European Journal of Preventive Cardiology

BackgroundSex hormone alterations, such as estrogen deficiency or testosterone excess, substantially increase cardiovascular disease (CVD) risk in females. Dietary fibre and its microbial by-products, short-chain fatty acids (SCFAs), have cardioprotective effects, but it remains unclear whether these benefits extend to females with an altered sex hormone profile. In this study, we aim to investigate whether dietary fibre intake, measured via plasma acetate--the most abundant SCFA--is associated with improved cardiovascular outcomes in females with altered sex hormone profiles. MethodsThis cohort study included 116,235 female participants from the UK Biobank and Biobank Japan with up to 10 years of follow-up. We analysed early menopause (as a surrogate for estrogen insufficiency) and plasma free testosterone (in a subset). The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes were blood pressure. Proteomics analyses explored potential mechanisms. ResultsAcetate levels were associated with lower 10-year MACE incidence (-0.618/1000 woman-year, HR=0.900, p=0.002) and systolic blood pressure (-0.231 mmHg per 1 SD, p<0.001) in the UK Biobank. High acetate levels attenuated the increased MACE risk associated with early menopause (HR=1.158, p=0.057) compared with low acetate (HR=1.425, p<0.001), with similar patterns replicated in Biobank Japan (high: HR=1.322, p=0.090; low: HR=1.385, p=0.042). Proteomics analyses suggested a mechanism involving pro-inflammatory proteins. Moreover, high acetate levels attenuated the increased MACE associated with elevated free testosterone in the UK Biobank (high: HR=1.238, p=0.024; low: HR=1.056, p=0.666). A significant interaction between acetate and free testosterone on systolic blood pressure indicated that the effect of rising testosterone on blunting acetates effect ({beta}=0.167, 95% CI: [5.212x10-2-2.818x10-1], p=0.004) was partially mediated by central obesity (waist-to-hip ratio). ConclusionsHigher plasma acetate levels were associated with lower cardiovascular risk, particularly in females with early menopause or elevated free testosterone, potentially via inflammatory pathways. These findings underscore the importance of hormonal context in shaping cardiometabolic resilience and support personalised CVD prevention strategies for females with altered sex hormone profiles, including increasing dietary fibre intake.

Background and AimSedentary lifestyle and obesity are considered to be significant risk factors that create a pathway for the appearance of the sedentary cardiac phenotype consisting of cardiac atrophy, myocardial stiffening, and altered haemodynamics. Although exercise training has the potential to reverse this detrimental process, the literature data on the magnitude of improvements and the certainty of evidence are inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of exercise interventions on cardiac morphology, systolic/diastolic function, and haemodynamics in sedentary and obesity-prone individuals. MethodIn accordance with the PRISMA guidelines, the study was conducted by searching the PubMed, Web of Science, and Scopus databases from 1990 to 2025 without applying any filters, using Covidence software. As a result of this comprehensive search, 15 randomised controlled trials (RCTs; N=559) comparing exercise training with a control group in sedentary individuals were included in the analysis. Data were pooled using the Standardised Mean Difference (SMD) and a random-effects model. Publication bias and methodological robustness of the results were tested using the Egger regression test, the Trim-and-Fill method, and Leave-One-Out sensitivity analysis. The certainty of the evidence was graded using the GRADE system. ResultsExercise training was associated with a significant reduction in resting HRs and SBPs, which was a strong improvement in the haemodynamic profile. The improvements in SV and LVEF, although on the statistical threshold in the primary analysis, were statistically significant and methodologically stable in the Leave-One-Out sensitivity analysis, which excluded confounding studies. The exercise training was associated with a marked improvement in the E/A ratio and S wave, and the triggering of a physiological athletes heart-like eccentric hypertrophy, defined by improvements in LVMass and LVEDV. The exercise training was associated with diastolic adaptation and mass increase, with HIIT being the most superior method for diastolic adaptation and mass increase, and aerobic exercise being the most effective method for blood pressure reduction. Importantly, the meta-regression analyses revealed two important findings: first, the improvement in blood pressure and diastolic function was independent of weight loss; second, the improvement in structure and function was linearly related to improvements in body composition. ConclusionExercise acts as a cardiac polypill reversing the sedentary phenotype by improving hemodynamics and diastolic function independently of weight loss, while linking structural remodeling to BMI optimization; our data prioritize HIIT for structural/diastolic gains and Aerobic training for blood pressure control.

BackgroundAngiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are commonly prescribed alongside exercise to manage hypertension in individuals with metabolic syndrome (MetS). However, their potential to interfere with exercise-induced physiological adaptations remains unclear. MethodsIn this prospective, parallel-group study, 62 sedentary obese adults with MetS completed a 16-week supervised high-intensity interval training (HIIT) program. Participants were either chronically medicated with ACEi or ARBs (antihypertensive medication group, AHM, n=27) or a non-medicated control group (CONTROL, n=35). Primary outcomes included changes in resting and graded exercise blood pressure, MetS components, and cardiorespiratory fitness (CRF). ResultsBoth groups exhibited significant comparable improvements (all p time x group > 0.05) in cardiometabolic health (MetS Z-score; AHM -0.22{+/-}0.42; CONTROL - 0.30{+/-}0.33; p time < 0.001) and CRF (VO2MAX: AHM 3.9{+/-}2.1; CONTROL 5.0{+/-}3.1 mL{middle dot}kg-{superscript 1}{middle dot}min-{superscript 1}; p time = 0.003). Resting blood pressure decreased similarly in both groups (Mean Arterial Pressure: AHM -4.2{+/-}8.7; CONTROL -6.5{+/-}6.3 mmHg; both p time = 0.005; p time x group > 0.05). Additionally, antihypertensive medication did not interfere with the maximal (MAP; p time = 0.008) and submaximal (DBP; p time = 0.047) blood pressure exercise responses following training with no significant time x group interaction (both p > 0.05) ConclusionsChronic treatment with angiotensin antagonist medication to treat hypertension does not restrain the effects of supervised HIIT program on improving cardiovascular function, cardiorespiratory fitness, or reducing the components of MetS. Our findings support aerobic exercise training as an effective nonpharmacological co-therapy for hypertensive patients treated with angiotensin antagonists.

