Association between weekend warrior physical activity pattern and all-cause mortality among adults living with type 2 diabetes: a prospective cohort study from NHANES 2007 to 2018.

BACKGROUND: It is uncertain whether the weekend warrior pattern is associated with all-cause mortality among adults living with type 2 diabetes. This study explored how the 'weekend warrior' physical activity (PA) pattern was associated with all-cause mortality among adults living with type 2 diabetes. METHODS: This prospective cohort study investigated US adults living with type 2 diabetes in the National Health and Nutrition Examination Survey (NHANES). Mortality data was linked to the National Death Index. Based on self-reported leisure-time and occupational moderate-to-vigorous PA (MVPA), participants were categorized into 3 groups: physically inactive (< 150 min/week of MVPA), weekend warrior (≥ 150 min/week of MVPA in 1 or 2 sessions), and physically active (≥ 150 min/week of MVPA in 3 or more sessions). RESULTS: A total of 6067 participants living with type 2 diabetes [mean (SD) age, 61.4 (13.5) years; 48.0% females] were followed for a median of 6.1 years, during which 1206 deaths were recorded. Of leisure-time and occupational activity, compared with inactive individuals, hazard ratios (HRs) for all-cause mortality were 0.49 (95% CI 0.26-0.91) and 0.57 (95% CI 0.38-0.85) for weekend warrior individuals, and 0.55 (95% CI 0.45-0.67) and 0.64 (95% CI 0.53-0.76) for regularly active individuals, respectively. However, when compared leisure-time and occupational weekend warrior with regularly active participants, the HRs were 0.82 (95% CI 0.42-1.61) and 1.00 (95% CI 0.64-1.56) for all-cause mortality, respectively. CONCLUSIONS: Weekend warrior PA pattern may have similar effects on lowering all-cause mortality as regularly active pattern among adults living with type 2 diabetes, regardless of leisure-time or occupational activity. Therefore, weekend warrior PA pattern may be sufficient to reduce all-cause mortality for adults living with type 2 diabetes.

Atherogenic lipid profile in patients with statin treatment after acute coronary syndrome: a real-world analysis from Chinese cardiovascular association database.

BACKGROUND: Adverse atherogenic lipid profile is associated with an increased risk of major adverse cardiac events in patients after acute coronary syndrome (ACS). Knowledge regarding the impact of statins on lipid profile remains limited. METHODS: We retrospectively analysed multicenter, real-world data from the Chinese Cardiovascular Association Database-iHeart Project. Patients with a primary diagnosis of ACS from 2014 to 2021 during index hospitalisation and having at least one lipid panel record after discharge within 12 months were enrolled. We analysed target achievement of atherogenic lipid profile, including apolipoprotein B (< 80 mg/dL), low-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L), lipoprotein(a) [Lp(a)] (< 30 mg/dL), triglycerides (< 1.7 mmol/L), remnant cholesterol (RC) (< 0.78 mmol/L), non-high-density lipoprotein cholesterol (< 2.6 mmol/L) at baseline and follow-up. Multivariate Cox regression models were employed to investigate the association between patient characteristics and target achievement. RESULTS: Among 4861 patients, the mean age was 64.9 years. Only 7.8% of patients had all atherogenic lipids within the target range at follow-up. The proportion of target achievement was for LDL-C 42.7%, Lp(a) 73.3%, and RC 78.5%. Patients with female sex, younger age, myocardial infarction, hypertension, and hypercholesteremia were less likely to control LDL-C, Lp(a), and RC. An increase in the burden of comorbidities was negatively associated with LDL-C and Lp(a) achievements but not with RC. CONCLUSIONS: A substantial gap exists between lipid control and the targets recommended by contemporary guidelines. Novel therapeutics targeting the whole atherogenic lipid profile will be warranted to improve cardiovascular outcomes.

Causal effects of risky behaviours on heart failure: a two-sample Mendelian randomisation study.

