Differences between brachial and aortic blood pressure in adolescence and their implications for diagnosis of hypertension.

OBJECTIVES: Blood pressure (BP) is the leading global cause of mortality, and its prevalence is increasing in children and adolescents. Aortic BP is lower than brachial BP in adults. We aimed to assess the extent of this difference and its impact on the diagnosis of hypertension among adolescents. METHODS: We used data from 3850 participants from a UK cohort of births in the early 1990s in the Southwest of England, who attended their ∼17-year follow-up and had valid measures of brachial and aortic BP at that clinic [mean (SD) age 17.8 (0.4) years, 66% female individuals]. Data are presented as mean differences [95% prediction intervals] for both sexes. RESULTS: Aortic systolic BP (SBP) was lower than brachial SBP [male, -22.3 (-31.2, -13.3) mmHg; female, -17.8 (-25.5, -10.0) mmHg]. Differences between aortic and brachial diastolic BP (DBP) were minimal. Based on brachial BP measurements, 101 male individuals (6%) and 22 female individuals (1%) were classified as hypertensive. In contrast, only nine male individuals (<1%) and 14 female individuals (<1%) met the criteria for hypertension based on aortic BP, and the predictive value of brachial BP for aortic hypertension was poor (positive-predictive value = 13.8%). Participants with aortic hypertension had a higher left ventricular mass index than those with brachial hypertension. CONCLUSION: Brachial BP substantially overestimates aortic BP in adolescents because of marked aortic-to-brachial pulse pressure amplification. The use of brachial BP measurement may result in an overdiagnosis of hypertension during screening in adolescence.

Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction.

The pathogenesis of exercise intolerance and persistent fatigue which can follow an infection with the SARS-CoV-2 virus ("long COVID") is not fully understood. Cases were recruited from a long COVID clinic (N = 32; 44 ± 12 years; 10 (31%) men), and age-/sex-matched healthy controls (HC) (N = 19; 40 ± 13 years; 6 (32%) men) from University College London staff and students. We assessed exercise performance, lung and cardiac function, vascular health, skeletal muscle oxidative capacity, and autonomic nervous system (ANS) function. Key outcome measures for each physiological system were compared between groups using potential outcome means (95% confidence intervals) adjusted for potential confounders. Long COVID participant outcomes were compared to normative values. When compared to HC, cases exhibited reduced oxygen uptake efficiency slope (1847 (1679, 2016) vs. 2176 (1978, 2373) mL/min, p = 0.002) and anaerobic threshold (13.2 (12.2, 14.3) vs. 15.6 (14.4, 17.2) mL/kg/min, p < 0.001), and lower oxidative capacity, measured using near infrared spectroscopy (τ: 38.7 (31.9, 45.6) vs. 24.6 (19.1, 30.1) s, p = 0.001). In cases, ANS measures fell below normal limits in 39%. Long COVID is associated with reduced measures of exercise performance and skeletal muscle oxidative capacity in the absence of evidence of microvascular dysfunction, suggesting mitochondrial pathology. There was evidence of attendant ANS dysregulation in a significant proportion. These multisystem factors might contribute to impaired exercise tolerance in long COVID sufferers.

Associations of carotid atherosclerosis with cognitive function and brain health: Findings from a UK tri-ethnic cohort study (Southall and Brent Revisited).

