Composite Cardiovascular Disease Research Articles

Chronic Obstructive Pulmonary Disease Exacerbations Increase the Risk of Subsequent Cardiovascular Events: A Longitudinal Analysis of the COPDGene Study.

Cardiovascular disease (CVD) is the most important comorbidity in patients with chronic obstructive pulmonary disease (COPD). COPD exacerbations not only contribute to COPD progression but may also elevate the risk of CVD. This study aimed to determine whether COPD exacerbations increase the risk of subsequent CVD events using up to 15 years of prospective longitudinal follow-up data from the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study. The COPDGene study is a large, multicenter, longitudinal investigation of COPD, including subjects at enrollment aged 45 to 80 years with a minimum of 10 pack-years of smoking history. Cox proportional hazards models and Kaplan-Meier survival curves were used to assess the risk of a composite end point of CVD based on the COPD exacerbation rate. Frequent exacerbators exhibited a higher cumulative incidence of composite CVD end points than infrequent exacerbators, irrespective of the presence of CVD at baseline. After adjusting for covariates, frequent exacerbators still maintained higher hazard ratios (HRs) than the infrequent exacerbator group (without CVD: HR, 1.81 [95% CI, 1.47-2.22]; with CVD: HR, 1.92 [95% CI, 1.51-2.44]). This observation remained consistently significant in moderate to severe COPD subjects and the preserved ratio impaired spirometry population. In the mild COPD population, frequent exacerbators showed a trend toward more CVD events. COPD exacerbations are associated with an increased risk of subsequent cardiovascular events in subjects with and without preexisting CVD. Patients with COPD experiencing frequent exacerbations may necessitate careful monitoring and additional management for subsequent potential CVD. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00608764.

Association between gait video information and general cardiovascular diseases: a prospective cross-sectional study

Abstract Aims Cardiovascular disease (CVD) may not be detected in time with conventional clinical approaches. Abnormal gait patterns have been associated with pathological conditions and can be monitored continuously by gait video. We aim to test the association between non-contact, video-based gait information and general CVD status. Methods and results Individuals undergoing confirmatory CVD evaluation were included in a prospective, cross-sectional study. Gait videos were recorded with a Kinect camera. Gait features were extracted from gait videos to correlate with the composite and individual components of CVD, including coronary artery disease, peripheral artery disease, heart failure, and cerebrovascular events. The incremental value of incorporating gait information with traditional CVD clinical variables was also evaluated. Three hundred fifty-two participants were included in the final analysis [mean (standard deviation) age, 59.4 (9.8) years; 25.3% were female]. Compared with the baseline clinical variable model [area under the receiver operating curve (AUC) 0.717, (0.690–0.743)], the gait feature model demonstrated statistically better performance [AUC 0.753, (0.726–0.780)] in predicting the composite CVD, with further incremental value when incorporated with the clinical variables [AUC 0.764, (0.741–0.786)]. Notably, gait features exhibited varied association with different CVD component conditions, especially for peripheral artery disease [AUC 0.752, (0.728–0.775)] and heart failure [0.733, (0.707–0.758)]. Additional analyses also revealed association of gait information with CVD risk factors and the established CVD risk score. Conclusion We demonstrated the association and predictive value of non-contact, video-based gait information for general CVD status. Further studies for gait video-based daily living CVD monitoring are promising.

Risk of cancer history in cardiovascular disease among individuals with hypertension.

Hypertension is the leading risk factor for cardiovascular disease (CVD). Although cancer has recently been increasingly recognized as a novel risk factor for CVD events, little is known about whether co-morbid cancer in individuals with hypertension could further increase the risk of CVD events. We sought to determine the association between the cancer history and the risk of CVD in individuals with hypertension. We retrospectively analyzed a large cohort of 747,620 individuals diagnosed with hypertension from January 2005 through May 2022 using the JMDC Claims Database. Composite CVD events, including myocardial infarction (MI), angina pectoris (AP), stroke, heart failure (HF), and atrial fibrillation (AF), were recorded, and a Cox proportional hazard regression was done to estimate hazard ratios (HR) based on the history of cancer and chemotherapy. 26,531 individuals had a history of cancer. During the mean follow-up period of 1269 ± 962 days, 67,154 composite CVD events were recorded. Compared with individuals without a cancer history, cancer survivors had a higher risk of developing composite CVD events (HR: 1.21, 95% confidence interval [CI]: 1.17-1.26). The HRs (95% CIs) associated with cancer history for MI, AP, stroke, HF, and AF were 1.07 (0.90-1.27), 1.13 (1.06-1.20), 1.14 (1.06-1.24), 1.31 (1.25-1.38), and 1.22 (1.10-1.35), respectively. Lastly, individuals who had received chemotherapy for cancer had a particularly higher risk of developing CVD compared to those who did not undergo chemotherapy. A history of cancer was associated with a greater risk of developing CVD among individuals with hypertension.

