Jeffrey Carr

Association of Obesity in Early Adulthood and Middle Age With Incipient Left Ventricular Dysfunction and Structural Remodeling : The CARDIA Study (Coronary Artery Risk Development in Young Adults)

OBJECTIVESnThe goal of this study was to investigate the relationship of body mass index (BMI) and its 25-year changexa0to left ventricular (LV) structure and function.nnnBACKGROUNDnLongstanding obesity may be associated with clinical cardiac dysfunction and heart failure. Whether obesity relates to cardiac dysfunction during young adulthood and middle age has not been investigated.nnnMETHODSnThe CARDIA (Coronary Artery Risk Development in Young Adult) study enrolled white and black adults ages 18 to 30 years in 1985 to 1986 (Year-0). At Year-25, cardiac function was assessed by conventional echocardiography, tissue Doppler imaging (TDI), and speckle tracking echocardiography (STE). Twenty-five-year change in BMI (classified as low:xa0<27 kg/m(2) and high:xa0≥27 kg/m(2)) was categorized into 4 groups (Low-Low, High-Low, Low-High, and High-High). Multiple linear regression was used to quantify the association between categorical changes in BMI (Low-Low as reference) with LV structural and functional parameters obtained in middle age, adjusting for baseline and 25-year change in risk factors.nnnRESULTSnThe mean BMI was 24.4 kg/m(2) in 3,265 participants included at Year-0. Change in BMI adjusted for risk factors was directly associated with incipient myocardial systolic dysfunction assessed by STE (High-High: β-coefficientxa0= 0.67; Low-High: β-coefficientxa0= 0.35 for longitudinal peak systolic strain) and diastolic dysfunction assessed by TDI (High-High: β-coefficientxa0=xa0-074; Low-High: β-coefficientxa0=xa0-0.45 for e) and STE (High-High: β-coefficientxa0=xa0-0.06 for circumferential early diastolic strain rate). Greater BMI was also significantly associated with increased LV mass/height (High-High: β-coefficientxa0= 26.11; Low-High: β-coefficientxa0= 11.87).nnnCONCLUSIONSnLongstanding obesity from young adulthood to middle age is associated with impaired LV systolic andxa0diastolic function assessed by conventional echocardiography, TDI, and STE in a large biracial cohort of adults agexa043xa0to 55xa0years.

Strength Training for Arthritis Trial (START): design and rationale

BackgroundMuscle loss and fat gain contribute to the disability, pain, and morbidity associated with knee osteoarthritis (OA), and thigh muscle weakness is an independent and modifiable risk factor for it. However, while all published treatment guidelines recommend muscle strengthening exercise to combat loss of muscle mass and strength in knee OA patients, previous strength training studies either used intensities or loads below recommended levels for healthy adults or were generally short, lasting only 6 to 24xa0weeks. The efficacy of high-intensity strength training in improving OA symptoms, slowing progression, and affecting the underlying mechanisms has not been examined due to the unsubstantiated belief that it might exacerbate symptoms. We hypothesize that in addition to short-term clinical benefits, combining greater duration with high-intensity strength training will alter thigh composition sufficiently to attain long-term reductions in knee-joint forces, lower pain levels, decrease inflammatory cytokines, and slow OA progression.Methods/DesignThis is an assessor-blind, randomized controlled trial. The study population consists of 372 older (age ≥ 55 yrs) ambulatory, community-dwelling persons with: (1) mild-to-moderate medial tibiofemoral OA (Kellgren-Lawrence (KL) = 2 or 3); (2) knee neutral or varus aligned knee ( -2° valgus ≤ angle ≤ 10° varus); (3) 20 kg.m-2 ≥ BMI ≤ 45 kg.m-2; and (3) no participation in a formal strength-training program for more than 30 minutes per week within the past 6 months. Participants are randomized to one of 3 groups: high-intensity strength training (75-90% 1Repetition Maximum (1RM)); low-intensity strength training (30-40%1RM); or healthy living education. The primary clinical aim is to compare the interventions’ effects on knee pain, and the primary mechanistic aim is to compare their effects on knee-joint compressive forces during walking, a mechanism that affects the OA disease pathway. Secondary aims will compare the interventions’ effects on additional clinical measures of disease severity (e.g., function, mobility); disease progression measured by x-ray; thigh muscle and fat volume, measured by computed tomography (CT); components of thigh muscle function, including hip abductor strength and quadriceps strength, and power; additional measures of knee-joint loading; inflammatory and OA biomarkers; and health-related quality of life.DiscussionTest-retest reliability for the thigh CT scan was: total thigh volume, intra-class correlation coefficients (ICC)u2009=u20090.99; total fat volume, ICCu2009=u20090.99, and total muscle volume, ICCu2009=u20090.99. ICC for both isokinetic concentric knee flexion and extension strength was 0.93, and for hip-abductor concentric strength was 0.99. The reliability of our 1RM testing was: leg press, ICCu2009=u20090.95; leg curl, ICCu2009=u20090.99; and leg extension, ICCu2009=u20090.98. Results of this trial will provide critically needed guidance for clinicians in a variety of health professions who prescribe and oversee treatment and prevention of OA-related complications. Given the prevalence and impact of OA and the widespread availability of this intervention, assessing the efficacy of optimal strength training has the potential for immediate and vital clinical impact.Trial registrationClinicalTrials.gov,NCT01489462

