A matched cohort study was conducted comparing patients with first-time acute coronary syndromes infected with human immunodeficiency virus (HIV) to non-HIV-infected patients with and without diabetes matched for smoking, gender, and type of acute coronary syndrome who underwent first-time coronary angiography. A total of 48 HIV-infected patients were identified from a national database. Coronary angiography showed that the HIV-infected patients had significantly fewer lesions with classification B2/C than the 2 control groups (p <0.001) but the same extent of multivessel disease. The HIV-infected patients were a decade younger than the non-HIV-infected controls and had significantly higher concentrations of total cholesterol (6.3 vs 4.8 and 4.5 mmol/L, p <0.0001), low-density lipoprotein (4.0 vs 2.9 and 2.5 mmol/L, p <0.001), and triglycerides (2.8 vs 1.0 and 1.4 mmol/L, p <0.01) compared to the nondiabetic and diabetic non-HIV-infected groups, respectively. In conclusion, HIV-infected patients with first-time acute coronary syndromes have fewer complex lesions than non-HIV-infected patients. This finding supports the idea that the pathogenesis of atherosclerotic disease in HIV patients is different from that in the general population.
Patients infected with human immunodeficiency virus (HIV) and patients with diabetes mellitus are at increased risk for myocardial infarction. In this study, we aimed to compare angiographic features and risk factors of HIV-infected patients with 2 matched groups of non-HIV-infected and non-HIV-infected diabetic patients who underwent coronary angiography (CAG) performed after first-time acute coronary syndromes (ACS).
Methods
We conducted a matched cohort study of HIV-infected and non-HIV-infected patients matched for smoking, gender, and type of ACS who underwent first-time CAG from 2000 to 2009. We identified all HIV-infected patients aged ≥18 years followed at the outpatient clinic in the departments of infectious diseases at Rigshospitalet and Hvidovre Hospital (Copenhagen, Denmark) who were registered with the diagnosis code for ACS in the Danish National Hospital Registry. Patients who previously had been diagnosed with ACS or had diabetes were excluded. Data regarding baseline CAG were obtained from a database under the Danish Heart Registry.
On hospital admission for ACS, patients were asked about hypertension, hypercholesterolemia, smoking, diabetes, and family history of premature coronary artery disease. When answers were not available, data were obtained from recordings from the last visit to the HIV clinic before the ACS. Hypertension was defined as systolic blood pressure >140 mm Hg and/or diastolic blood pressure >90 mm Hg or the use of antihypertensive medication. Hypercholesterolemia was defined as total cholesterol ≥7.5 mmol/L or the use of lipid-lowering medication.
Smoking was defined in 3 strata: never, former (smoking abstinence >1 year), or active, which included recent cessation or current smoking. Biologic parameters were likewise obtained from the admission date or last visit.
CAG was performed at 1 of 3 centers in the greater Copenhagen area by trained cardiologists and provided information on the number of vessels diseased and the number of lesions, which were considered significant when stenoses were >50%.
Grading of the lesions was done when patients underwent percutaneous coronary intervention and was performed according to the American Heart Association and American College of Cardiology classification, which scores coronary lesions as type A, B1, B2, or C on the basis of lesion-specific characteristics such as length, calcification, and contour.
All HIV-infected patients were given diagnoses of ACS, which consists of ST-segment elevation myocardial infarction, non–ST-segment elevation myocardial infarction, and unstable angina pectoris on the basis of international standard criteria.
Non-HIV-infected patients were included from the Danish Heart Registry fulfilling the criteria of undergoing CAG for first-time ACS and were matched individually for smoking status (current, former, or never), gender, and type of ACS. The non-HIV-infected patients with diabetes were likewise included from the Danish Heart Registry fulfilling the same criteria but were also matched for age. The study was approved by the scientific ethics committee of the capital region of Denmark (reference number H-D-2008-108).
Data are expressed as mean ± SEM or as medians and interquartile ranges as appropriate. All biologic parameters were tested for distribution using the Kolmogorov-Smirnov test, and normal distribution was obtained by log 10 transformation before statistical analysis. However, results are presented as untransformed data for easier biologic interpretation. All statistical analysis was performed using SPSS version 20 (IBM, Armonk, New York). Comparisons between groups were made using independent-samples Student’s t tests for continuous variables despite the matching and chi-square tests for categorical variables. A p value <0.05 was considered significant.
