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Introduction With an increasing burden of cardiovascular disease, there has been rising demands for outpatient cardiology services. In this study, we reviewed the cardiology referral patterns from primary care to a tertiary cardiac centre, and evaluated their longer term clinical outcomes based on referral symptomatology as well as risk stratification. Methods Consecutive outpatients referred from primary care to a national cardiac centre between March 2015 to December 2020 were included. Patients with known coronary artery disease (CAD) were excluded. Chest pain patients were stratified by pre-test probability (PTP) of obstructive CAD using chest pain risk scores and the rest by age and sex. Outcomes studied included mortality and major adverse cardiovascular events (MACE). Results A total of 33,244 patients (11,865 chest pain, 3427 palpitations, 2844 dyspnoea) were included. In patients with chest pain, the 3-year mortality and MACE rates were 1.25% and 3.19% respectively. Patients with higher PTP of CAD demonstrated significantly higher rates of adverse events. In patients with palpitations, the 3-year mortality and MACE rates were 0.86% and 1.55% respectively. Males aged >65years had significantly higher risk of 3-year mortality ( p < .00.5). In patients with dyspnoea, the 3-year mortality and MACE rates were 3.34 and 4.44% respectively. Subsets of younger age and/or female sex had lower rates of adverse events. Conclusions While long term adverse clinical outcomes were generally low in this stable outpatient cohort, risk stratification allowed for identification of an even lower risk subset of patients for whom additional testing may potentially not yield incremental clinical benefit.

Abstract Activated partial thromboplastin time (aPTT)-based clot waveform analysis (CWA) is a plasma-based global haemostatic assay. Elevated CWA parameters have been associated with hypercoagulability in venous thromboembolism, but its role in arterial thrombotic disease is uncertain. This study aims to explore the relationship between aPTT-based CWA and acute myocardial infarction (AMI) and its complications. In a retrospective cohort study of patients with AMI who underwent emergency cardiac catheterisation, pre-procedural aPTT and CWA parameters—min1, min2 and max2 were measured. These were compared against a control group of patients, consisting of patients who underwent elective orthopaedic and urological procedures. Within the AMI cohort, we also compared aPTT and CWA parameters of those with and without clinical complications of AMI. Results: Compared to controls (N = 109), patients with AMI (N = 214) had shorter aPTT (26.7 ± 3.3 s vs 27.9 ± 1.7 s, P

Chest pain is a common presenting complaint among patients visiting primary care1 and is a frequent reason for referral to the outpatient cardiology clinic. The European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines advocate estimating pre-test probability (PTP) of obstructive coronary artery disease (CAD) in the evaluation of stable chest pain in order to guide the need for and type of downstream investigations.2,3 The PTP of obstructive CAD depends on the clinical characteristics of the patient and disease prevalence. Since the introduction of the Diamond-Forrester model in 1979,4 contemporary risk scores, such as the CAD consortium score5 (CCS) and the ESC 2019 PTP risk score,2 have been developed.

Summary: Background: Given the rapidly growing burden of cardiovascular disease (CVD) in Asia, this study forecasts the CVD burden and associated risk factors in Asia from 2025 to 2050. Methods: Data from the Global Burden of Disease 2019 study was used to construct regression models predicting prevalence, mortality, and disability-adjusted life years (DALYs) attributed to CVD and risk factors in Asia in the coming decades. Findings: Between 2025 and 2050, crude cardiovascular mortality is expected to rise 91.2% despite a 23.0% decrease in the age-standardised cardiovascular mortality rate (ASMR). Ischaemic heart disease (115 deaths per 100,000 population) and stroke (63 deaths per 100,000 population) will remain leading drivers of ASMR in 2050. Central Asia will have the highest ASMR (676 deaths per 100,000 population), more than three-fold that of Asia overall (186 deaths per 100,000 population), while high-income Asia sub-regions will incur an ASMR of 22 deaths per 100,000 in 2050. High systolic blood pressure will contribute the highest ASMR throughout Asia (105 deaths per 100,000 population), except in Central Asia where high fasting plasma glucose will dominate (546 deaths per 100,000 population). Interpretation: This forecast forewarns an almost doubling in crude cardiovascular mortality by 2050 in Asia, with marked heterogeneity across sub-regions. Atherosclerotic diseases will continue to dominate, while high systolic blood pressure will be the leading risk factor. Funding: This was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03), National Medical Research Council Research Training Fellowship (MH 095:003/008-303), National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Fellowship Scheme, NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS) and the CArdiovascular DiseasE National Collaborative Enterprise (CADENCE) National Clinical Translational Program (MOH-001277-01).

Introduction Cardiorespiratory fitness (CRF) in young adulthood is a determinant of chronic disease risk. To better understand whether CRF might also behave as a modifiable risk factor, we examined the associations between longitudinal changes in 2.4 km run times and health outcomes in a cohort of healthy young men.Methods Our dataset comprised individual run times and health outcomes captured in four national registries. Cox proportional hazards models were used to examine the association between baseline run times and relative hazards of first major adverse cardiovascular events (MACE) and all-cause mortality (ACM). Relative hazards associated with longitudinal change in run times were estimated using models that were adjusted for run-time at baseline.Results The study sample comprised 148 825 healthy men ages 18–34 years who had undergone at least two routine fitness tests that were 5–9 years apart. During 1 294 778 person-years of follow-up, we observed 1275 first MACE and 764 ACM events occurring at mean ages of 43.2 (SD 6.0) years and 39.2 (SD 6.6) years, respectively. A 1% increase in run-time per annum was associated with a 1.13 (95% CI 1.10 to 1.16) times greater hazard of first MACE and a 1.06 (95% CI 1.02 to 1.10) times greater hazard of ACM. The association between longitudinal change in run times and first MACE was preserved in sensitivity analyses using models adjusted for body mass index at baseline.Conclusion Among men under the age of 35 years, longitudinal change in run times was associated with the risk of cardiovascular disease two decades onwards.

