Risk Of Subsequent Cardiovascular Disease Research Articles

General obesity, abdominal obesity, and the risk of cardiovascular disease including stroke in 5-year breast cancer survivors.

To assess the association between discrepancies between general obesity and abdominal obesity and the risk of subsequent cardiovascular disease (CVD), including stroke, in breast cancer survivors. We undertook a retrospective cohort study using data from the National Health Insurance Service of South Korea. Among 72,174 5-year breast cancer survivors aged 40 years and above, body mass index (BMI) and waist circumference (WC) were used to determine obesity status. Cox proportional hazards models were used to evaluate the association of obesity and risk of CVD, including stroke. Compared to those with normal WC and BMI, those who were overweight without abdominal obesity, had abdominal obesity only, and overweight with abdominal obesity, had higher risks of CVD [aHR(95% CI) 1.23(1.02-1.48), 1.51(1.16-1.95), and 1.55(1.31-1.75), respectively] and total stroke [1.09(0.86-1.38), 1.63(1.20-2.23), and 1.40(1.17-1.68), respectively]. Compared to those overweight, those with abdominal obesity only had a significantly higher risk of ischemic stroke [2.04(1.14-3.65)]. Breast cancer survivors with higher BMI and/or abdominal obesity were associated with an elevated risk of CVD, including stroke.

Cardiovascular disease risk in cancer survivors: a population-based cohort study from the UK Biobank, and meta-analysis of cohort studies

IntroductionIn addition to the well-recognised cardiotoxicity of cancer treatment, possible aetiological links between cancer diagnosis and cardiovascular disease (CVD) have gained growing research interests. We aimed to estimate the CVD...

Childhood Exposure to Interparental Physical Violence and Adult Cardiovascular Disease

Childhood adverse experiences have been linked with long-term risk of cardiovascular disease (CVD), yet the transgenerational associations between interparental behaviors and CVD remain poorly understood. To explore the association between exposure to childhood interparental physical violence and the subsequent risk of CVD and to examine whether the association is modified by adult depressive symptoms. This population-based cohort study included data from the China Health and Retirement Longitudinal Study (CHARLS), an ongoing study recruiting individuals aged 45 years or older, dated between June 1, 2011, and December 31, 2020, with a follow-up duration of 9 years. The data were analyzed from October 1, 2023, to May 10, 2024. An early life exposure questionnaire with information on the frequency of witnessing interparental physical violence was administered. Depressive symptoms were assessed via the validated 10-item Center for Epidemiologic Studies Depression Scale. The outcome measures included self-reported physician-diagnosed heart disease (defined as myocardial infarction, angina, coronary heart disease, heart failure, or other heart problems) and stroke. Multivariate Cox proportional hazards regression models using attained age as the time scale were conducted. Of 10 424 participants, the mean (SD) age was 58.1 (9.0) years, 5332 (51.2%) were female, and 872 (8.4%) reported exposure to interparental physical violence. Exposure to childhood interparental physical violence was associated with increased risks of adult-onset CVD (hazard ratio [HR], 1.36; 95% CI, 1.20-1.55), heart disease (HR, 1.36; 95% CI, 1.17-1.57), and stroke (HR, 1.28; 95% CI, 1.03-1.61). Participants exposed to childhood interparental physical violence had a greater prevalence of depressive symptoms (2371 of 9335 participants [25.4%]), which mediated 11.0% of the association between childhood interparental physical violence and CVD (HR, 1.26; 95% CI, 1.09-1.45). In this cohort study, childhood exposure to interparental physical violence was associated with a higher risk of adult-onset CVD, which was partially mediated by adult depressive symptoms. The findings emphasize the need for comprehensive strategies and policy efforts that address the social determinants of interparental violence and provide household education opportunities.

Causal Pathways Between Breast Cancer and Cardiovascular Disease Through Mediator Factors: A Two-Step Mendelian Randomization Analysis.

