Assessment of Clinical Features in HIV-Infected Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention in China

Objectives We aimed to compare coronary risk factors, burden of coronary artery disease (CAD), and 1-year prognosis of people living with HIV (PLWH) and HIV-negative controls who underwent percutaneous coronary intervention (PCI) for acute coronary syndromes (ACSs). Background Cardiovascular disease is drawing more and more attention in PLWH since effective antiretroviral therapy (ART) has been available. Clinical characteristics and outcomes of PLWH undergoing PCI for ACS in China remain unknown. Methods We compared demographic characteristics, angiographic features, and 1-year outcomes of 48 PLWH versus 48 HIV-negative controls matched for age (±2 years), sex, diabetes mellitus, and year of PCI (±2 years) in Beijing Ditan Hospital, Capital Medical University from January 2008 to November 2020. Results In PLWH (mean age: 53.6 ± 10.6 years, 95.8% male, and 79.2% on ART), high-density lipoprotein cholesterol was lower than in HIV-negative controls; however, the statin use was more common, the incidence of hypertension was lower, and low-density lipoprotein cholesterol, and the body mass index were significantly lower than in controls. Two groups had a similar extent of coronary atherosclerosis as measured by the presence of multivessel diseases and the median Gensini score; however, lesions of PLWH were longer and were more likely to locate at the proximal segment of the coronary artery. In addition, the risk of major adverse cardiac and cerebrovascular events at 1 year was similar in both groups. Conclusion PLWH undergoing PCI displayed similar CAD burden and 1-year prognosis compared with HIV-negative patients. Early detection of cardiovascular risk factors and appropriate secondary prevention of CAD in PLWH might alleviate the risk of severe adverse cardiovascular events.


Introduction
e introduction of antiretroviral therapy (ART) resulting in care of HIV has dramatically changed the natural history of people living with HIV (PLWH) [1,2]. Today, PLWH have a life expectancy not significantly different from HIV-negative people. However, concerns remain about all the comorbidities associated with aging and the effects of chronic therapies in this population, including coronary artery disease (CAD) [3].
Chronic immune activation, inflammation, metabolic disturbances secondary to antiretroviral drugs, and high prevalence of traditional risk factors are involved in the development of premature atherosclerosis and atherothrombosis in PLWH [4,5]. However, studies focusing on percutaneous coronary intervention (PCI) in PLWH with acute coronary syndrome (ACS) are sparse [6], and discrepancies have been reported in coronary risk factors, angiographic features, and prognosis during the acute and longer-term phases [7][8][9][10]. e aim of our study was to compare coronary risk factors, angiographic features, and 1year clinical outcomes post PCI of PLWH and HIV-negative patients with ACS.

Study Design and Population.
e data for all PLWH admitted for ACS in Beijing Ditan Hospital, Capital Medical University from January 2008 to December 2020 were collected from the Tongren medical information system, which included medical record data for all inpatient hospitalizations in Beijing Ditan Hospital since 2008. Diagnoses at discharge are coded according to the International Classification of Diseases, ninth revision (ICD-9). All PLWH diagnosed with unstable angina (UA, n � 27) or myocardial infarction (MI, n � 50) were included in the study. After excluding those underwent plain old balloon angioplasty alone (n � 7), coronary angiography alone (n � 16), thrombolysis alone (n � 3), and failed PCI (n � 3), our study population included 48 PLWH who underwent PCI with at least one stent. As age (±2 years), sex, diabetes mellitus, and year of PCI (±2 years) are strong risk factors for cardiovascular disease, we applied the method of individual matching to enroll the HIV-negative patients who underwent PCI due to MI or UA as the control group by 1 : 1 matching. e study was approved by the Human Science Ethical Committee of Beijing Ditan Hospital, Capital Medical University (No. 2021-021-02).

Data Collection.
Baseline characteristics, quantitative CAG, and one-year major adverse cardiac and cerebrovascular events (MACCEs) were compared in PLWH with matched HIV-negative patients. MACCE were defined as recurrent ACS, reintervention, stroke, and all-cause death. Data were also collected concerning HIV infection. Loss of follow-up was defined as no clinic visit every 3 months and no inpatient record within 1 year. We assessed ACS severity using a 6-month mortality prediction scale, and the GRACE score was performed the last week before discharge [11].

