The prospective association between high-density lipoprotein (HDL) cholesterol and risk of incident fractures in the general population.

Abstract

Elevated HDL-C levels are generally regarded as prognostically favorable in cardiovascular disease. Our study shows that higher HDL cholesterol levels are prospectively associated with 18% increased risk of new-onset fractures in men but not in women. Higher HDL cholesterol may be a novel risk factor for developing fractures in men. Increased high-density lipoprotein cholesterol (HDL-C) is associated with reduced risk of cardiovascular disease but inversely associated with bone mineral density. We assessed the relationship between HDL-C and incident fractures using a prospective population-based cohort. In total 18,240 subjects had available data on HDL-C levels (mean age 69 years, 37% women, mean follow-up 13 years). Fracture endpoints were identified through national registers. Follow-up was from 2002 until the first episode of incident fracture or end of follow-up December 31, 2020. The primary and secondary outcomes were total incident fractures and incident fractures of the hip and lower limb, respectively. Incident fractures occurred in 26% (n = 4,710) of all subjects (mean follow-up of 13 years). Subjects with incident fractures had higher HDL-C levels (mmol/L ± standard deviation) compared with subjects without fractures (1.5 ± 0.4 vs. 1.4 ± 0.4 mmol/L). In multivariate regression analysis, higher HDL-C levels were associated with increased risk of total incident fractures in the general population (HR 1.12, 95%CI 1.03-1.22, p = 0.006), and in men (HR 1.18, 95%CI 1.04-1.35, p = 0.02). No statistically significant relationship was found in women or between incident fractures of hip and lower limb fractures (p > 0.05). Higher HDL cholesterol levels are prospectively associated with 18% increased risk of new-onset fractures in men from the general population but not in women. Higher HDL cholesterol may be a novel risk factor for developing fractures in men.