Osteoporosis and coronary heart disease: a bi-directional Mendelian randomization study.

Background: Osteoporosis (OP) and cardiovascular disease (CVD) are major global public health issues, especially exacerbated by the challenges of an aging population. As these problems intensify, the associated burden on global health is expected to increase significantly. Despite extensive epidemiological investigations into the potential association between OP and CVD, establishing a clear causal relationship remains elusive. Methods: Instrumental variables were selected from summary statistics of the IEU GWAS database. Five different components of BMD (heel BMD, LS BMD, FA BMD, FN BMD, and TB BMD) were used as OP phenotypes. CHD, MI, and stroke were selected to represent CVD. Multiple analysis methods were used to evaluate the causal relationship between CVD and OP comprehensively. In addition, sensitivity analyses(Cochran's Q test, MR-Egger intercept test, and "leave one out" analysis) were performed to verify the reliability of the results. Results: The MR showed a significant causal relationship between CHD on heel BMD and TB BMD; in the reverse analysis, there was no evidence that OP has a significant causal effect on CVD. The reliability of the results was confirmed through sensitivity analysis. Conclusion: The study results revealed that CHD was causally associated with Heel BMD and TB BMD, while in the reverse MR analysis, the causal relationship between OP and CVD was not supported. This result posits CHD as a potential etiological factor for OP and prompts that routine bone density assessment at traditional sites (forearm, femoral neck, lumbar spine) using DAX may inadequately discern underlying osteoporosis issues in CHD patients. The recommendation is to synergistically incorporate heel ultrasound or DAX for total body bone density examinations, ensuring clinical diagnostics are both precise and reliable. Moreover, these findings provide valuable insights for public health, contributing to the development of pertinent prevention and treatment strategies.

Association between triglyceride glucose-waist to height ratio and coronary heart disease: a population-based study.

BACKGROUND: The Triglyceride glucose (TyG) index-related indicators improve risk stratification by identifying individuals prone to atherosclerosis early in life. This study aimed to examine the relation between TyG-waist circumference-to-height ratio (TyG-WHtR) and coronary heart disease. METHODS: Data from four National Health and Nutrition Examination Surveys (NHANES) cycles between 2011 and 2018 were used for a cross-sectional study. The association between TyG-WHtR and coronary heart disease risk was examined using a multifactorial logistic regression model, and corresponding subgroup analyses were performed. Nonlinear correlations were analyzed using smooth curve fitting and threshold effects analysis. When nonlinear connections were discovered, appropriate inflection points were investigated using recursive methods. RESULTS: TyG-WHtR and coronary heart disease were significantly positively correlated in the multifactorial logistic regression analysis. Subgroup analyses and interaction tests revealed that gender, age, smoking status, and cancer were not significantly associated with this correlation (P for interaction > 0.05). Furthermore, utilizing threshold effect analysis and smooth curve fitting, a nonlinear connection with an inflection point of 0.36 was observed between TyG-WHtR and coronary heart disease. CONCLUSIONS: According to this study, the American population is far more likely to have coronary heart disease if they have higher TyG-WHtR levels.

Bayesian network analysis of factors influencing type 2 diabetes, coronary heart disease, and their comorbidities.

