Cardiovascular Disease Risk Research Articles

Pericoronary adipose tissue computed tomography attenuation (PCAT) as a marker of premature CVD in asymptomatic people living with HIV (PLWH) without traditional risk factors: H-ART to heart study

Abstract Background Controversy exists regarding the contribution of HIV, ART or traditional risk factors to CVD risk in PLWH. The H-ART to Heart study investigates the prevalence of subclinical CVD in asymptomatic PLWH without cardiovascular risk factors compared to negative controls(-). Vascular inflammation inhibits local adipogenesis in pericoronary adipose tissue (PCAT) and thus can be detected on coronary computed tomography angiography (CTCA) as an increase in CT attenuation of PCAT surrounding the proximal right coronary artery (RCA). Methods This cross-sectional study compared PLWH aged 35-55yrs (diagnosed >10 yrs, on ART) to matched controls. Included were Caucasian men who have sex with men(MSM) and Black African/Caribbean women (BW) with traditional risk factors excluded (hypertension, hyperlipidaemia, diabetes, kidney disease, smoking, depression, inflammatory conditions, etc.). Detailed vitals, 10 year CVD risk calculation (Q-RISK 3) were recorded. CTCA were performed with novel analysis using PCAT to assess for coronary inflammation (Figure 1.) Results 98 participants were recruited (49M; 51 PLWH). Mean Q Risk 3 (10yr CVD risk - %) was low across the groups (HIV+MSM 4.65±2.1, HIV-MSM 3.88±2.7;p=0.29; HIV+BW 2.03±1.3, HIV-BW 1.38±0.98 p=0.66). 79 participants (42 PLWH; 37 controls) completed a CTCA with only 2 PLWH having clinically significant disease (CAD-RAD 3+ ie. >50% luminal stenosis) and none in the control group. (p=0.49) The CT scans of 69 patients were assessed for peri-coronary adipose tissue (PCAT) density, 2 were ruled out due to a small non-dominant RCA. The PCAT density of PLWH was higher than that of the controls (-71.2±27.6 vs -75.5±30.3 P=<0.05). Multivariate linear regression demonstrated that HIV status was an independent predictor of coronary inflammation (p=0.037) after adjusting for age, gender and BMI. Conclusion PWLH without traditional CV risk factors did not have significant evidence of more clinically relevant stenosis than controls on CTCA. However PCAT demonstrated a higher signal of coronary inflammation, despite stable disease, compliance with ART and low CVD risk scores. PLWH remain at risk of CV disease, this study supports the rationale for early preventative strategies for CVD prevention in PLWH.PCAT showing HIV inflammation Vs Control

Proteomics in low CVD risk black women living with HIV: H-ART to Heart Study

Abstract Background 39 million people worldwide are living with HIV (human immunodeficiency virus), acquired immune deficiency syndrome (AIDS)-related deaths have reduced by 51% since the peak in 2004. BWLWH represent 42% of those infected but only 9% are represented in clinical trials. HIV/AIDS has been shown to be associated with the development of heart failure, pulmonary hypertension and myocarditis. Previous studies in asymptomatic PLWH have revealed a high burden of underlying CVD and subclinical disease. The H-ART to Heart study is designed to examine potential signals and pathways of cardiovascular disease (CVD) in asymptomatic BWLWH with no traditional CV risk factors compared to HIV negative controls (-). Methods A cross-sectional study comparing asymptomatic BWLWH aged 35-55yrs (diagnosed >10 yrs, with undetectable viral loads) to HIV negative controls. Black African/Caribbean women without known CV risk factors (hypertension, hyperlipidaemia, diabetes, smoking, inflammatory arthritis, depression, severe mental illness) or hepatitis co-infection were included. Assessment included blood pressure (BP), 10yr CVD risk calculation % (Q-Risk 3), bloods including lipids. A targeted discovery proteomics approach was used to evaluate 92 unique proteins using the O-link Target 96 Cardiovascular II panel. Results 48 participants were recruited (23 BWLWH; 25 controls), mean duration of HIV was 17.6 years, mean duration of ART was 11.5 years, demographic details - Age 47.7± 44.7±; p=0.06, BP 125/77 v 123/79 ; p=0.89; BMI (kg/m²) 30.1±5.1 v 28.51±4.27 p=0.25; cLDL 3.49±1.22 v 2.42±0.74 p<0.02; Total Chol:HDL ratio 3.01±0.98 v 2.77±0.56 p=0.353; Q-Risk 3 1.92%±1.27 v 1.49%±1.12 p=0.219; There were no significant differences in baseline data apart from higher mean cLDL in BWLWH. Of the 92 proteins tested, 9 were significant in BWLWH (Figure 1). As demonstrated by the Heat map. Conclusion Data from our study of asymptomatic low risk BWLWH with no CVD risk factors indicates several pathways (Figure 2.) for further investigation in this previously under investigated vulnerable patient sub group. Whether this finding is of importance in CV risk assessment of BWLWH remains to be seen.

Impact of addressing modifiable risk factors on the 10-year risk of cardiovascular disease in individuals with familial hypercholesterolemia: a causal analysis utilising UK biobank

Abstract Background Familial hypercholesterolemia (FH) is a prevalent autosomal dominant disorder characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels from birth. These elevated LDL-C levels significantly amplify the lifetime risk of cardiovascular disease (CVD). While the impact of early and effective initiation of lipid-lowering medication (LLM) on CVD risk is well documented in genetically confirmed FH, the additional impact of addressing modifiable lifestyle risk factors (MLRF) in that patient population remains largely unquantified. Methods This study quantified the potential effects of successfully managing 4 MLRF (smoking, obesity, alcohol consumption, and low physical activity) on the 10-year incidence of a first CVD diagnosis in adults with genetically confirmed FH treated with LLM within the UK Biobank. The synthesised causal estimates of these 4 MLF were obtained using two recent causal analysis frameworks, namely the doWhy causal calculus framework and the Causal Forest Double Machine Learning Method. Results In 660 FH individuals (mean age 56±8 years; 60.15% women), smoking cessation and reducing body mass index below 30 kg/m2 delivered the most substantial risk reductions (pooled estimates, adjusted for the 3 other MLRF: -6.5% and -3.2%, respectively; both p<0.001), followed by initiating moderate or high physical activity (-1.7%; p<0.001; Figure). Notably, cessation of alcohol consumption significantly increased CVD risk (+2.5%; p<0.001), aligning with existing literature. Conclusion In over 10 years, reductions in CVD risk ranging from 1.7% to 6.5% were achievable through smoking cessation, BMI reduction, and enhanced physical activity in FH individuals. Leveraging causal inference methodologies facilitates the discernment of which risk factors offer the most pronounced additional benefits beyond lipid-lowering interventions in this high-risk population.Forest Plot of Causal Effect Estimates

