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Objectives: Gait speed indicates the individual’s functional status and predicts overall health. This study aims to determine (1) the intra- and inter-rater and test–retest reliability of the dynamic 4 m gait speed test protocol; (2) establish the normative reference values of habitual and fast gait speeds in community-dwelling healthy Singaporean adults aged 21 to 80; and (3) explore the association of age, gender, height, weight, and body mass index (BMI) on gait speed. Methods: This prospective cross-sectional study recruited healthy ambulatory community-dwelling Singaporeans aged 21 to 80 who could ambulate independently without aid. Participants were excluded if they required walking aids; were pregnant; or had physical, medical, or cognitive conditions that may affect gait. Each participant completed at least two habitual and fast gait speed test trials via a 4 m walkway with a dynamic start. The data were analysed by descriptive statistics, the Mann–Whitney test, the Spearman coefficient, and the interclass correlation coefficient (ICC). Results: In total, 178 males and 201 females were included in the data analysis. The median age was 45.0 years [interquartile range (IQR) 26.2–59.0], and the median height was 1.64 metres (m) (IQR 1.58–1.70). The median habitual gait speed was 1.08 metre/second (m/s) (IQR 0.97–1.22), and the fast gait speed was 1.55 m/s (IQR 1.40–1.70). The ICC for reliability ranged from 0.84 to 0.99, indicating that the 4 m gait speed test had good-to-excellent reliability. Conclusions: Gait speeds were not influenced by gender but declined with age advancement. Age and height and age and BMI were weakly correlated to habitual and fast gait speed, respectively. We established the norm values for the 4 m gait speeds in Singapore and proved it to be a reliable gait speed assessment ready for immediate community applications.

Abstract Biobanking in health care has evolved over the last few decades from simple biological sample repositories to complex and dynamic units with multi‐organizational infrastructure networks and has become an essential tool for modern medical research. Cardiovascular tissue biobanking provides a unique opportunity to utilize cardiac and vascular samples for translational research into heart failure and other related pathologies. Current techniques for diagnosis, classification, and treatment monitoring of cardiac disease relies primarily on interpretation of clinical signs, imaging, and blood biomarkers. Further research at the disease source (i.e. myocardium and blood vessels) has been limited by a relative lack of access to quality human cardiac tissue and the inherent shortcomings of most animal models of heart disease. In this review, we describe a model for cardiovascular tissue biobanking and databasing, and its potential to facilitate basic and translational research. We share techniques to procure endocardial samples from patients with hypertrophic cardiomyopathy, heart failure with reduced ejection fraction, and heart failure with preserved ejection fraction, in addition to aortic disease samples. We discuss some of the issues with respect to data collection, privacy, biobank consent, and the governance of tissue biobanking. The development of tissue biobanks as described here has significant scope to improve and facilitate translational research in multi‐omic fields such as genomics, transcriptomics, proteomics, and metabolomics. This research heralds an era of precision medicine, in which patients with cardiovascular pathology can be provided with optimized and personalized medical care for the treatment of their individual phenotype.

Heritable aortic aneurysm is an increasingly recognized cause of morbidity and mortality. Whilst Marfan syndrome (MFS) is well-known, the clinical presentation and prognosis of more newly described genetic syndromes is less familiar to clinicians. There is a particular lack of knowledge regarding clinical outcomes for non-syndromal heritable aortic disease. This study investigated the presentation, clinical course and survival of patients with syndromal [Loeys-Dietz, aneurysm-osteoarthritis, and aneurysm-cerebral arteriopathy (ACTA2) syndrome] and non-syndromal heritable aortic disease in comparison to MFS. The study group includes 536 individuals (283 Marfan, 176 non-syndromal heritable aortopathy, 36 aneurysm-osteoarthritis, 32 Loeys-Dietz, and 9 ACTA2 aneurysm) enrolled in a longitudinal clinical follow-up between 1990 and 2022. Age at diagnosis differed between groups: Marfan = 22.0 ± 16.6; Loeys-Dietz = 29.6 ± 21.5; aneurysm-osteoarthritis = 36.4 ± 18.8; ACTA2 aneurysm = 43.4 ± 18.6; non-syndromal heritable aortopathy = 47.2 ± 16.6 years (p < 0.001). Aortic dissection was the presenting event in 8% individuals with Marfan compared to 27% with non-syndromal heritable aortopathy and 34% with Loeys-Dietz syndrome (p < 0.01). Mean follow-up duration for the group was 16.4 years (range 0.2–30 years) and 74 individuals died during follow-up (Marfan = 52, Loeys-Dietz = 6, aneurysm-osteoarthritis = 4, ACTA2 aneurysm = 1, heritable non-syndromal aortopathy = 11). At 10 years follow-up, actuarial mean survivals were: aneurysm-osteoarthritis = 77.5 ± 10.4%; Loeys-Dietz = 90.0 ± 6.8%; Marfan = 94.6 ± 1.4%; heritable non-syndromal aortopathy = 95.9 ± 2.1% (NS). There were 60 aortic dissections (24 Type A, 36 Type B) during follow-up. At 10 years, survival free of dissection was comparable between groups: aneurysm-osteoarthritis = 90.7 ± 6.4%; Loeys-Dietz = 94.4 ± 5.4%; Marfan = 96.1 ± 1.2%; heritable non-syndromal aortopathy = 93.9 ± 2.3%, with similar findings at 20 years. Prophylactic aortic surgery was a first event during follow-up for 196 individuals (ACTA2 aneurysm = 3; aneurysm-osteoarthritis = 10; Loeys-Dietz = 19; Marfan = 119; heritable non-syndromal aortopathy = 45). A second surgical intervention was required in 45 individuals and a third intervention in 21 individuals. At 10 years follow-up, survival free of surgery differed between groups: aneurysm-osteoarthritis = 68.5 ± 10.1%; Loeys-Dietz = 40.8 ± 11.2%; Marfan = 75.5 ± 2.7%; heritable non-syndromal aortopathy = 63.8 ± 4.7% (p < 0.001). At 20 years follow-up mean survival free of surgery was: aneurysm-osteoarthritis = 26.6 ± 14.7%; Loeys-Dietz = 9.1 ± 8.2%; Marfan = 57.2 ± 3.4%; heritable non-syndromal aortopathy = 41.6 ± 8.2% (p < 0.001). Diagnosis of newer syndromic and non-syndromal heritable aortopathies is delayed compared to MFS, with associated complications of presentation with aortic dissection. Survival of individuals enrolled in follow-up surveillance is comparable between different genetic aortopathies, however aortic dissections still occur and need for surgical intervention is high.

