Shaoguang Chen

Positive remodeling of the coronary arteries detected by magnetic resonance imaging in an asymptomatic population: MESA (Multi-Ethnic Study of Atherosclerosis).

OBJECTIVES The purpose of this study was to assess coronary arterial remodeling as a marker of subclinical atherosclerosis using coronary wall magnetic resonance imaging (MRI) in an asymptomatic population-based cohort. BACKGROUND In early atherosclerosis, compensatory enlargement of both the outer wall of the vessel as well as the lumen, termed compensatory enlargement or positive remodeling, occurs before luminal narrowing. METHODS One hundred seventy-nine participants in the MESA (Multi-Ethnic Study of Atherosclerosis) trial were evaluated using black-blood coronary wall MRI. Coronary cross-sectional area (vessel size), lumen area, and mean wall thickness of the proximal coronary arteries were measured. RESULTS Men had a greater vessel size, lumen area, and mean wall thickness than women (38.3 +/- 11.3 mm2 vs. 32.6 +/- 9.4 mm2, 6.7 +/- 3.2 mm2 vs. 5.3 +/- 2.4 mm2, and 2.0 +/- 0.3 mm vs. 1.9 +/- 0.3 mm, respectively, p < 0.05). No significant coronary artery narrowing was present by magnetic resonance angiography. Overall, coronary vessel size increased 25.9 mm2 per millimeter increase in coronary wall thickness, whereas lumen area increased only slightly at 3.1 mm2 for every millimeter increase in wall thickness (difference in slopes, p < 0.0001). Adjusting for age and sex, participants with an Agatston score >0 were more likely to have wall thickness >2.0 mm (odds ratio: 2.0, 95% confidence interval: 1.01 to 3.84). CONCLUSIONS Coronary wall MRI detected positive arterial remodeling in asymptomatic men and women with subclinical atherosclerosis.

The Association of Pericardial Fat with Coronary Artery Plaque Index at MR Imaging: The Multi-Ethnic Study of Atherosclerosis (MESA)

PURPOSE To determine the relationship of pericardial fat, which secretes proinflammatory markers that have been implicated in coronary atherosclerosis, with atherosclerotic plaque in an asymptomatic population-based cohort. MATERIALS AND METHODS In this institutional review board-approved study, all participants supplied written informed consent. One hundred eighty-three participants (89 women, 94 men; mean age, 61 years ± 9 [standard deviation]) from the community-based Multi-Ethnic Study of Atherosclerosis (MESA) were included. The coronary artery eccentricity (ratio of maximal to minimal coronary artery wall thickness) was determined by using magnetic resonance (MR) imaging and served as an index of plaque burden. The pericardial fat volume was determined by using computed tomography. Linear regression coefficient analysis was used to correlate pericardial fat volume with coronary artery wall thickness and plaque eccentricity. RESULTS Pericardial fat volume correlated significantly with degree of plaque eccentricity (P < .05) in both men and women. After adjustments for body mass index (BMI) and waist circumference, traditional risk factors, C-reactive protein level, and coronary artery calcium content, the relationship between pericardial fat and plaque eccentricity remained significant in men (P < .01) but not in women. BMI and waist circumference correlated with degree of plaque eccentricity in the univariate model (P < .05) but not after adjustment for pericardial fat volume or traditional risk factors. CONCLUSION Pericardial fat volume, rather than BMI and waist circumference, was more strongly related to plaque eccentricity as a measure of coronary atherosclerotic plaque burden. The results support the proposed role of pericardial fat in association with atherosclerosis.

Vitamin D Deficiency is Associated With Silent Coronary Artery Disease in Cardiovascularly Asymptomatic African Americans With HIV Infection

