Multi-Ethnic Study Of Atherosclerosis Study Research Articles

Predicting the risk of coronary artery calcium progression in the general population: insights from the MESA and CARDIA studies

AIMCoronary artery calcium (CAC) progression is a strong predictor of cardiovascular disease. This study aims to develop and validate a practical tool for predicting individual CAC progression in the general population. METHODSData were utilized from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, comprising 5486 participants (47.3% male, mean ± SD age: 61.9 ± 10.2 years), who were randomly assigned to either a training set or an internal validation set at a 7:3 ratio. Additionally, a separate cohort of 2447 participants (44.6% male, mean ± SD age: 40.4 ± 3.5 years) from the Coronary Artery Risk Development in Young Adults (CARDIA) study served as the external validation set. A nomogram was developed based on a Cox regression model incorporating 10 variables selected by the least absolute shrinkage and selection operator (LASSO) method to predict CAC progression. RESULTSFrom the 61 features considered, 10 key variables were identified: age, male sex, smoking status, waist circumference, systolic blood pressure, fasting glucose, lipid abnormalities, and the use of antihypertensive, glucose-lowering, and lipid-lowering medications. The nomogram demonstrated good discrimination, with a C-statistic of 0.682 (95% CI, 0.665–0.699) in the training set and 0.750 (95% CI, 0.729–0.771) in the external validation set. Decision curve analysis further confirmed the nomogram’s clinical utility in predicting the risk of CAC progression. CONCLUSIONOur nomogram offers a practical tool for individualized prediction of CAC progression, potentially aiding in the primary prevention of cardiovascular disease in clinical practice. Registration URLhttps://www.clinicaltrials.gov; Unique identifier: NCT00005130 (CARDIA), NCT00005487 (MESA)

Association of Cardiovascular Fibrosis, Remodeling, and Dysfunction With Frailty, Prefrailty, and Functional Performance: The Multi-Ethnic Study of Atherosclerosis.

Cardiovascular disease is associated with higher incidence of frailty. However, the nature of the mechanisms underlying this association remains unclear. The purpose of this study is to identify cardiovascular phenotypes most associated with physical frailty and functional performance in the Multi-Ethnic Study of Atherosclerosis (MESA). As part of the MESA study, 3 045 participants underwent cardiovascular magnetic resonance and computed tomography between 2010 and 2012. Of these, 1 743 completed a Six-Minute Walk test (6MWT) and questionnaires (follow-up exam: 2016-2018) which were used to generate a binary combined frail/prefrail versus robust score according to a modified FRAIL Scale (self-report questionnaire). Multivariable logistic (binary frail outcome) or linear (6MWT) regression assessed the association between frailty and cardiovascular structure and function, aortic stiffness, coronary artery calcium, and myocardial fibrosis (ECV, extracellular volume fraction). Participants were 66 ± 8 years, 52% female at the time of imaging, and 29.4% were classified as frail or prefrail. Older age and female gender were associated with greater odds of being in the frail/prefrail group. Concentric left ventricular remodeling (odds ratio [OR] 1.89, p = .008; Coef. -52.9, p < .001), increased ECV (OR 1.10, p = .002; Coef. -4.0, p = .001), and worsening left atrial strain rate at early diastole (OR 1.56, p ≤ .001; Coef. -22.75, p = .027) were found to be associated with a greater likelihood of being in a frail state and lower 6MWT distance (m). All associations with 6MWT performance were attenuated with adjustments for risk factors whereas ECV and LA strain rate remained independently associated with frailty. These findings suggest a significant overlap in pathways associated with subclinical cardiac dysfunction, cardiovascular fibrosis, and physical frailty.

Association of cardiovascular health with subclinical coronary atherosclerosis progression among five racial and ethnic groups: The MASALA and MESA studies