Background: Cognitive function has an important role in determining the quality of life of older adults. Cardiovascular disease (CVD) is common in older people and may compromise cognitive performance; however, the extent to which this is related to carotid atherosclerosis is unclear. Aim: We investigated associations between carotid atherosclerosis and cognitive function and neuroimaging markers of brain health in a UK multi-ethnic community-based sample including older people of European, South Asian, and African-Caribbean ethnicity. Methods: Carotid plaques and intima-media thickness (cIMT) were assessed using ultrasound in 985 people (mean age 73.2y, 56 % male). Associations of carotid atherosclerosis with cognitive function (memory, executive function, language and CSI-D, a global measure of cognitive state) and neuroimaging measures (total brain volume, hippocampal volume, white matter (WM) lesion volume and coalescence score) were analysed using regression analyses, with and without adjustment for potential confounders using two models: 1) adjustment for age, sex, and ethnicity; 2) model 1 plus education, physical activity category, body mass index, hypertension, diabetes, total and high density lipoprotein cholesterol, atrial fibrillation, smoking, previous CVD, alcohol consumption, and presence of chronic kidney disease. Results: People with carotid plaque or higher cIMT had lower CSI-D score, poorer memory poorer executive function and higher WM lesion volume and coalescence. Language was poorer in people with plaque but was not correlated with cIMT. Associations with plaque were preserved after full adjustment (model 2) but relationships for cIMT were attenuated. Associations with other plaque characteristics were generally unconvincing after adjustment. Conclusions: This multi-ethnic cohort study provides evidence that presence of carotid plaque, is associated with poorer cognitive function and brain health.

Does 3D-speckle tracking echocardiography improve prediction of major cardiovascular events in a multi-ethnic general population? A Southall and Brent Revisited (SABRE) cohort study.

3D-speckle tracking echocardiography(3D-STE) allows simultaneous assessment of ejection fraction(EF) and multidirectional strains, but its prognostic utility in the general population is unknown. We investigated if 3D-STE strains predicted a composite of major cardiac endpoints(MACE) beyond cardiovascular risk factors(CVDRF), and whether they were superior to 3D-EF. 529 participants in SABRE, a UK-based tri-ethnic general population cohort (69±6y; 76.6% male) with acceptable 3D-STE imaging were studied. Associations between 3D-EF or multidirectional myocardial strains and MACE(coronary heart disease(fatal/non-fatal), heart failure hospitalization, new-onset arrhythmia and cardiovascular mortality) were determined using Cox regression including adjustment for CVDRF and 2D-EF. Whether 3D-EF, global longitudinal strain(3D-GLS) and principle tangential strain(3D-PTS/3D-strain) improved cardiovascular risk stratification over CVDRF was investigated using a likelihood ratio test on a series of nested Cox proportional hazards models and Harrell's C statistics. During follow-up(median, 12y), there were 92 events. 3D-EF, 3D-GLS and 3D-PTS and 3D-RS were associated with MACE in unadjusted and models adjusted for CVDRF but not CVDRF+2D-EF. Compared to 3D-EF, both 3D-GLS and 3D-PTS slightly improved the predictive value over CVDRF for MACE, but the improvement was modest(C statistic increased from 0.698(0.647, 0.749) to 0.715(0.663, 0.766) comparing CVDRF with CVDRF +3D-GLS). 3D-STE-derived LV myocardial strains predicted MACE in a multi-ethnic general population sample of elderly individuals from the UK; however the added prognostic value of 3D-STE myocardial strains was small.

Sex-differences in associations of LV structure and function measured by echocardiography with long-term risk of mortality and cardiovascular morbidity.

Background: Three-dimensional echocardiography (3DE) measures of the left ventricle (LV) predict outcomes in high risk individuals, but their prognostic value in the general population is unknown. We aimed to establish whether 3DE was associated with mortality and morbidity in a multi-ethnic community-based sample, if associations differed by sex, and explored potential mechanisms explaining sex differences. Methods: 922 individuals (69.7 ± 6.2 years; 717 men) from the SABRE study underwent a health examination including echocardiography. Associations between 3DE LV measures (ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), LV remodeling index (LVRI) and LV sphericity index (LVSI), and all-cause mortality and a composite cardiovascular endpoint [comprising new onset (non)fatal coronary heart disease, heart failure hospitalization, new-onset arrhythmias and cardiovascular mortality] were determined using multivariable Cox regression over a median follow-up of 8 years (all-cause mortality) and 7 years (composite cardiovascular endpoint). Results: There were 123 deaths and 151 composite cardiovascular endpoints. Lower EF, higher LV volumes and LVSI were associated with increased all-cause mortality, and higher LV volumes were associated with the composite cardiovascular endpoint independent of potential confounders. Associations between LV volumes, LVRI, LVSI, and mortality differed by sex (p interaction <0.1). In men increased LV volumes and LVSI and decreased LVRI and EF were associated with higher mortality, but associations were null or reversed in women (hazard ratios (95% CI) men vs. women: EDV 1.25 (1.05, 1.48) vs. 0.54 (0.26, 1.10); ESV, 1.36 (1.12, 1.63) vs. 0.59 (0.33, 1.04); LVRI, 0.79 (0.64, 0.96) vs. 1.70 (1.03, 2.80); LVSI, 1.27 (1.05, 1.54) vs. 0.61 (0.32, 1.15); and EF, 0.78 (0.66, 0.93) vs. 1.27 (0.69, 2.33). Similar sex differences were observed for associations with the composite cardiovascular outcome. Adjustment for LV diastolic stiffness and arterial stiffness marginally attenuated these differences. Conclusions: 3DE measures of LV volume and remodeling are associated with all-cause mortality and cardiovascular morbidity; however, some associations differ by sex. Sex-differences in LV remodeling patterns may influence mortality and morbidity risk in the general population.

