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.

BACKGROUNDObesity and metabolic abnormalities were associated with increased risk of cardiovascular diseases (CVD). However, much remains unknown about which metabolic weight phenotypes and how relate to CVD, especially in postmenopausal women. METHODS AND RESULTSWe included 15,575 postmenopausal women aged 35 to 75 years (median age, 60.6 [IQR: 55.0-65.7]) free of CVD at baseline from a subcohort of the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project between 1 January 2016 and 31 December 2020 in Guangdong Province at 8 sites. Cox regression models were used to investigate the associations of metabolic and overweight/obese status with the risk of developing CVD. Over a median follow-up period of 3.32 years, a total of 1354 CVD events occurred. Overall, 30.3% were metabolically heathy among the 9404 overweight/obese participants, while 49.2% were metabolically unhealthy among the 6171 normal weight subjects. Compared with the metabolically healthy normal weight group, the remaining three groups of participants were all at higher risk of combined CVD, with multivariate-adjusted hazard ratios and 95% confidence intervals of 1.41 (1.16-1.71) for metabolically unhealthy normal weight, 1.42 (1.16-1.73) for metabolically healthy overweight/obesity, and 1.75 (1.47-2.07) for metabolically unhealthy overweight/obesity. When subdividing overweight/obesity separately into overweight and obesity, combined CVD risk was only greater in metabolically unhealthy individuals across different weight categories. CONCLUSIONSPostmenopausal women with metabolically healthy overweight/obesity and metabolically unhealthy normal weight had a higher risk of cardiovascular disease than those with metabolically healthy normal weight, and the association of metabolically unhealthy overweight/obesity was greatest among four categories, suggesting that metabolic abnormalities and overweight/obesity should be monitored and controlled. CLINICAL PERSPECTIVEWhat Is New? O_LIPostmenopausal women with metabolic abnormalities combined with overweight/obesity and even normal weight had a higher risk of cardiovascular disease (CVD) than those with metabolically healthy normal weight. C_LIO_LIMetabolically healthy overweight/obesity were associated with greater risk of CVD, indicating that overweight/obesity alone may contribute to CVD risk in postmenopausal women. C_LI What Are the Clinical Implications? O_LIIndividuals who are metabolically unhealthy and overweight/obese warrant close clinical supervision, while those of normal weight should not be ignored. C_LI

Evidence supports associations of lifestyle-including diet and physical activity--and weight with cognitive functioning, but the pathways responsible for these associations have not been fully elucidated. Because healthier lifestyles have been associated with better left atrial structure and function, which in turn is associated with better cognitive functioning, we tested the hypothesis that left atrial structure and function is a potential mediator of the association between lifestyles and cognition. We included 476 participants with overweight or obesity and metabolic syndrome from three centers in Spain who underwent lifestyle assessment and transthoracic echocardiography at baseline and had repeated measurements of the Trail Making A test, a measure of executive function, at baseline and at the two-year follow-up. We conducted mediation analyses to test if measures of left atrial structure and function mediated associations between adherence to the Mediterranean diet scores, physical activity, or weight at baseline, and two-year change in Trail Making A scores. The analysis did not find an effect between these factors and Trail Making A scores, and no indirect effects mediated through the echocardiographic measurements. The modest sample size in this analysis is a limitation, and larger studies should be conducted to determine potential cardiovascular factors mediating the association between lifestyle and cognition.

