Chronic Stress and Cardiovascular Health: The MESA and MASALA Studies.

Introduction: Research suggests chronic stress is associated with individual cardiovascular health (CVH) metrics (e.g., physical activity and diet quality); however, the association between chronic stress and overall CVH is less well understood.

Adverse pregnancy outcomes and lung function later in life: The CARDIA lung study.

Background: Pregnancy events are linked to future maternal health, although relationships between adverse pregnancy outcomes (APOs) and maternal respiratory health are unknown.

Methods: This is a secondary analysis of CARDIA, a multicenter cohort study. We included all women who had delivered a live infant.

Prepregnancy Cardiovascular Health, Gestational Diabetes, and Coronary Artery Calcium.

Importance: Poor cardiovascular health (CVH) and gestational diabetes (GD) are each associated with higher risk for cardiovascular disease (CVD). Individuals with poor CVH also have a higher risk of GD, but it remains unclear if GD mediates the association between prepregnancy CVH and CVD.

Objective: To examine whether GD is a mediator or marker of the association between prepregnancy CVH and midlife subclinical CVD.

Molecular architecture of human atherosclerosis revealed through integrative human genetics.

Current genetic discovery methods are largely restricted to profiling circulating molecules or genetic architecture, limited in use of tissue-based molecular genetics to identify pathogenic and therapeutic targets. Here, we leverage a multi-level genetic discovery platform integrating population-level proteomics with functional genomic analyses based on human coronary artery tissue to reveal determinants of coronary disease susceptibility. Using aptamer-based proteomics (~7,000 aptamers) across ~3,000 individuals, we first identified the circulating proteome of prevalent and incident coronary artery calcium (CAC), a sensitive marker of subclinical coronary artery disease (CAD), with causal implication in calcified plaque formation or disease phenotypes via parallel genetic approaches (Mendelian randomization, MR) and proteome-wide association (PWAS).

Proteomic Risk Score of Increased Respiratory Susceptibility: A Multi-Cohort Study.

Rationale: Accelerated decline in lung function is associated with incident COPD, hospitalizations and death. However, identifying this trajectory with longitudinal spirometry measurements is challenging in clinical practice.

Objective: To determine whether a proteomic risk score trained on accelerated decline in lung function can assess risk of future respiratory disease and mortality.

Fatherhood and Cardiovascular Health, Disease, and Mortality: Associations From the Multi-Ethnic Study of Atherosclerosis.

Introduction: Emerging literature links fatherhood to men's health but lacks comprehensive assessment of health outcomes, especially among multiethnic populations. This study's objective was to evaluate the associations of fatherhood (age at onset and status) with cardiovascular health scores, incident cardiovascular disease, cardiovascular disease death, and all-cause mortality, examining differences by race/ethnicity.

Methods: The study sample included men from Multi-Ethnic Study of Atherosclerosis, prospective cohort study that enrolled adults aged 45-84 years without known cardiovascular disease at baseline.

Proteomic analysis of cardiorespiratory fitness for prediction of mortality and multisystem disease risks.

Despite the wide effects of cardiorespiratory fitness (CRF) on metabolic, cardiovascular, pulmonary and neurological health, challenges in the feasibility and reproducibility of CRF measurements have impeded its use for clinical decision-making. Here we link proteomic profiles to CRF in 14,145 individuals across four international cohorts with diverse CRF ascertainment methods to establish, validate and characterize a proteomic CRF score. In a cohort of around 22,000 individuals in the UK Biobank, a proteomic CRF score was associated with a reduced risk of all-cause mortality (unadjusted hazard ratio 0.

Proteomics, Human Environmental Exposure, and Cardiometabolic Risk.

Background: The biological mechanisms linking environmental exposures with cardiovascular disease pathobiology are incompletely understood. We sought to identify circulating proteomic signatures of environmental exposures and examine their associations with cardiometabolic and respiratory disease in observational cohort studies.

Methods: We tested the relations of >6500 circulating proteins with 29 environmental exposures across the built environment, green space, air pollution, temperature, and social vulnerability indicators in ≈3000 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults) across 4 centers using penalized and ordinary linear regression.

Association between secondhand smoke exposure and incident heart failure: The Multi-Ethnic Study of Atherosclerosis (MESA).

Aims: There are no studies on the association between secondhand smoke (SHS) exposure and incident heart failure (HF). This cohort study aimed to examine the associations of self-reported and urinary cotinine-assessed SHS exposure with incident HF.

Methods And Results: This study included 5548 non-active smoking participants aged 45-84 years and free of known cardiovascular diseases and HF at baseline who self-reported SHS exposure time in the Multi-Ethnic Study of Atherosclerosis (MESA) at baseline (2000-2002).

Implications of metabolism on multi-systems healthy aging across the lifespan.

Aging is increasingly thought to involve dysregulation of metabolism in multiple organ systems that culminate in decreased functional capacity and morbidity. Here, we seek to understand complex interactions among metabolism, aging, and systems-wide phenotypes across the lifespan. Among 2469 adults (mean age 74.

Association of 20-Year Longitudinal Depressive Symptoms With Left Ventricular Geometry Outcomes in the Coronary Artery Risk Development in Young Adults Study: A Role for Androgens?

Objective: Depression is a risk factor for coronary heart disease and left ventricular hypertrophy (LVH) is a potent predictor of coronary heart disease events. Whether depression is associated with LVH has received limited investigation. This study assessed cross-sectional and 20-year longitudinal associations of depressive symptoms with LVH outcomes after accounting for important known confounders.

