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In 2010, the American Heart Association defined a novel construct of cardiovascular health to promote a paradigm shift from a focus solely on disease treatment to one inclusive of positive health promotion and preservation across the life course in populations and individuals. Extensive subsequent evidence has provided insights into strengths and limitations of the original approach to defining and quantifying cardiovascular health. In response, the American Heart Association convened a writing group to recommend enhancements and updates. The definition and quantification of each of the original metrics (Life's Simple 7) were evaluated for responsiveness to interindividual variation and intraindividual change. New metrics were considered, and the age spectrum was expanded to include the entire life course. The foundational contexts of social determinants of health and psychological health were addressed as crucial factors in optimizing and preserving cardiovascular health. This presidential advisory introduces an enhanced approach to assessing cardiovascular health: Life's Essential 8. The components of Life's Essential 8 include diet (updated), physical activity, nicotine exposure (updated), sleep health (new), body mass index, blood lipids (updated), blood glucose (updated), and blood pressure. Each metric has a new scoring algorithm ranging from 0 to 100 points, allowing generation of a new composite cardiovascular health score (the unweighted average of all components) that also varies from 0 to 100 points. Methods for implementing cardiovascular health assessment and longitudinal monitoring are discussed, as are potential data sources and tools to promote widespread adoption in policy, public health, clinical, institutional, and community settings. [ABSTRACT FROM AUTHOR]

The National Institute of Mental Health's Research Domain Criteria (RDoC) framework has prompted a paradigm shift from categorical psychiatric disorders to considering multiple levels of vulnerability for probabilistic risk of disorder. However, the lack of neurodevelopmentally based tools for clinical decision making has limited the real-world impact of the RDoC. Integration with developmental psychopathology principles and statistical methods actualize the clinical implementation of RDoC to inform neurodevelopmental risk. In this conceptual paper, we introduce the probabilistic mental health risk calculator as an innovation for such translation and lay out a research agenda for generating an RDoC- and developmentally informed paradigm that could be applied to predict a range of developmental psychopathologies from early childhood to young adulthood. We discuss methods that weigh the incremental utility for prediction based on intensity and burden of assessment, the addition of developmental change patterns, considerations for assessing outcomes, and integrative data approaches. Throughout, we illustrate the risk calculator approach with different neurodevelopmental pathways and phenotypes. Finally, we discuss real-world implementation of these methods for improving early identification and prevention of developmental psychopathology. We propose that mental health risk calculators can build a needed bridge between the RDoC multiple units of analysis and developmental science. [ABSTRACT FROM AUTHOR]

The ability of a 1-time measurement of non–high-density lipoprotein cholesterol (non–HDL-C) or low-density lipoprotein cholesterol (LDL-C) to predict the cumulative exposure to these lipids during early adulthood (age 18-40 years) and the associated atherosclerotic cardiovascular disease (ASCVD) risk after age 40 years is not clear. The objectives of this study were to evaluate whether a 1-time measurement of non-HDL-C or LDL-C in a young adult can predict cumulative exposure to these lipids during early adulthood, and to quantify the association between cumulative exposure to non-HDL-C or LDL-C during early adulthood and the risk of ASCVD after age 40 years. We included CARDIA (Coronary Artery Risk Development in Young Adults Study) participants who were free of cardiovascular disease before age 40 years, were not taking lipid-lowering medications, and had ≥3 measurements of LDL-C and non–HDL-C before age 40 years. First, we assessed the ability of a 1-time measurement of LDL-C or non–HDL-C obtained between age 18 and 30 years to predict the quartile of cumulative lipid exposure from ages 18 to 40 years. Second, we assessed the associations between quartiles of cumulative lipid exposure from ages 18 to 40 years with ASCVD events (fatal and nonfatal myocardial infarction and stroke) after age 40 years. Of 4,104 CARDIA participants who had multiple lipid measurements before and after age 30 years, 3,995 participants met our inclusion criteria and were in the final analysis set. A 1-time measure of non–HDL-C and LDL-C had excellent discrimination for predicting membership in the top or bottom quartiles of cumulative exposure (AUC: 0.93 for the 4 models). The absolute values of non–HDL-C and LDL-C that predicted membership in the top quartiles with the highest simultaneous sensitivity and specificity (highest Youden's Index) were >135 mg/dL for non–HDL-C and >118 mg/dL for LDL-C; the values that predicted membership in the bottom quartiles were <107 mg/dL for non–HDL-C and <96 mg/dL for LDL-C. Individuals in the top quartile of non–HDL-C and LDL-C exposure had demographic-adjusted HRs of 4.6 (95% CI: 2.84-7.29) and 4.0 (95% CI: 2.50-6.33) for ASCVD events after age 40 years, respectively, when compared with each bottom quartile. Single measures of non–HDL-C and LDL-C obtained between ages 18 and 30 years are highly predictive of cumulative exposure before age 40 years, which in turn strongly predicts later-life ASCVD events. [ABSTRACT FROM AUTHOR]

