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Background: Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) participants with the haptoglobin (Hp) 2-2 phenotype only. It remains unknown whether Hp phenotype modifies the effect of an intensive lifestyle intervention (ILI) on CAD in type 2 diabetes., Methods: Haptoglobin phenotype was measured in 4542 samples from the Action for Health in Diabetes (Look AHEAD) study. Cox regression models assessed the effect of ILI (focused on weight loss from caloric restriction and physical activity) versus diabetes support and education (DSE) on CAD events in each phenotype group, and within pre-specified subgroups including race/ethnicity, sex, history of cardiovascular disease, diabetes medication use, and diabetes duration., Results: 1590 (35%) participants had the Hp2-2 phenotype. The ILI did not lower glycated hemoglobin (%HbA1c) to < 6.5% in either phenotype, with a peak significant difference between treatment arms of 0.5% [non-Hp2-2] and 0.6% [Hp2-2]. The cumulative CAD incidence was 13.4% and 13.8% in the DSE arm and 12.2% and 13.6% in the ILI arm for non-Hp2-2 and Hp2-2 groups, respectively. Compared to DSE, the ILI was not associated with CAD among participants without (HR = 0.95, 95% CI 0.78-1.17) or with (0.89, 0.68-1.19) the Hp2-2 phenotype (p-interaction between Hp phenotype and ILI = 0.58). After Bonferroni correction, there were no significant results among any subgroups., Conclusions: Hp phenotype did not modify the effect of the weight loss ILI on risk of CAD in Look AHEAD, potentially because it did not substantially impact glycemic control among participants with or without the Hp2-2 phenotype. Further research is needed to determine if these results are conclusive., (© 2024. The Author(s).)

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. Predictive accuracy for ASCVD of the PDAY risk score, calculated at baseline (mean age 24) and at all six CARDIA examinations up until year 15, was examined. We also examined whether the presence of CAC improved model discrimination. The cohort for this study comprised 5004 Black and White men and women, at baseline and 3558 with data at year 15. Each standard deviation increase in PDAY score, at each examination, was significantly associated with future ASCVD. Hazard ratios (per standard deviation) increased from 1.74 to 2.04 from year 0 to year 15. C-statistics ranged from 0.771 to 0.794. Coronary artery calcium measurement at age 33-45 years improved risk prediction only if the score was 0. Cumulative risk exposure over the first 15 years of the CARDIA study also had high-predictive value (c-statistic 0.798, 95% confidence interval 0.762-0.835)., Conclusion: The PDAY risk score may be used in young adults, prior to age 40 years to predict ASCVD events., Competing Interests: Conflict of interest The authors have no conflicts of interest to report other than grant funding from NHLBI to complete this work., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cardiovascular health (CVH) from young adulthood is strongly associated with an individual's future risk of cardiovascular disease (CVD) and total mortality. Defining epigenomic biomarkers of lifelong CVH exposure and understanding their roles in CVD development may help develop preventive and therapeutic strategies for CVD., Methods: In 1085 CARDIA study (Coronary Artery Risk Development in Young Adults) participants, we defined a clinical cumulative CVH score that combines body mass index, blood pressure, total cholesterol, and fasting glucose measured longitudinally from young adulthood through middle age over 20 years (mean age, 25-45). Blood DNA methylation at >840 000 methylation markers was measured twice over 5 years (mean age, 40 and 45). Epigenome-wide association analyses on the cumulative CVH score were performed in CARDIA and compared in the FHS (Framingham Heart Study). We used penalized regression to build a methylation-based risk score to evaluate the risk of incident coronary artery calcification and clinical CVD events., Results: We identified 45 methylation markers associated with cumulative CVH at false discovery rate <0.01 ( P =4.7E-7-5.8E-17) in CARDIA and replicated in FHS. These associations were more pronounced with methylation measured at an older age. CPT1A , ABCG1 , and SREBF1 appeared as the most prominent genes. The 45 methylation markers were mostly located in transcriptionally active chromatin and involved lipid metabolism, insulin secretion, and cytokine production pathways. Three methylation markers located in genes SARS1 , SOCS3 , and LINC-PINT statistically mediated 20.4% of the total effect between CVH and risk of incident coronary artery calcification. The methylation risk score added information and significantly ( P =0.004) improved the discrimination capacity of coronary artery calcification status versus CVH score alone and showed association with risk of incident coronary artery calcification 5 to 10 years later independent of cumulative CVH score (odds ratio, 1.87; P =9.66E-09). The methylation risk score was also associated with incident clinical CVD in FHS (hazard ratio, 1.28; P =1.22E-05)., Conclusions: Cumulative CVH from young adulthood contributes to midlife epigenetic programming over time. Our findings demonstrate the role of epigenetic markers in response to CVH changes and highlight the potential of epigenomic markers for precision CVD prevention, and earlier detection of subclinical CVD, as well.

Importance: Steps per day is a meaningful metric for physical activity promotion in clinical and population settings. To guide promotion strategies of step goals, it is important to understand the association of steps with clinical end points, including mortality., Objective: To estimate the association of steps per day with premature (age 41-65 years) all-cause mortality among Black and White men and women., Design, Setting, and Participants: This prospective cohort study was part of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants were aged 38 to 50 years and wore an accelerometer from 2005 to 2006. Participants were followed for a mean (SD) of 10.8 (0.9) years. Data were analyzed in 2020 and 2021., Exposure: Daily steps volume, classified as low (<7000 steps/d), moderate (7000-9999 steps/d), and high (≥10 000 steps/d) and stepping intensity, classified as peak 30-minute stepping rate and time spent at 100 steps/min or more., Main Outcomes and Measures: All-cause mortality., Results: A total of 2110 participants from the CARDIA study were included, with a mean (SD) age of 45.2 (3.6) years, 1205 (57.1%) women, 888 (42.1%) Black participants, and a median (interquartile range [IQR]) of 9146 (7307-11 162) steps/d. During 22 845 person years of follow-up, 72 participants (3.4%) died. Using multivariable adjusted Cox proportional hazards models, compared with participants in the low step group, there was significantly lower risk of mortality in the moderate (hazard ratio [HR], 0.28 [95% CI, 0.15-0.54]; risk difference [RD], 53 [95% CI, 27-78] events per 1000 people) and high (HR, 0.45 [95% CI, 0.25-0.81]; RD, 41 [95% CI, 15-68] events per 1000 people) step groups. Compared with the low step group, moderate/high step rate was associated with reduced risk of mortality in Black participants (HR, 0.30 [95% CI, 0.14-0.63]) and in White participants (HR, 0.37 [95% CI, 0.17-0.81]). Similarly, compared with the low step group, moderate/high step rate was associated with reduce risk of mortality in women (HR, 0.28 [95% CI, 0.12-0.63]) and men (HR, 0.42 [95% CI, 0.20-0.88]). There was no significant association between peak 30-minute intensity (lowest vs highest tertile: HR, 0.98 [95% CI, 0.54-1.77]) or time at 100 steps/min or more (lowest vs highest tertile: HR, 1.38 [95% CI, 0.73-2.61]) with risk of mortality., Conclusions and Relevance: This cohort study found that among Black and White men and women in middle adulthood, participants who took approximately 7000 steps/d or more experienced lower mortality rates compared with participants taking fewer than 7000 steps/d. There was no association of step intensity with mortality.

The CARDIA (Coronary Artery Risk Development in Young Adults) study began in 1985 to 1986 with enrollment of 5,115 Black or White men and women ages 18 to 30 years from 4 US communities. Over 35 years, CARDIA has contributed fundamentally to our understanding of the contemporary epidemiology and life course of cardiovascular health and disease, as well as pulmonary, renal, neurological, and other manifestations of aging. CARDIA has established associations between the neighborhood environment and the evolution of lifestyle behaviors with biological risk factors, subclinical disease, and early clinical events. CARDIA has also identified the nature and major determinants of Black-White differences in the development of cardiovascular risk. CARDIA will continue to be a unique resource for understanding determinants, mechanisms, and outcomes of cardiovascular health and disease across the life course, leveraging ongoing pan-omics work from genomics to metabolomics that will define mechanistic pathways involved in cardiometabolic aging., Competing Interests: Funding Support and Author Disclosures CARDIA is supported by contracts HHSN268201800003I, HHSN268201800004I, HHSN268201800005I, HHSN268201800006I, and HHSN268201800007I from the National Heart, Lung, and Blood Institute. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the U.S. Department of Health and Human Services. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. All rights reserved.)

