Association of Cardiovascular Health Through Young Adulthood With Genome-Wide DNA Methylation Patterns in Midlife: The CARDIA Study.

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.

Epigenetic Age Acceleration Reflects Long-Term Cardiovascular Health.

[Figure: see text].

Association between county-level risk groups and COVID-19 outcomes in the United States: a socioecological study.

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.

Development and Validation of a Large Synthetic Cohort for the Study of Cardiovascular Health Across the Life Span.

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.

Influential Periods in Longitudinal Clinical Cardiovascular Health Scores.

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.

Moderate and Vigorous Intensity Exercise During Pregnancy and Gestational Weight Gain in Women with Gestational Diabetes.

Objectives To estimate the associations of moderate and vigorous intensity exercise during pregnancy with the rate of gestational weight gain (GWG) from gestational diabetes (GDM) diagnosis to delivery, overall and stratified by prepregnancy overweight/obesity. Methods Prospective cohort study with physical activity reported shortly after the GDM diagnosis and prepregnancy weight and post-diagnosis GWG obtained from electronic health records (n = 1055). Multinomial logistic regression models in the full cohort and stratified by prepregnancy overweight/obesity estimated associations of moderate and vigorous intensity exercise with GWG below and above the Institute of Medicine's (IOM) prepregnancy BMI-specific recommended ranges for weekly rate of GWG in the second and third trimesters. Results In the full cohort, any participation in vigorous intensity exercise was associated with decreased odds of GWG above recommended ranges as compared to no participation [odds ratio (95 % confidence interval): 0.63 (0.40, 0.99)], with a significant trend for decreasing odds of excess GWG with increasing level of vigorous intensity exercise. Upon stratification by prepregnancy overweight/obesity, significant associations were only observed for BMI ≥ 25.0 kg/m(2): any vigorous intensity exercise, as compared to none, was associated with 54 % decreased odds of excess GWG [0.46 (0.27, 0.79)] and significant trends were detected for decreasing odds of GWG both below and above the IOM's recommended ranges with increasing level of vigorous exercise (both P ≤ 0.03). No associations were observed for moderate intensity exercise. Conclusions for Practice In women with GDM, particularly overweight and obese women, vigorous intensity exercise during pregnancy may reduce the odds of excess GWG.

Incorporating longitudinal history of risk factors into atherosclerotic cardiovascular disease risk prediction using deep learning.

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.

A Proposed Pediatric Clinical Cardiovascular Health Reference Standard.

INTRODUCTION: Clinical cardiovascular health is a construct that includes 4 health factors-systolic and diastolic blood pressure, fasting glucose, total cholesterol, and body mass index-which together provide an evidence-based, more holistic view of cardiovascular health risk in adults than each component separately. Currently, no pediatric version of this construct exists. This study sought to develop sex-specific charts of clinical cardiovascular health for age to describe current patterns of clinical cardiovascular health throughout childhood. METHODS: Data were used from children and adolescents aged 8-19 years in six pooled childhood cohorts (19,261 participants, collected between 1972 and 2010) to create reference standards for fasting glucose and total cholesterol. Using the models for glucose and cholesterol as well as previously published reference standards for body mass index and blood pressure, clinical cardiovascular health charts were developed. All models were estimated using sex-specific random-effects linear regression, and modeling was performed during 2020-2022. RESULTS: Models were created to generate charts with smoothed means, percentiles, and standard deviations of clinical cardiovascular health for each year of childhood. For example, a 10-year-old girl with a body mass index of 16 kg/m2 (30th percentile), blood pressure of 100/60 mm Hg (46th/50th), glucose of 80 mg/dL (31st), and total cholesterol of 160 mg/dL (46th) (lower implies better) would have a clinical cardiovascular health percentile of 62 (higher implies better). CONCLUSIONS: Clinical cardiovascular health charts based on pediatric data offer a standardized approach to express clinical cardiovascular health as an age- and sex-standardized percentile for clinicians to assess cardiovascular health in childhood to consider preventive approaches at early ages and proactively optimize lifetime trajectories of cardiovascular health.

Cardiac Structure and Function Phenogroups and Risk of Incident Heart Failure (from the Multi-ethnic Study of Atherosclerosis).