Results
A total of 48 HIV-infected patients were eligible with first-time ACS, CAG, and no exclusion criteria. Forty-five (94%) were men, with a mean age of 48.6 years (range 32 to 69). At the time of ACS, 80% of the HIV-infected patients had undetectable viral loads (≤50 copies/ml). In the remaining patients receiving antiretroviral therapy, the median viral load was 138 copies/ml (range 62 to 3,700). A total of 90% of the HIV-infected patients were infected from sexual contact and 5% from intravenous drug abuse. Other parameters of the HIV-infected group are listed in Table 1 , and baseline characteristics of the 3 groups of patients are listed in Table 2 .
| Variable | Value |
|---|---|
| Time since HIV diagnose (yrs) | 9 (7–14) |
| Patients receiving ART with viral load <50 copies/ml | 35 (80%) |
| Median CD4+ cell count/mm 3 | 574 (400–755) |
| Median nadir of CD4+ cell count/mm 3 | 147 (79–218) |
| Patients receiving ART | 43 (98%) |
| Median duration of therapy (yrs) | 6.5 (4–9) |
| Patients receiving protease inhibitors | 21 (49%) |
| Patients receiving NNRTI | 26 (60%) |
| Patients receiving NRTI | 42 (98%) |
| Patients receiving lipid-lowering treatment | 5 (11%) |
| Patients receiving antihypertensive drugs | 6 (13%) |
| Variable | HIV-Infected (n = 48) ∗ | Non-HIV-Infected (n = 48) ∗ | Non-HIV-Infected Diabetic (n = 48) ∗ | p Value | |
|---|---|---|---|---|---|
| HIV-Infected vs Non-HIV-Infected | HIV-Infected vs Non-HIV-Infected Diabetic | ||||
| Age (yrs) | 48.6 ± 9.3 | 58.8 ± 11.8 | 48.9 ± 9.7 | <0.0001 ‡ | — |
| Men | 45 (94%) | 45 (94%) | 45 (94%) | — | — |
| Body mass index (kg/m 2 ) | 24 (22–27) | 26 (24–28) | 29 (26–32) | 0.05 ‡ | <0.0001 ‡ |
| Active smokers | 36 (78%) | 36 (75%) | 32 (68%) | 0.92 § | 0.41 § |
| Former smokers | 7 (15%) | 8 (17%) | 11 (23%) | — | |
| Never smokers | 3 (7%) | 4 (8%) | 4 (9%) | — | |
| Hypercholesterolemia † | 17 (37%) | 13 (32%) | 23 (56%) | 0.61 § | 0.74 § |
| Hypertension | 14 (33%) | 11 (24%) | 22 (48%) | 0.40 § | 0.14 § |
| Family history of premature coronary artery disease | 11 (27%) | NA | 16 (42%) | — | 0.15 § |
| Diabetes | 0 (0%) | 0 (0%) | 48 (100%) | — | |
| ST-segment elevation myocardial infarction | 33 (69%) | 32 (67%) | 33 (69%) | — | |
| Non–ST-segment elevation myocardial infarction | 12 (25%) | 13 (27%) | 13 (27%) | — | |
| Unstable angina | 2 (4%) | 2 (4%) | 2 (4%) | — | |
| Cardiogenic shock | 1 (2%) | 1 (2%) | 0 (0%) | — | |
∗ Some variables had missing data, and therefore percentages are calculated only for patients having the given information.
† Taking lipid-lowering medication or total cholesterol >7.5 mmol/L (>290 mg/dl).
The non-HIV-infected diabetic group consisted of 6 patients with type 1 diabetes (12.5%) and 42 (87.5%) with type 2 diabetes. Except for 1 HIV-infected patient, none reported use of cocaine. The 2 patients in the HIV-infected group infected from intravenous drug abuse were coinfected with hepatitis C but not hepatitis B, whereas no other patients were found to be infected with hepatitis B or hepatitis C.
Metabolic parameters are listed in Table 3 . The HIV-infected group showed significant increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides. Levels of high-density lipoprotein (HDL) cholesterol did not differ between the HIV-infected and non-HIV-infected group, with the 2 groups having approximately 20% of patients with HDL cholesterol <0.9 mmol/L. The diabetic group, in contrast, had significantly lower values of HDL cholesterol, and >40% of the patients had HDL cholesterol values <0.9 mmol/L.
