Increased coronary artery calcium score and noncalcified plaque among HIV-infected men: relationship to metabolic syndrome and cardiac risk parameters.

OBJECTIVE: In this study, the effects of traditional cardiac risk factors on coronary artery calcium (CAC) score and presence of plaque, including noncalcified plaque, measured by computed tomography coronary angiography, were compared among HIV-infected and non-HIV-infected subjects, with respect to the presence of the metabolic syndrome (MS). DESIGN AND METHODS: HIV-infected men recruited for the presence of the MS (HIV + MS, n = 27) were compared with 2 control groups, HIV-infected men recruited without regard to metabolic criteria (HIV, n = 87), and HIV-negative control men (C, n = 40), also recruited without regard to any metabolic criterion. RESULTS: All 3 groups were similar in age, demographic parameters, and smoking. MS was seen in 100% of the HIV + MS group, compared with 28% in the HIV-infected control group and 11% in the HIV-negative controls. HIV + MS subjects had higher mean CAC score than HIV-infected controls (72 ± 25 vs. 30 ± 8, P = 0.04, HIV + MS vs. HIV) and HIV-negative controls (72 ± 25 vs. 18 ± 7; P = 0.02, HIV + MS vs. C). With respect to CAC, only the HIV + MS group had increased CAC compared with non-HIV. In contrast, both HIV groups demonstrated an increased prevalence of plaque [63% vs. 38%, P = 0.04 (HIV + MS vs. C) and 59% vs. 38%, P = 0.02, (HIV vs. C)] and increased number of noncalcified plaque segments compared with the HIV-negative group [1.26 ± 0.31 vs. 0.45 ± 0.16, P = 0.01 (HIV + MS vs. C); 1.02 ± 0.18 vs. 0.45 ± 0.16, P = 0.04 (HIV vs. C)]. Plaque and noncalcified plaque did not differ significantly between the HIV groups. CONCLUSIONS: Metabolic abnormalities in HIV patients are specifically associated with increased coronary artery calcification, whereas HIV itself or other factors may be associated with the development of noncalcified lesions.

Increased epicardial adipose tissue volume in HIV-infected men and relationships to body composition and metabolic parameters.

Epicardial fat accumulation may have important clinical consequences, yet little is known regarding this depot in HIV patients. We compared epicardial fat volume in 78 HIV-infected men and 32 HIV-negative controls. Epicardial fat volume was higher in HIV-infected patients than that in controls (P = 0.04). In HIV patients, epicardial fat volume was strongly associated with visceral adipose tissue area (rho = 0.76, P < 0.0001), fasting glucose (rho = 0.41, P = 0.001) and insulin (rho = 0.44, P = 0.0003). Relationships with glucose and insulin remained significant controlling for age, race, BMI, adiponectin, visceral adipose tissue and antiretroviral therapy. Epicardial fat may be an important fat depot in HIV-infected patients.

Perceived usefulness of cardiac computed tomography as assessed by referring physicians and its effect on patient management.

Despite the growing use of computed tomographic angiography (CTA), the effect on patient management is less clear. We sought to determine the perceived usefulness of the results provided by CTA and to assess whether and how it influences patient management. Comprehensive prospective data were collected from 184 consecutive patients who presented for clinical CTA for the evaluation of coronary artery disease from March to July 2008. In addition, a detailed survey was sent to each referring physician for each patient examined to assess whether they found the results of the CTA useful and whether it had any influence on subsequent patient management. Of 184 CTA examinations, which had been ordered by 82 different providers, 108 surveys (59%) were completed by 53 different physicians. No significant differences were found in either the patient or provider characteristics for the completed versus noncompleted surveys. Of the 184 CTA examinations, the severity of coronary disease detected by CTA was severe for 26%, mild to moderate in 47%, and not present in 27% of the patients. Clinicians considered the test results to be useful in virtually all cases and thought the results led to significant risk reclassification in 58% of the patients. If CTA had not been available, the clinicians indicated that they would have ordered an invasive test for 46% of the patients and noninvasive tests for 32%. After CTA, changes in medical therapies were made for 31%, invasive angiography was planned for 19%, and noninvasive testing was scheduled for 6% of the patients. In conclusion, of 53 different referring clinicians from different medical specialties, CTA was considered to almost always be useful; however, the effect on subsequent medical management was more variable.

Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men.

OBJECTIVE: The degree of subclinical coronary atherosclerosis in HIV-infected patients is unknown. We investigated the degree of subclinical atherosclerosis and the relationship of traditional and nontraditional risk factors to early atherosclerotic disease using coronary computed tomography angiography. DESIGN AND METHODS: Seventy-eight HIV-infected men (age 46.5 +/- 6.5 years and duration of HIV 13.5 +/- 6.1 years, CD4 T lymphocytes 523 +/- 282; 81% undetectable viral load), and 32 HIV-negative men (age 45.4 +/- 7.2 years) with similar demographic and coronary artery disease (CAD) risk factors, without history or symptoms of CAD, were prospectively recruited. 64-slice multidetector row computed tomography coronary angiography was performed to determine prevalence of coronary atherosclerosis, coronary stenosis, and quantitative plaque burden. RESULTS HIV-infected men demonstrated higher prevalence of coronary atherosclerosis than non-HIV-infected men (59 vs. 34%; P = 0.02), higher coronary plaque volume [55.9 (0-207.7); median (IQR) vs. 0 (0-80.5) microl; P = 0.02], greater number of coronary segments with plaque [1 (0-3) vs. 0 (0-1) segments; P = 0.03], and higher prevalence of Agatston calcium score more than 0 (46 vs. 25%, P = 0.04), despite similar Framingham 10-year risk for myocardial infarction, family history of CAD, and smoking status. Among HIV-infected patients, Framingham score, total cholesterol, low-density lipoprotein, CD4/CD8 ratio, and monocyte chemoattractant protein 1 were significantly associated with plaque burden. Duration of HIV infection was significantly associated with plaque volume (P = 0.002) and segments with plaque (P = 0.0009) and these relationships remained significant after adjustment for age, traditional risk factors, or duration of antiretroviral therapy. A total of 6.5% (95% confidence interval 2-15%) of our study population demonstrated angiographic evidence of obstructive CAD (>70% luminal narrowing) as compared with 0% in controls. CONCLUSION: Young, asymptomatic, HIV-infected men with long-standing HIV disease demonstrate an increased prevalence and degree of coronary atherosclerosis compared with non-HIV-infected patients. Both traditional and nontraditional risk factors contribute to atherosclerotic disease in HIV-infected patients.

Assessment of coronary plaque progression in coronary computed tomography angiography using a semiquantitative score.

OBJECTIVES: We sought to describe the progression of coronary atherosclerotic plaque over time by computed tomography (CT) angiography stratified by plaque composition and its association with cardiovascular risk profiles. BACKGROUND: Data on the progression of atherosclerosis stratified by plaque composition with the use of noninvasive assessment by CT are limited and hampered by high measurement variability. METHODS: This analysis included patients who presented with acute chest pain to the emergency department but initially showed no evidence of acute coronary syndromes. All patients underwent contrast-enhanced 64-slice CT at baseline and after 2 years with the use of a similar protocol. CT datasets were coregistered and assessed for the presence of calcified and noncalcified plaque at 1 mm cross sections of the proximal 40 mm of each major coronary artery. Plaque progression over time and its association with risk factors were determined. Measurement reproducibility and correlation to plaque volume was performed in a subset of patients. RESULTS: We included 69 patients (mean age 55 +/- 12 years, 59% male patients) and compared 8,311 coregistered cross sections at baseline and follow-up. At baseline, any plaque, calcified plaque, and noncalcified were detected in 12.5%, 10.1%, and 2.4% of cross sections per patient, respectively. There was significant progression in the mean number of cross sections containing any plaque (16.5 +/- 25.3 vs. 18.6 +/- 25.5, p = 0.01) and noncalcified plaque (3.1 +/- 5.8 vs. 4.4 +/- 7.0, p = 0.04) but not calcified plaque (13.3 +/- 23.1 vs. 14.2 +/- 22.0, p = 0.2). In longitudinal regression analysis, the presence of baseline plaque, number of cardiovascular risk factors, and smoking were independently associated with plaque progression after adjustment for age, sex, and follow-up time interval. The semiquantitative score based on cross sections correlated closely with plaque volume progression (r = 0.75, p < 0.0001) and demonstrated an excellent intraobserver and interobserver agreement (kappa = 0.95 and kappa = 0.93, respectively). CONCLUSIONS: Coronary plaque burden of patients with acute chest pain significantly increases during the course of 2 years. Progression over time is dependent on plaque composition and cardiovascular risk profile. Larger studies are needed to confirm these results and to determine the effect of medical treatment on progression.

