Coronary Artery Risk Development In Young Adults Research Articles

Intensity of hypertensive exposure in young adulthood and subclinical atherosclerosis in middle age: Evidence from the CARDIA study.

Chronically high blood pressure (HBP) is a known risk factor for cardiovascular diseases. We measured the intensity of hypertensive exposure in young adults and calculated its prognostic significance for subclinical atherosclerosis in middle age. The Coronary Artery Risk Development in Young Adults (CARDIA) study enrolled 5,115 healthy black and white Americans who were 18-30 years old at baseline (1985-1986). The intensity of hypertensive exposure was calculated as the area under the curve (mm Hg × years) from baseline to year 15. Coronary artery calcium (CAC) was identified at years 15, 20, and 25, and intima-media thickness (IMT) was identified at year 20. At baseline, the mean age was 40.1 years; 55.1% of participants were women, and 46.5% were black. After adjustment, cumulative systolic BP (SBP) was positively associated with CAC [hazard ratio (HR) = 1.23 (1.14, 1.32)] and IMT [β = 0.022 (0.017, 0.028)]. For CAC, the C-statistic for cumulative SBP was 0.643 (0.619, 0.667); compared to baseline SBP, the net reclassification index (NRI) of cumulative SBP was 0.180 (0.115, 0.256) and the integrated discrimination improvement (IDI) was 0.023 (0.012, 0.036). For IMT, the C-statistic for cumulative SBP was 0.674 (0.643, 0.705), the NRI was 0.220 (0.138, 0.305), and the IDI was 0.008 (0.004, 0.0012). Greater intensity of hypertensive exposure in early adulthood is associated with subclinical atherosclerosis in middle age and provides better prognostic value than baseline BP for early cardiovascular risk.

Premature Cardiovascular Disease and Brain Health in Midlife: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

AbstractBackgroundCardiovascular disease (CVD) is associated with cognitive impairment and dementia risk in late life, yet little is known about the role of premature (defined younger than 60 years) CVD events with cognition and brain health earlier in the life course, including in midlife. As part of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, we investigated the association of premature CVD events in young and middle adulthood with cognition and white‐matter health in midlife.MethodsWe studied 3,146 Black and White participants (57% women, 48% Black) aged 18‐30 years at baseline (1985‐86) who were followed up to Year 30 (mean age 55.1±3.6 years) when 5 cognitive tests measuring different domains were administered. A subset (656 participants) had brain MRI with measures of white matter hyperintensity (WMH) burden and white matter integrity. Premature CVD events were adjudicated based on participants' history and medical records of coronary heart disease, stroke/TIA, cardiac revascularization, congestive heart failure, carotid artery disease, and peripheral artery disease. We conducted linear regression to determine the association of premature CVD with cognitive and structural brain measures.ResultsFive percent (n = 147) of participants had premature CVD events over the 30 years. Having premature CVD events was associated with lower cognitive function in all domains. After adjustment for demographics, education, depressive symptoms, physical activity, diet, APOE ε4, and cardiovascular risk factors (CVRFs), premature CVD was associated with lower cognition (z‐standardized) except for verbal fluency: global cognition (‐0.19, 95% CI ‐0.35 to ‐0.03), verbal memory (‐0.24, 95% CI ‐0.41 to ‐0.07), processing speed (‐0.46, 95% CI ‐0.63 to ‐0.30), and executive function (‐0.38, 95% CI ‐0.56 to ‐0.20). Premature CVD was also associated with greater WMH volumes (total, frontal, temporal, and parietal lobes) and alternations of white matter integrity (higher total and temporal lobe mean diffusivity and lower parietal lobe fractional anisotropy) after adjusting for demographics, total intracranial volume, and CVRFs.ConclusionPremature CVD is associated with worse midlife cognition and white‐matter health independent of CVRFs. Young and middle adulthood is a critical time for CVD prevention, the efforts of which may delay the onset of cognitive decline and dementia later in life.

