Abstract P025: Associations of Fetuin-A with Incident Heart Failure in Participants with and without Diabetes and Insulin Resistance: The Cardiovascular Health Study

Abstract

Background: In animal models, the hepatic secretory protein fetuin-A simultaneously inhibits arterial calcification and causes insulin resistance. Increased calcification and insulin resistance lead to arterial stiffness, an important risk factor for heart failure (HF). The relationship between serum fetuin-A concentrations and HF, and whether it is modified by diabetes or insulin resistance has not been extensively studied. Research Design, Methods, and Objectives: In a prospective study of 4182 community-dwelling participants aged ≥ 65 years, Cox proportional hazards models were used to determine the association of fetuin-A (measured in 1992) with incident HF (followed up through June 2008). Multiplicative interaction terms determined whether diabetes or insulin resistance status modified the association. Results: Mean age was 75 ∓ 5 years, fetuin-A levels were 0.47 ∓ 0.10 g/L, and 1,186 incident HF events occurred during follow-up. In multivariable models adjusting for demographics and CVD risk factors, fetuin-A was not significantly associated with incident HF [HR per SD fetuin-A: 0.97, 95% CI (0.91, 1.04), p-value=0.40] and was not modified by prevalent diabetes status (p-interaction=0.54). However, when prevalent insulin resistant status was defined as previously by the presence of diabetes, or HOMA IR > median (2.22), or obesity (body mass index, kg/m 2 > 30), a significant interaction was observed (p-interaction=0.03). In 1,679 participants with no evidence of insulin resistance by the definition, each SD greater fetuin-A level was associated with a 12% lower risk of HF (95% CI: 2-22%) in a fully adjusted model (Table 1). Conclusions: Future studies should consider the presence of insulin resistance when evaluating the relationship between serum fetuin-A with adverse health outcomes.