Incidence Of Cardiovascular Disease Research Articles

Use of bisphosphonates in chronic kidney disease is associated with cardiovascular death.

Chronic kidney disease (CKD) is associated with increased cardiovascular risk, which may be mediated by vascular calcification. Based on evidence that bisphosphonates inhibit vascular calcification, we hypothesized use of bisphosphonates in CKD would be associated with lower incident cardiovascular disease (CVD), CVD-related mortality, and all-cause mortality. This was a longitudinal observational study including 2,593 Framingham Offspring participants. We used propensity score-adjusted Cox regression models to determine the association between bisphosphonate use and outcomes: time to incident CVD, time to CVD-related mortality, and time to all-cause mortality. The data were stratified by presence or absence of CKD, defined as estimated glomerular filtration rate <60 mL/min/1.73m2. The propensity score included age, sex, hypertension, smoking status, diabetes, total cholesterol, high-density lipoprotein, and self-reported history of fracture. In unadjusted and propensity score-adjusted analyses, those with CKD using bisphosphonates had a trend toward increased incident CVD risk (adjusted hazard ratio (HR) 1.66 (95% CI, 93-2.97)) compared to those with CKD not using bisphosphonates. Those with CKD using bisphosphonates also had increased risk of cardiovascular mortality in the propensity score-adjusted model (adjusted HR 2.20 (95% CI, 1.12-4.32)). There was no significant association between bisphosphonate use and all-cause mortality in participants with CKD. Among individuals without CKD, bisphosphonate use was significantly associated with an increase in all-cause mortality in the propensity-score adjusted analysis (adjusted HR 1.59 (95% CI, 1.27-1.98)). However, there was no significant association between bisphosphonate use and incident CVD events (adjusted HR 0.85 95% CI, 0.63-1.16) or CVD-related death (adjusted HR 0.70 (95% CI 0.36-1.37) in those without CKD. Contrary to our hypothesis, bisphosphonate use was associated with a trend toward increased incident CVD and a two-fold higher risk of CVD mortality in CKD.

Combined Effect of Air Pollution and Genetic Risk on Incident Cardiovascular Diseases.

Whether genetic susceptibility to cardiovascular diseases (CVDs) enhances the vulnerability to adverse cardiovascular outcomes by air pollution is unknown. We assessed the combined effect of air pollution and genetic predispositions on CVD risk. From the UK Biobank cohort, we selected genetically unrelated White British participants without CVD. Levels of ambient particulate matter with a diameter of <2.5 μm (PM2.5) and <10 μm were estimated using land use regression models. An individual's genetic predisposition to CVDs was determined by polygenic risk scores for coronary artery disease, myocardial infarction, stroke, ischemic stroke, heart failure, and atrial fibrillation. We stratified mortality and CVD risk by PM2.5 exposure across high and low genetic risk groups. A total of 249 082 participants (aged 56.9±8.0 years, 46.8% men) were followed for a median of 10.8 years. The combined effect of PM2.5 exposure and the genetic predisposition of CVD demonstrated the highest risk of cardiovascular death in the high genetic risk group with the greatest PM2.5 exposure (adjusted hazard ratios ranging from 1.73 to 2.12 across the polygenic risk score of each CVD). The combination of higher exposure to ambient PM2.5 and high genetic risk was associated with higher incidence of all CVDs, although no significant interactions were observed between genetic risk and PM2.5 exposure on cardiovascular death or CVD events. A combination of greater PM2.5 exposure and higher genetic predisposition to particular CVDs was modestly associated with elevated risks of cardiovascular death and CVDs. Not only alleviating PM2.5 exposure in the general population but also implementing individualized preventive approach for those at high genetic risk might be beneficial.

Latent class analysis of cardiac structure and function and association with premature cardiovascular disease: The Coronary Artery Risk Development in Young Adults (CARDIA) study

ObjectiveTo generate data-driven phenogroups of cardiac structure and function based on echocardiographic measures assessed in asymptomatic middle-aged adults free of CVD, and examine associations between these newly defined phenogroups and incident premature cardiovascular disease (CVD). MethodsData were analyzed from participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study free of CVD who underwent an echocardiogram at the Year 25 (2010-2011) in-person examination. Continuous echocardiographic measures of left heart structure, left ventricular systolic function (including strain) and diastolic function, right ventricular systolic function, and hemodynamic measures were included in latent class analysis to generate novel phenogroups. Associations between data-driven phenogroups and risk of premature CVD (coronary artery disease, stroke, or heart failure) were estimated using Cox proportional hazards regression adjusted for traditional CVD risk factors. ResultsAmong 3361 participants, mean (standard deviation) age was 50.1 (3.6) years, 57% were female, and 46% were non-Hispanic Black. Three overall phenogroups were identified and labeled as: (1) optimal cardiac mechanics (36.2%); (2) suboptimal systolic function (38.2%); and (3) suboptimal diastolic function (25.6%). Over a median 8.9 years of follow-up, 121 premature CVD events occurred. Risk of CVD was higher in the suboptimal diastolic function group (unadjusted hazard ratio [HR] 4.08 [95% CI: 2.48, 6.71] and adjusted HR 1.95 [1.12, 3.40]) compared with the optimal group. The suboptimal systolic function group had a higher unadjusted risk of CVD (1.86 [1.10, 3.15]), which was attenuated after adjustment for CVD risk factors (1.36 [0.79, 2.36]). Conclusions and relevanceUnbiased, data-driven clustering of echocardiographic measures in middle-aged adults identified distinct patterns of cardiac remodeling that were associated with risk of premature CVD. Premature CVD risk was highest with the pattern of suboptimal diastolic function. This suggests potential utility of a composite echocardiography-based index for prioritizing prevention strategies earlier in the life course.