Aims/Background Previous studies have indicated correlations between various risky behaviours, increased risk tolerance, and the likelihood of heart failure. However, the causative nature of these correlations remains to be established. Therefore, our research aims to explore the causality between phenotypes of risky behaviour and the incidence of heart failure. Methods To assess causality, a two-sample Mendelian randomisation analysis was employed. Genetic variants of risky behaviours and risk tolerance (n=251,151-939,908) were sourced from existing genome-wide association summary statistics. For heart failure, genetic links were derived from a separate genome-wide association summary statistics dataset involving 977,323 individuals, comprising 47,309 heart failure cases and 930,014 controls. The primary method for this analysis was the inverse variance weighted technique. Results Mendelian randomisation analysis indicated a positive association between the number of offspring an individual has and the likelihood of heart failure (odds ratio, 1.841; 95% confidence interval, 1.528-2.217, p=1.26 × 10-10). Additionally, a modest statistically significant link was found between overall risk tolerance and heart failure (odds ratio, 1.249; 95% confidence interval, 1.003-1.556, p=0.047). Conversely, a genetic predisposition towards frequent automobile speeding showed a protective effect against heart failure (odds ratio, 0.732; 95% confidence interval, 0.545-0.982, p=0.037). Conclusion This Mendelian randomisation study confirmed genetically that risky behaviours are causally linked to the likelihood of heart failure. This finding may offer fresh perspectives on the pathogenic mechanisms underlying the progression of heart failure.

Coronary computed tomographic angiography-derived anatomic and hemodynamic plaque characteristics in prediction of cardiovascular events.

This study investigated the association of anatomic and hemodynamic plaque characteristics based on deep learning coronary computed tomography angiography (CCTA) with high-risk plaques that caused subsequent major adverse cardiovascular events (MACE). A retrospective analysis was conducted on patients who underwent CCTA between 1 month and 3 years prior to the occurrence of a MACE. Deep learning and computational fluid dynamics algorithms based on CCTA were applied to extract adverse plaque characteristics (low-attenuation plaque, positive remodeling, napkin-ring sign, and spotty calcification), and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFRCT], change in FFRCT across the lesion [△FFRCT], wall shear stress [WSS], and axial plaque stress [APS]). Correlation analysis, logistic regression, and Cox proportional risk analysis were conducted to understand the relationship between these measures and the occurrence of MACE and assess the value of hemodynamic parameters in predicting the incidence of MACE events and their prognosis. Our study included 86 patients with a total of 134 vessels exhibiting plaque formation and 83 culprit vessels with a subsequent coronary event. Culprit vessels had percent diameter stenosis [%DS] (0.54 ± 0.16 vs. 0.62 ± 0.13, P = 0.003), larger non-calcified plaque volume (45.8 vs. 101.7, P < 0.001), larger low-attenuation plaque volume (3.6 vs. 14.5, P < 0.001), more lesions with ≥ 3 adverse plaque characteristics (APC) (4 vs.26, P = 0.002), and worse hemodynamic features of adverse plaque. FFRCT demonstrated better visualization of maximum achievable flow in the presence of coronary stenosis and better correlation with the stenosis severity, while maximum of wall shear stress (WSSmax) was highly correlated with low-attenuation plaques and APC. The inclusion of hemodynamic parameters improved the efficacy of the predictive model, and a high WSS suggested a higher probability of MACE. Hemodynamic parameters based on CCTA are significantly correlated with plaque morphology. Importantly, integrating CCTA-derived parameters can refine the predictive performance of MACE occurrence.

The effect and mechanism of inulin on atherosclerosis is mediated by the characteristic intestinal flora and metabolites.