Background: Protein-rich foods are major parts of the human diet and are highly heterogeneous in nutrient composition and health effects. Designing healthy diets for disease prevention requires careful consideration of substituting unhealthier protein foods with healthier protein foods.Methods: This was a pooled analysis of six prospective cohort studies of 29 682 US participants. Data were collected in 1985-2016. Adjusted hazard ratios (HRs) and 30-year absolute risk differences (ARDs) were calculated for the associations between simultaneous substitution of one or more animal protein foods with other animal or plant protein foods at various amounts, and incident cardiovascular disease (CVD) and all-cause mortality.Results: Substituting eggs, processed meat, unprocessed red meat or poultry with nuts, whole grains, legumes or fish was associated with lower risks of incident CVD and all-cause mortality. According to different substitution amounts (varying from one serving per week to one serving per day) and different numbers of protein foods being simultaneously substituted (varying from one to four), estimates ranged between 1%: HR, 0.99 [95% confidence interval (CI), 0.98-1.00], and 54%: HR, 0.46 (0.35-0.60), lower risks on the relative scale and between 0.3%: ARD, -0.29% (-0.48% to -0.05%), and 14.0%: ARD, -13.96% (-17.29% to -9.96%) lower risks on the absolute scale.Conclusions: Nuts, whole grains, legumes and fish appeared to be healthier protein sources than eggs, processed meat, unprocessed red meat and poultry for preventing incident CVD and premature death. The magnitude of lower risk for incident CVD and all-cause mortality was driven by amount and number of animal protein foods substituted. [ABSTRACT FROM AUTHOR]

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. [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 (ie, 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]

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]

Objective: To determine whether the duration of diabetes and duration of prediabetes estimated during a 25-year period in early adulthood are each independently associated with coronary artery calcified plaque (CAC) and abnormalities in left ventricular structure and function later in life.Research Design and Methods: Participants were 3,628 white and black adults aged 18-30 years without diabetes or prediabetes at baseline (1985-1986) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Durations of diabetes and prediabetes were estimated based on their identification at examinations 7, 10, 15, 20, and 25 years later. CAC was identified by computed tomography at years 15, 20, and 25. Left ventricular structure and function were measured via echocardiogram at year 25.Results: Of the 3,628 individuals, 12.7% and 53.8% developed diabetes and prediabetes, respectively; average (SD) duration was 10.7 (10.7) years and 9.5 (5.4) years. After adjustment for sociodemographic characteristics and other cardiovascular risk factors, and mutual adjustment for each other, the hazard ratio for the presence of CAC was 1.15 (95% CI 1.06, 1.25) and 1.07 (1.01, 1.13) times higher for each 5-year-longer duration of diabetes and prediabetes, respectively. Diabetes and prediabetes duration were associated with worse subclinical systolic function (longitudinal strain [Ptrend < 0.001 for both]) and early diastolic relaxation (e' [Ptrend 0.004 and 0.002, respectively]). Duration of diabetes was also associated with a higher diastolic filling pressure (E-to-e' ratio [Ptrend 0.001]).Conclusions: Durations of diabetes and prediabetes during adulthood are both independently associated with subclinical atherosclerosis and left ventricular systolic and diastolic dysfunction in middle age. [ABSTRACT FROM AUTHOR]

