Subsequent Cardiovascular Disease Research Articles

Gestational Diabetes Mellitus and Subsequent Risks of Diabetes and Cardiovascular Diseases: the Life Course Perspective and Implications of Racial Disparities.

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications worldwide and the prevalence is continuously rising globally. Importantly, GDM is not an isolated complication of pregnancy. Growing evidence suggests that individuals with GDM, compared to those without GDM, have an increased risk of subsequent type 2 diabetes (T2D) and cardiovascular diseases (CVD). Substantial racial and ethnic disparities exist in the risk of GDM. However, the role of race and ethnicity in the progression from GDM to T2D and CVD remains unclear. The purpose of the current review is to summarize recent research about GDM and its life-course impacts on cardiometabolic health, including 1) the peak time of developing T2D and CVD risks after GDM, 2) the racial and ethnic disparities in the risk cardiometabolic diseases after GDM, 3) the biological plausibility and underlying mechanisms, and 4) recommendations for screening and prevention of cardiometabolic diseases among individuals with GDM, collectively to provide an updated review to guide future research. Growing evidence has indicated that individuals with GDM had greater risks of T2D (7.4 to 9.6 times), hypertension (78% higher), and CDV events (74% higher) after GDM than their non-GDM counterparts. More recently, a few studies also suggested that GDM could slightly increase the risk of mortality. Available evidence suggests that key CVD risk factors such as blood pressure, plasma glucose, and lipids levels are all elevated as early as < 1year postpartum in individuals with GDM. The risk of T2D and hypertension is likely to reach a peak between 3-6years after the index pregnancy with GDM compared to normal glycemia pregnancy. Cumulative evidence also suggests that the risk of cardiometabolic diseases including T2D, hypertension, and CVD events after GDM varies by race and ethnicity. However, whether the risk is higher in certain racial and ethnic groups and whether the pattern may vary by the postpartum cardiometabolic outcome of interest remain unclear. The underlying mechanisms linking GDM and subsequent T2D and CVD are complex, often involving multiple pathways and their interactions, with the specific mechanisms varying by individuals of different racial and ethnic backgrounds. Diabetes and CVD risk screening among individuals with GDM should be initiated early during postpartum and continue, if possible, frequently. Unfortunately, adherence to postpartum glucose testing with either obstetrician or primary care providers remained poor among individuals with GDM. A life-course perspective may provide critical information to address clinical and public health gaps in postpartum screening and interventions for preventing T2D and CVD risks in individuals with GDM. Future research investigating the racial- and ethnic-specific risk of progression from GDM to cardiometabolic diseases and the role of multi-domain factors including lifestyle, biological, and socio-contextual factors are warranted to inform tailored and culture-appropriate interventions for high-risk subpopulations. Further, examining the barriers to postpartum glucose testing among individuals with GDM is crucial for the effective prevention of cardiometabolic diseases and for enhancing life-long health.

Cardiovascular Health Starts in the Womb.

Hypertension has largely been viewed as a disorder of adulthood. Historically, blood pressure (BP) was not routinely measured in children because hypertension was considered uncommon in childhood. It was not until the 1970s that it was apparent that in childhood BP levels were normally lower compared with those in adults, were related to age and growth, and that abnormal BP in children needed different definitions. Based on the distribution of BP levels in available child cohorts, the 95th percentile of BP levels became the definition of hypertension in children and adolescents-an epidemiological definition. Subsequent clinical and epidemiological research identified associated risk factors in childhood that linked abnormal BP in youth with hypertension in adulthood. In the 1980s, the Barker hypothesis, based on observations that low birth weight could be linked to cardiovascular disease in adulthood, promoted further research spanning epidemiological, clinical, and basic science on the childhood origins of hypertension. This review focuses on recent findings from both longitudinal maternal-child cohorts and experimental models that examine both maternal and offspring conditions associated with risks of subsequent cardiovascular disease.

