Pre-existing Cardiovascular Disease Research Articles

Abstract 4137917: Eligibility and Preventable CVD Events in US Adults with Cardiovascular Disease and Overweight or Obesity: Projections from the SELECT Trial

Background: The Trial to Evaluate Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT) showed cardiovascular disease (CVD) benefits of semaglutide therapy in patients with preexisting CVD and overweight or obesity. Purpose: To estimate the number of US adults with CVD and overweight or obesity that may be eligible for semaglutide based on SELECT eligibility criteria and the number of preventable CVD events from semaglutide treatment based on observed CVD event reductions in SELECT. Methods: We included US adults from the National Health and Nutrition Examination Survey (NHANES) 2011-2020 who had eligibility criteria from SELECT. This included patients aged > 45 years who had preexisting CVD and a BMI of > 27kg/m 2 but no history of diabetes. Using NHANES sample weighting, we estimated the number of SELECT-eligible US adults and primary composite and secondary CVD endpoints that would occur based on SELECT treated and placebo published event rates, with the difference indicating the number of preventable events (and annualized based on mean 3.3-year follow-up). Results: Among 8783 (projected to 77.9 million [M]) adults with overweight or obesity, we estimated 493 (4.1 million) (5.61%) to fit SELECT eligibility criteria. Compared to SELECT trial participants, our sample had a higher proportion of Black participants and was older with higher levels of diastolic blood pressure, total, LDL and HDL-cholesterol, and lower BMI, HbA1c, eGFR and triglycerides. Prior myocardial infarction was less common, but stroke was more common in our sample. From SELECT semaglutide and placebo primary composite CVD event rates of 6.5% and 8.0%, respectively, we estimated 79949 and 98399 CVD events would occur annually, the difference being 18450 potentially preventable CVD events. Moreover, we similarly estimated 104,549 and 357,928 annual preventable cases of diabetes and pre-diabetes, respectively. The Figure shows the estimated number of primary and secondary CVD outcomes that could be prevented annually. Conclusion: Semaglutide may prevent many fatal and non-fatal CVD events, as well as incident cases of diabetes and pre-diabetes if provided to US adults meeting SELECT eligibility criteria. More efforts are needed to educate clinicians and patients on the benefits of semaglutide 2.4mg in those with preexisting CVD and overweight or obesity.

Abstract 4117414: Risk Factors Associated with Cardiac Hospital Admissions in Cancer Patients Treated with Immune Checkpoint Inhibitors

Background: Immune checkpoint inhibitors (ICIs) are highly effective anti-cancer treatments for several cancers. However, treatment with ICIs is associated with metabolic perturbations, accelerated atherosclerosis, and increased risks of adverse cardiovascular events. In this study, we aimed to determine risk factors associated with cardiac hospital admissions in patients treated with ICIs for their cancer. Methods: Retrospective data was collected for all patients treated with ICIs between 1 January 2010 and 1 January 2020 through the Hunter New England Local Health District (HNELHD), Australia. Patient medical history and demographics were collected through electronic medical records. Outcome data was obtained from the HNELHD Institutional Cardiac and Stroke Outcomes Unit database. Cardiac admission was defined as cardiac disease based on hospital administration ICD-10 codes. Binary logistic regression was used for multivariate analysis and performed through SPSS version 28. Results: A total of 1,080 patients were included in the final analysis. Mean age of patients was 66.9 ± 11.7 years, with the majority male sex ( n =685; 63.4%). Primary cancer diagnosis of patients treated with ICIs included melanoma ( n =417; 38.7%), and cancer of the lung ( n =327; 30.3%). Nivolumab monotherapy was the most used first-line ICI treatment ( n =475; 44.0%) followed by pembrolizumab monotherapy ( n =428; 39.6%). A total of 266 (24.6%) patients had at least one cardiac hospital admission. On univariate analysis, pre-existing cardiovascular disease (CVD) ( p <0.001), diabetes mellitus ( p <0.001), chronic kidney disease ( p <0.001), and prior CVD medications ( p <0.001) were associated with cardiac hospitalisation. On multivariate analysis, prior history of heart failure ( p <0.001), hypertension ( p =0.003), ischaemia, and peripheral vascular disease ( p =0.049) were independently associated with an increased risk of cardiac hospital admission. Conclusions: In cancer patients treated with ICIs, pre-existing CVD risk factors increases the risk of cardiac-associated hospitalisations. Adequate CVD risk modification and monitoring during treatment with ICIs may be necessary to reduce cardiac hospitalisations.

