Coronary Artery Risk Development Research Articles

Longitudinal albuminuria patterns predict coronary artery calcification progression: Findings from the coronary artery risk development in young adults study

Background and aimsAlbuminuria is an established risk factor for adverse cardiovascular outcomes. However, few studies have characterized longitudinal albuminuria patterns based on long-term measurement of urine albumin-to-creatinine ratio (UACR) levels. We aimed to evaluate the association between longitudinal albuminuria patterns in midlife adults and subsequent CAC progression. MethodsWe included 1919 participants with CAC assessment by computed tomography from CARDIA (Coronary Artery Risk Development in Young Adults) study. CAC progression was determined for each individual as the difference of logarithmic CAC scores at follow-up and baseline. Albuminuria patterns across a 10-year span were estimated by longitudinal UACR levels. Multivariable general linear models were used to evaluate the association of long-term albuminuria patterns with CAC progression. ResultsOf the 1919 included participants, 583 (30.4%) participants experienced CAC progression, and the mean (SD) age was 50.4 (3.5) years at year 25. A total of four dynamic albuminuria patterns were identified. After multivariable adjustment, there were significant differences in CAC progression by albuminuria patterns as demonstrated as percent change in CAC with 36.0% (SE, 1.5) progression for mid- and late-life normoalbuminuria group, 46.0% (SE, 7.6) for midlife normoalbuminuria and late-life high albuminuria group, 52.4% (SE, 7.1) for midlife high albuminuria and late-life normoalbuminuria group, and 54.5% (SE, 8.7) for mid- and late-life high albuminuria group (p = 0.019). Similar findings were also observed in CAC volume score changes. ConclusionsLongitudinal albuminuria patterns across a 10-year span were associated with worse CAC progression independent of baseline CAC level and albuminuria changes, suggesting that it may provide early identification of high-risk individuals with dynamic rises in albuminuria who may benefit from aggressive risk factor modification.

Association of Cardiovascular Health in Young Adulthood with Long-Term Blood Pressure Trajectories.

Cardiovascular health (CVH) in young adulthood (YA) has been associated with cardiovascular outcomes in older age. However, little is known about the relationship between YA CVH and mid-life BP trajectories. Baseline CVH (defined by 7 of AHA's Life's Essential 8 [LE8] metrics, excluding BP) was measured in YA with individual metrics scored and averaged as a composite LE8 score. Categorical CVH status was defined as high, moderate, and low. Latent class analysis was used to identify trajectories of mid-BP (mean of SBP and DBP) from average ages 35 to 55 years. Multinomial logistic regression was used to estimate the association of YA CVH status (continuously and categorically) with mid-life BP trajectory group membership. There were 3,688 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study in YA with follow-up data for mid-life BP trajectories. We observed 3 BP trajectory groups, labeled as Persistently-Low, Middle, and High-Increasing. On average, each 10-points higher baseline LE8 score (mean [SD] of 73.5 [13.1]) in YA was associated with adjusted odds ratios of 0.78 (95% CI, 0.72-0.84) for membership in the Middle and 0.65 (0.57-0.73) for membership in the High-Increasing trajectory groups. Compared with categorical low CVH status at baseline, those with high CVH were significantly less likely to be in the Middle and High-Increasing BP trajectory groups. Moderate or low CVH status in YA is associated with elevated mid-life BP trajectory. These data suggest that young adult CVH promotion may be important for primordial prevention of hypertension.

Proteomics, Human Environmental Exposure, and Cardiometabolic Risk.

Rationale: The biological mechanisms linking environmental exposures with cardiovascular disease (CVD) pathobiology are incompletely understood. We sought to identify circulating proteomic signatures of environmental exposures, and examine their associations with cardiometabolic and respiratory disease (CMD) 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 nearly 3000 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study across 4 centers using penalized and ordinary linear regression. In >3500 participants from the Framingham Heart Study (FHS) and Jackson Heart Study (JHS), we evaluated the prospective relations of proteomic signatures of the envirome with CVD and mortality using Cox models.Results: Proteomic signatures of the envirome identified novel/established CVD-relevant pathways including DNA damage, fibrosis, inflammation, and mitochondrial function. The proteomic signatures of the envirome were broadly related to CMD and respiratory phenotypes (e.g., body mass index, lipids, and left ventricular mass) in CARDIA, with replication in FHS/JHS. A proteomic signature of social vulnerability was associated with a composite of CVD/mortality (1428 events; FHS: HR=1.16, 95% CI 1.08-1.24, P=1.77e-05; JHS: HR=1.25 95% CI 1.13-1.38, P=6.38e-06; HR expressed as per 1 standard deviation increase in proteomic signature), robust to adjustment for known clinical risk factors. Conclusions: Environmental exposures are related to an inflammatory-metabolic proteome, which identifies individuals with CMD and respiratory phenotypes and outcomes. Future work examining the dynamic impact of the environment on human cardiometabolic health is warranted.