Risk of Cardiovascular Disease Hospitalization After Common Psychiatric Disorders: Analyses of Disease Susceptibility and Progression Trajectory in the UK Biobank

AbstractWhether associations between psychiatric disorders and hospitalization for cardiovascular diseases (CVDs) can be modified by disease susceptibility and the temporal pattern of these associated CVDs remain unknown. In our study, we conducted a matched cohort study of the UK Biobank including 44,430 patients with common psychiatric disorders (anxiety, depression, and stress-related disorders) between 1997 and 2019, together with 222,150 sex-, Townsend deprivation index-, and birth year- individually matched unexposed individuals. The hazard ratios (HRs) for CVD hospitalization associated with a prior psychiatric disorder were derived from Cox models, adjusted for multiple confounders. We then stratified the analyses by self-reported family history of CVD and CVD polygenic risk score (PRS) calculated based on summary statistics of independent genome-wide association studies. We further conducted disease trajectory analysis and visualized the temporal pattern of CVDs after common psychiatric disorders. During a mean follow-up of 12.28 years, we observed an elevated risk of CVD hospitalization among patients with psychiatric disorders, compared with matched unexposed individuals (hazard ratios [HRs] = 1.20, 95% confidence interval [CI]: 1.18–1.23), especially during the first six months of follow-up (1.72 [1.55–1.91]). The stratification analyses by family history of CVD and by CVD PRS obtained similar estimates between subgroups with different susceptibilities to CVD. We conducted trajectory analysis to visualize the temporal pattern of CVDs after common psychiatric disorders, identifying primary hypertension, acute myocardial infarction, and stroke as three main intermediate steps leading to further increased risk of other CVDs. In conclusion, the association between common psychiatric disorders and subsequent CVD hospitalization is not modified by predisposition to CVD. Hypertension, acute myocardial infarction, and stroke are three initial CVDs linking psychiatric disorders to other CVD sequelae, highlighting a need of timely intervention on these targets to prevent further CVD sequelae among all individuals with common psychiatric disorders.

Association of retinal age gap with chronic kidney disease and subsequent cardiovascular disease sequelae: a cross-sectional and longitudinal study from the UK Biobank.

Chronic kidney disease (CKD) increases the risk of cardiovascular disease (CVD) and is more prevalent in older adults. Retinal age gap, a biomarker of aging based on fundus images, has been previously developed and validated. This study aimed to investigate the association of retinal age gap with CKD and subsequent CVD complications. A deep learning model was trained to predict the retinal age using 19200 fundus images of 11052 participants without any medical history at baseline. Retinal age gap, calculated as retinal age predicted minus chronological age, was calculated for the remaining 35906 participants. Logistic regression models and Cox proportional hazards regression models were used for the association analysis. A total of 35906 participants (56.75±8.04 years, 55.68% female) were included in this study. In the cross-sectional analysis, each 1-year increase in retinal age gap was associated with a 2% increase in the risk of CKD prevalence [odds ratio 1.02, 95% confidence interval (CI) 1.01-1.04, P=.012]. A longitudinal analysis of 35039 participants demonstrated that 2.87% of them developed CKD in follow-up, and each 1-year increase in retinal age gap was associated with a 3% increase in the risk of CKD incidence (hazard ratio 1.03, 95% CI 1.01-1.05, P=.004). In addition, a total of 111 CKD patients (15.81%) developed CVD in follow-up, and each 1-year increase in retinal age gap was associated with a 10% increase in the risk of incident CVD (hazard ratio 1.10, 95% CI 1.03-1.17, P=.005). We found that retinal age gap was independently associated with the prevalence and incidence of CKD, and also associated with CVD complications in CKD patients. This supports the use of this novel biomarker in identifying individuals at high risk of CKD and CKD patients with increased risk of CVD.