Body adiposity index and other indexes of body composition in predicting cardiovascular disease in the Chinese population: A Cohort study.

The purpose of this study was to compare the ability of four obesity indicators, including waist circumference (WC), body mass index (BMI), body adiposity index (BAI), and waist-to-height ratio (WHtR) on prediction for incident cardiovascular disease (CVD) in Chinese Han population. We analyzed data from a prospective population cohort of 3598 participants aged 35 to 74 years from Jiangsu China. The logistic regression model was used to analyze the association between four obesity indicators and CVD risk. The ROC curve was used to assess and compare the diagnostic performance of four obesity indicators. During 8 years (median 6.3 years) of follow-up time, 82 CVD endpoints were collected during follow up (36 men and 46 women). After adjustment for age, smoking status, alcohol consumption and family history of CVD, in men, WC, BMI, and BAI were associated with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and hypertension. In women, WC, BMI and WHtR were associated with TG, HDL-C, hyperglycemia and hypertension, BAI was only associated with HDL-C, hyperglycemia, and hypertension. ROC curve analysis indicated that BAI have the highest area under the curve to identify CVD, and BMI has the lowest area under the curve to identify CVD in Chinese males. WHtR has the highest area under the curve to identify CVD, and BMI has the lowest area under the curve to identify CVD in Chinese females. CVD risk was more consistently correlated with BAI in Chinese men and more consistently correlated with WHtR and WC in Chinese women.

Polygenic Risk Scores and Extreme Coronary Artery Calcium Phenotypes (CAC=0 and CAC≥1000) in Adults ≥75 Years Old: The ARIC Study.

Coronary artery calcium (CAC) is heterogeneous in older age and is incompletely explained by traditional atherosclerotic cardiovascular disease risk factors. The extremes of subclinical atherosclerosis burden are strongly associated with either a low or high 10-year risk of incident atherosclerotic cardiovascular disease, respectively. However, the genetic underpinnings of differences in arterial aging remain unclear. We sought to determine the independent association of 2 polygenic scores for coronary heart disease (CHD) with CAC in adults ≥75 years of age. There were 1865 ARIC (Atherosclerosis Risk in Communities) participants who underwent genetic testing at visit 1 (1987-1989) and CAC scans at visit 7 (2018-2019). In the primary analysis, an externally derived multi-ancestry polygenic CHD risk score was calculated for both White and Black participants. Results were confirmed using a separate ARIC-derived polygenic CHD risk score, including ≥6 million variants computed for White participants. We used multivariable logistic regression models to assess the association of polygenic CHD risk with CAC, after adjusting for baseline, time-averaged lifestyle, traditional risk factors, and local ancestry principal components. In the primary analysis, the average age was 80.6 years old, 61.6% were women, and the median CAC score was 246 (189 participants with CAC=0, 364 participants with CAC≥1000). Compared with persons below the 20th percentile of polygenic CHD risk, persons with polygenic-CHD risk above the 80th percentile had 82% lower odds of having CAC=0 (odds ratio, 0.18 [95% CI, 0.09-0.37]) and had >4-fold higher odds of CAC≥1000 (odds ratio, 4.77 [95% CI, 2.88-7.88]). On a continuous scale, each SD increment increase in the polygenic risk score was associated with a 78% higher CAC score. Results were nearly identical using a second confirmatory polygenic CHD risk score in White participants. Polygenic CHD risk is robustly associated with a lower prevalence of CAC=0 and a higher prevalence of CAC≥1000 in adults ≥75 years of age, beyond lifestyle and traditional risk factors. These results suggest a heritable contribution to distinct healthy and unhealthy arterial aging phenotypes that persist throughout the life course.

Cryomedical technologies as a key to effective decellularization in the creation of scaffolds for vascular transplantation

Background. Cardiovascular diseases (CVDs) rank among the top three causes of death worldwide. In Europe, 3.9 million deaths annually are attributed to CVDs, with 1.8 million occurring among citizens of European Union (EU) countries. The total cost of treating patients with CVDs in EU countries amounts to €210 billion per year. Currently, the primary treatment strategy for patients with advanced stages of CVD remains bypass surgery. A significant increase in demand for vascular grafts over the past decade, particularly small-caliber vessels for cardiovascular bypass procedures, combined with a shortage of donor vessels and the limitations of artificial prostheses, makes the tissue engineering of vascular grafts a high-demand field. Purpose – to characterize modern approaches to creating decellularized vascular scaffolds based on data from open sources. Materials and Methods. The selection of publications was conducted using databases such as PubMed, Clinical Key Elsevier, Cochrane Library, eBook Business Collection, and others, focusing on contemporary methods for creating decellularized scaffolds. The first stage involved searching for literature sources using Keywords: decellularization, extracellular matrix, scaffold. In the second stage, article abstracts were reviewed, and publications not meeting the study criteria were excluded. The third stage involved examining the full texts of selected articles for compliance with inclusion criteria and research relevance. Inclusion criteria for publications subjected to content analysis included: 1) coverage of current information on the creation of decellularized scaffolds; 2) alignment of studies with key principles of evidence-based medicine; 3) open access to the full-text article. Results. The first attempt to create a blood vessel substitute using tissue engineering methods was made by Weinberg C.B. &amp; Bell E. in 1986. Biological scaffolds, composed of extracellular matrix (ECM), are commonly used for various reconstructive surgical procedures and are increasingly employed in regenerative medicine strategies for tissue and organ replacement. ECM is a complex network of macromolecules that provides an appropriate local microenvironment for cell survival and activity in vivo, influencing cell shape, metabolism, function, migration, proliferation, and differentiation. A scaffold, in turn, can be defined as a three-dimensional platform necessary for actions ranging from cell-biomaterial interaction and cell adhesion to controlled biodegradation rates that correspond to tissue regeneration. Decellularization is a method for removing cellular components from organs or tissues to create an acellular scaffold composed of tissue ECM capable of providing a biomimetic microenvironment. The physicochemical signals and biological efficacy of ECM scaffolds can be maintained after decellularization, thus providing a substrate for mechanical support and a biological 3D carrier for subsequent recellularization. The complexity and duration of decellularization protocols are generally proportional to the degree of geometric and biological preservation desired for the tissue after processing. Conclusions. The rising incidence of CVDs and the need for surgical intervention have underscored the necessity, among other things, of creating artificial small-caliber vascular grafts – substitutes for blood vessels, especially those under 6 mm in diameter. Various sources, including human and animal cadavers, have been identified as sources of native vessels for decellularization. The creation of a cellular pattern is a new trend that is actively pursued, directly offering spatial control over angiogenesis, closely mimicking the natural environment. Cryopreservation is one of the most common procedures for graft storage. The freezing-thawing process effectively lyses cells in tissues and organs and is one of the most promising approaches to decellularization in the development of vascular scaffolds.

