The association between preconception cannabis use and gestational diabetes mellitus: The Preconception Period Analysis of Risks and Exposures Influencing health and Development (PrePARED) consortium.

BACKGROUND: The metabolic changes that ultimately lead to gestational diabetes mellitus (GDM) likely begin before pregnancy. Cannabis use might increase the risk of GDM by increasing appetite or promoting fat deposition and adipogenesis. OBJECTIVES: We aimed to assess the association between preconception cannabis use and GDM incidence. METHODS: We analysed individual-level data from eight prospective cohort studies. We identified the first, or index, pregnancy (lasting ≥20 weeks of gestation with GDM status) after cannabis use. In analyses of pooled individual-level data, we used logistic regression to estimate study-type-specific odds ratios (OR) and 95% confidence intervals (CI), adjusting for potential confounders using random effect meta-analysis to combine study-type-specific ORs and 95% CIs. Stratified analyses assessed potential effect modification by preconception tobacco use and pre-pregnancy body mass index (BMI). RESULTS: Of 17,880 participants with an index pregnancy, 1198 (6.7%) were diagnosed with GDM. Before the index pregnancy, 12.5% of participants used cannabis in the past year. Overall, there was no association between preconception cannabis use in the past year and GDM (OR 0.97, 95% CI 0.79, 1.18). Among participants who never used tobacco, however, those who used cannabis more than weekly had a higher risk of developing GDM than those who did not use cannabis in the past year (OR 2.65, 95% CI 1.15, 6.09). This association was not present among former or current tobacco users. Results were similar across all preconception BMI groups. CONCLUSIONS: In this pooled analysis of preconception cohort studies, preconception cannabis use was associated with a higher risk of developing GDM among individuals who never used tobacco but not among individuals who formerly or currently used tobacco. Future studies with more detailed measurements are needed to investigate the influence of preconception cannabis use on pregnancy complications.

Characterizing the spectrum of bladder health and lower urinary tract symptoms among men: Results from the CARDIA study.

OBJECTIVES: To operationalize a new definition for bladder health, we examined the distribution and impact of lower urinary tract symptoms (LUTS), along with risk factors, among men in the Coronary Artery Risk Development in Young Adults (CARDIA) study. METHODS: LUTS were defined by American Urologic Association Symptom Index (AUASI) scores and impact on quality of life (QoL). Separate questions assessed urinary incontinence (UI) and postvoid dribbling. We performed cluster analyses using AUASI scores, with and without urine incontinence and postvoid dribbling, and impact collected in 2010-11. We performed analyses to evaluate sociodemographic and cardiovascular risk factors between clusters. RESULTS: Among CARDIA men (mean age: 50.0, SD = 3.6; range: 42-56 years) with complete LUTS data (n = 929), we identified and compared four clusters: men who reported no or very mild symptoms and no impact on well-being (bladder health, n = 696, 75%), men with moderate symptoms and moderate impact on well-being (moderate symptoms/impact, n = 84, 9%), men with high symptoms and high impact on well-being (severe symptoms/impact, n = 117, 13%), and a separate group that reported moderate symptoms and UI with a high impact on well-being (UI + moderate symptoms/severe impact, n = 32, 3%). Exploration of the groupings showed a large percentage of postvoid dribbling across groups (overall 69%). Sociodemographic and cardiovascular risk factors were not associated with symptom/impact groups. CONCLUSIONS: Bladder health clustered into four categories. A majority of middle-aged men in the community showed no or mild bladder symptoms without impact on QoL. Postvoid dribbling is pervasive but did not cluster with a specific LUTS or impact category.

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.

Associations of Clinical and Social Risk Factors With Racial Differences in Premature Cardiovascular Disease.

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 ß 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 ß estimate for race occurred with adjustment for clinical (87%), neighborhood (32%), and socioeconomic (23%) factors. In men, the largest magnitude percent reduction in the ß 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.

Epigenetic Age Acceleration Reflects Long-Term Cardiovascular Health.