The association between cognitive reserve, cognition and brain age in Midlife: The CARDIA Study

AbstractBackgroundCognitive reserve (CR) factors have been suggested to be protective of cognitive function in older adults. Less is known about this relationship in midlife, and whether the protective effect of CR may depend on brain age (relative to chronological age) in midlife. We aimed to investigate whether CR factors are associated with cognition in midlife, independent of brain age.MethodsAs part of the ongoing prospective Coronary Artery Risk Development in Young Adults (CARDIA) study, we identified 612 Black and White participants (mean age 55 SD 3.5) with brain MRI and cognitive testing. We generated a CR composite score from structural equation modeling including four CR‐enhancing factors: education, cognitive activities, occupational cognitive complexity, and adult literacy. Cognitive function was assessed at Year 30 with a composite measure of tests of memory, processing speed, executive function, and language. Brain age was ascertained using a previously validated high dimensional neuroimaging pattern analysis, based on machine learning algorithms, that quantifies individual differences in age‐related atrophy using MRI‐derived structural brain characteristics. We used linear regression to assess the associations between CR composite above or below median (high versus low), brain aging, and cognitive function, adjusting for chronological age, sex, race, intracranial volume, and scanning site.ResultsThere was a modest association between the CR composite and brain age; higher CR was associated with lower brain age (β‐0.40, CI: ‐0.67 to ‐0.13). High CR was associated with better performance on all cognitive tests compared to low CR (p<0.001 for all). These associations remained with the inclusion of brain age as a covariate. Having high CR is associated with better cognitive performance regardless of brain age (Figure 1).ConclusionOur findings suggest that CR factors are associated with better cognitive function in midlife, and that brain aging and CR are two independent factors that may contribute to cognitive aging in midlife.

Physical Activity Trajectories, Autonomic Balance and Cognitive Function: the CARDIA Study

AbstractBackgroundPhysical activity (PA), and particularly moderate to vigorous intensity PA (MVPA), may protect against cognitive decline. However, the underlying mechanisms are not fully understood. Cardiac autonomic balance is influenced by PA and implicated in dementia pathogenesis. Therefore, the study aimed to examine whether autonomic balance mediates the association between PA and cognitive function.MethodThe sample included 1,939 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study. MVPA was obtained in 7 consecutive examinations from baseline (1985‐86; 18‐30 years) to the Year 20 exam. Cardiac autonomic balance was assessed at Year 20 via resting heart rate, and via measures of heart rate variability: standard deviation normal to normal (SDNN) and root mean square of successive differences (RMSDD). A comprehensive cognitive assessment was performed at Year 30. Group‐based trajectory modeling was used to identify homogenous MVPA trajectory groups, and formal mediation analysis was used to test whether cardiac autonomic function indices lie on the causal pathway between MVPA trajectories and cognitive function.ResultThree distinct PA trajectory patterns were identified: (1) Below MVPA guidelines (n = 1,122; 57.9%); (2) Meeting MVPA guidelines (n = 652; 33.6%); and (3) Exceeding MVPA guidelines (n = 165; 8.5%) (Figure). Meeting and exceeding MVPA guidelines were related to lower resting heart rate and higher heart rate variability, which indicate improved autonomic balance. Meeting and exceeding MVPA guidelines were additionally associated with improved semantic fluency performance. The association between higher MVPA level and semantic fluency performance was fully mediated by RMSDD and partially mediated by SDNN. No additional associations were observed between MVPA trajectories and other cognitive outcomes, and no statistically significant mediation by autonomic balance indices was found for these associations (Table).ConclusionHigher MVPA levels across the young adult to midlife transition were associated with better cardiac autonomic function, which in turn explained some of the associations between PA trajectories and better semantic fluency performance. Future studies, particularly among older individuals are warranted to clarify the role of autonomic balance in the link between physical activity and brain health. These findings may lead to more targeted PA recommendations across the life‐course to slow cognitive decline and decrease dementia risk.

Dietary metabolic signatures and cardiometabolic risk.

