Burden Of Cardiovascular Disease Research Articles

From Cord to Cure: Repurposing Biological Waste for UAE's Health Revolution with Umbilical Cord Stem Cell Therapy

In the UAE, current hospital policies mandate the disposal of biological waste, such as umbilical cords. However, this tissue represents a valuable source of therapeutic material like mesenchymal stem cells (MSCs) and their secretome. The disposal of this valuable therapeutic material imposes a significant burden on public health. In the United States alone, approximately 18,000 people per year are diagnosed with diseases that could be ameliorated with stem cell therapy. These individuals often remain untreated due to the lack of available stem cells, as current methods for MSC obtention, such as Bone Marrow-MSCs, require an invasive bone marrow aspirate procedure, which is painful and can pose risks to donors, including infection and prolonged recovery times. This paper advocates for policy reform to facilitate the collection, storage, and utilization of umbilical cords. By addressing regulatory barriers and implementing standardized protocols, hospitals in the UAE can not only contribute to advancements in regenerative medicine but also solidify the nation’s position as a leader in this emerging field, ultimately improving patient outcomes and reducing the disease burden both locally and regionally. This is particularly relevant given the significant burden of cardiovascular diseases and type 2 diabetes mellitus (T2DM) in the UAE, where 17.3% of the population aged 20 to 79 is affected with T2DM. Cardiovascular diseases and T2DM are few of the many disorders that can benefit from MSC therapy. Utilizing umbilical cord biowaste for such diseases can further build the UAE’s status as a hub for medical tourism and accentuate it’s growing prominence in the field of regenerative medicine.

Heart disease detection using an acceleration-deceleration curve-based neural network with consumer-grade smartwatch data

Cardiovascular disease (CVD) is the most important cause of morbidity and mortality worldwide. Early detection, prevention or even prediction is of pivotal importance to reduce the burden of cardiovascular disease and its associated costs. Low cost, consumer-grade smartwatches have the potential to revolutionize cardiovascular medicine by enabling continuous monitoring of heart rate and activity. When combined with machine learning(ML), the resulting large amounts of time series data hold the potential of detection, or exclusion of CVD. However, analyzing such large datasets is challenging due to the sparse presence of informative segments. Efficient selection of these segments is essential for developing predictive models for clinical deployment. The objective of this paper was to investigate the potential of an acceleration-deceleration curvebased ML model as a novel clinical indicator for the detection of cardiovascular diseases. We used data from the ME-TIME study; 42 participants from which 21 have a cardiovascular disease and 21 are health controls. Data from each subject was normalized to decrease inter-subject variability. A neural network model aggregated predictions per week. We showed that per-subject normalization by the peak value of curves during inactivity, aggregation of model predictions over a week, and using a contrastive loss, resulted in a predictive model with 99 % ± 3 % specificity and 40 % ± 49 % sensitivity on the development set, and 100 % specificity with 67 % ± 47 % sensitivity on the test set. Acceleration-deceleration curves are effective patterns for ruling out the presence of cardiovascular disease, but caution must be taken to properly pre-process the curves and carefully choosing a model that reduces the variability in the extracted curves.

Cardiovascular Risks With SGLT2 Inhibitors in Clinical Practice Among Patients With Type 2 Diabetes

Cardiovascular disease (CVD) can be recurrent during type 2 diabetes (T2D) progression in this aging population. The effectiveness of sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy on total (ie, first and subsequent) CVD among patients with T2D in clinical practice remains uncertain. To analyze the comparative association of SGLT2i vs dipeptidyl peptidase 4 inhibitor (DPP4i) therapy with total CVD among patients with T2D in clinical practice. This retrospective cohort study used electronic medical records at the National Cheng Kung University Hospital, a leading medical center in Taiwan, from 2015 through 2021. Adult patients with T2D who initiated first use of the study drugs from 2016 through 2019, with up to 6 years of follow-up, were identified. The primary outcomes included total composite CVD events and individual CVD subtypes (ie, atrial fibrillation, coronary heart disease, heart failure, stroke, myocardial infarction, and transient ischemic attack). A shared frailty model analysis was used to assess the association of treatment with repeat CVD events. Data from patients at high risk for CVD recurrence were further analyzed. Data were analyzed from September 1, 2022, to December 31, 2023. Overall, 8384 patients with T2D were identified (mean [SD] age, 63.7 [12.4] years; 4645 [55.4%] male). A total of 1632 propensity score-matched pairs of SGLT2i (mean [SD] age, 57.8 [12.0] years; 673 [41.2%] female and 959 [58.8%] male) and DPP4i (mean [SD] age, 58.2 [12.9] years; 655 [40.1%] female and 977 [59.9%] male) users were included. SGLT2i was associated with reduced total CVD risk vs DPP4i therapy (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98]) but not the first CVD event (with the use of SGLT2i therapy were more prominent for patients at high risk of CVD (ie, HR, 0.70 [95% CI, 0.62-0.80] for individuals with estimated glomerular filtration rate lower than 60 mL/min/1.73 m2; HR, 0.70 [95% CI, 0.64-0.78]; for individuals having any diabetes-related complications; and HR, 0.72 [95% CI, 0.65-0.80] for individuals with a history of CVD) compared with the overall cohort. Among patients at high risk of CVD, greater reduced total CVD burden associated with SGLT2i therapy was observed for women vs men (eg, HR, 0.59 [95% CI, 0.49-0.72] in the subgroup with CVD history). In this cohort study of patients with T2D, the use of SGLT2is vs DPP4is was associated with reduced total cardiovascular burden, suggesting that long-term use of this therapy may optimize treatment benefit among patients with chronic CVD. The SGLT2i-associated benefit among patients with high risk of CVD encourages the prioritization of SGLT2i use for these vulnerable individuals.