Background and aimsSouth Asian adults (SA) are at higher risk for atherosclerotic cardiovascular disease (ASCVD) compared with other racial/ethnic groups. Life's Simple 7 (LS7) is a guideline-recommended, cardiovascular health (CVH) construct to guide optimization of cardiovascular risk factors. We sought to assess if the LS7 metrics predict coronary artery calcium (CAC) incidence and progression in asymptomatic SA compared with four other racial/ethnic groups. MethodsWe assessed the distribution of CVH metrics (inadequate: score 0–8, average: 9–10, optimal: 11–14, and per 1-unit higher score) and its association with incidence and progression of CAC among South Asians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study compared with other race/ethnic groups from the Multiethnic Study of Atherosclerosis (MESA). ResultsWe included 810 SA, 2622 Non-Hispanic White (NHW), and 4192 Other adults (collectively 1893 Black, 1496 Hispanic and 803 Chinese American participants, respectively). SA and White participants compared to Other race/ethnicity groups were more likely to have optimal CVH metrics (26% SA vs 28% White participants vs 21% Other, respectively, p < 0.001). Similar to NHW and the Other race/ethnic group, SA participants with optimal baseline CVH were less likely to develop incident CAC on follow-up evaluation compared to participants with inadequate CVH metrics, optimal CVH/CAC = 0: 24% SA, 28% NHW, and 15% Other (p < 0.01). In multivariable linear and logistic regression models, there was no difference in annualized CAC incidence or progression between each race/ethnic group (pinteraction = 0.85 and pinteraction = 0.17, respectively). Optimal blood pressure control was associated with lower CAC incidence among SA participants [OR (95% CI): 0.30 (0.14–0.63), p < 0.01] and Other race and ethnicity participants [0.32 (0.19–0.53), p < 0.01]. ConclusionsOptimal CVH metrics are associated with lower incident CAC and CAC progression among South Asians, similar to other racial groups/ethnicities. These findings underscore the importance of optimizing and maintaining CVH to mitigate the future risk of subclinical atherosclerosis in this higher risk population.

Obstructive Sleep Apnea and Longitudinal Changes in Interstitial Lung Imaging and Lung Function: The MESA Study.

Rationale: Obstructive sleep apnea (OSA) has been hypothesized to be a risk factor in interstitial lung disease (ILD) and is associated with radiological markers that may represent the earlier stages of ILD. Prior studies have been limited by their cross-sectional design and potential confounding by body habitus. Objectives: To test the hypothesis that OSA severity is associated with more high-attenuation areas (HAAs) on computed tomography and worse lung function over time among older community-dwelling adults. Methods: We used data from participants in the MESA (Multi-Ethnic Study of Atherosclerosis) who had apnea-hypopnea index (AHI) measured from polysomnography (2010-2013), high attenuation areas (HAAs, -600 to -250 Hounsfield units, n = 784), assessments from exams 5 (2010-2012) and 6 (2016-2018) full-lung computed tomography scans, and spirometry assessments (n = 677). Linear mixed-effects models with random intercept were used to examine associations of OSA severity (i.e., AHI and hypoxic burden) with changes in HAAs, total lung volumes, and forced vital capacity (FVC) between exams 5 and 6. Potential confounders were adjusted for in the model, including age, sex, smoking history, height, and weight. Results: Among those with a higher AHI there were more men and a higher body mass index. Participants with AHI ⩾ 15 events/h and in the highest hypoxic burden quartile each had increases in HAAs of 11.30% (95% confidence interval [CI], 3.74-19.35%) and 9.85% (95% CI, 1.40-19.01%) per 10 years, respectively. There was a more rapid decline in total lung volumes imaged and FVC among those with AHI ⩾ 15 events/h of 220.2 ml (95% CI, 47.8-392.5 ml) and 3.63% (95% CI, 0.43-6.83%) per 10 years, respectively. Conclusions: A greater burden of hypoxia related to obstructive events during sleep was associated with increased lung densities over time and a more rapid decline in lung volumes regardless of body habitus. Our findings suggest OSA may be a contributing factor in the early stages of ILD.

Heterogeneity in the Association Between the Presence of Coronary Artery Calcium and Cardiovascular Events: A Machine-Learning Approach in the MESA Study.

Coronary artery calcium (CAC) has been widely recognized as an important predictor of cardiovascular disease (CVD). Given the finite resources, it is important to identify individuals who would receive the most benefit from detecting positive CAC by screening. However, the evidence is limited as to whether the burden of positive CAC on CVD differs by multidimensional individual characteristics. We sought to investigate the heterogeneity in the association between positive CAC and incident CVD. This cohort study included adults from MESA (Multi-Ethnic Study of Atherosclerosis) ages ≥45 years and free of cardiovascular disease. After propensity score matching in a 1:1 ratio, we applied a machine learning causal forest model to (1) evaluate the heterogeneity in the association between positive CAC and incident CVD, and (2) predict the increase in CVD risk at 10-years when CAC>0 (versus CAC=0) at the individual level. We then compared the estimated increase in CVD risk when CAC>0 to the absolute 10-year atherosclerotic CVD (ASCVD) risk calculated by the 2013 American College of Cardiology/American Heart Association pooled cohort equations. Across 3328 adults in our propensity score-matched analysis, our causal forest model showed the heterogeneity in the association between CAC>0 and incident CVD. We found a dose-response relationship of the estimated increase in CVD risk when CAC>0 with higher 10-year ASCVD risk. Almost all individuals (2293 of 2428 [94.4%]) with borderline risk of ASCVD or higher showed ≥2.5% increase in CVD risk when CAC>0. Even among 900 adults with low ASCVD risk, 689 (69.2%) showed ≥2.5% increase in CVD risk when CAC>0; these individuals were more likely to be male, Hispanic, and have unfavorable CVD risk factors than others. The expected increases in CVD risk when CAC>0 were heterogeneous across individuals. Moreover, nearly 70% of people with low ASCVD risk showed a large increase in CVD risk when CAC>0, highlighting the need for CAC screening among such low-risk individuals. Future studies are needed to assess whether targeting individuals for CAC measurements based on not only the absolute ASCVD risk but also the expected increase in CVD risk when CAC>0 improves cardiovascular outcomes.

