From the Journals

High HDL-C levels linked to increased fracture risk


High levels of high-density lipoprotein cholesterol (HDL-C) in older adults are associated with a higher risk of sustaining a fracture than lower HDL-C levels, a new study suggests.

Intertrochanteric hip fracture Raycat/Getty Images

Intertrochanteric hip fracture

“Two animal studies showing that HDL-C reduces bone mineral density by reducing osteoblast number and function provide a plausible explanation for why high HDL-C may increase the risk of fractures,” Monira Hussain, MBBS, MPH, PhD, of Monash University in Melbourne, told this news organization. “So, it was not surprising when our analyses provided evidence that amongst those in the highest quintile of HDL-C (> 74 mg/dL), there was a [33%] increased risk of fractures.”

After adjustment, one standard deviation increment in HDL-C level was associated with a 14% higher risk of fracture during a 4-year follow-up.

Based on this and other studies, Dr. Hussain said, “I believe that the finding of a very high HDL-C [should] alert clinicians to a higher risk of mortality, fractures, and possibly other threats to their patient’s health.”

The study was published online in JAMA Cardiology.

Independent risk factor

For this report, the researchers conducted a post hoc analysis of data from the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial and the ASPREE-Fracture substudy.

ASPREE was a double-blind, randomized, placebo-controlled primary prevention trial of aspirin. Participants were 16,703 community-dwelling Australians and 2,411 individuals from the United States with a mean age of 75 and without evident cardiovascular disease, dementia, physical disability, or life-limiting chronic illness.

The ASPREE-Fracture substudy collected data on fractures reported post randomization from the Australian participants. Fractures were confirmed by imaging and adjudicated by an expert panel and included both traumatic and minimal trauma fractures.

Of the 16,262 participants who had a plasma HDL-C measurement at baseline (55% women), 1,659 (10.2%) experienced at least one fracture over a median of 4 years. This included 711 minimal trauma fractures (for example, falls from standing height) and 948 other trauma fractures, mainly falls on stairs, ladders, or stools.

Higher rates of fractures occurred in the highest quintile of HDL-C level where the mean level was 89 mg/dL. At baseline, participants in that quintile had a lower BMI, a high prevalence of current/former smoking and current alcohol use, 12 years or longer of school, more physical activity, and higher use of antiosteoporosis medication. They also had less chronic kidney disease, diabetes, prefrailty/frailty, or treatment with lipid-lowering drugs.

In a fully adjusted model, each standard deviation increment in HDL-C level was associated with a 14% higher risk of fractures (hazard ratio, 1.14). When analyzed in quintiles, compared with participants in Q1, those in Q5 had a 33% higher risk for fracture (HR, 1.33).

Prevalence rates were similar between the sexes. The increase in fracture risk appeared to be independent of traditional risk factors for fractures, including age, sex, physical activity, alcohol use, frailty, BMI, smoking status, diabetes, chronic kidney disease, use of lipid-lowering or antiosteoporosis drugs, and education, the authors note.

The results persisted in sensitivity analyses in restricted subgroups of interest and in stratified analyses – including, for example, only minimal fractures; participants not taking antiosteoporosis drugs or statins; never smokers; nondrinkers; and those engaging in minimal physical activity (walking less than 30 minutes per day).

No association was observed between non–HDL-C levels and fractures.

The authors conclude that the study “provides robust evidence that higher levels of HDL-C are associated with incident fractures in both male and female individuals, independent of conventional risk factors.”


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