Indices of cardiac structure and function, such as left ventricular (LV) mass and ejection fraction, have been associated with risk of incident heart failure (HF), but the clinical relevance of data-driven grouping of a comprehensive set of cardiac parameters is unclear. In Multi-Ethnic Study of Atherosclerosis participants, latent class analysis was applied in the sample stratified by gender to define phenogroups on the basis of cardiovascular magnetic resonance imaging parameters of right ventricular and LV structure and function at baseline. Cox proportional hazard models in gender-stratified analyses were used to assess the association between phenogroup membership and risk of HF subtypes adjusting for potential confounders. In the 4,204 participants (mean age 61 ± 10 years, 53% women), the mean follow-up time was 14 ± 4 years for men and 15 ± 4 years for women. For both genders, 4 distinct phenogroups were identified: (1) ideal cardiac mechanics; (2) higher output/hypertrophied LV; (3) impaired ejection fraction/dilated LV; and (4) higher output/hyperdynamic (LV). Men in phenogroups 4 (hazard ratio [HR] 2.91, 95% confidence interval [CI] 1.60 to 5.31, p = 0.0005), 3 (HR 3.52, 95% CI 1.90 to 6.53, p <0.0001), and 2 (HR 3.49, 95% CI 1.94 to 6.28, p <0.0001) had higher rates of incident HF than did men in phenogroup 1, in fully adjusted models. No significant associations were found between phenogroup membership and incident HF in women. In conclusion, phenogroup membership based on cardiac structure and function in men was significantly associated with incident HF. Integration of cardiac magnetic resonance imaging variables may help identify differential risk for HF in men.

Using electronic health record data to link families: an illustrative example using intergenerational patterns of obesity.

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.

Race- and Sex-Specific Factors Associated With Age-Related Slopes in Systolic Blood Pressure: Findings From the CARDIA Study.

BACKGROUND: Although blood pressure (BP) increases throughout young adulthood for most individuals, the age-related slope is not uniform. This study aimed to assess associations of demographic, clinical, behavioral, psychosocial, and neighborhood characteristics with age-related BP slope among 4 race-sex groups who participated in the Coronary Artery Risk Development in Young Adults study. METHODS: Individuals (n=3554) aged 18 to 30 years were included in this analysis if they had normal BP at baseline and ≥2 BP measurements during the years 1985/1986 to 2015/2016. Associations of exposure variables with systolic BP slope were assessed using multivariate linear models. RESULTS: Over a mean follow-up of ~30 years, greater decade increases in systolic BP were estimated among Black than White participants (mean difference between Black females and White females: 3.0 mm Hg/decade; between Black males and White males: 4.7 mm Hg/decade). The exposure risk factors associated with greater increases in systolic BP throughout adulthood varied by race and sex. None of these factors were associated with increases in systolic BP in all race-sex groups. Parent history of high BP was associated with a steeper positive slope among Black females (effect size per decade: 1.1 [95% CI, 0.6-1.6]; P<0.01), Black males (0.6 [95% CI, 0.02-1.2]; P<0.05), and White females (0.6 [95% CI, 0.2-1.0]; P<0.01). Other risk factors were associated with greater age-related yearly increases in systolic BP among 1 or 2 of the 4 race-sex groups or were not statistically significant. CONCLUSIONS: Culturally tailored BP reduction approach should be considered in conjunction with primordial prevention, to moderate increases in BP throughout adulthood.

Rationale and design for Healthy Hearts for Michigan (HH4M): A pragmatic single-arm hybrid effectiveness-implementation study.

Background: The burden of cardiovascular disease (CVD) is particularly high in several US states, which include the state of Michigan. Hypertension and smoking are two major risk factors for mortality due to CVD. Rural Michigan is disproportionally affected by CVD and by primary care shortages. The Healthy Hearts for Michigan (HH4M) study aims to promote hypertension management and smoking cessation through practice facilitation and quality improvement efforts and is part of the multi-state EvidenceNOW: Building State Capacity initiative to provide external support to primary care practices to improve care delivery. Methods: Primary care practices in rural and underserved areas of Michigan were recruited to join HH4M, a pragmatic, single-arm hybrid Type 2 effectiveness-implementation study during which practice facilitation was delivered at the practice level for 12 months, followed by a 3-month maintenance period. Results: Fifty-four practices were enrolled over a 12-month recruitment period. At baseline, the mean proportion (standard deviation) of patients at the practice level meeting the clinical quality measures were: blood pressure, 0.72 (0.12); tobacco screening, 0.80 (0.30); tobacco cessation intervention, 0.57 (0.28); tobacco screening and cessation intervention: 0.78 (0.26). Conclusion: This three-year research program will evaluate the ability of rural and medically underserved primary care practices to implement the quality improvement model by identifying drivers of and barriers to sustainable implementation, and test whether the model improves (a) blood pressure control and (b) tobacco use screening and cessation.

