Characterizing the influence of cardiorespiratory fitness on left atrial size and function in the general population.

Increased left atrial (LA) size and reduced LA function have been associated with heart failure and atrial fibrillation (AF) in at-risk populations. However, atrial remodeling has also been associated with exercise training and the relationship between fitness, LA size, and function has not been defined across the fitness spectrum. In a cross-sectional study of 559 ostensibly healthy participants, comprising 304 males (mean age, 46 ± 20 yr) and 255 females (mean age, 47 ± 15 yr), we sought to define the relationship between cardiorespiratory fitness (CRF), LA size, and function. We also aimed to interrogate sex differences in atrial factors influencing CRF. Echocardiographic measures included biplane measures of LA volumes indexed to body surface area (LAVi) and atrial deformation using two-dimensional speckle tracking. CRF was measured as peak oxygen consumption (V̇o2peak) during cardiopulmonary exercise testing (CPET). Using multivariable regression, age, sex, weight, and LAVi (P < 0.001 for all) predicted V̇o2peak (P < 0.001, R2 = 0.66 for combined model). After accounting for these variables, heart rate reserve added strength to the model (P < 0.001, R2 = 0.74) but LA strain parameters did not predict V̇o2peak. These findings add important nuance to the perception that LA size is a marker of cardiac pathology. LA size should be considered in the context of fitness, and it is likely that the adverse prognostic associations of increased LA size may be confined to those with LA enlargement and low fitness.NEW & NOTEWORTHY Left atrial (LA) structure better predicts cardiorespiratory fitness (CRF) than LA function. LA function adds little statistical value to predictive models of peak oxygen uptake (V̇o2peak) in healthy individuals, suggesting limited discriminatory for CRF once LA size is factored. In the wider population of ostensibly healthy individuals, the association between increased LA volume and higher CRF provides an important counter to the association between atrial enlargement and heart failure symptoms in those with cardiac pathology.

Ultrasensitive Troponin I and Incident Cardiovascular Disease.

BACKGROUND: To examine the association of ultrasensitive cTnI (cardiac troponin I) with incident cardiovascular disease events (CVDs) in the primary prevention setting. METHODS: cTnI was analyzed in the baseline plasma (2008-2012) of CVD-free volunteers from the Paris Prospective Study III using a novel ultrasensitive immunoassay (Simoa Troponin-I 2.0 Kit, Quanterix, Lexington) with a limit of detection of 0.013 pg/mL. Incident CVD hospitalizations (coronary heart disease, stroke, cardiac arrhythmias, deep venous thrombosis or pulmonary embolism, heart failure, or arterial aneurysm) were validated by critical review of the hospital records. Hazard ratios were estimated per log-transformed SD increase of cTnI in Cox models using age as the time scale. RESULTS: The study population includes 9503 participants (40% women) aged 59.6 (6.3) years. cTnI was detected in 99.6% of the participants (median value=0.63 pg/mL, interquartile range, 0.39-1.09). After a median follow-up of 8.34 years (interquartile range, 8.0-10.07), 516 participants suffered 612 events. In fully adjusted analysis, higher cTnI (per 1 SD increase of log cTnI) was significantly associated with CVD events combined (hazard ratio, 1.18 [1.08-1.30]). Among all single risk factors, cTnI had the highest discrimination capacity for incident CVD events (C index=0.6349). Adding log cTnI to the SCORE 2 (Systematic Coronary Risk Evaluation) risk improved moderately discriminatory capacity (C index 0.698 versus 0.685; bootstrapped C index difference: 0.0135 [95% CI, 0.0131-0.0138]), and reclassification of the participants (categorical net reclassification index, 0.0628 [95% CI, 0.023-0.102]). Findings were consistent using the US pooled cohort risk equation. CONCLUSIONS: Ultrasensitive cTnI is an independent marker of CVD events in the primary prevention setting.

The Ultrasound Window Into Vascular Ageing: A Technology Review by the VascAgeNet COST Action.

