Pre-existing Cardiovascular Disease Research Articles

Associations of Serum Lipid Traits With Fracture and Osteoporosis: A Prospective Cohort Study From the UK Biobank.

Previous studies reveal inconsistent associations between serum lipid traits and the risks of fractures and osteoporosis in the general population. This prospective cohort study analysed data from 414 302 UK Biobank participants (223 060 women and 191 242 men, aged 37-73 years) with serum lipid measurements: apolipoprotein A (Apo A), apolipoprotein B (Apo B), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and lipoprotein A (Lp(a)). Multivariable Cox proportional hazard models with penalized cubic splines were used to explore potential nonlinear associations of each lipid trait with the risks of fractures and osteoporosis. Subgroup analyses by age, sex, BMI categories and pre-existing cardiovascular disease were conducted. Mediation analyses using the g-formula were performed to quantify to which extent bone mineral density (BMD) may mediate the association between serum lipids and fracture risk. Over a median follow-up period of 13.8 years, 25 918 (6.8%) of the 383 530 participants without prior fracture had incident fracture cases, and 7591 (4.1%) of the 184 919 participants with primary care data and without baseline osteoporosis were diagnosed with osteoporosis. TG had nonlinear associations with fractures and osteoporosis, whereas Apo B, TC and LDL-C had linear associations. There were also nonlinear associations of Apo A and HDL-C with fractures. Individuals in the highest quintiles for Apo A (fracture: HR 1.15 [95% CI 1.10, 1.21]; osteoporosis: HR 1.13 [1.02, 1.25]) and HDL-C (fracture: HR 1.27 [1.20, 1.34]; osteoporosis: HR 1.31 [1.18, 1.46]) were associated with higher risks of fractures and osteoporosis. Conversely, those in the highest quintile for Apo B (fracture: HR 0.85 [0.81, 0.89]; osteoporosis: HR 0.86 [0.79, 0.94]), LDL-C (fracture: HR 0.89 [0.85, 0.93]; osteoporosis: HR 0.91 [0.83, 1.00]) and TG (fracture: HR 0.78 [0.74, 0.82]; osteoporosis: HR 0.75 [0.68, 0.82]) were associated with lower risks. The associations of Apo A (ratio of HR [RHR] 1.05 [1.02, 1.09]) and HDL-C (RHR 1.06 [1.03, 1.09]) with fracture risk were more pronounced in men compared to women. Except for TG and Lp(a), the associations between serum lipids and fractures appear to be partially mediated through BMD (mediation proportions: 5.30% to 40.30%), assuming causality. Our study reveals a complex interplay between different lipid markers and skeletal health, potentially partially mediated through BMD. Routine lipid profile assessments, including HDL-C and Apo A among other lipid traits, may be integrated into the strategies for fracture risk stratification.

Preliminary data on short-term outcomes within the cardio-obstetrics registry

Abstract Background Pregnancy leads to physiological changes within the cardiovascular system such as increased plasma volume and cardiac output or hypercoagulability. These changes can be challenging for women with pre-existing cardiovascular disease with higher risks of complications. The guidelines of the European Society of Cardiology recommend treating high-risk patients in specialized centres by an interdisciplinary pregnancy heart team. In a team-based approach, the Pregnancy Heart Team was founded at our university hospital, in order to establish specific structures of communication and responsibility. Methods A prospective registry of all patients treated by the Pregnancy Heart Team between November 2022 and March 2024 was established. Patients consisted of women with pre-existing cardiovascular disease undergoing pregnancy as well as women who developed pregnancy-associated cardiovascular disease. Patients were evaluated throughout pregnancy by lab work and echocardiography during each trimester as well as in the postpartum period. Results In total 39 women (mean age 34±5 years) were prospectively included in the registry. 17 patients (43.5%) were classified as mWHO ≥ III. 17 patients (43.5 %) with pre-existing (pregnancy-associated) cardiovascular disease were managed throughout pregnancy and delivery. 9 patients (18.4 %) developed pregnancy-associated cardiovascular diseases such as peripartum cardiomyopathy or spontaneous coronary artery dissection. Preliminary data shows that mean left-ventricular ejection fraction remained stable during pregnancy with a non-significant trend towards lower values postpartum. Cardiac biomarkers such as high-sensitivity troponin T and NT-pro-BNP showed a non-significant trend towards increased values in the third trimester and postpartum. Adverse maternal outcomes occurred in 14 patients (35.9 %), including preterm premature rupture of membranes (12.2%), gestational hypertension (7.6%), gestational diabetes (5.1%), preeclampsia/eclampsia (7.6%) and delivery-associated complications (10.2%). Fetal complications included macrosomia (10.2%) or intrauterine growth retardation (5.1%). Discussion These preliminary data of a real-world patient collectivedemonstrate that a significant number of patients experienced adverse pregnancy outcomes which was associated with a trend towards increased cardiac biomarkers throughout pregnancy and postpartum. As recent studies have shown, interpretation of standard parameters such as cardiac biomarkers is not fully understood during pregnancy, especially in women with pre-existing cardiovascular disease. Our data may aid to understand prognostic implications of cardiac biomarkers during pregnancy.

