Environmental Exposome and Atrial Fibrillation: Emerging Evidence and Future Directions.

There has been increased awareness of the linkage between environmental exposures and cardiovascular health and disease. Atrial fibrillation is the most common sustained cardiac arrhythmia, affecting millions of people worldwide and contributing to substantial morbidity and mortality. Although numerous studies have explored the role of genetic and lifestyle factors in the development and progression of atrial fibrillation, the potential impact of environmental determinants on this prevalent condition has received comparatively less attention. This review aims to provide a comprehensive overview of the current evidence on environmental determinants of atrial fibrillation, encompassing factors such as air pollution, temperature, humidity, and other meteorologic conditions, noise pollution, greenspace, and the social environment. We discuss the existing evidence from epidemiological and mechanistic studies, critically evaluating the strengths and limitations of these investigations and the potential underlying biological mechanisms through which environmental exposures may affect atrial fibrillation risk. Furthermore, we address the potential implications of these findings for public health and clinical practice and identify knowledge gaps and future research directions in this emerging field.

Established and Emerging Nucleic Acid Therapies for Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is a genetic disease that leads to elevated low-density lipoprotein cholesterol levels and risk of coronary heart disease. Current therapeutic options for FH remain relatively limited and only partially effective in both lowering low-density lipoprotein cholesterol and modifying coronary heart disease risk. The unique characteristics of nucleic acid therapies to target the underlying cause of the disease can offer solutions unachievable with conventional medications. DNA- and RNA-based therapeutics have the potential to transform the care of patients with FH. Recent advances are overcoming obstacles to clinical translation of nucleic acid-based medications, including greater stability of the formulations as well as site-specific delivery, making gene-based therapy for FH an alternative approach for treatment of FH.

Optimal Screening for Predicting and Preventing the Risk of Heart Failure Among Adults With Diabetes Without Atherosclerotic Cardiovascular Disease: A Pooled Cohort Analysis.

BACKGROUND: The optimal approach to identify individuals with diabetes who are at a high risk for developing heart failure (HF) to inform implementation of preventive therapies is unknown, especially in those without atherosclerotic cardiovascular disease (ASCVD). METHODS: Adults with diabetes and no HF at baseline from 7 community-based cohorts were included. Participants without ASCVD who were at high risk for developing HF were identified using 1-step screening strategies: risk score (WATCH-DM [Weight, Age, Hypertension, Creatinine, HDL-C, Diabetes Control, QRS Duration, MI, and CABG] ≥12), NT-proBNP (N-terminal pro-B-type natriuretic peptide ≥125 pg/mL), hs-cTn (high-sensitivity cardiac troponin T ≥14 ng/L; hs-cTnI ≥31 ng/L), and echocardiography-based diabetic cardiomyopathy (echo-DbCM; left atrial enlargement, left ventricular hypertrophy, or diastolic dysfunction). High-risk participants were also identified using 2-step screening strategies with a second test to identify residual risk among those deemed low risk by the first test: WATCH-DM/NT-proBNP, NT-proBNP/hs-cTn, NT-proBNP/echo-DbCM. Across screening strategies, the proportion of HF events identified, 5-year number needed to treat and number needed to screen to prevent 1 HF event with an SGLT2i (sodium-glucose cotransporter 2 inhibitor) among high-risk participants, and cost of screening were estimated. RESULTS: The initial study cohort included 6293 participants (48.2% women), of whom 77.7% without prevalent ASCVD were evaluated with different HF screening strategies. At 5-year follow-up, 6.2% of participants without ASCVD developed incident HF. The 5-year number needed to treat to prevent 1 HF event with an SGLT2i among participants without ASCVD was 43 (95% CI, 29-72). In the cohort without ASCVD, high-risk participants identified using 1-step screening strategies had a low 5-year number needed to treat (22 for NT-proBNP to 37 for echo-DbCM). However, a substantial proportion of HF events occurred among participants identified as low risk using 1-step screening approaches (29% for echo-DbCM to 47% for hs-cTn). Two-step screening strategies captured most HF events (75-89%) in the high-risk subgroup with a comparable 5-year number needed to treat as the 1-step screening approaches (30-32). The 5-year number needed to screen to prevent 1 HF event was similar across 2-step screening strategies (45-61). However, the number of tests and associated costs were lowest for WATCH-DM/NT-proBNP ($1061) compared with other 2-step screening strategies (NT-proBNP/hs-cTn: $2894; NT-proBNP/echo-DbCM: $16 358). CONCLUSIONS: Selective NT-proBNP testing based on the WATCH-DM score efficiently identified a high-risk primary prevention population with diabetes expected to derive marked absolute benefits from SGLT2i to prevent HF.

