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More than 40 years after the 1978 Bethesda Conference on the Declining Mortality from Coronary Heart Disease provided the scientific community with a blueprint for systematic analysis to understand declining rates of coronary heart disease, there are indications the decline has ended or even reversed despite advances in our knowledge about the condition and treatment. Recent data show a more complex situation, with mortality rates for overall cardiovascular disease, including coronary heart disease and stroke, decelerating, whereas those for heart failure are increasing. To mark the 40th anniversary of the Bethesda Conference, the National Heart, Lung, and Blood Institute and the American Heart Association cosponsored the "Bending the Curve in Cardiovascular Disease Mortality: Bethesda + 40" symposium. The objective was to examine the immediate and long-term outcomes of the 1978 conference and understand the current environment. Symposium themes included trends and future projections in cardiovascular disease (in the United States and internationally), the evolving obesity and diabetes epidemics, and harnessing emerging and innovative opportunities to preserve and promote cardiovascular health and prevent cardiovascular disease. In addition, participant-led discussion explored the challenges and barriers in promoting cardiovascular health across the lifespan and established a potential framework for observational research and interventions that would begin in early childhood (or ideally in utero). This report summarizes the relevant research, policy, and practice opportunities discussed at the symposium.

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ObjectiveTo test the hypothesis that end-stage renal disease (ESRD) risk exposure during young adulthood is related to worse cognitive performance in midlife.MethodsWe included 2,604 participants from the population-based Coronary Artery Risk Development in Young Adults (CARDIA) Study (mean age 35 years, 54% women, 45% Black). Estimated glomerular filtration rate and albumin-to-creatinine ratio were measured every 5 years at year (Y) 10 through Y30. At each visit, moderate/high risk of ESRD according to the Kidney Disease: Improving Global Outcomes guidelines (estimated glomerular filtration rate 30 mg/g) was defined, totaled over examinations, and categorized into 0 episodes, 1 episode, and >1 episodes of ESRD risk. At Y30, participants underwent global and multidomain cognitive assessment. We used analysis of covariance to assess the association of ESRD risk categories with cognitive function, controlling for cardiovascular risk factors.ResultsOver the course of 20 years, 427 participants (16% of the study population) had ≥1 episodes of ESRD risk exposure. Individuals with more risk episodes had lower composite cognitive function (p < 0.001), psychomotor speed (p < 0.001), and executive function (p = 0.007). All these associations were independent of sociodemographic status and cardiovascular risk factors.ConclusionsIn this population-based longitudinal study, we show that episodes of decline in kidney function over the young-adulthood course are associated with worse cognitive performance at midlife. Preserving kidney function in young age needs to be investigated as a potential strategy to preserve cognitive function in midlife.

Psychosocial factors are associated with the achievement of optimal cardiovascular disease risk factor (CVDRF) levels. To date, little research has examined multiple psychosocial factors simultaneously to identify distinguishing psychosocial profiles among individuals with CVDRF. Further, it is unknown whether profiles are associated with achievement of CVDRF levels longitudinally. Therefore, we characterized psychosocial profiles of individuals with CVDRF and assessed whether they are associated with achievement of optimal CVDRF levels over 15 years. We included 1148 CARDIA participants with prevalent hypertension, hypercholesterolemia and/or diabetes mellitus in 2000-2001. Eleven psychosocial variables reflecting psychological health, personality traits, and social factors were included. Optimal levels were deemed achieved if: Hemoglobin A1c (HbA1c) < 7.0%, low-density lipoprotein (LDL) cholesterol < 100 mg/dl, and systolic blood pressure (SBP) < 140 mm Hg. Latent profile analysis revealed three psychosocial profile groups 'Healthy', 'Distressed and Disadvantaged' and 'Discriminated Against'. There were no significant differences in achievement of CVDRF levels of the 3 targets combined across profiles. Participants in the 'Distressed and Disadvantaged' profile were less likely to meet optimal HbA1c levels compared to individuals in the 'Healthy' profile after demographic adjustment. Associations were attenuated after full covariate adjustment. Distinct psychosocial profiles exist among individuals with CVDRF, representing meaningful differences. Implications for CVDRF management are discussed., Author(s): Emily A. Vargas [sup.1] , Diana A. Chirinos [sup.1] , Mandy Wong [sup.1] , Mercedes R. Carnethon [sup.1] , Allison J. Carroll [sup.2] , Catarina I. Kiefe [sup.3] , [...]