Abstract Rare genetic diseases affect 5–8% of the population but are often undiagnosed or misdiagnosed. Electronic health records (EHR) contain large amounts of data, which provide opportunities for analysing and mining. Data analysis in the form of visualisation and statistical testing, was performed on a database containing deidentified health records of 1.28 million patients across 3 major hospitals in Singapore, in a bid to improve the diagnostic process for patients who are living with an undiagnosed rare disease, specifically focusing on Fabry Disease and Familial Hypercholesterolaemia (FH). On a baseline of 4 patients, we identified 2 additional patients with potential diagnosis of Fabry disease, suggesting a potential 50% increase in diagnosis. Similarly, we identified > 12,000 individuals who fulfil the clinical and laboratory criteria for FH but had not been diagnosed previously. This proof-of-concept study showed that it is possible to perform mining on EHR data albeit with some challenges and limitations.

Introduction: Cardiovascular disease was the top cause of deaths and disability in Singapore in 2018, contributing extensively to the local healthcare burden. Primary prevention identifies at-risk individuals for the swift implementation of preventive measures. This has been traditionally done using the Singapore-adapted Framingham Risk Score (SG FRS). However, its most recent recalibration was more than a decade ago. Recent changes in patient demographics and risk factors have undermined the accuracy of SG FRS, and the rising popularity of wearable health metrics has led to new data types with the potential to improve risk prediction. Methods: In healthy Singaporeans enrolled in SingHEART study (absence of any clinical outcomes), we investigated improvements in SG FRS to predict myocardial infarction risk based on high/low classification of the Agatston score (surrogate outcome). Logistic regression, receiver operating characteristic and net reclassification index (NRI) analyses were conducted. Results: We demonstrated a significant improvement in the area under curve (AUC) of SG FRS (AUC = 0.641) after recalibration and incorporation of additional variables (fasting blood glucose and wearable-derived activity levels) (AUC = 0.774) (P < 0.001). SG FRS++ significantly increases accuracy in risk prediction (NRI = 0.219, P = 0.00254). Conclusion: Existing Singapore cardiovascular disease risk prediction guidelines should be updated to improve risk prediction accuracy. Recalibrating existing risk functions and utilising wearable metrics that provide a large pool of objective health data can improve existing risk prediction tools. Lastly, activity levels and prediabetic state are important factors for coronary heart disease risk stratification, especially in low-risk individuals.

Introduction: In 2022, the Minister for Health of Singapore launched Healthier SG, a national strategy in championing the shift towards a population health approach. Method: The Singapore Heart Foundation conducted a series of roundtable discussions, also attended by representatives of the Singapore Cardiac Society and the Chapter of Cardiologists of the Academy of Medicine Singapore. During the meetings, the authors formulated interventions supportive of Healthier SG that specifically aimed to uplift the state of cardiovascular (CV) preventive care in Singapore. Results: In line with Healthier SG, the authors propose a 3-pronged approach (“Healthier Heart SG”) to augment the success of Healthier SG in achieving good CV outcomes. This proposal includes the following components: (1) a call to update the standards of care in addressing the 5 main modifiable risk factors of cardiovascular disease (CVD); (2) patient education through cooperation between healthcare professionals and community partners for a whole-of-system approach; and (3) support for integrated care, including access to cardiac rehabilitation in the community, improved referral processes and access to nutrition/dietetics counselling and tobacco cessation, optimal use of information technology, and continued CV research. Conclusion: Healthier Heart SG would bring the standards of care and CV care delivery in Singapore closer to achieving the vision of proactive prevention of CVD and CV morbidity and mortality. This can only be achieved through the concerted efforts of healthcare professionals, policymakers and community partners, coupled with the cooperation of community members.

Clinically significant genetic variation in Asian populations is under-characterized. Here, the authors show the diversity in prevalence and spectrum of human disease and pharmacogenetic variants in a multi-ethnic Asian population.

Abstract The prediction utility of Framingham Risk Score in populations with low conventional cardiovascular risk burden is limited, particularly among women. Gender-specific markers to predict cardiovascular risk in overtly healthy people are lacking. In this study we hypothesize that postprandial responses triggered by a high-calorie meal test differ by gender in their ability to triage asymptomatic subjects into those with and without subclinical atherosclerosis. A total of 101 healthy Chinese subjects (46 females, 55 males) at low risk of coronary heart disease completed the study. Subjects underwent cardiovascular imaging and postprandial blood phenotyping after consuming a standardized macronutrient meal. Prediction models were developed using logistic regression and subsequently subjected to cross-validation to obtain a de-optimized receiver operating characteristic (ROC) curve. Distinctive gender differences in postprandial trajectories of glucose, lipids and inflammatory markers were observed. We used gender-specific association with different combinations of postprandial predictors to develop 2 models for predicting risk of subclinical atherosclerosis in males (ROC AUC = 0.7867, 95% CI 0.6567, 0.9166) and females (ROC AUC = 0.9161, 95% CI 0.8340, 0.9982) respectively. We report novel postprandial models for predicting subclinical atherosclerosis in apparently healthy Asian subjects using a gender-specific approach, complementing the conventional Framingham Risk Score. Clinical Trial Registration: The trial was registered at clinicaltrials.gov as NCT03531879.

Background : Cardiac evaluation before deceased donor kidney transplant (DDKT) remains a matter of debate. Data on Asian countries and countries with prolonged waiting times are lacking. This study aimed to assess the outcomes of patients referred for DDKT after a cardiac evaluation at an Asian tertiary transplant center. Methods : This single-center retrospective review analyzed patients who were referred for waitlist placement and underwent cardiac stress testing between January 2009 and December 2015. Patients with cardiac symptoms were excluded. The primary outcome was three-point major adverse cardiovascular events (MACE), a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. Results : Of 468 patients referred for DDKT, 198 who underwent cardiac stress testing (myocardial perfusion studies in 159 patients and stress echocardiography in 39 patients) were analyzed. MACE occurred in 20.7% of the patients over a median follow-up of 4.6 years. Cardiac stress tests were positive for ischemia in 19.7% of the patients. Coronary angiography was performed in 63 patients, including 29 patients with diabetic kidney disease and negative cardiac stress tests. Significant coronary artery disease (CAD) was detected in 27 patients (42.8%), of whom 18 underwent revascularization. MACE was associated with significant CAD on coronary angiography in the multivariable analysis. Cardiac stress test results were not associated with MACE. Amongst diabetic patients who had negative cardiac stress tests, 37.9% had significant CAD on coronary angiography. Conclusions: The cardiovascular disease burden is significant amongst DDKT waitlist candidates. Pretransplant cardiac screening may identify patients with significant CAD at higher risk of MACE.