Low-Density Lipoprotein Cholesterol Is Predominantly Associated With Atherosclerotic Cardiovascular Disease Events in Patients With Evidence of Coronary Atherosclerosis: The Western Denmark Heart Registry.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, a sizable proportion of middle-aged individuals with elevated LDL-C level have not developed coronary atherosclerosis as assessed by coronary artery calcification (CAC). Whether presence of CAC modifies the association of LDL-C with ASCVD risk is unknown. We evaluated the association of LDL-C with future ASCVD events in patients with and without CAC. METHODS: The study included 23 132 consecutive symptomatic patients evaluated for coronary artery disease using coronary computed tomography angiography (CTA) from the Western Denmark Heart Registry, a seminational, multicenter-based registry with longitudinal registration of patient and procedure data. We assessed the association of LDL-C level obtained before CTA with ASCVD (myocardial infarction and ischemic stroke) events occurring during follow-up stratified by CAC>0 versus CAC=0 using Cox regression models adjusted for baseline characteristics. Outcomes were identified through linkage among national registries covering all hospitals in Denmark. We replicated our results in the National Heart, Lung, and Blood Institute-funded Multi-Ethnic Study of Atherosclerosis. RESULTS: During a median follow-up of 4.3 years, 552 patients experienced a first ASCVD event. In the overall population, LDL-C (per 38.7 mg/dL increase) was associated with ASCVD events occurring during follow-up (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.04-1.24]). When stratified by the presence or absence of baseline CAC, LDL-C was only associated with ASCVD in the 10 792/23 132 patients (47%) with CAC>0 (aHR, 1.18 [95% CI, 1.06-1.31]); no association was observed among the 12 340/23 132 patients (53%) with CAC=0 (aHR, 1.02 [95% CI, 0.87-1.18]). Similarly, a very high LDL-C level (>193 mg/dL) versus LDL-C <116 mg/dL was associated with ASCVD in patients with CAC>0 (aHR, 2.42 [95% CI, 1.59-3.67]) but not in those without CAC (aHR, 0.92 [0.48-1.79]). In patients with CAC=0, diabetes, current smoking, and low high-density lipoprotein cholesterol levels were associated with future ASCVD events. The principal findings were replicated in the Multi-Ethnic Study of Atherosclerosis. CONCLUSIONS: LDL-C appears to be almost exclusively associated with ASCVD events over ≈5 years of follow-up in middle-aged individuals with versus without evidence of coronary atherosclerosis. This information is valuable for individualized risk assessment among middle-aged people with or without coronary atherosclerosis.

Social Determinants of Health Framework to Identify and Reduce Barriers to Imaging in Marginalized Communities.

Social determinants of health (SDOH) are conditions influencing individuals' health based on their environment of birth, living, working, and aging. Addressing SDOH is crucial for promoting health equity and reducing health outcome disparities. For conditions such as stroke and cancer screening where imaging is central to diagnosis and management, access to high-quality medical imaging is necessary. This article applies a previously described structural framework characterizing the impact of SDOH on patients who require imaging for their clinical indications. SDOH factors can be broadly categorized into five sectors: economic stability, education access and quality, neighborhood and built environment, social and community context, and health care access and quality. As patients navigate the health care system, they experience barriers at each step, which are significantly influenced by SDOH factors. Marginalized communities are prone to disparities due to the inability to complete the required diagnostic or screening imaging work-up. This article highlights SDOH that disproportionately affect marginalized communities, using stroke and cancer as examples of disease processes where imaging is needed for care. Potential strategies to mitigate these disparities include dedicating resources for clinical care coordinators, transportation, language assistance, and financial hardship subsidies. Last, various national and international health initiatives are tackling SDOH and fostering health equity.