Personality and cardiovascular mortality risk: a multi-cohort analysis in individuals with and without pre-existing cardiovascular disease

AbstractThis study investigated the associations between personality traits of the Five Factor Model and cardiovascular mortality, with a specific focus on whether pre-existing cardiovascular conditions modified these associations. We used data from 43,027 participants across five cohort studies: Health and Retirement Study (HRS); Wisconsin Longitudinal Study (WLS); National Social Life, Health, and Aging Project (NSHAP); Midlife in the United States (MIDUS); Household, Income, and Labour Dynamics in Australia (HILDA) with a mean age 55.9 years and 6493 individuals with pre-existing cardiovascular disease. We conducted meta-analyses examining conscientiousness, emotional stability, agreeableness, openness to experience, and extraversion in relation to mortality due to coronary heart disease and stroke. During a mean follow-up of 12.1 years, 1620 participants died from coronary heart disease and 454 from stroke. Lower conscientiousness was associated with higher mortality risk from both coronary heart disease (hazard ratio per 1SD = 0.82, 95%CI = 0.75–0.90) and stroke (HR = 0.84, CI = 0.72–0.99). Lower emotional stability predicted increased coronary heart disease mortality (HR = 0.91, CI = 0.85–0.97). The association between conscientiousness and cardiovascular mortality did not differ between individuals with or without baseline cardiovascular conditions. In addition, adjustments for health behaviors and other covariates only slightly attenuated this association. Other personality traits were not associated with cardiovascular disease mortality. Our findings highlight the role of low conscientiousness, and to a lesser extent low emotional stability, in the development and progression of fatal cardiovascular disease through pathways that may extend beyond established health behaviors.

Exploratory mediation analysis of the effect of semaglutide on cardiovascular outcomes in people with overweight or obesity in the SELECT randomised trial

Abstract Background Glucagon-like peptide 1 (GLP-1) receptor agonists have been shown to reduce major adverse cardiovascular (CV) events (MACE) in people with diabetes. The SELECT trial investigated weekly subcutaneous semaglutide 2.4 mg versus placebo in people with pre-existing CV disease and body mass index ≥27kg/m², but without diabetes at randomisation. Over a mean duration of follow-up of 39.8 months, risk of MACE was lower in patients treated with semaglutide vs placebo (6.5% vs 8.0%, hazard ratio, 0.80; 95% CI, 0.72, 0.90; P<0.001). There were improvements in several CV risk factors; however, mechanisms underlying the MACE reduction are unclear. Purpose This prespecified analysis explored whether the effects on measured CV risk factors may mediate the 20% reduction in MACE in SELECT. Methods CV risk factors measured during the trial and included as potential mediators in the analysis were: body weight, waist circumference, high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA1c), lipids, blood pressure, estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR). Mediation analyses were performed using the Vansteelandt repeated regression approach. First, the observed difference in MACE-free survival between semaglutide and placebo at 36 months was estimated as the total effect. The direct effect of semaglutide was then estimated as the difference in MACE-free survival, had the semaglutide arm experienced the values of the mediator observed in the placebo arm during follow-up. The % mediation was then calculated as 100 × (1 – [direct effect] / [total effect]). A reversed counterfactual approach estimating the direct effect as the difference between arms in MACE-free survival, had the placebo arm experienced the mediator values observed in the semaglutide arm, was also conducted. A large disparity between the % mediation from the two approaches can indicate potential treatment–mediator interaction or hidden confounding. Results Statistically significant (P<0.05) improvements in all potential mediators were observed with semaglutide. Table 1 shows the estimated mediation of each potential mediator when evaluated separately. Point estimates for the % mediation were largest for waist circumference (64.0%), hsCRP (42.1%), HbA1c (29.0%) and body weight (19.5%), but with wide 95% CIs. For waist circumference, the estimated mediation was markedly lower using the reversed counterfactual approach, suggesting potential hidden confounding or treatment–mediator interaction (Figure 1). In a multivariable analysis, the estimated joint mediation was 31.4% (−30.1%, 143.6%). Conclusions The results suggest that neither change in body weight nor other measured CV risk factors fully explain the effect of semaglutide on MACE in SELECT. Substantial unmeasured pleiotropic effects of semaglutide on MACE not mediated through these risk factors remain possible.

Generalizability of SELECT to a contemporary cohort of cardiac surgical patients: analysis of the TRICS III Randomized Trial

Abstract Background The SELECT trial reported a significant reduction in cardiovascular (CV) outcomes with semaglutide amongst patients without diabetes who had pre-existing CV disease and a body-mass index (BMI) of 27 or greater. Patients undergoing cardiac surgery represent a high-risk subset of those with established CV disease, and may benefit from treatment with semaglutide. Purpose This study evaluated the generalizability of SELECT to a contemporary international cohort of cardiac surgical patients, and assessed whether differences between SELECT-eligible and non-eligible patients translated to altered risks of CV outcomes. Methods Present data was gathered from the TRICS III trial, a multicentre, randomized trial of restrictive versus liberal red-cell transfusion thresholds amongst 5243 cardiac surgical patients with a EuroSCORE I of ≥6. The proportion of cardiac surgical patients eligible for SELECT was determined by applying its selection criteria to the TRICS III cohort. Finally, baseline characteristics and outcomes stratified by SELECT eligibility were compared. Results A total of 4887 patients from the TRICS III cohort had available data for analysis, of which 452 (9.2%) were deemed to have been eligible for the SELECT trial. A comparison of baseline characteristics between SELECT-eligible and non-eligible patients are presented in Table 1; while SELECT-eligible patients were more likely to have preserved left ventricular function (71.7% vs. 61.0%), EuroSCORE I values were comparable between the two groups (7.8±2.1 vs. 7.9±1.9). The rate of a 3-point MACCE of Death, MI or stroke in the present cohort of SELECT-eligible patients undergoing cardiac surgery (16.6%) was numerically higher than those enrolled in SELECT receiving semaglutide (8.1%) or placebo (10.0%), despite the shorter follow-up (6 months vs. 39.8 months). Six month outcomes following cardiac surgery were similar regardless of SELECT eligibility (Figure 1); no difference in risk of outcomes was documented for the 3-point MACCE [SELECT Eligible vs. Non-eligible – 16.6% vs. 14.5%; OR 1.17 (0.9-1.53); P=0.24] and the TRICS III primary composite of Death, MI, Stroke, or New-Onset Renal Failure with Dialysis [17.0% vs. 17.0%; OR 1.0 (0.77-1.29); P=0.98]. There was a trend towards higher rates of MI at 6 months amongst SELECT-eligible patients, but this difference failed to reach statistical significance [8.5% vs. 6.3%; OR 2.0 (0.96-1.39); P=0.08). Conclusions In this large international cohort of contemporary cardiac surgical patients, nearly 10% would have met eligibility for SELECT. SELECT-eligible patients undergoing cardiac surgery in TRICS III had a numerically higher rate of MACCE than those enrolled in SELECT, highlighting the high risk nature of this patient subgroup. However, amongst SELECT-eligible and non-eligible patients undergoing cardiac surgery, no significant difference in CV outcomes was uncovered.

