High level of HDL-C associated with higher risk of mortality in patients with coronary artery disease

New data suggest that patients with coronary artery disease (CAD) with very high levels of high-density lipoprotein cholesterol (HDL-C) may have an increased risk of death from all causes and cardiovascular disease.

Multicenter cohort study results show that elevated HDL-C levels were paradoxically associated with higher mortality risk in 2 cohorts at high risk of CAD in 2 countries, independent of common polymorphisms associated with higher levels .

“Our study fills an important knowledge gap, as current risk calculators used in the general population incorporate high HDL-C as a protective factor, whereas at very high levels this protective effect does not appear to be protective. verify itself and, in fact, may confer increased risk,” wrote study author Arshed A. Quyyumi, MD, Division of Cardiology, Department of Medicine, Emory University School of Medicine.

The study

Researchers sought to investigate the association between very high levels of HDL-C and the risk of all-cause and cardiovascular mortality in 2 independent groups of coronary artery disease patients in the UK Biobank (UKB) and the Emory Cardiovascular Biobank ( EmCAB).

UKB and EmCAB patients were prospectively followed for a median of 8.9 years and 6.7 years, respectively. In the UK, people aged 40-72 years with a history of coronary artery disease at enrollment were included in the general UK population between 2006 and 2010. The EmCAB is a prospective cohort currently being developed. adults ≥ 18 years of age undergoing left heart catheterization for suspected or confirmed coronary artery disease at 3 Emory Healthcare sites in Atlanta, Georgia.

All-cause death was considered the primary outcome of the study, while the secondary outcome was cardiovascular death.

The investigators excluded patients without confirmed coronary artery disease from the study. They used the analysis of variance, Mann-Whitney you test, and x2 tests to compare the basic characteristics between 5 categories of HDL-C:

  • 30 mg/dL or less
  • 30 – 40mg/dL
  • 40 to 60mg/dL
  • 60 to 80mg/dL
  • ≥ 80mg/dL

A total of 14,478 participants (mean age, 62.1 years; 11,034 men [76.2%]) from UKB were included in the study and 5467 participants (mean age, 63.8 years; 3632 men [66.4%]) of EmCAB were included in the study.

The results

In patients with HDL-C levels ≥ 80 mg/dL in UKB, death from all causes was reported in 43 of 255 participants (16.9%) and cardiovascular death was reported in 22 of 255 attendees (8.6%). Meanwhile, in EmCAB in patients with HDL-C levels ≥ 80 mg/dL, all-cause and cardiovascular deaths were observed in 27 of 90 participants (30%) and 15 of 90 participants (16 .7%), respectively.

Over a median follow-up of 8.9 years in UKB and 6.7 years in EmCAB, data show that a U-shaped association with outcomes was found with higher risk in people with low and very high HDL-C levels, compared to those with average values.

After adjusting for UKB, the highest HDL-C group had an increased risk of death from all causes (RR, 1.96; 95% CI, 1.42, 2.71; P P = 0.02) compared to those with HDL-C levels between 40 and 60 mg/dL.

Based on the fully adjusted EmCAB models, the group with the lowest HDL-C levels had a higher all-cause risk (HR, 1.22; 95% CI, 1.03 – 1 .45; P = 0.02) and cardiovascular death (HR, 1.35; 95% CI, 1.06, 1.72; P = .01). Meanwhile, the highest group had a significantly or near-significantly higher risk of death from all causes (RR, 1.63; 95% CI, 1.09, 2.43; P = 0.02) and cardiovascular death (HR, 1.57; 95% CI, 0.95, 2.61; P = 0.08).

In addition, sensitivity analyzes demonstrated that the risk of all-cause mortality in the very high HDL-C group was higher in men than in women in the UKB (HR, 2.63; CI at 95%, 1.75 – 3.95; P P = 0.23).

“Future studies are warranted to investigate the association of a very high HDL-C level with other cause-specific outcomes,” Quyyumi concluded.

The study, “Association between high-density lipoprotein cholesterol levels and adverse cardiovascular outcomes in high-risk populations,” was published in JAMA Cardiology.

Comments are closed.