BACKGROUND Growing evidence suggests that vitamin D deficiency Is associated with clinical coronary artery disease (CAD). The relationship between vitamin D deficiency and subclinical CAD in HIV-infected individuals is not well-characterized. METHODS Computed tomographic (CT) coronary angiography was performed using contrast-enhanced 64-slice multidetector CT imaging, and vitamin D levels and the presence of traditional and novel risk factor for CAD were obtained in 674 HIV-infected African American (AA) participants aged 25-54 years in Baltimore, MD, without symptoms/clinical evidence of CAD. RESULTS The prevalence of vitamin D deficiency (25-hydroxy vitamin D <10 ng/mL) was 20.0% (95% confidence interval [CI], 16.9-23.1). Significant (≥50%) coronary stenosis was present in 64 (9.5%) of 674 participants. Multiple logistic regression analysis revealed that male gender (adjusted odds ratio [OR], 2.19; 95% CI, 1.17-4.10), diastolic BP ≥85 mmHg (adjusted OR: 1.94, 95% CI: 1.02 -3.68), low-density lipoprotein cholesterol ≥100 mg/dL (adjusted OR, 1.95; 95% CI, 1.13-3.36), cocaine use for ≥15 years (adjusted OR, 1.77; 95% CI, 1.01-3.10), use of antiretroviral therapies for ≥6 months (adjusted OR, 2.26; 95% CI, 1.17-4.36), year of enrollment after 2005 (adjusted ORs for 2006-2007, 2008-2009, and 2010 were 0.32 [95% CI, 0.13-0.76], 0.26 [95% CI, 0.12-0.56], and 0.32 (95% CI, 0.15-0.65], respectively), and vitamin D deficiency (adjusted OR, 2.28; 95% CI, 1.23-4.21) were independently associated with significant coronary stenosis. CONCLUSIONS Both vitamin D deficiency and silent CAD are prevalent in HIV-infected AAs. In addition to management of traditional CAD risk factors and substance abuse, vitamin D deficiency should be evaluated in HIV-infected AAs. These data support the conduct of a prospective trial of vitamin D in this high-risk patient population.

HIV Infection Itself May Not Be Associated With Subclinical Coronary Artery Disease Among African Americans Without Cardiovascular Symptoms

Background The key objectives of this study were to examine whether HIV infection itself is associated with subclinical coronary atherosclerosis and the potential contributions of cocaine use and antiretroviral therapies (ARTs) to subclinical coronary artery disease (CAD) in HIV‐infected persons. Methods and Results Between June 2004 and February 2015, 1429 African American (AA) adults with/without HIV infection in Baltimore, Maryland, were enrolled in an observational study of the effects of HIV infection, exposure to ART, and cocaine use on subclinical CAD. The prevalence of subclinical coronary atherosclerosis was 30.0% in HIV‐uninfected and 33.7% in HIV‐infected (P=0.17). Stratified analyses revealed that compared to HIV‐uninfected, HIV‐infected ART naïve were at significantly lower risk for subclinical coronary atherosclerosis, whereas HIV‐infected long‐term ART users (≥36 months) were at significantly higher risk. Thus, an overall nonsignificant association between subclinical coronary atherosclerosis and HIV was found. Furthermore, compared to those who were ART naïve, long‐term ART users (≥36 months) were at significantly higher risk for subclinical coronary atherosclerosis in chronic cocaine users, but not in those who never used cocaine. Cocaine use was independently associated with subclinical coronary atherosclerosis. Conclusions Overall, HIV infection, per se, was not associated with subclinical coronary atherosclerosis in this population. Cocaine use was prevalent in both HIV‐infected and ‐uninfected individuals and itself was associated with subclinical disease. In addition, cocaine significantly elevated the risk for ART‐associated subclinical coronary atherosclerosis. Treating cocaine addiction must be a high priority for managing HIV disease and preventing HIV/ART‐associated subclinical and clinical CAD in individuals with HIV infection.

Vitamin D deficiency is associated with development of subclinical coronary artery disease in HIV-infected African American cocaine users with low Framingham-defined cardiovascular risk

Chronic cocaine use may lead to premature atherosclerosis, but the prevalence of and risk factors for coronary artery disease (CAD) in asymptomatic cocaine users have not been reported. The objective of this study was to examine whether vitamin D deficiency is associated with the development of CAD in human immunodeficiency virus (HIV)-infected African American cocaine users with low CAD risk. Methods In this prospective follow-up study, we investigated 169 HIV-infected African American cocaine users with low Framingham risk at baseline. The main outcome measures were incidence of subclinical CAD and development of subclinical CAD. Results Fifty of the 169 African Americans had evidence of subclinical disease on the initial cardiac computed tomography. A second cardiac computed tomography was performed on the 119 African Americans without disease on the first scan. The total sum of person-years of follow-up was 289.6. Subclinical CAD was detected in 11 of these, yielding an overall incidence of 3.80/100 person-years (95% confidence interval 1.90–6.80). Among the factors investigated, only vitamin D deficiency was independently associated with development of subclinical CAD. The study did not find significant associations between CD4 count, HIV viral load, or antiretroviral treatment use and the incidence of subclinical CAD. This study appears to suggest that there is a threshold level of vitamin D (10 ng/mL) above which the effect of vitamin D on subclinical CAD is diminished. Conclusion The incidence of subclinical CAD in HIV-infected African American cocaine users with low CAD risk is high, especially in those with vitamin D deficiency. Well designed randomized clinical trials are warranted to confirm the role of vitamin D deficiency in the development of CAD in HIV-infected African American cocaine users with low CAD risk.

Cocaine Abstinence and Reduced Use Associated With Lowered Marker of Endothelial Dysfunction in African Americans: A Preliminary Study.

