Circulating miRNAs and Vascular Injury Markers Associate with Cardiovascular Function in Older Patients Reaching End-Stage Kidney Disease

The prevalence of end-stage kidney disease (ESKD) is rapidly increasing and mostly occurring in patients aged 65 years or older. The main cause of death in these patients is cardiovascular disease (CVD). Novel markers of vascular integrity may thus be of clinical value for identifying patients at high risk for CVD. Here we associated the levels of selected circulating angiogenic miRNAs, angiopoietin-2 (Ang-2) and asymmetric dimethylarginine (ADMA) with cardiovascular structure and function (as determined by cardiovascular MRI) in 67 older patients reaching ESKD that were included from ‘The Cognitive decline in Older Patients with End stage renal disease’ (COPE) prospective, multicentered cohort study. We first determined the association between the vascular injury markers and specific heart conditions and observed that ESKD patients with coronary heart disease have significantly higher levels of circulating ADMA and miR-27a. Moreover, circulating levels of miR-27a were higher in patients with atrial fibrillation. In addition, the circulating levels of the vascular injury markers were associated with measures of cardiovascular structure and function obtained from cardiovascular MRI: pulse wave velocity (PWV), ejection fraction (EF) and cardiac index (CI). We found Ang-2 and miR-27a to be strongly correlated to the PWV, while Ang-2 also associated with ejection fraction. Finally, we observed that in contrast to miR-27a, Ang-2 was not associated with a vascular cause of the primary kidney disease, suggesting Ang-2 may be an ESKD-specific marker of vascular injury. Taken together, among older patients with ESKD, aberrant levels of vascular injury markers (miR-27a, Ang-2 and ADMA) associated with impaired cardiovascular function. These markers may serve to identify individuals at higher risk of CVD, as well as give insight into the underlying (vascular) pathophysiology.

Effect of aging and sex on cardiovascular structure and function in wildtype mice assessed with echocardiography

This study employed traditional and advanced echocardiographic techniques to assess comprehensively age- and sex-related changes in cardiovascular structure and function in wildtype (WT) mice. Forty-five normal adult wildtype mice were apportioned to groups based on age and sex: 2-month (young) male or female, and 24-month (old) male or female (n = 13, 13, 13, and 6, respectively). Each underwent 2-dimensional (2D) imaging echocardiography, Doppler, tissue Doppler imaging echocardiography, and speckle-tracking echocardiography (STE) for comparison of cardiovascular structure and function parameters. Compared to the young mice, the old had significantly higher body weight (BW), and lower diastolic and mean arterial pressure. The left ventricular (LV) end-diastolic and end-systolic volumes, and left ventricular mass, were significantly higher in the old mice. Within each sex, the cardiac diastolic and systolic function parameters were comparable between the young and old. Isovolumetric relaxation time (IVRT)/diastolic time interval (DT) and the maximum drop rate of pressure in LV (− dP/dtmax) were significantly lower in the old mice, while the LV relaxation time constant (Tau) was significantly higher. Spearman’s rank correlation showed a positive association between IVRT/DT and − dp/dtmax (male r = 0.663; female r = 0.639). Among the males, the maximum rise rate of pressure in LV (+ dp/dtmax), and systolic global longitudinal strains and rates (S-GLS, S-GLSR) were significantly different between the young and old. Spearman’s rank correlation showed positive association between S-GLS, S-GLSR and + dp/dtmax (r = 0.709 and r = 0.499). Regarding vascular structure, the ascending aorta systolic and diastolic diameters were significantly higher in the old mice compared with the young. The male mice had progressive, age-related aortic stiffness. Ageing in mice leads to changes in cardiovascular structure and cardiac diastolic function, but systolic function is relatively well preserved in females. Changes in cardiac function and arterial stiffness were more significant in males than females. Traditional ECG is better than STE for evaluating LV diastolic function; STE is better for LV systolic function.

