Alzheimer's disease (AD) has been well documented. Low cholesterol levels are associated with a higher risk of AD in cross-sectional and longitudinal analyses, probably representing a preclinical AD state. Dementia is frequent in elderly populations and might contribute to the association between low cholesterol and mortality. The relationship between plasma lipids and subsequent mortality in younger and older nondemented elderly was examined in the Washington Heights Inwood Columbia Aging Project cohort, taking cardiovascular risk factors, chronic disease, smoking status, and treatment with lipid-lowering drugs into account.
Objectives: To investigate the relationship between plasma lipids and risk of death from all causes in nondemented elderly.
Design: Prospective cohort study.
Setting: Community-based sample of Medicare recipients, aged 65 years and older, residing in northern Manhattan.
Participants: Two thousand two hundred seventy-seven nondemented elderly, aged 65 to 98; 672 (29.5%) white/non-Hispanic, 699 (30.7%) black/non-Hispanic, 876 (38.5%) Hispanic, and 30 (1.3%) other.
Measurements: Anthropometric measures: fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and non-HDL-C, body mass index, and apolipoprotein E (APOE) genotype. Clinical measures: neuropsychological, neurological, medical, and functional assessments; medical history of diabetes mellitus, heart disease, hypertension, stroke, and treatment with lipid-lowering drugs. Vital status measure: National Death Index date of death. Survival methods were used to examine the relationship between plasma lipids and subsequent mortality in younger and older nondemented elderly, adjusting for potential confounders.
Results: Nondemented elderly with levels of total cholesterol, non-HDL-C, and LDL-C in the lowest quartile were approximately twice as likely to die as those in the highest quartile (rate ratio (RR)=1.8, 95% confidence interval (CI)=1.3–2.4). These results did not vary when analyses were adjusted for body mass index, APOE genotype, diabetes mellitus, heart disease, hypertension, stroke, diagnosis of cancer, current smoking status, or demographic variables. The association between lipid levels and risk of death was attenuated when subjects with less than 1 year of follow-up were excluded (RR=1.4, 95% CI=1.0–2.1). The relationship between total cholesterol, non-HDL-C, HDL-C, and triglycerides and risk of death did not differ for older (≥75) and younger participants (>75), whereas the relationship between LDL-C and risk of death was stronger in younger than older participants (RR=2.4, 95% CI=1.2–4.9 vs RR=1.6, 95% CI=1.02–2.6, respectively). Overall, women had higher mean lipid levels than men and lower mortality risk, but the risk of death was comparable for men and women with comparable low lipid levels.
Conclusion: Low cholesterol level is a robust predictor of mortality in the nondemented elderly and may be a surrogate of frailty or subclinical disease. More research is needed to understand these associations.
High levels of cholesterol and low-density lipoprotein cholesterol (LDL-C) are associated with greater cardiovascular and all-cause mortality in middle-aged populations. Trials of lipid-lowering agents have demonstrated a reduction in cardiovascular outcomes in these populations, but there are conflicting data exploring these associations in elderly subjects. A persistent association between high cholesterol and LDL-C and mortality remains, particularly in the youngest old, but studies have also found that lower high-density lipoprotein cholesterol (HDL-C) levels are a stronger predictor of mortality than total cholesterol in the elderly. There is increasing evidence of an inverse association between total cholesterol levels and risk of cardiovascular and all-cause mortality. A U-shaped or J-shaped relationship between total cholesterol and mortality has also been found. No relationship was found between cholesterol levels and mortality risk in the elderly in Framingham Study or in the Established Populations for Epidemiologic Studies in the Elderly.
Cholesterol levels decline with age and with chronic disease, inflammation, malnutrition, or poor health status in elderly persons. Thus, lower cholesterol levels in the elderly may represent a surrogate for comorbidity, frailty, or subclinical disease. Although elevated total cholesterol levels have been related to mortality from coronary heart disease after adjustment for frailty or comorbidity and cardiovascular risk factors such as stroke, serum albumin, and iron, other studies have found that low cholesterol is related to mortality even with adjustment for health status and indicators of frailty.
No study, to the authors' knowledge, has taken dementia status into account in the relationship between cholesterol and mortality. Weight loss and greater mortality in patients with Alzheimer's disease (AD) has been well documented. Low cholesterol levels are associated with a higher risk of AD in cross-sectional and longitudinal analyses, probably representing a preclinical AD state. Dementia is frequent in elderly populations and might contribute to the association between low cholesterol and mortality. The relationship between plasma lipids and subsequent mortality in younger and older nondemented elderly was examined in the Washington Heights Inwood Columbia Aging Project cohort, taking cardiovascular risk factors, chronic disease, smoking status, and treatment with lipid-lowering drugs into account.
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