CRP and Cholesterol: What a New Study Says About Statins and Heart Disease

The first email from a patient came in on Sunday evening at 8:15 pm., just a few hours after the JUPITER trial had been presented at the American Heart Association meetings in New Orleans. The Internet was already humming with summaries of its findings, which suggested that millions of people not currently treated with statins might benefit from these drugs. My patient wanted to know if she should be on a statin, too.

First, a quick summary: JUPITER was a huge multi-nation research study that tested the impact of the statin rosuvastatin (Crestor) in nearly 18,000 people who would not qualify for treatment of their cholesterol according to current guidelines. These people did not have histories of heart disease, and their "bad" cholesterol (LDL) was either normal or low (less than 130 mg/dL). These patients did have to have one abnormal lab result in order to get enrolled in the study-a high-sensitivity C-reactive protein (hs-CRP) level of 2.0 mg/L or more.

CRP is a test that measures inflammation in the body-for example, if you have pneumonia or rheumatoid arthritis, your CRP goes up. But it also goes up if you have atherosclerosis in your arteries, because of the inflammation that goes with the constant damage-and-repair process within the walls of your blood vessels. Researchers at Boston's Brigham and Women's Hospital have shown that high CRP levels indicate an increased risk for heart disease even if LDL cholesterol levels are low.

Patients in JUPITER were selected because researchers wanted to see if cholesterol lowering with a powerful statin would be beneficial in patients with some evidence of inflammation (elevated hs-CRP), even if their cholesterol levels were not worrisome. The study was stopped early because the benefit was so clear-the patients who took a statin were almost 50% less likely to suffer a stroke or to need heart procedures, and 20% less likely to die than patients who took a placebo. The benefits of statins were apparent for women and men, old and young, white and non-white, thin and fat, and every other subgroup of patients considered.

The implications of the study could be profound. They might mean that hs-CRP testing should be routinely used to evaluate a person's risk of heart disease. (Note: Brigham and Women's Hospital has a patent for the test for hs-CRP; the researchers and the author of this article work there. I was not one of the researchers, but I do also work at Brigham and Women's) And they might mean that the universe of people who would benefit from a statin is much larger than just those with elevated LDL cholesterol levels. They could mean that everyone should be on a statin unless you have a low LDL and a low hs-CRP level.

If these possible implications become guidelines for care, the impact will be enormous-but many experts are urging caution before ordering this test on everyone, and prescribing statins to nearly everyone. Why the hesitation?

First, the overall heart risk in this population was not very high. The risk of definite cardiac problems in the placebo group in JUPITER was only 1.8%, compared with 0.9% in patients who took the statins. The researchers had to treat 120 patients for 1.9 years to prevent one event. In short, the relative benefit was large (50% reduction, from 1.8% to 0.9%) but the absolute benefit was small (less than 1%).

Second, experts need to pour through these data to determine whether guidelines for hs-CRP use should change. Current guidelines recommend measurement in people without symptoms of heart disease who have an intermediate risk on the basis of their standard risk markers (e.g., LDL cholesterol, diabetes status, etc.) if the decision to initiate drug therapy might be influenced by hs-CRP level. This "selective" strategy focuses use of hs-CRP testing on patients if and only if the test result would change decisions about use of medications-as opposed to ordering the test on everyone. Many experts do not think JUPITER should lead to a change to this approach.

So what did I tell my patient? She is 60, has no evidence of heart disease, and has a fantastic lipid profile-her LDL cholesterol is naturally low (less than 70 mg/dL), and her HDL cholesterol is high (also in the 60 to 70 mg/dL range). Her hs-CRP is 2.3 md/L-high enough to make her eligible for JUPITER, had she been approached. Strictly speaking, she fits the profile of the patients in this study, who had that 50% reduction in risk of heart problems when taking rosuvastatin.

For the time being, though, we are going to watch and wait. One reason is that her lipid profile is so good. Another is that her hs-CRP is only minimally elevated at 2.3 mg/L, while the median level in JUPITER was 4.2 mg/L. So her risk for events without treatment is probably lower than the 1.8% in the JUPITER patients who took a placebo.

Watch and wait for what? Certainly, for any evidence of cardiovascular problems, or trends in her laboratory risk factors in the wrong directions. But we will also be watching and waiting for more studies, and for the expert guidelines that will emerge from analysis of JUPITER's findings over time.

Have you had your CRP level measured? What did you and your doctor do with that number? What do you think of the JUPITER findings?

Thomas H. Lee, M.D., is an internist and cardiologist who is a Professor of Medicine at Harvard Medical School. He is also the Network President of Partners Healthcare System, the integrated delivery system founded by Brigham and Women's Hospital and Massachusetts General Hospital.

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