Unfavorable social determinants of health and mortality risk by cardiovascular disease status: Findings from a National Study of United States Adults.

BACKGROUND: The association between cumulative burden of unfavorable social determinants of health (SDoH) and all-cause mortality has not been assessed by atherosclerotic cardiovascular disease (ASCVD) status on a population level in the United States. METHODS: We assessed the association between cumulative social disadvantage and all-cause mortality by ASCVD status in the National Health Interview Survey, linked to the National Death Index. RESULTS: In models adjusted for established clinical risk factors, individuals experiencing the highest level of social disadvantage (SDoH-Q4) had over 1.5 (aHR = 1.55; 95%CI = 1.22, 1.96) and 2-fold (aHR = 2.21; 95% CI = 1.91, 2.56) fold increased risk of mortality relative to those with the most favorable social profile (SDoH-Q1), respectively for adults with and without ASCVD; those experiencing co-occurring ASCVD and high social disadvantage had up to four-fold higher risk of mortality (aHR = 3.81; 95%CI = 3.36, 4.32). CONCLUSIONS: These findings emphasize the importance of a healthcare model that prioritizes efforts to identify and address key social and environmental barriers to health and wellbeing, particularly in individuals experiencing the double jeopardy of clinical and social risk.

Design and rationale of the social determinants of the risk of hypertension in women of reproductive age (SAFE HEART) study: An American Heart Association research goes red initiative.

BACKGROUND: Cardiovascular health literacy (CVHL) and social determinants of health (SDoH) play interconnected and critical roles in shaping cardiovascular health (CVH) outcomes. However, awareness of CVH risk has declined markedly, from 65% of women being aware that cardiovascular disease (CVD) is the leading cause of death for women in 2009 to just 44% being aware in 2019. The American Heart Association Research Goes Red (RGR) initiative seeks to develop an open-source, longitudinal, dynamic registry that will help women to be aware of and participate in research studies, and to learn about CVD prevention. We proposed to leverage this platform, particularly among Black and Hispanic women of reproductive age, to address CVHL gaps and advance health equity. METHODS: The primary objective of the study is to evaluate the cross-sectional association of CVHL, SDoH using a polysocial score, and CVH in women of reproductive age at increased risk of developing hypertension (HTN). To achieve this we will use a cross-sectional study design, that engages women already enrolled in the RGR registry (registry-enrolled). To enhance the racial and ethnic/social economic diversity of the cohort, we will additionally enroll 300 women from the Baltimore and Washington D.C. community into the Social Determinants of the Risk of Hypertension in Women of Reproductive Age (SAFE HEART) Study. Community-enrolled and registry-enrolled women will undergo baseline social phenotyping including detailed SDoH questionnaire, CVH metrics assessment, and CVHL assessment. The secondary objective is to assess whether a 4-month active health education intervention will result in a change in CVHL in the 300 community-enrolled women. DISCUSSION: The SAFE HEART study examines the association between CVHL, SDoH, and CVH, with a focus on racial and ethnic minority groups and socioeconomically disadvantaged women of reproductive age, and the ability to improve these parameters by an educational intervention. These findings will inform the future development of community-engaged strategies that address CVHL and SDoH among women of reproductive age.

Use of E-Cigarette, Traditional Cigarettes, and C-Reactive Protein: The Cross Cohort Collaboration.

This cross-sectional study included 18,797 participants from six longitudinal cohorts (CARDIA, FHS Gen III, HCHS/SOL, MESA, MiHeart, and REGARDS). 5,806 of them were with high-sensitivity C-reactive protein (hs-CRP) measurements. We found that among exclusive electronic cigarette (EC) use was associated with significantly lower high-sensitivity C-reactive protein (hs-CRP) levels compared to exclusive combustible cigarette use, suggesting a potentially lower inflammatory burden. hs-CRP levels in dual users and former smokers currently using EC were comparable to those observed in exclusive cigarette smokers. In contrast, individuals who exclusively used ECs showed no significant difference in hs-CRP levels compared to never smokers. These findings have important implications for tobacco regulation, public health, and clinical practice, highlighting the need for continued monitoring of EC-related health impacts.