Incorporating longitudinal history of risk factors into atherosclerotic cardiovascular disease risk prediction using deep learning.

Background: 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. Objective: To develop a ASCVD risk prediction model that incorporates longitudinal risk factors using deep learning. Methods: 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. Results: Of the 15,565 participants in our dataset, 2,170 (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. Conclusion: Incorporating longitudinal risk factors in ASCVD risk prediction using DL can improve model discrimination and calibration.

Cardiovascular health trajectories from age 2-12: a pediatric electronic health record study.

PURPOSE: Many children have non-ideal cardiovascular health (CVH), but little is known about the course of CVH in early childhood. We identified CVH trajectories in children and assess the generalizability of these trajectories in an external sample. METHODS: We used data spanning 2010-2018 from children aged 2-12 years within the Chicago Area Patient-Centered Outcomes Research Network-an electronic health record network. Four clinical systems comprised the derivation sample and a fifth the validation sample. Body mass index, blood pressure, cholesterol, and blood glucose were categorized as ideal, intermediate, and poor using clinical measurements, laboratory readings, and International Classification of Diseases diagnosis codes and summed for an overall CVH score. Group-based trajectory modeling was used to create CVH score trajectories which were assessed for classification accuracy in the validation sample. RESULTS: Using data from 122,363 children (47% female, 47% non-Hispanic White) three trajectories were identified: 59.5% maintained high levels of clinical CVH, 23.4% had high levels of CVH that declined, and 17.1% had intermediate levels of CVH that further declined with age. A similar classification emerged when the trajectories were fitted in the validation sample. CONCLUSIONS: Stratification of CVH was present by age 2, implicating the need for early life and preconception prevention strategies.

Association of Body Mass Index in Midlife With Morbidity Burden in Older Adulthood and Longevity.

Importance: Abundant evidence links obesity with adverse health consequences. However, controversies persist regarding whether overweight status compared with normal body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is associated with longer survival and whether this occurs at the expense of greater long-term morbidity and health care expenditures. Objective: To examine the association of BMI in midlife with morbidity burden, longevity, and health care expenditures in adults 65 years and older. Design, Setting, and Participants: Prospective cohort study at the Chicago Heart Association Detection Project in Industry, with baseline in-person examination between November 1967 and January 1973 linked with Medicare follow-up between January 1985 and December 2015. Participants included 29 621 adults who were at least age 65 years in follow-up and enrolled in Medicare. Data were analyzed from January 2020 to December 2021. Exposures: Standard BMI categories. Main Outcomes and Measures: (1) Morbidity burden at 65 years and older assessed with the Gagne combined comorbidity score (ranging from -2 to 26, with higher score associated with higher mortality), which is a well-validated index based on International Classification of Diseases, Ninth Revision codes for use in administrative data sets; (2) longevity (age at death); and (3) health care costs based on Medicare linkage in older adulthood (aged ≥65 years). Results: Among 29 621 participants, mean (SD) age was 40 (12) years, 57.1% were men, and 9.1% were Black; 46.0% had normal BMI, 39.6% were overweight, and 11.9% had classes I and II obesity at baseline. Higher cumulative morbidity burden in older adulthood was observed among those who were overweight (7.22 morbidity-years) and those with classes I and II obesity (9.80) compared with those with a normal BMI (6.10) in midlife (P < .001). Mean age at death was similar between those who were overweight (82.1 years [95% CI, 81.9-82.2 years]) and those who had normal BMI (82.3 years [95% CI, 82.1-82.5 years]) but shorter in those who with classes I and II obesity (80.8 years [95% CI, 80.5-81.1 years]). The proportion (SE) of life-years lived in older adulthood with Gagne score of at least 1 was 0.38% (0.00%) in those with a normal BMI, 0.41% (0.00%) in those with overweight, and 0.43% (0.01%) in those with classes I and II obesity. Cumulative median per-person health care costs in older adulthood were significantly higher among overweight participants ($12 390 [95% CI, $10 427 to $14 354]) and those with classes I and II obesity ($23 396 [95% CI, $18 474 to $28 319]) participants compared with those with a normal BMI (P < .001). Conclusions and Relevance: In this cohort study, overweight in midlife, compared with normal BMI, was associated with higher cumulative burden of morbidity and greater proportion of life lived with morbidity in the context of similar longevity. These findings translated to higher total health care expenditures in older adulthood for those who were overweight in midlife.