Vendor independent coronary calcium scoring improves individual risk assessment – the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract Background Coronary artery calcium (CAC) scoring improves event prediction of coronary heart disease (CHD) and can be used to guide initiation or deferral of statin therapy in asymptomatic individuals at low-to-intermediate risk. However, there is substantial variation of CAC scores acquired with different CT scanners. Therefore, CAC scoring discrepancies may lead to suboptimal patients' treatment and harmonization is needed. Purpose The aim of our study was twofold. Our first aim was to develop a calibration tool resulting in vendor neutral Agatston Score (vnAS). Second, we aimed to assess the effect of using this calibration tool in the existing Multi-Ethnic Study of Atherosclerosis (MESA) study cohort on both risk prediction of coronary heart disease (CHD), and initiation of statin therapy. Methods Two static anthropomorphic phantoms containing multiple CAC inserts were imaged on seven different CT systems and one EBT system. For each CT system, the vnAS calculator parameters were derived using regression analysis based on Agatston scores from EBT and CT. To validate our vnAS, we used CAC scoring information and clinical data of participants from MESA study. All included participants (Cohort I, n=3181) were assigned to one out of four calcium groups, which were defined as zero-calcium (AS and vnAS of 0), low-calcium (AS and vnAS of 1–99) high-calcium (AS and vnAS ≥100), and reclassified individuals (AS &amp;lt;100 and vnAS ≥100). The occurrence of CHD events in each group was assessed and multivariable Cox regression models were used to assess the added value of the vnAS in the prediction of CHD events For a sub-cohort of 890 participants at intermediate cardiovascular risk, the potential benefit from statin therapy was estimated based on the number needed to treat (NNT). NNT were determined for patients with vnAS ≥100 and vnAS ≥300 with original AS below 100 (group I) or 300 (group II), respectively. Results For all CT systems, a high degree of correlation with EBT Agatston scores was shown (R2 &amp;gt;0.932). Using the vnAS, 85 individuals (2.7%) were reclassified from a lower to a higher risk category. For the reclassified participants, CHD event rates increased significantly from 7% to 15% (p=0.008) with a CHD hazard ratio of 3.39 (95% CI 1.82–6.35, p=0.001) (Figure 1). In intermediate risk cohort, the NNT was smaller for reclassified individuals as compared to their original (low) calcium group, at 7 vs 12 for group I and 2 vs 15 for group II, respectively. The summary of vnAS applicability is depicted in Figure 2. Conclusions We developed a calibration tool, which enables to calculate vendor neutral AS (vnAS). Based on vnAS, 85 individuals from MESA study, who were reclassified from a lower to a higher calcium category, did indeed have a higher CHD event rate. Consequently, the potential benefit from statin therapy, based on vnAS, was also increased for reclassified participants at intermediate cardiovascular risk. Funding Acknowledgement Type of funding sources: None.

Prognostic value of a left atrioventricular coupling index (LACI) in pre- and post-menopausal women. from the multi-ethnic study of atherosclerosis (MESA)

Abstract Background Endogenous sex hormones associated with both the left atrial (LA) and left ventricular (LV) structures in peri-menopausal women, but the association of menopause status with left atrioventricular coupling is not well established. Purpose To assess the prognostic value of a left atrioventricular coupling index (LACI) in pre- and post-menopausal women without a history of cardiovascular disease (CVD) at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods In women participating in the MESA study, the LACI was measured as the ratio of the left atrial (LA) end-diastolic volume to the left ventricular (LV) end-diastolic volume using cardiovascular magnetic resonance (CMR). Cox proportional hazard models were used to assess the association between the LACI and the outcomes of atrial fibrillation (AF), heart failure (HF), and hard CVD defined by myocardial infarction, resuscitated cardiac arrest, stroke, or coronary heart disease death. Results Among the 2,087 women participants (61±10 years), 485 cardiovascular events were observed during the mean follow-up period of 13.2±3.3 years. A higher LACI was independently associated with AF (HR 1.70; 95% CI [1.51–1.90]), HF (HR 1.62; [1.33–1.97]), and hard CVD (HR 1.30; [1.13–1.51], all p&amp;lt;0.001). Adjusted models with the LACI showed significant improvement in model discrimination and reclassification when compared to currently used standard models used to predict the incidence of AF (C-statistic=0.82 vs. 0.79; NRI=0.325; IDI=0.036), HF (C-statistic=0.84 vs. 0.81; NRI=0.571; IDI=0.023), hard CVD (C-statistic=0.78 vs. 0.76; NRI=0.229; IDI=0.012). Conclusion In a multi-ethnic population of pre- and post-menopausal women, the LACI is an independent predictor of HF, AF, and hard CVD. In both pre- and post-menopausal women, the LACI has an incremental prognostic value for predicting cardiovascular events over traditional risk factors and sex hormone levels. ClinicalTrials: gov Identifier: NCT00005487 Funding Acknowledgement Type of funding sources: None.

