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      Low Total Cholesterol and Increased Risk of Dying: Are Low Levels Clinical Warning Signs in the Elderly? Results from the Italian Longitudinal Study on Aging

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          Abstract

          To analyze the relationship between serum total cholesterol (TC) and all-cause mortality, taking into account various potential confounders. Population-based prospective cohort study. Older Italians residing in the general community. Four thousand five hundred twenty-one men and women aged 65-84. Vital status data were available for 1992-95. The hazard ratios of dying for subjects in the second, third, and fourth quartiles compared with the first quartile of TC were computed using Cox proportional hazards, adjusting for lifestyle factors, anthropomorphic and biochemical measures, preexisting medical conditions, and frailty indicators. Blood samples were obtained from 3,295 (73%) of the participants, of whom 399 died during almost 3 years of follow-up. Low TC was associated with a higher risk of death. Those with TC in the second, third, and fourth quartiles (TC>189 mg/dL or 4.90 mmol/L) had lower hazard ratios (HRs) of death than subjects in the first quartile (0.57, 95% confidence interval (CI) = 0.38-0.87; 0.56, 95% CI = 0.36-0.88; and 0.53, 95% CI = 0.33-0.84, respectively). Few subjects taking lipid-lowering drugs (LLDs) were in the lowest quartile of cholesterol, suggesting that these individuals have low TC values for reasons other than LLD use. Subjects with low TC levels (<189 mg/dL) are at higher risk of dying even when many related factors have been taken into account. Although more data are needed to clarify the association between TC and all-cause mortality in older individuals, physicians may want to regard very low levels of cholesterol as potential warning signs of occult disease or as signals of rapidly declining health.

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          Cholesterol and all-cause mortality in elderly people from the Honolulu Heart Program: a cohort study.

          A generally held belief is that cholesterol concentrations should be kept low to lessen the risk of cardiovascular disease. However, studies of the relation between serum cholesterol and all-cause mortality in elderly people have shown contrasting results. To investigate these discrepancies, we did a longitudinal assessment of changes in both lipid and serum cholesterol concentrations over 20 years, and compared them with mortality. Lipid and serum cholesterol concentrations were measured in 3572 Japanese/American men (aged 71-93 years) as part of the Honolulu Heart Program. We compared changes in these concentrations over 20 years with all-cause mortality using three different Cox proportional hazards models. Mean cholesterol fell significantly with increasing age. Age-adjusted mortality rates were 68.3, 48.9, 41.1, and 43.3 for the first to fourth quartiles of cholesterol concentrations, respectively. Relative risks for mortality were 0.72 (95% CI 0.60-0.87), 0.60 (0.49-0.74), and 0.65 (0.53-0.80), in the second, third, and fourth quartiles, respectively, with quartile 1 as reference. A Cox proportional hazard model assessed changes in cholesterol concentrations between examinations three and four. Only the group with low cholesterol concentration at both examinations had a significant association with mortality (risk ratio 1.64, 95% CI 1.13-2.36). We have been unable to explain our results. These data cast doubt on the scientific justification for lowering cholesterol to very low concentrations (<4.65 mmol/L) in elderly people.
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            Total cholesterol and risk of mortality in the oldest old

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              Clarifying the direct relation between total cholesterol levels and death from coronary heart disease in older persons.

              The importance of total cholesterol level as a risk factor for coronary heart disease in older adults is controversial. To determine whether findings showing that total cholesterol level is not an important risk factor for coronary heart disease in older adults are the result of inadequate adjustment for co-occurring diseases and frailty. Multicenter, longitudinal study with 5-year follow-up for death. 4066 men and women from East Boston, Massachusetts; Iowa and Washington counties, Iowa; and New Haven, Connecticut. In 1988, participants were interviewed about their health status and had blood samples taken. Mortality follow-up was through 1992. In analyses that included all fatal coronary heart disease events (252 deaths) and did not adjust for risk factors for coronary heart disease and measures of frailty, persons with the lowest total cholesterol levels ( or = 6.20 mmol/L [> or = 240 mg/dL]) seemed to have a lower risk for death from coronary heart disease (P for trend = 0.04). After adjustment for established risk factors for coronary heart disease and markers of poor health (including chronic conditions, low serum iron and albumin levels) and exclusion of 44 deaths from coronary heart disease that occurred within the first year, elevated total cholesterol levels predicted increased risk for death from coronary heart disease, and the risk for death from coronary heart disease decreased as cholesterol levels decreased (P for trend = 0.005). Elevated total cholesterol level is a risk factor for death from coronary heart disease in older adults, and the apparent adverse effects associated with low cholesterol levels are secondary to comorbidity and frailty. This suggests that excluding older persons from cholesterol screening is inappropriate, but interpretation of screening results in older persons requires clinical judgment. Results from controlled clinical trials are needed to clarify this issue.
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                Author and article information

                Journal
                Journal of the American Geriatrics Society
                Journal of the American Geriatrics Society
                Wiley
                00028614
                15325415
                July 2003
                July 2003
                : 51
                : 7
                : 991-996
                Article
                10.1046/j.1365-2389.2003.51313.x
                12834520
                8b575ab1-f090-4ef1-b570-e2d7b33f9585
                © 2003

                http://doi.wiley.com/10.1002/tdm_license_1.1

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