Coronary artery bypass grafting outcomes of patients with human immunodeficiency virus: a population-based study of National Inpatient Sample from 2015 to 2020

Individuals affected by human immunodeficiency virus (HIV) have a growing demand for coronary artery bypass grafting (CABG) due to heightened risk for cardiovascular diseases and extended life expectancy. However, CABG outcomes in HIV patients are not well-established, with insights only from small case series studies. This study conducted a comprehensive, population-based examination of in-hospital CABG outcomes in HIV patients. Patients underwent CABG were identified in National Inpatient Sample from Q4 2015–2020. Patients with age < 18 years and concomitant procedures were excluded. A 1:5 propensity-score matching was used to address preoperative group differences. Among patients who underwent CABG, 613 (0.36%) had HIV and were matched to 3119 out of 167,569 non-HIV patients. For selected HIV patients, CABG is relatively safe, presenting largely similar outcomes. After matching, HIV and non-HIV patients had comparable in-hospital mortality rates (2.13% vs. 1.67%, p = 0.40). Risk factors associated with mortality among HIV patients included previous CABG (aOR = 14.32, p = 0.01), chronic pulmonary disease (aOR = 8.24, p < 0.01), advanced renal failure (aOR = 7.49, p = 0.01), and peripheral vascular disease (aOR = 6.92, p = 0.01), which can be used for preoperative risk stratification. While HIV patients had higher acute kidney injury (AKI; 26.77% vs. 21.77%, p = 0.01) and infection (8.21% vs. 4.18%, p < 0.01), other complications were comparable between the groups.


Preoperative variables
Preoperative variables were compared between patients with and without HIV as shown in Tables 1 and 2. Table 1 includes patients' sex, age, race and ethnicity, socioeconomic status, primary payer status, hospital characteristics, transfer status, and admission status.The average household income from the patient's ZIP code was estimated and then used to stratify the patients into four quartiles based on the income of their neighborhood.Hospital characteristics included hospital bed size, location, and teaching status.Hospital bed sizes were stratified into small, medium, and large based on the American Hospital Association's yearly survey of hospitals as well as the hospital's location and teaching status.Table 2 includes the patient's comorbidities and relevant diagnoses.Elixhauser comorbidities are a set of common comorbidities measured in administrative databases 14 .The patient's comorbidities were identified by Elixhauser measure as well as by additional ICD-10-CM codes as listed in Table S1 14 .

Postoperative variables
In-hospital outcomes after CABG were examined (Table 3).The outcomes included mortality, major adverse cardiovascular event (MACE), myocardial infarction (MI), stroke, transient ischemic attack (TIA), neurological complications, pericardial complications, pacemaker implantation, cardiogenic shock, respiratory complications, mechanical ventilation, acute kidney injury (AKI), post-procedural renal failure, venous thromboembolism (VTE), pulmonary embolism (PE), hemorrhage/hematoma, infection, sepsis, deep wound complication, superficial wound complication, vascular complication, diaphragmatic paralysis, and reopen surgery for bleeding control.MACE was defined as MI, stroke, postprocedural, cardiogenic shock, postprocedural heart failure, and/ or postprocedural cardiac insufficiency.In addition, transfer out rate, time from admission to operation, hospital length of stay (LOS), and total hospital charge were examined.The ICD10-CM/PCS codes were used to define these outcomes, as listed in Table S2.

Statistical analysis
Fisher's exact test was used to compare the pre-operative variables between patients with and without HIV.To account for the preoperative differences between the HIV and non-HIV cohorts as well as their significant differences in sample sizes, a propensity-score matching was conducted between the two groups in a 1:5 ratio (HIV: non-HIV) using the Greedy Matching algorithm with a 2% caliper.After the matching, Fisher's exact test was used to compare postoperative outcomes that were binary.Two-tailed independent t-tests were used to compare continuous outcomes.
In addition, among HIV patients, risk factors associated with in-hospital mortality were identified by a multivariable logistic regression model with stepwise backward selection.Multicollinearity tests were then used to confirm the independency of the identified risk factors, indicated by tolerance > 0.20 and condition index < 10.
All statistical analyses were conducted using SAS, version 9.4.A p-value less than 0.05 was defined as statistically significant.The authors had full access to the dataset and took responsibility for the integrity of all analyses.Given this retrospective study used a de-identified NIS dataset, the study was not considered a human-subject study and was exempted from Institutional Review Board (IRB) review at The George Washington University.Informed patient consent was therefore not required.All methods were performed in accordance with the relevant guidelines and regulations of The George Washington University.

Ethics approval
This study was exempt from the IRB approval by The George Washington University as it analyzed retrospective, deidentified NIS data.

Results
Between the last quarter of 2015 and 2020, 613 (0.36%) patients with HIV underwent CABG, who were matched to 3,119 out of 167,569 patients who did not have HIV.

