Few studies have explored hospitalization outcome differences between patients who are seropositive for human immunodeficiency virus (HIV) compared to HIV-seronegative patients with acute myocardial infarctions (AMIs). The aim of this study was to explore in-hospital AMI mortality risk in seropositive and seronegative patients. A secondary analysis of the Nationwide Inpatient Sample from 1997 to 2006 was conducted. This sample allows the approximation of all United States hospitalizations. All AMI encounters with and without co-occurring HIV were identified using appropriate International Classification of Diseases and procedure codes. Descriptive and Cox proportional-hazards analyses were then conducted to estimate mortality differences between seropositive and seronegative patients while adjusting for demographic, clinical, hospital, and care factors. The results demonstrated higher AMI hospitalization mortality hazard in seropositive compared to seronegative patients after adjustment for age, gender, ethnicity, medical co-morbidities, hospital type, and number of in-hospital procedures (HR 1.38, 95% confidence interval 1.01 to 1.87, p = 0.04). Stratified analysis demonstrated greater although not statistically significant mortality hazard for non–ST-segment elevation myocardial infarction and ST-segment elevation myocardial infarction in seropositive compared to seronegative patients. Typical AMI care procedures occurred at significantly lower rates in seropositive versus seronegative patients, including thrombolytic and anticoagulant agents (18% vs 22%), coronary arteriography (48% vs 63%), left cardiac catheterization (52% vs 66%), and coronary artery bypass graft (6% vs 14%). In conclusion, additional mortality burden and lower procedure rates occur for HIV-seropositive patients receiving AMI care. Health care providers should be alert to the increased mortality burden when treating seropositive patients with AMI.
Cardiovascular disease remains the leading cause of mortality in the United States despite advancements in medicine, and acute myocardial infarctions (AMIs) contribute significantly to overall cardiovascular disease mortality. Human immunodeficiency virus (HIV)–associated AMI treatment outcomes are important to examine because of the increased risk for AMI in HIV-positive patients related to unique pathophysiologic associations and, paradoxically, greater life expectancy in HIV-positive patients. Some of these pathophysiologic mechanisms include HIV viremia, associated with coronary vessel endothelial irritation, platelet dysfunction, activation of proinflammatory cytokines, and thrombosis from reduced coronary blood flow and ischemia. No study has evaluated the additional burden associated with co-morbid HIV infection on AMI hospitalization outcomes. The objective of this study was to explore in-hospital AMI mortality risk in HIV-positive patients compared to HIV-negative patients.
Methods
Data were obtained from the Nationwide Inpatient Sample (NIS), developed as part of the Healthcare Cost and Utilization Project, a federal-state-industry partnership sponsored by the Agency for Healthcare Research and Quality. The NIS is designed to approximate a stratified 20% sample of all nonfederal, short-term, general, and specialty hospitals serving adults in the United States. The sampling strategy selects hospitals nationwide from the state inpatient database according to defined strata on the basis of ownership, bed size, teaching status, urban or rural location, and region. All discharges from sampled hospitals for the calendar year are then selected for inclusion into the NIS. To allow extrapolation for national estimates, hospital and discharge weights are provided. Detailed information on the design of the NIS is available at http://www.hcup-us.ahrq.gov . From 1997 to 2006, the NIS captured discharge-level information on primary and secondary diagnoses and procedures, discharge vital status, and demographics on discharges by year. Data elements that could directly or indirectly identify patients were excluded; we thus considered all discharge encounters to be independent. The unit of analysis was the discharge or encounter rather than the patient. A unique hospital identifier allows linkage of discharge data to an NIS data set with hospital characteristics.
Our sample included hospitalization events for AMIs from 1997 to 2006 in patients aged 18 to 65 years with >1-day hospital stays recorded for the encounters. To analyze AMI hospitalizations, we identified all discharges for which an International Classification of Diseases, Ninth Revision, Clinical Modification code of 410.xx (AMI) was listed as the primary diagnosis. This approach has been used in other studies and was taken to specifically focus on encounters that presented with acute myocardial ischemia and not those encounters with AMIs secondary to surgery, hypotension, or other events after admission. Total numbers of myocardial infarctions were obtained by summation across all 410.xx International Classification of Diseases, Ninth Revision, Clinical Modification, codes. For encounters with >1 reported code of 410.xx, only the first reported code was used. Similarly, procedure codes for the 10 most common procedures were also identified using the reported International Classification of Diseases, Ninth Revision, Clinical Modification, code. ST-segment elevation AMI (STEMI) and non–ST-segment elevation AMI (NSTEMI) were also identified and coded using appropriate International Classification of Diseases coding. We were careful to account for code changes that occurred in 2005 while extracting the data (single vessel percutaneous transluminal coronary angioplasty or coronary atherectomy with and without a thrombolytic agent; 36.01 and 36.02 were newly added procedures at that time). HIV co-morbidity was identified using the NIS clinical classification software. In-hospital mortality was defined as “died” during the hospitalization encounter in the NIS data set.