Interleukin-6 signalling, lipoprotein (a) lowering and cardiovascular disease: a mendelian randomisation study

Abstract Background Elevated lipoprotein(a) (Lp[a]) levels and chronic low-grade inflammation play causal roles in cardiovascular disease (CVD) development, representing promising targets for managing residual risk. CVD prevention trials are currently assessing the efficacy of IL-6 pathway inhibition in ameliorating chronic pro-atherogenic inflammation. Lp(a) increases in response to interleukin 6 (IL-6) and acute inflammatory states, and Lp(a) itself induces an inflammatory response that accelerates atherosclerosis. Recent studies indicate that IL-6-receptor inhibitors may lower Lp(a) levels and reduce inflammation, potentially decreasing CVD risk in an additive manner. Purpose This drug-target Mendelian Randomisation (MR) study aims to elucidate the on-target effects of pharmacological IL-6R and LPA inhibition on CVD and explore the relationship between downregulated IL6R signalling and Lp(a) levels. Methods Independent genetic variants associated with C-reactive protein levels from around the IL6R gene locus, and Lp(a) lowering variants from around the LPA gene locus were utilised to assess the effect of genetically proxied IL6R and LPA inhibition on CVD risk in large genomic consortia. Two-step cis-MR was then employed to estimate the effect of lower genetically predicted IL6R signalling on CVD, after adjusting for its influence on Lp(a) levels. Results Genetically proxied LPA inhibition was associated with reduced odds of coronary artery disease (CAD) (OR 0.88, 95% CI 0.86-0.89), ischaemic stroke (IS) (OR 0.98, 95% CI 0.96-1.00), cardioembolic stroke (OR 0.95, 95% CI 0.92-0.97), heart failure (HF) (OR 0.96, 95% CI 0.92-1.00), and aortic stenosis (OR 0.88, 95% CI 0.85-0.91). IL6R inhibition was associated with reduced odds of CAD (OR 0.76, 95% CI 0.68-0.86), IS (OR 0.89, 95% CI 0.80-0.98), small vessel stroke (SVS) (OR 0.72, 95% CI 0.59-0.89), large artery stroke (LAS) (0.61, 95% CI 0.48-0.78) and atrial fibrillation (OR 0.73, 95% CI 0.65-0.83). Furthermore, downregulated IL6R signalling was associated with lower Lp(a) levels (SD change -0.04, 95% CI -0.08,-0.01). In two-step cis-MR, Lp(a) levels partially mediated the total effect of IL6R inhibition on CAD (proportion-mediated = -11.33%, 95% CI -11.35, -11.31%) and LAS (proportion mediated = -4.19%, 95% CI -4.21, -4.17%), but had little effect on IS (proportion-mediated = -1.78%, 95% CI -1.80, -1.76%), SVS (proportion-mediated = -2.50%, 95% CI -2.52, -2.48%), or atrial fibrillation (proportion-mediated = -0.20%, 95% CI -0.22, -0.18%). Conclusion IL6R and Lp(a) inhibition are independently associated with reduced risk of CVD. Furthermore, IL6R inhibition is associated with lower Lp(a) and its effect on CVD is independent of its Lp(a)-lowering effects. Targeting the IL6 signalling pathway offers a promising approach to mitigate residual CVD risk in individuals with elevated Lp(a) levels. Future trials should investigate the additive effects of combined IL-6 inhibition and Lp(a) lowering therapies.

Lipoprotein(a) cardiovascular disease risk not captured by low density lipoprotein cholesterol and apolipoprotein B

Abstract Background Elevated lipoprotein(a) affects 1 in 5 individuals and is considered a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis (AVS). However, lipoprotein(a) measurements are not widely implemented in clinical practice. Low-density lipoprotein (LDL) cholesterol and apolipoprotein B (ApoB) measurements include contributions from lipoprotein(a), yet whether these measurements can replace measurements of lipoprotein(a) in assessing cardiovascular disease risk from this causal risk factor is unknown. Purpose We tested the hypotheses that lipoprotein(a) risk of ASCVD and AVS is captured by LDL cholesterol or ApoB. Methods We included 70,189 individuals from a prospective contemporary cohort study of the general population. Mediated risk by LDL cholesterol and ApoB in the association between lipoprotein(a) and risk of ASCVD and AVS was examined using four-way decomposition analyses stratified by statin treatment at baseline. Results During a median follow-up of 10.8 years, 7,127 developed ASCVD and 1,516 AVS. Per 50 mg/dL higher lipoprotein(a), multivariable adjusted hazard ratios were 1.22 (95% CI: 1.18-1.26) for ASCVD and 1.36 (1.28-1.46) for AVS. In individuals without statin use, LDL cholesterol mediated 19% (15%-24%) of the risk of ASCVD from lipoprotein(a) and 7.7% (1.5%-14%) of the risk of AVS from lipoprotein(a) (Figure 1). Corresponding values for ApoB were 14.0% (11%-18%) and 6.6% (2.8%-10%). In statin users (n=9,570), LDL cholesterol did not mediate risk of ASCVD from lipoprotein(a) but mediated 8.0% (0.8%-15%) of the risk of AVS from lipoprotein(a). Correspondingly, ApoB mediated 9.8% (2.2%-17%) of the risk of ASCVD and 4.2% (0.4%-8.0%) of the risk of AVS from lipoprotein(a). Conclusion Lipoprotein(a) risk of ASCVD and AVS is not adequately captured by LDL cholesterol and ApoB. Therefore, lipoprotein(a) measurement is needed in all individuals to capture the cardiovascular disease risk from this causal risk factor.

