Effects of short-term moderate intensity exercise on the serum metabolome in older adults: a pilot randomized controlled trial.

BACKGROUND: We previously reported changes in the serum metabolome associated with impaired myocardial relaxation in an asymptomatic older community cohort. In this prospective parallel-group randomized control pilot trial, we subjected community adults without cardiovascular disease to exercise intervention and evaluated the effects on serum metabolomics. METHODS: Between February 2019 to November 2019, thirty (83% females) middle-aged adults (53 ± 4 years) were randomized with sex stratification to either twelve weeks of moderate-intensity exercise training (Intervention) (n = 15) or Control (n = 15). The Intervention group underwent once-weekly aerobic and strength training sessions for 60 min each in a dedicated cardiac exercise laboratory for twelve weeks (ClinicalTrials.gov: NCT03617653). Serial measurements were taken pre- and post-intervention, including serum sampling for metabolomic analyses. RESULTS: Twenty-nine adults completed the study (Intervention n = 14; Control n = 15). Long-chain acylcarnitine C20:2-OH/C18:2-DC was reduced in the Intervention group by a magnitude of 0.714 but increased in the Control group by a magnitude of 1.742 (mean difference -1.028 age-adjusted p = 0.004). Among Controls, alanine correlated with left ventricular mass index (r = 0.529, age-adjusted p = 0.018) while aspartate correlated with Lateral e' (r = -764, age-adjusted p = 0.016). C20:3 correlated with E/e' ratio fold-change in the Intervention group (r = -0.653, age-adjusted p = 0.004). Among Controls, C20:2/C18:2 (r = 0.795, age-adjusted p = 0.005) and C20:2-OH/C18:2-DC fold-change (r = 0.742, age-adjusted p = 0.030) correlated with change in E/A ratio. CONCLUSIONS: Corresponding relationships between serum metabolites and cardiac function in response to exercise intervention provided pilot observations. Future investigations into cellular fuel oxidation or central carbon metabolism pathways that jointly impact the heart and related metabolic systems may be critical in preventive trials.

Prior studies have found changes in cellular biological processes in both cardiac aging and heart failure suggesting a common underlying mechanism. I has also been shown that exercise in healthy participants can reverse the signs of early cardiac aging. In this experimental study, we examined the effects of exercise on biological markers and cardiac function among healthy community older adults. After twelve weeks of exercise, there were changes in biological components associated with cardiac function. These findings highlight the potential of exercise as a strategy to target biological alterations in early cardiac aging and potentially prevent it.

Comparing the pooled cohort equations and coronary artery calcium scores in a symptomatic mixed Asian cohort.

Background: The value of pooled cohort equations (PCE) as a predictor of major adverse cardiovascular events (MACE) is poorly established among symptomatic patients. Coronary artery calcium (CAC) assessment further improves risk prediction, but non-Western studies are lacking. This study aims to compare PCE and CAC scores within a symptomatic mixed Asian cohort, and to evaluate the incremental value of CAC in predicting MACE, as well as in subgroups based on statin use. Methods: Consecutive patients with stable chest pain who underwent cardiac computed tomography were recruited. Logistic regression was performed to determine the association between risk factors and MACE. Cohort and statin-use subgroup comparisons were done for PCE against Agatston score in predicting MACE. Results: Of 501 patients included, mean (SD) age was 53.7 (10.8) years, mean follow-up period was 4.64 (0.66) years, 43.5% were female, 48.3% used statins, and 50.0% had no CAC. MI occurred in 8 subjects while 9 subjects underwent revascularization. In the general cohort, age, presence of CAC, and ln(Volume) (OR = 1.05, 7.95, and 1.44, respectively) as well as age and PCE score for the CAC = 0 subgroup (OR = 1.16 and 2.24, respectively), were significantly associated with MACE. None of the risk factors were significantly associated with MACE in the CAC > 0 subgroup. Overall, the PCE, Agatston, and their combination obtained an area under the receiver operating characteristic curve (AUC) of 0.501, 0.662, and 0.661, respectively. Separately, the AUC of PCE, Agatston, and their combination for statin non-users were 0.679, 0.753, and 0.734, while that for statin-users were 0.585, 0.615, and 0.631, respectively. Only the performance of PCE alone was statistically significant (p = 0.025) when compared between statin-users (0.507) and non-users (0.783). Conclusion: In a symptomatic mixed Asian cohort, age, presence of CAC, and ln(Volume) were independently associated with MACE for the overall subgroup, age and PCE score for the CAC = 0 subgroup, and no risk factor for the CAC > 0 subgroup. Whilst the PCE performance deteriorated in statin versus non-statin users, the Agatston score performed consistently in both groups.

