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It is increasingly clear that longitudinal risk factor levels and trajectories are related to risk for atherosclerotic cardiovascular disease (ASCVD) above and beyond single measures. Currently used in clinical care, the Pooled Cohort Equations (PCE) are based on regression methods that predict ASCVD risk based on cross-sectional risk factor levels. Deep learning (DL) models have been developed to incorporate longitudinal data for risk prediction but its benefit for ASCVD risk prediction relative to the traditional Pooled Cohort Equations (PCE) remain unknown. Our study included 15,565 participants from four cardiovascular disease cohorts free of baseline ASCVD who were followed for adjudicated ASCVD. Ten-year ASCVD risk was calculated in the training set using our benchmark, the PCE, and a longitudinal DL model, Dynamic-DeepHit. Predictors included those incorporated in the PCE: sex, race, age, total cholesterol, high density lipid cholesterol, systolic and diastolic blood pressure, diabetes, hypertension treatment and smoking. The discrimination and calibration performance of the two models were evaluated in an overall hold-out testing dataset. Of the 15,565 participants in our dataset, 2170 (13.9%) developed ASCVD. The performance of the longitudinal DL model that incorporated 8 years of longitudinal risk factor data improved upon that of the PCE [AUROC: 0.815 (CI 0.782–0.844) vs 0.792 (CI 0.760–0.825)] and the net reclassification index was 0.385. The brier score for the DL model was 0.0514 compared with 0.0542 in the PCE. Incorporating longitudinal risk factors in ASCVD risk prediction using DL can improve model discrimination and calibration. [ABSTRACT FROM AUTHOR]

Key Points: Question: What is the impact of dietary sodium intake on blood pressure in middle-aged to elderly individuals? Findings: In this prospectively allocated diet order crossover study of 213 individuals, 1 week of a low-sodium diet resulted in an average 8–mm Hg reduction in systolic blood pressure vs a high-sodium diet, with few adverse events. The low-sodium diet lowered systolic blood pressure in nearly 75% of individuals compared with the high-sodium diet. Meaning: In this trial, the blood pressure–lowering effect of dietary sodium reduction was comparable with a commonly used first-line antihypertensive medication. Importance: Dietary sodium recommendations are debated partly due to variable blood pressure (BP) response to sodium intake. Furthermore, the BP effect of dietary sodium among individuals taking antihypertensive medications is understudied. Objectives: To examine the distribution of within-individual BP response to dietary sodium, the difference in BP between individuals allocated to consume a high- or low-sodium diet first, and whether these varied according to baseline BP and antihypertensive medication use. Design, Setting, and Participants: Prospectively allocated diet order with crossover in community-based participants enrolled between April 2021 and February 2023 in 2 US cities. A total of 213 individuals aged 50 to 75 years, including those with normotension (25%), controlled hypertension (20%), uncontrolled hypertension (31%), and untreated hypertension (25%), attended a baseline visit while consuming their usual diet, then completed 1-week high- and low-sodium diets. Intervention: High-sodium (approximately 2200 mg sodium added daily to usual diet) and low-sodium (approximately 500 mg daily total) diets. Main Outcomes and Measures: Average 24-hour ambulatory systolic and diastolic BP, mean arterial pressure, and pulse pressure. Results: Among the 213 participants who completed both high- and low-sodium diet visits, the median age was 61 years, 65% were female and 64% were Black. While consuming usual, high-sodium, and low-sodium diets, participants' median systolic BP measures were 125, 126, and 119 mm Hg, respectively. The median within-individual change in mean arterial pressure between high- and low-sodium diets was 4 mm Hg (IQR, 0-8 mm Hg; P <.001), which did not significantly differ by hypertension status. Compared with the high-sodium diet, the low-sodium diet induced a decline in mean arterial pressure in 73.4% of individuals. The commonly used threshold of a 5 mm Hg or greater decline in mean arterial pressure between a high-sodium and a low-sodium diet classified 46% of individuals as "salt sensitive." At the end of the first dietary intervention week, the mean systolic BP difference between individuals allocated to a high-sodium vs a low-sodium diet was 8 mm Hg (95% CI, 4-11 mm Hg; P <.001), which was mostly similar across subgroups of age, sex, race, hypertension, baseline BP, diabetes, and body mass index. Adverse events were mild, reported by 9.9% and 8.0% of individuals while consuming the high- and low-sodium diets, respectively. Conclusions and Relevance: Dietary sodium reduction significantly lowered BP in the majority of middle-aged to elderly adults. The decline in BP from a high- to low-sodium diet was independent of hypertension status and antihypertensive medication use, was generally consistent across subgroups, and did not result in excess adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT04258332 This crossover trial assesses whether high-sodium and low-sodium dietary interventions affect 24-hour ambulatory blood pressure measures among middle-aged to elderly adults with normotension, controlled hypertension, uncontrolled hypertension, or untreated hypertension. [ABSTRACT FROM AUTHOR]

Background: Inhibitory control develops in early childhood, and atypical development may be a measurable marker of risk for the later development of psychosis. Additionally, inhibitory control may be a target for intervention. Methods: Behavioral performance on a developmentally appropriate Go/No-Go task including a frustration manipulation completed by children ages 3–5 years (early childhood; n = 107) was examined in relation to psychotic-like experiences (PLEs; 'tween'; ages 9–12), internalizing symptoms, and externalizing symptoms self-reported at long-term follow-up (pre-adolescence; ages 8–11). ERP N200 amplitude for a subset of these children (n = 34) with electrophysiological data during the task was examined as an index of inhibitory control. Results: Children with lower accuracy on No-Go trials compared to Go trials in early childhood (F (1,101) = 3.976, p = 0.049), evidenced higher PLEs at the transition to adolescence 4–9 years later, reflecting a specific deficit in inhibitory control. No association was observed with internalizing or externalizing symptoms. Decreased accuracy during the frustration manipulation predicted higher internalizing, F (2,202) = 5.618, p = 0.004, and externalizing symptoms, F (2,202) = 4.663, p = 0.010. Smaller N200 amplitudes were observed on No-Go trials for those with higher PLEs, F (1,101) = 6.075, p = 0.020; no relationship was observed for internalizing or externalizing symptoms. Conclusions: Long-term follow-up demonstrates for the first time a specific deficit in inhibitory control behaviorally and electrophysiology, for individuals who later report more PLEs. Decreases in task performance under frustration induction indicated risk for internalizing and externalizing symptoms. These findings suggest that pathophysiological mechanisms for psychosis are relevant and discriminable in early childhood, and further, suggest an identifiable and potentially modifiable target for early intervention. [ABSTRACT FROM AUTHOR]