Postpartum haemorrhage and risk of cardiovascular disease in later life: A population‐based record linkage cohort study

AbstractObjectiveTo investigate the association between postpartum haemorrhage (PPH) and subsequent cardiovascular disease.DesignPopulation‐based retrospective cohort study, using record linkage between Aberdeen Maternity and Neonatal Databank (AMND) and Scottish healthcare data sets.SettingGrampian region, Scotland.PopulationA cohort of 70 904 women who gave birth after 24 weeks of gestation in the period 1986–2016.MethodsWe used extended Cox regression models to investigate the association between having had one or more occurrences of PPH in any (first or subsequent) births (exposure) and subsequent cardiovascular disease, adjusted for sociodemographic, medical, and pregnancy and birth‐related factors.Main Outcome MeasuresCardiovascular disease identified from the prescription of selected cardiovascular medications, hospital discharge records or death from cardiovascular disease.ResultsIn our cohort of 70 904 women (with 124 795 birth records), 25 177 women (36%) had at least one PPH. Compared with not having a PPH, having at least one PPH was associated with an increased risk of developing cardiovascular disease, as defined above, in the first year after birth (adjusted hazard ratio, aHR 1.96; 95% confidence interval, 95% CI 1.51–2.53; p &lt; 0.001). The association was attenuated over time, but strong evidence of increased risk remained at 2–5 years (aHR 1.19, 95% CI 1.11–1.30, P &lt; 0.001) and at 6–15 years after giving birth (aHR 1.17, 95% CI 1.05–1.30, p = 0.005).ConclusionsCompared with women who have never had a PPH, women who have had at least one episode of PPH are twice as likely to develop cardiovascular disease in the first year after birth, and some increased risk persists for up to 15 years.

Exposure to ambient air pollutants during circadian syndrome and subsequent cardiovascular disease and its subtypes and death: A trajectory analysis

BackgroundThe association between exposure to air pollutants and cardiovascular disease (CVD) trajectory in individuals with circadian syndrome remains inconclusive. MethodsThe individual exposure levels of air pollutants, including particulate matter (PM) with aerodynamic diameter ≤ 2.5 μm (PM2.5), PM with aerodynamic diameter ≤ 10 μm (PM10), PM2.5 absorbance, PM with aerodynamic diameter between 2.5 μm and 10 μm, nitrogen dioxide (NO2), nitrogen oxides (NOx), and air pollution score (overall air pollutants exposure), were estimated for 48,850 participants with circadian syndrome from the UK Biobank. Multistate regression models were employed to estimate associations between exposure to air pollutants and trajectories from circadian syndrome to CVD/CVD subtypes (including coronary heart disease [CHD], atrial fibrillation [AF], heart failure [HF], and stroke) and death. Mediation roles of CVD/CVD subtypes in the associations between air pollutants and death were evaluated. ResultsAfter a mean follow-up time over 12 years, 12,570 cases of CVD occurred, including 8192 CHD, 1693 AF, 1085 HF, and 1600 stroke cases. In multistate model, per-interquartile range increment in PM2.5 (hazard ratio: 1.08; 95 % confidence interval: 1.06, 1.10), PM10 (1.04; 1.01, 1.06), PM2.5 absorbance (1.04; 1.02, 1.06), NO2 (1.07; 1.03, 1.11), NOx (1.08; 1.04, 1.12), or air pollution score (1.06; 1.03, 1.08) was associated with trajectory from circadian syndrome to CVD. Significant associations between the above-mentioned air pollutants and trajectories from circadian syndrome and CVD to death were observed. CVD, particularly CHD, significantly mediated the associations of PM2.5, NO2, NOx, and air pollution score with death. ConclusionsLong-term exposure to air pollutants during circadian syndrome was associated with subsequent CVD and death. CHD emerged as the most prominent CVD subtype in CVD progression driven by exposure to air pollutants during circadian syndrome. Our study highlights the importance of controlling air pollutants exposure and preventing CHD in people with circadian syndrome.

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.

Treatment modifications and mortality among female patients with subsequent breast cancer: A report from the Childhood Cancer Survivor Study (CCSS).