BACKGROUND: Inflammation and hyperlipidemia can cause atherosclerosis. Prebiotic inulin has been proven to effectively reduce inflammation and blood lipid levels. Utilizing a mouse model induced by a high-fat diet, this study aimed to explore whether the characteristic intestinal flora and its metabolites mediate the effects of inulin intervention on atherosclerosis and to clarify the specific mechanism. METHODS: Thirty apolipoprotein E-deficient (ApoE-/-) mice were randomly divided into three groups. They were fed with a normal diet, a high-fat diet or an inulin+high-fat diet for 16 weeks. The total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in the three groups were compared. The gross aorta and aortic sinus of mice were stained with oil red O, and the area of atherosclerotic plaque was observed and compared. The diversity and structure of the mouse fecal flora were detected by sequencing the V3-V4 region of the 16S rRNA gene, and the levels of metabolites in mouse feces were assessed by gas chromatography-mass spectrometry. The plasma lipopolysaccharide (LPS) levels and aortic inflammatory factors were measured by multi-index flow cytometry (CBA). RESULTS: ApoE-/- mice fed with the high-fat diet exhibited an increase of approximately 46% in the area of atherosclerotic lesions, and the levels of TC, TG and LDL-C were significantly increased ( P < 0.05) compared with levels in the normal diet group. After inulin was added to the high-fat group, the area of atherosclerotic lesions, the level of serum LPS and aortic inflammation were reduced, and the levels of TC, TG and LDL-C were decreased ( P  < 0.05). Based on 16S rRNA gene detection, we found that the composition of the intestinal microbiota, such as Prevotella, and metabolites, such as L-arginine, changed significantly due to hyperlipidemia, and the dietary inulin intervention partially reversed the relevant changes. CONCLUSION: Inulin can inhibit the formation of atherosclerotic plaques, which may be related to the changes in lipid metabolism, the composition of the intestinal microbial community and its metabolites, and the inhibition of the expression of related inflammatory factors. Our study identified the relationships among the characteristic intestinal microbiota, metabolites and atherosclerosis, aiming to provide a new direction for future research to delay or treat atherosclerosis by changing the composition and function of the host intestinal microbiota and metabolites.

Circulating Cytokines and Venous Thromboembolism: A Bidirectional Two-Sample Mendelian Randomization Study.

BACKGROUND: Epidemiological evidence has linked circulating cytokines to venous thromboembolism (VTE). However, it remains uncertain whether these associations are causal due to confounding factors or reverse causality. We aim to explore the causality between circulating cytokines and VTE, encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE). METHODS: In the current bidirectional Mendelian randomization (MR) study, instrumental variables of 41 circulating cytokines were obtained from the genome-wide association study meta-analyses (8,293 individuals). Summary statistics for the association of VTE (17,048 cases and 325,451 controls), DVT (8,077 cases and 295,014 controls), and PE (8,170 cases and 333,487 controls) were extracted from the FinnGen Study. A multivariable MR study was conducted to adjust for potential confounders. The inverse-variance weighted method was employed as the main analysis, and comprehensive sensitivity analyses were conducted in the supplementary analyses. RESULTS: The MR analysis indicated stromal cell-derived factor-1α was suggestively associated with a reduced risk of VTE (odds ratio [OR]: 0.90; 95% confidence interval [CI]: 0.81-0.99; p = 0.033) and DVT (OR: 0.85; 95% CI: 0.75-0.97; p = 0.015). In addition, suggestive association of granulocyte colony-stimulating factor with PE (OR: 1.20; 95% CI: 1.06-1.37; p = 0.005) was observed. Multivariable MR analysis showed that the effect of cytokines on VTE was partly mediated through hemoglobin A1c and systolic blood pressure. Reverse MR analysis revealed that VTE was linked to decreased levels of several cytokines. CONCLUSION: We provide suggestive genetic evidence supporting the bidirectional causal effect between circulating cytokines and VTE, highlighting the importance of targeting circulating cytokines to reduce the incidence of VTE.

Proteomic insights into the associations between obesity, lifestyle factors, and coronary artery disease.

BACKGROUND: We aimed to investigate the protein pathways linking obesity and lifestyle factors to coronary artery disease (CAD). METHODS: Summary-level genome-wide association statistics of CAD were obtained from the CARDIoGRAMplusC4D consortium (60,801 cases and 123,504 controls) and the FinnGen study (R8, 39,036 cases and 303,463 controls). Proteome-wide Mendelian randomization (MR) analysis was conducted to identify CAD-associated blood proteins, supplemented by colocalization analysis to minimize potential bias caused by linkage disequilibrium. Two-sample MR analyses were performed to assess the associations of genetically predicted four obesity measures and 13 lifestyle factors with CAD risk and CAD-associated proteins' levels. A two-step network MR analysis was conducted to explore the mediating effects of proteins in the associations between these modifiable factors and CAD. RESULTS: Genetically predicted levels of 41 circulating proteins were associated with CAD, and 17 of them were supported by medium to high colocalization evidence. PTK7 (protein tyrosine kinase-7), RGMB (repulsive guidance molecule BMP co-receptor B), TAGLN2 (transgelin-2), TIMP3 (tissue inhibitor of metalloproteinases 3), and VIM (vimentin) were identified as promising therapeutic targets. Several proteins were found to mediate the associations between some modifiable factors and CAD, with PCSK9, C1S, AGER (advanced glycosylation end product-specific receptor), and MST1 (mammalian Ste20-like kinase 1) exhibiting highest frequency among the mediating networks. CONCLUSIONS: This study suggests pathways explaining the associations of obesity and lifestyle factors with CAD from alterations in blood protein levels. These insights may be used to prioritize therapeutic intervention for further study.