Objective: To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy?Methods: Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses.Results: Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of <130 mm Hg may reduce the risk of several important outcomes including risk of myocardial infarction, stroke, heart failure, and major cardiovascular events. No class of medications (i.e., angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta blockers) was significantly better than thiazides and thiazide-like diuretics as a first-line therapy for any outcome. [ABSTRACT FROM AUTHOR]

Introduction: The burden of cardiovascular (CV) risk factors accumulates over the lifespan: however, little information on CV risk across the full lifespan is available. Synthetic cohorts offer the opportunity to understand CV health across the lifespan. In this study we developed and validated a synthetic cohort approach to examine CV risk factors from age 18-90 years of age. Methods: This study included African American and Caucasian participants from 7 cohorts in the Lifetime Risk Pooling Project. Individuals' demographics (age, birth year, sex, race, SES), CV risk factors (smoking, total cholesterol, SBP, DBP, glucose, diabetes, lipid-lowering and antihypertensive meds) and outcomes (incident CVD and death) at each exam were included. To generate a complete set of values from age 18 to 90 for each participant, we multiply imputed the participant's CV risk profile and outcome using the available exam records based on a joint multi-level imputation model. To validate our imputed values, we removed the observed CARDIA data with exam ages 18-30, MESA data with exam ages 50-59 and CHS data with exam ages 80-90. We then imputed the CV risk profile of these deleted values and compared imputed and observed values. Results: We included 41,387 participants (55% female, 30% African American, mean age 51 at baseline, avg follow-up time 20 yrs). In our validation sample, imputed CV risk factor levels were consistent with observed values at both younger and older ages (table) for BMI, SBP, DBP, glucose and total cholesterol. The prevalence of antihypertensive meds was 14.6% in the observed and 14.9% in the imputed data. Similar findings were shown for the prevalence of diabetes, current smoking, CVD events and death. Imputed prevalence of lipid-lowering meds was lower than observed rates (5% vs 12%). Conclusions: This synthetic cohort approach provides valid and unbiased estimates of CV risk factors across the lifespan. Future studies using this synthetic cohort can provide novel insights into the origins and accumulation of CVD. [ABSTRACT FROM AUTHOR]

Introduction: Racial disparities in healthy lifestyles may begin in youth and increase over the lifespan. Hypothesis: Maintaining healthy lifestyles until 50 years of age will be lower in blacks compared with whites. Methods: The population-based Coronary Artery Risk Development in Young Adults (CARDIA) study enrolled 5115 blacks and whites aged 18-30 years in 1985-1986. Eight exams were completed over 25 years of follow-up. At each exam, optimal lifestyles were defined as body mass index (BMI) < 25 kg/m², never smoking status, moderate or vigorous physical activity ≥ 150 minutes per week, no or moderate alcohol intake (drinks per week [women / men]: 0-7 / 0-14) and Dietary Approaches to Stop Hypertension (DASH) adherence score ≥ 15. Optimal cardiovascular health (CVH) was defined as having ≥ 4 optimal lifestyles. The age-specific percentage of blacks and whites maintaining optimal lifestyles was calculated using a modified Kaplan Meier method. Hazard ratios (HR) were calculated for maintaining optimal lifestyles over 25 years in blacks compared with whites. Results: At the baseline exam, 4900 participants (mean age: 26 years; black: 51%) had ≥ 1 optimal lifestyle. By 50 years of age, maintaining BMI < 25 kg/m², never smoking status, moderate or vigorous physical activity ≥ 150 minutes per week, DASH diet adherence and optimal CVH were lower in blacks versus whites while maintaining no or moderate alcohol intake was higher (Table). The multivariable adjusted HR (95% confidence interval) comparing blacks to whites for maintaining BMI < 25 kg/m² was 0.57 (0.52-0.63), never smoking status was 0.82 (0.66-1.01), moderate or vigorous physical activity ≥ 150 minutes per week was 0.83 (0.76-0.91), no or moderate alcohol intake was 1.19 (1.03-1.37), DASH diet adherence was 0.71 (0.61-0.82) and optimal CVH was 0.63 (0.56-0.72). Conclusion: Blacks were less likely to maintain optimal lifestyles until 50 years of age. Reducing racial differences in the maintenance of optimal CVH may help prevent racial disparities in cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: A prolonged duration of diabetes has been shown to be independently associated with incident cardiovascular disease (CVD). Whether duration of prediabetes is similarly associated with CVD is unknown. We sought to determine whether the duration of prediabetes during young adulthood is associated with the presence of coronary artery calcified plaque (CAC) and cardiac structure/function in middle-age. Methods: Participants were 3244 white and black adults aged 18-30 years without prediabetes or diabetes at baseline (1985-86) or diabetes during follow-up in the multicenter community-based CARDIA Study. Prediabetes was defined at follow-up examinations 7, 10, 15, 20, and 25 years after baseline as fasting glucose 100-125 mg/dL, 2-hour oral glucose tolerance 140-199 mg/dL or HbA1c 5.7-6.4%. Presence of CAC was measured by computed tomography at follow-up years 15, 20, and 25. Measures of cardiac structure and function were obtained from echocardiography performed at year 25. Results: Of the 3244 individuals, 1561 (48.2%) developed prediabetes during follow-up. Among those who developed prediabetes, the median (IQR) duration was 10 (5-12) years. After adjustment for age, sex, race, education, study center, and CVD risk factors, the hazard ratio for the presence of CAC was 1.21 times higher for each 10-year increase in duration of prediabetes (95% CI: 1.06, 1.37). Duration of prediabetes was also associated with worse global longitudinal strain (per 10 years: 0.2%; 95% CI: 0.1, 0.4; P=.005), e′ (-0.2 cm/s; 95% CI: -0.3, -0.1; P < .001), and E/e′ ratio (0.113; 95% CI: -0.007, 0.233; P=.06) (Table). These results did not differ significantly by race or sex. Conclusions: Exposure to a longer duration of prediabetes is associated with subclinical atherosclerosis and cardiac dysfunction in middle-age. Further research is needed to better understand the pathophysiology of these relationships. [ABSTRACT FROM AUTHOR]

