Atlanta—Pharmacists who fill prescriptions for medications to raise high-density lipoprotein (HDL) cholesterol every day might be surprised by the results of a new study presented recently at the European Society Cardiology (ESC) Conference in Munich, Germany.

Emory University School of Medicine researchers reported at the meeting that very high HDL cholesterol levels appear to be associated with an increased risk of heart attack and death.

“It may be time to change the way we view HDL cholesterol,” explained presenter Marc Allard-Ratick, MD. “Traditionally, physicians have told their patients that the higher your ‘good’ cholesterol, the better. However, the results from this study and others suggest that this may no longer be the case.”

Because the HDL molecule is involved in helping cholesterol move away from blood and blood-vessel walls, high levels have been considered protective against clogged arteries and atherosclerosis. It has been unknown, however, how high is too high.

This study, conducted as part of the Emory Cardiovascular Biobank, sought to answer that question, analyzing the link between elevated HDL cholesterol levels and the risk of heart attack and death in 5,965 participants, most of whom had heart disease. 

Participants, who had an average age of 63 years and were 65% male, were divided into five groups according to their HDL cholesterol level: 
• Less than 30 mg/dl (0.78 mmol/L) 
• 31-40 mg/dl (0.8-1 mmol/L) 
• 41-50 mg/dl (1.1-1.3 mmol/L) 
• 51-60 mg/dl (1.3-1.5 mmol/L) 
• Greater than 60 mg/dl (1.5 mmol/L)

Over the median follow-up of 3.9 years (interquartile range 1.6 to 6.6 years), 769 participants either died from a cardiovascular event or had a nonfatal myocardial infarction.

Researchers determined that the study subjects with the lowest and highest HDL cholesterol levels had the greatest increased risk. Specifically, they reported, the hazard ratio was 1.62 (95% CI: 1.16-2.26, P = .005) for those with the lowest levels and 1.44 (95% CI: 1.01-2.06, P = .04) for those with the highest levels, after adjusting for a number of factors including use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor blockers, beta blockers, statins, or aspirin.

Participants with HDL cholesterol of 41 to 60 mg/dl (1.1-1.5 mmol/L) had the lowest risk of heart attack or cardiovascular death, the study team writes.

“Elevated HDL-C levels are paradoxically associated with an increased risk of adverse CV events in an at-risk population, suggesting dysfunctional HDL and impaired atheroprotection,” study authors conclude.

Allard-Ratick noted that the results, while surprising, are in line with recent research, adding, “Our results are important because they contribute to a steadily growing body of evidence that very high HDL cholesterol levels may not be protective, and because unlike much of the other data available at this time, this study was conducted primarily in patients with established heart disease.”

While emphasizing that the mechanisms are not fully understand, he posited in an ESC press release that “One possible explanation is that extremely elevated HDL cholesterol may represent ‘dysfunctional HDL’ which may promote rather than protect against cardiovascular disease.”

Allard-Ratick concluded, “One thing is certain: the mantra of HDL cholesterol as the ‘good’ cholesterol may no longer be the case for everyone.”

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