Abstract 4129036: Air pollution and Cardiovascular Disease Incidence in a Pooled Analysis of 6 U.S. Cohorts

Introduction/Background: Long term air pollution is associated with cardiovascular disease (CVD) incidence, however the effects at low levels in the US are unknown. Research Questions/Hypothesis: To assess the effect of long-term exposure to ambient air pollution CVD incidence (myocardial infarction [MI], stroke, and all CVD) in a pooled analysis of epidemiological cohorts. Materials and Methods: We harmonized data from six cohorts (Cardiovascular Health Study, Nurses’ Health Study II, Multi-Ethnic Study of Atherosclerosis, and Reasons for Geographic And Racial Differences in Stroke Study, Sister Study, and Women’s Health Initiative) with both CVD incidence data and extensive covariate information. We predicted time-varying two-year average concentrations of particulate matter &lt;2.5 microns (PM 2.5 ) and nitrogen dioxide (NO 2 ) from 1990-2019 at participant residential addresses using validated regionalized spatio-temporal models, combining spatio-temporal universal kriging and partial least squares regression with inputs from monitoring data from regulatory and researcher-deployed networks, satellite remote-sensing data and chemical transport modeling. Cox proportional hazards regression models adjusted for individual and area-level information, including smoking status, socio-economic factors, anthropometry, blood pressure, cholesterol, and other clinical variables. Results: Our analysis included over 300,000 participants and 10,229 incident CVD events. The median residential concentration of PM 2.5 was 10.1 µg/m 3 and NO 2 was 9.3 ppb. A 5 µg/m 3 increase in PM 2.5 was not significantly associated with a higher hazard ratio for all outcomes: 1.03 (95%CI: 0.96, 1.10) for CVD incidence, 1.03 (95%CI 0.93, 1.15) for MI, and 1.00 (95%CI 0.90, 1.10) for stroke. We found that a 10ppb increase in NO 2 was associated with a 1.06 (95%CI: 1.01, 1.11) higher hazard ratio for CVD, 1.07 (95%CI: 1.01, 1.11) for MI, and 1.02 (95%CI 0.96, 1.09) for stroke. Conclusions: In this analysis of a large, pooled cohort with excellent exposure, outcome, and covariate information, we found an association of NO 2 exposure—considered a surrogate for traffic-related air pollution—with CVD incidence and MI. Associations with particulate matter were not statistically significant, but could not exclude a small increased risk. We are extending this analysis to include 6 additional cohorts and an additional 700,000 participants to allow for generation of a highly resolved concentration-response function.

Abstract 4132351: Soluble Urokinase Plasminogen Activator Receptor Levels Predict Incident Cardio-Kidney-Metabolic Disease Risk

Introduction: Given the rising global incidence of cardio-kidney-metabolic (CKM) syndrome, there is an urgent need for novel risk prediction strategies for CKM disease. Hypothesis: As soluble urokinase plasminogen activator receptor (suPAR) levels have been associated with the development of cardio-kidney disease, we hypothesized that elevated suPAR levels would predict incident CKM disease risk. Methods: A total of 25,596 UK Biobank participants without CKM disease at enrollment were analyzed for the association of suPAR levels and incident CKM disease. CKM disease was defined as the first occurrence of CVD (heart failure, atrial fibrillation/flutter, coronary heart disease, stroke, and peripheral artery disease), chronic kidney disease (CKD), or metabolic disease (type 2 diabetes mellitus and obesity). Incident CVD, CKD, and metabolic disease were also analyzed separately as secondary outcomes. Kaplan-Meier analysis was performed to visualize the association between suPAR levels and the primary composite CKM outcome. Competing-risk regression, while accounting for competing non-CKM disease death, was performed to examine the association between suPAR levels and the primary composite CKM outcome. Models were adjusted for demographics, traditional risk factors, and CRP levels. Results: The mean age was 56.0 (SD 8.3) years, 44% were male, and 94% were White. suPAR levels were associated with a significantly higher rate of composite CKM events (P&lt;0.001) (Figure 1). During a median follow-up of 13.5 [IQR 1.7] years, 5,012 (20.0%) composite CKM events, 3,599 (8.3%) incident CVD events, 863 (3.4%) incident CKD events, and 1,397 (4.7%) incident metabolic disease events occurred. suPAR levels (per SD) significantly predicted the primary composite CKM outcome (sHR 1.23, 95% CI 1.19-1.27) after adjustment. suPAR levels (per SD) also significantly predicted incident CVD (sHR 1.24, 95% CI 1.19-1.29), incident CKD (sHR 1.41, 95% CI 1.30-1.53), and incident metabolic disease (sHR 1.17, 95% CI 1.10-1.24) after adjustment. Conclusion(s): In this large, longitudinal cohort study of UKB participants, plasma suPAR levels were a significant predictor of CKM disease risk, independent of demographics, traditional risk factors, and CRP levels.

