Mortality and Cholesterol Metabolism in Subjects Aged 75 Years and Older: The Helsinki Businessmen Study.

Abstract

In many studies, low serum cholesterol is paradoxically associated with a higher mortality risk among older adults. Therefore, we studied whole-body cholesterol metabolism and its role in all-cause mortality of older men in two subcohorts of different ages. Prospective long-term cohort. Home-dwelling men of the Helsinki Businessmen Study. Two partly overlapping subcohorts were recruited, in 2003 (n = 660; mean age = 76 years) and in 2011 (n = 398; mean age = 83 years). The younger subcohort was followed up after 3 and 11 years, and the older subcohort was followed up after 3 years. Cholesterol metabolism was assessed via serum noncholesterol sterol-cholesterol ratios, and quantification was performed by gas-liquid chromatography with flame ionization detection. All statistical analyses were performed with age and statin treatment as covariates. At the end of the 3-year follow-up, 10% of the younger and 13% of the older subcohort had died; and at the end of the 11-year follow-up, 40% of the younger subcohort had died. Serum total and low-density lipoprotein (LDL) cholesterol and cholesterol precursors reflecting cholesterol synthesis were lower in the older than in the younger subcohort (P < .001 for all). In the older subcohort, low serum campesterol and sitosterol, reflecting decreased cholesterol absorption efficiency, predicted all-cause mortality (P < .05). This was supported by a trend toward low serum campesterol and sitosterol predicting mortality (P = .088 and P = .079, respectively) in the younger subcohort after 11 years. Cholesterol synthesis did not predict mortality, but in the older subcohort, decreased cholesterol absorption was less efficiently compensated for by decreased cholesterol synthesis. Low cholesterol absorption efficiency predicted all-cause mortality, especially in men aged 83 years on average, and cholesterol synthesis was lowered. These metabolic changes could contribute to the lowering of serum total and LDL-cholesterol in older men. J Am Geriatr Soc 68:281-287, 2020.