Background Cardiovascular disease risk scores are widespread in research and clinical settings. The MESA (Multi‐Ethnic Study of Atherosclerosis) risk score estimates the 10‐year risk of coronary heart disease and was novel in its use of coronary artery calcium alongside traditional risk factors, including race/ethnicity. However, including race/ethnicity in a risk score model requires careful consideration. We developed a race‐free MESA risk score and compared it with the original. Methods We used data from the MESA cohort, a community‐based cohort of individuals aged 45 to 84 years who identified as White, Hispanic/Latino, Black, or Chinese and were free of prevalent cardiovascular disease upon study entry, to develop a race‐free risk score estimating 10‐year coronary heart disease risk. We used the same 2‐step regularization procedure as that for the original MESA risk score: (1) least absolute shrinkage and selection operator for variable selection, and (2) ridge regression to prevent overfitting. Neither race/ethnicity nor any interaction term with race/ethnicity was included as a candidate predictor. Results When excluding race/ethnicity, several interaction terms were retained that were not retained in the original MESA risk score. The area under the receiver operating characteristic curve for the race‐free risk score was 0.820 (95% CI, 0.801–0.840), and the difference in area under the receiver operating characteristic curve was not significant (estimate, 0.0032 [95% CI, −0.0008 to 0.0073]). The discrimination slope in the race‐free model was 0.101, while that of the original MESA risk score was 0.0937. Conclusions We developed a race‐free MESA risk score that performs comparably to the MESA risk score in both calibration and discrimination.

Historically, hypertension (HTN) and osteoporosis, as indicated by bone mineral density (BMD), were viewed as distinct conditions. However, current understanding highlights the role of vascular inflammation and immune cell activation in both diseases. The exact relationship between HTN and BMD, however, remains poorly defined. Participants from the MESA study, both with and without hypertension (defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg, or the use of antihypertensive drugs), underwent thoracic spine BMD measurement using non-contrast CT chest. Linear regression was used to assess the relationship between BMD and HTN. BMD was also categorized by T-scores (normal, osteopenia, osteoporosis) and analyzed using proportional odds logistic regression. The models were adjusted for variables such as age, gender, race/ethnicity, BMI, and osteoporosis medication use to assess these associations. Among the 6,814 participants, those with hypertension (HTN) were older and more likely to be Black and female. Osteoporosis was more prevalent among hypertensive individuals (30

Left ventricular (LV) mass and left atrial (LA) strain are physiologically coupled and individually predict adverse cardiovascular outcomes. Their imbalance may reflect early atrioventricular uncoupling and atrial myopathy before overt structural disease. We evaluated whether a cardiac magnetic resonance (CMR)-derived LV mass-to-LA strain ratio identifies early atrioventricular mechanical uncoupling and predicts cardiovascular events. Participants from the Multi-Ethnic Study of Atherosclerosis underwent CMR at exams 1 (2000-2002) and 5 (2010-2012). The LV mass-to-LA strain ratio was calculated as indexed end-diastolic LV mass divided by peak LA strain. Classification and regression tree analysis identified cut points for baseline ratio and longitudinal change, defining low (<1.04), reference (1.04-3.26), and high (>3.26) groups, and lesser-(≤130%) versus greater-change (>130%) groups. Multivariable Cox models assessed associations with heart failure (HF), atrial fibrillation (AF), myocardial infarction (MI), and all-cause mortality. Among 4,232 participants (mean age 61.5 ± 10.1 yr; 52.8% female), the mean ratio was 1.95 ± 0.72. Over a median 18-yr follow-up, 6.0% developed HF, 5.2% MI, 18.7% AF, and 25.6% died. A high LV mass-to-LA strain ratio independently predicted HF [hazard ratio (HR) 2.85], AF (HR 2.00), MI (HR 1.96), and death (HR 1.70; all P ≤ 0.003). With repeat CMR, an increasing ratio also predicted cardiovascular events, including among individuals with normal LV mass and LA strain. Higher baseline ratios were associated with progression toward abnormal volumetric atrioventricular coupling over time. A higher LV mass-to-LA strain ratio and its increase independently predict cardiovascular events before overt chamber abnormalities, supporting impaired atrial adaptation as an early stage of atrial myopathy.NEW & NOTEWORTHY Left atrial failure underlies two of the most consequential conditions in cardiovascular medicine: atrial fibrillation, with predisposition to stroke and dementia, and heart failure with preserved ejection fraction, a leading cause of hospitalization and mortality. By examining the relationship between left ventricular hypertrophy and left atrial deformation at the population level, we demonstrate that the LV mass-to-LA strain ratio identifies a threshold beyond which adverse atrial remodeling independently predicts incident cardiovascular events-even within normal ranges.

