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PURPOSE Cardiac computed tomography has a clear clinical role in the evaluation of coronary artery disease and assessment of coronary artery calcium (CAC) but the use of ionizing radiation limits the clinical use. Beam-shaping "bow-tie" filters determine the radiation dose and the effective scan field-of-view diameter (SFOV) by delivering higher X-ray fluence to a region centered at the isocenter. A method for positioning the heart near the isocenter could enable reduced SFOV imaging and reduce dose in cardiac scans. However, a predictive approach to center the heart, the extent to which heart centering can reduce the SFOV, and the associated dose reductions have not been assessed. The purpose of this study is to build a heart-centered patient positioning model, to test whether it reduces the SFOV required for accurate CAC scoring, and to quantify the associated reduction in radiation dose. METHODS The location of 38,184 calcium lesions (3151 studies) in the Multi-Ethnic Study of Atherosclerosis was utilized to build a predictive heart-centered positioning model and compare the impact of SFOV on CAC scoring accuracy in heart-centered and conventional body-centered scanning. Then, the positioning model was applied retrospectively to an independent, contemporary cohort of 118 individuals (81 with CAC > 0) at our institution to validate the model's ability to maintain CAC accuracy while reducing the SFOV. In these patients, the reduction in dose associated with a reduced SFOV beam-shaping filter was quantified. RESULTS Heart centering reduced the SFOV diameter 25.7% relative to body centering while maintaining high CAC scoring accuracy (0.82% risk reclassification rate). In our validation cohort, imaging at this reduced SFOV with heart-centered positioning and tailored beam-shaping filtration led to a 26.9% median dose reduction (25-75th percentile: 21.6%-29.8%) without any calcium risk reclassification. CONCLUSIONS Heart-centered patient positioning enables a significant radiation dose reduction while maintaining CAC accuracy.

The MESA (Multi-Ethnic Study of Atherosclerosis) is a National Heart, Lung, and Blood Institute-sponsored prospective study aimed at studying the prevalence, progression, determinants, and prognostic significance of subclinical cardiovascular disease in a sex-balanced, multiethnic, community-dwelling U.S. cohort. MESA helped usher in an era of noninvasive evaluation of subclinical atherosclerosis presence, burden, and progression for the evaluation of atherosclerotic cardiovascular disease risk, beyond what could be predicted by traditional risk factors alone. Concepts developed in MESA have informed international patient care guidelines, providing new tools to effectively guide public health policy, population screening, and clinical decision-making. MESA is grounded in an open science model that continues to be a beacon for collaborative science. In this review, we detail the original goals of MESA, and describe how the scope of MESA has evolved over time. We highlight 10 significant MESA contributions to cardiovascular medicine, and chart the path forward for MESA in the year 2021 and beyond.

Objectives This study sought to quantify and model conversion of a normal coronary artery calcium (CAC) scan to an abnormal CAC scan. Background Although the absence of CAC is associated with excellent prognosis, progression to CAC >0 confers increased risk. The time interval for repeated scanning remains poorly defined. Methods This study included 3,116 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) with baseline CAC = 0 and follow-up scans over 10 years after baseline. Prevalence of incident CAC, defined by thresholds of CAC >0, CAC >10, or CAC >100, was calculated and time to progression was derived from a Weibull parametric survival model. Warranty periods were modeled as a function of sex, race/ethnicity, cardiovascular risk, and desired yield of repeated CAC testing. Further analysis was performed of the proportion of coronary events occurring in participants with baseline CAC = 0 that preceded and followed repeated CAC testing at different time intervals. Results Mean participants’ age was 58 ± 9 years, with 63% women, and mean 10-year cardiovascular risk of 14%. Prevalence of CAC >0, CAC >10, and CAC >100 was 53%, 36%, and 8%, respectively, at 10 years. Using a 25% testing yield (number needed to scan [NNS] = 4), the estimated warranty period of CAC >0 varied from 3 to 7 years depending on sex and race/ethnicity. Approximately 15% of participants progressed to CAC >10 in 5 to 8 years, whereas 10-year progression to CAC >100 was rare. Presence of diabetes was associated with significantly shorter warranty period, whereas family history and smoking had small effects. A total of 19% of all 10-year coronary events occurred in CAC = 0 prior to performance of a subsequent scan at 3 to 5 years, whereas detection of new CAC >0 preceded 55% of future events and identified individuals at 3-fold higher risk of coronary events. Conclusions In a large population of individuals with baseline CAC = 0, study data provide a robust estimation of the CAC = 0 warranty period, considering progression to CAC >0, CAC >10, and CAC >100 and its impact on missed versus detectable 10-year coronary heart disease events. Beyond age, sex, race/ethnicity, diabetes also has a significant impact on the warranty period. The study suggests that evidence-based guidance would be to consider rescanning in 3 to 7 years depending on individual demographics and risk profile.

AimsTo investigate associations of health insurance with measures of glucose metabolism, and whether associations vary by diabetes status or insurance type.MethodsCross-sectional analysis of baseline data from the Multi-Ethnic Study of Atherosclerosis. Cohort a priori stratified by age

Rationale and objectives Left Atrial (LA) adverse remodeling is an important predictor of morbidity and mortality in several cardiovascular (CV) diseases. Our goals were to quantify and provide reference ranges for LA structure and function using feature tracking cine cardiac magnetic resonance. Materials and methods 2526 participants of the Multiethnic Study of Atherosclerosis study who had feature tracking cine cardiac magnetic resonance derived LA data and were free of atrial fibrillation/flutter and prior CV events at year five follow-up examination (2010–2012) were included in this study. LA phasic indexed volumes: maximum (LAVi max), minimum (LAVi min), and preatrial contraction (LAVi preA); LA empty fractions: total, passive, and active (LAtEF, LApEF, and LAaEF); LA longitudinal strain: maximum and preatrial contraction (S max and S preA); and LA longitudinal strain rate: systolic (SR max) and early/late diastolic (SR e and SR a) were measured. Age, gender, and race/ethnicity-specific reference ranges were identified. Also, reference values in a select subgroup of healthy participants free of traditional CV risk factors at the time of exam date were reported. Results The mean ± SD for LAVi max, LAVi min, LAVi preA, S max, SR e, and SR a were in the 45–65-year-old participants: (33.8 ± 10 mL/m2), (14.5 ± 6.4 mL/m2), (24.8 ± 8.2 mL/m2), (34.6 ± 13.8 %), (−1.4 ± 0.7 s−1), (−2.1 ± 1 s−1) and in the ≥ 65-year-old participants: (35 ± 11.5 mL/m2), (16.6 ± 8.3 mL/m2), (27.6 ± 9.9 mL/m2), (31.2 ± 14.3 %), (−1 ± 0.6 s−1), (−2.1 ± 1 s−1) respectively. Younger individuals had Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation smaller LA volumes and better LA function compared to their older counterparts. Similar findings were observed in Chinese-Americans as compared to Whites. Conclusion This study provides reference values of LA structure and function parameters from a healthy multiethnic community-based population aged 53–94 years evaluated by FTMRI.