Does HFpEF represent a risk factor and a marker of cardiotoxicity in patients undergoing cancer treatment?

Abstract Background The prevalence of heart failure with preserved ejection fraction (HFpEF) increases with the aging of our population and shares risk factors with cancer. Furthermore, HFpEF conveys a worse prognosis if it remains unrecognized and untreated. However, it is not considered as a surrogate marker in the baseline risk stratificatoin of patients that will undergo potentially cardiotoxic cancer treatments. Moreover, the definition of cardiotoxicity focuses mainly on systolic dysfunction, based on left ventricular ejection fraction and global longitudinal strain changes. Data on the prevalence of new-onset HFpEF during cancer treatment are limited. Purpose We evaluated the prevalence of HFpEF in cancer patients followed in our cardio-oncology clinic, with new cancer therapy-related cardiovascular toxicity (CTR-CVT) events in patients with known HFpEF prior to cancer therapy. We also assessed the prevalence of patients diagnosed with HFpEF while undergoing cancer therapy. Methods A total of 630 cancer patients referred for either baseline evaluation, on-treatment surveillance, long-term follow-up or new complaints suspect for cardiovascular disease were included in this real-world observational study, with a mean follow-up duration of 507 days. They underwent comprehensive workup in accordance with the ESC guidelines, including clinical assessment, electrocardiogram, echocardiography and biomarker testing. Results From the total population, 36 (5.7%) were diagnosed with HFpEF prior to cancer treatment initiation. Among these, 18 (50%) developed CTR-CVT during follow-up, mainly heart failure events (cancer-therapy related cardiac dysfunction or HFpEF decompensation). Independent of baseline characteristics, 233 patients (37.0%) developed a heart failure event during or after cancer treatment. Of these, 92 patients (14.6% of the total population, 39.5% of all HF events on treatment) developed a HFpEF event during or after cancer treatment. Of these HFpEF events, 42 patients (45.7%) were known with pre-existing cardiovascular disease, of whom only 14 (15.2%) with pre-existing HFpEF. In 50 patients (54.3%) the HFpEF diagnosis was made de novo during (or after) cancer treatment. Patients developing HFpEF were mostly female (n=54, 58.7%) and relatively young (mean age 62.0 years). Most HFpEF events occurred in breast cancer patients (n=32, 34.7%), prostate cancer patients (n=13, 14.1%) and multiple myeloma patients (n=9, 9.8%). Conclusions HFpEF is frequently overlooked, but conveys a high risk of developing CTR-CVT and should therefore be taken into account in the baseline risk stratification. Furthermore, HFpEF is responsible for an important morbidity burden during or after cancer cardiotoxic treatments, even in patients without prior diagnosis of HFpEF at baseline evaluation. Further studies are needed to evaluate if this population may benefit from specific management and treatment strategies in order to improve prognosis.Prevalence of HFpEF in cancer patients

Cardiovascular comorbidities and risk stratification in normotensive acute pulmonary embolism patients with right ventricular dysfunction and normal cardiac troponin: insights from a regional registry

Abstract Background Acute pulmonary embolism (PE) management guidelines categorize normotensive patients with right ventricle dysfunction (RVD) and normal cardiac troponin (cTn) as intermediate low risk. This study explores the prevalence of cardiovascular comorbidities and their impact on risk stratification in this specific cohort. Purpose To investigate the characteristics of normotensive acute PE patients with RVD and normal cTn, emphasizing the role of pre-existing cardiovascular diseases in determining the intermediate-low risk status. Methods A total of 1675 PE patients from a regional registry were screened, excluding high-risk and intermediate-high-risk cases. Among the remaining 400 normotensive patients with RVD, 353 with echocardiography and normal cTn were included. Patients were categorized into low or intermediate-low risk based on RVD presence. Cardiovascular comorbidities were assessed, and logistic regression analyzed their association with intermediate-low risk. Results Intermediate-low-risk patients (n=137) exhibited significantly higher rates of chronic heart failure, arterial hypertension, coronary artery disease, diabetes, and atrial fibrillation compared to low-risk patients (n=216). A substantial 77.4% of intermediate-low-risk patients had at least one cardiovascular comorbidity, significantly elevating the risk of RV dysfunction (adjusted OR 2.954, p<0.001). The all-cause hospital mortality was 5.1% in intermediate-low-risk and 1.4% in low-risk PE. Conclusions Normotensive acute PE patients with RVD and normal cTn are predominantly burdened with chronic cardiovascular conditions. The majority of intermediate-low-risk patients have at least one cardiovascular comorbidity, indicating an increased risk of death during hospitalization compared to low-risk patients. This study underscores the necessity for nuanced risk stratification considering pre-existing cardiovascular diseases for tailored and effective management. These findings have important implications for optimizing treatment strategies and improving outcomes in this high-risk population.