Coronary CT Angiography-based Morphologic Index for Predicting Hemodynamically Significant Coronary Stenosis.

Purpose To develop a new coronary CT angiography (CCTA)-based index, α×LL/MLD4, that considers lesion entrance angle (α) in addition to lesion length (LL) and minimal lumen diameter (MLD) and to evaluate its efficacy in predicting hemodynamically significant coronary stenosis compared with invasive coronary angiography (ICA)-derived fractional flow reserve (FFR). Materials and Methods This prospective study enrolled participants (September 2016-March 2020) from two centers who underwent CCTA followed by ICA (ClinicalTrials.gov identifier: NCT03054324). CCTA images were processed semiautomatically to measure LL, MLD, and α for calculating α×LL/MLD4. Diagnostic performance and accuracy of α×LL/MLD4 and LL/MLD4 in detecting hemodynamically significant coronary stenosis were compared against the reference standard (invasive FFR ≤ 0.80). Results In total, 133 participants (mean age, 63 years ± 9 [SD]; 99 [74%] men) with 210 stenosed coronary arteries were analyzed. Median α×LL/MLD4 was 54.0 degree/mm3 (IQR, 25.3-128.7) in participants with invasive FFR of 0.80 or less and 6.7 degree/mm3 (IQR, 3.3-12.8) in participants with invasive FFR of more than 0.80 (P < .001). The per-vessel accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for discriminating ischemic lesions were 86.2%, 83.1%, 88.4%, 84.1%, and 87.7% for α×LL/MLD4 and 80.5%, 66.3%, 90.9%, 84.3%, and 78.6% for LL/MLD4, respectively. Area under the receiver operating characteristic curve for discriminating hemodynamically significant stenosis was 0.93 for α×LL/MLD4, which was significantly greater than the values of 0.84 for LL/MLD4 and 0.63 for diameter stenosis (both P < .001). Conclusion The new morphologic index, α×LL/MLD4, incorporating lesion entrance angle achieved higher diagnostic performance in detecting hemodynamically significant lesions compared with diameter stenosis and LL/MLD4. Keywords: CT Angiography, Cardiac, Coronary Arteries, Ischemia, Infarction, Technology Assessment Clinical trial registration no. NCT03054324 Supplemental material is available for this article. © RSNA, 2023 See also the commentary by Fairbairn and Nørgaard in this issue.

Impact of aortic annular size and valve type on haemodynamics and clinical outcomes after transcatheter aortic valve implantation.

INTRODUCTION: Data on patients with small aortic annuli (SAA) undergoing transcatheter aortic valve implantation (TAVI) are limited. We aim to describe the impact of aortic annular size, particularly SAA and TAVI valve type on valve haemodynamics, durability and clinical outcomes. METHOD: All patients in National Heart Centre Singapore who underwent transfemoral TAVI for severe symptomatic native aortic stenosis from July 2012 to December 2019 were included. Outcome measures include valve haemodynamics, prosthesis-patient mismatch (PPM), structural valve degeneration (SVD) and mortality. RESULTS: A total of 244 patients were included. The mean Society of Thoracic Surgeons score was 6.22±6.08, with 52.5% patients with small aortic annulus (<23mm), 33.2% patients with medium aortic annulus (23-26mm) and 14.3% patients with large aortic annulus (>26mm). There were more patients with self-expanding valve (SEV) (65.2%) versus balloon-expandable valve (BEV) (34.8%). There were no significant differences in indexed aortic valve area (iAVA), mean pressure gradient (MPG), PPM, SVD or mortality across all aortic annular sizes. However, specific to the SAA group, patients with SEV had larger iAVA (SEV 1.19±0.35cm2/m2 vs BEV 0.88±0.15cm2/m2, P<0.01) and lower MPG (SEV 9.25±4.88 mmHg vs BEV 14.17±4.75 mmHg, P<0.01) at 1 year, without differences in PPM or mortality. Aortic annular size, TAVI valve type and PPM did not predict overall mortality up to 7 years. There was no significant difference in SVD between aortic annular sizes up to 5 years. CONCLUSION: Valve haemodynamics and durability were similar across the different aortic annular sizes. In the SAA group, SEV had better haemodynamics than BEV at 1 year, but no differences in PPM or mortality. There were no significant differences in mortality between aortic annular sizes, TAVI valve types or PPM.