The causal relationship of breast cancer (BC) with cardiovascular disease (CVD) and the underlying mediating pathways remains elusive. Our study endeavors to investigate the causal association between BC and CVD, with a focus on identifying potential metabolic mediators and elucidating their mediation effects in this causality. In this study, we conducted two-sample Mendelian randomization (MR) to estimate the causal effect of BC (overall BC, ER+ BC, ER- BC) from the Breast Cancer Association Consortium (BCAC) on CVD including coronary heart disease (CHD), hypertensive heart disease (HHD), ischaemic heart disease (IHD), and heart failure (HF) from the FinnGen consortium. Then, we used two-step MR to evaluate 18 metabolic mediators of the association and calculate the mediated proportions. Genetically predicted ER+ BC was causally associated with an increased risk of CVD including CHD (OR = 1.034, 95% CI: 1.004-1.065, p = 0.026), HHD (OR = 1.061, 95% CI: 1.002-1.124, p = 0.041), IHD (OR = 1.034, 95% CI: 1.007-1.062, p=0.013), and HF (OR = 1.055, 95% CI: 1.013-1.099, p = 0.010), while no causality was observed for overall BC and ER- BC. Furthermore, high-density lipoprotein cholesterol (HDL-C) was identified as a mediator of the association between ER+BC and CVD, including CHD (with 15.2% proportion)) and IHD (with 15.5% proportion), respectively. This study elucidates the potential causal impact of ER+ BC on subsequent risk of CVD, including CHD, HHD, IHD, and HF. We also outline the metabolic mediator HDL-C as a priority target for preventive measures to reduce excessive risk of CVD among patients diagnosed with ER+BC.

Sleep characteristics in relation to cardiovascular disease incidence and mortality in individuals with diabetes

Abstract Background/Introduction Evidence regarding the potential health effects of sleep characteristics among individuals with type 2 diabetes (T2D) is limited. Purpose We aimed to examine sleep characteristics in relation to subsequent risk of cardiovascular disease (CVD), including coronary heart disease (CHD), and stroke, and all-cause and cause-specific mortality among individuals with T2D. Methods We prospectively followed 21,902 men and women with T2D at baseline or diagnosed during follow-up (Nurses' Health Study: 1986-2018, Health Professionals Follow-Up Study: 1986-2018). Sleep characteristics, including sleep duration, snoring, sleep apnea, and sleep quality, were repeatedly assessed using self-reported questionnaires at baseline and follow-up. Associations of sleep characteristics with CVD risk and mortality were assessed using Cox proportional hazards models with adjustments for demographic, dietary and lifestyle factors, and medical history. Results During 170,355 and 196,458 person-years of follow-up in participants with T2D, there were 2,486 incident CVD events and 3,922 deaths, respectively. Compared with sleeping for 7-8 h/day, the multivariable-adjusted hazard ratios (HRs) of sleeping for ≤5 h/day were 1.21 (1.02, 1.45) for CVD incidence, 1.24 (1.20, 1.51) for CHD incidence, 1.40 (1.24, 1.58) for total mortality, 1.52 (1.20, 1.92) for CVD mortality, and 1.27 (1.01, 1.61) for other non-CVD and non-cancer mortality, while the HRs of ≥10 h/day were 1.42 (1.21, 1.66) for total mortality, and 1.63 (1.20, 2.10) for other non-CVD and non-cancer mortality. Furthermore, compared with participants without habitual snoring, those with habitual snoring had a 21%, 24%, 18%, and 33% higher risk for CVD incidence, CHD incidence, CVD mortality, and total mortality, respectively. Compared with participants without diagnosed sleep apnea, those with sleep apnea had a 27%-58% higher risk for CVD incidence, CVD mortality, and total mortality. In addition, lower habitual sleep quality, including sleep difficulties and restless sleep, was associated with a substantially higher risk of CVD, CHD, or CVD mortality. No associations were observed between sleep characteristics with risk of stroke and cancer mortality in individuals with T2D. Conclusions Short and long sleep durations as well as habitual snoring, sleep apnea, and lower sleep quality were independently associated with higher risks of CVD incidence and mortality, particularly CVD mortality in individuals with T2D.

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.

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.

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.

