Mortality and Health Service Use Following Acute Myocardial Infarction Among Persons with HIV: A Population-Based Study

Abstract

People with HIV have higher rates of acute myocardial infarction (AMI) than HIV-negative individuals. We compared mortality risk and health service use following AMI among people with and without HIV between January 1, 2002, and March 31, 2015. We conducted a population-based study using Ontario's administrative databases. Our primary outcomes were risk of inpatient death and death at 30 days following hospital discharge. In secondary analyses, we compared use of revascularization procedures within 90 days of AMI, as well as readmission or emergency department visits for heart disease and cardiology follow-up within 90 days of discharge. We studied 259,475 AMI patients, of whom 345 (0.13%) were people with HIV. AMI patients with HIV were younger than HIV-negative patients (mean age ± standard deviation: 54.4 ± 10.5 years vs. 69.3 ± 14.3 years). Following multivariable adjustment, the odds ratios for inpatient death and death at 30 days following discharge were 1.04 [95% confidence intervals (CI) 0.64–1.56] and 2.42 (95% CI 1.00–4.92), respectively. In secondary analyses, no differences were observed in receipt of revascularization procedures (hazard ratio (HR) 0.98; 95% CI 0.85–1.12), readmission or emergency department visit for heart disease (HR 1.18; 95% CI 0.85–1.62), or cardiology follow-up (HR 0.88; 95% CI 0.76–1.01). People with HIV experience AMI at younger ages and may be at higher risk of death in the 30 days following hospital discharge, underscoring the importance of targeting modifiable cardiovascular disease risk factors in these patients.

Introduction

Cardiovascular disease is an important cause of morbidity and mortality in people with HIV, accounting for 4.6%–15% of deaths in this population and representing the leading cause of death in individuals over the age of 55 years.^1

–5 Although recent studies have found a decreasing trend in the excess risk of myocardial infarction among people with HIV relative to the general population,^6,7 rates have remained nearly twofold higher in observational studies.^8

–11 Several mechanisms have been proposed for this heightened risk, including HIV-related chronic inflammation and immunosuppression, exposure to certain antiretroviral drugs, and a high prevalence of traditional risk factors for coronary heart disease.^9,12,13 In addition to imparting a higher risk of illness, evidence exists that HIV influences health service use and outcomes following acute myocardial infarction (AMI). A recent analysis of the United States Nationwide Inpatient Sample found that HIV-infected patients with AMI were at greater risk of in-hospital mortality relative to uninfected individuals [adjusted odds ratio 1.36; 95% confidence interval (CI) 1.13–1.64], a finding that was driven, in part, by less use of revascularization procedures in these patients.¹⁴

Analogous population-based studies characterizing outcomes and health service use following hospital discharge for AMI among people with HIV are lacking. These data are important for several reasons. First, a higher risk for death, readmission, or cardiovascular disease-related emergency department room visits among people with HIV in the period shortly following discharge for AMI could reflect disparities in timely access to specialist care for these patients. Second, people with HIV are disproportionately represented in low socioeconomic strata and low-income neighborhoods,^15
–17 findings that are relevant to postmyocardial infarction outcomes in people with HIV because low-income individuals are less likely to receive coronary angiography, cardiac rehabilitation, or cardiologist follow-up than high-income individuals.^18,19 In this context, gaps in health service use and clinical outcomes following AMI in people with HIV warrant examination. Accordingly, we compared postmyocardial infarction outcomes and health service use between adults living with and without HIV in Ontario, Canada.

Materials and Methods

Setting

We conducted a population-based study comparing the risk of death and health service outcomes following incident AMI among people living with and without HIV in Ontario between January 1, 2002, and December 31, 2014. This study was approved by the Research Ethics Board of Sunnybrook Health Sciences Centre, Toronto, Ontario.