Non-invasive ultrasound (US) imaging enables the assessment of the properties of superficial blood vessels. Various modes can be used for vascular characteristics analysis, ranging from radiofrequency (RF) data, Doppler- and standard B/M-mode imaging, to more recent ultra-high frequency and ultrafast techniques. The aim of the present work was to provide an overview of the current state-of-the-art non-invasive US technologies and corresponding vascular ageing characteristics from a technological perspective. Following an introduction about the basic concepts of the US technique, the characteristics considered in this review are clustered into: 1) vessel wall structure; 2) dynamic elastic properties, and 3) reactive vessel properties. The overview shows that ultrasound is a versatile, non-invasive, and safe imaging technique that can be adopted for obtaining information about function, structure, and reactivity in superficial arteries. The most suitable setting for a specific application must be selected according to spatial and temporal resolution requirements. The usefulness of standardization in the validation process and performance metric adoption emerges. Computer-based techniques should always be preferred to manual measures, as long as the algorithms and learning procedures are transparent and well described, and the performance leads to better results. Identification of a minimal clinically important difference is a crucial point for drawing conclusions regarding robustness of the techniques and for the translation into practice of any biomarker.

Acute effects of interrupting prolonged sitting on vascular function in type 2 diabetes.

In healthy and overweight/obese adults, interrupting prolonged sitting with activity bouts mitigates impairment in vascular function. However, it is unknown whether these benefits extend to those with type 2 diabetes (T2D), nor whether an optimal frequency of activity interruptions exist. We examined the acute effects on vascular function in T2D of interrupting prolonged sitting with simple resistance activities (SRA) at different frequencies. In a randomized crossover trial, 24 adults with T2D (35-70 yr) completed three 7-h conditions: 1) uninterrupted sitting (SIT), 2) sitting with 3-min bouts of SRA every 30 min (SRA3), and 3) sitting with 6 min bouts of SRA every 60 min (SRA6). Femoral artery flow-mediated dilation (FMD), resting shear rate, blood flow, and endothelin-1 were measured at 0, 1, 3.5, 4.5, and 6.5-7 h. Mean femoral artery FMD over 7 h was significantly higher in SRA3 (4.1 ± 0.3%) compared with SIT (3.7 ± 0.3%, P = 0.04) but not in SRA6. Mean resting femoral shear rate over 7 h was increased significantly for SRA3 (45.3 ± 4.1/s, P < 0.001) and SRA6 (46.2 ± 4.1/s, P < 0.001) relative to SIT (33.1 ± 4.1/s). Endothelin-1 concentrations were not statistically different between conditions. Interrupting sitting with activity breaks every 30 min, but not 60 min, significantly increased mean femoral artery FMD over 7 h, relative to SIT. Our findings suggest that more frequent and shorter breaks may be more beneficial than longer, less frequent breaks for vascular health in those with T2D.NEW & NOTEWORTHY This is the first trial to examine both the effects of interrupting prolonged sitting on vascular function in type 2 diabetes and the effects of the frequency and duration of interruptions. Brief, simple resistance activity bouts every 30 min, but not every 60 min, increased mean femoral artery flow-mediated dilation over 7 h, relative to uninterrupted sitting. With further supporting evidence, these initial findings can have important implications for cardiovascular health in type 2 diabetes.

Type 2 Diabetes Mellitus Is Independently Associated With Decreased Neural Baroreflex Sensitivity: The Paris Prospective Study III.