Background: Previous studies have examined blood pressure (BP) and lipid changes through childhood and adolescence using population averages. We hypothesized that trajectories for these are heterogeneous, with sub-groups of the population showing different patterns in BP and lipid changes through childhood and adolescence. Methods: This study includes 678 children in Project HeartBeat!. Children were ages 8, 11, or 14 at baseline in 1991 and were examined every 4 mos for up to 4 yrs (mean number of exams, 8). At each exam, lifestyle, anthropometric and laboratory data was collected. Group-based modeling (PROC TRAJ) was used to identify trajectories in systolic BP (SBP), fifth phase diastolic BP (DBP5), total cholesterol (Chol), HDL Chol, LDL Chol and triglycerides as a function of age. The optimal number of race- and sex-adjusted trajectories was determined using the Bayesian Information Criterion and clinical expertise. Results: Among 678 children (49% female; 75% nonblack), 314 were enrolled at age 8, 197 at age 11, and 167 at age 14. Four distinct BP trajectories were identified (figure panels A-B). For SBP the low, low-intermediate, high-intermediate and high groups contained 16.4%, 36.3%, 34.5% and 12.7% of the sample, respectively; for DBP5, they contained 9.5%, 34.2%, 41.0%, and 15.3%. Three trajectories were identified for lipids (panels C-F). The low, intermediate, and high groups included 43.9%, 49.0% and 7.0% of the sample for total Chol, respectively. Corresponding figures were 33.4%, 49.3%, and 17.2% for HDL; 33.5%, 53.9%, and 12.7% for LDL; and 75.3%, 20.3%, and 4.5% for triglycerides, respectively. Girls were less likely (39% vs 61%) to be in the highest SBP groups as compared to the lowest. Blacks were more likely to be in the higher risk trajectories for DBP5 and HDL (p<0.01). Conclusion: Significant heterogeneity exists in BP and lipid trajectories throughout childhood. Finding predictors of the low and high trajectory classes may help target interventions to preserve low risk and manage high risk for future CVD. [ABSTRACT FROM AUTHOR]

Objective: To estimate the long-term absolute risk for cardiovascular disease (CVD) according to fasting glucose (FG) levels below the threshold of diabetes.Research Design and Methods: We pooled data from seven observational cohorts of U.S. black and white men and women followed from 1960 to 2015. We categorized FG as follows: <5.0, 5.0-5.5, 5.6-6.2, 6.3-6.9 mmol/L, and diabetes (FG ≥7.0 mmol/L or use of diabetes medications). CVD was defined as fatal/nonfatal coronary heart disease and fatal/nonfatal stroke. We estimated the risk of CVD by FG category at index age 55 years using a modified Kaplan-Meier survival analysis, adjusted for the competing risk of non-CVD death. We also assessed risk for incident CVD according to change in FG before 50 years of age, specifically among the categories <5.6 mmol/L, 5.6-6.9 mmol/L, and diabetes.Results: Our sample included 19,630 individuals (6,197 blacks and 11,015 women) without a prior CVD event. Risk for CVD through 85 years of age ranged from 15.3% (<5.0 mmol/L) to 38.6% (diabetes levels) among women and from 21.5% (5.0-5.5 mmol/L) to 47.7% (diabetes levels) among men. An FG of 6.3-6.9 mmol/L was associated with higher long-term CVD risk compared with the lowest FG among men but not women. Increases in glucose during midlife with conversion to diabetes were associated with higher cardiovascular risk (1.3- to 3.6-fold) than increases in glucose below the diabetes threshold.Conclusions: Middle-age individuals with diabetes have high long-term absolute risk for CVD. These data strongly support the importance of blood glucose monitoring in midlife for CVD prevention. [ABSTRACT FROM AUTHOR]