10026 Background: Childhood cancer survivors are at high risk for developing subsequent breast cancer with higher mortality than females in the general population with primary breast cancer. Whether therapeutic tradeoffs in treating primary versus subsequent breast cancer alter survival is unknown. Methods: Breast cancer treatment data were abstracted from medical records for female survivors from the CCSS and a multi-institutional sample of females with primary breast cancer matched one-to-one by demographics, diagnosis age/year, and breast cancer characteristics. Survivors’ excess mortality risk was evaluated as hazard ratios (HRs), adjusting for receipt of historically-appropriate guideline-concordant treatment established for primary breast cancer. Results: Subsequent breast cancers were diagnosed between 1981-2016 among 431 survivors, with a median diagnosis age of 40 years (IQR: 35-44). Most subsequent breast cancers were invasive (77%), with hormone receptor profiles similar to the general population (78% ER-positive; 26% HER2-positive). Guideline-concordant breast cancer treatment did not differ between survivors and controls (N = 688; 94% versus 93%), but treatment selection differed, reflecting survivors’ complex clinical history and guidelines’ multiple treatment options. Anthracyclines were used in 47% of survivors (controls 66%), mastectomy in 81% of survivors (controls 60%), and radiotherapy in 18% of survivors (controls 61%). In the subgroup treated with surgery and chemotherapy (survivors 31%, controls 26%), survivors did not have greater likelihood of dose reductions or omissions, treatment delays, or hospitalization for fever and neutropenia, but they were more likely to experience hematological toxicities (21% vs. 9%, p = 0.033) and other organ system-specific toxicities (36% vs. 11%, p &lt; 0.001). Over one-third (38%) of survivors died during follow-up (median follow-up 9 years, IQR 6-14) after breast cancer. Strikingly higher all-cause mortality was observed among survivors than controls (HR = 3.5, 95% CI 2.2-5.6), especially after in situ disease (HR = 9.9, 95% CI 2.2-44.2). Among survivors with invasive disease, breast cancer accounted for most deaths (51%), followed by other subsequent malignancies (15%) and cardiovascular diseases (15%). Other health conditions accounted for 67% of deaths following in situ disease. Conclusions: Childhood cancer survivors with subsequent breast cancer generally receive guideline-concordant breast cancer treatment. While the treatments survivors receive differ from females with primary breast cancer, they do not experience higher rates of on-therapy treatment modifications. Despite this, they face excess mortality, primarily driven by other health conditions. Managing comorbidities is critical to enhancing long-term survival for this high-risk population.

DCNeT: A disease comorbidity network-based temporal deep learning framework to predict cardiovascular risk in patients with mental disorders

Patients with mental disorders (MDs) are at higher subsequent risk of developing cardiovascular diseases (CVDs) than the general population. Early identification of cardiovascular risk in patients with MDs is beneficial for timely intervention and reducing disease burden. Recently, deep learning approaches have been increasingly applied in CVDs risk prediction. However, these methods have three major issues: 1) mostly relying on multiple types of clinical data, 2) not sufficiently mining and utilizing comorbidity patterns hidden in complex correlations among various diseases, and 3) not fully leveraging the time information, including the irregular intervals. To address these issues, we propose a disease comorbidity network-based temporal deep learning framework (DCNeT) to predict the subsequent CVDs risk for patients with MDs based on routinely collected administrative health data. Firstly, to identify the comorbidity patterns of MDs, we construct a disease comorbidity network (DCN) for MDs and apply graph embedding method to generate disease embeddings for each disease in the DCN. Then, a code attention mechanism is proposed to obtain the weight of each disease which is embedded into dense vectors based on the structure of DCN. We present a view attention mechanism to compute the attention weights of different types of features including disease embeddings, basic features, and disease indicators for generating the final representations of patients’ hospitalizations. Furthermore, to fully utilize the information on the irregular time intervals between hospitalizations, a time encoding module is designed, and the time-aware LSTM is adopted to model the irregular time intervals and capture the temporal patterns of patients’ hospitalizations. The experimental results show that DCNeT outperforms the state-of-the-art methods, with the area under the receiver operating characteristic curve of 0.7658, 0.8143, 0.8110, and 0.7839 on four datasets, respectively. The ablation experiments further demonstrate that each module of DCNeT, including the code attention, view attention, and time encoding module, contributes to its superior performance, with average improvements of 1.20 %, 1.65 %, and 1.13 % in accuracy, respectively. Our DCNeT could be utilized as an efficient framework for identifying high-risk groups of CVDs among patients with MDs that may benefit from screening and preventive strategies.