Abstract 4136040: Wearable Device-Measured Physical Activity and Incident Cardiovascular Diseases In Cancer Survivors

Background: Cardiovascular diseases (CVD) is the leading cause of non-cancer mortality among cancer survivors. Despite the known benefits of physical activity on cardiovascular health in the general population, evidence regarding post-diagnosis physical activity and CVD risk among cancer survivors is limited. Objectives: To explore the associations of wearable device-measured moderate-to-vigorous intensity physical activity (MVPA) with CVD risk in long-term cancer survivors. Methods: The retrospective analysis involved a prospective cohort of 6109 cancer survivors without CVD from the UK Biobank accelerometry subsample. Cancer diagnoses were obtained from national cancer registries (International Classification of Diseases-10 [ICD-10], C00-C97, except for non-melanoma skin cancer, in situ, and non-well-defined cancers), and participants were followed up through December 31, 2022. A machine-learning algorithm was utilized to categorize MVPA into four groups based on guideline-recommend MVPA duration (0-75 min/week, 75-150 min/week, 150-300 min/week, ≥300 min/week). Results: Over a median follow-up of 7.88 years, there were 539 incident CVD events, including 361 incident CAD events, 155 incident HF events, and 109 incident stroke events. A clear inverse linear dose-response relationship between MVPA volume and the incidence of CVD was observed (P for nonlinear=0.49), with no maximal threshold for the benefits. Adjusted CVD incidence rates (95% confidence intervals [CIs]) across MVPA groups (0-75 min/week, 75-150 min/week, 150-300 min/week, ≥300 min/week) were 15.30 (12.90, 18.10), 13.50 (11.00, 16.40), 12.00 (10.20, 14.10), and 9.86 (8.35, 11.60) per 1000 person-years, respectively. Adjusted hazard ratios (95% CI) for CVD, CAD, HF, and stroke in the highest MVPA group (≥300 min/week) compared with those with the lowest MVPA group (0-75 min/week) were 0.63 (0.49, 0.80), 0.68 (0.51, 0.91), 0.66 (0.42,1.06), 0.72 (0.42, 1.23), respectively. Conclusions: Findings from the UK Biobank study suggest that longer durations of MVPA are associated with reduced incident CVD risk in cancer survivors, particularly in CAD risk reduction, underscoring the potential for physical activity to serve as a key component in cardio-oncology care.

Abstract 4147617: Depression and the Development of Cardiovascular Disease: Insights from All of Us Research Program

Introduction/Background: Depression is recognized as a risk factor for worse outcomes in patients with cardiovascular disease, but there is limited research on whether individuals with depression have an increased incidence of future cardiovascular disease. Research questions/Hypothesis: Do individuals with depression have an increased incidence of cardiovascular disease? Goals/Aims: This study was conducted to evaluate the association between a diagnosis of depression and the risk of developing future cardiovascular events, to determine whether the treatment of depression should be considered as a primary form of cardiovascular disease prevention. Methods/Approach: We conducted a prospective analysis using the “All Of Us” Research Program dataset. Participants who responded to the historical depression status in the “Personal/Family History Survey” and with linked electronic health records data were considered eligible for this study. We used Cox regression models to calculate the incidence of myocardial infarction (MI), stroke, heart failure (HF), and atrial fibrillation (AF) and the hazard ratio (HR) of a diagnosis of depression. Models were adjusted for sex, race, age, and prevalent hypertension, diabetes mellitus, hyperlipidemia, and smoking. The survival analysis of the four outcomes was conducted in parallel. We conducted sensitivity analysis by excluding participants with documentation of prior MI, stroke, HF, and/or AF. Results/Data: 100,030 participants were included in this study, with a mean age of 53.2 (standard deviation of 16.5). 68.4% of participants were female, 10% were Hispanic, 9.6% were Black, and 37.1% had a diagnosis of depression. The median follow up time was 3 years. Compared to participants without depression, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.05–1.41), stroke (aHR 1.68, 95% CI 1.06–2.68), HF (aHR 1.28, 95% CI 1.15–1.43), and AF (aHR 1.14, 95% CI 1.02–1.27). In the sensitivity analysis, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.03–1.44), stroke (aHR 1.68, 95% CI 1.06–2.68), and HF (aHR 1.31, 95% CI 1.15–1.48) but not AF (aHR 1.12, 95% CI 0.99–1.27). Conclusions: This study indicates that patients with a diagnosis of depression were more likely to develop cardiovascular disease, even if they had no known history of cardiovascular disease. Providers should include the treatment of depression as a part of a holistic approach to cardiovascular disease prevention.

