Left ventricular strain-volume loops in bicuspid aortic valve disease: new insights in cardiomechanics.

Aims: By combining temporal changes in left ventricular (LV) global longitudinal strain (GLS) with LV volume, LV strain-volume loops can assess cardiac function across the cardiac cycle. This study compared LV strain-volume loops between bicuspid aortic valve (BAV) patients and controls, and investigated the loop's prognostic value for clinical events. Methods and results: From a prospective cohort of congenital heart disease patients, BAV patients were selected and compared with healthy volunteers, who were matched for age and sex at group level. GLS analysis from apical views was used to construct strain-volume loops. Associations with clinical events, i.e. a composite of all-cause mortality, heart failure, arrhythmias, and aortic valve replacement, were assessed by Cox regression. A total of 113 BAV patients were included (median age 32 years, 40% female). BAV patients demonstrated lower Sslope (0.21%/mL, [Q1-Q3: 0.17-0.28] vs. 0.27%/mL [0.24-0.34], P < 0.001) and ESslope (0.19%/mL [0.12-0.25] vs. 0.29%/mL [0.21-0.43], P < 0.001) compared with controls, but also greater uncoupling during early (0.48 ± 1.29 vs. 0.05 ± 1.21, P = 0.04) and late diastole (0.66 ± 1.02 vs. -0.07 ± 1.07, P < 0.001). Median follow-up duration was 9.9 [9.3-10.4] years. Peak aortic jet velocity (HR 1.22, P = 0.03), enlarged left atrium (HR 3.16, P = 0.003), E/e' ratio (HR 1.17, P = 0.002), GLS (HR 1.16, P = 0.008), and ESslope (HR 0.66, P = 0.04) were associated with the occurrence of clinical events. Conclusion: Greater uncoupling and lower systolic and diastolic slopes were observed in BAV patients compared with healthy controls, suggesting presence of altered LV cardiomechanics. Moreover, lower ESslope was associated with clinical events, highlighting the strain-volume loop's potential as prognostic marker.

Paravalvular regurgitation after transcatheter aortic valve replacement: incidence, quantification, and prognostic impact.

Transcatheter aortic valve replacement (TAVR) is the standard of care in aortic stenosis with results comparable to surgical aortic valve replacement. However, paravalvular regurgitation (PVR) is more common after TAVR. With the alteration of devices and implantation techniques, the incidence of moderate or more PVR has declined. Mild PVR is still common in around 30% of TAVR patients in low-risk trials. Progression of AS causes myocardial hypertrophy and varying degrees of diastolic dysfunction which may cause heart failure even in combination with small volumes of PVR. Any degree of PVR is associated with an increased risk of overall and cardiovascular mortality. Predictors of PVR are annular eccentricity, severe calcification of the aortic valve, bicuspid aortic valves, and type of prosthesis where balloon-expandable devices are associated with less PVR. PVR is diagnosed using echocardiography, aortic angiogram with or without videodensitometry, haemodynamic parameters, or cardiac magnetic resonance. PVR can be treated using post-dilation, interventional treatment using a vascular plug, or implantation of a second device. Successful post-dilation depends on balloon size which should at least be equal to or >95% of the mean annulus diameter. Implantation of a second device to reduce PVR is successful in ∼90% of cases, either through lengthening of the sealing skirt in case of inadequate position or through further expansion of the index device. Implantation of a vascular plug can successfully reduce PVR and reduce mortality.

Randomized controlled trial of intermittent hypoxia in Parkinson's disease: study rationale and protocol.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that repeated exposure to intermittent hypoxia might have short- and long-term benefits in PD. In a previous exploratory phase I trial, we demonstrated that in-clinic intermittent hypoxia exposure is safe and feasible with short-term symptomatic effects on PD symptoms. The current study aims to explore the safety, tolerability, feasibility, and net symptomatic effects of a four-week intermittent hypoxia protocol, administered at home, in individuals with PD. METHODS/DESIGN: This is a two-armed double-blinded randomized controlled trial involving 40 individuals with mild to moderate PD. Participants will receive 45 min of normobaric intermittent hypoxia (fraction of inspired oxygen 0.16 for 5 min interspersed with 5 min normoxia), 3 times a week for 4 weeks. Co-primary endpoints include nature and total number of adverse events, and a feasibility-tolerability questionnaire. Secondary endpoints include Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II and III scores, gait tests and biomarkers indicative of hypoxic dose and neuroprotective pathway induction. DISCUSSION: This trial builds on the previous phase I trial and aims to investigate the safety, tolerability, feasibility, and net symptomatic effects of intermittent hypoxia in individuals with PD. Additionally, the study aims to explore induction of relevant neuroprotective pathways as measured in plasma. The results of this trial could provide further insight into the potential of hypoxia-based therapy as a novel treatment approach for PD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05948761 (registered June 20th, 2023).