Depression Onset After a Spouse’s Cardiovascular Event

Although cardiovascular disease (CVD) is a known risk factor for depression, evidence is lacking regarding whether and to what extent a spouse's CVD is associated with the subsequent mental health of individuals. To examine the association between CVD onset in spouses and subsequent depression. This cohort study examined 277 142 matched married couples enrolled in the Japan Health Insurance Association health insurance program between April 2015 and March 2022, covering approximately 40% of the working-age population in Japan. Index individuals (primary insured) whose spouses (dependent) experienced incident CVD between April 2016 and March 2022 were 1:1 matched to controls whose spouses did not experience CVD. Matching was based on age, sex, income, or the onset date of the spouses' CVD. Data analysis was conducted from April 2016 to March 2022. Spousal onset of CVD between fiscal years 2016 and 2021. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes were used to identify the composite CVD outcomes (stroke, heart failure, and myocardial infarction). Multivariate Cox proportional hazards models were used to investigate the association between spouses' new-onset CVD and individuals' depression, adjusting for sociodemographic characteristics and comorbidities of index individuals (diabetes, hypertension, and CVD) and spouses (diabetes, hypertension, and depression). Subgroup analyses were conducted according to sex, age, income levels, and history of CVD. Among 277 142 matched pairs of married couples, 263 610 (95.1%) had a male index individual; the mean (SD) age of index individuals was 58.2 (10.2) years. A new onset of depression was observed in 4876 individuals (1.8%). In multivariable Cox models, there was an association between the spouse's CVD and the individuals' depression (hazard ratio, 1.13 [95% CI, 1.07-1.20]). The subgroup analysis found no evidence of heterogeneity in sex, age, income level, or CVD history. The results were consistent when additionally adjusted for health behaviors (smoking, alcohol consumption, physical activity, and use of antihypertensive drugs) and objectively measured physical health conditions (body mass index, blood pressure, cholesterol levels, glucose levels, and estimated glomerular filtration rate) (hazard ratio, 1.16 [95% CI, 1.06-1.28]). In this nationwide cohort study of matched couples, a spouse's onset of CVD was associated with an increased risk of an individual's depression. These findings highlight the importance of preventive care for mental health disorders in individuals whose spouses experience incident CVD.

Awareness of Being Prescribed Antihypertensive Medications and Cardiovascular Outcomes.

Hypertension is a major cause of cardiovascular disease (CVD). In patients with hypertension, unawareness of the disease often results in poor blood pressure control and increases the risk of CVD. However, data in nationwide surveys regarding the proportion of unaware individuals and the implications of such on their clinical outcomes are lacking. We aimed to clarify the association between unawareness of being prescribed antihypertensive medications among individuals taking antihypertensive medications and the subsequent risk of developing CVD.Methods and Results: This retrospective cohort study analyzed data from the JMDC Claims Database, including 313,715 individuals with hypertension treated with antihypertensive medications (median age 56 years). The primary endpoint was a composite of myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Overall, 19,607 (6.2%) individuals were unaware of being prescribed antihypertensive medications. During the follow-up period, 33,976 composite CVD endpoints were documented. Despite their youth, minimal comorbidities, and the achievement of better BP control with a reduced number of antihypertensive prescriptions, unawareness of being prescribed antihypertensive medications was associated with a greater risk of developing composite CVD. Hazard ratios of unawareness of being prescribed antihypertensive medications were 1.16 for myocardial infarction, 1.25 for angina pectoris, 1.15 for stroke, 1.36 for heart failure, and 1.28 for atrial fibrillation. The results were similar in several sensitivity analyses, including the analysis after excluding individuals with dementia. Among individuals taking antihypertensive medications, assessing the awareness of being prescribed antihypertensive medications may help identify those at high risk for CVD-related events.

Unawareness of being prescribed medications for diabetes and incident cardiovascular disease

BackgroundSome patients with diabetes are unaware that they are prescribed medications for diabetes. The purpose of this study is to determine, using a Japanese nationwide epidemiologic database, the association between unawareness of being prescribed medication for diabetes and the risk of developing cardiovascular disease (CVD) in patients with diabetes. MethodsThis observational cohort study analyzed data from the JMDC Claims Database between 2005 and 2022, including 94,048 patients with diabetes treated with medications. The primary endpoint was a composite endpoint including myocardial infarction (MI), stroke, heart failure (HF), and atrial fibrillation (AF). ResultsWe identified 7561 composite CVD endpoints during a mean follow-up of 1199 ± 902 days. Overall, 7779 (8.3 %) patients were unaware of being prescribed medications for diabetes. Those who did not know they were prescribed drugs were younger and had better glycemic control, but these individuals were at higher risk of developing combined CVD [hazard ratio (HR) 1.13, 95 % confidence interval (95 % CI) 1.04–1.22]. HRs of unawareness of being prescribed medications for diabetes were 1.33 (95 % CI 1.06–1.68) for MI, 1.13 (95 % CI 0.97–1.31) for stroke, 1.10 (95 % CI 1.00–1.21) for HF, and 1.19 (95 % CI 0.97–1.47) for AF, respectively. ConclusionsIn patients with diabetes taking medications for diabetes, even if they are young and have good glycemic control, unawareness of being prescribed medications for diabetes was associated with a greater risk of developing CVD. It is important that they receive adequate education from their healthcare providers to accurately identify their treatment status.