Baseline Characteristics.
Baseline characteristics included demographic characteristic, medical history, physical examination, the laboratory data, and echocardiographic parameters on admission.

HIV-Related Characteristics. Data on HIV infection
were collected, including CD4 counts and HIV load (VL) within 6 months before ACS, prior exposure to ART, time since HIV diagnosis, ART regimen, history of opportunistic infections, and comorbidities.

Angiographic Data Collection.
e characteristics and severity of CAD were assessed according to lesion characteristics, the number of diseased vessels, the thrombolysis in myocardial infarction (TIMI) flow grade before and after PCI, and the Gensini score. Lesion characteristics included the lesion length (>20 mm as long lesions), lesion location, and degree of stenosis with or without a thrombus. e diseased vessel was defined as the vessel with stenosis. e culprit vessel was defined as the vessel that was registered as the primary-treated vessel during PCI [12]. For the Gensini score, grading scales were applied according to the degree of stenosis for each coronary lesion. e score was further multiplied depending on the artery type (left anterior descending, left circumflex, and right coronary) and the location (proximal, mid, and distal). e final Gensini score was the summation of each individual lesion score [13].

Statistical Analysis.
Continuous variables were presented as the mean ± standard deviation (SD) and the median (interquartile range (IQR)) and were compared using Student's t-test and the Wilcoxon rank-sum test, respectively. Categorical variables were presented as frequency (percentage) and compared using the chi-squared test. Survival curves were analyzed using the Kaplan-Meier curves.
Multivariate Cox regression analysis was performed to determine the hazard ratio (HR) for the one-year MACCE. e body mass index (BMI), hypertension, and use of statins on admission were used for our multivariate analysis. P values <0.05 were considered statistically significant. All analyses were performed using SPSS statistical software version 26.0.

Baseline Characteristics.
A total of 48 PLWH (95.8% men) with confirmed ACS who underwent PCI were enrolled in the present analysis. e mean age was 53.6 years, with 43.8% of patients having diabetes mellitus. A total of 16 PLWH presented as ST-segment-elevation myocardial infarction (STEMI, 33.3%), 11 PLWH presented as non-STsegment-elevation myocardial infarction (NSTEMI, 22.9%), and 21 PLWH presented as UA (43.8%). e incidence of UA tended to be higher in PLWH but not statistically significant (43.8% vs. 33.3%, P � 0.577). Table 1 depicts the main clinical characteristics of two groups. e proportions of current smokers (56.3% vs. 66.7%) and of those with chronic kidney disease (4.2% vs. 8.3%) were similar to the two groups (all P values >0.05). e incidence of hypertension was significantly higher in the HIV-negative group (64.6% vs. 37.5%, P � 0.008), but the blood pressure at admission was similar (P � 0.315). A family history of CVD was more common but not significant (41.7% vs. 25%, P � 0.083) in the HIV-negative group. Prescription of most drugs for secondary prevention of CVD (aspirin, clopidogrel, β receptor blockers, and renin angiotensin aldosterone system (RAAS) inhibitors) at admission was comparable between groups (all P values >0.05). However, PLWH received statin more frequently (47.9% vs. 10.4%, P < 0.001).