BackgroundObese adults who are free from metabolic risk factors may develop risk factors over time. Our objective was to characterize development of obesity and duration of metabolically healthy obese (MHO) over 30 years.MethodsParticipants in CARDIA who developed obesity (BMI ≥ 30 kg/m2) at follow-up exams during years 7, 10, 15, 20, 25, and 30 were analyzed. MHO was defined as obese and having 0 or 1 risk factor: ≥SBP/DBP 130/85 mmHg; fasting glucose ≥100 mg/dL/5.55 mmol/L; fasting triglycerides (≥150 mg/dL/1.69 mmol/L); and HDL-C (men

ObjectiveWe examined associations among socioeconomic adversity, social resources, and allostatic load in Hispanic/Latino youth, who are at high risk for obesity and related cardiometabolic risks.MethodsParticipants were 1343 Hispanic/Latino youth (51% male; ages 8-16 years) offspring of Hispanic Community Health Study/Study of Latinos participants. Between 2012 and 2014, youth underwent a fasting blood draw and anthropometric assessment, and youth and their enrolled caregivers provided social and demographic information. A composite indicator of allostatic load represented dysregulation across general metabolism, cardiovascular, glucose metabolism, lipid, and inflammation/hemostatic systems. Socioeconomic adversity was a composite of caregiver education, employment status, economic hardship, family income relative to poverty, family structure, and receipt of food assistance. Social resources were a composite of family functioning, parental closeness, peer support, and parenting style variables.ResultsMultivariable regression models that adjusted for sociodemographic factors, design effects (strata and clustering), and sample weights revealed a significant, positive, association between socioeconomic adversity and allostatic load (β = .10, p = .035), and a significant, inverse association between socioeconomic adversity and social resources (β = -.10, p = .013). Social resources did not relate to allostatic load and did not moderate or help explain the association of adversity with allostatic load (all p values > .05).ConclusionsStatistically significant, but small associations of socioeconomic adversity with both allostatic load and social resources were identified. The small effects may partially reflect range restriction given overall high socioeconomic adversity and high social resources in the cohort.

BackgroundHigher fibroblast growth factor-23 (FGF23) concentrations have been found to be associated with incident heart failure (HF). Experimental data suggest FGF23 directly stimulates myocardial hypertrophy. FGF23 may also enhance renin-angiotensin-aldosterone system activity. Whether FGF23 is associated with increased HF risk in populations with hypertension and whether this association is weaker in the presence of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy is unknown.MethodsWe studied 2,858 adults with hypertension free of cardiovascular disease at baseline (65.6 ± 9.5 years, 46.2% male) participating in the Multi-Ethnic Study of Atherosclerosis (MESA). We investigated the association of baseline serum intact FGF23 with incident HF over a 14-year median follow-up and whether ACEI/ARB therapy modified this risk. We also investigated the relationship of FGF23 with aldosterone and plasma renin activity in a random subgroup of the entire MESA cohort with available assays (N = 1,642).ResultsIn adjusted Cox regression models, higher FGF23 was associated with a 63% greater hazard of incident HF (hazard ratio: 1.63, 95% confidence interval: [1.13-2.36] per 1-unit increase in log-transformed FGF23), which persisted after exclusion of participants with chronic kidney disease (hazard ratio: 1.94 [1.10-3.43]). There was no heterogeneity by ACEI/ARB use (Pinteraction = 0.438). FGF23 improved model fit over covariables (likelihood ratio χ2 = 6.67, P = 0.010). In multivariable linear regression models, there was no association between FGF23 and aldosterone or plasma renin activity.ConclusionsHigher FGF23 concentrations are associated with a significantly increased risk of HF in hypertension but this risk did not differ by ACEI/ARB treatment status. FGF23 may be a useful biomarker for HF risk in hypertensive populations.