OBJECTIVE: Impaired baroreflex function is an early indicator of cardiovascular autonomic imbalance. Patients with type 2 diabetes mellitus (T2D) have decreased baroreflex sensitivity (BRS), however, whether the neural BRS (nBRS) and mechanical component of the BRS is altered in those with high metabolic risk (HMR, impaired fasting glucose and metabolic syndrome) or with overt T2D, is unknown. We examined this in a community-based observational study, the Paris Prospective Study III (PPS3). Approach and Results: In 7626 adults aged 50 to 75 years, resting nBRS (estimated by low-frequency gain, from carotid distension rate and RR [time elapsed between two successive R waves] intervals) and mechanical BRS were measured by high-precision carotid echotracking. The associations between overt T2D or HMR as compared with subjects with normal glucose metabolism and nBRS or mechanical BRS were quantified using multivariable linear regression analysis. There were 319 subjects with T2D (61±6 years, 77% male), 1450 subjects with HMR (60±6 years, 72% male), and 5857 subjects with normal glucose metabolism (59±6 years, 57% male). Compared with normal glucose metabolism, nBRS was significantly lower in HMR subjects (ß=-0.07 [95% CI, -0.12 to -0.01]; P=0.029) and in subjects with T2D (ß=-0.18 [95% CI, -0.29 to -0.07]; P=0.002) after adjustment for confounding and mediating factors. Subgroup analysis suggests significant and independent alteration in mechanical BRS only among HMR patients who had both impaired fasting glucose and metabolic syndrome. CONCLUSIONS: In this community-based study of individuals aged 50 to 75, a graded decrease in nBRS was observed in HMR subjects and patients with overt T2D as compared with normal glucose metabolism subjects.

Effects of sedentary behaviour interventions on biomarkers of cardiometabolic risk in adults: systematic review with meta-analyses.

CONTEXT/PURPOSE: Observational and acute laboratory intervention research has shown that excessive sedentary time is associated adversely with cardiometabolic biomarkers. This systematic review with meta-analyses synthesises results from free living interventions targeting reductions in sedentary behaviour alone or combined with increases in physical activity. METHODS: Six electronic databases were searched up to August 2019 for sedentary behaviour interventions in adults lasting for ≥7 days publishing cardiometabolic biomarker outcomes covering body anthropometry, blood pressure, glucose and lipid metabolism, and inflammation (54 studies). The pooled effectiveness of intervention net of control on 15 biomarker outcomes was evaluated using random effects meta-analyses in the studies with control groups not providing other relevant interventions (33 studies; 6-25 interventions analysed). RESULTS: Interventions between 2 weeks and <6 months in non-clinical populations from North America, Europe and Australia comprised much of the evidence base. Pooled effects revealed small, significant (p<0.05) beneficial effects on weight (≈ -0.6 kg), waist circumference (≈ -0.7 cm), percentage body fat (≈ -0.3 %), systolic blood pressure (≈ -1.1 mm Hg), insulin (≈ -1.4 pM) and high-density lipoprotein cholesterol (≈ 0.04 mM). Pooled effects on the other biomarkers (p>0.05) were also small, and beneficial in direction except for fat-free mass (≈ 0.0 kg). Heterogeneity ranged widely (I2=0.0-72.9). CONCLUSIONS: Our review of interventions targeting sedentary behaviour reductions alone, or combined with increases in physical activity, found evidence of effectiveness for improving some cardiometabolic risk biomarkers to a small degree. There was insufficient evidence to evaluate inflammation or vascular function. Key limitations to the underlying evidence base include a paucity of high-quality studies, interventions lasting for ≥12 months, sensitive biomarkers and clinical study populations (eg, type 2 diabetes). PROSPERO TRIAL REGISTRATION NUMBER: CRD42016041742.

Vascular Ageing in Youth: A Call to Action.

Extensive evidence shows that risk factors for cardiovascular disease (CVD) begin to develop early in life. Childhood obesity and elevated blood pressure (BP) have become overwhelmingly challenging, with 57% of today's children predicted to be obese by the age of 35 years, and global rates of hypertension in children and adolescents increasing by 75% from 2000 to 2015. Thus, there is an urgent need for tools that can assess early CVD risk in youth, which may lead to better risk stratification, preventative intervention, and personalised medicine. Vascular ageing (the deterioration in vascular structure and function) is a pivotal progenitor of health degeneration associated with elevated BP. Exposure to adverse environmental and genetic factors from fetal life promotes the development and accumulation of subclinical vascular changes that direct an individual towards a trajectory of early vascular ageing (EVA)-an independent predictor of target organ damage in the heart, brain, and kidneys. Therefore, characterising vascular ageing from youth may provide a window into cardiovascular risk later in life. However, vascular ageing measurements only have value when techniques are accurate/validated and when reliable thresholds are available for defining normal ranges and ranges that signal increased risk of disease. The aim of this paper is to summarise current evidence on the importance of vascular ageing assessment in youth and the impact of interventions to prevent or delay EVA, to highlight the need for standardisation and validation of measurement techniques in children and adolescents, and the importance of establishing reference values for vascular ageing measures in this population.