Influence of early use of sodium-glucose transport protein 2 inhibitors, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors on the legacy effect of hyperglycemia.

A phenomenon known as legacy effect was observed that poor glycemic control at early stage of patients with newly-diagnosed type 2 diabetes (T2D) increases the risk of subsequent cardiovascular diseases (CVD). Early use of some novel anti-hyperglycemic agents, such as sodium-glucose transport protein 2 inhibitors (SGLT-2i), may attenuate this effect, but the evidence is limited. Two retrospective cohorts of newly diagnosed T2D patients from 2010-2023 were assembled using the Yinzhou Regional Health Care Database (YRHCD) with different definitions of the early exposure period - the 1-year exposure cohort and 2-year exposure cohort, which were comprised of subjects who had HbA1c measurement data within 1 year and 2 years after their T2D diagnosis, respectively. Using Cox proportional hazards models, we examined the association between high HbA1c level (HbA1c>7%) during the early exposure period and the risk of subsequent CVD. This analysis was performed in the overall cohort and three subpopulations with different treatments during the early exposure period, including patients initiating SGLT-2i or glucagon-like peptide-1 receptor agonists (GLP-1RA), patients using dipeptidyl peptidase-4 inhibitors (DPP-4i), and patients without using SGLT-2i, GLP-1RA, and DPP-4i. Besides, subgroup analyses were performed by stratifying patients into age <55 and ≥55 years. A total of 21,477 and 22,493 patients with newly diagnosed T2D were included in the two final cohorts. Compared with patients with mean HbA1c ≤ 7% during the early exposure period, those with HbA1c>7% had higher risks of incident CVD, with a HR of 1.165 (95%CI, 1.056-1.285) and 1.143 (95%CI, 1.044-1.252) in 1-year and 2-year exposure period cohort. Compared to non-users, in patients initiating SGLT-2i/GLP-1RA within 1 or 2 years after T2D diagnosis, higher HbA1c level at baseline was not associated with CVD in both two cohorts. In subgroup analyses, results were generally consistent with the main analysis. Poor glycemic control in the early stage of T2D increased later CVD risk in Chinese adults with newly diagnosed T2D. Compared to non-users, this association was smaller and non-significant in patients receiving SGLT-2i/GLP-1RA during the early stage of T2D, indicating early use of these drugs may have the potential to mitigate legacy effects of hyperglycemia.

Association of Hypertensive Disorders of Pregnancy With Coronary Microvascular Dysfunction 8 to 10 Years After Delivery.