Background: We sought to identify depressive symptom subgroups in a community sample of young adults, investigate their stability over time, and determine their association with prevalent and incident cardiovascular disease (CVD) risk factors. Method: Participants were 3377 adults from the Coronary Artery Risk Development in Young Adults study. Using latent class and latent transition analysis, we derived subgroups based on items of the 20-item version of the Center for Epidemiologic Studies Depression Scale in 1990, and examined patterns of change over a 10-year period (1990–2000). Cox regression models were used to examine associations between subgroup membership and prevalent (2000) and incident (2000 to 2016) obesity, hypertension, and diabetes. Results: Three baseline subgroups were identified and labeled: "No Symptoms" (63.5%), "Lack of Positive Affect" (PA, 25.6%), and "Depressed Mood" (10.9%). At 10-year follow-up, individuals in "No Symptoms" subgroup had the highest probability (0.84) of being classified within the same subgroup. Participants classified as "Lack of PA" were likely (0.46) to remain in the same subgroup or be classified as "No Symptoms." Participants in the "Depressed Mood" were most likely to transition to the "Lack of PA" subgroup (0.38). Overall, 30.5% of participants transitioned between subgroups, with 11.4% classified as "Worsening" and 19.1% as "Improving." Relative to the "No Symptoms Stable," other subgroups ("Depressed Stable," "Worsening," and "Improving") were associated with prevalent obesity and hypertension. Conclusion: We identified distinct depressive symptom subgroups that are variably stable over time, and their change patterns were differentially associated with CVD risk factor prevalence. [ABSTRACT FROM AUTHOR]

We examined the population distribution of urinary sodium concentrations and the validity of existing equations predicting 24-hour sodium excretion from a single spot urine sample among older adults with and without hypertension. In 2013, 24-hour urine collections were obtained from 554 participants in the Multi-Ethnic Study of Atherosclerosis and the Coronary Artery Risk Development in Young Adults study, who were aged 45-79 years and of whom 56%were female, 58%were African American, and 54%had hypertension, in Chicago, Illinois. One-third provided a second 24-hour collection. Four timed (overnight, morning, afternoon, and evening) spot urine specimens and the 24-hour collection were analyzed for sodium and creatinine concentrations. Mean 24-hour sodium excretion was 3,926 (standard deviation (SD), 1,623) mg for white men, 2,480 (SD, 1,079) mg for white women, 3,454 (SD, 1,651)mg for African-Americanmen, and 3,397 (SD, 1,641)mg for African-American women, and did not differ significantly by hypertensive status.Mean bias (difference) in predicting 24-hour sodiumexcretion fromthe timed spot urine specimens ranged from -182 (95% confidence interval: -285, -79) to 1,090 (95% confidence interval: 966, 1,213) mg/day overall. Although the Tanaka equation using the evening specimen produced the least bias overall, no single equation worked well across subgroups of sex and race/ethnicity. A single spot urine sample is not a valid indicator of individual sodiumintake. New equations are needed to accurately estimate 24-hour sodiumexcretion for older adults. [ABSTRACT FROM AUTHOR]

