HDL: is higher really better?
We usually refer to LDL (low-density lipoprotein) as “bad cholesterol,” and HDL (high-density lipoprotein) as “good cholesterol.” Observational studies, such as the Framingham Heart Study, have shown that low HDL is a risk factor for cardiovascular disease.1 Thus it is thought that raising HDL may reduce risk, but it’s not that simple.
Cholesterol is packaged into lipoproteins when circulated in the blood — LDL transports cholesterol to the cells, and HDL picks up excess cholesterol and delivers it back to the liver where it can be broken down. Theorectically, having more HDL would mean that more cholesterol would be disposed of, and as a result LDL would decrease, and therefore cardiovascular risk would decrease. So raising HDL when LDL is high would make sense, but what about raising HDL when LDL is not high? Would there be any benefit?
High-dose niacin (vitamin B3), is one substance that can raise HDL, and a government funded clinical trial (the AIM-HIGH trial) was undertaken in 2006 evaluating the use of niacin together with an LDL-lowering drug (a statin) for preventing heart attacks and strokes. The individuals selected for the trial had favorable LDL levels (below 80 mg/dl; due to the statin drugs), but were considered to be at risk for heart attack and stroke based on low HDL levels, high triglyceride levels, and a history of cardiovascular disease. This study sought to determine whether raising HDL would decrease their risk.
The subjects that took niacin in addition to a statin drug indeed did experience an increase in HDL and decrease in triglycerides. However, the clinical trial was stopped early because the subjects taking niacin plus the statin were just as likely to have a cardiovascular event as those taking a statin plus placebo. Furthermore, the subjects who were taking niacin had a small increase in the rate of strokes.2 Niacin is not the first drug that has raised HDL levels and failed to reduce the risk of cardiovascular events. A few years ago, an HDL-elevating drug called torcetrapib was found to increase the risk of cardiovascular events, presumably because it raised blood pressure and impaired endothelial function.3 Pfizer’s development of the drug was halted during clinical trials.
This is yet another study showing that raising HDL does not reduce risk in patients with already favorable LDL levels. Often, adopting a healthful diet reduces both HDL and LDL, and this is often a source of concern. But the truth is that it is not harmful — there is simply less need for HDL when LDL decreases, and the body adapts to this change by producing less HDL.
LDL and HDL numbers on a blood test are simply markers that indicate the development of cardiovascular disease. They are not necessarily an accurate depiction of the extent of the disease, and they are not the only factors that take part in the disease process. The development of atherosclerotic plaque is complex, involving elements of inflammation and oxidative stress in addition to cholesterol. Manipulating cholesterol levels with drugs is simply not enough to resolve cardiovascular disease and prevent future heart attacks and strokes. This 52 million dollar study has confirmed what we already know: only healthy living which addresses multiple parameters simultaneously can restore cardiovascular health.
1. Castelli WP, Garrison RJ, Wilson PW, et al: Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA 1986;256:2835-2838.
2. NIH stops clinical trial on combination cholesterol treatment. 2011. NIH News. http://www.nih.gov/news/health/may2011/nhlbi-26.htm. Accessed June 14, 2011.
3. Connelly MA, Parry TJ, Giardino EC, et al: Torcetrapib produces endothelial dysfunction independent of cholesteryl ester transfer protein inhibition. J Cardiovasc Pharmacol 2010;55:459-468.