Objectives:Clinical and epidemiological evidence suggests that cocaine use is associated with an increased risk of premature atherosclerosis. The objectives of this study were to explore (1) whether cocaine abstinence is associated with a reduced marker of endothelial dysfunction, (2) whether cocaine abstinence is associated with a slower coronary plaque progression, and (3) whether reduction in cocaine use is associated with a reduced marker of endothelial dysfunction in African American chronic cocaine users with contrast-enhanced coronary CT angiography-confirmed less than 50% coronary stenosis. Methods:Between March and June 2014, a total of 57 African American cocaine users with contrast-enhanced CT angiography-confirmed less than 50% coronary stenosis in Baltimore, Maryland, were enrolled in a 6-month follow-up study to investigate whether cocaine abstinence or reduction in cocaine use is associated with decreased endothelin-1 (ET-1) levels and coronary plaque progression at the 6-month follow-up. A voucher-based incentive approach was used to systematically reinforce cocaine abstinence, and urine benzoylecgonine test was implemented to confirm cocaine use. Results:Among the 57 participants, 44 were HIV-infected. The median of duration of cocaine use was 18 (interquartile range, 7–30) years. According to generalized estimating equation analyses, both cocaine abstinence and reduction in cocaine use in the 6 months were independently associated with decreased ET-1. The incidence of coronary plaque progression was 7.4/100 person-years and 23.1/100 person-years in those who were totally abstinent from cocaine and those who continued to use cocaine, respectively. However, the difference in the incidence between these 2 groups was not significant (exact P = 0.30). Conclusions:The findings of this study revealed a possible association of cocaine abstinence/reduction with lowered ET levels, which suggests that such changes in cocaine use might be beneficial for preventing endothelial damage. Further studies should be conducted to investigate whether ET-1 could be used as a marker for cocaine abstinence and reduction in cocaine use.

Vitamin D deficiency is associated with coronary artery calcification in cardiovascularly asymptomatic African Americans with HIV infection

Objective Patients with HIV infection are at increased risk for coronary artery disease (CAD), and growing evidence suggests a possible link between vitamin D deficiency and clinical/subclinical CAD. However, the relationship between vitamin D deficiency and coronary artery calcification (CAC), a sensitive marker for subclinical CAD, in those with HIV infection is not well investigated. Methods CAC was quantified using a Siemens Cardiac 64 scanner, and vitamin D levels and the presence of traditional and novel risk factors for CAD were obtained in 846 HIV-infected African American (AA) participants aged 25 years or older in Baltimore, MD, USA without symptoms or clinical evidence of CAD. Results The prevalence of vitamin D deficiency (25-hydroxy vitamin D <10 ng/mL) was 18.7%. CAC was present in 238 (28.1%) of the 846 participants. Logistic regression analysis revealed that the following factors were independently associated with CAC: age (adjusted odds ratio [OR]: 1.11; 95% confidence interval [CI]: 1.08–1.14); male sex (adjusted OR: 1.71; 95% CI: 1.18–2.49); family history of CAD (adjusted OR: 1.53; 95% CI: 1.05–2.23); total cholesterol (adjusted OR: 1.006; 95% CI: 1.002–1.010); high-density lipoprotein cholesterol (adjusted OR: 0.989; 95% CI: 0.979–0.999); years of cocaine use (adjusted OR: 1.02; 95% CI: 1.001–1.04); duration of exposure to protease inhibitors (adjusted OR: 1.004; 95% CI: 1.001–1.007); and vitamin D deficiency (adjusted OR: 1.98; 95% CI: 1.31–3.00). Conclusion Both vitamin D deficiency and CAC are prevalent in AAs with HIV infection. In order to reduce the risk for CAD in HIV-infected AAs, vitamin D levels should be closely monitored. These data also suggest that clinical trials should be conducted to examine whether vitamin D supplementations reduce the risk of CAD in this AA population.

Vitamin D Deficiency is Associated with the Development of Subclinical Coronary Artery Disease in African Americans with HIV Infection: A Preliminary Study

