Risk Of Disease Research Articles

Practicing what you preach. Do cardiology trainees in the United Kingdom follow the lifestyle advice that they would give to patients?

Abstract Background The role of lifestyle factors in determining the risk of cardiovascular disease is well established. As a result, lifestyle modification is recommended as part of numerous European Society of Cardiology guidelines. However, it remains uncertain how closely cardiologists adhere to guidelines in their personal life. Poor lifestyle among clinicians can contribute to poor health and may increase absenteeism and potentially reduce the quality of patient care. Purpose To establish whether cardiology trainees in the UK follow appropriate guideline-directed lifestyle advice in their personal life. Methods All cardiology trainees within the UK were eligible to participate in the 2023 British Junior Cardiologists' Association (BJCA) training survey and the survey was advertised through national and local campaigns. The survey contained questions on smoking status, alcohol intake, healthy diet, partaking in regular exercise, frequency of adequate quality of sleep, and demographic questions. Responders were eligible for inclusion if they consented to participate in health and wellbeing survey questions, and if they had completed four demographic questions. Results Of the 398 responders to the 2023 BJCA survey, 212 consented to answer health and wellbeing questions (66% male, age 34±4 years, 42% had dependents) and were included. Responders included trainees representing all four UK nations. Very few cardiology trainees were current smokers either of cigarettes/cigars (n=2, 1%), or e-cigarettes (n=2, 1%), with 12 (6%) being ex-smokers. Few trainees (n=13, 6%) consumed alcohol above the UK recommended maximum of 14 units per week (Fig 1A). However, only 14% (n=29) regularly achieved 30 minutes of moderate or 15 minutes of intense exercise on at least 5 days each week (Fig 1B). Most trainees (n=167, 80%) only obtained adequate sleep on four or fewer nights each week (Fig 1C). Only 37% (n=78) of trainees agreed or strongly agreed that they were able to maintain a healthy diet most days (Fig 1D). Conclusions Most UK cardiology trainees followed guidance related to smoking and alcohol intake. However, far fewer trainees followed healthy lifestyle guidance relating to exercise, sleep, and diet. Whether these findings are similar across other ESC nations should be investigated. Further work is required to establish the impact of healthy living on clinician working activity and subsequent quality of patient care. Training bodies should consider how occupational factors may contribute to a trainee’s adverse healthy living.

Prognostic assessment based on the trajectory of artificial intelligence-enabled electrocardiograms for age estimation

Abstract Background Artificial Intelligence (AI) estimation of age using data from the 12-lead electrocardiogram (ECG) has demonstrated its utility as a biomarker in predicting the future risk of cardiac diseases and mortality. However, expected long-term outcomes based on temporal changes in the AI-ECG age gap remain unclear. Purpose This study aims to utilize the difference between ages predicted by AI-ECG and actual ages longitudinally for follow-up and to assess whether there are significant clinical differences in mortality among specific groups. Methods Among patients at a hospital who had not been used for the AI-ECG age prediction model (121,702 individuals, 522,261 ECGs), 6,685 individuals with 31,858 ECGs who had an index ECG and the subsequent ECG in the fifth year, with at least one intervening ECG were included for analysis. The absolute age gap, defined as the absolute difference between ECG-predicted and chronological age, was limited to ±10 for analysis. Latent class trajectory modeling was then utilized to classify groups based on the AI-ECG age gap. Results Data-driven analysis revealed four distinct trajectory groups based on age gap trajectories: Consistently Young ECG (27.2%), Reversed ECG Aging (35.3%), Accelerated ECG Aging (8.0%), and Consistently Old ECG (29.5%). Notably, the Accelerated ECG Aging group exhibited a significantly higher cumulative incidence of all-cause death (adjusted hazard ratio (HR) 1.66 (95% confidence interval (CI) 1.30-2.12, p-value <0.001) and non-cardiac death (adjusted HR 1.83 (95% CI 1.38-2.43, p-value <0.001) compared to the Consistently Young ECG group. Conclusion Among 4 distinct trajectories based on the changes in the AI-ECG age gap, Accelerated ECG Aging was associated with a heightened risk of all-cause mortality. Additional in-depth analysis of factors associated with Accelerated ECG Aging is warranted.

Pregnancy complications and long-term risk of cardiovascular events in women with heart disease

Abstract Background/Introduction Women with congenital heart or acquired heart disease are at increased risk of atherosclerotic cardiovascular disease. Pregnancy complications are established risk factors for cardiovascular disease in the general population, but their prognostic value for cardiovascular outcomes in the population with congenital or acquired heart disease is unknown. Purpose To determine the frequency and prognostic value of pregnancy complications for the risk of cardiovascular outcomes in women with congenital or acquired heart disease. Methods This nationwide registry-based cohort study included women in Sweden with heart disease (pulmonary arterial hypertension, congenital heart disease or acquired valvular heart disease) with singleton births registered in the national Medical Birth Register between 1973 and 2014. Exposures of pregnancy complications (preeclampsia/gestational hypertension, preterm birth or birth of an infant small for gestational age) were collected from the Medical Birth Register, and cardiovascular outcomes (mortality and hospitalizations) from the Cause of Death Register and the National Inpatient Register. Cox regression models were performed with time-dependent covariates, to determine the possible prognostic value of the studied pregnancy complications for cardiovascular outcomes including atherosclerotic cardiovascular disease, heart failure and arrythmias after adjustment for major confounding including smoking and body mass index. Results Among the total of 2,134,239 women included from the Medical Birth Register, 2,554 women with 5,568 singleton births were affected by heart disease. Preeclampsia/gestational hypertension affected 5.8% of pregnancies, preterm birth 9.7%, and birth of an infant small for gestational age 2.8%. Preterm birth (adjusted HR 1.91 (95% CI 1.38-2.64)) was associated with an increased risk of maternal all-cause mortality. Preeclampsia/gestational hypertension (adjusted HR 1.64 (95% CI 1.18-2.29)) and preterm birth (adjusted HR 1.56 (95% CI 1.19-2.04)) were associated with an increased risk of hospitalizations for atherosclerotic cardiovascular disease. Conclusions Pregnancy complications were frequent in women with congenital or acquired heart disease. With a median follow-up time of 22 years, preterm birth was associated with a higher risk of cardiovascular mortality, and preeclampsia/gestational hypertension and preterm birth were associated with cardiovascular morbidity. In women with heart disease, pregnancy complications may provide additional information for the risk assessment of future cardiovascular outcomes.Overview of study designPrevalence and risk estimation