Inflammatory, Metabolic and Endothelial Biomarkers Before and After Pregnancy Complications.

Women with gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB) have excess cardiovascular disease compared to those with uncomplicated births, perhaps related to pre-pregnancy inflammation, dysmetabolism or endothelial dysfunction. We included 1238 women in the Coronary Artery Risk Development in Young Adults Study (1985-2011) with 2215 births classified according to outcomes (term, uncomplicated births were the referent). Repeated measures ANOVA estimated pre-pregnancy, post-pregnancy and biomarker change according to pregnancy outcomes, adjusted for confounders. GDM and HDP groups had higher pre-pregnancy hsCRP (+0.37 [0.08, 0.65]; +0.29 [0.04, 0.55] log mg/L), leptin (+0.29 [0.09, 0.50]; +0.37 [0.17, 0.56] log ng/ml), and lower adiponectin (-0.25 [-0.36, -0.13); -0.11 [-0.22, -0.01] log ng/ml) than those with uncomplicated births and these profiles persisted in magnitude post-pregnancy. Controlling for BMI attenuated most profiles, except lower pre-pregnancy adiponectin remained associated with GDM. PTB without HDP or GDM was related to lower pre-pregnancy hsCRP and sICAM-1 (-0.31 [-0.56, -0.06] log mg/L; -0.05 [-0.09, - 0.01] log ng/ml) and a larger leptin increase from pre- to post-pregnancy, (+0.20 [0.02, 0.37] log ng/ml). Pre-pregnancy inflammation and metabolic dysfunction contributed to GDM and HDP, perhaps due to higher BMI. PTB may be related to adverse metabolic changes post-pregnancy, though the unexpected endothelial biomarker profile warrants further study.

A Comparison of 5 Measures of Accelerated Biological Aging and Their Association With Incident Cardiovascular Disease: The CARDIA Study.

Accelerated biological aging is an increasingly popular way to track the acceleration of biology over time that may not be captured by calendar time. Biological aging has been linked to external and internal chronic stressors and has the potential to be used clinically to understand a person's personalized functioning and predict future disease. We compared the association of different measures of biological aging and incident cardiovascular disease (CVD) overall and by race. We used multiple informants models to compare the strength of clinical marker-derived age acceleration, 5 measures of epigenetic age acceleration (intrinsic and extrinsic epigenetic age acceleration, GrimAge acceleration, and PhenoAge acceleration), and 1 established clinical predictor of future CVD, Framingham 10-year risk score, with incident CVD over an 11-year period (2007-2018). Participants were 913 self-identified Black or White (41% and 59%, respectively) female or male (51% and 49%, respectively) individuals enrolled in the US-based CARDIA (Coronary Artery Risk Development in Young Adults) cohort study. The analytic baseline for this study was the 20-year follow-up examination (2005-2006; median age 45 years). We also included race-specific analysis. We found that all measures were modestly correlated with one another. However, clinical marker-derived age acceleration and Framingham 10-year risk score were more strongly associated with incident CVD than all the epigenetic measures. Clinical marker-derived age acceleration and Framingham 10-year risk score were not significantly different than one another in their association with incident CVD. The type of accelerated aging measure should be taken into consideration when comparing their association with clinical outcomes. A multisystem clinical composite shows associations with incident CVD equally to a well-known clinical predictor.