Longitudinal Associations of Physical Activity Patterns and the Environment: An 18-Year Follow-Up to the MESA Study.

Introduction: Cross-sectional association between the neighborhood-built environment and physical activity (PA) has been demonstrated previously, indicating the importance of neighborhood perception characteristics such as walkability, safety, and the connectivity of streets on PA levels. Our study aimed to assess the longitudinal data from participants of the Multi-Ethnic Study of Atherosclerosis (MESA) to evaluate the potential relationship between perceived environment and PA patterns. Methods: We analyzed data from a subset of participants (n = 3097) with available PA data who participated in a prospective cohort conducted from 2000 to 2018. The exposure variables were the perceived aspects of the neighborhood environment and the perception of safety, and the outcome was patterns of PA. Patterns were defined as categories reflecting meeting versus not meeting PA guidelines over time. We created the following categories: adopters (individuals who did not meet guidelines at baseline but met guidelines at Exam 6), relapsers (individuals who met guidelines at baseline but did not meet guidelines at Exam 6), maintainers (individuals who met guidelines both at baseline and Exam 6), and insufficiently active (individuals who did not meet guidelines at either baseline or Exam 6). The maintainers’ group was considered the reference category. We estimated the relative risk to assess the magnitude effect of the association between environmental perceptions and the outcome. Results: Individuals who reported that lack of parks and playgrounds was “not a problem” in their neighborhood had a 2.3-times higher risk of decreasing their physical activity (i.e., the “relapser” category) compared to maintainers. After full adjustment, perceiving poor sidewalks as “somewhat a serious problem” was associated with a 64% lower risk of becoming an adopter than a maintainer. When compared to those who perceive the neighborhood as “very safe”, perception of the neighborhood as “safe” to “not at all safe” (ratings 3, 4, and 5, respectively, on the perceived safety scale) was significantly associated with being classified in the adopter category. Conclusions: As the first longitudinal study of the association of perceived environment and physical activity within the MESA cohort, we conclude that a few aspects are longitudinally associated with being physically active among adults.

Deep Learning-based Automated Aortic Area and Distensibility Assessment: the Multi-Ethnic Study of Atherosclerosis (MESA).

This study details application of deep learning for automatic segmentation of the ascending and descending aorta from 2D phase-contrast cine magnetic resonance imaging for automatic aortic analysis on the large MESA cohort with assessment on an external cohort of thoracic aortic aneurysm (TAA) patients. This study includes images and corresponding analysis of the ascending and descending aorta at the pulmonary artery bifurcation from the MESA study. Train, validation, and internal test sets consisted of 1123 studies (24,282 images), 374 studies (8067 images), and 375 studies (8069 images), respectively. The external test set of TAAs consisted of 37 studies (3224 images). CNN performance was evaluated utilizing a dice coefficient and concordance correlation coefficients (CCC) of geometric parameters. Dice coefficients were as high as 97.55% (CI: 97.47-97.62%) and 93.56% (CI: 84.63-96.68%) on the internal and external test of TAAs, respectively. CCC for maximum and minimum and ascending aortic area were 0.969 and 0.950, respectively, on the internal test set and 0.997 and 0.995, respectively, for the external test. The absolute differences between manual and deep learning segmentations for ascending and descending aortic distensibility were 0.0194 × 10-4 ± 9.67 × 10-4 and 0.002 ± 0.001mmHg-1, respectively, on the internal test set and 0.44 × 10-4 ± 20.4 × 10-4 and 0.002 ± 0.001mmHg-1, respectively, on the external test set. We successfully developed a U-Net-based aortic segmentation and analysis algorithm in both MESA and in external cases of TAA.