Unveiling the heartbeat of hope: exploring cardiovascular morbidity, mortality, and socioeconomic threads in 65,173 Child, Adolescent, and Young Adult (caya) cancer patients

Abstract Background Despite significant progress in managing cancer in children, adolescents, and young adults (CAYAs), persistent complications impact their quality of life with some being severe or life-threatening.(1,2) Long-term outcomes depend on common risk factors for malignancy and cardiovascular diseases (CVD) that overlap, and treatments are known to increase the risk for CVD. (3,4) Healthcare inequality due to socioeconomic status is omnipresent and may significantly impact outcomes. Purpose This study aims to comprehensively cover morbidity, mortality, demographic, and socioeconomic factors among CAYAs and investigate their impact on cardiovascular outcomes. Methods This retrospective matched cohort study included the entire Swedish population under 25 with cancer from 1958 to 2021. The study population was identified from the National Board of Health and Welfare's Cancer Register, with controls paired 1:5 based on age, sex, and residence. Multiple registers provided data on morbidity, mortality, and demographics. Results Covering 63 years, identified 65,173 CAYAs (1.24 million patient-years) and matched with 312,935 controls (7.45 million person-years), a total of 378,108 individuals (74% females). The mean follow-up was 19.5 (SD16.9) years for CAYAs, and 23.8 (16.8) for controls, (p<0.001). At the end of the study, the median age of CAYAs was 33.4 (IQR 27.9) years and controls 39.2 (28.3) (p<0.0001), with an age span of <1-88 years in both groups. CVD was detected in 16.9 % of the CAYAs, representing a 1.21-time elevated risk (95% CI 1.18-1.23, p<0.0001) compared to controls. CAYAs had a higher mortality rate, and 5-years survivors lived a mean of 26.9 years shorter than controls. CV mortality was also increased in CAYAs, (1.9% compared to 0.7% in controls) but at a higher age, although at a mean of 22.8 years younger than their controls. The 5-year survivors were older at CV mortality and lived in mean 6.5 years shorter than controls (p<0.0001). After adjusting for socioeconomic factors, individuals born outside Europe and those with greater sick leave had a higher mortality risk, while education and marriage showed a beneficial association with mortality. (p<0.0001). Interpretation The Rebuc study, spanning six decades, revealed a significantly increased risk of serious complications among young cancer patients in Sweden. Not only do young cancer patient survivors face a significantly higher risk for cardiovascular disease, but the higher mortality risk before middle age also underscores the severity of the health challenges they confront. Furthermore, these young individuals are more susceptible to socioeconomic factors that may adversely affect their survival.

The use of myocardial perfusion scintigraphy to screen for asymptomatic coronary artery disease prior to kidney transplantation

Abstract Background and Objectives Advanced chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease (CVD), including significant asymptomatic coronary artery disease (CAD) [1], compared to the general general public. Additionally, CVD is the leading cause of mortality in kidney transplant recipients [2]. Given the relative scarcity of available organs, individuals are commonly screened for CAD with non-invasive cardiac testing such as Myocardial Perfusion Scintigraphy (MPS). However, the benefits of screening for asymptomatic CAD are unproven and in the absence of an established screening protocol, investigations vary centre to centre and can result in uncertain interpretation of results and unnecessary delays in transplantation. The objective of this study was to assess the benefits of asymptomatic CVD screening of potential kidney transplant recipients, and its impact on transplantation outcomes. Methods This retrospective analysis included all MPS requested by the transplant team during patients’ assessment process between 2015 and 2023. Any resultant coronary angiograms (CA) were reviewed for evidence of significant CAD. Transplant decisions were reviewed to assess the impact of CVD screening on individuals’ transplant status. Results 689 individuals underwent MPS. Of these, 90% required no further cardiovascular investigations. 6% (42 individuals) had subsequent CA. <1% (5) required percutaneous intervention (PCI) whilst the rest (37) were deemed to have no significant CAD. A further 4% (29) required coronary angiography at a later date (>2 years after their MPS), with similar rates of PCI (1%). All three outcome groups (negative MPS, CA referral, CA in the future) had similar rates of diabetes (40%) and previous diagnoses of CAD (14%). The average wait for CA was 283 days post-MPS. Transplant decisions took a further 286 days after CA, which in combination with the delays associated with CA resulted in average delays of 1.5 years. Conclusions The use of MPS to screen for significant asymptomatic CAD identifies only a small proportion of individuals requiring intervention prior to kidney transplantation and significantly delays transplant decisions. These results suggest transplant centres should review their use of CVD screening prior to listing.

The role of coronary artery calcium score and european score2 in primary prevention of cardiovascular disease