Metabolic syndrome and cardiovascular disease in cancer survivors.

The risk of subsequent cardiovascular disease (CVD) is high in cancer survivors. Although metabolic syndrome is an established risk factor for CVD, its association with cancer survivors has not yet been established. This study aimed to clarify whether metabolic syndrome is associated with subsequent CVD risk in patients with cancer using a nationwide epidemiological dataset. We retrospectively analysed 53510 patients with a history of breast, colorectal, or stomach cancer, which is reportedly a major site for developing cancer in Japan. Study participants were categorized into two groups based on the presence of metabolic syndrome, defined using the Japanese criteria (high waist circumference and ≥2 metabolic parameters including elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, or elevated fasting plasma glucose). The clinical outcomes were collected between 2005 and 2021. The primary endpoint was defined as the composite CVD outcome, including myocardial infarction, angina pectoris, stroke, and heart failure. The median patient age was 54years, and 37.5% of the patients were men. Metabolic syndrome was observed in 5558 (10.4%) patients. Over a mean follow-up period of 973±791days, 3085 composite CVD outcomes were recorded. Multivariable Cox regression analyses showed that metabolic syndrome was associated with a greater risk of developing CVD events (HR=1.29, 95% CI=1.15-1.45). Metabolic syndrome was also associated with an increased risk of CVD in patients with a follow-up period ≥1year (HR=1.33, 95% CI=1.15-1.53). This relationship was also observed when metabolic syndrome was defined according to the International Diabetes Federation criteria (HR=1.34, 95% CI=1.21-1.49) and the National Cholesterol Education Program Adult Treatment Panel III criteria (HR=1.32, 95% CI=1.19-1.46). Subgroup analyses showed that the relationship between metabolic syndrome and incident CVD was more pronounced in the non-obese participants than in the obese participants. Metabolic syndrome is associated with a greater risk of developing CVD, even among cancer survivors.

Long-Term Body Mass Index Variability and Adverse Cardiovascular Outcomes

Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is a commonly used estimate of obesity, which is a complex trait affected by genetic and lifestyle factors. Marked weight gain and loss could be associated with adverse biological processes. To evaluate the association between BMI variability and incident cardiovascular disease (CVD) events in 2 distinct cohorts. This cohort study used data from the Million Veteran Program (MVP) between 2011 and 2018 and participants in the UK Biobank (UKB) enrolled between 2006 and 2010. Participants were followed up for a median of 3.8 (5th-95th percentile, 3.5) years. Participants with baseline CVD or cancer were excluded. Data were analyzed from September 2022 and September 2023. BMI variability was calculated by the retrospective SD and coefficient of variation (CV) using multiple clinical BMI measurements up to the baseline. The main outcome was incident composite CVD events (incident nonfatal myocardial infarction, acute ischemic stroke, and cardiovascular death), assessed using Cox proportional hazards modeling after adjustment for CVD risk factors, including age, sex, mean BMI, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking status, diabetes status, and statin use. Secondary analysis assessed whether associations were dependent on the polygenic score of BMI. Among 92 363 US veterans in the MVP cohort (81 675 [88%] male; mean [SD] age, 56.7 [14.1] years), there were 9695 Hispanic participants, 22 488 non-Hispanic Black participants, and 60 180 non-Hispanic White participants. A total of 4811 composite CVD events were observed from 2011 to 2018. The CV of BMI was associated with 16% higher risk for composite CVD across all groups (hazard ratio [HR], 1.16; 95% CI, 1.13-1.19). These associations were unchanged among subgroups and after adjustment for the polygenic score of BMI. The UKB cohort included 65 047 individuals (mean [SD] age, 57.30 (7.77) years; 38 065 [59%] female) and had 6934 composite CVD events. Each 1-SD increase in BMI variability in the UKB cohort was associated with 8% increased risk of cardiovascular death (HR, 1.08; 95% CI, 1.04-1.11). This cohort study found that among US veterans, higher BMI variability was a significant risk marker associated with adverse cardiovascular events independent of mean BMI across major racial and ethnic groups. Results were consistent in the UKB for the cardiovascular death end point. Further studies should investigate the phenotype of high BMI variability.