Apolipoprotein B and interleukin 1 receptor antagonist: reversing the risk of coronary heart disease.

Aims: Epidemiological evidence for the link of interleukin 1 (IL-1) and its inhibition with cardiovascular diseases (CVDs) remains controversial. We aim to investigate the cardiovascular effects of IL-1 receptor antagonist (IL-1Ra) and underlying mechanisms. Methods: Genetic variants identified from a genome-wide association study involving 30,931 individuals were used as instrumental variables for the serum IL-1Ra concentrations. Genetic associations with CVDs and cardiometabolic risk factors were obtained from international genetic consortia. Inverse-variance weighted method was utilized to derive effect estimates, while supplementary analyses employing various statistical approaches. Results: Genetically determined IL-1Ra level was associated with increased risk of coronary heart disease (CHD; OR, 1.07; 95% CI: 1.03-1.17) and myocardial infarction (OR, 1.13; 95% CI: 1.04-1.21). The main results remained consistent in supplementary analyses. Besides, IL-1Ra was associated with circulating levels of various lipoprotein lipids, apolipoproteins and fasting glucose. Interestingly, observed association pattern with CHD was reversed when adjusting for apolipoprotein B (OR, 0.84; 95%CI: 0.71-0.99) and slightly attenuated on accounting for other cardiometabolic risk factors. Appropriate lifestyle intervention was found to lower IL-1Ra concentration and mitigate the heightened CHD risk it posed. Conclusion: Apolipoprotein B represents the key driver, and a potential target for reversal of the causal link between serum IL-1Ra and increased risk of CHD/MI. The combined therapy involving IL-1 inhibition and lipid-modifying treatment aimed at apolipoprotein B merit further exploration.

Prediction of fractional flow reserve with enhanced ant lion optimized support vector machine.

The evaluation of coronary morphology provides important guidance for the treatment of coronary heart disease (CHD). A chaotic Gaussian mutation antlion optimizer algorithm (CGALO) is proposed in the paper, and it is combined with SVM to construct a classification prediction model for Fractional flow reserve (FFR). To overcome the limitations of the original antlion optimizer (ALO) algorithm, the chaotic Gaussian mutation strategy is introduced, which leads to an improvement in its convergence speed and accuracy. To evaluate the proposed algorithm's performance, comparative experiments were conducted on 23 benchmark functions alongside 12 other cutting-edge optimization algorithms. The experimental outcomes demonstrate that the proposed algorithm achieves superior convergence accuracy and speed compared to the alternative comparison algorithms. Additionally, it is combined with SVM and FS to construct a hierarchical FFR classification model, which is utilized to make effective predictions for 84 patients at the affiliated hospital of medical school, Ningbo university. The experimental results demonstrate that the proposed model achieves an average accuracy of 92%. Moreover, it concludes that smoking history, number of lesion vessels, lesion location, diffuse lesions and ST segment changes, and other factors are the most critical indicators for FFR. Therefore, the model that has been established is a new FFR intelligent classification prediction technology that can effectively assist doctors in making corresponding decisions and evaluation plans.

PRMT5 knockdown enhances cell viability and suppresses cell apoptosis, oxidative stress, inflammation and endothelial dysfunction in ox-LDL-induced vascular endothelial cells via interacting with PDCD4.