Hypertensive disorders of pregnancy (HDP) are associated with subsequent adverse cardiac remodeling and cardiovascular disease. The role of myocardial microvascular disease among individuals with HDP and left ventricular (LV) remodeling as a potential link to cardiovascular disease is unknown. We aimed to determine whether individuals with HDP history have coronary microvascular dysfunction measured by coronary flow reserve 8 to 10 years after delivery and whether microvascular dysfunction correlates with LV remodeling. Individuals with pregnancies delivered from 2008 to 2010 underwent burst-replenishment myocardial contrast echocardiography (2017-2020) to quantify myocardial perfusion at rest and during dobutamine stress. Video intensity versus time data were used to derive β, the rate of rise of video intensity, a correlate for myocardial blood flow. Coronary flow reserve was calculated as the ratio of β at peak stress to β at rest, averaged across LV myocardial regions of interest. We studied 91 individuals (aged 38±6 and 9.1±0.9 years postdelivery) and 19 with a history of HDP. Individuals with coronary microvascular dysfunction (coronary flow reserve <2.0; n=13) had a higher proportion of HDP (46.2% versus 16.7%; P=0.026) and higher prepregnancy body mass index, baseline heart rate, and hemoglobin A1c compared with those without microvascular dysfunction. The association of coronary flow reserve and HDP was attenuated after adjusting for cardiometabolic factors (P=0.133). In exploratory subgroup analyses, individuals with both LV remodeling (relative wall thickness >0.42) and HDP (n=12) had the highest proportion of microvascular dysfunction (41.7% versus +HDP-LV remodeling [n=7] 14.3%; -HDP+LV remodeling [n=26] 7.7%; P=0.0498). In this small study, HDP history is associated with coronary microvascular dysfunction 1 decade after delivery, findings that may, in part, be driven by metabolic factors including obesity and diabetes. Microvascular dysfunction may contribute to cardiovascular disease among individuals with a history of HDP.

Oxidative Stress, Endothelial Dysfunction, and N-Acetylcysteine in Type 2 Diabetes Mellitus.

Significance: Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality globally. Endothelial dysfunction is closely associated with the development and progression of CVDs. Patients with diabetes mellitus (DM) especially type 2 DM (T2DM) exhibit a significant endothelial cell (EC) dysfunction with substantially increased risk for CVDs. Recent Advances: Excessive reactive oxygen species (ROS) and oxidative stress are important contributing factors to EC dysfunction and subsequent CVDs. ROS production is significantly increased in DM and is critically involved in the development of endothelial dysfunction in diabetic patients. In this review, efforts are made to discuss the role of excessive ROS and oxidative stress in the pathogenesis of endothelial dysfunction and the mechanisms for excessive ROS production and oxidative stress in T2DM. Critical Issues: Although studies with diabetic animal models have shown that targeting ROS with traditional antioxidant vitamins C and E or other antioxidant supplements provides promising beneficial effects on endothelial function, the cardiovascular outcomes of clinical studies with these antioxidant supplements have been inconsistent in diabetic patients. Future Directions: Preclinical and limited clinical data suggest that N-acetylcysteine (NAC) treatment may improve endothelial function in diabetic patients. However, well-designed clinical studies are needed to determine if NAC supplementation would effectively preserve endothelial function and improve the clinical outcomes of diabetic patients with reduced cardiovascular morbidity and mortality. With better understanding on the mechanisms of ROS generation and ROS-mediated endothelial damages/dysfunction, it is anticipated that new selective ROS-modulating agents and effective personalized strategies will be developed for the management of endothelial dysfunction in DM.

The effect of obesity and subsequent weight reduction on cardiac morphology and function in cats

BackgroundIn people, obesity is a risk factor for cardiovascular disease, associated with systemic hypertension, cardiac remodelling and systolic and diastolic dysfunction. Weight reduction can reverse myocardial remodelling and reduce risk of subsequent cardiovascular disease. In cats, far less is known regarding the effects of obesity and subsequent weight reduction on cardiovascular morphology and function. This prospective study aimed to assess cardiac morphology and function, heart rate variability, cardiac biomarkers and body composition before and after controlled weight reduction in cats with obesity. Body composition analysis (by dual energy x-ray absorptiometry, DEXA) and cardiovascular assessment (echocardiography, systemic arterial systolic blood pressure, electrocardiography, plasma cardiac biomarkers) were performed prior to weight management in twenty cats with obesity. These investigations were repeated in eleven cats that reached target weight.ResultsAt baseline, systemic hypertension was not documented, but the majority of cats with obesity (15 out of 19) showed echocardiographic evidence of diastolic dysfunction. Eleven of 20 cats had increased maximal end-diastolic septal or left ventricular free wall thickness (≥ 6.0 mm) at baseline. Median (interquartile range) percentage of weight lost in the cats reaching target weight was 26% (17–29%), with a median reduction in body fat mass of 45% (26–64%). Both the end-diastolic left ventricular free wall (median magnitude of change -0.85 mm, IQR -0.05 mm to -1.55 mm, P = 0.019; median percentage reduction 14.0%) and end-diastolic interventricular septum (median magnitude of change -0.5 mm, IQR -0.2 mm to -1.225 mm, P = 0.047; median percentage reduction 7.9%) thickness decreased after weight reduction. Following weight reduction, pulsed wave tissue Doppler imaging of the left ventricular free wall was consistent with improved diastolic function in 4 out of 8 cats, however there was no significant difference in overall diastolic function class. Further, there was no change in heart rate variability or cardiac biomarkers with weight reduction.ConclusionAn increase in left ventricular wall thickness and diastolic dysfunction were common echocardiographic features in cats with obesity within our study and may be reversible with successful weight and fat mass loss. Further studies are required to clarify the clinical consequences of these findings.

