Plaque stability and the southern European paradox.

Differences between European countries in coronary heart disease mortality were initially described in the 20th century, and albeit less dramatic than first reported, these differences remain substantial. Three main hypotheses have been proposed to explain the so-called "Mediterranean paradox": a) underestimation of coronary heart disease mortality due to methodological flaws; b) the "lag time" hypothesis, and c) the traditional Mediterranean diet and lifestyle. In this manuscript we present and discuss another possible explanation for the Mediterranean paradox related to the higher prevalence and and incidence of stable atheromatous plaques in this area.

A comparative study of biomarkers for risk prediction in acute coronary syndrome-Results of the SIESTA (Systemic Inflammation Evaluation in non-ST-elevation Acute coronary syndrome) study.

OBJECTIVE: We compared the 1-year predictive value of several inflammatory and non-inflammatory biomarkers in ACS patients. METHODS: In 610 patients (73.0% male)--36.0% unstable angina (UA) and 64.0% NSTEMI--we assessed high-sensitivity C-reactive protein (hs-CRP), interleukins 6, 10 and 18, soluble CD40 ligand, P- and E-selectin, NT-proBNP, fibrinogen and cystatin C at hospital admission. Two outcomes at 1-year follow up were selected for analysis: (1) all-cause death, MI, UA, or coronary revascularization, and (2) all-cause death, and non-fatal MI. The effect of biomarker levels on endpoints was examined by the Cox proportional hazards model, and their discrimination ability with the C statistic (AUC). RESULTS: Of 549 patients (90.0%) who completed the 1-year follow up, 206 (37.5%) and 54 (8.9%) reached the first and second composite endpoints, respectively. None of the biomarkers studied improved prediction of the first endpoint. However, considered as continuous variables, and in combination, NT-proBNP and fibrinogen, increased the AUC from 0.64 (95% CI 0.55-0.72) to 0.73 (95% CI 0.64-0.81; p=0.02) for prediction of the second endpoint. Cut-off values for NT-proBNP and fibrinogen, regarding best sensitivity and specificity for prediction of the secondary endpoint were 1043.9 ng/L and 4.47 mg/dL, respectively. For these cut-off points, sensitivity, specificity, positive predictive value and negative predictive value were 40.5% vs 59.5%, 83.3% vs 67.1%, 18.8% vs 14.9% and 93.5% vs 94.4% for NT-proBNP and fibrinogen, respectively. CONCLUSION: In ACS patients, inflammatory biomarkers offer modest incremental information to that provided by clinical risk markers. Fibrinogen and NT-proBNP measurements, however, improve cardiovascular risk prediction.

Plasma cystatin C for prediction of 1-year cardiac events in Mediterranean patients with non-ST elevation acute coronary syndrome.

OBJECTIVE: Evaluation of renal function (RF) is important for management of patients with non-ST elevation acute coronary syndrome (NSTE-ACS). Cystatin C, a sensitive marker of RF, appears to be also a marker of cardiovascular risk. Little is known regarding its predictive role in NSTE-ACS patients. METHODS: We assessed 525 patients taking part in the "Systemic Inflammation Evaluation in patients with NSTE-ACS" (SIESTA) study. Patients were subdivided in quartiles according to cystatin C plasma concentrations (mg/L), i.e., Q1<0.81; Q2=0.81-0.92; Q3=0.93-1.10; Q4>or=1.11. Glomerular filtration rate (eGFR) was estimated using the modification of diet in renal disease (MDRD) equation. The study end-point was the composite of cardiac death, non-fatal myocardial infarction and unstable angina at 1-year follow up. RESULTS: Few patients (0.8%) had severely impaired RF (MDRD<30ml/min/1.73m(2)). 157 patients reached (30%) the study end-point. Patients in Q3 and Q4 showed a higher cumulative probability of cardiac events compared to patients in the lowest quartile. On multivariable analysis, patients in Q3 and Q4 had an increased incidence of cardiac events (adjusted HR=1.57 95%CI 1.04-2.49; p=0.036). Patients with TIMI risk score >or=3 or in-hospital heart failure were also at higher risk for acute cardiac events. Conventional markers of RF, i.e., serum creatinine and eGRF, were not predictors for the study end-point. CONCLUSIONS: Increased levels of cystatin C were an independent predictor of cardiac events at 1-year follow up in this contemporary series of Mediterranean patients with NSTE-ACS.

Elevated serum neopterin levels and adverse cardiac events at 6 months follow-up in Mediterranean patients with non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Little information exists regarding the prognostic role of biomarkers of inflammation in Mediterranean patients. High C-reactive protein and neopterin levels - a marker of macrophage activation - predict cardiovascular events in stable angina patients and patients with acute coronary syndromes (ACS). We sought to assess whether plasma neopterin levels predict adverse clinical outcomes in Mediterranean patients with non-ST elevation (NSTE) ACS, i.e. unstable angina (UA) and NSTE myocardial infarction (MI). METHODS: We prospectively assessed 397 patients (74% men) admitted with NSTEACS, 147 (37%) had unstable angina and 250 (63%) NSTEMI. Blood samples for neopterin and CRP assessment were obtained at admission. The study endpoint was the composite of cardiac death, acute myocardial infarction and unstable angina at 180 days. RESULTS: Baseline neopterin concentrations (nmol/L) were similar in unstable angina and NSTEMI patients (8.3 [6.6-10.7] vs. 7.9 [6.2-10.9]; p=0.4). Fifty-nine patients (14.9%) had events during follow-up. Twenty-nine (21.5%) patients with neopterin levels in the highest third experienced the combined endpoint, compared to 30 (11.5%) patients with neopterin levels in the second and the lowest thirds (log-rank 7.435, p=0.024). On multivariable hazard Cox regression, neopterin (highest vs. 1st and 2nd thirds, HR 1.762, 95% CI [1.023-3.036]) was independently associated with the combined endpoint. CONCLUSION: Increased neopterin levels are an independent predictor of 180-day adverse cardiac events in Mediterranean patients with NSTEACS.