Background The postmenopausal period is associated with a more adverse cardiometabolic risk factor profile as well as unfavourable cardiac remodelling patterns. However, it remains unclear whether and how the associations between risk factors and cardiac remodelling differ before and after menopause and in the corresponding age groups in men. Methods We used cross-sectional data from the baseline examination of the population-based German National Cohort (NAKO, age range 19-74 years). Cardiovascular resonance imaging (CMR) was performed on 3T MRI, and morphofunctional data of both ventricles were derived from standard short-axis cine balanced steady-state free precession. Associations between cardiometabolic risk factors and cardiac parameters were evaluated using adjusted multivariable linear regression, stratified by menopausal status in women and age group (<50 / [&ge;]50 years) in men. Results The final sample comprised 20,152 participants (40% women; mean age 47{+/-}12 years) from the NAKO MRI subsample. Cardiometabolic risk factor profiles differed across the stratified groups, with higher systolic blood pressure and less favourable lipid profiles in older participants. Ventricular volumes declined and concentric remodelling increased with age in both sexes, with a steeper age-related pattern observed in women than in men. Higher BMI in women was associated with higher left ventricular concentricity index (LVCI) in postmenopausal than in premenopausal women (0.097 vs. 0.047; p for difference = 0.016). Associations between triglycerides and ventricular volumes were strongest in premenopausal women and significantly stronger than in men younger than 50 years (e.g., right ventricular end-diastolic volume (RVEDV): -0.173 vs. -0.064, p for difference < 0.001). Sleep problems were more strongly associated with cardiac parameters in men, with significant sex differences in older men compared with postmenopausal women (e.g. left ventricular end-diastolic volume (LVEDV): -0.105 vs. 0.043, p for difference = 0.023). Conclusions Less favourable cardiac remodelling observed in postmenopausal women appeared to be associated with a higher burden of cardiometabolic risk factors rather than stronger associations between these risk factors and cardiac structure. Several associations showed sex- and age-specific patterns, including Body Mass Index (BMI), triglyceride levels, and sleep problems. These findings highlight the importance of controlling cardiometabolic risk factors across adulthood, and raising awareness for sex-specific differences.

BackgroundConflicting results have been reported as to the relative importance of apoA-1 versus HDL-C as markers of ASCVD risk. MethodsResidual discordance analysis with Cox proportional hazard models comparing apoA-1 and HDL-C as markers of ASCVD risk was applied to a sample of 291,995 UK Biobank, followed for a median of 11 years. Interaction test for the two markers and estimation of the effects of partitioning HDL-C into apoA-I, log-triglyceride and the remaining residual were also performed. ResultsApoA-1 and HDL-C had similar associations with ASCVD risk (HRs of 0.85, p-value < 0.001 for both). The residual of HDL-C added significantly to the risk associated with apoA-1 as did the residual of apoA-1 to HDL-C. There was a statistically significant interaction between apoA-I and HDL-C (HR=1.05, 95% CI: (1.04, 1.06); p < 0.001). Decomposing HDL-C into the 3 components, apoA-I accounted for the largest portion of the effect with a HR of 0.85 95%CI: (0.83, 0.86) with smaller effects for lnTG: 1.04 (1.02, 1.06) and residual of HDL-C: 0.98 95%CI: (0.96, 0.995). ConclusionsHDL-C and apoA-1 have associations of equivalent strength with ASCVD risk with significant interaction modifying the effect of one by the other. Upon decomposition, ApoA-I retained more of the effect of HDL-C as compared to log-triglycerides. While only observational, the results are consistent with the relation of HDL to risk not being determined by the concurrent level of triglyceride. Clinical PerspectiveThe plasma levels of HDL-C and apoA-I are potent predictors of cardiovascular risk. However, there are few data comparing the relative precision of HDL-C and apoA-I for this purpose. Moreover, the risk of low HDL-C has been attributed to concurrent hypertriglyceridemia, consequently downgrading the potential importance of HDL in predicting or explaining risk. Novel FindingsBased on residual discordance analysis, HDL-C and apoA-I have similar predictive precision for ASCVD risk. However, each adds significantly to the other and. Moreover, triglycerides account for only a small portion of the risk attributable to HDL with apoA-I accounting for the principal portion. Clinical SignificanceHDL, whether measured as HDL-C or apoA-I, is a potent predictor of ASCVD risk. It remains essential to search for the biological basis or bases for these relationships.