Background: Blood pressure (BP) measured in the office setting increases from early through later adulthood. However, it is unknown to what extent out-of-office BP derived via ambulatory BP monitoring (ABPM) increases over time, and which participant characteristics and risk factors might contribute to these increases., Methods: We assessed 25-year change in office- and ABPM-derived BP across sex, race, diabetes mellitus (DM), and body mass index (BMI) subgroups in the Coronary Artery Risk Development in Young Adults study using multivariable-adjusted linear mixed effects models., Results: We included 288 participants who underwent ABPM at the Year 5 Exam (mean [SD] age, 25.1 [3.7]; 45.8% men) and 455 participants who underwent ABPM at the Year 30 Exam (mean [SD] age, 49.5 [3.7]; 42.0% men). Office, daytime, and nighttime systolic BP (SBP) increased 12.8 (95% confidence interval [CI], 7.6-17.9), 14.7 (95% CI, 9.7-19.8), and 16.6 (95% CI, 11.4-21.8) mm Hg, respectively, over 25 years. Office SBP increased 6.5 (95% CI, 2.3-10.6) mm Hg more among black compared with white participants. Daytime SBP increased 6.3 (95% CI, 0.2-12.4) mm Hg more among participants with a BMI ≥25 vs. <25 kg/m2. Nighttime SBP increased 4.7 (95% CI, 0.5-8.9) mm Hg more among black compared with white participants, and 17.3 (95% CI, 7.2-27.4) mm Hg more among participants with vs. without DM., Conclusions: Office- and ABPM-derived BP increased more from early through middle adulthood among black adults and participants with DM and BMI ≥25 kg/m2., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Recent results from the Cardiovascular Trial of the Testosterone Trials showed that testosterone treatment of older men with low testosterone was associated with greater progression of noncalcified plaque (NCP). We evaluated the effect of anthropometric measures and cardiovascular biomarkers on plaque progression in individuals in the Testosterone Trial., Methods: The Cardiovascular part of the trial included 170 men aged 65 years or older with low testosterone. Participants received testosterone gel or placebo gel for 12 months. The primary outcome was change in NCP volume from baseline to 12 months, as determined by coronary computed tomography angiography (CCTA). We assayed several markers of cardiovascular risk and analyzed each marker individually in a model as predictive variables and change in NCP as the dependent variable., Results: Of 170 enrollees, 138 (73 testosterone, 65 placebo) completed the study and were available for the primary analysis. Of 10 markers evaluated, none showed a significant association with the change in NCP volume, but a significant interaction between treatment assignment and waist-hip ratio (WHR) (P = 0.0014) indicated that this variable impacted the testosterone effect on NCP volume. The statistical model indicated that for every 0.1 change in the WHR, the testosterone-induced 12-month change in NCP volume increased by 26.96 mm3 (95% confidence interval, 7.72-46.20)., Conclusion: Among older men with low testosterone treated for 1 year, greater WHR was associated with greater NCP progression, as measured by CCTA. Other biomarkers and anthropometric measures did not show statistically significant association with plaque progression., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background The relationship of coronary artery calcium (CAC) with adverse cardiac remodeling is not well established. We aimed to study the association of CAC in middle age and change in CAC from early adulthood to middle age with left ventricular (LV) function. Methods CAC score was measured by computed tomography at CARDIA study (Coronary Artery Risk Development in Young Adults) year-15 examination and at year-25 examination (Y25) in 3043 and 3189 participants, respectively. CAC score was assessed as a continuous variable and log-transformed to account for nonlinearity. Change in CAC from year-15 examination to Y25 was evaluated as the absolute difference of log-transformed CAC from year-15 examination to Y25. LV structure and function were evaluated by echocardiography at Y25. Results At Y25, mean age was 50.1±3.6 years, 56.6% women, 52.4% black. In the multivariable analysis at Y25, higher CAC was related to higher LV mass (β=1.218; adjusted P=0.007), higher LV end-diastolic volume (β=0.811; adjusted P=0.007), higher LV end-systolic volume (β=0.350; adjusted P=0.048), higher left atrial volume (β=0.214; adjusted P=0.009), and higher E/e' ratio (β=0.059; adjusted P=0.014). CAC was measured at both year-15 examination and Y25 in 2449 individuals. Higher change in CAC score during follow-up was independently related to higher LV mass index in blacks (β=4.789; adjusted P<0.001), but not in whites (β=1.051; adjusted P=0.283). Conclusions Higher CAC in middle age is associated with higher LV mass and volumes and worse LV diastolic function. Being free of CAC from young adulthood to middle age correlates to better LV function at middle age. Higher change in CAC score during follow-up is independently related to higher LV mass index in blacks.

Background: It is well known that total and intentional weight loss (IWL) are associated with reductions in cardiovascular disease (CVD) risk factors, however, associations with unintentional weight loss (UWL) have not been studied., Methods: We examined annual changes in blood pressure and lipids associated with UWL versus IWL in 576 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study who had lost weight over one of two time intervals (i.e., study years 5-7 or 7-10) and reported whether the weight loss was intentional at the end of the interval., Results: After adjusting for age, sex, race, and field center, an annual weight loss smaller than 6% resulted in small improvements in lipids that were similar regardless of intentionality. When annual weight loss was ≥6%, UWL was associated with less reduction in total cholesterol (-0.2 vs. -10.4 mg/dL), low-density lipoprotein cholesterol (-3.2 vs. -9.4 mg/dL), and triglycerides (-0.5 vs. -19.0 mg/dL) compared with IWL. Intentionality was not associated with the size of changes in blood pressure (systolic blood pressure: -2.7 vs. -2.0 mmHg; diastolic blood pressure: -2.2 vs. -1.3 mmHg) and high-density lipoprotein cholesterol (3.2 vs. 2.7 mg/dL)., Conclusions: Substantial UWL may be accompanied or preceded by other biological changes in this young adult population that alter changes in CVD risk factors that are associated with IWL.

Introduction: Earlier development of cardiovascular disease risk factors in blacks versus whites may result from differences in maintaining health behaviors. Age-specific racial differences in maintaining health behaviors from ages 18 to 50 years were determined., Methods: In 1985-1986, the population-based Coronary Artery Risk Development in Young Adults study enrolled 5,115 participants aged 18-30 years. In 2017, a total of 2,485 blacks and 2,407 whites with one or more optimal health behaviors at baseline who attended one or more of seven follow-up exams over 25 years (i.e., through 2010-2011) were analyzed. The primary outcome, maintaining four or more optimal health behaviors, included BMI <25; never smoking; ≥150 minutes/week of moderate to vigorous physical activity; no/moderate alcohol intake (women/men: zero to seven/zero to 14 drinks per week); and Dietary Approaches to Stop Hypertension diet adherence score ≥15 (i.e., baseline highest quartile). Hazard ratios comparing blacks with whites for maintaining optimal health behaviors were calculated among participants with each optimal behavior at baseline., Results: From ages 18 to 50 years, 2.6% of blacks and 9.2% of whites maintained four or more optimal health behaviors (for optimal BMI: 16.0% and 30.1%, smoking status: 74.6% and 78.4%, physical activity: 17.7% and 21.4%, alcohol intake: 68.4% and 64.6%, diet adherence: 3.9% and 10.3%, respectively). The multivariable adjusted hazard ratio comparing blacks with whites was 0.63 (95% CI=0.56, 0.72) for maintaining four or more optimal health behaviors (for optimal BMI: 0.82 [95% CI=0.66, 1.01], smoking status: 0.57 [95% CI=0.52, 0.62], physical activity: 0.83 [95% CI=0.75, 0.91], alcohol intake: 1.19 [95% CI=1.03, 1.37], diet adherence: 0.71 [95% CI=0.61, 0.82])., Conclusions: Fewer blacks than whites maintained four or more optimal health behaviors until age 50 years, but maintenance was low among both races., (Copyright © 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

We describe 10-year changes in accelerometer-determined physical activity (PA) and sedentary time in a midlife cohort of the Coronary Artery Risk Development in Young Adults Study, within and by race and sex groups. Participants (n = 962) wore the accelerometer with valid wear (≥4 of 7 days, ≥10 hours per day) at baseline (2005-2006; ages 38-50 years) and 10-year follow-up (2015-2016; ages 48-60 years). Data were calibrated to account for accelerometer model differences. Participants (mean age = 45.0 (standard deviation, 3.5) years at baseline) had reduced accelerometer counts overall (mean = -65.5 (standard error (SE), 10.2) counts per minute/day), and within race and sex groups (all P < 0.001). Sedentary time increased overall (mean = 37.9 (SE, 3.7) minutes/day) and within race and sex groups, whereas light-intensity PA (mean = -30.6 (SE, 2.7) minutes/day) and moderate- to vigorous-intensity PA (mean = -7.5 (SE, 0.8) minutes/day) declined overall and within race and sex groups (all P < 0.001). Significant differences in 10-year change estimates were noted by race and sex groups for accelerometer counts, sedentary time, and moderate- to vigorous-intensity PA bouts; black men had the greatest reductions in PA compared with other groups. PA declines during midlife were characterized by reductions in light-intensity PA with increases in sedentary time, which may have important health consequences. Targeted efforts are needed to preserve PA, regardless of intensity level, across midlife.

Objective: Determine associations of cardiorespiratory fitness, exercise systolic blood pressure (SBP) and heart rate recovery (HRR) following a maximal exercise test performed years preceding pregnancy with odds of preterm birth (PTB; <37 weeks' gestation) and small for gestational age (SGA; birthweight <10 th percentile) delivery., Design: Prospective, longitudinal., Setting: Multi-site, observational cohort study initially consisting of 2787 black and white women aged 18-30 at baseline (1985-86) and followed for 25 years (Y25; 2010-2011)., Population: 768 nulliparous women at baseline who reported ≥1 live birth by the Y25 exam., Methods: We used Poisson regression to determine associations of exposures with PTB/SGA., Main Outcome Measures: PTB and/or SGA births., Results: Women with PTB (n = 143) and/or SGA (n = 88) were younger, had completed fewer years of education and were more likely to be black versus women without PTB/SGA (n = 546). Women with PTB/SGA had lower fitness (501 ± 9 versus 535 ± 6 seconds, P < 0.002) and higher submaximal SBP than women without PTB/SGA (144 ± 1 versus 142 ± 1 mmHg, P < 0.04). After adjustment, no exercise test variables were associated with PTB/SGA, though the association with HRR and submaximal SBP approached significance in the subset of women who completed the exercise test <5 years before the index birth., Conclusions: Neither fitness nor haemodynamic responses to exercise a median of 5 years preceding pregnancy, were associated with PTB/SGA. These findings indicate excess likelihood of PTB/SGA is not detectable by low fitness or exercise haemodynamic responses 5 years preceding pregnancy, but exercise testing, especially HRR and submaximal SBP, may be more useful when conducted closer to the onset of pregnancy., Tweetable Abstract: Exercise testing conducted >5 years before pregnancy may not detect women likely to have PTB/SGA., (© 2018 Royal College of Obstetricians and Gynaecologists.)