OBJECTIVE: Bayesian network (BN) models were developed to explore the specific relationships between influencing factors and type 2 diabetes mellitus (T2DM), coronary heart disease (CAD), and their comorbidities. The aim was to predict disease occurrence and diagnose etiology using these models, thereby informing the development of effective prevention and control strategies for T2DM, CAD, and their comorbidities. METHOD: Employing a case-control design, the study compared individuals with T2DM, CAD, and their comorbidities (case group) with healthy counterparts (control group). Univariate and multivariate Logistic regression analyses were conducted to identify disease-influencing factors. The BN structure was learned using the Tabu search algorithm, with parameter estimation achieved through maximum likelihood estimation. The predictive performance of the BN model was assessed using the confusion matrix, and Netica software was utilized for visual prediction and diagnosis. RESULT: The study involved 3,824 participants, including 1,175 controls, 1,163 T2DM cases, 982 CAD cases, and 504 comorbidity cases. The BN model unveiled factors directly and indirectly impacting T2DM, such as age, region, education level, and family history (FH). Variables like exercise, LDL-C, TC, fruit, and sweet food intake exhibited direct effects, while smoking, alcohol consumption, occupation, heart rate, HDL-C, meat, and staple food intake had indirect effects. Similarly, for CAD, factors with direct and indirect effects included age, smoking, SBP, exercise, meat, and fruit intake, while sleeping time and heart rate showed direct effects. Regarding T2DM and CAD comorbidities, age, FBG, SBP, fruit, and sweet intake demonstrated both direct and indirect effects, whereas exercise and HDL-C exhibited direct effects, and region, education level, DBP, and TC showed indirect effects. CONCLUSION: The BN model constructed using the Tabu search algorithm showcased robust predictive performance, reliability, and applicability in forecasting disease probabilities for T2DM, CAD, and their comorbidities. These findings offer valuable insights for enhancing prevention and control strategies and exploring the application of BN in predicting and diagnosing chronic diseases.

Association between triglyceride glucose-body mass index and long-term adverse outcomes of heart failure patients with coronary heart disease.

BACKGROUND: The triglyceride glucose-body mass index (TyG-BMI) is recognized as a reliable surrogate for evaluating insulin resistance and an effective predictor of cardiovascular disease. However, the link between TyG-BMI index and adverse outcomes in heart failure (HF) patients remains unclear. This study examines the correlation of the TyG-BMI index with long-term adverse outcomes in HF patients with coronary heart disease (CHD). METHODS: This single-center, prospective cohort study included 823 HF patients with CHD. The TyG-BMI index was calculated as follows: ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI. To explore the association between the TyG-BMI index and the occurrences of all-cause mortality and HF rehospitalization, we utilized multivariate Cox regression models and restricted cubic splines with threshold analysis. RESULTS: Over a follow-up period of 9.4 years, 425 patients died, and 484 were rehospitalized due to HF. Threshold analysis revealed a significant reverse "J"-shaped relationship between the TyG-BMI index and all-cause mortality, indicating a decreased risk of all-cause mortality with higher TyG-BMI index values below 240.0 (adjusted model: HR 0.90, 95% CI 0.86-0.93; Log-likelihood ratio p = 0.003). A distinct "U"-shaped nonlinear relationship was observed with HF rehospitalization, with the inflection point at 228.56 (adjusted model: below: HR 0.95, 95% CI 0.91-0.98; above: HR 1.08, 95% CI 1.03-1.13; Log-likelihood ratio p < 0.001). CONCLUSIONS: This study reveals a nonlinear association between the TyG-BMI index and both all-cause mortality and HF rehospitalization in HF patients with CHD, positioning the TyG-BMI index as a significant prognostic marker in this population.

Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study.

BACKGROUND AND AIMS: Atherosclerosis is the main cause of stroke and coronary heart disease (CHD), both leading mortality causes worldwide. Proteomics, as a high-throughput method, could provide helpful insights into the pathological mechanisms underlying atherosclerosis. In this study, we characterized the associations of plasma protein levels with CHD and with carotid intima-media thickness (CIMT), as a surrogate measure of atherosclerosis. METHODS: The discovery phase included 1000 participants from the KORA F4 study, whose plasma protein levels were quantified using the aptamer-based SOMAscan proteomics platform. We evaluated the associations of plasma protein levels with CHD using logistic regression, and with CIMT using linear regression. For both outcomes we applied two models: an age-sex adjusted model, and a model additionally adjusted for body mass index, smoking status, physical activity, diabetes status, hypertension status, low density lipoprotein, high density lipoprotein, and triglyceride levels (fully-adjusted model). The replication phase included a matched case-control sample from the independent KORA F3 study, using ELISA-based measurements of galectin-4. Pathway analysis was performed with nominally associated proteins (p-value < 0.05) from the fully-adjusted model. RESULTS: In the KORA F4 sample, after Bonferroni correction, we found CHD to be associated with five proteins using the age-sex adjusted model: galectin-4 (LGALS4), renin (REN), cathepsin H (CTSH), and coagulation factors X and Xa (F10). The fully-adjusted model yielded only the positive association of galectin-4 (OR = 1.58, 95% CI = 1.30-1.93), which was successfully replicated in the KORA F3 sample (OR = 1.40, 95% CI = 1.09-1.88). For CIMT, we found four proteins to be associated using the age-sex adjusted model namely: cytoplasmic protein NCK1 (NCK1), insulin-like growth factor-binding protein 2 (IGFBP2), growth hormone receptor (GHR), and GDNF family receptor alpha-1 (GFRA1). After assessing the fully-adjusted model, only NCK1 remained significant (ß = 0.017, p-value = 1.39e-06). Upstream regulators of galectin-4 and NCK1 identified from pathway analysis were predicted to be involved in inflammation pathways. CONCLUSIONS: Our proteome-wide association study identified galectin-4 to be associated with CHD and NCK1 to be associated with CIMT. Inflammatory pathways underlying the identified associations highlight the importance of inflammation in the development and progression of CHD.