We examined the association between in-hospital AMI mortality in HIV-seropositive versus HIV-seronegative AMI encounters. First, the distribution of all study variables was examined for normality. These variables included the primary outcome (AMI mortality) and the primary predictor (HIV serostatus).
Other independent predictors and covariates used for the analysis included (1) sociodemographic characteristics (age, race [white, black, Hispanic, other], primary payer [Medicare, Medicaid, private, other]), (2) dyslipidemia, (3) hospital type, and (4) clinical factors, including medical co-morbidities and procedures performed. Co-morbid medical conditions are defined by the NIS protocol as documented International Classification of Diseases, Ninth Revision, diagnoses and documentation of such conditions.
The number and severity of co-morbid conditions were assessed using Charlson’s co-morbidity index (CCI). We used the modified version of the CCI on the basis of recent work by Quan et al. The CCI is a numerically weighted score composed of 17 co-morbid conditions: congestive heart failure, chronic pulmonary disease, cerebrovascular disease, dementia, diabetes without complications, liver disease, peptic ulcer disease, peripheral vascular disease, rheumatologic disease, hemiplegia or paraplegia, diabetes with complication, malignancy, renal disease, metastatic solid tumor, and HIV/acquired immune deficiency syndrome (excluded here and used as an independent predictor). For the purpose of the multivariate Cox regression analysis, the CCI score was used as a numerical categorical variable. The CCI has been used in HIV and cardiovascular studies as a validated index for acute care outcomes.
We initially conducted tests to rule out collinearity among the predictors and covariates and the final mortality comparison was adjusted for demographic factors, medical co-morbidities, dyslipidemia, hospital type, and in-hospital procedures. Appropriate NIS sampling and design parameters were used during this analysis. All data analyses were conducted using PASW version 18.0 (with the complex samples module; SAS Institute Inc., Cary, North Carolina). Statistical hypotheses were tested using p <0.05 as the level of statistical significance. This study was approved by the Arrowhead Regional Medical Center’s institutional review board.
Results
The frequency and distribution of all study variables are listed in Table 1 . The results demonstrate that most in-hospital encounters for AMI were in patients aged ≥55 years who were white, male, and privately insured. Most AMI encounters occurred in patients with CCI scores ≤2, and the mean length of hospital stay was 5.29 days (SE 0.03). The most common medical co-morbidities for patients with AMI were hypertension (51.0%), diabetes without complications (23.6%), congestive heart failure (19.7%), and chronic pulmonary disease (15.7%). The most common in-hospital AMI-associated procedures reported were left-sided cardiac catheterization (66.0%), coronary arteriography (62.5%), and angiography of left-sided cardiac structures (56.2%). A total of 13.8% had coronary artery bypass grafts, and 22.2% received thrombolytic agents, antiplatelet agents, or anticoagulant agents during the hospitalization event. Dyslipidemia and tobacco use occurred in 41.6% and 29.6% of the sample, respectively. Most AMIs were treated in urban teaching hospital settings (50.2%). There were 5,984 AMI encounters (population adjusted) in patients with co-occurring HIV. Overall AMI encounter mortality was 2.4% in the sample. Finally, STEMI was more common in the sample than NSTEMI (56.2% vs 43.8%).