Abstract Background There is limited evidence about the role of using coronary artery calcium (CAC) score in conjunction with the European SCORE2 (systematic coronary risk evaluation) for the identification of individuals at higher risk of cardiovascular disease. Purpose To evaluate the relationship between CAC score and the European SCORE2 for cardiovascular risk stratification in an asymptomatic population in primary prevention. Methods This is a preliminary analysis from a single-centre, prospective, randomised 1:1, controlled trial assessing the use of CAC score vs standard preventive strategies in asymptomatic individuals undergoing primary cardiovascular prevention. The 10-year risk of cardiovascular events was assessed with either SCORE2 (ages 45-69) or SCORE2-OP (ages 70-89). Subjects were classified as 1) low to moderate risk, 2) high risk, and 3) very high risk according to SCORE2/SCORE2-OP. CAC score was assessed by ECG gated low-dose computed tomography with no contrast administration. A CAC score of zero was considered to reclassify risk one level downward in high or very-high risk patients. CAC score ≥ 100 was used to reclassify risk one level upward in patients with low to moderate risk and a CAC score > 1000 to reclassify risk upward in subjects with high risk. Results A total of 1,252 participants: 627 in the CAC group and 625 in the control group, median age 55 yrs, 25th-75th 50-61 yrs, with availability of SCORE2 and SCORE2-OP were included in this analysis. SCORE2/SCORE 2-OP was similar in the CAC and control groups. Among the subjects in the CAC group, there was a highly significant difference in SCORE2/SCORE 2-OP between participants with CAC score = zero and those with CAC > zero (median 5.6, 25th-75th 3.6-8.55 vs 2.9, 1.8-4.6, p< 0.001) as well as between those with CAC ≥ 100 and those with CAC score < 100 [median 6.8, 25th-75th (10.3-4.5) vs 3.3 (2.0-5.3), p<0.001]. The prevalence of CAC score = zero was 75% in the low to moderate risk group, 47% in the high risk, and 20% in the very high risk, p<0.001. By contrast the prevalence of CAC score ≥ 100 was 7% in the low to moderate risk group, 24% in the high risk, and 45% in the very high risk, p< 0.001. The proportion of patients classified as low to moderate risk group was 72% with CAC score vs 59% without CAC score, high risk 23% with CAC score vs 35% without CAC score, very high risk 5% vs 6% respectively, p<0.001. Using CAC score risk reclassification occurred in 48% downward and 2% upward in originally classified high risk subjects, 7% upward in originally classified low to moderate risk, and 20% downward in originally classified very high risk subjects. Conclusions CAC score may lead to risk reclassification in a substantial proportion of individuals, in particular among those originally classified as high risk by the SCORE2/SCORE2-OP. The cardiovascular risk prediction accuracy of adding CAC score to SCORE2/SCORE2-OP awaits validation at long-term follow-up.

Lipoprotein(a) metabolomic and proteomic features and atherosclerotic cardiovascular disease in young, asymptomatic adults

Abstract Background Lipoprotein (a) [Lp(a)] is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events. Although Lp(a) is a powerful genetic risk factor for ASCVD, the pathways that mediate this risk and the associated metabolomic and proteomic features that capture this risk are unknown. Methods In young, asymptomatic Coronary Artery Risk Development in Young Adults (CARDIA) participants, we defined the relationships between Lp(a) and metabolomic (n=563)/proteomic (n=184) features, derived quantitative Lp(a)-omic scores from these features, and related these quantitative scores to ASCVD phenotypes. Results CARDIA subjects had a mean age of 32 years and a median follow-up of 27 years. In the overall cohort (n=3920), Lp(a) levels at year 7 (Y7) were significantly associated with ASCVD endpoints, including hs-CRP, coronary artery calcification (CAC), death, and incident CHD (Figure 1A). In the subcohort (n=2290) that had measurements of Lp(a), proteomics, and metabolomics, Y7 Lp(a) levels were associated with distinct proteomic and metabolomic features indicative of immune responses, lipoprotein metabolism, atherogenesis, and arginine/steroid biosynthesis. Using machine learning approaches, Lp(a) metabolomic, proteomic, and transomic quantitative scores were derived. After adjustment, the Lp(a) transomic score was more strongly related to incident CAC, degree of CAC, CRP, and incident CHD than Lp(a) itself (Figure 1B). Conclusions To our knowledge, this is the first study to examine the relationship between Lp(a), metabolomic/proteomic features, and ASCVD phenotypes in young, asymptomatic adults. The multi-omics approaches employed here provide insight into the pathobiology of Lp(a)-driven ASCVD and enable more nuanced mechanistic risk assessment compared with Lp(a) alone.

Artificial intelligence-enhanced electrocardiography derived body mass index as a predictor of future cardiometabolic disease

Abstract Background Obesity, a key risk factor for cardiometabolic diseases, is poorly evaluated by body mass index (BMI), which doesn't account for visceral fat and fat distribution. Given that obesity-related cardiac changes can manifest in surface ECG changes, we hypothesised that an AI-ECG model could predict BMI, and the discrepancy between AI-predicted and actual BMI (delta-BMI) could indicate cardiometabolic health. We also sought to understand the biological mechanisms contributing to the AI-ECG-derived delta-BMI. Methods The AI-ECG model was developed using a data split of 60/10/30% in a USA secondary care dataset of 512,950 ECGs and externally validated in the UK Biobank (N = 42,386), employing a residual neural network architecture. Model performance was evaluated using Mean Absolute Error (MAE), Pearson correlation coefficient (r), and coefficient of determination (R2). The study aimed at identifying incident cardiometabolic diseases, using Cox regression analyses adjusted for BMI, age, and sex. To assess the underlying biological associations of delta-BMI, phenome-wide, genome-wide, metabolome-wide, and proteome-wide association studies were performed. Results In the test set, the model achieved an MAE of 3.95 (3.93–3.97), r of 0.65 (0.65-0.66), and R2 of 0.43 (0.42-0.43). In the UKB, the model achieved an MAE of 2.94 (2.91–2.96), r of 0.62 (0.62–0.63) and R2 of 0.39 (0.38-0.40). The top tertile of delta-BMI showed an increased risk of future cardiometabolic disease (test set: HR 1.15, p<0.001; UKB: HR 1.58, p<0.001) and diabetes mellitus (test set: HR 1.25, p<0.001; UKB: HR 2.28, p<0.001) after adjusting for covariates including measured BMI. Phenotypic profiling highlighted associations between delta-BMI and cardiometabolic diseases, anthropometric measures of truncal obesity, and pericardial fat mass. Metabolic and proteomic profiling associates delta-BMI positively with valine, lipids in small HDL, syntaxin-3, and carnosine dipeptidase 1, and inversely with glutamine, glycine, colipase, and adiponectin. A genome-wide association study revealed associations with regulators of cardiovascular/metabolic traits. These results highlight delta-BMI's potential as a non-invasive, ECG-based biomarker for cardiometabolic risk stratification. Conclusion Our study demonstrates the effectiveness of an AI-enhanced ECG model in accurately predicting BMI, validated across diverse populations. The introduction of delta-BMI as a predictor of cardiometabolic disease offers valuable additional prognostic insights beyond traditional BMI assessments. Our exploration of biological pathways, spanning phenotypic, genotypic, metabolomic, and proteomic associations, contributes to a comprehensive understanding of the association between delta-BMI and cardiometabolic disease. The clinical implications could extend to enhanced screening strategies, personalised risk assessment, and motivation for lifestyle interventions.

