Galectin‐3, Metabolic Risk, and Incident Heart Failure: The ARIC Study

Background It is unclear how metabolic syndrome (MetS) and diabetes affect Gal‐3 (galectin 3) levels and the resulting implications for heart failure (HF) risk. We assessed relationships of MetS and diabetes with Gal‐3, and their joint associations with incident HF. Methods and Results We included 8445 participants without HF (mean age, 63 years; 59% men; 16% Black race) at ARIC (Atherosclerosis Risk in Communities) study visit 4 (1996–1999). We categorized participants as having MetS only, MetS with diabetes, or neither, and by quartiles of MetS severity Z score. We assessed cross‐sectional associations of metabolic risk categories with high Gal‐3 level (≥75th percentile) using logistic regression. We used Cox regression to evaluate combined associations of metabolic risk categories and Gal‐3 quartiles with HF. In cross‐sectional analyses, compared with no MetS and no diabetes, MetS only (odds ratio OR, 1.24 95% CI, 1.10–1.41) and MetS with diabetes (OR, 1.59 95% CI, 1.32–1.92) were associated with elevated Gal‐3. Over a median follow‐up of 20.5 years, there were 1749 HF events. Compared with individuals with neither diabetes nor MetS and with Gal‐3 in the lowest quartile, the combination of MetS with diabetes and Gal‐3 ≥75th percentile was associated with a 4‐fold higher HF risk (hazard ratio, 4.35 95% CI, 3.30–5.73). Gal‐3 provided HF prognostic information above and beyond MetS, NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), high‐sensitivity cardiac troponin T, and CRP (C‐reactive protein) (ΔC statistic for models with versus without Gal‐3: 0.003; P =0.004). Conclusions MetS and diabetes are associated with elevated Gal‐3. The HF risk significantly increased with the combination of greater metabolic risk and higher Gal‐3.