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The aim of this study was to assess the causal relationship between habitual walking pace and cardiovascular disease risk using a Mendelian randomisation approach. We performed both one- and two-sample Mendelian randomisation analyses in a sample of 340,000 European ancestry participants from UK Biobank, applying a range of sensitivity analyses to assess pleiotropy and reverse causality. We used a latent variable framework throughout to model walking pace as a continuous exposure, despite being measured in discrete categories, which provided more robust and interpretable causal effect estimates. Using one-sample Mendelian randomisation, we estimated that a 1 mph (i.e., 1.6 kph) increase in self-reported habitual walking pace corresponds to a 63% (hazard ratio (HR) = 0.37, 95% confidence interval (CI), 0.25–0.55, P = 2.0 × 10–6) reduction in coronary artery disease risk. Using conditional analyses, we also estimated that the proportion of the total effect on coronary artery disease mediated through BMI was 45% (95% CI 16–70%). We further validated findings from UK Biobank using two-sample Mendelian randomisation with outcome data from the CARDIoGRAMplusC4D consortium. Our findings suggest that interventions that seek to encourage individuals to walk more briskly should lead to protective effects on cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

The cause of sudden sensorineural hearing loss (SSNHL) remains unknown in a significant number of cases, but vascular involvement in its pathophysiology has been proposed. Our study aimed to assess the incidence of stroke following idiopathic SSNHL (iSSNHL) and to evaluate associated cardiovascular risk factors and comorbidities. We extracted electronic medical record data from iSSNHL patients aged ≥ 50 years retrospectively from 84 general practices. Patients were matched for age, sex and general practice in a 1:4 ratio to controls. Primary outcome was the 5-years stroke risk following iSSNHL diagnosis. 480 iSSNHL cases could be matched to 1911 controls. The hazard ratio for iSSNHL compared with controls was 1.25 (95%CI 0.50–3.27; P = 0.646) for CVA (cerebrovascular accident) alone and 0.92 (95% CI 0.50–1.71; P = 0.804) for CVA and TIA (transient ischemic attack) combined. The hazard ratio for the interaction term between iSSNHL and age ≥ 60 years was 4.84 (95% CI 1.02–23.05; P = 0.048) for CVA and TIA combined. Patients with iSSNHL used antihypertensives and beta-blocking agents more frequently than controls (P = 0.006 and P = 0.022, respectively). In conclusion, no overall significant difference in the risk of stroke was observed, but the hazard ratio for stroke increased in iSSNHL patients aged 60 and older, suggesting potential vascular involvement in older subjects presenting with sudden sensorineural hearing loss. [ABSTRACT FROM AUTHOR]

This study aims at identifying risk-related patterns of left ventricular contraction dynamics via novel volume transient characterization. A multicenter cohort of AMI survivors (n = 1021) who underwent Cardiac Magnetic Resonance (CMR) after infarction was considered for the study. The clinical endpoint was the 12-month rate of major adverse cardiac events (MACE, n = 73), consisting of all-cause death, reinfarction, and new congestive heart failure. Cardiac function was characterized from CMR in 3 potential directions: by (1) volume temporal transients (i.e. contraction dynamics); (2) feature tracking strain analysis (i.e. bulk tissue peak contraction); and (3) 3D shape analysis (i.e. 3D contraction morphology). A fully automated pipeline was developed to extract conventional and novel artificial-intelligence-derived metrics of cardiac contraction, and their relationship with MACE was investigated. Any of the 3 proposed directions demonstrated its additional prognostic value on top of established CMR indexes, myocardial injury markers, basic characteristics, and cardiovascular risk factors (P < 0.001). The combination of these 3 directions of enhancement towards a final CMR risk model improved MACE prediction by 13% compared to clinical baseline (0.774 (0.771—0.777) vs. 0.683 (0.681—0.685) cross-validated AUC, P < 0.001). The study evidences the contribution of the novel contraction characterization, enabled by a fully automated pipeline, to post-infarction assessment. [ABSTRACT FROM AUTHOR]

The relationship between noise annoyance and risk of cardiovascular disease (CVD) still needs to be fully elucidated. Thus, we examined the relationship between noise annoyance and CVD risk in a large population-based cohort study. Cross-sectional (N = 15,010, aged 35–74 years, baseline investigation period 2007–2012) and prospective data (5- and 10-year follow-up from 2012 to 2022) from the Gutenberg Health Study were used to examine the relationship between noise annoyance due to different sources and risk of prevalent and incident CVD comprising atrial fibrillation, coronary artery disease, myocardial infarction, stroke, chronic heart failure, peripheral artery disease, and venous thromboembolism. In cross-sectional analyses, noise annoyance was an independent risk factor for prevalent CVD, with the strongest associations seen for noise annoyance during sleep (e.g., neighborhood noise annoyance: odds ratio 1.20, 95% confidence interval 1.13–1.27, p < 0.0001). While in the 10-year follow-up, mostly positive associations (although not significant) between noise annoyance and incident CVD were observed, no indication of increased CVD risk was observed after 5 years of follow-up. Noise annoyance due to different sources was associated with prevalent CVD, whereas only weak associations with incident CVD were found. Further large-scale studies are needed to establish the relationship between noise annoyance and risk of CVD. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the long-term pattern of plasma aldosterone concentration (PAC) trajectories and to explore the relationship between PAC trajectory patterns and cardiovascular disease (CVD) risk in patients with hypertension. Participants were surveyed three times between 2010 and 2016, and latent mixed modeling was employed to determine the trajectory of PAC over the exposure period (2010–2016). A Cox regression analysis was used to examine the association between PAC trajectory patterns and the risk of CVD (stroke and myocardial infarction). Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated and reported. During a median follow-up of 4.10 (3.37–4.50) years, 82 incident CVD cases (33 myocardial infarction cases and 49 stroke cases) were identified. Among all three PAC models, the high-stability PAC pattern exhibited the highest risk of CVD. After full adjustment for all covariables, HRs were 2.19 (95% CI 1.59–3.01) for the moderate-stable pattern and 2.56 (95% CI 1.68–3.91) for the high-stable pattern in comparison to the low-stable pattern. Subgroup and sensitivity analyses verified this association. The presence of a high-stable PAC trajectory pattern is associated with an elevated risk of CVD in hypertensive patients. Nevertheless, more studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Whether cardiovascular risk scores geographically aggregate and inform on spatial development of atherosclerotic cardiovascular diseases (ASCVD) remains unknown. Our aim is to determine the spatial distribution of 10-year predicted cardiovascular risk and ASCVD, and to compare the overlap of the resulting spatial distributions. Using prospective data from the CoLaus|PsyCoLaus cohort study (2003–2021) we computed SCORE2 in participants free from ASCVD. Geographical distributions of predicted risk and events were determined using the Gi* Getis-Ord autocorrelation statistic. 6203 individuals (54% women, mean age 52.5 ± SD 10.7, ASCVD incidence rate 5.7%) were included. We identified clusters of high versus low predicted risk (4%, 6%, respectively) and ASCVD (5%, 5% respectively) at baseline. They persisted at follow-up. Overlap of SCORE2 and ASCVD clusters was marginal. Body-mass index and alcohol consumption explained most of the predicted risk distribution. For ASCVD, high clusters persisted or were reinforced after multivariate adjustment, while low incidence clusters were reduced, multifactorial determinants. Incidence rate of ASCVD was 2.5% higher (IC 95%, 1.4–3.7) in clusters of higher incidence of ASCVD. To develop up-to-date, geographically targeted prevention strategies, there is a need to study novel geographically risk factors affecting ASCVD and to update commonly used prediction models for a population approach. [ABSTRACT FROM AUTHOR]

This study aimed at modelling the underlying predictor of ASCVD through the Bayesian network (BN). Data for the AZAR Cohort Study, which evaluated 500 healthcare providers in Iran, was collected through examinations, and blood samples. Two BNs were used to explore a suitable causal model for analysing the underlying predictor of ASCVD; Bayesian search through an algorithmic approach and knowledge-based BNs. Results showed significant differences in ASCVD risk factors across background variables' levels. The diagnostic indices showed better performance for the knowledge-based BN (Area under ROC curve (AUC) = 0.78, Accuracy = 76.6, Sensitivity = 62.5, Negative predictive value (NPV) = 96.0, Negative Likelihood Ratio (LR−) = 0.48) compared to Bayesian search (AUC = 0.76, Accuracy = 72.4, Sensitivity = 17.5, NPV = 93.2, LR− = 0.83). In addition, we decided on knowledge-based BN because of the interpretability of the relationships. Based on this BN, being male (conditional probability = 63.7), age over 45 (36.3), overweight (51.5), Mets (23.8), diabetes (8.3), smoking (10.6), hypertension (12.1), high T-C (28.5), high LDL-C (23.9), FBS (12.1), and TG (25.9) levels were associated with higher ASCVD risk. Low and normal HDL-C levels also had higher ASCVD risk (35.3 and 37.4), while high HDL-C levels had lower risk (27.3). In conclusion, BN demonstrated that ASCVD was significantly associated with certain risk factors including being older and overweight male, having a history of Mets, diabetes, hypertension, having high levels of T-C, LDL-C, FBS, and TG, but Low and normal HDL-C and being a smoker. The study may provide valuable insights for developing effective prevention strategies for ASCVD in Iran. [ABSTRACT FROM AUTHOR]