Trajectories in depressive symptoms and midlife brain health

Depressive symptoms may either be a risk factor or prodromal to dementia. Investigating this association in midlife may help clarify the role of depression in cognitive aging. We aimed to identify trajectories in depressive symptoms in early to mid-life and related cognitive and brain outcomes in midlife. This study includes 3944 Black and White participants (ages 26−45 years at baseline) from the Coronary Artery Risk Development in Young Adults (CARDIA) study with 20 years of follow-up. Depressive symptoms were assessed using the Center for Epidemiological Studies Depression scale at five time points over 20 years. Growth mixture modeling (GMM) was used to identify depressive symptom trajectories. Participants completed a neuropsychological battery 20 years after baseline, including the Digit Symbol Substitution Test (DSST), Rey-Auditory Verbal Learning Test (RAVLT), Stroop Test, Montreal Cognitive Assessment (MoCA), and category and letter fluency tests. A sub-sample of participants (n = 662) underwent brain magnetic resonance imaging (MRI) to characterize gray matter volumes and white matter hyperintensities (WMHs). We identified four classes of depressive symptom trajectories: a “declining” class (n = 286, 7.3%) with initially high symptoms and subsequent decline, a class with consistently high symptoms (“steady high”; n = 264, 6.7%), a class with late increases in symptoms (“increasing”; n = 277, 7%), and a class with consistently low symptoms (“steady low”; n = 3117, 79.0%). The steady high and the increasing classes had poorer performance on all cognitive tests, while the declining class had poorer performance on the DSST, verbal fluency, and MoCA. Compared to the steady low symptom class, the steady high class had lower volumes in the entorhinal cortex (β: −180.80, 95% CI: −336.69 to −24.91) and the amygdala (β: −40.97, 95% CI: −74.09 to −7.85), the increasing class had more WMHs (β: 0.55, 95% CI: 0.22 to 0.89), and the declining class was not significantly different in any brain measures. Trajectories in depressive symptoms in young to mid-adulthood show distinct cognitive and brain phenotypes in midlife. Steady high depressive symptoms may represent a group that is at risk for dementia, whereas increasing symptoms in midlife may be associated with white matter damage.

Dietary Fructose and Sodium Consumed during Early Mid-Life Are Associated with Hypertensive End-Organ Damage by Late Mid-Life in the CARDIA Cohort.

We aimed to investigate how dietary fructose and sodium impact blood pressure and risk of hypertensive target organ damage 10 years later. Data from n = 3116 individuals were obtained from the Coronary Artery Risk Development in Young Adults (CARDIA) study. Four groups were identified based on the four possible combinations of the lower and upper 50th percentile for sodium (in mg) and fructose (expressed as percent of total daily calories). Differences among groups were ascertained and logistic regression analyses were used to assess the risk of hypertensive target organ damage (diastolic dysfunction, coronary calcification and albuminuria). Individuals in the low-fructose + low-sodium group were found to have lower SBP compared to those in the low-fructose + high-sodium and high-fructose + high-sodium groups (p < 0.05). The highest risk for hypertensive target organ damage was found for albuminuria only in the high-fructose + high-sodium group (OR = 3.328, p = 0.006) while female sex was protective across all groups against coronary calcification. Our findings highlight that sodium alone may not be the culprit for hypertension and hypertensive target organ damage, but rather when combined with an increased intake of dietary fructose, especially in middle-aged individuals.

The longitudinal association of adipose-to-lean ratio with incident cardiometabolic morbidity: The CARDIA study

AimTo assess the association of adipose-to-lean ratio (ALR) with incident type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia in middle adulthood. MethodBlack and White Coronary Artery Risk Development in Young Adults participants without T2DM, hypertension, or dyslipidemia in 2005–06 (baseline) were included. Baseline adipose and lean mass were assessed via dual-energy X-ray absorptiometry. ALR was calculated as adipose divided by lean mass and then standardized within sex strata. Single time-point incident morbidity was assessed every five years from baseline through 2016. Cox proportional hazards regression was used to estimate hazard ratios (HR) for morbidity over 10 years per 1-SD increment in ALR adjusted for cardiovascular risk factors. ResultThe cumulative incidence of T2DM was 7.9 % (129 events/N = 1643; 16,301 person-years), 26.7 % (485 events/N = 1819; 17,895 person-years) for hypertension, and 49.1 % (435 events/N = 855, 8089 person-years) for dyslipidemia. In the adjusted models, ALR was positively associated with a risk of T2DM (HR [95 % CI]; 1.69 [1.31, 2.19]) and hypertension (1.23 [1.08, 1.40]). There was no significant interaction between ALR and sex for any morbidity. ConclusionALR in middle adulthood is associated with incident T2DM and hypertension. The extent to which localized body composition measures might inform morbidity risk merits further investigation.