| Variable | Value |
|---|---|
| Age (years) ⁎ | |
| 18–34 | 2% |
| 35–44 | 12% |
| 45–54 | 34% |
| 55–65 | 53% |
| Mean ± SE | 53.94 ± 0.02 |
| Race/ethnicity | |
| White | 77% |
| African American | 11% |
| Hispanic | 7% |
| Other † | 5% |
| Gender | |
| Male | 72% |
| Female | 28% |
| Primary payer | |
| Medicare | 15% |
| Medicaid | 10% |
| Private (including health maintenance organizations) | 61% |
| Other ‡ | 14% |
| Total in-hospital charge | |
| <$10,000 | 11% |
| $10,000–$49,999 | 65% |
| ≥$50,000 | 24% |
| Length of hospital stay (days), mean ± SE | 5 ± 0.03 |
| CCI score | |
| <1 | 49% |
| 1 | 28% |
| 2 | 13% |
| ≥3 | 10% |
| Mean ± SE | 0.95 ± 0.01 |
| Co-morbid medical conditions | |
| Cancer | 1% |
| Cerebrovascular disease | 3% |
| Chronic pulmonary disease | 16% |
| Congestive heart failure | 20% |
| Connective tissue disease | 1% |
| Dementia | 0.1% |
| Diabetes with complications | 4% |
| Diabetes without complications | 24% |
| Hypertension | 51% |
| Metastatic carcinoma | 0.4% |
| Mild liver disease | 1% |
| Atrial fibrillation or flutter | 7% |
| Moderate to severe liver disease | 0.1% |
| Paraplegia/hemiplegia | 0.4% |
| Peptic ulcer disease | 1% |
| Peripheral vascular disease | 5% |
| Renal disease | 5% |
| Valvular heart disease | 7% |
| Other cardiovascular disease risk factors | |
| Dyslipidemia (International Classification of Diseases, Ninth Revision) | 42% |
| Smoker | 30% |
| Primary in-hospital procedures | |
| Left-sided cardiac catheterization | 66% |
| Coronary arteriography | 63% |
| Angiocardiography of left-sided cardiac structures | 56% |
| Single-vessel percutaneous transluminal coronary angioplasty or coronary atherectomy with or without mention of thrombolytic agent | 35% |
| Insertion of non-drug-eluting coronary artery stent(s) | 28% |
| Injection or infusion of platelet inhibitor | 18% |
| Insertion of drug-eluting coronary artery stent(s) | 14% |
| Extracorporeal circulation auxiliary to open-heart surgery | 11% |
| Single internal mammary coronary artery bypass | 11% |
| Diagnostic ultrasound of heart (echocardiography, transesophageal echocardiography) | 6% |
| Coronary artery bypass grafting | 14% |
| Number of procedures | |
| 0 or 1 | 17% |
| 2 or 3 | 20% |
| 4 or 5 | 26% |
| ≥6 | 38% |
| Mean ± SE | 4.36 ± 0.04 |
| Thrombolytic, antiplatelet, and anticoagulant agents § | 22% |
| Mortality status | |
| Died in-hospital | 2% |
| HIV status | |
| HIV seropositive | 0.2% |
⁎ Sample includes participants in the NIS data set with AMI encounters from 1997 to 2006, aged 18 to 65 years, with >1-day hospital stays recorded for the encounters.
† Asian/Pacific Islander, Native American, and unspecified.
‡ No pay, self-pay, and unspecified.
The associations between study variables and HIV serostatus are listed in Table 2 . The results demonstrate that compared with the seronegative patients, most of the seropositive patients were younger (age <54 years), male (85%), and insured primarily by Medicare and Medicaid (63%). Total costs were slightly higher in the seropositive sample. The mean length of hospital stay was higher in HIV-positive encounters (6 vs 5 days). The co-morbidity burden was also higher in HIV-positive encounters (CCI score 1.14 vs 0.94). The prevalence of the following co-morbidities was higher in seropositive encounters: renal disease (13% vs 5%), mild liver disease, (8% vs 1%), and congestive heart failure (26% vs 19%). Dyslipidemia and tobacco use were significantly lower in seropositive patients. Among seropositive encounters, statistically significant lower procedure rates were also recorded for the most common in-hospital AMI procedures: left-sided cardiac catheterization (52% vs 66%), coronary arteriography (48% vs 63%), and angiography of left-sided cardiac structures (44% vs 56%). Coronary artery bypass grafting was performed at significantly lower rates in seropositive patients (6% vs 14%). Thrombolytic, antiplatelet, and anticoagulant use was also significantly lower in seropositive patients (18% vs 22%). STEMI was more common than NSTEMI in seropositive and seronegative individuals. Overall, in-hospital AMI encounter mortality was higher among seropositive compared to seronegative encounters (4% vs 2%).
