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Original Investigation
May 2017

Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy EraResults From the Veterans Aging Cohort Study

Author Affiliations
  • 1Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 2Geriatric Research Education and Clinical Centers, Veterans Affairs Tennessee Valley Healthcare System, Nashville
  • 3Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • 4Research Division, Veterans Affairs Connecticut Health Care System, West Haven Veterans Administration Medical Center, West Haven
  • 5Department of Veterans Affairs Salt Lake City Health Care System, Salt Lake City
  • 6Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City
  • 7Department of Emergency Medicine, Yale University School of Medicine, New Haven, Connecticut
  • 8Division of General Internal Medicine, Boston University, Boston, Massachusetts
  • 9Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
  • 10Department of Medicine, University of Maryland School of Medicine, Baltimore
  • 11Division of Infectious Diseases, Baltimore Veterans Affairs Health Care System, Baltimore, Maryland
  • 12Division of Cardiology, Baltimore Veterans Affairs Health Care System, Baltimore, Maryland
  • 13Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles
  • 14Department of Medicine, Baylor College of Medicine, Houston, Texas
  • 15Division of Infectious Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
  • 16Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington
  • 17Department of Medicine, George Washington University School of Medicine, Washington, DC
  • 18Division of Infectious Diseases, Washington DC Veterans Affairs Medical Center, Washington, DC
  • 19Department of Medicine, Emory University School of Medicine, Atlanta, Georgia
  • 20Division of Infectious Diseases, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia
  • 21Department of Medicine, Veterans Affairs North Texas Health Care System, Dallas
  • 22Division of Infectious Diseases, James J. Peters Veterans Affairs Medical Center, Bronx, New York
  • 23Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
  • 24Division of Infectious Diseases, Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California
  • 25Division of Cardiology, Veterans Affairs Greater Los Angeles Health Care System, Los Angeles, California
  • 26Department of Medicine, University of Washington School of Medicine, Seattle
  • 27Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 28Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
  • 29Department of Medicine, Yale School of Medicine, New Haven, Connecticut
  • 30Department of Medicine, Weill Cornell Medical College, New York, New York
JAMA Cardiol. 2017;2(5):536-546. doi:10.1001/jamacardio.2017.0264
Key Points

Question  Does HIV infection increase the risk of heart failure with reduced ejection fraction, heart failure with preserved ejection fraction, or both, and do these risks vary by age, race/ethnicity, HIV–specific biomarkers, and receipt of antiretroviral therapy?

Findings  In this cohort study of 98 015 veterans, individuals with HIV infection had a 61% increased risk of heart failure with reduced ejection fraction (ejection fraction <40%), a 21% increased risk of heart failure with preserved ejection fraction (ejection fraction ≥50%), and a 37% increased risk of borderline heart failure with preserved ejection fraction (ejection fraction 40%-49%) compared with uninfected veterans. These risks are significant, even after adjusting for possible confounders, and the association between HIV infection and types of heart failure varies by age, race/ethnicity, HIV–specific biomarkers, and receipt of antiretroviral therapy.

Meaning  A strategy that encompasses HIV infection treatment, heart failure risk factor prevention and management, and the development of heart failure risk stratification tools would be beneficial for this high-risk population.

Abstract

Importance  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.

Objectives  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.

Design, Setting, and Participants  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.

Exposure  Human immunodeficiency virus infection.

Main Outcomes and Measures  Outcomes included HFpEF (EF≥50%), borderline HFpEF (EF 40%-49%), HFrEF (EF<40%), and HF of unknown type (EF missing).

Results  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.

Conclusions and Relevance  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.

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