Computed tomography measure of lung injury and future interstitial features: the CARDIA Lung Study.

Introduction: Visually normal areas of the lung with high attenuation on computed tomography (CT) imaging, termed CT lung injury, may represent injured but not yet remodelled lung parenchyma. This prospective cohort study examined if CT lung injury is associated with future interstitial features on CT and restrictive spirometry abnormality among participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Methods: CARDIA is a population-based cohort study.

Secondhand tobacco smoke exposure, urine cotinine, and risk of incident atrial fibrillation: The multi-ethnic study of atherosclerosis.

Background: Secondhand tobacco smoke (SHS) exposure may reduce heart rate variability and lead to atrial fibrillation (AF); however prior study findings have not been confirmed using objective measures for both SHS and AF events.

Methods: We prospectively examined the association between SHS exposure and incident AF in 5731 participants, ages of 45-84 years and free of known AF and other cardiovascular diseases (CVD) at baseline (2000-2002), who were followed through 2015 in the Multi-Ethnic Study of Atherosclerosis (MESA). SHS weekly exposure time was identified by self-report.

Blood-Based Fingerprint of Cardiorespiratory Fitness and Long-Term Health Outcomes in Young Adulthood.

Background Cardiorespiratory fitness is a powerful predictor of health outcomes that is currently underused in primary prevention, especially in young adults. We sought to develop a blood-based biomarker of cardiorespiratory fitness that is easily translatable across populations. Methods and Results Maximal effort cardiopulmonary exercise testing for quantification of cardiorespiratory fitness (by peak oxygen uptake) and profiling of >200 metabolites at rest were performed in the FHS (Framingham Heart Study; 2016-2019).

Comparing Racial Differences in Emphysema Prevalence Among Adults With Normal Spirometry: A Secondary Data Analysis of the CARDIA Lung Study.

Background: Computed tomography (CT) imaging complements spirometry and may provide insight into racial disparities in respiratory health.

Objective: To determine the difference in emphysema prevalence between Black and White adults with different measures of normal spirometry results.

Design: Observational study using clinical data and spirometry from the CARDIA (Coronary Artery Risk Development in Young Adults) study obtained in 2015 to 2016 and CT scans done in 2010 to 2011.

Associations of Chronic Burden, Sleep Characteristics, and Metabolic Syndrome in the Coronary Artery Risk Development in Young Adults Study.

Objective: Chronic exposure to stress is associated with metabolic syndrome (MetS), but the mechanism is unclear. We investigated the associations between chronic burden, sleep, and MetS in the Coronary Artery Risk Development in Young Adults Study.

Methods: Chronic burden was self-reported (2000-2001) according to experiences with stressors for longer than 6 months.

Genetic variation in sodium glucose co-transporter 1 and cardiac structure and function at middle age.

Aims: The effects of inhibition of sodium glucose cotransporter (SGLT)-1, as opposed to SGLT2, on cardiovascular structure and function are not well known. We assessed the associations of a missense genetic variant of SGLT1 with cardiac structure and function.

Methods And Results: We evaluated associations of a functionally modifying variant of SLC5A1 (rs17683011 [p.

PDAY risk score predicts cardiovascular events in young adults: the CARDIA study.

Aims: Atherosclerotic cardiovascular disease (ASCVD) risk prediction equations apply to older adults. For this study, the Pathobiologic Determinants of Atherosclerosis in Youth (PDAY) risk score, based on post-mortem measurements of atherosclerosis in 15-34-year olds dying accidentally, was used to predict ASCVD events, specifically myocardial infarction and revascularization, in middle age, from risk measured at ≤40 years of age.

Methods And Results: The Coronary Artery Risk Development in Young Adults Study (CARDIA) collected longitudinal cardiovascular risk data, coronary artery calcium (CAC) scores, and ASCVD data beginning at age 18 and 30 years with 30-year follow-up.

Neighborhood Socioeconomic Deprivation in Young Adulthood and Future Respiratory Health: The CARDIA Lung Study.

Purpose: There are limited data on the relationship between neighborhood level factors and their association with lung health independent of individual socioeconomic status. We sought to determine whether baseline neighborhood level socioeconomic deprivation in young adults is associated with greater 20-year decline in lung function and higher risk of future lung disease, independent of baseline individual income, education, and smoking status.

Methods: This multicenter population-based cohort study included 2689 participants in Coronary Artery Risk Development in Young Adults (CARDIA) for whom neighborhood deprivation was determined at year 10 (baseline for study) and who had complete lung function measurements at years 10 and 30.

Urinary sodium and potassium excretions in young adulthood and blood pressure by middle age: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Objective: Data are sparse regarding the impact of sodium and potassium intakes on serial blood pressure (BP) levels during long-term follow-up.

Methods: Among 1007 Coronary Artery Risk Development in Young Adults participants (mean age, 30.2 years; 53% blacks; 57% women) who had at least two 24-h urine samples collected at year 5 (Y5) examination, we assessed associations of urinary sodium and potassium excretions with BP trends and incident hypertension in the subsequent 25 years.

Does Lowering Low-Density Lipoprotein Cholesterol With Statin Restore Low Risk in Middle-Aged Adults? Analysis of the Observational MESA Study.

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) <100 mg/dL (reference) and other groups, adjusting for CVD risk factors.