Enabling and supporting discoverability of research outputs and datasets are key functions of university and academic health center institutional repositories. Yet adoption rates among potential repository users are hampered by a number of factors, prominent among which are difficulties with basic usability. In their efforts to implement a local instance of InvenioRDM, a turnkey next generation repository, team members at Northwestern University's Galter Health Sciences Library & Learning Center supplemented agile development principles and methods and a user experience design-centered approach with observations of users' microinteractions (interactions with each part of the software's interface that requires human intervention). Microinteractions were observed through user testing sessions conducted in Fall 2019. The result has been a more user-informed development effort incorporating the experiences and viewpoints of a multidisciplinary team of researchers spanning multiple departments of a highly ranked research university. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does discrimination change when either a coronary artery calcium score or a polygenic risk score is added to a coronary heart disease (CHD) prediction model based on traditional risk factors? Findings: In 2 population-based studies involving 3208 adults aged 45 years through 79 years (Multi-Ethnic Study of Atherosclerosis [MESA], median age 61 years and the Rotterdam Study [RS], median age, 67 years) and of European ancestry, a coronary artery calcium score significantly improved discrimination when added to a traditional risk factor–based score (MESA, 0.09; Rotterdam Study, 0.06), but the polygenic risk score did not. Similar findings were observed when stratified by median age. Meaning: In middle-aged to older adults, the coronary artery calcium score but not the polygenic risk score improved CHD risk discrimination. Importance: Coronary artery calcium score and polygenic risk score have each separately been proposed as novel markers to identify risk of coronary heart disease (CHD), but no prior studies have directly compared these markers in the same cohorts. Objective: To evaluate change in CHD risk prediction when a coronary artery calcium score, a polygenic risk score, or both are added to a traditional risk factor–based model. Design, Setting, and Participants: Two observational population-based studies involving individuals aged 45 years through 79 years of European ancestry and free of clinical CHD at baseline: the Multi-Ethnic Study of Atherosclerosis (MESA) study involved 1991 participants at 6 US centers and the Rotterdam Study (RS) involved 1217 in Rotterdam, the Netherlands. Exposure: Traditional risk factors were used to calculate CHD risk (eg, pooled cohort equations [PCEs]), computed tomography for the coronary artery calcium score, and genotyped samples for a validated polygenic risk score. Main Outcomes and Measures: Model discrimination, calibration, and net reclassification improvement (at the recommended risk threshold of 7.5%) for prediction of incident CHD events were assessed. Results: The median age was 61 years in MESA and 67 years in RS. Both log (coronary artery calcium+1) and polygenic risk score were significantly associated with 10-year risk of incident CHD (hazards ratio per SD, 2.60; 95% CI, 2.08-3.26 and 1.43; 95% CI, 1.20-1.71, respectively), in MESA. The C statistic for the coronary artery calcium score was 0.76 (95% CI, 0.71-0.79) and for the polygenic risk score, 0.69 (95% CI, 0.63-0.71). The change in the C statistic when each was added to the PCEs was 0.09 (95% CI, 0.06-0.13) for the coronary artery calcium score, 0.02 (95% CI, 0.00-0.04) for the polygenic risk score, and 0.10 (95% CI, 0.07-0.14) for both. Overall categorical net reclassification improvement was significant when the coronary artery calcium score (0.19; 95% CI, 0.06-0.28) but was not significant when the polygenic risk score (0.04; 95% CI, −0.05 to 0.10) was added to the PCEs. Calibration of the PCEs and models with coronary artery calcium and/or polygenic risk scores was adequate (all χ2<20). Subgroup analysis stratified by the median age demonstrated similar findings. Similar findings were observed for 10-year risk in RS and in longer-term follow-up in MESA (median, 16.0 years). Conclusions and Relevance: In 2 cohorts of middle-aged to older adults from the US and the Netherlands, the coronary artery calcium score had better discrimination than the polygenic risk score for risk prediction of CHD. In addition, the coronary artery calcium score but not the polygenic risk score significantly improved risk discrimination and risk reclassification for CHD when added to traditional risk factors. This study involving 2 large, community-based, longitudinal, cohort studies whether adding 2 markers—coronary artery calcium score and polygenic risk score—to traditional risk factor–based scores improves predicting coronary heart disease among middle-aged to older adults. [ABSTRACT FROM AUTHOR]

The quantitative relationship of incident cardiovascular disease (CVD) to lifetime cumulative risk factor exposure is not well understood. Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we examined the quantitative associations of cumulative exposure over time to multiple, simultaneously operating risk factors with CVD incidence and the incidence of its components. Regression models were developed quantifying the influence of the time course and severity of multiple CVD risk factors, operating simultaneously, on risk of incident CVD. The outcomes were incident CVD and the incidence of its components: coronary heart disease, stroke, and congestive heart failure. Our study included 4,958 asymptomatic adults enrolled in CARDIA from 1985 to 1986 (ages 18 to 30 years) who were followed for 30 years. Risk of incident CVD depends on the time course and severity of a series of independent risk factors, the impact of which is mediated by their effects on individual CVD components after age 40 years. Cumulative exposure (AUC vs time) to low-density lipoprotein cholesterol and triglycerides was independently associated with risk of incident CVD. Of the blood pressure variables, areas under the mean arterial pressure vs time curve and the pulse pressure vs time curve were strongly and independently associated with incident CVD risk. The quantitative description of the link between risk factors and CVD informs the construction of individualized CVD mitigation strategies, design of primary prevention trials, and assessment of public health impact of risk factor-based interventions. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The Pooled Cohort Equations (PCEs) are race- and sex-specific Cox proportional hazards (PH)-based models used for 10-year atherosclerotic cardiovascular disease (ASCVD) risk prediction with acceptable discrimination. In recent years, neural network models have gained increasing popularity with their success in image recognition and text classification. Various survival neural network models have been proposed by combining survival analysis and neural network architecture to take advantage of the strengths from both. However, the performance of these survival neural network models compared to each other and to PCEs in ASCVD prediction is unknown. Methods: In this study, we used 6 cohorts from the Lifetime Risk Pooling Project (with 5 cohorts as training/internal validation and one cohort as external validation) and compared the performance of the PCEs in 10-year ASCVD risk prediction with an all two-way interactions Cox PH model (Cox PH-TWI) and three state-of-the-art neural network survival models including Nnet-survival, Deepsurv, and Cox-nnet. For all the models, we used the same 7 covariates as used in the PCEs. We fitted each of the aforementioned models in white females, white males, black females, and black males, respectively. We evaluated models' internal and external discrimination power and calibration. Results: The training/internal validation sample comprised 23216 individuals. The average age at baseline was 57.8 years old (SD = 9.6); 16% developed ASCVD during average follow-up of 10.50 (SD = 3.02) years. Based on 10 × 10 cross-validation, the method that had the highest C-statistics was Deepsurv (0.7371) for white males, Deepsurv and Cox PH-TWI (0.7972) for white females, PCE (0.6981) for black males, and Deepsurv (0.7886) for black females. In the external validation dataset, Deepsurv (0.7032), Cox-nnet (0.7282), PCE (0.6811), and Deepsurv (0.7316) had the highest C-statistics for white male, white female, black male, and black female population, respectively. Calibration plots showed that in 10 × 10 validation, all models had good calibration in all race and sex groups. In external validation, all models overestimated the risk for 10-year ASCVD. Conclusions: We demonstrated the use of the state-of-the-art neural network survival models in ASCVD risk prediction. Neural network survival models had similar if not superior discrimination and calibration compared to PCEs. [ABSTRACT FROM AUTHOR]