Subclinical left ventricular dysfunction detected by speckle tracking echocardiography predicts mortality in COVID-19 patients

Abstract In COVID-19 patients, both preexisting cardiovascular disease and cardiac injury resulting from SARS-CoV-2 infection are associated with increased mortality. In this patient population the value of speckle tracking echocardiography (STE) for detecting high-risk patients has not been evaluated thoroughly. Aim The aim of study was to determine the prevalence of subclinical myocardial dysfunction revealed by STE and its association with in-hospital and two-year mortality in patients with COVID-19 and preserved left ventricular ejection fraction (LVEF). Methods The study group comprised 163 consecutive patients with preserved LVEF(>/=50%) and maintained right ventricular function evaluated by assessment of tricuspid annular plane systolic excursion (TAPSE >14 mm) hospitalized in the cardiology department due to COVID-19 in 2020 and 2021. All patients underwent transthoracic echocardiographic examination with off-line analysis using STE. Left ventricular global longitudinal strain(GLS), right ventricular global longitudinal strain (RV-GLS), right ventricular free wall strain(RV-FWS) and myocardial work parameters: global work index(GWI), global wasted work(GWW), global constructive work(GCW) and global work efficiency(GWE) were measured. The primary outcome was in-hospital and two-year mortality. Results 96 patients (mean age 66 years, 59 [61%] male) had adequate image quality to evaluate deformation-derived parameters.19 patients (19.8%) died during hospitalization and 9 (9,4%) patients died within two years after discharge. In-hospital non-survivors were older, had lower baseline oxygen saturation(SpO2) and had higher NTproBNP. In non-survivors STE revealed significant impairment of LV and RV function compared to the group of survivors(Table 1). The independent predictors of in-hospital death were: age (OR 1.1 [95% CI 1.01 – 1.19]), SpO2 on admission (OR 0.83 [95% CI 0.75 – 0.93]), NTproBNP (OR 1.0003 [95% CI 1.0001 – 1.0006]) and LV-GLS (OR 1.45 (1.06 – 1.99)]. Based on the analysis of the ROC curves, the cut-off points optimal for predicting in-hospital death were identified: age >71 years (sensitivity [sens.] 74%, specificity [spec.] 68%) , baseline SpO2 value ≤ 89% (sens. 89%, spec. 74%,) NTproBNP >951 pg/ml (sens. 79%, spec. 58%) and GLS >-16% (sens. 63%, spec. 89%). The independent predictors of two-year mortality were: age (OR 1.10 [95% CI 1.02 – 1.19]), Sp02 on admission (OR 0.82 [95% CI 0.73 – 0.91]) and NTproBNP (OR 1.0006 [95% CI 1.0001 – 1.0011]).Based on the ROC curve analysis, the cut-off points optimal for predicting death within 24 months after COVID-19 were also identified: age>71 years (sens. 71%; spec. 72%), Sp02 <89% (sens. 69%, spec. 73%), NTproBNP >520 pg/ml (sens. 89%, spec. 48%). Conclusions STE allows for the detection of subclinical myocardial dysfunction in COVID-19 patients with preserved LVEF. However, LV GLS is the only independent STE-based predictor of in-hospital mortality in this patient population.

Cost-effectiveness of semaglutide for secondary prevention of cardiovascular disease in the United States

Abstract Background In the SELECT trial, semaglutide produced a 20% reduction in the composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke in individuals with overweight or obesity who did not have diabetes but had established pre-existing cardiovascular disease (CVD). Cost is an important barrier to widespread uptake of semaglutide, particularly in the US, and the cost-effectiveness for the secondary prevention of CVD is uncertain. Purpose To evaluate the cost-effectiveness of semaglutide vs. no obesity treatment for the secondary prevention of CVD from a US healthcare sector perspective. Methods The CVD Policy Model is an established, validated simulation model of fatal and non-fatal CVD outcomes and costs in the US population. Using data from the National Health and Nutrition Examination Survey, we created a nationally representative cohort of SELECT-eligible individuals (age ≥45, BMI ≥27kg/m2, no diabetes, pre-existing CVD). Healthcare costs associated with acute and chronic CVD were estimated from national survey and claims data and inflated to 2023 US dollars. The simulated control arm received usual care; the intervention arm received weekly semaglutide 2.4mg injections (assuming 8% discontinuation, which occurs year one). We reproduced the effectiveness of semaglutide based on results of the SELECT trial primary cardiovascular composite endpoint (non-fatal MI, non-fatal strokes and CVD death). The base case assumed 7% of patients receiving semaglutide developed injection-site reactions. Monthly cost of semaglutide was assumed to be $717 (US price net of rebates and discounts), but this was varied in sensitivity analyses. The analysis adopted a health system perspective over lifetime horizon. Results Approximately 4.7 million US adults would meet SELECT trial eligibility criteria. Over a lifetime horizon, semaglutide is projected to avert 538,000 major adverse cardiovascular events (241,000 nonfatal MIs; 80,000 nonfatal stokes, and 217,000 cardiovascular deaths) at an incremental cost of $613 billion. The incremental cost effectiveness ratio for semaglutide was $443,000 per quality-adjusted life year (QALY) gained. In order to meet cost-effectiveness thresholds of $50,000/QALY, $100,000/QALY, $150,000/QALY, drug costs would have to decline 90%, 79%, and 69% respectively. In sensitivity analyses, lowering drug cost to the current UK price (~ $220 per patient per month) would improve the incremental cost-effectiveness of semaglutide to <$150,000 per QALY gained, a potential upper threshold for cost-effectiveness in the US. Conclusion Widespread uptake of semaglutide in the SELECT-eligible U.S. population would prevent a large number of cardiovascular events, but its use would be low economic value at current US prices. Lowering prices in line with those in Europe (e.g., monthly price from $717 to $223) would make the therapy cost-effective at a threshold of $150,000 per QALY gained.