Skeletal Muscle Tissue Saturation Changes Measured Using Near Infrared Spectroscopy During Exercise Are Associated With Post-Occlusive Reactive Hyperaemia.

Measuring local haemodynamics in skeletal muscle has the potential to provide valuable insight into the oxygen delivery to tissue, especially during high demand situations such as exercise. The aim of this study was to compare the skeletal muscle microvascular response during post-occlusive reactive hyperaemia (PORH) with the response to exercise, each measured using near-infrared spectroscopy (NIRS) and to establish if associations exist between muscle measures and exercise capacity or sex. Participants were from a population-based cohort study, the Southall and Brent Revisited (SABRE) study. Skeletal muscle measures included changes in tissue saturation index at the onset of exercise (∆TSIBL-INC) and across the whole of exercise (∆TSIBL-EE), time to 50%, 95% and 100% PORH, rate of PORH recovery, area under the curve (AUC) and total oxygenated Haemoglobin (oxy-Hb) change during PORH. Exercise capacity was measured using a 6-min stepper test (6MST). Analysis was by multiple linear regression. In total, 558 participants completed the 6MST with NIRS measures of TSI (mean age±SD: 73 ± 7years, 59% male). A sub-set of 149 participants also undertook the arterial occlusion. Time to 100% PORH, recovery rate, AUC and ∆oxy-Hb were all associated with ∆TSIBL-EE (ß-coefficient (95%CI): 0.05 (0.01, 0.09), p = 0.012; -47 (-85, -9.9), p = 0.014; 1.7 (0.62, 2.8), p = 0.002; 0.04 (0.002.0.108), p = 0.041, respectively). Time to 95% & 100% PORH, AUC and ∆oxy-Hb were all associated with ∆TSIBL-INC (ß-coefficient (95%CI): -0.07 (-0.12,-0.02), p = 0.02; -0.03 (-0.05, -0.003), p = 0.028; 0.85 (0.18, 1.5), p = 0.013 & 0.05 (0.02, 0.09), p = 0.001, respectively). AUC and ∆Oxy-Hb were associated with steps achieved (ß-coefficient (95%CI): 18.0 (2.3, 33.7), p = 0.025; 0.86 (0.10, 1.6), p = 0.027). ∆TSIBL-EE was associated with steps and highest VO2 (1.7 (0.49, 2.9), p = 0.006; 7.7 (3.2, 12.3), p = 0.001). ∆TSIBL-INC was associated with steps and VO2 but this difference was attenuated towards the null after adjustment for age, sex and ethnicity. ∆TSIBL-EE was greater in women (3.4 (0.4, 8.9) versus 2.1 (0.3, 7.4), p = 0.017) and ∆TSIBL-INC was lower in women versus men (2.4 (0.2, 10.2) versus 3.2 (0.2, 18.2), p = 0.016). These Local microvascular NIRS-measures are associated with exercise capacity in older adults and several measures can detect differences in microvascular reactivity between a community-based sample of men and women.

Antihypertensive treatment effect on exercise blood pressure and exercise capacity in older adults.

