ORLANDO – An elevated circulating galactin-3 level after an acute MI is a potent long-term predictor of both heart failure and mortality, independent of known prognostic markers, Rabea Asleh, MD, PhD, reported at the annual meeting of the American College of Cardiology.
“These findings suggest that galectin-3 measurement may have a role in the risk stratification of patients presenting with MI,” according to Dr. Asleh, an Israeli cardiologist doing a fellowship in advanced heart failure and transplant cardiology at the Mayo Clinic in Rochester, Minn.
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Dr. Rabea Asleh
Galectin-3 is a protein implicated in the development of cardiac fibrosis and pathologic myocardial remodeling. As such, it may be of particular value as a biomarker of key clinical outcomes in these changing times in the epidemiology of acute MI, according to Dr. Asleh.
“The changing clinical presentation of MI necessitates evolution in our approach to risk stratification,” he explained. “Over the last 2 decades we’ve observed a change in the epidemiology of MI, with more patients developing non-ST-elevation MI compared to STEMI. They present at an older age and develop heart failure with preserved ejection fraction more than heart failure with reduced ejection fraction.”
He presented a prospective population-based community cohort study of 1,401 Olmsted County, Minn., residents who had a validated MI during 2002-2012. Their mean age was 67 years, 61% were men, and 79% presented with non-STEMI. During a mean follow-up of 5.3 years, 389 of the participants developed heart failure and 512 patients died.
Galectin-3 was measured a median of 2 days post MI. The median level was 18.4 ng/mL. Patients were divided into tertiles based upon their galactin-3 measurement: Tertile 1 required a post-MI galectin-3 level below 15.2 ng/mL; tertile 2 had a level of 15.2-22.6 ng/mL; and the top tertile was for individuals with a galectin-3 above 22.6 ng/mL.
Of note, patients with a higher galectin-3 level were older, had a higher prevalence of diabetes, hypertension, hyperlipidemia, anterior MI, a higher Killip class, a higher Charlson comorbidity score, and a lower peak troponin T level. They also had a lower estimated glomerular filtration rate; indeed, the median eGFR in the top tertile for galactin-3 was 48 mL/min per 1.73 m2, compared with 68 mL/min in the lowest galectin-3 tertile. Women accounted for 27% of patients in tertile 1, 41% in tertile 2, and fully half of those in tertile 3.
In an unadjusted analysis, the risk of mortality during follow-up was sixfold greater for patients in galectin-3 tertile 3 than in tertile 1; the risk of heart failure was increased 5.5-fold.
More meaningfully, in a Cox multivariate analysis extensively adjusted for age, gender, comorbidities, malignancy, standard cardiovascular risk factors, MI characteristics, eGFR, Killip class, cardiac troponin T, and other potential confounders, patients in galectin-3 tertile 2 had a 1.6-fold increased risk of death and a 1.62-fold increased likelihood of heart failure during follow-up, compared with subjects in tertile 1, Dr. Asleh noted.
Patients in tertile 3 had a 2.4-fold increased risk of death and were at 2.1 times greater risk of heart failure than those in tertile 1. The degree of risk for heart failure associated with elevated galactin-3 was virtually identical for heart failure with preserved as compared with reduced ejection fraction, he added.
Session cochair L. Kristin Newby, MD, of Duke University, Durham, N.C., noted that the Mayo study did not adjust for brain natriuretic peptide (BNP) or N-terminal pro hormone BNP (NT-proBNP), both of which are known to be strong predictors of both heart failure and mortality after acute MI. Doesn’t their absence weaken the strength of galactin-3’s prognostic power as demonstrated in the study? she asked.
Dr. Asleh replied that those biomarkers weren’t collected in this study, which began in 2002.
“What I can tell you is, other studies show there is only a weak correlation between galactin-3 and NT-proBNP post MI. Some studies have even shown an inverse correlation,” he said. “The pathophysiological explanation is that galactin-3 is more implicated in fibrosis before the stage of development of left ventricular loading and stretching of the myocardium. So galactin-3 may be implicated in LV fibrosis leading to heart failure before the NT-proBNP comes into play.”
Also, he cited a study by other investigators conducted in patients with a left ventricular assist device for advanced heart failure. Upon device-induced left ventricular unloading the patients’ NT-proBNP levels dropped significantly while their galactin-3 remained high and unchanged. This suggests the two biomarkers are implicated in different disease pathways.
Both animal and human studies indicate galactin-3 is involved specifically in fibrosis, as opposed to, say, C-reactive protein, a well established marker of systemic inflammation, the cardiologist added.
Dr. Asleh reported having no financial conflicts of interest regarding his study, which was supported by the National Institutes of Health.
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