Challenges posed by climate hazards to cardiovascular health and cardiac intensive care: implications for mitigation and adaptation.

Global warming, driven by increased greenhouse gas emissions, has led to unprecedented extreme weather events, contributing to higher morbidity and mortality rates from a variety of health conditions, including cardiovascular disease (CVD). The disruption of multiple planetary boundaries has increased the probability of connected, cascading, and catastrophic disasters with magnified health impacts on vulnerable populations. While the impact of climate change can be manifold, non-optimal air temperatures (NOTs) pose significant health risks from cardiovascular events. Vulnerable populations, especially those with pre-existing CVD, face increased risks of acute cardiovascular events during NOT. Factors such as age, socio-economic status, minority populations, and environmental conditions (especially air pollution) amplify these risks. With rising global surface temperatures, the frequency and intensity of heatwaves and cold spells are expected to increase, emphasizing the need to address their health impacts. The World Health Organization recommends implementing heat-health action plans, which include early warning systems, public education on recognizing heat-related symptoms, and guidelines for adjusting medications during heatwaves. Additionally, intensive care units must be prepared to handle increased patient loads and the specific challenges posed by extreme heat. Comprehensive and proactive adaptation and mitigation strategies with health as a primary consideration and measures to enhance resilience are essential to protect vulnerable populations and reduce the health burden associated with NOTs. The current educational review will explore the impact on cardiovascular events, future health projections, pathophysiology, drug interactions, and intensive care challenges and recommend actions for effective patient care.

Validation of digital cardiovascular risk score (DiCAVA) in the United States All of Us dataset

Abstract Introduction The cardiovascular disease (CVD) risk score DiCAVA was developed in 2021 using UK Biobank data with the aim to be used for population health screening by deriving its predictions only from variables readily available to every individual, omitting difficult-to-obtain measurements such as blood pressure and invasive blood tests for metrics like cholesterol or HbA1c, which are commonly used in clinical CVD risk assessment tools. The original set of variables was reduced to 30 in the DiCAVA Lite score to further improve usability in a digital solution accessible to the general population, while maintaining its discrimination ability. Purpose Like many countries, the US has a large burden of CVD and would benefit from easily accessible screening tools. However, to ensure generalisability of the UK-developed score, it is necessary to evaluate its performance in a population where the score is intended to be used. Methods Data from a large real-world modern observational study in the US, All of Us, was used to evaluate discrimination and calibration metrics of the risk score. Participants with pre-existing CVD and without available electronic health records were excluded from the study. Variables from the All of Us dataset were matched to the original variables and any missing values were imputed using multiple imputation. Results 216,985 participants with a median follow-up time of 3.44 years were included in the study. The median age was 51 years and 63% of the population were female. Discrimination ability in the All of Us dataset (C-index 0.76) slightly surpassed the discrimination achieved at training with UK Biobank (C-index 0.73), and that of Framingham risk score calculated for the All of Us population (C-index 0.72), demonstrating the score’s usability in the US. The score showed very good discrimination in both males (C-index 0.74) and females (C-index 0.77), all ethnic groups and age groups, with the exception of the population over 65 years of age, where the C-index dropped to 0.65 as expected (similar to that observed in the UK Biobank). Calibration of the original model was assessed at 3 years and showed under-estimation of the predicted risk (calibration-in-the-large of 2.37%). Following re-calibration, the algorithm demonstrated excellent results with the average predicted 3-year risk showing 0.59% difference from the observed CVD rate (calibration plot in Figure). Conclusions Overall, the DiCAVA Lite score has shown very good discrimination in the US, showing its generalisability in different demographic populations. Its re-calibrated form is now validated for use in the US population and because of its ability to be utilised outside clinical settings, it can be deployed widely in the general population as an initial screening tool and potentially boost awareness of cardiovascular health in an effort to drive preventative care of CVD.Re-calibration of the DiCAVA Lite score

Rationale and Design of a Multi-National Study of Physicians' Opinions, Attitudes, and Practices Regarding Influenza Vaccination in Patients with Cardiovascular Diseases: A Mixed Methods Designs. The FLUence Project.