Cardiac rehabilitation and adverse events among adult patients with simple congenital heart disease and heart failure.

Aims: Improved care has resulted in prolonged survival of patients with congenital heart disease (ConHD), increasing age-related cardiovascular comorbidities. Although cardiovascular rehabilitation (CR) represents evidence-based care for heart failure (HF), the clinical impact of CR in patients with ConHD who developed HF during adulthood is unclear. We investigated 12-month mortality and morbidity in patients with simple ConHD diagnosed with HF with CR versus without CR. Methods: A retrospective cohort study was conducted for the time period February 2004 - February 2024. Utilizing TriNetX, a global federated health research network, a real-world dataset of simple ConHD patients was acquired to compare patients with vs. without (controls) prescription for exercise-based CR. Patients were propensity-score matched for age, sex, ethnicity, comorbidities, procedures, and medication. The primary outcome was a composite of all-cause mortality, ischemic stroke, and acute coronary syndrome (major adverse cardiovascular events; MACE) within 12 months. Results: Following propensity score matching, the total cohort consisted of 6,866 simple ConHD patients with HF. CR was associated with significantly lower odds for MACE (odds ratio (OR) 0.61 [95 % confidence interval (CI): 0.54-0.69]) and its individual components all-cause mortality (OR 0.40 [95 % CI 0.33-0.47]) and ischemic stroke (OR 0.75 [95 % CI 0.64-0.88]), but not acute coronary syndrome (OR 1.24 [95 % CI 0.91-1.69]). Conclusion: CR was associated with significantly lower 12-month MACE in patients with simple ConHD with concomitant HF compared to usual care.

Left and right ventricular strain-volume/area loops: a narrative review of current physiological understanding and potential clinical value.

Traditionally, echocardiography is used for volumetric measurements to aid in assessment of cardiac function. Multiple echocardiographic-based assessment techniques have been developed, such as Doppler ultrasound and deformation imaging (e.g., peak global longitudinal strain (GLS)), which have shown to be clinically relevant. Volumetric changes across the cardiac cycle can be related to deformation, resulting in the Ventricular Strain-Volume/Area Loop. These Loops allow assessment of the dynamic relationship between longitudinal strain change and volumetric change across both systole and diastole. This integrated approach to both systolic and diastolic function assessment may offer additional information in conjunction with traditional, static, measures of cardiac function or structure. The aim of this review is to summarize our current understanding of the Ventricular Strain-Volume/Area Loop, describe how acute and chronic exposure to hemodynamic stimuli alter Loop characteristics, and, finally, to outline the potential clinical value of these Loops in patients with cardiovascular disease. In summary, several studies observed Loop changes in different hemodynamic loading conditions and various (patho)physiological conditions. The diagnostic and prognostic value, and physiological interpretation remain largely unclear and have been addressed only to a limited extent.

Intensive antihypertensive treatment does not lower cerebral blood flow or cause orthostatic hypotension in frail older adults.

This study aimed to examine the effects of intensive antihypertensive treatment (AHT), i.e., systolic blood pressure target ≤ 140 mmHg, on cerebral blood flow, cerebral autoregulation, and orthostatic hypotension, in a representative population of frail older adults. Fourteen frail hypertensive patients (six females; age 80.3 ± 5.2 years; Clinical Frailty Scale 4-7; unattended SBP ≥ 150 mmHg) underwent measurements before and after a median 7-week AHT targeting SBP ≤ 140 mmHg. Transcranial Doppler measurements of middle cerebral artery velocity (MCAv), reflecting changes in cerebral blood flow (CBF), were combined with finger plethysmography recordings of continuous BP. Transfer function analysis assessed cerebral autoregulation (CA). ANCOVA analysed AHT-induced changes in CBF and CA and evaluated non-inferiority of the relative change in CBF (margin: -10%; covariates: pre-AHT values and AHT-induced relative mean BP change). McNemar-tests analysed whether the prevalence of OH and initial OH, assessed by sit/supine-to-stand challenges, increased with AHT. Unattended mean arterial pressure decreased by 15 mmHg following AHT. Ten (71%) participants had good quality TCD assessments. Non-inferiority was confirmed for the relative change in MCAv (95%CI: -2.7, 30.4). CA remained normal following AHT (P > 0.05), and the prevalence of OH and initial OH did not increase (P ≥ 0.655). We found that AHT in frail, older patients does not reduce CBF, impair autoregulation, or increase (initial) OH prevalence. These observations may open doors for more intensive AHT targets upon individualized evaluation and monitoring of hypertensive frail patients.Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT05529147; September 1, 2022) and EudraCT (2022-001283-10; June 28, 2022).