[Figure: see text].

Sociopolitical stress and acute cardiovascular disease hospitalizations around the 2016 presidential election.

Previous research suggests that stressors may trigger the onset of acute cardiovascular disease (CVD) events within hours to days, but there has been limited research around sociopolitical events such as presidential elections. Among adults ≥18 y of age in Kaiser Permanente Southern California, hospitalization rates for acute CVD were compared in the time period immediately prior to and following the 2016 presidential election date. Hospitalization for CVD was defined as an inpatient or emergency department discharge diagnosis of acute myocardial infarction (AMI) or stroke using International Classification of Diseases, 10th revision codes. Rate ratios (RR) and 95% confidence intervals (CIs) were calculated comparing CVD rates in the 2 d following the 2016 election to rates in the same 2 d of the prior week. In a secondary analysis, AMI and stroke were analyzed separately. The rate of CVD events in the 2 d after the 2016 presidential election (573.14 per 100,000 person-years [PY]) compared to the rate in the window prior to the 2016 election (353.75 per 100,000 PY) was 1.62 times higher (95% CI 1.17, 2.25). Results were similar across sex, age, and race/ethnicity groups. The RRs were similar for AMI (RR 1.67, 95% CI 1.00, 2.76) and stroke (RR 1.59, 95% CI 1.03, 2.44) separately. Transiently heightened cardiovascular risk around the 2016 election may be attributable to sociopolitical stress. Further research is needed to understand the intersection between major sociopolitical events, perceived stress, and acute CVD events.

Gestational Diabetes History and Glucose Tolerance After Pregnancy Associated With Coronary Artery Calcium in Women During Midlife: The CARDIA Study.

BACKGROUND: Gestational diabetes (GD) leads to earlier onset and heightened risk of type 2 diabetes, a strong risk factor for cardiovascular disease (CVD). However, it is unclear whether attaining normoglycemia can ameliorate the excess CVD risk associated with GD history. This study sought to evaluate GD history and glucose tolerance after pregnancy associated with coronary artery calcification (CAC) in women, a manifestation of atherosclerotic CVD and a predictor of CVD clinical events. METHODS: Data were obtained from the CARDIA study (Coronary Artery Risk Development in Young Adults), a US multicenter, community-based prospective cohort of young Black (50%) and White adults aged 18 to 30 years at baseline (1985-1986). The sample included 1133 women without diabetes at baseline, who had ≥1 singleton births (n=2066) during follow-up, glucose tolerance testing at baseline and up to 5 times during 25 years (1986-2011), GD status, and CAC measurements obtained from 1 or more follow up examinations at years 15, 20, and 25 (2001-2011). CAC was measured by noncontrast cardiac computed tomography; dichotomized as Any CAC (score>0) or No CAC (score=0). Complementary log-log models for interval-censored data estimated adjusted hazard ratios of CAC and 95% confidence intervals for GD history and subsequent glucose tolerance groups (normoglycemia, prediabetes, or incident diabetes) on average 14.7 years after the last birth adjusted for prepregnancy and follow-up covariates. RESULTS: Of 1133 women, 139 (12.3%) reported GD and were 47.6 years of age (4.8 SD) at follow-up. CAC was present in 25% (34/139) of women with GD and 15% (149/994) of women with no GD. In comparison with no GD/normoglycemia, adjusted hazard ratios (95% CIs) were 1.54 (1.06-2.24) for no GD/prediabetes and 2.17 (1.30-3.62) for no GD/incident diabetes, and 2.34 (1.34-4.09), 2.13 (1.09-4.17), and 2.02 (0.98-4.19) for GD/normoglycemia, GD/prediabetes, and GD/incident diabetes, respectively (overall P=0.003). CONCLUSIONS: Women without previous GD showed a graded increase in the risk of CAC associated with worsening glucose tolerance. Women with a history of GD had a 2-fold higher risk of CAC across all subsequent levels of glucose tolerance. Midlife atherosclerotic CVD risk among women with previous GD is not diminished by attaining normoglycemia.