Decreased consumption of nicotine and other drugs during pregnancy appears to be a cross-species phenomenon from which mechanism(s) capable of interrupting addictive processes could be elucidated. Whether pregnancy influences smoking behaviour independent of women's knowledge of the pregnancy, however, has not been considered. Using repeated measures analysis of variance (ANOVA), we estimated within-person change in mean cigarettes/day smoked across the estimated date of conception but prior to individually reported dates of pregnancy recognition using longitudinal smoking data from two independent observational cohorts, the Growing Up Healthy (GUH, n = 271) and Midwest Infant Development Studies (MIDS, n = 145). Participants smoked an average of half a pack/day in the month immediately before conception (M (SD) = 12(8.1) and 9.5(6.7) cigarettes/day in GUH and MIDS, respectively). We observed within-person declines in smoking after conception, both before (MGUH  = -0.9; 95% CI -1.6, -0.2; p = 0.01; MMIDS  = -1.1; 95% CI -1.9, -0.3; p = 0.01) and after (MGUH  = -4.8; 95% CI -5.5, -4.1; p < 0.001; MMIDS  = -3.3; 95% CI -4.4, -2.5; p < 0.001) women were aware of having conceived, even when women who had quit and women who were planning to conceive were excluded from analyses. Pregnancy may interrupt smoking-related processes via mechanisms not previously considered. Plausible candidates and directions for future research are discussed. [ABSTRACT FROM AUTHOR]

Background: The American Heart Association recently published an updated algorithm for quantifying cardiovascular health (CVH)-the Life's Essential 8 score. We quantified US levels of CVH using the new score.Methods: We included individuals ages 2 through 79 years (not pregnant or institutionalized) who were free of cardiovascular disease from the National Health and Nutrition Examination Surveys in 2013 through 2018. For all participants, we calculated the overall CVH score (range, 0 [lowest] to 100 [highest]), as well as the score for each component of diet, physical activity, nicotine exposure, sleep duration, body mass index, blood lipids, blood glucose, and blood pressure, using published American Heart Association definitions. Sample weights and design were incorporated in calculating prevalence estimates and standard errors using standard survey procedures. CVH scores were assessed across strata of age, sex, race and ethnicity, family income, and depression.Results: There were 23 409 participants, representing 201 728 000 adults and 74 435 000 children. The overall mean CVH score was 64.7 (95% CI, 63.9-65.6) among adults using all 8 metrics and 65.5 (95% CI, 64.4-66.6) for the 3 metrics available (diet, physical activity, and body mass index) among children and adolescents ages 2 through 19 years. For adults, there were significant differences in mean overall CVH scores by sex (women, 67.0; men, 62.5), age (range of mean values, 62.2-68.7), and racial and ethnic group (range, 59.7-68.5). Mean scores were lowest for diet, physical activity, and body mass index metrics. There were large differences in mean scores across demographic groups for diet (range, 23.8-47.7), nicotine exposure (range, 63.1-85.0), blood glucose (range, 65.7-88.1), and blood pressure (range, 49.5-84.0). In children, diet scores were low (mean 40.6) and were progressively lower in higher age groups (from 61.1 at ages 2 through 5 to 28.5 at ages 12 through 19); large differences were also noted in mean physical activity (range, 63.1-88.3) and body mass index (range, 74.4-89.4) scores by sociodemographic group.Conclusions: The new Life's Essential 8 score helps identify large group and individual differences in CVH. Overall CVH in the US population remains well below optimal levels and there are both broad and targeted opportunities to monitor, preserve, and improve CVH across the life course in individuals and the population. [ABSTRACT FROM AUTHOR]