Adenosine-induced stress myocardial perfusion imaging using dual-source cardiac computed tomography.

OBJECTIVES: This study sought to determine the feasibility of performing a comprehensive cardiac computed tomographic (CT) examination incorporating stress and rest myocardial perfusion imaging together with coronary computed tomography angiography (CTA). BACKGROUND: Although cardiac CT can identify coronary stenosis, very little data exist on the ability to detect stress-induced myocardial perfusion defects in humans. METHODS: Thirty-four patients who had a nuclear stress test and invasive angiography were included in the study. Dual-source computed tomography (DSCT) was performed as follows: 1) stress CT: contrast-enhanced scan during adenosine infusion; 2) rest CT: contrast-enhanced scan using prospective triggering; and 3) delayed scan: acquired 7 min after rest CT. Images for CTA, computed tomography perfusion (CTP), and single-photon emission computed tomography (SPECT) were each read by 2 independent blinded readers. RESULTS: The DSCT protocol was successfully completed for 33 of 34 subjects (average age 61.4 +/- 10.7 years; 82% male; body mass index 30.4 +/- 5 kg/m(2)) with an average radiation dose of 12.7 mSv. On a per-vessel basis, CTP alone had a sensitivity of 79% and a specificity of 80% for the detection of stenosis > or =50%, whereas SPECT myocardial perfusion imaging had a sensitivity of 67% and a specificity of 83%. For the detection of vessels with > or =50% stenosis with a corresponding SPECT perfusion abnormality, CTP had a sensitivity of 93% and a specificity of 74%. The CTA during adenosine infusion had a per-vessel sensitivity of 96%, specificity of 73%, and negative predictive value of 98% for the detection of stenosis > or =70%. CONCLUSIONS: Adenosine stress CT can identify stress-induced myocardial perfusion defects with diagnostic accuracy comparable to SPECT, with similar radiation dose and with the advantage of providing information on coronary stenosis.

Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial.

BACKGROUND: A growing population of patients with coronary artery disease experiences angina that is not amenable to revascularization and is refractory to medical therapy. Preclinical studies have indicated that human CD34+ stem cells induce neovascularization in ischemic myocardium, which enhances perfusion and function. METHODS AND RESULTS: Twenty-four patients (19 men and 5 women aged 48 to 84 years) with Canadian Cardiovascular Society class 3 or 4 angina who were undergoing optimal medical treatment and who were not candidates for mechanical revascularization were enrolled in a double-blind, randomized (3:1), placebo-controlled dose-escalating study. Patients received granulocyte colony-stimulating factor 5 microg x kg(-1) x d(-1) for 5 days with leukapheresis on the fifth day. Selection of CD34+ cells was performed with a Food and Drug Administration-approved device. Electromechanical mapping was performed to identify ischemic but viable regions of myocardium for injection of cells (versus saline). The total dose of cells was distributed in 10 intramyocardial, transendocardial injections. Patients were required to have an implantable cardioverter-defibrillator or to temporarily wear a LifeVest wearable defibrillator. No incidence was observed of myocardial infarction induced by mobilization or intramyocardial injection. The intramyocardial injection of cells or saline did not result in cardiac enzyme elevation, perforation, or pericardial effusion. No incidence of ventricular tachycardia or ventricular fibrillation occurred during the administration of granulocyte colony-stimulating factor or intramyocardial injections. One patient with a history of sudden cardiac death/ventricular tachycardia/ventricular fibrillation had catheter-induced ventricular tachycardia during mapping that required cardioversion. Serious adverse events were evenly distributed. Efficacy parameters including angina frequency, nitroglycerine usage, exercise time, and Canadian Cardiovascular Society class showed trends that favored CD34+ cell-treated patients versus control subjects given placebo. CONCLUSIONS: A randomized trial of intramyocardial injection of autologous CD34+ cells in patients with intractable angina was completed that provides evidence for feasibility, safety, and bioactivity. A larger phase IIb study is currently under way to further evaluate this therapy.