BACKGROUND: An exaggerated blood pressure (BP) response to exercise and low exercise capacity are risk factors for cardiovascular disease (CVD). The effect of pharmacological antihypertensive treatment on exercise BP in older adults is largely unknown. This study investigates these effects accounting for differences in exercise capacity. METHODS: Participants enrolled in the Southall and Brent Revisited (SABRE) study undertook a 6-min stepper test with expired gas analysis and BP measured throughout exercise. Participants were stratified by antihypertensive treatment status and resting BP control. Exercise systolic and diastolic BP (exSBP and exDBP) were compared between groups using potential outcome means [95% confidence intervals (CIs)] adjusted for exercise capacity. Exercise capacity was also compared by group. RESULTS: In total, 659 participants were included (mean age ±â€ŠSD: 73 ±â€Š6.6 years, 57% male). 31% of normotensive and 23% of hypertensive older adults with controlled resting BP had an exaggerated exercise BP. ExSBP was similar between normotensive and treated/controlled individuals [mean (95%CI): 180 (176 184) mmHg vs. 177 (173 181) mmHg, respectively] but was higher in treated/uncontrolled and untreated/uncontrolled individuals [mean (95% CI): 194 (190 197) mmHg, P  < 0.001 and 199 (194 204) mmHg, P  < 0.001, respectively]; these differences persisted after adjustment for exercise capacity and other confounders. Exercise capacity was lower in treated vs. normotensive individuals [mean (95% CI) normotensive: 16.7 (16.0,17.4) ml/kg/min]; treated/controlled: 15.5 (14.8,16.1) ml/kg/min, P  = 0.009; treated/uncontrolled: [15.1 (14.5,15.7) ml/kg per min, P  = 0.001] but was not reduced in untreated/uncontrolled individuals [mean (95% CI): 17.0 (16.1,17.8) ml/kg per min, P  = 0.621]. CONCLUSION: Irrespective of resting BP control and despite performing less exercise, antihypertensive treatment does not fully mitigate an exaggerated BP response to exercise suggesting residual CVD risk in older adults.

Association between carotid atherosclerosis and brain activation patterns during the Stroop task in older adults: An fNIRS investigation.

There is an increasing body of evidence suggesting that vascular disease could contribute to cognitive decline and overt dementia. Of particular interest is atherosclerosis, as it is not only associated with dementia, but could be a potential mechanism through which cardiovascular disease directly impacts brain health. In this work, we evaluated the differences in functional near infrared spectroscopy (fNIRS)-based measures of brain activation, task performance, and the change in central hemodynamics (mean arterial pressure (MAP) and heart rate (HR)) during a Stroop color-word task in individuals with atherosclerosis, defined as bilateral carotid plaques (n = 33) and healthy age-matched controls (n = 33). In the healthy control group, the left prefrontal cortex (LPFC) was the only region showing evidence of activation when comparing the incongruous with the nominal Stroop test. A smaller extent of brain activation was observed in the Plaque group compared with the healthy controls (1) globally, as measured by oxygenated hemoglobin (p = 0.036) and (2) in the LPFC (p = 0.02) and left sensorimotor cortices (LMC)(p = 0.008) as measured by deoxygenated hemoglobin. There were no significant differences in HR, MAP, or task performance (both in terms of the time required to complete the task and number of errors made) between Plaque and control groups. These results suggest that carotid atherosclerosis is associated with altered functional brain activation patterns despite no evidence of impaired performance of the Stroop task or central hemodynamic changes.

Corrigendum: Imaging Protocol, Feasibility, and Reproducibility of Cardiovascular Phenotyping in a Large Tri-Ethnic Population-Based Study of Older People: The Southall and Brent Revisited (SABRE) Study.

[This corrects the article DOI: 10.3389/fcvm.2020.591946.].

Age matters: differences in exercise-induced cardiovascular remodelling in young and middle aged healthy sedentary individuals.

