Fasting and Post-Load Glucose and Non-Esterified Fatty Acids and Risk of Heart Failure and Its Subtypes in Older Adults

BACKGROUND: Glucose and non-esterified fatty acids (NEFA) are myocardial fuels whose fasting and post-prandial levels are under different homeostatic regulation. The relationships of fasting and post-load glucose and NEFA with incident heart failure (HF) remain incompletely defined. METHODS: Serum glucose and NEFA were measured during fasting and 2 hours post-oral glucose tolerance test, performed in Cardiovascular Health Study participants not receiving hypoglycemic medication. Participants with prevalent HF or lacking relevant data were excluded. Outcomes were incident HF (primary), and HF with preserved (HFpEF) and reduced (HFrEF) ejection fraction (secondary). RESULTS: Among 2 238 participants (age 78 ± 4) with a median follow-up of 9.9 years, there were 737 HF events. After adjustment for demographic and lifestyle factors, both fasting (hazard ratio [HR] = 1.11 per SD [95% confidence interval {CI} = 1.01-1.23], p = .040) and post-load (HR = 1.14 per SD [1.05-1.24], p = 0.002) glucose were significantly associated with incident HF. No association was seen for fasting or post-load NEFA. Upon mutual adjustment, only post-load glucose (HR = 1.11 [1.003-1.22], p = .044), but not fasting glucose (HR = 1.06 [0.94-1.20], p = .340), remained associated with HF. Further adjustment for cardiovascular disease and other risk factors in the causal pathway did not affect the association for post-load glucose, but eliminated that for fasting glucose. Associations for fasting and post-load glucose appeared stronger with higher adiposity and were observed specifically for HFrEF but not HFpEF. CONCLUSIONS: Fasting and post-load glucose, but not NEFA, were associated with incident HF. The association was especially robust for post-load glucose, suggesting that pathways involved in post-prandial dysglycemia could offer new targets for HF prevention late in life.