Data sources

We used Ontario's administrative health databases, which are securely linked using unique, encoded identifiers and analyzed at the Institute for Clinical Evaluative Sciences (ICES, www.ices.on.ca). We identified adults diagnosed with HIV using the Ontario HIV Database, an administrative data registry of Ontario residents with diagnosed HIV infection, which was generated using a validated case-finding algorithm.²⁰ We obtained hospitalization and emergency department data from the Canadian Institute for Health Information's Discharge Abstract Database and National Ambulatory Care Reporting System, respectively. We used the Ontario Health Insurance Plan database to identify claims for physician services, and used validated disease registries to define the presence of diabetes, hypertension, chronic obstructive pulmonary disease, congestive heart failure, and asthma.^21

–25 We obtained basic demographic data from the Registered Persons Database, a registry of all Ontario residents eligible for health insurance.

Study population

We used the Discharge Abstract Database and National Ambulatory Care Reporting System database to identify all adults aged 18 years and older with incident myocardial infarction during the study accrual period [International Classification of Diseases (ICD-10) codes I20, I21, I22]. The sensitivity, specificity, and positive predictive value of these codes in our databases are ∼90%.²⁶ We established incident cases by selecting only those patients with no prior history of myocardial infarction in our databases since 1991. From within this cohort, we identified individuals who had been diagnosed with HIV using the Ontario HIV Database. Individuals with incident AMI who did not have an HIV diagnosis comprised the control group.

Outcomes

The primary outcomes were (1) inpatient mortality, defined as death occurring in hospital any time before hospital discharge and (2) death at 30 days following hospital discharge among those individuals who survived their admission. In secondary analyses, we compared the cumulative incidence of (1) the first receipt of revascularization procedures within 90 days of AMI; (2) the first readmission or emergency department room visit for cardiovascular disease within 90 days of hospital discharge, and (3) cardiologist follow-up within 90 days of hospital discharge. The specific revascularization procedures we examined were coronary artery bypass graft surgery and percutaneous transluminal coronary angiography. The positive predictive values of codes for these procedures in our databases are 97% and 94%, respectively.²⁷ For each secondary outcome, we excluded all individuals who died during admission and followed the remaining patients from the date of admission (revascularization procedures) or discharge (readmission or emergency department visits for heart disease and cardiology follow-up) for up to 90 days until the occurrence of the outcome, death, or end of follow-up (90 days), whichever occurred first.

Statistical analysis

We computed standardized differences (SD) to examine intergroup balance in the distribution of baseline variables. SD of less than 0.1 indicate good balance between groups for a given covariate.²⁸

For the primary outcomes, we compared the proportion of patients with and without HIV who died during admission and within 30 days of discharge using multivariable penalized logistic regression. Because of the small number deaths, we used penalized logistic regression to minimize small sample bias.²⁹ Next, we computed the cumulative incidence of each secondary outcome and used multivariable Cox proportional hazard models to examine the association between HIV and each secondary outcome, using HIV-negative individuals as the reference group. To assess the contribution of demographic and clinical risk factors for each outcome, we adjusted for these variables in a stepwise manner. Specifically, we adjusted first for age (model 1), next added sex, neighborhood income quintile, and urban versus rural residence (model 2), and finally added comorbidity burden in the preceding year, visit with a cardiologist in the preceding year, and presence of diabetes, hypertension, chronic obstructive pulmonary disease, and congestive heart failure at any time before presentation with myocardial infarction (model 3).

We determined patient socioeconomic status at the neighborhood level using postal code information and Statistics Canada census data. We used the Johns Hopkins Adjusted Clinical Groups Case-Mix System to adjust for differences in comorbidity burden.³⁰ This system uses diagnostic information from administrative databases to describe and predict use of healthcare resources. In this study, we used aggregated diagnosis groups (ADGs), which are clusters of diagnostic codes that are similar in terms of severity and expected persistence. The number of ADGs ranges from 0 to a maximum of 32, with a higher number reflecting a higher level of comorbidity. We also adjusted mortality models for receipt of revascularization procedure during admission and secondary outcome models for length to admission. All analyses were conducted using SAS version 9.3 (SAS institute, Cary, NC).