Atherosclerosis (AS) is an important pathological basis of cardiovascular disease (CVD). The development of AS commences with endothelial dysfunction due to vascular endothelial cell injury. It is well documented that protein arginine methyltransferase 5 (PRMT5) is highly related to cardiovascular events. BioGRID database analysis indicates that PRMT5 may interact with programmed cell death 4 (PDCD4), which is reported to be involved in AS progression. This present research was formulated to elucidate the biological roles of PRMT5/PDCD4 in vascular endothelial cell injury during AS. In this current work, HUVECs were stimulated with 100 mg/L ox-LDL for 48 h to construct an in vitro AS model. Expression levels of PRMT5 and PDCD4 were analyzed by performing RT-qPCR and western blot. The viability and apoptosis of HUVECs were determined using CCK-8, flow cytometry and western blot assays. The status of oxidative stress and inflammation was assessed via commercial detection kits and ELISA assay, respectively. Besides, biomarkers of endothelial dysfunction were detected via commercial detection kit and western blot assay. In addition, the interacting relationship between PRMT5 and PDCD4 was verified by Co-IP assay. Highly expressed PRMT5 was observed in ox-LDL-stimulated HUVECs. Knockdown of PRMT5 enhanced the viability and inhibited the apoptosis of ox-LDL-induced HUVECs as well as alleviated ox-LDL-triggered oxidative stress, inflammation and endothelial dysfunction in HUVECs. PRMT5 interacted and bound with PDCD4. Furthermore, the enhancing effect on cell viability as well as the suppressing effects on cell apoptosis, oxidative stress, inflammation and endothelial dysfunction of PRMT5 knockdown in ox-LDL-induced HUVECs were partially abolished upon up-regulation of PDCD4. To conclude, down-regulation of PRMT5 might exert protective effects against vascular endothelial cell injury during AS by suppressing PDCD4 expression.

DHX9 Strengthens Atherosclerosis Progression By Promoting Inflammation in Macrophages.

Atherosclerosis (AS) is the main cause of cerebrovascular diseases, and macrophages play important roles in atherosclerosis. DExH-Box helicase 9 (DHX9), as a member of DExD/H-box RNA helicase superfamily II, is identified as an autoantigen in the sera of systemic lupus erythematosus patients to trigger inflammation. The aim of this study was to investigate whether DHX9 is involved in AS development, especially in macrophages-mediated-inflammatory responses. We find that DHX9 expression is significantly increased in oxLDL or interferon-γ-treated macrophages and peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Knockdown of DHX9 inhibits lipid uptake and pro-inflammatory factors expression in macrophages, and ameliorates TNF-α-mediated monocyte adhesion capacity. Furthermore, we find that oxLDL stimulation promotes DHX9 interaction with p65 in macrophages, and further enhances the transcriptional activity of DHX9-p65-RNA Polymerase II complex to produce inflammatory factors. Moreover, using ApoE -/- mice fed with western diet to establish AS model, we find that knockdown of DHX9 mediated by adeno-associated virus-Sh-DHX9 through tail vein injection evidently alleviates AS progression in vivo. Finally, we also find that knockdown of DHX9 inhibits p65 activation, inflammatory factors expression, and the transcriptional activity of p65-RNA Polymerase II complex in PBMCs from patients with CAD. Overall, these results indicate that DHX9 promotes AS progression by enhancing inflammation in macrophages, and suggest DHX9 as a potential target for developing therapeutic drug.

Increased selenium and decreased iron levels in relation to risk of coronary artery disease in patients with diabetes.

Background: Observational studies have reported inconsistent associations between micronutrient levels and the risk of coronary artery disease (CAD) in diabetic patients. We aim to explore the causal association between genetically predicted concentrations of micronutrients (phosphorus, magnesium, selenium, iron, zinc, and copper) and CAD in patients with diabetes. Methods: Single nucleotide polymorphisms (SNPs) connected to serum micronutrient levels were extracted from the corresponding published genome-wide association studies (GWASs). Summary-level statistics for CAD in diabetic patients were obtained from a GWAS of 15,666 patients with diabetes. The primary analysis was carried out with the inverse variance weighted approach, and sensitivity analyses using other statistical methods were further employed to assess the robustness of the results. Results: Genetically predicted selenium level was causally associated with a higher risk of CAD in diabetic patients (odds ratio [OR]: 1.25; 95% confidence interval [CI]: 1.10-1.42; p = 5.01 × 10-4). While, genetically predicted iron concentrations in patients with diabetes were inversely associated with the risk of CAD (OR: 0.82; 95% CI: 0.75-0.90; p = 2.16 × 10-5). The association pattern kept robust in most sensitivity analyses. Nominally significant associations were observed for magnesium and copper with the risk of CAD in patients with diabetes. No consistent evidence was found for the causal associations between phosphorus and zinc levels, and the risk of CAD in patients with diabetes. Conclusion: We provide consistent evidence for the causal effect of increased selenium and decreased iron levels on CAD in patients with diabetes, highlighting the necessity of micronutrient monitoring and application in these patients.