Housing items and amenities a non-traditional risk factors for all-cause and cardiovascular mortality

Abstract Background Higher satisfaction levels are associated with improved psychological well-being (PWB), such as housing amenities being a determinant of health. However, their potentially influencing effect on mortality risk at this moment is not enough. For this reason, searching for non-traditional risk factors that could reduce all-cause and cardiovascular disease (CVD) mortality risk is our primary objective of this study. Methods The cohort study was based on the framework of the international study Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE). Data from the Official Lithuanian Mortality Register were used to evaluate mortality from the baseline survey (2006- 2008) to 31 December 2022. The 20 housing items and amenities were used. The items were categorized into three groups: basic needs, socially oriented needs, and luxury. Results A total of 6472 participants aged 45-72 years were examined in the baseline survey. Cox proportional hazards regression analysis results show that increasing the number of housing items per 1 unit decreased the risk of all-cause mortality by 8% (Hazard ratio (HR)=0.92;95%CI 0.90-0.94) in males and by 7% (HR = 0.93;95%CI 0.91-0.96) in females. Increasing the number of housing items per 1 unit decreased the risk of mortality from CVD by 10% (HR = 0.90;95%CI 0.87-0.93) in males and by 9% (HR = 0.91;95% CI 0.87-0.95) in females (data adjusted by age, education, smoking, metabolic syndrome, PWB, CVD at baseline survey). Once more, the increased number of items from the luxury group (4-7 vs. 0-1) significantly decreased all-cause and CVD mortality risk (respectively in males HR = 0.74(95%CI 0.60-0.91) and HR = 0.71(95%CI 0.52-0.96); in females HR = 0.66(95%CI 0.48-0.91) and HR = 0.57(95%CI 0.33-0.96). Conclusions These data suggest that the increasing number of household items and amenities, as an essential aspect of people’s lives, may be used as non-traditional risk factors in assessing the risk of all-cause mortality and CVD. Key messages • Household items and amenities may be used as non-traditional risk factors in assessing the risk of all-cause mortality and CVD. • Increasing the number of housing items decreased the risk of all-cause and CVD mortality.

Spinal cord injury and risk of overall and type specific cardiovascular diseases: A meta-analysis.

Cardiovascular disease (CVD) is a growing concern among people with spinal cord injury (SCI). This meta-analysis aims to explore the risk of overall CVD and specific types of cardiovascular events among SCI patients. This meta-analysis is registered on PROSPERO (CRD CRD42024537888). The data sources comprised PubMed, Embase, the Cochrane Library, and reference lists of the included studies. The literature collection span is from database establishment until April 17, 2024. This meta-analysis encompassed observational studies investigating the association between SCI and the risk of overall types of CVD or specific CVD types. Risk of bias was evaluated utilizing the Newcastle-Ottawa Quality Assessment Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) Scale. Odds ratios (ORs) with 95% confidence intervals (CIs) were aggregated using a random-effects model. Our initial search generated 5357 relevant records form these international databases. This meta-analysis encompassed 9 observational studies involving 2,282,691 individuals, comprising 193,045 patients with SCI and 2,209,646 controls. We observed a 1.56-fold [OR = 1.56, 95% CI (1.43, 1.70), I2 = 91.3%, P < 0.001] rise in the risk of overall types of CVD among SCI patients, with a 1.82-fold increase in males and a 1.76-fold increase in females. SCI patients without comorbidities exhibited a 2.10-fold elevated risk of overall CVD types, while those with comorbidities had a 1.48-fold increased risk. Concerning specific CVD types, SCI patients showed a 1.58-fold [OR = 1.57, 95% CI (1.22, 2.03), I2 = 92.4%] higher risk of myocardial infarction, a 1.52-fold [OR = 1.52, 95% CI (1.07, 2.16), I2 = 88.7%] increase in atrial fibrillation, a 1.64-fold [OR = 1.64, 95% CI (1.22, 2.20), I2 = 95.5%] elevation in heart failure risk, and 2.38-fold [OR = 2.38, 95% CI (1.29, 4.40), I2 = 92.5%] increments in stroke risk. But there was no statistically significant difference in the risk of hypertension [OR = 1.54, 95% CI (0.98, 2.42), I2 = 96.6%]. The risk of overall CVD in SCI patients surpassed that of the non-SCI control group, with elevated risks of specific cardiovascular events like myocardial infarction, atrial fibrillation, heart failure, and stroke. Clinicians should prioritize awareness of CVD risks in SCI patients.

Artificial intelligence-enhanced electrocardiography predicts 10-year risk of atherosclerotic cardiovascular disease

