HIV-infected patients are known to be at risk for premature coronary artery disease. This emerging paradigm is a rising concern for clinicians. Due to advances in the treatment of HIV, this once fatal infection has been transformed into a chronic illness. Traditional risk factors paired with the long-term use of antiretroviral therapy (ART) and chronic inflammation leads to premature atherosclerosis, particularly progression of atherosclerotic plaque. This population of patients requires early recognition of subclinical atherosclerosis, as well aggressive primary and secondary prevention strategies among the multi-disciplinary team of physicians caring for them. We sought to present a comprehensive review of the available literature related to HIV and atherosclerosis and cardiovascular risk.

Aim The aim of this study was to assess the effect on adherence to statin therapy and assess the effect of beneficial changes in behavior that resulted in weight loss in patients who underwent coronary artery calcium (CAC) scoring with cardiac computed tomography. Background Despite convincing data demonstrating the benefits of HmGCoA inhibitors for both primary and secondary prevention of coronary heart disease, they remain underused. Also, despite convincing data demonstrating the benefits of weight loss for both primary and secondary prevention of coronary heart disease, it remains difficult to motivate behavioral changes resulting in weight loss. In this study, we assess whether higher CAC scores are associated with increased compliance with statin medication and whether higher CAC scores are associated with beneficial lifestyle behaviors resulting in weight loss. Methods We retrospectively analyzed patients that had undergone baseline CAC testing and returned for a follow-up scan. All patients had weight documented and were administered a questionnaire regarding compliance to medications. The primary endpoint was measurable weight loss between visit one and visit two and the self-reported compliance to statin use. Results The study population with data regarding statin compliance consisted of 2608 individuals (72% men, mean age 58±8 years) who were followed for a mean of 4.1±3.2 years after an initial CAC scan. Overall, statin compliance was lowest (27.4%) among those with CAC=0, and gradually increased with higher CAC scores (1-99, 39.2%; 100-399, 53.6%; ≥400, 58.8%; P<0.001 for trend). In the group analyzed for weight loss the study population consisted of 1078 individuals (68% men, mean age 60±8 years) who were followed for a mean of 4.1±3.2 years after an initial CAC scan. Conclusion Overall, behavioral modification resulting in weight loss was lowest (19.8%) among those with CAC=0, and gradually increased with higher CAC scores (1-99, 23.4%; 100-399, 30.8%; ≥400, 33.6%; P<0.001 for trend). In addition to being a robust risk stratification tool, a higher rate of adherences with statin therapy was observed in patients with higher CAC scores.

Aims

The metabolic syndrome (MetS) is a clustering of low levels of HDL cholesterol, hyperglycaemia, high waist circumference, hypertension and elevated triglycerides, and is associated with cardiovascular disease. Calcified atherosclerotic plaque in the thoracic aorta (TAC), measured by non-contrast cardiac computed tomography (CT) scans, is a marker for atherosclerosis and relates to mortality. We sought to evaluate the independent association of MetS and TAC on cardiac CT scans.

Methods

We examined the relation of the MetS, and each of its components, to the prevalence of TAC, measured from 2000 to 2002 in 6778 white, Chinese, African-American and Hispanic participants in the Multi-Ethnic Study of Atherosclerosis (MESA).

Results

Adjusting for age, gender, race, smoking, LDL cholesterol and lipid-lowering medications, relative risks and 95% confidence intervals (CI) for a TAC score > 0 were: 1.19 (95% CI 1.11 to 1.28) for participants with MetS, 1.34 (95% CI 1.21 to 1.49) for those with diabetes and MetS, and 1.33 (95% CI 1.11, 1.58) for those with diabetes and no MetS compared with participants who were free of the MetS and diabetes. Associations were found for most of the components of the MetS with TAC.

Conclusions

We conclude that in adults without known heart disease, the MetS, most of its components and diabetes are associated with a higher prevalence of calcified atherosclerotic plaque in the thoracic arteries in a multi-ethnic population of men and women.