A novel polygenic risk score improves prognostic prediction of heart failure with preserved ejection fraction in the Chinese Han population.

AIMS: Mortality risk assessment in patients with heart failure (HF) with preserved ejection fraction (HFpEF) presents a major challenge. We sought to construct a polygenic risk score (PRS) to accurately predict the mortality risk of HFpEF. METHODS AND RESULTS: We first carried out a microarray analysis of 50 HFpEF patients who died and 50 matched controls who survived during 1-year follow-up for candidate gene selection. The HF-PRS was developed using the independent common (MAF > 0.05) genetic variants that showed significant associations with 1-year all-cause death (P < 0.05) in 1442 HFpEF patients. Internal cross-validation and subgroup analyses were performed to evaluate the discrimination ability of the HF-PRS. In 209 genes identified by microarray analysis, 69 independent variants (r < 0.1) were selected to develop the HF-PRS model. This model yielded the best discrimination capability for 1-year all-cause mortality with an area under the curve (AUC) of 0.852 (95% CI 0.827-0.877), which outperformed the clinical risk score consisting of 10 significant traditional risk factors for 1-year all-cause mortality (AUC 0.696, 95% CI 0.658-0.734, P = 4 × 10-11), with net reclassification improvement (NRI) of 0.741 (95% CI 0.605-0.877; P < 0.001) and integrated discrimination improvement (IDI) of 0.181 (95% CI 0.145-0.218; P < 0.001). Individuals in the medium and the highest tertile of the HF-PRS had nearly a five-fold (HR = 5.3, 95% CI 2.4-11.9; P = 5.6 × 10-5) and 30-fold (HR = 29.8, 95% CI 14.0-63.5; P = 1.4 × 10-18) increased risk of mortality compared to those in the lowest tertile, respectively. The discrimination ability of the HF-PRS was excellent in cross validation and throughout the subgroups regardless of comorbidities, gender, and patients with or without a history of heart failure. CONCLUSION: The HF-PRS comprising 69 genetic variants provided an improvement of prognostic power over the contemporary risk scores and NT-proBNP in HFpEF patients.

We performed integrated analyses of mRNA transcriptional and genetic data to construct an HF-PRS comprised of 69 genetic variants in 1442 HFpEF patients from the China PEACE 5p-HF study. We found that the HF-PRS yielded a satisfactory discrimination capability with an AUC of 0.852, which outperformed the clinical risk score consisting of 10 significant traditional risk factors by 15.6% for 1-year all-cause mortality. The discrimination ability of the HF-PRS was excellent in cross validation and throughout the subgroups regardless of comorbidities, gender and patients with or without history of heart failure.

Causal association between sleep traits and the risk of coronary artery disease in patients with diabetes.

Background and aims: The association between sleep traits and coronary artery disease (CAD) in patients with diabetes has been reported in previous observational studies. However, whether these potential relationships are causal remains unclear. We aim to assess the causal relationship between sleep traits and CAD in diabetic. Methods: Genetic instrumental variables associated with five sleep-related traits (insomnia, sleep duration, ease of getting up, morningness and snoring) were extracted from corresponding genome-wide association studies (GWAS). The associations of genetic variants with CAD were based on 15,666 individuals with diabetes (3,968 CAD cases and 11,696 controls). The primary analysis was derived using the inverse variance weighting method. Further sensitivity analysis was conducted to confirm the robustness and consistency of the main results. Results: Genetic liability to insomnia was significantly related to the increased risk of CAD in individuals with diabetes [odds ratio (OR): 1.163; 95% CI: 1.072-1.254; p = 0.001]. Suggestive evidence was found for the borderline associations between both sleep duration (OR: 0.629; 95% CI: 0.380-1.042, p = 0.072) and snoring (OR: 1.010, 95% CI: 1.000-1.020, p = 0.050) with CAD risk. However, no consistent evidence was found for the association between ease of getting up and morningness with the risk of CAD in diabetic. Similar results can be verified in most sensitivity analyses. Conclusions: We provide consistent evidence for the causal effect of insomnia on the increased risk of CAD in individuals with diabetes. The management of sleep health should be emphasized to prevent CAD in diabetic patients.