Less favorable body composition and adipokines in South Asians compared with other US ethnic groups: results from the MASALA and MESA studies.

Background:Small studies have shown that South Asians (SAs) have more total body, subcutaneous, visceral and hepatic fat and abnormal adipokine levels compared with Whites. However, comprehensive studies of body composition and adipokines in SAs compared with other ethnic groups are lacking.Methods:Using harmonized data, we performed a cross-sectional analysis of two community-based cohorts: Mediators of Atherosclerosis of South Asians Living in America (MASALA, n=906) and Multi-Ethnic Study of Atherosclerosis (MESA which included 2622 Whites, 803 Chinese Americans, 1893 African Americans and 1496 Latinos). General linear models were developed to assess the ethnic differences in ectopic fat (visceral, intermuscular and pericardial fat; and hepatic attenuation), lean muscle mass and adipokines (adiponectin and resistin). Models were adjusted for age, sex, site, alcohol use, smoking, exercise, education, household income and body mass index. Ectopic fat models were additionally adjusted for hypertension, diabetes, high-density lipoprotein and triglycerides. Adipokine models were adjusted for subcutaneous, visceral, intermuscular and pericardial fat; and hepatic attenuation.Results:Compared with all ethnic groups in MESA (Whites, Chinese Americans, African Americans and Latinos), SAs had greater intermuscular fat (pairwise comparisons with each MESA group, P<0.01), lower hepatic attenuation (P<0.001) and less lean mass (P<0.001). SAs had greater visceral fat compared with Chinese Americans, African Americans and Latinos (P<0.05) and greater pericardial fat compared with African Americans (P<0.001). SAs had lower adiponectin levels compared with other ethnic groups (P<0.01; except Chinese Americans) and higher resistin levels than all groups (P<0.001), even after adjusting for differences in body composition.Conclusion:There are significant ethnic differences in ectopic fat, lean mass and adipokines. A less favorable body composition and adipokine profile in SAs may partially explain the increased predisposition to cardiometabolic disease. The mechanisms that underlie these differences warrant further investigation.

Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Risk Score in Young Adults Predicts Coronary Artery and Abdominal Aorta Calcium in Middle Age The CARDIA Study

Background— We explored whether, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary and abdominal risk scores measured at 18 to 30 years of age and changes in these scores would more strongly predict coronary artery calcium (CAC) and abdominal aortic calcium (AAC) assessed 25 years later, than scores measured 25 years later. Methods and Results— In the Coronary Artery Risk Development in Young Adults (CARDIA) study, 3008 participants had measurements of risk score components at 5-year intervals beginning at 18 to 30 years of age. CAC and AAC were assessed at 43 to 55 years of age. Odds ratios (ORs) for the presence and extent of CAC/AAC per/point higher score and c-statistics for predicting CAC/AAC were calculated. The prevalence of CAC was 28% and AAC was 53%. For each 1 point higher PDAY score, the odds of CAC were higher using baseline scores than year 25 scores (OR, 1.29; 95% confidence interval [CI], 1.25–1.33 versus OR, 1.12; 95% CI, 1.11–1.14). For AAC, ORs at years 0 and 25 were similar (OR, 1.29; 95% CI, 1.24–1.34 versus OR, 1.22; 95% CI, 1.19–1.26). C-statistic for CAC prediction was higher at year 0 than year 25 (0.731 versus 0.705) but similar at years 0 and 25 for AAC (0.665 versus 0.670). ORs for CAC were highest at baseline, and, for AAC, ORs were highest at year 10. Including change in PDAY scores with baseline scores improved prediction. Conclusions— Atherosclerosis risk and change in risk assessed in young adulthood years before subclinical atherosclerosis imaging provide strong prediction of future subclinical atherosclerosis. CAC and AAC reflect chronic risk exposure in addition to risk measured at the time of study.