Disparities by region, age, and sex in cardiovascular disease burden attributable to high fasting plasma glucose in China, 2010-2018: a nationwide, population-based study

Abstract Background Elaborating and understanding disparities in the burden of cardiovascular disease (CVD) attributable to high fasting plasma glucose (FPG) is important to improve diabetes prevention and promote cardiovascular health. In this study, we aimed to estimate the burden of CVD and its subtypes attributable to high FPG between 2010 and 2018 in China, by age, sex, region and socio-demographic index (SDI). Methods We pooled data on 791 373 people aged 25 years and older from three population-based surveys, and the temporal-spatial Bayesian hierarchical model was used to estimate age- specific, sex- specific, province- specific, and year-specific average FPG levels from 2010 to 2018. We estimated population attributable fraction for CVD by age and sex for 31 provinces. Data on CVD deaths at the provincial level were obtained from surveillance systems, which were used to compute death numbers and years of life lost (YLLs) due to CVD that could be attributed to high FPG using the counterfactual scenario of theoretical minimum risk level. We also decomposed changes in attributable burdens into four explanatory components, including population growth, population aging, risk exposure to FPG, and in risk-deleted mortality rates for CVD. Results In 2018, an estimated total of 512·29 thousand (95% uncertainty interval [UI] 488·60 to 538·65) adults aged 25 or older were attributable to high FPG in China, with 281·54 thousand (95%UI 267·89 to 295·05) of these deaths occurring in men and 229·75 thousand (95%UI 210·98 to 251·89) in women. The age composition of CVD mortality caused by high FPG suggested a trend toward older ages from 2010 to 2018 (Figure 1). High FPG accounted for 1 093·45 crude YLLs per 100 000 people (95%UI 1 059·13 to 1 131·73) due to FPG-related CVD in 2018, with substantial variation across provinces. The age-standardised CVD mortality rate attributable to high FPG increased by 3·99%, from 41·93 per 100 000 people (95%UI 40·07 to 43·88) in 2010 to 43·60 per 100 000 (95%UI 41·77 to 45·62) in 2018. In 2018, the higher age-standardised CVD mortality rate attributable to high FPG was observed in the high-middle SDI region and the middle SDI region. By province, the age-standardised mortality rate due to FPG-related CVD in both sexes combined varied from 21·31 per 100 000 people in Tibet to 77·66 per 100 000 people in Heilongjiang in 2018. Nationally, compared to 2010, exposure to high FPG and population aging in 2018 were the primary drivers of increased FPG-related deaths due to CVD (Figure 2). Conclusions The CVD burden attributable to high FPG was still large in China, and varied markedly across regions and provinces. Exposure to high FPG and population ageing were associated with substantial changes in the number of FPG-related CVD deaths between 2010 and 2018. Findings of this study emphasize the importance of developing population-specific tailored measures in China and other regions with similar condition.Figure 1Figure 2

The Cardiovascular Disease Burden Associated with secondhand smoke, 1990-2019: an age-period-cohort analysis of the Global Burden of Disease study

Abstract Background Over the past three decades, global regions have shown significant differences in the burden of cardiovascular disease (CVD), and secondhand smoke is a major risk factor contributing to this burden. Nevertheless, a comprehensive understanding of the global trends and associations between second-hand smoke and cardiovascular disease is lacking. Methods Using data from the Global Burden of Disease (GBD) study 1990-2019, an age-period-cohort (APC) analysis was conducted to investigate trends in cardiovascular disease-related mortality in populations affected by secondhand smoke globally over the past 30 years and its association with age, period, and birth cohort. Results Over the past 30 years, the number of cardiovascular deaths caused by secondhand smoke has increased significantly worldwide, from 432.6 thousand in 1990 (95% UI: 357.4-508.3) to 598.5 thousand in 2019 (95% UI: 489.7-713.5), an increase of 38.4% (95% UI: 26.8%-49.5%). In 2019, cardiovascular disease accounted for 45.9% of all deaths attributable to secondhand smoke in both men and women globally. Among cardiovascular diseases, ischemic heart disease became the main component, accounting for 66.4% compared with stroke. The gender composition of cardiovascular deaths due to secondhand smoke is slightly lower in men (46.5%) than in women (53.5%). Longitudinal analyses using age-time-cohort models show that global CVD-related mortality from secondhand smoke has improved overall over the past three decades, but there are differences between regions, genders, and CVD subtypes. It is worth noting that the higher the socio-demographic index (SDI) level, the greater the reduction in mortality, with a staggering 39.1% reduction in high SDI areas (95% UI: 35.6%-42.3%), in sharp contrast to virtually no change in mortality in low SDI areas (0.1% (95% UI: -52.4%-62.2%)). During the period 2003-2007, cardiovascular disease-related mortality decreased significantly, with an average annual percentage change of -1.48%. Conclusion The study highlights the importance of using secondhand smoke as a modifiable risk factor for the global burden of cardiovascular disease. Further research is vital to understand the factors that lead to differences in countries and regions at different levels of development, gender differences and differences in cardiovascular disease subtypes.

