Abstract: Objectives. Human immunodeficiency virus (HIV) seropositive individuals are predisposed to acute myocardial infarction (AMI). We sought to evaluate management strategies and outcomes of AMI in patients with HIV in the contemporary era. Methods. We analyzed data from the National Inpatient Sample from 2002 to 2011 for patients admitted with AMI with or without HIV. Propensity-score matching was used to identify HIV seropositive AMI patients with similar characteristics who were managed invasively (cardiac catheterization, percutaneous coronary intervention [PCI], or coronary artery bypass graft surgery [CABG]) or conservatively. The primary outcome was in-hospital all-cause mortality. Results. Among 1,363,570 patients admitted with AMI, 3788 (0.28%) were HIV seropositive. The frequency of HIV diagnosis among AMI patients increased over time (0.20% in 2002 to 0.35% in 2011; P for trend <.001). Patients with HIV had lower odds of invasive management (adjusted odds ratio [OR], 0.59; 95% confidence interval [CI], 0.55-0.65) and were less likely to undergo CABG (OR, 0.66; 95% CI, 0.57-0.76) or receive drug-eluting stents (OR, 0.83; 95% CI, 0.76-0.92) than HIV-seronegative patients. Patients with HIV had higher in-hospital mortality (adjusted OR, 1.36; 95% CI, 1.13-1.64) than those without HIV. In a propensity-matched cohort of 1608 patients with HIV treated for AMI with invasive vs conservative management, invasive management was associated with lower in-hospital mortality (3.0% vs 8.2%; P<.001; OR, 0.34; 95% CI, 0.21-0.56). Conclusions. Disparities exist in management of AMI by HIV status. HIV seropositive patients were less likely to receive invasive management, CABG, and drug-eluting stents, and had higher in-hospital mortality vs patients without HIV.
J INVASIVE CARDIOL 2016;28(10):403-409
Key words: acute coronary syndrome, coronary angiography, human immunodeficiency virus, HIV, myocardial infarction, percutaneous coronary intervention
Human immunodeficiency virus (HIV) infection is present in nearly 1.2 million individuals in the United States (US), with 47,352 new diagnoses of HIV in 2013 alone.1 As a result of improved life expectancy due to advances in antiretroviral therapy, cardiovascular disease has emerged as the third-most common cause of death in HIV-seropositive patients, and the leading cause of death in HIV-seropositive patients age >55 years.2,3 Chronic inflammation associated with HIV viremia, antiretroviral therapy, and conventional cardiovascular risk factors such as smoking, dyslipidemia, and metabolic syndrome may contribute to accelerated atherosclerosis, atherothrombosis, and acute coronary syndromes in these patients. Consequently, the incidence of acute myocardial infarction (AMI) in HIV-seropositive adults is up to 2-fold higher than in the general population.4-11 Although clinical practice guidelines recommend an early invasive strategy in high-risk patients with AMI, contemporary approaches to management of AMI in HIV-seropositive patients have not been reported.12,13 Our objectives were to evaluate the influence of HIV seropositive status on the management of patients presenting with AMI.
Study population. We obtained data from the Healthcare Cost and Utilization Project’s National Inpatient Sample (NIS) from 2002 to 2011.14 The NIS is the largest administrative inpatient health-care database in the US, with discharge-level data from a 20% stratified sample of all US hospitals. Patients with a primary diagnosis of AMI were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes for acute ST-elevation MI (STEMI; code 410.x1) and non-ST elevation MI (NSTEMI; code 410.71). HIV infection was determined by Clinical Classifications Software (CCS) diagnosis code 5, which represents an aggregate of relevant ICD-9 codes into a single diagnosis category.
In-hospital management and outcomes. Invasive management of AMI was defined as in-hospital coronary angiography, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG), identified by ICD-9 and CCS procedure codes. Patients who did not undergo coronary angiography or revascularization were considered to have received conservative management. The primary study outcome was mortality.
Statistical analysis. Categorical variables were reported as percentages and were compared by c2 tests. Continuous variables were reported as mean ± standard deviation and compared using the Student’s t-test. Multivariable logistic regression models were generated to estimate odds ratios (ORs) adjusted for demographics, cardiovascular risk factors, and relevant comorbidities. Changes in proportions over time were tested with the Cochran-Armitage test for linear trend.