Sibling Death in Childhood and Early Adulthood and Risk of Early-Onset Cardiovascular Disease

Sibling death is a highly traumatic event, but empirical evidence on the association of sibling death in childhood and early adulthood with subsequent risk of incident cardiovascular disease (CVD) remains limited. To evaluate the association between sibling death in the early decades of life and subsequent risk of incident early-onset CVD. This population-based cohort study included 2 098 659 individuals born in Denmark from 1978 to 2018. Follow-up started at age 1 year or the date of the first sibling's birth, whichever occurred later, and it ended at the first diagnosis of CVD, the date of death, emigration, or December 31, 2018, whichever came first. Data analyses were conducted from November 1, 2021, through January 10, 2022. The death of a sibling. The outcome was early-onset CVD. Cox models were used to estimate hazard ratios (HRs) with 95% CIs. This study included 2 098 659 individuals (1 076 669 [51.30%] male; median [IQR] age at death of sibling, 11.48 [4.68-21.32] years). During the median (IQR) follow-up of 17.52 (8.85-26.05) years, 1286 and 76 862 individuals in the bereaved and nonbereaved groups, respectively, were diagnosed with CVD. Sibling death in childhood and early adulthood was associated with a 17% increased risk of overall CVD (HR, 1.17; 95% CI, 1.10-1.23; cumulative incidence in bereaved individuals, 1.96% [1.61%-2.34%]; cumulative incidence in nonbereaved individuals at age 41 years, 1.35% [1.34%-1.37%]; cumulative incidence difference: 0.61% [95% CI, 0.24%-0.98%]). Increased risks were also observed for most type-specific CVDs, in particular for myocardial infarction (HR, 1.66; 95% CI, 1.12-2.46), ischemic heart disease (HR, 1.52; 95% CI, 1.22-1.90), and heart failure (HR, 1.50; 95% CI, 1.00-2.26). The association was observed whether the sibling died due to CVD (HR, 2.54; 95% CI, 2.04-3.17) or non-CVD (HR, 1.13; 95% CI, 1.06-1.19) causes. The increased risk of CVD was more pronounced for individuals who lost a twin or younger sibling (HR, 1.25; 95% CI, 1.15-1.36) than an elder sibling (HR, 1.11; 95% CI, 1.03-1.20). In this cohort study of the Danish population, sibling death in childhood and early adulthood was associated with increased risks of overall and most type-specific early-onset CVDs, with the strength of associations varying by cause of death and age difference between sibling pairs. The findings highlight the need for extra attention and support to the bereaved siblings to reduce CVD risk later in life.

Associations of offspring birthweight and placental weight with subsequent parental coronary heart disease: survival regression using the walker cohort.

Low birth weight (BW) is consistently correlated with increased parental risk of subsequent cardiovascular disease, but the links with offspring placental weight (PW) are mostly unexplored. We have investigated the associations between parental coronary heart disease (CHD) and offspring BW and PW using the Walker cohort, a collection of 48,000 birth records from Dundee, Scotland, from the 1950s and 1960s. We linked the medical history of 13,866 mothers and 8,092 fathers to their offspring's records and performed Cox survival analyses modelling maternal and paternal CHD risk by their offspring's BW, PW, and the ratio between both measurements. We identified negative associations between offspring BW and both maternal (hazard ratio [HR]: 0.91, 95% confidence interval [CI]: 0.88-0.95) and paternal (HR: 0.96, 95% CI: 0.93-1.00) CHD risk, the stronger maternal correlation being consistent with previous reports. Offspring PW to BW ratio was positively associated with maternal CHD risk (HR: 1.14, 95% CI: 1.08-1.21), but the associations with paternal CHD were not significant. These analyses provide additional evidence for intergenerational associations between early growth and parental disease, identifying directionally opposed correlations of maternal CHD with offspring BW and PW, and highlight the importance of the placenta as a determinant of early development and adult disease.

Cardiovascular disease risk in early rheumatoid arthritis: the impact of cartilage oligomeric matrix protein (COMP) and disease activity