Genetic liability to mental disorders in relation to the risk of hypertension.

Background: Observational studies have indicated that psychosocial factors contribute to hypertension; however, the causality of these associations remains unclear due to reverse causality and confounders. We aim to assess the causal associations of mental health disorders with hypertension. Methods: Instrumental variables of anxiety disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, depression, obsessive-compulsive disorder, post-traumatic stress disorder, schizophrenia, and subjective well-being measure were obtained from the corresponding largest genome-wide association studies. Summary statistics for the association of essential hypertension were obtained from the FinnGen Study (42,857 cases and 162,837 controls) and UK Biobank cohort (54,358 cases and 408,652 controls). The multiplicative random-effects inverse-variance weighted method was utilized as the primary analysis and three other statistical methods were conducted in the supplementary analyses. The results were combined using the fixed-effects method. Results: In the pooled analyses, genetic liability to depression was associated with higher risk of hypertension (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.17-1.35; p < 0.001). Besides, a suggestive association was found between genetically predicted higher weighted neuroticism sum-score and increased risk of hypertension (OR, 1.16; 95% CI, 1.02-1.33; p < 0.05). No associations were found for other mental health disorders. Sensitivity analyses revealed consistent evidence as the main results. Conclusion: We provide consistent evidence for the causal effect of genetic liability to depression on hypertension, which highlights the importance of blood pressure measurement and monitoring in patients with depression.

Microbiota-related metabolites fueling the understanding of ischemic heart disease.

Up-to-date knowledge of gut microbial taxa associated with ischemic heart disease (IHD). Microbial metabolites for mechanistic dissection of IHD pathology. Microbiome-based therapies in IHD prevention and treatment.

Genetic liability to sedentary behavior in relation to myocardial infarction and heart failure: A mendelian randomization study.

BACKGROUND AND AIMS: Observational studies have indicated that sedentary behavior is associated with myocardial infarction (MI), heart failure (HF), and atrial fibrillation (AF). Nevertheless, whether these associations are causal remain controversial, due to confounding factors (e.g., physical activity) and reverse causality. METHODS AND RESULTS: Instrumental variables were obtained from the largest genome-wide association studies of sedentary behavior (408,815 individuals) to date. We obtained summary statistics of MI from the CARDIoGRAMplusC4D consortium (171,875 individuals), HF from the HERMES Consortium (977,323 individuals), and AF from the Atrial Fibrillation Consortium (588,190 individuals). The inverse-variance weighted method was applied to obtain Mendelian randomization (MR) estimates, and other statistical methods were conducted in the sensitivity analyses. The main analyses were repeated using data from the FinnGen study. Multivariable MR analysis and mediation analysis were performed to evaluate the role of physical activity and other confounders. Genetically determined television watching was associated with MI (odds ratio [OR], 1.38; 95% CI, 1.19-1.59; p = 1.9 × 10-5) and HF (OR, 1.23; 95%CI, 1.09-1.38; p = 7.0 × 10-4) but not AF. The main results kept robust in most sensitivity analyses. The effect of sedentary behavior on MI and HF was partly mediated by body mass index (BMI). No consistent evidence was found for the causal effect of computer use and driving on MI, HF, or AF. CONCLUSIONS: Genetic liability to prolonged television watching is associated with higher risks of MI and HF. Interventions for reducing television watching time, such as public education and awareness campaigns, should be further investigated.

Serum urate and heart failure: a bidirectional Mendelian randomization study.