Current risk stratification strategies do not fully explain cardiovascular disease (CVD) risk. We aimed to evaluate the association of low-density lipoprotein (LDL-P) and high-density lipoprotein (HDL-P) particles with progression of coronary artery calcium and carotid wall injury. All participants in the Multi-Ethnic Study Atherosclerosis (MESA) with LDL-P and HDL-P measured by ion mobility, coronary artery calcium score (CAC), carotid intima-media thickness (IMT), and carotid plaque data available at Exam 1 and 5 were included in the study. CAC progression was annualized and treated as a categorical or continuous variable. Carotid IMT and plaque progression were treated as continuous variables. Fully adjusted regression models included established CVD risk factors, as well as traditional lipids. Mean (±SD) follow-up duration was 9.6 ± 0.6 years. All LDL-P subclasses as well as large HDL-P at baseline were positively and significantly associated with annualized CAC progression, however, after adjustment for established risk factors and traditional lipids, only the association with medium and very small LDL-P remained significant (β -0.02, p = 0.019 and β 0.01, p = 0.003, per 1 nmol/l increase, respectively). Carotid plaque score progression was positively associated with small and very small LDL-P (p

Zinc is considered protective against atherosclerosis; however, the association between dietary zinc intake and cardiovascular disease remains debated. We investigated whether dietary zinc intake was associated with coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis (MESA). This analysis included 5186 participants aged 61.9 ± 10.2 years (48.8% men; 41.3% white, 25.0% black, 21.6% Hispanic, and 12.1% Chinese American) from the MESA. Dietary zinc intake was assessed by a self-administered, 120-item food frequency questionnaire at baseline (2000–2002). Baseline and follow-up CAC were measured by computed tomography. CAC progression was defined as CAC > 0 at follow-up for participants with CAC = 0 at baseline; and an annualized change of 10 or percent change of ≥ 10% for those with 0 0.05). In this multiethnic population free of clinically apparent cardiovascular disease, higher dietary zinc intake from non-red meat sources was independently associated with a lower risk of CAC progression. The MESA trial was registered at clinicaltrials.gov as NCT00005487.

Background and aims South 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. Methods We 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. Results Our 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. Conclusions SA 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.

Introduction Sleep, sedentary behavior, and physical activity are each independently associated with cardiovascular health (CVH). It is unknown how substituting time in sedentary behavior with sleep or physical activity affects overall CVH. Methods Data for this analysis were taken from the Multi-Ethnic Study on Atherosclerosis Sleep Ancillary Study. Eligible participants (N = 1718) wore Actiwatch accelerometers for 24 h and had at least 3 d of valid accelerometry. The American Heart Association's Life's Simple 7 was used to represent the CVH score after excluding the physical activity component, with higher scores indicating more favorable CVH. Isotemporal substitution modeling was conducted to examine the effect of substituting 30 min of sedentary time for an equivalent amount of sleep, light-intensity physical activity (LIPA), or moderate to vigorous physical activity (MVPA). Results Substituting 30 min of sedentary time to sleep, LIPA, and MVPA was associated with a significantly higher CVH score [β (95% confidence interval) = 0.077 (0.056), 0.039 (0.033), and 0.485 (0.127), respectively]. Substituting 30 min of sedentary time to sleep was associated with lower body mass index (BMI). Substituting 30 min of sedentary time to LIPA was associated with higher diastolic blood pressure and total cholesterol, and lower BMI. Substituting 30 min of sedentary time to MVPA was associated with lower systolic and diastolic blood pressure, and lower BMI. Conclusions Sleep, LIPA, and MVPA are all associated with more favorable overall CVH and several key risk factors for cardiovascular disease. These findings underscore the importance of lifestyle modifications in improving CVH.

Background and aims Prevalent valvular calcification (VC) is associated with stroke but little is known about associations of VC progression with stroke. Methods Progression (interval increase >0 Agatston units/year) of aortic valvular calcification (AVC) and mitral annular calcification (MAC) was assessed by two cardiac CTs over a median of 2.4 years. We determined the risk of adjudicated total and ischemic stroke using Cox regression adjusted for cardiovascular disease (CVD) risk factors. Results We studied 5,539 MESA participants free of baseline CVD and atrial fibrillation. Baseline mean±SD age was 62±10 years; 53% were women; 83% had no progression of VC; 15%, progression at one site (AVC or MAC), and 3%, progression at both sites. Over a median of 12 years, 211 total and 167 ischemic strokes occurred. The number of sites with VC progression (range 0-2) was not associated with total and ischemic stroke (all p>0.05). We found MAC progression to be associated with increased risk of total stroke [adjusted hazard ratio (95% CI) 1.59 (1.11, 2.28)] and ischemic stroke [1.64 (1.10, 2.45)]. Results remained significant after further adjustment for baseline coronary artery calcification. After excluding participants with interim atrial fibrillation and coronary heart disease, findings were no longer statistically significant in fully-adjusted models. There was no interaction by age, sex, or race/ethnicity. There was no association with AVC progression and stroke. Conclusions Progression of MAC but not AVC over 2.4 years is associated with increased risk of total and ischemic stroke.

Background While studies of the left atrium (LA) have demonstrated associations between volumes and emptying fraction with atrial fibrillation (AF), the contribution of right atrial (RA) abnormalities to incident AF remains poorly understood. Objectives Assess the association between RA structure and function with incident AF using feature-tracking cardiovascular magnetic resonance (CMR). Methods This is a prospective cohort study of all participants in the Multi-Ethnic Study of Atherosclerosis with baseline CMR, sinus rhythm, and free of clinical cardiovascular disease at study initiation. RA volume, strain, and emptying fraction in participants with incident AF (n = 368) were compared against AF-free (n = 2779). Cox proportional-hazards models assessed association between variables. Results Participants were aged 60 ± 10 yrs., 55% female, and followed an average 11.2 years. Individuals developing AF had higher baseline RA maximum volume index (mean ± standard deviation [SD]: 24 ± 9 vs 22 ± 8 mL/m2, p = 0.002) and minimum volume index (13 ± 7 vs 12 ± 6 mL/m2, p p = 0.02), peak global strain (34 ± 17% vs 36 ± 19%, p p = 0.049) compared with the AF-free population. After adjusting for traditional cardiovascular risk factors and LA volume and function, we found RA maximum volume index (hazards ratio [HR]: 1.13 per SD, p = 0.041) and minimum volume index (HR: 1.12 per SD, p = 0.037) were independently associated with incident AF. Conclusions In a large multiethnic population, higher RA volume indices were independently associated with incident AF after adjustment for conventional cardiovascular risk factors and LA parameters. It is unclear if this predictive value persists when additional adjustment is made for ventricular parameters.