BackgroundTo investigate whether baseline serum cartilage oligomeric matrix protein (COMP), patient characteristics, traditional cardiovascular disease (CVD) risk factors and disease activity over time predict CVD, in early rheumatoid arthritis (RA).MethodsThis study included patients with early RA (< 12 months disease duration) (n = 233) recruited 1995–2005. Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression.ResultsA first ever diagnosis of CVD occurred in 70 patients, and CAD in 52. Age, sex, hypertension and diabetes predicted CVD and CAD. COMP was associated with increased risk of CVD and CAD [crude hazard ratios (HRs) per SD 1.45; 95% CI 1.17–1.80 and 1.51; 95% CI 1.18–1.92, respectively]. When adjusted for age, sex, hypertension, diabetes and ESR, results where similar but did not reach significance [HRs 1.32, 95% CI 0.99–1.74 and 1.35, 95% CI 0.99–1.86]. Baseline disease activity did not independently predict CVD. High DAS28 (> 5.1) at two years was associated with increased risk of subsequent CVD [adjusted HR 2.58; 95% CI 1.10–6.04] and CAD. ESR and CRP at two years as well as cumulative disease activity over 2 years independently predicted CVD and CAD.ConclusionCOMP may be a novel predictor of CVD and CAD in RA. Active disease two years after RA diagnosis, as well as cumulative disease activity, was associated with increased risk of CVD and CAD, independent of traditional CVD risk factors. Awareness of the particularly increased CVD risk among difficult to treat patients is important in order to further reduce CVD in RA.

Abstract 17569: Changes in Adherence to “Life’s Essential 8” and Subsequent Risk of Cardiovascular Disease

Introduction: The American Heart Association recently released an updated algorithm for evaluating cardiovascular health (CVH)—Life’s Essential 8 (LE8). However, very few studies have evaluated associations between changes in LE8 score over time and risk of cardiovascular disease (CVD). Hypothesis: We hypothesized that improving adherence to LE8 score over time was associated with lower CVD risk. Methods: We examined associations between 6-year changes (from 2006 to 2012) in LE8 score (score range, 0-100) and risk of CVD, including heart disease and stroke (from 2012 to 2020). Participants were 53328 Chinese adults from the Kailuan Study who were free from CVD in 2012. Diet, lifestyle and health conditions were repeatedly assessed every 2 years. The LE8 score was calculated based on scores for 8 components: diet quality, physical activity, smoking status, sleep health, BMI, blood lipids, blood glucose, and blood pressure. We used Cox proportional-hazard models to estimate hazard ratios (HRs) with adjustment for age, sex, alcohol intake, education, income, and family history of CVD. Results: We documented 4264 incident CVD cases (2159 heart disease and 2311 stroke) (some individuals had both heart disease and stroke) during a median of 7.7 years of follow-up. Compared with participants whose LE8 scores remained stable, those with the largest increase of LE8 score had a 30% lower CVD risk, 30% lower heart disease risk, and 28% lower stroke risk (HR and 95%CI: 0.70 (0.63, 0.78) for CVD, 0.70 (0.61, 0.82) for heart disease, 0.72 (0.63, 0.83) for stroke); while participants with the largest decrease had a 47%, 57%, and 35% higher risk for CVD, heart disease, and stroke, respectively. Each 10 points increase of LE8 score was associated with 27%-29% lower risk for these diseases. Similar results were observed in secondary analyses of 4-year changes (2006 - 2010) and 8-year changes (2006 - 2014) in LE8 score with CVD risk. These associations persisted in subgroup analysis stratified by risk factors of CVD. Conclusions: Improving adherence to LE8 score over a 6-year period was associated with lower risk of CVD, heart disease, and stroke, whereas decreased adherence to LE8 score was associated with higher risk. These findings support greater adherence to LE8 for improving CVH.

Dietary Glutamine and Glutamate in Relation to Cardiovascular Disease Incidence and Mortality in the United States Men and Women with Diabetes Mellitus