Bending the Curve in Cardiovascular Disease Mortality: Bethesda + 40 and Beyond.

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

Early to Midlife Smoking Trajectories and Cognitive Function in Middle-Aged US Adults: the CARDIA Study.

BACKGROUND: Smoking starts in early adulthood and persists throughout the life course, but the association between these trajectories and midlife cognition remains unclear. OBJECTIVE: Determine the association between early to midlife smoking trajectories and midlife cognition. DESIGN: Prospective cohort study. PARTICIPANTS: Participants were 3364 adults (mean age = 50.1 ± 3.6, 56% female, 46% Black) from the Coronary Artery Risk Development in Young Adults (CARDIA) study: 1638 ever smokers and 1726 never smokers. MAIN MEASURES: Smoking trajectories were identified in latent class analysis among 1638 ever smokers using smoking measures every 2-5 years from baseline (age 18-30 in 1985-1986) through year 25 (2010-2011). Poor cognition was based on cognitive domain scores ≥ 1 SD below the mean on tests of processing speed (Digit Symbol Substitution Test), executive function (Stroop), and memory (Rey Auditory Verbal Learning Test) at year 25. RESULTS: Five smoking trajectories emerged over 25 years: quitters (19%), and minimal stable (40%), moderate stable (20%), heavy stable (15%), and heavy declining smokers (5%). Heavy stable smokers showed poor cognition on all 3 domains compared to never smoking (processing speed AOR = 2.22 95% CI 1.53-3.22; executive function AOR = 1.58 95% CI 1.05-2.36; memory AOR = 1.48 95% CI 1.05-2.10). Compared to never smoking, both heavy declining (AOR = 1.95 95% CI 1.06-3.68) and moderate stable smokers (AOR = 1.56 95% CI 1.11-2.19) exhibited slower processing speed, and heavy declining smokers additionally had poor executive function. For minimal stable smokers (processing speed AOR = 1.12 95% CI 0.85-1.51; executive function AOR = 0.97 95% CI 0.71-1.31; memory AOR = 1.21 95% CI 0.94-1.55) and quitters (processing speed AOR = 0.96 95% CI 0.63-1.48; executive function AOR = 0.98 95% CI 0.63-1.52; memory AOR = 0.97 95% CI 0.67-1.39), no association was observed. CONCLUSIONS: The association between early to midlife smoking trajectories and midlife cognition was dose-dependent. Results underscore the cognitive health risk of moderate and heavy smoking and the potential benefits of quitting on cognition, even in midlife.

Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure.

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 Pjoint < 5 × 10-8), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (Pint < 5 × 10-8). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (Pint = 2 × 10-6). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (Pint < 10-3). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.

Physical activity from young adulthood to middle age and premature cardiovascular disease events: a 30-year population-based cohort study.

BACKGROUND: Although physical activity is generally protective of cardiovascular disease (CVD), less is known about how young adult physical activity relates to premature CVD events. The objective of this study was to determine the association between level and change in physical activity from young adulthood to middle age and incidence of premature CVD events before age 60. METHODS: We analyzed data collected across four urban sites from nine visits over 30 years of follow-up (1985-2016) from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective community-based cohort study of 5115 Black and White women and men aged 18-30 years at baseline (1985-1986). Linear mixed models were used to develop individualized moderate-to-vigorous intensity self-reported physical activity trajectories per participant. Fatal and nonfatal coronary heart disease (CHD), heart failure, and stroke outcomes were analyzed separately and as a combined CVD event outcome. RESULTS: Overall, physical activity declined in young adults as they progressed through middle age. Lower physical activity scores (per 100 exercise units) in 18 year-olds were associated with higher odds of premature CHD (AOR 1.14, 95% CI 1.02-1.28), heart failure (AOR 1.21, 95% CI 1.05-1.38), stroke (AOR 1.20, 95% CI 1.04-1.39), and any CVD (AOR 1.15, 95% CI 1.06-1.24) events. Each additional annual 1-unit reduction in the physical activity score was associated with a higher annual odds of incident heart failure (1.07, 95% CI 1.02-1.13), stroke (1.06, 95% CI 1.00-1.13), and CVD (1.04, 95% CI 1.01-1.07) events. Meeting the minimum (AOR 0.74, 95% CI 0.0.57-0.96) and twice the minimum (AOR 0.55, 95% CI 0.34-0.91) Department of Health and Human Services physical activity guidelines through follow up was protective of premature CVD events. CONCLUSIONS: Given recent trends in declining physical activity with age and associated premature CVD events, the transition from young adult to midlife is an important time period to promote physical activity.