BackgroundChronic psychological distress has been associated with increased risk of cardiovascular disease (CVD). However, mechanistic evidence explaining the observed associations remains limited and, with data are particularly sparse among women. This study examined if a metabolite profile linked with distress would be associated with increased risk of CVD. MethodsA plasma metabolite-based distress score (MDS) of twenty metabolites was derived in a cross-sectional, 1:1 matched case-control dataset (n=558 women) in the Nurses Health Study (NHS). We then calculated this score in two other cohorts, the Womens Health Initiative Observational Cohort (WHI-OS) and the Prevencion con Dieta Mediterranea (PREDIMED) trial, and tested association with risk of developing adjudicated measures of CVD in each cohort. We considered incident coronary heart disease (CHD) in the WHI-OS dataset which included 944 postmenopausal women (472 CHD cases; mean time to event of 5.8 years), and incident CVD (including stroke, myocardial infarction, CVD death) in the PREDIMED dataset which included 980 men and women (224 CVD cases, mean time to event of 3.1 years). ResultsIn the WHI-OS, a 1-SD increase in the plasma MDS was associated with a 14% increased risk of incident CHD (odds ratio [OR]=1.14, 95% CI: 1.03 - 1.26), adjusting for known CVD risk factors excluding total and HDL cholesterol. This association was attenuated after including total and HDL cholesterol (OR=1.09; 95% CI: 0.98 - 1.21). Of the component metabolites in the MDS, tryptophan and threonine were inversely associated with incident CHD risk. In PREDIMED, each one SD increase in the MDS was associated with a 17% increased incident CVD risk (OR=1.17, 95% CI: 1.00 - 1.38), after adjusting for risk factors including total and HDL cholesterol. Similar associations were observed in men and women. Four individual metabolites in the MDS were associated with incident CVD risk in fully adjusted models in PREDIMED. Biliverdin and C36:5 PC plasmalogen had inverse associations, whereas C16:0 ceramide and C18:0 LPE each had positive associations with CVD risk. ConclusionsOur study sheds light on the key molecular alterations that characterize chronic distress and are predictive of subsequent CVD risk in men and women. These findings provide additional evidence for the role of distress in CVD development.

Background/AimThe possible association between serum monounsaturated fatty acids (MUFAs) and the risk of cardiovascular diseases (CVDs) has been examined in observational studies, which indicate controversial findings. In the current study, we used the Mendelian randomization (MR) analysis to determine the causal relationship of genetically determined serum MUFAs with the risk of various CVD outcomes, including angina, atherosclerotic, ischemic heart disease (IHD), myocardial infarction (MI), and high blood pressure (BP). MethodThe summary statistics dataset on the genetic variants related to serum MUFAs was used from the published GWAS of European descent in UK Biobank participants (N=114,999). Genetic variants underlying angina, atherosclerotic, IHD, MI, and BP events were ascertained using a GWAS dataset of 461,880 (case= 14,828, control= 447,052), 463,010 (case= 12,171, control= 450,839), 361,194 (case= 20,857, control= 340,337), 462,933 (case= 10,616, control= 452,317), and 461,880 (case= 124,227, control= 337,653) European descent participants from the UK Biobank, respectively. ResultsOur results showed that MUFAs were associated with angina [ORIVW= 1.005, 95% CI: 1.003- 1.007, p = <0.001; Cochrans Q=23.89, p=0.717, I2=0.0%; Egger intercept= -0.0003, p=0.289], atherosclerotic [ORIVW= 1.005, 95% CI: 1.003-1.007, p = <0.001; Cochrans Q=42.71, p=0.078, I2=27.4%; Egger intercept= -0.0004, p=0.146], IHD [ORIVW= 1.004, 95% CI: 1.001-1.007, p = 0.005; Cochrans Q=42.75, p=0.172, I2=18.1%; Egger intercept= -0.0001, p=0.827], MI [ORIVW= 1.001, 95% CI: 0.999- 1.003, p = 0.199; Cochrans Q= 23.03, p=0.631, I2=0.0%; Egger intercept= -0.0003, p=0.196], and BP [ORWM= 1.008, 95% CI: 1.001-1.015, p = 0.022; Cochrans Q= 52.87, p=0.015, I2= 37.6%; Egger intercept= 0.0002, p=0.779]. These results remained consistent using different Mendelian randomization methods and sensitivity analyses. ConclusionIn the present MR analysis, serum MUFA levels were associated with the risk of angina, atherosclerotic, IHD, MI, and BP. These findings prompt significant questions about the function of MUFAs in the progression of CVD events. Further research is required to elucidate the connections between MUFAs and CVD to contribute to health policy decisions in reducing CVD risk.