Background: We examined the association of cardiovascular health at younger ages with the proportion of life lived free of morbidity, the cumulative burden of morbidity, and average healthcare costs at older ages.Methods: The CHA study (Chicago Heart Association Detection Project in Industry) is a longitudinal cohort of employed men and women 18 to 74 years of age at baseline examination in 1967 to 1973. Baseline measurements included blood pressure, cholesterol, diabetes mellitus, body mass index, and smoking. Individuals were classified into 1 of 4 strata of cardiovascular health: favorable levels of all factors, 0 factors high but ≥1 elevated risk factors, 1 high risk factor, and ≥2 high risk factors. Linked Medicare and National Death Index data from 1984 to 2010 were used to determine morbidity in older age. An individual's all-cause morbidity score and cardiovascular morbidity score were calculated from International Classification of Disease, Ninth Revision codes for each year of follow-up.Results: We included 25 804 participants who became ≥65 years of age by 2010, representing 65% of all original CHA participants (43% female; 90% white; mean age, 44 years at baseline); 6% had favorable levels of all factors, 19% had ≥1 risk factors at elevated levels, 40% had 1 high risk factor, and 35% had ≥2 high risk factors. Favorable cardiovascular health at younger ages extended survival by almost 4 years and postponed the onset of all-cause and cardiovascular morbidity by 4.5 and 7 years, respectively, resulting in compression of morbidity in both absolute and relative terms. This translated to lower cumulative and annual healthcare costs for those in favorable cardiovascular health (P<0.001) during Medicare eligibility.Conclusions: Individuals in favorable cardiovascular health in early middle age live a longer, healthier life free of all types of morbidity. These findings provide strong support for prevention efforts earlier in life aimed at preserving cardiovascular health and reducing the burden of disease in older ages. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to examine the association between ideal cardiovascular health (CVH) and health-related quality of life and health status indicators.Methods: This cross-sectional study included adult NHANES participants from 2001 to 2010 without CVD (N = 7115). CVH was defined according to AHA definitions with poor, intermediate and ideal levels of the seven factors (diet, BMI, physical activity, smoking, blood pressure, glucose, and cholesterol) assigned scores of 0, 1, and 2, respectively. A CVH score (CVHS) was calculated as the sum of the scores from each individual health factor (range 0-14; higher score indicating greater CVH). CVHS was categorized as poor (0-7), intermediate (8-10), and ideal (11-14). Linear regression models examined the association between CVHS category with health status and number of unhealthy days per month, adjusted for socio-demographic characteristics and disability.Results: Among US adults 20-79 years, 14, 46 and 40% had ideal, intermediate and poor CVHS, respectively. Compared to those with poor CVH, individuals in intermediate and ideal CVH were 44 and 71% less likely to report being in fair/poor health. Participants with ideal CVH scores reported a mean of 2.4 fewer unhealthy days over the past month, including one less day in which their physical health was not good and two fewer days in which their mental health was not good.Conclusions: Ideal CVH is associated with greater overall health status and fewer physically and mentally unhealthy days. [ABSTRACT FROM AUTHOR]

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 H U 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. [ABSTRACT FROM AUTHOR]

