Jennifer Lovejoy, Arivale Chief Science Officer, PhD
HDL-cholesterol is often called “good” cholesterol because having higher levels of it has been associated with a reduced risk of cardiovascular disease and lower cardiovascular mortality in many large observational studies.
Paradoxically, however, other data raise a question about whether very high levels of good cholesterol might actually be harmful. For example, raising HDL-C using medication hasn’t been shown to be beneficial and in some studies was even harmful. Furthermore, certain genetic variants associated with higher concentrations of HDL-C have been associated with a higher – rather than lower – risk of heart disease (here and here, for example).
While about 19 percent of the US population has low levels of HDL-C – which we know is associated with greater heart disease risk – roughly 8 percent has what are considered to be “very high” levels of HDL-C. This condition, known as “hyperalphalipoproteinemia” or HALP, is more common in women and people of Asian and Asian-Indian descent.
There has been considerable research on whether HALP is associated with greater cardiovascular mortality and morbidity, and two recent studies contribute to this topic.
The first study, conducted by researchers at Emory University, has not been published but was presented at the 2018 European Society of Cardiology meeting in Germany and covered by HealthDay. This study tracked approximately 6,000 men and women with an average age of 63 for four years. During the study, 13 percent of the individuals had a heart attack or died from a cardiovascular cause. Those with HDL-C less than 41 mg/dl or greater than 60 mg/dl had the highest risk of having a cardiovascular event. However, the researchers note that the highest risk is likely in those with HDL-C over 80 mg/dl or 90 mg/dl, consistent with previous studies of HALP.
The second study – published in the European Heart Journal and covered by the New York Times – involved analysis of two large population cohorts in Denmark. This study followed more than 116,000 adults for between six and 20 years and examined the relationship between HDL-C levels and all-cause and cardiovascular mortality. Similar to the previous study, the researchers found a “U-shaped” relationship between HDL-C and mortality – both low and high levels of HDL-C were associated with high all-cause mortality. In men, the optimal range of HDL-C was 54-77 mg/dl and in women it was 69-97 mg/dl. Men with HDL-C greater than 116 mg/dl had double the mortality risk compared to men in the optimal range, and women with HDL-C greater than 135 mg/dl had a 68 percent higher risk. Levels of HDL-C less than 39 mg/dl were associated with greater risk in both sexes.
Despite the results of these two recent studies, the literature overall concerning HALP is too conflicted to draw firm conclusions. It seems that in some cases high HDL-C can be harmful, but it’s not possible at this time to predict when this will be the case.
HALP is most often caused by genetic factors that may have other impacts on the cardiovascular system beyond elevated HDL-C. A small percentage of people with very high HDL-C have a secondary form of HALP due to non-genetic factors, such as estrogen-replacement therapy, long-term heavy alcohol use, high levels of aerobic exercise (e.g. marathon runners), or treatment with certain cholesterol drugs. In most of these secondary cases, it’s rare for HDL-C to exceed 100 mg/dl; however, this is still within the risk range identified in some studies.
There is no specific treatment or approach to manage very high HDL-C levels. HDL-C levels in general should be looked at as one piece of the puzzle, taking into account the many other factors that influence heart health, including LDL-C, triglycerides, blood pressure, inflammation, BMI, and lifestyle factors.
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[Arivale Hot Topics address health stories currently in the news. The Arivale Clinical Team’s commentary on these news articles is not a review of the scientific evidence, nor an endorsement of a specific study, and is not meant as official medical opinion.]