(LifeWire) - While having high HDL cholesterol is good, the type of HDL you have might put you at risk of heart disease. There are currently no medications that only increase HDL levels.
You are probably used to hearing high-density lipoprotein (HDL) described as the "good cholesterol." If your doctor is urging you to lower your total cholesterol, you may wonder why you are also supposed to be increasing your HDL levels.
What is So Good About the "Good Cholesterol"?
Compared to its low-density counterpart (LDL, the "bad cholesterol"), HDL is indeed an asset. It appears to work by whisking harmful cholesterol away from artery walls and off to the liver, where it is processed and passed from the system.
The American Heart Association recommends a HDL level of at least 40 milligrams per deciliter (mg/dL) for men, and at least 50 mg/dL for women. Higher HDL levels have been associated with reducing the risk of heart attack and stroke, while lower HDL levels are considered to be an indicator of heart disease.
This is why, in recent years, medical attention has turned from focusing on lowering LDL levels to finding new ways to increase HDL levels. It seems simple enough; when there is a battle between good and evil in your arteries, you want to help the good guys.
Unfortunately, it is not that easy.
Pfizer's Big Disappointment
Pharmaceutical giant Pfizer was banking on a breakthrough when it developed torcetrapib, a drug used to increase HDL in patients with high cholesterol. It worked by inhibiting a protein called cholesteryl ester transfer protein (CETP), which acted to raise the level of HDL in lab tests.
Combining this drug with Lipitor (atorvastatin), an existing drug chosen for its status as the most researched statin on the market, researchers began a study called ILLUMINATE.
Early results were promising; individuals taking the experimental combination showed a 61% increase in HDL levels. Later in the research process, more than 15,000 subjects, all deemed at high risk for coronary heart disease, were enrolled. Some were given the torcetrapib/Lipitor combination, while individuals in the control group were given Lipitor alone.
In late 2006, three years into the research study, a routine review of the gathered data showed an alarmingly high number of deaths in subjects taking the combination drug (82 study subjects had died, compared to just 51 subjects in the Lipitor-alone group).
With this news and upon receipt of a recommendation from the data safety monitoring board, Pfizer immediately terminated the trial, citing patient safety concerns.
So What Now?
Upon termination of the trial, several questions still remained: Why would patients with higher HDL levels, a factor so widely accepted as beneficial, have worse outcomes than patients with lower HDL levels? Is there something in the torcetrapib itself that does harm, or do high HDL levels not provide the solution we expected?
Subsequent research has deepened these questions. Dutch researchers analyzing two earlier studies of HDL -- the IDEAL study and EPIC study -- concluded that HDL levels and large HDL particles may increase cardiovascular risk when present at very high levels.
In recent years, researchers have attempted to determine why very high HDL levels would cause health problems. One theory is that, just as there are good and bad forms of cholesterol, there may be good and bad forms of HDL itself. One potential troublemaker is large-particle HDL. This was the type of HDL most elevated in the subjects who participated in the failed Pfizer drug. There may be other components (or subfractions) of HDL that raise, rather than lower, cardiovascular risk, but there is no clear scientific consensus.
In the meantime, there is plenty of good news. First, these problems with HDL only occur at very high levels, not at the levels that current guidelines set out as targets.
Second, healthy lifestyle changes are still a great way to safely raise your HDL levels. Healthy lifestyle changes do not contribute to raising large-particle HDL. In fact, extensive evidence from numerous long-term health studies confirms that healthy lifestyle choices not only raise your good cholesterol, but also lower your risk for other conditions as well.
Finally, none of the existing treatments that raise HDL levels (such as niacin, medications known as fibrates, and -- to a limited extent -- the LDL-lowering statin drugs) have been associated with the sort of problems found with torcetrapib. These drugs act to boost HDL levels while reducing the risk of developing heart disease.
What Can I Do?
Until more is known about drug therapies to raise HDL, it is important to remember that simple lifestyle changes to boost HDL levels do lower your risk of heart disease. The American Heart Association has established several guidelines to help boost HDL levels:
- Do not smoke; And if you do smoke, consider quitting
- Maintain a healthy weight
- Exercise 40-60 minutes most days of the week
Sources:
American Heart Association Staff, "Effects of Torcetrapib in Patients at High Risk for Coronary Events." Americanheart.org. 22 Nov. 2007. American Heart Association. 6 Apr. 2008. <http://www.americanheart.org/presenter.jhtml?identifier=3052561>.American Heart Association Staff, "LDL and HDL Cholesterol: What's Bad and What's Good?." Americanheart.org. 18 Mar. 2008. American Heart Association. 6 Apr. 2008. <http://www.americanheart.org/presenter.jhtml?identifier=180>.
Food and Drug Administration Staff. "Pfizer Stops All Torcetrapib Clinical Trials in Interest of Patient Safety." FDA.gov. Food and Drug Administration. 4 Apr. 2008. <http://www.fda.gov/bbs/topics/NEWS/2006/NEW01514.html>.
Honey, Karen. "Drug Designed to Raise HDL Levels Falls Down." The Journal of Clinical Investigation. 117. 2. Feb. 2007. 282. <http://www.jci.org/articles/view/JCI31253>.
Nissen, Steven, et. al.. "Effect of Torcetrapib on the Progression of Coronary Atherosclerosis." New England Journal of Medicine. 356. 13. 29 Mar. 2007. 1304-1316. <http://content.nejm.org/cgi/content/abstract/356/13/1304>.
van der Steeg, Wim. "High-Density Lipoprotein Cholesterol, High-Density Lipoprotein Particle Size, and Apolipoprotein A-I: Significance for Cardiovascular Risk in the IDEAL and EPIC-Norfolk Studies." Journal of the American College of Cardiology. 51. 6. 12 Feb. 2008. 634-642. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T18-4RS5P4P-7&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=a2313e22af727863226a129aefb09d7e