Youth Vascular Consortium (YVC) Protocol: Establishing Reference Intervals for Vascular Ageing in Children, Adolescents and Young Adults.

BACKGROUND: In the last two decades, the global prevalence of paediatric hypertension increased by approximately 75%. Nearly 25% of children are now classified as obese or overweight. Substantial evidence suggests that risk factors for cardiovascular disease (CVD) begin to develop in childhood, thus warranting the need for tools to better screen for early CVD risk in youth. Vascular ageing, the deterioration of vascular structure and function, may be a potentially useful tool for detecting the early and asymptomatic signs of CVD burden. However, it is currently unclear what differentiates normal from pathological ageing in youth as existing reference values for vascular ageing in youth are limited by small sample size or homogenous populations. The international Youth Vascular Consortium (YVC) has been established to address these issues. AIMS: The primary aim of the YVC is to develop reference intervals of normal vascular ageing in children, adolescents, and young adults. The secondary, exploratory, aim is to perform head-to-head comparisons of vascular ageing biomarkers to determine which biomarker is most strongly related to cardiometabolic health. STUDY DESIGN: The YVC is a retrospective, multicentre study and will collate data on vascular ageing in children (5-12 years), adolescents (13-18 years) and young adults (19-40 years), as well as routine clinical biochemistry, lifestyle, sociodemographic factors and parental health. CONCLUSION: To date, 31 research groups from 19 countries have joined the YVC. To our knowledge, this will be the largest study of its kind to investigate vascular ageing in youth.

Lack of Strategic Funding and Long-Term Job Security Threaten to Have Profound Effects on Cardiovascular Researcher Retention in Australia.

BACKGROUND: Cardiovascular disease is the leading cause of death in Australia. Investment in research solutions has been demonstrated to yield health and a 9.8-fold return economic benefit. The sector, however, is severely challenged with success rates of traditional peer-reviewed funding in decline. Here, we aimed to understand the perceived challenges faced by the cardiovascular workforce in Australia prior to the COVID-19 pandemic. METHODS: We used an online survey distributed across Australian cardiovascular societies/councils, universities and research institutes over a period of 6 months during 2019, with 548 completed responses. Inclusion criteria included being an Australian resident or an Australian citizen who lived overseas, and a current or past student or employee in the field of cardiovascular research. RESULTS: The mean age of respondents was 42±13 years, 47% were male, 85% had a full-time position, and 40% were a group leader or laboratory head. Twenty-three per cent (23%) had permanent employment, and 82% of full-time workers regularly worked >40 hours/week. Sixty-eight per cent (68%) said they had previously considered leaving the cardiovascular research sector. If their position could not be funded in the next few years, a staggering 91% of respondents would leave the sector. Compared to PhD- and age-matched men, women were less likely to be a laboratory head and to feel they had a long-term career path as a cardiovascular researcher, while more women were unsure about future employment and had considered leaving the sector (all p<0.05). Greater job security (76%) and government and philanthropic investment in cardiovascular research (72%) were highlighted by responders as the main changes to current practices that would encourage them to stay. CONCLUSION: Strategic solutions, such as diversification of career pathways and funding sources, and moving from a competitive to a collaborative culture, need to be a priority to decrease reliance on government funding and allow cardiovascular researchers to thrive.

Sleep apnoea is associated with hearing impairment: The Paris prospective study 3.

