The interplay between circulating high-density lipoprotein, age and fracture risk: a new cohort study and systematic...

Previous findings on the association between high-density lipoprotein cholesterol (HDL-C) and fracture have yielded inconsistent results and it is unclear if the association varies with age and sex. We sought to evaluate the prospective association between HDL-C levels and fracture risk and assess if the association is modified by age and sex. Circulating HDL-C levels were measured at baseline in a population-based sample of 2,448 men aged 42-61 years. Cox regression was used to estimate hazard ratios (HRs) and 95% CIs. Incident fractures (n = 134) occurred during a median follow-up of 25.7 years. In analysis adjusted for several risk factors, the HR (95% CI) for fractures was 1.00 (0.85-1.20) per 1 standard deviation (SD) increase in HDL-C levels. Comparing the extreme tertiles of HDL-C levels, the corresponding adjusted HR (95% CI) was 0.94 (0.62-1.45). In a meta-analysis of eight cohort studies (including the current study) comprising 74,378 participants and 4,621 fracture cases, the fully-adjusted risk estimate (95% CI) for fracture was 1.03 (0.96-1.10) per 1SD increase in HDL-C levels and 1.05 (0.92-1.20) comparing extreme tertiles of HDL-C. The pooled risk estimate (95% CIs) for fracture per 1SD increase were 1.09 (1.01-1.17) and 0.98 (0.93-1.04) for age groups ≥ 60 and < 60 years, respectively, and the corresponding risks comparing the extreme tertiles of HDL-C levels were 1.21 (1.09-1.33) and 0.95 (0.85-1.07) (p-value for interaction < 0.05). Age may modify the association between HDL-C levels and fracture risk - an increased fracture risk associated with increased HDL-C levels is only evident in older age (≥ 60 years).