Association of postexercise blood pressure with cardiovascular outcomes and mortality: The CARDIA study.

Postexercise blood pressure (BP) may be a better predictor of cardiovascular risk than office BP, but there is a lack of data supporting this claim. We hypothesized that postexercise BP may be an important prognostic marker. Our aim was to evaluate the association of postexercise BP with major adverse cardiovascular events (MACE) and all-cause mortality. A total of 2581 participants (median age, 46 years; 55.9% women) from the Coronary Artery Risk Development in Young Adults study at year 20 (2005-2006) who underwent a graded exercise treadmill test using a modified Balke graded protocol were included. Postexercise BP was measured at baseline. Cox models were used to estimate the associations of postexercise BP with MACE and all-cause mortality. Participants were followed up until December 31, 2021. In the entire population, postexercise systolic BP showed no significant association with MACE or all-cause mortality, while postexercise diastolic BP was associated with MACE (hazard ratios [HR], 1.27 [95% CI, 1.06-1.52], per 10mmHg increase) and all-cause mortality (HR, 1.26 [95% CI, 1.05-1.51], per 10mmHg increase). In the normal BP group, postexercise systolic BP was not significantly associated with MACE or all-cause mortality, and postexercise diastolic BP was strongly associated with MACE (HR, 1.57 [95% CI, 1.18-2.09], per 10mmHg increase). In this population-based cohort study, postexercise diastolic BP was significantly associated with the risk of MACE and all-cause mortality. Among individuals with normal BP, postexercise diastolic BP could identify those at a higher risk of cardiovascular events.

Comparing coronary artery cross-sectional area among asymptomatic South Asian, White, and Black participants: the MASALA and CARDIA studies

BackgroundSouth Asian individuals have high risk of atherosclerotic cardiovascular disease (ASCVD). Some investigators suggest smaller coronary artery size may be partially responsible.MethodsWe compared the left anterior descending (LAD) artery cross-sectional area (CSA) (lumen and arterial wall) among South Asians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with White and Black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, adjusting for BMI, height, and other ASCVD risk factors. We used thin-slice non-contrast cardiac computed tomography to measure LAD CSA. We used linear regression models to determine whether race/ethnicity was associated with LAD CSA after adjusting for demographic factors, BMI, height, coronary artery calcium (CAC), and traditional cardiovascular risk factors.ResultsOur sample included 3,353 participants: 513 self-identified as South Asian (44.4% women), 1286 as Black (59.6% women), and 1554 as White (53.5% women). After adjusting for age, BMI, height, there was no difference in LAD CSA between South Asian men and women compared to White men and women, respectively. After full adjustment for CVD risk factors, LAD CSA values were: South Asian women (19.9 mm2, 95% CI [18.8 – 20.9]) and men (22.3 mm2, 95% CI [21.4 – 23.2]; White women (20.0 mm2, 95% CI [19.4—20.5]) and men (23.6 mm2, 95% CI [23.0—24.2]); and Black women (21.6 mm2, 95% CI [21.0 – 22.2]) and men (26.0 mm2, 95% CI [25.3 – 26.7]). Height, BMI, hypertension, CAC, and age were positively associated with LAD CSA; current and former cigarette use were inversely associated.ConclusionsSouth Asian men and women have similar LAD CSA to White men and women, and smaller LAD CSA compared to Black men and women, respectively, after accounting for differences in body size. Future studies should determine whether LAD CSA is associated with future ASCVD events.