External validation of the HFA-ICOS risk stratification tool for prediction of cardiovascular complications after cancer treatment

Abstract Background The 2022 ESC Guidelines on Cardio-oncology recommends using the HFA-ICOS (Heart Failure Association and the International Cardio-Oncology Society) four-category risk stratification tool to predict risk of heart failure (HF) and other cardiovascular disease (CVD) complications during and after cancer therapy. However, the actual risk associated with assignment to these categories is unknown. Purpose We aimed to assess the prognostic performance the HFA-ICOS risk stratification tool in a large cancer subpopulation of a general health survey linked to Norwegian health registries. Methods Participants in a large-scale population study diagnosed with cancer between 2006 and 2012 were included (n=2290) and followed for CVD endpoints until Sept 2023. CVD risk factors were measured at baseline between 2006 and 2008. The Norwegian Cancer Registry provided detailed information about cancer characteristics and therapy. We retrieved CVD endpoints from the local hospitals’ registries and the national causes of death registry. Kaplan Meier survival curves were used to estimate the risk of the combined endpoint of HF hospitalization, myocardial infarction (MI), stroke and CVD death, as well as HF hospitalization alone and non-CVD death. Harrel’s C-statistic was used to validate the discriminative abilities. Results Mean (SD) age was 65.8 (12.4) years, 48% were female, cancer types and cardiovascular risk factors are shown in Table 1. During a median (interquartile range) follow-up of 6.9 (1.4 to 12.2) years, there were 460 first CVD events (HF hospitalizations 87 (19%), MIs 161 (35%), strokes 130 (28%), CVD deaths 82 (18%)) and 1003 (44%) non-CVD deaths. When applying the HFA-ICOS tool, 649 (28%) were assigned to the low-risk category, 912 (40%) to medium, 661 (29%) to high-risk and 68 (3%) to the very high-risk category. Between the HFA-ICOS risk categories, there were clear differences in the observed risk of CVD events, HF hospitalizations and non-CVD mortality (Figure 1). CVD incidence was highest in the highest HFA-ICOS risk categories (7% in the low risk group, 21% in the medium risk group, 31% in the high risk group and 37% in the very high-risk group (p-value <0.001)). C-statistics for predicting CVD events was 0.696 (95% CI, 0.674 to 0.718). When only assessing patients with HF hospitalizations as (first) outcome (n=116), the risk of HF was higher in the high and very high-risk groups (0% in the low risk group, 4% in the medium, 9% in high and 21% in the very high risk group (C-statistics 0.794 (95% CI, 0.762 to 0.827)). Conclusion The HFA-ICOS baseline risk assessment was useful to identify patients at risk of both clinical overt heart failure and other major CV complications and non-CV death in a population with a variety of cancers. These results can help communicate absolute risks to cancer patients, which may be helpful in the shared decision-making for cardioprotective treatment and intensified follow-up.

ASCVD risk scores versus a novel cancer-specific Machine Learning-based calculator among patients with breast, colorectal, lung or prostate cancer

Abstract Background Patients with cancer have up to a 3-fold higher risk for cardiovascular disease (CVD) than the general population. Consequently, traditional risk scores developed to predict CVD in the general population (i.e., Pooled Cohort Equations (PCE), Predicting Risk of cardiovascular disease EVENTs [PREVENT]) may provide less accurate risk prediction for this population. Purpose Compare cancer-specific Machine Learning (ML)-based score to PCE and PREVENT to predict 10-year CVD risk in patients with breast cancer (BC), colorectal cancer (CRC), lung cancer (LC), or prostate cancer (PC). Methods Patients aged ≥18 years, diagnosed with BC, CRC, LC, or PC between 2005-2012 at a large hybrid academic-community practice in Northeast Ohio, United States, were included. An ML Extreme Gradient Boosting (XGBoost) algorithm, adapted for survival modeling, was developed using a training subset of the cohort (55% train + 20% test) and ranked 40 to 50 covariates (including social determinants of health, cancer treatment) for predicting 10-year CVD risk for each cancer type using SHAP (SHapley Additive exPlanations) values. The top 10 ML predictors were utilized to create a predictive equation using logistic regression models. This equation was then tested in the cohort validation subset (25%) and subsequently compared to the PCE and PREVENT (both simple and enhanced versions) using the area under the curve (AUC) of the time-dependent receiver operating characteristic curve. The CVD events were identified using ICD codes corresponding to Acute Coronary Syndrome, Ischemic Stroke, and Heart Failure. CVD risk was assessed through Kaplan-Meier. Results We included 10,240 patients (Table 1). The actual 10-year CVD events were: BC 21% (95% CI 19-23), CRC 10% (95% CI 8-12), LC 27% (95% CI 24-30), and PC 20% (95% CI 17-23). The ACC/AHA PCE predicted mean 10-year CVD risks of 16% (95% CI 15-18) for BC, 19% (95% CI 17-21) for CRC, 28% (95% CI 25-32) for LC, and 19% (95% CI 19-20) for PC, with corresponding AUCs of 0.75, 0.65, 0.76, and 0.61, respectively. The PREVENT simple version predicted mean 10-year CVD risks of 13% (95% CI 13-14) for BC, 13% (95% CI 12-13) for CRC, 15% (95% CI 14-15) for LC, and 16% (95% CI 12-19) for PC, with AUCs of 0.55, 0.55, 0.55, and 0.53, respectively. The PREVENT enhanced equation predicted mean 10-year CVD risks of 17% (95% CI 17-18) for BC, 15% (95% CI 14-15) for CRC, 15% (95% CI 15-16) for LC, and 17% (95% 16-19) for PC, with AUCs of 0.75, 0.62, 0.79, and 0.63, respectively. The predictive equation derived from the top 10 ML predictors (Table 2) achieved AUCs of 0.84 for BC, 0.76 for CRC, 0.83 for LC, and 0.71 for PC. Conclusion(s) Conventional CVD equations inadequately assess the risk in patients with BC, CRC, LC, or PC, often resulting in underestimation or overestimation. Cancer-specific ML-derived equations show good performance and emphasize the importance of integrating cancer-related covariates for precise prediction.Table 1Table 2