Discussion
Our study reported the coronary risk factors, angiographic pattern, and clinical outcome of ACS in PLWH undergoing PCI. PLWH were compared with the control group of HIVnegative patients matched for age, sex, diabetes mellitus, and year of PCI. e results suggested PLWH had a similar extent of CAD according to the presence of multivessel disease and the median Gensini score as compared with HIV-negative patients. However, lesions of PLWH were characterised by a longer and more proximal stenosis. e risk of MACCE did not significantly differ between the two groups, even after multivariable adjustments.
HIV infection has become a chronic disease with non-AIDS defining illnesses as the main cause of morbidity and mortality, particularly CAD [14]. PLWH are at increased risk for CAD compared with the general population of the same age [15,16]. e presence of CAD is usually revealed by the occurrence of ACS, and PCI is the primary method of revascularization in PLWH [6,17]. Available data suggest the presence of an accelerated process of coronary atherosclerosis in this population due to a higher prevalence of traditional risk factors, chronic inflammation, immune activation, and aging related to HIV infection [18]. In the present study, most of PLWH undergoing PCI were receiving ART. Some of the antiretroviral drugs such as efavirenz and PIs, which are widely used in China, are associated with severe lipodystrophy, disturbed glucose metabolism, and dyslipidemia [19]. However, the prescription rate of the drugs for secondary prevention of CVD in our study was extremely high in PLWH both on admission and at discharge. e incidence of lipid metabolic abnormalities including an elevated serum cholesterol level and hypertriglyceridemia did not show a significant increase in PLWH of our cohort, which might be due to the high rate of statin use. e good adherence of cardiovascular drugs in PLWH of our cohort may benefit from close outpatient follow-up and physicians' awareness of taking intervention to mitigate risk of non-AIDS events. In addition, the prevalence of traditional cardiovascular factors including hypertension and a high BMI was lower in PLWH than that in HIV-negative patients, suggesting the contribution of HIV infection-associated factors in the pathogenesis of CAD. Previous studies have reported that PLWH had a higher prevalence of LVDD and a higher LVMI than those in HIV-negative controls, which might be associated with low nadir and recent CD4 count, higher levels of inflammation, side effects from medication, and the direct effect of virus on the myocardium [20,21]. However, in patients with ACS, we observed similar echocardiographic findings between groups. e predominant mechanism may be ischemic heart disease and atherosclerosis in the setting of ACS [20].
In the previous studies, the most common presentation is STEMI (29% to 64%), followed by NSTEMI (20% to 48%), and UA (18% to 46%) [4]. e risk of myocardial infarction (MI) increased by 50%-100% in HIV-infected patients compared with control individuals without HIV infection [2,22,23], probably due to the increased prevalence of noncalcified coronary atherosclerotic plaque and high-risk morphological plaque [6,24]. However, whether the type of ACS differs in the HIV-infected population compared with the uninfected population is not obvious. Hsue et al. reported more UA in PLWH, and Boccara et al. described the similar spectrum of ACS in PLWH and HIV-negative patients with a first episode of ACS [7,25]. In our study, UA was slightly more common in PLWH and STEMI was slightly more common in HIV-negative patients. However, there was no significant difference in these rates between the two groups.
We provided the angiographic description of coronary vasculopathy and lesion characteristics in patients with HIV. e degree of CAD assessed by the number of diseased vessels was reported in PLWH, with 35% to 56% of patients had single-vessel disease, 18% to 28% of patients had doublevessel disease, and 13% to 76% of patients had triple-vessel disease [26][27][28]. We investigated by quantifying the CAD burden with the presence of multivessel disease as well as the Gensini score and reported similar prevalence of multivessel disease and the median Gensini score in both groups. In addition, the lesions of PLWH were characterised by longer stenosis and were localized in more proximal coronary segments, which were also reported in other studies [8,29]. e angiographic differences and the discord between the angiographic profile and clinical presentation may reflect substantial differences in the pathogenesis of atherosclerosis in PLWH [8]. In the future, intravascular imaging (intravascular optical coherence tomography, intravascular ultrasound imaging, etc.) would provide more accurate assessments. e long-term prognosis of PLWH with ACS has been evaluated in a few studies. PLWH exhibited a higher rate of recurrent ischemic events compared with HIV-negative patients, but long-term cardiovascular and total mortality did not differ significantly [7,26,30]. In the present study, the risk of overall MACCE at 1 year was similar in both groups. A slightly higher incidence of reintervention was observed in PLWH. e absence of difference in prognosis may be attributed to the high rate of evidence-based medications.
is suggests that there is now a need to improve the completeness of secondary prevention medication among PLWH with ACS to ensure that all the potential benefits of secondary prevention are realised.

Study Limitations.
e present study had several limitations. First, this study is limited by the small size, single center, and retrospective nature. Second, the rate of loss to follow-up was relatively high, which might have an impact on reliability of results. In addition, a one-year MACCE may not reflect the true picture, and a long-term study may reflect different results.

Conclusion
In conclusion, our study suggests that PLWH undergoing PCI displayed longer and more proximal lesions but similar CAD burden compared with age and sex matched HIVnegative patients. e 1-year prognosis after PCI does not significantly worsen compared with HIV-negative controls. Taking early detection of cardiovascular risk factors and appropriate secondary prevention of CAD in PLWH might alleviate the risk of severe adverse cardiovascular events.
Data Availability e data that support the findings of this study are available from the corresponding author upon reasonable request.

Conflicts of Interest
e authors declare that there are no conflicts of interest.