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1.  Cocaine Abstinence and Reduced Use Associated With Lowered Marker of Endothelial Dysfunction in African Americans: A Preliminary Study 
Journal of addiction medicine  2015;9(4):331-339.
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.
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.
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).
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.
PMCID: PMC4711371  PMID: 26164164
African Americans; cocaine use; coronary plaque progression; endothelin-1; incidence
2.  Chronic Cocaine Use and Its Association with Myocardial Steatosis Evaluated by 1H Magnetic Resonance Spectroscopy in African Americans 
Journal of addiction medicine  2015;9(1):31-39.
Cardiac steatosis is a manifestation of ectopic fat deposition and is associated with obesity. The impact of chronic cocaine use on obesity measures and on the relationship between obesity measures and cardiac steatosis is not well-characterized. The objectives of this study were to compare obesity measures in chronic cocaine users and non-users, and to explore which factors, in addition to obesity measures, are associated with myocardial triglyceride in African Americans (AAs), using noninvasive magnetic resonance spectroscopy (MRS).
Between June 2004 and January 2014, 180 healthy AA adults without HIV infection, hypertension and diabetes were enrolled in an observational proton MRS and imaging study investigating factors associated with cardiac steatosis.
Among these 180 participants, 80 were chronic cocaine users, and 100 were non-users. The median age (with IQR) was 42 (34-47) years. Obesity measures trended higher in cocaine users than non-users. The median myocardial triglyceride was 0.6% (IQR:0.4-1.1%). Among the factors investigated, years of cocaine use, leptin and visceral fat were independently associated with myocardial triglyceride. BMI and visceral fat, which were significantly associated with myocardial triglyceride in non-cocaine users, were not associated with myocardial triglycerides content in cocaine users.
This study shows (1) cocaine users may have more fat than nonusers and (2) myocardial triglyceride is independently associated with duration of cocaine use, leptin, and visceral fat in all subjects, while leptin and HDL-cholesterol, but not visceral fat or BMI, in cocaine users, suggesting that chronic cocaine use may modify the relationships between obesity measures and myocardial triglyceride.
PMCID: PMC4310799  PMID: 25325298
Cardiac steatosis; African Americans; Obesity; MR spectroscopy; Cocaine Use
3.  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.
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.
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.
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.
PMCID: PMC3833705  PMID: 24265555
vitamin D deficiency; subclinical coronary artery disease; cocaine use; prospective follow-up study; African Americans
4.  Vitamin D deficiency is associated with coronary artery calcification in cardiovascularly asymptomatic African Americans with HIV infection 
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.
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.
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).
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.
PMCID: PMC3758221  PMID: 24009422
African Americans; HIV infection; antiretroviral therapy; coronary artery calcification; vitamin D deficiency
5.  Vitamin D Deficiency Is Associated With Silent Coronary Artery Disease in Cardiovascularly Asymptomatic African Americans With HIV Infection 
Human immunodeficiency virus (HIV)–infected African Americans (AAs) may have a higher risk of cardiovascular complications. Our study suggests that vitamin D deficiency Is independently associated with silent coronary artery disease (CAD) in HIV-infected AAs without symptoms/clinical evidence of CAD. Further longitudinal studies are needed.
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.
PMCID: PMC3404715  PMID: 22423137
7.  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 
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.
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.
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.
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.
PMCID: PMC3355645  PMID: 22327293
Carotid artery; Cholesterol; Lipid core; Risk factors; Stroke
8.  Coronary Vessel Wall Evaluation by Magnetic Resonance Imaging in the Multi-Ethnic Study of Atherosclerosis: Determinants of Image Quality 
Coronary artery wall magnetic resonance imaging (MRI) has been developed to assess coronary lumen diameter and wall thickness. The purpose of this study was to evaluate the physiological parameters that affect the measures of coronary wall thickness using black-blood MRI pulse sequences.
Eighty-seven participants (38 men and 49 women) of the Multi-Ethnic Study of Atherosclerosis were enrolled in the coronary artery wall MRI study. Cine 4-chamber imaging was used to determine the coronary artery rest period. Free-breathing whole-heart magnetic resonance angiography with motion adaptor navigator was performed to localize the coronary arteries in 64 participants. Cross-sectional free-breathing black-blood images were acquired using electrocardiogram-gated, turbo spin echo sequence. Imaging parameters were as follows: repetition time = 2 R-R intervals, time to echo = 33 milliseconds, echo train length = 13, bandwidth = 305 Hz/pixel, matrix = 416 × 416, field of view = 420 × 420 mm, and slice thickness = 4 to 5 mm.