Cigarette smoking is a known contributor to cardiovascular disease (CVD) and is associated with increased prevalence of coronary artery calcium. However, despite this clinical significance, calcium deposition in other vascular beds, specifically the aortic arch, has yet to be thoroughly investigated among cigarette smokers.The study population comprised participants who underwent non-contrast chest CT scans in MESA exam 5 (2010–2012). Aortic arch calcium (AAC) is defined as calcification in the transverse aortic arch, as measured using the Agatston method on chest CT scans. Log-transformed AAC scores were used for all analyses. Multivariable linear regression models were fit to assess the relationship between log-AAC and cigarette smoking status (never-smoked, former smoker, current smoker). Cox proportional hazard models were fit to investigate the relationship between log-AAC and incident CVD and mortality for those with a history of smoking (former current smokers). All models were adjusted for demographic and traditional clinical risk factors. After excluding those with missing variables or prevalent CVD prior to the chest CT, 2,191 participants were included in the final analysis, of which 1,091 self-identified as never smokers, 918 as former smokers, and 182 as current smokers. Estimated mean log-AAC was 0.58 (p < 0.001) log-Agatston units higher in former smokers compared with never smokers [95

Background: Hypertension (HTN) is a key driver of cardiovascular disease (CVD). Racial and ethnic disparities in HTN have been noted, yet the contributions of socioeconomic, lifestyle, and psychosocial factors underlying disparities remain understudied. We examined the associations between race/ethnicity and HTN outcomes, accounting for these factors. Methods: We analyzed 5,492 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort of adults aged 45-84 years free of clinical CVD at baseline. Outcomes included baseline prevalent HTN (BP≥140/90 mmHg and/or BP medication use), HTN treatment and control, and incident HTN over ~16 years. Multivariable regression models were used to estimate associations between race/ethnicity and each outcome using sequential modeling, adjusting for age, sex, education, income, insurance, neighborhood SES, BMI, exercise, diet, smoking, alcohol, social support, discrimination, and chronic stress. Results: (See figure) At baseline, 47% had HTN. Prevalence was highest among Black followed by Hispanic, White, and Chinese participants. Adjustment for socioeconomic, lifestyle, and psychosocial factors reduced the prevalence ratio for Black compared to White participants, but remained significantly elevated. Chinese participants had lower HTN odds in partially adjusted models, but this association was not significant after full adjustment. Among those with HTN, all non-White groups had higher odds of being in the “treated but uncontrolled” category compared to “treated and controlled,” relative to White participants, even after full adjustment. Black participants were more aware of their HTN. Among 2,906 normotensive participants with follow-up data, Black participants had the highest HTN incidence, which, although attenuated, remained significant after full adjustment. The higher incidence for Hispanic participants was not significant after full adjustment. Conclusion: Adjustment for socioeconomic, lifestyle, and psychosocial factors substantially reduced the magnitude of racial and ethnic disparities in HTN outcomes, suggesting a significant contribution of these factors. These findings underscore the importance of addressing barriers to improve HTN outcomes.

Most prior studies of cardiovascular disease (CVD) events have focused on incident events. Here, differences were analyzed by race/ethnicity in incident and recurrent CVD events in the Multi-Ethnic Study of Atherosclerosis from baseline in 2000-2002 through 2019 using joint and multivariable adjusted Cox proportional hazards modeling. Among 6814 men and women aged 45-85 years without known CVD at enrollment, during median follow-up of 17.7 years, 1206 incident and 695 recurrent CVD events occurred; 891 individuals with a nonfatal incident event were at risk for recurrent events. Rates of combined incident and recurrent CVD events among Black, White, Chinese, and Hispanic participants were 16.8, 18.6, 13.3, and 19.3 per 1000 person-years, respectively. First recurrent CVD event rates in Black, White, Chinese, and Hispanic participants were 87.7, 68.7, 78.1, and 80.7 per 1000 person-years, respectively. Revascularization rates were lower in Black compared with White participants (3.8 vs 6.4 per 1000 person-years; P < .0001). The adjusted hazard for CVD death was higher for Black than White participants (hazard ratio = 1.85; 95% CI, 1.03-3.29). In this multiethnic cohort, Black participants had a lower or similar rate of incident and recurrent CVD events, lower rate of revascularization, and higher rate of fatal CVD than did White participants.