BackgroundMore than half of the worlds population have been infected with H. pylori, however the relationship between H. pylori infection and coronary heart disease (CHD) is unknown. MethodsThis study used mendelian randomization (MR) analyses. The instrument variables for H. pylori infection were genetic variables (rs10004195 and rs368433) obtained from a published study. The outcome data included diagnosis, prognosis, and pathogenesis data for CHD, which were extracted from the public genome-wide association studies database, mainly from the CARDIoGRAMplusC4D consortium, UK Biobank, IEU database, and FinnGen database. MR analyses were performed per outcome database and were conducted by reverse analysis. Two step MR analyses were used to explore indirect pathogenic factors of H. pylori infection. ResultsGenetically-predicted H. pylori infection was causally associated with body mass index (BMI) ({beta}, 0.022; 95% CI, 0.008-0.036; p-value = 0.001), but not with the diagnosis of CHD (OR, 0.991; 95%CI, 0.904-1.078; p-value = 0.842, IEU database; OR, 1.049; 95% CI, 0.980-1.118; p-value = 0.178, FinnGen database) and prognosis of CHD (OR, 0.999; 95% CI, 0.997-1.001; p-value = 0.391, IEU database; OR, 1.022; 95% CI, 0.922-1.123; p-value = 0.663, FinnGen database). The causal effect of H. pylori infection on CHD is mediated by BMI. Inverse MR showed no causal effect of CHD on H. pylori infection. ConclusionsOur findings confirm the causal effect of H. pylori infection on CHD is mediated by BMI. Eradication or prevention of H. pylori infection may have a clinical benefit for patients with CHD indirectly. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LIGenetically-predicted H. pylori infection was causally associated with body mass index, but not with the diagnosis and prognosis (major adverse cardiovascular events) of coronary heart disease. C_LIO_LIThe causal effect of H. pylori infection on coronary heart disease is mediated by body mass index. Inverse mendelian randomization analyses showed no causal effect of coronary heart disease on H. pylori infection. C_LI What Are the Clinical Implications?O_LIOur findings confirm that the causal effect of H. pylori infection on coronary heart disease is partially mediated by body mass index. C_LIO_LIEradication or prevention of H. pylori infection may have a clinical benefit for patients with CHD indirectly. C_LI

Background & AimsObesity is associated with an increased risk of atherosclerosis, though recent evidence shows conflicting results. This study aimed to evaluate whether obesity or its associated metabolic abnormalities play a more significant role in atherosclerosis development in a primary care population. MethodsA cross-sectional study using data from the Cardiometabolic Risk Factor Registry (CARFARE) at Hospital Universitario Austral included adults undergoing their first healthcare visit for primary cardiovascular prevention. Participants were classified into four groups: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO), according to the BioShare-EU criteria and body mass index. Metabolic abnormalities (MAs) were defined by the same criteria. Atherosclerosis prevalence was analyzed using univariate analysis and multivariable logistic regression models. ResultsAmong 6,735 participants, 23.3% were MHNO, 3.13% MHO, 45.6% MUNO, and 25.9% MUO. MHO subjects were 10.1% of the obese population. In univariate analysis, atherosclerosis prevalence was higher in obese than non-obese individuals (57.1% vs. 52.0%, p=0.001), but lower in MHNO and MHO compared to MUNO and MUO groups (33.1% and 34.4% vs. 60.4% and 59.5%, p<0.0001). In multivariate regressions, these latter groups presented an increased adjusted odds ratio (aOR) of atherosclerosis compared to MHNO, while atherosclerosis prevalence was no different between the MHO and MHNO groups [aOR: 0.79 (95% CI 0.55-1.11)]. Moreover, in a second logistic regression model, MAs were independently associated with atherosclerosis [aOR: 1.84 (95% CI: 1.60-2.11)], while obesity was not [aOR: 0.91 (95% CI: 0.79-1.04)]. ConclusionIn this primary care population, the MHO phenotype was not associated with increased atherosclerosis. MAs, rather than obesity alone, were independently associated with atherosclerosis. These findings highlight the need for further longitudinal studies to clarify the interactions between obesity and metabolic health in atherosclerosis development.