Cross-sectionally measured NT-proBNP (N-terminal pro-B-type natriuretic peptide) is related to incident dementia. However, data linking changes in NT-proBNP to risk of future dementia are lacking. We aimed to examine the association of change in NT-proBNP over 3.2 years with incident dementia. We included 4563 participants in MESA (Multi-Ethnic Study of Atherosclerosis) prospective cohort who were free of cardiovascular disease at enrollment, had NT-proBNP level measured at MESA exams 1 (baseline, 2000–2002) and 3 (2004–2005), and had no diagnosis of dementia before exam 3. The association of change in NT-proBNP level between MESA exams 1 through 3 and all-cause hospitalized dementia (by International Classification of Diseases, Ninth Revision , codes) after MESA exam 3 (2004–2005) through 2015 was assessed using competing-risks Cox proportional hazard regression analysis. During 45 522 person-years of follow-up, 223 dementia cases were documented. Increase in log-NT-proBNP from MESA exams 1 through 3 was positively associated with incidence of dementia (multivariable hazard ratio, 1.28 [95% CI, 1.001–1.64]; P =0.049). An increase of at least 25% in NT-proBNP level from MESA exam 1 through 3 was associated with a 55% ( P =0.02) increase in the risk of dementia in multivariable analysis. Addition of temporal NT-proBNP change to a model including risk factors and baseline NT-proBNP improved the prediction of dementia (Harrell C statistic from 0.85 to 0.87, P =0.049). Increase in NT-proBNP is independently associated with future all-cause hospitalized dementia and offers a moderately better predictive performance for risk of dementia compared with risk factors and baseline NT-proBNP. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00005487.

Objectives: Urinary incontinence (UI) can affect up to 50% of the population of women over the age of 50. In order to objectively assess discomfort in women with UI prior to initiating treatment and monitoring the outcomes of the treatment, validated questionnaires need to be used to examine the impact of UI on health-related quality of life (HR-QoL). The Urogenital Distress Inventory — Short Form (UDI-6) and the Medical Epidemiologic and Social Aspects of Ageing (MESA) questionnaires are used typically. Assessment of the Polish translation of the MESA and UDI-6 questionnaires. Material and methods: 155 patients with symptoms of UI were enrolled. Each of the patients completed the MESA and UDI questionnaires prior to being examined. The final diagnosis was made after diagnostic tests were carried out in the patients. Results: Principle component analysis showed division of the Polish versions of the questionnaires into domains identical to the original version. Analyses of internal consistency reliability revealed high internal consistency for the MESA questionnaire (0.90) and a low reliability of the UDI-6 questionnaire (0.44). Conclusions: The Polish version of the MESA questionnaire was demonstrated to be a clinically useful diagnostic tool in the studied population, UDI-6 did not reached a sufficiently high reliability in the study group to be recommended as a diagnostic tool.

Funding Acknowledgements Type of funding sources: None. BACKGROUND Left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic values as predictors of atrial fibrillation (AF). PURPOSE To investigate the prognostic value of a left atrioventricular coupling index (LACI) and average annualized change in LACI measured by cardiac MRI to predict incident AF in a population-based sample from the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS In a secondary analysis of the prospective Multi-Ethnic Study of Atherosclerosis (MESA) study, 1,911 study participants, free of clinically recognized AF and cardiovascular disease at baseline, had LACI assessed with cardiac MRI at baseline (Exam 1, 2000-2002), and ten years later (Exam 5, 2010-2012). LACI was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with incident AF. RESULTS Among the 1,911 participants (mean age 59 ± 9 years and 907 men), 87 incident AF events occurred over 3.9 ± 0.9 years following the second imaging (Exam 5). After adjustment for traditional risk factors, greater LACI and ΔLACI were independently associated with AF (HR 1.69, 95% CI[1.46-1.96] and HR 1.71, 95% CI[1.50-1.94], respectively; both p CONCLUSIONS Atrioventricular coupling (LACI) and coupling change (ΔLACI) were strong predictors for AF in a multi-ethnic population. Both had incremental prognostic value for predicting AF over traditional risk factors, and superior discrimination compared to the CHARGE-AF score and to individual LA or LV parameters. ClinicalTrials.gov Identifier: NCT00005487 Abstract Figure. Kaplan-Meier curves by change in LACI Abstract Figure. Kaplan-Meier curves by ΔLACI and LACI

Background The complexity of physical activity (PA) and DNA methylation interaction in the development of cardiovascular disease (CVD) is rarely simultaneously investigated in one study. We examined the role of DNA methylation on the association between PA and CVD. Results The Multi-Ethnic Study of Atherosclerosis (MESA) cohort Exam 5 data with 1065 participants free of CVD were used for final analysis. The quartile categorical total PA variable was created by activity intensity (METs/week). During a median follow-up of 4.0 years, 69 participants developed CVD. Illumina HumanMethylation450 BeadChip was used to provide genome-wide DNA methylation profiles in purified human monocytes (CD14+). We identified 23 candidate DNA methylation loci to be associated with both PA and CVD. We used the structural equation modeling (SEM) approach to test the complex relationships among multiple variables and the roles of mediators. Three of the 23 identified loci (corresponding to genes VPS13D, PIK3CD and VPS45) remained as significant mediators in the final SEM model along with other covariates. Bridged by the three genes, the 2nd PA quartile (β = − 0.959; 95%CI: − 1.554 to − 0.449) and the 3rd PA quartile (β = − 0.944; 95%CI: − 1.628 to − 0.413) showed the greatest inverse associations with CVD development, while the 4th PA quartile had a relatively weaker inverse association (β = − 0.355; 95%CI: − 0.713 to − 0.124). Conclusions The current study is among the first to simultaneously examine the relationships among PA, DNA methylation, and CVD in a large cohort with long-term exposure. We identified three DNA methylation loci bridged the association between PA and CVD. The function of the identified genes warrants further investigation in the pathogenesis of CVD.