Abstract Background The ACC/AHA pooled cohort equations (PCE) calculates the 10-year primary risk of atherosclerotic cardiovascular disease (ASCVD), an indication to initiate primary prevention statin therapy in international guidelines. The validity of PCE is limited by its overestimation of risk in high-risk cohorts and an ethnic heterogeneity. Electrocardiography (ECG) has not been incorporated in current ASCVD risk estimation tools. Artificial Intelligence (AI)-based models are capable to capture patterns that are informative for cardiovascular prognosis. Purpose We explored the predictive value of a discrete-time survival model in 10-year ASCVD risk in comparison to PCE. Methods We developed an AI-ECG model to predict the 10-year ASCVD risk in an unselected secondary care population from the USA comprised of 1,163,401 ECGs from 189,539 patients. Data was split into training/validation and hold-out test sets by patient ID. Our AI-ECG model uses deep learning with a residual convolutional neural network with a discrete-time survival loss function to output subject-specific survival curves, accounting for both time to event and censorship (i.e., loss to follow up). We compared the performance of out AI-ECG model using a subset of outpatient data (n=4590) of the BIDMC dataset to PCE and ASCVD risk factors including systolic blood pressure, total cholesterol, HDL cholesterol, hypertension, smoking history, diabetes mellitus, and ethnicity. Performances were evaluated using cox survival analysis. Our AI-ECG model was externally validated in the UKB Biobank (UKB), where we compared the performance of our AI-ECG model to predictions of existing AI-ECG models such as the Stanford Estimator of Electrocardiogram Risk (SEER) model. Results Our AI-ECG successfully predicted future ASCVD events in individuals (C-index 0.721 (0.719-0.723), 5-year AUC 0.761 (0.758-0.763), and differentiated between high and low risk group with an adjusted HR of 2.33 (2.26-2.41). Upon internal validation our AI-ECG model showed a superior performance (C-index 0.679 (0.651-0.708)) than PCE (0.605 (0.577-0.634)) and all risk factors combined (C index 0.642 (0.613-0.672)). When combining AI-ECG predictions with all risk factors, the model showed additional predictive value (0.686 (0.657-0.715)) (Figure 1). Our AI-ECG model showed modest predictive value within the UKB dataset (C-index 0.655 (0.637-0.673)), but significantly outperformed the SEER model (C-index 0.547 (0.527-0.567), p &amp;lt;0.0001 for comparison with AIRE). Conclusion We have shown the potential of AI-ECG models in predicting future ASCVD risks. AI-ECG models demonstrated accurate discrete time survival prediction and good classification performance superior to that of the SEER model, as well as PCE and ASCVD risk factors. . Accurate risk assessment of ASCVD may help prevent adverse events in high risk subjects and save unnecessary pharmacological interventios in low risk subjects.Figure 1

Antibodies against phosphorylcholine in prediction of cardiovascular disease among women: a population-based prospective cohort study

Abstract Background and aims Antibodies against phosphorylcholine (anti-PC) have been reported as associated with protection against atherosclerosis, cardiovascular disease (CVD) and other chronic inflammatory diseases. Underlying potential mechanisms have been demonstrated and include anti-inflammatory, clearance of dead cells and inhibition of oxidized low-density lipoprotein-effects. The aim is to study the role of IgM anti-PC and incident CVD among women, where less is known than among men in the general population. Methods In a total of 932 women, 66 ± 6 years old at baseline, from the population-based Swedish Mammography Cohort IgM anti-PC levels of sera were measured using ELISA. Prospective associations with any first CVD, ischemic heart disease (IHD), myocardial infarction (MI) and ischemic stroke were assessed using Cox proportional hazard regression, generating hazard ratios (HR) and 95% confidence intervals (CI). The model was adjusted for potential confounding factors. Results Over the course of 16 years (14,900 person-years), we identified 113 cases of composite CVD, - 69 cases of ischemic heart disease (IHD), 44 cases of myocardial infarction (MI) and 50 cases of ischemic stroke. IgM antiPC was statistically significantly inversely associated with risk of CVD, IHD and MI, but not with ischemic stroke. Comparing the highest tertile with lowest, we observed multivariable-adjusted HR of 0.26 (95% CI: 0.10–0.66; p-trend &amp;lt;0.01) for MI. Conclusions IgM anti-PC may play an active role in inhibition of CVD development in women, especially MI. Elevating anti-PC concentration through immunization, may be a future development in CVD prevention.

Effect of interleukin 1b inhibition with canakinumab on inflammation and viral persistence in people with human immunodeficiency virus

Abstract Introduction Effectively treated people with HIV (PWH) have elevated risk of cardiovascular disease (CVD). Inflammatory markers are predictive of CVD and mortality among PWH. The role of the myeloid system in driving inflammation and atherosclerosis has been recently recognized. Canakinumab (a monoclonal antibody to IL-1β) reduces inflammation and CVD events among people with elevated hsCRP after myocardial infarction without HIV. We evaluated the impact of IL-1β inhibition using canakinumab on HIV parameters, inflammation, HIV persistence markers, arterial inflammation, and hematopoietic activity in PWH. Methods PWH on effective ART who had CVD or were at risk for CVD were randomized 2:1 to receive 150 mg of canakinumab subcutaneously or matched placebo at weeks 0 and 12. Arterial inflammation and bone marrow metabolic activity were assessed using F18 FDG PET/CT at baseline and week 18. T cell and monocyte activation were evaluated using multiparameter spectral cytometry. The viral reservoir was quantified using Tat/rev Induced Limiting Dilution Assay (TILDA), HIV DNA and cell-associated RNA. The primary endpoints were change in CD4 and CD8 count. We assessed group effects over time using linear mixed effects models. Results 33 individuals were randomized (median age of 60 years old (IQR 57.5, 64.5) and 94% male); 25 received canakinumab and 8 received placebo. There were no significant differences at baseline. As expected, IL-1β increased among those treated with canakinumab at weeks 4- 24 (p&amp;lt;0.01 for each) and returned to baseline at week 36. There was one death from sepsis in an individual aged 84 with CVD and poorly controlled diabetes who received canakinumab. There were no significant changes in CD4 count, CD8 count, platelet count, creatinine, AST, or ALT by group. Treatment was not associated with a greater reduction in arterial inflammation in the most diseased segment compared to placebo (-6.9%; 95% CI -30.4 to 24.5%; p=0.62). However, bone marrow metabolic activity decreased in the canakinumab group versus placebo (-14.4%, 95% CI -26.5% to -0.2%; p=0.047). Treatment was associated with increased CD163 expression on monocytes at weeks 24 (p=0.03) and 36 (p&amp;lt;0.001), and lower caspase activity at week 36 (p=0.02). There was expansion of anti-inflammatory CD16+ patrolling monocytes that co-express CD163+CX3CR1+ and a decrease in pro-inflammatory CD16+ patrolling monocytes that are Caspase1+CCR2+. Treatment was not associated with differences in hsCRP, IL-6, IL-16, IL-18, MCP-1, sCD14, sCD163, T cell subsets, NK cell subsets, or viral persistence markers. Conclusion Among treated PWH, targeted inhibition of IL-1β using canakinumab results in decreased bone marrow metabolic activity and a shift toward anti-inflammatory monocyte populations. These findings shed light on mechanisms underlying how targeted IL-1β inhibition using canakinumab prevents CVD events by altering monocyte populations and reducing systemic inflammation.

