Alberta Warner

HIV Infection and the Risk of Acute Myocardial Infarction

IMPORTANCE Whether people infected with human immunodeficiency virus (HIV) are at an increased risk of acute myocardial infarction (AMI) compared with uninfected people is not clear. Without demographically and behaviorally similar uninfected comparators and without uniformly measured clinical data on risk factors and fatal and nonfatal AMI events, any potential association between HIV status and AMI may be confounded. OBJECTIVE To investigate whether HIV is associated with an increased risk of AMI after adjustment for all standard Framingham risk factors among a large cohort of HIV-positive and demographically and behaviorally similar (ie, similar prevalence of smoking, alcohol, and cocaine use) uninfected veterans in care. DESIGN AND SETTING Participants in the Veterans Aging Cohort Study Virtual Cohort from April 1, 2003, through December 31, 2009. PARTICIPANTS After eliminating those with baseline cardiovascular disease, we analyzed data on HIV status, age, sex, race/ethnicity, hypertension, diabetes mellitus, dyslipidemia, smoking, hepatitis C infection, body mass index, renal disease, anemia, substance use, CD4 cell count, HIV-1 RNA, antiretroviral therapy, and incidence of AMI. MAIN OUTCOME MEASURE Acute myocardial infarction. RESULTS We analyzed data on 82 459 participants. During a median follow-up of 5.9 years, there were 871 AMI events. Across 3 decades of age, the mean (95% CI) AMI events per 1000 person-years was consistently and significantly higher for HIV-positive compared with uninfected veterans: for those aged 40 to 49 years, 2.0 (1.6-2.4) vs 1.5 (1.3-1.7); for those aged 50 to 59 years, 3.9 (3.3-4.5) vs 2.2 (1.9-2.5); and for those aged 60 to 69 years, 5.0 (3.8-6.7) vs 3.3 (2.6-4.2) (P < .05 for all). After adjusting for Framingham risk factors, comorbidities, and substance use, HIV-positive veterans had an increased risk of incident AMI compared with uninfected veterans (hazard ratio, 1.48; 95% CI, 1.27-1.72). An excess risk remained among those achieving an HIV-1 RNA level less than 500 copies/mL compared with uninfected veterans in time-updated analyses (hazard ratio, 1.39; 95% CI, 1.17-1.66). CONCLUSIONS AND RELEVANCE Infection with HIV is associated with a 50% increased risk of AMI beyond that explained by recognized risk factors.

HIV infection, cardiovascular disease risk factor profile, and risk for acute myocardial infarction

Background:Traditional cardiovascular disease risk factors (CVDRFs) increase the risk of acute myocardial infarction (AMI) among HIV-infected (HIV+) participants. We assessed the association between HIV and incident AMI within CVDRF strata. Methods:Cohort—81,322 participants (33% HIV+) without prevalent CVD from the Veterans Aging Cohort Study Virtual Cohort (prospective study of HIV+ and matched HIV− veterans) participated in this study. Veterans were followed from first clinical encounter on/after April 1, 2003, until AMI/death/last follow-up date (December 31, 2009). Predictors—HIV, CVDRFs (total cholesterol, cholesterol-lowering agents, blood pressure, blood pressure medication, smoking, diabetes) used to create 6 mutually exclusive profiles: all CVDRFs optimal, 1+ nonoptimal CVDRFs, 1+ elevated CVDRFs, and 1, 2, 3+ major CVDRFs. Outcome—Incident AMI [defined using enzyme, electrocardiogram (EKG) clinical data, 410 inpatient ICD-9 (Medicare), and/or death certificates]. Statistics—Cox models adjusted for demographics, comorbidity, and substance use. Results:Of note, 858 AMIs (42% HIV+) occurred over 5.9 years (median). Prevalence of optimal cardiac health was <2%. Optimal CVDRF profile was associated with the lowest adjusted AMI rates. Compared with HIV− veterans, AMI rates among HIV+ veterans with similar CVDRF profiles were higher. Compared with HIV− veterans without major CVDRFs, HIV+ veterans without major CVDRFs had a 2-fold increased risk of AMI (HR: 2.0; 95% confidence interval: 1.0 to 3.9; P = 0.044). Conclusions:The prevalence of optimal cardiac health is low in this cohort. Among those without major CVDRFs, HIV+ veterans have twice the AMI risk. Compared with HIV− veterans with high CVDRF burden, AMI rates were still higher in HIV+ veterans. Preventing/reducing CVDRF burden may reduce excess AMI risk among HIV+ people.

