Galectin-3, a Marker of Cardiac Fibrosis, Predicts Incident Heart Failure in the Community

Study Questions:

Do galectin-3 (Gal-3) elevations precede the development of incident heart failure (HF)?

Methods:

This study included patients (n = 3,353) without HF who were enrolled in the Framingham Offspring Cohort. Echocardiograms were completed in 2,425 patients. HF was defined according to Framingham criteria, regardless of left ventricular ejection fraction (LVEF). Plasma Gal-3 levels were measured prior to HF diagnosis (1995-1999), and crude HF incidence rates were estimated based on sex-specific Gal-3 quartiles. Adjusted Cox proportional hazards (hazard ratio [95% confidence interval]) were calculated for mortality based on Gal-3 quartiles.

Results:

The mean cohort age was 59 years, and 53% were female. Median [interquartile range] Gal-3 levels were higher in women (14.3 [12-16.8]) than in men (13.1 [11.1-15.4]) (p < 0.05). Levels were also higher in those who were older and in those with a larger body mass index, lower estimated glomerular filtration rate (eGFR), or a previous history of hypertension or coronary disease (p < 0.0001). At baseline, Gal-3 was not associated with EF, but was positively correlated with LV mass. After a mean follow-up of 8 years, there were 166 (5.1%) incident HF events. A 1-standard deviation increase in Gal-3 was associated with an adjusted 1.23 [1.04-1.47] increased risk of incident HF. There were 468 deaths (14% of the cohort). Each standard deviation increase in Gal-3 was associated with an adjusted 1.14 [1.02-1.27] increased risk of death. The highest quartile of Gal-3 had a 60% increased risk of mortality compared with the lowest quartile. The c-statistic was marginally increased when adding Gal-3 to a model containing B-type natriuretic peptide (BNP) (0.785-0.786).

Conclusions:

The authors concluded that higher levels of Gal-3 are associated with incident HF development.

Perspective:

Gal-3 is a lectin (carbohydrate binding) protein that has been shown to be a mediator of fibrosis. Gal-3 is elevated in a number of conditions associated with fibrosis, including cirrhosis, pulmonary fibrosis, and HF, and levels are higher in females and those with lower eGFR. While Gal-3 added little to risk stratification when traditional risks (including BNP, hypertension, coronary artery disease, and smoking history) were included in modeling, the predictive nature of elevated Gal-3 levels highlights the indolent nature of cardiac fibrosis and the transition from stage A/B HF to stage C. The next step is to determine if pharmacotherapy and lifestyle intervention improves outcomes in patients with elevated Gal-3 levels.

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound, Hypertension

Keywords: Risk, Life Style, Coronary Artery Disease, Follow-Up Studies, Ventricular Function, Left, Galectin 3, Heart Diseases, Incidence, Biological Markers, Heart Failure, Glomerular Filtration Rate, Pulmonary Fibrosis, Hypertension, Echocardiography


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