Refined selection of individuals for preventive cardiovascular disease treatment with a transformer-based risk model

Abstract Background Although statistical models have been commonly used to identify patients at risk of cardiovascular disease (CVD) for preventive therapy, these models tend to over-recommend therapy [1]. Moreover, in populations with pre-existing diseases, the current approach is to indiscriminately treat all individuals, as modelling in this context is currently inadequate. Aims To develop and validate a novel deep learning model, the Transformer-based Risk assessment survival model (TRisk) model, for prediction of 10-year risk of CVD in both the general population and individuals with diabetes. Methods An open cohort of 3 million adults aged 25 to 84 years free of CVD and statin use was identified using linked primary and secondary electronic health records from 291 and 98 general practices in England, which were used for TRisk model development and external validation, respectively. Comparison against two commonly recommended statistical models (QRISK3 [2] and SCORE2 [3]) and a deep learning derivation of QRISK3 was conducted. Additional analyses compared discriminatory performance in other age groups, by sex, and across categories of socioeconomic status. Similar analyses were conducted in a subgroup of 59 thousand patients with diabetes. Results TRisk demonstrated superior discrimination (C index in the general population: 0.910; 95% confidence interval [CI]: 0.906 to 0.913). TRisk’s performance was found to be less sensitive to population age range than the benchmark models and outperformed other models also in all stratified analyses. All models were overall well-calibrated. In decision curve analyses, TRisk demonstrated greater net benefit than benchmark models across the range of relevant thresholds. In impact analyses, at the widely recommended 10% risk threshold and the higher 15% threshold for the general population, TRisk reduced both the total number of patients classified at high risk (by 27% and 39% respectively) and the number of false negatives as compared with currently recommended strategies. TRisk similarly outperformed other models in patients with diabetes. Compared with the widely recommended treat-all policy approach for patients with diabetes, TRisk at a 10% risk threshold would lead to deselection of 24% of individuals with a small fraction of false negatives (0.2% of cohort). Conclusion TRisk enabled a more targeted selection of individuals at risk of CVD compared to benchmark statistical and deep learning models, in both the general population and patients with diabetes. Incorporation of TRisk into routine clinical care would allow a reduction in the number of treatment-eligible patients in general population and subgroup with diabetes by approximately one-third and one-quarter respectively while preventing at least as many events as with currently adopted approaches.Models' discrimination on both cohortsImpact analyses for both cohorts

Independent associations of educational attainment and its joint associations with LE8 score for risk of cardiovascular disease incidence and mortality among Chinese people

Abstract Background/Introduction Educational attainment is a social determinant of health. Quantifying its associations with risk of cardiovascular disease (CVD) incidence and mortality has public health importance. Recently, the American Heart Association introduced the Life’s Essential 8 (LE8) score to evaluate CVD risk. However, it remains unclear how educational attainment and the LE8 score interact in their joint associations with CVD and mortality. Purpose To examine the associations of educational level with the incidence of CVD, including coronary heart disease (CHD) and stroke, and total mortality. Also, we examined the joint associations of educational level and the LE8 score with CVD incidence and total mortality. Methods We prospectively followed 91,744 Chinese adults from the Kailuan Study (2006-2021), who were free of CVD at baseline. Information on educational level, diet, lifestyle, and health conditions was collected every 2 years. LE8 score was calculated based on eight components: diet quality, physical activity, smoking status, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. We used time-dependent Cox models to assess the associations of educational level with the outcomes as well as the joint associations of educational level and LE8 score, with adjustments for demographics, dietary and lifestyle factors, and medical history. Results During a mean follow-up of 13.1 years, there were 12,916 incident CVD cases and 13,090 deaths. Compared with the participants who only received illiteracy or elementary education, those who received high school education and above had a lower risk of CVD incidence (HR = 0.82, 95% CI = 0.76, 0.88), stroke incidence (0.72, (0.66, 0.79)), and total mortality (0.73, (0.68, 0.77)). Educational level was not associated with risk of CHD. Furthermore, significant additive interactions between educational attainment and LE8 score on the risk of CVD and mortality were observed (all p values for additive interactions &amp;lt;0.01). Compared with the participants who only received illiteracy or elementary education and had a low LE8 score, those who only received illiteracy or elementary education but had a high LE8 score still had a 27%-47% lower risk of CVD and total mortality, while those who received high school education and above and had a high LE8 score had a 51%-74% lower risk of CVD and total mortality. Conclusions Higher educational level was associated with a lower risk of CVD and mortality. These inverse associations were most apparent among participants with both a high educational level and a high LE8 score, while the participants with a low educational level but with a high LE8 score still had a significantly lower risk. These findings highlight the importance of improvement in educational attainment in preventing CVD events and deaths, and suggest that CVD events and deaths attributable to lower levels of education may be reduced by improving LE8 score.

Food additive monosodium glutamate and risk of cardiovascular diseases - NutriNet-Santé cohort

Abstract Background One may add monosodium glutamate (MSG) to food for its flavour-enhancing properties. However, its implication in long-term cardiovascular health is uncertain due to a lack of precise epidemiological evidence. This study aimed to investigate the associations between food additive glutamate exposures and cardiovascular disease (CVD) risk, including cerebrovascular disease (CVA) and coronary heart disease (CHD) risks in a large prospective cohort of French adults. Methods Participants (n = 108,932, 79.3% women, mean age=42.4 years, SD = 14.5) were 15 years old and above from the French NutriNet-Santé prospective cohort (2009-2023). We assessed dietary intakes using repeated 24h-dietary records and exposure to food additive glutamate using food composition databases and laboratory assays. We characterised associations between cumulative time-dependent continuous exposures to total glutamate, natural glutamic acid, MSG and risk of CVD, CVA, and CHD using multivariable proportional hazards Cox models adjusted for known risk factors for standardised increments of glutamate intake. Results During follow-up (median 7.92 years), 2397, 1113, and 1284 participants were diagnosed with CVD, CVA, and CHD respectively. Higher intakes of naturally occurring glutamic acid (HR per 3000 mg/d increment=1.08, 95% CI [1.01-1.16], p-value=0.03), food additive MSG (HR per 200 mg/d increment=1.05, 95% CI [1.01-1.09], p-value=0.03), and total glutamate (HR per 3000 mg/d increment=1.09, 95% CI [1.01-1.17], p-value=0.02) were associated with higher risks of CHD (p-value for non-linearity&amp;gt;0.6). Conclusions This large prospective cohort study revealed positive associations between exposure to the widely used glutamate food additives, especially MSG (E621) and CVD, CVA, and CHD risks. Key messages • This large prospective cohort study revealed positive associations between exposure to the widely used glutamate food additives, especially MSG (E621) and CVD, CVA, and CHD risks. • If confirmed, our findings regarding MSG could lead to a re-evaluation of the safety of these food additives by European and international public health agencies to improve consumer protection.