Quantifying Cardiovascular Disease Burden and Quality of Care Index across Four Visegrád Countries

Abstract Background Cardiovascular diseases (CVDs) have surged to become the leading cause of premature death in Europe. Yet, analyses examining the Quality of Care Index (QCI) and CVD burden within the 4-Visegrád (4V) nations remain notably sparse. This study aims to address this gap by comprehensively assessing both the QCI and CVDs burden across these countries. Methods The burden of CVDs was assessed using data extracted from the GBD-study 2019. We employed min-max normalization to standardize each health indicator, including Mortality-to-Incidence Rate, Prevalence-to-Incidence Rate, Disability-Adjusted Life Years-to-Prevalence rate, and Years of Life Lost-to-Years Lived with Disability. Subsequently, we utilized a weighted sum approach to aggregate the normalized values of the health indicators. The QCI was then derived as the sum of the products of normalized values and their corresponding weights. Results In 2019, age-standardized rates (per 100,000) significantly decreased compared to those in 1990. Ischemic heart disease remained the primary cause of death in all 4V countries, followed by stroke. Czechia exhibited the most substantial reduction in 2019 compared to the rates in 1990, with incidence and mortality rates decreasing by -252.55 and -308.95, respectively. Poland demonstrated the highest reduction, compared to the Central European average rates, in both incidence (-113.73; 95% CI: -125.08_-103.79) and death rates (-74.79; 95% CI: -73.53_-75.31) in 1990, and in 2019 (-175.22; 95% CI: -169.52_-178.29 and -41.55; 95% CI: -40.12_-40.64, respectively). Poland scored highest in QCI among the 4V countries, with Czechia scoring the lowest. Conclusions The findings underscore the imperative for continued efforts to boost cardiovascular healthcare and outcomes in the region. While the reduced ratio signals improvement, there remain avenues for refining disease management, prevention strategies, and access to care to further enhance patient outcomes. Key messages • Our study on 4V nations’ QCI and CVD burden underscores urgent need for sustained efforts in cardiovascular healthcare, with notable rate reductions since 1990. • Challenges persist in managing heart disease and stroke in the 4-Visegrád (4V) countries.

Cardiovascular disease burden and risk factor management in cancer survivors: insights from a large-scale East London cohort

Abstract Introduction Improvements in cancer survival have led to an urgent need to address long-term health issues among survivors, notably increased risk of cardiovascular disease (CVD). Shared risk factors may underpin at least part of this excess risk. Aims To investigate differences in cardiovascular risk profile between cancer survivors and controls; and to assesses the management of hypertension and statin use among cancer survivors compared with controls in a multi-ethnic and socio-economically diverse population. Methods The data were obtained from electronic health records of 1.2 million people registered with general practices in East London. It provides a snapshot of health records at the time of data extraction (01/01/2023). We identify individuals with record of past cancer (grouped into 20 cancer types) and their cardiovascular profile. Each cancer-exposed patient was age- and sex-matched to four non-cancer comparators. Multivariable logistic regression, with extensive adjustment for demographic and health-related variables, was used to elucidate the independent associations of past cancer with a range of cardiovascular outcomes. Patterns of guideline-directed risk factor control among cancer patients with hypertension and ischaemic CVDs (vs non-cancer controls) were assessed. Results The study consisted of 18,839 cancer survivors and 75,356 matched controls (64±15 years, 43% male), with marked ethnic diversity (cancer survivors: 48% White, 24% Black and 22% Asian) and socio-economic deprivation. Compared to matched controls, patients with past cancer had a higher prevalence of hypertension (44% vs. 41%) and chronic kidney disease (18% vs. 14%). We observed a higher prevalence of CVDs including venous thromboembolism (VTE) (5.6% vs. 2.8%), atrial fibrillation (AF) (6.5% vs. 5%), and heart failure (HF) (4.4% vs. 3.4%) among cancer survivors. Regression models fully adjusted for shared risk factors demonstrated an increased risk of a range of CVDs in patients with (any) past cancer, including VTE (OR 2.01), HF (OR 1.31) and AF (OR 1.27). CVD risk varied across cancer types (Figure 1). For example, lung cancer survivors had an elevated risk of VTE (OR 4.02), AF (OR 2.47), IHD (OR 1.45) and peripheral artery disease (OR 1.67) while colorectal cancer survivors had increased risks of VTE (OR 2.68), HF (OR 1.4) and AF (OR 1.32). In subgroup analyses, control of blood pressure and cholesterol did not differ significantly across cancer survivors and matched controls with hypertension and ischaemic CVDs, respectively. Conclusion We show higher burden of VRFs and an increased risk of CVDs among cancer survivors compared with non-cancer controls, with notable variation across cancer types. The lack of difference in control of blood pressure and cholesterol between cancer survivors and controls suggests that these risk factors did not explain the increased risk. Suggesting that an individualised approach to risk management is likely to be warranted.Risk of CVDs in Cancer Survivors

Association of Altitude with Mortality among Patients with Hypertension - A Cohort Study

Abstract Background Available evidence falls short in assessing the risk of all-cause mortality and cardiovascular disease (CVD) mortality among individuals with hypertension residing at various altitudes. This study’s objective was to investigate the correlation between residential altitude and the rates of all-cause mortality and CVD mortality among hypertensive patients. Methods This prospective cohort study encompassed 67,275 hypertensive individuals aged 35 years and above in the year 2018. Participants were categorized into four distinct groups based on their residence altitude: those living below 500 meters, between 500 and 1499 meters, 1500 to 2500 meters, and above 2500 meters. The study spanned a mean follow-up duration of 4.78 years. The associations between residential altitude and the risks of all-cause and CVD mortality were analyzed using Cox proportional hazards regression models. Results Among the 67,275 hypertensive patients included in the study (mean age of 63.9 years, with 45.3% being male), 8,768 deaths were recorded, of which 5,666 were attributed to CVD. Following multivariate adjustment, when compared to the group residing at altitudes below 500 meters, the groups living at altitudes of 500-1499 meters, 1500-2500 meters, and above 2500 meters exhibited significantly elevated risks of all-cause mortality [hazard ratio, HR = 1.45 (95% CI: 1.36-1.54), 1.35 (95% CI: 1.36), and 1.41 (95% CI: 1.28-1.54), respectively] and CVD mortality [HR = 1.47 (95% CI: 1.35-1.58), 1.42 (95% CI: 1.33-1.52), and 1.46 (95% CI: 1.31-1.62), respectively]. For each 500-meter increment in altitude, the risk of all-cause and CVD mortality increased by 10% and 11%, respectively. Subgroup analyses and sensitivity assessments consistently supported this association. Conclusions This study’s findings indicate a substantial connection between long-term residential high-altitude exposure and increased risks of all-cause mortality and CVD mortality among individuals with hypertension. Key messages • Increased altitude of residence increases the risk of subsequent all-cause and CVD mortality in hypertensive patients. • This study highlights that relevant guidelines and healthcare providers should consider altitude as an important factor in reducing the burden of hypertension and CVD.