Summary: Genomic researchers increasingly utilize commercial cloud service providers (CSPs) to manage data and analytics needs. CSPs allow researchers to grow Information Technology (IT) infrastructure on demand to overcome bottlenecks when combining large datasets. However, without adequate security controls, the risk of unauthorized access may be higher for data stored on the cloud. Additionally, regulators are mandating data access patterns and specific security protocols for the storage and use of genomic data. While CSP provides tools for security and regulatory compliance, building the necessary controls required for cloud solutions is not trivial. Research Assets Provisioning and Tracking Online Repository (RAPTOR) by the Genome Institute of Singapore is a cloud-native genomics data repository and analytics platform that implements a “five-safes” framework to provide security and governance controls to data contributors and users, leveraging CSP for sharing and analysis of genomic datasets without the risk of security breaches or running afoul of regulations.

Abstract This study looked at novel data sources for cardiovascular risk prediction including detailed lifestyle questionnaire and continuous blood pressure monitoring, using ensemble machine learning algorithms (MLAs). The reference conventional risk score compared against was the Framingham Risk Score (FRS). The outcome variables were low or high risk based on calcium score 0 or calcium score 100 and above. Ensemble MLAs were built based on naive bayes, random forest and support vector classifier for low risk and generalized linear regression, support vector regressor and stochastic gradient descent regressor for high risk categories. MLAs were trained on 600 Southeast Asians aged 21 to 69 years free of cardiovascular disease. All MLAs outperformed the FRS for low and high-risk categories. MLA based on lifestyle questionnaire only achieved AUC of 0.715 (95% CI 0.681, 0.750) and 0.710 (95% CI 0.653, 0.766) for low and high risk respectively. Combining all groups of risk factors (lifestyle survey questionnaires, clinical blood tests, 24-h ambulatory blood pressure and heart rate monitoring) along with feature selection, prediction of low and high CVD risk groups were further enhanced to 0.791 (95% CI 0.759, 0.822) and 0.790 (95% CI 0.745, 0.836). Besides conventional predictors, self-reported physical activity, average daily heart rate, awake blood pressure variability and percentage time in diastolic hypertension were important contributors to CVD risk classification.

PurposeThe COVID-19 pandemic has drastically disrupted global healthcare systems. With the higher demand for healthcare and misinformation related to COVID-19, there is a need to explore alternative models to improve communication. Artificial Intelligence (AI) and Natural Language Processing (NLP) have emerged as promising solutions to improve healthcare delivery. Chatbots could fill a pivotal role in the dissemination and easy accessibility of accurate information in a pandemic. In this study, we developed a multi-lingual NLP-based AI chatbot, DR-COVID, which responds accurately to open-ended, COVID-19 related questions. This was used to facilitate pandemic education and healthcare delivery.MethodsFirst, we developed DR-COVID with an ensemble NLP model on the Telegram platform (https://t.me/drcovid_nlp_chatbot). Second, we evaluated various performance metrics. Third, we evaluated multi-lingual text-to-text translation to Chinese, Malay, Tamil, Filipino, Thai, Japanese, French, Spanish, and Portuguese. We utilized 2,728 training questions and 821 test questions in English. Primary outcome measurements were (A) overall and top 3 accuracies; (B) Area Under the Curve (AUC), precision, recall, and F1 score. Overall accuracy referred to a correct response for the top answer, whereas top 3 accuracy referred to an appropriate response for any one answer amongst the top 3 answers. AUC and its relevant matrices were obtained from the Receiver Operation Characteristics (ROC) curve. Secondary outcomes were (A) multi-lingual accuracy; (B) comparison to enterprise-grade chatbot systems. The sharing of training and testing datasets on an open-source platform will also contribute to existing data.ResultsOur NLP model, utilizing the ensemble architecture, achieved overall and top 3 accuracies of 0.838 [95% confidence interval (CI): 0.826–0.851] and 0.922 [95% CI: 0.913–0.932] respectively. For overall and top 3 results, AUC scores of 0.917 [95% CI: 0.911–0.925] and 0.960 [95% CI: 0.955–0.964] were achieved respectively. We achieved multi-linguicism with nine non-English languages, with Portuguese performing the best overall at 0.900. Lastly, DR-COVID generated answers more accurately and quickly than other chatbots, within 1.12–2.15 s across three devices tested.ConclusionDR-COVID is a clinically effective NLP-based conversational AI chatbot, and a promising solution for healthcare delivery in the pandemic era.

ObjectiveWe examined the association between cardiorespiratory fitness (CRF), body mass index (BMI), incidence of major acute cardiovascular events (MACE), and all-cause mortality (ACM).MethodsWe conducted a retrospective cohort study involving 212,631 healthy young men aged 16 to 25 years who had undergone medical examination and fitness testing (2.4 km run) from 1995 to 2015. Information on the outcomes of major acute cardiovascular events (MACE) and all-cause mortality (ACM) were obtained from the national registry data.ResultsDuring 2,043,278 person-years of follow-up, 371 first MACE and 243 ACM events were recorded. Compared against the first run-time quintile, adjusted hazard ratios (HR) for MACE in the second to fifth quintiles were 1.26 (95% CI 0.84–1.91), 1.60 (95% CI 1.09–2.35), 1.60 (95% CI 1.10–2.33), and 1.58 (95% CI 1.09–2.30). Compared against the “acceptable risk” BMI category, the adjusted HRs for MACE in the “underweight,” “increased risk,” and “high-risk” categories were 0.97 (95% CI 0.69–1.37), 1.71 (95% CI 1.33–2.21), and 3.51 (95% CI 2.61–4.72), respectively. The adjusted HRs for ACM were increased in participants from the fifth run-time quintile in the “underweight” and “high-risk” BMI categories. The combined associations of CRF and BMI with MACE showed elevated hazard in the “BMI≥23-fit” category, which was more pronounced in the “BMI≥23-unfit” category. The hazards for ACM were elevated across the “BMI