High-fat diet-induced obesity is a pandemic caused by an inactive lifestyle and increased consumption of Western diets and is a major risk factor for diabetes and cardiovascular diseases. In contrast, exercise can positively influence gut microbial diversity and is linked to a decreased inflammatory state. To understand the gut microbial variations associated with exercise and high-fat diet over time, we conducted a longitudinal study to examine the effect of covariates on gut microbial diversity and composition. Young mice were divided into four groups: Chow-diet (CHD), high-fat diet (HFD), high-fat diet + exercise (HFX), and exercise only (EXE) and underwent experimental intervention for 12 weeks. Fecal samples at week 0 and 12 were collected for DNA extraction, followed by 16S library preparation and sequencing. Data were analyzed using QIIME 2, R and MicrobiomeAnalyst. The Bacteroidetes-to-Firmicutes ratio decreased fivefold in the HFD and HFX groups compared to that in the CHD and EXE groups and increased in the EXE group over time. Alpha diversity was significantly increased in the EXE group longitudinally (p < 0.02), whereas diversity (Shannon, Faith's PD, and Fisher) and richness (ACE) was significantly reduced in the HFD (p < 0.005) and HFX (p < 0.03) groups over time. Beta diversity, based on the Jaccard, Bray–Curtis, and unweighted UniFrac distance metrics, was significant among the groups. Prevotella, Paraprevotella, Candidatus arthromitus, Lactobacillus salivarius, L. reuteri, Roseburia, Bacteroides uniformis, Sutterella, and Corynebacterium were differentially abundant in the chow-diet groups (CHD and EXE). Exercise significantly reduced the proportion of taxa characteristic of a high-fat diet, including Butyricimonas, Ruminococcus gnavus, and Mucispirillum schaedleri. Diet, age, and exercise significantly contributed to explaining the bacterial community structure and diversity in the gut microbiota. Modulating the gut microbiota and maintaining its stability can lead to targeted microbiome therapies to manage chronic and recurrent diseases and infections. [ABSTRACT FROM AUTHOR]

Galectin-3 levels have been studied as a potential biomarker for predicting cardiovascular (CV) risk and mortality in hemodialysis (HD) patients. Recently, a close relationship between galectin-3 and vascular calcification (VC) has been reported. Here, we investigated the role of VC as a mediating factor in the association between galectin-3 and mortality. Serum galectin-3 and baseline aortic arch calcification (AoAC) score were measured in 477 incident HD patients. Mortality data were obtained at a median follow-up of 40 months. Causal mediation analysis was performed to examine the effect of vascular risk factors on galectin-3-related mortality. The prevalence of AoAC in HD patients was 57% (n = 272), and elevated galectin-3 levels were associated with a significantly increased risk of AoAC. When the galectin-3 level was divided by the median level of 37 ng/mL, a higher galectin group increased the risk of all-cause mortality by 1.71-fold (95% CI 1.02–2.92, p = 0.048), even after adjustment for multiple CV risk factors. Mediation analysis showed that both the direct effect of the galectin-3 on mortality (β = 0.0368, bootstrapped 95% CI [0.0113–0.0622]) and the indirect effects were significant. AoAC score and high-sensitivity CRP levels significantly mediated the association between galectin-3 and mortality (total indirect effects: β = 0.0188, bootstrapped 95% CI [0.0066–0.0352]). This study suggests that the association between high galectin-3 and mortality may be partially mediated by higher VC and inflammatory state in HD patients. [ABSTRACT FROM AUTHOR]

The inability to tolerate sufficient doses of statins, statin intolerance (SI), contributes to the non-achievement of guideline-recommended low-density lipoprotein cholesterol (LDL-C) treatment targets. Patients with SI require alternative lipid-lowering therapies (LLT). We conducted a simulation study on LDL-C target achievement with oral LLT (ezetimibe, bempedoic acid) in patients with SI, using representative data of 2.06 million German outpatients. SI was defined using literature-informed definitions based on electronic medical records (EMR). Among n = 130,778 patients with hypercholesterolaemia, available LDL-C measurement, and high or very-high cardiovascular risk, 8.6% met the definition of SI. Among patients with SI, 7.7% achieved the LDL-C target at baseline. After simulation of the stepwise addition of treatment with ezetimibe and bempedoic acid, 22.6 and 52.0% achieved the LDL-C target, respectively. The median achieved LDL-C was 80 and 62 mg/dL, the corresponding reductions from baseline were 20.0 and 38.0%, respectively. A higher proportion of patients classified as high risk achieved the target compared to those at very-high risk (58.1 vs. 49.9%). In conclusion, in patients with increased cardiovascular risk meeting the definition of SI based on EMR, combination LLT with ezetimibe and bempedoic acid has the potential to substantially increase the proportion of patients achieving clinically relevant LDL-C reductions. [ABSTRACT FROM AUTHOR]

The inflammatory burden as measured by high-sensitivity C-reactive Protein (hsCRP) is recognized as a cardiovascular risk factor, which can however be affected by lifestyle-related risk factors (LRF). Up-to-date the interplay between hsCRP, LRF and presence and extent of atherosclerotic disease is still largely unknown, which we therefore sought to investigate in a contemporary population-based cohort. We included participants from the cross-sectional population-based Hamburg City Health Study. Affected vascular beds were defined as coronary, peripheral, and cerebrovascular arteries. LRF considered were lack of physical activity, overweight, active smoking and poor adherence to a Mediterranean diet. We computed multivariable analyses with hsCRP as the dependent variable and LRF as covariates according to the number of vascular beds affected. In the 6765 individuals available for analysis, we found a stepwise increase of hsCRP concentration both according to the number of LRF present as well as the number of vascular beds affected. Adjusted regression analyses showed an independent association between increasing numbers of LRF with hsCRP levels across the extent of atherosclerosis. We demonstrate increasing hsCRP concentrations according to both the number of LRF as well as the extent of atherosclerosis, emphasizing the necessity of lifestyle-related risk factor optimization. [ABSTRACT FROM AUTHOR]

We investigated sex-specific associations and their differences between major cardiovascular risk factors and the risk of incident coronary heart disease (CHD) and hard CHD (defined as nonfatal myocardial infarction and CHD death). A total of 7518 (3377 men) participants from the Tehran Lipid and Glucose Study were included. Cox models were used to estimate the hazard ratios (HRs) and women-to-men ratios of HRs for CHD events associated with each risk factor. During 20 years of follow-up (1999–2018), 1068 (631 men) and 345 (238 men) new cases of CHD and hard CHD, respectively, were documented. In total population, the incidence rates per 1000 person-years were 9.5 (9.0–10.1) and 2.9 (2.6–3.2) for CHD and hard CHD, respectively. Hypertension, diabetes, pre-diabetes, and a high waist-to-hip ratio (WHR) were associated with a greater HR of hard CHD in women than men; the women-to-men HRs were 2.85 [1.36–5.98], 1.92 [1.11–3.31], 2.04 [1.09–3.80] and 1.42 [1.10–1.82], respectively. Diabetes was associated with a higher HR of CHD in women than men (ratio of HRs 1.49 (1.10–2.01). In conclusion, we found that hypertension, diabetes, pre-diabetes, and high WHR conferred a greater excess risk of CHD events in women than in men, suggesting that Iranian women may require greater attention for the prevention of CHD events. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the effects of administration of overnight 1 mg dexamethasone on vascular function in patients with nonfunctioning adrenal adenomas (NFA). Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were measured to assess vascular function in 22 patients with NFA who had hypertension and/or diabetes mellitus (DM) and 272 patients without adrenal incidentalomas who had hypertension and/or DM (control patients with hypertension and/or DM). FMD and NID were measured in the morning before and after administration of 1 mg of dexamethasone at 2300 h in 18 patients with NFA. There were no significant differences in FMD and NID between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM (3.4 ± 2.8% vs. 2.9 ± 1.9% and 11.5 ± 5.7% vs. 11.4 ± 4.3%, P = 0.46, and P = 0.99, respectively). There were no significant differences in vascular function between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM even after adjustment for cardiovascular risk factors. Overnight 1 mg dexamethasone increased FMD from 2.4 ± 1.9% to 5.3 ± 3.2% (P < 0.01) and increased NID from 12.1 ± 4.2% to 14.0 ± 2.8% (P < 0.01) in patients with NFA. The overnight 1 mg dexamethasone suppression test does not impair FMD and NID in patients with NFA. Decreases in circulating levels of cortisol may improve vascular function. Clinical Trial Registration: This study was approved by principal authorities and ethical issues in Japan (URL for Clinical Trial: http://www.umin.ac.jp/ctr/index.htm Registration Number for Clinical Trial: UMIN000039512). [ABSTRACT FROM AUTHOR]