Discussion
This study conducted a population-based analysis of the in-hospital outcomes of CABG among patients affected by HIV.Patients with HIV had more demographic/socioeconomic disparities and comorbid burdens.After propensity-score matching, patients with HIV had higher AKI and infection, as well as higher transfer rates and hospital charges.However, mortality and other complications were comparable between HIV and non-HIV patients.Risks associated with in-hospital mortality among HIV patients included previous CABG, chronic pulmonary disease, advanced renal failure, and peripheral vascular disease.
In the US, approximately 1.2 million individuals, representing about 0.3% of the population, are living with HIV 15 .While care for individuals with HIV has received increased attention, research on CABG outcomes for this group remains very limited, likely due to their low representation in the population which constrains meaningful analysis with adequate statistical power.For instance, previous studies have shown that the prevalence of HIV among those undergoing any cardiac surgery was a mere 0.2% 8,9 .However, Polanco et al. revealed that the proportion of HIV patients in cardiac surgeries doubled from 0.1 to 0.2% between 2000 and 2010, likely due to the expansion of effective antiviral treatment 9 .While a previous study found HIV patients to be less likely to undergo CABG 13 , this study, which used the latest NIS dataset from 2015 to 2020, found the prevalence of HIV among CABG patients to be as high as 0.36%.This significant difference in representation may suggest an ongoing increase in the accessibility of CABG for HIV patients, aligning with the trend found by Polanco et al. 9 .However, it is also worth considering that the use of the more granular ICD-10 coding system in this study could offer better identification of HIV patients compared to the ICD-9 system used in previous NIS studies 8,9 .
Patients with HIV have an increased risk of developing cardiovascular diseases by 50-100% 16 .This elevated risk can be attributed to inherent HIV-related factors such as chronic inflammation and platelet dysfunction as well as side effects from antiretroviral therapies, including hypertension, hyperlipidemia, and metabolic syndrome [4][5][6][7][8] .For instance, our study revealed a markedly higher prevalence of complicated hypertension among HIV patients by almost one-third.Furthermore, this study found demographic and socioeconomic disparities that might be linked to the development of CAD in HIV-positive individuals.HIV patients were more likely to be African Americans or come from lower-income neighborhoods, both of which have been recognized as independent risk factors for CAD [17][18][19] .Additionally, the HIV cohort in this study exhibited higher rates of drug abuse and tobacco usage, which are well-established contributors to cardiovascular diseases [20][21][22] .
Previous small case series studies did not find any differences in short-or mid-term mortality rates between HIV and non-HIV patients undergoing CABG [10][11][12] .However, these conclusions can be significantly constrained by the small sample sizes, which range from only 5 to 26 HIV patients [10][11][12] .Larger-scale national registry studies also found no disparities in in-hospital mortality following cardiac surgeries for both cohorts, but these studies did not differentiate CABG from other cardiac procedures 8,9,13 .This study aligns with these findings, noting no significant mortality differences between the HIV and non-HIV groups.However, the unique strength of this study lies in its expansive, population-based dataset.This allowed for the identification of risk factors associated with in-hospital mortality in HIV patients, which can enhance pre-operative risk stratification for these patients set to undergo CABG.
Although various case series studies found similar short-and mid-term morbidities after CABG for HIV and non-HIV patients [10][11][12] , Boccara et al. found HIV patients might be at a higher risk for long-term MACE, primarily due to an increased risk for repeated revascularization 10 .In the present study, most in-hospital complications, including MACE, were comparable between the HIV and non-HIV cohorts.However, HIV patients exhibited elevated risks for AKI and infections.The heightened infection risk among HIV patients after surgery is expected, given their compromised immune response.The predisposition of HIV patients to AKI can be attributed to factors such as immunodeficiency, immune system reconstitution, or the nephrotoxic effects associated with antiretroviral therapy [23][24][25][26] .
This study has several limitations to acknowledge.Firstly, the NIS, being an administrative database, does not record clinical data including CD4 counts, viral loads, or the usage of antiviral therapies in HIV patients.www.nature.com/scientificreports/Also, several factors that can influence revascularization outcomes, such as ejection fraction, coronary segment, stenosis diameter, lesion presence, coronary artery dominance, and small vessel diffusion, are not recorded in the NIS 27,28 .The absence of the information in the NIS dataset also prevents the calculation of surgical risk calculators like the Society of Thoracic Surgeons (STS) or the European System for Cardiac Operative Risk Evaluation (EuroSCORE) scores.Additionally, the NIS database only has in-hospital outcomes with no followups, limiting the analysis of long-term prognosis among HIV patients after CABG.Nevertheless, the NIS is the most comprehensive all-payer database in the US, accounting for 20% of nationwide hospital discharges.While other large-scale cardiac surgery databases, like the STS databases, provide more granular records, they do not allow the identification of patients with HIV.Hence, the NIS is likely to be one of the few sources with both the statistical power and enough details to investigate CABG outcomes in patients with HIV.
In conclusion, using the NIS database, this study offers a comprehensive, population-based examination of short-term CABG outcomes in HIV patients.For selected HIV patients, CABG is relatively safe, presenting largely similar outcomes with the exceptions of higher AKI and infection rates.Factors associated with inhospital mortality among HIV patients include prior CABG, chronic pulmonary disease, advanced renal failure, and peripheral vascular disorders, which can enhance preoperative risk stratification for HIV patients.Future population-based research should further explore the long-term prognosis of CABG in HIV-affected individuals.

Table 3 .
Comparison of in-hospital outcomes between patients with and without HIV who underwent CABG after 1:5 propensity-score matching.AKI, acute kidney injury; CABG, coronary artery bypass grafting; HIV, human immunodeficiency virus; LOS, length of stay; MACE, major adverse cardiovascular event; MI, myocardial infarction; NA, not applicable; PE, pulmonary embolism; SD, standard deviation; TIA, transient ischemic attack; VTE, venous thromboembolism.= 0.04) and higher total hospital charges (261,011 ± 337,816 vs. 230,783 ± 241,233 US dollars, p = 0.04).Other risks of complications, time from admission to operation, and LOS were all comparable between the two groups.

Table 4 .
Risk factors associated with in-hospital mortality among patients with HIV who underwent CABG.aOR, adjusted odds ratio; CI, confidence interval; CABG, coronary artery bypass grafting; HIV, human immunodeficiency virus.