ObjectiveTo determine whether intraindividual variability in fasting glucose (FG) below the threshold of diabetes is associated with cognitive function in middle adulthood beyond increasing FG.Research design and methodsWe studied 3,307 CARDIA (Coronary Artery Risk Development in Young Adults) Study participants (age range 18-30 years and enrolled in 1985-1986) at baseline and calculated two measures of long-term glucose variability: the coefficient of variation about the mean FG (CV-FG) and the absolute difference between successive FG measurements (average real variability [ARV-FG]) before the onset of diabetes over 25 and 30 years of follow-up. Cognitive function was assessed at years 25 (2010-2011) and 30 (2015-2016) with the Digit Symbol Substitution Test (DSST), Rey-Auditory Verbal Learning Test (RAVLT), Stroop Test, Montreal Cognitive Assessment, and category and letter fluency tests. We estimated the association between glucose variability and cognitive function test score with adjustment for clinical and behavioral risk factors, mean FG level, change in FG level, and diabetes development, medication use, and duration.ResultsAfter multivariable adjustment, 1-SD increment of CV-FG was associated with worse cognitive scores at year 25: DSST, standardized regression coefficient -0.95 (95% CI -1.54, -0.36); RAVLT, -0.14 (95% CI -0.27, -0.02); and Stroop Test, 0.49 (95% CI 0.04, 0.94). Findings were similar between CV-FG with each cognitive test score at year 30 and when we used an alternative measure of variability (ARV-FG) that captures variability in successive FG values.ConclusionsHigher intraindividual FG variability during young adulthood below the threshold of diabetes was associated with worse processing speed, memory, and language fluency in midlife independent of FG levels.

ObjectivesMounting evidence links positive psychological functioning to restorative health processes and favourable medical outcomes. However, very little is known about the relationship between optimism, an indicator of psychological functioning and the American Heart Association (AHA)-defined concept of cardiovascular health (CVH), particularly in Hispanics/Latinos of diverse backgrounds. To address limitations of existing literature, this study investigated the association between dispositional optimism and CVH in a heterogeneous sample of Hispanics/Latinos residing in the USA.DesignCross-sectional study.Participants and settingData were analysed from 4919 adults ages 18-75 of the Hispanic Community Health Study/Study of Latinos parent study and the Sociocultural Ancillary Study.Main outcome measuresOptimism was assessed using the 6-item Life Orientation Test-Revised (range from 6 to 30). AHA classification standards were used to derive an additive CVH score with operationalisation of indicators as Ideal, Intermediate and Poor. The overall CVH score included indicators of diet, body mass index, physical activity, cholesterol, blood pressure, fasting glucose and smoking status. Multivariate linear and logistic regressions were used to examine associations of optimism with CVH (Life's Simple 7), after adjusting for sociodemographic factors and depressive symptoms.ResultsEach increase in the optimism total score was associated with a greater CVH score (β=0.03 per unit increase, 95% CI 0.01 to 0.05). When modelling tertiles of optimism, participants with moderate (β=0.24 to 95% CI 0.06 to 0.42) and high (β=0.12, 95% CI 0.01 to 0.24) levels of optimism displayed greater CVH scores when compared with their least optimistic peers.ConclusionThis study offers preliminary evidence for an association between optimism and CVH in a large heterogeneous group of Hispanic/Latino adults. Our study adds scientific knowledge of psychological assets that may promote CVH and suggests a novel therapeutic target for consideration. Future studies are needed to explore causality and potential mechanism underlying the relationship between positive emotion and heart health.