Muscular strength represents a specific component of health-related fitness. Hand grip strength is used as a simple and dynamic marker of maximum voluntary force of the hand and to estimate overall strength. Today, little is known about the relationship between grip strength and health in forcibly displaced populations. In the present study, we examined whether grip strength is associated with various health outcomes in a sample of forcibly displaced people living in a Greek refugee camp. The present analyses are part of a larger pragmatic randomized controlled trial. In this paper, cross-sectional baseline data of 143 participants (71 men, 72 women) will be presented. In addition to grip strength, the following physical and mental health outcomes were assessed: body weight and body composition, blood pressure, total cholesterol, low- and high-density lipoprotein cholesterol, triglycerides, blood glucose levels (HbA1c), post-traumatic stress disorder (PTSD) symptoms, depressive and anxiety symptoms, pain, and quality of life. Linear regression analyses were carried out to examine how grip strength is associated with the health outcomes, separately for absolute and normalized grip strength scores. Grip strength was positively and strongly associated with percentage muscle mass (normalized grip strength: Stand. B = 0.58, p <.001), whereas a negative association existed for percentage body fat (normalized grip strength: Stand. B = − 0.58, p <.001). No statistically significant associations occurred between grip strength and the other cardiovascular risk markers. In contrast, we found that participants with higher normalized grip strength reported higher levels of PTSD (normalized grip strength: Stand. B = 0.36, p <.05) and depressive symptoms (normalized grip strength: Stand. B = 0.29, p <.05). No significant association occurred between grip strength, anxiety, pain and quality of life. Measuring grip strength in forcibly displaced people can be a useful way to assess their overall muscle strength. Grip strength tests are easy to implement, and results can be used to assess the effects of specific intervention measures. Nevertheless, our results question the usefulness of grip strength as a marker of cardiovascular health and mental wellbeing in a refugee camp setting. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a multiple hormonal deficiency syndrome which includes alterations in the serum concentration of thyroid hormones (TH). This cross-sectional study enrolled 215 male patients hospitalised for acute HF. Data on cardiovascular risk factors, chronic medications, cardiac function assessed by echocardiography, and clinical parameters of HF were prospectively collected. The independent predictive association of TH with all investigated parameters of the HF severity were assessed. The patient's mean age was 74.4 years, 57.2% had arterial hypertension, 54.0% were consuming alcohol, and 42.3% were diabetics. Multivariate analysis revealed that total triiodothyronine (TT3) was an independent predictor of greater left ventricular ejection fraction (LVEF; β = 0.223, p = 0.008), less progressed left ventricular diastolic dysfunction (LVDD; β = − 0.271, p = 0.001) and lower N-terminal pro-brain natriuretic peptide (NT-proBNP; β = − 0.365, p < 0.001). None of the TH other than TT3 was associated with LVDD or NT-proBNP, whereas free triiodothyronine (β = − 0.197, p = 0.004), free thyroxine (β = − 0.223, p = 0.001) and total thyroxine (β = − 0.140, p = 0.041) were inversely associated with LVEF. The present study suggests that, among TH, serum TT3 level is most closely associated with echocardiographic, laboratory and clinical parameters of the severity of HF in men. [ABSTRACT FROM AUTHOR]

There are reports of link of osteoprotegerin (OPG) gene polymorphism to type-2 diabetes (T2D) and hypertension (HTN). The objective of the study was to assess the allele frequency of OPG (rs2073618) gene polymorphism and its association with heart rate variability (HRV) and blood pressure variability profile as CVD risks in diabetes mellitus patients with hypertension undergoing treatment. T2D patients on treatment without hypertension (n = 172), with hypertension (n = 177) and 191 healthy volunteers were recruited for the study. Their blood pressure variability including baroreflex sensitivity (BRS), heart rate variability (HRV), OPG, insulin, lipid profile, receptor-activator for NFkB (RANK), receptor-activator for NFkB-Ligand (RANKL), and tumor necrosis factor-α (TNF-α) were estimated. Allele frequency of OPG (rs2073618) gene polymorphism was assessed from the DNA samples. BRS and HRV indices were decreased, and RANKL/OPG and TNF-α were increased in T2D and T2D + HTN groups, respectively compared to healthy control group. The reduction in BRS was contributed by increased inflammation and reduced SDNN of HRV in GG genotype in T2D + HTN. In GG + GC subgroup, it was additionally contributed by rise in RANKL/OPG level (β − 0.219; p 0.008). Presence of mutant GG genotype contributed to the risk of hypertension among T2D patients (OR 3.004) as well as in general population (OR 2.79). It was concluded that CV risks are more in T2D patients with HTN expressing OPG rs2073618 gene polymorphism. [ABSTRACT FROM AUTHOR]

Predicting cardiorespiratory fitness levels can be useful for measuring progress in an exercise program as well as for stratifying cardiovascular risk in asymptomatic adults. This study proposes a model to predict fitness level in terms of maximal oxygen uptake using anthropometric, heart rate, and step count data. The model was trained on a diverse cohort of 3115 healthy subjects (1035 women and 2080 men) aged 42 ± 10.6 years and tested on a cohort of 779 healthy subjects (260 women and 519 men) aged 42 ± 10.18 years. The developed model is capable of making accurate and reliable predictions with the average test set error of 3.946 ml/kg/min. The maximal oxygen uptake labels were obtained using wearable devices (Apple Watch and Garmin) during recorded workout sessions. Additionally, the model was validated on a sample of 10 subjects with maximal oxygen uptake determined directly using a treadmill protocol in a laboratory setting and showed an error of 4.982 ml/kg/min. Unlike most other models, which use accelerometer readings as additional input data, the proposed model relies solely on heart rate and step counts—data readily available on the majority of fitness trackers. The proposed model provides a point estimation and a probabilistic prediction of cardiorespiratory fitness level, thus it can estimate the prediction's uncertainty and construct confidence intervals. [ABSTRACT FROM AUTHOR]

Gut microbiota is an emerging editable cardiovascular risk factor. We aim to investigate gut and coronary plaque microbiota, using fecal samples and angioplasty balloons from patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS) and control subjects. We examined bacterial communities in gut and coronary plaques by 16S rRNA sequencing and we performed droplet digital PCR analysis to investigate the gut relative abundance of the bacterial genes CutC/CntA involved in trimethylamine N-oxide synthesis. Linear discriminant analysis effect size (LEfSe) at the genus and species levels displayed gut enrichment in Streptococcus, Granulicatella and P. distasonis in ACS compared with CCS and controls; Roseburia, C. aerofaciens and F. prausnitzii were more abundant in controls than in patients. Principal component analysis (PCA) of 41 differentially abundant gut taxa showed a clustering of the three groups. In coronary plaque, LEfSe at the genus level revealed an enrichment of Staphylococcus and Streptococcus in ACS, and Paracoccus in CCS, whereas PCA of 15 differentially abundant plaque taxa exhibited clustering of ACS and CCS patients. CutC and CntA genes were more abundant in ACS and CCS than in controls while no significant difference emerged between ACS and CCS. Our results indicate that ACS and CCS exhibit a different gut and plaque microbial signature, suggesting a possible role of these microbiotas in coronary plaque instability. [ABSTRACT FROM AUTHOR]

Arterial hypertension is considered a risk factor for the development of heart failure. Here we investigate cross-sectional associations of systolic and diastolic blood pressure with subtle functional and morphological changes of left ventricular echocardiographic parameters representing early dysfunction in three representative German population-based studies. We assessed 26,719 individuals without symptomatic heart failure from the Hamburg City Health Study (HCHS, n = 7396, derivation cohort), the Gutenberg Health Study (GHS, 14,715, validation cohort) and the Study of Health in Pomerania (SHIP, 4608, validation cohort). Multivariable linear regression analyses with systolic and diastolic blood pressure as continuous exposure variables were adjusted for common cardiovascular risk factors and antihypertensive medication. Both systolic and diastolic blood pressure were consistently associated with measures of left ventricular hypertrophy (β per standard deviation (SD) for LV mass (g) and systolic blood pressure: 5.09 (p < 0.001); diastolic blood pressure: 2.29 (p < 0.001) in HCHS). Systolic blood pressure correlated with declining diastolic function (β per SD for E/e′: 0.29, p < 0.001 in HCHS) and diastolic blood pressure with declining systolic function (β per SD for LVEF, in %: − 0.15; p = 0.041 in HCHS) in all cohorts. Pending further validation, our results from three independent German population samples suggest differential effects of systolic versus diastolic blood pressure on left ventricular structure and function. [ABSTRACT FROM AUTHOR]

Triglyceride-glucose (TyG) index is an independent risk factor for cardiovascular diseases (CVD). Our study determined the trends of the TyG index and its relationship to predicted CVD risk among patients with type 2 diabetes (T2D). A serial cross-sectional study was conducted including 63,815 participants with T2D aged 30–74 years without a history of CVD. The predicted CVD risk was based on the Framingham Heart Study (FHS). The receiver operating characteristic (ROC) curve was utilized for identifying the cutoff point of TyG index to predict intermediate-to-high CVD risk. The relationship between TyG index and predicted CVD risk was tested using linear and logistic regression. Decreasing trends of TyG index were observed between 2014 and 2018 (p < 0.001). ROC curve analysis of the TyG index indicated an AUC of 0.57 (95% CI 0.56–0.57, p < 0.001) in predicting intermediate-to-high predicted CVD risk, with a cutoff value of TyG index > 9.2 (sensitivity of 55.7%, specificity of 46.8%). An independent relationship between the TyG index and predicted CVD risk was observed. High TyG index was independently associated with intermediate-to-high predicted CVD risk. From our study, the TyG index was positively related to predicted 10-year CVD risk. However, the predictive ability of the TyG index in predicting the intermediate-to-high predicted 10-year CVD risk among patients with T2D remained questionable. [ABSTRACT FROM AUTHOR]