Background: Many studies have focused on the association between a single blood pressure (BP) measurement and risk for adverse outcomes. However, the association of BP trajectories during young adulthood with subsequent decline in kidney function has not been well defined., Study Design: Observational cohort study., Setting & Participants: 3,429 participants in the Coronary Artery Risk Development in Young Adulthood (CARDIA) Study enrolled between the ages of 18 and 30 years., Predictors: BP slope during the first 10 years of participation in CARDIA, derived from linear mixed models incorporating all repeated BP measures., Outcome: Decline in estimated glomerular filtration rate (eGFR) during the interval between years 10 and 20 of CARDIA participation using cystatin C measured at years 10, 15, and 20., Results: Mean age of CARDIA participants at year 0 was 25.1 years, 56% were women, and 53% were white. Every 10-mmHg higher level of systolic (SBP) and diastolic BP (DBP) in year 10 was associated with change in eGFR of -0.09 (95% CI, -0.13 to -0.06) and -0.07 (95% CI, -0.12 to -0.03) mL/min/1.73m 2 per year, respectively. Every 10-mmHg increase in SBP slope between years 0 and 10 was associated with a subsequent -0.52 (95% CI, -1.02 to -0.03) mL/min/1.73m 2 per year change in kidney function after adjustment for comorbid conditions and SBP at year 10. Similarly, every 10-mmHg increase in DBP slope between years 0 and 10 was associated with a subsequent change in kidney function of -0.65 (95% CI, -1.23 to -0.07) mL/min/1.73m 2 per year, after adjustment for comorbid conditions and DBP in year 10., Limitations: Observational design., Conclusions: During young adulthood, increasing SBP and DBP are associated with a higher rate of subsequent kidney function decline, independent of BP measured at the beginning of eGFR assessment., (Copyright © 2018 National Kidney Foundation, Inc. All rights reserved.)

Women who delivered preterm infants have excess cardiovascular disease, but vascular pathways linking these conditions are not understood. We considered that higher blood pressure over 25 years among women with preterm delivery may be associated with coronary artery calcification (CAC). The CARDIA study (Coronary Artery Risk Development in Young Adults) enrolled 1049 black and white women with births between 1985 and 2010 (n=272 ever preterm [<37 weeks]; n=777 all term births [≥37 weeks]). Latent mixture modeling identified blood pressure trajectories across 20 years, and these were related to CAC at years 20 and 25. Three systolic blood pressure (SBP) patterns were identified: low stable (n=563; 53%), moderate (n=416; 40%), and moderate increasing (n=70; 7%). Women with moderate-increasing SBP were more likely to have delivered preterm compared with those in the low-stable group (40% versus 21%; P <0.0001), and they were more likely to have CAC (38.5% versus 12.2%). The SBP and CAC association varied by preterm birth ( P interaction=0.04). Women with preterm delivery and a moderate-increasing SBP had a 2.17-fold higher hazards of CAC (95% confidence interval, 1.14-4.12) compared with women with term births and a lower SBP pattern, adjusted for cardiovascular disease risk factors and other pregnancy features. There was no excess CAC in women with moderate-increasing SBP and term births (adjusted hazard ratio, 1.02; 95% confidence interval, 0.49-2.14). Associations were stronger in women with hypertensive disorders of pregnancy but also detected in those with normotensive preterm deliveries. Women who deliver preterm infants are more likely to follow a high-risk blood pressure pattern throughout the childbearing years that is associated with CAC at midlife., (© 2018 American Heart Association, Inc.)

Introduction: There are known racial differences in cardiovascular health behaviors, including smoking, physical activity, and diet quality. A better understanding of these differences may help identify intervention targets for reducing cardiovascular disease disparities. This study examined whether socioeconomic, psychosocial, and neighborhood environmental factors, in isolation or together, mediate racial differences in health behaviors., Methods: Participants were 3,081 men and women from the Coronary Artery Risk Development in Young Adults study who were enrolled in 1985-1986 (Year 0) and completed a follow-up examination in 2015-2016 (Year 30). A health behavior score was created at Years 0, 7, 20, and 30 using smoking, physical activity, and diet assessed that year. The race difference in health behavior score was estimated using linear regression in serial cross-sectional analyses. Mediation analyses computed the proportion of the race and health behavior score association attributable to socioeconomic, psychosocial, and neighborhood factors., Results: Data analysis conducted in 2016-2017 found that blacks had significantly lower health behavior scores than whites across 30 years of follow-up. Individual socioeconomic factors mediated 48.9%-70.1% of the association between race and health behavior score, psychosocial factors 20.3%-30.0%, and neighborhood factors 22.1%-41.4% (p<0.01 for all)., Conclusions: Racial differences in health behavior scores appear to be mediated predominately by correspondingly large differences in socioeconomic factors. This study highlights the profound impact of socioeconomic factors, which are mostly not under an individual's control, on health behaviors. Policy action targeting socioeconomic factors may help reduce disparities in health behaviors., (Copyright © 2018 American Journal of Preventive Medicine. All rights reserved.)

Background and Aims: Unlike tobacco, the effect of marijuana smoke on subclinical atherosclerosis, a surrogate measure for cardiovascular disease, is not known. This study aimed to determine the association between lifetime exposure to marijuana and measures of subclinical atherosclerosis in mid-life., Design, Setting and Participants: We used data from the US-based Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of black and white men and women aged 18-30 years at baseline in 1985-86, with up to seven follow-up examinations over 25 years. A total of 3498 participants in the CARDIA study were included in this study., Measurements: Cumulative years of exposure to marijuana (expressed in 'marijuana-years', with 1 marijuana-year equivalent to 365 days of use) using repeated assessments every 2-5 years for 25 years. Abdominal artery calcium (AAC) and coronary artery calcium (CAC) scores were measured by computed tomography at year 25 examination., Results: Among 3117 participants with AAC and CAC measurements, 2627 (84%) reported past marijuana use and 1536 (49%) past daily tobacco smoking. Compared with tobacco smokers, 46% of whom reported 10 or more pack-years of use, only 12% of marijuana users reported 5 or more marijuana-years of use and only 6% reported having used marijuana daily. We found a significant interaction between never and ever tobacco users on the association between cumulative marijuana use and AAC (P = 0.05). Among those who never smoked tobacco, cumulative marijuana-years were not associated with AAC or CAC in models adjusted for demographics, cardiovascular risk factors, licit and illicit drug exposure and depression symptoms. However, among ever tobacco smokers, marijuana exposure was associated with AAC and CAC. At 5 marijuana-years of exposure, using AAC = 0 and CAC = 0 as a reference group, the odds ratio (OR) was 1.97 [95% confidence interval (CI) = 1.21-3.21, P = 0.007] for AAC > 0/CAC = 0 and 1.83 (95% CI = 1.02-3.31, P = 0.04) for CAC > 0), regardless of AAC. Tobacco smoking was associated strongly with both AAC and CAC., Conclusion: Marijuana use appears to be associated with subclinical atherosclerosis, but only among ever tobacco users., (© 2017 Society for the Study of Addiction.)

Endothelial dysfunction is a form of subclinical cardiovascular disease that may be involved in preterm birth and small-for-gestational-age deliveries. However, concentrations of biomarkers of endothelial dysfunction before pregnancy have rarely been measured. We hypothesized that higher levels of biomarkers of endothelial dysfunction (cellular adhesion molecules and selectins) would be associated with odds of preterm birth and/or small-for-gestational-age deliveries. We included 235 women from the Coronary Artery Risk Development in Young Adults (CARDIA) study who were nulliparous at Y7, reported ≥1 live birth through Y25, and had ≥1 biomarker measured at Y7. We tested for associations between individual biomarkers and an averaged z-score representing total endothelial dysfunction with preterm birth and/or small-for-gestational-age deliveries using Poisson regression, adjusted for demographic and clinical characteristics at the exam immediately preceding index birth. At Y7, total evidence of  endothelial dysfunction was similar in women who did (n = 59) and did not have (n = 176) preterm birth and/or small-for-gestational-age deliveries. There was no association between biomarkers of endothelial dysfunction (either individual biomarker or total score) with odds of preterm birth and/or small-for-gestational-age deliveries after adjustment: IRR = 1.01, 95% CI: 0.74, 1.39, p = 0.93 for total endothelial biomarker score. Associations were not modified by race. We conclude that biomarkers of endothelial dysfunction in nulliparous women, measured ~3 years before pregnancy, did not identify women at risk for preterm birth and/or small-for-gestational-age deliveries. This suggests that the maternal endothelial dysfunction that is believed to contribute to these birth outcomes may not be detectable before pregnancy.

Prior studies reported associations of APOL1 nephropathy risk variants with subclinical atherosclerosis. However, these findings were limited to older individuals with high comorbidities. To evaluate this in younger individuals, we calculated associations of APOL1 risk variants (high risk [2 risk variants] vs. low risk [0-1 risk variant]) with prevalent, incident, or progressive coronary artery calcification, a carotid intima media thickness over the 90th percentile, and left ventricular hypertrophy in 1315 black participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study. The mean age of this cohort was 44.6 years and their mean estimated glomerular filtration rate was 102.5 ml/min/1.73m 2 . High-risk participants were found to be younger and have a higher prevalence of albuminuria than low-risk participants. In Poisson regression models adjusted for comorbidities and kidney function, the risk of prevalent coronary artery calcification (relative risk [95% confidence interval] 1.12 [0.72,1.71]), the incident coronary artery calcification (1.50 [0.87,2.59]), and the progression of coronary artery calcification (1.40 [0.88,2.23]) did not significantly differ in high vs. low-risk participants. Furthermore, the risk of carotid intima media thickness over the 90th percentile (1.28 [0.78,2.10]) and left ventricular hypertrophy (1.02[0.73,1.43]) did not significantly differ in high vs. low-risk participants in fully-adjusted models. Thus, APOL1 risk variants did not associate with subclinical markers of atherosclerosis or left ventricular hypertrophy in middle-aged black adults with preserved kidney function., (Copyright © 2017 International Society of Nephrology. All rights reserved.)