Abstract 4131100: Effect of metabolic surgery on cardiovascular outcomes in people with obesity and pre-existing cardiovascular disease: A systematic review and meta-analysis

Background: Previous literature shows that metabolic surgery effectively decreases the risk of cardiovascular disease (CVD) events in patients with obesity. The use of metabolic surgery has, however, been limited in people with obesity and pre-existing CVD due to concerns of poor post-operative cardiovascular outcomes. This study aims to determine the effectiveness and safety of metabolic surgery in patients with pre-existing CVD. Methods: A search of electronic databases, PubMed, Cochrane Central and SCOPUS was conducted from their inception till May 2024. The study was conducted adhering to the PRISMA guidelines. Outcomes of interest were risk of all-cause mortality, major adverse cardiovascular events (MACE), risk of myocardial infarction (MI), and cerebrovascular events in patients with and without prior CVD undergoing bariatric surgery. Data was pooled as generic inverse variance using a random effects model, and presented as hazard ratios (HR) with their 95% confidence intervals (CI). Results: We included four studies in our analysis (n = 5,244). Our pooled analysis shows that metabolic surgery leads to significant reduction in risk of all-cause mortality (HR = 0.51, 95% CI: [0.42, 0.61]; p<0.01). We also observed a significant risk reduction of 43% in MACE with metabolic surgery (HR = 0.57, 95% CI: [0.5, 0.64]; p<0.01). Metabolic surgery was not associated with a significant reduction in the risk of MI (HR = 0.53, 95% CI: [0.24, 1.18]; p = 0.12, I 2 = 83%). Similarly, a non-significant decrease in risk of cerebrovascular events was observed with metabolic surgery (HR = 0.89, 95% CI: [0.65, 1.22]; p = 0.48) Conclusion: Metabolic surgery is associated with decreased risk of all-cause mortality and MACE in patients with obesity and established CVD. These results are thought to be mediated through reduction in risk factors such as obesity, but also by reducing inflammatory mediators and having other beneficial effects on cardiac structure and left ventricular workload.

Abstract 4135517: Echocardiographic Biomarkers Enhance Mortality Predictions in Cirrhosis Patients

Introduction: Cirrhosis, a late-stage liver disease, is associated with numerous systemic complications, making long-term mortality prediction challenging. Traditional models like Child-Pugh and MELD are primarily designed for short-term (3-month) mortality. This study evaluates the impact of incorporating echocardiographic (echo) variables in predicting long-term mortality in cirrhosis patients. Methods: A retrospective cohort study was conducted using data from 60 patients with clinically diagnosed cirrhosis from Hippokration Hospital, Greece, spanning 2018 to 2022. Patients were followed for up to 52 months. Exclusion criteria included pre-existing cardiovascular diseases and significant co-morbidities. Patients were categorized into survived to end of study (n=31) and died during study (n=29) groups. Outcomes were analyzed using multivariate logistic regression and Cox proportional hazards models, and include parameters for age, blood pressure, lab-based biomarkers (potassium, pro-brain natriuretic peptide, hemoglobin, platelet count, aspartate transaminase, gamma-glutamyl transferase, uric acid), and echo/ecg measurements (QT interval, left ventricular (LV) ejection fraction, LV global longitudinal strain (GLS), left atrial GLS, annulus velocities, and E/A ratio). Results: The multivariate logistic regression model (MELD+) that included echo variables showed a 10% improvement in area under the curve (AUC: 0.901) compared to the MELD model alone (AUC: 0.817). MELD+ improved risk classification accuracy by nearly 10% with a conservative threshold. The Cox proportional hazards model with MELD+ also demonstrated superior performance (AUC: 0.923; C-index: 0.875; Brier Score: 0.097) compared to the MELD model alone (AUC: 0.892; C-index: 0.831; Brier Score: 0.134). The MELD+ model showed less variation in hazard ratio confidence intervals, indicating more consistent risk estimation. Conclusion: Incorporating echocardiographic measurements enhances the accuracy of long-term mortality predictions in cirrhosis patients. These findings suggest that cardiac imaging should be considered in risk assessments for cirrhosis patients, particularly for predicting survival beyond three months.