Quality of health care for patients with coronary heart disease and comorbid mental disorders: a prospective cohort study.

BACKGROUND: Coronary heart disease (CHD) is often associated with mental disorders (MDs). Comorbid MDs reduce the quality of life and increase cardiac morbidity and mortality. Nevertheless, there is little and inconsistent research on the management of MDs in CHD patients. To bridge this gap, this study aims to gain insight into the long-term course of MD-related health care for patients with CHD, in order to identify opportunities for care improvement. METHODS: In this prospective cohort study, we investigated whether CHD patients with or without expert-rated MD at baseline (N = 364) received different MD-related health care from either their general practitioner (GP) or cardiologist at follow-up, M = 2.7 [2.0-4.0] years later. In the follow-up assessment, N = 131 CHD patients participated and received questionnaires capturing sociodemographic, mental health, and MD-related health care characteristics. Descriptive statistics, t-tests and chi-squared tests were used for analyses. RESULTS: We found significant differences in MD-related health care. CHD patients with MD were more likely to be examined psychologically/psychiatrically (MD 55.9%, non-MD 16.7%, p = < .001) and diagnosed with MD (MD 55.9%, non-MD 13.5%, p = .020) by their GP or cardiologist. Recommendations for and responses to requests for psychotherapy were more likely in MD patients compared to non-MD patients (MD 38.7%, non-MD 11.8%, p = .012 and MD 38.5%, non-MD 11.8%, p = .031, respectively). No significant differences were found concerning physicians' active demand for patients' mental health, referral to a specialist for additional diagnostics, provision of information about the diagnosed MD and further treatment options, response to the patients' request for psychopharmacotherapy, help received in finding psychotherapy or psychopharmacotherapy, and actual receipt of these treatments. CONCLUSIONS: The results indicate differences in MD-related health care of CHD patients with and without comorbid MD. However, they still highlight the need to further encourage primary care physicians treating CHD to adequately address MDs, provide further diagnostics, support, and information to affected patients. To address this, physicians may benefit from awareness training on the association between CHD and MDs and on appropriate communication with MD patients. TRIAL REGISTRATION: German clinical trials register (Deutsches Register Klinischer Studien, DRKS) Registration Number: ID DRKS00022154, date of registration: 02.11.2021.

Mediation Mendelian randomisation study on the effects of shift work on coronary heart disease and traditional risk factors via gut microbiota.

Background: Epidemiological evidence suggests that there is an increased risk of coronary heart disease (CHD) related to jobs involving shift work (JSW), but the causality of and mechanism underlying such a relationship remain unclear. Therefore, we aimed to explore the relationship between JSW and CHD, investigating both causality and potential mediating factors. Methods: We performed univariate, multivariate, and mediation Mendelian randomisation (MR) analyses using data from large genome-wide association studies focussed on JSW and CHD, as well as data on some CHD risk factors (type 2 diabetes, hypertension, obesity, and lipids measurement) and 196 gut microbiota taxa. Single-nucleotide polymorphisms significantly associated with JSW acted as instrument variables. We used inverse-variance weighting as the primary method of analysis. Results: Bidirectional MR analysis indicated a robust effect of JSW on increased CHD risk; however, the existence of CHD did not affect the choice of JSW. We identified a mediating effects of type 2 diabetes and hypertension in this relationship, accounting for 11.89% and 14.80% of the total effect of JSW on CHD, respectively. JSW were also causally associated with the risk of type 2 diabetes and hypertension and had an effect on nine microbial taxa. The mediating influence of the Eubacterium brachy group at the genus level explained 16.64% of the total effect of JSW on hypertension. We found limited evidence for the causal effect of JSW on obesity and lipids measurements. Conclusions: Our findings suggest a causal effect of JSW on CHD, diabetes, and hypertension. We also found evidence for a significant connection between JSW and alterations in the gut microbiota. Considering that certain microbial taxa mediated the effect of JSW on hypertension risk, targeting gut microbiota through therapeutics could potentially mitigate high risks of hypertension and CHD associated with JSW.

