High serum cholesterol: lower noncardiovascular deaths

Association Between Serum Cholesterol and Noncardiovascular Mortality in Older Age
Journal of the American Geriatric Society, November 2011

Objectives: To clarify the association between cholesterol and noncardiovascular mortality and to evaluate how this association varies across age groups.

Participants: Adults aged 55 to 99 (5,750)

Measurements: Participants were evaluated for total cholesterol and subfractions and followed for mortality for a median of 13.9 years. Total cholesterol and its subfractions were evaluated in relation to noncardiovascular mortality within age-groups (55–64, 65–74, 75–84, ≥85).

Results: Age- and sex-adjusted analyses showed that each 1-mmol/L increase in total cholesterol was associated with an approximately 12% lower risk of noncardiovascular mortality. Age group–specific analyses demonstrated that this association reached significance after the age of 65 and increased in magnitude across each subsequent decade. This was driven largely by non-high-density lipoprotein cholesterol and was partly attributable to cancer mortality. HDL-C was not significantly associated with noncardiovascular mortality.

Conclusion: Higher total cholesterol was associated with a lower risk of noncardiovascular mortality in older adults. This association varied across the late-life span and was stronger in older age groups.

If you read between the lines, this study seems to suggest that for cardiovascular risk, keeping HDL high is more important than total or LDL. For noncardiovascular risk, keeping total and LDL high seems to be more protective.

Details of Study

Although it has been reported that total cholesterol has a strong inverse association with noncardiovascular mortality, such that people with higher levels of total cholesterol have a lower risk of noncardiovascular mortality, other studies have found that the effect of total cholesterol on noncardiovascular mortality is neutral. Few studies have examined the subfractions of cholesterol in relation to noncardiovascular mortality. Clarifying the role of total cholesterol and its subfractions as a risk factor for noncardiovascular mortality is of great consequence to primary and secondary prevention efforts. This study also provided a unique opportunity to examine this association in a sample in which cholesterol was measured before statins were introduced into the general population.

Although there was no significant association for total cholesterol in those aged 55 to 64, each 1-mmol/L increase in total cholesterol in those aged 65 to 74 reduced the risk of noncardiovascular mortality 12%. As age increased, this risk decreased, the reduction being 14% in those aged 75 to 84 and 20% in those aged 85 and older.

Whereas the two earlier studies with neutral findings had included participants with CVD at baseline, the current study included only healthy older adults. This suggests that total cholesterol is potentially a better predictor of noncardiovascular mortality in people who are free from CVD. Additionally, in the current study, cholesterol was not shown to be strongly associated with cardiovascular mortality.

Several factors added to the validity of these findings. First, the study population was drawn from a large, established, prospective, population-based cohort study, providing enough power to test the hypotheses of interest. Second, the availability of a long follow-up period (median 13.9 years) provided sufficient case numbers and enough time to evaluate trends. Third, total and HDL-C were evaluated at the same time and in the same participants, which also enabled the evaluation of non-HDL-C and the relationship between total and HDL-C (ratio measure). This enhanced the ability to make comparisons across these markers of cholesterol and thus to identify trends and differences and their individual utility as clinical markers in older adults. Fourth, specialists in the field confirmed cause of death, increasing the certainty to which a classification of cause of death can be attributed. Finally, because the baseline for the current study predated the introduction of statins, concurrent or prior drug use did not influence the measures of cholesterol at baseline.

Bonnie - this study seems to suggest that for cardiovascular risk, keeping HDL high is more important than lowering total or LDL. For noncardiovascular risk, high total and LDL seems to be more protective. The plot thickens.