Prediction of subclinical atherosclerosis in low Framingham risk score individuals by using the metabolic syndrome criteria and insulin sensitivity index.

Background: Subclinical 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. Methods: A 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. Results: Twenty three individuals (23%) had subclinical atherosclerosis with elevated CT Agatston score ≥1. Presence of both insulin resistance (ISI-cal <9.23) and fulfillment of at least one metabolic syndrome criterion denoted high risk, resulting in significantly improved AUC (0.706 95%CI 0.588-0.822) over the Framingham risk score in predicting elevated CT Agatston score ≥1, with net reclassification index of 50.9 ± 23.7%. High-risk patients by the new classification also exhibited significantly increased carotid intima thickness. Conclusions: The overlap of insulin resistance and presence of ≥1 criterion for metabolic syndrome may play an instrumental role in identifying traditionally low-risk individuals predisposed to future risk of atherosclerosis and its sequelae.

Evaluating the Coronary Artery Disease Consortium Model and the Coronary Artery Calcium Score in Predicting Obstructive Coronary Artery Disease in a Symptomatic Mixed Asian Cohort.

Background The utility of a given pretest probability score in predicting obstructive coronary artery disease (CAD) is population dependent. Previous studies investigating the additive value of coronary artery calcium (CAC) on pretest probability scores were predominantly limited to Western populations. This retrospective study seeks to evaluate the CAD Consortium (CAD2) model in a mixed Asian cohort within Singapore with stable chest pain and to evaluate the incremental value of CAC in predicting obstructive CAD. Methods and Results Patients who underwent cardiac computed tomography and had chest pain were included. The CAD2 clinical model comprised of age, sex, symptom typicality, diabetes, hypertension, hyperlipidemia, and smoking status and was compared with the CAD2 extended model that added CAC to assess the incremental value of CAC scoring, as well as to the corresponding locally calibrated local assessment of the heart models. A total of 522 patients were analyzed (mean age 54±11 years, 43.1% female). The CAD2 clinical model obtained an area under the curve of 0.718 (95% CI, 0.668-0.767). The inclusion of CAC score improved the area under the curve to 0.896 (95% CI, 0.867-0.925) in the CAD2 models and from 0.767 (95% CI, 0.721-0.814) to 0.926 (95% CI, 0.900-0.951) in the local assessment of the heart models. The locally calibrated local assessment of the heart models showed better discriminative performance than the corresponding CAD2 models (P<0.05 for all). Conclusions The CAD2 model was validated in a symptomatic mixed Asian cohort and local calibration further improved performance. CAC scoring provided significant incremental value in predicting obstructive CAD.

Patterns of motivators and barriers to heart health behaviors among adults with behavior-modifiable cardiovascular risk factors: A population-based survey in Singapore.