To evaluate the association between invasive management and in-hospital outcomes, propensity-score matching was used to generate HIV-seropositive cohorts with similar baseline characteristics who underwent invasive and conservative management of AMI. Propensity-score matching was performed using a 1:1 matching protocol (without replacement) and with a caliper width of 0.2 of the standard deviation of the logit of the propensity score. Covariates in the model included baseline demographics, cardiovascular risk factors, relevant comorbidities, and year of hospitalization.
A total of 1,363,570 patients with a primary diagnosis of AMI satisfied our inclusion criteria (Figure 1). Among patients with MI, a total of 3788 HIV-seropositive patients were identified (0.28%). The frequency of an HIV diagnosis among AMI patients increased over time (0.20% in 2002 to 0.35% in 2011; P for trend <.001) (Figure 2). Baseline characteristics of patients with AMI with and without HIV are displayed in Table 1. Patients with HIV were younger (51.5 ± 9.3 years vs 67.8 ± 14.5 years; P<.001), more likely to be male (82.6% vs 59.7%; P<.001), and less likely to be white (40.3% vs 59.7%; P<.001). Conventional risk factors for coronary artery disease, such as obesity, hypertension, hyperlipidemia, and diabetes mellitus were less common in HIV-seropositive patients vs those without HIV. Kidney disease and substance abuse were more common among HIV-seropositive patients (Table 1). NSTEMI was present in similar proportions of patients with and without HIV (58.9% vs 60.4%, respectively; P=.05).
Invasive management of AMI was performed in a greater proportion of patients with HIV vs patients without HIV in unadjusted analyses (72.9% vs 64.6%, respectively; P<.001) (Table 2). In a model adjusted for demographic and clinical variables and relevant comorbidities, HIV was associated with lower odds of invasive management (adjusted OR, 0.59; 95% confidence interval [CI], 0.55-0.65) and coronary revascularization (adjusted OR, 0.72; 95% CI, 0.67-0.77), with similar findings in both STEMI and NSTEMI subgroups (Table 2). Predictors of invasive management are shown in Table 3. Trends in invasive management for myocardial infarction in patients with and without HIV are shown in Figure 3. Rates of coronary revascularization among patients with HIV and AMI increased from 2002 to 2011 (42% in 2002 to 63% in 2011; P for trend <.001). Among those who underwent revascularization, PCI was performed more frequently in patients with HIV (89.9% vs 82.3%; P<.001; adjusted OR, 1.53; 95% CI, 1.32-1.77) and CABG was performed less frequently (11.5% vs 19.4%; P<.001; adjusted OR, 0.66; 95% CI, 0.57-0.76). HIV-seropositive AMI patients undergoing PCI were significantly less likely to receive a drug-eluting stent than patients without HIV (50.8% vs 59.3%, respectively; P<.001; adjusted OR, 0.83; 95% CI, 0.76-0.92).
In unadjusted analyses, in-hospital mortality was lower among HIV-seropositive AMI patients vs those without HIV (3.7% vs 6.5%, respectively; P<.01). After adjustment for demographic and baseline clinical variables and comorbidities, HIV was associated with an increased risk of in-hospital mortality (adjusted OR, 1.36; 95% CI, 1.13-1.64).
Patients with AMI and HIV who underwent invasive management had lower in-hospital mortality than patients who were managed conservatively (2.0% vs 8.4%; adjusted OR, 0.22; 95% CI, 0.15-0.31). In a propensity-matched cohort of 1608 patients with AMI and HIV (Table 4), invasive management was associated with a lower mortality than conservative management (3.0% vs 8.2%; P<.001; OR, 0.34, 95% CI, 0.21-0.56), a finding that was consistent in STEMI and NSTEMI subgroups (Table 5).
In a nationwide cohort of more than 1.3 million patients with AMI, HIV was present in 0.3% of patients and was independently associated with increased in-hospital mortality. Patients who were HIV seropositive were less likely to receive invasive management, CABG, and drug-eluting stent implantation, with significantly higher in-hospital mortality vs patients without HIV. Although HIV was a negative predictor for an invasive management in multivariate analyses, those who were managed invasively had significantly lower in-hospital mortality vs those managed conservatively. This is the first report detailing in-hospital management and outcomes of HIV-seropositive AMI patients in the US in the contemporary era.