HIV Infection and Cardiovascular Disease in Women

Background HIV infection is associated with increased risk of cardiovascular disease (CVD) in men. Whether HIV is an independent risk factor for CVD in women has not yet been established. Methods and Results We analyzed data from the Veterans Aging Cohort Study on 2187 women (32% HIV infected [HIV+]) who were free of CVD at baseline. Participants were followed from their first clinical encounter on or after April 01, 2003 until a CVD event, death, or the last follow‐up date (December 31, 2009). The primary outcome was CVD (acute myocardial infarction [AMI], unstable angina, ischemic stroke, and heart failure). CVD events were defined using clinical data, International Classification of Diseases, Ninth Revision, Clinical Modification codes, and/or death certificate data. We used Cox proportional hazards models to assess the association between HIV and incident CVD, adjusting for age, race/ethnicity, lipids, smoking, blood pressure, diabetes, renal disease, obesity, hepatitis C, and substance use/abuse. Median follow‐up time was 6.0 years. Mean age at baseline of HIV+ and HIV uninfected (HIV−) women was 44.0 versus 43.2 years (P<0.05). Median time to CVD event was 3.1 versus 3.7 years (P=0.11). There were 86 incident CVD events (53%, HIV+): AMI, 13%; unstable angina, 8%; ischemic stroke, 22%; and heart failure, 57%. Incident CVD/1000 person‐years was significantly higher among HIV+ (13.5; 95% confidence interval [CI]=10.1, 18.1) than HIV− women (5.3; 95% CI=3.9, 7.3; P<0.001). HIV+ women had an increased risk of CVD, compared to HIV− (hazard ratio=2.8; 95% CI=1.7, 4.6; P<0.001). Conclusions HIV is associated with an increased risk of CVD in women.

Prehypertension, Hypertension, and the Risk of Acute Myocardial Infarction in HIV-Infected and -Uninfected Veterans

BACKGROUND Compared to uninfected people, human immunodeficiency virus (HIV)-infected individuals may have an increased risk of acute myocardial infarction (AMI). Currently, HIV-infected people are treated to the same blood pressure (BP) goals (<140/90 or <130/80 mm Hg) as their uninfected counterparts. Whether HIV-infected people with elevated BP have excess AMI risk compared to uninfected people is not known. This study examines whether the association between elevated BP and AMI risk differs by HIV status. METHODS The Veterans Aging Cohort Study Virtual Cohort (VACS VC) consists of HIV-infected and -uninfected veterans matched 1:2 on age, sex, race/ethnicity, and clinical site. For this analysis, we analyzed 81 026 people with available BP data from VACS VC, who were free of cardiovascular disease at baseline. BP was the average of the 3 routine outpatient clinical measurements performed closest to baseline (first clinical visit after April 2003). BP categories used in the analyses were based on criteria of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Analyses were performed using Cox proportional hazards regression. RESULTS Over 5.9 years (median), 860 incident AMIs occurred. Low/high prehypertensive and untreated/treated hypertensive HIV-infected individuals had increased AMI risk compared to uninfected, untreated normotensive individuals (hazard ratio [HR], 1.60 [95% confidence interval {CI}, 1.07-2.39]; HR, 1.81 [95% CI, 1.22-2.68]; HR, 2.57 [95% CI, 1.76-3.76]; and HR, 2.76 [95% CI, 1.90-4.02], respectively). CONCLUSIONS HIV, prehypertensive BP, and hypertensive BP were associated with an increased risk of AMI in a cohort of HIV-infected and -uninfected veterans. Future studies should prospectively investigate whether HIV interacts with BP to further increase AMI risk.

Low referral rate for prophylactic implantation of cardioverter-defibrillators in a tertiary care medical center.

Background: Implantable cardioverter‐defibrillators (ICDs) for primary prevention became standard of care after the publication of the second Multicenter Automatic Defibrillator Implantation Trial (MADIT‐II) and Sudden Cardiac Death in Heart Failure Trial (SCD‐HeFT).

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

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.

Impact of a Multidisciplinary Heart Failure Post-hospitalization Program on Heart Failure Readmission Rates

Background: Specialized chronic heart failure (HF) clinics have demonstrated significant reductions in readmissions. Limited evidence is available regarding HF clinics in the immediate post-discharge period. Objective: To evaluate the effect of a multidisciplinary HF clinic on 90-day readmission rates and all-cause mortality in those recently discharged from a HF hospitalization. Methods: In this retrospective cohort study, patients discharged with a primary HF diagnosis who attended the HF postdischarge clinic in 2010-2012 were compared with controls from 2009. During 6 clinic visits, patients were seen by a physician assistant, clinical pharmacist specialist, and case manager, with care overseen by a cardiologist. The program focused on optimizing therapy, identifying HF etiology/precipitating factors, medication titration, education, and medication adherence. The primary outcome was 90-day HF readmission. A multivariate Cox proportional hazards model was used to compare outcomes. Results: Among the 277 patients (144 clinic, 133 control) in the study, 7.6% of patients in the clinic and 23.3% of patients in the control group were readmitted for HF within 90 days (aHR (adjusted hazard ratio) = 0.17; 95% CI = 0.07-0.41; P < 0.001; ARR (absolute risk reduction) = 15.7%; NNT (number needed to treat) = 7). Clinic patients had lower 90-day time-to-first HF readmission or all-cause mortality (9.0% vs 28.6%; aHR = 0.28; 95% CI = 0.06-0.31; P < 0.001; ARR = 19.6%; NNT = 6). Conclusions: The multidisciplinary HF posthospitalization outpatient program was associated with a significant reduction in 90-day HF readmissions in patients who were recently discharged from a HF hospitalization.