AIMS: Observational studies indicate that serum urate level is associated with heart failure (HF). However, whether this association is causal remains controversial, due to confounding factors and reverse causality. We aim to evaluate the causal relationship of genetically predicted serum urate level with HF. METHODS AND RESULTS: A bidirectional Mendelian randomization (MR) study was performed. Instrumental variables were obtained from the largest genome-wide association studies of serum urate (457 690 individuals) to date. We obtained summary statistics of HF from HERMES consortium (47 309 cases; 930 014 controls), the FinnGen study (13 087 cases; 195 091 controls), and the UK Biobank study (1088 cases; 360 106 controls). Inverse-variance-weighted method was applied to obtain MR estimates and other statistical methods were conducted in the sensitivity analyses. The reverse MR analysis was performed to evaluate the effect of HF on serum urate levels. Genetically determined serum urate level was associated with HF [odds ratio (OR), 1.07; 95% confidence interval (CI), 1.03-1.10; P = 8.6×10-5]. The main results kept robust in the most sensitivity analyses. The association pattern remained for the HF in FinnGen (OR, 1.10; 95% CI, 1.03-1.19; P = 0.008) and the combined results of three data sources (OR, 1.08; 95% CI, 1.04-1.13; P < 0.001). No consistent evidence was found for the causal effect of HF on serum urate levels. CONCLUSION: We provide consistent evidence for the causal effect of genetically predicted serum urate level on HF, but not the reverse effect of HF. Urate-lowering therapy may be of cardiovascular benefit in the prevention of HF.

Multiple Sclerosis and the Risk of Cardiovascular Diseases: A Mendelian Randomization Study.

Background: Observational studies suggested that multiple sclerosis (MS) is associated with cardiovascular diseases (CVDs). However, the causal association has not been fully elucidated. Thus, we aim to assess the causality of the associations of MS with risk of CVDs. Methods: A two-sample Mendelian randomization (MR) study was performed to explore the causality. Genetic instruments were identified for MS from a genome-wide association study (GWAS) involving 115,803 individuals. Summary-level data for CVDs were obtained from different GWAS meta-analysis studies. MR analysis was conducted mainly using the inverse-variance weighted (IVW) method. Sensitivity analyses were further performed to ensure the robustness of the results. Results: This MR study found suggestive evidence that genetic liability to MS was associated with an increased risk of coronary artery disease (CAD) [odds ratio (OR), 1.02; 95% confidence interval (CI), 1.00-1.04; p = 0.03], myocardial infarction (MI) (OR, 1.03; 95% CI, 1.00-1.06; p = 0.01), heart failure (HF) (OR, 1.02; 95% CI, 1.00-1.04; p = 0.02), all-cause stroke (AS) (OR, 1.02; 95% CI, 1.00-1.05; p = 0.02), and any ischemic stroke (AIS) (OR, 1.02; 95% CI, 1.00-1.05; p = 0.04). The null-association was observed between MS and the other CVDs. Further analyses found little evidence of pleiotropy. Conclusions: We provided suggestive genetic evidence for the causal associations of MS with increased risk of CAD, MI, HF, AS, and AIS, which highlighted the significance of active monitoring and prevention of cardiovascular risk to combat cardiovascular comorbidities in MS patients.

Low Intelligence Predicts Higher Risks of Coronary Artery Disease and Myocardial Infarction: Evidence From Mendelian Randomization Study.

Background: Low intelligence has been shown to be associated with a high risk of cardiovascular disease in observational studies. It remains unclear whether the association is causal. This study aimed to explore the causal association of intelligence with coronary artery disease (CAD) and myocardial infarction (MI). Methods: A two-sample Mendelian randomization study was designed to infer the causality. A total of 121 single nucleotide polymorphisms were selected as a genetic instrumental variable for intelligence. Summary data on CAD (n = 184,305) and MI (n = 171,875) were obtained from the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium and the FinnGen study. Inverse variance weighting method was used to calculate the effect estimates. Sensitivity analyses including other statistical models and leave-one-out analysis were conducted to verify the robustness of results. MR-Egger test was performed to assess the pleiotropy. Results: Genetically predicted higher intelligence was significantly associated with lower risk of CAD (OR, .76; 95%CI, .69-.85; p = 1.5 × 10-7) and MI (OR, .78; 95%CI, .70-.87; p = 7.9 × 10-6). The results remained consistent in the majority of the sensitivity analyses and were repeated in the FinnGen datasets. MR-Egger test suggested no evidence of directional pleiotropy for the association with coronary artery disease (intercept = -.01, p = .19) and myocardial infarction (intercept = -.01, p = .06). Conclusion: This Mendelian randomization analysis provided genetic evidence for the causal association between low intelligence and increased risks of CAD and MI.