Cardiometabolic Abnormalities Among Normal-Weight Persons From Five Racial/Ethnic Groups in the United States: A Cross-sectional Analysis of Two Cohort Studies

Overweight and obesity are well-known cardiometabolic risk factors (13). However, some persons with normal weight have elevated cardiometabolic risk (47), and the relationship between excess adiposity and cardiometabolic abnormality may vary by race/ethnicity (47). Although some information is available regarding the prevalence and correlates of metabolic abnormality but normal weight (MAN) in non-Hispanic whites, non-Hispanic African Americans, and Mexican Americans (4, 5), no direct comparisons have been made among East or South Asians who are at high risk for cardiometabolic abnormalities, even at relatively low levels of body mass index (BMI) (813). We therefore compared the prevalence of MAN among members of 5 racial/ethnic groups, including 2 Asian subgroups, by using data from 2 large, well-characterized community-based U.S. cohorts. We also examined the correlates associated with MAN in the 4 racial/ethnic minority groups compared with whites. Lastly, we determined the BMI values in the racial/ethnic minority participants that would yield a MAN prevalence equal to that in whites with a BMI of 25 kg/m2. Methods We conducted a cross-sectional analysis of pooled data from MESA (Multi-Ethnic Study of Atherosclerosis) and the MASALA (Mediators of Atherosclerosis in South Asians Living in America) study. To maintain consistency with the lower age limit of MESA participants, we excluded 94 MASALA participants younger than 44 years. Excluded participants differed from those who remained in the study only by age-related clinical outcomes. We compared 803 South Asian participants from MASALA with 2622 white, 803 Chinese American, 1893 African American, and 1496 Hispanic participants from MESA. MESA Study The design and conduct of the MESA study have been described elsewhere (14). In brief, study participants included members of 4 racial/ethnic groups (white, Chinese American, African American, and Hispanic) aged 45 to 84 years recruited from the greater New York, New York; Baltimore, Maryland; Chicago, Illinois; Los Angeles, California; MinneapolisSaint Paul, Minnesota; and Winston-Salem, North Carolina, areas. Baseline data collection and examinations were conducted between July 2000 and July 2002. Questionnaires were used to assess demographic and behavioral characteristics, and seated blood pressure readings, anthropometric measurements, and abdominal and cardiac computed tomography (CT) scans were obtained. Physical activity was assessed by using the Typical Week Physical Activity Questionnaire (15). Fasting serum glucose levels were evaluated by using the glucose oxidase method (Ortho Clinical Diagnostics). Insulin levels were determined by the Access system (Beckman Coulter) and harmonized with an Elecsys assay (Roche Diagnostics). C-reactive protein values were assessed by using a BN II nephelometer (N High-Sensitivity C-reactive protein test, Dade Behring). Total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels were determined by using the cholesterol oxidase method (Roche Diagnostics), and low-density lipoprotein cholesterol concentrations were calculated. Triglyceride levels were measured by using Triglyceride GB reagent (Roche Diagnostics). Usual dietary intake over the past year was assessed by using a 120-item food-frequency questionnaire that was validated in white, African American, and Hispanic populations and modified to include Chinese foods (16). MASALA Study The MASALA study involved measures and methods similar to those of MESA to allow for specific cross-racial/ethnic comparisons (17). Its design and objectives also have been described (17). In brief, MASALA studied a community-based sample of South Asian Americans who were aged 40 to 84 years, had no previously known cardiovascular disease, and were living in the greater San Francisco Bay and Chicago areas. To be eligible for the study, participants had to report South Asian ethnicity (defined as having 3 or more grandparents born in India, Pakistan, Nepal, Bangladesh, or Sri Lanka) and be able to speak and read English, Hindi, or Urdu. All other eligibility criteria were identical to those of MESA (17). Recruitment occurred between October 2010 and March 2013. All participants were screened by telephone and invited to either the University of California, San Francisco, or the Northwestern University field center for a baseline clinical examination (17). Bilingual study staff assisted participants in completing the questionnaires, which were the same as those used in MESA. Because dietary intake is distinct in South Asians, the MASALA investigators used the SHARE (Study of Health Assessment and Risk in Ethnic groups) food-frequency questionnaire, which was developed for and validated in South Asians (17). Mean caloric intake was calculated by summing the product of the frequency of consumption, nutrient composition, and portion size of each item