Elevated plasma galectin-3 is associated with near-term rehospitalization in heart failure: a pooled analysis of 3 clinical trials.

BACKGROUND: Rehospitalization is a major cause for heart failure (HF)-related morbidity and is associated with considerable loss of quality of life and costs. The rate of unplanned rehospitalization in patients with HF is unacceptably high; current risk stratification to identify patients at risk for rehospitalization is inadequate. We evaluated whether measurement of galectin-3 would be helpful in identifying patients at such risk. METHODS: We analyzed pooled data from patients (n = 902) enrolled in 3 cohorts (COACH, n = 592; PRIDE, n = 181; and UMD H-23258, n = 129) originally admitted because of HF. Mean patient age was between 61.6 and 72.9 years across the cohorts, with a wide range of left ventricular ejection fraction. Galectin-3 levels were measured during index admission. We used fixed and random-effects models, as well as continuous and categorical reclassification statistics to assess the association of baseline galectin-3 levels with risk of postdischarge rehospitalization at different time points and the composite end point all-cause mortality and rehospitalization. RESULTS: Compared with patients with galectin-3 concentrations less than 17.8 ng/mL, those with results exceeding this value were significantly more likely to be rehospitalized for HF at 30, 60, 90, and 120 days after discharge, with odds ratios (ORs) of 2.80 (95% CI 1.41-5.57), 2.61 (95% CI 1.46-4.65), 3.01 (95% CI 1.79-5.05), and 2.79 (95% CI 1.75-4.45), respectively. After adjustment for age, gender, New York Heart Association class, renal function (estimated glomerular filtration rate), left ventricular ejection fraction, and B-type natriuretic peptide, galectin-3 remained an independent predictor of HF rehospitalization. The addition of galectin-3 to risk models significantly reclassified patient risk of postdischarge rehospitalization and fatal event at each time point (continuous net reclassification improvement at 30 days of +42.6% [95% CI +19.9%-65.4%], P < .001). CONCLUSIONS: Among patients hospitalized for HF, plasma galectin-3 concentration is useful for the prediction of near-term rehospitalization.

Risk factors for near-term myocardial infarction in apparently healthy men and women.

BACKGROUND: Limited information is available regarding risk factors for the near-term (4 years) onset of myocardial infarction (MI). We evaluated established cardiovascular risk factors and putative circulating biomarkers as predictors for MI within 4 years of measurement. METHODS: We conducted a matched, nested case-control study (252 cases and 499 controls) drawing on 45 735 men and women participating in the Copenhagen City Heart Study and the Copenhagen General Population Study. Established risk factors and 17 putative biomarkers, including inflammation-sensitive plasma proteins (C-reactive protein, fibrinogen, alpha(l)-antitrypsin, complement 3), apolipoproteins (A1, B, E, B/A1 ratio), markers of iron overload (iron, transferrin, transferrin saturation), creatinine, alkaline phosphatase, gamma-glutamyl transpeptidase, and leukocytes (lymphocyte count, neutrophil count, neutrophil/lymphocyte ratio) were assessed. RESULTS: Among women and men, only 13% and 50%, respectively, of those with near-term MI were classified as high risk by Framingham risk score at baseline. After adjustment for established risk factors, odds ratios for near-term MI, which compared highest to lowest quintiles, were 2.87(95% CI 1.51-5.48; P = 0.001) for alpha(l)-antitrypsin, 2.84(1.42-5.67; P = 0.003) for C-reactive protein, 1.97(1.09-3.57; P = 0.03) for creatinine, 1.99(1.09-3.65; P = 0.03) for fibrinogen, and 0.37(0.19-0.73; P = 0.004) for iron. The corresponding odds ratio for all biomarkers combined was 7.24 (3.28-16.0; P < 0.001). CONCLUSIONS: We identified 5 biomarkers associated with increased near-term risk of MI independently of established risk factors. All putative biomarkers combined explained a 7-fold increase in the odds of near-term MI.