Abstract 9731: Improved Risk Stratification with Vendor Independent Coronary Calcium Scores: Data from the Multi-Ethnic Study of Atherosclerosis (mesa)

Introduction: Coronary calcium score (CCS) plays a role in cardiovascular disease (CVD) risk calculators, but also reclassifies patients when considering statin therapy. However, CCS is still calculated following the Agatston methodology as developed on electron beam tomography (EBT) in the early 1990s. EBT has been replaced by multidetector computed tomography (MDCT). It is known that CCS differs substantially between MDCT-systems from different manufacturers, which can lead to risk reclassifications for 6.5% of examined individuals Aims: Our first aim was to identify CT system specific conversion factors to calculate a vendor-neutral Agatston score (rCCS). Second, we aimed to validate rCCS risk stratification for participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: As a first step, we calculated conversion factors between six state-of the-art CT systems and the reference EBT system used in the MESA study. For this purpose, we scanned two calcium-containing inserts, which were placed in a small and large anthropomorphic thorax phantom. Linear regression was used to find a model which converts vendor-specific CCS to vendor-independent rCCS. As a second step, we recalculated the non-zero Agatston scores of 550 MESA participants. Following the Youden method, we calculated an optimal cut-off point for rCCS. Results: The linear model for each CT system allowed for prediction of Agatston scores as measured on the EBT system (p=0.001). rCCS for GE LightSpeed, used in MESA, was calculated as rCCS=0.049+1.97xMESA Agatston score and rCCS=1.903+1.37xMESA Agatston score for small and large size, respectively. The median MESA Agatston score was 100.5 (26.3-379.5), and the median rCCS was 135.8 (35.6-508.6). Participants were assigned to a high Agatston category with Agatston scores exceeding 100 (50.2%) and 187 (43.1%) for CCS and rCCS, respectively. The hazard ratio for CVD of individuals with high Agatston scores increased from 1.88 (95%CI: 1.31-2.68, p=0.001) with MESA scores to 2.15 (95%CI: 1.52-3.05, p=0.001) with rCCS. rCCS reclassified 39 participants into the lower risk group, without statin therapy. Conclusions: In conclusion, based on these preliminary results, rCCS may improve patient classification for statin therapy.

Association of Pro-B-Type Natriuretic Peptide With Cardiac Magnetic Resonance-Measured Global and Regional Cardiac Function and Structure Over 10Years: The MESA Study.

BackgroundNT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) is widely used to diagnose and manage patients with heart failure. We aimed to investigate associations between NT‐proBNP levels and development of global and regional myocardial impairment, dyssynchrony, and risk of developing myocardial scar over time.Methods and ResultsWe included 2416 adults (45–84 years) without baseline clinical cardiovascular disease from MESA (Multi‐Ethnic Study of Atherosclerosis). NT‐proBNP was assessed at baseline (2000–2002). Cardiac magnetic resonance–measured left ventricular parameters were assessed at baseline and year 10 (2010–2012). Tagged cardiac magnetic resonance and myocardial dyssynchrony were assessed. We used linear and logistic regression models to study the relationships between quartiles of NT‐proBNP levels and outcome variables. Left ventricular parameters decreased over time. After 10‐year follow‐up and adjusting for cardiovascular disease risk factors, people in the highest quartile had significantly greater decline in left ventricular ejection fraction (−1.60%; 95% CI, −2.26 to −0.94; P<0.01) and smaller decline in left ventricular end systolic volume index (−0.47 mL/m2; 95% CI, −1.18 to 0.23; P<0.01) compared with those in the lowest quartile. Individuals in the highest quartile had more severe risk factor adjusted global, mid, and apical regional dyssynchrony compared with those in the lowest, second, and third quartiles (all P‐trend<0.05). Compared with the lowest‐quartile group, the adjusted odds ratios for having myocardial scar was 1.3 (95% CI, 0.7–2.2) for quartile 2; 1.2 (95% CI, 0.6–2.3) for quartile 3; and 2.7 (95% CI, 1.4–5.5) for quartile 4 (P‐trend=0.012) for the total sample.ConclusionsAmong participants without baseline clinical cardiovascular disease, higher baseline NT‐proBNP concentration was significantly associated with subclinical changes in developing myocardial dysfunction, more severe cardiac dyssynchrony, and higher odds of having myocardial scar over a 10‐year period independent of traditional cardiovascular disease risk factors.