BackgroundEvidence regarding the potential health effects of dietary amino acids glutamine and glutamate among individuals with type 2 diabetes (T2D) is limited. ObjectivesThe aim was to examine dietary glutamine and glutamate in relation to subsequent risk of cardiovascular disease (CVD) and mortality among individuals with T2D. MethodsWe prospectively followed 15,040 men and women with T2D at baseline or diagnosed during follow-up (Nurses' Health Study: 1980–2014 and Health Professionals Follow-Up Study: 1986–2018). Diet was repeatedly assessed using validated food frequency questionnaires every 2–4 y. Associations of energy-adjusted glutamine and glutamate intake, as well as their ratio, with CVD risk and mortality, were assessed using Cox proportional-hazards models with adjustments for demographics, dietary and lifestyle factors, and medical history. ResultsDuring 196,955 and 225,371 person-years of follow-up in participants with T2D, there were 2927 incident CVD cases and 4898 deaths, respectively. Higher intake of glutamine was associated with lower risk of CVD incidence, CVD mortality, and total mortality: comparing extreme quintiles, the hazard ratios (HRs) (95% confidence intervals [CIs]) were 0.88 (0.77, 0.99), 0.78 (0.65, 0.92), and 0.84 (0.76, 0.92), respectively (all P-trend < 0.05). In contrast, higher intake of glutamate was associated with a higher risk of CVD incidence, CVD mortality, and total mortality; the HRs were 1.30 (1.15, 1.46), 1.46 (1.24, 1.72), and 1.20 (1.09, 1.32), respectively (all P-trend < 0.05). Furthermore, comparing extreme quintiles, a higher dietary glutamine-to-glutamate ratio was associated with a lower risk of CVD incidence (0.84 [0.75, 0.95]), CVD mortality (0.66 [0.57, 0.77]), and total mortality (0.82 [0.75, 0.90]). In addition, compared with participants with stable or decreased consumption of glutamine-to-glutamate ratio from prediabetes to postdiabetes diagnosis, those who increased the ratio had a 17% (5%, 27%) lower CVD mortality. ConclusionsIn adults with T2D, dietary glutamine was associated with a lower risk of CVD incidence and mortality, whereas the opposite was observed for glutamate intake.

Metabolomic profiles of chronic distress are associated with cardiovascular disease risk and inflammation-related risk factors

BackgroundChronic psychological distress is associated with increased risk of cardiovascular disease (CVD) and investigators have posited inflammatory factors may be centrally involved in these relationships. However, mechanistic evidence and molecular underpinnings of these processes remain unclear, and data are particularly sparse among women. This study examined if a metabolite profile linked with distress was associated with increased CVD risk and inflammation-related risk factors. MethodsA plasma metabolite-based distress score (MDS) of twenty chronic psychological distress-related metabolites was developed in cross-sectional, 1:1 matched case-control data comprised of 558 women from the Nurses’ Health Study (NHS; 279 women with distress, 279 controls). This MDS was then evaluated in two other cohorts: the Women’s Health Initiative Observational Cohort (WHI-OS) and the Prevención con Dieta Mediterránea (PREDIMED) trial. We tested the MDS's association with risk of future CVD in each sample and with levels of C-reactive protein (CRP) in the WHI-OS. The WHI-OS subsample included 944 postmenopausal women (472 CHD cases; mean time to event = 5.8 years); the PREDIMED subsample included 980 men and women (224 CVD cases, mean time to event = 3.1 years). ResultsIn the WHI-OS, a 1-SD increase in the plasma MDS was associated with a 20% increased incident CHD risk (odds ratio [OR] = 1.20, 95% CI: 1.04 – 1.38), adjusting for known CVD risk factors excluding total and HDL cholesterol. This association was attenuated after including total and HDL cholesterol. CRP mediated an average 12.9% (95% CI: 4.9% – 28%, p < 10-15) of the total effect of MDS on CHD risk when adjusting for matching factors. This effect was attenuated after adjusting for known CVD risk factors. Of the metabolites in the MDS, tryptophan and threonine were inversely associated with incident CHD risk in univariate models. In PREDIMED, each one SD increase in the MDS was associated with an OR of 1.19 (95% CI: 1.00 – 1.41) for incident CVD risk, after adjusting all risk factors. Similar associations were observed in men and women. Four metabolites in the MDS were associated with incident CVD risk in PREDIMED in univariate models. Biliverdin and C36:5 phosphatidylcholine (PC) plasmalogen had inverse associations; C16:0 ceramide and C18:0 lysophosphatidylethanolamine(LPE) each had positive associations with CVD risk. ConclusionsOur study points to molecular alterations that may underlie the association between chronic distress and subsequent risk of cardiovascular disease in adults.

