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BACKGROUND/OBJECTIVES: 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. DESIGN: Prospective long-term cohort. SETTING: Home-dwelling men of the Helsinki Businessmen Study. PARTICIPANTS: 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. MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: 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.

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