Associations of a plant-centered diet and lung function across early to mid-adulthood: The CARDIA Lung Study

BackgroundLung function throughout adulthood predicts morbidity and mortality even among adults without chronic respiratory disease. Diet quality may represent a modifiable risk factor for lung function impairment later in life. We investigated associations between nutritionally-rich plant-centered diet and lung function across early and middle adulthood from the Coronary Artery Risk Development in Young Adults (CARDIA) Study.MethodsDiet was assessed at baseline and years 7 and 20 of follow-up using the validated CARDIA diet history questionnaire. Plant-centered diet quality was scored using the validated A Priori Diet Quality Score (APDQS), which weights food groups to measure adherence to a nutritionally-rich plant-centered diet for 20 beneficially rated foods and 13 adversely rated foods. Scores were cumulatively averaged over follow-up and categorized into quintiles. The primary outcome was lung function decline, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), measured at years 0, 2, 5, 10, 20, and 30. We estimated the association of APDQS with annual pulmonary function changes and cross-sectional differences in a repeated measures regression model, adjusting for clinically relevant covariates.ResultsThe study included 3,787 Black and White men and women aged 18–30 in 1985–86 and followed for 30 years. In multivariable repeated measures regression models, individuals in the lowest APDQS quintile (poorest diet) had declines in FEV1 that were 1.6 ml/year greater than individuals in the highest quintile (35.0 vs. 33.4 ml/year, ß ± SE per 1 SD change APDQS 0.94 ± 0.36, p = 0.009). Additionally, declines in FVC were 2.4 ml/year greater in the lowest APDQS quintile than those in the highest quintile (37.0 vs 34.6 ml/year, ß ± SE per 1 SD change APDQS 1.71 ± 0.46, p < 0.001). The association was not different between never and ever smokers (pint = 0.07 for FVC and 0.32 for FEV1). In sensitivity analyses where current asthma diagnosis and cardiorespiratory fitness were further adjusted, results remained similar. Cross-sectional analysis at each exam year also showed significant differences in lung function according to diet after covariate adjustment.ConclusionsIn this 30-year longitudinal cohort study, long-term adherence to a nutritionally-rich plant-centered diet was associated with cross-sectional differences in lung function as well as slower decline in lung function, highlighting diet quality as a potential treatable trait supporting long-term lung health.

Longitudinal changes in diet quality and food intake before and after diabetes awareness in American adults: the Coronary Artery Risk Development in Young Adults (CARDIA) study

IntroductionLimited longitudinal research is available examining how American adults make dietary changes after learning they have diabetes. We examined the associations between diabetes awareness and changes in dietary quality and...

Impact of optimal cholesterol levels on subclinical atherosclerosis in the absence of risk factors in young adults

Background and aimsTo assess the association of blood lipids with the prevalence, incidence, and progression of subclinical atherosclerosis among young individuals without dyslipidemia and other traditional cardiovascular risk factors (CVRFs). MethodsA total of 1270 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study aged 32–46 years who were free of cardiovascular disease, diabetes, hypertension, current smoking, and dyslipidemia (total cholesterol [TC] ≥ 240 mg/dL, triglycerides [TG] ≥ 150 mg/dL, low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL, high-density lipoprotein cholesterol [HDL-C] < 40 mg/dL, or taking lipid-lowering medications) were included. A subgroup with optimal lipids within the low-CVRF group was defined with TC < 200 mg/dL, LDL-C < 100 mg/dL, non-HDL-C < 130 mg/dL, and women with HDL-C ≥ 50 mg/dL. ResultsA 1-SD higher TC (25.9 mg/dL), LDL-C (24.7 mg/dL), and non-HDL-C (26.6 mg/dL) were associated with a greater risk of presence (hazard ratios: 1.30–1.36), incidence (1.30–1.32), and progression (1.31–1.35) of coronary artery calcium (CAC) and a 42–44% greater odds of composite mean carotid intima-media thickness (CIMT) ≥ 75th percentile [780 μm] (p < 0.05). Repeating the analyses in a subset of participants with a CAC score of zero did not alter the association of TC, LDL-C, and non-HDL-C with CIMT. In the subgroup with optimal lipids, these lipid indices remained associated with an increased risk of presence and incidence of CAC and greater CIMT measures. ConclusionsAmong adults aged 32–46 years, in the absence of traditional CVRFs, elevated cholesterol levels, even within what is considered optimal, are associated with atherosclerosis and arteriopathy.

Association of Plasma YKL-40 With MRI, CSF, and Cognitive Markers of Brain Health and Dementia.

Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk. We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS). YKL-40 was measured from stored plasma by a single laboratory using Mesoscale Discovery with levels log transformed and standardized within each cohort. Outcomes included MRI total brain volume, hippocampal volume, and white matter hyperintensity volume (WMHV) as a percentage of intracranial volume, a general cognitive composite derived from neuropsychological testing (SD units [SDU]), and the risk of incident dementia. We sought to replicate associations with dementia in the clinic-based ACE csf cohort, which also had YKL-40 measured from the CSF. Meta-analyses of MRI outcomes included 6,558 dementia-free participants, and for analysis of cognition, 6,670. The blood draw preceded MRI/cognitive assessment by up to 10.6 years across cohorts. The mean ages ranged from 50 to 76 years, with 39%-48% male individuals. In random-effects meta-analysis of study estimates, each SDU increase in log-transformed YKL-40 levels was associated with smaller total brain volume (β = -0.33; 95% CI -0.45 to -0.22; p < 0.0001) and poorer cognition (β = -0.04; 95% CI -0.07 to -0.02; p < 0.01), following adjustments for demographic variables. YKL-40 levels did not associate with hippocampal volume or WMHV. In the FHS, each SDU increase in log YKL-40 levels was associated with a 64% increase in incident dementia risk over a median of 5.8 years of follow-up, following adjustments for demographic variables (hazard ratio 1.64; 95% CI 1.25-2.16; p < 0.001). In the ACE csf cohort, plasma and CSF YKL-40 were correlated (r = 0.31), and both were associated with conversion from mild cognitive impairment to dementia, independent of amyloid, tau, and neurodegeneration status. Higher plasma YKL-40 levels were associated with lower brain volume, poorer cognition, and incident dementia. Plasma YKL-40 may be useful for studying the association of inflammation and its treatment on dementia risk.

Associations of Polycystic Ovary Syndrome With Indicators of Brain Health at Midlife in the CARDIA Cohort.

Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with an adverse cardiometabolic profile early in life. Increasing evidence links cardiovascular risk factors, such as diabetes and hypertension, to accelerated cognitive aging. However, less is known about PCOS and its relationship to brain health, particularly at midlife. Our goal was to investigate possible associations between PCOS and midlife cognitive function and brain MRI findings in an ongoing prospective study. We used data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a geographically diverse prospective cohort study of individuals who were 18-30 years at baseline (1985-1986) and followed for 30 years. We identified women with PCOS from an ancillary study (CARDIA Women's study (CWS); n = 1,163) as those with elevated androgen levels and/or hirsutism in conjunction with symptoms of oligomenorrhea. At year 30, participants completed cognitive testing, including the Montreal Cognitive Assessment, Rey Auditory Verbal Learning Test (RAVLT) (verbal learning and memory), Digit Symbol Substitution Test (processing speed and executive function), Stroop test (attention and cognitive control), and category and letter fluency tests (semantics and attention). A subset completed brain MRI to assess brain structure and white matter integrity. Multivariable linear regression models estimated the association between PCOS and outcomes, adjusting for age, race, education, and study center. Of the 1163 women in CWS, 907 completed cognitive testing, and of these, 66 (7.1%) met criteria for PCOS (age 54.7 years). Women with and without PCOS were similar for age, BMI, smoking/drinking status, and income. At year 30, participants with PCOS performed lower (mean z score; 95% CI) on Stroop (-0.323 (-0.69 to -7.37); p = 0.008), RAVLT (-0.254 (-0.473 to -0.034); p = 0.002), and category fluency (-0.267 (-0.480 to -0.040); p = 0.02) tests. Of the 291 participants with MRI, 25 (8.5%) met PCOS criteria and demonstrated lower total white matter fractional anisotropy, a measure of white matter integrity (coefficient (95% CI) -0.013 (-0.021 to -0.005); p = 0.002), though not abnormal white matter. Our results suggest that women with PCOS have lower cognitive performance and lower white matter integrity at midlife. Additional research is needed to confirm these findings and to determine potential mechanistic pathways including potential modifiable factors.

Characterizing the spectrum of bladder health and lower urinary tract symptoms among men: Results from the CARDIA study.