Background: Racial differences in cardiovascular disease (CVD) are likely related to differences in clinical and social factors. The relative contributions of these factors to Black-White differences in premature CVD have not been investigated.Methods: In Black and White adults aged 18 to 30 years at baseline in the CARDIA study (Coronary Artery Risk Development in Young Adults), the associations of clinical, lifestyle, depression, socioeconomic, and neighborhood factors across young adulthood with racial differences in incident premature CVD were evaluated in sex-stratified, multivariable-adjusted Cox proportional hazards models using multiply imputed data assuming missing at random. Percent reduction in the β estimate (log-hazard ratio [HR]) for race quantified the contribution of each factor group to racial differences in incident CVD.Results: Among 2785 Black and 2327 White participants followed for a median 33.9 years (25th-75th percentile, 33.7-34.0), Black (versus White) adults had a higher risk of incident premature CVD (Black women: HR, 2.44 [95% CI, 1.71-3.49], Black men: HR, 1.59 [1.20-2.10] adjusted for age and center). Racial differences were not statistically significant after full adjustment (Black women: HR, 0.91 [0.55-1.52], Black men: HR 1.02 [0.70-1.49]). In women, the largest magnitude percent reduction in the β estimate for race occurred with adjustment for clinical (87%), neighborhood (32%), and socioeconomic (23%) factors. In men, the largest magnitude percent reduction in the β estimate for race occurred with an adjustment for clinical (64%), socioeconomic (50%), and lifestyle (34%) factors.Conclusions: In CARDIA, the significantly higher risk for premature CVD in Black versus White adults was statistically explained by adjustment for antecedent multilevel factors. The largest contributions to racial differences were from clinical and neighborhood factors in women, and clinical and socioeconomic factors in men. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: DNA methylation-based GrimAge acceleration (GrimAA) is associated with a wide range of age-related health outcomes including cardiovascular disease. Since DNA methylation is modifiable by external and behavioral exposures, it is important to identify which of these exposures may have the strongest contributions to differences in GrimAA, to help guide potential intervention strategies. Here, we assessed the relative contributions of lifestyle- and health-related components, as well as their collective association, to GrimAA. Results: We included 744 participants (391 men and 353 women) from the Coronary Artery Risk Development in Young Adults (CARDIA) study with blood DNA methylation information at CARDIA Exam Year (Y) 20 (2005–2006, mean age 45.9 years). Six cumulative exposures by Y20 were included in the analysis: total packs of cigarettes, total alcohol consumption, education years, healthy diet score, sleep hours, and physical activity. We used quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods to assess the relative contribution of each exposure to a single overall association with GrimAA. We also assessed the collective association of the six components combined with GrimAA. Smoking showed the greatest positive contribution to GrimAA, accounting for 83.5% of overall positive associations of the six exposures with GrimAA (QGC weight = 0.835). The posterior inclusion probability (PIP) of smoking also achieved the highest score of 1.0 from BKMR analysis. Healthy diet and education years showed inverse contributions to GrimAA. We observed a U-shaped pattern in the contribution of alcohol consumption to GrimAA. While smoking was the greatest contributor across sex and race subgroups, the relative contributions of other components varied by subgroups. Conclusions: Smoking, alcohol consumption, and education showed the highest contributions to GrimAA in our study. Higher amounts of smoking and alcohol consumption were likely to contribute to greater GrimAA, whereas achieved education was likely to contribute to lower GrimAA. Identifying pertinent lifestyle- and health-related exposures in a context of collective components can provide direction for intervention strategies and suggests which components should be the primary focus for promoting younger GrimAA. [ABSTRACT FROM AUTHOR]

Background Vascular risk scores are associated with incident dementia. Information regarding their association with cognitive performance and decline in racially/ethnically diverse cohorts is lacking. Method In 4 392 Multi-Ethnic Study of Atherosclerosis participants (aged 60.1 ± 9.4 years; 53% women; 41% White, 11% Chinese American, 26% African American, 21% Hispanic), we compared associations of Exam 1 (2000–2002) Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE), Framingham Stroke Risk Profile (FSRP), and atherosclerotic cardiovascular disease pooled cohort equation (ASCVD-PCE) risk scores with Exam 5 (2010–2012) Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC), and Digit Span (DS) cognitive test performance using multivariable linear regression, and examined racial/ethnic interactions. In 1 838 participants with repeat CASI data at Exam 6 (2016–2018), we related risk scores to odds of a 1- SD decline in CASI performance using multivariable logistic regression. Results SD increments in each risk score were associated with worse cognitive performance. CAIDE had stronger associations with CASI performance than the FSRP and ASCVD-PCE, but associations of ASCVD-PCE with the DSC and DS were similar to CAIDE (difference in β [95% CI] = −0.57 [−1.48, 0.34] and −0.21 [−0.43, 0.01], respectively). Race/ethnicity modified associations. For example, associations between CAIDE and CASI were greater in African Americans and Hispanics than in Whites (difference in β = 0.69 [0.02, 1.36] and 1.67 [0.95, 2.39], respectively). Risk scores were comparably associated with decline in CASI performance. Conclusions Antecedent vascular risk scores are associated with cognitive performance and decline in the 4 most common U.S. racial/ethnic groups, but associations differ among risk scores and by race/ethnicity. [ABSTRACT FROM AUTHOR]

Cerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. The retina allows for visualization of a microvascular bed that shares similarities with the cerebral microvasculature. We investigated the associations between baseline retinal arteriolar and venular calibers (central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively) and incident depressive symptoms in the Multi-Ethnic Study of Atherosclerosis (MESA). We used longitudinal data on 4,366 participants (mean age = 63.2 years; 48.5% women, 28.4% Black) without baseline depressive symptoms. Depressive symptoms, defined as Center for Epidemiologic Studies Depression Scale score ≥16 and/or use of antidepressant medication, were determined between 2002 and 2004 (baseline; MESA visit 2) and at 3 follow-up examinations conducted every 1.5–2 years thereafter. Fundus photography was performed at baseline. After a mean follow-up period of 6.1 years, 21.9% (n  = 958) had incident depressive symptoms. After adjustment for sociodemographic, lifestyle, and cardiovascular factors, a 1–standard-deviation larger baseline CRVE was associated with a higher risk of depressive symptoms (hazard ratio = 1.10, 95% confidence interval: 1.02, 1.17), and a 1–standard-deviation larger baseline CRAE was not statistically significantly associated with incident depressive symptoms (hazard ratio = 1.04, 95% confidence interval: 0.97, 1.11). In this study, larger baseline CRVE, but not CRAE, was associated with a higher incidence of depressive symptoms. [ABSTRACT FROM AUTHOR]