Human immunodeficiency virus is associated with a 1.5-fold to 2-fold increased risk of AMI in large observational studies comparing HIV patients to matched uninfected controls.6,7,9,15 Even without established cardiovascular risk factors, patients with HIV have a 2-fold increased risk for AMI.15 The incidence of AMI in HIV is attributed to accelerated atherosclerosis and a propensity for atherothrombosis, but the mechanisms of these well-described phenomena remain uncertain. Thrombotic events may be related to chronic inflammation associated with HIV viremia, immunosuppression, dyslipidemia, tobacco use, and other cardiovascular risk factors.16,17 Cardiovascular disease may also be an unintended sequelae of treatment with antiretroviral therapy, as exposure to protease inhibitors and other antiretroviral agents has been associated with an increased incidence of AMI.18-20
The frequency of HIV diagnosis in patients with AMI increased steadily from 2002 to 2011. Although a true increase in incidence of HIV-associated AMI cannot be excluded, this finding may also reflect greater numbers of new HIV diagnoses related to revised screening recommendations published during the study period.21
In the present study, AMI patients with HIV were younger, more likely to be men, and had fewer conventional cardiovascular risk factors vs those without HIV. These demographic findings are similar to data reported from other large registries.22-24 In a pooled analysis of 11 prospective and retrospective studies with 2442 HIV-seropositive AMI patients, in-hospital mortality was reported to be 8.0%. Among those who survived to discharge, recurrent AMI occurred in 9.4% over long-term follow-up, with a median of 26 months.25 In contrast, NIS data from 1997-2006 reported in-hospital mortality of 4% in HIV-seropositive individuals with AMI.26 In the present study, we report a similar 3.7% in-hospital mortality rate associated with HIV and AMI in the contemporary era. However, after adjusting for demographic and clinical factors, HIV was associated with an increased hazard for mortality, a finding that is also consistent with prior analyses of NIS data.26
Among HIV-seropositive AMI patients, invasive management was associated with lower in-hospital mortality than conservative management. We also identified disparities in the approach to revascularization in AMI patients with and without HIV. A diagnosis of HIV was associated with a reduced likelihood of invasive management after adjusting for demographic and clinical factors. These data suggest that patient, caregiver, or provider biases may favor conservative management of AMI in the setting of HIV. Concerns regarding risks to interventional cardiologists and other health-care professionals may blunt enthusiasm for invasive procedures in this population. Although rates of HIV seroconversion following exposure are exceedingly low (0.3%), percutaneous injuries remain the most common route of transmission of occupationally acquired HIV.27,28 Alternatively, it is possible that disease severity and the diagnosis of acquired immunodeficiency syndrome (AIDS), the presence of concomitant infectious complications, or other unmeasured covariates in the HIV-seropositive AMI cohort may complicate invasive management, or at least alter the perception of its risks and benefits.
Although rates of PCI increased steadily among HIV-seropositive patients from 2002 through 2011, the proportion of drug-eluting stents implanted remained lower vs patients without HIV. This is a surprising finding given that current generations of drug-eluting stents have low rates of stent thrombosis and in-stent restenosis, superior clinical outcomes to bare-metal stents, and are widely considered the standard of care for management of AMI.29 Furthermore, data from small, single-center case-control studies suggest a benefit of drug-eluting stent vs bare-metal stent in patients with HIV, with reduced major cardiovascular events over long-term follow-up.30 Although lower rates of drug-eluting stent use in HIV-seropositive AMI patients in clinical practice may reflect provider concerns about patient compliance with dual-antiplatelet therapy, this finding warrants further investigation.