To operationalize a new definition for bladder health, we examined the distribution and impact of lower urinary tract symptoms (LUTS), along with risk factors, among men in the Coronary Artery Risk Development in Young Adults (CARDIA) study. LUTS were defined by American Urologic Association Symptom Index (AUASI) scores and impact on quality of life (QoL). Separate questions assessed urinary incontinence (UI) and postvoid dribbling. We performed cluster analyses using AUASI scores, with and without urine incontinence and postvoid dribbling, and impact collected in 2010-11. We performed analyses to evaluate sociodemographic and cardiovascular risk factors between clusters. Among CARDIA men (mean age: 50.0, SD = 3.6; range: 42-56 years) with complete LUTS data (n = 929), we identified and compared four clusters: men who reported no or very mild symptoms and no impact on well-being (bladder health, n = 696, 75%), men with moderate symptoms and moderate impact on well-being (moderate symptoms/impact, n = 84, 9%), men with high symptoms and high impact on well-being (severe symptoms/impact, n = 117, 13%), and a separate group that reported moderate symptoms and UI with a high impact on well-being (UI + moderate symptoms/severe impact, n = 32, 3%). Exploration of the groupings showed a large percentage of postvoid dribbling across groups (overall 69%). Sociodemographic and cardiovascular risk factors were not associated with symptom/impact groups. Bladder health clustered into four categories. A majority of middle-aged men in the community showed no or mild bladder symptoms without impact on QoL. Postvoid dribbling is pervasive but did not cluster with a specific LUTS or impact category.

Associations of Historical Redlining With BMI and Waist Circumference in Coronary Artery Risk Development in Young Adults

Historical maps of racialized evaluation of mortgage lending risk (i.e., redlined neighborhoods) have been linked to adverse health outcomes. Little research has examined whether living in historically redlined neighborhoods is associated with obesity, differentially by race or gender. This is a cross-sectional study to examine whether living in historically redlined neighborhoods is associated with BMI and waist circumference among Black and White adults in 1985-1986. Participants' addresses were linked to the 1930s Home Owners' Loan Corporation maps that evaluated mortgage lending risk across neighborhoods. The authors used multilevel linear regression models clustered on Census tract, adjusted for confounders to estimate main effects, and stratified, and interaction models by (1) race, (2) gender, and (3) race by gender with redlining differentially for Black versus White adults and men versus women. To better understand strata differences, they compared Census tract-level median household income across race and gender groups within Home Owners' Loan Corporation grade. Black adults (n=2,103) were more likely than White adults (n=1,767) to live in historically rated hazardous areas and to have higher BMI and waist circumference. Redlining and race and redlining and gender interactions for BMI and waist circumference were statistically significant (p<0.10). However, in stratified analyses, the only statistically significant associations were among White participants. White participants living in historically rated hazardous areas had lower BMI ( [95% CI= -1.11, -0.15]) and lower waist circumference ( [95% CI= -2.62, -0.38]) than those living in declining areas. Within each Home Owners' Loan Corporation grade, residents in White participants' neighborhoods had higher incomes than those living in Black participants' neighborhoods (p<0.0001). The difference was largest within historically redlined areas. Covariate associations differed for men, women, Black, and White adults, explaining the difference between the interaction and the stratified models. Race by redlining interaction did not vary by gender. White adults may have benefitted from historical redlining, which may have reinforced neighborhood processes that generated racial inequality in BMI and waist circumference 50 years later.

Migraines, vasomotor symptoms, and cardiovascular disease in the Coronary Artery Risk Development in Young Adults study.

To examine whether vasomotor symptoms (VMS) and migraine headaches, hypothesized to be vasoactive conditions, are associated with greater risk for cardiovascular disease (CVD) events including strokes. We performed a secondary data analysis of a subset of women (n = 1,954) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort, which began data collection at 18 to 30 y of age. We examined whether migraine headaches and VMS trajectories (characterized as minimal, increasing, and persistent) at CARDIA year 15 examination were associated with higher risk of CVD events and stroke (both ischemic and hemorrhagic) using Cox proportional hazards regression models and adjustment for traditional CVD risk factors (age, cigarette use, and levels of systolic and diastolic blood pressure, fasting glucose, high- and low-density cholesterol, and triglycerides) and reproductive factors. Among women with minimal VMS (n = 835), increasing VMS (n = 521), and persistent VMS (n = 598), there were 81 incident CVD events including 42 strokes. Women with histories of migraine and persistent VMS had greater risk of CVD (hazard ratio [HR], 2.25; 95% CI, 1.15-4.38) after adjustment for age, race, estrogen use, oophorectomy, and hysterectomy compared with women without migraine histories and with minimal/increasing VMS. After adjustment for CVD risk factors, these associations were attenuated (HR, 1.51; 95% CI, 0.73-3.10). Similarly, women with histories of migraine and persistent VMS had greater risk of stroke (HR, 3.15; 95% CI, 1.35-7.34), but these associations were attenuated after adjustment for CVD risk factors (HR, 1.70; 95% CI, 0.66-4.38). Migraines and persistent VMS jointly associate with greater risk for CVD and stroke, although risk is attenuated with adjustment for traditional CVD risk factors.