Background and Purpose: Of the 795,000 strokes occurring in the USA each year, over 20% are recurrent events. Little is known about how the rates of recurrent stroke in the country have changed over time. Our objective was to determine national trends in 1-year recurrent ischemic stroke rates by US county among the elderly from 1994 to 2002. Methods: One-year recurrent stroke rates following incident ischemic stroke (ICD-9 433, 434, 436) among all fee-for-service Medicare beneficiaries were determined by US county for 1994-1996, 1997-1999, and 2000-2002. Bayesian spatiotemporal Poisson modeling was used to determine county-specific trends in recurrent stroke rates over time with risk adjustment for demographics, medical history and comorbid conditions. Results: The analysis included more than 2.5 million beneficiaries (56% women; mean age: 78 years; 87% white; n = 957,933 for 1994-1996; n = 838,330 for 1996-1999; n = 895,916 for 2000-2002) aggregated to all 3,118 US counties. After adjustment for changing patient demographics and comorbidities, there was a 4.5% decrease in recurrent stroke rates from 1994-1996 (13.2%) to 2000-2002 (12.6%; p for trend <0.0001). The geographic and temporal patterns were not uniform; the recurrent stroke rates decreased within sections of the Southeast (the 'stroke belt'), but increased in counties in the middle and western sections of the USA. Conclusions: The overall recurrent ischemic stroke rates declined by almost 5% from 1994 to 2002, but temporal patterns varied markedly by region. Additional research is needed to identify the reasons for this geographic disparity. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background and Purpose: Differences in the management of women and men with acute coronary symptoms are well documented, but relatively little is known about practices for patients with ischemic stroke. We sought to determine whether there are sex-associated differences in the utilization of diagnostic tests for ischemic stroke patients treated at academic hospitals in the United States. Methods: Medical records were abstracted for consecutive ischemic stroke patients admitted to 32 US academic medical centers from January through June, 2004, as part of the University HealthSystem Consortium Ischemic Stroke Benchmarking Project. We compared the utilization rates of diagnostic tests including neuroimaging (CT or MRI), electrocardiogram (ECG), ultrasound of the carotid arteries, and echocardiography (transthoracic or transesophageal) for women and men. Multivariate logistic regression was used to test for sex differences with adjustment for potential confounders. Results: The study included 1,256 ischemic stroke patients (611 women; 645 men; mean age 66.6 ± 14.6 years; 56% white). There were no differences between women and men in the use of neuroimaging (odds ratio, OR = 1.37; 95% confidence interval, CI = 0.58–3.24), ECG (OR = 1.00, 95% CI = 0.70–1.44), carotid artery ultrasound (OR = 0.93, 95% CI = 0.72–1.21) or echocardiography (OR = 0.70, 95% CI = 0.70–1.22). The results were similar after covariate adjustment. Conclusions: Women and men admitted to US academic hospitals receive comparable diagnostic evaluations, even after adjusting for sociodemographic and clinical factors. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: We evaluated whether there were sex-related differences in the administration of intravenous tissue plasminogen activator (IV-tPA) to patients with acute ischemic stroke admitted to US academic medical centers. Methods: Medical records were abstracted for consecutive ischemic stroke patients admitted to 32 academic medical centers from January through June, 2004, as part of the University HealthSystem Consortium Ischemic Stroke Benchmarking Project. Multivariate logistic models were used to test for sex-related differences in the receipt of IV-tPA with adjustment for demographic and clinical factors. Results: The study included 1,234 patients (49% women; mean age 66.6 years; 56% white). IV-tPA was given to 7% (6.5% of women versus 7.5% of men, p = 0.49). Women and men were equally likely to receive IV-tPA in risk-adjusted analyses (OR 1.02, 95% CI 0.64–1.64). Approximately 77% of women and men who did not receive IV-tPA did not meet the 3-hour treatment window or their time of onset was unknown. Conclusions: Women admitted to academic hospitals receive IV-tPA as often as men; however, a substantial percentage of both women and men are not arriving within the 3-hour time window required for diagnostic assessment and administration of intravenous thrombolytic therapy. Additional efforts are needed to improve the rapid identification, evaluation and treatment of stroke patients. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A major challenge in prenatal drug exposure research concerns the balance of measurement quality with sample sizes necessary to address confounders. To inform the selection of optimal exposure measures for the HEALthy Brain and Child Development (HBCD) Study, we employed integrated analysis to determine how different methods used to characterize prenatal tobacco exposure influence the detection of exposure-related risk, as reflected in normal variations in birth weight. Participants were N = 2323 mother-infant dyads derived from 7 independent developmental cohorts harmonized on measures of exposure, outcome (birthweight), and covariates. We compared estimates of PTE-related effects on birthweight derived from linear regression models when PTE was categorized dichotomously based on any fetal exposure (30% exposed; 69% not exposed); versus categorically, based on common patterns of maternal smoking during pregnancy (never smoked 69%; quit smoking 16%; smoked intermittently 2%; smoked persistently 13%). We secondarily explored sex differences in PTE-birthweight associations across these categorization methods. When PTE was categorized dichotomously, exposure was associated with a − 125-g difference in birthweight (95% C.I. -173.7 – −76.6, p <.0001). When PTE was characterized categorically based on maternal smoking patterns, however, exposure was associated with either no difference in birthweight if mothers quit smoking by the end of the first trimester (B = -30.6, 95% C.I. -88.7–27.4, p =.30); or a − 221.8 g difference in birthweight if mothers did not [95% C.I. (−161.7 to −282.0); p <.001]. Qualitative sex differences were also detected though PTE x sex interactions did not reach statistical significance. Maternal smoking cessation during pregnancy was associated with a 239.3 g increase in birthweight for male infants, and a 114.0 g increase in birthweight for females infants (p =.07). Categorization of PTE based on patterns of maternal smoking rather than the presence or absence of exposure alone revealed striking nuances in estimates of exposure-related risk. The described method that captures both between-individual and within-individual variability in prenatal drug exposure is optimal and recommended for future developmental investigations such as the HBCD Study. • Prenatal exposures are conventionally categorized dichotomously (exposed or not). • Within-person fluctuation in prenatal use is not captured by a dichotomous measure. • Maternal smoking cessation during pregnancy is a source of error in risk estimates. • Boys may be more sensitive to protective effects of prenatal smoking cessation. • Categorization of patterns of exposure is recommended for optimal risk detection. [ABSTRACT FROM AUTHOR]