Abstract 4119535: Aspirin Use and Cardiovascular Disease Incidence in Adults with High Lipoprotein(a): A Multi-Cohort Study

Introduction: There is an active debate about who may benefit from taking aspirin to reduce their incidence of cardiovascular disease (CVD). Some prior cohort studies with small sample size suggest that aspirin use may be associated with a lower incidence of CVD or coronary heart disease (CHD) in adults with Lp(a) ≥50 mg/dL but not in those with Lp(a) &lt;50 mg/dL, a hypothesis that needs confirmation. Research question: Does the association of aspirin use with incident CVD or CHD vary by Lp(a) among US adults? Methods: We analyzed publicly available data from adults without CVD at baseline in the ARIC (n=13,085, mean age 54 years), CHS (n=3,956, mean age 72 years), and MESA (n=6,324, mean age 62 years) studies. Lp(a) ≥50 mg/dL was defined as high. Participants were followed for incident CVD (myocardial infarction, stroke, or CVD death) and CHD (myocardial infarction or CHD death; median follow-up: ARIC 26 years, CHS 12 years, MESA 14 years). Hazard ratios associated with aspirin use were calculated after propensity score matching (primary analysis) and in all participants using multivariable adjustment (secondary analysis). Mixed-effects models were used to obtain pooled hazard ratios. Results: Aspirin use was 25.1% in ARIC, 29.6% in CHS, and 19.9% in MESA. In MESA, adults taking aspirin were older, had higher blood pressure, and were more likely to have diabetes and a low estimated glomerular filtration rate and to be taking antihypertensive medication and a statin versus those not taking aspirin. These differences were attenuated or not present in ARIC and CHS. The CVD incidence rate per 1,000 person-years (95%CI) was higher in adults with versus without high Lp(a): 16.3 (15.3-17.4) and 12.5 (12.1-13.0), respectively, in ARIC, 35.8 (31.5-40.1) and 32.3 (30.6-34.0) in CHS, and 10.8 (9.1-12.4) and 8.2 (7.5-8.9) in MESA. Aspirin use was not associated with CVD or CHD incidence in adults with or without high Lp(a) in the primary analysis ( Figure ). No association between aspirin use and CVD or CHD incidence was present in the secondary analysis using multivariable adjustment (data not shown). Conclusion: The association of aspirin use with CVD and CHD incidence did not differ by Lp(a) in this multi-cohort study.

Abstract 4138672: Blood Pressure and Cardiovascular Outcomes in Adults with Diabetes and Chronic Kidney Disease

Background: Most international guidelines recommend intensive blood pressure (BP) targets (e.g., &lt;130/80 mm Hg) for patients with chronic kidney disease (CKD). However, the data supporting these recommendations are limited, particularly for those with concomitant diabetes. Hypothesis: Systolic BP (SBP) &lt;130 mm Hg and diastolic BP (DBP) &lt;80 mm Hg are associated with a reduced risk of cardiovascular disease (CVD) in adults with diabetes and CKD. Aims: To determine the association of BP with incident CVD risk among adults with diabetes and CKD. Methods: From a Korean nationwide health screening database, we identified 373,966 adults aged 20-79 with both diabetes and CKD who: (1) underwent baseline health examinations in 2009-2013; (2) had ≥3 BP measurements; and (3) did not have CVD at baseline. The associations of baseline average SBP and DBP with CVD risk were assessed using multivariable-adjusted cause-specific Cox models. The primary outcome was CVD event, defined as a composite of myocardial infarction, stroke, heart failure, or death from CVD. Results: The median (Q1-Q3) age of the participants was 62 (53-70) years; 40.8% were female. Over a median follow-up of 10.2 years, a total of 40,781 incident CVD events occurred. Compared with SBP 130 to &lt;140 mm Hg as the referent group, the multivariable-adjusted HRs (95% CIs) for CVD event in the SBP ≥150 mm Hg, 140 to &lt;150 mm Hg, 120 to &lt;130 mm Hg, and &lt;120 mm Hg groups were 1.34 (1.29-1.39), 1.11 (1.08-1.14), 0.89 (0.87-0.91), and 0.77 (0.74-0.80), respectively. Compared with DBP 80 to &lt;90 mm Hg as the referent group, the HRs (95% CIs) in the DBP ≥100 mm Hg, 90 to &lt;100 mm Hg, 70 to &lt;80 mm Hg, and &lt;70 mm Hg groups were 1.70 (1.56-1.85), 1.19 (1.15-1.24), 0.88 (0.86-0.90), and 0.83 (0.80-0.87), respectively (Figure A). SBP &lt;130 mm Hg and DBP &lt;80 mm Hg were each associated with a reduced CVD risk in a log-linear manner (Figure B, Figure C). The findings were consistent when examining kidney instead of cardiovascular outcomes. Conclusion: Among patients with diabetes and CKD, SBP below 130 mm Hg and DBP below 80 mm Hg were associated with a reduced risk of CVD.

Abstract 4134249: Cardiovascular Risk Factors and Associations of Chronic Inflammatory-Related Disease in the Multi-Ethnic Study of Atherosclerosis