| Variable | HIV Seronegative | HIV Seropositive | p Value § |
|---|---|---|---|
| (n = 2,501,904) | (n = 5,984) | ||
| Age (years) ⁎ | <0.001 | ||
| 18–34 | 2% | 6% | |
| 35–44 | 12% | 28% | |
| 45–54 | 34% | 44% | |
| 55–65 | 53% | 22% | |
| Mean ± SE | 54 ± 0.02 | 48 ± 0.27 | |
| Race/ethnicity | <0.001 | ||
| White | 77% | 50% | |
| African American | 11% | 35% | |
| Hispanic | 7% | 10% | |
| Other † | 5% | 5% | |
| Gender | <0.001 | ||
| Male | 72% | 85% | |
| Female | 28% | 15% | |
| Primary payer | <0.001 | ||
| Medicare | 15% | 39% | |
| Medicaid | 10% | 23% | |
| Private (including health maintenance organizations) | 61% | 28% | |
| Other ‡ | 14% | 10% | |
| Total in-hospital charge | 0.03 | ||
| <$10,000 | 11% | 11% | |
| $10,000–$49,999 | 65% | 60% | |
| ≥$50,000 | 24% | 29% | |
| Length of hospital stay (days), mean ± SE | 5 ± 0.03 | 6 ± 0.02 | 0.005 |
| CCI score | <0.001 | ||
| <1 | 49% | 43% | |
| 1 | 28% | 26% | |
| 2 | 13% | 16% | |
| ≥3 | 10% | 15% | |
| Mean ± SE | 0.94 ± 0.01 | 1.14 ± 0.05 | 0.007 |
| Co-morbid medical conditions | |||
| Cancer | 1% | 3% | <0.001 |
| Cerebrovascular disease | 3% | 3% | NS |
| Chronic pulmonary disease | 16% | 14% | NS |
| Congestive heart failure | 20% | 26% | <0.001 |
| Connective tissue disease | 1% | 0.5% | 0.02 |
| Dementia | 0.1% | 1% | <0.001 |
| Diabetes with complications | 4% | 3% | 0.01 |
| Diabetes without complications | 24% | 17% | <0.001 |
| Hypertension | 51% | 46% | <0.001 |
| Metastatic carcinoma | 7% | 3% | <0.001 |
| Mild liver disease | 0.4% | 0.2% | NS |
| Atrial fibrillation or flutter | 1% | 8% | <0.001 |
| Moderate to severe liver disease | 0.1% | 0.3% | 0.05 |
| Paraplegia/hemiplegia | 0.4% | 0.6% | NS |
| Peptic ulcer disease | 1% | 0.6% | NS |
| Peripheral vascular disease | 5% | 3% | 0.01 |
| Renal disease | 5% | 13% | <0.001 |
| Valvular heart disease | 7% | 7% | NS |
| Other cardiovascular disease risk factors | <0.0001 | ||
| Dyslipidemia (International Classification of Diseases, Ninth Revision) | 42% | 25% | |
| Smoker | 30% | 25% | |
| Primary in-hospital procedures | 0.001 | ||
| Left-sided cardiac catheterization | 66% | 52% | <0.001 |
| Coronary arteriography | 63% | 48% | <0.001 |
| Angiocardiography of left-sided cardiac structures | 56% | 44% | <0.001 |
| Single-vessel percutaneous transluminal coronary angioplasty or coronary atherectomy with or without mention of thrombolytic agent | 35% | 24% | <0.001 |
| Insertion of non-drug-eluting coronary artery stent(s) | 28% | 20% | <0.001 |
| Injection or infusion of platelet inhibitor | 18% | 14% | 0.003 |
| Insertion of drug-eluting coronary artery stent(s) | 14% | 13% | NS |
| Extracorporeal circulation auxiliary to open-heart surgery | 11% | 4% | <0.001 |
| Single internal mammary coronary artery bypass | 11% | 5% | <0.001 |
| Diagnostic ultrasound of heart (echocardiography, transesophageal echocardiography) | 6% | 7% | NS |
| Coronary artery bypass grafting (includes 36.10–36.19) | 14% | 6% | <0.001 |
| Number of procedures | 0.009 | ||
| 0 or 1 | 17% | 29% | |
| 2 or 3 | 20% | 19% | |
| 4 or 5 | 26% | 23% | |
| ≥6 | 38% | 29% | |
| Mean ± SE | 4.36 ± 0.04 | 3.71 ± 0.11 | |
| Thrombolytic, antiplatelet, and anticoagulant agents ∥ | 22% | 18% | 0.001 |
| Hospital type | <0.001 | ||
| Rural | 9% | 4% | |
| Urban nonteaching | 41% | 34% | |
| Urban teaching | 50% | 62% | |
| Mortality status | |||
| Died in-hospital | 2% | 4% | <0.001 |
| AMI type | <0.001 | ||
| STEMI | 56% | 50% | |
| NSTEMI | 44% | 50% |
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