Treadmill exercise test as a screening tool in the development of hypertension

Abstract Background Guidelines promote screening people with high normal BP for the presence of end-organ damage because their presence is associated with a 2- to 3-fold increase in the risk of CVD. Purpose Office blood pressure measurements may be unable to detect early subclinical cardiac damage of adverse prognostic significance in subjects with high normal blood pressure. Methods 100 consecutive subjects with high normal BP [systolic BP=130-139mmHg and/or diastolic BP=85-89mmHg] were examined for early signs of hypertension-mediated organ damage (HMOD). They underwent an echocardiographic study, a negative for ischemia treadmill exercise test (Bruce protocol) where the index SBP/MET-slope [(peak SBP—resting SBP)/(peakMET-1)] was used. Arterial stiffness was evaluated based on carotid-femoral pulse wave velocity (PWV). The sympathetic drive was assessed by MSNA. Follow-up was scheduled every 6 months for 3 consecutive years, where BP measurements were assessed in the office and with ambulatory BP monitoring (ABPM). All participants offered lifestyle advice to lower their BP. The endpoint was the development of HTN either with Office BP or ABPM. Results Of 100 subjects (54±8 years, 42 males, baseline office BP: 132/82 mmHg, 24-hour BP: 122/76 mmHg), 40 developed HTN in 3 years. 34 subjects developed Hypertensive Response to Exercise (HRE) (BP &amp;gt;210mmHg in men and &amp;gt;190mmHg in women) and all of them developed HTN. The SBP/MET-slope in future hypertensives was increased in all stages till peak exercise independently of sex type (stage1: 6.7vs4.9 p=0.049, stage2: 8.4vs4.8 p=0.001, peak: 6.7vs4.9, p=0.001). Their exercise capacity was reduced (10vs11.3METs, p=0.002) as well as their maximum exercise heart rate (156vs164, p=&amp;lt;0.0001). Those with HRE had higher 24hSBP (124vs121mmHg, p=0.009), Night SBP (117vs111mmHg, p&amp;lt;0.001), Day SBP (127vs124mmHg, p=0.012) Office Pulse Pressure (51vs47mmHg, p=0.01). Additionally, they had increased PWV (8.3vs7.5m/sec, p=&amp;lt;0.0001), MSNA levels (36vs28 bursts, p=&amp;lt;0.0001), LVMI (38vs34 gr/m2.7, p=0.02), and a statistically significant deterioration of 2021 CKD-EPI eGFR (90 vs 97 mL/min/1.73 m², p=0.02). All of them correlated with development of hypertension (p=0.002), while they did not differ regarding their metabolic profile at the follow-up. Conclusion Detecting exaggerated blood pressure response and specifically an increased SBP/MET-slope in the end of second stage of Bruce protocol at treadmill exercise test is associated with increased systemic vascular resistance and early subclinical HMOD which may upgrade an individual’s cardiovascular disease (CVD) risk as they progress to HTN indicating a need for instituting a BP-lowering strategy.

Cardiovascular related polypharmacy and its association with liver and kidney impairment amongst individuals on lipid-lowering therapy: a cross-sectional study using primary care data

Abstract Background Individuals with risk factors for cardiovascular disease (CVD) frequently require concurrent treatment with various medications, a phenomenon known as polypharmacy. This study aimed to investigate the association between CVD-related polypharmacy and the presence of liver and kidney impairment amongst patients receiving lipid-lowering therapy within the Australian primary care setting. Methods This study utilised electronic medical records from general practices retrieved between January 2013 and December 2023. Multivariate logistic regression identified independent risk factors associated with CVD-related polypharmacy, defined as the concurrent use of five or more CVD protective medications. The analysis included individuals on lipid lowering therapy who are at risk for CVD. The relationship between CVD-related polypharmacy and the presence of liver and kidney dysfunction was further assessed, defined by exceeding established reference ranges for relevant biomarkers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], bilirubin, creatinine, and estimated glomerular filtration rate [eGFR]) as per Australian guidelines. Results A total of 13,568 participants (median age: 63 years [IQR 54-72], 54% males) were included. Independent factors associated with CVD-related polypharmacy included diabetes (OR=5.40, 95% CI: 4.96-5.93), chronic kidney disease (CKD) (OR=2.39, 95% CI: 2.00-2.86), hypertension (OR=1.91, 95% CI: 1.75-2.07), and smoking (OR=1.05, 95% CI: 0.97-1.14). Compared to the 18-35 age group, individuals aged ≥80 years displayed a significantly higher likelihood of CVD-related polypharmacy (OR=8.17, 95% CI: 5.47-12.21). While no significant association was observed between CVD-related polypharmacy and liver impairment (OR=1.19, 95% CI: 0.59-2.37), an independent positive association was identified with kidney impairment (OR=1.38, 95% CI: 1.24-1.54), adjusted for established CVD risk factors including age, sex, smoking, diabetes, hyperlipidaemia, hypertension, and CKD. Conclusion This study suggests a positive association between CVD-related polypharmacy and increased risk of kidney impairment in Australian primary care. Further research is warranted to explore potential causal mechanisms and evaluate the efficacy of medication review strategies, enhanced kidney function monitoring, and potential medication deprescribing in managing patients at risk of CVD who are on multiple medications.