To maintain normal level of thyroid hormone, especially for free thyroxine (FT4), individuals with latent thyroid gland damage might have required higher thyroid stimulating hormone (TSH) than those without latent thyroid gland damage. Anti-thyroid peroxidase antibody (TPO-Ab) is a main cause of auto-immune thyroiditis, and therefore euthyroid individuals positive for TPO-Ab might have latent damage to the thyroid gland. Therefore, the association between TSH values and TPO-Ab positivity may be useful to determine the influence of latent thyroid gland damage on requirement of TSH. Furthermore, because latent damage of thyroid might elevate TSH level but not FT4 level, those associations should be observed independent from FT4. This cross-sectional study analyzed 1431 Japanese with normal ranges of free triiodothyronine (FT3) and FT4. Since TPO-Ab is associated with atherosclerosis in euthyroid individuals, cardiovascular risk factors might underlie the association between TPO-Ab and TSH values. After adjusting for FT4 and known cardiovascular risk factors, the adjusted odds ratio (95% confidence interval) of TPO-Ab positivity for logarithmic value of TSH was 1.53 (1.20, 1.95). Essentially the same association was observed when the analysis was restricted to individuals without subclinical hypothyroidism (1.54 [1.15, 2.13]). Euthyroid individuals with latent thyroid gland damage might have increased the requirement of TSH. [ABSTRACT FROM AUTHOR]

This study aims to (1) assess the distribution of variables within the population and the prevalence of cardiovascular disease (CVD) behavioural risk factors in patients, (2) identify target risk factor(s) for behaviour modification intervention, and (3) develop an analytical model to define cluster(s) of risk factors which could help make any generic intervention more targeted to the local patient population. Study patients with at least one CVD behavioural risk factor living in a rural region of the Scottish Highlands. The study used the STROBE methodology for cross-sectional studies. Demographic and clinical data of patients (n = 2025) in NHS Highlands hospital were collected at the point of admission for PCI between 04.01.2016 and 31.12.2019. Collected data distributions were analysed by CVD behavioural risk factors for prevalence, associations, and direction of associations. Cluster definition was measured by assignment of a unit score each for the overall level of prevalence and significance of associations, and general logistics modelling for direction and significance of the risk. The mean (SD) age was 69.47(± 10.93) years [95% CI (68.99–69.94)]. The key risk factors were hyperlipidaemia, hypertension, and elevated body mass index (BMI). Approximately 40% of the population have multiple risk factor counts of two. Analytical measures revealed a population risk factor cluster with elevated BMI [77.5% (1570/2025)] that is mostly either hyperlipidaemic [9.43%, co-eff. (17), P = 0.007] or hypertensive [22.72%, co-eff. (17), P = 0.99] as key risk factor clusters. Carefully modelled analyses revealed clustered risk associated with elevated BMI. This information would support a strategy for targeting risk factor clusters in novel interventions to improve implementation efficiency. Exposure to and outcome of an elevated BMI is linked more to the population's socio-economic outcomes rather than to regional rurality or urbanity. [ABSTRACT FROM AUTHOR]

Anthracycline-induced cardiomyopathy is a leading cause of late morbidity in childhood cancer survivors. Aberrant DNA methylation plays a role in de novo cardiovascular disease. Epigenetic processes could play a role in anthracycline-induced cardiomyopathy but remain unstudied. We sought to examine if genome-wide differential methylation at 'CpG' sites in peripheral blood DNA is associated with anthracycline-induced cardiomyopathy. This report used participants from a matched case–control study; 52 non-Hispanic White, anthracycline-exposed childhood cancer survivors with cardiomyopathy were matched 1:1 with 52 survivors with no cardiomyopathy. Paired ChAMP (Chip Analysis Methylation Pipeline) with integrated reference-based deconvolution of adult peripheral blood DNA methylation was used to analyze data from Illumina HumanMethylation EPIC BeadChip arrays. An epigenome-wide association study (EWAS) was performed, and the model was adjusted for GrimAge, sex, interaction terms of age at enrollment, chest radiation, age at diagnosis squared, and cardiovascular risk factors (CVRFs: diabetes, hypertension, dyslipidemia). Prioritized genes were functionally validated by gene knockout in human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) using CRISPR/Cas9 technology. DNA-methylation EPIC array analyses identified 32 differentially methylated probes (DMP: 15 hyper-methylated and 17 hypo-methylated probes) that overlap with 23 genes and 9 intergenic regions. Three hundred and fifty-four differential methylated regions (DMRs) were also identified. Several of these genes are associated with cardiac dysfunction. Knockout of genes EXO6CB, FCHSD2, NIPAL2, and SYNPO2 in hiPSC-CMs increased sensitivity to doxorubicin. In addition, EWAS analysis identified hypo-methylation of probe 'cg15939386' in gene RORA to be significantly associated with anthracycline-induced cardiomyopathy. In this genome-wide DNA methylation profile study, we observed significant differences in DNA methylation at the CpG level between anthracycline-exposed childhood cancer survivors with and without cardiomyopathy, implicating differential DNA methylation of certain genes could play a role in pathogenesis of anthracycline-induced cardiomyopathy. [ABSTRACT FROM AUTHOR]

Cardiovascular events remain a substantial global health concern, necessitating innovative strategies for prevention. This study aims to assess the potential impact of influenza vaccination on major cardiovascular events. A search of the medical English literature was conducted using PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL up to 1 August 2023. Meta-analysis and stratified analyses were performed to investigate specific outcomes, including myocardial infarction (MI), cardiovascular death, and stroke. Pooled relative risks (RR) along with their 95% confidence intervals (CI) were calculated to evaluate the associations. A comprehensive analysis was conducted on a total of 9059 patients, with 4529 patients receiving the influenza vaccine and 4530 patients receiving a placebo. Among patients who received the influenza vaccine, a notable reduction in the occurrence of major cardiovascular events was observed, with 517 cases compared to 621 cases in the placebo group (RR 0.70; 95% CI 0.55–0.91). The stratified analysis revealed a decreased risk of MI in vaccinated patients (RR 0.74; 95% CI 0.56–0.97) and a significant reduction in cardiovascular death events (RR 0.67; 95% CI 0.45–0.98). This study provides compelling evidence that influenza vaccination is associated with a decreased risk of major cardiovascular events, particularly myocardial infarction, and cardiovascular death. These findings highlight the potential of influenza vaccination as an adjunctive strategy in cardiovascular disease prevention. Further research and exploration of underlying mechanisms are warranted to elucidate the observed beneficial effects. [ABSTRACT FROM AUTHOR]

As an important risk factor for many cardiovascular diseases, hypertension requires convenient and reliable methods for prevention and intervention. This study designed a visualization risk prediction system based on Machine Learning and SHAP as an auxiliary tool for personalized health management of hypertension. We used ten Machine Learning algorithms such as random forests and 1617 anonymized health check data to build ten hypertension risk prediction models. The model performance was evaluated through indicators such as accuracy, F1-score, and ROC curve. We used the best-performing model combined with the SHAP algorithm for feature importance analysis and built a visualization risk prediction system on the web page. The LightGMB model exhibited the best predictive performance, and age, alkaline phosphatase, and triglycerides were important features for predicting the risk of hypertension. Users can obtain their risk probability of hypertension and determine the focus of intervention through the visualization system built on the web page. Our research helps doctors and patients to develop personalized prevention and intervention programs for hypertension based on health check data, which has significant clinical and public health significance. [ABSTRACT FROM AUTHOR]

We aimed to investigate the sex-related differences in the clinical course of patients with Atrial Fibrillation (AF) enrolled in the Asia–Pacific-Heart-Rhythm-Society Registry. Logistic regression was utilized to investigate the relationship between sex and oral anticoagulant, rhythm control strategies and the 1-year chance to maintain sinus rhythm. Cox-regression was utilized to assess the 1-year risk of all-cause, and cardiovascular death, thromboembolic events, acute coronary syndrome, heart failure, and major bleeding. In the whole cohort (4121 patients, 69 ± 12 years,34.3% female), females had different cardiovascular risk factors, clinical manifestations, and disease perceptions than men, with more advanced age (72 ± 11 vs 67 ± 12 years, p < 0.001) and dyslipidemia (36.7% vs 41.7%, p = 0.002). Coronary artery disease was more prevalent in males (21.1% vs 16.1%, p < 0.001) as well as the use of antiplatelet drugs. Females had a higher use of oral anticoagulant (84.9% vs 81.3%, p = 0.004) but this difference was non-significant after adjustment for confounders. On multivariable analyses, females were less often treated with rhythm control strategies (Odds Ratio [OR] 0.44,95% Confidence Interval [CI] 0.38–0.51) and were less likely to maintain sinus rhythm (OR 0.27, 95% CI 0.22–0.34) compared to males. Cox-regressions analysis showed no sex-related differences for the risk of death, cardiovascular, and bleeding. The clinical management of Asian AF patients should consider several sex-related differences. [ABSTRACT FROM AUTHOR]