Background: Inflammation plays a role in the development of cardiovascular disease (CVD). We have defined various non-cardiovascular and non-cancer conditions, both infectious and non-infectious, with a common basis of inflammation; collectively termed Chronic Inflammatory-Related Disease (ChrIRD). We have previously described that ChrIRD is common, associated with baseline inflammatory marker levels, associated with high mortality, and has a bidirectional association with CVD. The clinical implications of these data require further study. Aims: We hypothesize that many traditional risk factors for CVD are also associated with ChrIRD and that ChrIRD has additional unique risk factors. We also hypothesize that the treatment of traditional CVD risk factors is associated with a decreased likelihood of ChrIRD. Methods: We studied MESA participants free of overt CVD or significant illness at baseline. ChrIRD was determined based on review of ICD codes for hospitalizations and deaths. Incident CVD was adjudicated by review of medical records. We performed proportional hazards regression (time-dependent for CVD) to identify factors associated with a first diagnosis of ChrIRD. All variables were simultaneously entered into the model. Results: Participants (n=6155) had mean age 62±10 years and 47% male gender. ChrIRD was observed in 24% and CVD in 18%; including 8% with both conditions. Participants with a diagnosis of CVD, older age, higher heart rate, higher BMI, current or ever smoking status, higher HDL, higher baseline IL6 and GlycA levels, and NSAID use had increased likelihood of ChrIRD. Whereas those with female sex, higher total cholesterol, and statin use had a decreased likelihood of ChrIRD. Participant race/ethnicity, blood pressure, diabetes status, antihypertensive use, aspirin use, baseline CRP level, and baseline D-dimer level were not associated with ChrIRD. Regression results are summarized in Table 1. Conclusions: ChrIRD shares some risk factors with CVD, while other risk factors are opposite. Better understanding of ChrIRD could eventually lead to improved patient care.

Abstract 4130314: High sodium, low potassium diet is associated with incident cardiovascular disease among US Hispanic/Latino adults: results from the Hispanic Community Health Study/Study of Latinos.

Background: Diets high in sodium and low in potassium are associated with increased blood pressure level but associations with cardiovascular disease (CVD) remain controversial. Few studies have evaluated this relationship among Hispanic/Latino adults. Objective: To assess whether dietary sodium and potassium are associated with incident CVD among diverse US Hispanics/Latino adults. Methods: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) is a cohort of 16,415 self-identifying Hispanic/Latino adults aged 18-74 four US urban communities in 2008-2011 (visit 1; V1). V1 included a comprehensive examination with in-person measurement of health information and interviewer administered questionnaires. Dietary sodium (mg/day) and potassium (mg/day) intakes were assessed from the average of two 24-hour dietary recall surveys administered by bilingual registered dietitians. CVD events occurring from V1 through 2019 were adjudicated by an expert panel of clinicians. We used Poisson regression to determine the association (incidence rate ratio, IRR) between sodium, potassium, and the sodium-to-potassium ratio, with CVD, using time to CVD as an offset. Models accounted for HCHS/SOL complex survey design and were adjusted for demographic, including Hispanic/Latino background, socioeconomic, and behavioral factors along with energy consumption, body mass index, cholesterol, and family history of CVD. Results: Among 15,291 participants without self-reported CVD at V1, mean age was 40 years, with 53% female. Mean daily intakes of sodium and potassium were 3,040 mg/day and 2,422 mg/day, respectively. Molar ratio of sodium to potassium was 1.33. Over 9.7 years of follow-up, there were 311 CVD events (2.0 events per 1,000 person years, 95% CI: 1.6, 2.5). In adjusted models, nutrients were associated with increased risk of CVD: by 17% for each 1g/day increment of sodium (IRR: 1.17, 95% CI: 1.03, 1.33); by 29% for each 1g/day decrement of potassium (IRR: 1.29, 95% CI: 1.01, 1.64); and by 112% for each 0.5 molar increment of sodium to potassium ratio (IRR: 2.12, 95% CI: 1.13, 4.11). Conclusions: In a large diverse sample of Hispanic/Latino adults, high dietary sodium and low dietary potassium were independently associated with an increased risk of CVD. Results underscore the importance of intensifying public health interventions to improve nutrient quality, by reducing dietary sodium and increasing dietary potassium consumption as a means of preventing CVD.

Abstract 4136996: Co-morbid Insomnia and Obstructive Sleep Apnea (COMISA) are Related to Incident Hypertension in a 20-Year Retrospective Cohort Study of 1.3 million Younger Men and Women Veterans: Associations by Sex

Introduction: Insomnia and obstructive sleep apnea (OSA) each increase risk for hypertension (HTN). Among older adults, there is a negative synergistic association of comorbid insomnia and OSA (i.e., COMISA) on incident cardiovascular disease (CVD) but it is unknown if this comorbidity is associated with HTN risk earlier in the lifespan. Research Questions: 1) Is COMISA associated with incident HTN among younger adults? 2) Do COMISA-HTN associations differ by sex? Hypotheses: We hypothesized that 1) COMISA would be associated with a greater risk of HTN than having no sleep disorder, 2) the hazard would be larger than for insomnia and OSA alone, and 3) distinct COMISA-HTN associations would be observed among men and women, respectively. Methods: Analyses included Veterans who enrolled in Veterans Health Administration (VA) care 2001-2021, a group selected because of its early adult age distribution. We merged administrative data, including outpatient and inpatient encounters, diagnoses, (ICD-9-CM/10 codes/dates) and pharmacy records. Veterans without demographic data, a history of other sleep disorders or CVD, or &lt;2 clinical encounters were excluded. Sleep disorders were defined by 1 inpatient or ≥2 outpatient encounters. HTN was defined by 1 inpatient or ≥2 outpatient encounters and/or ≥1 antihypertensive medication fill. Time-varying Cox proportional hazard models were adjusted for sociodemographic, behavioral/lifestyle, and clinical factors, and stratified analyses by sex. We used multiple imputation to address missing data. Results: Analyses included 1,293,165 Veterans (12% women; mean age 32.8) with an average follow-up of 7.6 years. Men with COMISA showed a 19% greater risk of HTN vs. no sleep diagnosis (95% CL: 1.17-1.20). Risks were slightly lower – but still significant – for men with only insomnia (HR:1.08 [95% CL: 1.06-1.09]) or only OSA (HR:1.15 [95% CL: 1.13-1.16]). Women with COMISA had a 21% greater risk of HTN vs. those without a sleep diagnosis (95% CL: 1.16-1.26), and those with insomnia (HR:1.15 [95% CL: 1.11-1.19]) or OSA (HR:1.13 [95% CL: 1.09-1.17]) showed a lower, though still significant risk. Conclusion: In this younger group, Veterans with COMISA had a 19-21% greater risk of HTN than without a disorder, and this risk was similar by sex and slightly higher than that attributable to insomnia or OSA alone. Increased identification of disordered sleep among younger adults should be a cardiovascular prevention priority.