Background The association between daily carbohydrate intake and right ventricular (RV) morphology has not been well studied. We aimed to figure out the relationship between daily carbohydrate intake and right ventricular structure and function in a large multiethnic population-based cohort. Methods The Multi-ethnic Study of Atherosclerosis (MESA) -Right Ventricle Study measured RV mass and volumes by cardiac MRI in participants aged 45 to 84 years without clinical cardiovascular disease (CVD) in the MESA study. Participants were divided into three groups based on average daily carbohydrate intake: low (≤45%), medium (45–55%), and high (≥55%). Results The study sample included 3,776 participants which were aged 61.5±10.1 years, 47.5% male, 40.0% white, 24.9% African American, 21.8% Hispanic, and 13.3% Chinese. Higher levels of daily carbohydrate intake were linearly associated with greater RV stroke volume (RVSV), and RV ejection fraction (RVEF) (P Conclusions Carbohydrate intake was independently associated with differences in RV morphology after adjustment for all covariates. This association may be explained by the decreased intake of specific nutrients from carbohydrates. Given the nature of the study, causality cannot be proven. Therefore, further studies are needed to extend these findings, which if confirmed, may suggest a need to rethink recommendations for carbohydrate intake in clinical practice, for optimal nutrient achievement, meals need to be well formulated. Funding Acknowledgement Type of funding sources: None.

Highlights • Improving hypertension control will reduce heart disease and mortality. • After age 65 years, women are less likely than men to have controlled hypertension. • Sex differences in hypertension control widen with advancing age. • Sex differences in hypertension control appear independent of obesity and diabetes., Objective Determine sex differences in hypertension control by age group in a diverse cohort of adults age 45–84 years at baseline followed for an average of 12 years. Methods The Multi-Ethnic Study of Atherosclerosis enrolled 3213 men and 3601 women from six communities in the U.S. during years 2000–2002 with follow-up exams completed approximately every two years. At each exam, resting blood pressure (BP) was measured in triplicate, and the last two values were averaged. Hypertension was defined as a BP ≥ 140/90 mmHg and/or use of antihypertensive medications. Hypertension control was defined as a BP < 140/90 mmHg and in separate analyses as < 130/90 mmHg. Generalized linear mixed effects models with a binomial function were used to calculate the odds of hypertension control by age group (45–64,75–74, 75+) at a given exam and by sex, while accounting for the intra-individual correlation, and adjustment for demographics, co-morbidities, smoking, alcohol use, education and site among participants with hypertension at any of the first five exams. Results At baseline, mean age was 64.1 (9.1 [SD]) years, 48.0% were men, and race/ethnicity was Non-Hispanic white in 34.1%, 10.1% Chinese, 35.1% Non-Hispanic Black and 20.7% Hispanic. Average SBP was lower while average DBP was higher among men vs. women at each exam. Adjusted odds ratios of hypertension control defined as BP < 140/90 mmHg among men vs. women was 0.89 (95% CI 0.67, 1.19) for age 45–64 years, 1.37 (95% CI 1.04, 1.81) for age 65–74 years and 2.08 (95% CI 1.43, 3.02) for age 75+ years. When defined as < 130/80 mmHg, adjusted odds of hypertension control among men vs. women was 0.60 (OR 0.60; 95% CI 0.46, 0.79) at age 45–64 years, 1.01 (OR 1.01; 95% CI 0.77, 1.31) at age 65–74 years and 1.71 (95% CI 1.19, 2.45) at age 75+ years. Conclusion Sex disparities in hypertension control increase with advancing age and are greatest among adults age 75+ years.

Pulmonary emphysema overlaps considerably with chronic obstructive pulmonary disease (COPD), and is traditionally subcategorized into three subtypes previously identified on autopsy. Unsupervised learning of emphysema subtypes on computed tomography (CT) opens the way to new definitions of emphysema subtypes and eliminates the need of thorough manual labeling. However, CT-based emphysema subtypes have been limited to texture-based patterns without considering spatial location. In this work, we introduce a standardized spatial mapping of the lung for quantitative study of lung texture location and propose a novel framework for combining spatial and texture information to discover spatially-informed lung texture patterns (sLTPs) that represent novel emphysema subtype candidates. Exploiting two cohorts of full-lung CT scans from the MESA COPD (n = 317) and EMCAP (n = 22) studies, we first show that our spatial mapping enables population-wide study of emphysema spatial location. We then evaluate the characteristics of the sLTPs discovered on MESA COPD, and show that they are reproducible, able to encode standard emphysema subtypes, and associated with physiological symptoms.

Objectives This study sought to assess the association of baseline left atrial (LA) phasic function measured with cardia magnetic resonance (CMR) and incident ischemic cerebrovascular events (CVE). Background LA remodeling is a known predictor of atrial fibrillation (AF), which is a risk factor for ischemic CVE. Despite studies showing an association between LA remodeling and ischemic CVE, the association of LA mechanical function with ischemic CVE in a population free of known cardiovascular disease is not fully studied. Methods Phasic LA volumes; total, passive, and active LA emptying fractions (LAEF); and peak longitudinal LA strain were measured using feature-tracking CMR in 4,261 MESA (Multi-Ethnic Study of Atherosclerosis) participants (61 ± 10 years of age; 48% male). All individuals were free of clinical cardiovascular disease at baseline. Participants were followed for 11.6 ± 3.5 years for the diagnosis of incident ischemic CVE, defined as ischemic stroke or transient ischemic attack adjudicated by vascular neurologists. Results During the follow-up, 193 (1.26 per 1,000 person-years) ischemic CVE (134 ischemic strokes and 59 TIAs) occurred. Individuals with incident ischemic CVE had larger LA volumes and lower passive, active, and total LAEFs at baseline. In multivariate analysis adjusted for known CVE risk factors, left ventricular mass and interim AF, total LAEF was associated with incident ischemic CVE (hazard ratio [HR]: 0.85 per SD; 95% confidence interval [CI]: 0.74 to 0.98; p = 0.027). The unadjusted HR for the lowest tertile of total LAEF compared to the highest tertile was 2.0 (95% CI: 1.43 to 2.79; p Conclusions Reduced total LAEF was associated with incident ischemic CVE independent of known cerebrovascular risk factors and incident AF. Assessment of LA function may add further information in stratifying asymptomatic individuals at risk for ischemic stroke.

