Editorial comment.

BACKGROUND: Inflammation is important in atherogenesis. Interleukin (IL)-1 is the prototypic inflammatory cytokine. We hypothesized a dysbalance between inflammatory and anti-inflammatory mediators in the IL-1 family in coronary artery disease (CAD) and a possible modulation of these mediators by HMG-CoA inhibitors (statins). METHODS AND RESULTS: In a microarray screening experiment examining peripheral blood mononuclear cells (PBMCs) from 6 CAD patients and 4 healthy control subjects, IL-1beta was identified as 1 of 25 genes whose expression were upregulated in CAD and downregulated by statins. In the following, we studied the role of IL-1beta and related mediators in CAD. Our major findings were as follows. (1) Although mRNA levels of IL-1alpha and IL-1beta were markedly reduced in PBMCs from CAD patients after 6 months of simvastatin (20 mg/d, n=15) and atorvastatin (80 mg/d, n=15) therapy, the reduction in IL-1 receptor antagonist (IL-1Ra) was more modest. Statins also reduced the spontaneous release of IL-1beta and IL-1Ra from PBMCs in CAD patients. (2) mRNA levels of IL-1alpha, IL-1beta, and IL-1Ra were increased in PBMCs from patients with stable (n=20) and unstable (n=20) angina compared with healthy control subjects (n=15). Although the unstable patients had particularly high levels of IL-1beta and IL-1alpha, IL-1Ra was not correspondingly increased. (3) IL-1beta induced release of proatherogenic cytokines from PBMCs, whereas atorvastatin partly abolished this effect. CONCLUSIONS: Our findings suggest that cytokines in the IL-1 family may represent therapeutic targets in CAD. The ability of statins to modulate these cytokines in an anti-inflammatory direction underscores their immunomodulatory potential.

Angina Pectoris↗

PubMed2004

Implication of different cardiac troponin I levels for clinical outcomes and prognosis of acute chest pain patients.

OBJECTIVES: We compared outcomes in patients with non-ST-segment elevation acute coronary syndromes (ACS) according to the degree of cardiac troponin I (cTnI) elevation. BACKGROUND: Controlled trials of high-risk patients have found that troponin elevations identify an even higher risk subset. It is unclear whether outcomes are similar among a lower risk, heterogeneous patient group. Also, few studies have reported outcomes other than myocardial infarction (MI) or death, based on the peak troponin value. METHODS: Consecutively, admitted patients without ST-segment elevation on the initial electrocardiogram underwent serial marker sampling using creatine kinase (CK), CK-MB fraction, and cTnI. Patients were grouped according to peak cTnI: negative = no detectable cTnI; low = peak greater than the lower limit of detectability but less than the optimal diagnostic value; intermediate = peak greater than or equal to the optimal diagnostic value but less than the manufacturer's suggested upper reference limit (URL); and high = peak greater than or equal to the URL. Thirty-day outcomes included cardiac death, MI based on CK-MB, revascularization, significant disease, and a reversible defect on stress testing. Six-month mortality was also determined. Negative evaluations for ischemia included nonsignificant disease, no reversible stress defect, and negative rest perfusion imaging. RESULTS: Of the 4,123 patients admitted, 893 (22%) had detectable cTnI values. Cardiac events and positive test results at 30 days and 6-month mortality increased significantly with increasing cTnI values. Negative evaluations for ischemia were significantly and inversely related to peak cTnI values. Although adverse events were significantly more common in patients with a low cTnI value than in those with negative cTnI, negative evaluations for ischemia were frequent. CONCLUSIONS: Increased cTnI values are associated with worse outcomes. Although low cTnI values are associated with adverse events, they do not have the same implication as higher cTnI values, and nonischemic evaluations are frequent.

Angina Pectoris↗