Independent and joint associations of urinary potassium excretion with cardiovascular death: a national population-based cohort study

Abstract Background Elevated potassium excretion is associated with lower blood pressure, as well as reduced risks of cardiovascular disease (CVD) death. However, the impact of varied sodium levels on this association remains a topic of debate, and the mediators of this association besides blood pressure remain uncertain. Purpose To examine the joint association of potassium and sodium with CVD mortality risk, and to identify potential mediating factors of this association. Methods Based on the ChinaHEART (China Health Evaluation And risk Reduction through nationwide Teamwork) project, participants aged 35-75 from 239 sites across all 31 provinces in the mainland of China were recruited from November 2014 to December 2022. We collected spot urine samples from participants and estimated 24-hour sodium and potassium excretion using the Kawasaki formula. Death records were captured through data linkage with the National Mortality Surveillance System and Vital Registration. Multiple regressions were used to analyze the association between potassium excretion and CVD death, as well as to examine the addictive interaction of potassium and sodium. Results This study included 270,991 participants with a mean age of 55.8±9.8 years, and 60.5% of them were female. The mean potassium excretion was 54.36±12.58 mmol/d , which was higher in males and people living in the north. Findings revealed a positive correlation between low urinary potassium levels and CVD death , and the lowest adjusted hazard rate for CVD mortality was 0.65 (95% CI: 0.58-0.73) in the group with the highest potassium excretion (i.e. ≥64.27 mmol/d) compared with the reference group (<43.79 mmol/d), after adjusting for sociodemographic characteristics, medical histories, and lifestyles. Age modified the association between potassium excretion and risk of CVD death (P for interaction=0.031). In addition to systolic blood pressure (16.6%), heart rate (2.2%) also served as the significant mediator between urinary potassium excretion and CVD death. The relative excess risk of interaction (RERI) of lower potassium excretion and lower sodium was significantly positive (RERI=0.22, 95% CI: 0.02-0.42), which implied the synergy effect. Conclusion Potassium intake in the Chinese population is evidently lower than the guideline recommendations, and increasing potassium intake, especially in the population aged <65 years, may reduce the risk and burden of cardiovascular and other diseases. Moreover, when sodium intake is insufficient, supplementation with both sodium and potassium salt can achieve greater health benefits.Graphic abstract

Defining high risk in the cardiovascular-kidney-metabolic syndrome and associated cardiovascular disease outcomes

Abstract Background The American Heart Association (AHA) recently developed the cardiovascular-kidney-metabolic (CKM) syndrome construct with stages 0-4 to comprehensively characterize the spectrum of cardiovascular disease (CVD) risk [1]. CKM Stage 3 is defined by subclinical CVD or high (≥20%) estimated 10-year CVD risk according to the newly-derived PREVENT models [2]. However, within CKM Stage 3, the burden of subclinical atherosclerosis equivalent to a ≥20% estimated CVD risk, and long-term CVD outcomes associated with CKM Stage 3, are not known. Purpose To (1) characterize the distribution of subclinical atherosclerosis by coronary artery calcium (CAC) according to PREVENT estimated CVD risk categories, and (2) quantify long-term CVD risk associated with CKM Stage 3, in two international cohorts of adults without prior CVD. Methods In participants of the Multi-Ethnic Study of Atherosclerosis (MESA, age 45-84 years) and the Rotterdam Study (age ≥55 years), the burden of CAC was calculated across estimated 10-year CVD risk (low, 0 to <5%; borderline 5 to <7.5%; intermediate, 7.5 to <20%; high, ≥20%). Participants were categorized into CKM stages according to CVD risk factors (body mass index, waist circumference, glycemic status, blood pressure, lipids, kidney function), estimated 10-year CVD risk (by AHA PREVENT model), and presence of CAC. The association of CKM syndrome stage with fatal or nonfatal CVD outcomes was evaluated with covariate-adjusted proportional hazards regression. Results Among 6,123 MESA participants (52% female, mean age 61.4 years) and 1,691 Rotterdam Study participants (46% female, mean age 67.1 years), the distribution of CAC across absolute 10-year CVD risk categories is shown in Figure 1. In high (≥20%) CVD risk adults, CAC score ≥100 was present in 50% of MESA participants and 48% of Rotterdam Study participants. Most participants were classified as CKM Stage 3 (53% in MESA, 83% in Rotterdam). Over a median follow-up of 17.5 years in MESA, CVD events occurred in 5% of CKM Stage 0, 6% of Stage 1, 9% of Stage 2, and 26% of Stage 3 participants. Over a median follow-up of 10.2 years in the Rotterdam Study, CVD events occurred in 0% of CKM Stage 0 and 1, 8% of Stage 2, and 17% of Stage 3 participants (Figure 2). The risk of total CVD was significantly higher in CKM Stage 3 participants relative to CKM Stage 0-2 (MESA: adjusted HR 2.74, 95% CI 2.32, 3.23; Rotterdam: adjusted HR 2.18, 95% CI 1.34, 3.54). Conclusions In an international, multi-ethnic sample of middle-aged adults, adults with high (≥20%) absolute 10-year CVD risk by PREVENT had substantial burden of CAC. Adults in CKM Stage 3 had approximately 2.2- to 2.7-times higher risk for CVD, compared with adults in lower CKM stages. Accounting for estimated CVD risk and burden of cardiovascular, kidney, and metabolic risk factors informs prevention of subclinical and clinical CVD.