AIMS: Remodelling of the cardiovascular system (including heart and vasculature) is a dynamic process influenced by multiple physiological and pathological factors. We sought to understand whether remodelling in response to a stimulus, exercise training, altered with healthy ageing. METHODS: A total of 237 untrained healthy male and female subjects volunteering for their first time marathon were recruited. At baseline and after 6 months of unsupervised training, race completers underwent tests including 1.5T cardiac magnetic resonance, brachial and non-invasive central blood pressure assessment. For analysis, runners were divided by age into under or over 35 years (U35, O35). RESULTS: Injury and completion rates were similar among the groups; 138 runners (U35: n = 71, women 49%; O35: n = 67, women 51%) completed the race. On average, U35 were faster by 37 minutes (12%). Training induced a small increase in left ventricular mass in both groups (3 g/m2, P < 0.001), but U35 also increased ventricular cavity sizes (left ventricular end-diastolic volume (EDV)i +3%; left ventricular end-systolic volume (ESV)i +8%; right ventricular end-diastolic volume (EDV)i +4%; right ventricular end-systolic volume (ESV)i +5%; P < 0.01 for all). Systemic aortic compliance fell in the whole sample by 7% (P = 0.020) and, especially in O35, also systemic vascular resistance (-4% in the whole sample, P = 0.04) and blood pressure (systolic/diastolic, whole sample: brachial -4/-3 mmHg, central -4/-2 mmHg, all P < 0.001; O35: brachial -6/-3 mmHg, central -6/-4 mmHg, all P < 0.001). CONCLUSION: Medium-term, unsupervised physical training in healthy sedentary individuals induces measurable remodelling of both heart and vasculature. This amount is age dependent, with predominant cardiac remodelling when younger and predominantly vascular remodelling when older.

Sex differences in the contribution of different physiological systems to physical function in older adults.

Having the physical function to undertake activities of daily living (ADLs) is essential in order to maintain independence. The aim of this study is to investigate factors associated with physical function in older adults and determine if these associations differ in men versus women. In total, 726 participants (57% men; 73±7 years old) from a population-based cohort, the Southall and Brent Revisited (SABRE) study, completed questionnaires permitting a physical function score (PFS) to be calculated. Detailed phenotyping was performed including cardiovascular (echocardiography and macrovascular and microvascular functions), skeletal muscle (grip strength and oxidative capacity) and lung (pulmonary) function measurements. In a sub-group, maximal aerobic capacity was estimated from a sub-maximal exercise test. In women versus men, the association between grip strength and PFS was nearly 3 times stronger, and the association between microvascular dysfunction and PFS was over 5 times stronger (standardized ß-coefficient (95% CI) 0.34 (0.22, 0.45) versus 0.11 (0.01,0.22) and -0.27 (-0.37, -0.17) versus -0.05 (-0.14, 0.04), respectively). In men, the association between cardiorespiratory fitness and PFS was 3 times greater than that in women (standardized ß-coefficient (95% CI) 0.33 (0.22, 0.45) versus 0.10 (-0.04, 0.25). Cardiovascular, skeletal muscle and pulmonary factors all contribute to self-reported physical function, but the relative pattern of contribution differs by sex. Grip strength and microvascular function are most strongly associated with physical function in women while cardiorespiratory fitness is most strongly associated with physical function in men. This is relevant to the design of effective interventions that target maintenance of physical function in old age.

Imaging Protocol, Feasibility, and Reproducibility of Cardiovascular Phenotyping in a Large Tri-Ethnic Population-Based Study of Older People: The Southall and Brent Revisited (SABRE) Study.