Patients with HIV and AMI who were referred for coronary revascularization were also significantly less likely to undergo CABG vs those without HIV, even though 30-day major adverse cardiovascular event rate was similar in HIV-infected patients and matched controls referred for CABG in a small retrospective case-control study.31
Study limitations. There are a number of limitations of this analysis. In small studies, left ventricular systolic dysfunction and HIV treatment without a nucleoside-reverse transcriptase inhibitor were significant predictors of long-term cardiac death after acute coronary syndromes in patients with HIV.32 However, in-hospital medical therapy, including antiplatelet and antiretroviral therapy, and the results of cardiac imaging, including echocardiography and the results of diagnostic coronary angiography, were not available from this administrative dataset. Similarly, CD4 counts and clinical diagnoses of AIDS were not captured in this analysis. Although a number of clinical covariates were available to adjust for treatment strategy in propensity-matched analyses, unmeasured confounding may account for some of the mortality associated with an invasive approach. Given the magnitude of risk reduction observed in this non-randomized study, selection bias cannot be excluded. Finally, long-term outcomes associated with AMI in HIV could not be assessed. Still, this is among the largest analyses of the real-world management of AMI in patients with HIV in the US. These findings highlight the differences in care rendered to individuals with vs without HIV. Additional efforts to reduce mortality and improve the delivery of care are necessary for high-risk patients with comorbid HIV and AMI.
HIV-seropositive patients are at risk for AMI in the absence of traditional cardiovascular risk factors and HIV is independently associated with increased in-hospital AMI mortality. HIV patients were less likely to receive invasive management, drug-eluting stent implantation, or to undergo CABG surgery vs patients without HIV. Among HIV-seropositive patients with AMI, those managed invasively had a significantly lower mortality rate vs those managed conservatively. Patients with HIV and AMI may warrant more aggressive management with invasive risk stratification. Further studies are needed to test these associations.
1. Centers for Disease Control and Prevention. HIV Surveillance Report, 2013; vol. 25. http://www.cdc.gov/hiv/library/reports/surveillance/. Published February 2015. Accessed November 10, 2015.
2. Palella FJ Jr, Baker RK, Moorman AC, et al. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr. 2006;43:27-34.
3. Sackoff JE, Hanna DB, Pfeiffer MR, Torian LV. Causes of death among persons with AIDS in the era of highly active antiretroviral therapy: New York City. Ann Intern Med. 2006;145:397-406.
4. Currier JS, Taylor A, Boyd F, et al. Coronary heart disease in HIV-infected individuals. J Acquir Immune Defic Syndr. 2003;33:506–512.
5. Mary-Krause M, Cotte L, Simon A, Partisani M, Costagliola D, Clinical Epidemiology Group from the French Hospital D. Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men. AIDS. 2003;17:2479-2486.
6. Obel N, Thomsen HF, Kronborg G, et al. Ischemic heart disease in HIV-infected and HIV-uninfected individuals: a population-based cohort study. Clin Infect Dis. 2007;44:1625-1631.
7. Lang S, Mary-Krause M, Cotte L, et al. Increased risk of myocardial infarction in HIV-infected patients in France, relative to the general population. AIDS. 2010;24:1228-1230.
8. Durand M, Sheehy O, Baril JG, Lelorier J, Tremblay CL. Association between HIV infection, antiretroviral therapy, and risk of acute myocardial infarction: a cohort and nested case-control study using Quebec’s public health insurance database. J Acquir Immune Defic Syndr. 2011;57:245-253.
9. Freiberg MS, Chang CC, Kuller LH, et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013;173:614-622.
10. Silverberg MJ, Leyden WA, Xu L, et al. Immunodeficiency and risk of myocardial infarction among HIV-positive individuals with access to care. J Acquir Immune Defic Syndr. 2014;65:160-166.
11. Klein DB, Leyden WA, Xu L, et al. Declining relative risk for myocardial infarction among HIV-positive compared with HIV-negative individuals with access to care. Clin Infect Dis. 2015;60:1278-1280.
12. Anderson JL, Adams CD, Antman EM, et al. 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;61:e179-e347.
13. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;64:e139-e228.
14. Steiner C, Elixhauser A, Schnaier J. The healthcare cost and utilization project: an overview. Eff Clin Pract. 2002;5:143-151.
15. Paisible AL, Chang CC, So-Armah KA, et al. HIV infection, cardiovascular disease risk factor profile, and risk for acute myocardial infarction. J Acquir Immune Defic Syndr. 2015;68:209-216.