Association of Urinary Dickkopf-3 Levels with Cardiovascular Events and Kidney Disease Progression in Systolic Blood Pressure Intervention Trial.

Urinary Dickkopf-3 (uDKK3) is a tubular epithelial-derived profibrotic protein secreted into the urine under tubular stress. It is associated with kidney disease progression in persons with chronic kidney disease (CKD) and diabetes, and post-operative and contrast-associated acute kidney injury (AKI). We explored associations of uDKK3 with cardiovascular disease (CVD), kidney and mortality outcomes within the subset of Systolic Blood Pressure Intervention Trial (SPRINT) participants with non-diabetic CKD. We included 2,344 participants with estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 at baseline. We used Cox proportional hazards models to evaluate associations of uDKK3 with CVD (acute decompensated heart failure, myocardial infarction, acute coronary syndrome, stroke or CVD death), kidney outcomes (incident end stage kidney disease [ESKD], incident AKI, and eGFR decline ≥30%), and all-cause mortality. We used linear mixed models to examine the association of uDKK3 with annual percentage change in eGFR. Models were adjusted for demographic and clinical characteristics, eGFR and albuminuria. Over a median follow up of 3.5 years, there were 292 CVD, 73 ESKD, 183 AKI, 471 eGFR decline, and 228 mortality events. In multivariable models without adjustment for eGFR and albuminuria, uDKK3 was strongly associated with CVD, ESKD, AKI, eGFR decline ≥30%, and mortality. However, after further adjustment for eGFR and albuminuria, uDKK3 was no longer associated with risks for composite CVD (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.92-1.23), ESKD (0.80; 0.62-1.02), AKI (1.01; 0.85-1.21), eGFR decline >30% (0.88; 0.79-0.99) or mortality (1.02; 0.87-1.20). For the linear eGFR change outcome, higher uDKK3 also had no association in the fully adjusted model (-0.03; -0.41-0.36). Among individuals with hypertension and non-diabetic CKD, higher uDKK3 appeared to have associations with a greater risk of CVD events, incident ESKD, incident AKI, eGFR decline ≥30%, and mortality, but was not independent of eGFR and albuminuria.

Sex Differences in the Association Between Depression and Incident Cardiovascular Disease

BackgroundDepression is a known risk factor for cardiovascular disease (CVD), but the potential sex differences in this association remain unclear. ObjectivesThe aim of this study was to investigate the association between depression and subsequent CVD events, and to explore potential sex differences. MethodsThe authors conducted a retrospective analysis using the JMDC Claims Database between 2005 and 2022. The study population included 4,125,720 individuals aged 18 to 75 years without a history of cardiovascular disease or renal failure and missing data at baseline. Participants were followed up for a mean of 1,288 days to assess the association between depression and subsequent CVD events, such as myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. ResultsOur analysis revealed a significant association between depression and subsequent composite CVD events in both men and women, with a stronger association observed in women. The HR for the composite endpoint was 1.64 (95% CI: 1.59-1.70) in women and 1.39 (95% CI: 1.35-1.42) in men after multivariable adjustment (P for interaction <0.001). Furthermore, the individual components of the composite endpoint were also associated with depression in both men and women, each of which was also observed to be more strongly associated in women. ConclusionsOur study provides evidence of a significant association between depression and subsequent CVD events in both men and women, with a more pronounced association observed in women. These findings highlight the importance of addressing depression and tailoring prevention and management strategies according to sex-specific factors.

Sex Differences in the Relationship Between Schizophrenia and the Development of Cardiovascular Disease.

There are few data on sex differences in the association between schizophrenia and the development of cardiovascular disease (CVD). We sought to clarify the relationship of schizophrenia with the risk of developing CVDs and to explore the potential modification effect of sex differences. We conducted a retrospective analysis using the JMDC Claims Database between 2005 and 2022. The study population included 4 124 508 individuals aged 18 to 75 years without a history of CVD or renal replacement therapy. The primary end point is defined as a composite end point that includes myocardial infarction, angina pectoris, stroke, heart failure, atrial fibrillation, and pulmonary thromboembolism. During a mean follow-up of 1288±1001 days, we observed 182 158 composite end points. We found a significant relationship of schizophrenia with a greater risk of developing composite CVD events in both men and women, with a stronger association observed in women. The hazard ratio for the composite end point was 1.63 (95% CI, 1.52-1.74) in women and 1.42 (95% CI, 1.33-1.52) in men after multivariable adjustment (P for interaction=0.0049). This sex-specific difference in the association between schizophrenia and incident CVD was consistent for angina pectoris, heart failure, and atrial fibrillation. Our analysis using a large-scale epidemiologic cohort demonstrated that the association between schizophrenia and subsequent CVD events was more pronounced in women than in men, suggesting the clinical importance of addressing schizophrenia and tailoring the CVD prevention strategy based on sex-specific factors.

