Homocysteine and long-term recurrent infarction following an acute coronary syndrome.

BACKGROUND: There are no well-established predictors of recurrent ischemic coronary events after an acute coronary syndrome (ACS). Higher levels of homocysteine have been reported to be associated with an increased atherosclerotic burden. The primary endpoint was to assess the relationship between homocysteine at discharge and very long-term recurrent myocardial infarction (MI). METHODS: 1306 consecutive patients with ACS were evaluated (862 with non-ST-segment elevation ACS [NSTEACS] and 444 with ST-segment elevation myocardial infarction [STEMI]) discharged from October 2000 to June 2003 in a single teaching-center. The relationship between homocysteine at discharge and recurrent MI was evaluated through bivariate negative binomial regression accounting for mortality as a competitive event. RESULTS: The mean age was 66.8 ± 12.4 years, 69.1% were men, and 32.2% showed prior diabetes mellitus. Most of the patients were admitted for an NSTEACS (66.0%). The median (interquartile range) GRACE risk score, Charlson comorbidity index, and homocysteine were 144 (122-175) points, 1 (1-2) points, and 11.9 (9.3-15.6) µmol/L, respectively. In-hospital revascularization was performed in 26.3% of patients. At a median follow-up of 9.7 (4.5-15.1) years, 709 (54.3%) deaths were registered and 779 recurrent MI in 478 (36.6%) patients. The rates of recurrent MI were higher in patients in the upper homocysteine quartiles (p < 0.001). After a multivariate adjustment, homocysteine along its continuum remained almost linearly associated with a higher risk of recurrent MI (p = 0.001) and all-cause mortality (p < 0.001). CONCLUSIONS: In patients with ACS, higher homocysteine levels identified those at a higher risk of recurrent MI at very long-term follow-up.

Factors associated with plasma antigen carbohydrate 125 and amino-terminal pro-B-type natriuretic peptide concentrations in acute heart failure.

BACKGROUND: Plasma amino-terminal pro-B-type natriuretic peptide and antigen carbohydrate 125 levels are positively associated with a higher risk of adverse clinical outcomes in acute heart failure. As a proxy of congestion, antigen carbohydrate 125 has also been proposed as a right-sided heart failure marker. Thus, we aimed to determine in this population the main factors - including echocardiographic right-sided heart failure parameters - associated with antigen carbohydrate 125 and amino-terminal pro-B-type natriuretic peptide. METHODS AND RESULTS: We prospectively included 2949 patients admitted with acute heart failure. Amino-terminal pro-B-type natriuretic peptide and antigen carbohydrate 125 were used as dependent variables in a multivariable linear regression analysis. The mean age of the sample was 73.9±11.1 years; 48.9% were female, 35.8% showed ischaemic aetiology, and 51.6% exhibited heart failure with preserved ejection fraction. The median (interquartile range) for amino-terminal pro-B-type natriuretic peptide and antigen carbohydrate 125 were 4840 (2111-9204) pg/ml and 58 (26-129) U/ml, respectively. In a multivariable setting, and ranked in order of importance (R2), estimated glomerular filtration rate (43.7%), left ventricle ejection fraction (15.1%), age (12.4%) and high-sensitivity troponin T (10.9%) emerged as the most important factors associated with amino-terminal pro-B-type natriuretic peptide. The five main factors associated with antigen carbohydrate 125 were, in order of importance: the presence of pleural effusion (36.8%), tricuspid regurgitation severity (25.1%), age (11.9%), amino-terminal pro-B-type natriuretic peptide (6.5%) and peripheral oedema (4.3%). CONCLUSION: In patients with acute heart failure the main factors associated with amino-terminal pro-B-type natriuretic peptide were renal dysfunction, left ventricle ejection fraction and age. For antigen carbohydrate 125, clinical parameters of congestion and the severity of tricuspid regurgitation were the most important predictors. These results endorse the value of antigen carbohydrate 125 as a useful marker of right-sided heart failure.

CA125 outperforms NT-proBNP in acute heart failure with severe tricuspid regurgitation.

BACKGROUND: In acute heart failure (AHF) with right ventricular dysfunction, the roles of amino-terminal pro-brain natriuretic peptide (NT-proBNP) and carbohydrate antigen 125 (CA125) are poorly understood, and functional tricuspid regurgitation (TR) severity is thought to indicate a poor prognosis. We examined the prognostic abilities of NT-proBNP and CA125 according to TR status among patients with AHF. METHODS: TR severity was assessed during index hospitalization (108 ± 24 h after admission) and classified as none/trivial, mild, moderate, or severe. Multivariable Cox regression analysis was performed to assess how pre-discharge CA125 and NT-proBNP were associated with long-term all-cause mortality relative to TR severity. RESULTS: We prospectively included 2961 patients discharged following hospitalization for AHF (mean age 74 ± 11 years; 49.0% women; 51.8% with left ventricular ejection fraction >50%). Median NT-proBNP was 4823 ng/L (IQR: 2086-9183) and CA125 was 58.1 U/mL (IQR: 25-129). Severe TR was present in 300 patients (10.1%), and 1821 patients (61.5%) died (mean follow-up, 3.3 ± 3.2 years). Multivariate analysis revealed a differential prognostic effect across TR status for both biomarkers (p-value for both interactions<0.05). NT-proBNP was significantly linearly associated with mortality in non-severe TR (p < 0.001), but not in severe TR (p = 0.308). Higher CA125 values were significantly associated with mortality risk in all patients (HR: 1.09; 95% CI:1.03-1.14; p = 0.001), with a greater effect in those with severe TR (HR: 1.28; 98% CI:1.11-1.48; p = 0.001). CONCLUSIONS: In patients with AHF and severe TR, CA125 outperforms NT-proBNP in predicting long-term mortality. In AHF with right ventricular involvement, CA125 may be the preferred biomarker for risk stratification.