Association of Genetic Variation in Coronary Artery Disease–Related Loci With the Risk of Heart Failure With Preserved Versus Reduced Ejection Fraction

• coronary artery disease
• genetic variation
• heart failure
• risk factors
• ventricular function, left

Heart failure (HF) with preserved ejection fraction (HFPEF) is a common syndrome of increasing prevalence. The observation of the co-occurrence of fluid overload and overt HF in the presence of a normal left ventricular ejection fraction was made >3 decades ago, yet the pathophysiology behind HFPEF is incompletely understood. Currently, the incidence and the hospitalization rates of HF with reduced ejection fraction (HFREF) are declining in the Western world, in part because of better management of coronary artery disease (CAD) and its risk factors.¹ In contrast, the prevalence of HFPEF is increasing, but it is unknown if a changing presentation of CAD may contribute to this trend.¹ Indeed, individuals with HFPEF have a high burden of CAD (as assessed by autopsy and angiographic studies), and CAD may adversely affect the clinical course of HFPEF, but a causal role of CAD in HFPEF development is uncertain.² We used the community-based sample of the Framingham Heart Study to test whether a genetic risk score (GRS) associated with CAD was also associated with HFREF versus HFPEF risk. We further investigated the prognostic importance of a CAD-related GRS in survival after HFPEF and HFREF.

We followed attendees from the Original and Offspring cohorts, who had blood drawn for DNA extraction, from the date of blood draw until the occurrence of HF, death, or the end of …