Lipoprotein(a) as a cardiovascular risk factor among patients with and without diabetes Mellitus: the Mass General Brigham Lp(a) Registry.

BACKGROUND: Diabetes mellitus (DM) and Lp(a) are well-established predictors of coronary artery disease (CAD) outcomes. However, their combined association remains poorly understood. OBJECTIVE: To investigate the relationship between elevated Lp(a) and DM with CAD outcomes. METHODS: Retrospective analysis of the MGB Lp(a) Registry involving patients ≥ 18 years who underwent Lp(a) measurements between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasms, and prior atherosclerotic cardiovascular disease (ASCVD). The primary outcome was a combination of cardiovascular death or myocardial infarction (MI). Elevated Lp(a) was defined as > 90th percentile (≥ 216 nmol/L). RESULTS: Among 6,238 patients who met the eligibility criteria, the median age was 54, 45% were women, and 12% had DM. Patients with DM were older, more frequently male, and had a higher prevalence of additional cardiovascular risk factors. Over a median follow-up of 12.9 years, patients with either DM or elevated Lp(a) experienced higher rates of the primary outcome. Notably, those with elevated Lp(a) had a higher incidence of the primary outcome regardless of their DM status. The annual event rates were as follows: No-DM and Lp(a) < 90th% - 0.6%; No-DM and Lp(a) > 90th% - 1.3%; DM and Lp(a) < 90th% - 1.9%; DM and Lp(a) > 90th% - 4.7% (p < 0.001). After adjusting for confounders, elevated Lp(a) remained independently associated with the primary outcome among both patients with DM (HR = 2.66 [95%CI: 1.55-4.58], p < 0.001) and those without DM (HR = 2.01 [95%CI: 1.48-2.74], p < 0.001). CONCLUSIONS: Elevated Lp(a) constitutes an independent and incremental risk factor for CAD outcomes in patients with and without DM.

Food Environment Quality and Cardiovascular Disease Mortality in the United States: a County-Level Analysis from 2017 to 2019.

BACKGROUND: Upstream socioeconomic circumstances including food insecurity and food desert are important drivers of community-level health disparities in cardiovascular mortality let alone traditional risk factors. The study assessed the association between differences in food environment quality and cardiovascular mortality in US adults. DESIGN: Retrospective analysis of the association between cardiovascular mortality among US adults aged 45 and above and food environment quality, measured as the food environment index (FEI), in 2615 US counties. FEI was measured by equal weights of food insecurity (limited access to a reliable food source) and food desert (limited access to healthy food), ranging from 0 (worst) to 10 (best). Age-adjusted cardiovascular mortality rates per 100,000 adults aged 45 and above in the calendar year 2017-2019. County-level association between CVD mortality rate and FEI was modeled using generalized linear regression. Data were weighted using county population. RESULT: Median CVD deaths per 100,000 population were 645.4 (IQR 561.5, 747.0) among adults aged 45 years and above across US counties in 2017-2019. About 12.8% (IQR 10.7%, 15.1%) of residents were food insecure and 6.3% (IQR 3.6%, 9.9%) were living in food desert areas. Comparing counties by FEI quartiles, the CVD mortality rate was higher in the least healthy FE counties (704.3 vs 598.6 deaths per 100,000 population) compared to the healthiest FE counties. One unit increase in FEI was associated with - 12.95 CVD deaths/100,000 population. In the subgroup analysis of counties with higher income inequality, the healthiest food environment was associated with 46.4 lower CVD deaths/100,000 population than the least healthy food environment. One unit increase in FEI in counties with higher income inequality was associated with a fivefold decrease in CVD mortality difference in African American counties (- 18.4 deaths/100,000 population) when compared to non-African American counties (- 3.63 deaths/100,000 population). CONCLUSION: In this retrospective multi-county study in the USA, a higher food environment index was significantly associated with lower cardiovascular mortality.

Social Phenotyping for Cardiovascular Risk Stratification in Electronic Health Registries.