Cardiovascular Profile of Patients With COVID-19 Infection Admitted in a Tertiary Care Hospital in Manila, Philippines: A 2-Year Single-Center Retrospective Study

INTRODUCTION: Respiratory symptoms are the most commonly observed clinical manifestations in patients with COVID-19 infection; however, some patients may present with cardiovascular complications. Patients with underlying cardiovascular diseases are associated with increased mortality risk. This study aimed to provide local data on the clinical profile and cardiovascular outcomes and to determine predictors of in-hospital mortality among COVID-19 patients admitted to a tertiary care hospital in the Philippines. METHODS: This single-center retrospective study included hospitalized patients diagnosed with COVID-19 between March 2020 and May 2022. Clinical parameters were subjected to univariate and multivariate regression analyses, with in-hospital mortality as the dependent variable. RESULTS: A total of 1341 patients were admitted with a mean age of 50 years, half of whom were males. Hypertension is the most common comorbidity (728 [54.3%]), followed by diabetes mellitus (393 [29.3%]) and heart disease (136 [10.1%]). Patients admitted to the intensive care unit had significantly higher systolic blood pressure than non–intensive care unit patients (127 ± 19 vs 139 ± 26 mm Hg; P < 0.001), as well as higher plasma erythrocyte sedimentation rate, C-reactive protein, D-dimer, troponin, ferritin, and lactate dehydrogenase. The most common cardiac complications observed were heart failure (39%), acute cardiac injury (30%), and arrhythmia (30%). During hospitalization, 100 patients (7.4%) died; almost half were admitted to the critical care unit, and 84 had cardiac complications, with heart failure (21%) being the most common. Sinus tachycardia was the most common electrocardiographic abnormality (436 [32%]). Univariate analysis showed diabetes (odds ratio [OR], 2.7; P = 0.029) and hypertension (OR, 3.4; P = 0.11). Multivariate analysis revealed that age (OR, 1.095; P < 0.05) and admission duration (OR, 0.906; P < 0.05) were significantly associated with mortality. CONCLUSION: This study highlights the clinical characteristics of patients contracted with COVID-19 who may experience several cardiac conditions. Therefore, particular attention should be given to the role of preexisting cardiovascular diseases and cardiac complications that may contribute to long-term outcomes. KEYWORDS: cardiac complications, COVID-19, cardiovascular outcomes

Association of Homelessness and Unstable Housing With Cardiovascular Care Utilization Among Veterans.

Veterans are disproportionately more likely to experience homelessness and unstable housing (HUH) compared with the general population. Cardiovascular disease is the leading cause of death among Veterans experiencing HUH. We aimed to understand whether HUH status among Veterans with preexisting cardiovascular disease was associated with disparities in cardiovascular care access and utilization. Retrospective study of all Veterans with preexisting cardiovascular disease between 2017 and 2019 using Veterans Affairs Corporate Data Warehouse and Homeless registry data. Primary outcomes were annual outpatient visits for cardiovascular disease management and visits with cardiovascular disease-related specialists. Secondary outcomes included cardiovascular disease-related procedures and emergency department visits and hospitalizations. HUH status was determined based on response to a screener, diagnostic codes, or use of homelessness services, and outcomes were assessed in the first year HUH status was determined. After applying inverse probability of treatment weighting, negative binomial and logistic regression models were fit to estimate the association between experiencing HUH and the outcomes of interest. Among 1 357 973 Veterans (mean age, 71.6 [SD=10.6] years; 2.5% female) with preexisting cardiovascular disease, 56 093 were identified as experiencing HUH during the study period. Veterans experiencing HUH had fewer outpatient visits for cardiovascular disease management or with cardiovascular disease-related specialists (4.3% [95% CI, 2.5%-6.1%] and 14.1% [95% CI, 12.5%-15.8%], respectively) compared with housed Veterans. HUH status was associated with lower rates of receiving certain procedures including coronary artery bypass graft, lower extremity revascularization, and carotid artery stenosis interventions and higher rates of all-cause and cardiovascular emergency department visits and hospitalizations. Veterans with chronic cardiovascular conditions experiencing HUH had lower rates of outpatient visits for cardiovascular disease management and higher rates of emergency department visits and hospitalizations. Given the disproportionate burden of cardiovascular disease in this population, interventions to improve access to cardiovascular care are needed.

Tuberculosis and increased incidence of cardiovascular disease: Cohort study using US and UK health records.