Particulate Matter and Cardiovascular Risk in Adults with Chronic Obstructive Pulmonary Disease.

Rationale: People with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular disease and may be more susceptible to air pollution exposure. However, no study has examined the association between long-term fine particulate matter exposure (≤2.5 µm in aerodynamic diameter) and risk of cardiovascular events in this potentially vulnerable population. Objectives: To estimate the association between long-term fine particulate matter and risk of cardiovascular events among adults with COPD. Methods: This retrospective cohort study included 169,714 adults with COPD who were members of the Kaiser Permanente Northern California health plan during 2007-2016. Electronic health record data were linked to 1 km modeled particulate matter ≤2.5 µm in aerodynamic diameter exposure estimates. We fit Cox proportional hazard models, adjusting for age, sex, race/ethnicity, calendar year, smoking, body mass index, comorbidities, medications, and socioeconomic status. In low exposure analyses, we examined effects below the current regulation limit (12 µg/m3). Measurements and Main Results: Among adults with COPD, a 10-µg/m3 increase in 1-year mean fine particulate matter exposure was associated with an elevated risk of cardiovascular mortality (hazard ratio, 1.10; 95% confidence interval [CI], 1.01-1.20). Effects were stronger in low exposure analyses (hazard ratio, 1.88; 95% CI, 1.56-2.27). Fine particulate matter exposure was not associated with acute myocardial infarction or stroke in overall analyses. Conclusions: Long-term fine particulate matter exposure was associated with an increased risk of cardiovascular mortality among adults with COPD. Current regulations may not sufficiently protect those with COPD.

Moderate-to-vigorous intensity physical activity from young adulthood to middle age and metabolic disease: a 30-year population-based cohort study.

OBJECTIVES: To determine the association between moderate-to-vigorous intensity physical activity (MVPA) trajectories (course over age and time) through the adult life course and onset of metabolic disease (diabetes and dyslipidaemia). METHODS: We analysed prospective community-based cohort data of 5115 participants in the Coronary Artery Risk Development in Young Adults study, who were black and white men and women aged 18-30 years at baseline (1985-1986) at four urban sites, collected through 30 years of follow-up. Individualised MVPA trajectories were developed for each participant using linear mixed models. RESULTS: Lower estimated MVPA score at age 18 was associated with a 12% (95% CI 6% to 18%) higher odds of incident diabetes, a 4% (95% CI 1% to 7%) higher odds of incident low high-density lipoprotein (HDL) and a 6% (95% CI 2% to 11%) higher odds of incident high triglycerides. Each additional annual 1-unit reduction in the MVPA score was associated with a 6% (95% CI 4% to 9%) higher annual odds of diabetes incidence and a 4% (95% CI 2% to 6%) higher annual odds of high triglyceride incidence. Analysing various MVPA trajectory groups, participants who were in the most active group at age 18 (over 300 min/week), but with sharp declines in midlife, had higher odds of high low-density lipoprotein and low HDL incidence, compared with those in the most active group at age 18 with subsequent gains. CONCLUSION: Given recent trends in declining MVPA across the life course and associated metabolic disease risk, young adulthood is an important time period for interventions to increase and begin the maintenance of MVPA.

Elevated blood pressure is associated with advanced brain aging in mid-life: A 30-year follow-up of The CARDIA Study.