Observational studies of diet in cardiometabolic-cardiovascular disease (CM-CVD) focus on self-reported consumption of food or dietary pattern, with limited information on individual metabolic responses to dietary intake linked to CM-CVD. Here, machine learning approaches were used to identify individual metabolic patterns related to diet and relation to long-term CM-CVD in early adulthood. In 2259 White and Black adults (age 32.1 ± 3.6 years, 45% women, 44% Black) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, multivariate models were employed to identify metabolite signatures of food group and composite dietary intake across 17 food groups, 2 nutrient groups, and healthy eating index-2015 (HEI2015) diet quality score. A broad array of metabolites associated with diet were uncovered, reflecting food-related components/catabolites (e.g. fish and long-chain unsaturated triacylglycerols), interactions with host features (microbiome), or pathways broadly implicated in CM-CVD (e.g. ceramide/sphingomyelin lipid metabolism). To integrate diet with metabolism, penalized machine learning models were used to define a metabolite signature linked to a putative CM-CVD-adverse diet (e.g. high in red/processed meat, refined grains), which was subsequently associated with long-term diabetes and CVD risk numerically more strongly than HEI2015 in CARDIA [e.g. diabetes: standardized hazard ratio (HR): 1.62, 95% confidence interval (CI): 1.32-1.97, P < 0.0001; CVD: HR: 1.55, 95% CI: 1.12-2.14, P = 0.008], with associations replicated for diabetes (P < 0.0001) in the Framingham Heart Study. Metabolic signatures of diet are associated with long-term CM-CVD independent of lifestyle and traditional risk factors. Metabolomics improves precision to identify adverse consequences and pathways of diet-related CM-CVD.

Abstract 13600: Performance of a Multi-Metabolite Score Added to a Risk Prediction Model for Incident Diabetes in Young Adults: The CARDIA Study

Introduction: The Finnish Diabetes Risk Score (FINDRISC) is a risk prediction tool used to estimate absolute risk for type 2 diabetes mellitus (DM), a critical risk factor for cardiovascular disease. The Diabetes Risk Index (DRI) is a multi-metabolite DM risk score developed by combining the Lipoprotein Insulin Resistance Index (LP-IR), calculated from six lipoproteins, and the branched chain amino acids, valine and leucine. Although the DRI is independently associated with future DM in middle-aged adults, the performance of this novel biomarker when added to FINDRISC to predict incident DM in young adults is not known. Hypothesis: The addition of DRI to FINDRISC will improve the 10-year(y) risk prediction of DM across all ages in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Methods: We measured the DRI using NMR spectroscopy in CARDIA participants across different age categories: 20-30y (n=1,911), 30-40y (n=2,716), 40-50y (n=2,232). We used Cox proportional hazards regression to evaluate the association of the DRI with incident 10-y DM risk. We assessed FINDRISC model performance using C-statistic and continuous Net Reclassification Index (NRI) with and without the addition of the DRI as a covariate. Results: DRI was associated with 10-y DM risk across all age categories. Addition of the DRI modestly improved the C-statistic in the 30-40-y age category. Addition of DRI to FINDRISC improved the overall NRI in the 30-40- and 40-50-y age categories. The non-event NRI was significant across all 3 age categories and reclassified 25-36% of participants who did not develop DM to a lower estimate of incident DM risk (Table). Conclusions: Among young and middle-aged adults, DRI scores were associated with 10-y risk of DM. The addition of DRI to FINDRISC led to improvements in reclassification of DM risk, as the addition of DRI to FINDRISC correctly classified up to 36% of participants who did not develop DM (over 10y) to a lower estimate of incident DM risk.

Abstract 10191: Associations of Urine Biomarkers of Kidney Tubule Health With Incident Hypertension and Blood Pressure Trajectories in Middle-Aged Adults

Introduction: Kidney tubules play a key role in regulating blood pressure (BP). Urine biomarkers of kidney tubule injury associate with incident hypertension (HTN) in older adults with multiple comorbidities. Less is known about these associations in younger adults. Hypothesis: Urine biomarkers of kidney tubular injury and dysfunction associate with incident HTN and greater 10-year rise in BP in middle-aged adults. Methods: In 1,170 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study (mean age 45±4, 40% black, 56% women) without HTN, cardiovascular disease or kidney disease at the year 20 exam (baseline for this analysis), we measured urine monocyte chemoattractant protein-1, alpha-1-microglobulin, kidney injury molecule-1, epidermal growth factor [EGF], interleukin-18, chitinase-3-like protein 1, and uromodulin. We examined associations of biomarkers with incident HTN (onset of systolic BP ≥130 mmHg or diastolic BP ≥80 mmHg or initiation of BP meds) after baseline in interval-censored Cox models and BP trajectories in linear mixed models adjusted for established risk factors. Results: During a median 9.9 years of follow up (IQR 5.9-10.2), 376 incident HTN events occurred. Compared to the lowest tertile of EGF, the risk of incident HTN was lower in the two higher tertiles in the model adjusted for age, sex, race, and urine creatinine, and in the fully adjusted model (Figure). The mean increase in SBP over 10 years was 3.4 mmHg lower in Tertile 3 vs. Tertile 1 of EGF (95%CI -6.1, -0.7). There were no statistically significant associations of urine EGF with incident HTN or BP trajectories when EGF was modeled as a continuous predictor. There were no statistically significant associations of other biomarkers with incident HTN or BP trajectory. Conclusions: In middle aged adults without HTN, cardiovascular or kidney disease, higher urine EGF levels associated with lower risk of incident HTN and lower 10-year mean rise in BP.