OBJECTIVES: Hearing impairment (HI) is a leading impairment worldwide, and identifying modifiable risk factors of HI may have major public health implications. The aim of this study was to investigate the association between obstructive sleep apnoea (OSA) and HI. DESIGN: Observational longitudinal study (the Paris Prospective Study 3). SETTING: Population-based. PARTICIPANTS: Volunteers aged 50-75 years and consulting at a preventive medical centre were included between 2008 and 2012. 6797 participants were included in the present analysis. MAIN OUTCOME MEASURES: Audiometry testing was performed in both ears in all participants, and HI was defined by a pure-tone average (PTA) >25 decibels (dB) hearing level in the better ear. RESULTS: Obstructive sleep apnoea (estimated by the Berlin questionnaire) was present in 18.6% (n = 1267) and HI in 13.9% (n = 947) of the participants. Mean age was 59.5 years (SD 6.2) and 63.5% were male (n = 4317). In multiple logistic regression modelling, OSA was significantly associated with a 1.21-increased odds of HI (95% confidence interval 1.01-1.44). Several sensitivity analyses supported this finding. CONCLUSION: Obstructive sleep apnoea is associated with a 21% increased odds of HI. These results support active screening of HI in subjects with OSA, and future studies should evaluate whether the treatment of OSA can delay the onset of HI.

Building an Academic-Industry Partnership to Tackle Australia's Biggest Health Burden.

Cardiovascular disease (CVD) poses a highly significant health and economic burden in Australia and worldwide, with the latest global burden of disease study identifying cardiovascular disease as an "expanding threat to global health" [1]. Australian cardiovascular researchers are recognised internationally for their broad expertise spanning from fundamental molecular and cellular biology, through innovative bioengineering approaches, patient-focussed clinical trials, and impactful community interventions for improved public health. However, funding challenges have resulted in a fragmented research sector struggling to survive, let alone work together as an effective national team with strategic leadership and collaboration. The Australian Cardiovascular Alliance have successfully advocated for a federally supported Mission for Cardiovascular Helath ($220 Million). A key element of success in their goal of enhancing the CV health of Austrlaians, is partnering with industry.

Physical Activity and Sedentary Behavior Subsequent to Serious Orthopedic Injury: A Systematic Review.

OBJECTIVE: To systematically review and synthesize the evidence on physical activity and sedentary behavior after serious orthopedic injury. DATA SOURCES: Eight electronic databases and reference lists of relevant articles were searched from inception to March 2016. STUDY SELECTION: Studies on physical activity and sedentary behavior measured objectively or via self-report among patients with a serious orthopedic injury (acute bone or soft tissue injury requiring emergency hospital admission and/or nonelective surgery) were included. DATA EXTRACTION: Data extraction and methodological quality assessment were independently performed by 2 reviewers using standardized checklists. DATA SYNTHESIS: Twelve of 2572 studies were included: 8 were on hip fractures and 4 on other orthopedic injuries. Follow-up ranged from 4 days to 2 years postinjury. When measured objectively, physical activity levels were low at all time points postinjury, with individuals with hip fracture achieving only 1% of recommended physical activity levels 7 months postinjury. Studies using objective measures also showed patients to be highly sedentary throughout all stages of recovery, spending 76% to 99% of the day sitting or reclining. For studies using self-report measures, no consistent trends were observed in postinjury physical activity or sedentary behavior. CONCLUSIONS: For studies using objective measures, low physical activity levels and high levels of sedentary behaviors were found consistently after injury. More research is needed not only on the impact of immobility on long-term orthopedic injury outcomes and the risk of chronic disease, but also the potential for increasing physical activity and reducing sedentary behavior in this population.

Pulsatile interaction between the macro-vasculature and micro-vasculature: proof-of-concept among patients with type 2 diabetes.