Association between plant-based diets and the risk of coronary heart disease predicted using the Framingham Risk Score in Korean men: data from the HEXA cohort study.

OBJECTIVES: This study investigated the potential correlation between 4 plant-based diet indices and the predicted risk of coronary heart disease (CHD) in Korean men using the Framingham Risk Score. METHODS: The study included 12,356 men participants (aged ≥40 years) from the Health Examinees Study. Dietary intake was estimated using a validated food frequency questionnaire. Four plant-based diet indices were measured, including the overall plant-based diet index, the healthy plant-based diet index (hPDI), the unhealthy plant-based diet index (uPDI), and the pro-vegetarian diet index. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the predicted 10-year risk of CHD. RESULTS: The study found that individuals in the highest hPDI quintile had a 19% lower risk score for CHD based on the Framingham Risk Score (model 3: HR, 0.80; 95% CI, 0.69 to 0.93; p for trend=0.010). In stratified analyses, the highest pro-vegetarian diet index was associated with a lower risk score for CHD in physically active individuals (HR, 0.74; 95% CI, 0.59 to 0.93; p for interaction=0.020). Conversely, the highest uPDI was associated with the highest risk score for CHD in those with a body mass index of ≥25 kg/m2 and a waist circumference ≥90 cm. CONCLUSIONS: This prospective cohort study highlights the positive role of adhering to a high hPDI diet in the prevention of CHD in Korean men. Further prospective studies are needed to determine the association between various plant-based diet indices and the risk of CHD in Asian populations with different dietary habits.

Blood Lipids, Lipoproteins, and Apolipoproteins With Risk of Coronary Heart Disease: A Prospective Study Among Racially Diverse Populations.

BACKGROUND: Comprehensive blood lipoprotein profiles and their association with incident coronary heart disease (CHD) among racially and geographically diverse populations remain understudied. METHODS AND RESULTS: We conducted nested case-control studies of CHD among 3438 individuals (1719 pairs), including 1084 White Americans (542 pairs), 1244 Black Americans (622 pairs), and 1110 Chinese adults (555 pairs). We examined 36 plasma lipids, lipoproteins, and apolipoproteins, measured by nuclear magnetic resonance spectroscopy, with incident CHD among all participants and subgroups by demographics, lifestyle, and metabolic health status using conditional or unconditional logistic regression adjusted for potential confounders. Conventionally measured blood lipids, that is, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol, were each associated with incident CHD, with odds ratios (ORs) being 1.33, 1.32, 1.24, and 0.79 per 1-SD increase among all participants. Seventeen lipoprotein biomarkers showed numerically stronger associations than conventional lipids, with ORs per 1-SD among all participants ranging from 1.35 to 1.57 and a negative OR of 0.78 (all false discovery rate <0.05), including apolipoprotein B100 to apolipoprotein A1 ratio (OR, 1.57 [95% CI, 1.45-1.7]), low-density lipoprotein-triglycerides (OR, 1.55 [95% CI, 1.43-1.69]), and apolipoprotein B (OR, 1.49 [95% CI, 1.37-1.62]). All these associations were significant and consistent across racial groups and other subgroups defined by age, sex, smoking, obesity, and metabolic health status, including individuals with normal levels of conventionally measured lipids. CONCLUSIONS: Our study highlighted several lipoprotein biomarkers, including apolipoprotein B/ apolipoprotein A1 ratio, apolipoprotein B, and low-density lipoprotein-triglycerides, strongly and consistently associated with incident CHD. Our results suggest that comprehensive lipoprotein measures may complement the standard lipid panel to inform CHD risk among diverse populations.