Abstract 14252: Cumulative Apolipoprotein B Blood Concentrations During Early Adulthood and Incident Atherosclerotic Cardiovascular Disease Risk After Age 40 Years: The Coronary Artery Risk Development in Young Adults Study

Introduction: The associations between cumulative exposure to apolipoprotein B (apoB) containing lipoproteins across early adult life and incident ASCVD in later life have not been quantified. Methods: Of 4945 eligible Coronary Artery Risk Development in Young Adults (CARDIA) cohort participants we used NMR to measure apoB in 3110 participants who had samples available from the years 2, 7, 15, and 30 exams. To mitigate biases from missingness of data we conducted multiple imputation for apoB levels for the residual 1,835 participants without NMR measures of apoB. We estimated the participant-specific apoB throughout the exposure period (ages 19 to 40y) using nonparametric spline models. The area under the apoB/age curve was calculated as cumulative exposure and expressed in mg/dL*years. To quantify the association between cumulative apoB exposure during early life with incident ASCVD after age 40y we used demographic- and risk factor-adjusted* Cox regression models (see table). We used a restricted cubic spline to examine the pattern of association across the range of cumulative apoB exposure. Results: 4945 CARDIA participants were followed for a total of 88664 person*years; 255 incident ASCVD events occurred after age 40y. Participants with higher cumulative apoB levels were more likely to be men; and have higher BMI, BP, glucose, and tobacco use. In demographic and risk factor adjusted models a 100mg/dL*yr difference in cumulative apoB from ages 19 to 40y (representing a mean yearly difference of about +5mg/dL) was associated with HR 1.15 (95% CI:1.10-1.19) and HR 1.10 (95%CI:1.06-1.15) for ASCVD events, respectively. At apoB exposures &gt;1700mg/dL*y (&gt;80mg/dL/y) there was a strong, direct association with incident ASCVD after age 40y. Conclusion: Prevention strategies that reduce apoB exposures in early adult life will likely attenuate ASCVD risks later in life; targeting a usual apoB level &lt; 80mg/dL may provide maximal benefit.

Abstract 13588: Association of Longitudinal Trajectories of Branched Chain Amino Acids Through Young Adulthood With Diabetes in Later Life: The CARDIA Study

Introduction: Branched chain amino acids (BCAA), measured at a single timepoint in midlife, are directly associated with risk for incident type 2 diabetes mellitus (DM), a strong determinant of cardiovascular disease risk. However, the trajectories (traj) of BCAAs through young adulthood and their associations with DM in midlife are unknown. Methods: We used NMR spectroscopy to measure serum BCAA levels from up to 3,081 Coronary Artery Risk Development in Young Adults (CARDIA) participants who attended the Year(Y) 2, 7, 15, 20, and 30 exams. We used latent class modeling to generate BCAA traj groups. To quantify associations between BCAA traj and prevalent DM* at the Y30 exam, we excluded participants with DM at Y2, and modeled traj groups from Y2 to Y30. To quantify associations between BCAA traj and incident DM by the Y30 exam, we excluded participants who developed DM by the Y20 exam and modeled traj from Y2 to Y20. We used adjusted** logistic regression to quantify the associations between traj group and prevalent and incident DM (at Y30), separately. Results: Among 3,081 participants (mean age at Y2: 27y), there were 3 BCAA traj groups: 1,427 participants in the low-stable group, 1,384 in the moderate-stable group, and 270 in the high-increasing group. Male sex, Black race, and higher body mass index were more common in the higher BCAA traj groups. Compared with the low-stable BCAA traj group (reference), the moderate-stable and high-increasing BCAA traj groups were associated with prevalent DM at Y30 (OR [95 th CI]: moderate-stable, 2.59 [1.90-3.55]; high-increasing, 6.03 [3.86-9.43]). Moderate-stable and high-increasing traj groups were associated with incident DM at Y30 (OR [95 th CI]: moderate-stable, 1.56 [1.02-2.39]; high-increasing, 2.20 [1.25-3.87]; low-stable, reference). Conclusions: BCAA levels track, on average, over a 28-year span in most young adults, but serial measurements identify subpopulations with rising levels and high risk of DM in later life.