Objective

To investigate whether leptin and adiponectin are associated with body fat composition in a South Asian population independent of metabolic variables.

Design

Cross-sectional study.

Subjects

150 South Asian men and women, between the ages of 45-79 years, in the San Francisco Bay Area without pre-existing clinical cardiovascular disease.

Measurements

Blood samples were obtained to measure glucose metabolism variables, lipid profiles and adipokines. Total body fat was determined using dual-energy X-ray absorptiometry. Abdominal computed tomography was used to measure subcutaneous, visceral and hepatic fat.

Results

Average body mass index (BMI) was overweight at 26.1±4.6 kg m(-2) and did not differ by sex. However, women had significantly more total body fat (P<0.001) and subcutaneous fat (P<0.001) than men, whereas men had significantly more visceral fat (P<0.001) and hepatic fat (P=0.04) than women. Women had significantly higher levels of adiponectin (P<0.01) and leptin (P<0.01). In sex-stratified analyses, leptin was strongly associated with all-body composition measures in women (P<0.05) as well as in men (P<0.05 except for hepatic fat), whereas there was an insignificant trend towards an inverse association between adiponectin and body composition in both women and men, which was significant in combined bivariate analyses. In multivariate analyses, leptin was strongly associated with all measures of adiposity, including BMI (P<0.001), total body fat (P<0.001), visceral fat (P<0.001) and hepatic fat (P=0.01). However, adiponectin's inverse association with adiposity was significantly attenuated by high-density lipoprotein (HDL), triglycerides and insulin resistance. The association between adipokines and diabetes was markedly attenuated after adjusting for body composition.

Conclusion

Despite only modestly elevated BMI, South Asians have elevated levels of total and regional adiposity. Leptin is strongly associated with adiposity, whereas adiponectin's association with adiposity is attenuated by metabolic variables in South Asians. Adipokines in association with adiposity have an important role in the development of diabetes.

We hypothesized that anthropometric measures of abdominal obesity would have a stronger positive association with nonalcoholic fatty liver disease (NAFLD) measured by noncontrast computed tomography versus general measures of obesity. The Multiethnic Study of Atherosclerosis comprised participants aged 45 to 84 years free of known cardiovascular disease. We studied 4,088 participants with adequate liver and spleen computed tomography imaging and no previous use of oral steroids, class 3 antiarrhythmics, moderately heavy alcohol use, or cirrhosis. Prevalent NAFLD was defined as a liver:spleen Hounsfield attenuation ratio of <1. Multivariable log-linear regression modeled the association of 4 obesity measures - weight, body mass index (BMI), waist circumference, and waist-to-hip ratio - with prevalent NAFLD. Receiver-operator curve analysis compared NAFLD discrimination. Median age was 63 years, and 55% were women. For each obesity measure, adjusted prevalence ratios for NAFLD were fourfold to fivefold greater in the highest versus the lowest quartile (p <0.001). Waist circumference and BMI had the highest prevalence ratios, and waist circumference had the best discrimination, for NAFLD in the total population, although an abnormal BMI categorized subjects with NAFLD as well if not better than waist circumference. In ethnic-specific analysis, whites and Chinese had the strongest association of obesity and NAFLD compared with other ethnicities. In conclusion, although waist circumference provided the best discrimination for NAFLD, BMI may perform similarly well in clinical settings to screen for NAFLD.

Aims

In individuals with chronic kidney disease (CKD), including those undergoing maintenance hemodialysis (MHD), coronary artery calcification (CAC) is common. We hypothesized that, in MHD patients, intake of the calcium-free phosphate binder sevelamer is associated with lower CAC compared to calcium-based phosphate binders (CBPB).