Trends in overall and abdominal obesity among Korean adults, 2007-2022: an Age-period-cohort analysis

Abstract Overall and abdominal obesity, often defined as having high body mass index (BMI) and waist circumference (WC), are associated with an increased risk of chronic disease. A comprehensive understanding of trends and contributing factors is necessary to reduce the disease burdens. This study investigated the nationwide trends and independent effects of age, period, and birth cohort on BMI and WC in Korean adults. We conducted hierarchical age-period-cohort (cross-classified random-effects models) analyses using measured BMI and WC data from 85,292 Korean adults (aged ≥19) in the Korea National Health and Nutrition Examination Survey 2007-2022. We also examined whether the age, period, and cohort effects varied by socioeconomic subgroups. In 2007-2022, the age-standardized mean BMI (23.6 to 24.2 kg/m2) and WC (81.7 to 83.5 cm) increased in the overall population. An upward trend was evident among men, while only a slight change was observed in women. The mean BMI was highest at age 47 (25.1 kg/m2) in men and age 60 (24.2 kg/m2) in women and it decreased at older ages. Controlling for age and period effects, mean BMI was lowest among the birth cohorts of 1960-1964 (24.15 kg/m2), with the highest mean BMI observed among the birth cohorts of 1919-1939 (24.97 kg/m2) and 1990-2003 (24.99 kg/m2). The mean WC was highest at age 55 (88.0 cm) in men and age 79 (83.4 cm) in women. Similar U-shaped birth cohort effect was observed with WC, with the lowest mean observed among the birth cohorts of 1960-1964 [82.92 (0.30)]. At most age, period, and birth cohorts, mean BMI and WC were consistently higher among adults at lower income and education. The overall period effect was consistently found in all socioeconomic subgroups, but the gap in BMI between income and education subgroups widened over time. Our findings suggest that BMI and WC slightly increased in overall Korean adults in 2007-2022, with some inequalities among age, sex, birth cohort, and socioeconomic subgroups. Key messages • The obesity indices increased from 2007 to 2022, but the cohort effect on BMI and WC showed a U-shaped pattern with the lowest mean among birth cohorts of 1960-1964. • The obesity prevalence is varied by socioeconomic status, suggesting that more intense interventions may be needed to target the susceptible groups.

Physician disagreement with treatment guidelines as a critical barrier to achieving low-density lipoprotein cholesterol targets in very high-risk patients: an implementation science study

Abstract Background/Introduction The challenges that physicians face in implementing evidence-based lipid-lowering therapy in patients at high risk of atherosclerotic cardiovascular disease (ASCVD) are relatively undocumented. Purpose This study aimed to provide insights into the challenges that Korean physicians face in assisting their high-risk ASCVD patients in achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) levels. Methods We enrolled 704 patients from 10 tertiary hospitals in South Korea, between November 2020 and November 2022. These patients were at very high risk of ASCVD, with baseline LDL-C levels ≥70mg/dL (1.8 mmol/L) while receiving maximally tolerated statins and/or ezetimibe. We measured the proportion of participants achieving LDL-C levels <70mg/dL at visit 1(0)/ visit 2(6-16)/ visit 3 (18-30 weeks), and recorded physician feedback on lipid-lowering treatment strategies. Results Out of the 704 enrolled patients (mean [IQR] age, 66.0 [59–72] years; 580 men [82.4%]), the median (IQR) baseline LDL-C level was 82.0 (74.0–94.5) mg/dL. Lipid-lowering therapy at baseline included statins in 99.0% (with 1.0% statin intolerant) or statins and ezetimibe in 56.4%. The proportion of participants achieving LDL-C levels <70mg/dL at each visit were 0%, 56.3%, and 58.7%, respectively. Among 307 patients on maximally tolerated statins at baseline, physicians did not have an intention to intensify the lipid-lowering treatment regimen in 171 (55.7%) of those patients. (Figure 1) Physician disagreement with the guidelines was the major reason for not using the recommended therapy (70.8%), followed by the patient’s refusal for reasons other than the cost (8.2%), medical limitations such as comorbidities (7.0%), and drug costs (6.4%). Among 397 patients on maximally tolerated statins and ezetimibe at baseline, physicians did not have an intention to intensify the lipid-lowering treatment regimen in 299 (75.3%) of those patients. (Figure 2) Physician disagreement with the guidelines was the major reason for not using the recommended therapy (46.2%), followed by the patient’s refusal for reasons other than the cost (15.7%), medical limitations such as comorbidities (14.4%), and drug costs (12.7%). Conclusion In this implementation science study, the proportion of patients at very high risk of ASCVD who achieved LDL-C levels <70mg/dL via lipid-lowering therapy was less than 60%. Physician disagreement with the guidelines was the main reason for not adopting the recommended intensified LDL-C lowering therapy.Figure 1Figure 2

Rationale and design of the SHASTA-3 and SHASTA-4 studies: randomized, double-blind, placebo-controlled, phase 3 studies of plozasiran in patients with severe hypertriglyceridemia

