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Low Cholesterol Levels Associated with Increased Mortality


Am Fam Physician. 2005 Nov 1;72(9):1859-1860.

Even though high levels of cholesterol and low-density lipoprotein (LDL) are associated with increased cardiovascular and all-cause mortality in middle-age persons, this association is less clear in older patients. Lower cholesterol levels may be a marker for other illnesses. Studies have shown that even after adjusting for frailty, comorbidity, and cardiovascular risk factors, low LDL cholesterol levels remain associated with increased mortality. Schupf and colleagues account for dementia status in addition to other comorbid factors in examining the relationship between cholesterol and mortality in older patients.

This prospective study of aging and dementia involved 4,309 patients 65 years and older who were receiving Medicare. Of these patients, 2,277 met inclusion criteria of sufficient baseline information, such as plasma lipid levels and body mass index (BMI), and remained free of dementia for the duration of the study. Patients with dementia were excluded from the study.

All study participants received a complete physical and functional assessment at baseline; were screened for stroke, diabetes, hypertension, and coronary artery disease; had lipid measurements and apolipoprotein E genotyping; and had their BMI calculated. It also was determined whether patients were receiving cholesterol-lowering treatment.

The mean age of participants was 76.1 years and the mean duration of follow-up was three years. Low levels of total cholesterol, non–high-density lipoprotein cholesterol, and LDL cholesterol were associated with a greater mortality risk. After adjustment for demographic factors such as sex, age, ethnic group, and education level, the authors found that patients with cholesterol levels less than or equal to 175 mg per dL (4.53 mmol per L) were twice as likely to die as those with cholesterol levels greater than 226 mg per dL (5.84 mmol per L). Additional adjustment for illness factors, such as diabetes or smoking status, did not alter these findings.

Lipid-lowering treatment reduced the risk of death, although it did not eliminate the association between low cholesterol levels and mortality risk. The strength of the association was attenuated when study participants followed for more than one year were included. Low cholesterol levels predicted a slightly higher mortality risk in younger patients compared with older patients.

The authors conclude that low cholesterol levels are associated with greater risk of all-cause mortality in older patients without dementia. These results were not affected by comorbid illnesses, but were attenuated by lipid-lowering treatment and longer follow up. The reasons lower cholesterol levels might be associated with a greater risk of death are not known. This study confirms findings of other studies with similar results, but by excluding patients with dementia, indicates that dementiarelated confounding factors, such as nutritional or physical decline, are not the cause.

Schupf N, et al. Relationship between plasma lipids and all-cause mortality in nondemented elderly. J Am Geriatr Soc. 2005;53:219–26.

editor’s note: Increased mortality in older patients has been associated with the highest and lowest lipid levels. As this study shows, low lipid levels as “markers” for underlying illness do not fully account for the association between low lipid levels and mortality. Questions arise as to whether it is prudent to lower lipid levels in older patients and how far to lower them. A recent study1 of an elderly Japanese cohort treated for six years with statin therapy shows a similar J-shaped mortality curve as those who are not treated. Consequently, lowering cholesterol in patients with the highest lipid levels does appear to be warranted. Those whose lipid levels drop into the lowest quartile are at increased risk regardless of whether they are receiving lipid-lowering treatment. It is not known whether stopping lipid-lowering therapy in this subset of patients has any impact on motality risk, but a rule of thumb would be not to push lipid lowering targets as low as are currently advocated for other age groups.—c.w.



1. Matsuzaki M, Kita T, Mabuchi H, Matsuzawa Y, Nakaya N, Oikawa S, et al. Large scale cohort study of the relationship between serum cholesterol concentration and coronary events with low-dose simvastatin therapy in Japanese patients with hypercholesterolemia. Primary prevention cohort study of the Japan Lipid Intervention Trial (J-LIT). Circ J. 2002;66:1087–95.



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