Material and methods

This is a cross-sectional study of MHD patients, who underwent computerized tomography to assess coronary artery calcium scores (CACS). Patients were stratified into two mutually exclusive groups based on taking only a CBPB vs. sevelamer. Logistic regression was used to calculate adjusted odds ratio (OR) of CACS > or = 400, CACS 100 < or =; CACS < 400, 10 < or =; CACS < 100 vs. CACS < 10.

Results

117 MHD patients were either on a CBPB alone (n = 60) or sevelamer alone (n = 57). Despite increased prevalence of DM in the sevelamer group (58%) as compared to the CBPB group (35%), CACS was significantly lower with sevelamer use (283 + or - 83 vs. 494 + or - 94, p = 0.02). The OR of significant CACS > or =; 400 vs. CAC < 10 was 4.35 (95% confidence interval: 1.5 - 9.9, p = 0.008) for CBPB compared with sevelamer, after controlling for case-mix, cholesterol-lowering medication, DM, and inflammatory markers.

Conclusion

In our cohort, significant CAC was significantly more prevalent among MHD patients taking CBPB as compared to sevelamer monotherapy.

Although coronary computed tomographic angiography (CCTA) has been a robust diagnostic tool to identify anatomical significance of coronary artery disease (CAD), the utility of CCTA to assess hemodynamic significance of CAD remains unclear. We investigated the diagnostic performance of transluminal attenuation gradient (TAG) and fractional flow reserve derived from CCTA (FFRCT) to predict lesion-specific ischemia by invasive FFR. We identified 103 patients with suspected or known CAD enrolled from the DISCOVER-FLOW and DeFACTO studies who underwent invasive coronary angiography with FFR and high quality ≥64-slice CCTA. Diagnostic performance for predicting abnormal invasive FFR (≤0.80) was assessed for TAG [≤−1.1 HU/mm by the area under the curve (AUC) by receiver-operating characteristic curve analysis (ROC)], FFRCT (≤0.80), and CCTA stenosis (≥50 %). On a per-vessel analysis (n = 146), 52 vessels (35.6 %) had ischemia by invasive FFR. The sensitivity, specificity, positive predictive value and negative predictive value were 53.8, 45.7, 35.4, 64.2 % for TAG, 82.7, 74.5, 64.2, 88.6 % for FFRCT, 84.6, 39.4, 43.6, 82.2 % for CCTA stenosis, respectively. The AUC by ROC curve analysis for FFRCT (0.79) demonstrated greater discrimination of hemodynamic ischemia compared to TAG (0.50, p < 0.0001 vs. FFRCT), CCTA stenosis (0.62, p = 0.0004 vs. FFRCT) and the combination of the two (0.63, p = 0.004 vs. FFRCT). These results remained consistent regardless of the number of CCTA slices. FFRCT allows identification of lesion-specific ischemia using invasive FFR as a reference standard with greater diagnostic accuracy than TAG, CCTA stenosis, or the combination of the two.

Levels of circulating of sex hormones are associated with glucose metabolism and adiposity, but little is known about their association with ectopic fat. We aimed to characterize the association between circulating sex hormones and liver fat. Methods: We conducted a cross-sectional analysis by using data from the Multiethnic Study of Atherosclerosis to assess the association of the circulating levels of bioavailable testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) with fatty liver. Fatty liver was defined as a reduction of ≤40 Hounsfield units, measured by computed tomography, in 2835 postmenopausal women and 2899 men (45-84 years old; white, black, Hispanic, or Chinese) at 6 centers in the United States. Results: Women in the highest tertile of bioavailable testosterone were significantly more likely to have fatty liver than women in the lowest tertile (odds ratio, 1.77; 95% confidence interval, 1.07-2.92). We found an even greater difference for level of estradiol (odds ratio, 2.49; 95% confidence interval, 1.41-4.39) after adjusting for age, race/ethnicity, waist-to-hip ratio, hypertension, total and high-density lipoprotein cholesterol, smoking, insulin sensitivity, and hormone replacement therapy use. Men in the highest tertile of estradiol level were significantly more likely to have fatty liver than men in the lowest tertile (odds ratio, 2.10; 95% confidence level, 1.29-3.40). Men in the highest tertile of SHBG were less likely to have fatty liver than those in the lowest tertile (odds ratio, 0.46; 95% confidence interval, 0.27-0.77). Other associations between hormone levels and fatty liver were not statistically significant. Conclusions: On the basis of a cross-sectional study, postmenopausal women with high levels of bioavailable testosterone are at greater risk for fatty liver. In men, higher levels of SHBG are associated with reduced risk for fatty liver. Higher levels of estradiol are associated with fatty liver in both sexes. This pattern is consistent with the sex-specific associations of sex hormones with other cardiometabolic risk factors.