The correlation between cardiovascular risk scoring systems and the severity of coronary artery diseases (CAD) is not clear. The present research aimed to evaluate the Multi-Ethnic Study of Atherosclerosis (MESA) risk score and Framingham risk score (FRS), using the Gensini score (GS) system as reference, so as to determine which model is better for the prediction of CAD severity.This research was a single-center and cross-sectional observational study. In total, 1423 patients were included in our study. Three different groups were formed according to GS: 0 GS ≤ 22 (low GS group, n = 484); 22 GS ≤ 42 (intermediate GS group, n = 468); GS 42 (high GS group, n = 471). Logistic and linear regression analyses were carried out to explore the relationship between the risk score models and the GS. The performance of the risk models was determined by receiver operating characteristic curve (ROC) analysis.The MESA risk score and the FRS both had a statistically significant power for the prediction of CAD severity (MESA area under curve: 0.630; FRS area under curve: 0.613). Furthermore, the MESA had a better performance in predicting the severity (p 0.05) of CAD compared with the FRS. In the subgroup analysis, the MESA showed a better performance in the male (p 0.05), diabetes mellitus (p 0.05), and smoking subgroups (p 0.05) compared with the FRS.The MESA and FRS predicted the severity of CAD in the Chinese population of this study. Moreover, the MESA had a better performance than the FRS model in predicting the severity of CAD in the overall population as well as in the male, smoking, diabetes, and non-diabetes subgroups.

The evidence linking low-carbohydrate diets to cardiovascular disease is controversial, and results from epidemiologic studies are inconsistent. We aimed to assess the relationship between low-carbohydrate-diet (LCD) patterns and coronary artery calcium (CAC) scores from computed tomography in the MESA cohort. Our sample included 5,614 men and women free of clinical cardiovascular disease at baseline (2000–2002) who had a food frequency questionnaire, a baseline measure and ≥1 measure of CAC during follow-up. We excluded those with implausible energy intake or daily physical activity. The overall, animal-based, and plant-based LCD scores were calculated based on intakes of macronutrients. Relative risk regression and robust regression models were used to examine the cross-sectional and longitudinal relationship between LCD score quintile and CAC outcomes, after adjustment for multiple cardiovascular risk factors. The mean age of participants was 63 years. The median intakes of total carbohydrate, fat, and protein were 53.7%, 30.5%, and 15.6% energy/d, respectively. Among 2,892 participants with zero CAC scores at baseline, 264 developed positive scores during 2.4-year follow-up (11–59 months). Among those with positive scores at baseline, the median increase in CAC was 47 units over the course of follow-up. Neither the overall, nor the animal-based nor the plant-based LCD scores were associated with CAC prevalence, incidence, and progression. In conclusion, diets low in carbohydrate and high in fat and/or protein, regardless of the sources of protein and fat, were not associated with higher levels of CAC, a validated predictor of cardiovascular events, in this large multi-ethnic cohort.

Background It is unclear if statin therapy in midlife can restore low cardiovascular risk in hypercholesterolemic individuals. Methods and Results At baseline, we grouped 5687 MESA (Multi‐Ethnic Study of Atherosclerosis) participants aged ≥50 years without clinical cardiovascular disease (CVD) by Adult Treatment Panel III statin treatment recommendation and statin treatment status. We used Cox regression to compare the risks for coronary heart disease and CVD between the untreated group with low‐density lipoprotein cholesterol (LDL‐C) 0 Agatston units), and statin status (untreated or treated) with the untreated LDL‐C 0 Agatston units, treated to LDL‐C Conclusions Individuals treated with statins to LDL‐C 0 Agatston units have substantially higher risks despite lipid‐lowering therapy, suggesting that statin treatment in midlife may not restore a low‐risk state in primary prevention patients with established coronary atherosclerosis.

Introduction: Increasing research demonstrates psychosocial factors are associated with blood pressure control (BPC) among individuals with hypertension. To date, little research has examined multiple psychosocial factors simultaneously to identify distinguishing profiles among individuals with hypertension. The association of psychosocial profiles and BPC remains unknown. Thus, the goal of this study was to characterize the psychosocial profiles of individuals with hypertension and assess whether they are associated with BPC over 14 years. Hypothesis: We hypothesize that discrete psychosocial profiles will emerge, and they will be associated with BPC longitudinally. Methods: We included 2,665 MESA participants (38.57% Black; 55.43% Female) with prevalent hypertension in 2002-2004. Latent Profile Analysis (LPA) was used to identify distinct psychosocial profiles based on a combination of nine psychosocial variables (Table). We used generalized estimating equations to determine associations of the psychosocial profiles with BPC, defined as systolic blood pressure (SBP) < 140 mm Hg and diastolic blood pressure (DBP) < 90 mm Hg. Results: The LPA revealed an optimal model of three psychosocial profile groups (AIC 121,229; entropy = .88) namely “Healthy”, “Depressed Mood” and “Discriminated Against”. There were no significant differences in BPC of both targets (SBP and DBP) combined across the profiles. Examining SBP and DBP separately, participants in the “Depressed Mood” profile group were 60% less likely [95% CI: 0.43, 0.84] to have their DBP < 90 mm Hg as compared to the “Healthy” profile in the unadjusted model, but there was no association with covariate adjustment. Conclusions: Discrete psychosocial profiles exist among individuals with hypertension, but were not associated with BPC after full covariate adjustment.

