Galectin-3 and the Development of Heart Failure after Acute Coronary Syndrome: Pilot Experience from PROVE IT-TIMI 22

Abstract

BACKGROUND Galectin-3 is a β-galactoside–binding lectin that has been implicated in cardiac fibrosis and remodeling, is increased in models of failure-prone hearts, and has prognostic value in patients with heart failure (HF). The relationship between galectin-3 and the development of HF after acute coronary syndrome (ACS) is unknown. METHODS In a nested case-control study among patients with ACS in PROVE IT-TIMI 22, we identified 100 cases with a hospitalization for new or worsening HF. Controls were matched (1:1) for age, sex, ACS type, and randomized treatment. Serum galectin-3 was measured at baseline (within 7 days post-ACS). RESULTS Patients who developed HF had higher baseline galectin-3 [median 16.7 μg/L (25th, 75th percentile 14.0, 20.6) vs 14.6 μg/L (12.0, 17.6), P = 0.004]. Patients with baseline galectin-3 above the median had an odds ratio of 2.1 (95% CI 1.2–3.6) for developing HF, P = 0.010. Galectin-3 showed a graded relationship with risk of HF. Cases were more likely to have hypertension, diabetes, prior MI, and prior HF; after adjustment for these factors, this graded relationship with galectin-3 quartile and HF remained significant [adjusted OR 1.4 (95% CI 1.1–1.9), P = 0.020]. When BNP was added to the model, the relationship between galectin-3 and HF was attenuated [adjusted OR 1.3 (95% CI: 0.96–1.9), P = 0.08]. CONCLUSIONS The finding that galectin-3 is associated with the risk of developing HF following ACS adds to emerging evidence supporting galectin-3 as a biomarker of adverse remodeling contributing to HF as well as a potential therapeutic target.

Galectin-3 Predicts Long-Term Cardiovascular Death in High-Risk Patients With Coronary Artery Disease

“…Hence, with the strength of a prospective cohort study design and of a large cohort of consecutively enrolled patients, our data demonstrate that Gal-3 predicts cardiovascular mortality in patients with CAD regardless of the presence or absence of left ventricular systolic dysfunction. This finding is at variance with previous reports in the general population, 24 in smaller CAD cohorts, [13][14][15][16] and in a large cohort of patients with angiographically demonstrated CAD. 32 A prognostic role of Gal-3 on nonfatal cardiovascular events could not, however, be confirmed at variance with previous studies, [13][14][15][16] possibly because in those cohorts most of the effect on cumulative end points was driven by heart failure-related events.…”

“…This finding is at variance with previous reports in the general population, 24 in smaller CAD cohorts, [13][14][15][16] and in a large cohort of patients with angiographically demonstrated CAD. 32 A prognostic role of Gal-3 on nonfatal cardiovascular events could not, however, be confirmed at variance with previous studies, [13][14][15][16] possibly because in those cohorts most of the effect on cumulative end points was driven by heart failure-related events. Another possibility is that adjustment for the Duke CAD Index Score, one of the strongest predictors of cardiovascular events and death in patients with CAD, might have concealed an effect of Gal-3 on these end points in the our study.…”

“…23 Gal-3 was shown to predict all-cause and cardiovascular death, and incident heart failure also in healthy subjects, 19,24,25 in patients with peripheral artery disease, 17 and in those with acute coronary syndrome. In the latter, it also predicted hospitalizations for heart failure, 14 reinfarction, 15 heart failure, and cardiovascular mortality. 13,16 Thus, our findings extend to the patients with CAD, the adverse prognostic role of high Gal-3.…”

The Factors Influencing Galectin-3 Levels in Acute Coronary Syndrome with Decreased Left Ventricular Function

“…Three covariates, LVEF < 45%, RVSP and age, were significant, but in a multivariate model, after excluding RVSP, which predicts 33.2% of LAVI variance, none of the dependent variables remained independently significant. Previous clinical findings showed that serum Gal-3 levels are correlated with LAstructural remodeling (9). Atrial size is an important determinant of AF and patients with larger atria have a higher probability for the initiation and maintenance of rotor-driven fibrillatory activity.…”

Risk Factors of Reсurrent Cardiovascular Events in Patients during Half-year after Acute Myocardial Infarction in the Presence of Obesity

“…Збільшення концентрації креатиніну в плазмі кро-ві на ≥0,5 мг/дл у першу добу госпіталізації підвищує ризик смерті впродовж наступних 12 місяців, а зрос-тання рівня креатиніну в плазмі крові до 1,5-2,4 мг/дл супроводжується збільшенням ризику смерті впро-довж 1-го року після розвитку ГІМ в 2-3 рази [9]. Що стосується галектину-3, у дослідженні PROVE IT-TIMI 22 було показано стійкий зв'язок даного пока-зника з розвитком патологічного ремоделювання міокарда у пацієнтів, які мали гострий коронарний синдром в анамнезі, а також визначено галектин-3 як незалежний маркер прогресування серцевої недо-статності [8]. За даними В.Й.…”