Abstract 12796: Fasting and Post-Load Glucose and Non-Esterified Fatty Acids and Risk of Heart Failure and Its Subtypes in Older Adults

Abstract

Introduction: Glucose and non-esterified fatty acids (NEFA) are myocardial fuels whose fasting and postprandial levels are under different homeostatic regulation. The relationships of fasting and postload glucose and NEFA with incident HF and its subtypes remain incompletely defined. Methods: We hypothesized that fasting and postload glucose and NEFA are positively associated with incident HF in older adults, with postload levels bearing stronger associations. Serum glucose and NEFA levels were measured during fasting and 2 hours post oral glucose tolerance test in the Cardiovascular Health Study. HF with preserved (HFpEF) and reduced ejection fraction (HFrEF) were examined secondarily. Results: Among 2238 people (age 78±4) with median follow-up of 9.9 years, there were 737 HF events (257 classifiable as HFpEF, 197 as HFrEF). After adjustment for demographic and lifestyle factors (main model), both fasting (HR per SD 1.11 [95% CI 1.01-1.23]) and postload (HR per SD 1.14 [1.05-1.24]) glucose was significantly associated with incident HF. No association was seen for fasting or postload NEFA. When adjusted for each other, only postload glucose (HR 1.11 [1.003-1.22]), but not fasting glucose (HR 1.06 [0.94-1.20]), remained associated with HF. Further adjustment for prevalent atherosclerotic cardiovascular disease, atrial fibrillation and other risk factors in the causal pathway did not affect the association for postload glucose, but eliminated that for fasting glucose. There was no interaction by sex, but associations for fasting and postload glucose appeared stronger with higher BMI (p<0.025). Assessment of HF subtypes showed no associations for glucose or NEFA with HFpEF. Both fasting glucose (HR 1.23 [1.03-1.48]) and postload glucose (HR 1.24 [1.07-1.45]) were significantly associated with HFrEF, but relationships disappeared on mutual adjustment. Conclusions: Fasting and postload glucose, but not NEFA, were associated with incident HF, particularly HFrEF. The association proved especially robust for postload glucose, which reflects pancreatic β-cell insufficiency and skeletal muscle decline. Our findings suggest that targeting relevant pathways in these two organ-tissues could offer new approaches for HF prevention in elders.