There are reports of link of osteoprotegerin (OPG) gene polymorphism to type-2 diabetes (T2D) and hypertension (HTN). The objective of the study was to assess the allele frequency of OPG (rs2073618) gene polymorphism and its association with heart rate variability (HRV) and blood pressure variability profile as CVD risks in diabetes mellitus patients with hypertension undergoing treatment. T2D patients on treatment without hypertension (n = 172), with hypertension (n = 177) and 191 healthy volunteers were recruited for the study. Their blood pressure variability including baroreflex sensitivity (BRS), heart rate variability (HRV), OPG, insulin, lipid profile, receptor-activator for NFkB (RANK), receptor-activator for NFkB-Ligand (RANKL), and tumor necrosis factor-α (TNF-α) were estimated. Allele frequency of OPG (rs2073618) gene polymorphism was assessed from the DNA samples. BRS and HRV indices were decreased, and RANKL/OPG and TNF-α were increased in T2D and T2D + HTN groups, respectively compared to healthy control group. The reduction in BRS was contributed by increased inflammation and reduced SDNN of HRV in GG genotype in T2D + HTN. In GG + GC subgroup, it was additionally contributed by rise in RANKL/OPG level (β − 0.219; p 0.008). Presence of mutant GG genotype contributed to the risk of hypertension among T2D patients (OR 3.004) as well as in general population (OR 2.79). It was concluded that CV risks are more in T2D patients with HTN expressing OPG rs2073618 gene polymorphism. [ABSTRACT FROM AUTHOR]

Predicting cardiorespiratory fitness levels can be useful for measuring progress in an exercise program as well as for stratifying cardiovascular risk in asymptomatic adults. This study proposes a model to predict fitness level in terms of maximal oxygen uptake using anthropometric, heart rate, and step count data. The model was trained on a diverse cohort of 3115 healthy subjects (1035 women and 2080 men) aged 42 ± 10.6 years and tested on a cohort of 779 healthy subjects (260 women and 519 men) aged 42 ± 10.18 years. The developed model is capable of making accurate and reliable predictions with the average test set error of 3.946 ml/kg/min. The maximal oxygen uptake labels were obtained using wearable devices (Apple Watch and Garmin) during recorded workout sessions. Additionally, the model was validated on a sample of 10 subjects with maximal oxygen uptake determined directly using a treadmill protocol in a laboratory setting and showed an error of 4.982 ml/kg/min. Unlike most other models, which use accelerometer readings as additional input data, the proposed model relies solely on heart rate and step counts—data readily available on the majority of fitness trackers. The proposed model provides a point estimation and a probabilistic prediction of cardiorespiratory fitness level, thus it can estimate the prediction's uncertainty and construct confidence intervals. [ABSTRACT FROM AUTHOR]

Sleep restriction is associated with increased cardiovascular risk, which is more pronounced in female than male persons. We reported recently first causal evidence that mild, prolonged sleep restriction mimicking "real-life" conditions impairs endothelial function, a key step in the development and progression of cardiovascular disease, in healthy female persons. However, the underlying mechanisms are unclear. In model organisms, sleep restriction increases oxidative stress and upregulates antioxidant response via induction of the antioxidant regulator nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Here, we assessed directly endothelial cell oxidative stress and antioxidant responses in healthy female persons (n = 35) after 6 weeks of mild sleep restriction (1.5 h less than habitual sleep) using randomized crossover design. Sleep restriction markedly increased endothelial oxidative stress without upregulating antioxidant response. Using RNA-seq and a predicted protein–protein interaction database, we identified reduced expression of endothelial Defective in Cullin Neddylation-1 Domain Containing 3 (DCUN1D3), a protein that licenses Nrf2 antioxidant responses, as a mediator of impaired endothelial antioxidant response in sleep restriction. Thus, sleep restriction impairs clearance of endothelial oxidative stress that over time increases cardiovascular risk. Trial Registration: NCT02835261 [ABSTRACT FROM AUTHOR]

Gut microbiota is an emerging editable cardiovascular risk factor. We aim to investigate gut and coronary plaque microbiota, using fecal samples and angioplasty balloons from patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS) and control subjects. We examined bacterial communities in gut and coronary plaques by 16S rRNA sequencing and we performed droplet digital PCR analysis to investigate the gut relative abundance of the bacterial genes CutC/CntA involved in trimethylamine N-oxide synthesis. Linear discriminant analysis effect size (LEfSe) at the genus and species levels displayed gut enrichment in Streptococcus, Granulicatella and P. distasonis in ACS compared with CCS and controls; Roseburia, C. aerofaciens and F. prausnitzii were more abundant in controls than in patients. Principal component analysis (PCA) of 41 differentially abundant gut taxa showed a clustering of the three groups. In coronary plaque, LEfSe at the genus level revealed an enrichment of Staphylococcus and Streptococcus in ACS, and Paracoccus in CCS, whereas PCA of 15 differentially abundant plaque taxa exhibited clustering of ACS and CCS patients. CutC and CntA genes were more abundant in ACS and CCS than in controls while no significant difference emerged between ACS and CCS. Our results indicate that ACS and CCS exhibit a different gut and plaque microbial signature, suggesting a possible role of these microbiotas in coronary plaque instability. [ABSTRACT FROM AUTHOR]

Dyslipidaemia is an established cardiovascular risk factor. This study aimed to determine the pooled prevalence of dyslipidaemia in Malaysian adults. A systematic review and meta-analysis of all cross-sectional, longitudinal observational studies which reported the prevalence of elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), and reduced high-density lipoprotein cholesterol (HDL-c) in adults 18 years old and older, was conducted. A comprehensive search of PubMed and Cochrane Central Register of Controlled Trials (which included Medline, EMBASE and major trial registers) from inception to October 18, 2022, was performed. Risk-of-bias was evaluated using the Johanna-Briggs Institute Prevalence Critical Appraisal Tool, while certainty of evidence was assessed using an adapted version of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Random-effects meta-analyses were performed using MetaXL. This report follows the PRISMA reporting guidelines. The protocol was registered with PROSPERO (CRD42020200281). 26 556 studies were retrieved and 7 941 were shortlisted initially. From this, 70 Malaysian studies plus two studies from citation searching were shortlisted; 46 were excluded, and 26 were included in the review (n = 50 001). The pooled prevalence of elevated TC (≥ 5.2 mmol/L), elevated LDL-c (≥ 2.6 mmol/L), elevated TG (≥ 1.7 mmol/L), and low HDL-c (< 1.0 mmol/L in men and < 1.3 mmol/L in women) were 53% (95% CI 39–67%, I2 = 100%), 73% (95% CI 50–92%, I2 = 100%), 36% (95% CI 32–40%, I2 = 96%), and 40% (95% CI 25–55%, I2 = 99%), respectively. This review found that the prevalence of all dyslipidaemia subtypes is high in Malaysian adults. Ongoing efforts to reduce cardiovascular diseases in Malaysia should integrate effective detection and treatment of dyslipidaemia. [ABSTRACT FROM AUTHOR]

Aspirin may be considered for primary prevention in non-elderly patients with high cardiovascular risk. However, contemporary management aimed at aggressive cardiovascular risk factor control may alter benefit-risk ratio of aspirin. Therefore, we aimed to examine the effect of aspirin for primary prevention on the long-term MACEs in a large cohort registry. Cohort Of patients with high Risk for cardiovascular Events (CORE-Thailand) registry is a prospective, multicenter, observational, longitudinal study of Thai patients with high atherosclerotic risk. Patients with established atherosclerotic cardiovascular diseases were excluded. Among 4259 patients with multiple cardiovascular risk factors, 1945 (45.7%) patients used aspirin. After propensity score matching, there were 3228 patients remained in post-matching analysis. During the median follow-up period of 58.2 months, we demonstrated that aspirin use increased risk of long-term MACEs in pre-matching cohort (unadjusted HR 1.76, 95% CI 1.43–2.17, P < 0.001) and post-matching cohort (HR 1.66 (1.31–2.10), P < 0.001). In addition, patients taking aspirin had a higher risk of bleeding than non-aspirin users in pre-matching cohort (unadjusted HR 2.28, 95% CI 1.09–4.75, P = 0.028). We demonstrated that aspirin was associated with increased risk of long-term MACEs in patients with multiple cardiovascular risk factors. Due to the non-randomized design, our results should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Arterial hypertension is considered a risk factor for the development of heart failure. Here we investigate cross-sectional associations of systolic and diastolic blood pressure with subtle functional and morphological changes of left ventricular echocardiographic parameters representing early dysfunction in three representative German population-based studies. We assessed 26,719 individuals without symptomatic heart failure from the Hamburg City Health Study (HCHS, n = 7396, derivation cohort), the Gutenberg Health Study (GHS, 14,715, validation cohort) and the Study of Health in Pomerania (SHIP, 4608, validation cohort). Multivariable linear regression analyses with systolic and diastolic blood pressure as continuous exposure variables were adjusted for common cardiovascular risk factors and antihypertensive medication. Both systolic and diastolic blood pressure were consistently associated with measures of left ventricular hypertrophy (β per standard deviation (SD) for LV mass (g) and systolic blood pressure: 5.09 (p < 0.001); diastolic blood pressure: 2.29 (p < 0.001) in HCHS). Systolic blood pressure correlated with declining diastolic function (β per SD for E/e′: 0.29, p < 0.001 in HCHS) and diastolic blood pressure with declining systolic function (β per SD for LVEF, in %: − 0.15; p = 0.041 in HCHS) in all cohorts. Pending further validation, our results from three independent German population samples suggest differential effects of systolic versus diastolic blood pressure on left ventricular structure and function. [ABSTRACT FROM AUTHOR]