Progression of Chronic Kidney Disease Risk Categories and Risk of Cardiovascular Disease and Total Mortality: Coronary Artery Risk Development in Young Adults Cohort.

Background Previous studies of worsening chronic kidney disease (CKD) based on declining estimated glomerular filtration rate (eGFR) or increasing urine albumin-creatinine ratio (UACR) are limited to later middle-age and older adults. We examined associations of CKD progression and incident cardiovascular disease (CVD) and mortality in younger adults. Methods and Results We studied 4382 adults in CARDIA (Coronary Artery Risk Development in Young Adults) initially aged 27 to 41 years and prospectively over 20 years. Five-year transition probabilities across CKD risk categories were based on eGFR and UACR measured at each exam. Proportional hazards models predicted incident CVD and all-cause mortality by time-varying CKD risk category, adjusting for demographics and CVD risk factors. Progression of CKD risk categories over 20 years occurred in 28.7% (1256/4382) of participants, driven by increases in UACR, but including 5.8% (n=255) with eGFR<60 mL/min per 1.73 m2 or UACR ≥300 mg/g. Compared with eGFR ≥60 and UACR <10, demographic and smoking-adjusted hazard ratios for CVD were 1.62 (95% CI, 1.21-2.18) for low CKD risk (eGFR ≥60 with UACR 10-29) and 13.65 (95% CI, 7.52-24.79) for very high CKD risk (eGFR <30 or eGFR 30-44 with UACR 30-299; or eGFR 30-59 with UACR ≥300). Corresponding hazard ratios for all-cause mortality were 1.42 (95% CI, 1.08-1.88) and 14.75 (95% CI, 9.97-21.82). Although CVD associations were attenuated after adjustment for mediating CVD risk factors, all-cause mortality associations remained statistically significant. Conclusions Among young to middle-aged adults, progression to higher CKD risk category was common. Routine monitoring eGFR and UACR holds promise for prevention of CVD and total mortality.

Prepregnancy Protein Source and BCAA Intake Are Associated with Gestational Diabetes Mellitus in the CARDIA Study.

Diet quality and protein source are associated with type 2 diabetes, however relationships with GDM are less clear. This study aimed to determine whether prepregnancy diet quality and protein source are associated with gestational diabetes mellitus (GDM). Participants were 1314 Black and White women without diabetes, who had at least one birth during 25 years of follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study. The CARDIA A Priori Diet Quality Score (APDQS) was assessed in the overall cohort at enrollment and again at Year 7. Protein source and branched-chain amino acid (BCAA) intake were assessed only at the Year 7 exam (n = 565). Logistic regression analysis was used to determine associations between prepregnancy dietary factors and GDM. Women who developed GDM (n = 161) were more likely to have prepregnancy obesity and a family history of diabetes (p < 0.05). GDM was not associated with prepregnancy diet quality at enrollment (Year 0) (odds ratio [OR]: 1.01; 95% confidence interval [CI] 0.99, 1.02) or Year 7 (odds ratio [OR]: 0.97; 95% confidence interval [CI] 0.94, 1.00) in an adjusted model. Conversely, BCAA intake (OR:1.59, 95% CI 1.03, 2.43) and animal protein intake (OR: 1.06, 95% CI 1.02, 1.10) as a proportion of total protein intake, were associated with increased odds of GDM, while proportion of plant protein was associated with decreased odds of GDM (OR: 0.95, 95% CI 0.91, 0.99). In conclusion, GDM is strongly associated with source of prepregnancy dietary protein intake but not APDQS in the CARDIA study.