Background: People of South Asian and African Caribbean ethnicities living in UK have a high risk of cardiometabolic disease. Limited data exist regarding detailed cardiometabolic phenotyping in this population. Methods enabling this are widely available, but the practical aspects of undertaking such studies in large and diverse samples are seldom reported. Methods: The Southall and Brent Revisited (SABRE) study is the UK's largest tri-ethnic longitudinal cohort. Over 1,400 surviving participants (58-85 years) attended the 2nd study visit (2008-2011); during which, comprehensive cardiovascular phenotyping, including 3D-echocardiography [3D-speckle-tracking (3D-STE)], computed tomography, coronary artery calcium scoring, pulse wave velocity, central blood pressure, carotid artery ultrasound, and retinal imaging, were performed. We describe the methods used with the aim of providing a guide to their feasibility and reproducibility in a large tri-ethnic population-based study of older people. Results: Conventional echocardiography and all vascular measurements showed high feasibility (>90% analyzable of clinic attendees), but 3D-echocardiography (3DE) and 3D-STE were less feasible (76% 3DE acquisition feasibility and 38% 3D-STE feasibility of clinic attendees). 3D-STE feasibility differed by ethnicity, being lowest in South Asian participants and highest in African Caribbean participants (p < 0.0001). Similar trends were observed in men (P < 0.0001) and women (P = 0.005); however, in South Asians, there were more women with unreadable 3D-images compared to men (67 vs. 58%). Intra- and inter-observer variabilities were excellent for most of conventional and advanced echocardiographic measures. The test-retest reproducibility was good-excellent and fair-good for conventional and advanced echocardiographic measures, respectively, but lower than when re-reading the same images. All vascular measures demonstrated excellent or fair-good reproducibility. Conclusions: We describe the feasibility and reproducibility of detailed cardiovascular phenotyping in an ethnically diverse population. The data collected will lead to a better understanding of why people of South Asian and African Caribbean ancestry are at elevated risk of cardiometabolic diseases.

Study Protocol - Insight 46 Cardiovascular: A Sub-study of the MRC National Survey of Health and Development.

The commonest causes of dementia are Alzheimer's disease and vascular cognitive impairment. Although these conditions have been viewed as distinct entities, there is increasing evidence that neurodegenerative and vascular pathologies interact or overlap to cause cognitive decline, and that at least in some cases individuals at risk of cognitive decline exhibit abnormal cardiovascular physiology long before emergence of disease. However, the mechanisms linking haemodynamic disturbances with cognitive impairment and the various pathologies that cause dementia are poorly understood. A sub-sample of 502 participants from the Medical Research Council National Survey of Health and Development (NSHD) have participated in the first visit of a neuroscience sub-study referred to as Insight 46, where clinical, cognitive, imaging, and lifestyle data have been collected for the purpose of elucidating the pathological changes preceding dementia. This paper outlines the cardiovascular phenotyping performed in the follow-up visit of Insight 46, with the study participants now aged 74. In addition to standard cardiovascular assessments such as blood pressure measurements, echocardiography, and electrocardiography (ECG), functional Near Infrared Spectroscopy (fNIRS) has been included to provide an assessment of cerebrovascular function. A detailed description of the fNIRS protocol along with preliminary results from pilot data is presented. The combination of lifestyle data, brain structure/function, cognitive performance, and cardiovascular health obtained not only from Insight 46, but also from the whole NSHD provides an exciting opportunity to advance our understanding of the cardiovascular mechanisms underlying dementia and cognitive decline, and identify novel targets for intervention.

Correction to: Improvements in Skeletal Muscle Can Be Detected Using Broadband NIRS in First-Time Marathon Runners.

This chapter was inadvertently published as an open access chapter. However, the open access for this chapter has now been reverted.

Recreational marathon running does not cause exercise-induced left ventricular hypertrabeculation.

BACKGROUND: Marathon running in novices represents a natural experiment of short-term cardiovascular remodeling in response to running training. We examine whether this stimulus can produce exercise-induced left ventricular (LV) trabeculation. METHODS: Sixty-eight novice marathon runners aged 29.5 ± 3.2 years had indices of LV trabeculation measured by echocardiography and cardiac magnetic resonance imaging 6 months before and 2 weeks after the 2016 London Marathon race, in a prospective longitudinal study. RESULTS: After 17 weeks unsupervised marathon training, indices of LV trabeculation were essentially unchanged. Despite satisfactory inter-observer agreement in most methods of trabeculation measurement, criteria defining abnormally hypertrabeculated cases were discordant with each other. LV hypertrabeculation was a frequent finding in young, healthy individuals with no subject demonstrating clear evidence of a cardiomyopathy. CONCLUSION: Training for a first marathon does not induce LV trabeculation. It remains unclear whether prolonged, high-dose exercise can create de novo trabeculation or expose concealed trabeculation. Applying cut off values from published LV noncompaction cardiomyopathy criteria to young, healthy individuals risks over-diagnosis.