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

AimsThe diagnosis and assessment of coronary artery disease (CAD) in women remain challenging, as conventional diagnostic tools often show limited sensitivity and risk underdiagnosis. This study aimed to examine the associations between routinely available clinical and laboratory parameters and the severity of coronary artery lesions, quantified by the Gensini score, in female patients. In addition, we sought to develop and validate a predictive model to identify women at high risk of severe atherosclerosis. MethodsThis retrospective, cross-sectional study was conducted at the Second Hospital of Shanxi Medical University and included 91 patients with established CAD. Laboratory assessments comprised complete blood counts, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), lipid profiles, and uric acid (UA). Sleep quality was measured using the Athens Insomnia Scale (AIS). Statistical analyses included Spearman correlation, multiple linear regression, and logistic regression to evaluate the relationships between these variables and the Gensini score, and to assess their predictive value for high-risk disease. ResultsIn univariate analysis, the Gensini score was significantly correlated with inflammatory markers (IL-6: r = 0.61, P < 0.001; hs-CRP: r = 0.43, P = 0.012) and diabetes (r = 0.36, P = 0.037). Multiple linear regression identified insomnia, hypertension, diabetes, IL-6, and hs-CRP as independent predictors of the Gensini score, yielding a high goodness of fit (R{superscript 2} = 0.823, adjusted R{superscript 2} = 0.783, F = 20.19, P < 0.001). A logistic regression model for predicting high-risk disease (Gensini score >20) demonstrated excellent discrimination, with an area under the curve (AUC) of 0.964 in the training set and 0.833 in the test set. ConclusionIn women with CAD, the severity of coronary atherosclerosis is strongly associated with inflammation, metabolic dysregulation, and insomnia, with risk profiles distinct from those observed in men. A significant interaction between hs-CRP and diabetes was identified as a key modulator of CAD severity. These findings highlight the value of integrated statistical models that account for interacting risk factors, offering improved risk stratification and supporting proactive, personalized interventions in female patients with CAD.

IntroductionVisceral adiposity is emerging as a key driver of cardio-metabolic risk factors and cardiovascular disease (CVD), but its relationship with cardiac structure and function is not well characterized across sexes. Using the Canadian Alliance for Healthy Heart and Minds (CAHHM), a large population-based cohort study, we sought to determine the association of visceral adipose tissue (VAT) on subclinical left ventricular (LV) remodeling in males and females. MethodsAs part of the CAHHM study, 6522 participants free of clinical CVD (mean age: 57.4 [8.8 SD] years; 3,671 females, 56%) underwent magnetic resonance imaging (MRI) in which LV parameters and VAT volume were measured. Information about demographic factors, CV risk factors, and anthropometric measurements were obtained. Subclinical cardiac remodelling was defined as altered LV concentricity, represented by increased LV mass-to-volume ratio (LVMV). ResultsMales had a higher VAT volume (80.8 mL; 95% CI: 74.6 t 86.9) compared to females (64.7 mL; 95% CI: 58.5 to 70.8), adjusted for age and height. Among both males and females, VAT was significantly associated with subclinical cardiac remodeling (increased LVMV), independent of other CV risk factors. In multiple regression models adjusted for cardiovascular risk factors, age, and height, every 1 sex-specific standard deviation increase in VAT corresponded to an increase of 0.037 g/mL in LVMV (95% CI: 0.032 to 0.041; p<0.001), which was consistent across both sexes. Notably, a 1 standard deviation increase in VAT is associated with a LVMV that is 20 times higher than what is observed with natural aging alone (0.0020 g/mL rise in LVMV (95% CI 0.0016 to 0.0025), and 1.5 times higher than the impact of an integrated measure of CV risk factors (0.024 g/mL; 95% CI: 0.020 to 0.028). ConclusionVAT significantly influences subclinical cardiac remodeling in both males and females, independent of other cardiovascular risk factors and age. Further research to understand the pathways by which VAT contributes to accelerated cardiac aging is needed.