Background: Gestational diabetes mellitus (GDM) is associated with increased risk for diabetes mellitus, metabolic syndrome, and cardiovascular disease. We evaluated whether GDM is associated with incident chronic kidney disease (CKD), controlling for prepregnancy risk factors for both conditions., Study Design: Prospective cohort., Setting & Participants: Of 2,747 women (aged 18-30 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study in 1985 to 86, we studied 820 who were nulliparous at enrollment, delivered at least 1 pregnancy longer than 20 weeks' gestation, and had kidney function measurements during 25 years of follow-up., Predictor: GDM was self-reported by women for each pregnancy., Outcomes: CKD was defined as the development of estimated glomerular filtration rate (eGFR)<60mL/min/1.73m 2 or urine albumin-creatinine ratio ≥ 25mg/g at any one CARDIA examination in years 10, 15, 20, or 25., Measurements: HRs for developing CKD were estimated for women who developed GDM versus women without GDM using complementary log-log models, adjusting for prepregnancy age, systolic blood pressure, dyslipidemia, body mass index, smoking, education, eGFR, fasting glucose concentration, physical activity level (all measured at the CARDIA examination before the first pregnancy), race, and family history of diabetes. We explored for an interaction between race and GDM., Results: During a mean follow-up of 20.8 years, 105 of 820 (12.8%) women developed CKD, predominantly increased urine albumin excretion (98 albuminuria only, 4 decreased eGFR only, and 3 both). There was evidence of a GDM-race interaction on CKD risk (P=0.06). Among black women, the adjusted HR for CKD was 1.96 (95% CI, 1.04-3.67) in GDM compared with those without GDM. Among white women, the HR was 0.65 (95% CI, 0.23-1.83)., Limitations: Albuminuria was assessed by single untimed measurements of urine albumin and creatinine., Conclusions: GDM is associated with the subsequent development of albuminuria among black women in CARDIA., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Cardiovascular disease (CVD) is the leading cause of death among patients with nonalcoholic fatty liver disease (NAFLD). Moderate drinking (vs abstinence) is associated with lower risk of CVD in the general population. We assessed whether alcohol use is associated with CVD risk in patients with NAFLD., Methods: We analyzed data from participants in the Coronary Artery Risk Development in Young Adults longitudinal cohort study of 5115 black and white young adults, 18-30 years old, recruited from 4 cities in the United States from 1985 through 1986. Participants self-reported alcohol use at study entry and then again after 15, 20, and 25 years. At year 25 (2010-2011), participants underwent computed tomography examination of the thorax and abdomen and tissue Doppler echocardiography with myocardial strain measured by speckle tracking. Coronary artery calcification was defined as an Agatston score above 0. NAFLD was defined as liver attenuation <51 Hounsfield Units after exclusions. Drinkers reported 1-21 (men) or 1-14 (women) standard drinks/week at years 15, 20, or 25. Nondrinkers reported no alcohol use at years 15, 20, and 25., Results: Of the 570 participants with NAFLD (mean age, 50 years; 54% black; 46% female), 332 (58%) were drinkers; significantly higher proportions of drinkers were white, male, and with higher levels of education compared with nondrinkers (P < .05 for all). Higher proportions of drinkers had obesity, diabetes, and metabolic syndrome compared with nondrinkers (P < .01). There was no difference in liver attenuation between groups (P = .12). After multivariable adjustment, there was no association between alcohol use and CVD risk factors (diabetes, hypertension, hyperlipidemia) or subclinical CVD measures (coronary artery calcification, early transmitral velocity/late (atrial) transmitral velocity (E/A) ratio, global longitudinal strain)., Conclusions: In a population-based sample of individuals with NAFLD in midlife, prospectively assessed alcohol use is not associated with significant differences in risk factors for CVD or markers of subclinical CVD. In contrast to general population findings, alcohol use may not reduce the risk of CVD in patients with NAFLD., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Importance: Coronary artery calcium (CAC) is associated with coronary heart disease (CHD) and cardiovascular disease (CVD); however, prognostic data on CAC are limited in younger adults., Objective: To determine if CAC in adults aged 32 to 46 years is associated with incident clinical CHD, CVD, and all-cause mortality during 12.5 years of follow-up., Design, Setting, and Participants: The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a prospective community-based study that recruited 5115 black and white participants aged 18 to 30 years from March 25, 1985, to June 7, 1986. The cohort has been under surveillance for 30 years, with CAC measured 15 (n = 3043), 20 (n = 3141), and 25 (n = 3189) years after recruitment. The mean follow-up period for incident events was 12.5 years, from the year 15 computed tomographic scan through August 31, 2014., Main Outcomes and Measures: Incident CHD included fatal or nonfatal myocardial infarction, acute coronary syndrome without myocardial infarction, coronary revascularization, or CHD death. Incident CVD included CHD, stroke, heart failure, and peripheral arterial disease. Death included all causes. The probability of developing CAC by age 32 to 56 years was estimated using clinical risk factors measured 7 years apart between ages 18 and 38 years., Results: At year 15 of the study among 3043 participants (mean [SD] age, 40.3 [3.6] years; 1383 men and 1660 women), 309 individuals (10.2%) had CAC, with a geometric mean Agatston score of 21.6 (interquartile range, 17.3-26.8). Participants were followed up for 12.5 years, with 57 incident CHD events and 108 incident CVD events observed. After adjusting for demographics, risk factors, and treatments, those with any CAC experienced a 5-fold increase in CHD events (hazard ratio [HR], 5.0; 95% CI, 2.8-8.7) and 3-fold increase in CVD events (HR, 3.0; 95% CI, 1.9-4.7). Within CAC score strata of 1-19, 20-99, and 100 or more, the HRs for CHD were 2.6 (95% CI, 1.0-5.7), 5.8 (95% CI, 2.6-12.1), and 9.8 (95% CI, 4.5-20.5), respectively. A CAC score of 100 or more had an incidence of 22.4 deaths per 100 participants (HR, 3.7; 95% CI, 1.5-10.0); of the 13 deaths in participants with a CAC score of 100 or more, 10 were adjudicated as CHD events. Risk factors for CVD in early adult life identified those above the median risk for developing CAC and, if applied, in a selective CAC screening strategy could reduce the number of people screened for CAC by 50% and the number imaged needed to find 1 person with CAC from 3.5 to 2.2., Conclusions and Relevance: The presence of CAC among individuals aged between 32 and 46 years was associated with increased risk of fatal and nonfatal CHD during 12.5 years of follow-up. A CAC score of 100 or more was associated with early death. Adults younger than 50 years with any CAC, even with very low scores, identified on a computed tomographic scan are at elevated risk of clinical CHD, CVD, and death. Selective use of screening for CAC might be considered in individuals with risk factors in early adulthood to inform discussions about primary prevention.

Importance: Recent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk., Objective: To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume., Design, Setting, and Participants: Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older with an average of 2 serum testosterone levels lower than 275 ng/dL (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism who were enrolled in the Testosterone Trials between June 24, 2010, and June 9, 2014., Intervention: Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months., Main Outcomes and Measures: The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis)., Results: Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204 mm3 to 232 mm3 vs 317 mm3 to 325 mm3, respectively; estimated difference, 41 mm3; 95% CI, 14 to 67 mm3; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm3 to 318 mm3 in the testosterone group vs from 499 mm3 to 541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13 to 80 mm3; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 503 Agatston units in the placebo group (estimated difference, -27 Agatston units; 95% CI, -80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group., Conclusions and Relevance: Among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding., Trial Registration: clinicaltrials.gov Identifier: NCT00799617.

Background: Despite evidence suggesting that early metabolic dysfunction impacts cardiovascular disease risk, current guidelines focus on risk assessments later in life, missing early transitions in metabolic risk that may represent opportunities for averting the development of cardiovascular disease., Methods and Results: In 4420 young adults in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we defined a "metabolic" risk score based on components of the Third Report of the Adult Treatment Panel's definition of metabolic syndrome. Using latent class trajectory analysis adjusted for sex, race, and time-dependent body mass index, we identified 6 distinct metabolic trajectories over time, specified by initial and final risk: low-stable, low-worsening, high-stable, intermediate-worsening, intermediate-stable, and high-worsening. Overall, individuals gained weight over time in CARDIA with statistically but not clinically different body mass index trend over time. Dysglycemia and dyslipidemia over time were highest in initially high or worsening trajectory groups. Divergence in metabolic trajectories occurred in early adulthood (before age 40), with 2 of 3 individuals experiencing an increase in metabolic risk over time. Membership in a higher-risk trajectory (defined as initially high or worsening over time) was associated with greater prevalence and extent of coronary artery calcification, left ventricular mass, and decreased left ventricular strain at year 25. Importantly, despite similar rise in body mass index across trajectories over 25 years, coronary artery calcification and left ventricular structure and function more closely tracked risk factor trajectories., Conclusions: Transitions in metabolic risk occur early in life. Obesity-related metabolic dysfunction is related to subclinical cardiovascular phenotypes independent of evolution in body mass index, including coronary artery calcification and myocardial hypertrophy and dysfunction., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Purpose: We assessed whether longitudinal changes in body mass index (BMI) are positively associated with changes in 10-year American College of Cardiology/American Heart Association atherosclerotic cardiovascular disease (ASCVD) risk scores in middle-aged blacks compared to whites., Methods: Data were from 1691 participants enrolled in the Coronary Artery Risk Development in Young Adults Study aged 40 years or more in 2000-2001, who had follow-up examinations 5 and 10 years later., Results: The prevalence of obesity increased from 32.3% in 2000-2001 (mean age: 42.8 years) to 41.7% in 2010-2011, higher in blacks than whites. The corresponding change in 10-year ASCVD risk was significantly higher for blacks (men: 4.5%-9.6%, women: 1.7%-5.0%) than whites (men: 2.4%-5.2%, women: 0.7%-1.6%). In 2010-2011, 57.5% of black men had ASCVD risk scores of 7.5% or more compared to white men (14.7%), black women (17.4%), and white women (1.6%). Although BMI trends were positively associated with 10-year change in ASCVD risk scores (0.07% per 1 kg/m(2) increase), it explained very little variance in risk score trends in all race-sex groups., Conclusions: In middle-aged adults, longitudinal changes in BMI had little independent influence on changes in 10-year ASCVD risk scores as its effect may be largely mediated through ASCVD risk factors already accounted for in the risk score., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Reproductive factors provide an early window into a woman's coronary heart disease (CHD) risk; however, their contribution to CHD risk stratification is uncertain., Methods and Results: In the Women's Health Initiative Observational Study, we constructed Cox proportional hazards models for CHD including age, pregnancy status, number of live births, age at menarche, menstrual irregularity, age at first birth, stillbirths, miscarriages, infertility ≥1 year, infertility cause, and breastfeeding. We next added each candidate reproductive factor to an established CHD risk factor model. A final model was then constructed with significant reproductive factors added to established CHD risk factors. Improvement in C statistic, net reclassification index (or net reclassification index with risk categories of <5%, 5 to <10%, and ≥10% 10-year risk of CHD), and integrated discriminatory index were assessed. Among 72 982 women (CHD events, n=4607; median follow-up,12.0 [interquartile range, 8.3-13.7] years; mean [standard deviation] age, 63.2 [7.2] years), an age-adjusted reproductive risk factor model had a C statistic of 0.675 for CHD. In a model adjusted for established CHD risk factors, younger age at first birth, number of still births, number of miscarriages, and lack of breastfeeding were positively associated with CHD. Reproductive factors modestly improved model discrimination (C statistic increased from 0.726 to 0.730; integrated discriminatory index, 0.0013; P<0.0001). Net reclassification for women with events was not improved (net reclassification index events, 0.007; P=0.18); and, for women without events, net reclassification was marginally improved (net reclassification index nonevents, 0.002; P=0.04) CONCLUSIONS: Key reproductive factors are associated with CHD independently of established CHD risk factors, very modestly improve model discrimination, and do not materially improve net reclassification., (© 2016 American Heart Association, Inc.)