Most nutritional epidemiology studies investigating trends between diet and heart disease use outcome-independent dimension reduction methods, like principal component analysis, to create dietary patterns. While these methods construct patterns that describe important aspects of food consumption, these patterns are not inherently related to heart disease. Incorporating disease data into the pattern construction offers the possibility of more concisely summarizing the most disease-related foods. Sparse partial least squares (SPLS), one such method, was found to have favorable interpretation and prediction properties in the continuous outcome setting; while selecting a subset of relevant foods, it constructed a few dietary patterns that were correlated with BMI while also capturing variation in diet composition. These results were validated with simulated data. We propose incorporating SPLS into the Cox proportional hazards model to analyze a right-censored survival outcome. We hypothesized that this method would inherit the beneficial parsimony properties seen in the continuous setting, and we assessed whether this proposed method could use the most relevant covariates to create a few patterns that were associated with a survival outcome. While the proposed method targets covariate-level sparsity (i.e. variable selection), one competitor method exists that integrates pattern-level parsimony and partial least squares (PLS) in the Cox model, but it imposes more model parameters than the proposed method. We compared the variable selection, pattern selection, and predictive performance of four survival methods (Lasso, PLS, competitor sparse PLS, and proposed SPLS) via a simulation study. Simulation settings were informed in part by the Multi-Ethnic Study of Atherosclerosis (MESA), which has detailed food frequency questionnaire data on a large multi-ethnic population-based sample (6814 participants aged 45-84), as well as subsequent cardiovascular disease follow-up for over 15 years. In most studied simulation settings, the proposed method selected all 9 relevant predictors and the fewest number of irrelevant predictors (of 15) while creating a similar number of patterns and maintaining predictive ability of the outcome. In the setting most comparable to MESA, PLS chose all 24 predictors (by default) and 3.4 patterns (C-statistic=0.90), the competitor SPLS selected 21.1 predictors and 4.4 patterns (C-statistic=0.91), Lasso chose 16.4 predictors (C-statistic=0.91), and the proposed SPLS selected 11.7 predictors and 4.3 patterns (C-statistic=0.91), on average. We will also present an analysis of a coronary event in MESA using these four survival methods. In conclusion, we propose that using methods like SPLS to summarize food intake can create more heart disease-tailored dietary patterns that can complement the current nutritional epidemiology literature.

Background High blood pressure (BP) is a well‐known risk factor for atrial fibrillation (AF), but a single BP measurement may provide limited information about AF risk in older adults. Methods and Results This study included 1256 MESA (Multi‐Ethnic Study of Atherosclerosis) and 1948 ARIC (Atherosclerosis Risk in Communities) study participants who underwent extended ambulatory electrocardiographic monitoring and who were free of clinically detected cardiovascular disease, including AF. Using BP measurements from 6 examinations (2000–2018 in MESA and 1987–2017 in ARIC study), we calculated individual long‐term mean, trend, and detrended visit‐to‐visit variability in systolic BP and pulse pressure for each participant. Outcomes, assessed at examination 6, included subclinical AF and supraventricular ectopy. Results from each study were combined with inverse variance‐weighted meta‐analysis. At examination 6, the mean age was 73 years in MESA and 79 years in ARIC study, and 4% had subclinical AF. Higher visit‐to‐visit detrended variability in systolic BP was associated with a greater prevalence of subclinical AF (odds ratio [OR], 1.20; 95% CI, 1.02–1.38) and with more premature atrial contractions/hour (geometric mean ratio, 1.08; 95% CI, 1.01–1.15). For pulse pressure as well, higher visit‐to‐visit detrended variability was associated with a greater prevalence of AF (OR, 1.18; 95% CI, 1.00–1.37). In addition, higher long‐term mean pulse pressure was associated with a greater prevalence of subclinical AF (OR, 1.36; 95% CI, 1.08–1.70). Conclusions Antecedent visit‐to‐visit variability in systolic BP and pulse pressure, but not current BP, is associated with a higher prevalence of subclinical atrial arrhythmias. Prior longitudinal BP assessment, rather than current BP, may be more helpful in identifying older adults who are at higher risk of atrial arrhythmias.

BackgroundThere is growing interest in utilizing machine learning techniques for routine atherosclerotic cardiovascular disease (ASCVD) risk prediction. We investigated whether novel deep learning survival models can augment ASCVD risk prediction over existing statistical and machine learning approaches.Methods6,814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed over 16 years to assess incidence of all-cause mortality (mortality) or a composite of major adverse events (MAE). Features were evaluated within the categories of traditional risk factors, inflammatory biomarkers, and imaging markers. Data was split into an internal training/testing (four centers) and external validation (two centers). Both machine learning (COXPH, RSF, and lSVM) and deep learning (nMTLR and DeepSurv) models were evaluated.ResultsIn comparison to the COXPH model, DeepSurv significantly improved ASCVD risk prediction for MAE (AUC: 0.82 vs. 0.79, P≤0.001) and mortality (AUC: 0.86 vs. 0.80, P≤0.001) with traditional risk factors alone. Implementing non-categorical NRI, we noted a 65% increase in correct reclassification compared to the COXPH model for both MAE and mortality (P≤0.05). Assessing the relative risk of participants, DeepSurv was the only learning algorithm to develop a significantly improved risk score criteria, which outcompeted COXPH for both MAE (4.07 vs. 2.66, P≤0.001) and mortality (6.28 vs. 4.67, P=0.014). The addition of inflammatory or imaging biomarkers to traditional risk factors showed minimal/no significant improvement in model prediction.ConclusionDeepSurv can leverage simple office-based clinical features alone to accurately predict ASCVD risk and cardiovascular outcomes, without the need for additional features, such as inflammatory and imaging biomarkers.

The morphology of the proximal human airway tree is highly variable in the general population, and known variants in airway branching patterns are associated with increased risk of COPD and with polymorphisms in growth factors involved in pulmonary development. Variation in the geometry and topology of the airway tree remains incompletely characterized, and their clinical implications are not yet understood. In this work, we present an approach to unsupervised clustering of airway tree structures in Billera-Holmes-Vogtmann tree-space. We validate our pipeline on synthetic airway tree data, and apply our algorithm to identify reproducible and morphologically distinct airway tree subtypes in the MESA Lung CT cohort.

ObjectiveTo determine the prevalence, risk factors and natural history of hiatal hernia (HH) on CT in the general population.Materials and methodsThe Multi-Ethnic Study of Atherosclerosis (MESA) acquired full-lung CT on 3200 subjects, aged 53–94 years. Three blinded observers independently determined presence/absence and type (I–IV) of HH. Associations between HH and participant characteristics were assessed via unadjusted and multivariable-adjusted relative risk regression. HH natural history was assessed compared with prior MESA CT.ResultsExcellent interobserver agreement was found for presence (κ=0.86) and type of HH (κ=0.97). Among 316 HH identified (prevalence=9.9%), 223 (71%) were type I and 93 (29%) were type III. HH prevalence increased with age, from 2.4% in 6th decade to 16.6% in 9th decade (unadjusted prevalence ratio (PR)=1.1 (95% CI 1.04 to 1.1)). HH prevalence was greater in women (12.7%) than men (7.0%) (unadjusted PR=1.8 (95% CI 1.5 to 2.3)) and associated with proton pump inhibitor use (p2 to 17.9 cm2 (p=0.02) with a higher mean body mass index (BMI) in subjects with increasing HH size compared with HH decreasing in size: mean BMI=30.2±6.2 vs 26.8±7.2 (p=0.02).ConclusionHH on non-contrast CT is prevalent in the general population, increasing with age, female gender and BMI. Its association with proton pump inhibitor use confirms a role in gastro-oesophageal reflux disease and HH progression is associated with increased BMI.Trial registration numberNCT00005487.