The Multi-Ethnic Study of Atherosclerosis individual response to vitamin D trial: Building a randomized clinical trial into an observational cohort study

The INdividual response to VITamin D (INVITe) trial was a randomized, placebo-controlled, parallel group trial of vitamin D3 supplementation (2000 IU daily) designed to determine clinical and genetic characteristics that modify the response to vitamin D supplementation. To enhance internal and external validity and reduce cost, the INVITe trial was nested within the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing prospective observational cohort study. The INVITe trial enrolled a community-based population of 666 racially and ethnically diverse participants from January 2017 to April 2019. This represents 30% of 2210 MESA participants approached for screening, and 96% of those found to be eligible. Barriers to enrollment included delayed initiation of the trial relative to scheduled MESA study visits, a lower number of available MESA participants than expected, and a high prevalence (18%) of high-dose vitamin D supplementation (>1000 IU daily, an exclusion criterion). The final study visit was attended by 611 participants (92%), and median adherence was 98%. Our experience suggests that integration of a randomized trial into an existing observational cohort study may leverage strengths of the source population and enhance enrollment, retention, and adherence, although with limited enrollment capacity. The INVITe trial will use rigorously-collected data to advance understanding of individual determinants of vitamin D response.

Association of Diabetes Subgroups With Race/Ethnicity, Risk Factor Burden and Complications: The MASALA and MESA Studies.

There are known disparities in diabetes complications by race and ethnicity. Although diabetes subgroups may contribute to differential risk, little is known about how subgroups vary by race/ethnicity. Data were pooled from 1293 (46% female) participants of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and the Multi-Ethnic Study of Atherosclerosis (MESA) who had diabetes (determined by diabetes medication use, fasting glucose, and glycated hemoglobin [HbA1c]), including 217 South Asian, 240 non-Hispanic white, 125 Chinese, 387 African American, and 324 Hispanic patients. We applied k-means clustering using data for age at diabetes diagnosis, body mass index, HbA1c, and homeostatic model assessment measures of insulin resistance and beta cell function. We assessed whether diabetes subgroups were associated with race/ethnicity, concurrent cardiovascular disease risk factors, and incident diabetes complications. Five diabetes subgroups were characterized by older age at diabetes onset (43%), severe hyperglycemia (26%), severe obesity (20%), younger age at onset (1%), and requiring insulin medication use (9%). The most common subgroup assignment was older onset for all race/ethnicities with the exception of South Asians where the severe hyperglycemia subgroup was most likely. Risk for renal complications and subclinical coronary disease differed by diabetes subgroup and, separately, race/ethnicity. Racial/ethnic differences were present across diabetes subgroups, and diabetes subgroups differed in risk for complications. Strategies to eliminate racial/ethnic disparities in complications may need to consider approaches targeted to diabetes subgroup.

Race, Body Mass Index, and the Risk of Atrial Fibrillation: The Multi‐Ethnic Study of Atherosclerosis

BackgroundHigher body mass index (BMI) is associated with increased risk of incident atrial fibrillation (AF), but it is not known whether this relationship varies by race/ethnicity.Methods and ResultsEligible participants (6739) from MESA (Multi‐Ethnic Study of Atherosclerosis) were surveilled for incident AF using MESA hospital surveillance, scheduled MESA study ECG, and Medicare claims data. After a median 13.8 years of follow‐up, 970 participants (14.4%) had incident AF. With BMI modeled categorically in a Cox proportional hazards model, only those with grade II and grade III obesity had increased risks of AF (hazard ratio [HR], 1.50; 95% CI, 1.14–1.98, P=0.004 for grade II obesity and HR, 2.13; 95% CI, 1.48–3.05, P<0.0001 for grade III obesity). The relationship between BMI and AF risk was J‐shaped. However, the risk of AF as a function of BMI varied substantially by race/ethnicity (P value for interaction=0.02), with Chinese‐American participants having a much higher risk of AF with higher BMI and Black participants having minimal increased risk of AF with higher BMI.ConclusionsObesity is associated with an increased risk of incident AF, but the relationship between BMI and the risk of AF is J‐shaped and this relationship differs by race/ethnicity, such that Chinese‐American participants have a more pronounced increased risk of AF with higher BMI, while Black participants have minimal increased risk. Further exploration of the differential effects of BMI by race/ethnicity on cardiovascular outcomes is needed.