BACKGROUND: High blood pressure (BP) is a risk factor for late-life brain health; however, the association of elevated BP with brain health in mid-life is unclear. METHODS: We identified 661 participants from the Coronary Artery Risk Development in Young Adults Study (age 18-30 at baseline) with 30 years of follow-up and brain magnetic resonance imaging at year 30. Cumulative exposure of BP was estimated by time-weighted averages (TWA). Ideal cardiovascular health was defined as systolic BP < 120 mm Hg, diastolic BP < 80 mm Hg. Brain age was calculated using previously validated high dimensional machine learning pattern analyses. RESULTS: Every 5 mmHg increment in TWA systolic BP was associated with approximately 1-year greater brain age (95% confidence interval [CI]: 0.50-1.36) Participants with TWA systolic or diastolic BP over the recommended guidelines for ideal cardiovascular health, had on average 3-year greater brain age (95% CI: 1.00-4.67; 95% CI: 1.45-5.13, respectively). CONCLUSION: Elevated BP from early to mid adulthood, even below clinical cut-offs, is associated with advanced brain aging in mid-life.

Recommendations for Cardiovascular Health and Disease Surveillance for 2030 and Beyond: A Policy Statement From the American Heart Association.

The release of the American Heart Association's 2030 Impact Goal and associated metrics for success underscores the importance of cardiovascular health and cardiovascular disease surveillance systems for the acquisition of information sufficient to support implementation and evaluation. The aim of this policy statement is to review and comment on existing recommendations for and current approaches to cardiovascular surveillance, identify gaps, and formulate policy implications and pragmatic recommendations for transforming surveillance of cardiovascular disease and cardiovascular health in the United States. The development of community platforms coupled with widespread use of digital technologies, electronic health records, and mobile health has created new opportunities that could greatly modernize surveillance if coordinated in a pragmatic matter. However, technology and public health and scientific mandates must be merged into action. We describe the action and components necessary to create the cardiovascular health and cardiovascular disease surveillance system of the future, steps in development, and challenges that federal, state, and local governments will need to address. Development of robust policies and commitment to collaboration among professional organizations, community partners, and policy makers are critical to ultimately reduce the burden of cardiovascular disease and improve cardiovascular health and to evaluate whether national health goals are achieved.

Guidance to Reduce the Cardiovascular Burden of Ambient Air Pollutants: A Policy Statement From the American Heart Association.

In 2010, the American Heart Association published a statement concluding that the existing scientific evidence was consistent with a causal relationship between exposure to fine particulate matter and cardiovascular morbidity and mortality, and that fine particulate matter exposure is a modifiable cardiovascular risk factor. Since the publication of that statement, evidence linking air pollution exposure to cardiovascular health has continued to accumulate and the biological processes underlying these effects have become better understood. This increasingly persuasive evidence necessitates policies to reduce harmful exposures and the need to act even as the scientific evidence base continues to evolve. Policy options to mitigate the adverse health impacts of air pollutants must include the reduction of emissions through action on air quality, vehicle emissions, and renewable portfolio standards, taking into account racial, ethnic, and economic inequality in air pollutant exposure. Policy interventions to improve air quality can also be in alignment with policies that benefit community and transportation infrastructure, sustainable food systems, reduction in climate forcing agents, and reduction in wildfires. The health care sector has a leadership role in adopting policies to contribute to improved environmental air quality as well. There is also potentially significant private sector leadership and industry innovation occurring in the absence of and in addition to public policy action, demonstrating the important role of public-private partnerships. In addition to supporting education and research in this area, the American Heart Association has an important leadership role to encourage and support public policies, private sector innovation, and public-private partnerships to reduce the adverse impact of air pollution on current and future cardiovascular health in the United States.

Relationships of inflammation trajectories with white matter volume and integrity in midlife.