Background: Data from prior studies have yielded inconsistent results on the association of serum testosterone levels with the risk for cardiovascular disease. There are no clinical trial data on the effects of testosterone replacement therapy on plaque progression., Objective: We designed a study to investigate the effect of testosterone therapy on coronary artery plaque progression using serial coronary computed tomographic angiography (CCTA). In this paper, we describe the study design, methods, and characteristics of the study population., Methods: The Cardiovascular Trial of the Testosterone Trials (TTrials; NCT00799617) is a double-blind, placebo-controlled trial of 1 year of testosterone therapy in men 65 years or older with clinical manifestations of androgen deficiency and unequivocally low serum testosterone concentrations (<275 ng/dl). CCTA performed at baseline and after 12 months of therapy will determine the effects of testosterone on the progression of the total volume of noncalcified plaques. All scans are evaluated at a central reading center by an investigator blinded to treatment assignment., Results: A total of 165 men were enrolled. The average age is 71.1 years, and the average BMI is 30.7. About 9% of men had a history of myocardial infarction, 6% angina, and 10% coronary artery revascularization. A majority reported hypertension and/or high cholesterol; 31.8% reported diabetes. Total noncalcified plaque at baseline showed a slight but nonsignificant trend toward lower plaque volume with higher serum testosterone concentrations (P=0.12)., Conclusion: The Cardiovascular Trial will test the hypothesis that testosterone therapy inhibits coronary plaque progression, as assessed by serial CCTA.

Background: The classic view of blood pressure (BP) reactivity to psychological stress in relation to cardiovascular risks assumes that excess reactivity is worse and lower reactivity is better. Evidence addressing how stress-induced BP reactivity in young adults is associated with midlife cognitive function is sparse., Methods and Results: We assessed BP reactivity during a star tracing task and a video game in adults aged 20 to 32 years. Twenty-three years later, cognitive function was assessed with use of the Digit Symbol Substitution Test (a psychomotor speed test), the Rey Auditory Verbal Learning Test (a verbal memory test), and the modified Stroop test (an executive function test). At the time of follow-up, participants (n=3021) had a mean age of 50.2 years; 56% were women, and 44% were black. In linear regression models adjusted for demographic and clinical characteristics including baseline and follow-up resting BP, lower systolic BP (SBP) reactivity during the star tracing and video game was associated with worse Digit Symbol Substitution Test scores (β [SE]: 0.11 [0.02] and 0.05 [0.02], respectively) and worse performance on the Stroop test (β [SE]: -0.06 [0.02] and -0.05 [0.02]; all P<0.01). SBP reactivity was more consistently associated than diastolic BP reactivity with cognitive function scores. The associations between SBP reactivity and cognitive function were mostly similar between blacks and whites., Conclusions: Lower psychological stress-induced SBP reactivity in younger adults was associated with lower cognitive function in midlife. BP reactivity to psychological stressors may have different associations with target organs in hypertension., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Importance: Although cardiorespiratory fitness (CRF) is prognostic in older adults, the effect of CRF during early adulthood on long-term cardiovascular structure, function, and prognosis is less clear., Objective: To examine whether CRF in young adults is associated with long-term clinical outcome and subclinical cardiovascular disease (CVD)., Design, Setting, and Participants: Prospective study of 4872 US adults aged 18 to 30 years who underwent treadmill exercise testing at a baseline study visit from March 25, 1985, to June 7, 1986, and 2472 individuals who underwent a second treadmill test 7 years later. Median follow-up was 26.9 years, with assessment of obesity, left ventricular mass and strain, coronary artery calcification (CAC), and vital status and incident CVD. Follow-up was complete on August 31, 2011, and data were analyzed from recruitment through the end of follow-up., Main Outcomes and Measures: The presence of CAC was assessed by computed tomography at years 15 (2000-2001), 20 (2005-2006), and 25 (2010-2011), and left ventricular mass was assessed at years 5 (1990-1991) and 25 (with global longitudinal strain). Incident CVD and all-cause mortality were adjudicated., Results: Of the 4872 individuals, 273 (5.6%) died and 193 (4.0%) experienced CVD events during follow-up. After comprehensive adjustment, each additional minute of baseline exercise test duration was associated with a 15% lower hazard of death (hazard ratio [HR], 0.85; 95% CI, 0.80-0.91; P < .001) and a 12% lower hazard of CVD (HR, 0.88; 95% CI, 0.81-0.96; P = .002). Higher levels of baseline CRF were associated with significantly lower left ventricular mass index (β = -0.24; 95% CI, -0.45 to -0.03; P = .02) and significantly better lobal longitudinal strain (β = -0.09; 95% CI, -0.14 to -0.05; P < .001) at year 25. Fitness was not associated with CAC. A 1-minute reduction in fitness by year 7 was associated with 21% and 20% increased hazards of death (HR, 1.21; 95% CI, 1.07-1.37; P = .002) and CVD (HR, 1.20; 95% CI, 1.06-1.37; P = .006), respectively, along with a more impaired strain (β = 0.15; 95% CI, 0.08-0.23; P < .001). No association between change in fitness and CAC was found., Conclusions and Relevance: Higher levels of fitness at baseline and improvement in fitness early in adulthood are favorably associated with lower risks for CVD and mortality. Fitness and changes in fitness are associated with myocardial hypertrophy and dysfunction but not CAC. Regular efforts to ascertain and improve CRF in young adulthood may play a critical role in promoting cardiovascular health and interrupting early CVD pathogenesis., Competing Interests: Disclosures: None reported.

Background: The relationship between intake of fruits and vegetables (F/V) during young adulthood and coronary atherosclerosis later in life is unclear., Methods and Results: We studied participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of young, healthy black and white individuals at baseline (1985-1986). Intake of F/V at baseline was assessed using a semiquantitative interview administered diet history, and coronary artery calcium was measured at year 20 (2005-2006) using computed tomography. We used logistic regression to adjust for relevant variables and estimate the adjusted odds ratios and 95% confidence intervals across energy-adjusted, sex-specific tertiles of total servings of F/V per day. Among our sample (n=2506), the mean (SD) age at baseline was 25.3 (3.5) years, and 62.7% were female. After adjustment for demographics and lifestyle variables, higher intake of F/V was associated with a lower prevalence of coronary artery calcium: odds ratio (95% confidence interval) =1.00 (reference), 0.78 (0.59-1.02), and 0.74 (0.56-0.99), from the lowest to the highest tertile of F/V, P value for trend <0.001. There was attenuation of the association between F/V and coronary artery calcium after adjustment for other dietary variables, but the trend remained significant: odds ratio (95% confidence interval): 1.00 (reference), 0.84 (0.63-1.11), and 0.92 (0.67-1.26), P value for trend <0.002]., Conclusions: In this longitudinal cohort study, higher intake of F/V during young adulthood was associated with lower odds of prevalent coronary artery calcium after 20 years of follow-up. Our results reinforce the importance of establishing a high intake of F/V as part of a healthy dietary pattern early in life., (© 2015 American Heart Association, Inc.)

Objective: To evaluate lactation duration in relation to subsequent atherosclerosis in women during midlife., Methods: The Coronary Artery Risk Development in Young Adults study is a multicenter prospective cohort that enrolled 2,787 women in 1985-1986 (ages 18-30 years, 52% black, 48% white), of whom 2,014 (72%) attended the 20-year follow-up examination in 2005-2006. We selected 846 women (46% black) without heart disease or diabetes at baseline who delivered one or more times after the baseline evaluation, had cardiometabolic risk factors measured at baseline, and had maximum common carotid intima-media thickness (mm) measured at the 20-year follow-up examination in 2005-2006. Lactation duration was summed across all postbaseline births for each woman and (n, women) categorized as: 0 to less than 1 month (n=262), 1 to less than 6 months (n=210), 6 to less than 10 months (n=169), and 10 months or greater (n=205). Multiple linear regression models estimated mean common carotid intima-media thickness (95% confidence interval) and mean differences among lactation duration groups compared with the 0 to less than 1-month group adjusted for prepregnancy obesity, cardiometabolic status, parity, and other risk factors., Results: Lactation duration had a graded inverse association with common carotid intima-media thickness; mean differences between 10 months or greater compared with 0 to less than 1 month ranged from -0.062 mm for unadjusted models (P trend <.001) to -0.029 mm for models fully adjusted for prepregnancy body mass index (BMI) and cardiometabolic risk factors, parity, smoking, and sociodemographics (P trend=.010). Stepwise addition of potential mediators (BMI, systolic blood pressure at the 20-year follow-up examination) modestly attenuated the lactation and common carotid intima-media thickness association to -0.027 and -0.023 mm (P trend=.019 and .054)., Conclusion: Shorter lactation duration is associated with subclinical atherosclerosis independent of prepregnancy cardiometabolic risk factors and traditional risk factors. The magnitude of differences in carotid artery intima-media thickness may represent greater vascular aging. Lactation may have long-term benefits that lower cardiovascular disease risk in women., Level of Evidence: II.