Results

We studied 259,475 patients with AMI, of whom 345 (0.13%) were people with HIV. Compared with HIV-negative individuals, people with HIV were younger (mean age ± standard deviation: 54.4 ± 10.5 vs. 69.3 ± 14.3; SD = 1.06), and less likely to be female (13.0% vs. 38.3%; SD = 0.6) and rural residents (5.8% vs. 15.2%; SD = 0.31) (Table 1). In addition, with the exception of chronic kidney disease, people with HIV had a lower prevalence of comorbid conditions associated with poor outcomes following AMI and a shorter mean length of hospital stay (7.4 days vs. 9.2 days; SD = 0.14) (Table 1).

Table 1.

Baseline Characteristics of Acute Myocardial Infarction Patients With and Without HIV, 2002–2014

Variable	HIV (n = 345)	Comparison group (n = 259,475)	Standardized difference
Age, mean ± SD	54.4 ± 10.5	69.4 ± 14.3	1.06
Female, n (%)	45 (13.0)	99,308 (38.3)	0.6
Age category, n (%)
<36	1–5	1,873 (0.7)	0.05
36–55	208 (60.3)	49,385 (19.0)	0.93
56–75	116 (33.6)	108,010 (41.6)	0.17
>75	15–20	100,207 (38.6)	0.89
Income quintile, n (%)
1 (lowest)	124 (35.9)	58,322 (22.5)	0.3
2	75 (21.7)	55,227 (21.3)	0.01
3	45 (13.0)	51,082 (19.7)	0.18
4	48 (13.9)	48,579 (18.7)	0.13
5 (highest)	50 (14.5)	45,072 (17.4)	0.08
Rural residence, n (%)
No	324 (93.9)	219,915 (84.8)
Yes	20 (5.8)	39,351 (15.2)	0.31
Number of primary care visits in year before cohort entry, mean ± SD	7.81 ± 9.96	6.96 ± 8.16	0.09
Number of ADGs in 1 year before cohort entry, mean ± SD	5.88 ± 3.79	5.36 ± 3.67	0.14
Diabetes, n (%)	62 (18.0)	82,623 (31.8)	0.32
Hypertension, n (%)	129 (37.4)	171,227 (66.0)	0.6
COPD, n (%)	49 (14.2)	65,124 (25.1)	0.28
CHF, n (%)	19 (5.5)	45,732 (17.6)	0.39
Chronic kidney disease, n (%)	41 (11.9)	32,449 (12.5)	0.02
Seen cardiologist in prior year, n (%)	42 (12.2)	39,727 (15.3)	0.09
Length of stay, mean ± SD	7.4 ± 12.3	9.2 ± 13.3	0.14

ADGs, aggregated diagnosis groups; CHF, congestive heart failure.

Overall, 24 (7.0%) patients with HIV died during their admission, compared with 35,770 (13.8%) HIV-negative individuals (unadjusted odds ratio 0.47; 95% CI 0.30–0.69). Respective figures for death at 30 days following discharge were 7 (2.2%) and 6413 (2.5%) (unadjusted odds ratio 0.76; 95% CI 0.32–1.48). Following multivariable adjustment, the odds ratios for inpatient death and death at 30 days following discharge were 1.04 (95% CI 0.64–1.56) and 2.42 (95% CI 1.00–4.92), respectively (Table 2). In the stepwise regression analysis, age was observed to be the main confounder for the association between HIV and 30-day mortality. Specifically, following adjustment for age, the odds ratio for the association between HIV and death 30 days following discharge was 2.73 (95% CI 1.15–5.45).

Table 2.