Background Given the increasing prevalence of diabetes mellitus (DM) in the United States, estimating the effects of population‐level increases in obesity on incident DM has substantial implications for public health policy. Therefore, we determined the population attributable fraction, which accounts for the prevalence and excess risk of DM associated with obesity. Methods and Results We included non‐Hispanic White, non‐Hispanic Black, and Mexican American participants without DM at baseline from MESA (Multi‐Ethnic Study of Atherosclerosis) with available data on body mass index and key covariates from 2000 to 2017 to calculate unadjusted and adjusted (age, study site, physical activity, diet, income, and education level) hazard ratios (HR) for obesity‐attributable DM. We calculated national age‐adjusted prevalence estimates for obesity using data from NHANES (National Health and Nutrition Examination Survey) in 4 pooled cycles (2001–2016) among adults with similar characteristics to MESA participants. Last, we calculated unadjusted and adjusted population attributable fractions from the race/ethnic and sex‐specific HR and prevalence estimates. Of 4200 MESA participants, the median age was 61 years, 46.8% were men, 53.9% were non‐Hispanic White, 32.9% were non‐Hispanic Black, and 13.3% were Mexican. Among MESA participants, incident DM occurred in 11.6% over a median follow‐up of 9.2 years. The adjusted HR for obesity‐related DM was 2.7 (95% CI, 2.2–3.3). Adjusted population attributable fractions were 0.35 (95% CI, 0.29–0.40) in 2001 to 2004 and 0.41 (95% CI, 0.36–0.46) in 2013 to 2016, and greatest among non‐Hispanic White women. Conclusions The contribution of obesity towards DM in the population remains substantial and varies significantly by race/ethnicity and sex, highlighting the need for tailored public health interventions to reduce obesity. Registration URL: https://www.clinicaltrials.gov ; Unique identifiers: NC00005487, NCT00005154.

Untreated hypertension may contribute to increased atherosclerotic cardiovascular disease (ASCVD) risk in South Asians (SA). We assessed HTN prevalence among untreated adults free of baseline ASCVD from the MASALA & MESA studies. The proportion of participants who received discordant recommendations regarding antihypertensive pharmacotherapy use by the 2017-ACC/AHA and JNC7 Guidelines across CAC score categories in each race/ethnic group was calculated. Compared with untreated MESA participants (n=3896), untreated SA (n=445) were younger (55±8 versus 59±10 years), had higher DBP (73±10 versus 70±10mmHg), total cholesterol (199±34 versus 196±34mg/dL), statin use (16% versus 9%) and CAC=0 prevalence (69% versus 58%), with fewer current smokers (3% versus 15%) and lower 10-year-ASCVD-risk (6.4% versus 9.9%) (all p100 and thus may be better at informing hypertension management in American South Asians.

Background End-of-shift assessments (ESA) can provide representative data on medical trainee performance but do not occur routinely and are not documented systematically. Objective To evaluate the implementation of a web-based tool with text message prompts to assist mobile ESA (mESA) in an emergency medicine (EM) residency program. Methods mESA used timed text messages to prompt faculty/trainees to expect in-person qualitative ESA in a milestone content area and for the faculty to record descriptive performance data through a web-based platform. We assessed implementation between January 2018 and November 2019 using the RE-AIM framework (reach, effectiveness, adoption, implementation, and maintenance). Results Reach: 96 faculty and 79 trainees participated in the mESA program. Effectiveness: From surveys, approximately 72% of faculty and 58% of trainees reported increases in providing and receiving ESA feedback after program implementation. From ESA submissions, trainees reported receiving in-person feedback on 90% of shifts. Residency leadership confirmed perceived utility of the mESA program. Adoption: mESA prompts were sent on 7792 unique shifts across 4 EDs, all days of week, and different times of day. Faculty electronically submitted ESA feedback on 45% of shifts. Implementation quality: No technological errors occurred. Maintenance: Completion of in-person ESA feedback and electronic submission of feedback by faculty was stable over time. Conclusions We found mixed evidence in support of using a web-based tool with text message prompts for mESA for EM trainees.

Introduction: Misalignment of lifestyle behaviors with circadian rhythms is related to hypertension (HTN) risk in experimental studies. Estimation of the circadian rhythm of 24 h rest-activity patterns, which serves as a measure of circadian rhythmicity in a free-living population setting, has been linked to health outcomes but its association with HTN is unknown. Hypothesis: Less robust and irregular 24 h rest-activity patterns will be associated with higher blood pressure (BP) and HTN. Methods: Participants were n=1667 diverse adults (mean age: 67 ± 9 y) in the MESA Sleep Study (2010-13) who completed 7 days of wrist actigraphy. Interdaily stability (IS), intradaily variability (IV), most active 10 h period (M10) and least active 5 h period (L5) timing and counts, and relative amplitude (RA) (defined in Table) were derived from actigraphy data using nonparametric rhythm analysis. Multivariable linear and logistic regression was used to examine associations with BP level and prevalent and incident HTN after 6 y of follow-up at Exam 6 (2016-18). Results: Greater RA (more robust rest-activity pattern i.e. higher wake-time activity and lower activity at night), IS (more day-to-day stability in rest-activity patterns), and M10 counts (more active wake period) were associated with lower BP (Table). Higher L5 midpoint and count (later timing and less restful sleep) was associated with higher BP. In sensitivity analyses excluding those taking HTN medication, associations persisted. Those in the highest vs. lowest category of RA and M10 counts had lower prevalent and incident HTN risk, while those in the highest vs. lowest category of L5 midpoint and counts and IV (more fragmented rhythm, lower sleep efficiency) had higher HTN risk. Conclusions: A less robust and stable rest-activity pattern, lower wake-time activity, and a less restful and later sleep period are associated with HTN. The timing and regularity of rest-activity patterns may be a novel target for HTN prevention.

