Association Between HIV Infection and the Risk of Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction in the Antiretroviral Therapy Era

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.

Protease Inhibitors and Cardiovascular Outcomes in Patients With HIV and Heart Failure

“…Indeed, the prevalence of HF in that group was 30% in patients who died as compared with 9% in those patients with HIV who did not die (22). There are limited data on CV mortality in PHIV with HF (10,13). Janjua et al (13) reported increased CV mortality in women living with HIV; however, analyses testing the association of factors such as ART classes with CV outcomes were limited by the small sample and number of outcomes.…”

“…It is therefore plausible that the use of PI-based ART may be associated with adverse outcomes in PHIV with heart failure (HF). Determination of whether PI-based ART regimens affect HF outcomes may be important for the following reasons: 1) the risk of incident HF is increased more than 2-fold among PHIV (10,11) and, as the group of PHIV ages, rates of incident HF are projected to increase dramatically (12); and 2) once HF is established in HIV infection, there is a 4-fold increased risk of being admitted for decompensated HF and a 3-fold increase in CV mortality (13). Therefore, we aimed to study the association between PI use and CV outcomes in PHIV with HF.…”

Prognostic Significance of Baseline Serum Sodium in Heart Failure With Preserved Ejection Fraction

“…If an outpatient HF diagnosis was followed by hospitalization within 48 hours or if the diagnosis was made as an inpatient, the discharge date was used as the index date. As validated before,17, 18, 19 a natural language processing tool was used to extract EF values from text integration utilities documents, including history and physical examination notes, progress notes, discharge summary notes, echocardiography reports, nuclear medicine reports, cardiac catheterization reports, and other cardiology notes. All recorded LVEF values were used for classifying cases as HFpEF.…”

Incidence, Predictors, and Outcomes of Implantable Cardioverter‐Defibrillator Discharge Among People Living With HIV

“…The mechanisms involved in the increase in SCD in PHIV are incompletely understood but are likely related, in part, to the increase in the prevalence of heart failure (HF) and coronary artery disease (CAD) 2, 3, 4. For example, PHIV taking antiretroviral therapy (ART) experience rates of incident HF that are 50% to 200% higher than matched uninfected controls 5, 6, 7. Implantable cardioverter‐defibrillators (ICDs) are a standard intervention for both the primary and secondary prevention of SCD 8, 9.…”