Decision Tree-Based Classification for Maintaining Normal Blood Pressure Throughout Early Adulthood and Middle Age: Findings From the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

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.

The Timing and Sequence of Cardiovascular Health Decline.

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

Cardiovascular Health Trajectories From Childhood Through Middle Age and Their Association With Subclinical Atherosclerosis.

Importance: Cross-sectional measures of cardiovascular health (CVH) have been associated with cardiovascular disease in older age, but little is known about longitudinal trajectories in CVH and their association with subclinical atherosclerosis in middle age. Objectives: To model long-term patterns in CVH starting in childhood and to assess their association with subclinical atherosclerosis in middle age. Design, Setting, and Participants: This cohort study used data from 5 prospective cardiovascular cohort studies from the United States and Finland from 1973 to 2015. A total of 9388 participants aged 8 to 55 years had at least 3 examinations and were eligible for this study. Statistical analysis was performed from December 1, 2015, to June 1, 2019. Exposures: Clinical CVH factors (body mass index, total cholesterol level, blood pressure, and glucose level) were classified as ideal, intermediate, or poor, and were summed as a clinical CVH score. Group-based latent class modeling identified trajectories in this score over time. Main Outcomes and Measures: Carotid intima-media thickness (cIMT) was measured for participants in 3 cohorts, and high cIMT was defined as a value at or above the 90th percentile. The association between CVH trajectory and cIMT was modeled using both linear and logistic regression adjusted for demographics, baseline health behaviors, and baseline (or proximal) CVH score. Results: Among 9388 participants (5146 [55%] female; 6228 [66%] white; baseline mean [SD] age, 17.5 [7.5] years), 5 distinct trajectory groups were identified: high-late decline (1518 participants [16%]), high-moderate decline (2403 [26%]), high-early decline (3066 [32%]), intermediate-late decline (1475 [16%]), and intermediate-early decline (926 [10%]). The high-late decline group had significantly lower adjusted cIMT vs other trajectory groups (high-late decline: 0.64 mm [95% CI, 0.63-0.65 mm] vs intermediate-early decline: 0.72 mm [95% CI, 0.69-0.75 mm] when adjusted for demographics and baseline smoking, diet, and physical activity; P < .01). The intermediate-early declining group had higher odds of high cIMT (odds ratio, 2.4; 95% CI, 1.3-4.5) compared with the high-late decline group, even after adjustment for baseline or proximal CVH score. Conclusions and Relevance: In this study, CVH declined from childhood into adulthood. Promoting and preserving ideal CVH from early life onward may be associated with reduced CVD risk later in life.

Coronary Artery Calcium Progression Among the US and Japanese Men.

Background The risk of coronary heart disease remains low in Japan, although distributions of several coronary risk factors have become comparable with those in the United States. We prospectively compared coronary atherosclerosis burden, measured with coronary artery calcium (CAC) progression, between men in the 2 countries. Methods In 2 population-based samples of 1712 US White, Black, Hispanic, Chinese men (baseline, 2000-2002) and 697 Japanese men in Japan (2006-2008) aged 45-74 years without clinical cardiovascular disease, we quantified CAC progression by serial computed tomography with medians of 3.4 and 5.2 years between scans, respectively. Results Among White, Black, Hispanic, Chinese, and Japanese men free of baseline CAC, CAC incidence was observed in 35.2%, 26.9%, 29.2%, 18.9%, and 29.2%, respectively. After adjustment for times between scans, demographics, behaviors, coronary risk factors, and their changes between scans, White men had significantly higher CAC incidence than Japanese men (relative risk, 1.68; 95% CI, 1.13-2.50). Among those with detectable baseline CAC, after similar adjustments, all the US race/ethnic groups had significantly greater annual changes in CAC score (mean [95% CI]: 39.4 [35.2-43.6] for White, 26.9 [21.4-32.4] for Black, 30.6 [24.7-36.5] for Hispanic, and 30.2 [22.6-37.8] for Chinese men) than Japanese men (15.9 [10.1-21.8]). Conclusions We found a higher CAC incidence among US White men and greater increases in existing CAC among all the US race/ethnic groups than among Japanese men in Japan. These differences persisted despite adjustment for differences in coronary risk factors.