Objective. We evaluated the association of apolipoprotein B (apoB) with low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides (TG) in early adulthood with concordant/discordant associations and midlife NAFLD. Methods. Participants from the CARDIA study were included (n = 2,655; baseline mean age: 25.0, 59.1% female, and 48.6% black). NAFLD was defined as liver attenuation ≤40 Hounsfield units after excluding other causes of liver fat. Logistic regression models assessed the odds of Y25 NAFLD among tertiles of apoB, LDL-C, non-HDL-C, and TG and quartiles of the apoB/TG ratio. Discordance/concordance analyses examined the association of apoB with each lipid marker and Y25 NAFLD. Results. The Y25 NAFLD prevalence was 10%. The high-tertile TG group (OR 1.87, 95% CI, and 1.30–2.69) and the low- (OR 1.98, 95% CI, and 1.30–3.01) and middle-apoB/TG ratio groups (OR 1.78, 95% CI, and 1.17–2.72) had the greatest odds of midlife NAFLD. Using discordance/concordance analysis, the high-apoB/high-TG group had the highest odds of NAFLD (OR 1.69, 95% CI, and 1.09–2.61) followed by the low-apoB/high-TG group. The high apoB/low TG group had the lowest odds of NAFLD. Conclusions. Among the studied lipid markers in early adulthood, TG levels have the strongest and most consistent association with midlife NAFLD. [ABSTRACT FROM AUTHOR]

Background: Geographic heterogeneity in COVID-19 outcomes in the United States is well-documented and has been linked with factors at the county level, including sociodemographic and health factors. Whether an integrated measure of place-based risk can classify counties at high risk for COVID-19 outcomes is not known.Methods: We conducted an ecological nationwide analysis of 2,701 US counties from 1/21/20 to 2/17/21. County-level characteristics across multiple domains, including demographic, socioeconomic, healthcare access, physical environment, and health factor prevalence were harmonized and linked from a variety of sources. We performed latent class analysis to identify distinct groups of counties based on multiple sociodemographic, health, and environmental domains and examined the association with COVID-19 cases and deaths per 100,000 population.Results: Analysis of 25.9 million COVID-19 cases and 481,238 COVID-19 deaths revealed large between-county differences with widespread geographic dispersion, with the gap in cumulative cases and death rates between counties in the 90th and 10th percentile of 6,581 and 291 per 100,000, respectively. Counties from rural areas tended to cluster together compared with urban areas and were further stratified by social determinants of health factors that reflected high and low social vulnerability. Highest rates of cumulative COVID-19 cases (9,557 [2,520]) and deaths (210 [97]) per 100,000 occurred in the cluster comprised of rural disadvantaged counties.Conclusions: County-level COVID-19 cases and deaths had substantial disparities with heterogeneous geographic spread across the US. The approach to county-level risk characterization used in this study has the potential to provide novel insights into communicable disease patterns and disparities at the local level. [ABSTRACT FROM AUTHOR]

Background: Raised low-density lipoprotein cholesterol (LDL-C) in young adulthood (aged 18-39 years) is associated with atherosclerotic cardiovascular disease (ASCVD) later in life. Most young adults with elevated LDL-C do not currently receive lipid-lowering treatment.Objectives: This study aimed to estimate the prevalence of elevated LDL-C in ASCVD-free U.S. young adults and the cost-effectiveness of lipid-lowering strategies for raised LDL-C in young adulthood compared with standard care.Methods: The prevalence of raised LDL-C was examined in the U.S. National Health and Nutrition Examination Survey. The CVD Policy Model projected lifetime quality-adjusted life years (QALYs), health care costs, and incremental cost-effectiveness ratios (ICERs) for lipid-lowering strategies. Standard care was statin treatment for adults aged ≥40 years based on LDL-C, ASCVD risk, or diabetes plus young adults with LDL-C ≥190 mg/dL. Lipid lowering incremental to standard care with moderate-intensity statins or intensive lifestyle interventions was simulated starting when young adult LDL-C was either ≥160 mg/dL or ≥130 mg/dL.Results: Approximately 27% of ASCVD-free young adults have LDL-C of ≥130 mg/dL, and 9% have LDL-C of ≥160 mg/dL. The model projected that young adult lipid lowering with statins or lifestyle interventions would prevent lifetime ASCVD events and increase QALYs compared with standard care. ICERs were US$31,000/QALY for statins in young adult men with LDL-C of ≥130 mg/dL and US$106,000/QALY for statins in young adult women with LDL-C of ≥130 mg/dL. Intensive lifestyle intervention was more costly and less effective than statin therapy.Conclusions: Statin treatment for LDL-C of ≥130 mg/dL is highly cost-effective in young adult men and intermediately cost-effective in young adult women. [ABSTRACT FROM AUTHOR]

The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. Data were pooled from 5 longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults, Special Turku Coronary Risk Factor Intervention Project) from the United States and Finland from 1973 to 2012. Individuals with clinical CVH factors (i.e. body mass index, blood pressure, cholesterol, blood glucose) measured from ages 8 to 55 years were included. These factors were categorized and summed into a clinical CVH score ranging from 0 (worst) to 8 (best). Adjusted, segmented, linear mixed models were used to estimate the change in CVH over time. Among the 18,343 participants, 9,461 (52%) were female and 12,346 (67%) were White. The baseline mean (standard deviation) clinical CVH score was 6.9 (1.2) at an average age of 17.6 (8.1) years. Two inflection points were estimated: at 16.9 years (95% confidence interval: 16.4, 17.4) and at 37.2 years (95% confidence interval: 32.4, 41.9). Late adolescence and early middle age appear to be influential periods during which the loss of CVH accelerates. [ABSTRACT FROM AUTHOR]