BackgroundLifes Essential 8 (LE8) are the key health behaviors and factors for improving and maintaining cardiovascular health, as defined by the American Heart Association. However, despite the association of cardiovascular diseases with inflammation, LE8 does not include inflammatory markers as a component. We analyzed the longitudinal association of LE8 components and inflammatory measures with health outcomes among a community-based population. MethodsBaseline LE8 metrics and inflammatory markers (interleukin-6 [IL-6] and high sensitivity C-reactive protein [hsCRP]) were measured among 1,869 participants (age 59{+/-}7.5 years, 41.9% Black) in the longitudinal Heart SCORE study. Cox-proportional hazard ratios were used to assess the association of incident atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality across quartiles of LE8 score, and to assess inflammatory markers as an independent risk factor. ResultsCompared to the lowest quartile, all higher quartiles of LE8 Score were significantly associated with lower risk of all-cause mortality and ASCVD over a median of 12 years of follow-up. After adjusting for all other LE8 metrics as well as by age, sex, race and socioeconomic risk, ideal level of blood glucose was the single most significant factor associated with lower risk of ASCVD (HR 0.26 [0.12-0.58], p=0.001). For all-cause mortality, no smoking emerged as the main protective LE8 component (HR 0.29 [0.16-0.53], p<0.001). When added to LE8, interleukin-6 (IL-6) was independently associated with ASCVD (HR 1.54 [1.05-2.25], p=0.03),while lower IL-6 was associated with lower all-cause mortality (HR 0.52 [0.30-0.90] p=0.02). HsCRP was not associated with either outcome. ConclusionsHigher LE8 Score and metrics are associated with lower risk of all-cause and ASCVD mortality as well as non-fatal events in this longitudinal cohort of White and Black adults. Additionally, elevated IL-6 levels were associated with higher risk of ASCVD and all-cause mortality even when accounting for total LE8 score. Future studies should investigate the role of modifying inflammatory burden in addition to LE8 components in prevention of adverse health outcomes. Journal Subject CodesCardiovascular disease, Atherosclerosis, Lifes essential 8, Cardiovascular health, aging, inflammation, sleep

BackgroundThis population-based prospective cohort study aimed to investigate whether accelerometer-measured step count is associated with incident cardiovascular disease (CVD), independently from genetic risk. MethodsThe study included participants in the UK Biobank with valid accelerometer and genetic data and without prevalent CVD at baseline. Genetic risk for CVD was categorised as low (1st fifth), moderate (2nd-4th fifths), and high (5th fifth). Median daily step count was categorised as low (<6,500), moderate (6,500-12,499), and high ([&ge;]12,500). The association of genetic risk and step count with incident CVD, defined as a composite of coronary artery disease and ischaemic stroke, was examined using adjusted Cox proportional hazards models. ResultsOf 84,286 participants, 4,847 were diagnosed with CVD during follow-up (median 7.9 years). High genetic risk and low daily step count had a log-additive association with incident CVD. In low genetic risk individuals, step count was not associated with incident CVD. However, in the moderate and high genetic risk groups, those with low step counts had 24% (HR 1.24; 95% Confidence Interval [CI] 1.10-1.40) and 37% (HR 1.37; 95% CI 1.14-1.65) higher risk of incident CVD compared to those with high step counts. There was an inverse dose-response association between the hazard of CVD and step counts up to 10,000 steps/day, which then plateaued in moderate and high genetic risk groups. ConclusionsHigh daily step count was associated with lower CVD risk in individuals with moderate and high genetic risk, indicating that walking should be encouraged for all, especially those predisposed to CVD.

