Coronary Artery Disease and Heart Failure With Preserved Ejection Fraction: The ARIC Study

Abstract

Background Whether coronary artery disease (CAD) is a significant risk factor for heart failure (HF) with preserved ejection fraction (HFpEF) is unclear. Methods and Results Among 9902 participants in the ARIC (Atherosclerosis Risk in Communities) study, we assessed the association of incident CAD with subsequent incident HFpEF (left ventricular ejection fraction [≥50%]) and HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction <50%) using survival models with time-updated variables. We also assessed the extent to which echocardiographic correlates of prevalent CAD account for the relationship between CAD and incident HFpEF. Over 13-year follow-up, incident CAD developed in 892 participants and 178 subsequently developed HF (86 HFrEF, 71 HFpEF). Incident HFrEF and HFpEF risk were both greatest early after the CAD event. At >1 year post-CAD event, adjusted incidence of HFrEF and HFpEF were similar (7.2 [95% CI, 5.2-10.0] and 6.7 [4.8-9.2] per 1000 person-years, respectively) and CAD remained predictive of both (HFrEF: hazard ratio, 2.76 [95% CI, 1.99-3.84]; HFpEF: 1.85 [1.35-2.54]) after adjusting for demographics and common comorbidities. Among 4779 HF-free participants at Visit 5 (2011-2013), the 490 with prevalent CAD had lower left ventricular ejection fraction and higher left ventricular mass index, E/e', and left atrial volume index (all P<0.01). The association of prevalent CAD with incident HFpEF post-Visit 5 was not significant after adjusting for echocardiographic measures, with the greatest attenuation observed for left ventricular diastolic function. Conclusions CAD is a significant risk factor for incident HFpEF after adjustment for demographics and common comorbidities. This relationship is partially accounted for by echocardiographic alterations, particularly left ventricular diastolic function.

Keywords: atherosclerosis; coronary artery disease; diastolic function; echocardiography; heart failure with preserved ejection fraction.

Figure 1. Study design.

A, Design of Analysis 1 (analysis of incident CAD as a risk factor for subsequent incident HF) and Analysis 2 (analysis of echocardiographic correlates of CAD). B, Derivation of study sample from overall ARIC cohort for Analysis 1 and 2. ARIC indicates Atherosclerosis Risk in Communities; CAD, coronary artery disease; echo, echocardiogram; EF, ejection fraction; and HF, heart failure.

Figure 2. Incidence of HFrEF and HFpEF following CAD event.

Cumulative incidence of HFrEF (blue) and HFpEF (red) after CAD diagnosed by MI or revascularization. CAD indicates coronary artery disease; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; and MI, myocardial infarction.

Figure 3. Risk of incident HFrEF and HFpEF associated with incident CAD compared to no CAD.

Analysis 1 hazard ratios for incident CAD as a risk factor for incident HFrEF and HFpEF events occurring >1 year afterward. Models are adjusted for age, combined self‐reported race and sex variable, hypertension, atrial fibrillation, stroke, eGFR, and BMI, with current/prior smoking, diabetes, and field center as stratification factors. Boxes represent the hazard ratios, and the horizontal lines indicate the 95% CIs. The vertical dashed line marks a hazard ratio of 1. Blue represents the hazard ratios for all HFrEF and HFpEF events. Red represents sex subgroups and green represents self‐reported race subgroups. BMI indicates body mass index; CAD, coronary artery disease; eGFR, estimated glomerular filtration rate; HFpEF, heart failure with preserved ejection fraction; and HFrEF, heart failure with reduced ejection fraction.