OBJECTIVES: Motivators and barriers are pivotal factors in the adoption of health behaviors. This study aims to identify patterns of the motivators and barriers influencing heart health behaviors among multi-ethnic Asian adults with behavior-modifiable risk factors for heart disease, namely obesity, physical inactivity and smoking. METHODS: A population-based survey of 1,000 participants was conducted in Singapore. Participants were assessed for behavior-modifiable risk factors and asked about motivators and barriers to heart health behaviors. Exploratory and confirmatory factor analyses were conducted to identify factors underlying motivator and barrier question items. Logistic regression was conducted to examine the associations of motivator and barrier factors with sociodemographic characteristics. RESULTS: The twenty-five motivator and barrier items were classified into three (outcome expectations, external cues and significant others including family and friends) and four (external circumstances, limited self-efficacy and competence, lack of perceived susceptibility, benefits and intentions and perceived lack of physical capability) factors respectively. Among participants with behavior-modifiable risk factors, those with lower education were more likely to be low in motivation factor of "outcome expectations" and "external cues". The well-educated were more likely to be high in the barrier factor of "lack of perceived susceptibility, benefits and intention" and were less likely to have the motivation factor of "significant others (family or friends)". Those aged 60-75 years had low motivations and high barriers compared to their younger counterparts. Older age was more likely to be low in motivation factor of "outcome expectations" and "external cues" and high in barrier factor of "limited self-efficacy and competence" and "perceived lack of physical capability". CONCLUSIONS: Findings underscore the importance of a targeted intervention and communication strategy addressing specific motivation and barrier factors in different population segments with modifiable risk factors.

Asian Pacific Society of Cardiology Consensus Recommendations for Pre-participation Screening in Young Competitive Athletes.

Sports-related sudden cardiac death is a rare but devastating consequence of sports participation. Certain pathologies underlying sports-related sudden cardiac death could have been picked up pre-participation and the affected athletes advised on appropriate preventive measures and/or suitability for training or competition. However, mass screening efforts - especially in healthy young populations - are fraught with challenges, most notably the need to balance scarce medical resources and sustainability of such screening programmes, in healthcare systems that are already stretched. Given the rising trend of young sports participants across the Asia-Pacific region, the working group of the Asian Pacific Society of Cardiology (APSC) developed a sports classification system that incorporates dynamic and static components of various sports, with deliberate integration of sports events unique to the Asia-Pacific region. The APSC expert panel reviewed and appraised using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed, which were then put to an online vote. Consensus was reached when 80% of votes for a recommendation were agree or neutral. The resulting statements described here provide guidance on the need for cardiovascular pre-participation screening for young competitive athletes based on the intensity of sports they engage in.

Diagnostic Performance of Fractional Flow Reserve From CT Coronary Angiography With Analytical Method.

The aim of this study was to evaluate a new analytical method for calculating non-invasive fractional flow reserve (FFRAM) to diagnose ischemic coronary lesions. Patients with suspected or known coronary artery disease (CAD) who underwent computed tomography coronary angiography (CTCA) and invasive coronary angiography (ICA) with FFR measurements from two sites were prospectively recruited. Obstructive CAD was defined as diameter stenosis (DS) ≥50% on CTCA or ICA. FFRAM was derived from CTCA images and anatomical features using analytical method and was compared with computational fluid dynamics (CFD)-based FFR (FFRB) and invasive ICA-based FFR. FFRAM, FFRB, and invasive FFR ≤ 0.80 defined ischemia. A total of 108 participants (mean age 60, range: 30-83 years, 75% men) with 169 stenosed coronary arteries were analyzed. The per-vessel accuracy, sensitivity, specificity, and positive predictive and negative predictive values were, respectively, 81, 75, 86, 81, and 82% for FFRAM and 87, 88, 86, 83, and 90% for FFRB. The area under the receiver operating characteristics curve for FFRAM (0.89 and 0.87) and FFRB (0.90 and 0.86) were higher than both CTCA- and ICA-derived DS (all p < 0.0001) on per-vessel and per-patient bases for discriminating ischemic lesions. The computational time for FFRAM was much shorter than FFRB (2.2 ± 0.9 min vs. 48 ± 36 min, excluding image acquisition and segmentation). FFRAM calculated from a novel and expeditious non-CFD approach possesses a comparable diagnostic performance to CFD-derived FFRB, with a significantly shorter computational time.

Computed Tomography Coronary Angiography and Computational Fluid Dynamics Based Fractional Flow Reserve Before and After Percutaneous Coronary Intervention.