Despite optimization with lifestyle modifications and medications, complications of coronary artery disease (CAD) remain the leading cause of adult mortality worldwide. This study aimed to identify proteins and pathways linked to recurrent CAD events to better understand residual risk. We used data from 1,009 participants in the UK Biobank (UKB) with baseline Olink plasma proteomic measures and CAD. Among 1,463 proteins tested, 102 proteins were independently associated with recurrent CAD events. Molecular functions were significantly enriched for tumor necrosis factor receptor (TNFR) activity by 100-fold (p-value = 6.37x10-10). Of the 16 proteins related to TNF annotated by Gene Ontology, TNF-alpha, TNFR1, and TNFR2 were all significantly associated with increased risk of recurrent CAD events. While TNFR1 and TNFR2 were initially thought to have opposing roles in cardiac remodeling post-MI, this study highlights the complex interaction between these pathways and the need to identify specific inflammation-related targets to therapeutic strategies.

AimsTo provide a comprehensive evaluation of the biomedical effects of circulating concentrations of cholesterol-containing lipoproteins and apolipoproteins. Methods and ResultsNuclear magnetic resonance (NMR) spectroscopy was used to measure the cholesterol content of high density (HDL-C), very low-density (VLDL-C), intermediate-density (IDL-C), and low-density (LDL-C) lipoprotein fractions; apolipoproteins Apo-A1 and Apo-B; as well as total triglycerides (TG), remnant-cholesterol (Rem-chol) and total cholesterol (TC). The causal effects of these exposures were assessed against 33 cardiovascular as well as non-cardiovascular outcomes using two-sample univariable and multivariable Mendelian randomization. We observed that most cholesterol containing lipoproteins and apolipoproteins affected coronary heart disease (CHD), cIMT, carotid plaque, CRP and blood pressure. Through MVMR we showed that many of these exposures acted independently of the more commonly measured blood lipids: HDL-C, LDL-C and TG. We furthermore found that HF risk was increased by higher concentrations of TG, VLDL-C, Rem-Chol and Apo-B, often independently of LDL-C, HDL-C or TG. Finally, a smaller subset of these exposures could be robustly mapped to non-CVD traits such as Alzheimers disease (HDL-C, LDL-C, IDL-C, Apo-B), type 2 diabetes (VLDL-C, IDL-C, LDL-C), and inflammatory bowel disease (LDL-C, IDL-C). ConclusionThe cholesterol content of a wide range of lipoprotein and apolipoproteins affected measures of atherosclerosis and CHD, implicating subfractions beyond LDL-C. Many of the observed effects acted independently of LDL-C, HDL-C, and TG, supporting the potential for additional, non-LDL-C, avenues to disease prevention.

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.

BackgroundNeighbourhood socioeconomic disadvantage is a known determinant of cardiovascular disease (CVD) risk. However, its impact on subclinical atherosclerosis across the life course remains inadequately understood. This study examined the association between cumulative neighbourhood socioeconomic disadvantage from childhood to midlife and carotid artery plaques-- a marker of subclinical atherosclerosis--independent of genetic and behavioral CVD risk factors. MethodsWe analysed data from 2,051 participants in the Cardiovascular Risk in Young Finns Study, a prospective cohort followed from childhood (mean age 10.7 years in 1980) to adulthood (mean age 48.6 years in 2018-2020). Neighbourhood disadvantage was derived from national grid-based socioeconomic data and computed cumulatively across childhood/adolescence, adulthood, and the entire life course. The number of carotid artery plaques (plaque count) were assessed by standardized ultrasound imaging. Multivariable Poisson regression models were used to evaluate associations, adjusting for age, sex, individual and parental socioeconomic status, genetic predisposition, and cardiovascular risk profiles. Mediation analyses assessed the role of ideal cardiovascular health (CVH) metrics. ResultsNo cross-sectional association was found between current neighbourhood disadvantage and carotid plaque count. However, higher cumulative neighbourhood disadvantage over the life course was associated with increased plaque count (rate ratio [RR] {approx} 1.20 per 1 SD increase). This relationship persisted after controlling for parental carotid artery plaques, polygenic coronary artery disease risk score, and Framingham risk score. The effect was partially mediated by ideal CVH metrics, particularly smoking and blood pressure, which collectively explained up to 50% of the association. ConclusionsLong-term exposure to neighbourhood socioeconomic disadvantage beginning in childhood is associated with subclinical atherosclerosis in midlife independently of achieved socioeconomic position. Behavioural risk factors partially mediate this link, highlighting the importance of early and sustained interventions targeting both social environments and health behaviours to mitigate cardiovascular risk.