PURPOSE: It is widely thought that excess pulsatile pressure from increased stiffness of large central arteries (macro-vasculature) is transmitted to capillary networks (micro-vasculature) and causes target organ damage. However, this hypothesis has never been tested. We sought to examine the association between macro- and micro-vasculature waveform features in patients with type 2 diabetes (i.e., those with elevated stiffness; T2D) compared with non-diabetic controls. METHODS: Among 13 T2D (68 ± 6 years, 39% male) and 15 controls (58 ± 11 years, 40% male) macro-vascular stiffness was determined via aortic pulse wave velocity (aPWV) and macro-vascular waveforms were measured using radial tonometry. Forearm micro-vascular waveforms were measured simultaneously with macro-vascular waveforms via low power laser Doppler fluxmetry. Augmentation index (AIx) was derived on macro- and micro-vascular waveforms. Target organ damage was assessed by estimated glomerular filtration rate (eGFR) and central retinal artery equivalent (CRAE). RESULTS: aPWV was higher among T2D (9.3 ± 2.5 vs 7.5 ± 1.4 m/s, p = 0.046). There was an obvious pulsatile micro-vascular waveform with qualitative features similar to macro-vasculature pressure waveforms. In all subjects, macro- and micro-vasculature AIx were significantly related (r = 0.43, p = 0.005). In T2D alone, micro-vasculature AIx was associated with eGFR (r = - 0.63, p = 0.037), whereas in controls, macro-vasculature AIx and AP were associated with CRAE (r = - 0.58, p = 0.025 and r = - 0.61, p = 0.015). CONCLUSIONS: Macro- and micro-vasculature waveform features are related; however, micro-vasculature features are more closely related to markers of target organ damage in T2D. These findings are suggestive of a possible interaction between the macro- and micro-circulation.

Association of Change in Cardiovascular Risk Factors With Incident Cardiovascular Events.

Importance: There is consistent evidence of the association between ideal cardiovascular health and lower incident cardiovascular disease (CVD); however, most studies used a single measure of cardiovascular health. Objective: To examine how cardiovascular health changes over time and whether these changes are associated with incident CVD. Design, Setting, and Participants: Prospective cohort study in a UK general community (Whitehall II), with examinations of cardiovascular health from 1985/1988 (baseline) and every 5 years thereafter until 2015/2016 and follow-up for incident CVD until March 2017. Exposures: Using the 7 metrics of the American Heart Association (nonsmoking; and ideal levels of body mass index, physical activity, diet, blood pressure, fasting blood glucose, and total cholesterol), participants with 0 to 2, 3 to 4, and 5 to 7 ideal metrics were categorized as having low, moderate, and high cardiovascular health. Change in cardiovascular health over 10 years between 1985/1988 and 1997/1999 was considered. Main Outcome and Measure: Incident CVD (coronary heart disease and stroke). Results: The study population included 9256 participants without prior CVD (mean [SD] age at baseline, 44.8 [6.0] years; 2941 [32%] women), of whom 6326 had data about cardiovascular health change. Over a median follow-up of 18.9 years after 1997/1999, 1114 incident CVD events occurred. In multivariable analysis and compared with individuals with persistently low cardiovascular health (consistently low group, 13.5% of participants; CVD incident rate per 1000 person-years, 9.6 [95% CI, 8.4-10.9]), there was no significant association with CVD risk in the low to moderate group (6.8% of participants; absolute rate difference per 1000 person-years, -1.9 [95% CI, -3.9 to 0.1]; HR, 0.84 [95% CI, 0.66-1.08]), the low to high group, (0.3% of participants; absolute rate difference per 1000 person-years, -7.7 [95% CI, -11.5 to -3.9]; HR, 0.19 [95% CI, 0.03-1.35]), and the moderate to low group (18.0% of participants; absolute rate difference per 1000 person-years, -1.3 [95% CI, -3.0 to 0.3]; HR, 0.96 [95% CI, 0.80-1.15]). A lower CVD risk was observed in the consistently moderate group (38.9% of participants; absolute rate difference per 1000 person-years, -4.2 [95% CI, -5.5 to -2.8]; HR, 0.62 [95% CI, 0.53-0.74]), the moderate to high group (5.8% of participants; absolute rate difference per 1000 person-years, -6.4 [95% CI, -8.0 to -4.7]; HR, 0.39 [95% CI, 0.27-0.56]), the high to low group (1.9% of participants; absolute rate difference per 1000 person-years, -5.3 [95% CI, -7.8 to -2.8]; HR, 0.49 [95% CI, 0.29-0.83]), the high to moderate group (9.3% of participants; absolute rate difference per 1000 person-years, -4.5 [95% CI, -6.2 to -2.9]; HR, 0.66 [95% CI, 0.51-0.85]), and the consistently high group (5.5% of participants; absolute rate difference per 1000 person-years, -5.6 [95% CI, -7.4 to -3.9]; HR, 0.57 [95% CI, 0.40-0.80]). Conclusions and Relevance: Among a group of participants without CVD who received follow-up over a median 18.9 years, there was no consistent relationship between direction of change in category of a composite metric of cardiovascular health and risk of CVD.