Cardiovascular Remodeling Experienced by Real-World, Unsupervised, Young Novice Marathon Runners.

AIMS: Marathon running is a popular ambition in modern societies inclusive of non-athletes. Previous studies have highlighted concerning transient myocardial dysfunction and biomarker release immediately after the race. Whether this method of increasing physical activity is beneficial or harmful remains a matter of debate. We examine in detail the real-world cardiovascular remodeling response following competition in a first marathon. METHODS: Sixty-eight novice marathon runners (36 men and 32 women) aged 30 ± 3 years were investigated 6 months before and 2 weeks after the 2016 London Marathon race in a prospective observational study. Evaluation included electrocardiography, cardiopulmonary exercise testing, echocardiography, and cardiovascular magnetic resonance imaging. RESULTS: After 17 weeks unsupervised marathon training, runners revealed a symmetrical, eccentric remodeling response with 3-5% increases in left and right ventricular cavity sizes, respectively. Blood pressure (BP) fell by 4/2 mmHg (P < 0.01) with reduction in arterial stiffness, despite only 11% demonstrating a clinically meaningful improvement in peak oxygen consumption with an overall non-significant 0.4 ml/min/kg increase in peak oxygen consumption (P = 0.14). CONCLUSION: In the absence of supervised training, exercise-induced cardiovascular remodeling in real-world novice marathon runners is more modest than previously described and occurs even without improvement in cardiorespiratory fitness. The responses are similar in men and women, who experience a beneficial BP reduction and no evidence of myocardial fibrosis or persistent edema, when achieving average finishing times.

Training for a First-Time Marathon Reverses Age-Related Aortic Stiffening.

BACKGROUND: Aging increases aortic stiffness, contributing to cardiovascular risk even in healthy individuals. Aortic stiffness is reduced through supervised training programs, but these are not easily generalizable. OBJECTIVES: The purpose of this study was to determine whether real-world exercise training for a first-time marathon can reverse age-related aortic stiffening. METHODS: Untrained healthy individuals underwent 6 months of training for the London Marathon. Assessment pre-training and 2 weeks post-marathon included central (aortic) blood pressure and aortic stiffness using cardiovascular magnetic resonance distensibility. Biological "aortic age" was calculated from the baseline chronological age-stiffness relationship. Change in stiffness was assessed at the ascending (Ao-A) and descending aorta at the pulmonary artery bifurcation (Ao-P) and diaphragm (Ao-D). Data are mean changes (95% confidence intervals [CIs]). RESULTS: A total of 138 first-time marathon completers (age 21 to 69 years, 49% male) were assessed, with an estimated training schedule of 6 to 13 miles/week. At baseline, a decade of chronological aging correlated with a decrease in Ao-A, Ao-P, and Ao-D distensibility by 2.3, 1.9, and 3.1 × 10-3 mm Hg-1, respectively (p < 0.05 for all). Training decreased systolic and diastolic central (aortic) blood pressure by 4 mm Hg (95% CI: 2.8 to 5.5 mm Hg) and 3 mm Hg (95% CI: 1.6 to 3.5 mm Hg). Descending aortic distensibility increased (Ao-P: 9%; p = 0.009; Ao-D: 16%; p = 0.002), while remaining unchanged in the Ao-A. These translated to a reduction in "aortic age" by 3.9 years (95% CI: 1.1 to 7.6 years) and 4.0 years (95% CI: 1.7 to 8.0 years) (Ao-P and Ao-D, respectively). Benefit was greater in older, male participants with slower running times (p < 0.05 for all). CONCLUSIONS: Training for and completing a marathon even at relatively low exercise intensity reduces central blood pressure and aortic stiffness-equivalent to a ∼4-year reduction in vascular age. Greater rejuvenation was observed in older, slower individuals.

