Rosuvastatin, inflammation, C-reactive protein, JUPITER, and primary prevention of cardiovascular disease – a perspective

Abstract

The major public health concern worldwide is coronary heart disease, with dyslipidemia as a major risk factor. Statin drugs are recommended by several guidelines for both primary and secondary prevention. Rosuvastatin has been widely accepted because of its efficacy, potency, and superior safety profile. Inflammation is involved in all phases of atherosclerosis, with the process beginning in early youth and advancing relentlessly for decades throughout life. C-reactive protein (CRP) is a well-studied, nonspecific marker of inflammation which may reflect general health risk. Considerable evidence suggests CRP is an independent predictor of future cardiovascular events, but direct involvement in atherosclerosis remains controversial. Rosuvastatin is a synthetic, hydrophilic statin with unique stereochemistry. A large proportion of patients achieve evidence-based lipid targets while using the drug, and it slows progression and induces regression of atherosclerotic coronary lesions. Rosuvastatin lowers CRP levels significantly. The Justification for Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial was designed after the observation that when both low density lipoprotein and CRP were reduced, patients fared better than when only LDL was lowered. Advocates and critics alike acknowledge that the benefits of rosuvastatin in JUPITER were real. After a review, the US Food and Drug Administration extended the indications for rosuvastatin to include asymptomatic JUPITER-eligible individuals with one additional risk factor. The American Heart Association and Centers of Disease Control and Prevention had previously recognized the use of CRP in persons with “intermediate risk” as defined by global risk scores. The Canadian Cardiovascular Society guidelines went further and recommended use of statins in persons with low LDL and high CRP levels at intermediate risk. The JUPITER study focused attention on ostensibly healthy individuals with “normal” lipid profiles and high CRP values who benefited from statin therapy. The backdrop to JUPITER during this period was an increasing awareness of a rising cardiovascular risk burden and imperfect methods of risk evaluation, so that a significant number of individuals were being denied beneficial therapies. Other concerns have been a high level of residual risk in those who are treated, poor patient adherence, a need to follow guidelines more closely, a dual global epidemic of obesity and diabetes, and a progressively deteriorating level of physical activity in the population. Calls for new and more effective means of reducing risk for coronary heart disease are intensifying. In view of compelling evidence supporting earlier and aggressive therapy in people with high risk burdens, JUPITER simply offers another choice for stratification and earlier risk reduction in primary prevention patients. When indicated, and in individuals unwilling or unable to change their diet and lifestyles sufficiently, the benefits of statins greatly exceed the risks. ...

End-Stage Renal Disease, Inflammation and Cardiovascular Outcomes

“…Several epidemiologic studies have demonstrated that elevated levels of CRP, pentraxin-3 (PTX3), IL-6, and soluble adhesion molecules, such as intercellular adhesion molecule-1 and VCAM-1 are associated with CVD in ESRD patients. The concept that inflammation in general, or specifically CRP, may contribute to vascular risk, was further strengthened by the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin [26] , suggesting that decrease in high-sensitive CRP following rosuvastatin administration was associated with a substantially lower cardiovascular risk, even though cholesterol concentration was normal. In the elderly and ESRD patients on dialysis, the plasma IL-6 level is a stronger predictor of cardiovascular complications and mortality than IL-1β, TNF-α, CRP, or albumin levels.…”

Statins and the Risk of Diabetes Mellitus

“…Следует отметить, что у 77% пациентов, включенных в группу приема ста-тинов, у которых в дальнейшем развился сахарный диа-бет, исходно имелось нарушение толерантности к глю-козе. В отличие от более ранних исследований, одним из критериев для участия в исследовании JUPITER яв-лялось наличие повышенного уровня высокочувстви-тельного СРБ, что также ассоциируется с возрастанием риска развития сахарного диабета [8].…”

Statin use and risk of diabetes mellitus

“…Следует отметить, что у 77% пациентов, включенных в группы статинов, у которых в дальнейшем развился СД, изначально имелось нарушение толерант-ности к глюкозе. В отличие от более ранних исследова-ний, одним из критериев для участия в исследовании JUPITER являлось наличие повышенного уровня высо-коспецифичного СРБ -провоспалительного маркера, увеличение уровня которого ассоциировано с возраста-нием риска развития СД [8].…”