Background: Prior studies have demonstrated associations between eosinophil activation products and incident stroke. We sought to investigate associations between blood eosinophil count and imaging markers of atherosclerosis (carotid artery plaque [CAP] and coronary artery calcium [CAC]) in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: The MESA enrolled adults aged 45-84 years, free of atherosclerotic cardiovascular disease (ASCVD) at baseline. ASCVD risk factors, blood eosinophils, CAP presence and score (0-12) and CAC presence and Agatston score were measured at exam 5. Logistic and linear regression models were employed to test the association of blood eosinophils, CAP and CAC presence and score (log[score+1]) adjusted for biologic confounders. Results: The 2,166 participants were a mean (standard deviation [SD]) 69.6 (9.3) years old, 53% female, 29% Hispanic, 28% Black, 1% Chinese. The median (interquartile range) eosinophil count was 0.1 (0.1, 0.2)x10E3/uL, CAP score= 2 (0,4) and CAC score= 45 (0, 292) Agatston units. In risk-factor adjusted models (Table 1; model 5), increased blood eosinophil count (per 1 SD [0.15 x10E3/uL]) was associated with CAP (β = 0.05 [95% CI 0.02-0.08, p = 0.001) and CAC (β = 0.11, [95% CI: 0.01-0.21], p = 0.03) score. Similar associations were seen with eosinophils and CAP (Odds ratio [OR] = 1.12, [95% CI: 1.01-1.25], p = 0.03) and CAC (OR = 1.15, [95% CI: 1.02-1.30], p = 0.02) presence. Conclusions: In a large, contemporary, multiethnic, U.S. cohort, blood eosinophils were strongly associated with imaging measures of atherosclerosis even after adjustment for ASCVD risk factors. These data suggest potential roles of T2/eosinophilic inflammation in atherosclerosis.

Background/Objectives: While previous study results have suggested an elevated risk of type 2 diabetes with potato consumption, limited and inconsistent results are available on the association of potato consumption with the risk of cardiovascular disease (CVD) and hypertension (HTN). We assessed the associations of (i) total potato consumption with the risk of CVD and HTN as the primary aim and (ii) fried potatoes and combined baked, boiled, and mashed potatoes with the risk of CVD and HTN as the secondary aim. Methods: We conducted a meta-analysis using data from seven cohorts for CVD (n = 110,063) and five cohorts for HTN (n = 67,146). Cox regression was used to estimate multivariable adjusted hazard ratios separately in each cohort and the cohort-specific results were meta-analyzed using an inverse-variance weighted method. Results: The mean age ranged from 25 to 72 years, 65% of the respondents were women, and the mean consumption of total potatoes ranged from 1.9 to 4.3 times per week. In the primary analysis, total potato intake was not associated with the risk of either CVD or HTN: multivariable adjusted HR (95% CI) comparing 5+ servings/week to no potato intake: 0.96 (0.89-1.04) for CVD and 1.04 (0.99-1.08) for HTN. In secondary analyses, the consumption of combined baked, boiled, and mashed potatoes was not associated with CVD or HTN; while fried potato consumption was not associated with CVD risk, there was a 10% higher risk of HTN (95% CI: 4% to 17%) comparing 1+ servings/week to no fried potato intake. Conclusions: While the consumption of total potato was not associated with the risk of CVD or HTN risk, a modest elevated risk of HTN but not CVD was observed only with fried potato consumption.

Circulating non-esterified fatty acids (NEFAs) have toxic effects on a variety of organs central to cardiometabolic disease and can cross the blood-brain barrier. Whether NEFAs associate with cognitive decline or dementia remains unknown.Circulating total NEFA levels were measured in 3,242 participants without dementia among older adults of the Cardiovascular Health Study (CHS) and related to adjudicated dementia over 6 years (n=456 cases) and annually assessed cognitive decline. For confirmation, we related circulating NEFAs to cognition assessed 10 years later among 4,361 participants in the Multi-Ethnic Study of Atherosclerosis (MESA).In CHS participants, each SD higher NEFA levels were associated with a hazard ratio (HR) for all-cause dementia of 1.11 (95% CI: 1.01; 1.22). Baseline NEFA levels were also associated with more rapid decline in cognition over 6 years of follow-up. In MESA, circulating NEFA measurements were associated with lower cognitive scores measured 10 years later.’