A pilot randomised controlled trial of a structured, home-based exercise programme on cardiovascular structure and function in kidney transplant recipients: the ECSERT study design and methods

BackgroundCardiovascular disease (CVD) is a major cause of morbidity and mortality in kidney transplant recipients (KTRs). CVD risk scores underestimate risk in this population as CVD is driven by clustering of traditional and non-traditional risk factors, which lead to prognostic pathological changes in cardiovascular structure and function. While exercise may mitigate CVD in this population, evidence is limited, and physical activity levels and patient activation towards exercise and self-management are low. This pilot study will assess the feasibility of delivering a structured, home-based exercise intervention in a population of KTRs at increased cardiometabolic risk and evaluate the putative effects on cardiovascular structural and functional changes, cardiorespiratory fitness, quality of life, patient activation, healthcare utilisation and engagement with the prescribed exercise programme.Methods and analysisFifty KTRs will be randomised 1:1 to: (1) the intervention; a 12week, home-based combined resistance and aerobic exercise intervention; or (2) the control; usual care. Intervention participants will have one introductory session for instruction and practice of the recommended exercises prior to receiving an exercise diary, dumbbells, resistance bands and access to instructional videos. The study will evaluate the feasibility of recruitment, randomisation, retention, assessment procedures and the intervention implementation. Outcomes, to be assessed prior to randomisation and postintervention, include: cardiac structure and function with stress perfusion cardiac MRI, cardiorespiratory fitness, physical function, blood biomarkers of cardiometabolic health, quality of life and patient activation. These data will be used to inform the power calculations for future definitive trials.Ethics and disseminationThe protocol was reviewed and given favourable opinion by the East Midlands-Nottingham 2 Research Ethics Committee (reference: 19/EM/0209; 14 October 2019). Results will be published in peer-reviewed academic journals and will be disseminated to the patient and public community via social media, newsletter articles and presentations at conferences.Trial registration numberNCT04123951.

Cardiovascular causes of tracheobronchial compression: a decade experience in a Paediatric Congenital Heart Centre

Background: Vascular compression of the airway often complicates CHD management. This study evaluated the use of CT in determining cardiovascular causes, clinical manifestations, and outcome of tracheobronchial compression among children with CHD. Methods: A retrospective review of clinical records of all patients with CT scan evidence of tracheobronchial compression from January 2007 to December 2017 at National Heart Institute. Cardiovascular causes of tracheobronchial compression were divided into three groups; group I: vascular ring/pulmonary artery sling, II: abnormally enlarged or malposition cardiovascular structure due to CHD, III: post-CHD surgery. Results: Vascular tracheobronchial compression was found in 81 out of 810 (10%) patients who underwent CT scan. Group I lesions were the leading causes of vascular tracheobronchial compression (55.5%), followed by group II (34.6%) and group III (9.9%). The median age of diagnosis in groups I, II, and III were 16.8 months, 3 months, and 15.6 months, respectively. Half of group I patients are manifested with stridor and one-third with recurrent chest infections. Persistent respiratory symptoms, lung atelectasis, or prolonged respiratory support requirement were clues in groups II and III. Higher morbidity and mortality in younger infants with severe obstructive airway symptoms, associated airway abnormalities, and underlying complex cyanotic CHD. Conclusions: Vascular ring/pulmonary artery sling and abnormally enlarged or malposition cardiovascular structure were the leading causes of cardiovascular airway compression. A high index of suspicion is needed for early detection due to its non-specific presentation. The outcome often depends on the severity of airway obstruction and complexity of cardiac lesions.