BackgroundInflammation plays a key role in atrial fibrillation (AF) pathogenesis. The empirical dietary inflammatory potential (EDIP) score predicts circulating inflammatory biomarkers and adverse cardiac outcomes, but its association with incident AF is unclear. This study aimed to examine the relationship between EDIP score and AF risk. MethodsParticipants from the Atherosclerosis Risk in Communities (ARIC) free of baseline AF who completed a validated food frequency questionnaire were included. Correlation of EDIP with inflammatory biomarkers (factor VIII, fibrinogen, von Willebrand factor, and C-reactive protein) was examined at baseline. Incident AF was ascertained using electrocardiograms, hospital records, and death certificates. Cox proportional hazards models estimated hazard ratios of AF across EDIP quantiles and per SD increase, adjusting for sociodemographic and cardiovascular risk factors. ResultsAmong 8,277 participants (54.1 years old, 51.3% women, 80% white), higher EDIP score correlated with circulating inflammatory biomarkers at baseline. Over a median 24.2 years of follow-up, 1,453 had incident AF (incident rate 8.6 per 1,000 person-years). Compared with the most anti-inflammatory diet (EDIP Q1), the most pro-inflammatory diet (EDIP Q5) was associated with increased AF risk (HR 1.21; 95% CI 1.03-1.43). Sex-stratified analyses showed a stronger association in men (HR 1.43; 95% CI 1.14-1.79), while no significant association was observed in women. ConclusionsPro-inflammatory dietary patterns are independently associated with higher AF risk in a middle-aged cohort. These findings would support incorporating dietary inflammatory load into AF risk stratification. Clinical Perspective What Is New?O_LIHigher Empirical Dietary Inflammatory Potential (EDIP) scores, indicating a more pro inflammatory diet, were associated with an increased long-term risk of atrial fibrillation (AF) in a large, biracial, community-based cohort followed for over two decades. C_LIO_LISex stratified analyses revealed a significant sex difference: higher EDIP scores were consistently associated with increased AF risk in men, whereas no significant association was observed in women, suggesting sex-specific susceptibility to EDIP. C_LIO_LIObesity modified the association between EDIP and AF, with the strongest risk observed among individuals with BMI [&ge;]30, while an inverse or attenuated association was seen among normal weight participants. C_LI What Are the Clinical Implications?O_LIDietary inflammatory load may serve as a meaningful and modifiable upstream AF risk factor, complementing conventional cardiovascular risk assessment, particularly in men and individuals with obesity. C_LIO_LIIncorporating dietary pattern assessment into routine AF risk stratification may help identify individuals who could benefit most from targeted lifestyle interventions. C_LIO_LIPublic health and clinical prevention strategies promoting anti-inflammatory dietary patterns (e.g., increased intake of fruits, vegetables, and whole grains; reduced intake of processed meats and refined carbohydrates) could meaningfully reduce AF incidence. C_LIO_LIRecognition of sex specific differences in AF pathways reinforces the need for personalized preventive strategies, as diet inflammation mechanisms appear to influence AF development more prominently in men. C_LI

BackgroundVitamin D supplementation has been investigated for potential associations with cardiometabolic risk factors related to cardiovascular disease (CVD); however, findings from randomized controlled trials (RCTs) remain inconsistent. This meta-analysis aimed to assess the effects of vitamin D supplementation on cardiometabolic risk factors--including lipid profile, blood pressure, and glycaemic parameters--and to explore whether age and baseline serum vitamin D concentrations modify these associations. Research Design and MethodsWe conducted a systematic review and meta-analysis of RCTs comparing oral vitamin D supplementation with placebo in adults. PubMed, the Cochrane Library, and ClinicalTrials.gov. Risk of bias was evaluated using the Cochrane tool, and pooled effect sizes with 95% confidence intervals (CIs) were calculated using random-effects models. Results14,051 abstracts were retrieved, of which 45 were used for data analysis. Vitamin D supplementation reduced low-density lipoprotein cholesterol (LDL-C) by 0.136 mmol/L (95%CI: -0.215, -0.56), systolic blood pressure by 2.79 mm Hg (95% CI: -4.648, -0.938), fasting blood glucose by -0.11 (95%CI:-0.185, -0.036), and hemoglobin A1c by 0.164% (95%CI: -0.322, -0.006) compared with placebo. Subgroup analyses revealed reductions in SBP and LDL cholesterol among participants aged [&ge;]55 years and reductions in fasting blood glucose in participants with age < 55 years. While favourable effects on fasting blood glucose and hemoglobin A1c were observed with a baseline blood level of vitamin D of concentrations (<50 nmol/L). ConclusionsVitamin D supplementation may be associated with modest modifications in selected cardiometabolic risk factors; including systolic blood pressure, LDL-cholesterol, fasting blood glucose, and hemoglobin A1c. Age and baseline vitamin D status appear to modulate these effects. The clinical relevance of these modest effects remains uncertain. Well-designed RCTs with standardized protocols are required to clarify potential effect modification by age and baseline vitamin D status. Trial RegistrationPROSPERO (CRD42020165293) FundingThis research received funding from the Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan

BackgroundCardiovascular-Kidney-Metabolic (CKM) syndrome is a progressive spectrum where patients often struggle with daily exercise. The "Weekend Warrior" (WW) pattern offers a flexible alternative, but its efficacy across CKM stages remains unclear. We evaluated the association of accelerometer-derived WW activity with cardiovascular outcomes across CKM Stages 0-3. MethodsThis prospective study included 88,832 UK Biobank participants (CKM Stages 0-3). Physical activity was objectively measured via 7-day accelerometry and categorized by weekly moderate-to-vigorous physical activity (MVPA) volume and pattern: Inactive (<150 min), WW ([&ge;]150 min; [&ge;]50% volume in 1-2 days), or Regularly Active (RA). The primary outcome was incident cardiovascular disease (CVD), a composite of coronary heart disease (CHD), heart failure (HF), stroke, atrial fibrillation (AF), and peripheral artery disease (PAD). ResultsDuring a median 7.5-year follow-up, 9,125 incident CVD events were recorded. In fully adjusted models, both WW and RA patterns were associated with similar risk reductions for total CVD (WW: HR 0.87, 95% CI 0.83-0.91, P < 0.001; RA: HR 0.88, 95% CI 0.83-0.94, P < 0.001) and CHD (WW: HR 0.86, 95% CI 0.80- 0.93, P < 0.001; RA: HR 0.86, 95% CI 0.79-0.93, P < 0.001). Notably, the WW pattern demonstrated unique benefits for AF (HR 0.91, 95% CI 0.85-0.99, P = 0.024) and PAD (HR 0.85, 95% CI 0.78-0.93, P < 0.001). In CKM Stage 3, the WW pattern showed a 38% reduction in total CVD risk (HR 0.62, 95% CI 0.47-0.83, P = 0.001) and marked reductions in HF (HR 0.47, 95% CI 0.24-0.90, P = 0.022) and PAD (HR 0.52, 95% CI 0.31-0.89, P = 0.019). Dose-response analysis revealed a non-linear L-shaped association, with CVD risk reductions plateauing at 200-300 min/week of MVPA. Furthermore, the WW pattern significantly offset the risk conferred by high genetic susceptibility and elevated inflammation (Stage 3 with hs-CRP > 3 mg/L: HR 0.46, 95% CI 0.25-0.84, P = 0.012). Both patterns conferred substantial survival advantages, with the WW pattern showing a 24% lower risk of all-cause mortality (HR 0.76, 95% CI 0.70-0.81, P < 0.001). ConclusionsThe WW pattern is associated with significant reductions in CVD risk and mortality across the CKM spectrum. Concentrating activity into 1-2 days is a feasible, safe, and effective strategy, offering unique vascular protection in advanced disease. For CKM patients, achieving total MVPA volume--ideally 200-300 min/week--should be prioritized over frequency.

IMPORTANCEObese subjects with obstructive sleep apnea (OSA) are at risk of pulmonary hypertension (PH) and mortality. Positive airway pressure (PAP) treatment lowers pulmonary artery pressures and mortality risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduces body weight and cardiovascular risk, but their effectiveness in OSA remains unexplored. OBJECTIVETo assess whether GLP-1 RAs is associated with lower incident PH and all-cause mortality at 1 and 3 years in obese patients with OSA treated with PAP. DESIGNRetrospective cohort study. SETTINGUS Collaborative TriNetX Global Database analysis performed on January 5, 2026 encompassing data from 56 centers during December 1, 2017 and December 25, 2025. PARTICIPANTSObese patients diagnosed with OSA and treated with PAP (n=288,587). EXPOSUREPropensity score-matched comparisons of PAP vs PAP+semaglutide, PAP vs PAP+tirzepatide, PAP+semaglutide vs PAP+tirzepatide. MAIN OUTCOMES AND MEASURESIncident PH and all-cause mortality at 1 and 3 years. Risk ratios (RRs) with 95% CIs were estimated using the delta method; number needed to treat (NNT) was calculated from the absolute risk difference. RESULTSCompared with PAP, PAP+semaglutide was associated with lower incident PH at 1 year (RR:0.45; 95% CI:0.44-0.56, NNT=38) and at 3years (RR:0.50; 95% CI:0.45-0.54, NNT=23), and lower mortality at 1 year (RR:0.35; 95% CI:0.33-0.37, NNT=12) and 3 years (RR:0.37; 95% CI:0.35-0.39, NNT=8); PAP+tirzepatide was associated with lower incident PH at 1 year (RR:0.27; 95% CI:0.22-0.34, NNT=28) and 3 years (RR:0.22; 95% CI:0.18-0.27, NNT=15) and lower mortality at 1 year (RR:0.14; 95% CI:0.12-0.17, NNT=9) and 3 years (RR:0.12; 95% CI:0.10-0.14, NNT=6). Compared to PAP+semaglutide, PAP+tirzepatide showed lower incident PH at 1 year (RR:0.51; 95% CI:0.40-0.65, NNT=77) and 3 years (RR:0.42; 95% CI:0.34-0.51, NNT=39) and lower all-cause mortality at 1 year (RR:0.41; 95% CI:0.34-0.49, NNT=40) and 3 years (RR:0.33; 95% CI:0.28-0.39, NNT=22); all p-values<0.001. CONCLUSIONS AND RELEVANCEObese-OSA patients treated with PAP taking GLP-1RAs exhibited significantly lower 1-year and 3-year incident PH and all-cause mortality versus PAP. Tirzepatide exhibited further lowering of incident PH and all-cause mortality versus semaglutide, showing increased and sustained benefits over time. KEY POINTSO_ST_ABSQuestionC_ST_ABSAmong patients with obesity and obstructive sleep apnea (OSA) treated with positive airway pressure (PAP), is use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) associated with lower incident pulmonary hypertension (PH) and all-cause mortality at 1 and 3 years? FindingsIn a cohort study of 288,587 patients, PAP plus semaglutide or tirzepatide was associated with significantly lower incident PH and all-cause mortality versus PAP alone at 1 and 3 years. Tirzepatide was associated with lower risks than semaglutide. MeaningGLP-1 RAs may provide additional clinical benefit in obese patients with OSA treated with PAP.