Exposure-response associations between chronic exposure to fine particulate matter and risks of hospital admission for major cardiovascular diseases: population based cohort study

ObjectiveTo estimate exposure-response associations between chronic exposure to fine particulate matter (PM2.5) and risks of the first hospital admission for major cardiovascular disease (CVD) subtypes.DesignPopulation based cohort study.SettingContiguous US.Participants59 761...

Associations of trajectories in body roundness index with incident cardiovascular disease: a prospective cohort study in rural China.

The body roundness index (BRI) has good predictive ability for both body fat and visceral adipose tissue. Longitudinal BRI trajectories can reveal the potential dynamic patterns of change over time. This prospective study assessed potential associations between BRI trajectories and incident cardiovascular disease (CVD) in rural regions of Northeast China. In total, 13,209 participants (mean age: 49.0 ± 10.3 years, 6,856 [51.9%] male) were enrolled with three repeated times of BRI measurements at baseline (2004-2006), 2008, and 2010, and followed up until 2017 in this prospective study. Using latent mixture model, the BRI trajectories were determined based on the data from baseline, 2008 and 2010. Composite CVD events (myocardial infarction, stroke, and CVD death combined) was the primary endpoint. Cox proportional-hazards models were used to analyze the longitudinal associations between BRI trajectories and incident CVD. Three distinct BRI trajectories were identified: high-stable (n = 538), moderate-stable (n = 1,542), and low-stable (n = 11,129). In total, 1,382 CVD events were recorded during follow-up. After adjustment for confounders, the moderate-stable and high-stable BRI groups had a higher CVD risk than did the low-stable BRI group, and the HR (95%CI) were 1.346 (1.154, 1.571) and 1.751 (1.398, 2.194), respectively. Similar associations were observed between the trajectories of BRI and the risk of stroke and CVD death. The high-stable group was also significantly and independently associated with CVD, myocardial infarction, stroke, and CVD death in participants aged <50 years. BRI trajectory was positively associated with incident CVD, providing a novel possibility for the primary prevention of CVD in rural regions of China.

Epigenetic Contributions to Clinical Risk Prediction of Cardiovascular Disease.

Cardiovascular disease (CVD) is among the leading causes of death worldwide. The discovery of new omics biomarkers could help to improve risk stratification algorithms and expand our understanding of molecular pathways contributing to the disease. Here, ASSIGN-a cardiovascular risk prediction tool recommended for use in Scotland-was examined in tandem with epigenetic and proteomic features in risk prediction models in ≥12 657 participants from the Generation Scotland cohort. Previously generated DNA methylation-derived epigenetic scores (EpiScores) for 109 protein levels were considered, in addition to both measured levels and an EpiScore for cTnI (cardiac troponin I). The associations between individual protein EpiScores and the CVD risk were examined using Cox regression (ncases≥1274; ncontrols≥11 383) and visualized in a tailored R application. Splitting the cohort into independent training (n=6880) and test (n=3659) subsets, a composite CVD EpiScore was then developed. Sixty-five protein EpiScores were associated with incident CVD independently of ASSIGN and the measured concentration of cTnI (P<0.05), over a follow-up of up to 16 years of electronic health record linkage. The most significant EpiScores were for proteins involved in metabolic, immune response, and tissue development/regeneration pathways. A composite CVD EpiScore (based on 45 protein EpiScores) was a significant predictor of CVD risk independent of ASSIGN and the concentration of cTnI (hazard ratio, 1.32; P=3.7×10-3; 0.3% increase in C-statistic). EpiScores for circulating protein levels are associated with CVD risk independent of traditional risk factors and may increase our understanding of the etiology of the disease.

Association Between the Composite Cardiovascular Risk and mHealth Use Among Adults in the 2017-2020 Health Information National Trends Survey: Cross-Sectional Study.