Marijuana use and DNA methylation-based biological age in young adults

BackgroundMarijuana is the third most commonly used drug in the USA and efforts to legalize it for medical and recreational use are growing. Despite the increase in use, marijuana’s effect on aging remains understudied and understanding the effects of marijuana on molecular aging may provide novel insights into the role of marijuana in the aging process. We therefore sought to investigate the association between cumulative and recent use of marijuana with epigenetic age acceleration (EAA) as estimated from blood DNA methylation.ResultsA random subset of participants from The Coronary Artery Risk Development in Young Adults (CARDIA) Study with available whole blood at examination years (Y) 15 and Y20 underwent epigenomic profiling. Four EAA estimates (intrinsic epigenetic age acceleration, extrinsic epigenetic age acceleration, PhenoAge acceleration, and GrimAge acceleration) were calculated from DNA methylation levels measured at Y15 and Y20. Ever use and cumulative marijuana-years were calculated from the baseline visit to Y15 and Y20, and recent marijuana use (both any and number of days of use in the last 30 days) were calculated at Y15 and Y20. Ever use of marijuana and each additional marijuana-year were associated with a 6-month (P < 0.001) and a 2.5-month (P < 0.001) higher average in GrimAge acceleration (GAA) using generalized estimating equations, respectively. Recent use and each additional day of recent use were associated with a 20-month (P < 0.001) and a 1-month (P < 0.001) higher GAA, respectively. A statistical interaction between marijuana-years and alcohol consumption on GAA was observed (P = 0.011), with nondrinkers exhibiting a higher GAA (β = 0.21 [95% CI 0.05, 0.36], P = 0.008) compared to heavy drinkers (β = 0.05 [95% CI − 0.09, 0.18], P = 0.500) per each additional marijuana-year. No associations were observed for the remaining EAA estimates.ConclusionsThese findings suggest cumulative and recent marijuana use are associated with age-related epigenetic changes that are related to lifespan. These observed associations may be modified by alcohol consumption. Given the increase in use and legalization, these findings provide novel insight on the effect of marijuana use on the aging process as captured through blood DNA methylation.

Analysis of apoB Concentrations Across Early Adulthood and Predictors for Rates of Change Using CARDIA Study Data

The cumulative exposure to apolipoprotein B (apoB)-containing lipoproteins in the blood during early adult life is a central determinant of atherosclerotic cardiovascular disease risk. To date, the patterns and rates of change in apoB through early adult life have not been described. Here, we used NMR to measure apoB concentrations in up to 3055 Coronary Artery Risk Development in Young Adults (CARDIA) Study participants who attended the years 2 (Y2), 7 (Y7), 15 (Y15), 20 (Y20), and 30 (Y30) exams. We examined individual-level spaghetti plots of apoB change, and we calculated average annualized rate of apoB concentration change during follow-up. We used multivariable linear regression models to assess the associations between CARDIA participant characteristics and annualized rates of apoB change. Male sex, higher measures of adiposity, lower HDL-C, lower Healthy Eating Index, and higher blood pressures were observed more commonly in individuals with higher apoB level at Y2 and Y20. Inter- and intra-individual variation in apoB concentration over time was substantial—while the mean (SD) rate of change was 0.52 (1.0) mg/dl/year, the range of annualized rates of change was −6.26 to +9.21 mg/dl/year. At baseline, lower first apoB measurement, female sex, White race, lower BMI, and current tobacco use were associated with apoB increase. We conclude that the significant variance in apoB level over time and the modest association between baseline measures and rates of apoB change suggest that the ability to predict an individual’s future apoB serum concentrations, and thus their cumulative apoB exposure, after a one-time assessment in young adulthood is low.

Associations of Religious Service Attendance With Cognitive Function in Midlife: Findings From The CARDIA Study.