Distribution of calcium volume, density, number, and type of coronary vessel with calcified plaque in South Asians in the US and other race/ethnic groups: The MASALA and MESA studies

Background and aimsSouth Asians (SA) experience disproportionately higher rates of atherosclerotic cardiovascular disease (ASCVD) events than non-Hispanic whites (NHW) and several other Asian groups. The coronary artery calcium (CAC) Agatston score may not capture the unique characteristics of coronary plaque in SA. We therefore evaluated the prevalence and patterns of advanced CAC measures (specific coronary vessel involvement, CAC volume and density) in SA versus other race/ethnicities. MethodsWe combined data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts. We used multivariable-adjusted linear regression models to compare advanced CAC measures between SA and other ethnicities. ResultsOur analyses included 7,625 individuals (810 SA, 2,622 whites, 1,893 African Americans, 1,496 Hispanics, 803 Chinese Americans) with mean (SD) age 62 (10) years and 48% men. In adjusted analyses, compared to NHW, SA had lower overall CAC volume [beta coefficient (95% CI)] [-0.46 (−0.62,-0.29)] but higher overall CAC density [0.14 (0.11,0.18)]. These trends were similar when SA were compared to non-whites (Hispanics, Chinese Americans, and African Americans). SA had higher overall [0.07 (0.03,0.12)] and right coronary artery [0.09 (0.03,0.16)] CAC density compared to non-whites, while CAC volume was not significantly different between these two groups. ConclusionsSA have lower CAC volume compared to NHW but similar compared to non-whites. Overall CAC density is higher among SA compared to NHW and non-whites. Future longitudinal studies of ASCVD events are required to confirm the prognostic significance of these findings among SA.

Predicting Long-Term Absence of Coronary Artery Calcium in Metabolic Syndrome and Diabetes: The MESA Study

ObjectivesThe purpose of this study was to identify predictors of healthy arterial aging (long-term coronary artery calcification [CAC] of 0) among individuals with metabolic syndrome (MetS) or type 2 diabetes (T2D), which may improve primary prevention strategies. BackgroundIndividuals with MetS or T2D have a heterogeneously increased risk of atherosclerotic cardiovascular disease and not all have a high-intermediate risk. MethodsWe included 574 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with MetS or T2D who had CAC=0 at baseline and a repeat CAC scan 10 years later. Multivariable logistic regression assessed the association of traditional and novel atherosclerotic cardiovascular disease risk factors and the MetS severity score (based on the 5 MetS criteria) with healthy arterial aging. ResultsThe mean age of participants was 58.9 years, 67% were women, 422 participants had MetS, and 152 had T2D. The proportion with long-term CAC=0 was similar for MetS (42%) and T2D (44%). A younger age was the only individual low/normal traditional risk factor associated with an increased likelihood of long-term CAC=0 (odds ratio [OR]: 1.50; 95% confidence interval [CI]: 1.22 to 1.85 per 10-years younger). The strongest associations of nontraditional risk factors were observed for an absence of thoracic calcification (OR: 2.42; 95% CI: 1.24 to 4.72), absence of carotid plaque (OR: 1.81; 95% CI: 1.25 to 2.61), and among persons with a high sensitivity troponin <3 ng/ml (OR: 1.55; 95% CI: 1.01 to 2.38). In addition, persons with the lowest quartile MetS severity score had a substantially higher odds of healthy long-term CAC=0 (OR: 2.71; 95% CI: 1.27 to 5.76). ConclusionSMore than 40% of adults with MetS or T2D and baseline CAC=0 had long-term absence of CAC, which was most strongly associated with an absence of extracoronary atherosclerosis and a low MetS score. An optimal overall cardiovascular profile appears to be more important than an ideal value of any individual risk factor to maintain healthy arterial aging.

The association of long-term air pollution exposure with supraventricular arrhythmia and atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis

Background/Aim: Air pollution is an important contributor to cardiovascular morbidity and mortality. Acute exposure to O3 and PM2.5 is associated with episodes of atrial fibrillation (AF), and NO2 exposure is associated with same-day hospitalization for ventricular and supraventricular arrhythmias. Studies investigating longer-term exposures on AF risk have shown mixed results and additional work clarifying the role of pollutants on atrial electrophysiology is needed. This analysis used long-term individual-level ambient pollutant exposure and two-week ambulatory electrocardiographic (ECG) monitoring to investigate the association between pollutants and atrial arrhythmias.Methods: In the Multi-Ethnic Study of Atherosclerosis (MESA), we used estimated five-year average ambient PM2.5, NOX, and O3 from validated hierarchical spatio-temporal models, and conducted two-week ambulatory ECG monitoring of participants. Supraventricular arrhythmia measures of interest were presence of AF during monitoring, average count of premature atrial contractions (PACs) per hour, and average runs per day of supraventricular tachycardia (SVT). Generalized estimating equations were used to account for multiple exposure and outcome measurements in individual participants, adjusting for MESA study site and other a priori defined potential confounders. Secondary analyses explored two-week exposure windows.Results: In 1,324 participants, average age 74 years, five-year average ambient PM2.5, NOX, and O3 levels were not significantly associated with AF, PACs, or SVT. In secondary analyses of two-week exposures, higher PM2.5 was associated with greater runs of SVT, higher O3 with greater odds of AF, and higher NOX with lower odds of AF.Conclusions: Using recently developed study-specific exposure estimation and long-term ECG monitoring, we found no evidence that five-year average exposure to PM2.5, NOX, and O3 was associated with supraventricular arrhythmias. Secondary analyses using two-week exposures suggested moderate associations, but given multiple testing, these associations may have arisen by chance. Additional work is needed to further investigate the relationship of long-term pollution with supraventricular arrhythmias.