We performed a systematic review and meta-analysis of randomized controlled trials evaluating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus placebo in adults with heart failure (HF), searching PubMed, Cochrane CENTRAL, and ClinicalTrials.gov through February 2026. The primary outcome was the composite of cardiovascular death and first HF hospitalization. Random-effects meta-analysis used restricted maximum likelihood estimation with Hartung-Knapp-Sidik-Jonkman adjustment. We included 14 studies (6 dedicated HF trials and 8 cardiovascular outcomes trial HF subgroup analyses) encompassing 18,558 patients, of whom 2,499 were randomized in dedicated HF trials. The primary composite did not reach statistical significance (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.73-1.01; P=0.067; I2=47%). GLP-1 RAs significantly reduced all-cause mortality (HR 0.87, 95% CI 0.81-0.93; P<0.001; I2=0%), major adverse cardiovascular events (HR 0.83, 95% CI 0.73-0.95; P=0.019), and improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (+7.4 points, 95% CI 6.3-8.5) and 6-minute walk distance (+17.6 m, 95% CI 13.4-21.7). Excluding the FIGHT trial (acute HFrEF) yielded a significant primary composite (HR 0.83, P=0.011). The mortality signal was driven primarily by CVOT subgroups; the largest dedicated HFpEF trial (SUMMIT) showed numerically higher mortality (HR 1.25). The strongest evidence supports GLP-1 RAs in HFpEF with obesity. HighlightsO_LIPrimary composite of CV death + HHF was not significant (HR 0.86, P=0.067) C_LIO_LIGLP-1 RAs reduced all-cause mortality (HR 0.87) with no heterogeneity C_LIO_LIKCCQ-CSS improved by 7.4 points and 6MWD by 17.6 m in HFpEF trials C_LIO_LIMortality benefit driven by CVOT subgroups, not dedicated HF trials C_LIO_LIStrongest evidence supports GLP-1 RAs in HFpEF with obesity C_LI

BackgroundLeft ventricular hypertrophy (LVH) is a major independent risk factor for cardiovascular disease and is the leading cause of death among all U.S. groups, including Hispanic/Latino adults. LVH is commonly seen in the setting of hypertension and there is evidence that psychological factors, such as depression and anxiety, are risk factors in hypertension development. ObjectiveTo evaluate the association between symptoms of depression and trait anxiety with incident LVH among U.S. Hispanic/Latino adults. MethodsThe Hispanic Community Health Study/Study of Latinos is an ongoing population-based observational cohort study of Hispanic/Latino adults. Participants were examined in 2008-2011 at visit 1 (V1) and in 2014-2017 visit 2 (V2). Symptoms of depression and trait anxiety were assessed by self-reported questionnaire collection. LVH was assessed by echocardiography at V2. Multivariable Poisson regression models were used to determine the associations between symptoms of depression and trait anxiety at V1 with incident LVH at V2 among 6,612 participants after adjustment for potential confounders. All analyses accounted for the complex survey design and incorporated study weights. ResultsAfter an average follow-up of 6.0 years, the age-standardized cumulative incidence of LVH was 5.4% (95% CI: 4.9, 6.1). The cumulative incidence of LVH was higher among participants with (10.4%, 95% CI: 8.6, 12.4) compared to without elevated symptoms of depression (5.1%; 95% CI: 4.4, 5.9). Compared with the lowest trait anxiety tertile (5.2%; 95% CI: 4.3, 6.3), the cumulative incidence of LVH was higher in the highest trait anxiety tertile (9.6%; 95% CI: 8.1, 11.5). In multivariable Poisson models, each standard deviation increment in symptoms of depression was associated with a 10% greater liklihood (IDR:1.10, 95% CI: 1.00, 1.20) of LVH at V2. However, symptoms of trait anxiety at visit 1 were not independently associated with LVH at visit 2. ConclusionGreater depressive but not trait anxiety symptomatology was associated with LVH over six years. In fully adjusted models, a one-unit increase in depression symptomatology was associated with a 10% greater likelihood of LVH. Further studies are needed to examine the etiological role of negative affective psychological regulation.

Background and objectiveCardiovascular disease (CVD) is highly prevalent affecting one in six Australians. Tooth loss has consistently been associated with an increased risk of CVD, influenced by social determinants of health as well as effects on chewing function and diet. However, there is little evidence regarding the role of diet on the relationship between tooth loss and CVD. This study aimed to determine the impact of retaining a functional dentition (minimum of 20 teeth) on the risk of incident CVD and the role of diet in this relationship. MethodsThis prospective cohort study recruited Australian women from the 1946-51 cohort of the Australian Longitudinal Study on Womens Health. Tooth loss and diet quality were assessed from survey 5 (2007) and incident CVD from linked data over a 17-year follow-up period (2024). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for known risk factors (age, sociodemographic, lifestyle and medical history factors). ResultsA total of 8306 women, average age 58.5 {+/-} 1.5 years, 69.2% with a functional dentition were included. Over the 17-year follow-up period 1432 (17.2%) women developed incident CVD. The presence of a functional dentition was associated with a lower risk of incident CVD compared to women with a non-functional dentition, 15.5% vs 21.1% respectively, [HR 0.83 (95% CI 0.74, 0.93)]. A greater proportion of women with a functional dentition had a high-quality diet score, compared to those with a non-functional dentition (42% vs 36%, p <0.001). Controlling for diet quality did not attenuate this association [HR 0.82 (95% CI 0.73, 0.92)]. ConclusionAlthough tooth loss negatively impacts diet quality, dietary changes alone do not explain why tooth loss is a marker of incident CVD and loss of a functional dentition should prompt cardiovascular prevention action. What is already known on this topicO_LIPrevious studies have shown consistent associations between tooth loss and both a higher risk of cardiovascular disease, and poor diet quality. The role of diet in the relationship between tooth loss and cardiovascular disease is unclear. C_LI What this study addsO_LIThis prospective analysis of 8306 Australian women shows that maintaining a functional dentition (minimum 20 teeth) is associated with a lower risk of incident cardiovascular disease. C_LIO_LIRetaining teeth as part of a functional dentition is associated with a better diet quality. C_LIO_LIThe relationship between tooth loss and cardiovascular disease is not attenuated when adjusted for diet. C_LI How this study might affect research, practice or policyO_LILoss of a functional dentition should serve as a trigger for cardiovascular preventive measures C_LIO_LIDietary changes alone do not explain why tooth loss is a marker of incident cardiovascular disease, further research on the role of systemic inflammation is required. C_LI