BackgroundSubclinical atherosclerosis can be present in individuals with an optimal cardiovascular risk factor profile. Traditional risk scores such as the Framingham risk score do not adequately capture risk stratification in low-risk individuals. The aim of this study was to determine if markers of metabolic syndrome and insulin resistance can better stratify low-risk individuals.MethodsA cross-sectional study of 101 healthy participants with a low Framingham risk score and no prior morbidities was performed to assess prevalence of subclinical atherosclerosis using computed tomography (CT) and ultrasound. Participants were compared between groups based on Metabolic Syndrome (MetS) and Insulin-Sensitivity Index (ISI-cal) scores.ResultsTwenty three individuals (23%) had subclinical atherosclerosis with elevated CT Agatston score ≥1. Presence of both insulin resistance (ISI-cal

Background: The influence of age and sex on clinical atherosclerotic cardiovascular disease is well reported, but literature remains sparse on whether these extend to the disease in its preclinical stage. Objectives: The purpose of this study was to report the prevalence, risk factors, and impact of age and sex on the burden of subclinical coronary atherosclerosis in a healthy Asian population. Methods: Healthy subjects age 30 to 69 years, with no history of cardiovascular disease or diabetes were recruited from the general population. Subclinical coronary atherosclerosis was quantified via the coronary artery calcium score (CAC) with CAC of 0 indicating absence of calcified plaque, 1 to 10 minimal plaque, 11 to 100 mild plaque, and >100 moderate to severe plaque. Results: A total of 663 individuals (mean age 49.4 ± 9.2 years; 44.8% men) were included. The prevalence of any CAC was 29.3%, with 9% having CAC >100. The prevalence was significantly higher in men than women (43.1% vs 18.0%; P < 0.001). Multivariable analysis revealed significant associations of increasing age, male sex, higher blood pressure, increased glucose levels, and higher low-density lipoprotein cholesterol levels with the presence of any CAC. Low-density lipoprotein cholesterol was more significantly associated with CAC in women compared with men (Pinteraction = 0.022). Conclusions: The prevalence of preclinical atherosclerosis increased with age, and was higher in men, with sex-specific differences in associated risk factors. These results will better inform individualized future risk management strategies to prevent the development and progression of coronary artery disease within healthy individuals.

Xuling Chang et al. study whether low frequency variants are associated with leukocyte telomere length and whether these variants predispose to incident cancers and mortalities among East Asians. They find that three East Asian specific variants at POT1, TERF1 and STN1 loci are associated with leukocyte telomere length and report a mechanistic pathway linking TERF1, leukocyte telomere length and incident colon cancer.

More than 500 million people worldwide live with cardiovascular disease (CVD). Health systems today face fundamental challenges in delivering optimal care due to ageing populations, healthcare workforce constraints, financing, availability and affordability of CVD medicine, and service delivery. Digital health technologies can help address these challenges. They may be a tool to reach Sustainable Development Goal 3.4 and reduce premature mortality from non-communicable diseases (NCDs) by a third by 2030. Yet, a range of fundamental barriers prevents implementation and access to such technologies. Health system governance, health provider, patient and technological factors can prevent or distort their implementation. World Heart Federation (WHF) roadmaps aim to identify essential roadblocks on the pathway to effective prevention, detection, and treatment of CVD. Further, they aim to provide actionable solutions and implementation frameworks for local adaptation. This WHF Roadmap for digital health in cardiology identifies barriers to implementing digital health technologies for CVD and provides recommendations for overcoming them.

BackgroundConsumer-grade wearable devices enable detailed recordings of heart rate and step counts in free-living conditions. Recent studies have shown that summary statistics from these wearable recordings have potential uses for longitudinal monitoring of health and disease states. However, the relationship between higher resolution physiological dynamics from wearables and known markers of health and disease remains largely uncharacterized. ObjectiveWe aimed to derive high-resolution digital phenotypes from observational wearable recordings and to examine their associations with modifiable and inherent markers of cardiometabolic disease risk. MethodsWe introduced a principled framework to extract interpretable high-resolution phenotypes from wearable data recorded in free-living conditions. The proposed framework standardizes the handling of data irregularities; encodes contextual information regarding the underlying physiological state at any given time; and generates a set of 66 minimally redundant features across active, sedentary, and sleep states. We applied our approach to a multimodal data set, from the SingHEART study (NCT02791152), which comprises heart rate and step count time series from wearables, clinical screening profiles, and whole genome sequences from 692 healthy volunteers. We used machine learning to model nonlinear relationships between the high-resolution phenotypes on the one hand and clinical or genomic risk markers for blood pressure, lipid, weight and sugar abnormalities on the other. For each risk type, we performed model comparisons based on Brier scores to assess the predictive value of high-resolution features over and beyond typical baselines. We also qualitatively characterized the wearable phenotypes for participants who had actualized clinical events. ResultsWe found that the high-resolution features have higher predictive value than typical baselines for clinical markers of cardiometabolic disease risk: the best models based on high-resolution features had 17.9% and 7.36% improvement in Brier score over baselines based on age and gender and resting heart rate, respectively (P

Abstract Background Stress cardiovascular magnetic resonance (CMR) offers assessment of ventricular function, myocardial perfusion and viability in a single examination to detect coronary artery disease (CAD). We developed an in-scanner exercise stress CMR (ExCMR) protocol using supine cycle ergometer and aimed to examine the diagnostic value of a multiparametric approach in patients with suspected CAD, compared with invasive fractional flow reserve (FFR) as the reference gold standard. Methods In this single-centre prospective study, patients who had symptoms of angina and at least one cardiovascular disease risk factor underwent both ExCMR and invasive angiography with FFR. Rest-based left ventricular function (ejection fraction, regional wall motion abnormalities), tissue characteristics and exercise stress-derived (perfusion defects, inducible regional wall motion abnormalities and peak exercise cardiac index percentile-rank) CMR parameters were evaluated in the study. Results In the 60 recruited patients with intermediate CAD risk, 50% had haemodynamically significant CAD based on FFR. Of all the CMR parameters assessed, the late gadolinium enhancement, stress-inducible regional wall motion abnormalities, perfusion defects and peak exercise cardiac index percentile-rank were independently associated with FFR-positive CAD. Indeed, this multiparametric approach offered the highest incremental diagnostic value compared to a clinical risk model (χ 2 for the diagnosis of FFR-positive increased from 7.6 to 55.9; P