across all food items (18). The protocols used in the MASALA study for seated blood pressure and anthropometry were the same as those used in MESA. After resting in a seated position for 5 minutes, each participant had his or her blood pressure assessed with an automated blood pressure machine (V100 Vital Signs Monitor, GE Healthcare). Seated blood pressure was measured 3 times, and the last 2 readings were averaged to determine systolic and diastolic blood pressure. Participant weight was measured with a standing balance beam or digital scale, height with a stadiometer. Body mass index was calculated as weight in kilograms divided by height in square meters. Waist circumference was determined by using a flexible tape measure at the site of maximum circumference, halfway between the lower ribs and the anterior superior iliac spine. The circumference was measured twice, and the average was used for analysis. Blood samples were collected after a 12-hour overnight fast. Total cholesterol, triglyceride, and HDL-C levels were analyzed by enzymatic methods, and low-density lipoprotein cholesterol concentrations were calculated. Fasting plasma glucose levels were analyzed by using the hexokinase method. Serum insulin was measured by the sandwich immunoassay method (Elecsys 2010, Roche Diagnostics) (19). As in MESA, Luminex adipokine panel A (EMD Millipore) was used to measure adiponectin and resistin levels. The interassay coefficient of variations was 2.34% to 4.12% for adiponectin and 3.25% to 5.03% for resistin (19). Computed tomography scans of the abdomen (Philips Medical Systems, Toshiba Medical Systems, and Siemens Medical Solutions) were used to assess visceral, subcutaneous, and intermuscular fat mass. Noncontrast cardiac CT images were obtained with a cardiac-gated CT scanner (Phillips 16D or Toshiba MSD Aquillion 64 at the University of California, San Francisco, and Siemens Sensation Cardiac 64 at Northwestern University) to assess pericardial fat volume and hepatic fat attenuation. Measurement methods and reading centers were similar to those used in MESA (20). Classification of Cardiometabolic Abnormalities We used National Cholesterol Education ProgramAdult Treatment Panel III criteria to consider 4 cardiometabolic abnormalities (21). Decreased HDL-C was defined as a level lower than 1.03 mmol/L (<40 mg/dL) in men or 1.29 mmol/L (<50 mg/dL) in women, or any use of lipid-lowering medication (22). Elevated triglyceride was classified as a fasting triglyceride level of 1.7 mmol/L (150 mg/dL) or greater (22). Elevated glucose was classified as a fasting plasma glucose level of 5.6 mmol/L (100 mg/dL) or greater (23) or any use of glucose-lowering medication. High blood pressure was defined as 130/85 mm Hg or greater or any use of antihypertensive medication. The waist circumference criterion was not used because of collinearity with BMI (correlation coefficient, 0.85; P < 0.0001). On the basis of previous literature, cardiometabolic abnormality was defined as the presence of 2 or more of the aforementioned components (4, 2428). BMI Categories For white, African American, and Hispanic participants, BMI was classified according to World Health Organization (WHO) standard cut points for normal weight (BMI, 18.5 to 24.9 kg/m2), overweight (BMI, 25.0 to 29.9 kg/m2), and obesity (BMI, 30 kg/m2) (27). For South Asian and Chinese American participants, BMI was classified according to WHO Asian cut points for normal weight (BMI, 18.5 to 22.9 kg/m2), overweight (BMI, 23.0 to 27.4 kg/m2), and obesity (BMI, 27.5 kg/m2) (28). We also conducted sensitivity analyses by using the standard WHO BMI cut points for all racial/ethnic groups. Body size phenotypes were defined on the basis of a combination of BMI category (normal weight) and cardiometabolic health. Combinations of BMI and cardiometabolic status yielded 2 distinct phenotypes (normal weight without cardiometabolic abnormalities and normal weight with cardiometabolic abnormalities [MAN]). We focused our analysis on the discordant MAN phenotype. Statistical Analysis Analyses were conducted by using pooled data from the 2 cohorts. Participant characteristics were described as means, geometric means, and percentages by race/ethnicity. Differences in these characteristics across race/ethnicity were assessed by using chi-square tests or analysis of variance as appropriate. The prevalence of metabolic abnormality was calculated by BMI strata. Prevalence ratios of MAN in Chinese, African American, Hispanic, and South Asian participants compared with whites were estimated by using Poisson models with robust SEs (29). Multivariate models were adjusted for age, sex, education, physical activity, daily caloric intake, alcohol use, smoking status, hepatic fat attenuation, and pericardial fat volume. Additional, restricted models including only the subset of participants who had measures of visceral fat, adiponectin, and resistin also were performed. To estimate the BMI values for South Asian, African American, Hispanic, and Chinese American parti