Background: The primary objective of this review was to explore the contribution of oxidative stress to the pathogenesis of genetically-triggered thoracic aortic aneurysm (TAA). Genetically-triggered TAAs manifest substantial variability in onset, progression, and risk of aortic dissection, posing a significant clinical management challenge. There is a need for non-invasive biomarkers that predict the natural course of TAA and therapeutics that prevent aneurysm progression. Methods: An online systematic search was conducted within PubMed, MEDLINE, Scopus and ScienceDirect databases using keywords including: oxidative stress, ROS, nitrosative stress, genetically triggered thoracic aortic aneurysm, aortic dilatation, aortic dissection, Marfan syndrome, Bicuspid Aortic Valve, familial TAAD, Loeys Dietz syndrome, and Ehlers Danlos syndrome. Results: There is extensive evidence of oxidative stress and ROS imbalance in genetically triggered TAA. Sources of ROS imbalance are variable but include dysregulation of redox mediators leading to either insufficient ROS removal or increased ROS production. Therapeutic exploitation of redox mediators is being explored in other cardiovascular conditions, with potential application to TAA warranting further investigation. Conclusion: Oxidative stress occurs in genetically triggered TAA, but the precise contribution of ROS to pathogenesis remains incompletely understood. Further research is required to define causative pathological relationships in order to develop therapeutic options.

Marfan syndrome is consequent upon mutations in FBN1, which encodes the extracellular matrix microfibrillar protein fibrillin-1. The phenotype is characterised by development of thoracic aortic aneurysm. Current understanding of the pathogenesis of aneurysms in Marfan syndrome focuses upon abnormal vascular smooth muscle cell signalling through the transforming growth factor beta (TGFβ) pathway. Angiotensin II (Ang II) can directly induce aortic dilatation and also influence TGFβ synthesis and signalling. It has been hypothesised that antagonism of Ang II signalling may protect against aortic dilatation in Marfan syndrome. Experimental studies have been supportive of this hypothesis, however results from multiple clinical trials are conflicting. This paper examines current knowledge about the interactions of Ang II and TGFβ signalling in the vasculature, and critically interprets the experimental and clinical findings against these signalling interactions. Keywords: Aneurysm, Angiotensin blocker, Cell Signalling, Clinical trial

Genetically triggered thoracic aortic aneurysms (TAAs) are usually considered to exhibit minimal levels of inflammation. However, emerging data demonstrate that specific features of an inflammatory response can be observed in TAA, and that the extent of the inflammatory response can be correlated with the severity, in both mouse models and in human studies. Myeloperoxidase (MPO) is a key mediator of the inflammatory response, via production of specific oxidative species, e.g., the hypohalous acids. Specific tissue modifications, mediated by hypohalous acids, have been documented in multiple cardiovascular pathologies, including atherosclerosis associated with coronary artery disease, abdominal aortic, and cerebral aneurysms. Similarly, data are now emerging that show the capacity of MPO-derived oxidative species to regulate mechanisms important in TAA pathogenesis, including alterations in extracellular matrix homeostasis, activation of matrix metalloproteinases, induction of endothelial dysfunction and vascular smooth muscle cell phenotypic switching, and activation of ERK1/2 signaling. The weight of evidence supports a role for inflammation in exacerbating the severity of TAA progression, expanding our understanding of the pathogenesis of TAA, identifying potential biomarkers for early detection of TAA, monitoring severity and progression, and for defining potential novel therapeutic targets.

