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BACKGROUND Cardiovascular health (CVH) in young adulthood (YA) has been associated with cardiovascular outcomes in older age. However, little is known about the relationship between YA CVH and mid-life blood pressure (BP) trajectories. METHODS Baseline CVH (defined by 7 of the American Heart Association's [AHA] Life's Essential 8 [LE8] metrics, excluding BP) was measured in YA with individual metrics scored and averaged as a composite LE8 score. Categorical CVH status was defined as high, moderate, and low. Latent class analysis was used to identify trajectories of mid-BP (mean of systolic blood pressure [SBP] and diastolic blood pressure [DBP]) from average ages 35 to 55 years. Multinomial logistic regression was used to estimate the association of YA CVH status (continuously and categorically) with mid-life BP trajectory group membership. RESULTS There were 3,688 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study in YA with follow-up data for mid-life BP trajectories. We observed 3 BP trajectory groups, labeled as Persistently-Low, Middle, and High-Increasing. On average, each 10-points higher baseline LE8 score (mean [SD] of 73.5 [13.1]) in YA was associated with adjusted odds ratios of 0.78 (95% CI, 0.72–0.84) for membership in the Middle and 0.65 (0.57–0.73) for membership in the High-Increasing trajectory groups. Compared with categorical low CVH status at baseline, those with high CVH were significantly less likely to be in the Middle and High-Increasing BP trajectory groups. CONCLUSIONS Moderate or low CVH status in YA is associated with elevated mid-life BP trajectory. These data suggest that young adult CVH promotion may be important for the primordial prevention of hypertension. [ABSTRACT FROM AUTHOR]

Objective Electronic health record (EHR) data are a valuable resource for population health research but lack critical information such as relationships between individuals. Emergency contacts in EHRs can be used to link family members, creating a population that is more representative of a community than traditional family cohorts. Materials and Methods We revised a published algorithm: relationship inference from the electronic health record (RIFTEHR). Our version, Pythonic RIFTEHR (P-RIFTEHR), identifies a patient's emergency contacts, matches them to existing patients (when available) using network graphs, checks for conflicts, and infers new relationships. P-RIFTEHR was run on December 15, 2021 in the Northwestern Medicine Electronic Data Warehouse (NMEDW) on approximately 2.95 million individuals and was validated using the existing link between children born at NM hospitals and their mothers. As proof-of-concept, we modeled the association between parent and child obesity using logistic regression. Results The P-RIFTEHR algorithm matched 1 157 454 individuals in 448 278 families. The median family size was 2, the largest was 32 persons, and 247 families spanned 4 generations or more. Validation of the mother–child pairs resulted in 95.1% sensitivity. Children were 2 times more likely to be obese if a parent is obese (OR: 2.30; 95% CI, 2.23–2.37). Conclusion P-RIFTEHR can identify familiar relationships in a large, diverse population in an integrated health system. Estimates of parent–child inheritability of obesity using family structures identified by the algorithm were consistent with previously published estimates from traditional cohort studies. [ABSTRACT FROM AUTHOR]

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

Aims Atherosclerotic cardiovascular disease (ASCVD) risk prediction equations apply to older adults. For this study, the Pathobiologic Determinants of Atherosclerosis in Youth (PDAY) risk score, based on post-mortem measurements of atherosclerosis in 15–34-year olds dying accidentally, was used to predict ASCVD events, specifically myocardial infarction and revascularization, in middle age, from risk measured at ≤40 years of age. Methods and results The Coronary Artery Risk Development in Young Adults Study (CARDIA) collected longitudinal cardiovascular risk data, coronary artery calcium (CAC) scores, and ASCVD data beginning at age 18 and 30 years with 30-year follow-up. Predictive accuracy for ASCVD of the PDAY risk score, calculated at baseline (mean age 24) and at all six CARDIA examinations up until year 15, was examined. We also examined whether the presence of CAC improved model discrimination. The cohort for this study comprised 5004 Black and White men and women, at baseline and 3558 with data at year 15. Each standard deviation increase in PDAY score, at each examination, was significantly associated with future ASCVD. Hazard ratios (per standard deviation) increased from 1.74 to 2.04 from year 0 to year 15. C-statistics ranged from 0.771 to 0.794. Coronary artery calcium measurement at age 33–45 years improved risk prediction only if the score was 0. Cumulative risk exposure over the first 15 years of the CARDIA study also had high-predictive value (c-statistic 0.798, 95% confidence interval 0.762–0.835). Conclusion The PDAY risk score may be used in young adults, prior to age 40 years to predict ASCVD events. Key question Can risk for coronary artery disease be predicted by the PDAY risk score, derived from autopsied adolescents and young adults using atherosclerosis measures and post-mortem risk factors? Key finding The PDAY risk score was highly predictive of incident coronary artery disease occurring in young adulthood, beginning at 18–30 years of age. Coronary artery calcium (CAC) measurement obtained at age 33–45 years added to prediction only if zero. Take-home message Risk factors for atherosclerosis as measured in the PDAY study are highly predictive of coronary artery disease events in young adults. [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]

