Introduction
The introduction of antiretroviral therapy has increased life expectancy in HIV-infected patients.(1,2) With a growing elderly HIV-infected population, the number of HIV-infected patients requiring noncardiac surgery for HIV-related or HIV-unrelated pathologies is likely to increase in the near future. Poor cardiovascular outcomes are amongst the most severe adverse outcomes observed during the perioperative period in noncardiac surgery patients.(3,4) While predictors of poor cardiac outcomes following noncardiac surgery have been described in studies by Lee et al.,(3) and Botto et al.,(4) these studies do not present any data related to the potential impact of HIV infection on these outcomes, even though HIV infection appears to be associated with a higher risk for the development of cardiovascular disease in nonsurgical patients.(5) There are some studies which report HIV infection to be associated with a higher incidence of adverse perioperative cardiovascular events following noncardiac surgery; however these studies are limited in that only a few types of surgical procedures, namely orthopaedic surgeries,(6,7) were investigated. The purpose of this study was to determine whether HIV infection is an independent risk factor for adverse in-hospital cardiovascular events (AICEs) in patients undergoing various noncardiac surgery procedures.
Methods:
This study was a case-control analysis of data from adult (18-60 years old) noncardiac surgery patients contained in the publicly available 2009-2011 California State Inpatient Database (SID). As the data is in the public domain, ethical approval for the use of the data for research purposes was waived by the institutional review board of the University of KwaZulu-Natal, South Africa (Protocol EXM267/15). The SID was selected as the source for the data used in this analysis as it serves as a large, detailed source of patient hospitalization data. Appropriate Clinical Classification Software (CCS) discharge diagnosis codes (based on established groupings of International Classification of Disease, 9th Revision codes) and the “present on admission” label in the SID were used to identify established preoperative predictors of poor perioperative cardiovascular outcomes, such as a history of ischemic heart disease (CCS codes 100 and 101), cerebrovascular disease (CCS codes 109, 110, 111, 112, 113), congestive heart failure (CCS code 108), renal disease (CCS codes 156, 157, 158), peripheral vascular disease (CCS codes 114, 115, 116, 117), Chronic obstructive pulmonary disease (CCS code 127), hypertension (CCS codes 98,99) and diabetes (CCS codes 49, 50), for each patient. CCS codes were also used to identify patients with HIV infection (CCS code 5). The SID contains up to 25 discharge diagnoses for each patient, and it is likely that all patient discharge diagnoses were captured rather than just the most important discharge diagnoses. Surgeries were stratified according to procedural risk (Table 1). Demographic data and the route of hospital admission for included patients were also extracted from the SID. The study outcome was an adverse in-hospital cardiovascular event (AICE), which was a composite outcome of cardiac and cerebrovascular morbidity, and all-cause in-hospital mortality. A similar outcome has been used elsewhere in studies of perioperative medicine.(8,9) A patient was considered to have suffered an AICE if the patient record was linked to CCS discharge diagnosis codes 100, 101, and 109-113 which were not listed on the SID as “present on admission” to hospital, or if the patient had in-hospital death documented on the SID.
Table 1. Surgical procedures included in this study |
Above knee amputation |
Below knee amputation |
Carotid endarterectomy |
Colectomy* |
Cystectomy* |
Gastrectomy* |
Hip arthroplasty |
Knee arthroplasty |
Laparoscopic cholecystectomy |
Lower extremity peripheral bypass surgery |
Nephrectomy* |
Open abdominal aortic aneurysm repair* |
Open cholecystectomy* |
Pancreatic resection* |
Spinal fusion |
| *Defined as a high risk surgical procedure in this study |
A total of 3435 patients (1145 cases and 2290 controls) were included in this unmatched case-control analysis. This sample size was based on the following: HIV prevalence of 1.2% in noncardiac surgery patients with AICE, and an HIV prevalence of 0.3% in noncardiac surgery patients without AICE (calculated using the entire SID noncardiac surgery cohort of 230518 patients); a confidence level of 95%; power = 0.8; and a 2:1 ratio of controls and cases. Cases and controls were randomly selected from the SID noncardiac surgery cohort using a random number generator to minimize bias.
Statistics:
Data were analysed with the Statistical Package for the Social Sciences version 22.0 (IBM Corp., USA). Age data were analysed with a Mann-Whitney U test and are presented as a median with interquartile range. Data related to gender, race, admission route, and comorbidity where dichotomized and analysed with a χ2 test or Fisher’s exact test. These results are presented as frequencies and percentages. Independent associations between patient characteristics, and AICEs were identified with a logistic regression model, the results of which are presented as odds ratios (OR) with 95% confidence intervals (95% CI). A p-value <0.05 was considered statistically significant.