Introduction: Ideal cardiovascular health is present in <50% of children and <1% of adults, yet its prevalence from adolescence through adulthood has not been fully evaluated. This study characterizes the association of age with ideal cardiovascular health and compares these associations across sex, race/ethnicity, and SES subgroups.Methods: This study, conducted in 2020, analyzed adolescents and adults aged 12-79 years from the cross-sectional National Health and Nutrition Examination Survey 2005-2016 (N=38,706). Polynomial models were used to model the association of age with ideal cardiovascular health, defined using the American Heart Association's Life's Simple 7 criteria (scales 0-14, with higher values indicating better cardiovascular health).Results: Mean cardiovascular health was lower with increasing age, starting in early adolescence and dropping to a nadir by age 60 years before stabilizing. At age 20 years, only 45% of adults had ideal cardiovascular health (≥5 ideal cardiovascular health metrics), and >50% of adults had poor cardiovascular health (≤2 ideal cardiovascular health metrics) at age 53 years. Women had higher mean cardiovascular health than men in early life but lower mean cardiovascular health from age 60 years onward. Mean cardiovascular health scores were highest for non-Hispanic White and higher-income adults and lowest for non-Hispanic Black and low-income adults across all ages. Mean cardiovascular health scores fell from intermediate to poor levels approximately 30 years earlier for non-Hispanic Black than for non-Hispanic White adults and approximately 35 years earlier for low-income adults than in higher-income adults.Conclusions: Cardiovascular health scores are lower with increasing age from early adolescence through adulthood. Race/ethnicity and income disparities in cardiovascular health are observed at young ages and are more profound at older ages. [ABSTRACT FROM AUTHOR]

Higher levels of perceived stress are associated with adverse cardiovascular health. It is plausible that these associations are attenuated among individuals with positive psychological factors such as social support and health-enhancing behaviors. Therefore, this study examined longitudinal associations of chronic stress with cardiovascular disease (CVD) events, and whether social support and physical activity (PA) modify these associations. Data from 3,401 adults (mean age 40.2 years; 46.7% Black; 56.2% women) from the Coronary Artery Risk Development in Young Adults (CARDIA) study, with no prior CVD event in 2000–2001 were analyzed. Chronic stress lasting ≥6 months across 5 life domains (work, financial, relationships, health of self, and health of close other) was self-reported. Adjudicated CVD events (fatal/or nonfatal CVD event) were ascertained yearly through 2020. PA and social support were self-reported via questionnaires. Statistical analyses were conducted in 2023 using multivariable stepwise Accelerated Failure Time analysis to assess associations between key study variables. The mean chronic stress score was 1.30±1.33 stressors and, by 2020, 220 participants had experienced a CVD event. Chronic stress was associated with lowered survival (time ratio: 0.92; 95% CI: 0.854–0.989), when adjusted for sociodemographic and lifestyle variables but no longer significant when adjusting for clinical factors. Neither PA nor social support were significant modifiers (all p s>0.05). Chronic stress was associated with the risk of having a CVD event among middle-aged adults, due at least in part to clinical mediators. Studies should continue exploring positive psychosocial and behavioral factors that may modify this association. [ABSTRACT FROM AUTHOR]

Given the high rates at which individuals with alcohol use disorder (AUD) utilize health care for co-existing conditions, health systems are promising venues for interventions that will facilitate access to AUD treatment. However, how individuals with AUD interact with such systems and, thus, how systems should intervene is unclear. In this study, we seek to identify patterns in how individuals diagnosed with AUD within an academic health system interacted with the system prior to diagnosis. We use electronic health records from a single academic health system in a major US metropolitan area to create a deidentified retrospective cohort including all individuals age 18+ diagnosed with AUD 2010–2019 (n = 26,899). Latent class analysis (LCA) identified subgroups defined by aspects of previous system interaction and health status, including having an in-system primary care provider, previous utilization of primary and specialty care, diagnosis setting, payer, and presence of other chronic conditions. We then assessed subgroup differences in demographics and associations with in-system AUD treatment receipt in the year following diagnosis, adjusting for demographics. The population was on average 38.6 years old (standard deviation = 15.4) and predominantly male (66.1 %), White (64.5 %), and not of Hispanic/Latino ethnicity (87.8 %). Only 4.7 % received in-system treatment following diagnosis. We deemed the four-class model the optimal LCA model. This model identified subgroups that can be described as 1) average utilization (20.7 % of population), 2) low utilization (54.5 %), 3) high health burden and low utilization (14.2 %), and 4) high health burden and high utilization (10.6 %). Predicted membership in the high health burden and high utilization subgroup and low utilization subgroup were associated with higher and lower odds of treatment receipt, respectively, compared with predicted membership in the average utilization subgroup (odds ratio (OR) for high/high subgroup = 1.21, 95 % confidence interval (CI) = 1.01, 1.27; OR for low subgroup = 0.29 95 % CI = 0.24, 0.34). Individuals diagnosed with AUD within a health system interact with that system in markedly different ways and are unlikely to benefit uniformly from system-based interventions to facilitate treatment. Group-tailored interventions are more likely to have impact and provide returns on investments for systems. • Individuals with AUD interact with health systems in four unique patterns. • Interventions to increase access to treatment should be tailored to these patterns. • Both interaction with the health care system and comorbidity burden are important. [ABSTRACT FROM AUTHOR]

