Several large-scale studies have shown that the levels of high-sensitivity C-reactive protein (hsCRP) can predict the risks of new and recurrent coronary events, thereby indicating its prognostic value in acute coronary ischemia and post-coronary interventions. Now, the administration of rosuvastatin calcium (CRESTOR® | AstraZeneca) into evidently healthy people with elevated hsCRP levels, but without hyperlipidemia, has demonstrated a 44% reduction in the incidence of major cardiovascular events, according to a study published in the recent issue of The New England Journal of Medicine.
Paul M Ridker, Associate Physician, Brigham and Women’s Hospital, Harvard Medical School, Boston, led the long-term, double-blind study to assess the effect of 20mg daily dose of rosuvastatin in reducing the rates of major cardiovascular (CV) events. The primary end-point of the randomized placebo-controlled study conducted on 17,802 apparently healthy people, was the occurrence of arterial revascularization, hospitalization for unstable angina, MI, stroke, or CV death.
Subjects with ≤130mg/dL low-density lipoprotein (LDL) cholesterol and ≥2.0mg/L hsCRP were randomized to receive 20mg rosuvastatin daily, or placebo, and were followed for the occurrence of combined primary end point. The investigators observed that rosuvastatin reduced LDL cholesterol by 50% and hsCRP levels by 37%. Rosuvastatin also reduced the combined risk of heart attack, stroke or CV death by 47%; and their individual risks by 54%, 48%, and 20%, respectively, as compared to placebo. It was also observed that myopathy or cancer rate was not significantly enhanced in the rosuvastatin group; however, there was an increased incidence of physician-reported diabetes. Based on their findings, the researchers concluded that rosuvastatin considerably reduces the rate of first major CV event and death from any cause, in apparently healthy subjects without hyperlipidemia, but with high hsCRP levels, as compared to placebo.
Pai JK, et al. (The New England Journal of Medicine, 2004) conducted a study to evaluate inflammatory biomarkers such as soluble tumor necrosis factor receptors types 1 and 2 (sTNF-R1 and sTNF-R2), C-reactive protein (CRP) and interleukin-6 (IL-6), as independent predictors of CV events. Of the total number of cases without CV events at baseline, nonfatal MI or fatal coronary heart disease developed in 239 women and 265 men during the 8 years and 6 years of follow-up, respectively. Researchers observed an increased risk of coronary heart disease among both sexes with high levels of IL-6 and CRP, while only women with high levels of soluble TNF-α receptors were at a high risk. Researchers noted that elevated CRP levels were indicators for increased risk of coronary heart disease.
Rosuvastatin, an orally administered synthetic lipid-lowering agent, selectively and competitively inhibits the enzyme HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-CoA reductase). Rosuvastatin exerts its lipid-modifying effects in two ways: 1) By increasing the number of hepatic LDL receptors on the cell surface, thereby improving LDL uptake and catabolism. 2) Through the hepatic synthesis inhibition of very low-density lipoprotein (VLDL), thereby decreasing the total number of VLDL and LDL particles. In 2003, the U.S. Food and Drug Administration (FDA) granted approval to rosuvastatin calcium, indicated for mixed dyslipidemia, isolated hypertriglyceridemia, and primary hypercholesterolemia.
C-reactive protein, an acute phase plasma protein of hepatic and adipocytic origin, is an inflammatory biomarker associated with increased risk of CV events such as MI, stroke, sudden cardiac death, and peripheral vascular disease. It is considered to be a direct contributor to the atherothrombotic process and an important biomarker for the global prediction of vascular event risks.
With the current research suggesting the potential of rosuvastatin in reducing the incidence of cardiovascular events in apparently healthy people with raised high-sensitivity C-reactive protein levels, the statin could serve as a novel preventive option against cardiac ailments in such individuals.
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References
1. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. N Engl J Med. 2008 Nov 20;359(21):2195-2207. Epub 2008 Nov 9.
2. Pai JK, Pischon T, Ma J, et al. Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med. 2004 Dec 16;351(25):2599-610.
3. Ridker PM. Rosuvastatin in the Primary Prevention of Cardiovascular Disease Among Patients With Low Levels of Low-Density Lipoprotein Cholesterol and Elevated High-Sensitivity C-Reactive Protein. Circulation. 2003 Nov 11;108(19):2292-7.
