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.

Change in Alcohol Intake in Relation to Weight Change in a Cohort of US Men with 24 Years of Follow-Up.

OBJECTIVE: The aim of this study was to prospectively investigate the potential effects of alcohol by subtype on reported long-term weight change. METHODS: This study examined changes in alcohol intake (total, wine, light beer, regular beer, and liquor) and simultaneous changes in reported body weight within 4-year periods from 1986 to 2010 from US men in the Health Professionals Follow-Up Study. The study adjusted for age, changes in lifestyle and dietary covariates, and cardiovascular risk factors. RESULTS: The study included observations of 44,603 four-year periods from 14,971 men. Total alcohol, total beer, regular beer, and liquor intakes, modeled as the increase in weight per increase in drinks per day, were each directly associated with moderate weight gain over the 4-year periods, in pounds: total alcohol: 0.23 (0.10 to 0.35); total beer: 0.29 (0.08 to 0.51); regular beer: 0.61 (0.22 to 1.00); and liquor: 0.28 (0.09 to 0.48). Results for wine and light beer were as follows: wine: 0.16 (-0.04 to 0.36) and light beer: -0.38 (-1.07 to 0.08). Results were strongest for men < 55 years old. CONCLUSIONS: Increased alcohol consumption was associated with minor reported weight gain at levels unlikely to be clinically meaningful. Beverage-specific differences were not substantial enough to make dietary recommendations for weight loss or maintenance by beverage type. The greatest risk of weight gain was among men who increased consumption to levels well above moderation.

Associations between metabolic dysregulation and circulating biomarkers of fibrosis: the Cardiovascular Health Study.

AIM: Fibrosis is one postulated pathway by which diabetes produces cardiac and other systemic complications. Our aim was to determine which metabolic parameters are associated with circulating fibrosis-related biomarkers transforming growth factor-ß (TGF-ß) and procollagen type III N-terminal propeptide (PIIINP). METHODS: We used linear regression to determine the cross-sectional associations of diverse metabolic parameters, including fasting glucose, fasting insulin, body mass index, fatty acid binding protein 4, and non-esterified fatty acids, with circulating levels of TGF-ß (n = 1559) and PIIINP (n = 3024) among community-living older adults in the Cardiovascular Health Study. RESULTS: Among the main metabolic parameters we examined, only fasting glucose was associated with TGF-ß (P = 0.03). In contrast, multiple metabolic parameters were associated with PIIINP, including fasting insulin, body mass index, and non-esterified fatty acids (P<0.001, P<0.001, P=0.001, respectively). These associations remained statistically significant after mutual adjustment, except the association between BMI and PIIINP. CONCLUSIONS: Isolated hyperglycemia is associated with higher serum concentrations of TGF-ß, while a broader phenotype of insulin resistance is associated with higher serum PIIINP. Whether simultaneous pharmacologic targeting of these two metabolic phenotypes can synergistically reduce the risk of cardiac and other manifestations of fibrosis remains to be determined.