The association of chronic kidney disease and microalbuminuria with heart failure with preserved vs. reduced ejection fraction

Aims Chronic kidney disease (CKD) and microalbuminuria are associated with incident heart failure (HF), but their relative contributions to HF with preserved vs. reduced EF (HFpEF and HFrEF) are unknown. We sought to evaluate the associations of CKD and microalbuminuria with incident HF subtypes in the community-based Framingham Heart Study (FHS). Methods and results We defined CKD as glomerular filtration rate <60 mL/min/1.73 m(2), and microalbuminuria as a urine albumin to creatinine ratio (UACR) >= 17 mg/g in men and >= 25 mg/g in women. We observed 754 HF events (324 HFpEF/326 HFrEF/104 unclassified) among 9889 FHS participants with serum creatinine measured (follow-up 13 +/- 4 years). In Cox models adjusted for clinical risk factors, CKD (prevalence = 9%) was associated with overall HF [hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.01-1.51], but was not significantly associated with individual HF subtypes. Among 2912 individuals with available UACR (follow-up 15 +/- 4 years), 192 HF events (91 HFpEF/93 HFrEF/8 unclassified) occurred. Microalbuminuria (prevalence = 17%) was associated with a higher risk of overall HF (HR 1.71, 95% CI 1.25-2.34) and HFrEF (HR 2.10, 95% CI 1.35-3.26), but not HFpEF (HR 1.26, 95% CI 0.78-2.03). In cross-sectional analyses, microalbuminuria was associated with LV systolic dysfunction (odds ratio 3.19, 95% CI 1.67-6.09). Conclusions Microalbuminuria was associated with incident HFrEF prospectively, and with LV systolic dysfunction cross-sectionally in a community-based sample. In contrast, CKD was modestly associated with overall HF but not differentially associated with HFpEF vs. HFrEF. The mechanisms responsible for the relationship of microalbuminuria to future development of HFrEF warrant further investigation.