2015년 1월 7일 수요일

Harvard Health Publications Focus on Cholesterol: Part 4

Focus On CholesterolHarvard Medical School
ISSUE #4 OF 6 IN AN E-MAIL SERIES  
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Should you take a statin even if you have normal cholesterol?
The statin drugs are best known for their ability to lower LDL ("bad") cholesterol. High levels of LDL cholesterol can lead to heart disease. If your LDL cholesterol is not high, you probably think you don't need to take a statin. But a study nicknamed JUPITER may make you—and your doctor—question that assumption.
The JUPITER trial
The JUPITER trial was a large international study that found that the statin drug rosuvastatin (Crestor) slashed the rate of heart attacks and strokes in people with normal LDL cholesterol who had elevated levels of C-reactive protein (CRP). CRP is a marker of inflammation, and there is increasing evidence that low-grade inflammation raises heart risk.
The study involved 17,802 apparently healthy people from 26 countries. There were slightly more men than women—about a 60%-40% split. Here are some of their stats:
  • The men were 50 and over and the women were 60 and over—the ages when cardiovascular risk begins to rise.
  • Participants had no history of heart attacks or strokes, and their LDL cholesterol levels were below 130 milligrams per deciliter (mg/dL).
  • The average LDL cholesterol was 108 mg/dL, a level considered excellent for people with no cardiovascular risk factors.
  • The participants had high CRP levels, ranging from 2 to 7 milligrams per liter (less than 1 milligram per liter is considered normal).
Subjects were randomly assigned to take either 20 mg of Crestor or a placebo pill daily. They were monitored for cardiovascular events—heart attacks, strokes, bypass surgery or angioplasty, hospitalization for unstable angina, and death from a cardiovascular cause.
The results
JUPITER was designed to last for four years, but it was halted just short of two years because the statin takers were doing so much better than those taking the placebo. For example, people taking a statin:
  • were 54% less likely to have a stroke
  • were 48% less likely to have a heart attack
  • were 44% less likely to have any serious cardiovascular event, including cardiovascular death
  • lowered their LDL levels by an average of 50%
  • lowered their CRP levels by an average of 37%.
In the placebo group, CRP levels and LDL levels did not change. Side effects, such as muscle pain and problems with liver or kidney function, were the same in the two groups. However, there may have been an increase in diabetes among those taking Crestor.
Results of the study were published in The New England Journal of Medicine (online Nov. 9, 2008, and in print Nov. 20, 2008).
Some caveats
  1. First, it's important to note two areas of potential conflicts of interest:
    • The study was funded by Astra Zeneca, the maker of Crestor.
    • The patent rights to the hsCRP test are owned by the lead investigator, Dr. Paul M. Ridker, and Harvard-affiliated Brigham and Women's Hospital in Boston.
  2. With these results, about 95 people would need to be treated for two years to prevent a single cardiovascular event. Public health experts have to consider such numbers because they must weigh the absolute benefits against the costs and risks. Crestor, which is not available in a generic form, costs about $1,200 a year.
  3. Most people who take a statin take it for more than two years. Since the JUPITER study lasted only two years, it leaves questions about the long-term safety of people with above-normal CRP levels but normal LDL levels taking Crestor.
  4. The dose used in this study was higher than the typical starting dose of Crestor. Again, this raises questions about safety.
  5. The people taking Crestor in this study attained very low LDL levels. We don't know if maintaining them for longer than two years would be healthy, or continue to reduce cardiovascular risk as much as it did in the study.
  6. The possible small increase in diabetes risk found in study participants taking Crestor could mean trouble: diabetes is a major risk factor for heart attack, stroke, and death from cardiovascular disease.
What this means to you
Should you get an hsCRP test? The answer depends on your overall cardiovascular risk. The time-honored Framingham model uses age, cholesterol levels, blood pressure, smoking status, and diabetes to calculate a person's 10-year chance of having a heart attack. To calculate your Framingham risk score, go towww.nhlbi.nih.gov/guidelines/cholesterol/risk_tbl.htm.
If your risk is high...
You probably don't need the hsCRP test because you should be taking a statin anyway.
If your risk is low...
You probably don't need the test because it's still not clear that the benefit outweighs the cost and possible risk.
If your risk is moderate...
HsCRP results might help determine whether a statin, in addition to lifestyle changes, could reduce your risk of a heart attack or stroke. Talk to your doctor about it.
If you do get a CRP test, you can then reassess your cardiovascular risk using the newer Reynolds model (www.reynoldsriskscore.org). Unlike the Framingham tool, the Reynolds model adds hsCRP and some other factors to predict cardiovascular risk. The model reclassifies many people whose Framingham scores place them at moderate risk—sometimes into a higher risk category, sometimes into a lower risk one.
Your reason for taking a statin should still be your risk of having a heart attack. To find out about current LDL cholesterol goals and when you should consider taking a statin, consult the Adult Treatment Panel III Guidelines developed by the U.S. National Cholesterol Education Program, available atwww.nhlbi.nih.gov/guidelines/cholesterol/atglance.htm.
Statins have revolutionized cardiovascular disease prevention, and you should certainly take one if you have the appropriate risk factors. But also do everything you can to keep your statin dose low through exercise and diet to lower your LDL cholesterol.
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