OBJECTIVE: Elevated inflammation is associated with worse late-life cognitive functioning and brain health. Our goal was to examine the relationship between inflammation trajectories and white matter integrity in midlife. METHODS: Participants were 508 adults from the Coronary Artery Risk Development in Young Adults Study (CARDIA; 51% female). Latent class analysis was used to identify inflammation trajectories based on repeated measures of the inflammatory marker C-reactive protein (CRP) over the 18 years before brain magnetic resonance imaging (MRI). Outcomes were brain MRI measures of total and region-specific white matter volume and integrity at a mean age of 50.6 ± 3.4 years. Linear regression was used to examine if inflammation trajectories were associated with brain MRI outcomes, adjusting for potential confounds in all models and for disease and health behaviors in follow-up models. RESULTS: Lower-stable (38%), moderate-increasing (7%), and consistently-higher (54%), trajectories emerged. Compared to the lower-stable group, the moderate-increasing group showed lower white matter volume (ß = -0.18, 95% CI -0.29, -0.06) and worse white matter integrity as indexed by lower fractional anisotropy (FA; ß = -0.37, 95% CI -0.70, -0.04) and higher mean diffusivity (ß = 0.44, 95% CI 0.11, 0.78) in the whole brain. The consistently-higher group showed lower whole-brain FA (ß = -0.20, -0.38, -0.03). In exploratory analyses, the moderate-increasing group showed lower white matter volume, lower FA and higher MD in the frontal, temporal, and parietal lobes compared to the lower-stable group. The consistently-higher group showed lower white matter volume in the parietal lobe and lower FA in the frontal, temporal, and parietal lobes, but similar MD, compared to the lower-stable group. Findings for the moderate-increasing, but not the consistently-higher, group were robust to adjustment for disease and lifestyle factors. CONCLUSION: Increasing or high inflammation trajectories from early to mid adulthood are associated with worse brain health, as indexed by lower white matter volume and/or worse white matter integrity.

Bidirectional associations of accelerometer-derived physical activity and stationary behavior with self-reported mental and physical health during midlife.

BACKGROUND: Moderate-to-vigorous intensity physical activity (MVPA) is associated with favorable self-rated mental and physical health. Conversely, poor self-rated health in these domains could precede unfavorable shifts in activity. We evaluated bidirectional associations of accelerometer-estimated time spent in stationary behavior (SB), light intensity physical activity (LPA), and MVPA with self-rated health over 10 years in in the CARDIA longitudinal cohort study. METHODS: Participants (n = 894, age: 45.1 ± 3.5; 63% female; 38% black) with valid accelerometry wear and self-rated health at baseline (2005-6) and 10-year follow-up (2015-6) were included. Accelerometry data were harmonized between exams and measured mean total activity and duration (min/day) in SB, LPA, and MVPA; duration (min/day) in long-bout and short-bout SB (≥30 min vs. < 30 min) and MVPA (≥10 min vs. < 10 min) were also quantified. The Short-Form 12 Questionnaire measured both a mental component score (MCS) and physical component score (PCS) of self-rated health (points). Multivariable linear regression associated baseline accelerometry variables with 10-year changes in MCS and PCS. Similar models associated baseline MCS and PCS with 10-year changes in accelerometry measures. RESULTS: Over 10-years, average (SD) MCS increased 1.05 (9.07) points, PCS decreased by 1.54 (7.30) points, and activity shifted toward greater SB and less mean total activity, LPA, and MVPA (all p < 0.001). Only baseline short-bout MVPA was associated with greater 10-year increases in MCS (+ 0.92 points, p = 0.021), while baseline mean total activity, MVPA, and long-bout MVPA were associated with greater 10-year changes in PCS (+ 0.53 to + 1.47 points, all p < 0.005). In the reverse direction, higher baseline MCS and PCS were associated with favorable 10-year changes in mean total activity (+ 9.75 cpm, p = 0.040, and + 15.66 cpm, p < 0.001, respectively) and other accelerometry measures; for example, higher baseline MCS was associated with - 13.57 min/day of long-bout SB (p < 0.001) and higher baseline PCS was associated with + 2.83 min/day of MVPA (p < 0.001) in fully adjusted models. CONCLUSIONS: The presence of bidirectional associations between SB and activity with self-rated health suggests that individuals with low overall activity levels and poor self-rated health are at high risk for further declines and supports intervention programming that aims to dually increase activity levels and improve self-rated health.