Growing evidence suggests that religiosity is an important social determinant of health, including cognitive health. Yet most prior work focused on older adults or was conducted in racially and denominationally homogeneous regional samples. This study investigates the association of religious service attendance in midlife with cognitive function later in midlife. Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a racially and geographically diverse prospective cohort study, we explored the association of religious service attendance in midlife with cognitive function 5years later. Cognitive function was measured using four cognitive tests administered by CARDIA technicians. Multivariable linear regression was used for analyses. Primary analyses controlled for sociodemographics, physical health, depression, and prior religious involvement. Sensitivity analyses additionally controlled for baseline cognition and social support. Our study population included 2,716 participants (57.2% female, 44.9% Black, and mean age 50). In primary analyses, attending services more than weekly (compared to never) in midlife was associated with better global cognition (β=0.14 standard deviations, 95% [confidence interval] CI=0.02, 0.26) and verbal memory (β=0.17 standard deviations, 95% CI=0.04, 0.30), but not with processing speed (β=0.04 standard deviations, 95% CI=-0.08, 0.16). Areverse association was observed with executive function (β=-0.16 standard deviations, 95% CI=-0.30, -0.02). Most findings persisted in analyses accounting for loss to follow-up via inverse probability weighting. Our findings suggest that frequent involvement in religious services at midlife is associated with better global cognition and verbal memory but worse executive function. There was no association with processing speed.

Physical activity trajectories, autonomic balance and cognitive function: The Coronary Artery Risk Development in Young Adults (CARDIA) study

Physical activity (PA) plays an important role in cognitive health. However, the underlying mechanisms are not fully understood. Cardiac autonomic balance is influenced by PA and implicated in dementia pathogenesis. We examined whether autonomic balance mediates the association between PA and cognitive function. The sample included 1939 participants from the Coronary Artery Risk Development in Young Adults study who completed cognitive testing after 30-year follow-up (baseline: mean age 25.2 ± 3.5y; 58% women; 43% Black). Moderate to vigorous intensity PA (MVPA) was obtained in 7 consecutive examinations over 20 years (Year 0-Year 20). Cardiac autonomic balance was assessed at Year 20 via resting heart rate (RHR), standard deviation normal to normal (SDNN) and root mean square of successive differences (RMSSD). We used group-based trajectory modeling to identify homogenous MVPA trajectory groups, and formal mediation analysis to test whether autonomic function indices mediate the association between MVPA trajectories and cognition. We identified three distinct PA trajectory patterns: (1) Below MVPA guidelines (n = 1122; 57.9%); (2) Meeting MVPA guidelines (n = 652; 33.6%); and (3) Exceeding MVPA guidelines (n = 165; 8.5%). Meeting and exceeding MVPA guidelines were related to better autonomic balance overall, and to improved semantic fluency performance. Statistically, the association between higher MVPA level and verbal ability was mediated by SDNN and RMSSD, but not by RHR. In our sample of young and middle-aged adults, higher MVPA levels over time were associated with better cardiac autonomic function, which explained some of the associations between PA trajectories and better cognition.

POLYCYSTIC OVARY SYNDROME AND DIFFERENCES IN BRAIN HEALTH AT MID-LIFE: RESULTS FROM THE CARDIA COHORT

Increasing evidence links metabolic disorders, such as diabetes, to accelerated cognitive aging. Our objective was to use the Coronary Artery Risk Development in Young Adults (CARDIA) cohort to investigate the association between polycystic ovary syndrome (PCOS) and key indicators of mid-life brain health, including cognitive performance and brain MRI features.

CANCER INCIDENCE AMONG PCOS PARTICIPANTS IN THE CARDIA COHORT

To investigate whether participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort with polycystic ovary syndrome (PCOS) differ for incidence rates of cancer and/or time to develop cancer compared to participants without PCOS.

CARDIOVASCULAR AND METABOLIC OUTCOMES AMONG PCOS PARTICIPANTS IN THE CARDIA COHORT

To investigate the incidence of and time to development of cardiovascular events and multiple metabolic outcomes (hypertension, hyperlipidemia, diabetes) by polycystic ovary syndrome (PCOS) status among participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort.