Context: The independent contribution of young adult exposure to overweight and obesity to later-life incident diabetes is not well studied.Objective: To assess the associations of exposures to elevated body mass index (BMI) and waist circumference (WC) in young adulthood (ages 18-39 years) with incident diabetes later in life (≥40 years).Design: Pooled data from 6 US prospective cohorts (Atherosclerosis Risk in Communities Study, Cardiovascular Risk Development in Young Adults Study, Cardiovascular Health Study, (4) Framingham Heart Study Offspring Cohort, (5) Health, Aging and Body Composition Study, and (6) Multi-Ethnic Study of Atherosclerosis.Setting: Population-based cohort studies.Participants: 30 780 participants (56.1% female, 69.8% non-Hispanic white) without a diagnosis of diabetes by age 40.Interventions: We imputed BMI and WC trajectories from age 18 for every participant and estimated time-weighted average exposures to BMI or WC during young adulthood and later life.Main Outcome Measure(s): Incident diabetes defined as fasting glucose ≥126 mg/dL, nonfasting glucose ≥200 mg/dL, or use of diabetes medications.Results: During a 9-year median follow-up, 4323 participants developed incident diabetes. Young adult BMI and WC were associated with later-life incident diabetes after controlling for later-life exposures [hazard ratios (HR) 1.99 for BMI ≥ 30 kg/m2 and 2.13 for WC > 88cm (women)/>102cm (men) compared to normal ranges]. Young adult homeostatic model of insulin resistance mediated 49% and 44% of the association between BMI and WC with later-life incident diabetes. High-density lipoproteins and triglycerides mediated a smaller proportion of these associations.Conclusions: Elevated BMI and WC during young adulthood were independently associated with later-life incident diabetes. Insulin resistance may be a key mediator. [ABSTRACT FROM AUTHOR]

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

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

Background For most individuals, blood pressure (BP) is related to multiple risk factors. By utilizing the decision tree analysis technique, this study aimed to identify the best discriminative risk factors and interactions that are associated with maintaining normal BP over 30 years and to reveal segments of a population with a high probability of maintaining normal BP. Methods Participants from the Coronary Artery Risk Development in Young Adults study aged 18–30 years with normal BP level at baseline visit (Y0, 1985–1986) were included in this study. Results Of 3,156 participants, 1,132 (35.9%) maintained normal BP during the follow-up period and 2,024 (64.1%) developed higher BP. Systolic BP (SBP) within the normal range, race, and body mass index (BMI) were the most discriminative factors between participants who maintained normal BP throughout midlife and those who developed higher BP. Participants with a baseline SBP level ≤92 mm Hg and White women with baseline BMI < 23 kg/m2 were the two segments of the population with the highest probability for maintaining normal BP throughout midlife (69.2% and 59.9%, respectively). Among Black participants aged >26.5 years with BMI > 27 kg/m2, only 5.4% of participants maintained normal BP throughout midlife. Conclusions This study emphasizes the importance of early life factors to later life SBP and support efforts to maintain ideal levels of risk factors for hypertension at young ages. Whether policies to maintain lower BMI and SBP well below the clinical thresholds throughout young adulthood and middle age can reduce later age hypertension should be examined in future studies. [ABSTRACT FROM AUTHOR]

High blood pressure (BP) is a strong modifiable risk factor for cardiovascular disease (CVD). Longitudinal BP patterns themselves may reflect the burden of risk and vascular damage due to prolonged cumulative exposure to high BP levels. Current studies have begun to characterize BP patterns as a trajectory over an individual's lifetime. These BP trajectories take into account the absolute BP levels as well as the slope of BP changes throughout the lifetime thus incorporating longitudinal BP patterns into a single metric. Methodologic issues that need to be considered when examining BP trajectories include individual-level vs. population-level group-based modeling, use of distinct but complementary BP metrics (systolic, diastolic, mean arterial, mid, and pulse pressure), and potential for measurement errors related to varied settings, devices, and number of readings utilized. There appear to be very specific developmental periods during which divergent BP trajectories may emerge, specifically adolescence, the pregnancy period, and older adulthood. Lifetime BP trajectories are impacted by both individual-level and community-level factors and have been associated with incident hypertension, multimorbidity (CVD, renal disease, cognitive impairment), and overall life expectancy. Key unanswered questions remain around the additive predictive value of BP trajectories, intergenerational contributions to BP patterns (in utero BP exposure), and potential genetic drivers of BP patterns. The next phase in understanding BP trajectories needs to focus on how best to incorporate this knowledge into clinical care to reduce the burden of hypertensive-related outcomes and improve health equity. [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]