Odds Ratio (95% Confidence Interval) for Association of HIV and Inpatient and 30-Day Mortality Following Acute Myocardial Infarction

	Unadjusted	Model 1 ^a	Model 2 ^b	Model 3 ^c
Death during admission	0.47 (0.30–0.69)	1.11 (0.71–1.66)	1.09 (0.69–1.62)	1.04 (0.66–1.56)
Death within 30 days of discharge^d	0.76 (0.32–1.48)	2.73 (1.15–5.45)	2.64 (1.11–5.27)	2.42 (1.00–4.92)

Includes age.

Includes model 1 plus sex, neighborhood income quintile, and rural status.

Includes model 2 plus comorbidity (aggregated diagnosis groups), visit with cardiologist in preceding year, receipt of revascularization procedure during admission, number of primary care physician visits in preceding year, and presence of diabetes, hypertension, chronic obstructive pulmonary disease, and CHF at any time before acute myocardial infarction.

Excludes patients who died during admission.

In secondary analyses, the cumulative incidence of revascularization within 90 days of AMI in people with and without HIV was 0.60 (95% CI 0.55–0.65) and 0.44 (95% CI 0.44–0.44), respectively. Similarly, the cumulative incidence of cardiology follow-up was higher in people with HIV (0.59; 95% CI 0.54–0.65) relative to HIV-negative individuals (0.51; 95% CI 0.50–0.51). In contrast, the cumulative incidence of readmission or emergency department visits for heart disease within 90 days of hospital discharge was lower in people with HIV (0.12; 95% CI 0.09–0.16) relative to HIV-negative individuals (0.15; 95% CI 0.14–0.15). Following multivariable adjustment, there were no differences between people living with and without HIV in receipt of revascularization [adjusted hazard ratio (HR) 0.98; 95% CI 0.85–1.12], readmission, or emergency department visits for heart disease (adjusted HR 1.18; 95% CI 0.85–1.62) or cardiology follow-up (adjusted HR 0.88; 95% CI 0.76–1.01) (Table 3).

Table 3.

Hazard Ratio (95% Confidence Interval) for Association of HIV and Receipt of Cardiac Procedures, Seeing a Cardiologist, and Readmission/Emergency Department Visit for Heart Disease

	Unadjusted	Model 1 ^a	Model 2 ^b	Model 3 ^c
Cardiac procedures
PTCA	1.65 (1.44–1.89)	0.95 (0.83–1.09)	0.92 (0.80–1.06)	0.98 (0.85–1.12)
CABG
Postdischarge cardiologist visit	1.21 (1.05–1.40)	0.90 (0.78–1.04)	0.86 (0.75–1.00)	0.88 (0.76–1.01)
Readmission/ER visit for heart disease	0.81 (0.59–1.12)	1.14 (0.83–1.57)	1.16 (0.84–1.59)	1.18 (0.85–1.62)

Includes age.

Includes model 1 plus sex, neighborhood income quintile, and rural status.

Includes model 2 plus comorbidity (aggregated diagnosis groups), visit with cardiologist in preceding year, length of hospital stay, and presence of diabetes, hypertension, chronic obstructive pulmonary disease, and CHF at any time before acute myocardial infarction.

PTCA, percutaneous transluminal coronary angiography; CABG, coronary artery bypass graft; EM, emergency room.

Discussion

In our population-based study, we observed that AMI patients with HIV were younger, more likely to be men, and had a lower prevalence of illnesses conventionally associated with poor outcomes than HIV-negative patients. It is likely that these differences contributed to the lower crude rate of inpatient mortality among patients with HIV. Similar findings were observed in a population-based study from the United States, where inpatient mortality among myocardial infarction patients with and without HIV was 3.7% and 6.5%, respectively (p < .01).¹⁴ However, we observed no intergroup difference in inpatient mortality following multivariable adjustment, in contrast to a higher risk for people with HIV in the United States study. This discordant finding could be related to differences in the pattern of revascularization procedure use between the two studies. Specifically, we noted greater use of these procedures among patients with HIV, while the opposite was observed in the United States study. The greater use of revascularization procedures among patients with HIV in our study may again reflect the younger age and predominantly male composition of this group, as previous studies have found an inverse association between age and intensive management of acute coronary syndromes and that women are less likely to receive these procedures than men.^31,32