Blood lipid levels mediating the effects of sex hormone-binding globulin on coronary heart disease: Mendelian randomization and mediation analysis.

Observational studies indicate that serum sex hormone-binding globulin (SHBG) levels are inversely correlated with blood lipid levels and coronary heart disease (CHD) risk. Given that dyslipidemia is an established risk factor for CHD, we aim to employ Mendelian randomization (MR) in conjunction with mediation analysis to confirm the mediating role of blood lipid levels in the association between SHBG and CHD. First, we assessed the causality between serum SHBG levels and five cardiovascular diseases using univariable MR. The results revealed causality between SHBG levels and reduced risk of CHD, myocardial infarction, as well as hypertension. Specifically, the most significant reduction was observed in CHD risk, with an odds ratio of 0.73 (95% CI 0.63-0.86) for each one-standard-deviation increase in SHBG. The summary-level data of serum SHBG levels and CHD are derived from a sex-specific genome-wide association study (GWAS) conducted by UK Biobank (sample size = 368,929) and a large-scale GWAS meta-analysis (60,801 cases and 123,504 controls), respectively. Subsequently, we further investigated the mediating role of blood lipid level in the association between SHBG and CHD. Mediation analysis clarified the mediation proportions for four mediators: high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%). Summary-level data for each mediator were sourced from the UK Biobank and publicly available GWAS. The above results confirm negative causality between serum SHBG levels and the risk of CHD, myocardial infarction, and hypertension, with the causal effect on reducing CHD risk largely mediated by the improvement of blood lipid profiles.

Incidence of coronary heart disease among remote workers: a nationwide web-based cohort study.

Coronary heart disease (CHD) risk is influenced by socioeconomic status-related parameters, particularly occupation. We investigated occupational gaps in CHD risk and how the introduction of remote work moderated the observed occupational differences in CHD risk during the coronavirus disease 2019 pandemic in Japan. Data from a web-based, nationwide cohort study, comprising 17,640 workers (aged 20-65 years) with baseline data from December 2020, were analyzed. Participants were grouped by occupation as upper-level nonmanual workers (managers/professionals) and others (reference group). The primary outcome was CHD (angina pectoris/myocardial infarction) onset retrospectively confirmed at the 1-year follow-up survey. Upper-level nonmanual workers exhibited a higher CHD incidence than others (2.3% vs. 1.7%). This association was pronounced in the younger (20-49 years) population, with a significant CHD risk (adjusted risk ratio = 1.88). Upper-level nonmanual workers exhibited nearly 15% higher remote work prevalence, with a significant remote work-related CHD risk (adjusted risk ratio = 1.92). The mediating effects of remote work explained an overall disparity of 32% among the younger population. Occupational gaps in CHD incidence in Japan differ from those in Western countries, where upper-level nonmanual workers have lower cardiovascular risk. In Japan, remote work can mediate CHD risk in the younger population of upper-level nonmanual workers.

[Retrospective cross-sectional survey of clinical characteristics and syndrome elements distribution at different stages of coronary heart disease].