Background: Several ambulatory blood pressure monitoring (ABPM) measures have been associated with increased cardiovascular disease risk independent of clinic blood pressure (BP). African Americans have higher clinic BP compared with Whites but few data are available on racial differences in ABPM measures., Methods: We compared ABPM measures between African American (n = 178) and White (n = 103) participants at the Year 5 Coronary Artery Risk Development in Young Adults study visit. BP was measured during a study visit and the second and third measurements were averaged. ABPM was conducted over the following 24 hours., Results: Mean ± SD age of participants was 29.8 ± 3.8 years and 30.8 ± 3.5 years for African Americans and Whites, respectively. Mean daytime systolic BP (SBP) was 3.90 (SD 1.18) mm Hg higher among African Americans compared with Whites (P < 0.001) after age-gender adjustment and 1.71 (SD 1.03) mm Hg higher after multivariable adjustment including mean clinic SBP (P = 0.10). After multivariable adjustment including mean clinic SBP, nighttime SBP was 4.83 (SD 1.11) mm Hg higher among African Americans compared with Whites (P < 0.001). After multivariable adjustment, the African Americans were more likely than Whites to have nocturnal hypertension (prevalence ratio: 2.44, 95% CI: 0.99-6.05) and nondipping (prevalence ratio: 2.50, 95% CI: 1.39-4.48). The prevalence of masked hypertension among African Americans and Whites was 4.4% and 2.1%, respectively, (P = 0.49) and white coat hypertension was 3.3% and 3.9%, respectively (P = 0.99). Twenty-four hour BP variability on ABPM was higher among African Americans compared with Whites., Conclusions: These data suggest racial differences in several ABPM measures exist., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: We examined the association between neighborhood convenience stores and diet outcomes for 20 years of the Coronary Artery Risk Development in Young Adults study., Methods: We used dietary data from the Coronary Artery Risk Development in Young Adults study years 1985-1986, 1992-1993, and 2005-2006 (n = 3299; Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA) and geographically and temporally matched neighborhood-level food resource and US Census data. We used random effects repeated measures regression to estimate associations between availability of neighborhood convenience stores with diet outcomes and whether these associations differed by individual-level income., Results: In multivariable-adjusted analyses, greater availability of neighborhood convenience stores was associated with lower diet quality (mean score = 66.3; SD = 13.0) for participants with lower individual-level income (b = -2.40; 95% CI = -3.30, -1.51); associations at higher individual-level income were weaker. We observed similar associations with whole grain consumption across time but no statistically significant associations with consumption of sugar-sweetened beverages, artificially sweetened beverages, snacks, processed meats, fruits, or vegetables., Conclusions: The presence of neighborhood convenience stores may be associated with lower quality diets. Low-income individuals may be most sensitive to convenience store availability.

Background: We investigated race-ethnic and sex-specific relationships of left ventricular (LV) structure and LV function in African American and white men and women at 43 to 55 years of age., Methods and Results: The Coronary Artery Risk Development in Young Adults (CARDIA) Study enrolled African American and white adults, age 18 to 30 years, from 4 US field centers in 1985-1986 (Year-0) who have been followed prospectively. We included participants with echocardiographic assessment at the Year-25 examination (n=3320; 44% men, 46% African American). The end points of LV structure and function were assessed using conventional echocardiography and speckle-tracking echocardiography. In the multivariable models, we used, in addition to race-ethnic and gender terms, demographic (age, physical activity, and educational level) and cardiovascular risk variables (body mass index, systolic blood pressure, diastolic blood pressure, heart rate, presence of diabetes, use of antihypertensive medications, number of cigarettes/day) at Year-0 and -25 examinations as independent predictors of echocardiographic outcomes at the Year-25 examination (LV end-diastolic volume [LVEDV]/height, LV end-systolic volume [LVESV]/height, LV mass [LVM]/height, and LVM/LVEDV ratio for LV structural indices; LV ejection fraction [LVEF], Ell, and Ecc for systolic indices; and early diastolic and atrial ratio, mitral annulus early peak velocity, ratio of mitral early peak velocity/mitral annulus early peak velocity; ratio, left atrial volume/height, longitudinal peak early diastolic strain rate, and circumferential peak early diastolic strain rate for diastolic indices). Compared with women, African American and white men had greater LV volume and LV mass (P<0.05). For LV systolic function, African American men had the lowest LVEF as well as longitudinal (Ell) and circumferential (Ecc) strain indices among the 4 sex/race-ethnic groups (P<0.05). For LV diastolic function, African American men and women had larger left atrial volumes; African American men had the lowest values of Ell and Ecc for diastolic strain rate (P<0.05). These race/sex differences in LV structure and LV function persisted after adjustment., Conclusions: African American men have greater LV size and lower LV systolic and diastolic function compared to African American women and to white men and women. The reasons for these racial-ethnic differences are partially but not completely explained by established cardiovascular risk factors., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objective: Higher levels of hemoglobin A1c (HbA1c) are associated with increased cardiovascular disease risk among individuals without diabetes and may also be positively associated with coronary artery calcification (CAC). This study investigated the association of HbA1c with CAC progression in the Coronary Artery Risk Development in Young Adults study., Research Design and Methods: We included 2,076 participants with HbA1c and noncontrast computed tomography (CT) assessed at baseline (2005-2006), and CT repeated 5 years later (2010-2011). CAC progression was defined as 1) incident CAC (increase >0 Agatston units among those with no CAC at baseline), 2) any CAC progression (increase >10 Agatston units between examinations), and 3) advanced CAC progression (increase >100 Agatston units between examinations)., Results: During the 5-year follow-up period, 12.9% of participants without baseline CAC developed incident CAC; among all participants, 18.2% had any CAC progression and 5.4% had advanced CAC progression. Higher HbA1c was associated with incident CAC (risk ratio [RR] = 1.45; 95% CI 1.02, 2.06), any CAC progression (RR = 1.51; 95% CI 1.16, 1.96), and advanced CAC progression (RR = 2.42; 95% CI 1.47, 3.99) after adjustment for sociodemographic factors. Additional adjustment for cardiovascular risk factors attenuated the associations of HbA1c with incident CAC (RR = 1.05; 95% CI 0.74, 1.49) and any CAC progression (RR = 1.13; 95% CI 0.87, 1.47). In contrast, the association of HbA1c with advanced CAC progression persisted in multivariable adjusted models (RR = 1.78; 95% CI 1.08, 2.95)., Conclusions: Higher HbA1c was independently associated with advanced CAC progression among individuals without diabetes, while the associations with incident CAC and any CAC progression were accounted for by other established cardiovascular risk factors., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: To study the independent associations of polycystic ovary syndrome (PCOS), and its 2 components, hyperandrogenism and anovulation, with coronary artery calcification (CAC) and carotid artery intima-media thickness (IMT)., Approach and Results: At the year 20 of the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based multicenter cohort of young adults, women (mean age, 45 years) with information on menses and hirsutism in their twenties were assessed for CAC (n=982) and IMT (n=988). We defined PCOS as women who had both irregular menses and hyperandrogenism (n=55); isolated oligomenorrhea (n=103) as women who only had irregular menses; and isolated hyperandrogenism (n=156) as women who had either hirsutism or increased testosterone levels. Logistic regressions and general linear models were used to estimate the associations between components of PCOS and subclinical CVD. The prevalence of CAC was 10.3% overall. Women with PCOS had a multivariable adjusted odds ratio of 2.70 (95% confidence interval, 1.31-5.60) for CAC. Women with either isolated oligomenorrhea or isolated hyperandrogenism had no increased risk of CAC when compared with unexposed women. Women with PCOS had significantly increased bulb and internal carotid-IMT measurements; however, no significant differences were noted in bulb or internal carotid artery IMT among women with either isolated oligomenorrhea or isolated hyperandrogenism when compared with unexposed women. There were no differences in common carotid-IMT among the 4 study groups., Conclusions: In this study, women with PCOS, manifested as both anovulation and hyperandrogenism, but not women with one of these manifestations alone, were at increased risk for the development of subclinical CVD., (© 2014 American Heart Association, Inc.)

Background: History of gestational diabetes mellitus (GDM) increases lifetime risk of type 2 diabetes (DM) and the metabolic syndrome (MetS), which increase risk of cardiovascular disease. It is unclear, however, whether GDM increases risk of early atherosclerosis independent of pre-pregnancy obesity and subsequent metabolic disease., Methods and Results: Of 2787 women (18 to 30 years) enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study, we studied 898 (47% black) who were free of DM and heart disease at baseline (1985-1986), delivered ≥1 post-baseline births, reported GDM history, and had common carotid intima media thickness (ccIMT, mm) measured in 2005-2006. We used multivariable linear regression to assess associations between GDM and ccIMT adjusted for race, age, parity, and pre-pregnancy cardiometabolic risk factors. We assessed mediators (weight gain, insulin resistance, blood pressure), and effect modification by incident DM or MetS during the 20-year period. Of the 898 women, 119 (13%) reported GDM (7.6 per 100 deliveries). Average age was 31 at last birth and 44 at ccIMT measurement for GDM and non-GDM groups. Unadjusted mean ccIMT was 0.023 mm higher for GDM than non-GDM groups (P=0.029), but pre-pregnancy BMI attenuated the difference to 0.016 mm (P=0.109). In 777 women without subsequent DM or the MetS, mean ccIMT was 0.023 mm higher for GDM versus non-GDM groups controlling for race, age, parity, and pre-pregnancy BMI (0.784 versus 0.761, P=0.039). Addition of pre-pregnancy insulin resistance index had minimal impact on adjusted mean net ccIMT difference (0.22 mm). Mean ccIMT did not differ by GDM status among 121 women who developed DM or the MetS (P=0.58)., Conclusions: History of GDM may be a marker for early atherosclerosis independent of pre-pregnancy obesity among women who have not developed type 2 diabetes or the metabolic syndrome.