Mediation of cardiovascular risk factor effects through subclinical vascular disease: the Multi-Ethnic Study of Atherosclerosis.

Objective— It is unclear to what extent subclinical cardiovascular disease (CVD) such as coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and brachial flow-mediated dilation (FMD) are mediators of the known associations between traditional cardiovascular risk factors and incident CVD events. We assessed the portion of the effects of risk factors on incident CVD events that are mediated through CAC, CIMT, and FMD. Approach and Results— Six thousand three hundred fifty-five of 6814 Multi-Ethnic Study of Atherosclerosis participants were included. Nonlinear implementation of structural equation modeling (STATA mediation package) was used to assess whether CAC, CIMT, or FMD are mediators of the association between traditional risk factors and incident CVD event. Mean age was 62 years, with 47% men, 12% diabetics, and 13% current smokers. After a mean follow-up of 7.5 years, there were 539 CVD adjudicated events. CAC showed the highest mediation while FMD showed the least. Age had the highest percent of total effect mediated via CAC for CVD outcomes, whereas current cigarette smoking had the least percent of total effect mediated via CAC (percent [95% confidence interval]: 80.2 [58.8–126.7] versus 10.6 [6.1–38.5], respectively). Body mass index showed the highest percent of total effect mediated via CIMT (17.7 [11.6–38.9]); only a negligible amount of the association between traditional risk factors and CVD was mediated via FMD. Conclusions— Many of the risk factors for incident CVD (other than age, sex, and body mass index) showed a modest level of mediation via CAC, CIMT, and FMD, suggesting that current subclinical CVD markers may not be optimal intermediaries for gauging upstream risk factor modification.

Prognostic Implications of Left Ventricular Dyssynchrony for Major Adverse Cardiovascular Events in Asymptomatic Women and Men: The Multi-Ethnic Study of Atherosclerosis

Background Left ventricular (LV) dyssynchrony is related to adverse outcomes in systolic heart failure, but its prognostic importance in asymptomatic population is not known. Our objective was to assess the prognostic implications of LV mechanical dyssynchrony in a large multiethnic population before the occurrence of global LV dysfunction. Methods and Results A total of 1392 participants in the Multi‐Ethnic Study of Atherosclerosis (MESA; mean age: 64.7 years; 46% were women) with cardiac magnetic resonance imaging at baseline were followed for a median duration of 8.3 years. Harmonic phase imaging analysis was used to derive systolic circumferential strain. Greater standard deviation of time to peak systolic strain (SD‐TPS) indicates greater dyssynchrony. With SD‐TPS as a continuous variable, Cox proportional hazards analysis was used to assess hazards ratio after adjusting for demographics, cardiovascular risk factors, LV mass‐to‐volume ratio, and ejection fraction. Using the 75th percentile of SD‐TPS as a cutoff, Kaplan–Meier analysis was performed between 2 categorical groups for each gender. Higher values of dyssynchrony in women predicted major adverse cardiovascular events, defined as myocardial infarction, heart failure, stroke, and death (hazard ratio: 1.01 per 1‐ms increment in SD‐TPS, P=0.015), hard coronary events (hazard ratio: 1.05 per 1‐ms increment in SD‐TPS, P=0.026), and cerebrovascular events (hazard ratio: 1.03 per 1‐ms increment in SD‐TPS, P=0.013). In contrast, dyssynchrony in men was not predictive of events. Kaplan–Meier analyses in women revealed increased event occurrence in the higher dyssynchrony group, but this was not the case in men. Conclusions In an asymptomatic cohort, greater LV dyssynchrony determined by cardiac magnetic resonance imaging predicts adverse cardiovascular outcome in women but not in men. Clinical Trial Registration URL: http://clinicaltrials.gov. Unique identifier: NCT00005487.