The clinical data of coronary heart disease(CHD) patients treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine and Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to March 2023 were retrospectively collected. This study involved the descriptive analysis of demographic characteristics, clinical symptoms, and tongue and pulse features. The χ~2 test was conducted to analyze the distribution of syndrome elements and their combinations at diffe-rent stages of CHD, so as to reveal the clinical characteristics and syndrome patterns at various pathological stages of CHD. This study extracted 28 symptom entries, 10 tongue manifestation entries, and 7 pulse manifestation entries, summarized the 5 main disease locations of the heart, lung, liver, spleen, and kidney, and the 8 main disease natures of blood stasis, phlegm turbidity, Qi stagnation, heat(fire), fluid retention, Qi deficiency, Yin deficiency, and Yang deficiency and 8 combinations of disease natures. The χ~2 test showed significant differences in the distribution of syndrome elements including the lung, liver, spleen, kidney, blood stasis, heat(fire), Qi stagnation, heat syndrome, water retention, Qi deficiency, Yin deficiency, and Yang deficiency between different disease stages. Specifically, the liver, blood stasis, heat(fire), and Qi stagnation accounted for the highest proportion during unstable stage, and the lung, spleen, kidney, water retention, Qi deficiency, Yin deficiency, and Yang deficiency accounted for the highest proportion at the end stage. The distribution of Qi deficiency varied in the different time periods after percutaneous coronary intervention(PCI). As shown by the χ~2 test of the syndrome elements combination, the distribution of single disease location, multiple disease locations, single disease nature, double disease natures, multiple natures, excess syndrome, and mixture of deficiency and excess varied significantly at different stages of CHD. Specifically, single disease location, single disease nature, and excess syndrome accounted for the highest proportion during the stable stage, and double disease natures accounted for the highest proportion during the unstable stage. Multiple disease locations, multiple disease natures, and mixture of deficiency and excess accounted for the highest proportion during the end stage. In conclusion, phlegm turbidity and blood stasis were equally serious during the stable stage, and a pathological mechanism caused by blood stasis and toxin existed during the unstable stage. The overall Qi deficiency worsened after PCI, and the end stage was accompanied by the Yin and Yang damage and the aggravation of water retention. There were significant differences in the distribution of clinical characteristics and syndrome elements at different stages of CHD. The pathological process of CHD witnessed the growth and decline of deficiency and excess and the combination of phlegm turbidity and blood stasis, which constituted the basic pathogenesis.

Very short sleep duration reveals a proteomic fingerprint that is selectively associated with incident diabetes mellitus but not with incident coronary heart disease: a cohort study.

BACKGROUND: The molecular pathways linking short and long sleep duration with incident diabetes mellitus (iDM) and incident coronary heart disease (iCHD) are not known. We aimed to identify circulating protein patterns associated with sleep duration and test their impact on incident cardiometabolic disease. METHODS: We assessed sleep duration and measured 78 plasma proteins among 3336 participants aged 46-68 years, free from DM and CHD at baseline, and identified cases of iDM and iCHD using national registers. Incident events occurring in the first 3 years of follow-up were excluded from analyses. Tenfold cross-fit partialing-out lasso logistic regression adjusted for age and sex was used to identify proteins that significantly predicted sleep duration quintiles when compared with the referent quintile 3 (Q3). Predictive proteins were weighted and combined into proteomic scores (PS) for sleep duration Q1, Q2, Q4, and Q5. Combinations of PS were included in a linear regression model to identify the best predictors of habitual sleep duration. Cox proportional hazards regression models with sleep duration quintiles and sleep-predictive PS as the main exposures were related to iDM and iCHD after adjustment for known covariates. RESULTS: Sixteen unique proteomic markers, predominantly reflecting inflammation and apoptosis, predicted sleep duration quintiles. The combination of PSQ1 and PSQ5 best predicted sleep duration. Mean follow-up times for iDM (n = 522) and iCHD (n = 411) were 21.8 and 22.4 years, respectively. Compared with sleep duration Q3, all sleep duration quintiles were positively and significantly associated with iDM. Only sleep duration Q1 was positively and significantly associated with iCHD. Inclusion of PSQ1 and PSQ5 abrogated the association between sleep duration Q1 and iDM. Moreover, PSQ1 was significantly associated with iDM (HR = 1.27, 95% CI: 1.06-1.53). PSQ1 and PSQ5 were not associated with iCHD and did not markedly attenuate the association between sleep duration Q1 with iCHD. CONCLUSIONS: We here identify plasma proteomic fingerprints of sleep duration and suggest that PSQ1 could explain the association between very short sleep duration and incident DM.

Multiple coronary heart diseases are risk factors for mental health disorders: A mendelian randomization study.