Numerous studies have suggested that the relationship between cardiovascular disease (CVD) risk and the usage of mobile health (mHealth) technology may vary depending on the total number of CVD risk factors present. However, whether higher CVD risk is associated with a greater likelihood of engaging in specific mHealth use among US adults is currently unknown. We aim to assess the associations between the composite CVD risk and each component of mHealth use among US adults regardless of whether they have a history of CVD or not. This study used cross-sectional data from the 2017 to 2020 Health Information National Trends Survey. The exposure was CVD risk (diabetes, hypertension, smoking, physical inactivity, and overweight or obesity). We defined low, moderate, and high CVD risk as having 0-1, 2-3, and 4-5 CVD risk factors, respectively. The outcome variables of interest were each component of mHealth use, including using mHealth to make health decisions, track health progress, share health information, and discuss health decisions with health providers. We used multivariable logistic regression models to examine the association between CVD risk and mHealth use adjusted for demographic factors. We included 10,531 adults, with a mean age of 54 (SD 16.2) years. Among the included participants, 50.2% were men, 65.4% were non-Hispanic White, 41.9% used mHealth to make health decisions, 50.8% used mHealth to track health progress toward a health-related goal, 18.3% used mHealth to share health information with health providers, and 37.7% used mHealth to discuss health decisions with health providers (all are weighted percentages). Adults with moderate CVD risk were more likely to use mHealth to share health information with health providers (adjusted odds ratio 1.49, 95% CI 1.24-1.80) and discuss health decisions with health providers (1.22, 95% CI 1.04-1.44) compared to those with low CVD risk. Similarly, having high CVD risk was associated with higher odds of using mHealth to share health information with health providers (2.61, 95% CI 1.93-3.54) and discuss health decisions with health providers (1.56, 95% CI 1.17-2.10) compared to those with low CVD risk. Upon stratifying by age and gender, we observed age and gender disparities in the relationship between CVD risk and the usage of mHealth to discuss health decisions with health providers. Adults with a greater number of CVD risk factors were more likely to use mHealth to share health information with health providers and discuss health decisions with health providers. These findings suggest a promising avenue for enhancing health care communication and advancing both primary and secondary prevention efforts related to managing CVD risk factors through the effective usage of mHealth technology.

Association of pre-existing maternal cardiovascular diseases with neurodevelopmental disorders in offspring: a cohort study in Sweden and British Columbia, Canada.

We aimed to investigate the associations of pre-existing maternal cardiovascular disease (CVD) with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and intellectual disability (ID) in offspring. This population-based cohort study included singletons live-born without major malformations in Sweden (n = 2 699 675) and British Columbia (BC), Canada (n = 887 582) during 1990-2019, with follow-up from age 1 year until the outcome, death, emigration or December 2020, whichever came first. The primary exposure was defined as a composite CVD diagnosed prior to conception: cerebrovascular disease, arrhythmia, heart failure, valvular and congenital heart diseases. The incidences of ADHD, ASD and ID, comparing offspring of mothers with versus without CVD, were calculated as adjusted hazard ratios (aHRs). These results were compared with models using paternal CVD as negative control exposure. Compared with offspring of mothers without CVD, offspring of mothers with CVD had 1.15-fold higher aHRs of ADHD [95% confidence interval (CI): 1.10-1.20] and ASD (95% CI 1.07-1.22). No association was found between maternal CVD and ID. Stratification by maternal CVD subtypes showed increased hazards of ADHD for maternal heart failure (HR 1.31, 95% CI 1.02-1.61), cerebrovascular disease (HR 1.20, 95% CI 1.08-1.32), congenital heart disease (HR 1.18, 95% CI 1.08-1.27), arrhythmia (HR 1.13, 95% CI 1.08-1.19) and valvular heart disease (HR 1.12, 95% CI 1.00-1.24). Increased hazards of ASD were observed for maternal cerebrovascular disease (HR 1.25, 95% CI 1.04-1.46), congenital heart disease (HR 1.17, 95% CI 1.01-1.33) and arrythmia (HR 1.12, 95% CI 1.01-1.21). Paternal CVD did not show associations with ADHD, ASD or ID, except for cerebrovascular disease which showed associations with ADHD and ASD. In this large cohort study, pre-existing maternal CVD was associated with increased risk of ADHD and ASD in offspring.

Cardiovascular Outcomes Among Myeloproliferative Neoplasm Patients with or without Agent Orange Exposure Using a Large Veteran Database

