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Most everyone these days is aware that a high level of cholesterol is a risk factor for heart disease. For years, the thinking has been that there is “bad” cholesterol (LDL cholesterol) and “good” cholesterol (HDL cholesterol). Studies of populations (epidemiological research) have clearly demonstrated a strong association between low levels of LDL cholesterol and a lower risk of developing heart disease. LDL cholesterol reduction with drugs such as statins has been demonstrated to reduce cardiovascular risk. Thus, both the epidemiology and the randomized clinical trials support LDL cholesterol’s role as a risk factor for heart disease — and that by lowering LDL we can lower the chances of heart attack and stroke.
With respect to HDL cholesterol, the epidemiology supports an association between high levels of HDL cholesterol and lower cardiovascular risk. However, unlike the LDL cholesterol story, recent clinical trials of drugs that specifically raise HDL cholesterol have not been shown to improve cardiovascular outcomes. Why is there this disconnect? That has been a pressing question among cardiovascular researchers.
A paper that was just published in the Journal of the American College of Cardiology sheds some light on the answer. In total, 631,762 people were studied. The authors found that low HDL cholesterol levels were associated with a number of factors that affect health, including low incomes, unhealthy lifestyles, higher triglycerides levels, other cardiac risk factors, and medical problems. Thus, the association between low HDL cholesterol and worse cardiovascular outcomes could be due to these other factors and not the low HDL cholesterol itself.
This study found that lower HDL cholesterol levels were associated with a higher risk of death from cardiovascular causes, as prior studies have shown. However, there was also a higher risk of death from cancer and other causes compared with those having average levels of HDL cholesterol. That finding makes it seem as though low HDL cholesterol isn’t just predicting cardiovascular death — which might make sense if it is really causing heart disease — but it is also predicting cancer deaths and other causes of death. And there is not a good biological explanation for why a low HDL cholesterol level should do that. The conclusion the authors reach is that low HDL cholesterol isn’t really causing any of these problems such as heart disease or cancer, but rather the underlying cause of the low HDL cholesterol, such as an unhealthy lifestyle, is the real driver of worse outcomes.
What does all this mean practically? Well, first of all, more research on the relationship between low HDL cholesterol and heart disease is still needed. There are some large clinical trials of HDL cholesterol raising drugs that are ongoing, so these studies may provide even greater insight into whether raising low HDL cholesterol protects cardiovascular health. In the meantime, it probably means that it is unlikely to be useful to take medications solely for the purpose of raising low HDL cholesterol levels. And if you have a low HDL cholesterol level, this study reinforces that exercise and a heart healthy diet are the way to go and might decrease some of the health risks seen in people with low HDL cholesterol levels.