To maintain normal level of thyroid hormone, especially for free thyroxine (FT4), individuals with latent thyroid gland damage might have required higher thyroid stimulating hormone (TSH) than those without latent thyroid gland damage. Anti-thyroid peroxidase antibody (TPO-Ab) is a main cause of auto-immune thyroiditis, and therefore euthyroid individuals positive for TPO-Ab might have latent damage to the thyroid gland. Therefore, the association between TSH values and TPO-Ab positivity may be useful to determine the influence of latent thyroid gland damage on requirement of TSH. Furthermore, because latent damage of thyroid might elevate TSH level but not FT4 level, those associations should be observed independent from FT4. This cross-sectional study analyzed 1431 Japanese with normal ranges of free triiodothyronine (FT3) and FT4. Since TPO-Ab is associated with atherosclerosis in euthyroid individuals, cardiovascular risk factors might underlie the association between TPO-Ab and TSH values. After adjusting for FT4 and known cardiovascular risk factors, the adjusted odds ratio (95% confidence interval) of TPO-Ab positivity for logarithmic value of TSH was 1.53 (1.20, 1.95). Essentially the same association was observed when the analysis was restricted to individuals without subclinical hypothyroidism (1.54 [1.15, 2.13]). Euthyroid individuals with latent thyroid gland damage might have increased the requirement of TSH. [ABSTRACT FROM AUTHOR]

The Globorisk and WHO cardiovascular risk prediction models are country-specific and region-specific, respectively. The goal of this study was to assess the agreement and correlation between the WHO and Globorisk 10-year cardiovascular disease risk prediction models. The baseline data of 6796 individuals aged 40–74 years who participated in the Fasa cohort study without a history of cardiovascular disease or stroke at baseline were included. In the WHO and Globorisk models scores were calculated using age, sex, systolic blood pressure (SBP), current smoking, diabetes, and total cholesterol for laboratory-based risk and age, sex, SBP, current smoking, and body mass index (BMI) for non-laboratory-based risk (office-based or BMI-based). In Globorisk and WHO risk agreement across risk categories (low, moderate, and high) was examined using the kappa statistic. Also, Pearson correlation coefficients and scatter plots were used to assess the correlation between Globorisk and WHO models. Bland–Altman plots were presented for determination agreement between Globorisk and WHO risk scores in individual's level. In laboratory-based models, agreement across categories was substantial in the overall population (kappa values: 0.75) and also for females (kappa values: 0.74) and males (kappa values: 0.76), when evaluated separately. In non-laboratory-based models, agreement across categories was substantial for the whole population (kappa values: 0.78), and almost perfect for among males (kappa values: 0.82) and substantial for females (kappa values: 0.73). The results showed a very strong positive correlation (r ≥ 0.95) between WHO and Globorisk laboratory-based scores for the whole population, males, and females and also a very strong positive correlation (r > 0.95) between WHO and Globorisk non-laboratory-based scores for the whole population, males, and females. In the laboratory-based models, the limit of agreements was better in males (95%CI 2.1 to − 4.2%) than females (95%CI 4.3 to − 7.3%). Also, in the non-laboratory-based models, the limit of agreements was better in males (95%CI 2.9 to − 4.0%) than females (95%CI 3.2 to − 6.1%). There was a good agreement between both the laboratory-based and the non-laboratory-based WHO models and the Globorisk models. The correlation between two models was very strongly positive. However, in the Globorisk models, more people were in high-risk group than in the WHO models. The scatter plots and Bland–Altman plots showed systematic differences between the two scores that vary according to the level of risk. So, for these models may be necessary to modify the cut points of risk groups. The validity of these models must be determined for this population. [ABSTRACT FROM AUTHOR]

This study aims to (1) assess the distribution of variables within the population and the prevalence of cardiovascular disease (CVD) behavioural risk factors in patients, (2) identify target risk factor(s) for behaviour modification intervention, and (3) develop an analytical model to define cluster(s) of risk factors which could help make any generic intervention more targeted to the local patient population. Study patients with at least one CVD behavioural risk factor living in a rural region of the Scottish Highlands. The study used the STROBE methodology for cross-sectional studies. Demographic and clinical data of patients (n = 2025) in NHS Highlands hospital were collected at the point of admission for PCI between 04.01.2016 and 31.12.2019. Collected data distributions were analysed by CVD behavioural risk factors for prevalence, associations, and direction of associations. Cluster definition was measured by assignment of a unit score each for the overall level of prevalence and significance of associations, and general logistics modelling for direction and significance of the risk. The mean (SD) age was 69.47(± 10.93) years [95% CI (68.99–69.94)]. The key risk factors were hyperlipidaemia, hypertension, and elevated body mass index (BMI). Approximately 40% of the population have multiple risk factor counts of two. Analytical measures revealed a population risk factor cluster with elevated BMI [77.5% (1570/2025)] that is mostly either hyperlipidaemic [9.43%, co-eff. (17), P = 0.007] or hypertensive [22.72%, co-eff. (17), P = 0.99] as key risk factor clusters. Carefully modelled analyses revealed clustered risk associated with elevated BMI. This information would support a strategy for targeting risk factor clusters in novel interventions to improve implementation efficiency. Exposure to and outcome of an elevated BMI is linked more to the population's socio-economic outcomes rather than to regional rurality or urbanity. [ABSTRACT FROM AUTHOR]

Triglyceride-glucose (TyG) index is an independent risk factor for cardiovascular diseases (CVD). Our study determined the trends of the TyG index and its relationship to predicted CVD risk among patients with type 2 diabetes (T2D). A serial cross-sectional study was conducted including 63,815 participants with T2D aged 30–74 years without a history of CVD. The predicted CVD risk was based on the Framingham Heart Study (FHS). The receiver operating characteristic (ROC) curve was utilized for identifying the cutoff point of TyG index to predict intermediate-to-high CVD risk. The relationship between TyG index and predicted CVD risk was tested using linear and logistic regression. Decreasing trends of TyG index were observed between 2014 and 2018 (p < 0.001). ROC curve analysis of the TyG index indicated an AUC of 0.57 (95% CI 0.56–0.57, p < 0.001) in predicting intermediate-to-high predicted CVD risk, with a cutoff value of TyG index > 9.2 (sensitivity of 55.7%, specificity of 46.8%). An independent relationship between the TyG index and predicted CVD risk was observed. High TyG index was independently associated with intermediate-to-high predicted CVD risk. From our study, the TyG index was positively related to predicted 10-year CVD risk. However, the predictive ability of the TyG index in predicting the intermediate-to-high predicted 10-year CVD risk among patients with T2D remained questionable. [ABSTRACT FROM AUTHOR]

Dried blood spot (DBS) sample collection has been suggested as a less invasive, cheaper and more convenient alternative to venepuncture, which requires trained personnel, making it a potentially viable approach for self-collection of blood on a large scale. We examine whether participants in a longitudinal survey were willing to provide a DBS sample in different interview settings, and how resulting cardiovascular risk biomarkers compared with those from venous blood to calculate clinical risk. Participants of the Understanding Society Innovation Panel, a representative sample of UK households, were randomly assigned to three modes of interview. Most participants (84%) were interviewed in their allocated mode. Participants (n = 2162) were interviewed by a nurse who collected both a blood sample by venepuncture and a DBS card ('nurse collection') or participants were seen by an interviewer or took part in the survey online to self-collect a DBS card ('self-collection'). All DBS cards were returned in the post after the sample had dried. Lipids (total cholesterol, HDL-cholesterol, triglycerides), HbA1c and C-reactive protein were measured in venous and DBS samples and equivalence was calculated. The resultant values were used to confirm equivalent prevalence of risk of cardiovascular disease in each type of blood sample by mode of participation. Of participants interviewed by a nurse 69% consented to venous blood sample and 74% to a DBS sample, while in the self-collection modes, 35% consented to DBS collection. Demographic characteristics of participants in self-collection mode was not different to those in nurse collection mode. The percentage of participants with clinically raised biomarkers did not significantly differ between type of blood collection (for example, 62% had high cholesterol (> 5 mmol/l) measured by venepuncture and 67% had high cholesterol within the self-collected DBS sample (p = 0.13)). While self-collected DBS sampling had a lower response rate to DBS collected by a nurse, participation did not vary by key demographic characteristics. This study demonstrates that DBS collection is a feasible method of sample collection that can provide acceptable measures of clinically relevant biomarkers, enabling the calculation of population levels of cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