A significant challenge in multi-omic geroscience research is the collection of high quality, fit-for-purpose biospecimens from a diverse and well-characterized study population with sufficient sample size to detect age-related changes in physiological biomarkers. The Dog Aging Project designed the precision cohort to study the mechanisms underlying age-related change in the metabolome, microbiome, and epigenome in companion dogs, an emerging model system for translational geroscience research. One thousand dog-owner pairs were recruited into cohort strata based on life stage, sex, size, and geography. We designed and built a novel implementation of the REDCap electronic data capture system to manage study participants, logistics, and biospecimen and survey data collection in a secure online platform. In collaboration with primary care veterinarians, we collected and processed blood, urine, fecal, and hair samples from 976 dogs. The resulting data include complete blood count, chemistry profile, immunophenotyping by flow cytometry, metabolite quantification, fecal microbiome characterization, epigenomic profile, urinalysis, and associated metadata characterizing sample conditions at collection and during lab processing. The project, which has already begun collecting second- and third-year samples from precision cohort dogs, demonstrates that scientifically useful biospecimens can be collected from a geographically dispersed population through collaboration with private veterinary clinics and downstream labs. The data collection infrastructure developed for the precision cohort can be leveraged for future studies. Most important, the Dog Aging Project is an open data project. We encourage researchers around the world to apply for data access and utilize this rich, constantly growing dataset in their own work.

The current study aimed to identify the role of blood lipids in the air pollutant-cognition relationship. The study sample consisted of 1,518 adults aged 45+ in the Multi-Ethnic Study of Atherosclerosis (MESA). Outdoor residential concentrations of PM2.5, NO2, and NOx between Exams 1 (2000-2002) and 5 (2010-2012) were assessed using validated spatiotemporal models. Outcomes were three cognitive test scores of Cognitive Abilities Screening Instrument (CASI), the Digit Symbol Coding (DSC), and the Digit Span (DS) tests at Exam 6 (2016-2018). Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in blood at Exam 5 were evaluated as mediators or modifiers using linear regression models. The inverse odds ratio weighting approach was used for mediation analyses. Models assessed gender and race/ethnicity related heterogeneity in air pollutant-cognition and blood lipid-cognition associations. The direct effect of NO2 and NOx on DSC scores was significant (ß=-2.96 for NO2; ß=-3.20 for NOx, per interquartile range increase), but there was no evidence of mediation by cholesterol levels. Interaction terms of air pollutants and LDL-C were significantly associated with CASI scores (ß = 0.02, p = 0.01 for PM2.5; ß = 0.03, p < 0.001 for NO2; ß = 0.02, p < 0.01 for NOx). Associations of DSC scores with NO2 and NOx were only significant among Black participants (ß = -7.11 for NO2; ß = -6.18 for NOx). Findings of the study suggest that air pollution monitoring and control may be effective for protecting brain health and delaying the onset of cognitive impairment and dementia in late adulthood.

BACKGROUND:Normal reference ranges in cardiovascular imaging studies are typically established as the mean value plus and minus twice the standard deviation (SD) of a healthy reference cohort ("2 SD-method"). Although widely used for cardiac magnetic resonance (CMR), this approach has not been previously validated. The purpose of this study was to use longitudinal cohort data to assess the clinical predictive validity of normal reference values for cardiac CMR. METHODS:Normal reference ranges for left- and right ventricular (LV and RV) CMR parameters were derived from baseline exam data of 1518 participants (age 45-84years) in the Multi-Ethnic Study of Atherosclerosis (MESA) study without known CV disease and without established CV risk factors. Cut-off values at 1 and 2 SDs were obtained for the following LV and RV parameters indexed to body surface area: end-diastolic volume (LVEDVi, RVEDVi), end-systolic volume (LVESVi, RVESVi), mass (LVMi, RVMi), as well as for LVED diameter (LVEDD), LVED wall thickness, and ejection fraction (LVEF, RVEF). The relationship of reference values to CV events was then evaluated in the entire MESA cohort with CMR data (n=4915), including individuals with CV risk factors at the baseline exam. Cox proportional hazard models were calculated for major adverse and all CV events (MACE and ACE, respectively) at 5 and 10 years of follow-up. RESULTS:At 5 years of follow-up, LVEDVi, LVESVi, and LVEF beyond the 2SD-threshold of the mean reference values were predictors of MACE and ACE in men and women (HR 2.1-4.3; P<.001-.029). In men, LVMi and LVED wall thickness above the 1 SD-threshold were associated with CV events (HR 1.6-2.1; P<.001-.002). For women, LVED wall thickness above the 1 SD-threshold significantly increased risk of adverse events (HR 1.6-2.3; P.034-.002) while LVMi was associated with events only for values above the 2SD-threshold (HR 2.7-4.1; P<.001). Notably, LVEDD, RVMi, RVESVi, and RVEF were not associated with CV events in men or women. CV events over 10 years showed similar trends. CONCLUSION:Our results support the clinical relevance of CMR normal reference ranges for LV parameters. Most LV CMR parameters beyond the normal reference range (2SD-threshold) were associated with elevated CV risk at 5 and 10 years. Elevated LVEDDi, RVMi, RVESVi, and RVEF, however, were not associated with CV events.

