Abstract
Every cardiovascular clinical trial that has examined the beneficial effects of lowering LDL cholesterol to prevent cardiovascular events has demonstrated residual cardiovascular risk in the interventional treatment group. Residual risk is the term applied to the cardiovascular events (e.g., myocardial infarction, stroke, and cardiovascular death) that occur in spite of being on “optimal” medical therapy. This term is usually applied to secondary intervention studies, i.e., lipid lowering treatments in subjects who have already had at least one cardiovascular event. Studies that described residual risk have attributed it, at least in part, to the fact that the LDLc has not been lowered sufficiently to stop atherosclerotic plaque formation and rupture into the arterial lumen. However, a recent cardiovascular intervention clinical trial which achieved a very low group median LDLc of 30 mg/dl still demonstrated significant residual risk. Of more importance to reducing residual risk may be addressing the ongoing inflammation in the coronary arteries that results in cellular liberation of cytokines and proteases that attack the atherosclerotic plaque’s fibrous cap. Recent studies have shown that inflammation may act independently of LDL to cause cardiovascular events. This article provides evidence that inflammation is the primary cause of residual risk and will need to be treated as aggressively as LDL lowering if CVD events in the post treatment period are to be significantly reduced. Addressing major risk factors including obesity, diabetes, smoking, hypertension and hyperlipidemia are critical to reducing inflammation. Statins and aspirin are the mainstay medications to reduce ongoing inflammation. However, newer pharmaceuticals may also be required to reduce inflammation to undetectable levels. Targeting inflammation to eradicate residual cardiovascular risk will be the next therapeutic challenge facing primary care physicians.
Highlights
Inflammation is a characteristic of all chronic diseases in man
Residual risk is the term applied to the cardiovascular events that occur in spite of being on “optimal” medical therapy
In patients with an acute cardiovascular event treated with statins, it may be difficult to separate the beneficial effects of lowing LDL from the effects of reducing inflammation (i.e., CRP)
Summary
Inflammation is a characteristic of all chronic diseases in man. It is the primary defense mechanism against invading organisms and hostile environmental agents. Eaton have demonstrated that reversal of coronary atherosclerosis occurs when the LDL cholesterol approximates 65 to 70 mg/dl with statin therapy [8] This process has been shown to begin in the carotid artery within one month of initiating statin therapy and continuing at one year and thereafter [9]. All of the pharmaceutical studies demonstrating a beneficial reduction in LDL concentration in reducing cardiovascular events have demonstrated a large remaining group of individuals with residual cardiovascular risk (Figure 1) This risk includes myocardial infarction, thrombotic stroke, acute severe angina, and peripheral vascular occlusion. During the first several years of initiating LDL lowering therapy, many patients continue to experience major cardiovascular events (residual risk)
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