Abstract
Introduction: Diabetes and metabolic syndrome (MetS) confer an increased risk of heart failure (HF) through poorly understood mechanisms. Galectin-3 (Gal-3) is a marker of fibrosis linked to greater HF risk. The inter-relationships among diabetes, MetS and Gal-3, and related implications for HF risk, are not well understood. Hypothesis: Diabetes and MetS are associated with elevated Gal-3, and high Gal-3 indicates greater HF risk among those with diabetes or MetS. Methods: We included 8,445 participants (mean age 63, 59% male, 21% Black) at ARIC Visit 4 (1996-1999) without baseline HF. We categorized participants by metabolic risk (no diabetes/no MetS; MetS only; diabetes with or without MetS), and Gal-3 levels (gender-specific quartiles). We assessed the associations of metabolic risk categories with high Gal-3 (≥75 th percentile) using logistic regression. We used Cox regression to evaluate associations of cross-categories of metabolic risk group and Gal-3 quartiles with incident HF. Results: In cross-sectional analyses, those with MetS were more likely to have elevated Gal-3 levels than those with no diabetes or MetS (OR 1.29, 95%CI 1.13-1.47). The additional presence of diabetes did not change the likelihood of elevated Gal-3 (OR 1.29, 95%CI 1.08-1.55). Over 20.5 years of follow-up, there were 1,611 HF events. Higher Gal-3 was associated with higher HF risk in each metabolic risk group, and higher metabolic risk group was associated with greater HF risk in each Gal-3 quartile. There was no interaction between Gal-3 and metabolic risk group on HF risk ( P =0.15). The combination of diabetes &MetS and high Gal-3 was associated with an almost 5-fold higher risk of incident HF (HR 4.93; 95% CI: 3.77 - 6.44) than the combination of no diabetes/MetS and low Gal-3 (first quartile) ( Table ). Conclusions: MetS was associated with higher levels of Gal-3. Metabolic risk group and Gal-3 provided powerful complementary prognostic information regarding HF risk. Fibrosis likely plays a role in the development of HF linked to metabolic risk.