Background Premature coronary artery disease (CAD) is a major concern in human immunodeficiency virus (HIV)-infected African Americans. The objectives of the study were to estimate the incidence of subclinical CAD, defined by the presence of coronary plaque and/or calcification on cardiac computed tomography (CT), and to identify the associated risk factors in this vulnerable population. Subjects and Methods Between August 2003 and September 2010, 188 HIV-infected African Americans without known, or symptoms of, CAD underwent cardiac CT. The subset without demonstrable disease underwent a second cardiac CT approximately 2 years later. The incidence of disease over that period and the effects of antiretroviral treatment and other known and hypothesized risk factors were investigated. Results Sixty-nine of these 188 African Americans had evidence of subclinical disease on the initial cardiac CT, confirming prior high prevalence reports. A second cardiac CT was performed on 119 African Americans without disease approximately 2 years later. The total person-years of follow-up was 284.4. Subclinical CAD was detected in 14 of these, yielding an overall incidence of 4.92/100 person-years (95% confidence interval, 2.69–8.26). Among the factors investigated, only male sex and vitamin D deficiency were independently associated with the development of subclinical CAD. The study did not find significant associations between CD4 count, HIV viral load, antiretroviral treatment use, or cocaine use and the incidence of subclinical CAD. Conclusions The incidence of subclinical CAD in African Americans with HIV infection is provocatively high. Larger studies are warranted to confirm the role of vitamin D deficiency in the development of CAD in HIV-infected African Americans.

Cholesterol is associated with the presence of a lipid core in carotid plaque of asymptomatic, young-to-middle-aged African Americans with and without HIV infection and cocaine use residing in inner-city Baltimore, Md., USA.

Background: Stroke remains a leading cause of death in the United States. While stroke-related mortality in the USA has declined over the past decades, stroke death rates are still higher for blacks than for whites, even at younger ages. The purpose of this study was to estimate the frequency of a lipid core and explore risk factors for its presence in asymptomatic, young-to-middle-aged urban African American adults recruited from inner-city Baltimore, Md., USA. Methods: Between August 28, 2003, and May 26, 2005, 198 African American participants aged 30-44 years from inner-city Baltimore, Md., were enrolled in an observational study of subclinical atherosclerosis related to HIV and cocaine use. In addition to clinical examinations and laboratory tests, B-mode ultrasound for intima-media thickness of the internal carotid arteries was performed. Among these 198, 52 were selected from the top 30th percentile of maximum carotid intima-media thickness by ultrasound, and high-resolution black blood MRI images were acquired through their carotid plaque before and after the intravenous administration of gadodiamide. Of these 52, 37 with maximum segmental thickness by MRI >1.0 mm were included in this study. Lumen and outer wall contours were defined using semiautomated analysis software. The frequency of a lipid core in carotid plaque was estimated and risk factors for lipid core presence were explored using logistic regression analysis. Results: Of the 37 participants in this study, 12 (32.4%) were women. The mean age was 38.7 ± 4.9 years. A lipid core was present in 9 (17%) of the plaques. Seventy percent of the study participants had a history of cigarette smoking. The mean total cholesterol level was 176.1 ± 37.3 mg/dl, the mean systolic blood pressure was 113.1 ± 13.3 mm Hg, and the mean diastolic blood pressure was 78.9 ± 9.5 mm Hg. There were 5 participants with hypertension (13.5%). Twelve (32%) participants had a history of chronic cocaine use, and 23 (62%) were HIV positive. Among the factors investigated, including age, sex, blood pressure, cigarette smoking, C-reactive protein, fasting glucose, triglycerides, serum total cholesterol, coronary calcium, cocaine use, and HIV infection, only total cholesterol was significantly associated with the presence of a lipid core. Conclusions: This study revealed an unexpectedly high rate of the presence of lipid core in carotid plaque and highlights the importance of cholesterol lowering to prevent cerebrovascular disease in this population. Further population-based studies are warranted to confirm these results.

Interaction of sex steroid hormones and obesity on insulin resistance and type 2 diabetes in men: the Third National Health and Nutrition Examination Survey

AIMS We examined interaction of sex steroid hormones and obesity with regard to insulin resistance (IR) and type 2 diabetes (T2D) by using nationally representative data from the US. METHODS Data of 1461 men aged ≥20years who participated in the Third National Health and Nutrition Examination Survey were analyzed. Multiplicative interaction was calculated by cross-product interaction terms in multivariable logistic regression models. Additive interaction was assessed by the relative excess risk due to interaction (RERI). RESULTS After adjusting for demographic and lifestyle covariates, the odds of IR were greatest among obese men with low free testosterone and high androstanediol glucuronide. Multiplicative interactions for total testosterone, free testosterone, and free estradiol index (FEI) were statistically significant with central obesity but not with overweight and obesity regarding to T2D (P<0.05). Significant additive interactions with obesity or central obesity were detected for total testosterone (RERI=2.75, 95% CI=0.92,4.59), SHBG (RERI=5.71, 95% CI=0.77,10.64), and FEI (RERI=-9.96, 95% CI=-19.18,-0.74) with regard to IR, beta-cell dysfunction, and T2D. CONCLUSIONS Our findings add to the evidence suggesting that low testosterone and high estradiol may be associated greater risks of IR and T2D by interacting with overall and central obesity in adult men.