New evidence suggests an association between very high high-density lipoprotein cholesterol (HDL-C) levels and greater mortality risk among individuals with coronary artery disease (CAD), according to study findings published in the Journal of the American Medical Association Cardiology.
While previous studies linked higher HDL-C levels with reduced cardiovascular risk, more recent real-world evidence suggests greater risk of adverse outcomes at very high HDL-C levels. Researchers sought to investigate the relationship between death in patients with CAD and HDL-C levels above 80 mg/dL and to analyze a possible connection between high HDL-C level outcomes and known HDL-C genotypes.
To accomplish this, they conducted a prospective, multicenter, cohort study of 14,478 patients with CAD (aged 62.1±5.8 years; 23.8% women) from the UK Biobank (UKB) from 2006 until present and 5467 patients with CAD (aged 63.8±12.3 years; 33.6% women) from the Emory Cardiovascular Biobank (EmCAB) Atlanta, Georgia, from 2003 until present. The median follow-up for the UKB patients (8.9 years; IQR 8.0-9.7) and EmCAB patients (6.7 years; IQR 4.0-10.8) resulted in a U-shaped relationship with adverse outcomes. Patients with the greatest risk for adverse outcomes had low or very high HDL-C levels, with the least risk seen at midrange.
Increased risk of all-cause death was associated with HDL-C levels greater than 80 mg/dL (hazard ratio [HR], 1.96; 95% CI, 1.42-2.71; P <.001), as was increased risk of cardiovascular death (HR, 1.71; 95% CI, 1.09-2.68; P =.02) when compared with UKB patients with midrange HDL-C levels (40-60 mg/dL) adjusted for confounding. Among EmCAB patients, results were the same. All-cause death among patients in the UKB cohort in the very high HDL-C group was greater among men than women (HR, 2.63; 95% CI, 1.75-3.95; P <.001 vs HR, 1.39; 95% CI, 0.82-2.35; P =.23), and this result was not duplicated in the EmCAB.
Study limitations include that the results may not be generalizable to patients with nonatherosclerotic cardiovascular diseases. There was also differing measures of alcohol consumption between the cohorts, and UKB’s definition of CAD patients was based on International Classification of Diseases, 10th Revision codes only.
Researchers wrote that their results suggest that, “an HDL-C level greater than 80 mg/dL was associated with higher risk of all-cause and cardiovascular death in populations with CAD, compared with those with normal HDL-C levels, a finding that until now has only been reported in individuals without known CAD.”
Liu C, Dhindsa D, Almuwaqqat Z, et al. Association between high-density lipoprotein cholesterol levels and adverse cardiovascular outcomes in high-risk populations. JAMA Cardiol. Published online May 18, 2022. doi:10.1001/jamacardio.2022.0912