Limited evidence suggests elevated risks of cardiovascular disease (CVD) among people diagnosed with tuberculosis (TB) disease, though studies have not adjusted for pre-existing CVD risk. We carried out a cohort study using two separate datasets, estimating CVD incidence in people with TB versus those without. Using data from the United States (Veterans Health Administration) and the United Kingdom (Clinical Practice Research Datalink) for 2000-2020 we matched adults with incident TB disease and no CVD history 2-years before TB diagnosis (US n=2,121; UK n=15,820) with up to 10 people without TB on the basis of age, sex, race/ethnicity and healthcare practice. Participants were followed beginning 2-years before TB diagnosis and for 2-years subsequently. The acute period was defined as 3-months before/after TB diagnosis. TB, CVD and covariates were identified from electronic routinely collected data (primary and secondary care; mortality). Poisson models estimated incident rate ratios (IRR) for CVD events in people with TB compared to those without. CVD incidence was consistently higher in people with TB, including during the baseline period (pre-TB) and particularly in the acute period: IRRs were US 3.5 (95% Confidence Interval 2.7-4.4), UK 2.7 (2.2-3.3). Rate Ratios remained high after adjusting for differences in pre-existing CVD risk: US 3.2 (2.2-4.4), UK 1.6 (1.2-2.1). Increased CVD incidence was observed in people with TB versus those without, especially within months of TB diagnosis, persistent after adjustment for differences in pre-existing risk. Enhancing CVD screening and risk management may improve long-term outcomes in people with TB.

Association of testosterone replacement therapy with atrial fibrillation and acute kidney injury.

Secondary analyses of the Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men (TRAVERSE) trial revealed significantly higher rates of new-onset atrial fibrillation (AF) and acute kidney injury (AKI) in the testosterone replacement therapy (TRT) cohort. To validate the secondary findings of the TRAVERSE trial. We utilized the TriNetX Research Network to identify a cohort of men ages 45-80years old who met similar inclusion criteria to the TRAVERSE trial. We compared hypogonadal men (testosterone 100-300ng/dL) who had a prescription for topical testosterone therapy and men who did not. Propensity score matching was used to match patient populations. Kaplan Meier survival analysis was used to determine the relative risk of new-onset AF and AKI within 3years. New-onset AF and AKI within 3years. There were 2134 men included in each cohort after propensity score matching. Men on TRT had significantly lower testosterone (T) at the time of diagnosis compared to men not prescribed TRT (207 ± 66ng/dL vs 246 ± 140ng/dL, P< 0.001). Kaplan-Meier survival analysis showed a significantly increased risk of AKI among men on TRT (RR 1.53, 95% CI 1.07-2.18). However, TRT was not associated with a significantly increased risk of new-onset AF (RR 1.48, 95% CI 0.93-2.37). Hypogonadal men with underlying cardiovascular risk factors or pre-existing cardiovascular disease who receive TRT may be at increased risk of AKI after starting therapy. We evaluated a large global research database and utilized similar inclusion and exclusion to the TRAVERSE trial. However, our results are limited by the retrospective study design and reliance on documented claims data. Similar to the TRAVERSE trial, our study demonstrated an increased risk of AKI among men on TRT, but did not find increased risk of AF. However, further studies are required to validate these results.

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.

Reproductive factors predict risks of cardiovascular disease and premature death in postmenopausal women with type 2 diabetes: The Fukuoka Diabetes Registry

AimsReproductive factors (reproductive period, age at menarche, and age at menopause) are associated with a risk of cardiovascular disease (CVD) and death in individuals without focusing on comorbid diabetes. However, it remains unclear whether this association also applies to individuals with diabetes. This study investigated the relationship between reproductive factors and the risk of CVD and death in postmenopausal Japanese women with type 2 diabetes. Methods1,592 postmenopausal women with type 2 diabetes without pre-existing CVD were subclassified based on reproductive period (age at menopause minus age at menarche). The primary outcome was a composite of CVD incidence and all-cause death. ResultsThe risk of the outcome decreased with a longer reproductive period. Compared with a reproductive period of ≤ 29 years, the multivariable-adjusted hazard ratios (95 % CI) were 0.80 (0.39–1.66), 0.73 (0.37–1.43), and 0.43 (0.19–0.99) for reproductive periods of 30–34, 35–39, and ≥ 40 years, respectively (p for trend = 0.046). Earlier age at menarche and later age at menopause were also associated with a decreased risk of the outcome. ConclusionsEvaluating reproductive factors may help predict the risks of CVD and death in postmenopausal women with type 2 diabetes.

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&amp;lt;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&amp;lt;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&amp;lt;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(&amp;gt;/=50%) and maintained right ventricular function evaluated by assessment of tricuspid annular plane systolic excursion (TAPSE &amp;gt;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 &amp;gt;71 years (sensitivity [sens.] 74%, specificity [spec.] 68%) , baseline SpO2 value ≤ 89% (sens. 89%, spec. 74%,) NTproBNP &amp;gt;951 pg/ml (sens. 79%, spec. 58%) and GLS &amp;gt;-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&amp;gt;71 years (sens. 71%; spec. 72%), Sp02 &amp;lt;89% (sens. 69%, spec. 73%), NTproBNP &amp;gt;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 &amp;lt;$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