Imaging was completed in 215 (92%) of 234 coronary segments; 9 participants had incomplete scans. Mean age was 62.6 ± 8.4 years (range, 45–81 years). Mean body mass index was 29.2 ± 5.9 kg/m2. A higher proportion of images with quality of “good” was seen in the right coronary artery (40.5%) compared to the left main and left anterior descending coronary arteries (31.9% and 26.4%, respectively). There was a very good agreement between observers in the image quality scores (κ = 0.79, P < 0.001). Lower heart rate, male sex, and longer coronary rest period were associated with higher image quality score (P < 0.05). Signal-to-noise ratio was higher in participants with Agatston calcium score of more than 10 in the right coronary and left main arteries (48.5 vs 69.7, P = 0.001; and 53.4 vs 61.6, P = 0.032, respectively).
Improved depiction of the coronary artery wall with MRI is related to coronary rest period and atherosclerotic plaque burden as measured by calcium score and inversely related to heart rate. Because longer coronary artery rest periods are associated with improved image quality both for angiography with MRI and coronary artery wall imaging, heart rate–lowering methods in association with these techniques appear to be a logical application.
PMCID: PMC3037090  PMID: 19188777
coronary; magnetic resonance imaging; image quality; MRI; cardiac
9.  Positive remodeling of the coronary arteries detected by MRI in an asymptomatic population: the Multi-Ethnic Study of Atherosclerosis (MESA) 
The purpose of this study was to assess coronary arterial remodeling as a marker of subclinical atherosclerosis using coronary wall MRI in an asymptomatic population-based cohort.
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.
179 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) 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.
Men had a greater vessel size, lumen area, and mean wall thickness than women (38.3±11.3 versus 32.6±9.4 mm2, 6.7±3.2 versus 5.3±2.4 mm2, and 2.0±0.3 versus 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, while 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 gender, participants with Agatston score greater than zero were more likely to have wall thickness greater than 2.0 mm (odds ratio 2.0, 95% CI 1.01–3.84).
Coronary wall MRI detected positive arterial remodeling, in asymptomatic men and women with subclinical atherosclerosis.
PMCID: PMC2793325  PMID: 19406347
subclinical atherosclerosis; magnetic resonance imaging; coronary artery disease; plaque
10.  MRI detects increased coronary wall thickness in asymptomatic individuals: The Multi-Ethnic Study of Atherosclerosis (MESA) 
To evaluate the use of coronary wall MRI as a measure of atherosclerotic disease burden in an asymptomatic population free of clinical cardiovascular disease.
Coronary wall magnetic resonance imaging (MRI) is a noninvasive method for evaluation of arterial wall remodeling associated with atherosclerosis.
Materials and Methods
Asymptomatic participants of the Multi-Ethnic Study of Atherosclerosis (MESA) study were studied using black blood MRI. MRI assessed coronary wall thickness was compared to computed tomography calcium score, carotid intimal-medial thickness and risk factors for coronary artery disease.
Eighty eight arterial segments were evaluated in 38 MESA participants (mean age, 61.3 ± 8.7 years). The maximum coronary wall thickness was greater for participants with 2 or more cardiovascular risk factors than for those with 1 or no risk factors (2.59 ± 0.33 mm versus 2.36 ± 0.30 mm, respectively, p=0.05.) For participants with zero calcium score, the mean and maximum coronary wall thickness for subjects with 2 or more risk factors for coronary artery disease were greater than the wall thickness for subjects with 1 or no risk factors (mean thickness: 1.95 ± 0.17 mm versus 1.7 ± 0.19 mm; maximum thickness: 2.67 ± 0.24 mm versus 2.32 ± 0.27 mm, respectively, p <0.05). Subjects with increased carotid intimal-medial thickness also had increased coronary artery wall thickness (p< 0.05).
Coronary artery wall MRI detects increased coronary wall thickness in asymptomatic individuals with subclinical markers of atherosclerotic disease and in individuals with zero calcium score.
PMCID: PMC2577717  PMID: 18837001
coronary artery disease; atherosclerosis; MRI; plaque

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