Abstract Severe hypertriglyceridemia (sHTG) confers an increased risk of atherosclerotic cardiovascular disease (ASCVD) and acute pancreatitis (AP). sHTG-associated AP is a substantial source of morbidity, mortality, reduced quality of life and financial burden to health care systems. Currently available therapeutic approaches for sHTG are often insufficient to reduce triglyceride (TG) levels and prevent AP. Plozasiran, an investigational siRNA therapeutic, inhibits hepatic production of apolipoprotein C3 (APOC3), a key regulator of lipoprotein lipase-mediated TG metabolism and clearance. In a phase 2 study of sHTG patients [TG ≥500 mg/dL (≥5.65 mmol/L)], plozasiran demonstrated durable reductions in TG levels of up to -80%, 12 weeks after the last dose, and decreased TG below 500 mg/dL (5.65 mmol/L), a threshold of increased risk for AP in most participants. The SHASTA-3 and SHASTA-4 trials will evaluate safety and efficacy of plozasiran, including AP rates, in patients with sHTG. SHASTA-3 and SHASTA-4 are phase 3, randomized, double-blind, placebo-controlled, multi-center trials. Key inclusion criteria are prior sHTG and fasting TG ≥500 mg/dL (≥5.65 mmol/L), at screening. Key exclusion criteria include use of any hepatocyte targeted siRNA treatments that target lipids and/or TGs within 1 year (except inclisiran at least 4 weeks prior to enrollment), siRNA or ASO within 60 days, known FCS diagnosis, and AP within 4 weeks of screening. 700 adults with sHTG will be enrolled in these two trials in several sites across multiple countries. Patients will be randomized 2:1 to receive 4 quarterly subcutaneous injections of plozasiran 25 mg or matching placebo over a 1-year double-blinded period, followed by post-treatment evaluation or entry into the open-label extension study. The randomization will be stratified based on TG levels (≥880 mg/dL vs <880 mg/dL [≥ vs <10 mmol/L]) and prior history of AP, within 5 years of screening. The primary efficacy endpoint of the studies is placebo-adjusted percent change in fasting TG from baseline to month 12 with plozasiran. Secondary endpoints include percent change in fasting TG from baseline to month 10 compared to placebo, percent of patients achieving fasting TGs of <500 mg/dL (<5.65 mmol/L) and TGs of <150 mg/dL (<1.69 mmol/L) at month 10 and 12 compared to placebo, and event rate of adjudicated abdominal clinical events including ER visits and hospitalization for abdominal pain attributed to HTG and events of documented pancreatitis. The effect of plozasiran on other lipids and lipoproteins, inflammatory biomarkers, and liver fat content using magnetic resonance imaging-proton density fat fraction will be assessed. Adjudicated major adverse cardiovascular event rates, safety and tolerability will be assessed. SHASTA-3 and SHASTA-4 are designed to determine whether the quarterly-dosed APOC3 siRNA plozasiran, added to standard of care, safely reduces TG levels and the rate of AP in patients with sHTG.

Comorbidities in Japanese testicular cancer survivors: A multi-institutional, cross-sectional study.

To evaluate comorbidities in Japanese testicular cancer (TC) survivors in a multi-institutional, cross-sectional study. This study enrolled TC survivors who visited any of the eight high-volume institutions in Japan from 2018 to 2019. After obtaining informed consent, participants answered questionnaires about their comorbidities. We analyzed the impact of treatment on comorbidities rate in TC survivors. A total of 509 TC survivors responded to the comorbidity questionnaires. Median age at the time of response was 43 years (IQR 35-51 years) and median follow-up period after treatment was 5.1 years (IQR 2.1-9.2 years). TC survivors were divided according to the number of cycles of chemotherapy into the following groups: None (n = 153); 1-2 cycles (n = 34); 3-4 cycles (n = 234); or ≥5 cycles (n = 88). The prevalence of kidney disease increased significantly with increasing number of cycles of chemotherapy (p < 0.05). The relative risk of cardiovascular disease in the groups with three or more cycles was 2.6 compared to the group without chemotherapy. The present study showed that the prevalence of kidney disease in TC survivors was increased with increasing number of cycles of chemotherapy.

Beneficial effects of hydroxychloroquine on blood lipids and glycated haemoglobin: A randomised interventional study in patients with rheumatoid arthritis and systemic lupus erythematosus.

Hydroxychloroquine (HCQ) exerts a large reduction of cardiovascular risk in patients with inflammatory diseases, but the mechanisms are not fully known. The aim of this study was to study potential mechanisms for this. This interventional study (EudraCT 2014-005418-45) in 30 patients (23 with rheumatoid arthritis, 7 with systemic lupus erythematosus) investigates the effects of HCQ on cardiovascular risk factors and arterial stiffness in patients with inflammatory disease. Blood lipids, blood pressure, blood glucose, glycated haemoglobin (HbA1c) and arterial stiffness was assessed at initiation, after four weeks of treatment and after eight weeks of treatment with 200 mg HCQ daily. After four weeks of treatment with HCQ, total cholesterol had decreased from 5.4 mmol/L to 5.1 mmol/L (p<0.001), low-density lipoproteins from 3,0 mmol/L to 2.7 mmol/L (p<0.001) and apolipoprotein B from 0.96 g/L to 0.90 g/L (p<0.01). Those levels remained unchanged after eight weeks of treatment with HCQ. Levels of triglycerides, high-density lipoproteins and apolipoprotein A1 remained unchanged during the study. HbA1c decreased in most patients, especially in patients with high levels at start of HCQ, but increased HbA1c was seen in patients with low levels at start of treatment with HCQ. No significant effect was seen on blood pressure or any measure of arterial stiffness. This study does not identify the mechanisms of cardiovascular risk reduction from HCQ. Arterial stiffness is not affected by HCQ. The impact of HCQ on HbA1c and blood lipids is rapid, but of modest magnitude, and these effects do not fully explain the reduced risk of cardiovascular disease seen in observational studies. The mechanisms of cardiovascular risk reduction from HCQ are yet not completely known.

