Drug treatments that raise the “good” high density lipoprotein (HDL) cholesterol do not improve health outcomes, according to a new analysis. But some researchers suspect raising HDL through lifestyle changes may still be effective in treating heart disease.

HDL is the form of cholesterol that actively removes dangerous lipids from the blood, and has long been thought to be protective against heart disease. This form of cholesterol is believed to work in opposition to low density lipoprotein (LDL) cholesterol, which is strongly correlated with heart disease and cardiovascular mortality. Thus the ratio of HDL to LDL cholesterols is often considered the most important indicator of heart disease risk.

Strong clinical evidence shows that LDL lowering drugs like statins can protect against heart disease and cardiovascular mortality. However there is still no effective way of improving cardiovascular outcomes by directly targeting HDL cholesterol.

Pharmacological treatments that raise HDL cholesterol levels include fibrates, niacin and a Pfizer drug called Torcetrapib. However, trials that tested these drugs for improved cardiovascular outcome have yielded mixed results. Rather than lowering mortality risk, evidence suggests that fibrates and Torcetrapib actually increase mortality in patients. Some trials have shown niacin to be effective at reducing cardiovascular events, but the data are inconsistent.

A new meta-analysis published in the British Medical Journal asked whether pharmacological treatments that are known to raise HDL can improve cardiovascular outcomes. After adjusting for several known confounders (including the effect of LDL cholesterol) pharmacological treatments that raise HDL were not effective at protecting against heart disease.

Does this mean that HDL is not important for heart disease? Not necessarily.

The original studies that implicated HDL in heart protection were observational. For example, it was shown in the Framington Heart Study that people with HDL levels greater than 60 mg/dL have a reduced risk of heart disease compared to individuals with lower HDL. Likewise, individuals with less than 40 mg/dL of blood HDL are considered at risk for coronary heart disease, even when LDL cholesterol is relatively low.

Additionally, lifestyle choices that contribute to raising HDL are associated with a lower risk of heart disease. Examples of these are physical activity, weight loss, not smoking, increased omega-3 fatty acid consumption, decreased trans fat consumption, alcohol consumption and dietary soluble fiber. Also, diets low in saturated fat but relatively high in unsaturated fats have been shown to raise HDL and decrease heart disease risk.

All these HDL raising activities can improve cardiovascular outcome. However, this does not mean that HDL itself prevents heart disease. Rather, it seems to be a good biomarker (observational correlate) of heart disease.

Why are pharmacological methods of raising HDL not helpful (and possibly even harmful) at treating heart disease?

One possible explanation for this discrepancy is the observation that HDL has different forms, some that are protective and others that are harmful. For instance, some interventions may raise HDL cholesterol by limiting its breakdown (harmful), while others raise it by increasing HDL production (more beneficial). Also, some methods that increase HDL do so in a way that creates new problems, such as increased blood pressure.

The complex interaction between pharmacological interventions, HDL metabolism and cardiovascular outcome may have made it difficult to detect any benefit of raising HDL cholesterol in this meta-analysis. Since pharmacological intervention for raising HDL does not consistently help (and sometimes harms) cardiovascular outcome, lifestyle changes remain the most promising target for raising HDL to protect against heart disease.

Anyone want to guess how high my HDL cholesterol is??