Cardiovascular Disease (CVD) and its complications contribute significantly to the morbidity and mortality of individuals with Myeloproliferative Neoplasms (MPNs), apart from the increased incidence of untoward thrombosis and bleeding. The prevalence of CVD, such as Heart Failure (HF) and Pulmonary Hypertension (PH) in individuals with MPNs and its association with exposure to Agent Orange (AO), a dioxin-containing carcinogen, remain undefined. These findings will be essential in risk stratification and multidisciplinary management of MPNs to prevent progression of CVD. Utilizing the Veterans Affairs Informatics and Computing Infrastructure (VINCI) database, a case-control study was performed from January 1, 2006 - January 26, 2023 to characterize the association of CVD in Veterans with MPNs, arterial thrombosis (AT), venous thrombosis (VT), bleeding, and AO exposure. ICD-9 and -10 codes identified Veterans with MPN, AT, VT, bleeding, CV risk factors, such as hypertension (HTN), hyperlipidemia (HLD), diabetes (DM), smoking, and CVD sequelae, such as HF and PH. Age-, sex-, and race-matched controls (1:1) were selected from VINCI, who are Veterans without MPNs from Illinois, the state most representative of the U.S. population. Composite CVD outcome includes any Veteran with either HTN, HLD, DM, HF, or PH. Exposure to AO was self-reported and verified through Veterans' duration and location of service. Qualitative data were compared by chi-square tests. Among 93,269 Veterans with MPN, there were higher rates of composite CVD, CV risk factors, HF, PH, AT, VT, and bleeding (Figure 1) compared to matched controls. All MPN subtypes, Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PMF) were each associated with increased prevalence of HTN, HLD, DM, HF, and PH (p&amp;lt;0.0001). Among Veterans with MPNs with AT, VT, or bleeding, there was a significant association with each CV risk factors, HF, and PH (p&amp;lt;.001). Among Veterans with MPN with AO exposure, there were higher rates of composite CVD, CV risk factors, HF, PH, AT, and bleeding (Figure 1) when compared to those without AO exposure. Among matched controls with AO, there were higher rates of HLD and AT compared to matched controls without AO. Veterans born before 1960 with AO exposure had younger mean age at MPN diagnosis compared to those without AO, 66 ± 7 (SD) years vs. 69 ± 10 (SD) years, p&amp;lt;0.0001, respectively. Among the 24,385 (26.1%) Veterans with MPNs with HF vs. 1,749 (1.9%) Veterans with MPNs with PH: 46.1% vs. 38.9% had ET; 48.8% vs. 56% had PV; and 5.1% vs. 5.1% had PMF; 92.7% vs. 91.2% were born before 1960; 96.8% vs. 95.3% were male; 75.8% vs. 72.1% White; 14.7% vs. 19.3% Black; 7.5% vs. 6.9% unknown race, respectively. Among MPNs with PH, there is a higher rate of pulmonary embolism (4.87% vs. 1.1%, p&amp;lt;0.0001) when compared to matched controls. There is decreased overall survival among Veterans with MPNs with HF and PH (Figure 2) and Veterans with MPNs compared to matched controls. In summary, the CV risk factors, HF and PH, are increased in Veterans with MPNs and are associated with increased risk for AT, VT, and bleeding complications. Not only is AO exposure associated with development of MPN, as previously reported (J Clin Oncology 2023 41:16_suppl, 7011), but AO exposure appears to increase CVD complications among Veterans with MPNs. Further studies evaluating contributions of driver mutation and CHIPs to cardiac and vascular remodeling are needed and will elucidate the implications of AO and its imputed toxic effects on DNA to the accelerated development of MPNs and its CVD complications. Future targeted therapies and strategies should be developed to mitigate the consequences of progressive CVD, and prevention of AT, VT, and bleeding complications in individuals with MPNs.

Impact of Hypomethylating Agents on Cardiovascular Disease Risk Among Patients with Myelodysplastic Syndromes

Introduction: The association between clonal hematopoiesis (CH) and cardiovascular disease (CVD) risk has drawn attention to cardiovascular outcomes in myelodysplastic syndromes (MDS). CVD accounts for 25% of deaths in MDS, potentially via CH-mediated accelerated atherosclerosis from inflammatory vascular responses. We previously demonstrated that MDS was independently associated with increased risk of CVD in older adults from SEER-Medicare. We subsequently hypothesized that treatment with hypomethylating agents (HMA) could reduce CVD risk by ameliorating CH clones and reducing the inflammation. In this study, we aimed to define the impact of HMA on incident cardiovascular events among older adults with MDS. Methods: We identified subjects ≥66 years diagnosed with MDS from 2007 to 2017 in SEER-Medicare. Exclusion criteria including lacking continuous Medicare parts A, B, and D, enrolled in HMO, or incomplete follow-up. Demographics included age, sex, race, rurality, socioeconomic quintile, marital status, and geographic region. Baseline CVD risk factors, defined from ICD-9/10 codes, included hypertension, hyperlipidemia, diabetes, atrial fibrillation, pre-existing cardiac disease, obesity, and smoking. MDS factors, defined using HCPCS codes, ICD-O-3 codes and prescription records, included MDS subtype and histologic risk stratification, transfusion dependence and treatment with hypomethylating agents (HMA), lenalidomide, or erythropoietin-stimulating agents (ESA) as time-varying variables. Incident CVD was defined as new myocardial infarction (MI) and/or ischemic stroke occurring after MDS diagnosis, using published ICD-9/10 algorithms. We controlled for confounding using 2 complementary analytic approaches. First, we assessed the association between HMA use and CVD using propensity score adjusted cause-specific competing risk Cox hazard models with death as competing risk, Second, we used a case-crossover design with conditional logistic regression, in which subjects with CVD served as their own controls, using a 3-month HMA treatment window and a control period 6 months prior to the incident event. Results: We identified a cohort of 15,227 eligible patients with MDS. Of these, 1,125 patients had an MI and/or ischemic stroke within 1 year before MDS diagnoses and were excluded. We analyzed 14,102 MDS patients, with median age 82 years (IQR 77 - 86), who were predominantly male (53.8%), non-Hispanic white (88.6%), and from urban/suburban areas (86.2%). MDS was of low, intermediate, and high histologic risk in 14.7%, 72.8%, and 12.5%, respectively, and 28.6% were transfusion dependent. Pre-existing CVD risk factors at time of MDS diagnosis were present in 12,538 patients, with baseline cardiovascular risk defined as low, intermediate, and high in 11.1%, 32.3%, and 56.6% of the cohort. The cumulative incidences of MI, ischemic stroke and composite CVD events were 11.3%, 10.6% and 20.4%, respectively. The propensity score (PS) conditional probability for being treated with HMA included demographic variables, CVD risk factors, MDS histology and transfusion dependence. Our PS model adequately predicted HMA treatment propensity (AUC 0.76). Cause-specific regression with death as competing risk, adjusted for PS and other MDS-specific treatments (ESA and lenalidomide), showed no significant effect of HMA on the risk of composite CVD events, MI, or ischemic stroke (Table 1). Conditional logistic regression in the case-crossover analysis of 1,907 patients with composite CVD events showed no significant effect of HMA. Results were similar for analysis of patients with MI and ischemic stroke (Table 2). Conclusions: No study has previously investigated the effect of HMA therapy on cardiovascular outcomes in patients with MDS. We demonstrate that HMA therapy is not associated with a significant risk reduction in cardiovascular events among patients with MDS patients from the SEER-Medicare database. These results show that HMA therapy is unlikely to reduce cardiovascular mortality and underscore the need for alternative therapeutic strategies targeting cardiovascular health patients with MDS.