Abstract 4127990: Inactive Matrix Gla Protein and Cardiovascular Outcomes: the Multi-Ethnic Study of Atherosclerosis

Background: Matrix Gla protein (MGP) inhibits arterial calcification. Higher inactive MGP, dephosphorylated-uncarboxylated (dp-ucMGP), is positively associated with vascular calcification, possibly portending cardiovascular events. The objective was to determine the association of dp-ucMGP with incident cardiovascular disease (CVD) events and mortality in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: MESA is a cohort study of 45-84 year-old individuals enrolled between 2000-02 with adjudicated outcomes through 2019. Dp-ucMGP was measured at baseline in n=2663 participants with cardiac computed tomography at Exams 1 (2000-02) and 5 (2010-12). Using age-stratified Cox proportional hazard models, adjusted for sex, race-ethnicity, body mass index, systolic blood pressure, statin use, anti-hypertensive medication use, smoking status, physical activity, alcohol use, diabetes, high density lipoprotein, low density lipoprotein, triglycerides, phosphate, and estimated glomerular filtration rate, we determined the association of dp-ucMGP with risk of all CVD (mean follow-up 16 + 4 years), hard CVD (17 + 3 years), hard CHD (17 + 3 years), and all-cause mortality (18 + 2 years). Results: The youngest age quartile (45-53-years-old) with higher dp-ucMGP levels (520-2934 pmol/L) had an increased risk of all CVD (HR 3.01 [95% CI 1.56, 5.80], p=0.001), hard CVD (HR 2.78 [95% CI 1.29, 6.02], p=0.009), hard CHD (HR 3.37 [95% CI 1.29, 8.81], p=0.013) and all-cause mortality (HR 2.69 [95% CI 1.06, 6.79], p=0.037) compared to dp-ucMGP levels between 150-519 pmol/L in maximally adjusted models. There was no relationship with any outcomes for the other age quartiles (Table). Conclusions: Middle aged individuals with elevated dp-ucMGP levels ( &gt; 520 pmol/L) had an increased risk of incident CVD, CHD, and all-cause mortality.

Abstract 4113411: Long Term Outcomes of Hypertension and Antihypertensive Drugs in Young Healthy Adults: A Nationwide Population-based Prospective Cohort Study in Korea

Background: Long term follow-up data on elevated blood pressure (BP) or antihypertensive drugs in young adults are scarce. The effect of hypertension (HTN) and antihypertensive medications on the cardiovascular disease incidence in young healthy adults (20~45 years) was analyzed using a large-scale population medical use database in Korea. Methods: In total, 4,590,597 young Korean adults without comorbidities who underwent regular health examination were included in this study. They were stratified into four groups according to their BP (optimal BP, normal BP, high normal BP, and HTN). The primary outcome was a composite of the incidence of myocardial infarction and ischemic and hemorrhagic stroke, obtained by tracking the medical use data of the first-ever ICD-10 codes. Subgroup analysis was conducted by categorizing the HTN group into two subgroups according to the prescription ratios of the antihypertensive drugs during the follow-up period. Results: The average age was 33.8 years and median follow-up duration was 15.9 years. HTN elevated the incidence risk of major cardiovascular disease by 2.16 times compared to that of the optimal BP group. Dyslipidemia and HTN were the most dominant risk factors for myocardial infarction and stroke, respectively. In the subgroup analysis, antihypertensive medications decreased the incidence of cardiovascular disease by 70% in all diseases. Conclusions: Cardiovascular risk factors, including HTN, contribute to major cardiovascular disease incidence in young adults. The antihypertensive medications decreased the major cardiovascular disease incidence estimates.

Abstract 4137559: Assessing Veterans’ Risk of Cardiovascular Disease by Gender Identity