Abstract Background Family history has traditionally been an essential part of clinical care to assess health risks. However, declining sequencing costs have precipitated a shift towards genomics-first approaches in population screening programs rendering the value of family history unknown. We evaluated the utility of incorporating family history information for genomic sequencing selection. Methods To ascertain the relationship between family histories on such population-level initiatives, we analysed whole genome sequences of 1750 research participants with no known pre-existing conditions, of which half received comprehensive family history assessment of up to four generations, focusing on 95 cancer genes. Results Amongst the 1750 participants, 866 (49.5%) had high-quality standardised family history available. Within this group, 73 (8.4%) participants had an increased family history risk of cancer (increased FH risk cohort) and 1 in 7 participants (n = 10/73) carried a clinically actionable variant inferring a sixfold increase compared with 1 in 47 participants (n = 17/793) assessed at average family history cancer risk (average FH risk cohort) (p = 0.00001) and a sevenfold increase compared to 1 in 52 participants (n = 17/884) where family history was not available (FH not available cohort) (p = 0.00001). The enrichment was further pronounced (up to 18-fold) when assessing only the 25 cancer genes in the American College of Medical Genetics (ACMG) Secondary Findings (SF) genes. Furthermore, 63 (7.3%) participants had an increased family history cancer risk in the absence of an apparent clinically actionable variant. Conclusions These findings demonstrate that the collection and analysis of comprehensive family history and genomic data are complementary and in combination can prioritise individuals for genomic analysis. Thus, family history remains a critical component of health risk assessment, providing important actionable data when implementing genomics screening programs. Trial registration ClinicalTrials.gov NCT02791152 . Retrospectively registered on May 31, 2016.

Summary: The COVID-19 pandemic has had a substantial and global impact on health care, and has greatly accelerated the adoption of digital technology. One of these emerging digital technologies, blockchain, has unique characteristics (eg, immutability, decentralisation, and transparency) that can be useful in multiple domains (eg, management of electronic medical records and access rights, and mobile health). We conducted a systematic review of COVID-19-related and non-COVID-19-related applications of blockchain in health care. We identified relevant reports published in MEDLINE, SpringerLink, Institute of Electrical and Electronics Engineers Xplore, ScienceDirect, arXiv, and Google Scholar up to July 29, 2021. Articles that included both clinical and technical designs, with or without prototype development, were included. A total of 85 375 articles were evaluated, with 415 full length reports (37 related to COVID-19 and 378 not related to COVID-19) eventually included in the final analysis. The main COVID-19-related applications reported were pandemic control and surveillance, immunity or vaccine passport monitoring, and contact tracing. The top three non-COVID-19-related applications were management of electronic medical records, internet of things (eg, remote monitoring or mobile health), and supply chain monitoring. Most reports detailed technical performance of the blockchain prototype platforms (277 [66·7%] of 415), whereas nine (2·2%) studies showed real-world clinical application and adoption. The remaining studies (129 [31·1%] of 415) were themselves of a technical design only. The most common platforms used were Ethereum and Hyperledger. Blockchain technology has numerous potential COVID-19-related and non-COVID-19-related applications in health care. However, much of the current research remains at the technical stage, with few providing actual clinical applications, highlighting the need to translate foundational blockchain technology into clinical use.

The prevalence of dyslipidaemia has been increasing in the Asia-Pacific region and this is attributed to dietary changes and decreasing physical activity. While there has been substantial progress in dyslipidaemia therapy, its management in the region is hindered by limitations in awareness, adherence and healthcare costs. The Asian Pacific Society of Cardiology (APSC) developed these consensus recommendations to address the need for a unified approach to managing dyslipidaemia. These recommendations are intended to guide general cardiologists and internists in the assessment and treatment of dyslipidaemia and are hoped to pave the way for improving screening, early diagnosis and treatment. The APSC expert panel reviewed and appraised the evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed, which were then put to an online vote. The resulting consensus recommendations tackle contemporary issues in the management of dyslipidaemia, familial hypercholesterolaemia and lipoprotein(a) in the Asia-Pacific region.

Background Non-alcoholic fatty liver disease (NAFLD) is a well-established risk factor for cardiovascular disease, with ethnic and regional differences noted. With the recent surge of research within this field, we re-examine the evidence associating NAFLD with subclinical atherosclerosis, and investigate potential regional differences.Methods This is a systematic review and meta-analysis. PubMed and EMBASE were systematically searched for publications from January 1967 to July 2020 using standardised criteria. Original, observational studies investigating the association between NAFLD and either carotid intima-media thickness (CIMT) and/or coronary artery calcification (CAC) were included. Key outcomes included differences in mean CIMT, the presence of increased CIMT, the presence of CAC and the development/progression of CAC. Pooled ORs and pooled standard differences in means were calculated using random-effects models. Between-study heterogeneity was quantified using the Q statistic and I². Subgroup analyses stratified by region of study (Asian vs Western) were also conducted.Results 64 studies involving a total of 172 385 participants (67 404 with NAFLD) were included. 44 studies assessed the effect of NAFLD on CIMT, with the presence of NAFLD associated with increased CIMT (OR 2.00, 95% CI 1.56 to 2.56). 22 studies assessed the effects of NAFLD on CAC score, with the presence of NAFLD associated with the presence of any coronary calcification (OR 1.21, 95% CI 1.12 to 1.32), and the development/progression of CAC (OR 1.26, 95% CI 1.04 to 1.52). When stratified by region, these associations remained consistent across both Asian and Western populations (p>0.05). The majority (n=39) of studies were classified as ‘high quality’, with the remaining 25 of ‘moderate quality’.Conclusions There is a significant positive association between various measures of subclinical atherosclerosis and NAFLD, seen across both Western and Asian populations. These results re-emphasise the importance of early risk evaluation and prophylactic intervention measures to preclude progression to clinical cardiovascular disease in patients with NAFLD.