Association of Lifestyle Intervention With Risk for Cardiovascular Events Differs by Level of Glycated Hemoglobin.

We reevaluated the Action for Health in Diabetes (Look AHEAD) intensive lifestyle intervention (ILI) to assess whether the effect of ILI on cardiovascular disease (CVD) prevention differed by baseline glycated hemoglobin (HbA1c). Look AHEAD randomized 5145 adults, aged 45 to 76 years with type 2 diabetes and overweight/obesity to ILI or a diabetes support and education (DSE) control group for a median of 9.6 years. ILI focused on achieving weight loss through decreased caloric intake and increased physical activity. We assessed the parent trial's primary composite CVD outcome. We evaluated additive and multiplicative heterogeneity of the intervention on CVD risk by baseline HbA1c. Mean baseline HbA1c was 7.3% (SD 1.2) and ranged from 4.4% (quintile 1) to 14.5% (quintile 5). We observed additive and multiplicative heterogeneity of the association between ILI and CVD (all P < .001) by baseline HbA1c. Randomization to ILI was associated with lower CVD risk for HbA1c quintiles 1 [hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.53, 0.88] and 2 (HR: 0.80, 95% CI: 0.66, 0.96) and associated with higher CVD risk for HbA1c quintile 5 (HR: 1.27, 95% CI: 1.02, 1.58), compared to DSE. Among adults with type 2 diabetes and overweight/obesity, randomization to a lifestyle intervention was differentially associated with CVD risk by baseline HbA1c such that it was associated with lower risk at lower HbA1c levels and higher risk at higher HbA1c levels. There is a critical need to develop and tailor lifestyle interventions to be successful for individuals with type 2 diabetes and high HbA1c.

The intensity and duration of occupational noise exposure and cardiovascular disease in the United States: a nationally representative study, 2015 to 2020.

Occupational noise exposure may be associated with an increased risk of cardiovascular disease (CVD). Yet the findings are inconclusive. This study aimed to examine the association between self-reported occupational noise exposure and CVD (using a broad composite case definition and by each condition) and identify how these associations vary with the intensity and duration of noise exposure, and combinations thereof. This cross-sectional study included a nationally representative sample (n = 6,266) from the National Health and Nutrition Examination Survey (2015 to 2020), aged 20 and greater, in the United States. Survey-weighted logistic regression models were constructed from multiple imputed datasets. Relative to the unexposed, the adjusted odds ratio (95% confidence interval) of composite CVD was 1.33 (1.05 to 1.67) among the noise-exposed population, and ranged from 1.23 to 1.56 when examining CVD conditions separately. The odds ratios of composite CVD were 1.43 (1.06 to 1.93), 1.43 (1.04 to 1.95), and 1.51 (1.03 to 2.21) among those who had noise exposure with very loud intensity of any duration, with duration ≥10 years at any intensity, and with a combination of very loud noise ≥10 years, respectively, compared to those unexposed. Increased risk of CVD is associated with occupational noise exposure, particularly at higher intensities and longer durations. Policies and interventions for noise mitigation at workplaces are warranted, targeting individuals with chronic exposure to high-level noise.