This article is more than 5 years old. Information may no longer be current.

High HDL cholesterol levels linked to excessive mortality

Men and women with extremely high levels of HDL in their blood have an increased risk for all-cause mortality, according to a study published in the European Heart Journal.

“Through observational studies it has been established that HDL cholesterol is inversely associated with both cardiovascular disease and mortality across a wide range of concentrations,” Christian M. Madsen, MD, from the department of clinical biochemistry at the Herlev and Gentofte Hospital, Copenhagen, Denmark, and colleagues wrote. “This association does however not appear to be causal, as raising HDL cholesterol pharmacologically has not proven beneficial in randomized clinical trials, and has even paradoxically been associated with increased mortality in one study.”

Madsen and colleagues used data from two prospective population-based studies — Copenhagen City Heart Study and the Copenhagen General Population Study — to determine whether or not extremely high concentrations of HDL cholesterol increase all-cause mortality risk in men and women. The two studies included 52,268 men and 64,240 women and 745,452 person-years of follow-up.

There were 5,629 deaths in men (mortality rate, 17.1/1,000 person-years) and 5,059 deaths in women (mortality rate, 12.1/1,000 person-years) from any cause. Both extreme high and low concentrations of HDL were associated with high all-cause mortality. Men with extremely high and very high HDL concentrations had a 106% and 36%, respectively, higher mortality rate than those with normal concentrations. Women with extremely high HDL concentrations had a 68% higher mortality rate than those with normal concentrations.

In men, an HDL cholesterol concentration of 1.9 mmol/L (95% CI, 1.4–2) was associated with the lowest all-cause mortality risk, as was 2.4 mmol/L (95% CI, 1.8–2.5) in women. In comparison to men with the lowest risk, men with an HDL concentration of 2.4 mmol/L (95% CI, 1.8–2.5) had an adjusted HR for all-cause mortality of 1.36 (95% CI, 1.09–1.7) and men with an HDL cholesterol level of 3 mmol/L or higher had an adjusted HR of 2.06 (95% CI, 1.44–2.95). In women with HDL cholesterol concentrations of 3–3.49 mmol/L and 3.5 mmol/L or higher, HRs were 1.1 (95% CI, 0.83–1.46) and 1.68 (95% CI, 1.09–2.58), respectively.

“These results radically change the way we understand ‘good’ cholesterol,” Børge Nordestgaard, MD, coauthor of the study from department of clinical biochemistry at the Herlev and Gentofte Hospital, said in a related press release. “Doctors like myself have been used to congratulating patients who had a very high level of HDL in their blood. But we should no longer do so, as this study shows a dramatically higher mortality rate.”

“It appears that we need to remove the focus from HDL as an important health indicator in research, at hospitals and at the general practitioner,” he added. “These are the smallest lipoproteins in the blood, and perhaps we ought to examine some of the larger ones instead. For example, looking at blood levels of triglyceride and LDL, the ‘bad’ cholesterol, are probably better health indicators.” – by Alaina Tedesco

Disclosure: The authors report no relevant financial disclosures.