Introduction The current categorization of cardiovascular (CV) disease based on the Pooled Cohort Equations Risk (PCE) broadened the scope of candidates eligible for statin therapy. Coronary artery calcium score (CCS) identifies those who are most likely to benefit from statin therapy for primary prevention. The Multi-Ethnic Study of Atherosclerosis (MESA) score is the first that includes CCS for CV risk calculation. Aim To find whether MESA score can better predicts CV events than the PCE score and better allocates asymptomatic subjects for statin treatment Methods 632 consecutive subjects free of CV disease, mean age 56±7 years, 84% male, underwent clinical evaluation and CCS measuring. PCE and MESA risk scores were calculated for each subject. Patients were divided according to the 4 PCE categories of 10 years CV risk, and further analyzed according to a higher or lower risk groups than 7.5%, the cutoff above which statin is definitely indicated. Results During mean follow-up of 6.5±3.3 years, 54 subjects experienced a first CV event. Those with MESA risk score ≤7.5% had a favorable outcome even when the PCE indicated a risk of >7.5%. The MESA risk improves the discrimination, ROC curves C-statistics increased from 0.653 for the PCE risk to 0.770. 84% (99/118) of those with borderline risk (5 to ≤7.5%) according to the PCE score, were re-allocated by the MESA risk into an higher (>7.5%) or lower risk category ( Conclusion The MESA risk score better predicts CV events than the PCE score in asymptomatic, and contributes to better allocate them to statin treatment. Funding Acknowledgement Type of funding source: None

Aims The detection of cardiac valvular calcification on routine imaging may provide an opportunity to identify individuals at increased risk for peripheral artery disease (PAD). We investigated the associations of aortic valvular calcification (AVC) and mitral annular calcification (MAC) with risk of developing clinical PAD or a low ankle–brachial index (ABI). Methods and results AVC and MAC were measured on cardiac computed tomography in 6778 Multi-Ethnic Study of Atherosclerosis participants without baseline PAD between 2000 and 2002. Clinical PAD was ascertained through 2015. Incident low ABI, defined as ABI 0.9 at baseline and at least one follow-up ABI measurement 3–10 years later. Adjusted Cox proportional hazards and Poisson regression modelling were used to determine the association of valvular calcification with clinical PAD and low ABI, respectively. There were 117 clinical PAD and 198 low ABI events that occurred over a median follow-up of 14 years and 9.2 years, respectively. The presence of MAC was associated with an increased risk of clinical PAD [hazard ratio 1.79; 95% confidence interval (CI) 1.04–3.05] but not a low ABI (rate ratio 1.28; 95% CI 0.75–2.19). No significant associations were noted for the presence of AVC and risk of either clinical PAD. Conclusion MAC is associated with an increased risk of developing clinical PAD. Future studies are needed to corroborate our findings and better understand whether MAC holds any predictive value as a risk marker for PAD.

Purpose: Hyperpolarized helium (3He) MRI is used to assess ventilation defects in COPD and other pulmonary diseases. Existing segmentation methods are very operator-dependent and effort consuming. We aimed to develop a deep-learning based method to accelerate segmentation, eliminate operator dependence and improve reliability. Methods and Materials: The MESA COPD Study is a nested case-control study of COPD (post-bronchodilator FEV1/FVC ratio Results: The percentage of non-, low-, and normal- ventilated regions were 12±9%, 25±14%, and 62±20%, respectively. At patient level, the dice coefficient scores were not significantly different between participants with and without COPD (p=0.29-0.95, Table). Conclusion: The proposed deep learning method yields accurate, automated segmentation of ventilation defects among older smokers, independent of COPD status. Funding NIH/NHLBI R01-HL093081, R01-HL077612, R01-HL121270

Background: Coronary artery calcium (CAC) predicts atherosclerotic cardiovascular disease (ASCVD) events, inclusive of coronary heart disease (CHD) and stroke, and is a decision-making aid for primary prevention. The predictive value of CAC categories for CHD and stroke separately and across sex and race groups of an asymptomatic population is unclear. Methods: White, Black, and Hispanic participants of MESA (Multi-Ethnic Study of Atherosclerosis) and DHS (Dallas Heart Study) underwent CAC measurement at enrollment and were followed for incident ASCVD events. Ten-year CHD-to-stroke incidence ratios across CAC score categories 0, 1 to 99, and ≥100 were assessed. Associations of CAC with incident CHD and stroke events were evaluated using multivariable-adjusted Cox models and multiplicative interactions of CAC with sex/race were tested. Results: Among 7042 participants (mean age, 57 years, 54% women, 36% Black, 23% Hispanic, 49% CAC=0, 19% CAC ≥100), 574 incident ASCVD events (333 CHD and 241 stroke) were observed over 12.3-year follow-up. Ten-year CHD-to-stroke incidence ratio increased significantly across CAC categories in men, women, Whites, Blacks, and Hispanics (all P Conclusions: In 2 population-based cohorts of asymptomatic individuals, 10-year CHD-to-stroke incidence ratio was higher with increasing CAC score categories across sex and race groups, and CAC was consistently a better predictor of CHD than stroke. High CAC burden comparably associated with ASCVD risk across sex and race groups.

Arterial stiffness (AS) and obesity are recognized as important risk factors of cardiovascular disease (CVD). The purpose of this study was to investigate the relationship between AS and obesity. AS was defined as high augmentation index (AIx) and low elasticity (C1, large artery elasticity; C2, small artery elasticity) in participants enrolled in the Multi-Ethnic Study of Atherosclerosis at baseline. We compared AIx, C1, and C2 by body mass index (BMI) (< 25, 25–29.9, 30–39.9, ⩾ 40 kg/m2) and waist–hip ratio (WHR) (< 0.85, 0.85–0.99, ⩾ 1). The obesity–AS association was tested across 10-year age intervals. Among 6177 participants (62 ± 10 years old, 52% female), a significant inverse relationship was observed between obesity and AS. After adjustments for CVD risk factors, participants with a BMI > 40 kg/m2 had 5.4% lower AIx (mean difference [Δ] = −0.82%; 95% CI: –1.10, –0.53), 15.4% higher C1 (Δ = 1.66 mL/mmHg ×10; 95% CI: 1.00, 2.33), and 40.2% higher C2 (Δ = 1.49 mL/mmHg ×100; 95% CI: 1.15, 1.83) compared to those with a BMI < 25 kg/m2 (all p for trend < 0.001). Participants with a WHR ⩾ 1 had 5.6% higher C1 (∆ = 0.92 mL/mmHg ×10; 95% CI: 0.47, 1.37) compared to those with a WHR < 0.85. The WHR had a significant interaction with age on AIx and C2, but not with BMI; the inverse relationships of the WHR with AIx and C2 were observed only in participants < 55 years between the normal (WHR < 0.85) and the overweight (0.85 ⩽ WHR < 0.99) groups. Different associations of WHR and BMI with arterial stiffness among older adults should be further investigated.