T2238C ANP gene variant and risk of recurrent acute coronary syndromes in an Italian cohort of ischemic heart disease patients.

BACKGROUND: The role of C2238/atrial natriuretic peptide (ANP) minor allele, at the T2238C ANP gene variant, as a predisposing risk factor for acute cardiovascular events, has been previously reported. We aimed at evaluating, by a retrospective approach, the long-term impact of C2238/ANP-minor allele carrier status toward the risk of recurrent acute coronary syndromes (re-ACS) in an Italian cohort of ischemic heart disease patients. METHODS: A total of 379 patients (males = 80.5%; mean age = 62.5 ±â€Š9.2 years) presenting with ACS were retrospectively analyzed. Mean follow-up was 5.1 ±â€Š3.5 years (range 1-26 years). Occurrence of new episodes of unstable angina, non-ST-segment elevation myocardial infarction and STE myocardial infarction over the years was recorded and compared between subjects not carrying and carrying C2238/ANP-minor allele. RESULTS: At univariate analysis, C2238/ANP-minor allele carrier status and treatment with beta-blocker, aspirin and statin were associated with risk of re-ACS. Multivariate analysis confirmed that hypercholesterolemia (P < 0.0001) and C2238/ANP-minor allele carrier status (P < 0.05) were both significantly and independently associated with increased risk of re-ACS. Both treatments with beta-blocker and with statin were significantly associated with reduced risk of re-ACS (P = 0.01 and P < 0.01, respectively). Age above 55 years was associated with recurrence of ACS in C2238/ANP-minor allele carriers (hazard ratio 1.427, 95% confidence interval 1.066-1.911, P = 0.017). Kaplan-Meier curves confirmed highest risk of new events occurrence in C2238/ANP-minor allele carriers (P = 0.035). CONCLUSIONS: The present results demonstrate that C2238/ANP-minor allele carrier status is an independent risk factor for ACS recurrence in an Italian cohort of ischemic heart disease patients over the long term, and they support the role of C2238/ANP-minor allele as a negative prognostic factor in coronary artery disease patients.

Prediction of long-term survival in chronic heart failure by multiple biomarker assessment: a 15-year prospective follow-up study.

BACKGROUND: In chronic heart failure (CHF), several plasma biomarkers identify subjects at risk of death over the midterm. However, their long-term predictive value in the context of other candidate predictors has never been assessed. This information may prove valuable in the management of a chronic disease with a long natural history, as CHF is today. HYPOTHESIS: We aimed to assess the very-long-term prognostic power of a set of biomarkers to identify CHF patients at highest risk for all-cause mortality. METHODS: A group of 106 consecutive outpatients with CHF (85 male and 21 female, median age 56 y) was followed for 15 years. Echocardiographic tracings and blood samples were collected at study entry to evaluate cardiac function, plasma atrial natriuretic peptide (ANP), aldosterone, and erythropoietin, and plasma renin activity. The relationships between biomarkers, clinical and echocardiographic variables, and mortality were assessed. RESULTS: After 15 years, 86 of the 106 patients (81%) had died. Multivariate analysis showed that ANP was the best independent predictor of survival over several clinical, echocardiographic, and humoral variables (hazard ratio: 5.62, 95% confidence interval: 3.37-9.39, P < 0.001 for plasma levels < median value of 71 pg/mL). Plasma renin activity and erythropoietin provided prognostic information in univariate analysis, but lost their predictive power when adjusted for covariates. CONCLUSIONS: The present study represents the longest available follow-up of patients with CHF evaluating the prognostic power of multiple biomarkers. It shows that a simple assessment of plasma ANP levels is the strongest long-term predictor of death in all stages of heart failure.