Joint effect of tobacco and meat on cardiovascular disease and treatment adherence in Indian Women

Abstract Background Cardiovascular disease (CVD) is a leading cause of death for both men and women in India. But it is often overlooked in women. Tobacco and meat consumption are common risk factors for CVD. While individual studies have explored the link between tobacco or meat consumption and CVD, their joint effect remained understudied. Methods The study analyzed data from the National Family Health Survey 2019-21, of 711431 women aged 15 to 49 in India. Univariate and multivariate logistic regression were used to assess the risk of individual and joint effects of tobacco and meat consumptions on self-reported CVD prevalence. Age, BMI, education, wealth index, residency, region, religion, and alcohol were used as covariates. Additionally, interactions model was assessed. Lastly, treatment adherence for CVD was studied, considering treatment behavior, insurance, and healthcare access barriers. Results Cardiovascular disease prevalence was 0.72%. The risk of CVD was higher among the smokers [aOR: 2.26(1.83-2.73)] than smokeless tobacco [aOR: 1.34(1.21-1.49)] consumers. In contrast daily meat consumers showed higher risk [aOR: 1.23(1.03-1.47)] than meat non-consumers. Women who were consumers of both tobacco and meat had risk of [aOR: 1.15 (1.02 - 1.30)] CVD compared to who did not consume both tobacco and meat. Interaction was not detected between tobacco and meat consumption. CVD treatment adherence was higher among the women who possess an insurance [OR: 1.11(1.04-1.19)]. The risk of treatment non-adherence was higher among women who were aged below 40 with no education and from the poorest section of the society. Barriers for accessing health care facilities were solo attendance, provider availability, and drug access. Conclusions Tobacco and meat both need to be addressed to control CVD among women. Empowering women and bringing them under government insurance with an improve health care system are crucial. Key messages • The joint effect of tobacco and meat consumption increased the risk of cardiovascular diseases among women. However, there was no interaction effects observed between tobacco and meat consumption. • Healthcare facilities needs to be improved and awareness among young adults are extremely crucial for better CVD treatment management among women in India.

Lipid changes across menopause status point to increased cardiovascular risk

Abstract Background While women develop cardiovascular disease (CVD) approximately ten years later than men, risk of CVD in women rises precipitously following menopause. The mechanisms underlying this acceleration in CVD risk are not well elucidated, but adverse changes in lipid measures are known to occur during the perimenopause period. Previous investigations have been largely restricted to traditional lipid measures and have not examined changes in lipoprotein particles including lipid subfractions and particle number. Purpose We sought to examine longitudinal changes in lipoprotein particles that occur during the menopause transition. Methods A total of 1305 participants in the Dallas Heart Study with known menopause status underwent measurement of LDL-P, HDL-P, sd-LDL, and ld-HDL by NMR LipoProfile LP4 algorithm (LabCorp, Raleigh Durham, NC, U.S.A.) at 2 examinations (between 7-8 years between DHS studies). We compared longitudinal changes in lipoprotein measures between pre-, peri-, post-menopausal women and men using multivariable adjusted linear regression models. For our analysis peri- is the group that was pre-menopause at DHS I and post-menopause at DHS 2, not to mean the period before menopause. Results There 1346 men (referent group) included in the study with a mean age of 43 ± 9.4 years. There was a total of 1246 women with a mean age of 42 ± 5.6 for peri-group, 54 ± 6.2 for post-group, and 34 ± 3.08 for the pre-group. Of the women 440 (35.3%) were pre-menopausal, 298 (23.9%) were peri-menopausal, and 508 (40.8%) were post-menopausal. Over a median follow-up time of 7 years. All three groups had an increase in LDL-P but the greatest percent change is between peri and post, 18.30 (SE 3.05, P&amp;lt;0.001). When compared to men the post-group has the greatest percent change of HDL-P with a negative change of 4.77 (SE 0.948 P&amp;lt;0.0001). Small-dense LDL had the highest percent change in the peri- group when compared to men with a change of 578.62 (SE 288.45, P&amp;lt;0.045). Large-dense HDL had greatest percent change in the post- group when compared to men with negative change of 37.84 (SE 12.83, P&amp;lt;0.0032). Conclusions We found that menopause is associated with adverse changes in lipoprotein profiles, with the most pronounced changes in LDL-particles and subfractions observed for peri-menopausal women. By contrast, post-menopausal women demonstrated the greatest reductions in HDL-particles and subfractions. Taken together, these changes suggest that menopause is associated with a transition to a more atherogenic lipoprotein profile. Further research is needed to investigate whether these adverse changes in lipoproteins translate to greater CV risk.

Does perceived usability of a multi-component mobile device intervention improve health-related quality of life?

Abstract Background Good health-related quality of life (HRQL) is essential to healthy aging. Prior studies have demonstrated that mobile device technologies can promote HRQL in older adults. However, evidence of technology acceptance in older adults is often inconsistent and poorly understood. Purpose This study aims to 1) describe technology acceptance using efficiency, learnability, user experience (i.e., acceptability), and perceived control from the USABILITY survey of a multi-component mobile device intervention consisting of a wearable activity tracker (Fitbit Versa), access to Lose It app, and text messages (for experimental group only) in older adults at risk for cardiovascular disease, and 2) examine the correlation between technology acceptance and changes in HRQL before and after using each component of the digital intervention. Methods Data were collected using a purpose-built technology usability survey, and HRQL was assessed using the 12-Item Short Form Survey (SF-12), which measured perceived physical and mental health. Correlations were used to identify associations between technology acceptance and HRQL. Results The mean age of participants (n=54) was 65.4 ± 6.0 years; a majority were females (60%), married (53%), Hispanic (66%), and had a high school education or higher (76%). Table 1 shows that the experimental group had considerably higher HRQL at three months, but no differences in technology acceptance were noted. Fitbit technology adoption was found to be correlated with physical HRQL (r=304, p=0.027). The Lose It app showed no correlation with HRQL. Despite receiving higher usability ratings, SMS messages were not correlated with physical or mental HRQL. Conclusion Our findings demonstrate that older persons at risk for cardiovascular disease find mobile device intervention components acceptable. However, each component affected physical and mental health differently. These findings inform more complete technology acceptance models for older individuals' technology design, education, and deployment. Older persons prefer personalized communication, such as customized text messages, as the most favored aspect of the multi-component mobile device intervention. It warrants a larger clinical trial to determine its efficacy on HRQL.