Invasive fractional flow reserve (FFR) is recommended to guide stent deployment. We previously introduced a non-invasive FFR calculation (FFRB) based on computed tomography coronary angiography (CTCA) with reduced-order computational fluid dynamics (CFD) and resistance boundary conditions. Current study aimed to assess the feasibility and accuracy of FFRB for predicting coronary hemodynamics before and after stenting, with invasive FFR as the reference. Twenty-five patients who had undergone CTCA were prospectively enrolled before invasive coronary angiography (ICA) and FFR-guided percutaneous coronary intervention (PCI) on 30 coronary vessels. Using reduced-order CFD with novel boundary conditions on three-dimensional (3D) patient-specific anatomic models reconstructed from CTCA, we calculated FFRB before and after virtual stenting. The latter simulated PCI by clipping stenotic segments from the 3D coronary models and replacing them with segments to mimic the deployed coronary stents. Pre- and post-virtual stenting FFRB were compared with FFR measured pre- and post-PCI by investigators blinded to FFRB results. Among 30 coronary lesions, pre-stenting FFRB (mean 0.69 ± 0.12) and FFR (mean 0.67 ± 0.13) exhibited good correlation (r = 0.86, p < 0.001) and agreement [mean difference 0.024, 95% limits of agreement (LoA): -0.11, 0.15]. Similarly, post-stenting FFRB (mean 0.84 ± 0.10) and FFR (mean 0.86 ± 0.08) exhibited fair correlation (r = 0.50, p < 0.001) and good agreement (mean difference 0.024, 95% LoA: -0.20, 0.16). The accuracy of FFRB for identifying post-stenting ischemic lesions (FFR ≤ 0.8) (residual ischemia) was 87% (sensitivity 80%, specificity 88%). Our novel FFRB, based on CTCA with reduced-order CFD and resistance boundary conditions, accurately predicts the hemodynamic effects of stenting which may serve as a tool in PCI planning.

Public perceptions and knowledge of cholesterol management in a multi-ethnic Asian population: A population-based survey.

INTRODUCTION: Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Hyperlipidemia is one of the important modifiable risk factors for CVDs. Raising public awareness of CVD risks is an important step in reducing CVD burdens. In this study, we aimed to assess public awareness and knowledge of cholesterol and its management in a multiethnic Asian population. METHODS: We recruited 1000 participants from three major ethnic groups for this nationwide population-based survey. A structured questionnaire was used to collect socio-demographics, knowledge of cholesterol and cholesterol-lowering medications. Univariate and multivariate analyses were conducted to identify factors associated with good knowledge on cholesterol and its management. RESULTS: Of the participants, 65% thought that high cholesterol produces symptoms and that lifestyle modification would be as effective as medication at lowering cholesterol. Nearly 70% believed that long term statin could lead to kidney or liver damage, and 56% thought that statin was associated with higher risk of cancer. A third saw herbal medicine or supplements as healthier and safer. About 45% believed that statin therapy should not be taken long term and that one could stop taking cholesterol medication when cholesterol is under control. Malays were more likely to have poor knowledge (adjusted OR 0.68; 95% CI 0.47-0.98; P = 0.039) compared to Chinese. Participants with intermediate education were more likely to have good knowledge of cholesterol and its management (adjusted OR 1.67; 95% CI 1.11-2.51; P = 0.013) compared to those with primary education. CONCLUSION: Public knowledge and awareness of high cholesterol and its management remains poor in Asian multi-ethnic population. Understanding gaps in public knowledge can inform the implementation of health promotion programs to effectively raise awareness of cholesterol and its management.

Prognostic value of noninvasive combined anatomic/functional assessment by cardiac CT in patients with suspected coronary artery disease - Comparison with invasive coronary angiography and nuclear myocardial perfusion imaging for the five-year-follow up of the CORE320 multicenter study.