The association between cardiovascular disease and breast and gynecologic cancers among black female patients

IntroductionLittle is known about whether a breast or gynecologic cancer diagnosis increases long-term cardiovascular disease (CVD) risk among Black females. The purpose of this study was to determine whether a breast or gynecologic cancer diagnosis is associated with CVD risk and identify determinants of subsequent CVD risk among Black females with an incident breast or gynecologic cancer diagnosis. MethodsUsing the Southern Community Cohort Study data from 2002–2016, this study was designed to analyze CVD incidence among Black females without cancer or CVD at enrollment. Cox proportional hazards regression models with or without covariates were used to explore the relationship between a breast or gynecologic cancer diagnosis and CVD risk among women without cancer as well as without CVD at enrollment (N=11,486). In addition, Cox proportional hazards regression models, excluding those who developed CVD before breast and gynecologic cancer diagnosis and those with other types of cancers, were used to assess determinants of CVD risk among breast and gynecologic cancer survivors. ResultsOf 11,486 Black females, 531 developed a breast or gynecological cancer (4.6%) over a median follow-up of 140 months (interquartile range: 123-159 months). Compared to women without cancer, women with a breast or gynecological cancers had greater than 20% higher risk of incident CVD during the follow-up period. Without adjusting for covariates, positive association between CVD risk and breast cancer was observed (hazard ratio (HR) = 1.24; 95% confidence interval (CI) = 1.11 - 1.39; p < 0.001); as well as between CVD risk and a gynecological cancer (HR = 1.23; 95% CI = 1.03 - 1.46; p = 0.021). Yet, after adjusting for covariates, CVD risk was only significantly associated with breast cancer (p = 0.001) but not gynecologic cancer. In cancer case-only analyses, CVD risk was significantly increasing with age (p < 0.05). ConclusionsLike study populations of predominantly White females, our results suggest that, adjusting for covariates, Black females possess a higher risk of CVD following a breast cancer diagnosis compared to women who did not develop breast cancer. Our results suggest a need for active CVD surveillance in the cancer survivorship phase.

Exploring how enrolment in the TARGET-CTCA clinical trial may modify patient perception of heart health

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background The TARGET-CTCA trial aims to determine whether the use of high-sensitivity cardiac troponin to target computed tomography coronary angiography (CTCA) improves outcomes in patients presenting to hospital with suspected acute coronary syndrome in whom myocardial infarction has been ruled out. What patients understand of their subsequent risk of cardiovascular disease in this setting, and how intervention with CTCA may influence this is unknown. Purpose To explore how trial participants perceive their heart health and whether this has been modified by trial participation. Methods The TARGET-CTCA trial randomises patients with intermediate high sensitivity cardiac troponin levels to standard care, or CTCA plus standard care. Patients receive CTCA scan results informing them if they have a normal heart or they have mild, moderate or obstructive coronary artery disease. Forty semi-structured interviews were conducted with trial participants across standard care and intervention arms ensuring representation across disease category, age, sex and socioeconomic status groups. Data were coded and organized into themes. Results Emergent themes from the data included insights into attitudes to future health, perception of heart health, and health education needs. While some participants displayed a proactive approach to maintaining health, the consideration of future health goals was often a reactive process in response to the initial chest pain episode or the CTCA findings. While some patients discussed personal responsibility for health maintenance others described a passive approached requiring direct management from a health professional. For some standard care participants, the absence of myocardial infarction was a sign of a healthy heart. Others were left with unanswered questions after the hospital assessment. Confirmation of the absence of coronary artery disease with CTCA gave patients great confidence and a positive change to health seeking behaviour patterns was reported. Patients differed in their interpretation of the terms mild, moderate and obstructive coronary artery disease. This affected their subsequent action with some using the presence of disease as an opportunity to appraise their risk of future cardiac events and begin a preventative approach. Others reported fear and reducing activity to avoid precipitating a possible event. Many patients reported a desire to implement lifestyle changes but did not have the knowledge to do so. Conclusion Exploring how the information contained in participant result letters may contribute to the understanding of risk of future cardiac events has provided valuable information for application of the trial intervention outside of the main trial setting.

Psychiatric disorders and subsequent risk of cardiovascular disease: a longitudinal matched cohort study across three countries.