Few studies have examined longitudinal associations between close social relationships and weight change. Using data from 3,074 participants in the Coronary Artery Risk Development in Young Adults Study who were examined in 2000, 2005, and 2010 (at ages 33-45 years in 2000), we estimated separate logistic regression random-effects models to assess whether patterns of exposure to supportive and negative relationships were associated with 10% or greater increases in body mass index (BMI) (weight (kg)/height (m)(2)) and waist circumference. Linear regression random-effects modeling was used to examine associations of social relationships with mean changes in BMI and waist circumference. Participants with persistently high supportive relationships were significantly less likely to increase their BMI values and waist circumference by 10% or greater compared with those with persistently low supportive relationships after adjustment for sociodemographic characteristics, baseline BMI/waist circumference, depressive symptoms, and health behaviors. Persistently high negative relationships were associated with higher likelihood of 10% or greater increases in waist circumference (odds ratio = 1.62, 95% confidence interval: 1.15, 2.29) and marginally higher BMI increases (odds ratio = 1.50, 95% confidence interval: 1.00, 2.24) compared with participants with persistently low negative relationships. Increasingly negative relationships were associated with increases in waist circumference only. These findings suggest that supportive relationships may minimize weight gain, and that adverse relationships may contribute to weight gain, particularly via central fat accumulation.

Importance: Single measures of blood pressure (BP) levels are associated with the development of atherosclerosis; however, long-term patterns in BP and their effect on cardiovascular disease risk are poorly characterized., Objectives: To identify common BP trajectories throughout early adulthood and to determine their association with presence of coronary artery calcification (CAC) during middle age., Design, Setting, and Participants: Prospective cohort data from 4681 participants in the CARDIA study, who were black and white men and women aged 18 to 30 years at baseline in 1985-1986 at 4 urban US sites, collected through 25 years of follow-up (2010-2011). We examined systolic BP, diastolic BP, and mid-BP (calculated as [SBP+DBP]/2, an important marker of coronary heart disease risk among younger populations) at baseline and years 2, 5, 7, 10, 15, 20, and 25. Latent mixture modeling was used to identify trajectories in systolic, diastolic, and mid-BP over time., Main Outcomes and Measures: Coronary artery calcification greater than or equal to Agatston score of 100 Hounsfield units (HU) at year 25., Results: We identified 5 distinct mid-BP trajectories: low-stable (21.8%; 95% CI, 19.9%-23.7%; n=987), moderate-stable (42.3%; 40.3%-44.3%; n=2085), moderate-increasing (12.2%; 10.4%-14.0%; n=489), elevated-stable (19.0%; 17.1%-20.0%; n=903), and elevated-increasing (4.8%; 4.0%-5.5%; n=217). Compared with the low-stable group, trajectories with elevated BP levels had greater odds of having a CAC score of 100 HU or greater. Adjusted odds ratios were 1.44 (95% CI, 0.83-2.49) for moderate-stable, 1.86 (95% CI, 0.91-3.82) for moderate-increasing, 2.28 (95% CI, 1.24-4.18), for elevated-stable, and 3.70 (95% CI, 1.66-8.20) for elevated-increasing groups. The adjusted prevalence of a CAC score of 100 HU or higher was 5.8% in the low-stable group. These odds ratios represent an absolute increase of 2.7%, 5%, 6.3%, and 12.9% for the prevalence of a CAC score of 100 HU or higher for the moderate-stable, moderate-increasing, elevated-stable and elevated-increasing groups, respectively, compared with the low-stable group. Associations were not altered after adjustment for baseline and year 25 BP. Findings were similar for trajectories of isolated systolic BP trajectories but were attenuated for diastolic BP trajectories., Conclusions and Relevance: Blood pressure trajectories throughout young adulthood vary, and higher BP trajectories were associated with an increased risk of CAC in middle age. Long-term trajectories in BP may assist in more accurate identification of individuals with subclinical atherosclerosis.

Objective: To examine self-reported weight discrimination and differences based on race, sex, and BMI in a biracial cohort of community-based middle-aged adults., Design and Methods: Participants (3,466, mean age = 50 years, mean BMI = 30 kg/m²) of the Coronary Artery Risk Development in Young Adults (CARDIA) Study who completed the 25-year examination of this epidemiological investigation in 2010-2011 were reported. The sample included normal weight, overweight, and obese participants. CARDIA participants are distributed into four race-sex groups, with about half being African-American and half White. Participants completed a self-reported measure of weight discrimination., Results: Among overweight/obese participants, weight discrimination was lowest for White men (12.0%) and highest for White women (30.2%). The adjusted odds ratio (95% CI) for weight discrimination in those with class 2/3 obesity (BMI ≥ 35 kg/m²) versus the normal-weight was most pronounced: African American men, 4.59 (1.71-12.34); African American women, 7.82 (3.57-17.13); White men, 6.99 (2.27-21.49); and White women, 18.60 (8.97-38.54). Being overweight (BMI = 25-29.9 kg/m²) vs. normal weight was associated with increased discrimination in White women only: 2.10 (1.11-3.96)., Conclusions: Novel evidence for a race-sex interaction on perceived weight discrimination, with White women more likely to report discrimination at all levels of overweight and obesity was provided. Pychosocial mechanisms responsible for these differences deserve exploration., (Copyright © 2013 The Obesity Society.)

Left ventricular (LV) mass and the LV ejection fraction (LVEF) are major independent predictors of future cardiovascular disease. The association of LV mass with the future LVEF in younger populations has not been studied. The aim of this study was to investigate the relation of LV mass index (LVMI) at ages 23 to 35 years to LV function after 20 years of follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) study. CARDIA is a longitudinal study that enrolled young adults in 1985 and 1986. In this study, participants with echocardiographic examinations at years 5 and 25 were included. LVMI and the LVEF were assessed using M-mode echocardiography at year 5 and using M-mode and 2-dimensional imaging at year 25. Statistical analytic models assessed the correlation between LVMI and LV functional parameters cross-sectionally and longitudinally. A total of 2,339 participants were included. The mean LVEF at year 25 was 62%. Although there was no cross-sectional correlation between LVMI and the LVEF at year 5, there was a small but statistically significant negative correlation between LVMI at year 5 and the LVEF 20 years later (r = -0.10, p <0.0001); this inverse association persisted for LVMI in the multivariate model. High LVMI was an independent predictor of systolic dysfunction (LVEF <50%) 20 years later (odds ratio 1.46, p = 0.0018). In conclusion, LVMI in young adulthood in association with chronic risk exposure affects systolic function in middle age; the antecedents of heart failure may occur at younger ages than previously thought., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Few studies have investigated the association between overall diet and cardiorespiratory fitness (CRF)., Objective: We aimed to investigate associations of food groups, a diet-quality score, and dietary patterns with CRF in black and white adults., Design: We included 2632 participants aged 38-50 y who attended the year 20 exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study and Coronary Artery Risk Development in Young Adults Fitness Study (CFS) conducted in 2005-2006. Diet was assessed by using a validated diet history. A dietary score and 2 types of patterns were included as follows: the a priori diet-quality score and meat and fruit-vegetable dietary patterns derived from principal components analysis. CRF was assessed by using a graded exercise treadmill test. Linear regression models regressed the treadmill duration on food groups and dietary scores and patterns overall and in race-sex subgroups., Results: Grains (whole and refined), processed meats, and beverages (coffee, meal-replacement drinks, beer, and wine) were positively associated with the treadmill duration overall; whole fruit (not juices), organ meats, fried meats and fish, and soy and nondairy products were negatively associated. The a priori diet-quality score was positively associated with the duration overall and in all race-sex subgroups (P <0.05) except black men. The meat pattern was negatively associated with the duration in white men and white women only. The fruit-vegetable pattern was positively associated with duration in white women only., Conclusions: Overall, the a priori diet-quality score was positively associated with CRF in this cohort of black and white adults, whereas the meat dietary pattern was negatively associated only in whites. The CARDIA study and CFS were registered at clinicaltrials.gov as NCT00005130 and NCT00106457, respectively.

Objective: Health-care access is associated with improved control of multiple chronic diseases, but the association between health-care access and weight change is unclear. The present study aims to test the association between health-care access and weight change., Design: The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a multicentre population-based prospective study. Weight change was calculated at 3 and 13 years after CARDIA year 7 (1992-1993). Health-care access was defined as no barriers or one or more barriers to access (health insurance gap, no usual source of care, not seeking care due to expense). Intermediary variables evaluated included history of dieting and use of diet pills, meal replacements or weight-control programmes., Setting: Four cities in the USA., Subjects: Participants were aged 18-30 years at baseline (1985-1986). Analyses include 3922 black and white men and women with relevant data from CARDIA years 7, 10 and 20 (1992-1993, 1995-1996 and 2005-2006, respectively)., Results: Mean weight change was +2.22 kg (+4.9 lb) by 3 years and +8.48 kg (+18.7 lb) by 13 years, with no differences by health-care access. Being on a weight-reducing diet was not consistently associated with health-care access across examinations. Use of diet pills, meal replacements or organized weight-control programmes was low, and did not vary by health-care access., Conclusions: Weight gain was high irrespective of health-care access. Public health and clinical approaches are needed to address weight gain.