BACKGROUND: Few data exist on long-term outcome in patients undergoing combined coronary CT angiography (CTA) and myocardial CT perfusion imaging (CTP) as well as invasive coronary angiography (ICA) and single photon emission tomography (SPECT). METHODS: At 16 centers, 381 patients were followed for major adverse cardiac events (MACE) for the CORE320 study. All patients underwent coronary CTA, CTP, and SPECT before ICA within 60 days. Prognostic performance according binary results (normal/abnormal) was assessed by 5-year major cardiovascular events (MACE) free survival and area under the receiver-operating-characteristic curve (AUC). RESULTS: Follow up beyond 2-years was available in 323 patients. MACE-free survival rate was greater among patients with normal combined CTA-CTP findings compared to ICA-SPECT: 85 vs. 80% (95% confidence interval [CI] for difference 0.1, 11.3) though event-free survival time was similar (4.54 vs. 4.37 years, 95% CI for difference: -0.03, 0.36). Abnormal results by combined CTA-CTP was associated with 3.83 years event-free survival vs. 3.66 years after abnormal combined ICA-SPECT (95% CI for difference: -0.05, 0.39). Predicting MACE by AUC also was similar: 65 vs. 65 (difference 0.1; 95% CI -4.6, 4.9). When MACE was restricted to cardiovascular death, myocardial infarction, or stroke, AUC for CTA-CTP was 71 vs. 60 by ICA-SPECT (difference 11.2; 95% CI -1.0, 19.7). CONCLUSIONS: Combined CTA-CTP evaluation yields at least equal 5-year prognostic information as combined ICA-SPECT assessment in patients presenting with suspected coronary artery disease. Noninvasive cardiac CT assessment may eliminate the need for diagnostic cardiac catheterization in many patients. CLINICAL TRIAL REGISTRATION: NCT00934037.

End-to-End, Pixel-Wise Vessel-Specific Coronary and Aortic Calcium Detection and Scoring Using Deep Learning.

Conventional scoring and identification methods for coronary artery calcium (CAC) and aortic calcium (AC) result in information loss from the original image and can be time-consuming. In this study, we sought to demonstrate an end-to-end deep learning model as an alternative to the conventional methods. Scans of 377 patients with no history of coronary artery disease (CAD) were obtained and annotated. A deep learning model was trained, tested and validated in a 60:20:20 split. Within the cohort, mean age was 64.2 ± 9.8 years, and 33% were female. Left anterior descending, right coronary artery, left circumflex, triple vessel, and aortic calcifications were present in 74.87%, 55.82%, 57.41%, 46.03%, and 85.41% of patients respectively. An overall Dice score of 0.952 (interquartile range 0.921, 0.981) was achieved. Stratified by subgroups, there was no difference between male (0.948, interquartile range 0.920, 0.981) and female (0.965, interquartile range 0.933, 0.980) patients (p = 0.350), or, between age <65 (0.950, interquartile range 0.913, 0.981) and age ≥65 (0.957, interquartile range 0.930, 0.9778) (p = 0.742). There was good correlation and agreement for CAC prediction (rho = 0.876, p < 0.001), with a mean difference of 11.2% (p = 0.100). AC correlated well (rho = 0.947, p < 0.001), with a mean difference of 9% (p = 0.070). Automated segmentation took approximately 4 s per patient. Taken together, the deep-end learning model was able to robustly identify vessel-specific CAC and AC with high accuracy, and predict Agatston scores that correlated well with manual annotation, facilitating application into areas of research and clinical importance.

Performance of the coronary calcium score in an outpatient chest pain clinic and strategies for risk stratification.

BACKGROUND: Coronary artery calcium score (CAC) is an objective marker of atherosclerosis. The primary aim is to assess CAC as a risk classifier in stable coronary artery disease (CAD). HYPOTHESIS: CAC improves CAD risk prediction, compared to conventional risk scoring, even in the absence of cardiovascular risk factor inputs. METHODS: Outpatients presenting to a cardiology clinic (n = 3518) were divided into two cohorts: derivation (n = 2344 patients) and validation (n = 1174 patients). Adding logarithmic transformation of CAC, we built two logistic regression models: Model 1 with chest pain history and risk factors and Model 2 including chest pain history only without risk factors simulating patients with undiagnosed comorbidities. The CAD I Consortium Score (CCS) was the conventional reference risk score used. The primary outcome was the presence of coronary artery disease defined as any epicardial artery stenosis≥50% on CT coronary angiogram. RESULTS: Area under curve (AUC) of CCS in our validation cohort was 0.80. The AUC of Models 1 and 2 were significantly improved at 0.88 (95%CI 0.86-0.91) and 0.87 (95%CI 0.84-0.90), respectively. Integrated discriminant improvement was >15% for both models. At a pre-specified cut-off of ≤10% for excluding coronary artery disease, the sensitivity and specificity were 89.3% and 74.7% for Model 1, and 88.1% and 71.8% for Model 2. CONCLUSION: CAC helps improve risk classification in patients with chest pain, even in the absence of prior risk factor screening.