PURPOSE OF REVIEW: Evaluation of social influences on cardiovascular care requires a comprehensive analysis encompassing economic, societal, and environmental factors. The increased utilization of electronic health registries provides a foundation for social phenotyping, yet standardization in methodology remains lacking. This review aimed to elucidate the primary approaches to social phenotyping for cardiovascular risk stratification through electronic health registries. RECENT FINDINGS: Social phenotyping in the context of cardiovascular risk stratification within electronic health registries can be separated into four principal approaches: place-based metrics, questionnaires, ICD Z-coding, and natural language processing. These methodologies vary in their complexity, advantages and limitations, and intended outcomes. Place-based metrics often rely on geospatial data to infer socioeconomic influences, while questionnaires may directly gather individual-level behavioral and social factors. Z-coding, a relatively new approach, can capture data directly related to social determinant of health domains in the clinical context. Natural language processing has been increasingly utilized to extract social influences from unstructured clinical narratives-offering nuanced insights for risk prediction models. Each method plays an important role in our understanding and approach to using social determinants data for improving population cardiovascular health. These four principal approaches to social phenotyping contribute to a more structured approach to social determinant of health research via electronic health registries, with a focus on cardiovascular risk stratification. Social phenotyping related research should prioritize refining predictive models for cardiovascular diseases and advancing health equity by integrating applied implementation science into public health strategies.

Cardiovascular Health and Disease in the Pakistani American Population.

PURPOSE OF REVIEW: This narrative review seeks to elucidate clinical and social factors influencing cardiovascular health, explore the challenges and potential solutions for enhancing cardiovascular health, and identify areas where further research is needed to better understand cardiovascular issues in native and American Pakistani populations. RECENT FINDINGS: The prevalence of cardiometabolic disease is high not only in Pakistan but also among its global diaspora. This situation is further complicated by the inadequacy of current cardiovascular risk assessment tools, which often fall short of accurately gauging the risk among Pakistani individuals, underscoring the urgent need for more tailored and effective assessment methodologies. Moreover, social determinants play a crucial role in shaping cardiovascular health. The burden of cardiovascular disease and upstream risk factors is high among American Pakistani individuals. Future research is needed to better understand the heightened risk of cardiovascular disease among Pakistani individuals.

County-level socio-environmental factors and obesity prevalence in the United States.

AIMS: To investigate high-risk sociodemographic and environmental determinants of health (SEDH) potentially associated with adult obesity in counties in the United States using machine-learning techniques. MATERIALS AND METHODS: We performed a cross-sectional analysis of county-level adult obesity prevalence (body mass index ≥30 kg/m2) in the United States using data from the Diabetes Surveillance System 2017. We harvested 49 county-level SEDH factors that were used in a classification and regression trees (CART) model to identify county-level clusters. The CART model was validated using a 'hold-out' set of counties and variable importance was evaluated using Random Forest. RESULTS: Overall, we analysed 2752 counties in the United States, identifying a national median (interquartile range) obesity prevalence of 34.1% (30.2%, 37.7%). The CART method identified 11 clusters with a 60.8% relative increase in prevalence across the spectrum. Additionally, seven key SEDH variables were identified by CART to guide the categorization of clusters, including Physically Inactive (%), Diabetes (%), Severe Housing Problems (%), Food Insecurity (%), Uninsured (%), Population over 65 years (%) and Non-Hispanic Black (%). CONCLUSION: There is significant county-level geographical variation in obesity prevalence in the United States, which can in part be explained by complex SEDH factors. The use of machine-learning techniques to analyse these factors can provide valuable insights into the importance of these upstream determinants of obesity and, therefore, aid in the development of geo-specific strategic interventions and optimize resource allocation to help battle the obesity pandemic.

Predictors of incident stroke among individuals without coronary artery calcification: A pooled cohort analysis from the Multi-Ethnic Study of Atherosclerosis, Jackson Heart Study, and Framingham Heart Study.