A prospective cohort study of exposure to household pesticide with cardiovascular diseases mortality in older adults

ObjectivesWe examined the associations of self-reported exposures, and urinary metabolites related to household pesticide with cardiovascular disease (CVD) mortality in older adults based on the 2007 to 2014 waves of National Health and Nutrition Examination Survey (NHANES). MethodsInformation on application and urinary metabolites related to household pesticide exposure were collected. We estimated the risks of household pesticide exposure, urinary metabolites with subsequent incident CVD death using Cox proportional hazards regression models. The indirect effects of urinary metabolites and effect modifications were examined. ResultsThe participants who reported exposure to household pesticide had a higher risk of incident CVD death (adjusted HR 1.40, 95% CI 1.08 to 1.81). Per 1-log10 increase in urinary N, N-diethyl-3-methylbenzamide (DEET) related to household insect repellents was associated with a higher risk of incident CVD death (adjusted HR 1.97, 95% CI 1.14 to 3.40). Urinary DEET explained 4.21% of the total association between household pesticide exposure and CVD death risk. The participants who persisted a low level of health diet exhibited pronounced CVD death risks with household pesticide exposures. ConclusionsExposure to household pesticide, especially household insect repellents, was consistently associated with an elevated CVD death risk in older adults. A heatlhy diet could partly attenuate the associations.

Baseline characteristics including blood and urine metal levels in the Trial to Assess Chelation Therapy 2 (TACT2)

BackgroundThe reduction in cardiovascular disease (CVD) events with edetate disodium (EDTA) in the Trial to Assess Chelation Therapy (TACT) suggested that chelation of toxic metals might provide novel opportunities to reduce CVD in patients with diabetes. Lead and cadmium are vasculotoxic metals chelated by EDTA. We present baseline characteristics for participants in TACT2, a randomized, double-masked, placebo-controlled trial designed as a replication of the TACT trial limited to patients with diabetes. MethodsTACT2 enrolled 1,000 participants with diabetes and prior myocardial infarction, age 50 years or older between September 2016 and December 2020. Among 959 participants with at least one infusion, 933 had blood and/or urine metals measured at the Centers for Diseases Control and Prevention using the same methodology as in the National Health and Nutrition Examination Survey (NHANES). We compared metal levels in TACT2 to a contemporaneous subset of NHANES participants with CVD, diabetes and other inclusion criteria similar to TACT2’s participants. ResultsAt baseline, the median (interquartile range, IQR) age was 67 (60, 72) years, 27% were women, 78% reported white race, mean (SD) BMI was 32.7 (6.6) kg/m2, 4% reported type 1 diabetes, 46.8% were treated with insulin, 22.3% with GLP1-receptor agonists or SGLT-2 inhibitors, 90.2% with aspirin, warfarin or P2Y12 inhibitors, and 86.5% with statins. Blood lead was detectable in all participants; median (IQR) was 9.19 (6.30, 13.9) µg/L. Blood and urine cadmium were detectable in 97% and median (IQR) levels were 0.28 (0.18, 0.43) µg/L and 0.30 (0.18, 0.51) µg/g creatinine, respectively. Metal levels were largely similar to those in the contemporaneous NHANES subset. ConclusionsTACT2 participants were characterized by high use of medication to treat CVD and diabetes and similar baseline metal levels as in the general US population. TACT2 will determine whether chelation therapy reduces the occurrence of subsequent CVD events in this high-risk population. Clinical Trials RegistrationClinicalTrials.gov. Identifier: NCT02733185. https://clinicaltrials.gov/study/NCT02733185