Exercise excess pressure and exercise-induced albuminuria in patients with type 2 diabetes mellitus.

Exercise-induced albuminuria is common in patients with type 2 diabetes mellitus (T2DM) in response to maximal exercise, but the response to light-moderate exercise is unclear. Patients with T2DM have abnormal central hemodynamics and greater propensity for exercise hypertension. This study sought to determine the relationship between light-moderate exercise central hemodynamics (including aortic reservoir and excess pressure) and exercise-induced albuminuria. Thirty-nine T2DM (62 ± 9 yr; 49% male) and 39 nondiabetic controls (53 ± 9 yr; 51% male) were examined at rest and during 20 min of light-moderate cycle exercise (30 W; 50 revolutions/min). Albuminuria was assessed by the albumin-creatinine ratio (ACR) at rest and 30 min postexercise. Hemodynamics recorded included brachial and central blood pressure (BP), aortic stiffness, augmented pressure (AP), aortic reservoir pressure, and excess pressure integral (Pexcess). There was no difference in ACR between groups before exercise (P > 0.05). Exercise induced a significant rise in ACR in T2DM but not controls (1.73 ± 1.43 vs. 0.53 ± 1.0 mg/mol, P = 0.002). All central hemodynamic variables were significantly higher during exercise in T2DM (i.e., Pexcess, systolic BP and AP; P < 0.01 all). In T2DM (but not controls), exercise Pexcess was associated with postexercise ACR (r = 0.51, P = 0.002), and this relationship was independent of age, sex, body mass index, heart rate, aortic stiffness, antihypertensive medication, and ambulatory daytime systolic BP (ß = 0.003, P = 0.003). Light-moderate exercise induced a significant rise in ACR in T2DM, and this was independently associated with Pexcess, a potential marker of vascular dysfunction. These novel findings suggest that Pexcess could be important for appropriate renal function in T2DM.

Aortic reservoir characteristics and brain structure in people with type 2 diabetes mellitus; a cross sectional study.

BACKGROUND: Central hemodynamics help to maintain appropriate cerebral and other end-organ perfusion, and may be altered with ageing and type 2 diabetes mellitus (T2DM). We aimed to determine the associations between central hemodynamics and brain structure at rest and during exercise in people with and without T2DM. METHODS: In a sample of people with T2DM and healthy controls, resting and exercise measures of aortic reservoir characteristics (including excess pressure integral [P(excess)]) and other central hemodynamics (including augmentation index [AIx] and aortic pulse wave velocity [aPWV]) were recorded. Brain volumes (including gray matter volume [GMV] and white matter lesions [WML]) were derived from magnetic resonance imaging (MRI) scans. Multivariable linear regression was used to study the associations of hemodynamic variables with brain structure in the two groups adjusting for age, sex, daytime systolic BP (SBP) and heart rate. RESULTS: There were 37 T2DM (63 ± 9 years; 47% male) and 37 healthy individuals (52 ± 8 years; 51% male). In T2DM, resting aPWV was inversely associated with GMV (standardized ß = -0.47, p = 0.036). In healthy participants, resting P(excess) was inversely associated with GMV (ß = -0.23, p = 0.043) and AIx was associated with WML volume (ß = 0.52, p = 0.021). There were no associations between exercise hemodynamics and brain volumes in either group. CONCLUSIONS: Brain atrophy is associated with resting aortic stiffness in T2DM, and resting P(excess) in healthy individuals. Central vascular mechanisms underlying structural brain changes may differ between healthy individuals and T2DM.