Burden and economic impact of PM2.5 exposure on Acute Myocardial Infarction in Portugal, 2011-2021

Abstract Background Air pollution, specifically particulate matter with a diameter of 2.5 micrometers (PM2.5), is the primary environmental health risk in Europe. Exposure to PM2.5 increases the risk of cardiovascular diseases, including AMI, resulting in high direct costs associated with in-patient treatment. This study aims to estimate the avoidable and attributable disease and economic burden of AMI due to ambient PM2.5 exposure in Portugal between 2011 and 2021. Methods National databases were used to assess the annual number of hospitalisations and deaths due to AMI between 2011 and 2021. The annual mean costs were calculated using a direct cost analysis (bottom-up micro-costing) to assess the direct economic burden of AMI. In turn, these cases and associated costs were multiplied by the respective morbidity and mortality population attributable fraction (PAF) to estimate the number of hospital admissions and deaths, and their associated costs attributable to ambient PM2.5 exposure. For 2019 and 2021, an alternative scenario of exposure was considered (2021 WHO Air Quality Guidelines), and the avoidable morbidity and mortality costs were determined using the potential impact fraction (PIF). Results Between 2011 and 2021, there were 130,447 hospitalisations and 47,968 deaths due to AMI, with 4.79% and 28.90%, respectively, attributable to ambient PM2.5 exposure. This translates to a direct economic burden of morbidity of more than 44 million euros and mortality of almost 195 million euros. If the proposed scenario guidelines were met, 279 cases and 448 deaths would have been avoided in 2019, resulting in a savings of almost 9.7 million euros. In 2021, 93 cases and 355 deaths would have been avoided, with approximately 4 million euros saved. Conclusions Exposure to ambient PM2.5 significantly contributes to AMI cases and deaths in Portugal, imposing a significant economic burden. These findings highlight the urgent need for measures to improve air quality. Key messages • PM2.5 pollution in Portugal drives AMI cases and fatalities, entailing significant economic costs. • Adhering to WHO air quality guidelines promises substantial reductions in AMI incidence and save millions annually in healthcare expenditure.

Lipoprotein(a) levels in acute myocardial infarction patients and their associations with prior events and coronary artery disease severity: a real-world cohort study

Abstract Introduction Circulating lipoprotein(a) [Lp(a)] has been associated with the risk of atherosclerotic coronary artery disease (CAD) and is an emergent therapeutic target. The objective of this study is to explore the association between serum levels of Lp(a) and previous myocardial infarction (MI) and/or coronary revascularization and the extension of obstructive CAD in patients with acute MI undergoing coronary angiography. Methods All consecutive patients with MI who underwent coronary angiography and Lp(a) measurement between May and November 2023 were included. Patient data were either registered prospectively or completed retrospectively using electronic health records. Lp(a) was measured using the Immunoturbidimetric Assay method with reaction intensification by particles, employing the World Health Organization/International Federation of Clinical Chemistry and Laboratory Medicine (WHO/IFCC) International Reference Reagent (SRM2B), on the "Roche Cobas C702" chemistry analyzer. The number of major coronary arteries (left main, left anterior descending, left circumflex and right coronary arteries) with stenosis &amp;gt;50% on the coronary angiography were registered. In the primary analysis we explored the association between Lp(a) levels using tertiles and previous occurrence of MI/revascularization, as well as the extension of obstructive CAD. In the secondary analysis we compared Lp(a) levels in patients with and without previous MI/revascularization and patients with 3-4 major vessels CAD vs. 0-2 vessels. Results A total of 116 patients were enrolled, with a mean age of 62±13 years, 79% males, 29% with known coronary artery disease, 71% with dyslipidemia, 24% with diabetes, 65% with hypertension, and 58% were either active or former smokers. The median Lp(a) level was 72 (20-183) nmol/L. In the primary analysis (table 1), the number of previous MI/revascularizations was significantly higher in the third tertile of Lp(a) (T3) versus T1 (p=0.044). No significant differences were found for the remaining analyses. In the secondary analysis (figure 1) the level of Lp(a) was significantly higher in patients with 3-4 vessel CAD vs. 0-2 vessel (158.4±145.2 nmol/L vs. 103.16±104.6 p=0.044). Conclusion In this small real-world cohort population with acute MI, the number of previous MI or coronary revascularization was higher in patients with increased levels of Lp(a) and this marker of atherosclerotic disease was greater in patients with more extensive CAD.

Applicability of VICTORION-1 PREVENT Criteria to the US Population

Abstract Background VICTORION-1 PREVENT (V-1P) is an ongoing randomized clinical trial comparing inclisiran sodium 300mg every six months with placebo for primary prevention in patients with high cardiovascular (CV) risk. Purpose We evaluated the generalizability of V-1P trial enrollment criteria to the US population to understand the demographic and CV health characteristics of the trial target population. Methods We included data from the National Health and Nutrition Examination Survey (N=25,531, 2015-March 2020), a nationally representative sample of the US population. Enrollment criteria similar to V-1P were applied. Nonpregnant adults 40-79 years with low-density lipoprotein cholesterol (LDL-C) of 70-189 mg/dL were included. 10-year risk for CV disease was determined using the American Heart Association race-free 10-year PREVENT risk equations. Individuals with 10-year risk &amp;gt;20% or 7.5%-19.9% with two risk enhancing factors at baseline were included. Risk enhancing factors included elevated high sensitivity C-reactive protein (≥2 mg/L), inflammatory arthritis, estimated glomerular filtration rate &amp;lt;60 ml/min/1.73 m2, metabolic syndrome, or early family history of CV disease. Patients with history of atherosclerotic CV disease or liver disease were excluded. Estimates of demographics and health characteristics were nationally representative using survey weights. Results Among US adults, 21,576,506 (standard error [SE]: ±1,258,255) meet eligibility criteria for V-1P (weighted estimate). This represents 8.8% of all US adults or 15.1% of US adults 30-79 years. The V-1P eligible population had a mean age of 65.3 years (SE: ±0.5 years), and 55.0% (SE: ±2.5%) were female. Compared with the US adult population (≥18 years), V-1P eligible population had a higher mean body mass index (32.6 ± 0.3 kg/m2 vs 29.5 ± 0.2 kg/m2) and higher rates of obesity (61.0% ± 2.1% vs 40.0% ± 1.1%) (Table). V-1P eligible population also had higher mean systolic blood pressure (133.9 ± 1.0 mmHg vs 121.7 ± 0.3 mmHg), similar mean diastolic blood pressure (72.6 ± 0.8 mmHg vs 71.8 ± 0.2 mmHg), and higher rates of hypertension (85.8% ± 2.0% vs 45.9% ± 1.1%). Mean hemoglobin A1c percent (6.3 ± 0.1 vs 5.7 ± 0.02), fasting blood sugar (127.7 ± 1.9 mg/dL vs 109.2 ± 0.6 mg/dL), and diabetes rates (39.7% ± 2.6% vs 13.1% ± 0.7%) were higher in the V-1P eligible population. Mean low-density lipoprotein cholesterol (115.8 ± 1.5 mg/dL vs 110.2 ± 0.8 mg/dL) and fasting triglycerides (137.6 ± 5.0 mg/dL vs 110.4 ± 1.7 mg/dL) were higher, while mean high-density lipoprotein cholesterol was lower (49.9 ± 0.8 mg/dL vs 54.8 ± 0.4 mg/dL). The distribution of key CV risk factors is shown in the Figure. Conclusion V-1P enrollment criteria apply to many patients. These patients have significant cardiometabolic risk factor burden, and effective preventive therapies could have substantial health impact.