Abstract Background Cardiovascular disease (CVD) imposes much mortality and morbidity worldwide. The use of “deep learning”, advancements in genomics, metabolomics, proteomics and devices like wearables have the potential to unearth new insights in the field of cardiology. Currently, in Asia, there are no studies that combine the use of conventional clinical information with these advanced technologies. We aim to harness these new technologies to understand the development of cardiovascular disease in Asia. Methods Singapore is a multi-ethnic country in Asia with well-represented diverse ethnicities including Chinese, Malays and Indians. The SingHEART study is the first technology driven multi-ethnic prospective population-based study of healthy Asians. Healthy male and female subjects aged 21–69 years old without any prior cardiovascular disease or diabetes mellitus will be recruited from the general population. All subjects are consented to undergo a detailed on-line questionnaire, basic blood investigations, resting and continuous electrocardiogram and blood pressure monitoring, activity and sleep tracking, calcium score, cardiac magnetic resonance imaging, whole genome sequencing and lipidomic analysis. Outcomes studied will include mortality and cause of mortality, myocardial infarction, stroke, malignancy, heart failure, and the development of co-morbidities. Discussion An initial target of 2500 patients has been set. From October 2015 to May 2017, an initial 683 subjects have been recruited and have completed the initial work-up the SingHEART project is the first contemporary population-based study in Asia that will include whole genome sequencing and deep phenotyping: including advanced imaging and wearable data, to better understand the development of cardiovascular disease across different ethnic groups in Asia.

Abstract Background Air pollution has a significant health impact. Most data originate from temperate regions. We aim to study the health impact of air pollution, particularly among the elderly, in a tropical region. Methods A daily time-series analysis was performed to estimate excess risk (ER) of various air pollutants on daily death counts amongst the general population in Singapore from 2001 to 2013. Air pollutants included particulate matters smaller than 10 μm, and 2.5 μm (PM10, PM2.5), carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3) and sulphur dioxide (SO2). The studied outcomes were non-accidental and cardiovascular mortality. Single-day lag and distributed lag models were studied and adjusted for confounders. Results In single-day lag models, a 10 μg/m3 increase in particulate matter was associated with significant increases in non-accidental (PM10 ER: 0.627%; 95% confidence interval (CI): 0.260–0.995% and PM2.5 ER: 0.660%; 95% CI: 0.204–1.118%) and cardiovascular mortality (PM10 ER: 0.897; 95% CI: 0.283–1.516 and PM2.5 ER: 0.883%; 95% CI: 0.121–1.621%). This was significant in the elderly ≥ 65 years but not in those

Abstract Background The WHOQOL-BREF is a widely used questionnaire for measuring quality of life. It is important to establish the measurement equivalence of various language versions of WHOQOL-BREF so that scores from different language versions may be pooled together. The primary aim of this article was to evaluate the measurement equivalence of the English, Chinese and Malay versions of the WHOQOL-BREF. Methods We analysed data from the previously published, cross-sectional, WONDERS study and used linear regression models to adjust for potential confounding variables. Based on equivalence clinical trial methods, measurement equivalence was assessed by comparing 90% confidence interval (CI) of differences in scores across language versions with a predefined equivalence margin of 0.3 SD. Equivalence was achieved if the 90% CI fell within 0.3 SD. Data from 1203 participants, aged above 21 years, were analysed. Results Participants who completed the different language versions of WHOQOL-BREF expectedly differed in age, ethnicity, highest education level, marital status, smoking status and Body Mass Index (BMI). The English and Malay language versions were definitely equivalent for all domains. The English and Chinese language versions were definitely equivalent for physical and environmental domains but inconclusive for psychological and social domains. Likewise, for Chinese and Malay versions. Conclusion The English, Chinese and Malay language versions of the WHOQOL-BREF questionnaire may be considered equivalent, with evidence being more robust for some domains than the others. Given the large number of people who speak/ read Chinese and Malay, this study has widespread relevance.

The COVID-19 pandemic has created a huge burden on the healthcare industry worldwide. Pressures to increase the isolation healthcare facility to cope with the growing number of patients led to an exploration of the use of wearables for vital signs monitoring among stable COVID-19 patients. Vital signs wearables were chosen for use in our facility with the purpose of reducing patient contact and preserving personal protective equipment. The process of deciding on the wearable solution as well as the implementation of the solution brought much insight to the team. This paper presents an overview of factors to consider in implementing a vital signs wearable solution. This includes considerations before deciding on whether or not to use a wearable device, followed by key criteria of the solution to assess. With the use of wearables rising in popularity, this serves as a guide for others who may want to implement it in their institutions.

Transcatheter mitral valve repair with the MitraClip, a catheter-based percutaneous edge-to-edge repair technique to correct mitral regurgitation (MR), has been demonstrated in Western studies to be an effective and safe MR treatment strategy. However, randomised clinical trial data on its use in Asian-Pacific patients is limited. Hence, the Asian Pacific Society of Cardiology convened an expert panel to review the available literature on MitraClip and to develop consensus recommendations to guide clinicians in the region. The panel developed statements on the use of MitraClip for the management of degenerative MR, functional MR, and other less common indications, such as acute MR, dynamic MR, hypertrophic obstructive cardiomyopathy, and MR after failed surgical repair. Each statement was voted on by each panel member and consensus was reached when 80% of experts voted ‘agree’ or ‘neutral’. This consensus-building process resulted in 10 consensus recommendations to guide general cardiologists in the evaluation and management of patients in whom MitraClip treatment is being contemplated.

Background: Plasma branched-chain amino acids (BCAA) are consistently elevated in subjects with obesity and type 2 diabetes (T2DM) and correlate with insulin resistance. The association of BCAA with insulin secretion and clearance rates has not been adequately described.Objective: To evaluate the relationships between fasting and postprandial plasma BCAA, insulin secretion and insulin clearance.Design: Ninety-five non-diabetic Chinese subjects (43 females) underwent a mixed-meal tolerance test; blood biomarkers including BCAAs (leucine, isoleucine, valine) were measured for 6 h. Fasting and postprandial insulin secretion rates (ISR) and insulin clearance were determined by oral minimal modeling of glucose and C-peptide.Results: Fasting and postprandial plasma BCAA correlated strongly with each other (ρ = 0.796, P < 0.001), and both were positively associated with basal ISR (ρ = 0.45/0.36, P < 0.001), total postprandial ISR AUC (ρ = 0.37/0.45, P < 0.001), and negatively with insulin clearance (ρ = −0.29/−0.29, P < 0.01), after adjusting for sex and body mass index. These relationships largely persisted after adjusting further for insulin resistance and postprandial glucose. Compared with subjects in the middle and lowest tertiles for fasting or postprandial plasma BCAA, subjects in the highest tertile had significantly greater postprandial glucose (by 7–10%) and insulin (by 74–98%) concentrations, basal ISRs (by 34–53%), postprandial ISR AUCs (by 41–49%), and lower insulin clearance rates (by 17–22%) (all P < 0.05).Conclusions: Fasting and postprandial plasma BCAA levels are associated with greater fasting and postprandial insulin secretion and reduced insulin clearance in healthy Chinese subjects. These observations potentially highlight an additional layer of involvement of BCAA in the regulation of glucose homeostasis.

