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Am Fam Physician. 2004;69(5):1230

Studies have shown conflicting findings regarding the relationship between serum total cholesterol levels and all-cause mortality in persons who are at least 65 years of age. Brescianini and colleagues investigated the relationship between total cholesterol levels and all-cause mortality in a mixed cohort of Italians 65 to 84 years of age, with consideration of existing medical conditions, lifestyle factors, and other frailty indicators.

Researchers obtained blood samples from 3,295 study participants. Variables that might confound the outcome measure were placed into three groups. The first group consisted of risk factors for many chronic diseases, including age, sex, alcohol use, smoking status, and body mass index. The second group consisted of preexisting medical conditions, such as coronary heart disease and cancer. The third group consisted of frailty indicators, such as weight loss of at least 5 kg (11 lb) in the year preceding the entry interview. These variables provided the basis for three statistical models designed to explore the association between total cholesterol levels and all-cause mortality.

In one of several statistical approaches, analysis excluded subjects who died during the first year of follow-up, as well as patients taking a lipid-lowering medication. Participants were divided into quartiles based on their total cholesterol level: 78 to 189 mg per dL (2.02 to 4.89 mmol per L), 190 to 216 mg per dL (4.91 to 5.59 mmol per L), 217 to 275 mg per dL (5.61 to 7.11 mmol per L), and 276 to 417 mg per dL (7.14 to 10.78 mmol per L).

The authors found that the percentage of deaths in the first year decreased with increasing levels of total cholesterol, but the percentage of subjects taking lipid-lowering medications increased with total cholesterol level. These findings suggest that a higher percentage of persons were sicker or more frail in the quartile of patients with the lowest total cholesterol compared with patients in the other three quartiles, and that these low levels of total cholesterol were not caused by use of lipid-lowering medications.

In the first of the three models, a low total cholesterol level was associated with increased mortality. The hazard ratios for the second, third, and fourth quartiles, using the lowest quartile as a reference group, were 0.53, 0.52, and 0.59, respectively, and were all statistically significant. When preexisting chronic diseases were added in the second model, the hazard ratios remained similar. When frailty measures were added in the third model, hazard ratios also were around 0.5 and were statistically significant. In this model, weight loss and disability were found to correlate with mortality.

This epidemiologic study found a positive association between low total cholesterol levels and mortality risk in those 65 to 84 years of age. Subjects with moderate or high levels of total cholesterol had an approximately 45 percent lower risk of dying than persons in the reference group with total cholesterol levels less than 189 mg per dL. Important predictors of all-cause mortality were age, diabetes mellitus, coronary heart disease, fibrinogen levels, disability, and weight loss. The total cholesterol level certainly appeared to be an indicator of poor health, but it is unclear whether the total cholesterol level was a cause or an effect of this status. Because so few patients in the lowest quartile of cholesterol level were receiving lipid-lowering medications, these patients must have had low total cholesterol levels for reasons other than the use of lipid-lowering medications, suggesting that lipid-lowering medications do not increase mortality. The authors conclude that low levels of cholesterol may be potential warning signs of occult disease or rapidly declining health.

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