Association between high versus low cardiovascular risk in individuals with corresponding unexpected absent versus severe subclinical coronary atherosclerosis, a nationwide, multicenter study

Abstract Background It remains unclear as to why some individuals at low risk of cardiovascular disease (CVD) develop severe coronary atherosclerosis, while those at high CVD risk may remain free from coronary atherosclerosis. Purpose Using Coronary Computed Tomography Angiography (CCTA), we aimed to identify factors associated with absence and severe coronary atherosclerosis in subjects from the general population with very high and low-moderate CVD risk, respectively. Methods We assessed cross-sectionally a nationwide, multicenter population-based cohort, consisting of 30,154 individuals randomly recruited from the general population (age range 50-64 years, 51.4% women). Coronary calcified plaque burden was estimated by coronary artery calcium score (CACS) assessed by CCTA. Absent coronary atherosclerosis was defined as CACS 0 and severe coronary atherosclerosis was defined as CACS ≥301. We investigated only individuals with low-moderate (&amp;lt;5%) and very high CVD risk (≥10%) according to SCORE2 were included. Individuals with CACS 0 and prevalent CVD were excluded, as well as those with moderate CACS (1-300) or SCORE2 risk 5-9%. Out of 26 722 subjects with complete data on CACS and SCORE2, 13 075 were included. Logistic regression was performed adjusted for age and sex. Results The overall distribution of CACS in relation to SCORE2 CVD risk is illustrated in the Figure. Study characteristics are displayed in Table 1. Severe-extensive CACS in combination with low-moderate CVD risk was present in 2.3% (n=296). A further 2.3% (n=311) had very high CVD risk but CACS 0. Factors associated with CACS 0 despite a very-high estimated CVD risk included: lower age, being female, being born in Sweden, not having hypertension or hyperlipidemia, fewer pack-years of smoking, and lower waist circumference in men. On the contrary, severe-extensive CACS despite a low-moderate estimated CVD risk was associated with higher age, being male, being an ex-smoker, reporting more pack-years of smoking, having higher HbA1c, higher BMI, higher waist circumference, and prevalent hyperlipidemia and hypertension (Table 2). Conclusions We identified extreme cardiovascular risk phenotypes (subgroups) in the general population that either lacked coronary calcifications despite being at very high estimated CVD risk or had severe subclinical coronary atherosclerosis despite being at estimated low-moderate CVD risk. Further studies are warranted to elucidate putative enhancing or protective mechanisms explaining this unexpected phenomenon.

Effects of short-term exposures to lower air temperature and cold spells on myocardial infarction hospital admissions: a nationwide study in Sweden

Abstract Background Exposures to lower air temperature and cold spells have been associated with an increased risk of various diseases. However, the short-term effect of lower air temperature and cold spells on myocardial infarction (MI) remains incompletely understood. Purpose We aimed to evaluate the short-term effects of lower air temperature and cold spells on MI hospital admissions within the nationwide SWEDEHEART registry. Methods This population-based nationwide study included 120,380 MI cases admitted to hospitals in Sweden during the cold season (October to March) from 2005 to 2019. Daily mean air temperature was estimated at 1 km2 spatial resolution across Sweden using a three-stage machine learning approach and percentiles of daily temperatures experienced by individuals in the same municipality were employed as individual exposure indicators to account for potential geographic adaptation. Cold spells were defined as periods of at least two consecutive days with a daily mean temperature below the 10th percentile of the temperature distribution for each municipality. A time-stratified case-crossover design incorporating a conditional logistic regression model with distributed lag non-linear model using lag 0-1 and lag 2-6 days was employed to evaluate the short-term effects of lower air temperature and cold spells on total MI, non-ST-segment elevation MI (NSTEMI) and ST-segment elevation MI (STEMI). Results We found significant increases in risk for total MI, NSTEMI, and STEMI in association with a decrease of one percentile in temperature at a lag of 2-6 days, indicated by ORs (95% CI) of 1.099 (1.057-1.142), 1.110 (1.06-1.164), and 1.076 (1.004-1.153), respectively. Additionally, we found that cold spells were significantly associated with increased risks for total MI, NSTEMI, and STEMI at a lag of 2-6 days, with ORs (95% CI) of 1.077 (1.037-1.12), 1.069 (1.02-1.119), and 1.095 (1.023-1.172), respectively. Moreover, independent effects of lower air temperature and cold spells on MI occurrence were found after adjusting for each other. Conversely, we observed that lower air temperature and cold spells were associated with decreased risks for MI at a lag of 0-1 days. Conclusions This nationwide case-crossover study demonstrated a novel biphasic pattern in MI risk following exposure to lower air temperatures and cold spells, characterized by an initial transient reduction in risk at lags 0-1 day, followed by a significant increase in risk at lags 2-6 days. As climate change continues to induce complex shifts in regional weather patterns, enhancing protections to reduce future cold-related cardiac hospitalizations is crucial.