Longstanding evidence demonstrates that integrating sex-based biological factors and gendered social factors in health research enhances understanding of variation in risk factors, symptoms, progression, diagnoses, and treatments of diseases, and leads to more targeted interventions and improved health outcomes. Sex and gender-based analysis (SGBA) provides a framework for integrating sex/gender and other social constructs and locations throughout the research cycle, addressing the fundamental question: to whom does the evidence apply? Cardiovascular disease (CVD), as the major cause of mortality for men and women globally, and the major cause of premature death in women in Canada, provides a prime example of the gap between evidence that sex/gender matters and the routine uptake of SGBA in practice. This paper addresses some of the transformations needed to overcome this gap by exploring scientists perspectives on how sex/gender considerations can be routinely integrated in basic and clinical CVD research. Grounded in key informant interviews with 19 federally-funded CVD scientists in Canada, our thematic analysis generated three themes highlighting how barriers to integrating sex/gender in basic and clinical research practice become embedded in the everyday doing of research: (1) The science of sex/gender gets lost in practice, (2) Institutional and systemic processes maintain the status quo, and (3) Change must centre on accountability and community. While scientists appreciated how SGBA could strengthen research veracity, they identified major obstacles as well as mundane institutional practices and procedures that reinforced the status quo and impeded more varied approaches to research and data collection. Drawing together the bricolage of insights, examples, and suggestions provided by the scientists we spoke with, we offer key actions and guidance towards greater inclusivity of sex/gender in the scientific paradigm, and specifically, in CVD research that shapes clinical practice.

ObjectiveTo examine the association between Atherogenic Index of Plasma (AIP) and subclinical myocardial injury (SCMI), and their combined impact on cardiovascular disease (CVD) mortality in the general population. MethodsThis analysis included 7,093 participants without CVD from the Third National Health and Nutrition Examination Survey. AIP was calculated as the logarithmic ratio of triglycerides to HDL cholesterol. Participants were stratified into low or high AIP groups based on the median AIP value (0.958). Electrocardiographic SCMI was defined as Cardiac Infarction/Injury Score [&ge;]10 points. CVD mortality data were obtained from the National Death Index. Multivariable logistic regression models assessed the baseline cross-sectional association between AIP and SCMI, while Cox proportional hazards models examined the relationship between different baseline AIP/SCMI groups and CVD mortality. ResultsHigh AIP was associated with increased odds of SCMI [OR(95% CI): 1.20(1.07-1.35)] in multivariable logistic regression analysis. In multivariable Cox proportional hazard models, compared to participants with low AIP and absent SCMI, those with SCMI had a higher risk of CVD mortality regardless of AIP level [(HR(95% CI) 1.28(1.05-1.57) and 1.33(1.10-1.60)]. However, high AIP without SCMI was not associated with CVD mortality [HR (95% CI) 0.94(0.79-1.11)]. ConclusionsHigh AIP was associated with an increased risk of SCMI. SCMI was linked to a higher risk of CVD mortality regardless of AIP levels, while high AIP was only associated with CVD mortality when SCMI was present, suggesting that the reported adverse outcomes linked to high AIP may be driven by the development of SCMI.

BackgroundCarbohydrate-restricted diets are gaining popularity, including among lean individuals. In these populations, a lipid phenotype often emerges comprising elevated LDL cholesterol (LDL-C), alongside elevated HDL-C and low triglycerides, termed the lean mass hyper-responder (LMHR). ObjectiveTo evaluate one-year coronary plaque progression in LMHRs and near-LMHRs. MethodsThis prospective study followed 100 participants who developed the triad of high LDL-C, high HDL-C, and low triglycerides after adopting a ketogenic diet over one year. Coronary plaque changes were assessed using coronary CT angiography and analyzed using the prespecified QAngio(R) methodology (Leiden, the Netherlands), with AI-enabled coronary plaque analysis (AI-CPA; HeartFlow(R) Inc., Mountain View, CA) used as an independent, blinded confirmatory analysis. Plaque burden and plaque progression predictors were examined using linear regression. ResultsAll 100 participants with elevated LDL-C and a mean BMI of 22.5 {+/-} 2.7 kg/m2 completed the study. At baseline, 57 (57%) had zero CAC. After follow-up, most participants remained with low-risk plaque burden markers: 81% of participants had a CAC score <100, and 54% had a CAC of 0. The median increase in non-calcified plaque volume was 5.6 mm3 (37% relative increase). Notably, 15% of participants exhibited plaque regression despite sustaining elevated LDL-C (mean 242 mg/dL) and ApoB (mean 180 mg/dL). Additionally, 78% had percent atheroma volume (PAV) below the high-risk threshold of 2.6%, and 93% had total plaque volume (TPV) below the high-risk threshold of 254 mm3. Baseline plaque metrics were consistently predictive of plaque progression. By contrast, neither ApoB levels nor cumulative LDL-C exposure predicted plaque progression in this population of LMHR and near-LMHR individuals. ConclusionThese findings suggest that over one year, progression was modest and heterogeneous in this population, with baseline coronary plaque emerging as the strongest predictor of subsequent plaque progression in LMHRs, whereas traditional lipid markers such as ApoB and LDL are not.