Infections, particularly those involving the respiratory tract, are associated with an increased incidence of cardiovascular events, both de novo and as exacerbations of pre-existing cardiovascular diseases. Influenza vaccination has consistently been shown to reduce the incidence of cardiovascular events. Nonetheless, vaccination rates among adults remain suboptimal, both in the general population and among high-risk individuals. Multiple barriers hinder achieving adequate vaccination rates, with physicians' beliefs and attitudes towards these interventions being crucial. The FLUence project was developed within the framework of the World Heart Federation's Emerging Leaders program, to address this issue. This project has two phases: a global quantitative survey to assess the perceptions, opinions, and attitudes and challenges of physicians worldwide regarding the safety and efficacy of the influenza vaccination use, and a qualitative survey to further investigate the barriers and facilitators of recommending and using this vaccination. The quantitative survey was created and disseminated in five languages (English, Spanish, French, Italian, and Portuguese) to physicians of all specialties who care for adults, with a particular focus on patients with cardiovascular disease. The survey included eight domains with a total of 36 questions with closed options; a Likert scale with five possible answers was used to gauge participants' opinions. To gain deeper insights into the complexities behind the low vaccination rates in adults, the second part of the project comprises a qualitative survey, conducted in the two lower-middle- and upper-middle-income countries: India and Argentina, respectively. These countries were selected because patients with cardiovascular diseases have access to free influenza vaccination in Argentina, whereas patients must pay for the vaccine out of pocket in India. Thus, the FLUence study will provide valuable information to better understand the perceptions and barriers to improving influenza vaccination rates from the perspective of physicians. It is imperative to actively engage all healthcare providers to improve influenza vaccination rates.

Interaction between non-alcoholic fatty liver disease and obesity on the risk of developing cardiovascular diseases

BackgroundsThis investigation seeks to explore the correlation between nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs), and to to provide evidence for the prevention and treatment of CVDs.MethodsThis study utilized data from the Jinchang cohort platform, including 19,399 participants without pre-existing major CVDs. Based on the general population and gender stratification, Cox models were used to analyze the risk of NAFLD for CVDs. The combined effect of NAFLD and different obesity indicators on CVDs was analyzed by additive and multiplicative interaction models and subgroups.ResultsThere were 3129 NAFLD patients out of 19399 subjects, and 723 (23.11%) of them had the CVD. After adjusting for multiple confounding factors, the Cox model revealed a 1.17-fold increase in the risk of CVDs among patients with NAFLD compared to those without NAFLD. Moreover, there was no notable disparity in CVDs risk among most NAFLD patients at the same level of obesity. The results indicated no additive interaction between NAFLD and obesity concerning CVDs risk, but rather a positive multiplicative interaction. Using the normal population as a reference, it was found that people with both obesity and NAFLD significantly increased the risk of developing CVDs, with HRs and 95% CIs of 1.790 (1.508, 2.126), 1.356 (1.213, 1.517), and 1.807 (1.503, 2.174), respectively, for BMI, WC, and the combination of BMI and WC.ConclusionsNAFLD and obesity are independent risk factors for CVDs. The synergy of obesity and NAFLD implies that NAFLD patients should control weight gain. Larger BMI and WC values may increase the CVDs risk for NAFLD patients, especially women.

The Influence of Physical Activity and Diet Mobile Apps on Cardiovascular Disease Risk Factors: Meta-Review.

The literature on whether physical activity (PA) and PA and diet (PA+Diet) mobile apps improve cardiovascular disease (CVD) risk factors is promising. The aim of this meta-review is to provide an evidence synthesis of systematic reviews and meta-analyses examining the influence of PA and PA+Diet apps on the major CVD risk factors. We systematically searched 5 databases until January 12, 2022. Included systematic reviews and meta-analyses (1) reported the CVD risk factor outcomes of BMI, waist circumference, body weight, blood pressure (BP), hemoglobin A1c (HbA1c), fasting blood glucose, blood lipids, or PA; (2) enrolled healthy participants ≥18 years who may or may not have the metabolic syndrome, diabetes mellitus, or preexisting CVD risk factors; (3) reviewed PA or PA+Diet app interventions integrating behavioral change techniques (BCT) to deliver their information; and (4) had a nonapp control. In total, 17 reviews (9 systematic reviews and 8 meta-analyses) published between 2012 and 2021 qualified. Participants were middle-aged, mostly women ranging in number from 10 to 62,219. Interventions lasted from 1 to 24 months, with the most common behavioral strategies being personalized feedback (n=8), self-monitoring (n=7), and goal setting (n=5). Of the PA app systematic reviews (N=4), the following CVD risk factors improved: body weight and BMI (n=2, 50%), BP (n=1, 25%), HbA1c (n=1, 25%), and blood lipids (n=1, 25%) decreased, while PA (n=4, 100%) increased. Of the PA+Diet app systematic reviews (N=5), the following CVD risk factors improved: body weight and BMI (n=3, 60%), BP (n=1, 20%), and HbA1c (n=3, 60%) decreased, while PA (n=3, 60%) increased. Of the PA app meta-analyses (N=1), the following CVD risk factors improved: body weight decreased (-0.73 kg, 95% CI -1.45 to -0.01; P=.05) and PA increased by 25 minutes/week (95% CI 0.58-1.68; P<.001), while BMI (-0.09 kg/m2, 95% CI -0.29 to 0.10; P=.35) and waist circumference (-1.92 cm, 95% CI -3.94 to 0.09; P=.06) tended to decrease. Of the PA+Diet app meta-analyses (n=4), the following CVD risk factors improved: body weight (n=4, 100%; from -1.79 kg 95% CI -3.17 to -0.41; P=.01 to -2.80 kg 95% CI -4.54 to -1.06, P=.002), BMI (n=1, 25%; -0.64 kg/m2, 95% CI -1.09 to -0.18; P=.01), waist circumference (n=1, 25%; -2.46 cm, 95% CI -4.56 to -0.36; P=.02), systolic/diastolic BP (n=1, 25%; -4.22/-2.87 mm Hg, 95% CI -6.54 to -1.91/ -4.44 to -1.29; P<.01), and HbA1c (n=1, 25%; -0.43%, 95% CI -0.68 to -0.19; P<.001) decreased. PA and PA+Diet apps appear to be most consistent in improving PA and anthropometric measures with favorable but less consistent effects on other CVD risk factors. Future studies are needed that directly compare and better quantify the effects of PA and PA+Diet apps on CVD risk factors. PROSPERO CRD42023392359; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=392359.