INTRODUCTION: The absence of coronary artery calcium (CAC = 0) is associated with low risk of stroke events; however, predictors of incident stroke among those with CAC = 0 are not known. METHODS: Individual participant-level data were pooled from three prospective cohorts (Multi-Ethnic Study of Atherosclerosis, Jackson Heart Study, and Framingham Heart Study). Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors and incident adjudicated stroke among individuals with CAC = 0 who were free of clinical atherosclerotic cardiovascular disease at baseline. RESULTS: Among 6180 participants (mean age 53 [SD 11] years, 62% women, and 44% White, 36% Black, and 20% other individuals), over a median (IQR) follow up of 15 (12-16) years, there were 122 strokes (95 ischemic, 27 hemorrhagic) with an overall unadjusted event rate of 2.0 per 1000 person-years. After multivariable adjustment, risk factors associated with overall stroke included (hazard ratio [95% CI]) systolic blood pressure (SBP): 1.19 (1.05-1.36) per 10-mmHg increase and carotid intima-media thickness (CIMT): 1.21 (1.04-1.42) per 0.1-mm increment. Current cigarette smoking: 2.68 (1.11-6.50), SBP: 1.23 (1.06-1.42) per 10-mmHg increase, and CIMT: 1.25 (1.04-1.49) per 0.1-mm increment were associated with ischemic stroke, whereas C-reactive protein was associated with hemorrhagic stroke risk (0.49, 0.25-0.93). CONCLUSION: In a large cohort of individuals with CAC = 0, the rate for incident stroke was low (2.0 per 1000-person years) and was associated with modifiable risk factors.

Association of cardiovascular risk profile with premature all-cause and cardiovascular mortality in US adults: findings from a national study.

OBJECTIVE: To assess the association between cardiovascular risk factor (CRF) profile and premature all-cause and cardiovascular disease (CVD) mortality among US adults (age < 65). METHODS: This study used data from the National Health Interview Survey from 2006 to 2014, linked to the National Death Index for non-elderly adults aged < 65 years. A composite CRF score (range = 0-6) was calculated, based on the presence or absence of six established cardiovascular risk factors: hypertension, diabetes, hypercholesterolemia, smoking, obesity, and insufficient physical activity. CRF profile was defined as "Poor" (≥ 3 risk factors), "Average" (1-2), or "Optimal" (0 risk factors). Age-adjusted mortality rates (AAMR) were reported across CRF profile categories, separately for all-cause and CVD mortality. Cox proportional hazard models were used to evaluate the association between CRF profile and all-cause and CVD mortality. RESULTS: Among 195,901 non-elderly individuals (mean age: 40.4 ± 13.0, 50% females and 70% Non-Hispanic (NH) White adults), 24.8% had optimal, 58.9% average, and 16.2% poor CRF profiles, respectively. Participants with poor CRF profile were more likely to be NH Black, have lower educational attainment and lower income compared to those with optimal CRF profile. All-cause and CVD mortality rates were three to four fold higher in individuals with poor CRF profile, compared to their optimal profile counterparts. Adults with poor CRF profile experienced 3.5-fold (aHR: 3.48 [95% CI: 2.96, 4.10]) and 5-fold (aHR: 4.76 [3.44, 6.60]) higher risk of all-cause and CVD mortality, respectively, compared to those with optimal profile. These results were consistent across age, sex, and race/ethnicity subgroups. CONCLUSIONS: In this population-based study, non-elderly adults with poor CRF profile had a three to five-fold higher risk of all-cause and CVD mortality, compared to those with optimal CRF profile. Targeted prevention efforts to achieve optimal cardiovascular risk profile are imperative to reduce the persistent burden of premature all-cause and CVD mortality in the US.

Catheter ablation versus medical therapy in atrial fibrillation: an umbrella review of meta-analyses of randomized clinical trials.

This umbrella review synthesizes data from 17 meta-analyses investigating the comparative outcomes of catheter ablation (CA) and medical treatment (MT) for atrial fibrillation (AF). Outcomes assessed were mortality, risk of hospitalization, AF recurrence, cardiovascular events, pulmonary vein stenosis, major bleeding, and changes in left ventricular ejection fraction (LVEF) and MLHFQ score. The findings indicate that CA significantly reduces overall mortality and cardiovascular hospitalization with high strength of evidence. The risk of AF recurrence was notably lower with CA, with moderate strength of evidence. Two associations reported an increased risk of pulmonary vein stenosis and major bleeding with CA, supported by high strength of evidence. Improved LVEF and a positive change in MLHFQ were also associated with CA. Among patients with AF and heart failure, CA appears superior to MT for reducing mortality, improving LVEF, and reducing cardiovascular rehospitalizations. In nonspecific populations, CA reduced mortality and improved LVEF but had higher complication rates. Our findings suggest that CA might offer significant benefits in managing AF, particularly in patients with heart failure. However, the risk of complications, including pulmonary vein stenosis and major bleeding, is notable. Further research in understudied populations may help refine these conclusions.