BackgroundThe relationship between functional tooth units (FTU) and cardiovascular diseases (CVD) risk remains understudied. This study is to investigate the association between masticatory performance, measured by FTU, and CVD incidence and CVH, and mortality among individuals with CVD using data from the National Health and Nutrition Examination Survey (NHANES). MethodsMasticatory function was measured by FTU, CVD was determined by the self-reported questionnaire, CVH was assessed using the American Heart Associations Lifes Simple 7 (LS7), Lifes Essential 8 (LE8), and Lifes Crucial 9 (LC9). CVD mortality was determined from the National Death Index. Weighted logistic, linear regression and cox proportional hazards models were used to evaluate the associations between FTU and CVD incidence, CVH and mortality. ResultsHigher FTU was associated with a reduced risk of CVD. Participants with FTU scores of 9-12 had a 46% reduced risk of CVD compared to those with FTU scores of 0-3. FTU was also positively correlated with better CVH scores in LS7, LE8 and LC9. In the mortality analysis, those with FTU of 9-12 was associated with a 42%, 39% and 71%% reduction in all-cause, CVD- and cancer related mortality. The other masticatory function parameters and sensitivity analyses confirmed these relationships. ConclusionPreservation of masticatory function, measured by FTU, is associated with decreased CVD prevalence, improved CVH and reduced mortality in individuals with CVD. These findings suggest that the maintenance of optimal masticatory function may play a protective role in reducing CVD incidence and mortality. Clinical relevanceO_ST_ABSWhat is New?C_ST_ABSThis study provides novel insights into the association between masticatory function, assessed by functional tooth units (FTU), and cardiovascular disease (CVD) outcomes in individuals with CVD. It demonstrates that higher FTU scores are linked to a significantly lower risk of CVD, improved cardiovascular health (CVH) scores, and reduced mortality, including CVD- and cancer-related deaths. Importantly, this is one of the first studies to show the potential role of masticatory function as a modifiable factor in cardiovascular health and mortality reduction in a large, nationally representative cohort. What Are the Clinical Implications?The findings highlight the importance of maintaining masticatory function as part of a comprehensive approach to CVD prevention and management. Clinicians should consider the role of oral health, specifically masticatory function, in improving cardiovascular health outcomes and reducing mortality risk in CVD patients. These results suggest that enhancing masticatory function may be a simple, yet effective intervention for reducing CVD incidence and mortality, emphasizing the need for oral health preservation in clinical practice, particularly among individuals with cardiovascular disease.

BackgroundElevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease. Despite available lipid-lowering therapies (LLT), lipid control remains suboptimal. Bempedoic acid offers a non-statin oral treatment for hypercholesterolemia. However, real-world data in Asia are limited. The study aimed to investigate the effectiveness and safety of bempedoic acid in Taiwan. MethodsThis pragmatic phase IV study enrolled 180 patients with inadequately controlled hypercholesterolemia to receive bempedoic acid for 12 weeks in addition to background LLT. The primary endpoint was the percentage change in LDL-C. Secondary endpoints included changes in other lipid parameters, high-sensitivity C-reactive protein (hsCRP), and safety outcomes. ResultsAmong 180 patients, 160 (88.9%) completed the study. The median percentage change in LDL-C from baseline to week 12 was -19% (interquartile range [IQR]: -36.4% to -3.6%), decreasing from 117.5 to 92 mg/dL (p < 0.01). The median percentage changes from baseline to week 12 were -13.3% for non-high-density lipoprotein cholesterol (non-HDL-C), -10.8% for total cholesterol, -11.5% for apolipoprotein B, and -34.0% for hsCRP (all p < 0.01). Minimal effects were noted on triglycerides (+0.2%), HDL-C (-5.5%), and lipoprotein(a) (+2.6%) (all p > 0.05). At week 12, 31.3% of patients achieved LDL-C targets (< 100 mg/dL for primary prevention; < 55 or < 70 mg/dL for secondary prevention). The safety outcomes were consistent with the locally approved label, with no new safety signals identified. ConclusionsBempedoic acid offers an effective and safe oral therapeutic option for Taiwanese patients whose LDL-C levels remain inadequately controlled with existing LLT, including statins. RegistrationURL: https://clinicaltrials.gov/study/NCT06925100; Unique identifier: NCT06925100 Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABS{diamondsuit} This pragmatic phase IV study provides the first real-world evidence from Taiwan demonstrating that bempedoic acid leads to clinically meaningful reductions in LDL-C (median percentage change: -19%) at week 12 when added to background lipid-lowering therapy in patients with inadequately controlled hypercholesterolemia. {diamondsuit}Approximately one-third of patients achieved guideline-recommended LDL-C targets within 12 weeks, with a safety profile consistent with the locally approved label and no new safety signals identified. What Are the Clinical Implications?{diamondsuit} Bempedoic acid represents an effective and well-tolerated oral add-on lipid-lowering option for Taiwanese patients who fail to achieve LDL-C goals with existing therapies, including those unable to tolerate or intensify statin treatment.