Background: Youth use different forms of screen time (e.g., streaming, gaming) that may be related to body mass index (BMI). Screen time is non-independent from other behaviors, including physical activity and sleep duration. Statistical approaches such as isotemporal substitution or compositional data analysis (CoDA) can model associations between these non-independent behaviors and health outcomes. Few studies have examined different types of screen time, physical activity, and sleep duration simultaneously in relation to BMI. Methods: Data were baseline (2017–2018) and one-year follow-up (2018–2019) from the Adolescent Brain Cognitive Development Study, a multi-site study of a nationally representative sample of U.S. youth (N = 10,544, mean [SE] baseline age = 9.9 [0.03] years, 48.9% female, 45.4% non-White). Participants reported daily minutes of screen time (streaming, gaming, socializing), physical activity, and sleep. Sex-stratified models estimated the association between baseline behaviors and follow-up BMI z-score, controlling for demographic characteristics, internalizing symptoms, and BMI z-score at baseline. Results: In females, isotemporal substitution models estimated that replacing 30 min of socializing (β [95% CI] = -0.03 [-0.05, -0.002]), streaming (-0.03 [-0.05, -0.01]), or gaming (-0.03 [-0.06, -0.01]) with 30 min of physical activity was associated with a lower follow-up BMI z-score. In males, replacing 30 min of socializing (-0.03 [-0.05, -0.01]), streaming (-0.02 [-0.03, -0.01]), or gaming (-0.02 [-0.03, -0.01]) with 30 min of sleep was associated with a lower follow-up BMI z-score. In males, replacing 30 min of socializing with 30 min of gaming was associated with a lower follow-up BMI z-score (-0.01 [-0.03, -0.0001]). CoDA estimated that in males, a greater proportion of time spent in baseline socializing, relative to the remaining behaviors, was associated with a higher follow-up BMI z-score (0.05 [0.02, 0.08]). In females, no associations between screen time and BMI were observed using CoDA. Conclusions: One-year longitudinal associations between screen time and BMI may depend on form of screen time, what behavior it replaces (physical activity or sleep), and participant sex. The alternative statistical approaches yielded somewhat different results. Experimental manipulation of screen time and investigation of biopsychosocial mechanisms underlying the observed sex differences will allow for causal inference and can inform interventions. [ABSTRACT FROM AUTHOR]

Objective: We provide proof-of-principle for a mental health risk calculator advancing clinical utility of the irritability construct for identification of young children at high risk for common, early onsetting syndromes. Method: Data were harmonized from two longitudinal early childhood subsamples (total N = 403; 50.1% Male; 66.7% Nonwhite; Mage = 4.3 years). The independent subsamples were clinically enriched via disruptive behavior and violence (Subsample 1) and depression (Subsample 2). In longitudinal models, epidemiologic risk prediction methods for risk calculators were applied to test the utility of the transdiagnostic indicator, early childhood irritability, in the context of other developmental and social-ecological indicators to predict risk of internalizing/externalizing disorders at preadolescence (Mage = 9.9 years). Predictors were retained when they improved model discrimination (area under the receiver operating characteristic curve [AUC] and integrated discrimination index [IDI]) beyond the base demographic model. Results: Compared to the base model, the addition of early childhood irritability and adverse childhood experiences significantly improved the AUC (0.765) and IDI slope (0.192). Overall, 23% of preschoolers went on to develop a preadolescent internalizing/externalizing disorder. For preschoolers with both elevated irritability and adverse childhood experiences, the likelihood of an internalizing/externalizing disorder was 39–66%. Conclusions: Predictive analytic tools enable personalized prediction of psychopathological risk for irritable young children, holding transformative potential for clinical translation. [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]