Physical activity from young adulthood to middle age and premature cardiovascular disease events: a 30-year population-based cohort study

BackgroundAlthough physical activity is generally protective of cardiovascular disease (CVD), less is known about how young adult physical activity relates to premature CVD events. The objective of this study was to determine the association between level and change in physical activity from young adulthood to middle age and incidence of premature CVD events before age 60.MethodsWe analyzed data collected across four urban sites from nine visits over 30 years of follow-up (1985–2016) from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective community-based cohort study of 5115 Black and White women and men aged 18–30 years at baseline (1985–1986). Linear mixed models were used to develop individualized moderate-to-vigorous intensity self-reported physical activity trajectories per participant. Fatal and nonfatal coronary heart disease (CHD), heart failure, and stroke outcomes were analyzed separately and as a combined CVD event outcome.ResultsOverall, physical activity declined in young adults as they progressed through middle age. Lower physical activity scores (per 100 exercise units) in 18 year-olds were associated with higher odds of premature CHD (AOR 1.14, 95% CI 1.02–1.28), heart failure (AOR 1.21, 95% CI 1.05–1.38), stroke (AOR 1.20, 95% CI 1.04–1.39), and any CVD (AOR 1.15, 95% CI 1.06–1.24) events. Each additional annual 1-unit reduction in the physical activity score was associated with a higher annual odds of incident heart failure (1.07, 95% CI 1.02–1.13), stroke (1.06, 95% CI 1.00–1.13), and CVD (1.04, 95% CI 1.01–1.07) events. Meeting the minimum (AOR 0.74, 95% CI 0.0.57–0.96) and twice the minimum (AOR 0.55, 95% CI 0.34–0.91) Department of Health and Human Services physical activity guidelines through follow up was protective of premature CVD events.ConclusionsGiven recent trends in declining physical activity with age and associated premature CVD events, the transition from young adult to midlife is an important time period to promote physical activity.

Association of Cerebral Blood Flow With Longitudinal Changes in Cerebral Microstructural Integrity in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Decreased cerebral tissue integrity and cerebral blood flow (CBF) are features of neurodegenerative diseases. Brain tissue maintenance is an energy-demanding process, making it particularly sensitive to hypoperfusion. However, little is known about the association between blood flow and brain microstructural integrity, including in normative aging. To assess associations between CBF and changes in cerebral tissue integrity in white matter and gray matter brain regions. In this longitudinal cohort study, magnetic resonance imaging was performed on 732 healthy adults from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective longitudinal study (baseline age of 18-30 years) that examined participants up to 8 times during 30 years (1985-1986 to 2015-2016). Cerebral blood flow was measured at baseline (year 25 of the CARDIA study), and changes in diffusion tensor indices of fractional anisotropy (FA) and mean diffusivity (MD), measures of microstructural tissue integrity, were measured at both baseline and after approximately 5 years of follow-up (year 30). Analyses were conducted from November 5, 2020, to January 29, 2022. Automated algorithms and linear mixed-effects statistical models were used to evaluate the associations between CBF at baseline and changes in FA or MD. After exclusion of participants with missing or low-quality data, 654 at baseline (342 women; mean [SD] age, 50.3 [3.5] years) and 433 at follow-up (230 women; mean [SD] age, 55.1 [3.5] years) were scanned for CBF or FA and MD imaging. In the baseline cohort, 247 participants were Black (37.8%) and 394 were White (60.2%); in the follow-up cohort, 156 were Black (36.0%) and 277 were White (64.0%). Cross-sectionally, FA and MD were associated with CBF in most regions evaluated, with lower CBF values associated with lower FA or higher MD values, including the frontal white matter lobes (for CBF and MD: mean [SE] β = -1.4 [0.5] × 10-6; for CBF and FA: mean [SE] β = 2.9 [1.0] × 10-4) and the parietal white matter lobes (for CBF and MD: mean [SE] β = -2.4 [0.6] × 10-6; for CBF and FA: mean [SE] β = 4.4 [1.1] × 10-4). Lower CBF values at baseline were also significantly associated with steeper regional decreases in FA or increases in MD in most brain regions investigated, including the frontal (for CBF and MD: mean [SE] β = -1.1 [0.6] × 10-6; for CBF and FA: mean [SE] β = 2.9 [1.0] × 10-4) and parietal lobes (for CBF and MD: mean [SE] β = -1.5 [0.7] × 10-6; for CBF and FA: mean [SE] β = 4.4 [1.1] × 10-4). Results of this longitudinal cohort study of the association between CBF and diffusion tensor imaging metrics suggest that blood flow may be significantly associated with brain tissue microstructure. This work may lay the foundation for investigations to clarify the nature of early brain damage in neurodegeneration. Such studies may lead to new neuroimaging biomarkers of brain microstructure and function for disease progression.