Anthracycline-induced cardiomyopathy is a leading cause of late morbidity in childhood cancer survivors. Aberrant DNA methylation plays a role in de novo cardiovascular disease. Epigenetic processes could play a role in anthracycline-induced cardiomyopathy but remain unstudied. We sought to examine if genome-wide differential methylation at 'CpG' sites in peripheral blood DNA is associated with anthracycline-induced cardiomyopathy. This report used participants from a matched case–control study; 52 non-Hispanic White, anthracycline-exposed childhood cancer survivors with cardiomyopathy were matched 1:1 with 52 survivors with no cardiomyopathy. Paired ChAMP (Chip Analysis Methylation Pipeline) with integrated reference-based deconvolution of adult peripheral blood DNA methylation was used to analyze data from Illumina HumanMethylation EPIC BeadChip arrays. An epigenome-wide association study (EWAS) was performed, and the model was adjusted for GrimAge, sex, interaction terms of age at enrollment, chest radiation, age at diagnosis squared, and cardiovascular risk factors (CVRFs: diabetes, hypertension, dyslipidemia). Prioritized genes were functionally validated by gene knockout in human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) using CRISPR/Cas9 technology. DNA-methylation EPIC array analyses identified 32 differentially methylated probes (DMP: 15 hyper-methylated and 17 hypo-methylated probes) that overlap with 23 genes and 9 intergenic regions. Three hundred and fifty-four differential methylated regions (DMRs) were also identified. Several of these genes are associated with cardiac dysfunction. Knockout of genes EXO6CB, FCHSD2, NIPAL2, and SYNPO2 in hiPSC-CMs increased sensitivity to doxorubicin. In addition, EWAS analysis identified hypo-methylation of probe 'cg15939386' in gene RORA to be significantly associated with anthracycline-induced cardiomyopathy. In this genome-wide DNA methylation profile study, we observed significant differences in DNA methylation at the CpG level between anthracycline-exposed childhood cancer survivors with and without cardiomyopathy, implicating differential DNA methylation of certain genes could play a role in pathogenesis of anthracycline-induced cardiomyopathy. [ABSTRACT FROM AUTHOR]

Basal metabolic rate (BMR) is associated with cardiovascular health; however, the causal relationship between BMR and the risk of cardiovascular diseases (CVDs) remains unclear. This study aimed to investigate the potential causal relationship of BMR on common CVDs including aortic aneurysm (AA), atrial fibrillation and flutter (AFF), calcific aortic valvular stenosis (CAVS), heart failure (HF), and myocardial infarction (MI) by Mendelian randomization (MR). The univariable MR analysis using inverse variance weighted (IVW) model as the primary analysis method revealed that genetically predicted higher BMR causally increased the risk of AA [IVW odds ratio (OR) = 1.34, 95% confidence interval CI 1.09–1.65, p = 0.00527], AFF (IVW OR = 1.87, 95% CI 1.65–2.12, p = 1.697 × E-22), and HF (IVW OR = 1.35, 95% CI 1.20–1.51, p = 2.364 × E-07), while causally decreasing the risk of MI (IVW OR = 0.83, 95% CI 0.73–0.93, p = 0.00255). In the multivariable MR analysis, which controlled for common cardiovascular risk factors, direct effects of BMR on an increased risk of AA and AFF, as well as a decreased risk of MI, but an attenuated causal effect on HF, were observed. In conclusion, the current MR study provides evidence for a causal relationship between BMR and the risk of AA, AFF, HF, and MI. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a frequent side effect associated with nilotinib treatment. Patients with chronic myeloid leukemia (CML) under treatment with nilotinib who develop dyslipidemia have been shown to have a higher risk of presenting atherosclerotic cardiovascular disease (ACVD). Therapeutic discontinuation in selected individuals could be a strategy in order to prevent the development of ACVD. Observational study of patients with CML under nilotinib treatment. The lipid values were gathered before starting with nilotinib and after 3 months. Such values were also measured before discontinuation in patients who suspended nilotinib treatment, as well as 3 and 12 months later. 32 patients were included, 19 of them treated in monotherapy with nilotinib. The concentrations of total cholesterol and low-density lipoproteins (LDL) increased significantly after 3 months of treatment (27.29 mg/dL ± 22.88, p < 0.01). Of the total number of patients treated, 12 discontinued the treatment. LDL concentration was significantly reduced after 3 months of the nilotinib discontinuation (− 27.58 mg/dL ± 38.30, p = 0.030), remaining substantially lower after 12 months, compared to the time previous to discontinuation (− 24.58 mg/dL ± 37.31, p = 0.043). Nilotinib suspension reduces significantly LDL concentrations. These data support the strategy of therapeutic discontinuation in order to prevent future cardiovascular complications, especially in patients with prior cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Covid-19 patients who require admission to an intensive care unit (ICU) have a higher risk of mortality. Several risk factors for severe Covid-19 infection have been identified, including cardiovascular risk factors. Therefore, the aim was to investigate the association between cardiovascular (CV) risk and major adverse cardiovascular events (MACE) and mortality of Covid-19 ARDS patients admitted to an ICU. A prospective cross-sectional study was conducted in a university hospital in Graz, Austria. Covid-19 patients who were admitted to an ICU with a paO2/fiO2 ratio < 300 were included in this study. Standard lipid profile was measured at ICU admission to determine CV risk. 31 patients with a mean age of 68 years were recruited, CV risk was stratified using Framingham-, Procam- and Charlson Comorbidity Index (CCI) score. A total of 10 (32.3%) patients died within 30 days, 8 patients (25.8%) suffered from MACE during ICU stay. CV risk represented by Framingham-, Procam- or CCI score was not associated with higher rates of MACE. Nevertheless, higher CV risk represented by Procam score was significantly associated with 30- day mortality (13.1 vs. 6.8, p = 0.034). These findings suggest that the Procam score might be useful to estimate the prognosis of Covid-19 ARDS patients. [ABSTRACT FROM AUTHOR]

To investigate the longitudinal association of different phenotypes of diabetes and obesity with the incidence of cardiovascular disease (CVD), CVD- and all-cause mortality. A total of 5432 adults, aged ≥ 35 years and free of CVD were included in this cohort study. Diabesity phenotypes were defined in six categories based on the presence of diabetes (normal (NG), prediabetes and diabetes) and obesity (obese, non-obese). Fasting blood sugar, 2-h post prandial glucose, or using anti-diabetic medicines were used to define diabetes, and body mass index and waist circumference were used to define obesity. Cox proportional hazards models were used to estimate hazard ratios (HRs) for incident CVD, CVD- and all-cause mortality across these categories. After a median follow-up of 11.25 years, 819 CVD cases, 181 CVD deaths and 488 all-cause deaths occurred. In multivariable-adjusted models and irrespective of obesity definition, the phenotypes of normal glucose-obese, prediabetes-obese and pre-diabetes-non obese were not associated with CVD incidence in comparison with NG-non obese phenotype, however, the phenotypes of diabesity, either defined by general or abdominal obesity, were associated with increased risk of incident CVD events (HR = 1.42, 95% CI 1.01, 1.99, and HR = 1.46, 95% CI 1.07, 1.98, respectively). These findings were sex-specific and only in men with a phenotype of abdominal obesity-diabetes, a positive link was observed for CVD incidence (HR = 1.60, 95% CI 1.01, 2.52). No significant association was found between diabesity and death from CVD or all causes. Diabesity is a predictor of CVD and stroke incidence, but not CVD or all-cause mortality, among Iranians. This association is more pronounced amongst men than women. [ABSTRACT FROM AUTHOR]

Dyslipidaemia is an established cardiovascular risk factor. This study aimed to determine the pooled prevalence of dyslipidaemia in Malaysian adults. A systematic review and meta-analysis of all cross-sectional, longitudinal observational studies which reported the prevalence of elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG), and reduced high-density lipoprotein cholesterol (HDL-c) in adults 18 years old and older, was conducted. A comprehensive search of PubMed and Cochrane Central Register of Controlled Trials (which included Medline, EMBASE and major trial registers) from inception to October 18, 2022, was performed. Risk-of-bias was evaluated using the Johanna-Briggs Institute Prevalence Critical Appraisal Tool, while certainty of evidence was assessed using an adapted version of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Random-effects meta-analyses were performed using MetaXL. This report follows the PRISMA reporting guidelines. The protocol was registered with PROSPERO (CRD42020200281). 26 556 studies were retrieved and 7 941 were shortlisted initially. From this, 70 Malaysian studies plus two studies from citation searching were shortlisted; 46 were excluded, and 26 were included in the review (n = 50 001). The pooled prevalence of elevated TC (≥ 5.2 mmol/L), elevated LDL-c (≥ 2.6 mmol/L), elevated TG (≥ 1.7 mmol/L), and low HDL-c (< 1.0 mmol/L in men and < 1.3 mmol/L in women) were 52% (95% CI 32–71%, I2 = 100%), 73% (95% CI 50–92%, I2 = 100%), 36% (95% CI 32–40%, I2 = 96%), and 40% (95% CI 25–55%, I2 = 99%), respectively. This review found that the prevalence of all dyslipidaemia subtypes is high in Malaysian adults. Ongoing efforts to reduce cardiovascular diseases in Malaysia should integrate effective detection and treatment of dyslipidaemia. [ABSTRACT FROM AUTHOR]