Impact of Age and Sex on Subclinical Coronary Atherosclerosis in a Healthy Asian Population.

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 (P interaction = 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.

Knowledge of Heart Disease, Preventive Behavior and Source of Information in a Multi-ethnic Asian Population: A Population-Based Survey.

Several population-based studies have been conducted to better understand the public knowledge of cardiovascular disease (CVD) and behavior. However, most studies have predominantly focused on Western populations. This study aimed to investigate heart disease knowledge, preventive behavior and source of information on heart disease in a multi-ethnic Asian population. We conducted a nation-wide population-based survey of 1000 participants of three ethnic groups (Chinese, Malay, Indian) in Singapore. A structured questionnaire was used to collect sociodemographics, knowledge on CVD risk factors, symptoms, emergency action, preventive health behaviors and sources of information on heart disease. Univariate and multivariate analyses were conducted to identify factors associated with the CVD knowledge and behavior. Knowledge on CVD risk factors was generally high. Knowledge on emergency actions was low particularly in younger people. More than 60% did not meet the recommended levels of physical activity, and this was more evident for individuals of overweight/obese status, lower education and workforce. Chinese were less likely to be obese/overweight compared to the Malays and Indians. Malays were less likely to seek information from internet and social media compared to their ethnic counterparts. This study highlighted heterogeneity in the levels of knowledge and health behavior across population segments, suggesting the need for a tailored approach to heart health interventions and optimal channels for information dissemination. Our findings will form the basis for contextually and culturally appropriate interventions to combat the growing CVD burden and prevent its toll on a rapidly ageing population.

Treatment to reduce vascular calcification in hemodialysis patients using vitamin K (Trevasc-HDK): A study protocol for a randomized controlled trial.

INTRODUCTION: End stage renal failure patients on hemodialysis have significant vascular calcification This is postulated to be related to sub-clinical vitamin K deficiency, which is prevalent in hemodialysis patients. Vitamin K deficiency result in the failure of the matrix GLA protein (MGP) to undergo carboxylation. MGP is a natural local inhibitor of vascular calcification and the lack of functional carboxylated MGP may contribute to increase vascular calcification. Vitamin K supplement should therefore correct this anomaly and decrease the rate or severity of vascular calcification in this population of patients on long-term maintenance hemodialysis. Our study seeks to evaluate the prevalence and the progression of vascular calcification in a cohort of maintenance hemodialysis patients. It will also evaluate the efficacy of vitamin K supplementation in reducing the progression of vascular calcification in this group of patients. METHODS: This will be a single-center randomized, prospective and open-label interventional clinical trial of end stage renal failure patients on hemodialysis. We aim to recruit 200 patients. Eligible patients will be randomized to either the standard care arm or active treatment arm. Active treatment arm patients will receive standard care plus supplementation with oral vitamin K2 isoform 360 mcg 3 times weekly for a total duration of 18 months. Primary outcome measured will be absolute difference in coronary artery calcification score at 18-month between control and intervention arms. Secondary outcomes will be to compare absolute difference in aortic valve calcification, percentage of patients with regression of coronary artery calcification of at least 10%, absolute difference in aortic and systemic arterial stiffness, mortality from any cause and major adverse cardiovascular over the same period. DISCUSSION: Evidence of successful regression or retardation of vascular calcification will support the conduct of larger and longer-term trials aimed at reducing cardiovascular disease mortality and major adverse cardiovascular events in this high-risk population using a safe and inexpensive strategy TRIAL REGISTRATION:: ClinicalTrials.gov NCT02870829. Registered on 17 August 2016 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02870829National University Hospital's Institutional Review Board (2015/01000).

Quantification of effects of mean blood pressure and left ventricular mass on noninvasive fast fractional flow reserve.