AbstractRespiratory training benefits chronic heart failure (CHF) patients but is underused due to multiple barriers. Lifestyle-based active pursed-lip diaphragmatic breathing (PLDB) offers a feasible, device-independent alternative. This study aimed to evaluate its impact on CHF patients exercise tolerance, cardiac function, quality of life, and clinical outcomes. A prospective cohort study enrolled 58 hospitalized CHF patients (NYHA II-IV, Jan 2023-Feb 2024). All received standard therapy and PLDB instruction. Post-discharge, patients who self-administered PLDB were monitored via WeChat and grouped by adherence: the PLDB group ([&ge;]30 breaths/day, [&ge;]3 days/week, n=20) and the Control group (non-compliant, n=38). Outcomes included 6-minute walk test (6MWT), grip strength, serum N-terminal pro-brain natriuretic peptide, left ventricular ejection fraction (LVEF), and quality of life indicators (Minnesota Living with Heart Failure Questionnaire [MLHFQ], Self-rating Somatic Symptom Scale-China [SSS-CN], Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 [GAD-7], Pittsburgh Sleep Quality Index). Clinical endpoints were rehospitalization and major adverse cardiovascular events (MACE). Over 6 months, the PLDB group showed significant improvements in 6MWT (333.75 {+/-} 148.57 m to 407.9{+/-}153.29m, p=0.012), LVEF (46.67{+/-}13.86% to 51.81{+/-}14.89%, p=0.002), and quality of life (MLHFQ: 42.25{+/-}16.00 to 18.75{+/-}13.47, p<0.001; GAD-7: 3.90{+/-}3.81 to 1.50{+/-}2.14, p=0.029; SSS-CN: 35.35{+/-}5.84 to 29.05{+/-}8.61, p=0.005), with lower MACE incidence and higher MACE-free survival. Six-month lifestyle-based active PLDB training improves exercise capacity, cardiac function, quality of life, and reduces MACE in CHF patients, serving as an effective, practical rehabilitation strategy.

IntroductionCircadian misalignment is an emerging risk factor for poor cardiovascular health, and chronotype may reflect underlying circadian processes. While previous conventional observational studies have reported adverse associations between evening chronotype and individual cardiovascular risk factors, Mendelian randomization (MR) may provide further insights into the role of chronotype in overall cardiovascular health, as measured by the American Heart Associations Lifes Essential 8 (LE8; a composite lifestyle and cardiovascular health score ranging from 0 to 100; higher scores indicate better health). MethodsWe conducted both observational cross-sectional and one-sample MR analyses among 317,730 UK Biobank (UKB) participants of White ethnicity. Chronotype was self-reported and modeled on a five-level continuous scale from "definitely evening" to "definitely morning". A polygenic risk score including 341 morning chronotype-associated SNPs from a UKB GWAS served as the MR instrument. Two-stage least-squares regression estimated difference in LE8 per one-unit increment in chronotype towards more morningness, adjusting for age, sex, assessment center, genotyping batch, and 40 genetic principal components. To mitigate potential winners curse bias in UKB due to inflated GWAS estimates, we replicated the analysis in 13,396 White women in the Nurses Health Study II (NHSII). ResultsIn UKB, the multivariable-adjusted difference in LE8 score for each one-unit increment toward more morningness was 0.75-points higher (95% CI: 0.72, 0.78; P<0.001) in observational analysis and a 0.75-points higher (95% CI: 0.55, 0.96; P<0.001) in MR analysis. MR results were similar for men and women (P-heterogeneity = 0.70). In NHSII, while both estimates were positive, increased morningness was associated with higher overall LE8 scores in observational analysis ({beta} = 1.57, 95% CI: 1.40, 1.75; P<0.001), but not in MR analysis ({beta} = 0.89, 95% CI: - 0.67, 2.44; P = 0.26), although the MR association became significant when the score was based only on behavioral components ({beta} = 2.04; 95% CI: 0.43, 3.65; p = 0.0130). Further, morning chronotype was consistently associated with healthy diet across observational and MR analyses in both cohorts. ConclusionsOur findings suggest a modest causal relationship between morning chronotype and better cardiovascular health profiles, particularly diet quality, although replication in other populations remains necessary.

BACKGROUNDCardiorespiratory fitness (CRF) is a strong predictor of cardiovascular risk, yet scalable approaches to improve CRF among adults with high-normal or high blood pressure (BP) remain limited. Telehealth lifestyle programs may address this gap, but trials with rigorous CRF endpoints are scarce. METHODSWe conducted a two-center, assessor-blinded, randomized controlled trial in Beijing and Shenzhen, China, from July 2022 to September 2024. Adults with high-normal or high BP were enrolled and randomized 1:1 to a telehealth-based lifestyle modification program (Tele-LM) or enhanced usual care (EUC), stratified by BP category. Tele-LM combined app-based dietary coaching, individualized aerobic and resistance prescriptions, home BP monitoring, and motivational interviewing. EUC comprised standardized lifestyle counseling, home BP monitoring, and educational resources. The primary outcome was change in peak oxygen uptake (VO2peak) at 3 months. Secondary outcomes included changes in VO2peak at 9 months, home, ambulatory and office BP, lifestyle behaviors, metabolic parameters, and medication use. Analyses followed the intention-to-treat principle with multiple imputation for missing data. RESULTSAmong 424 randomized participants (mean age 50 years; 65% men), 314 completed the 3-month assessment and 377 completed the 9-month assessment. At 3 months, the adjusted between-group difference in VO2peak change favored Tele-LM by 1.5 mL/kg/min (95% confidence interval [CI], 0.6 to 2.3; P=0.001); at 9 months, a smaller difference persisted (1.0 mL/kg/min [95%CI, 0.1 to 1.9]; P=0.027). Subgroup analyses by BP category (randomization strata) revealed no significant heterogeneity for VO2peak. Tele-LM produced greater 3-month reductions in home BP (systolic BP -3.3 mmHg [95% CI, -5.3 to -1.4]; diastolic BP -2.6 mmHg [95%CI, -3.9 to -1.3]) and in 24-hour ambulatory BP (systolic BP -3.3 mmHg [95%CI, -6.0 to -0.6]; diastolic BP -1.9 mmHg [95%CI, -3.6 to -0.3]); between-group differences generally attenuated by 9 months. Adverse events were infrequent and similar between groups; no serious adverse events were observed. Average antihypertensive medication intensity was modestly lower in the Tele-LM (-0.27 agents [95% CI, -0.44 to -0.10]). Findings were consistent across prespecified sensitivity analyses. CONCLUSIONSIn adults with high-normal or high BP, telehealth lifestyle modification with minimal in-person contact significantly improved CRF and modestly lowered BP, supporting its scalability as a complement to routine hypertension care. REGISTRATIONURL: https://www.clinicaltrials.gov; Unique identifier: NCT05528068. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LIThis randomized trial evaluated a comprehensive telehealth-based lifestyle modification program, combining app-based dietary coaching, individualized aerobic and resistance prescriptions, wearable integration and motivational interviewing, in adults with high-normal blood pressure or well-controlled hypertension. C_LIO_LITelehealth-based lifestyle modification significantly improved cardiorespiratory fitness and modestly reduced blood pressure compared with enhanced usual care. C_LI What Are the Clinical Implications?O_LITelehealth lifestyle programs can extend preventive care to large at-risk populations with minimal in-person contact. C_LIO_LIBy reducing reliance on pharmacologic intensification and conserving healthcare resources, telehealth-based strategies offer a cost-effective model for scalable cardiovascular prevention. C_LIO_LISustaining adherence remains essential to maximize long-term benefits. C_LI