Context: A comprehensive characterization of racial/ethnic variations in vitamin D metabolism markers may improve our understanding of differences in bone and mineral homeostasis and the risk of vitamin D-related diseases.Objective: Describe racial/ethnic differences in vitamin D metabolism markers and their associations with genetic ancestry.Design, Setting, Participants: In a cross-sectional study within the Multi-Ethnic Study of Atherosclerosis (MESA), we compared a comprehensive panel of vitamin D metabolism markers across self-reported racial/ethnic groups of Black (N = 1759), White (N = 2507), Chinese (N = 788), and Hispanic (N = 1411). We evaluated associations of proportion African and European ancestry with this panel of markers in Black and Hispanic participants using ancestry informative markers. Latent class analysis evaluated associations between patterns of vitamin D measurements with race/ethnicity.Results: Compared with Black participants, White participants had significantly higher serum concentrations of 25-hydroxyvitamin D and fibroblast growth factor-23; lower concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D; circulating vitamin D metabolite ratios suggesting lower CYP27B1 and higher CYP24A1 activity; higher urinary concentrations of calcium and phosphorus with higher urinary fractional excretion of phosphorus; and differences in vitamin D binding globulin haplotypes. Higher percent European ancestry was associated with higher 25-hydroxyvitamin D and lower parathyroid hormone concentrations among Black and Hispanic participants. Latent classes defined by vitamin D measurements reflected these patterns and differed significantly by race/ethnicity and ancestry.Conclusions: Markers of vitamin D metabolism vary significantly by race/ethnicity, may serve to maintain bone and mineral homeostasis across ranges of 25-hydroxyvitamin D production, and be attributable, at least partly, to genetic ancestry. [ABSTRACT FROM AUTHOR]

Background physical and mental health are important risk factors for cardiovascular disease (CVD) incidence and death among postmenopausal women. The objective of this study was to assess whether changes in physical and mental health were associated with CVD incidence and death. Methods in the Women's Health Initiative Observational Study, 48,906 women (50–79 years) had complete data at baseline on physical and mental health (assessed with Short Form-36) and key covariates. Changes in self-reported physical and mental health were calculated between baseline and year 3. Incident CVD and death between year 3 and end of the study were verified with medical records. Results over a median 8.2-year follow-up, 2,319 women developed CVD, and 1,571 women died, including 361 CVD deaths. Women with continued poor health and those with worsened health had significantly increased risk of CVD incidence, CVD-specific death and all-cause death relative to women with continued good health. Both major and minor declines in physical health were associated with an increased risk of these outcomes relative to women with no change in physical health. Only major declines in mental health were associated with poor prognosis. Conclusions changes in physical and mental health over 3 years were independently associated with subsequent CVD events. [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]

We used electronic health record data from 162 patients enrolled in the NUgene Project (2002-2013) to determine demographic factors associated with long-term (from 1 to up to 9.5 (mean = 5.6) years) weight loss following Roux-en-Y gastric bypass surgery. Ninety-nine (61.1%) patients self-reported white, and 63 (38.9%) self-reported black, mixed, or missing race. The average percent weight loss was −33.4% (standard deviation, 9.3) at 1 year after surgery and −30.7% (standard deviation, 12.5) at the last follow-up point.We used linear mixed and semiparametric trajectory models to test the association of surgical and demographic factors (height, surgery age, surgery weight, surgery body mass index, marital status, sex, educational level, site, International Classification of Diseases code, Current Procedural Terminology code, Hispanic ethnicity, and self-reported race) with long-term percent weight loss and pattern of weight loss.We found that black, mixed, and missing races (combined) in comparison with white race were associated with a decreased percent weight loss of −4.31% (95% confidence interval: −7.30, −1.32) and were less likely to have higher and sustained percent weight loss (P = 0.04).We also found that less obese patients were less likely to have higher and sustained percent weight loss (P = 0.01). These findings may be helpful to patients in setting expectations after weight loss surgery. [ABSTRACT FROM AUTHOR]