Background: Cardiovascular diseases (CVD) are more common in lower occupational classes, but the mediating role of health behaviours remains unclear. This study aimed to quantify the extent to which health behaviours mediate the association between occupational class and CVD, evaluate their relative contributions to CVD risk, and assess occupational class differences in the effects of health behaviours. Methods: Municipal employees from Helsinki, aged 40-60 at baseline, were followed from 2000-2002 (response rate 67%) to 2022. CVD events were identified from national registers, including hospitalizations, long-term sickness absence, disability pensions, and mortality. Counterfactual mediation analysis using additive survival regression was used to assess the contribution of health behaviours - excessive alcohol consumption, smoking, unhealthy diet, and insufficient physical activity - to the association of occupational class and CVD. Occupational class differences in the effects of health behaviours were assessed with Cox regression. Results: During follow-up, 50% of participants in the low occupational class and 46% in the high occupational class had a CVD event. All unhealthy behaviours except heavy alcohol use were more common in the low occupational class. Health behaviours explained approximately 40% of the excess risk of CVD when moving from high occupational class to low occupational class. Insufficient physical activity (HR 1.44, 95% CI 1.35-1.54) was the strongest predictor of CVD. Unhealthy diet was more strongly associated with CVD in the high occupational class. Conclusion: Health behaviours explained a part of occupational class inequalities in CVD, but most of the inequality remained unexplained, highlighting broader social determinants.

BackgroundIn European cohorts, a higher Mediterranean diet or Lifes Simple 7 (LS7) score abolished or attenuated the risk associated with increasing Lipoprotein(a) [Lp(a)] on cardiovascular outcomes. This is unstudied in US cohorts. The impact of social determinants of health (SDOH) on the association of Lp(a) with cardiovascular outcomes remains unstudied. We sought to test if a SDOH score and LS7 score impacts the association of Lp(a) with myocardial infarction (MI) or stroke. MethodsObservational Cohort of US Adults from the Atherosclerosis Risk in Communities (ARIC) and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts. We performed sequential multivariable Cox proportional hazard analysis, first adjusting for age, gender, non-HDL-C, race and ethnicity, then added SDOH and LS7 scores sequentially. The primary outcomes were time until first fatal or nonfatal MI or stroke. ResultsARIC (n=15,072; median Lp(a)=17.3 mg/dL) had 16.2 years average follow up. MESA (n=6,822; median Lp(a)=18.3 mg/dL had 12.3 years average follow-up. In multivariable analyses adjusted for age, gender, race and ethnicity, and non-HDL-C, Lp(a) was associated (HR, p-value) with MI in ARIC (1.10, <0.001) and MESA (1.09, <0.001), and stroke in ARIC (1.08, <0.001) but not MESA (0.97, 0.50). With SDOH and LS7 added to the model associations remained similar (association of Lp(a) with MI in ARIC 1.09, <0.001 and in MESA 1.10, 0.001, with stroke in ARIC 1.06, <0.003 and in MESA 0.96, 0.39). In models with all covariates, each additional SDOH correlated positively with MI (ARIC 1.13, <0.001; MESA 1.11, <0.001) and stroke (ARIC 1.17, <0.001; HR 1.07, p=0.11) and each additional LS7 score point correlated negatively with MI (ARIC 0.81, <0.001; MESA 0.84, <0.001) and stroke (ARIC 0.82, <0.001; MESA 0.84, <0.001). Conclusions and RelevanceSDOH and lifestyle factors were predictors for MI and stroke that did not impact the association between Lp(a) and cardiovascular events. Our findings support that Lp(a) is an independent risk factor for MI and possibly stroke.