Improvements in Skeletal Muscle Can Be Detected Using Broadband NIRS in First-Time Marathon Runners.

Skeletal muscle metabolic function is known to respond positively to endurance exercise interventions, such as marathon training. Studies investigating skeletal muscle have typically used muscle biopsy samples or magnetic resonance spectroscopy (MRS) to interrogate metabolic function. We aimed to non-invasively detect exercise-training-induced improvements in muscle function using broadband near-infrared spectroscopy (NIRS). We used NIRS to determine concentration changes in oxygenated haemoglobin (HbO2) and the oxidation state of cytochrome-c-oxidase (oxCCO) in gastrocnemius during arterial occlusion in 14 volunteers. We also used a cardio-pulmonary exercise test (CPET) to assess peak total body oxygen uptake (peakVO2; a measure of fitness). Measurements were made at baseline (BL) which was prior to a period of at least 16 weeks of training for the 2017 London Marathon, and then within 3 weeks after completion of the marathon, follow-up (FU). We observed an increase in locally measured muscle oxygen consumption and rate of oxCCO concentration change, but not in cardio-respiratory fitness measured as whole-body peak oxygen consumption (peakVO2).

Type 2 diabetes does not account for ethnic differences in exercise capacity or skeletal muscle function in older adults.

AIMS/HYPOTHESIS: The aim of this study was to compare exercise capacity, strength and skeletal muscle perfusion during exercise, and oxidative capacity between South Asians, African Caribbeans and Europeans, and determine what effect ethnic differences in the prevalence of type 2 diabetes has on these functional outcomes. METHODS: In total, 708 participants (aged [mean±SD] 73 ± 7 years, 56% male) were recruited from the Southall and Brent Revisited (SABRE) study, a UK population-based cohort comprised of Europeans (n = 311) and South Asian (n = 232) and African Caribbean (n = 165) migrants. Measurements of exercise capacity using a 6 min stepper test (6MST), including measurement of oxygen consumption ([Formula: see text]) and grip strength, were performed. Skeletal muscle was assessed using near infrared spectroscopy (NIRS); measures included changes in tissue saturation index (∆TSI%) with exercise and oxidative capacity (muscle oxygen consumption recovery, represented by a time constant [τ]). Analysis was by multiple linear regression. RESULTS: When adjusted for age and sex, in South Asians and African Caribbeans, exercise capacity was reduced compared with Europeans ([Formula: see text] [ml min-1 kg-1]: ß = -1.2 [95% CI -1.9, -0.4], p = 0.002, and ß -1.7 [95% CI -2.5, -0.8], p < 0.001, respectively). South Asians had lower and African Caribbeans had higher strength compared with Europeans (strength [kPa]: ß = -9 [95% CI -12, -6), p < 0.001, and ß = 6 [95% CI 3, 9], p < 0.001, respectively). South Asians had greater decreases in TSI% and longer τ compared with Europeans (∆TSI% [%]: ß = -0.9 [95% CI -1.7, -0.1), p = 0.024; τ [s]: ß = 11 [95% CI 3, 18], p = 0.006). Ethnic differences in [Formula: see text] and grip strength remained despite adjustment for type 2 diabetes or HbA1c (and fat-free mass for grip strength). However, the differences between Europeans and South Asians were no longer statistically significant after adjustment for other possible mediators or confounders (including physical activity, waist-to-hip ratio, cardiovascular disease or hypertension, smoking, haemoglobin levels or ß-blocker use). The difference in ∆TSI% between Europeans and South Asians was marginally attenuated after adjustment for type 2 diabetes or HbA1c and was also no longer statistically significant after adjusting for other confounders; however, τ remained significantly longer in South Asians vs Europeans despite adjustment for all confounders. CONCLUSIONS/INTERPRETATION: Reduced exercise capacity in South Asians and African Caribbeans is unexplained by higher rates of type 2 diabetes. Poorer exercise tolerance in these populations, and impaired muscle function and perfusion in South Asians, may contribute to the higher morbidity burden of UK ethnic minority groups in older age.