BACKGROUND: Previous observational studies have suggested associations between Coronary Heart Disease (CHD) and Mental Health Disorders (MHD). However, the causal nature of these relationships has remained elusive. OBJECTIVE: The purpose of this study is to elucidate the causal relationships between eight distinct types of CHD and six types of MHD using Mendelian randomization (MR) analysis. METHODS: The MR analysis employed a suite of methods including inverse variance-weighted (IVW), MR-Egger, weighted mode, weighted median, and simple mode techniques. To assess heterogeneity, IVW and MR-Egger tests were utilized. MR-Egger regression also served to investigate potential pleiotropy. The stability of IVW results was verified by leave-one-out sensitivity analysis. RESULTS: We analyzed data from over 2,473,005 CHD and 803,801 MHD patients, informed by instrumental variables from large-scale genomic studies on European populations. The analysis revealed a causal increase in the risk of Major Depressive Disorder and Mania associated with Coronary Artery Disease and Myocardial Infarction. Heart Failure was found to causally increase the risk for Bipolar Disorder and Schizophrenia. Atrial Fibrillation and Ischemic Heart Diseases were positively linked to Generalized Anxiety Disorder and Mania, respectively. There was no significant evidence of an association between Hypertensive Heart Disease, Hypertrophic Cardiomyopathy, Pulmonary Heart Disease, and MHD. Reverse MR analysis indicated that MHD do not serve as risk factors for CHD. CONCLUSIONS: The findings suggest that specific types of CHD may act as risk factors for certain MHDs. Consequently, incorporating psychological assessments into the management of patients with CHD could be advantageous.

Sex-Associated Metabolites and Incident Stroke, Incident Coronary Heart Disease, Hypertension, and Chronic Kidney Disease in the REGARDS Cohort.

BACKGROUND: Sex disparities exist in cardiometabolic diseases. Metabolomic profiling offers insight into disease mechanisms, as the metabolome is influenced by environmental and genetic factors. We identified metabolites associated with sex and determined if sex-associated metabolites are associated with incident stoke, incident coronary heart disease, prevalent hypertension, and prevalent chronic kidney disease. METHODS AND RESULTS: Targeted metabolomics was conducted for 357 metabolites in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) case-cohort substudy for incident stroke. Weighted logistic regression models were used to identify metabolites associated with sex in REGARDS. Sex-associated metabolites were replicated in the HyperGEN (Hypertension Genetic Epidemiology Network) and using the literature. Weighted Cox proportional hazard models were used to evaluate associations between metabolites and incident stroke. Cox proportional hazard models were used to evaluate associations between metabolites and incident coronary heart disease. Weighted logistic regression models were used to evaluate associations between metabolites and hypertension and chronic kidney disease. Fifty-one replicated metabolites were associated with sex. Higher levels of 6 phosphatidylethanolamines were associated with incident stroke. No metabolites were associated with incident coronary heart disease. Higher levels of uric acid and leucine and lower levels of a lysophosphatidylcholine were associated with hypertension. Higher levels of indole-3-lactic acid, 7 phosphatidylethanolamines, and uric acid, and lower levels of betaine and bilirubin were associated with chronic kidney disease. CONCLUSIONS: These findings suggest that the sexual dimorphism of the metabolome may contribute to sex differences in stroke, hypertension, and chronic kidney disease.

Interplay Between Plasma Glycine and Branched-Chain Amino Acids Contributes to the Development of Hypertension and Coronary Heart Disease.