Clinical outcomes of erythropoietin use in heart failure patients with anemia of chronic kidney disease.

BACKGROUND Anemia and chronic kidney disease are common disorders in heart failure (HF) patients and are associated with increased morbidity and mortality. This study assessed clinical outcomes associated with erythropoietin (EPO) treatment in this cardiorenal anemia syndrome (CRAS) population. METHODS AND RESULTS This was a retrospective cohort study of Veterans Affairs patients with CRAS from January 2003 to December 2006. The primary outcome was a composite of death, acute coronary syndrome (ACS), HF, and stroke. Multiple Cox regression modeling was used to evaluate the outcome in patients prescribed (n = 213) and not prescribed EPO (n = 1845). Adjusted incidence of mortality was statistically significantly higher in EPO than in non-EPO users (33.8% vs 19.7%; hazard ratio 1.40, 95% confidence interval 1.06-1.85; P = .02). The unadjusted composite of cardiovascular events/death was higher in the EPO group, but not statistically significant when adjusted for confounders (P = .12). Crude ACS events were documented in 18.8% and 10.8% patients (P = .001), and stroke events occurred in 22.5% and 18.3% patients (P = .14) in EPO and non-EPO groups, respectively. CONCLUSIONS We found that in CRAS patients, EPO use was associated with increased risk of mortality and a trend toward increased cardiovascular events. Therefore, clinicians considering EPO use in CRAS patients should assess whether any potential benefits outweigh the risks of use.

Ambulatory Function in Men with and without HIV Infection: Association with Cardiorespiratory Fitness

Objective: The study purpose was to compare ambulatory function in men with and without HIV infection, and test the association with aerobic exercise capacity. Methods: We conducted a cross-sectional study of 45 HIV-infected men and 37 age and race-matched HIVuninfected men at the Baltimore VA Medical Center. Participants performed cardiorespiratory exercise testing, sixminute walk (6-MW) and the 400-meter long distance corridor walk (LDCW) as part of a study of veterans without history of CVD. Results: The mean (SD) age was 55 (6) years. Among the 82 male participants, 98% were African American race. The 6-MW distance correlated with aerobic exercise capacity (VO2peak) in both HIV-infected subjects (r=0.50, p 0.1). Between HIV groups, there was a significant difference in LDCW (p=0.01) but not in 6-MW (p=0.3). Conclusions: In HIV-infected men without known CVD the 6-MW and LDCW, provide similar estimates of aerobic exercise capacity. The findings are comparable to uninfected men with similar demographic and clinical characteristics, and support endurance walk tests to estimate aerobic exercise capacity in HIV-infected patients.

Impact of a Multidisciplinary Heart Failure Postdischarge Management Clinic on Medication Adherence

PURPOSE Disease management programs have been associated with improved adherence to heart failure (HF) medications. However, there remain limited data on the benefit of a comprehensive multidisciplinary HF postdischarge management (PDM) clinic that promptly follows HF-related hospitalization on evidence-based HF medication adherence. OBJECTIVE The aim of this study was to evaluate the effects of an HF-PDM clinic on adherence to evidence-based HF medication therapy. METHODS In this retrospective cohort study, we identified patients discharged from the Veterans Affairs Greater Los Angeles Healthcare System between 2009 and 2012 with a primary diagnosis of HF. Data from patients who attended the HF-PDM clinic immediately following HF-related hospitalization between 2010 and 2012 were compared with those from historical controls, who did not attend the HF-PDM clinic, from 2009. The main outcome was adherence to evidence-based HF medications during the 90 days after discharge. Adherence was defined as the proportion of days covered at 90 days after discharge (PDC-90) of ≥0.80. The percentages of patients adherent to each medication were compared between the 2 groups using the χ2 test. A logistic regression model adjusted for potential confounding variables was constructed to evaluate the percentages of patients adherent to evidence-based HF medications. FINDINGS A total of 277 patients (144 clinic, 133 control) were included in the study. Both univariate and multivariate analyses showed that the clinic was associated with improved medication adherence to angiotensin-converting enzyme inhibitors, a twice-daily β-blocker, and aldosterone antagonists compared with controls. The most significant increases were in adherence to angiotensin-converting enzyme inhibitors, with mean PDC-90 values of 0.84 (control) versus 0.93 (clinic) (P = 0.008) and 90-day adherence rates of 69% (control) versus 87% (clinic) (P = 0.005). IMPLICATIONS Care in the multidisciplinary HF-PDM clinic was associated with significant increases in 90-day adherence to evidence-based HF medications in patients who were recently discharged after an HF-related hospitalization.