| Variable | HIV-Infected (n = 48) | Non-HIV-Infected (n = 48) | Non-HIV-Infected Diabetic (n = 48) | p Value ∗ | |
|---|---|---|---|---|---|
| HIV-Infected vs Non-HIV-Infected | HIV-Infected vs Non-HIV-Infected Diabetic | ||||
| Fasting blood glucose | <0.0001 | <0.0001 | |||
| mmol/L | 5.2 (4.8–5.9) | 6.3 (5.6–7.0) | 12.0 (7.8–14.0) | ||
| mg/dl | 94 (86–107) | 114 (101–126) | 215 (141–251) | ||
| Serum creatinine (μmol/L) | 77 (70–86) | 73 (64–90) | 72 (62–84) | 0.152 | 0.09 |
| Total cholesterol | <0.0001 | <0.0001 | |||
| mmol/L | 6.3 (5.5–6.5) | 4.8 (4.2–5.8) | 4.5 (3.6–5.3) | ||
| mg/dl | 243 (212–290) | 185 (162–224) | 172 (138–205) | ||
| HDL cholesterol | 0.632 | 0.04 | |||
| mmol/L | 1.1 (0.9–1.3) | 1.1 (0.9–1.2) | 0.9 (0.8–1.1) | ||
| mg/dl | 42 (35–50) | 41 (35–46) | 35 (29–42) | ||
| Low-density lipoprotein cholesterol | 0.002 | <0.0001 | |||
| mmol/L | 4.0 (3.1–4.7) | 2.9 (2.4–3.9) | 2.5 (1.9–3.3) | ||
| mg/dl | 154 (120–181) | 110 (92–149) | 97 (74–126) | ||
| Triglycerides | <0.0001 | 0.007 | |||
| mmol/L | 2.8 (1.5–5.5) | 1.0 (0.6–1.7) | 1.4 (1.1–3.6) | ||
| mg/dl | 248 (133–484) | 88 (55–150) | 127 (96–315) | ||
Table 4 lists the main findings of CAG. When comparing the mean number of vessels diseased in the HIV-infected group with the non-HIV-infected and non-HIV-infected diabetic groups, no difference was found (1.5 vs 1.3 and 1.6, p = 0.20 and p = 0.50). However, the extent of atherosclerotic disease, measured as the number of vessels, was not evenly distributed among the 3 groups, as none of the patients in the HIV-infected group had zero vessels affected, whereas 6% and 8% had this finding in the 2 control groups, respectively. The number of patients with multivessel disease did not differ among the 3 groups (29% vs 31% and 48%, p = 1.00 and p = 0.10). The rate of Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow before intervention was 24% in the HIV-infected group and 34% (p = 0.40) and 33% (p = 0.60) in the non-HIV-infected and non-HIV-infected diabetic groups, respectively. After intervention, rates of TIMI grade 3 flow were 95% versus 100% and 94% (p = 0.50 and p = 1.00, respectively). One patient had received prehospital thrombolysis.
| Variable | HIV-Infected (n = 48) | Non-HIV-Infected (n = 48) | Non-HIV-Infected Diabetic (n = 48) | p Value | |
|---|---|---|---|---|---|
| HIV-Infected vs Non-HIV-Infected | HIV-Infected vs Non-HIV-Infected Diabetic | ||||
| Number of narrowed coronary arteries | 0.008 § | 0.01 § | |||
| 0 | 0 (0%) | 3 (6%) | 4 (8%) | ||
| 1 | 34 (71%) | 30 (63%) | 21 (44%) | ||
| 2 | 5 (10%) | 13 (27%) | 13 (27%) | ||
| 3 | 9 (19%) | 2 (4%) | 10 (21%) | ||
| Number of lesions | 2.1 ± 0.2 | 1.6 ± 0.2 | 2.2 ± 0.3 | 0.12 ∗ | 0.77 ∗ |
| Type of lesion † | <0.0001 § | 0.005 § | |||
| A | 3 (9%) | 0 (0%) | 2 (5%) | ||
| B1 | 18 (53%) | 2 (6%) | 6 (16%) | ||
| B2 | 10 (30%) | 25 (76%) | 22 (60%) | ||
| C | 3 (9%) | 6 (18%) | 7 (19%) | ||
| Number of patients with type B2/C or higher lesions | 13 (38%) | 31 (94%) | 29 (78%) | <0.0001 § | 0.001 § |
| Length of stenosis † (eyeballing) (mm) | 14.3 ± 1.3 | 13.6 ± 1.1 | 17.1 ± 1.3 | 0.86 ∗ | 0.08 ∗ |
| Length of total stenoses (mm) | 20.5 ± 2.4 | 15.3 ± 1.9 | 24.9 ± 3.0 | 0.07 ∗ | 0.29 ∗ |
| Length of stent segment † (mm) | 19.0 ± 1.5 | 18.7 ± 1.2 | 21.1 ± 1.6 | 0.93 ∗ | 0.29 ∗ |
| Procedural characteristics ‡ | |||||
| Number of lesions dilated | 1.34 ± 0.65 | 1.26 ± 0.57 | 1.57 ± 0.90 | 0.62 ∗ | 0.32 ∗ |
| Percutaneous coronary intervention | 39 (81%) | 30 (64%) | 35 (73%) | ||
| Balloon angioplasty | 4 (8%) | 4 (9%) | 2 (4%) | ||
| Coronary artery bypass graft | 4 (8%) | 4 (9%) | 6 (13%) | ||
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