Association of circulating sclerostin with vascular calcification in Afro-Caribbean men

OBJECTIVEnSclerostin, a Wingless (Wnt) pathway antagonist, is an established regulator of bone mineralization in humans but its potential importance in the regulation of vascular calcification is less clear. Therefore, our objective was to assess the relationship of serum sclerostin levels with coronary and aortic artery calcification (CAC and AAC, respectively) in Afro-Caribbean men on the island of Tobago.nnnMETHODSnSerum sclerostin levels and computed tomography of CAC and AAC were measured in 191 men (age mean(SD): 62.9(8.0)years) recruited without regard to health status. Multivariable logistic regression models were used to assess the cross-sectional association of sclerostin with prevalent arterial calcification.nnnRESULTSnMean(SD) sclerostin was 45.2xa0pmol/L (15.6xa0pmol/L). After adjusting for risk factors including age, physical and lifestyle characteristics, comorbidities, lipoproteins and kidney function, 1 SD greater sclerostin level was associated with a 1.61-times (95%CI 1.02-2.53) greater odds of having CAC. Sclerostin was not associated with AAC in any model.nnnCONCLUSIONSnThis is the first study to show that, among Afro-Caribbean men, greater serum sclerostin concentrations were associated with prevalence and extent of CAC. Further studies are needed to better define the role of the Wnt signaling pathway in arterial calcification in humans.

Mediation of Cardiovascular Risk Factor Effects Through Subclinical Vascular Disease

Objective— It is unclear to what extent subclinical cardiovascular disease (CVD) such as coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and brachial flow-mediated dilation (FMD) are mediators of the known associations between traditional cardiovascular risk factors and incident CVD events. We assessed the portion of the effects of risk factors on incident CVD events that are mediated through CAC, CIMT, and FMD. Approach and Results— Six thousand three hundred fifty-five of 6814 Multi-Ethnic Study of Atherosclerosis participants were included. Nonlinear implementation of structural equation modeling (STATA mediation package) was used to assess whether CAC, CIMT, or FMD are mediators of the association between traditional risk factors and incident CVD event. Mean age was 62 years, with 47% men, 12% diabetics, and 13% current smokers. After a mean follow-up of 7.5 years, there were 539 CVD adjudicated events. CAC showed the highest mediation while FMD showed the least. Age had the highest percent of total effect mediated via CAC for CVD outcomes, whereas current cigarette smoking had the least percent of total effect mediated via CAC (percent [95% confidence interval]: 80.2 [58.8–126.7] versus 10.6 [6.1–38.5], respectively). Body mass index showed the highest percent of total effect mediated via CIMT (17.7 [11.6–38.9]); only a negligible amount of the association between traditional risk factors and CVD was mediated via FMD. Conclusions— Many of the risk factors for incident CVD (other than age, sex, and body mass index) showed a modest level of mediation via CAC, CIMT, and FMD, suggesting that current subclinical CVD markers may not be optimal intermediaries for gauging upstream risk factor modification.

Ectopic Fat Depots And Coronary Artery Calcium in South Asians Compared With Other Racial/Ethnic Groups

Background South Asians have a low body mass index and high prevalence of cardiovascular disease (CVD) relative to other racial/ethnic groups. Radiographically detected ectopic fat distribution is better associated with CVD than body mass index. We assessed whether differences in ectopic fat depots explained differences in the prevalence/severity of coronary artery calcium (CAC), a predictor of incident CVD events, among South Asians compared with other racial/ethnic groups. Methods and Results We examined the associations of radiographically detected visceral, intermuscular, intrahepatic, and pericardial fat with CAC among adults without baseline CVD. We compared 803 South Asians in the Mediators of Atherosclerosis in South Asians Living in America to 4 racial/ethnic groups in the Multi‐Ethnic Study of Atherosclerosis: 2622 whites, 1893 blacks, 1496 Latinos, and 803 Chinese Americans. We adjusted for body mass index and known CVD risk factors. South Asians had the highest intrahepatic fat and lowest pericardial fat volume (PFV). There was a positive graded association between ectopic fat and higher CAC scores in all the groups with the strongest associations observed with PFV. PFV was independently associated with CAC severity in South Asians (P=0.01) and blacks (P=0.05) and borderline in whites (P=0.06). PFV partially explained the higher CAC burden in South Asians compared with blacks, but not the other racial/ethnic groups. Conclusions Differences in PFV explain a small fraction of the higher CAC burden in South Asians. Our findings suggest that ectopic fat depots may not explain the elevated CAC risk in South Asians.