Cardiovascular risk and functional burden at midlife: Prospective associations of isotemporal reallocations of accelerometer-measured physical activity and sedentary time in the CARDIA study.

Cardiovascular risk and functional burden, or the accumulation of cardiovascular risk factors coupled with functional decline, may be an important risk state analogy to multimorbidity. We investigated prospective associations of sedentary time (ST), light intensity physical activity (LPA), and moderate to vigorous intensity physical activity (MVPA) with cardiovascular risk and functional burden at midlife. Participants were 1648 adults (mean ± SD age = 45 ± 4 years, 61% female, 39% Black) from Coronary Artery Risk Development in Young Adults (CARDIA) who wore accelerometers in 2005-2006 and 2015-2016. Cardiovascular risk and functional burden was defined as ≥2 cardiovascular risk factors (untreated/uncontrolled hypertension and hypercholesterolemia, type 2 diabetes, reduced kidney function) and/or functional decline conditions (reduced physical functioning and depressive symptoms). Prospective logistic regression models tested single activity, partition, and isotemporal substitution associations of accelerometer-measured ST, LPA, and MVPA with cardiovascular risk and functional burden 10 years later. In isotemporal models of baseline activity, reallocating 24 min of ST to MVPA was associated with 15% lower odds of cardiovascular risk and functional burden (OR: 0.85; CI: 0.75, 0.96). Reallocating 24 min of LPA to MVPA was associated with a 14% lower odds of cardiovascular risk and functional burden (OR: 0.86; CI: 0.75, 0.99). In longitudinal isotemporal models, similar beneficial associations were observed when 10-year increases in MVPA replaced time in ST or LPA. Findings suggest that maintaining an MVPA dose reflecting daily physical activity recommendations in early midlife is associated with lower odds of cardiovascular risk and functional burden later in midlife.

Long-Term Levels of LDL-C and Cognitive Function: The CARDIA Study.

OBJECTIVES: It is uncertain if long-term levels of low-density lipoprotein-cholesterol (LDL-C) affect cognition in middle age. We examined the association of LDL-C levels over 25 years with cognitive function in a prospective cohort of black and white US adults. METHODS: Lipids were measured at baseline (1985-1986; age: 18-30 years) and at serial examinations conducted over 25 years. Time-averaged cumulative LDL-C was calculated using the area under the curve for 3,328 participants with ≥3 LDL-C measurements and a cognitive function assessment. Cognitive function was assessed at the Year 25 examination with the Digit Symbol Substitution Test [DSST], Rey Auditory Visual Learning Test [RAVLT], and Stroop Test. A brain magnetic resonance imaging (MRI) sub-study (N = 707) was also completed at Year 25 to assess abnormal white matter tissue volume (AWMV) and gray matter cerebral blood flow volume (GM-CBFV) as secondary outcomes. RESULTS: There were 15.6%, 32.9%, 28.9%, and 22.6% participants with time-averaged cumulative LDL-C <100 mg/dL, 101-129 mg/dL, 130-159 mg/dL, and ≥160 mg/dL, respectively. Standardized differences in all cognitive function test scores ranged from 0.16 SD lower to 0.09 SD higher across time-averaged LDL-C categories in comparison to those with LDL-C < 100 mg/dL. After covariate adjustment, participants with higher versus lower time-averaged LDL-C had a lower RAVLT score (p-trend = 0.02) but no differences were present for DSST, Stroop Test, AWMV, or GM-CBFV. CONCLUSION: Cumulative LDL-C was associated with small differences in memory, as assessed by RAVLT scores, but not other cognitive or brain MRI measures over 25 years of follow-up.