BackgroundLow heart rate variability (HRV), a marker of cardiac autonomic dysfunction, has been associated with major risk factors of cognitive impairment. Yet, the direct association of HRV with cognitive function remains relatively unexplored, particularly in midlife.MethodsIn 2005, 2 measures of short-term HRV, the SD of normal-to-normal intervals (SDNN) and the root mean square of successive differences (RMSSD), were calculated for participants of the Coronary Artery Risk Development in Young Adults study, and then categorized into quartiles. Five years later, 3 cognitive tests were administered for verbal memory ("Rey Auditory-Verbal Learning Test", RAVLT, range 0-15), processing speed ("Digit Symbol Substitution Test", DSST, range 0-133), and executive function ("Stroop interference").ResultsTwo thousand one hundred and eighteen participants (57.7% female, 42.2% Black) with a mean baseline age of 45.3 years were included in this analysis. In demographic-adjusted models, compared to participants with quartile 1 SDNN (lowest quartile), participants in the upper quartiles of SDNN scored better on the DSST (quartile 4: β = 1.83 points better, P = 0.03; and quartile 3: β = 1.95 points better, P = 0.03) and on the stroop (quartile 3: β = 1.19 points better, P < 0.05; and quartile2: β = 1.44 points better, P = 0.02). After adjusting for behavioral and cardiovascular risk factors, higher quartile SDNN remained significantly associated with better stroop score (quartile 3: β = 1.21 points better, P = 0.04; and quartile 2: β = 1.72 points better, P < 0.01) but not with DSST. There was no association between quartile of RMSSD and cognitive function, from fully adjusted models.ConclusionsOur findings suggest that higher quartile SDDN is associated with better executive function in midlife, above, and beyond cardiovascular risk factors.

ObjectiveTo evaluate 25-year physical activity (PA) trajectories from young to middle age and assess associations with the prevalence of coronary artery calcification (CAC).Patients and methodsThis study includes 3175 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study who self-reported PA by questionnaire at 8 follow-up examinations over 25 years (from March 1985-June 1986 through June 2010-May 2011). The presence of CAC (CAC>0) at year 25 was measured using computed tomography. Group-based trajectory modeling was used to identify PA trajectories with increasing age.ResultsWe identified 3 distinct PA trajectories: trajectory 1, below PA guidelines (n=1813; 57.1%); trajectory 2, meeting PA guidelines (n=1094; 34.5%); and trajectory 3, 3 times PA guidelines (n=268; 8.4%). Trajectory 3 participants had higher adjusted odds of CAC>0 (adjusted odds ratio [OR], 1.27; 95% CI, 0.95-1.70) vs those in trajectory 1. Stratification by race showed that white participants who engaged in PA 3 times the guidelines had higher odds of developing CAC>0 (OR, 1.80; 95% CI, 1.21-2.67). Further stratification by sex showed higher odds for white males (OR, 1.86; 95% CI, 1.16-2.98), and similar but nonsignificant trends were noted for white females (OR, 1.71; 95% CI, 0.79-3.71). However, no such higher odds of CAC>0 for trajectory 3 were observed for black participants.ConclusionWhite individuals who participated in 3 times the recommended PA guidelines over 25 years had higher odds of developing coronary subclinical atherosclerosis by middle age. These findings warrant further exploration, especially by race, into possible biological mechanisms for CAC risk at very high levels of PA.

BackgroundPrior studies indicate that chronic stress is associated with obesity in adults. However, whether parental/caregiver stress is associated with obesity in their offspring has not been widely examined in Hispanic/Latino populations. In this study, we evaluated the role of caregiver chronic stress on child obesity and whether home food environment or child lifestyle behaviors explained the association.MethodsThe study included a sample of Hispanic/Latino youth and their caregivers (n = 473) from the Study of Latinos (SOL) Youth study and the Hispanic Community Health Study/SOL Sociocultural Study, which enrolled children aged 8-16 years from four cities (Bronx, Chicago, Miami, and San Diego), and provided assessments of adult chronic stress. Poisson regression models were used to assess the association between parental/caregiver stress and child obesity, adjusting for potential confounders.ResultsTwenty-two percent of caregivers did not report any chronic stressors, 48% reported 1-2, and 29% reported ≥3 stressors. The prevalence of obesity in youth increased with number of caregiver stressors from 23% among those without caregiver stressors to 35% among those with ≥3 stressors (p for trend 0.03). After model adjustment, youths whose caregivers reported ≥3 stressors were more likely to be obese than youths whose caregivers reported no stressors (prevalence ratio = 1.53; 95% confidence interval 1.01-2.32). This association was independent of food home environment, child diet quality, and child physical activity, but it was not independent of caregiver obesity.ConclusionsThese findings suggest that parental/caregiver chronic stress is related to obesity in their children. Future research is needed to confirm this association in longitudinal studies and in other population groups.