BACKGROUND: Higher levels of plasma glycine are linked to a reduced risk, while increased levels of total branched-chain amino acids (tBCAAs) are associated with a higher risk of essential hypertension and coronary heart disease (CHD). As these metabolic components are interconnected, analyzing the tBCAAs/glycine ratio may help to understand their interplay in the pathogenesis of cardiovascular disease. METHODS: The Cox regression approach was combined with the development of novel genetic tools for assessments of associations between plasma metabolomic data (glycine, tBCAAs, and tBCAAs/glycine ratio) from the UK Biobank and the development of hypertension and CHD. Genome-wide association study was performed on 186 523 White UK Biobank participants to identify new independent genetic instruments for the 2-sample Mendelian randomization analyses. P-gain statistic >10 identified instruments associated with tBCAAs/glycine ratio significantly stronger compared with individual amino acids. Outcomes of genome-wide association study on hypertension and CHD were derived from the UK Biobank (nonoverlapping sample), FinnGen, and CARDIoGRAMplusC4D. RESULTS: The tBCAAs/glycine ratio was prospectively associated with a higher risk of developing hypertension and CHD (hazard ratio quintile Q5 versus Q1, 1.196 [95% CI, 1.109-1.289] and 1.226 [95% CI, 1.160-1.296], respectively). Mendelian randomization analysis demonstrated that tBCAAs/glycine ratio (P-gain >10) was a risk factor for hypertension (meta-analyzed inverse-variance weighted causal estimate 0.45 log odds ratio/SD (95% CI, 0.26-0.64) and CHD (0.48 [95% CI, 0.29-0.67]) with an absolute effect significantly larger compared with the effect of glycine (-0.06 [95% CI, -0.1 to -0.03] and -0.08 [95% CI, -0.11 to -0.05], respectively) or tBCAAs (0.22 [95% CI, 0.09-0.34] and 0.12 [95% CI, 0.01-0.24], respectively). CONCLUSIONS: The total BCAAs/glycine ratio is a key element of the metabolic signature contributing to hypertension and CHD, which may reflect biological pathways shared by glycine and tBCAAs.

Association between Diet Quality and Risk of Type 2 Diabetes Mellitus in Patients with Coronary Heart Disease: Findings from the CORDIOPREV Study.

The incidence of type 2 diabetes mellitus (T2DM) is growing in Western countries. Nutritional interventions that promote high-quality dietary patterns could help reverse this trend. We aimed to evaluate whether changes in Nutrient-Rich Food Index 9.3 (NRF9.3) were related to the risk of developing T2DM in patients with coronary heart disease (CHD). The study was carried out in the context of two healthy dietary interventions (a Mediterranean and a low-fat diet). For this purpose, we evaluated all the patients in the CORDIOPREV study without T2DM at baseline. Data were obtained during the first 5 years of dietary intervention. The score was calculated using the Food Frequency Questionnaires at baseline and after 1 year of intervention. After 5 years of follow-up, 106 patients developed T2DM (incident-T2DM), while 316 subjects did not (non-T2DM). Total NRF9.3 score and changes during the first year of intervention were compared between incident-T2DM and non-T2DM. Incident-T2DM showed less improvement in NRF9.3 than non-T2DM (p = 0.010). In the multi-adjusted Cox proportional hazard study, patients with greater improvement in NRF9.3 had over 50% less risk of developing T2DM compared with the lowest tertile (HR 2.10, 95%, CI = 1.12-3.56). In conclusion, improved diet quality in terms of nutrient density after the dietary intervention was associated with a lower risk of T2DM in patients with CHD.

The overall fractions of coronary heart diseases and depression attributable to multiple dependent psychosocial work factors in Europe.

OBJECTIVES: The literature is nonexistent on the assessment of overall fractions of diseases attributable to multiple dependent psychosocial work factors. The objectives of the study were to calculate the overall fractions of coronary heart diseases (CHD) and depression attributable to multiple dependent psychosocial work factors in 35 European countries. METHODS: We used already published fractions of CHD and depression attributable to each of the following psychosocial work factors: job strain, effort-reward imbalance, job insecurity, long working hours, and workplace bullying. We took all exposures and their correlations into account to calculate overall attributable fractions. Wald tests were performed to test differences in these overall attributable fractions between genders and between countries. RESULTS: The overall fractions of CHD and depression attributable to all studied psychosocial work factors together were found to be 8.1% [95% CI: 2.0-13.9] and 26.3% [95% CI: 16.2-35.5] respectively in the 35 European countries. There was no difference between genders and between countries. CONCLUSION: Our study showed that the overall fractions attributable to all studied psychosocial work factors were substantial especially for depression. These overall attributable fractions may be particularly useful to evaluate the burden and costs attributable to psychosocial work factors, and also to inform policies makers at European level.

Telomere length as biomarker of nutritional therapy for prevention of type 2 diabetes mellitus development in patients with coronary heart disease: CORDIOPREV randomised controlled trial.

BACKGROUND: Telomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years. METHODS: The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements. FINDINGS: 1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL < percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group. CONCLUSION: Patients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease. TRIAL REGISTRATION: Clinicaltrials.gov number NCT00924937.