Results:
Univariate Analysis:
Baseline characteristics of the study population:
The characteristics of the entire study population are shown in Table 2. Briefly, 25% of surgeries were high risk procedures. The study population was predominantly female (53.4%) with a median age of 52.0 (Interquartile range: 42.0-57.0) years. Almost half the study population was non-Caucasian. Almost 43% of admissions were emergencies. The three most prevalent comorbidities were hypertension (42.4%), diabetes (22.7%), and renal disease (14.0%). The prevalence of HIV infection was 0.6%.
Table 2: Characteristics of the study population expressed as a frequency (%) |
| Characteristic |
All patients (n=3435) |
Cases (n=1145) |
Controls (n=2290) |
p-value |
Median age in years (Interquartile Range) |
52.0 (42.0-57.0) |
54.0 (48.0-57.0) |
49.0 (40.0-55.0) |
<0.001 |
Male gender |
1600 (46.6) |
684 (59.7) |
916 (40.0) |
<0.001 |
Non-Caucasian race |
1681 (48.9) |
586 (51.2) |
1095 (47.8) |
0.063 |
Emergent admission |
1463 (42.6) |
676 (59.0) |
787 (34.4) |
<0.001 |
High risk procedure |
866 (25.2) |
517 (45.2) |
349 (15.2) |
<0.001 |
HIV infection |
20 (0.6) |
12 (1.0) |
8 (0.3) |
0.011 |
Diabetes |
780 (22.7) |
424 (37.0) |
356 (15.5) |
<0.001 |
Hypertension |
1456 (42.2) |
646 (56.4) |
810 (35.4) |
<0.001 |
Ischemic heart disease |
350 (10.2) |
265 (23.1) |
85 (3.7) |
<0.001 |
Congestive heart failure |
190 (5.5) |
160 (14.0) |
30 (1.3) |
<0.001 |
Cerebrovascular disease |
77 (2.2) |
51 (4.5) |
26 (1.1) |
<0.001 |
Renal disease |
482 (14.0) |
395 (34.5) |
87 (3.8) |
<0.001 |
Chronic obstructive pulmonary disease |
166 (4.8) |
107 (9.3) |
59 (2.6) |
<0.001 |
Vascular disease |
374 (10.9) |
280 (24.5) |
91 (4.1) |
<0.001 |
Baseline characteristics of cases and controls:
The baseline characteristics of cases and controls are also shown in Table 2. Approximately 45% of cases and 15% of controls had undergone high risk procedures (p<0.001). Almost 60% of cases were male, while 40% of controls were male (p<0.001). The median age of cases was older than that of the controls (p<0.001). The proportions of non-Caucasian patients were similar in the case and control groups (p=0.063). A larger proportion of cases were admitted as emergencies than controls (p<0.001). The prevalence of all established cardiovascular risk factors was higher in the case group versus the control group (p<0.001 for all established cardiovascular risk factors). The prevalence of HIV was three times higher in the cases when compared with controls (p=0.011).
Multivariate Analysis:
The logistic regression analysis did not identify an independent association between HIV infection and AICEs in this study (OR: 2.711, 95% CI: 0.874-8.405; p=0.084; Table 3). In addition, non-Caucasian race was not an independent predictor of AICEs (OR: 1.130, 95% CI: 0.941-1.358, p=0.191; Table 3). However, most of the established clinical risk factors, were found to be independent predictors of AICEs in this study (Table 3), with the exception of diabetes (OR: 1.150, 95% CI: 0.912-1.450; p=0.238) and hypertension (OR: 1.079, 95% CI: 0.877-1.328; p=0.470).