12213 Is Atrial Fibrillation An Adverse Cardiovascular Effect Of Romosozumab

Abstract Disclosure: S. Martinez: None. D. Anez: None. M. Shahid: None. Osteoporosis and cardiovascular disease are both common in older populations. Therefore, it is not uncommon to find the two disorders in a single individual and yet it may be difficult to establish whether the diseases are coincident or the result of complex hormonal processes interacting with multiple systems, including possibly sclerostin. Indeed, pre-existent cardiovascular disease predisposes to osteoporotic bone loss and increased fracture risk. To date, a number of studies have linked the incidence of major adverse cardiovascular events (MACE) with various osteoporosis treatments while other treatments have demonstrated no associated or a reduced cardiovascular risk. Here we discuss the possibility of romosozumab-induced sudden, new onset atrial fibrillation (a fib) in a 70-year-old female with no known risk factors other than age. A 70-year-old female with a 20-year history of osteoporosis presented to establish care. After 5 years of alendronate therapy, she was switched to denosumab injections, 60 mg every 6 months. During Covid the patient’s physicians closed their office and denosumab therapy was interrupted for approximately 18 months. Therefore, when the patient established care with a new rheumatologist she was started on romosozumab. After 6 months of romosozumab the patient developed new onset atrial fibrillation. The cardiovascular safety of romosozumab, in particular, has been adjudicated in two large trials describing predominantly major cardiovascular events such as myocardial infarction, stroke, heart failure and cardiovascular death. In one of those trials, two reports of atrial fibrillation were also included in the adverse events but further details were not available. These increased MACEs prompted a safety warning from the FDA such that use of romosozumab in patients who have experienced a myocardial infarction or stroke within the year prior to its use is contraindicated. Recently atrial fibrillation and congestive heart failure were documented in 78-year-old woman who had been receiving romosozumab for three months for the treatment of osteoporosis. Our case represents a second report of a temporal relationship between the initiation of romosozumab and the onset of atrial fibrillation raising the question of a possible cause and effect. Disclaimer: This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities. Presentation: 6/3/2024

Age, anticoagulants, hypertension and cardiovascular genetic traits predict cranial ischaemic complications in patients with giant cell arteritis

ObjectivesThis project aimed to determine whether cranial ischaemic complications at the presentation of giant cell arteritis (GCA) were associated with pre-existing cardiovascular (CV) risk factors, CV disease or genetic risk...

Evaluation of cardiovascular risk in patients with prostate cancer initiating novel hormonal therapy.

301 Background: Cardiovascular risk factor modification is crucial for cancer patients, particularly for those receiving hormonal therapy due to the increased risk of cardiovascular disease (CVD). However, the evaluation of cardiovascular risk in prostate cancer patients undergoing novel hormonal therapy (NHT) remains not well understood. This study aimed to assess the incidence of cardiovascular events in patients with prostate cancer initiating NHT and compare the risk with non-cancer matched controls. Methods: This study is a retrospective cohort analysis that examined electronic medical records from a global federated health research network, TriNetX. The study included male patients with prostate cancer who were 18 years or older and had initiated treatment with abiraterone, enzalutamide, apalutamide, or darolutamide between January 1, 2015, and December 31, 2020. The cohort was stratified based on diabetes mellitus (DM) and prior CVD status. We evaluated the incidence of myocardial infarction (MI) within 1 and 3 years after NHT initiation. MI risk was compared between each strata of cancer patients and propensity score matched non-cancer patients with cox proportional hazards models, with a significance threshold of p&lt;0.05. Results: There were 11,536 patients with prostate cancer receiving NHT, having a mean age of 70.4 years and predominately White (70%). Of this cohort, 22% had DM, 23% had CVD, and 62% had neither condition. One- and 3-year incidence of MI was 5% and 7% amongst all patients; those with DM, CVD, or both had higher incidences of MI at 3 years, with the rates of 13%, 18%, 22% respectively. Adjusted analyses showed that prostate cancer patients initiating NHT had significantly higher hazards of MI compared to matched non-cancer controls (HR: 1.57 [95% CI: 1.32-1.86] for DM, 1.31 [95% CI: 1.14-1.50] for CVD, and 1.29 [95% CI: 1.05-1.57] for both DM and CVD). Conclusions: The incidence of MI is relatively low in prostate cancer patients starting NHT without DM or CVD comorbidities. However, those patients with pre-existing DM and/or CVD are at significantly higher risk of MI, even more than age matched controls without cancer with those co-morbidities. This highlights the need for comprehensive cardiovascular risk stratification and management in high-risk patients with prostate cancer.

