title: Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy Era: Results From the Veterans Aging Cohort Study.
abstract: With improved survival, heart failure (HF) has become a major complication for individuals with human immunodeficiency virus (HIV) infection. It is unclear if this risk extends to different types of HF in the antiretroviral therapy (ART) era. Determining whether HIV infection is associated with HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), or both is critical because HF types differ with respect to underlying mechanism, treatment, and prognosis.
  
  
  
  To investigate whether HIV infection increases the risk of future HFrEF and HFpEF and to assess if this risk varies by sociodemographic and HIV-specific factors.
  
  
  
  This study evaluated 98 015 participants without baseline cardiovascular disease from the Veterans Aging Cohort Study, an observational cohort of HIV-infected veterans and uninfected veterans matched by age, sex, race/ethnicity, and clinical site, enrolled on or after April 1, 2003, and followed up through September 30, 2012. The dates of the analysis were October 2015 to November 2016.
  
  
  
  Human immunodeficiency virus infection.
  
  
  
  Outcomes included HFpEF (EF≥50%), borderline HFpEF (EF 40%-49%), HFrEF (EF<40%), and HF of unknown type (EF missing).
  
  
  
  Among 98 015 participants, the mean (SD) age at enrollment in the study was 48.3 (9.8) years, 97.0% were male, and 32.2% had HIV infection. During a median follow-up of 7.1 years, there were 2636 total HF events (34.6% were HFpEF, 15.5% were borderline HFpEF, 37.1% were HFrEF, and 12.8% were HF of unknown type). Compared with uninfected veterans, HIV-infected veterans had an increased risk of HFpEF (hazard ratio [HR], 1.21; 95% CI, 1.03-1.41), borderline HFpEF (HR, 1.37; 95% CI, 1.09-1.72), and HFrEF (HR, 1.61; 95% CI, 1.40-1.86). The risk of HFrEF was pronounced in veterans younger than 40 years at baseline (HR, 3.59; 95% CI, 1.95-6.58). Among HIV-infected veterans, time-updated HIV-1 RNA viral load of at least 500 copies/mL compared with less than 500 copies/mL was associated with an increased risk of HFrEF, and time-updated CD4 cell count less than 200 cells/mm3 compared with at least 500 cells/mm3 was associated with an increased risk of HFrEF and HFpEF.
  
  
  
  Individuals who are infected with HIV have an increased risk of HFpEF, borderline HFpEF, and HFrEF compared with uninfected individuals. The increased risk of HFrEF can manifest decades earlier than would be expected in a typical uninfected population. Future research should focus on prevention, risk stratification, and identification of the mechanisms for HFrEF and HFpEF in the HIV-infected population.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee2Geriatric Research Education and Clinical Centers, Veterans Affairs Tennessee Valley Healthcare System, Nashville.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Freiberg
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors.forename: Chung-Chou H
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Research Division, Veterans Affairs Connecticut Health Care System, West Haven Veterans Administration Medical Center, West Haven.
authors.forename: Melissa
authors.initials: M
authors.lastname: Skanderson
authors.affiliation: Department of Veterans Affairs Salt Lake City Health Care System, Salt Lake City6Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Patterson
authors.affiliation: Department of Veterans Affairs Salt Lake City Health Care System, Salt Lake City6Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City.
authors.forename: Scott L
authors.initials: SL
authors.lastname: DuVall
authors.affiliation: Research Division, Veterans Affairs Connecticut Health Care System, West Haven Veterans Administration Medical Center, West Haven7Department of Emergency Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Brandt
authors.affiliation: Division of General Internal Medicine, Boston University, Boston, Massachusetts.
authors.forename: Kaku A
authors.initials: KA
authors.lastname: So-Armah
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore11Division of Infectious Diseases, Baltimore Veterans Affairs Health Care System, Baltimore, Maryland12Division of Cardiology, Baltimore Veterans Affairs Health Care System, Baltimore, Maryland.
authors.forename: Kris Ann
authors.initials: KA
authors.lastname: Oursler
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore.
authors.forename: John
authors.initials: J
authors.lastname: Gottdiener
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gottlieb
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles.
authors.forename: David
authors.initials: D
authors.lastname: Leaf
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas15Division of Infectious Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Maria
authors.initials: M
authors.lastname: Rodriguez-Barradas
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.affiliation: Department of Medicine, George Washington University School of Medicine, Washington, DC18Division of Infectious Diseases, Washington DC Veterans Affairs Medical Center, Washington, DC.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Gibert
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia20Division of Infectious Diseases, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia.
authors.forename: David
authors.initials: D
authors.lastname: Rimland
authors.affiliation: Department of Medicine, Veterans Affairs North Texas Health Care System, Dallas.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Bedimo
authors.affiliation: Division of Infectious Diseases, James J. Peters Veterans Affairs Medical Center, Bronx, New York23Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Sheldon T
authors.initials: ST
authors.lastname: Brown
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles24Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California.
authors.forename: Matthew Bidwell
authors.initials: MB
authors.lastname: Goetz
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles25Division of Cardiology, Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California.
authors.forename: Alberta
authors.initials: A
authors.lastname: Warner
authors.affiliation: Department of Medicine, University of Washington School of Medicine, Seattle.
authors.forename: Kristina
authors.initials: K
authors.lastname: Crothers
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Tindle
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Charles
authors.initials: C
authors.lastname: Alcorn
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Bachmann
authors.affiliation: Research Division, Veterans Affairs Connecticut Health Care System, West Haven Veterans Administration Medical Center, West Haven29Department of Medicine, Yale School of Medicine, New Haven, Connecticut.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Justice
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Adeel A
authors.initials: AA
authors.lastname: Butt
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology*; D006333:Heart Failure / Q000453:epidemiology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D040242:Risk Reduction Behavior; D013318:Stroke Volume; D014481:United States / Q000453:epidemiology; D014493:United States Department of Veterans Affairs; D014728:Veterans; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents