COLORADO SPRINGS — Measurement of high-sensitivity C-reactive protein is particularly useful in deciding whether to “pull the trigger” on prescribing more aggressive pharmacotherapy in patients with the metabolic syndrome, John A. Merenich, M.D., said at the annual scientific meeting of the Colorado chapter of the American College of Physicians.
“I use hs-CRP as a tie breaker. It's a test that has to be done in conjunction with global risk assessment. If I'm already convinced a patient needs therapy, I don't need an hs-CRP—I just treat. If a patient is at low global risk, a test such as hs-CRP is going to have an unacceptable false-positive rate. But if I'm on the fence or the patient is on the fence, I'll use the hs-CRP to dictate how aggressive I'm going to be,” said Dr. Merenich, director of the Colorado Kaiser Permanente Care Management Institute, Denver.
Dr. Merenich was quick to add that although he considers it reasonable to use agents such as statins, fibrates, fish oil, aspirin, ACE inhibitors, and metformin to treat higher-risk patients with metabolic syndrome, such treatments are not yet truly evidence based.
He cited data from nearly 15,000 participants in the Women's Health Study to support his suggestion to use hs-CRP to further risk-stratify patients with metabolic syndrome. In a published analysis led by Paul M. Ridker, M.D., of Harvard Medical School, Boston, women who met criteria for metabolic syndrome and had a CRP value below 3 mg/L had a 2.3-fold increased relative risk of cardiovascular events during follow-up, compared with those without metabolic syndrome who had a CRP below 3 mg/L.
The relative risk rose to 4.0 in women with metabolic syndrome and an elevated CRP, and the increased relative risk associated with an elevated CRP applied even in women with metabolic syndrome who had an LDL below 130 mg/dL (Circulation 2003;107:391–7).
Despite the present lack of clinical outcome data for metabolic syndrome, Dr. Merenich considers more aggressive drug therapy “a reasonable option” in those at higher risk as defined by a Framingham risk score greater than 10%, an elevated CRP, or an abnormal fasting blood glucose despite the lifestyle measures that constitute the cornerstone interventions.
Metformin is a good fit for patients who have impaired glucose tolerance. Support for its use comes from the Diabetes Prevention Program, in which 3,234 obese patients with impaired glucose tolerance were randomized to metformin, an intensive lifestyle intervention, or placebo. After 3 years, the risk of developing diabetes was reduced by 31% in the metformin arm vs. placebo, and by 58% in the lifestyle intervention group (N. Engl. J. Med. 2002;346:393–403).
Preferential use of an ACE inhibitor to lower blood pressure in hypertensive patients with metabolic syndrome is supported by the Heart Outcomes Prevention Evaluation (HOPE) trial. HOPE participants randomized to 10 mg/day of ramipril showed a 34% reduction in new-onset diabetes vs. placebo, Dr. Merenich said.