Preliminary findings of the TB-HEART Study: prevalence of cardiac pathology among newly diagnosed patients with tuberculosis with and without HIV in Zambia

Abstract Background Cardiovascular diseases (CVD) burden is rapidly increasing in sub-Saharan Africa (SSA) where tuberculosis and HIV prevalence remain high.(1-3) Recent data suggest pulmonary tuberculosis (PTB) is associated with increased CVD morbidity.(4) However, the mechanisms of cardiac injury remain poorly understood. Purpose The TB-HEART study is a cross-sectional and natural history study consecutively recruiting participants with newly-diagnosed PTB, living with and without HIV in Zambia. The primary outcome is the burden of cardiac pathology in PTB patients with and without HIV. Methods Participants with bacteriologically-proven PTB, consecutively recruited from an outpatient settings in Zambia, undergo detailed clinical and functional assessments including point-of-care and standard two-dimensional (2D) echocardiography. Participants are reviewed at completion of TB treatment when all assessments are repeated. The target sample size is 250 participants with PTB, with and without HIV, matched 2: 1 to participants without PTB, stratified by HIV. Results Since 1 November 2023, we have recruited 73 participants with a mean age of 35.3±10.9 years of whom 51/73 (69.9%) are male and 19/73 (23.5%) are living with HIV. Baseline characteristics including cardiovascular risk factors, TB symptoms, anthropometry and clinical and functional observations at presentation, stratified by HIV status, are summarised in Table 1. We detected significant cardiac pathology (defined as left ventricular ejection fraction (LVEF) <51% and/or pericardial effusion >2cm in depth) in 8/65 (12.3%) participants for whom 2D-echocardiography had been completed. Median LVEF was 61.2% (IQR 57.7-67.8). LVEF was normal in 59/65 (91%); mildly abnormal in 5/65 (7.7%); and moderately abnormal in 1/65 (1.5%) participants, respectively. Pericardial effusion >0.5cm was detected in 16/65 (24.6% ) participants and maximum effusion depth was >2cm in 2/16 (3.1%), 1-2cm in 12/16 (75%) and <1cm in 2/16 (12.5%). 2D-echocardiography findings, stratified by HIV-status, are described in Table 2 alongside two echocardiography stills of typical pericardial effusion findings in one participant. Conclusions Our preliminary results demonstrate a higher than expected prevalence of cardiac pathology among participants with PTB with and without HIV, which ranges from 1-7% in autopsy studies and case series.(5-7) The most common cardiac pathology was pericardial effusion. Further analyses will include cardiac biomarkers; repeat clinical and echocardiographic assessments at TB treatment completion; and comparator data, to determine associations between prevalent cardiac pathology and PTB controlling for HIV and TB status, respectively. This may have important implications for clinical practice to prevent complications such as constrictive pericarditis; and policy design to better integrate TB and HIV patient services with preventative care to reduce future CVD risk.Table 1 - Baseline characteristicsFigure 1 and Table 2

Cardiovascular risk factors and kidney transplantation: a retrospective analysis

Abstract Introduction Cardiovascular disease (CVD) poses a significant risk to end-stage kidney disease (ESKD) patients and remains the leading cause of morbidity and mortality among kidney transplant (KT) recipients. With a global rise in ESKD patients dependent on dialysis, transplant programs face growing pressure to consider candidates with a greater burden of CVD for KT despite potential long-term risks. Enhancing pre-KT cardiac risk assessment is crucial to prevent cardiovascular complications post-transplant and meet the demand for KT globally. Purpose High-quality studies evaluating pre-KT cardiovascular risk factors in patients with ESKD are lacking. Our study aims to evaluate the association between pre-KT cardiovascular risk factors and the development of major adverse cardiac events (MACE) post-KT. Methods This retrospective cohort study of ESKD patients at a tertiary center consisted of consecutive patients referred for cardiovascular assessment prior to KT between January 2013 and January 2023. Clinical and demographic data prior to KT and outcomes 1-year post-KT were extracted. Patients who underwent multi-organ transplantation were excluded. The primary endpoint was MACE, defined as all-cause death, myocardial infarction (MI), ischemic stroke, coronary revascularization, heart failure requiring hospitalization, and cardiac resuscitation. Results A total of n=233 patients were referred for cardiac evaluation prior to KT. Of these, n=145 (62%) patients had a KT, n=69 (30%) patients died pre-KT, and n=19 (8%) patients were removed from the transplant program. Of the n=143 KT recipients that met our inclusion criteria, 122 (85%) were free of MACE, while 21 (15%) met the primary endpoint in the year following KT. Patients with MACE were significantly older (mean age = 65 vs. mean age = 59, p < 0.001), and more likely to have coronary artery disease (85.7% vs. 50.8%, p = 0.01), cardiomyopathy (42.9% vs. 17.2%, p = 0.04), smoking history (71.4% vs. 46.7%, p = 0.04), and diabetes (85.7% vs. 49.2%, p = 0.02). Furthermore, deceased donor KT was associated with a greater likelihood of MACE (85.0% vs. 57.5%, p = 0.02) compared to living donor recipients. There were no significant differences with respect to left ventricular ejection fraction, diagnosis of heart failure, or prior MI between MACE and non-MACE groups (p > 0.17 for all). Conclusion Among pre-KT patients with CVD, there is a high mortality rate (30%) prior to KT. Following a successful KT, 15% of patients experienced MACE within 1-year. Our findings underscore the urgency of developing strategies to facilitate timely kidney transplantation, particularly in light of the anticipated rise in demand for kidney transplants. The elevated incidence of major adverse events in the year following a successful KT emphasizes the necessity of collaborative care by cardiologists and nephrologists for these patients, and the need for further studies to improve long-term outcomes.