Clinical profile and outcomes of patients with chronic kidney disease on chronic hemodialysis hospitalized for acute coronary syndrome in a tertiary public hospital in the Philippines

Abstract Introduction Acute coronary syndrome (ACS) and end-stage renal disease (ESRD) are both prevalent globally. Of the many risk factors for ACS, chronic kidney disease (CKD) remains to be of great concern because the interplay of cardiac and renal disease is inherently complicated. Cardiovascular mortality rates are 10-30 times higher in the ESRD population. The risk for cardiovascular disease in CKD extends beyond the traditional risk factors. Purpose The guidelines for ACS may not be applicable to the ESRD population because the landmark ACS trials mostly excluded ESRD patients. Due to the gaps in knowledge regarding ACS in ESRD, our study sought to explore the clinical profile and outcomes of these patients in the our institution. Methods We did a retrospective cohort study among ESRD patients presenting with ACS in our institution from May 2021 to November 2023. The data was analyzed using univariate and bivariate statistics using PRISM software. Results A total of 48 patients with ESRD were admitted for ACS in this study - 8 with STEMI and 40 with NSTEMI. The mean age was 61 years old and 33 (68.8%) were male. The average length of hospital stay was 12 days. The most common comorbidities were hypertension (91.7%), heart failure (83.3%), and diabetes mellitus (60.4%). The most common cause of ESRD in our cohort is concomitant hypertensive and diabetic kidney disease (45.8%) with an average length of hemodialysis at 31 months. The most common chief complaints were chest pain (39.6%), dyspnea (29.2%), and decreased sensorium (10.4%). On admission, 18 (37.5%) presented with systolic BP &amp;gt;160mmHg, 7 (14.6%) presented with shock, and 4 (8.3%) presented with cardiac arrest. On electrocardiogram, 21 (43.8%) had left ventricular hypertrophy while 34 (70.8%) had cardiomegaly on chest radiography. On two-dimensional echocardiogram, the average left ventricular ejection fraction was 46% and 27 (90%) had segmental wall motion abnormalities. The most common angiographic finding was 3-vessel coronary artery disease (50%). Only 5 patients (10.4%) had an LDL-C greater than 55mg/dL. Among those with STEMI, 6 (75%) presented with Kilip II or more. While among those with NSTEMI, 27 (67.5%) had a TIMI risk score &amp;gt;2. Almost all patients received dual-antiplatelet therapy, high dose statin, and beta-blocker. The mortality rate was 43.8% with acute coronary syndrome being the most common cause of death. Conclusion Our study did not show significant associated predictors of mortality possibly due to the low sample size. Despite this, our study portrays that patients admitted for ACS with ESRD present with higher risk features reflected by derangement in vital signs, abnormal laboratories, significant imaging abnormalities, high prognostication scores, and high in-hospital morbidity.Predictors of Mortality

Albuminuria is associated with progression of diastolic dysfunction in patients at risk for cardiovascular disease

Abstract Background The number of the patients with heart failure with preserved ejection fraction (HFpEF) is increasing as society ages, which indicates that the number of pre-HFpEF patients is increasing even more. To combat this sociomedical burden, it is critical to establish cost-effective and simple biomarkers to identify the high-risk population at early phase of the disease. Recent studies demonstrated the association between albuminuria and incident heart failure, but the prognostic impact of albuminuria on diastolic dysfunction, an early phenotype of HFpEF, has not been elucidated. Purpose To examine the impact of albuminuria on the diastolic function over time in the patients with cardiovascular risks. Methods One hundred and fifty-eight patients with at least one cardiovascular risk factor without history of heart failure were followed up for 5 years. Echocardiogram was conducted at baseline, year 3, and year 5. Diastolic dysfunction was defined as E/e’ &amp;gt;14. Albuminuria was defined as urine albumin-to-creatinine ratio (UACR) 30 ≧mg/gCre. The patients with ejection fraction &amp;lt;40% and those had diastolic dysfunction at baseline were excluded from the study. The relationship between albuminuria at baseline and diastolic function at year 3 and 5 were investigated. Results Among 158 subjects, 27 showed albuminuria at baseline and the prevalence of hypertension, dyslipidemia, and diabetes was not significantly different between patients with and without albuminuria. The baseline E/e’ tended to be higher in patients with albuminuria, although the difference was not statistically significant (Fig1: E/e’ = 10.0±2.4 vs. 9.4±2.2, p = 0.08) . However, the patients with albuminuria showed a steeper increase in E/e’ than those without albuminuria, and the significant difference was observed at year 3, that was even greater at year 5 (Fig1: E/e’ = 11.1±2.8 vs 10.0±2.6, p = 0.04 in year 3, E/e’ = 12.5±4.1 vs 10.3±2.9, p = 0.002 in year 5, respectively). Furthermore, log UACR at baseline showed significant correlation with E/e’ at year 5 (p = 0.02, r = 0.21) and normo-, micro-, and macroalbuminuria (UACR&amp;lt;30, 30-300, and &amp;gt;300mg/gCre, respectively) at baseline showed elevated E/e’ at year 5 in this order ( p = 0.01 for UACR&amp;lt;30 vs. 30-300mg/gCre, and p = 0.04 for UACR&amp;lt;30 vs. &amp;gt;300mg/gCre, reapectively ). The prevalence of incident diastolic dysfunction increased greater in patients with albuminuria throughout the follow-up period and the difference reached statistical significance at year 5 (Fig2: 18.5% vs. 9.2%, p = 0.28 for year 3, and 25.9% vs. 8.4%, p = 0.009 for year 5, respectively). Conclusion In the patients with cardiovascular risk factors, albuminuria was associated with development and progression of diastolic dysfunction over subsequent 5 years. Future prospective study is warranted to investigate the effectiveness of albuminuria-directed care to prevent development of HFpEF.