The association between constipation and cardiovascular risk is unclear. This population-level matched cohort study compared the association of constipation with hypertension and incident cardiovascular events in 541,172 hospitalized patients aged ≥ 60 years. For each constipation admission, one exact age-matched non-constipated admission was randomly selected from all hospitalizations within 2 weeks to form the comparison cohort. The association of constipation with hypertension and cardiovascular events (myocardial infarction, angina, stroke and transient ischemic attack) were analysed using a series of binary logistic regressions adjusting for age, sex, cardiovascular risk factors, gastrointestinal disorders and sociological factors. Patients with constipation had a higher multivariate-adjusted risk for hypertension (odds ratio [OR], 1.96; 95% confidence interval [CI] 1.94–1.99; P < 0.001). Compared to patients with neither constipation nor hypertension, there was a higher multivariate-adjusted risk for cardiovascular events in patients with constipation alone (OR, 1.58; 95% CI 1.55–1.61; P < 0.001) or hypertension alone (OR, 6.12; 95% CI 5.99–6.26; P < 0.001). In patients with both constipation and hypertension, the risk for all cardiovascular events appeared to be additive (OR, 6.53; 95% CI 6.40–6.66; P < 0.001). In conclusion, among hospital patients aged 60 years or older, constipation is linked to an increased risk of hypertension and cardiovascular events. These findings suggest that interventions to address constipation may reduce cardiovascular risk in elderly patients. [ABSTRACT FROM AUTHOR]

Blood pressure (BP) reactivity to stress is associated with cardiovascular events and the incidence of hypertension, therefore, tolerance to stressors is important for better management of cardiovascular risks. Exercise training is among the strategies that have been investigated as blunting the peak response to stressors, however, its efficacy is poorly explored. The aim was to explore the effects of exercise training (at least four weeks) on BP responses to stressor tasks in adults. A systematic review was performed in five electronic databases (MEDLINE, LILACS, EMBASE, SPORTDiscus, and PsycInfo). Twenty-three studies and one conference abstract was included in the qualitative analysis, totaling 1121 individuals, and k = 17 and 695 individuals in the meta-analysis. Favorable results (random-effects) for exercise training were found, with attenuated peak responses in systolic (standardized mean difference (SMD) = −0.34 [−0.56; −0.11], representing average reductions of 2.5 ± 3.6 mmHg) and null effects on diastolic BP (SMD = −0.20 [−0.54; 0.14], representing average reductions of 2.0 ± 3.5 mmHg). The analysis removing outliers' studies improved the effects for diastolic (SMD = −0.21 [−0.38; −0.05]) but not systolic BP (SMD = −0.33 [−0.53; −0.13]). In conclusion, exercise training seems to lower stress-related BP reactivity, therefore has the potential to improve patients' ability to better respond to stressful situations. [ABSTRACT FROM AUTHOR]

We investigated the effects of gender and lifestyle on the association between frequency of depressive symptoms and CVD risk. The UK Biobank is a national prospective cohort study that recruited 502,505 participants aged 40–69 years between 2006 and 2010. Participants without CVD were classified as having low, moderate, high, or very high frequency of depressive symptoms according to the number of days they felt depressed in a 2-week period. UKBB data include self-reported questionnaires covering lifestyle behaviors such as smoking, physical activity, eating habits, and sleep duration. The primary outcomes included incident CVD including coronary artery disease, ischemic stroke, hemorrhagic stroke, peripheral artery disease, atrial fibrillation/flutter, and heart failure. Cox proportional hazard models were used to evaluate the effects of gender and lifestyle on the association of frequency of depressive symptoms and CVD risk. During a median follow-up of 8.9 years, 27,394 (6.3%) developed CVD. The frequency of depressive symptoms increased the risk of CVD according to low, moderate, high, and very high frequency of depressive symptoms (P for trend < 0.001). The adjusted CVD risk was 1.38-fold higher for participants with very high frequency of depressive symptoms compared to those with low frequency of depressive symptoms (HR 1.38, 95% CI 1.24–1.53, P < 0.001). The correlation between frequency of depressive symptoms and CVD risk was more remarkable in females than in males. In participants with high or very high frequency of depressive symptoms, the individual lifestyle factors of no current smoking, non-obesity, non-abdominal obesity, regular physical activity, and appropriate sleep respectively was associated with lower CVD risk by 46% (HR 0.54, 95% CI 0.48–0.60, P < 0.001), 36% (HR 0.64, 95% CI 0.58–0.70, P < 0.001), 31% (HR 0.69, 95% CI 0.62–0.76, P < 0.001), 25% (HR 0.75, 95% CI 0.68–0.83, P < 0.001), and 22% (HR 0.78, 95% CI 0.71–0.86, P < 0.001). In this large prospective cohort study, a higher frequency of depressive symptoms at baseline was significantly associated with increased risk of CVD in the middle-aged population, and this relationship was prominent in women. In the middle-aged population with depressive symptoms, engaging in a healthier lifestyle could prevent CVD risk. [ABSTRACT FROM AUTHOR]

In this study, we investigated whether toothbrushing timing affects cardiovascular disease risk. We enrolled 1675 patients aged ≥ 20 years who were hospitalized for surgery, examination, or medical treatment. The participants were categorized as follows based on toothbrushing: Group MN (brushing teeth after waking up and at night, n = 409), Group Night (brushing teeth at night but not upon waking up, n = 751), Group M (brushing teeth after waking up but not at night, n = 164), and Group None (not brushing teeth at all, n = 259). The participants' age, sex, smoking history, and follow-up results were evaluated. Group M had four times as many men as women. Multivariate analysis of cardiovascular events showed significantly higher survival estimates in Group MN (P = 0.021) and Group Night (P = 0.004) than in Group None. Kaplan–Meier analysis of subgroups based on smoking status revealed that smokers in Group None had significantly worse prognosis for cardiovascular onset events than smokers in other groups; non-smokers in Groups None and M showed significantly worse prognosis on hospitalization. Our findings are limited to cardiovascular diseases and cannot be generalized to healthy populations. However, we suggest that brushing teeth at night is important for lowering cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

Major post-cessation metabolic changes include weight gain and hyperglycemia. However, the association of post-cessation change in fasting serum glucose (FSG) with risk of fatty liver remains unclear. A total of 111,106 participants aged 40 and above who underwent health screening at least once in two examination periods were extracted from the Korean National Health Insurance Service-National Sample Cohort. Fatty liver status was evaluated using the Korean National Health and Nutrition Examination Survey nonalcoholic fatty liver disease (K-NAFLD) score. Linear and logistic regression were used to calculate the adjusted mean (aMean) and adjusted odds ratio (aOR) with 95% confidence intervals. Compared to stable (aMean 0.10; 95% CI 0.03–0.18) and decline (aMean − 0.60; 95% CI − 0.71 to 0.49) groups, FSG elevation (aMean 1.28; 95% CI 1.16–1.39) was associated with higher K-NAFLD score even within different body mass index change groups. Risk of fatty liver was significantly reduced among participants with stable (aOR 0.38; 95% CI 0.31–0.45) and declined (aOR 0.17; 95% CI 0.13–0.22) FSG levels after smoking cessation compared to FSG elevation group. This study suggests that quitters with elevated FSG are associated with higher NAFLD risk and may benefit from careful monitoring of FSG levels and management of other cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

The awareness of cardiovascular diseases (CVDs) contributes to the complications and fatality rates from these diseases among individuals; however, no previous study in Syria was conducted on this topic; thus, this study aims to assess Syrians' awareness of CVDs warning symptoms and risk factors. This online cross-sectional study was performed in Syria between the 1st and 25th of August 2022. The inclusion criteria for the sample were citizens of Syria over 18 who currently reside in Syria. The questionnaire included open- and closed-ended questions to assess the awareness of CVDs. A total of 1201 participants enrolled in the study with a response rate of 97.2%; more than half of the participants (61.4%) were aged 18–24. The most recognizable risk factors and warning signs when asking close-ended and open-ended questions were smoking (95.2%, 37.1%) and chest pain (87.8%, 24.8%), respectively. Overall knowledge scores for risk factors and warning signs were (61.5%). Regarding knowledge score of CVDs risk factors and warning signs, participants aged 45–54 scored higher than other age groups, and respondents with a university education level had a higher score than other educational levels (15.7 ± 0.3), (14.5 ± 0.1), respectively. Participants aged 45–54 have a higher probability of good knowledge of CVDs risk factors and warning signs than participants aged 18–24 (OR = 4.8, P value < 0.001), while participants living in the countryside were less likely to have good knowledge of CVDs risk factors and warning signs than city residents (OR = 0.6, P value < 0.05). According to our results, there is inadequate knowledge of the risk factors and warning signs of CVDs. Consequently, there is a greater need to raise CVD awareness and learning initiatives on the disease's risk factors and symptoms. [ABSTRACT FROM AUTHOR]