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.

Adverse cardiovascular and metabolic perturbations among older women: 'fat-craving' hearts.

BACKGROUND: Despite known sex-based differences in cardiovascular aging, differences in aging biology are poorly understood. We hypothesize that circulating metabolites studied cross-sectionally with cardiac aging may be associated with cardiovascular changes that distinguish cardiac aging in women. METHODS: A population-based cohort of community men and women without cardiovascular disease from Singapore underwent detailed clinical and echocardiography examinations. Cross-sectional associations between cardiac functional characteristics and metabolomics profiles were examined. RESULTS: Five hundred sixty-seven adults (48.9% women) participated. Women were younger (72 ± 4.4 years vs 73 ± 4.3 years, p = 0.022), had lower diastolic blood pressures (71 ± 11.0 mmHg vs 76 ± 11.2 mmHg, p < 0.0001, and less likely to have diabetes mellitus (18.0% vs 27.6%, p = 0.013) and smoking (3.8% vs 34.5%, p < 0.001). Body mass indices were similar (24 ± 3.8 kg/m2 vs 24 ± 3.4 kg/m2, p = 0.29), but women had smaller waist circumferences (81 ± 10.1 cm vs 85 ± 9.2 cm, p < 0.001). Women had a significantly higher E/e' ratios (10.9 ± 3.4 vs 9.9 ± 3.3, p = 0.007) and mitral A peak (0.86 ± 0.2 m/s vs 0.79 ± 0.2 m/s, p < 0.001) than men. Among women, lower E/e' ratio was associated with higher levels of C16 (OR 1.019, 95%CI 1.002-1.036, p = 0.029), C16:1 (OR 1.06, 95%CI 1.006-1.118, p = 0.028), serine (OR 1.019, 95%CI 1.002-1.036, p = 0.025), and histidine (OR 1.045, 95%CI 1.013-1.078, p = 0.006). Lower mitral A peak was associated with higher levels of histidine (OR 1.039, 95%CI 1.009-1.070, p = 0.011), isoleucine (OR 1.013, 95%CI 1.004-1.021, p = 0.004), and C20 (OR 1.341, 95%CI 1.067-1.684, p = 0.012). CONCLUSION: Impairments in diastolic functions were more frequent among older women compared to men, despite lower prevalence of vascular risk factors and preserved cardiac structure. Cardiac aging in women correlated with metabolites involved in fatty acid oxidation and tricyclic acid cycle fuelling.

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.

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.

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.

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.