Abstract P138: The Association of Long-Term Air Pollution Exposure With Left Atrial Structure and Function in the Multi-Ethnic Study of Atherosclerosis

Air pollution exposure is an important risk factor for cardiovascular morbidity and mortality. Acute exposure is associated with episodes of atrial fibrillation (AF), and long-term exposure may influence ventricular mass and volume. However, little is understood about the relationship between long-term pollution exposure and atrial structure and function, which may influence risk of AF and heart failure. We sought to determine the association of long-term exposure to oxides of nitrogen (NO X ), particulate matter smaller than 2.5 micrometers (PM 2.5 ), and ozone (O 3 ) with left atrial structure (LA) and function, as measured by LA volume, emptying fraction, and peak longitudinal strain. In the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal study of 6,814 participants in six United States communities, we used estimated 5-year average exposure to PM 2.5 , NO X , and O 3 prior to outcome measurement from validated hierarchical spatio-temporal models developed from extensive monitoring of MESA participants. Left atrial measures were calculated from cardiac magnetic resonance imaging occurring between 2010 and 2012. Linear regression was used, adjusting for MESA study site and potential confounding characteristics. In 2,250 MESA participants, 5-year average exposure to PM 2.5 , NO X , and O 3 varied greatly by study site and was not associated with LA volume, emptying fraction, or peak longitudinal strain. Results were particularly sensitive to adjustment for study site, suggesting that there was substantial unmeasured confounding by US city/region. Using recently developed study-specific exposure estimation and highly accurate imaging, we did not find evidence to suggest an association between long-term exposure to several common pollutants and measures of left atrial structure and function. Additional analyses in areas of higher pollution may be useful in determining whether associations are consistent across exposure levels.

Associations of Innate and Adaptive Immune Cell Subsets With Incident Type 2 Diabetes Risk: The MESA Study.

Cell-mediated immunity is implicated in glucose homeostasis and insulin resistance. Whether the levels of innate and adaptive immune cells in peripheral blood are risk factors for incident type 2 diabetes (T2D) remains unknown. We hypothesized that the proportions of naive, memory, CD28-, Th17, and T regulatory CD4+ cells would be associated with incident T2D. In secondary analyses, we evaluated the relationships of 28 additional immune cell phenotypes with T2D. Immune cell phenotypes (n = 33) were measured by flow cytometry using cryopreserved cells collected from 1113 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) at the baseline examination (2000-2002). Cox proportional hazards models were used to evaluate associations of immune cell phenotypes with incident T2D over a median follow-up of 9.1 years, adjusted for age, sex, race/ethnicity, educational status, and body mass index. Incident T2D was observed for 120 participants. None of the cell phenotypes included in the primary hypotheses were significantly associated with T2D (all P > 0.05). Among the secondary immune cells studied, a higher proportion of CD19+CD27+ B cells was associated with a reduced risk of T2D (hazard ratio: 0.72 (95% confidence interval: 0.56, 0.93), per 1-standard deviation (16%) increase). This association was no longer significant after correction for the multiple cell phenotypes tested (P > 0.0015). Our results suggest that the frequencies of several subsets of monocytes, innate lymphocytes, and CD4+ and CD8+ T cells in circulating blood are not related to the future onset of T2D. Higher levels of CD19+CD27+ B cells may be associated with decreased T2D risk.

Acute Aortic Dissection in a Postmenopausal Female in the Setting of Parenteral Testosterone, Estradiol, and Progesterone Therapy

The FDA has not approved the use of testosterone in women. However, parenteral testosterone is being used off-label in free standing clinics throughout America. The recent multi-ethnic study of atherosclerosis (MESA) population study showed that postmenopausal women with a higher testosterone/estradiol ratio had a higher incident of cardiovascular disease. This is a case of a postmenopausal woman who dissected her thoracic aorta after 8 months of parenteral testosterone. The clinical examination, radiographic, and laboratory findings of a patient are presented along with a review of the literature. A heathy postmenopausal women, whose only risk factor was parenteral testosterone, developed a dissection of her entire thoracic aorta. The MESA study and other conflicting publications on cardiovascular events in transgender patients receiving exogenous androgens indicates the need for further investigation to determine the safety of testosterone therapy for women and its possible role in contributing to aortic disease.