Introduction Diabetes mellitus is a growing public health epidemic in Asia. We examined the impact of type 2 diabetes, glycemic control and microvascular complications on mortality and cardiovascular outcomes in a multiethnic population-based cohort of Asians without prior cardiovascular disease.Research design and methods This was a prospective population-based cohort study in Singapore comprising participants from the three major Asian ethnic groups: Chinese, Malays and Indians, with baseline examination in 2004–2011. Participants with type 1 diabetes and those with cardiovascular disease at baseline were excluded. Type 2 diabetes, Hemoglobin A1c (HbA1c) levels and presence of microvascular complications (diabetic retinopathy and nephropathy) were defined at baseline. The primary outcome was all-cause mortality and major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular mortality, myocardial infarction, stroke and revascularization, collected using a national registry.Results A total of 8541 subjects were included, of which 1890 had type 2 diabetes at baseline. Subjects were followed for a median of 6.4 (IQR 4.8–8.8) years. Diabetes was a significant predictor of mortality (adjusted HR 1.74, 95% CI 1.45 to 2.08, p

With the global spread of abdominal obesity, cardiovascular disease continues to spread to all countries of the world. Given the large population, the challenges presented by cardiometabolic risk in the Asia Pacific region are considerable. In addition to the clinical consequences of cardiovascular disease, in terms of its morbidity and mortality, the diversity of the Asia Pacific region brings heterogeneity in approaches to prevention, diagnosis and treatment of cardiometabolic risk. In this manuscript, we will review the current state of knowledge of cardiometabolic risk in Asia Pacific and highlight the needs moving forward to tackle this public health challenge.

Information technology applications for patient-collection of family health history (FHH) increase identification of elevated-risk individuals compared to usual care. It is unknown if the method of collection impacts data collected or if simply going directly to the patient is what makes the difference. The objective of this study was to examine differences in data detail and risk identification rates between FHH collection directly from individuals using paper-based forms and an interactive web-based platform. This is a non-randomized epidemiologic study in Singaporean population from 2016 to 2018. Intervention was paper-based versus web-based interactive platform for FHH collection. Participant demographics, FHH detail, and risk assessment results were analyzed. 882 participants enrolled in the study, 481 in the paper-based group and 401 in the web-based group with mean (SD) age of 45.4 (12.98) years and 47.5% male. Web-based FHH collection participants had an increased number of conditions per relative (p-value

The receptiveness of patients towards involving medical trainees in their care is essential to clinical education. Data on patients’ attitude towards trainees and reasons for their attitude is currently lacking. Hence the aim was to explore the attitudes and factors influencing the attitudes of patients towards trainees at a tertiary centre for cardiovascular care. A cross-sectional survey was performed among consecutive patients from the cardiac clinics at our tertiary institution in 2014. Of the 723 patients included, nearly all (97.9%) believe that senior doctors make the final decision for their care, and the majority (94.1%) are willing to interact with trainees under supervision of senior doctors. However, less than 60% of patients have actually allowed trainees to participate in their care most or all of the time, with the most important reason for this being fear that care would be compromised ( n = 172). Top reasons why trainees were allowed include belief that it is important for trainees to get experience ( n = 538), that trainees obtained permission politely ( n = 360) and that trainees were professional ( n = 284). Multivariate analysis revealed that better education (odds ratio (OR) 2.055, 95% confidence interval (CI) 1.393–3.033, p < 0.01), male gender (OR 1.556, 95% CI 1.058–2.338, p = 0.03) and less worry about cost of treatment (OR 1.605, 95% CI 1.058–2.433, p = 0.03) increased receptiveness towards trainees. The study demonstrated largely positive attitudes towards trainees being involved in one’s care. The trainee’s politeness and professionalism, as well as the patient’s perceived importance of trainee education, were important in determining such receptiveness.

Introduction: In 2022, the Minister for Health of Singapore launched Healthier SG, a national strategy in championing the shift towards a population health approach. Method: The Singapore Heart Foundation conducted a series of roundtable discussions, also attended by representatives of the Singapore Cardiac Society and the Chapter of Cardiologists of the Academy of Medicine Singapore. During the meetings, the authors formulated interventions supportive of Healthier SG that specifically aimed to uplift the state of cardiovascular (CV) preventive care in Singapore. Results: In line with Healthier SG, the authors propose a 3-pronged approach ("Healthier Heart SG") to augment the success of Healthier SG in achieving good CV outcomes. This proposal includes the following components: (1) a call to update the standards of care in addressing the 5 main modifiable risk factors of cardiovascular disease (CVD); (2) patient education through cooperation between healthcare professionals and community partners for a whole-of-system approach; and (3) support for integrated care, including access to cardiac rehabilitation in the community, improved referral processes and access to nutrition/dietetics counselling and tobacco cessation, optimal use of information technology, and continued CV research. Conclusion: Healthier Heart SG would bring the standards of care and CV care delivery in Singapore closer to achieving the vision of proactive prevention of CVD and CV morbidity and mortality. This can only be achieved through the concerted efforts of healthcare professionals, policymakers and community partners, coupled with the cooperation of community members. [ABSTRACT FROM AUTHOR]

Erectile dysfunction is commonly faced by men with cardiovascular disease. We aimed to determine the prevalence of erectile dysfunction in patients with cardiovascular disease risk factors in Singapore. We conducted a cross-sectional survey on patients with cardiovascular disease risk factors from June 2014 to July 2014 at the outpatient cardiology clinics of our tertiary institution. The survey included patient demographics, comorbidities and an abridged version of the International Index of Erectile Function (IIEF-5). Erectile dysfunction severity was categorized as absent (IIEF-5 score: 22–25), mild (IIEF-5 score: 17–21), moderate (IIEF-5 score: 8–16) and severe (IIEF-5 score:

BackgroundST‐elevation acute myocardial infarction (STEMI) represents one of the leading causes of death. The time of STEMI onset has a circadian rhythm with a peak during diurnal hours, and the occurrence of STEMI follows a seasonal pattern with a salient peak of cases in the winter months and a marked reduction of cases in the summer months. Scholars investigated the reason behind the winter peak, suggesting that environmental and climatic factors concur in STEMI pathogenesis, but no studies have investigated whether the circadian rhythm is modified with the seasonal pattern, in particular during the summer reduction in STEMI occurrence. Methods and ResultsHere, we provide a multiethnic and multination epidemiological study (from both hemispheres at different latitudes, n=2270 cases) that investigates whether the circadian variation of STEMI onset is altered in the summer season. The main finding is that the difference between numbers of diurnal (6:00 to 18:00) and nocturnal (18:00 to 6:00) STEMI is markedly decreased in the summer season, and this is a prodrome of a complex mechanism according to which the circadian rhythm of STEMI time onset seems season dependent. ConclusionsThe “summer shift” of STEMI to the nocturnal interval is consistent across different populations, and the sunshine duration (a measure related to cloudiness and solar irradiance) underpins this season‐dependent circadian perturbation. Vitamin D, which in our results seems correlated with this summer shift, is also primarily regulated by the sunshine duration, and future studies should investigate their joint role in the mechanisms of STEMI etiogenesis.

The use of consumer-grade wearables for purposes beyond fitness tracking has not been comprehensively explored. We generated and analyzed multidimensional data from 233 normal volunteers, integrating wearable data, lifestyle questionnaires, cardiac imaging, sphingolipid profiling, and multiple clinical-grade cardiovascular and metabolic disease markers. We show that subjects can be stratified into distinct clusters based on daily activity patterns and that these clusters are marked by distinct demographic and behavioral patterns. While resting heart rates (RHRs) performed better than step counts in being associated with cardiovascular and metabolic disease markers, step counts identified relationships between physical activity and cardiac remodeling, suggesting that wearable data may play a role in reducing overdiagnosis of cardiac hypertrophy or dilatation in active individuals. Wearable-derived activity levels can be used to identify known and novel activity-modulated sphingolipids that are in turn associated with insulin sensitivity. Our findings demonstrate the potential for wearables in biomedical research and personalized health.

The growth in percutaneous transluminal devices has enabled operators to tackle more complex, native, and post-bypass surgery anatomy. However, complications such as coronary artery dissection, coronary perforation, retrograde aortic dissection, arrhythmias, and acute coronary syndrome still occur with resulting mortality rates of up to 4.2% in complex interventions. Perforation of the circumflex artery is of particular interest in view of its position and relation to the surrounding cardiac structures. This is a site of potential fluid collection, and as the left atrium is fixed to the parietal pericardium at the entry of the pulmonary veins, fluid in the oblique sinus can accumulate enough pressure to compress the left atrium and the coronary sinus. We present a case of left circumflex artery perforation which demonstrates the physiologic complications of coronary sinus and left atrial compression and the resultant functional mitral stenosis.

BackgroundWe examined the influence of sex, ethnicity, and time on competing cardiovascular and noncardiovascular causes of death following acute myocardial infarction in a multiethnic Asian cohort. Methods and ResultsFor 12 years, we followed a prospective nationwide cohort of 15 151 patients (aged 22–101 years, median age 63 years; 72.3% male; 66.7% Chinese, 19.8% Malay, 13.5% Indian) who were hospitalized for acute myocardial infarction between 2000 and 2005. There were 6463 deaths (4534 cardiovascular, 1929 noncardiovascular). Compared with men, women had a higher risk of cardiovascular death (age‐adjusted hazard ratio [HR] 1.3, 95% CI 1.2–1.4) but a similar risk of noncardiovascular death (HR 0.9, 95% CI 0.8–1.0). Sex differences in cardiovascular death varied by ethnicity, age, and time. Compared with Chinese women, Malay women had the greatest increased hazard of cardiovascular death (HR 1.4, 95% CI 1.2–1.6) and a marked imbalance in death due to heart failure or cardiomyopathy (HR 3.4 [95% CI 1.9–6.0] versus HR 1.5 [95% CI 0.6–3.6] for Indian women). Compared with same‐age Malay men, Malay women aged 22 to 49 years had a 2.5‐fold (95% CI 1.6–3.8) increased hazard of cardiovascular death. Sex disparities in cardiovascular death tapered over time, least among Chinese patients and most among Indian patients; the HR comparing cardiovascular death of Indian women and men decreased from 1.9 (95% CI 1.5–2.4) at 30 days to 0.9 (95% CI 0.5–1.6) at 10 years. ConclusionAge, ethnicity, and time strongly influence the association between sex and specific cardiovascular causes of mortality, suggesting that health care policy to reduce sex disparities in acute myocardial infarction outcomes must consider the complex interplay of these 3 major modifying factors.

Invasive fractional flow reserve (FFR) is the gold standard to assess the functional coronary stenosis. The non-invasive assessment of diameter stenosis (DS) using coronary computed tomography angiography (CTA) has high false positive rate in contrast to FFR. Combining CTA with computational fluid dynamics (CFD), recent studies have shown promising predictions of FFRCT for superior assessment of lesion severity over CTA alone. The CFD models tend to be computationally expensive, however, and require several hours for completing analysis. Here, we introduce simplified models to predict noninvasive FFR at substantially less computational time. In this retrospective pilot study, 21 patients received coronary CTA. Subsequently a total of 32 vessels underwent invasive FFR measurement. For each vessel, FFR based on steady-state and analytical models (FFRSS and FFRAM, respectively) were calculated non-invasively based on CTA and compared with FFR. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value were 90.6% (87.5%), 80.0% (80.0%), 95.5% (90.9%), 88.9% (80.0%) and 91.3% (90.9%) respectively for FFRSS (and FFRAM) on a per-vessel basis, and were 75.0%, 50.0%, 86.4%, 62.5% and 79.2% respectively for DS. The area under the receiver operating characteristic curve (AUC) was 0.963, 0.954 and 0.741 for FFRSS, FFRAM and DS respectively, on a per-patient level. The results suggest that the CTA-derived FFRSS performed well in contrast to invasive FFR and they had better diagnostic performance than DS from CTA in the identification of functionally significant lesions. In contrast to FFRCT, FFRSS requires much less computational time.