16. Boccara F, Lang S, Meuleman C, et al. HIV and coronary heart disease: time for a better understanding. J Am Coll Cardiol. 2013;61:511-523.
17. Farrugia PM, Lucariello R, Coppola JT. Human immunodeficiency virus and atherosclerosis. Cardiol Rev. 2009;17:211-215.
18. Group DADS, Friis-Moller N, Reiss P, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007;356:1723-1735.
19. Group DADS, Sabin CA, Worm SW, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet. 2008;371:1417-1426.
20. Friis-Moller N, Sabin CA, Weber R, et al. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med. 2003;349:1993-2003.
21. Branson BM, Handsfield HH, Lampe MA, et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55:1-17; quiz CE11-14.
22. Brenner DA, Dela Cruz M, Thomas K, et al. Emergency medical service utilization and door-to-balloon time for HIV-infected individuals with ST-elevation myocardial infarction. Int J Cardiol. 2013;168:4808-4809.
23. Perello R, Calvo M, Miro O, et al. Clinical presentation of acute coronary syndrome in HIV infected adults: a retrospective analysis of a prospectively collected cohort. Eur J Intern Med. 2011;22:485-488.
24. Lorgis L, Cottenet J, Molins G, et al. Outcomes after acute myocardial infarction in HIV-infected patients: analysis of data from a French nationwide hospital medical information database. Circulation. 2013;127:1767-1774.
25. D’Ascenzo F, Cerrato E, Biondi-Zoccai G, et al. Acute coronary syndromes in human immunodeficiency virus patients: a meta-analysis investigating adverse event rates and the role of antiretroviral therapy. Eur Heart J. 2012;33:875-880.
26. Pearce D, Ani C, Espinosa-Silva Y, et al. Comparison of in-hospital mortality from acute myocardial infarction in HIV sero-positive versus sero-negative individuals. Am J Cardiol. 2012;110:1078-1084.
27. Henderson DK, Fahey BJ, Willy M, et al. Risk for occupational transmission of human immunodeficiency virus type 1 (HIV-1) associated with clinical exposures. A prospective evaluation. Ann Intern Med. 1990;113:740-746.
28. Do AN, Ciesielski CA, Metler RP, Hammett TA, Li J, Fleming PL. Occupationally acquired human immunodeficiency virus (HIV) infection: national case surveillance data during 20 years of the HIV epidemic in the United States. Infect Control Hosp Epidemiol. 2003;24:86-96.
29. Bangalore S, Kumar S, Fusaro M, et al. Short- and long-term outcomes with drug-eluting and bare-metal coronary stents: a mixed-treatment comparison analysis of 117 762 patient-years of follow-up from randomized trials. Circulation. 2012;125:2873-2891.
30. Ren X, Trilesskaya M, Kwan DM, Nguyen K, Shaw RE, Hui PY. Comparison of outcomes using bare metal versus drug-eluting stents in coronary artery disease patients with and without human immunodeficiency virus infection. Am J Cardiol. 2009;104:216-222.
31. Boccara F, Cohen A, Di Angelantonio E, et al. Coronary artery bypass graft in HIV-infected patients: a multicenter case control study. Curr HIV Res. 2008;6:59-64.
32. D’Ascenzo F, Cerrato E, Appleton D, et al. Prognostic indicators for recurrent thrombotic events in HIV-infected patients with acute coronary syndromes: use of registry data from 12 sites in Europe, South Africa and the United States. Thromb Res. 2014;134:558-564.
From the 1New York University School of Medicine, New York, New York; and 2Medical College of Wisconsin, Milwaukee, Wisconsin.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Bangalore reports grant funds from Abbott Vascular; personal fees from Abbott Vascular, Merck, Gilead, Daiichi Sankyo, and Boehringer Ingelheim; non-financial support from Boston Scientific. The remaining authors report no conflicts of interest regarding the content herein.
Manuscript submitted March 21, 2016 and accepted March 28, 2016.
Address for correspondence: Sripal Bangalore, MD, Director of Research, Cardiac Catheterization Laboratory, Director, Cardiovascular Outcomes Group, Associate Professor of Medicine, New York University School of Medicine, New York, NY 10016. Email: email@example.com