Risk of short-term cardiovascular disease in relation to the mode of delivery in singleton pregnancies: a retrospective cohort study

Cardiovascular disease (CVD) is increasing in prevalence and affects up to 4% of pregnancies in otherwise healthy persons. The specific factors that drive the development of CVD in pregnant people are poorly characterised. This study aimed to determine whether the mode of delivery in singletons affects the risk of cardiovascular morbidity and mortality within one year in patients without prior CVD. We designed a retrospective cohort study utilising the Nationwide Readmissions Database (NRD) to identify singleton delivery hospitalisations in the United States from Jan 1, 2010 to Nov 30, 2018. International Classification of Disease (ICD) versions 9 and 10 codes were used to identify patients with readmission for CVD within the calendar year of index delivery. Patients aged 15-54 who underwent a singleton vaginal or caesarean delivery were included. Patients with pre-existing CVD hospitalisations before or during delivery, ectopic pregnancies, or abortive outcomes were excluded. Participant data was retrieved from the NRD database. The primary outcome was hospital readmission, defined by ICD 9 and 10 codes for fatal or non-fatal CVD in the same calendar year as delivery. Cox proportional hazard regression models were used to adjust for confounders. These included maternal age, hospital bed size, hospital type, hospital teaching status, income quartile, insurance, and year of delivery. Additional sub-analyses were performed adjusting for hypertensive disorders of pregnancy and diabetes mellitus. Of the 14,179,299 singleton deliveries, 32% (n=4,553,492) underwent a caesarean. CVD readmissions occurred in 255.2 per 100,000 (n=11,710) caesarean deliveries compared with 133.9 per 100,000 (n=12,507) vaginal deliveries (rate difference [RD], 121.4, 95% confidence interval [CI], 114.8-127.9; hazard ratio [HR] adjusted for all confounders including hypertensive disorders of pregnancy and diabetes mellitus was 1.42, 95% CI 1.35-1.50). This association was highest in the first 0-29 days following delivery (HR 1.68, 95% CI 1.59-1.78). The risk of readmission for CVD persisted for one year. These findings suggest that caesarean delivery of singletons is associated with a higher risk of cardiovascular morbidity in patients without pre-existing CVD. This risk was highest in the first month but remained elevated for one year after delivery. These findings add to the accumulating evidence that undergoing caesarean delivery may have long-standing health implications and support the extension of the post-partum surveillance period. Limitations of this study include the lack of adjustment for body mass index, race, and parity. We were also unable to determine the reason for the caesarean delivery. None.

Incidence and risk of post-COVID-19 thromboembolic disease and the impact of aspirin prescription; nationwide observational cohort at the US Department of Veteran Affairs.

COVID-19 triggers prothrombotic and proinflammatory changes, with thrombotic disease prevalent in up to 30% SARS-CoV-2 infected patients. Early work suggests that aspirin could prevent COVID-19 related thromboembolic disorders in some studies but not others. This study leverages data from the largest integrated healthcare system in the United States to better understand this association. Our objective was to evaluate the incidence and risk of COVID-19 associated acute thromboembolic disorders and the potential impact of aspirin. This retrospective, observational study utilized national electronic health record data from the Veterans Health Administration. 334,374 Veterans who tested positive for COVID-19 from March 2, 2020, to June 13, 2022, were included, 81,830 of whom had preexisting aspirin prescription prior to their COVID-19 diagnosis. Patients with and without aspirin prescriptions were matched and the odds of post-COVID acute thromboembolic disorders were assessed. 10.1% of Veterans had a documented thromboembolic disorder within 12 months following their COVID-19 diagnosis. Those with specific comorbidities were at greatest risk. Preexisting aspirin prescription was associated with a significant decrease risk of post-COVID-19 thromboembolic disorders, including pulmonary embolism (OR [95% CI]: 0.69 [0.65, 0.74]) and deep vein thrombosis (OR [95% CI]: 0.76 [0.69, 0.83], but an increased risk of acute arterial diseases, including ischemic stroke (OR [95% CI]: 1.54 [1.46, 1.60]) and acute ischemic heart disease (1.33 [1.26, 1.39]). Findings demonstrated that preexisting aspirin prescription prior to COVID-19 diagnosis was associated with significantly decreased risk of venous thromboembolism and pulmonary embolism but increased risk of acute arterial disease. The risk of arterial disease may be associated with increased COVID-19 prothrombotic effects superimposed on preexisting chronic cardiovascular disease for which aspirin was already prescribed. Prospective clinical trials may help to further assess the efficacy of aspirin use prior to COVID-19 diagnosis for the prevention of post-COVID-19 thromboembolic disorders.

Cardiac biomarkers in COVID-19: what did we learn?

COVID-19, caused by the SARS-CoV-2 virus, has generated a global pandemic with a wide range of clinical manifestations. Cardiovascular complications are frequently observed in individuals with COVID-19, particularly those with preexisting cardiovascular risk factors or diseases. Cardiac biomarkers, including troponin, natriuretic peptides, and inflammatory markers, play a vital role in risk stratification, diagnosis, monitoring, and prognosis in COVID-19 patients. These biomarkers provide valuable insights into cardiac injury, myocardial stress, inflammation, and the prediction of adverse cardiovascular outcomes. This review aims to provide better understanding of how Cardiac biomarkers correlate to clinical manifestation of COVID-19. We retrieved studies from PubMed, Medline, and Google Scholars that included results on cardiac biomarkers in COVID-19. Total of 14 studies were reviewed. 8 studies showed evidence of poor progression of the disease when there is increased troponin. 6 studies out of the 14 mentioned in this review showed positive correlation between mortality and elevation in cardiac biomarkers. This shows the significance of cardiac biomarkers in predicting the mortality in patients with COVID-19. It was shown that elevated cardiac biomarkers were associated significantly to poor outcome of covid-19 infection. The outcomes that were linked to increased cardiac biomarkers included increased length of hospitalization, need of life sustaining treatment, myocarditis, invasive and non-invasive respiratory support, and even death were linked to elevated cardiac biomarkers levels.