Objectives: Gait speed indicates the individual's functional status and predicts overall health. This study aims to determine (1) the intra- and inter-rater and test–retest reliability of the dynamic 4 m gait speed test protocol; (2) establish the normative reference values of habitual and fast gait speeds in community-dwelling healthy Singaporean adults aged 21 to 80; and (3) explore the association of age, gender, height, weight, and body mass index (BMI) on gait speed. Methods: This prospective cross-sectional study recruited healthy ambulatory community-dwelling Singaporeans aged 21 to 80 who could ambulate independently without aid. Participants were excluded if they required walking aids; were pregnant; or had physical, medical, or cognitive conditions that may affect gait. Each participant completed at least two habitual and fast gait speed test trials via a 4 m walkway with a dynamic start. The data were analysed by descriptive statistics, the Mann–Whitney test, the Spearman coefficient, and the interclass correlation coefficient (ICC). Results: In total, 178 males and 201 females were included in the data analysis. The median age was 45.0 years [interquartile range (IQR) 26.2–59.0], and the median height was 1.64 metres (m) (IQR 1.58–1.70). The median habitual gait speed was 1.08 metre/second (m/s) (IQR 0.97–1.22), and the fast gait speed was 1.55 m/s (IQR 1.40–1.70). The ICC for reliability ranged from 0.84 to 0.99, indicating that the 4 m gait speed test had good-to-excellent reliability. Conclusions: Gait speeds were not influenced by gender but declined with age advancement. Age and height and age and BMI were weakly correlated to habitual and fast gait speed, respectively. We established the norm values for the 4 m gait speeds in Singapore and proved it to be a reliable gait speed assessment ready for immediate community applications. [ABSTRACT FROM AUTHOR]

Biobanking in health care has evolved over the last few decades from simple biological sample repositories to complex and dynamic units with multi‐organizational infrastructure networks and has become an essential tool for modern medical research. Cardiovascular tissue biobanking provides a unique opportunity to utilize cardiac and vascular samples for translational research into heart failure and other related pathologies. Current techniques for diagnosis, classification, and treatment monitoring of cardiac disease relies primarily on interpretation of clinical signs, imaging, and blood biomarkers. Further research at the disease source (i.e. myocardium and blood vessels) has been limited by a relative lack of access to quality human cardiac tissue and the inherent shortcomings of most animal models of heart disease. In this review, we describe a model for cardiovascular tissue biobanking and databasing, and its potential to facilitate basic and translational research. We share techniques to procure endocardial samples from patients with hypertrophic cardiomyopathy, heart failure with reduced ejection fraction, and heart failure with preserved ejection fraction, in addition to aortic disease samples. We discuss some of the issues with respect to data collection, privacy, biobank consent, and the governance of tissue biobanking. The development of tissue biobanks as described here has significant scope to improve and facilitate translational research in multi‐omic fields such as genomics, transcriptomics, proteomics, and metabolomics. This research heralds an era of precision medicine, in which patients with cardiovascular pathology can be provided with optimized and personalized medical care for the treatment of their individual phenotype. [ABSTRACT FROM AUTHOR]

Background: The primary objective of this review was to explore the contribution of oxidative stress to the pathogenesis of genetically-triggered thoracic aortic aneurysm (TAA). Genetically-triggered TAAs manifest substantial variability in onset, progression, and risk of aortic dissection, posing a significant clinical management challenge. There is a need for non-invasive biomarkers that predict the natural course of TAA and therapeutics that prevent aneurysm progression. Methods: An online systematic search was conducted within PubMed, MEDLINE, Scopus and ScienceDirect databases using keywords including: oxidative stress, ROS, nitrosative stress, genetically triggered thoracic aortic aneurysm, aortic dilatation, aortic dissection, Marfan syndrome, Bicuspid Aortic Valve, familial TAAD, Loeys Dietz syndrome, and Ehlers Danlos syndrome. Results: There is extensive evidence of oxidative stress and ROS imbalance in genetically triggered TAA. Sources of ROS imbalance are variable but include dysregulation of redox mediators leading to either insufficient ROS removal or increased ROS production. Therapeutic exploitation of redox mediators is being explored in other cardiovascular conditions, with potential application to TAA warranting further investigation. Conclusion: Oxidative stress occurs in genetically triggered TAA, but the precise contribution of ROS to pathogenesis remains incompletely understood. Further research is required to define causative pathological relationships in order to develop therapeutic options. [ABSTRACT FROM AUTHOR]