We developed and validated a synthetic cohort approach to examine numbers of cardiovascular risk factors (CRFs) and adverse clinical events, including incident cardiovascular disease and all-cause mortality, across the life span from ages 20 years to 90 years. The current analysis included 40,875 participants from 7 large, population-based longitudinal epidemiologic studies (1948–2016). On the basis of a joint multilevel imputation model, we multiply imputed each participant's life-span numbers of CRFs and events using available records. To validate the imputed values, we partially removed the observed data and then compared the imputed and observed values. The complete life-span synthetic data set reflected the original observed data trends well. In our validation sample, the distributions of imputed CRFs and events were close to the observed distributions but with less variability. Bland-Altman plots indicated that there was a slightly negative trend in general, and the agreement bias was relatively small for the continuous CRFs. The hypothetical linear regression model suggested that the relationships between the CRFs and events were preserved in the imputed data set. This approach generated valid estimates of CRFs and events across the life span for African-American and White participants. The synthetic cohort may be sufficiently accurate to be useful in assessing the origins and timing of accumulating cardiovascular risk that can inform efforts to avoid cardiovascular disease development. [ABSTRACT FROM AUTHOR]

Introduction: Childhood declines in cardiovascular health have been linked to the development of subclinical atherosclerosis; however, less is known about the timing and sequence of the decline of the specific cardiovascular health components. The study objective is to identify the patterns of decline and associations with adulthood subclinical atherosclerosis.Methods: Data were pooled from 5 cardiovascular cohorts. Clinical components of cardiovascular health (BMI, blood pressure, cholesterol, and blood glucose) were categorized as ideal or nonideal using American Heart Association definitions. Multitrajectory models simultaneously fitted the probability ideal for each factor. Adjusted associations between trajectory groups and carotid intima-media thickness were modeled. Data were pooled from December 1, 2015 to June 1, 2019; statistical analysis occurred between June 1, 2019 and June 1, 2020.Results: This study included 9,388 individuals (55% female, 66% White). A total of 5 distinct trajectory groups were created: 1 maintained the ideal levels of all the 4 health factors, 2 had risk onset of a single factor in childhood, 1 had risk onset of multiple factors in childhood, and 1 had risk onset in adulthood. Those with childhood multiple risk onset had 8.1% higher carotid intima-media thickness (95% CI=0.067, 0.095) than those in the ideal group, childhood cholesterol risk onset had 5.9% higher carotid intima-media thickness (95% CI=0.045, 0.072), childhood BMI risk onset had 5.5% higher carotid intima-media thickness (95% CI=0.041, 0.069), and early adulthood multiple risk onset had 2.7% higher carotid intima-media thickness (95% CI=0.013, 0.041).Conclusions: Those who lost the ideal status of cardiovascular health in childhood and early adulthood had more subclinical atherosclerosis than those who retained the ideal cardiovascular health across the life course, underscoring the importance of preserving the ideal cardiovascular health beginning in childhood and continued into adulthood. [ABSTRACT FROM AUTHOR]

Background: Lower exercise capacity, as measured by 6-minute walk distance (6MWD), is associated with incident heart failure (HF). Among those without HF, the associations of measures of cardiac function with 6MWD are unclear, and may provide insight regarding the risk of incident HF.Objectives: The purpose of this study was to understand the relationships between cardiac function and exercise capacity.Methods: This study evaluated the associations of cardiac mechanics with 6MWD in the sixth examination of the Multi-Ethnic Study of Atherosclerosis. Echocardiography (2-dimensional, Doppler, and speckle-tracking) was performed at rest and after passive leg raise to evaluate functional reserve after intravascular volume challenge.Results: Of 2,096 participants without HF (mean age 73 years, 48% men, 58% non-White), individuals with lower (worse) left atrial (LA) reservoir strain were older and had higher blood pressure. Lower resting LA reservoir strain (β coefficient per SD decrease: -5.0; 95% confidence interval [CI]: -8.8 to -1.3 m; p = 0.009), inability to augment LA reservoir strain after passive leg raise (β coefficient per SD decrease: -5.8; 95% CI: -9.1 to -2.5 m; p < 0.001), and lower right atrial reservoir strain (β coefficient per SD decrease: -4.4; 95% CI: -7.8 to -1.1 m; p = 0.01) were associated with shorter 6MWD. Worse left ventricular (LV) diastolic function was also associated with lower 6MWD. There were no independent associations of measures of LV systolic function (global longitudinal strain, circumferential strain, ejection fraction) with 6MWD.Conclusions: Among individuals without HF, worse biatrial function, lack of LA functional reserve, and worse LV diastolic function were associated with reduced submaximal exercise capacity. Therapies aimed to improve these functional domains may increase exercise capacity and prevent HF. [ABSTRACT FROM AUTHOR]

DNA methylation (DNAm)-based biological age (epigenetic age) has been suggested as a useful biomarker of age-related conditions including type 2 diabetes (T2D), and its newest iterations (GrimAge measurements) have shown early promise. In this study, we explored the association between epigenetic age and incident T2D in the context of their relationships with obesity. A total of 1,057 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were included in the current analyses. We stratified the participants into three groups: normal weight, overweight, and obese. A 1-year increase of GrimAge was associated with higher 10-year (study years 15-25) incidence of T2D (odds ratio [OR] 1.06, 95% CI 1.01-1.11). GrimAge acceleration, which represents the deviation of GrimAge from chronological age, was derived from the residuals of a model of GrimAge and chronological age, and any GrimAge acceleration (positive GrimAA: having GrimAge older than chronological age) was associated with significantly higher odds of 10-year incidence of T2D in obese participants (OR 2.57, 95% CI 1.61-4.11). Cumulative obesity was estimated by years since obesity onset, and GrimAge partially mediated the statistical association between cumulative obesity and incident diabetes or prediabetes (proportion mediated = 8.0%). In conclusion, both older and accelerated GrimAge were associated with higher risk of T2D, particularly among obese participants. GrimAge also statistically mediated the associations between cumulative obesity and T2D. Our findings suggest that epigenetic age measurements with DNAm can potentially be used as a risk factor or biomarker associated with T2D development. [ABSTRACT FROM AUTHOR]