Lack of leisure time physical activity and variations in cardiovascular mortality across US communities: a comprehensive county-level analysis (2011-2019).

OBJECTIVES: To investigate the associations between county-level proportions of adults not engaging in leisure-time physical activity (no LTPA) and age-adjusted cardiovascular mortality (AACVM) rates in the overall US population and across demographics. METHODS: Analysing 2900 US counties from 2011 to 2019, we used the Centers for Disease Control and Prevention (CDC) databases to obtain annual AACVM rates. No LTPA data were sourced from the CDC's Behavioural Risk Factor Surveillance System survey and county-specific rates were calculated using a validated multilevel regression and poststratification modelling approach. Multiple regression models assessed associations with county characteristics such as socioeconomic, environmental, clinical and healthcare access factors. Poisson generalised linear mixed models were employed to calculate incidence rate ratios (IRR) and additional yearly deaths (AYD) per 100 000 persons. RESULTS: Of 309.9 million residents in 2900 counties in 2011, 7.38 million (2.4%) cardiovascular deaths occurred by 2019. County attributes such as socioeconomic, environmental and clinical factors accounted for up to 65% (adjusted R2=0.65) of variance in no LTPA rates. No LTPA rates associated with higher AACVM across demographics, notably among middle-aged adults (standardised IRR: 1.06; 95% CI (1.04 to 1.07)), particularly women (1.09; 95% CI (1.07 to 1.12)). The highest AYDs were among elderly non-Hispanic black individuals (AYD=68/100 000). CONCLUSIONS: Our study reveals a robust association between the high prevalence of no LTPA and elevated AACVM rates beyond other social determinants. The most at-risk groups were middle-aged women and elderly non-Hispanic black individuals. Further, county-level characteristics accounted for substantial variance in community LTPA rates. These results emphasise the need for targeted public health measures to boost physical activity, especially in high-risk communities, to reduce AACVM.

Determinants of Incident Atherosclerotic Cardiovascular Disease Events Among Those With Absent Coronary Artery Calcium: Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The 2018 American Heart Association/American College of Cardiology/Multisociety cholesterol guideline states that statin therapy may be withheld or delayed among intermediate-risk individuals in the absence of coronary artery calcium (CAC=0). We evaluated whether traditional cardiovascular risk factors are associated with incident atherosclerotic cardiovascular disease (ASCVD) events among individuals with CAC=0 over long-term follow-up. METHODS: We included participants with CAC=0 at baseline from the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective cohort study of individuals free of clinical ASCVD at baseline. We used multivariable-adjusted Cox proportional hazards models to study the association between cardiovascular risk factors (cigarette smoking, diabetes, hypertension, preventive medication use [aspirin and statin], family history of premature ASCVD, chronic kidney disease, waist circumference, lipid and inflammatory markers) and adjudicated incident ASCVD outcomes. RESULTS: We studied 3416 individuals (mean [SD] age 58 [9] years; 63% were female, 33% White, 31% Black, 12% Chinese American, and 24% Hispanic). Over a median follow-up of 16 years, there were 189 ASCVD events (composite of coronary heart disease and stroke) of which 91 were coronary heart disease, 88 were stroke, and 10 were both coronary heart disease and stroke events. The unadjusted event rates of ASCVD were ≤5 per 1000 person-years among individuals with CAC=0 for most risk factors with the exception of current cigarette smoking (7.3), diabetes (8.9), hypertension (5.4), and chronic kidney disease (6.8). After multivariable adjustment, risk factors that were significantly associated with ASCVD included current cigarette smoking: hazard ratio, 2.12 (95% CI, 1.32-3.42); diabetes: hazard ratio, 1.68 (95% CI, 1.01-2.80); and hypertension: hazard ratio, 1.57 (95% CI, 1.06-2.33). CONCLUSIONS: Current cigarette smoking, diabetes, and hypertension are independently associated with incident ASCVD over a 16-year follow-up among those with CAC=0.