The projected global burden of modifiable risk factors on cardiovascular disease from 2025 to 2100

Abstract Background Cardiovascular diseases (CVDs) are the primary cause of global mortality and morbidity. Controlling modifiable risk factors driving the CVD epidemic is a vital focus of primary prevention efforts worldwide. Understanding the epidemiological trends in these risk factors is therefore essential in designing effective countermeasures against CVDs for the years to come. Purpose This study aims to forecast the disability-adjusted life years (DALYs) associated with CVDs attributable to high systolic blood pressure (SBP), high body-mass index (BMI), high fasting plasma glucose (FPG), high low-density lipoprotein (LDL) and tobacco use from 2025 to 2100, stratified by GBD super-regions, sex, sociodemographic index (SDI), and age-groups. Methods Historical data on DALYs from 1990 to 2019 from the Global Burden of Disease (GBD) study was used to project DALYs associated with modifiable risk factors of CVDs from 2025 to 2100. Trends across GBD super-regions, sex, SDI, and age-groups were also examined. Results Between 2025 and 2100, age-standardised DALY rates (ASDR) per 100,000 population are forecasted to fall across all modifiable risk factors, with the greatest decline seen in tobacco use (-76.0%) and high LDL (-66.9%). Globally, high SBP and high BMI expect the greatest ASDR in 2100 (both 891 per 100,000 population), while tobacco use expects the least (213 per 100,000 population). High BMI is expected to rise 623.0% in South Asia and 221.5% in South-east Asia, East Asia and Oceania from 2025 to 2100, while high FPG is expected to rise 114.2% in North Africa and the Middle-east and 110.6% in South Asia. Females are expected to have lower overall and greater reductions in ASDR across all modifiable risk factors when compared to males from 2025 to 2100. Notably, males expect a 11.0% rise in high BMI worldwide across this period. The age-prevalence of modifiable risk factors is expected to be bimodal in 2100, highest in those aged 50-59 as well as 75-84 years old, possibly suggesting improvements in global screening efforts or the earlier development of metabolic dysfunction. All modifiable risk factors are predicted to fall in high and high-middle SDI regions from 2025 to 2100. In contrast, low, low-middle, and middle SDI regions expect a rise in high FPG and high BMI across this same time frame. The burden of modifiable CVD risk factors is expected to be highest in low-middle SDI regions in 2100, as compared to high-middle SDI regions in 2025. Conclusion While the global decline in ASDR of modifiable risk factors suggests overall improvements in the primary prevention of CVDs, regional spikes in high BMI and FPG calls for the implementation of timely, targeted interventions accounting for local trends in CVD. Moreover, the disproportionate metabolic burden expected in lower SDI regions in the coming decades requires concerted, international support to alleviate the global burden of CVDs.

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

Scaling up joint efforts to tackle cardiovascular diseases and diabetes in Europe

Abstract JACARDI, a Joint Action on cardiovascular diseases (CVD) and diabetes (DM), aims to support EU countries in reducing the burden of CVD and DM and related risk factors, both at individual and societal levels, while ensuring health systems sustainability and equity. In particular, JACARDI aims to implement best practices and pilot testing of innovative practices throughout the entire patient journey. Commencing by improving health literacy and raising awareness among general and target populations, moving through primary prevention and screening of CVD and DM among high-risk populations, and then address people living with CVD and DM and their health service providers, through the improvement of service paths and (self) management, including through digital tools, and completing the path by supporting and encouraging the labour participation of people living with these diseases. With 21 European countries and 76 partners engaged, JACARDI undertakes 142 pilot projects, promising to advance CVD and DM care for millions across Europe. In particular, through an innovative Work Package on methodology, JACARDI will develop and implement a methodological framework to guide all the pilot projects in the design, preparation, implementation, monitoring, reporting, and assessment processes. This framework will encompass transversal and intersectional aspects, ensuring a harmonized and efficient approach for all JA activities. Through rigorous and multidimensional evaluation, JACARDI aims to uncover new approaches to enhance healthcare systems, grounded in evidence-based practices and current needs, while adopting the lens of equity and sustainability throughout the entire methodological and implementation process.

Cardiovascular health in women with turner's syndrome: a 3-year single centre audit

Abstract Background Turner’s syndrome (TS) is the most common genetic abnormality affecting females and is characterised by complete or partial absence of the X chromosome. Mortality is predominantly related to cardiovascular disease (1). Risk of life-threatening aortic dissection is 40 per 100,000 (2). Indexed aorta size (ASI) to body surface area (BSA) >20mm/m² is considered abnormal. An ASI of ≥25mm/m² is associated with increased risk of aortic dissection (3). Despite this there is a paucity of data in the literature regarding TS cardiovascular disease and providing evidence-based care can be challenging. Purpose Define cardiovascular disease, with focus upon aortopathy in our TS Cardiovascular Clinic (TCC). Methods Single centre retrospective medical record analysis of 248 women with TS (2021-2024) Results Patient baseline characteristics; mean age 37 years (range 18-75yrs), height 150cm (132-169cm), weight 62kg (37-130kg), BSA 1.55m² (1.19-2.17m²). 65 patients (29%) had bicuspid aortic valve (BAV), 19 (8%) and 5 (3%) had repaired and un-repaired aortic coarctation (CoA) respectively. 30 (13%) had other congenital heart disease, with most common was partial anomalous pulmonary venous connection (12 patients: 5%). 22/248 patients had previous aortic root surgery; 20 elective (mean ASI 29mm/m², range 26-33mm/m², mean age at time of surgery 42 years); 2 presented with aortic dissection (ASI 21mm/m²; pregnant, BAV & 24mm/m²; tri-leaflet aortic valve, TAV). Data was available for 221 unoperated patients (figure 1). The site of maximal dimension was observed at the sinus of Valsalva in 70% compared to 30% at the ascending aorta. 130 patients (59%) had maximal ASI of <20mm/m². Dimensions of 20-23mm/m² and 23-25mm/m² were seen in 64 (29%) and 18 (8%) patients respectively. 7 patients (3%) had a maximal ASI of >25mm/m². 4 patients (2%) had an absolute maximal dimension of 40mm with ASI of 23mm/m² for all four. 9/11 patients with dimension ≥25mm/m² or 40mm had a body mass index (BMI) >25kg/m². Review of medical history for patients at and above threshold for risk of aortic dissection revealed referral to or previous discussion in an Aortic multi-disciplinary meeting (MDT) with a plan for ongoing surveillance. 57 patients (35%) with TAV had significant aortopathy (mean age 46years, range 19-75years) compared with 33 (51%) with BAV (mean age 39yrs, range 22-72 years) (figure 2). Review of patients >55years of age demonstrated a very similar burden of aortopathy in both TAV (14%) and BAV (15%) populations. Conclusions A high burden of cardiovascular disease exists within our TS population. There is a very high prevalence of aortopathy, increasingly with age and both with and without the presence of a bicuspid aortic valve. More published data is needed to help better define those at risk.