Proper inlet boundary conditions are essential for accurate computational fluid dynamics (CFD) modeling. We developed methodology to derive noninvasive FFRB using CFD and computed tomography coronary angiography (CTCA) images. This study aims to assess the influence of brachial mean blood pressure (MBP) and total coronary inflow on FFRB computation. Twenty-two patients underwent both CTCA and FFR measurements. Total coronary flow was computed from left ventricular mass (LVM) measured from CTCA. A total of 286 CFD simulations were run by varying MBP and LVM at 70, 80, 90, 100, 110, 120, and 130% of the measured values. FFRB increased with incrementally higher input values of MBP: 0.78 ± 0.12, 0.80 ± 0.11, 0.82 ± 0.10, 0.84 ± 0.09, 0.85 ± 0.08, 0.86 ± 0.08, and 0.87 ± 0.07, respectively. Conversely, FFRB decreased with incrementally higher inputs value of LVM: 0.86 ± 0.08, 0.85 ± 0.08, 0.84 ± 0.09, 0.84 ± 0.09, 0.83 ± 0.10, 0.83 ± 0.10, and 0.82 ± 0.10, respectively. Noninvasive FFRB calculated using measured MBP and LVM on a total of 30 vessels was 0.84 ± 0.09 and correlated well with invasive FFR (0.83 ± 0.09) (r = 0.92, P < 0.001). Positive association was observed between FFRB and MBP input values (mmHg) and negative association between FFRB and LVM values (g). Respective slopes were 0.0016 and -0.005, respectively, suggesting potential application of FFRB in a clinical setting. Inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions.NEW & NOTEWORTHY While brachial mean blood pressure (MBP) and left ventricular mass (LVM) measured from CTCA are the two CFD simulation input parameters, their effects on noninvasive fractional flow reserve (FFRB) have not been systematically investigated. We demonstrate that inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions. This is important in the clinical application of noninvasive FFR in coronary artery disease diagnosis.

Adding Coronary Calcium Score to Exercise Treadmill Test: An Alternative to Refine Coronary Artery Disease Risk Stratification in Patients with Intermediate Risk Chest Pain.

Introduction: Chest pain is a common symptom for cardiology referrals. The ACC-AHA guidelines recommend exercise stress electrocardiography (TMX) as the initial diagnostic test. However, the TMX only has moderate sensitivity and non-diagnostic cases may require further stress imaging studies. In this study we aimed to look at the feasibility of combining coronary artery calcium (CAC) score with TMX to refine risk stratification. This may be an alternative to stress imaging in cases of non low-risk TMX, with the added advantage of short time turnaround time and low radiation dose. Methods: A total of 145 patients who presented consecutively to the National Heart Centre Singapore with chest pain were included in this study. These were intermediate risk patients with an average Duke Clinical Score of 38.8%. All patients underwent both TMX and computed tomography scan of the coronary arteries (CTCA) which also includes CAC. The primary outcome was defined as obstructive coronary artery disease i.e. >50% left main artery stenosis and/or >70% stenosis in other epicardial arteries. Results: The combination of TMX and CAC was comparable to stress imaging in detecting obstructive coronary artery disease. When added to TMX, CAC has an integrated discriminative improvement of 74.1%, achieved an area under the curve of 0.974 and adjusted R2 of 0.670 in detecting the primary outcome. Conclusion: The strategy of combining TMX and CAC is feasible in clinical practice to refine risk stratification in outpatients with intermediate risk chest pain. The calcium score readout also further guides therapy for primary prevention. Highlights: Treadmill exercise is one of the first line tests for cardiac chest pain work up.Non diagnostic test treadmill results requires further adjunctive tests.Downstream stress imaging causes delay in time to diagnosis.Coronary artery calcium scoring needs minimal preparation with fast turnaround time.Addition of coronary artery calcium to treadmill performs comparably to stress imaging.This is a feasible alternative to risk stratify non diagnostic treadmill tests and guide therapy for primary prevention.

Harnessing technology and molecular analysis to understand the development of cardiovascular diseases in Asia: a prospective cohort study (SingHEART).

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.