Several psychiatric disorders have been associated with increased risk of cardiovascular disease (CVD), however, the role of familial factors and the main disease trajectories remain unknown. In this longitudinal cohort study, we identified a cohort of 900,240 patients newly diagnosed with psychiatric disorders during January 1, 1987 and December 31, 2016, their 1,002,888 unaffected full siblings, and 1:10 age- and sex-matched reference population from nationwide medical records in Sweden, who had no prior diagnosis of CVD at enrolment. We used flexible parametric models to determine the time-varying association between first-onset psychiatric disorders and incident CVD and CVD death, comparing rates of CVD among patients with psychiatric disorders to the rates of unaffected siblings and matched reference population. We also used disease trajectory analysis to identify main disease trajectories linking psychiatric disorders to CVD. Identified associations and disease trajectories of the Swedish cohort were validated in a similar cohort from nationwide medical records in Denmark (N=875,634 patients, same criteria during January 1, 1969 and December 31, 2016) and in Estonian cohorts from the Estonian Biobank (N=30,656 patients, same criteria during January 1, 2006 and December 31, 2020), respectively. During up to 30 years of follow-up of the Swedish cohort, the crude incidence rate of CVD was 9.7, 7.4 and 7.0 per 1000 person-years among patients with psychiatric disorders, their unaffected siblings, and the matched reference population. Compared with their siblings, patients with psychiatric disorders experienced higher rates of CVD during the first year after diagnosis (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.79-1.98) and thereafter (1.37; 95% CI, 1.34-1.39). Similar rate increases were noted when comparing with the matched reference population. These results were replicated in the Danish cohort. We identified several disease trajectories linking psychiatric disorders to CVD in the Swedish cohort, with or without mediating medical conditions, including a direct link between psychiatric disorders and hypertensive disorder, ischemic heart disease, venous thromboembolism, angina pectoris, and stroke. These trajectories were validated in the Estonian Biobank cohort. Independent of familial factors, patients with psychiatric disorders are at an elevated risk of subsequent CVD, particularly during first year after diagnosis. Increased surveillance and treatment of CVDs and CVD risk factors should be considered as an integral part of clinical management, in order to reduce risk of CVD among patients with psychiatric disorders. This research was supported by EU Horizon 2020 Research and Innovation Action Grant, European Research Council Consolidator grant, Icelandic Research fund, Swedish Research Council, US NIMH, the Outstanding Clinical Discipline Project of Shanghai Pudong, the Fundamental Research Funds for the Central Universities, and the European Union through the European Regional Development Fund; the Research Council of Norway; the South-East Regional Health Authority, the Stiftelsen Kristian Gerhard Jebsen, and the EEA-RO-NO-2018-0535.

Evaluation of Social Isolation Trajectories and Incident Cardiovascular Disease Among Middle-Aged and Older Adults in China: National Cohort Study.

Although the association between social isolation and the risk of subsequent cardiovascular disease (CVD) is well documented, most studies have only assessed social isolation at a single time point, and few studies have considered the association using repeatedly measured social isolation. This study aimed to examine the association between social isolation trajectories and incident CVD in a large cohort of middle-aged and older adults. This study used data from 4 waves (wave 1, wave 2, wave 3, and wave 4) of the China Health and Retirement Longitudinal Study. We defined the exposure period as from June 2011 to September 2015 (from wave 1 to wave 3) and the follow-up period as from September 2015 to March 2019 (wave 4). On the basis of the inclusion and exclusion criteria, our final analytic sample included 8422 individuals who had no CVD in the China Health and Retirement Longitudinal Study in waves 1 to 3 and were fully followed up in wave 4. Social isolation was ascertained using an extensively used questionnaire at 3 consecutive, biennial time points from waves 1 to 3, and individuals were assigned to 3 predefined social isolation trajectories based on their scores at each wave (consistently low, fluctuating, and consistently high). Incident CVD included self-reported physician-diagnosed heart disease and stroke combined. Cox proportional hazard models estimated the associations of social isolation trajectories with risks of incident CVD, adjusting for demographics, health behaviors, and health conditions. Of the 8422 participants (mean age 59.76, SD 10.33 years at baseline), 4219 (50.09%) were male. Most of the participants (5267/8422, 62.54%) had consistently low social isolation over time and 16.62% (1400/8422) of the participants had consistently high social isolation over the exposure period. During the 4-year follow-up, 746 incident CVDs occurred (heart disease: 450 cases and stroke: 336 cases). Compared with individuals with consistently low social isolation, those with fluctuating social isolation (adjusted hazard ratio 1.27, 95% CI 1.01-1.59) and consistently high social isolation (adjusted hazard ratio 1.45, 95% CI 1.13-1.85) had higher risks for incident CVD after adjusting for demographics (ie, age, sex, residence, and educational level), health behaviors (ie, smoking status and drinking status), and health conditions (ie, BMI; history of diabetes, hypertension, dyslipidemia, chronic kidney disease; use of diabetes medications, hypertension medications, and lipid-lowering therapy; and depressive symptoms scores). In this cohort study, middle-aged and older adults with fluctuating and consistently high social isolation exposure had higher risks of the onset of CVD than those without the exposure. The findings suggest that routine social isolation screenings and efforts to improve social connectedness merit increased attention for preventing CVD among middle-aged and older adults.