Importance: Younger individuals are experiencing a greater cumulative exposure to excess adiposity over their lifetime. However, few studies have determined the consequences of long-term obesity., Objective: To examine whether the duration of overall and abdominal obesity was associated with the presence and 10-year progression of coronary artery calcification (CAC), a subclinical predictor of coronary heart disease., Design, Setting, and Participants: Prospective study of 3275 white and black adults aged 18 to 30 years at baseline in 1985-1986 who did not initially have overall obesity (body mass index [BMI] ≥30) or abdominal obesity (men: waist circumference [WC] >102 cm; women: >88 cm) in the multicenter, community-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants completed computed tomography scanning for the presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration of overall and abdominal obesity was calculated using repeat measurements of BMI and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after baseline., Main Outcomes and Measures: Presence of CAC was measured by computed tomography at the year 15 (2000-2001), year 20 (2005-2006), or year 25 (2010-2011) follow-up examinations. Ten-year progression of CAC (2000-2001 to 2010-2011) was defined as incident CAC in 2010-2011 or an increase in CAC score of 20 Agatston units or greater., Results: During follow-up, 40.4% and 41.0% developed overall and abdominal obesity, respectively. Rates of CAC per 1000 person-years were higher for those who experienced more than 20 years vs 0 years of overall obesity (16.0 vs 11.0, respectively) and abdominal obesity (16.7 vs 11.0). Approximately 25.2% and 27.7% of those with more than 20 years of overall and abdominal obesity, respectively, experienced progression of CAC vs 20.2% and 19.5% of those with 0 years. After adjustment for BMI or WC and potential confounders, the hazard ratios for CAC for each additional year of overall or abdominal obesity were 1.02 (95% CI, 1.01-1.03) and 1.03 (95% CI, 1.02-1.05), respectively. The adjusted odds ratios for CAC progression were 1.04 (95% CI, 1.01-1.06) and 1.04 (95% CI, 1.01-1.07), respectively. Associations were attenuated but largely persisted following additional adjustment for potential intermediate metabolic factors during follow-up., Conclusions and Relevance: Longer duration of overall and abdominal obesity was associated with subclinical coronary heart disease and its progression through midlife independent of the degree of adiposity. Preventing or at least delaying the onset of obesity in young adulthood may lower the risk of developing atherosclerosis through middle age.

Background: Despite established relationships between physical activity (PA) or physical fitness (fitness) and metabolic risk, the prospective association is not well understood. The purpose of this study was to determine whether metabolic risk in young adults is associated with 20-year PA or fitness trajectories., Methods: Young adults were from the Coronary Artery Risk Development in Young Adults (CARDIA) study, baseline ages 18-30 years (n=4161). PA was determined from a self-reported questionnaire administered at baseline and at follow-up exams at years 2, 5, 7, 10, 15, and 20. Fitness (seconds) was estimated from a graded exercise treadmill test at baseline and years 7 and 20. Baseline metabolic risk was calculated using age-adjusted principal components analysis (elevated=top 10% of first factor), for each sex-race group, from mean arterial pressure, glucose, waist circumference, triglycerides, and high-density lipoprotein cholesterol. Repeated measures general linear modeling estimated PA and fitness trajectories over 20 years, separately in sex-race groups, adjusting for age and smoking status., Results: PA was significantly lower among those with elevated metabolic risk compared with normal risk at baseline and each subsequent time point (black and white men, white women; all P<0.0001; black women P=0.27). Significant and consistent results were also found with fitness trajectories for all sex-race groups (P<0.0001). Despite these lower PA and fitness levels at baseline in young adults with elevated metabolic compared with normal risk, 20-year trajectories declined at similar rates., Conclusion: Elevated metabolic risk is associated with lower levels of PA and fitness in early adulthood, and these differences persist over 20 years.

Background: The assessment of fat mass and fat-free mass in relation to the symptom-limited maximal exercise duration (Max(dur)) of a treadmill test allows for insight into the association of body composition with treadmill performance potential., Objective: We investigated the complex associations between fat mass and fat-free mass and Max(dur) in a population setting., Design: The Max(dur) of a graded exercise treadmill test and body composition by dual-energy X-ray absorptiometry were estimated in 2413 black and white men and women aged 38-50 y from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort., Results: The mean Max(dur) was ≈7.5 s shorter per kilogram of fat mass in both men and women and independent of fat-free mass, height, race, television watching, physical activity, systolic blood pressure, lung function, and education. Fat mass modified the association of fat-free mass with the Max(dur) (2-way interaction P < 0.001), and the interaction was stronger in women than in men. In men in the lowest fat-mass quartile, the Max(dur) was 1.3 s longer per kilogram of fat-free mass and was 0.5 s shorter per kilogram of fat-free mass in the highest fat-mass quartile. In contrast, in women with the least fat mass, the Max(dur) was 2.7 s longer per kilogram of fat-free mass and was 2.8 s shorter per kilogram of fat-free mass in the highest fat-mass quartile., Conclusions: The Max(dur) was negatively related to fat mass. Fat-free mass in obese people contributed little to the treadmill performance potential as assessed by the Max(dur), although the contribution of fat-free mass was positive in thinner people.

Purpose: To examine whether the relationship between cardiovascular disease risk factors and coronary artery calcification (CAC) is modified by race among those with diabetes., Methods: Data were pooled data from three studies (Multi-Ethnic Study of Atherosclerosis, Family Heart Study, Diabetes Heart Study) for a total of 835 blacks and 1122 whites with diabetes. CAC was quantified by cardiac computed tomography and risk factors were obtained using standard methods. Regression models examined the relationship between risk factors and presence and quantity of CAC., Results: The average age of the cohort was 60 years; 57% were women. Presence of CAC was lower in blacks compared to whites (odds ratio = 0.22 for men, 0.57 for women, p <0.01). Hemoglobin A1c, duration of diabetes, low-density lipoprotein, smoking, and body mass index were independently associated with presence of CAC; high-density lipoprotein, triglycerides, and C-reactive protein were not. Race did not modify these associations. Adjustment for multiple risk factors did not explain the race disparity in CAC., Conclusions: CAC was reduced in blacks compared to whites in persons with diabetes. This effect was most pronounced in men. The relationship between risk factors and CAC did not differ between races. Racial differences in CAC are likely due to unmeasured risk factors and/or genetic susceptibility., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Fitness and physical activity are each inversely associated with the development of hypertension. We tested whether fitness and physical activity were independently associated with the 20-year incidence of hypertension in 4618 men and women. Hypertension was determined in participants who had systolic blood pressure >or=140 mm Hg or diastolic blood pressure >or=90 mm Hg or who reported antihypertensive medication use. Fitness was estimated based on the duration of a symptom-limited graded exercise treadmill test, and physical activity was self-reported. The incidence rate of hypertension was 13.8 per 1000 person-years (n=1022). Both baseline fitness (hazard ratio: 0.63 [95% CI: 0.56 to 0.70 per SD]; 2.9 minutes) and physical activity (hazard ratio: 0.86 [95% CI: 0.79 to 0.84 per SD]; 297 exercise units) were inversely associated with incident hypertension when included jointly in a model that also adjusted for age, sex, race, baseline smoking status, systolic blood pressure, alcohol intake, high-density lipoprotein cholesterol, dietary fiber, dietary sodium, fasting glucose, and body mass index. The magnitude of association between physical activity and hypertension was strongest among participants in the high fitness (hazard ratio: 0.80 [95% CI: 0.68 to 0.94]) category, whereas the magnitude of association between fitness and hypertension was similar across tertiles of physical activity. The estimated proportion of hypertension cases that could be prevented if participants moved to a higher fitness category (ie, preventive fraction) was 34% and varied by race and sex group. Fitness and physical activity are each associated with incident hypertension, and low fitness may account for a substantial proportion of hypertension incidence.

Background: We hypothesized that individuals with low 10-year but high lifetime cardiovascular disease risk would have a greater burden of subclinical atherosclerosis than those with low 10-year but low lifetime risk., Methods and Results: We included 2988 individuals < or = 50 years of age at examination year 15 from the Coronary Artery Risk Development in Young Adults (CARDIA) study and 1076 individuals < or = 50 of age at study entry from the Multi-Ethnic Study of Atherosclerosis (MESA). The 10-year risk and lifetime risk for cardiovascular disease were estimated for each participant, permitting stratification into 3 groups: low 10-year (<10%)/low lifetime (<39%) risk, low 10-year (<10%)/high lifetime risk (> or = 39%), and high 10-year risk (> or = 10%) or diagnosed diabetes mellitus. Baseline levels and change in levels of subclinical atherosclerosis (coronary artery calcium or carotid intima-media thickness) were compared across risk strata. Among participants with low 10-year risk (91% of all participants) in CARDIA, those with a high lifetime risk compared with low lifetime risk had significantly greater common (0.83 versus 0.80 mm in men; 0.79 versus 0.75 mm in women) and internal (0.85 versus 0.80 mm in men; 0.80 versus 0.76 mm in women) carotid intima-media thickness, higher coronary artery calcium prevalence (16.6% versus 9.8% in men; 7.1% versus 2.3% in women), and significantly greater incidence of coronary artery calcium progression (22.3% versus 15.4% in men; 8.7% versus 5.3% in women). Similar results were observed in MESA., Conclusions: Individuals with low 10-year but high lifetime risk have a greater subclinical disease burden and greater incidence of atherosclerotic progression compared with individuals with low 10-year and low lifetime risk, even at younger ages.

Background: High blood pressure in middle age is a well-established risk factor for cardiovascular disease, but the consequences of low-level elevations during young adulthood are unknown., Objective: To measure the association between prehypertension exposure before age 35 years and coronary calcium later in life., Design: Prospective cohort study., Setting: Four communities in the United States., Participants: Black and white men and women age 18 to 30 years recruited for the CARDIA (Coronary Artery Risk Development in Young Adults) Study in 1985 through 1986 who were without hypertension before age 35 years., Measurements: Blood pressure trajectories for each participant were estimated by using measurements from 7 examinations over the course of 20 years. Cumulative exposure to blood pressure in the prehypertension range (systolic blood pressure of 120 to 139 mm Hg, or diastolic blood pressure of 80 to 89 mm Hg) from age 20 to 35 years was calculated in units of mm Hg-years (similar to pack-years of tobacco exposure) and related to the presence of coronary calcium measured at each participant's last examination (mean age, 44 years [SD, 4])., Results: Among 3560 participants, the 635 (18%) who developed prehypertension before age 35 years were more often black, male, overweight, and of lower socioeconomic status. Exposure to prehypertension before age 35 years, especially systolic prehypertension, showed a graded association with coronary calcium later in life (coronary calcium prevalence of 15%, 24%, and 38% for 0, 1 to 30, and >30 mm Hg-years of exposure, respectively; P < 0.001). This association remained strong after adjustment for blood pressure elevation after age 35 years and other coronary risk factors and participant characteristics., Limitation: Coronary calcium, although a strong predictor of future coronary heart disease, is not a clinical outcome., Conclusion: Prehypertension during young adulthood is common and is associated with coronary atherosclerosis 20 years later. Keeping systolic pressure below 120 mm Hg before age 35 years may provide important health benefits later in life.