Introduction: The Agatston score is a measure of coronary artery calcification (CAC) used to predict atherosclerotic cardiovascular disease (ASCVD) events. Notably, the score is upweighted for calcium density, despite evidence that density is inversely associated with cardiovascular disease after accounting for volume. Some studies have found associations between dietary components and the Agatston score, but none have evaluated diet in relation to CAC density and volume. Hypothesis: The Alternative Healthy Eating Index-2010 (AHEI), a measure of diet quality, is associated with lower CAC volume and higher CAC density. Methods: During the baseline exam of the Multi-Ethnic Study of Atherosclerosis, diet was assessed with a 120-item food frequency questionnaire from which the AHEI was derived. At the same exam, CAC was measured from computed tomography scans. In 3,099 participants with non-zero CAC volume, we modeled the associations of AHEI and natural log of Agatston score, natural log of volume, and density with linear regression. Models adjusted for age, sex, race/ethnicity, education, energy intake, cigarette smoking, and physical activity. We further adjusted for volume when density was the outcome and density when volume was the outcome. Results: The analytic sample included non-Hispanic White (45%), Black (23%), Hispanic (20%) and Chinese American (12%) individuals (mean age 66 years; 42% female). The median (Q1, Q3) Agatston score was 88 (22, 299) and volume was 85 mm 3 (25, 277). The mean (standard deviation [SD]) density score was 2.8 (0.7). After adjustment, the association of a one SD higher AHEI and Agatston score was not statistically significant (95% confidence interval [CI]: -0.10, 0.02; p=0.24). Conversely, in models assessing the relationship of AHEI with volume and density independent of one another, associations were significant (p=0.02 for volume; p=0.02 for density). A one SD higher AHEI was associated with a 0.05-unit lower log of volume (95% CI: -0.10, -0.01) and 0.02-unit higher density (95% CI: 0.00, 0.04). Conclusions : Our finding that higher AHEI was associated with lower CAC volume and higher CAC density aligns with research showing that diet is a risk factor for ASCVD. The null association with Agatston score appears to reflect the cancelling effects of the positive associations of density with higher AHEI and volume with lower AHEI, rather than the absence of a potential impact of dietary intake on subclinical atherosclerosis.

Cigarette smoking and aortic arch calcification (AAC) are powerful risk factors for incident cardiovascular disease (CVD), but their relationship is yet to be thoroughly investigated. We used data from the Multi-Ethnic Study of Atherosclerosis to examine the development and progression of AAC, and the extent to which AAC can risk stratify for CVD, among individuals with a history of smoking. Our study sample consisted of 2846 men and women in the US aged 53 to 93 years old who were scored for AAC at two exams roughly 5 years apart. We hypothesized that cigarette smoke exposure would be significantly associated with AAC at initial exam, with AAC progression between exams, and that AAC would improve risk prediction accuracy for CVD among smokers. We used linear mixed-effects models to assess AAC development and progression, proportional hazards models to investigate the relationship between AAC and incident CVD among smokers, and the area under the time-dependent receiver-operator characteristic curve (AUC) to characterize model prediction accuracy. All models were adjusted for demographic and cardiovascular risk factors. Relative to participants who never smoked, being a former or current smoker was significantly associated with higher AAC at initial exam (P=0.001), but not AAC progression between exams. Among current or former smokers, a one-unit increase of log-transformed AAC was associated with a 20.6% increased risk of CVD (P<0.001), and a 13.0% increased risk of all-cause mortality (P=0.01). The inclusion of AAC as a risk factor among smokers improved the 8-year AUC for CVD events from 0.731 to 0.778. In conclusion, AAC is a measure of atherosclerotic burden that can improve risk stratification for CVD in smokers.