Puberty timing and markers of cardiovascular structure and function at 25 years: a prospective cohort study

Background Whether earlier onset of puberty is associated with higher cardiovascular risk in early adulthood is not well understood. Our objective was to examine the association between puberty timing and markers of cardiovascular structure and function at age 25 years. Methods We conducted a prospective birth cohort study using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were born between April 1, 1991, and December 31, 1992. Exposure of interest was age at peak height velocity (aPHV), an objective and validated growth-based measure of puberty onset. Outcome measures included cardiovascular structure and function at age 25 years: carotid intima-media thickness (CIMT), left ventricular mass index (LVMI) and relative wall thickness (RWT), pulse wave velocity (PWV) and systolic blood pressure (SBP). Multiple imputation was used to impute missing data on covariates and outcomes. Linear regression was used to examine the association between aPHV and each measure of cardiac structure and function, adjusting for maternal age, gestational age, household social class, maternal education, mother’s partner’s education, breastfeeding, parity, birthweight, maternal body mass index, maternal marital status, maternal prenatal smoking status and height and fat mass at age 9. All analyses were stratified by sex. Results A total of 2752–4571 participants were included in the imputed analyses. A 1-year older aPHV was not strongly associated with markers of cardiac structure and function in males and females at 25 years and most results spanned the null value. In adjusted analyses, a 1-year older aPHV was associated with 0.003 mm (95% confidence interval (CI) 0.00001, 0.006) and 0.0008 mm (95% CI − 0.002, 0.003) higher CIMT; 0.02 m/s (95% CI − 0.05, 0.09) and 0.02 m/s (95% CI − 0.04, 0.09) higher PWV; and 0.003 mmHg (95% CI − 0.60, 0.60) and 0.13 mmHg (95% CI − 0.44, 0.70) higher SBP, among males and females, respectively. A 1-year older aPHV was associated with − 0.55 g/m2.7 (95% CI − 0.03, − 1.08) and − 0.89 g/m2.7 (95% CI − 0.45, − 1.34) lower LVMI and − 0.001 (95% CI − 0.006, 0.002) and − 0.002 (95% CI − 0.006, 0.002) lower RWT among males and females. Conclusions Earlier puberty is unlikely to have a major impact on pre-clinical cardiovascular risk in early adulthood.

Habitual Cannabis Use is Associated with Altered Cardiac Mechanics and Arterial Stiffness, but not Endothelial Function in Young Healthy Smokers

Cigarette smoking is amongst the most detrimental behaviours to cardiovascular health, resulting in arterial stiffening, endothelial dysfunction, and structural/functional alterations to the myocardium. Similar to cigarettes, cannabis is commonly smoked and next to alcohol, is the most commonly used recreational substance in the world. Despite this, little is known about the long-term cardiovascular effects of smoking cannabis. This study explored the associations of cardiovascular structure and function with cannabis use in ostensibly healthy young participants (n=35). Using echocardiography, carotid-femoral pulse wave velocity (cfPWV), and brachial flow-mediated dilation (FMD) we performed a cross-sectional assessment of cardiovascular function in cannabis users (n=18), and controls (n=17). There were no differences in cardiac morphology or traditional resting measures of systolic or diastolic function between cannabis users and controls (all p>0.05); whereas cannabis users demonstrated reduced peak apical rotation compared to controls (cannabis users: 5.5±3.8, controls: 9.6±1.5; p = 0.02). Cannabis users had higher cfPWV compared to controls (cannabis users: 5.8±0.6m/s, controls: 5.3±0.7m/s; p = 0.05), while FMD was similar between cannabis users and controls (cannabis users: 8.3±3.3%, controls: 6.8±3.6%; p= 0.7). Young, healthy, cannabis users demonstrate altered cardiac mechanics and greater aortic stiffness. Further studies should explore causal links between cannabis smoking and altered cardiovascular function.