Association of cardiovascular health score trajectory and risk of subsequent cardiovascular disease in non-diabetic population: a cohort study

BackgroundDiabetes is an important risk factor for cardiovascular disease (CVD), but in the non-diabetic population, high glucose values within the normal range are also positively associated with CVD risk. There is a lack of concern for people without diabetes and evidence is lacking regarding the association between changes in cardiovascular health score (CVHS) and CVD risk in the non-diabetic population.MethodsThe current study included 37,970 non-diabetic participants free of CVD events in or before 2010 from the Kailuan Study and calculated CVHS according to the overall status of 7 cardiovascular health metrics between the 2006 and 2010 waves. Latent mixture models were used to explore the subgroups with different development trends included in the context of the Kailuan non-diabetic population and to identify the trajectory of each subgroup. The outcomes of the current study were CVD events, including myocardial infarction and stroke. CVHS trajectory was developed to predict subsequent CVD risk from 2010 to 2020. The Cox proportional hazard model was established to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of CVD across different trajectory patterns.ResultsFive distinct CVHS trajectory patterns were identified, including low-stable pattern (n = 2835), moderate-increasing pattern (n = 3492), moderate-decreasing pattern (n = 7526), high-stable I pattern (n = 17,135), and high-stable II pattern (n = 6982). Compared with the low-stable pattern, participants with the high-stable II pattern had a lower subsequent risk of CVD (HR = 0.22, 95%CI = 0.18–0.28); In stratification analysis, the lower risk for CVD was observed in females (HR = 0.10, 95%CI = 0.05–0.23, P for interaction < 0.05) and those aged < 60 years (HR = 0.16, 95%CI = 0.11 to 0.22, P for interaction < 0.05).ConclusionsCVHS trajectory patterns were associated with an altered CVD risk in the non-diabetic population. When stratified by age and sex, the association was stronger in young adults and females.

Association Between Chronic Hypertension and the Risk of 12 Cardiovascular Diseases Among Parous Women: The Role of Adverse Pregnancy Outcomes.

Evidence on the association between chronic hypertension and the risk of cardiovascular disease (CVD) in mothers with adverse pregnancy outcomes (APOs) is limited. We investigated the association between chronic hypertension and risk of CVD, considering the role of APOs. We used linked electronic health records in the CALIBER platform to define a UK cohort of women with recorded births between 1997 and 2016. We conducted multivariable Cox regression to estimate the association between chronic hypertension, with and without APOs, and 12 subsequent CVD events. The study cohort comprised 1 784 247 births (1.2 million women); of these 12 698 (0.71%) records had chronic hypertension, and 16 499 women had incident CVD during follow-up, of which 66% occurred in women under 40 years. Chronic hypertension (versus no chronic hypertension) was associated with a 2-fold higher risk of first subsequent CVD (adjusted hazard ratios, 2.22 [95% CI, 2.03-2.42]). Compared to normotensive women without APOs, the associations were the strongest in women with chronic hypertension and APOs across the 12 CVD outcomes, varying from 9.65 (5.96-15.6) for heart failure to 2.66 (2.17-3.26) for stable angina. In women with chronic hypertension without APOs, adjusted hazard ratios varied from 5.25 (3.47-7.94) for subarachnoid hemorrhage to 1.26 (0.59-2.67) for peripheral arterial disease. In women with APOs, but without chronic hypertension, adjusted hazard ratios varied from 3.27 (2.48-4.31) for intracerebral hemorrhage to 1.33 (1.26-1.41) for stable angina. We found strong associations between chronic hypertension and the risk of premature CVD, with greater risk in women who additionally had APOs. Intervention programs focused on these groups might lower their risk of subsequent CVD.