Coronary artery calcium scoring for cardiovascular risk assessment in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with higher incidence of atherosclerotic cardiovascular disease (ASCVD). Data investigating the role of coronary artery calcium (CAC) scoring in identifying subclinical atherosclerotic disease in IBD patients is scarce. METHODS: Using data obtained from the CLARIFY registry, a prospective study of no-charge coronary artery calcium (CAC) testing at University Hospitals, we reviewed patients with ulcerative colitis (UC) or Crohn's disease (CD) who underwent CAC scoring from 2014 to 2020. We investigated the concordance between CAC risk and 10-year estimated ASCVD risk by AHA/ACC pooled cohort equation using pre-established thresholds for statin prescription (CAC≥100, 10-year ASCVD risk ≥7.5%). We additionally investigated the association between CAC, preventive therapy initiation and Major Adverse Cardiovascular Events (MACE). RESULTS: A total of 369 patients with IBD were included (174 UC, 195 CD), with median age of 60 years. The median CAC score was 14.9 with no significant difference between UC and CD (P = .76). Overall, 151 (41%) had CAC of 0, 108 (29%) had CAC 1-99, 61 (17%) had CAC 100 to 399, and 49 (13%) had CAC ≥400 with no difference in CAC distribution between CD and UC (P = .17). There was no difference in median CAC between IBD or age/sex-matched controls (P = .34). Approximately half of the patients (52%) with IBD had 10-year estimated ASCVD risk of 7.5% or higher. Among patients with ASCVD risk <7.5% (n = 163), 29 (18%) had CAC≥100 and among patients with ASCVD risk ≥7.5% (n = 178), 102 (57%) had CAC <100. There was no difference between CAC<100 vs CAC≥100 with respect to CRP, use of immunosuppressive or amino-salicylate therapy, IBD severity or complications. CAC score (AUROC 0.67 [0.56-0.78]), but not PCE ASCVD risk (AUROC 0.60 [0.48-0.73]), was predictive of MACE. The best cut-off for CAC score was 76 (sensitivity = 60%, specificity = 69%), and was associated with 4-fold increase in MACE (Hazard Ratio 4.0 [2.0-8.1], P < .001). CONCLUSION: Subclinical atherosclerosis, as evaluated by CAC scoring, is prevalent in patients with IBD, and is associated with cardiovascular events. Further studies are needed to understand underlying biological processes of increased atherosclerotic disease risk among adults with IBD.

Risk factor associations with individual myocardial infarction subtypes and acute non-ischemic myocardial injury in the Multi-Ethnic Study of Atherosclerosis (MESA): Design and rationale.

BACKGROUND: Despite different prevalence, pathobiology, and prognosis between etiologically distinct myocardial infarction (MI) subtypes, prospective study of risk factor for MI in large NHLBI-sponsored cardiovascular cohorts is limited to acute MI as a singular entity. Therefore, we sought to utilize the Multi-Ethnic Study of Atherosclerosis (MESA), a large prospective primary prevention cardiovascular study, to define the incidence and risk factor profile of individual myocardial injury subtypes. METHODS: We describe the rationale and design of re-adjudicating 4,080 events that occurred over the first 14 years of follow-up in MESA for the presence and subtype of myocardial injury as defined by the Fourth Universal Definition of MI: MI type 1 to 5, acute non-ischemic myocardial injury, and chronic myocardial injury. The project utilizes a 2-physician adjudication process via examination of medical records, abstracted data collection forms, cardiac biomarker results, and electrocardiograms of all relevant clinical events. Comparison of the magnitude and direction of associations between baseline traditional and novel cardiovascular risk factors with incident and recurrent acute MI subtypes and acute non-ischemic myocardial injury events will be made. CONCLUSIONS: This project will result in one of the first large prospective cardiovascular cohort with modern classification of acute MI subtypes, as well as a full accounting of non-ischemic myocardial injury events, with implications for numerous ongoing and future studies in MESA. By creating precise MI phenotypes, and defining their epidemiology, this project will allow for discovery of novel pathobiology-specific risk factors, allow for development of more accurate risk prediction, and suggest more targeted preventive strategies.