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]

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]

Background & Aims: Insulin resistance is a risk marker for non‐alcoholic fatty liver disease, and a risk factor for liver disease progression. We assessed temporal trajectories of insulin resistance and β‐cell response to serum glucose concentration throughout adulthood and their association with diabetes risk in non‐alcoholic fatty liver disease. Methods: Three thousand and sixty participants from Coronary Artery Risk Development in Young Adults, a prospective bi‐racial cohort of adults age 18‐30 years at baseline (1985‐1986; Y0) who completed up to 5 exams over 25 years and had fasting insulin and glucose measurement were included. At Y25 (2010‐2011), non‐alcoholic fatty liver disease was assessed by noncontrast computed tomography after exclusion of other liver fat causes. Latent mixture modelling identified 25‐year trajectories in homeostatic model assessment insulin resistance and β‐cell response homeostatic model assessment‐β. Results: Three distinct trajectories were identified, separately, for homeostatic model assessment insulin resistance (low‐stable [47%]; moderate‐increasing [42%]; and high‐increasing [12%]) and homeostatic model assessment‐β (low‐decreasing [16%]; moderate‐decreasing [63%]; and high‐decreasing [21%]). Y25 non‐alcoholic fatty liver disease prevalence was 24.5%. Among non‐alcoholic fatty liver disease, high‐increasing homeostatic model assessment insulin resistance (referent: low‐stable) was associated with greater prevalent (OR 95% CI = 8.0, 2.0‐31.9) and incident (OR = 10.5, 2.6‐32.8) diabetes after multivariable adjustment including Y0 or Y25 homeostatic model assessment insulin resistance. In contrast, non‐alcoholic fatty liver disease participants with low‐decreasing homeostatic model assessment‐β (referent: high‐decreasing) had the highest odds of prevalent (OR = 14.1, 3.9‐50.9) and incident (OR = 10.3, 2.7‐39.3) diabetes. Conclusion: Trajectories of insulin resistance and β‐cell response during young and middle adulthood are robustly associated with diabetes risk in non‐alcoholic fatty liver disease. Thus, how persons with non‐alcoholic fatty liver disease develop resistance to insulin provides important information about risk of diabetes in midlife above and beyond degree of insulin resistance at the time of non‐alcoholic fatty liver disease assessment. [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 The American Heart Association's 2020 Strategic Impact Goals define a new concept, cardiovascular (CV) health; however, current prevalence estimates of the status of CV health in US adults according to age, sex, and race/ethnicity have not been published. Methods and Results--We included 14 515 adults (≥20 years of age) from the 2003 to 2008 National Health and Nutrition Examination Surveys. Participants were stratified by young (20-39 years), middle (40-64 years), and older (≥65 years) ages. CV health behaviors (diet, physical activity, body mass index, smoking) and CV health factors (blood pressure, total cholesterol, fasting blood glucose, smoking) were defined as poor, intermediate, or ideal. Fewer than 1% of adults exhibited ideal CV health for all 7 metrics. For CV health behaviors, nonsmoking was most prevalent (range, 60.2%-90.4%), whereas ideal Healthy Diet Score was least prevalent (range, 0.2%-2.6%) across groups. Prevalences of ideal body mass index (range, 36.5%-45.3%) and ideal physical activity levels (range, 50.2%-58.8%) were higher in young adults compared with middle or older ages. Ideal total cholesterol (range, 23.7%-36.2%), blood pressure (range, 11.9%-16.3%), and fasting blood glucose (range, 31.2%-42.9%) were lower in older adults compared with young and middle-aged adults. Prevalence of poor CV health factors was lowest in young age but higher at middle and older ages. Prevalence estimates by age and sex were consistent across race/ethnic groups. Conclusions--These prevalence estimates of CV health represent a starting point from which effectiveness of efforts to promote CV health and prevent CV disease can be monitored and compared in US adult populations. [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]