Table 3: Results of the logistic regression analysis |
| Characteristic |
Odds Ratio (95% Confidence Interval) |
p-value |
Age (per 1 year increase) |
1.041 (1.030-1.052) |
<0.001 |
Male gender |
1.544 (1.285-1.855) |
<0.001 |
Non-Caucasian race |
1.130 (0.941-1.358) |
0.191 |
Emergent admission |
2.984 (2.464-3.614) |
<0.001 |
High risk procedure |
4.961 (4.073-6.041) |
<0.001 |
HIV infection |
2.711 (0.874-8.405) |
0.084 |
Diabetes |
1.150 (0.912-1.450) |
0.238 |
Hypertension |
1.079 (0.877-1.328) |
0.470 |
Ischemic heart disease |
3.667 (2.648-5.078) |
<0.001 |
Congestive heart failure |
3.383 (2.108-5.430) |
<0.001 |
Cerebrovascular disease |
3.130 (1.757-5.576) |
<0.001 |
Renal disease |
5.166 (3.829-6.971) |
<0.001 |
Chronic obstructive pulmonary disease |
1.847 (1.209-2.822) |
0.005 |
Vascular disease |
2.459 (1.812-3.337) |
<0.001 |
Discussion:
HIV infection was not an independent predictor of AICEs following noncardiac surgery in this study. Although we do not present data on antiretroviral therapy use, it is likely that as with the nonsurgical HIV-infected American population,(10) HIV infection was well controlled through antiretroviral therapy in our study population. It has been shown that adequate treatment of HIV infection with antiretroviral therapy reduces the circulating levels of cardiovascular risk markers,(10) which in the perioperative setting might translate to a lower risk for adverse cardiovascular events.
The potential impact of well controlled comorbid disease is supported by the findings related to hypertension and diabetes in our study, which have both been linked to poor perioperative outcomes elsewhere.(3,4) Furthermore, in keeping with the studies of Lee et al.,(3) and Botto et al.,(4) consequences of poorly controlled hypertensive and diabetic disease in the form of target organ damage (such as congestive heart failure, ischaemic heart disease, renal disease, and cerebrovascular disease) were independently associated with AICEs in our study. Therefore, although it appears that an HIV-seropositive status in itself does not contribute to increased risk, it might be possible that parameters of HIV infection, notably those related to the control of HIV infection, might be of greater prognostic importance in patients undergoing noncardiac surgery. Further prospectively designed research is required to confirm this.
There were limitations to this research. The data contained in the SID does not report post-discharge outcomes or outcomes at 30 days postoperatively, so this study only reports findings related to in-hospital outcomes. Medication data was not collected as part of the SID, and hence we could not control for this in our analysis. Prospective studies are required to determine the impact of these variables on patient cardiovascular outcomes. Furthermore the study outcome was based on a physician’s diagnosis of cardiac and cerebrovascular morbidity. It might be possible that a proportion of patients might have experienced asymptomatic study outcomes. Routine measurement of perioperative cardiovascular biomarkers, as performed in the VISION study,(4,11) will no doubt reduce the number of missed AICEs noncardiac surgery patients.
In conclusion, HIV infection was not found to be an independent predictor of AICEs following noncardiac surgery in this study. However, this might be a consequence of well controlled HIV infection in the study population. Further research is required to determine whether HIV infection is associated with a higher risk of AICEs following noncardiac surgery, particularly in settings with a high burden of poorly controlled HIV disease.
References:
- May MT, Gompels M, Delpech V, et al. Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. AIDS. 2014;28:1193-1202.
- Antiretroviral Therapy Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet. 2008;372:293-99.
- Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation. 1999;100:1043-49.
- Botto F, Alonso-Coello P, Chan MT, et al. Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology. 2014;120:564-78.
- Calmy A, Gayet-Ageron A, Montecucco F, et al. HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial. AIDS. 2009;23:929-39.
- Menendez ME, Memtsoudis SG, Opperer M, Boettner F, Gonzalez Della Valle A. A nationwide analysis of risk factors for in-hospital myocardial infarction after total joint arthroplasty. Int Orthop. 2015;39:777-86.
- Lin CA, Kuo AC, Takemoto S. Comorbidities and perioperative complications in HIV-positive patients undergoing primary total hip and knee arthroplasty. J Bone Joint Surg Am. 2013;95:1028-36.
- Jacob M, Smedira N, Blackstone E, Williams S, Cho, L. Effect of timing of chronic preoperative aspirin discontinuation on morbidity and mortality in coronary artery bypass surgery. Circulation. 2011;123:577-83.
- Gupta PK, Ramanan B, MacTaggart JN, et al. Risk index for predicting perioperative stroke, myocardial infarction, or death risk in asymptomatic patients undergoing carotid endarterectomy. J Vasc Surg. 2013;57:318-26.
- Beer L, Skarbinski J. Adherence to antiretroviral therapy among HIV-infected adults in the United States. AIDS Educ Prev. 2014;26:521-37.
- Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307:2295-2304.
|