Interrelationship between micronutrients and cardiovascular structure and function in type 2 diabetes

Micronutrients are important for normal cardiovascular function. They may play a role in the increased risk of cardiovascular disease observed in people with type 2 diabetes (T2D) and T2D-related heart failure. The aims of this study were to (1) examine micronutrient status in people with T2D v. healthy controls; (2) assess any changes following a nutritionally complete meal replacement plan (MRP) compared with routine care; (3) determine if any changes were associated with changes in cardiovascular structure/function. This was a secondary analysis of data from a prospective, randomised, open-label, blinded end-point trial of people with T2D, with a nested case–control [NCT02590822]. Anthropometrics, cardiac resonance imaging and fasting blood samples (to quantify vitamins B1, B6, B12, D and C; and iron and ferritin) were collected at baseline and 12 weeks following the MRP or routine care. Comparative data in healthy controls were collected at baseline. A total of eighty-three people with T2D and thirty-six healthy controls were compared at baseline; all had micronutrient status within reference ranges. Vitamin B1 was higher (148⋅9 v. 131⋅7; P 0⋅01) and B6 lower (37⋅3 v. 52⋅9; P 0⋅01) in T2D v. controls. All thirty participants randomised to routine care and twenty-four to the MRP completed the study. There was an increase in vitamins B1, B6, D and C following the MRP, which were not associated with changes in cardiovascular structure/function. In conclusion, changes in micronutrient status following the MRP were not independently associated with improvements in cardiovascular structure/function in people with T2D.

Importance of Vector Velocity Echocardiography and NT-proBNP in Identifying Individuals with Preclinical Hypertrophic Cardiomyopathy

Background and aim: Familial HCM gene mutation carriers without overt left ventricular hypertrophy (gene positive/phenotype negative G+/P-) can harbor subclinical changes in cardiovascular structure and function that precede the development of Hypertrophic Cardiomyopathy (HCM). Conventional echocardiography parameter ejection fraction is normal in HCM patients. We sought to investigate whether Velocity Vector Imaging (VVI) and NT-proBNP are more sensitive to evaluate heart function.

Coronary anomalies

Anomalous coronary arteries are relatively common, occurring in approximately 1.3% of the general population. Most variants of anomalous coronary arteries do not cause disability and have a benign course. Surgery is warranted to alleviate symptoms. However, some anomalies, such as a left coronary artery arising from the right sinus of Valsalva and passing between the great vessels or anomalous left coronary artery arising from the pulmonary artery, are considered malignant as they have been associated with sudden cardiac death or heart failure, and in these cases, surgery is indicated. Coronary artery fistulas are abnormal communications between a coronary artery and another cardiovascular structure. They are relatively rare, and surgical or transcatheter closure may be necessary in patients with large left-to-right shunts and/or regional myocardial ischaemia.

Changes in Cardiovascular Structure and Physiology Following Polystyrene Nanoparticle Exposure

Background Microplastic (MP) pollution has been a growing concern in recent decades due to the proliferation and ease of manufacturing regarding plastics products. Polystyrene (PS), being one the most abundant plastic polymers, is the subject of frequent studies due to its ubiquitous nature. Trophic transfer, inhalation, and dermal exposure are all routes by which humans may be exposed to MPs every day. There are undoubtedly more physiological consequences than we are currently aware of; however, many of these concerns are beginning to be better understood. Their distribution throughout the body dictates the potential threats to human health. The cardiovascular system is potentially the most susceptible, as it is the first medium the MPs are exposed to after entering the body. Consequently, the cardiovascular system and thrombus generation is one such area where much recent attention has been allocated. Project Methods Data was gathered from a variety of well-established research articles to review the relationship between PS exposure and thrombus formation in vivo. Additionally, this review looks at documented effects of MPs on platelet aggregation and discusses mechanisms through which these pathologies take place. Results PS plastics have varying impact on thrombus formation contingent upon both surface modifications and particle size. Aminated PS appears to be the most potent regarding the generation of thrombi in vivo. Literature on platelet aggregation is more consistent, with most studies revealing that carboxylated and aminated forms enhance aggregation while unmodified PS had insignificant effects. Conclusion/Potential Impact There is substantial ambiguity surrounding this field and more studies need to be conducted to reveal the full extent of pathologies caused by PS microplastics. Most studies have been done with marine life, which may not accurately reflect MPs effects in humans. Further research will allow us to begin developing viable solutions for those most susceptible to cardiovascular diseases.