Age and sex differences in the effects of short- and long-term exposure to air pollution on endothelial dysfunction

Abstract Background Endothelial dysfunction is an integrated index of risk factor burden and a marker of atherosclerotic cardiovascular disease. Air pollution is widely acknowledged as a significant non-traditional risk factor for cardiovascular disease. However, the impact of air pollutants at varying concentrations and exposure durations on endothelial function in different populations remains unclear. Purpose We aimed to use brachial artery flow-mediated dilatation (FMD) to identify demographic differences in the effects of short- and long-term exposure to air pollution on endothelial dysfunction. Methods We measured FMD in 850 participants from October 2016 to January 2020. Location-specific concentrations of fine particulate matter <2.5 μm aerodynamic diameter (PM2.5), inhalable particulate matter <10 μm aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) measured by fixed ambient air monitoring stations were collected for short- and long-term exposure assessment. We used the moving average 7- and 14-day exposures before the date of FMD measurements to estimate the short-term exposure effects and the moving average 12-month exposures before the date of FMD measurements to estimate the long-term exposure effects. Multiple linear regression models and restricted cubic splines were used to assess the associations before and after stratified by age and sex. Results This study eventually included 828 participants [551 (66.5%) younger than 65 years and 553 (66.8%) men]. Each 10 μg/m³ increase in 12-month exposure to PM10 and NO2 was significantly and linearly associated with -0.20% (95% CI: -0.37 to -0.03) and -0.58% (95% CI: -0.99 to -0.18) changes in FMD in all participants. 12-month exposure to gaseous pollutants was also significantly but nonlinearly associated with lower FMD. 7-day exposure to Quartile 4 of SO2 was significantly associated with a 0.70% decrease in FMD compared to Quartile 1 (β = -0.70, 95% CI: -1.40 to -0.008). No relationships were observed between 7- and 14-day exposure to PM2.5, PM10, NO2, CO, and endothelial dysfunction. Although interaction effects were limited to SO2 and sex, significant associations with different air pollutants were only found in men and those younger than 65 years after stratified. Conclusions Long-term exposure to air pollution is strongly associated with decreased endothelial function, and susceptibility to air pollution varies significantly with age and sex. Further identification of different susceptible populations and proactive measures to mitigate air pollution may be beneficial in reducing the burden of cardiovascular disease.

Social vulnerability and disparities in incidence of diagnosed diabetes in the united states, 2004 to 2019

Abstract Introduction Vulnerable populations experience a higher burden of cardiovascular disease.(1) However, the incidence of cardiovascular risk factors, such as diabetes, within these populations, is incompletely characterized. Recently, the United States Centers for Disease Control and Prevention (US CDC) developed the Social Vulnerability Index (SVI) to categorize counties that may be vulnerable to worse health outcomes. The SVI is composed of 4 themes: socioeconomic status (Theme 1), household composition & disability (Theme 2), minority status & language (Theme 3), and housing type & transportation (Theme 4).(2) We sought to evaluate the association of the 4 SVI themes with county incidence of diagnosed diabetes. Method We used CDC data (2004-2019; reported for 94% of US counties), on county incidence of diagnosed diabetes. The SVI themes were scored from 0 to 1 (low to high vulnerability) based on national percentile ranking. We used weighted least squares regression with restricted cubic splines to model the relationship between SVI themes and incidence of diagnosed diabetes (median data 2004−2019), adjusting for median age, sex ratio, state, percent uninsured, food environment index, healthcare providers, and rurality.(3) The partial effects of SVI themes and diabetes incidence were reported as F-statistics (P-values) and diabetes incidence rate ratios (IRR [95% confidence interval]), which were plotted for all values compared with the 50th percentile (SVI 0.5). For each theme, we also present the IRR for a 0.5-point increase when moving over the lower (SVI score 0.5 vs. 0.0) and the upper (1.0 vs. 0.5) half of the SVI score distribution. Results The 4 SVI theme rank scores were significantly associated with diabetes incidence (all, P<.001). However, Theme 1 and 2 scores showed stronger associations with IRR than Theme 3 and 4 (Figure). For Theme 1, SVI score 0.5 vs. 0.0 was associated with a 15% higher incidence (IRR 1.15 [1.13–1.18]) and score 1.0 vs. 0.5 was associated with a 13% higher incidence (IRR 1.13 [1.11–1.16]). For Theme 2, SVI score 0.5 vs. 0.0 was associated with a 16% higher incidence (IRR 1.16 [1.14–1.18]), but there was no difference between rates for SVI score 1.0 vs. 0.5 (IRR 1.01 [0.99–1.03]). For Theme 3, there was no difference between SVI score 0.5 vs. 0.0 (IRR 0.98 [0.96–1.00]), but rates were 8% lower for SVI score 1.0 vs. 0.5 (IRR 0.92 [0.90–0.94]). For Theme 4, SVI score 0.5 vs. 0.0 was associated with a 3% lower incidence (IRR 0.97 [0.96–0.99]) and score 1.0 vs. 0.5 was associated with a 2% higher incidence (IRR 1.02 [1.01–1.04]). Conclusion In US counties, the strength and directionality of the association between SVI themes and diabetes incidence differed by theme and level of SVI scores. These themes, particularly socioeconomic status and household composition & disability may be leveraged to identify high-risk counties for primary prevention of diabetes, with implications for reduction in cardiovascular risk.

