title: The association of chronic kidney disease and microalbuminuria with heart failure with preserved vs. reduced ejection fraction.
abstract: 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).
  
  
  
  We defined CKD as glomerular filtration rate <60 mL/min/1.73 m2, 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).
  
  
  
  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.
authors.affiliation: National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.|Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Nayor
authors.affiliation: National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.|Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.affiliation: Data Coordinating Center, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Section of Cardiovascular Medicine, Department of Medicine, Boston University, Boston, MA, USA.
authors.forename: Rajalakshmi
authors.initials: R
authors.lastname: Santhanakrishnan
authors.affiliation: Institute for Clinical Evaluative Sciences, University of Toronto, Toronto, Canada.|Peter Munk Cardiac Centre, University Health Network, Toronto, Canada.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Lee
authors.affiliation: National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.|Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Connie W
authors.initials: CW
authors.lastname: Tsao
authors.affiliation: National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.|Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.affiliation: National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.|Sections of Preventive Medicine & Epidemiology, and Cardiology, Department of Medicine, Boston University School of Medicine, and Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.|Sections of Preventive Medicine & Epidemiology, and Cardiology, Department of Medicine, Boston University School of Medicine, and Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.affiliation: National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.|Center for Population Studies of the National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.affiliation: National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.|Center for Population Studies of the National Heart, Lung, and Blood Institute, Bethesda, MD, USA.|Division of Endocrinology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.affiliation: National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA, USA.|Cardiology Division and Cardiovascular Research Center, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Ho
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006333:Heart Failure / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D012189:Retrospective Studies; D012307:Risk Factors; D013318:Stroke Volume / Q000502:physiology*; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers
keywords: Cardiorenal syndrome; Epidemiology; Heart failure; Kidney disease; Microalbuminuria; Prevention