Background: Extant literature suggests that transgender and gender diverse (TGD) individuals experience a higher burden of CVD risk factors and psychosocial stressors than their cisgender (cis) peers. However, prior studies have been limited by self-reported outcomes or small samples. Aim: To determine whether TGD veterans have greater CVD (MI, ischemic stroke, cardiac revascularization) incidence than cis veterans using large, nationwide data. Methods: We used EHR data from the Veterans Healthcare Administration to identify veterans with &gt;2 outpatient encounters in fiscal years 2010-2019. Veterans’ gender identity was classified using natural language processing in combination with gender-affirming hormone therapy (GAHT) and a previously validated algorithm for identifying TGD individuals using ICD codes and VHA data. Of 1,105,082 veterans without prior CVD, 42,149 were classified as TGD. We examined sample characteristics by gender identity and used Cox regression to assess the association of gender identity with incident CVD. Results: TGD veterans’ mean age (years) was 46 (cis females=40; cis males=53). Cis females had the fewest CVD risk factors, followed by TGD veterans and cis males. Adjusting for age, race, and Hispanic ethnicity, TGD veterans had 1.49 [1.42-1.56] and 0.93 [0.90-0.97] times the risk of CVD compared to cis females and cis males, respectively. Upon additional adjustment for other CVD risk factors, renal function, alcohol use disorder, depression, anxiety, and sexual minority status, results remained statistically significant. Significance also held in sensitivity analyses which matched each TGD veteran to cis female and male veterans on age within 2 years. In analyses stratified by gender identity, trans feminine (HR [95% CI]: 1.26 [1.14-1.40]) and uncategorized TGD veterans (HR [95% CI]: 1.29 [1.22-1.37]) were at higher CVD risk than cis female veterans; trans masculine (HR [95% CI]: 0.85 [0.77-0.93]) and trans feminine veterans (HR [95% CI]: 0.90 [0.82-0.99]) were at lower CVD risk than cis male veterans. Among TGD veterans, GAHT receipt was associated with an 11% decrease in CVD risk. Conclusion: TGD veterans’, particularly trans feminine and uncategorized TGD veterans’, CVD risk was greater than that of cis females. Contrary to prior findings, GAHT was associated with decreased CVD risk. These results invite further study into the mechanisms by which GAHT and other factors impact CV health across and within gender identities.

Abstract 4135835: Prevalence of Diabetes Mellitus in Calcutta Schoolteachers and its Relationship with Cardiovascular Risk as Assessed by the ASCVD Model

Introduction: Cardiovascular disease (CVD) is rising in prevalence in India with economic development and the adoption of a Western lifestyle. Hypothesis: The increase in incidence and prevalence of CVD is possibly due to a rise in the incidence of risk factors like diabetes mellitus (DM), hypertension, hyperlipidemia, lack of physical activity and obesity, among various other causes. Aims: 1. To estimate the prevalence of DM in the community of Calcutta schoolteachers 2. To examine the relationship between the prevalence of DM and CVD risk as assessed by the different traditional CVD risk factors (age, sex, hypertension, current smoking, DM, and hyperlipidemia). Methods: We recruited 4,150 schoolteachers from 400 schools in Calcutta, India between June, and August 2019 with approval of the Tufts IRB and the local Ethics Committee. Participants were asked questions about their different risk factors to ascertain their cardiovascular risk by the ASCVD risk calculator. Baseline values (total cholesterol 170 mg/dL, HDL-C 50 mg/dL, no DM) were used when a participant’s glycemic status or lipid profile was not available. Based on the risk score, participants were stratified as mild (&lt;5%), moderate (5-10%), or high (&gt;10%) risk for developing ASCVD. A total of 240 participants were randomly selected from a stratified sample of the participants for evaluation for diabetes using HbA1c. DM was diagnosed when the Hb A1 C was 6.5% or more. Results: The mean age of the participants was 44 years, and 41% were male. Out of a total of 4,150 participants, 85.7% (3,558) were in the low-risk for CVD category, 9.0% (374) were moderate-risk, and 5.3% (218) were high-risk. Among the 240 screened for DM, 17.1% (41) were found to have the condition, and 41.3% (99) were pre-diabetic. There was no significant difference in prevalence of DM between men and women in the overall study population and in the mild risk group. However, more women in the medium risk group and more men in the high-risk group were found to be diabetic (p value &lt;0.001 in both). Some participants were reclassified based on their new diagnosis of DM. Conclusions: The prevalence of DM was high among Calcutta schoolteachers, which contributes to being at increased risk for ASCVD. Most participants were unaware of their DM or cardiovascular risk, highlighting the need for increased testing and awareness. The estimates from this study may be used to understand the community burden of DM and cardiovascular risk.

Abstract 4137058: Clinical Characteristics and Outcomes of South Asians Presenting with Acute Coronary Syndrome

Background: Patients of South Asian descent have a higher incidence of atherosclerotic cardiovascular disease and are affected by clinically significant coronary artery disease at an earlier age when compared to the general population. As a result, they have been shown to have a higher rate of cardiovascular events. This at-risk population has not been well studied as it pertains to acute coronary syndrome. Methods: Out of 1610 patients who presented to one of two tertiary care centers between 2021-2022 with a diagnosis of acute coronary syndrome and underwent coronary angiography, 240 patients were identified as being South Asian and were included in the study. 480 non-South Asian patients were randomly selected as controls. A retrospective analysis was conducted to study the demographics, risk factors, clinical presentation, diagnostic features, and outcomes of the two groups. Results: South Asian patients who were diagnosed with acute coronary syndrome and underwent coronary angiography were significantly younger than non-South Asian patients (61 vs 65 years, p &lt; 0.001). Though they were less likely to be smokers, they were significantly more likely to have other known risk factors including hypertension, dyslipidemia, and a history of prior myocardial infarction (p &lt; 0.001). South Asians had mean lower HDL (p = 0.02), higher triglycerides (0.006), and higher Hgb A1C (p &lt; 0.001). Surprisingly, rates of multivessel disease (defined as stenosis of 50% or greater in two or three vessels) were similar between the two groups. South Asians were more likely to be referred for CABG after initial coronary angiography most likely due to diffuse disease (p = 0.014). Clinical outcomes including pre-discharge LVEF, and 2-year mortality were similar between the groups. Conclusions: South Asians are a notoriously high-risk group when it comes to early-onset and more severe coronary artery disease. The pathophysiology behind this disproportionate manifestation of cardiovascular disease is not entirely understood, but several efforts to delineate this are ongoing. Our data demonstrate that this is at least in part, due to a higher prevalence of conventional modifiable and nonmodifiable risk factors in South Asian patients.