Background: Myocardial CT perfusion (CTP) is a promising tool for the detection of myocardial ischemia. We hypothesize that regadenoson CTP is noninferior to regadenoson single photon emission CT (SPECT) for detecting or excluding myocardial ischemia. Methods: Patients (men ≥45years; women ≥50years) with known or suspected coronary artery disease (n= 124) were randomized to 1 of 2 diagnostic sequences: rest and regadenoson SPECT on day 1, then regadenoson CTP and rest CTP (and coronary CT angiography [CTA]) (CTA; same acquisition) on day 2 or regadenoson CTP and rest CTP (and CTA) on Day 1, then rest and regadenoson SPECT on day 2. Scanning platforms included 64-, 128-, 256-, and 320-slice systems. The primary analysis examined the agreement rate between CTP and SPECT for detecting or excluding reversible ischemia in ≥2 myocardial segments as assessed by independent, blinded readers. Results: Complete and interpretable CTP and SPECT scans were obtained for 110 patients. Regadenoson CTP was noninferior to SPECT for detecting or excluding reversible ischemia with an agreement rate of 0.87 (95% confidence interval [CI], 0.77-0.97) and sensitivity and specificity of 0.90 (95% CI, 0.71-1.00) and 0.84 (95% CI, 0.77-0.91), respectively. The agreement rate for detecting or excluding ≥1 fixed defects by regadenoson CTP and SPECT was 0.86 (95% CI, 0.74-0.98). With SPECT as the reference standard, the diagnostic accuracies for detecting or excluding ischemia by regadenoson CTP and CTA alone were 0.85 (95% CI, 0.78-0.91) and 0.69 (95% CI, 0.60-0.77), respectively. Conclusions: This study establishes the noninferiority of regadenoson CTP to SPECT for detecting or excluding myocardial ischemia.

Objective This study aims to present methods and baseline data from the Early versus Late Intervention Trial with Estradiol (ELITE), the only clinical trial designed to specifically test the timing hypothesis of postmenopausal hormone therapy (HT). The timing hypothesis posits that HT effects depend on the temporal initiation of HT relative to time since menopause. Methods ELITE is a randomized, double-blind, placebo-controlled trial with a 2 × 2 factorial design. Six hundred forty-three healthy postmenopausal women without cardiovascular disease were randomized to oral estradiol or placebo for up to 6 to 7 years according to time since menopause (<6 or ≥10 y). Carotid artery intima-media thickness (CIMT) and cardiac computed tomography were conducted to determine HT effects on subclinical atherosclerosis across menopause strata. Results Participants in the early and late postmenopausal strata were well-separated by mean age (55.4 vs 65.4 y) and median time since menopause (3.5 vs 14.3 y). Expected risk factors (age, blood pressure, and body mass index) were associated with CIMT at baseline in both strata. In the early postmenopausal group, but not in the late postmenopausal group, we observed significant associations between CIMT and factors that may play a role in the responsiveness of atherosclerosis progression according to timing of HT initiation. These include low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, sex hormone-binding globulin, and serum total estradiol. Conclusions The ELITE randomized controlled trial is timely and unique. Baseline data indicate that ELITE is well-positioned to test the HT timing hypothesis in relation to atherosclerosis progression and coronary artery disease.