Statin Reduces C-Reactive Protein and Interleukin-6 in Normocholesterolemic Patients with Acute Coronary Syndrome

Abstract

Many evidences suggest that atherosclerosis is an inflammatory disease and inflammatory markers can be an important prognostic factors in acute coronary syndrome. Hydroxymethylglutaryl (HMG-CoA) reductase inhibitors (statins) have been shown anti-inflammatory property that are independent of lipid-lowering effects. We evaluated the effects of 2-month treatment with simvastatin (40 mg/d, n=20) on plasma levels of circulating high-sensitivity C-reactive protein (hsCRP), inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6], and adhesion molecules [p-selectin and monocyte chemotactic peptide (MCP)-1] with placebo group (n=20) in 40 normocholesterolemic patients (LDL＜130 mg/dl) with acute coronary syndrome. Simvastatin therapy significantly reduced plasma levels of total cholesterol and LDL-cholesterol (p=0.05, p=0.02, respectively) compared with placebo group. Simvastatin therapy also significantly reduced plasma levels of hsCRP and IL-6 (p=0.03, p=0.03, respectively) compared with placebo group. But, the reduction of hsCRP and IL-6 levels with simvastatin was unrelated to the degree of LDL-cholesterol's reduction. The effect of simvastatin on the reduction of hsCRP and IL-6, but not on the other inflammatory cytokines and adhesion molecules, have potential implications in the management of acute coronary syndrome with normocholesterolemia.

Obesity indices and inflammatory markers in obese non-diabetic normo- And hypertensive patients. a comparative pilot study

“…Hypolipemic treatment led to significant decrease of hsCRP and IL-6 mean serum levels but without any impact on TNF-α serum concentration. These findings are in agreement with previously published data [38][39][40]. All the authors cited above observed a similar impact of statins or fibrates on hsCRP and IL-6 without changing plasma or serum levels of TNF-α [38][39][40].…”

“…These findings are in agreement with previously published data [38][39][40]. All the authors cited above observed a similar impact of statins or fibrates on hsCRP and IL-6 without changing plasma or serum levels of TNF-α [38][39][40]. Hypolipemic treatment might also have an impact on obtained results in the groups divided according hsCRP level.…”

“…Although TNF-α is also synthesized by adipocytes, its metabolism is not so directly associated with CRP as that of IL-6 [40]. These observations might also suggest that statins may act via different immune mechanisms in obesity-related chronic inflammation [40][41][42][43].…”

“…It is well documented that IL-6 is produced by adipocyte tissue in proportion to fat mass and hsCRP plasma levels are also associated with adipose tissue [40]. However, it was not established whether fibrates reduced hsCRP directly by their impact on the liver or on the vascular bed [38].…”

“…It is well known that CRP synthesis is also IL-6 dependent, so that decrease of IL-6 plasma levels in subjects receiving statins might also be partially responsible for reduction of plasma hs-CRP concentrations, but one cannot exclude a direct impact of statins on inhibition of CRP synthesis independently from IL-6 [40]. Although TNF-α is also synthesized by adipocytes, its metabolism is not so directly associated with CRP as that of IL-6 [40]. These observations might also suggest that statins may act via different immune mechanisms in obesity-related chronic inflammation [40][41][42][43].…”