Metabolic Syndrome: Anti-Inflammatory Effect of Statins

SACRAMENTO, Calif., Sept. 15 -- Statin therapy may have an anti-inflammatory benefit for patients with metabolic syndrome: researchers here reported.

The metabolic syndrome, which includes abdominal obesity and hypertension, is also characterized by low-grade inflammation, increasing the risk for cardiovascular disease and diabetes, said Ishwarlal Jialal, M.D., Ph.D., of the University of California Davis here and colleagues.

In a double-blind, randomized, placebo-controlled study, statin therapy reduced two biomarkers of inflammation-C-reactive protein (CRP) and interleukin-6 (IL6)-according to a study reported in the Sept. 12 issue of the Journal of Clinical Endocrinology and Metabolism.

Previously Dr. Jialal's group had held that statins, as a class of drugs, are anti-inflammatory. Numerous studies have shown that statins lower biomarkers of inflammation in patients with coronary artery disease, diabetes, and hypercholesterolemia, he said. However, he added, there is a "paucity of data" in individuals with the metabolic syndrome.

To study the direct effect of the drugs on biomarkers of inflammation in the circulation but also on monocytes, cells pivotal in plaque formation, the researchers gave 50 metabolic syndrome patients a standard dose of simvastatin (40 mg/day). Controls received a placebo.

After eight weeks, as expected, they found that statin therapy produced a significant reduction in total cholesterol (25%), LDL cholesterol (32%), and non-high-density lipoprotein levels (42%), compared with baseline and placebo. Triglycerides and high-density lipoprotein cholesterol were unchanged.

Dr. Jialal and his team also found marked reductions in the two pivotal biomarkers of inflammation. Although these markers are usually elevated in insulin resistance, simvastatin therapy had marked effects as shown by a 36% decrease in levels of hsCRP (P

Thus, Dr. Jialal said, "we demonstrate for the first time in subjects with metabolic syndrome that simvastatin results in significant reduction in inflammation, as shown by these changes." This, coupled with the in vitro observations of decreased Rho activity by lovastatin, provide direct evidence for the anti-inflammatory effects of statin therapy via protein effects on monocytes, he added.

Changes in diet and exercise are still the treatment of choice for preventing the consequences of metabolic syndrome, Dr. Jialal said, "However, people don't always adhere to those changes," he concluded. "Our results suggest that statin may be a way to forestall the deadly complications of the metabolic syndrome."

Future studies, Dr. Jialal wrote, will examine the role of statin therapy in directly reducing adipose tissue biology with respect to inflammation. "We also need long-term studies that look at the effects of statins on insulin resistance and diabetes prevention," he said.

The researchers wrote that this study was supported in part by a Merck Medical School grant.