BackgroundLong-term electrocardiogram (ECG) monitoring with wearable devices enables large-scale characterisation of cardiac rhythms, but population-based evidence remains limited. The UK Biobank Cardiac Monitoring Study integrates 14-day patch-based ECG monitoring with accelerometry and detailed phenotypic and lifestyle data. Here, we report the acquisition protocol, data processing, and initial findings from 27,658 participants. MethodsParticipants in the UK Biobank imaging study were invited to undergo 14-day cardiac monitoring using a Zio XT (pilot phase; 2015-18) or BodyGuardian MINI (main phase; 2019- ongoing) monitor. ECGs were analysed by certified technicians and automated algorithms to identify atrial, ventricular, and conduction arrhythmias. In parallel, beat-to-beat RR intervals were derived using in-house algorithms, and physical activity from calibrated triaxial accelerometer data. Analyses assessed wear time, arrhythmia prevalence, circadian patterns, and repeatability. FindingsIn total, 27,658 participants (mean age 71 years; 49.9% women) were analysed, including 7,795 from the pilot phase and 21,141 from the main phase; 1,353 (4.9%) had repeat recordings. In the main phase, median wear time was 13.2 days (IQR 11.9-13.9), and undiagnosed atrial fibrillation (AF) was detected more frequently in men than women (3.2% vs 1.7%; p<0.001); 68% was paroxysmal, with 27.4% detected during week two. Ventricular tachycardia occurred in 12.1% (8.4% in women), with sustained episodes rare (0.4%) but observed. Arrhythmia timing varied markedly with activity, with AF peaking during nocturnal inactivity and ventricular ectopy increasing during activity, peaking at midday. Repeat assessments showed strong reproducibility of diurnal heart rate and activity profiles, with more modest arrhythmia consistency. InterpretationExtended ECG monitoring enables detection of subclinical arrhythmias and long-term physiological rhythms in older adults. Linkage to imaging, multi-omics, and clinical outcomes in UK Biobank will enable unprecedented evaluation of the natural history of asymptomatic rhythm disturbances and their impact on brain health. FundingBritish Heart Foundation and Wellcome Trust.

BackgroundKetone bodies have shown potential to improve cardiac metabolism and function in patients with heart failure (HF). ObjectiveTo evaluate the effects of exogenous ketone-based interventions on cardiac function in patients with HF or related cardiometabolic risk factors. MethodsWe conducted a systematic review based on a search of MEDLINE, EMBASE, CINAHL, Cochrane Library, and Scopus from inception to January 2025. Eligible studies included randomized controlled trials evaluating exogenous ketones (oral ketones or ketone infusions) compared to placebo in adults with HF or patients with risk factors for HF including type 2 diabetes mellitus, hypertension, or coronary artery disease. Paired reviewers independently screened and identified hits at title-and-abstract and full-text levels to determine eligibility and extracted data from eligible studies. Random-effects meta-analysis was performed. Effects of interventions were summarized as mean differences (MD). Risk of bias was assessed using Cochrane RoB 2.0 tool. Certainty of evidence was evaluated using the GRADE (grading of recommendations assessment, development and evaluation) approach. ResultsOut of 565 unique records, 22 full-text articles were reviewed, and 8 studies met inclusion criteria. Exogenous ketone administration increased left ventricular ejection fraction (LVEF) (MD = 3.94, 95% CI 2.18-5.70, p = 0.001), cardiac output (CO) (MD = 1.11 L/min, 95% CI 0.55-1.67, p = 0.002), heart rate (4.85 bpm, 95% CI 2.24-7.46, p = 0.003), and stroke volume (SV) (MD = 10.21 mL, 95% CI 4.06-16.35, p = 0.005). Pulmonary capillary wedge pressure (PCWP) decreased (MD = -0.93 mmHg, 95% CI -1.44 to -0.43, p = 0.003), while mean arterial pressure showed no change (MD = -1.37 mmHg, 95% CI -3.53 to 0.79, p = 0.18). ConclusionsExogenous ketone-based therapies are associated with improvements in hemodynamic markers of cardiac function, including increases in LVEF, CO, and SV, along with a reduction in PCWP. These findings suggest that ketone supplementation may offer clinical benefits for patients with HF or vascular disease.