We observed a similar proportion of people with and without HIV who died in the first month following hospital discharge. However, we found an association between HIV and this outcome following adjustment for demographic characteristics and comorbid disease. The most important confounder was patient age, which reversed the association between HIV and death at 30 days. We emphasize that this finding warrants cautious interpretation because of the small number of events. Furthermore, we did not have reliable data regarding smoking in our databases, which is both more common in people with HIV and possibly associated with death in the period immediately following AMI.^16,33 Adjustment for this variable would therefore be expected to attenuate the association between HIV and death. The importance of smoking in the setting of HIV has been highlighted by research showing a population attributable risk for cardiovascular disease of 25% within populations of people with HIV, and that smoking accounts for more years of lost life among people with HIV who smoke than HIV itself.^34,35

In addition, we did not have reliable data on the use of evidence-based treatments for secondary prevention of AMI. Several studies have found that such therapies are underused among people with HIV. In one study, acetylsalicylic acid (ASA) was used among only 51.6% of people with HIV and known coronary heart disease, compared with 65.4% of HIV-negative individuals.³⁶ Similarly, in a different study, the use of high-intensity statin therapy following acute coronary syndrome was lower in people with HIV relative to HIV-negative individuals (15% vs. 45%), a disparity that likely contributed to the persistence of an atherogenic lipid profile in a greater proportion of individuals with HIV during the first 6 months of statin therapy.³⁷ These studies are in agreement with the body of literature demonstrating suboptimal use of therapies for primary prevention of AMI in high risk patients with HIV, including ASA, statins and antihypertensive drugs.^38

–41 Consequently, developing, implementing, and evaluating interventions to optimize primary and secondary prevention of AMI, including smoking cessation, is an increasing priority for people with HIV.

Our findings are strengthened by the population-based nature of our data, thereby allowing us to examine all Ontario residents with AMI during the study period. However, several limitations of our study merit emphasis. We used administrative databases and did not have access to clinical or laboratory data, including CD4 count, smoking, cholesterol levels and type of myocardial infarction. Similarly, we did not have access to reliable medication data. We did not examine long-term mortality in this study; however, we selected inpatient and 30-day postdischarge observation windows to increase the likelihood that death was causally related to AMI and to be consistent with other studies measuring performance-based outcomes for AMI.⁴² Finally, the small number of deaths among people with HIV may have resulted in model overfitting and limited precision.

In conclusion, we found no important disparities in myocardial infarction-related health service use and inpatient mortality among people with and without HIV. Although HIV imparted a more than twofold increased risk in death 30 days following discharge, this finding requires cautious interpretation and external validation because of the small number of events. In light of these findings and the lower age of AMI patients with HIV, research evaluating interventions that target modifiable risk factors for coronary heart disease in these patients is required.

Footnotes

Acknowledgments

This study was funded by the Ontario HIV Treatment Network and the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The sponsors had no role in the design or conduct of the study; in the collection, analysis, or interpretation of the data; or in the preparation, review, or approval of the article. The opinions, results, and conclusions reported in this article are those of the authors and are independent from the funding source. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. T.A. and C.E.K. are supported by a New Investigator Awards from the Canadian Institutes for Health Research-Ontario HIV Treatment Network. A.M.B. is supported by the Fondation Alma and Baxter Ricard Chair in Inner City Health at St. Michael's Hospital, Toronto, Canada, and the University of Toronto. M.L. is the recipient of salary support from Women's College Hospital, the University of Toronto, and the Women's College Research Institute.

Author Disclosure Statement

M.L. has served on advisory boards and spoken at CME events for ViiV Healthcare, Abbvie, Merck Canada, Inc. and Gilead Sciences. For the remaining authors, no conflicts of interest were declared.

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