Outcomes of post-acute coronary syndrome patients enrolled in a phase 2 cardiac rehabilitation program

Abstract Introduction Cardiac rehabilitation (CR) is a class I recommendation in the management of patients with acute coronary syndrome (ACS), namely ST-elevation myocardial infarction (STEMI) and non-ST acute coronary syndrome (NST-ACS). Reported mortality and recurrent cardiovascular (CV) events are still unacceptably high in these patients. Purpose To assess CV outcomes of patients enrolled in a CR program and its association with ACS presentation. Methods Single-center, retrospective observational study that included all consecutive post-ACS patients enrolled in a phase 2 CR program in 2017, with a follow-up of 24 months. Group 1 were patients with STEMI; group 2 were patients with NST-ACS. Major adverse cardiovascular events (MACE) were defined as a composite of death, non-fatal ACS, non-fatal stroke, and unplanned revascularization. Results Of the 202 ACS patients who attended the CR program in 2017, 4 were excluded due to missing data. Of the 198 patients analyzed (age 60.3±10.7 years, 82% male), 101 patients had a STEMI and 97 NST-ACS. STEMI patients were significantly younger (57±9.5 vs. 63±10, p<0.001), with fewer CV risk factors (diabetes 16% vs. 32%, p=0.008; hypertension 51% vs. 72%, p=0.002; obesity 17% vs. 31%, p=0.020; dyslipidemia 54% vs. 77%, p<0.001), except for active smoking (53% vs. 29%, p=0.001), and were less likely to have previous history of coronary artery disease (9% vs. 31%, p<0.001). During the 3-month CR program, both groups achieved significant reduction in body mass index, LDL-Cholesterol, functional capacity, and smoking cessation rates. At 3-, 12-, and 24-months evaluation, both groups showed no differences in risk factor management, nor differences in lipid-lowering therapy, namely percentage of high-intensity statin and ezetimibe use. STEMI patients were treated more frequently with ticagrelor (86% vs. 67%, p=0.001) at baseline. MACE occurrence was significantly lower in STEMI patients (11% vs. 28%, p=0.003), driven mainly by recurrent ACS (4% vs. 15%, p=0.006). Conclusions In our study, NST-ACS patients had significantly higher CV disease burden and worse outcomes at 24-month follow-up. Despite the heightened CV risk in this group, secondary prevention treatment intensity was similar in both groups.

Sub-Saharan Africa's contribution to clinical trials in international acute coronary syndromes and heart failure guidelines

Abstract Introduction There is a growing burden of acute coronary syndrome (ACS) and heart failure (HF) in sub-Saharan Africa (SSA), yet outcomes remain poor compared to high-income countries (HICs). Global clinical guidelines are pivotal to the delivery of evidence based cardiovascular care, however their applicability to populations in SSA remains unclear. Purpose To evaluate the extent to which populations from SSA contribute to pharmacotherapeutic randomised clinical trials informing international ACS and HF clinical guidelines. Methods We extracted details on pharmacotherapeutic randomised control trials (RCTs) contributing to Class I or II guideline recommendations from the 2023 European Society of Cardiology (ESC) guidelines for ACS and the 2021 ESC guidelines for HF. Data on RCTs contributing to these guidelines were extracted from the ClinicalTrials.gov or published articles. We analysed the proportion of RCTs which had a contribution from countries in each World Bank income group. Then we specifically assessed the contribution of SSA countries to clinical trials and analysed temporal trends. Results Of 119 RCTs from the ESC HF guidelines and the 343 pharmacotherapy RCTs from the ESC ASC guidelines 75.9% were exclusively conducted in high-income countries, 22.2% of the trials included at least one site from a middle-income country and none included sites from a low-income country (figure 1). The global distribution of HF (figure 2a) and ACS (figure 2b) pharmacotherapy guidelines is demonstrated in figure 2. The only country represented from SSA was South Africa which is an upper middle-income country. A site from South Africa was included in 17 (14.2%) HF RCTs and 28 (8.2%) ACS RCTs. There has been a significant increase in the proportion HF RCTs conducted in SSA, increasing from 2.6% between 1990 and 1999 to 50% since 2020 (OR 28.8, 95% CI 2.6 – 983.4, p-value for trend< 0.0001). For ACS RCTs, the proportion of trials conducted in SSA increased from 1.8% pre 1990 to 23.4% during 2000-2009 (OR 15.9, 95% CI 4.2 - 112.9, p value for trend = 0.003) then declined to 11.3% from 2010-2019. Conclusions There is a marked under-representation of SSA countries in ACS and HF pharmacotherapy RCTs, despite the region's escalating cardiovascular disease burden. South Africa is the sole contributor from the region, with all other SSA countries absent. This finding could potentially affect the applicability and generalisability of global guidelines to populations in SSA with distinct clinical presentations and healthcare challenges.Figure 1 Figure 2