Illustrating that Inflammation is Important in the Progression of Atherosclerosis

Atherosclerosis is a condition of macrophage dysfunction. Macrophages are responsible for clearing the excess and oxidized cholesterol that finds its way into blood vessel walls, but they falter at this task with advancing age. In part this is due to the inflammatory environment, which induces changes in the behavior of macrophages, tipping the balance of activities away from repair and towards further amplication of inflammatory signaling. The research noted here demonstrates the relevance of chronic inflammation to the progression of atherosclerosis in a population of patients on statins, looking at risk of subsequent cardiovascular mortality based on inflammatory status.

Once a patient is on statin therapy, cardiologists typically describe two conditions: "residual cholesterol risk" which can be further reduced with additional lipid-lowering therapy, and "residual inflammatory risk" which can be further reduced with certain drugs that impact vascular inflammation. Whether clinicians should choose to focus on further lowering cholesterol or inflammation has been uncertain and controversial.

Researchers examined data from three recently conducted clinical trials (PROMINENT, REDUCE-IT and STRENGTH) of patients with or at high risk for atherosclerotic disease to understand the relative importance of "residual inflammatory risk" as compared to "residual cholesterol risk" among contemporary statin-treated patients. All patients were receiving aggressive guideline directed medical care including statins, usually at high doses. But cardiovascular event rates in all three trials approached 10 percent at five years. In all three trials, blood levels of high-sensitivity C-reactive protein (hs-CRP, a measure of vascular inflammation) were significantly associated with major adverse cardiovascular events (MACE), cardiovascular mortality, and all-cause mortality.

Moreover, the researchers report that hs-CRP was a more potent predictor of future cardiovascular risk than LDL-cholesterol. For example, among aggressively treated patients already on higher intensity statins, the risks of cardiovascular death and all-cause mortality were more than twice as high among those with the highest levels of CRP when compared to those with the highest levels of cholesterol, differences that were highly statistically significant. Treatments that aggressively lower vascular inflammation need to be incorporated into daily practice if doctors are to maximize patient outcomes.


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