Childhood maltreatment and trajectories of cardiometabolic health across the reproductive life span among individuals with a first birth during the Coronary Artery Risk Development in Young Adults Study

ObjectiveChildhood adversity is associated with poor cardiometabolic health in adulthood; little is known about how this relationship evolves through childbearing years for parous individuals. The goal was to estimate differences in cardiometabolic health indicators before, during and after childbearing years by report of childhood maltreatment in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study. MethodsIncluding 743 individuals nulliparous at baseline (1985–1986) with one or more pregnancies >20 weeks during follow-up (1986–2022), we fit segmented linear regression models to estimate mean differences between individuals reporting or not reporting childhood maltreatment (physical or emotional) in waist circumference, triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, fasting glucose, and body mass index (BMI) prior to, during, and following childbearing years using generalized estimating equations, allowing for interaction between maltreatment and time within each segment, and adjusting for total parity, parental education, and race (Black or white, self-reported). ResultsIndividuals reporting maltreatment (19%; 141) had a greater waist circumference (post-childbearing: +2.9 cm, 95% CI (0.7, 5.0), higher triglycerides [post-childbearing: +8.1 mg/dL, 95% CI (0.7, 15.6)], and lower HDL cholesterol [post-childbearing: −2.1 mg/dL, 95% CI (−4.7, 0.5)] during all stages compared to those not reporting maltreatment. There were not meaningful differences in blood pressure, fasting glucose, or BMI. Individuals who reported maltreatment did not report faster changes over time. ConclusionDifferences in some aspects of cardiometabolic health between individuals reporting versus not reporting childhood maltreatment were sustained across reproductive life stages, suggesting potentially persistent impacts of childhood adversity.

Impact of coronary artery calcium on mortality and cardiovascular events in metabolic syndrome and diabetes among younger adults.

Whether coronary artery calcium (CAC) testing in younger individuals with metabolic syndrome (MetS) and diabetes mellitus (DM) helps predict cardiovascular disease (CVD) and death independent of traditional risk factors (RFs) remains less clear. We pooled data obtained from 5174 individuals aged 38-55 years from the CARDIA (Coronary Artery Risk Development in Young Adults; n = 3047, year 20) and MESA (Multi-Ethnic Study of Atherosclerosis; n = 2127, Visit 1) studies who completed computed tomography of CAC. The mean age (SD) of participants (44.7% men) was 47.3 (4.2) years. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of CVD, coronary heart disease (CHD), and all-cause death. There were 1085 participants (21.0%) with prevalent CAC at baseline. A total of 461 (8.9%) had DM, 1025 (19.8%) had MetS without DM, and 3688 (71.3%) had neither condition. Over a median follow-up of 14.2 years, 256 (5.0%) participants died, and 304 (5.9%) CVD and 188 (3.6%) CHD events occurred. The CAC score was independently associated with incident CVD in those with DM (HR: 95% CI; 1.22: 1.08-1.38), MetS (1.18: 1.08-1.31), and neither condition (1.36: 1.26-1.46). The corresponding HRs for CAC ≥ 100 were 2.70 (1.25-5.83), 3.29 (1.87-5.79), and 6.30 (4.02-9.86), respectively. Similar associations for CHD and death were found. The impact of CAC ≥ 100 on CVD and CHD was lower in the presence of DM (P interaction < 0.05). The association of CAC with all outcomes in individuals with DM remained significant after adjusting with haemoglobin A1c levels. Coronary artery calcium score is independently associated with cardiovascular events and death over nearly 15 years after screening at ages 38-55 years, with a less pronounced impact on CVD and CHD events in the presence of DM.