Cardiovascular Risk in Young Patients Diagnosed With Obstructive Sleep Apnea.

In older adults, obstructive sleep apnea (OSA) has been associated with several cardiovascular complications. Whether young patients diagnosed with OSA also are at higher risk of developing subsequent cardiovascular disease is uncertain. We aimed to estimate the risk of developing an incident cardiovascular event among young patients diagnosed with OSA. We linked nationwide Danish health registries to identify a cohort of patients aged ≤50 years with OSA using data from 2010 through 2018. Cases without OSA from the general population were matched as controls (1:5). The main outcome was any cardiovascular event (including hypertension, diabetes, atrial fibrillation, ischemic heart disease, ischemic stroke, heart failure, and venous thromboembolism). All-cause mortality was a secondary outcome. The study included 20 240 patients aged ≤50 years with OSA (19.6% female; mean±SD age 39.9±7.7 years) and 80 314 controls. After 5-year follow-up, 31.8% of the patients with OSA developed any cardiovascular event compared with 16.5% of the controls, with a corresponding relative risk (RR) of 1.96 (95% CI, 1.90-2.02). At 5-year follow-up, 27.3% of patients with OSA developed incident hypertension compared with 15.0% of the controls (RR, 1.84 [95% CI, 1.78-1.90]). Incident diabetes occurred in 6.8% of the patients with OSA and 1.4% of controls (RR, 5.05 [95% CI, 4.60-5.54]). Similar to older adults, young adults with OSA demonstrate increased risk of developing cardiovascular events. To prevent cardiovascular disease progression, accumulation of cardiovascular risk factors, and mortality, risk stratification and prevention strategies should be considered for these patients.

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.

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.

Association between body composition and subsequent cardiovascular diseases among 5-year breast cancer survivors

Background and aimsCardiovascular disease (CVD) remain one of the leading causes of mortality in breast cancer survivors. This study aimed to investigate the association between body composition and subsequent CVD in breast cancer survivors. Methods and resultsA retrospective cohort study of more than 70 thousand 5-year breast cancer survivors aged 40 years or older was conducted using data from the National Health Insurance Service of South Korea. Based on the percentage of predicted lean body mass (pLBMP), appendicular skeletal muscle mass (pASMP), and body fat mass (pBFMP), which were calculated using prediction equations with anthropometric data and health habits, groups were equally divided into quartiles. The risk of CVD was evaluated using multivariate Cox proportional hazards regression. Compared to those with the lowest pLBMP and pASMP, those with the highest pLBMP and pASMP had a 38% and 42% lower risk of CVD, respectively. In contrast, those with the highest pBFMP had a 57% higher risk of CVD compared to those with the lowest pBFMP. Each 1 % increase in pLBMP and pASMP was associated with a decreased risk of CVD [pLBMP, adjusted hazard ratio (aHR): 0.96, 95% CI 0.94–0.98, p < 0.05; pASMP, aHR: 0.91, 95% CI 0.87–0.95, p < 0.05] while each 1 % increase in pBFMP was associated with the increased risk of CVD (aHR: 1.05, 95% CI 1.03–1.07, p < 0.01). ConclusionIn this cohort study, a high pLBMP, a high pASMP, and a low pBFMP were associated with a lower risk of CVD.

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.