Effectiveness and cost-effectiveness of a web-based cardiac rehabilitation programme for people with chronic stable angina: protocol for the ACTIVATE (Angina Controlled Trial Investigating the Value of the 'Activate your heart' Therapeutic E-intervention) randomised controlled trial.

INTRODUCTION: Chronic stable angina is common and disabling. Cardiac rehabilitation is routinely offered to people following myocardial infarction or revascularisation procedures and has the potential to help people with chronic stable angina. However, there is insufficient evidence of effectiveness and cost-effectiveness for its routine use in this patient group. The objectives of this study are to compare the effectiveness and cost-effectiveness of the 'Activate Your Heart' cardiac rehabilitation programme for people with chronic stable angina compared with usual care. METHODS AND ANALYSIS: ACTIVATE is a multicentre, parallel-group, two-arm, superiority, pragmatic randomised controlled trial, with recruitment from primary and secondary care centres in England and Wales and a target sample size of 518 (1:1 allocation; allocation sequence by minimisation programme with built-in random element). The study uses secure web-based allocation concealment. The two treatments will be optimal usual care (control) and optimal usual care plus the 'Activate Your Heart' web-based cardiac rehabilitation programme (intervention). Outcome assessment and statistical analysis will be performed blinded; participants will be unblinded. Outcomes will be measured at baseline and at 6 and 12 months' follow-up. Primary outcome will be the UK version of Seattle Angina Questionnaire (SAQ-UK), physical limitations domain at 12 months' follow-up. Secondary outcomes will be the remaining two domains of SAQ-UK, dyspnoea, anxiety and depression, health utility, self-efficacy, physical activity and the incremental shuttle walk test. All safety events will be recorded, and serious adverse events assessed to determine whether they are related to the intervention and expected. Concurrent economic evaluation will be cost-utility analysis from health service perspective. An embedded process evaluation will determine the mechanisms and processes that explain the implementation and impacts of the cardiac rehabilitation programme. ETHICS AND DISSEMINATION: North of Scotland National Health Service Research Ethics Committee approval, reference 21/NS/0115. Participants will provide written informed consent. Results will be disseminated by peer-reviewed publication. TRIAL REGISTRATION NUMBER: ISRCTN10054455.

Relationship of device measured physical activity type and posture with cardiometabolic health markers: pooled dose-response associations from the Prospective Physical Activity, Sitting and Sleep Consortium.

AIMS/HYPOTHESIS: The aim of this study was to examine the dose-response associations of device-measured physical activity types and postures (sitting and standing time) with cardiometabolic health. METHODS: We conducted an individual participant harmonised meta-analysis of 12,095 adults (mean ± SD age 54.5±9.6 years; female participants 54.8%) from six cohorts with thigh-worn accelerometry data from the Prospective Physical Activity, Sitting and Sleep (ProPASS) Consortium. Associations of daily walking, stair climbing, running, standing and sitting time with a composite cardiometabolic health score (based on standardised z scores) and individual cardiometabolic markers (BMI, waist circumference, triglycerides, HDL-cholesterol, HbA1c and total cholesterol) were examined cross-sectionally using generalised linear modelling and cubic splines. RESULTS: We observed more favourable composite cardiometabolic health (i.e. z score <0) with approximately 64 min/day walking (z score [95% CI] -0.14 [-0.25, -0.02]) and 5 min/day stair climbing (-0.14 [-0.24, -0.03]). We observed an equivalent magnitude of association at 2.6 h/day standing. Any amount of running was associated with better composite cardiometabolic health. We did not observe an upper limit to the magnitude of the dose-response associations for any activity type or standing. There was an inverse dose-response association between sitting time and composite cardiometabolic health that became markedly less favourable when daily durations exceeded 12.1 h/day. Associations for sitting time were no longer significant after excluding participants with prevalent CVD or medication use. The dose-response pattern was generally consistent between activity and posture types and individual cardiometabolic health markers. CONCLUSIONS/INTERPRETATION: In this first activity type-specific analysis of device-based physical activity, ~64 min/day of walking and ~5.0 min/day of stair climbing were associated with a favourable cardiometabolic risk profile. The deleterious associations of sitting time were fully attenuated after exclusion of participants with prevalent CVD and medication use. Our findings on cardiometabolic health and durations of different activities of daily living and posture may guide future interventions involving lifestyle modification.

Single and 7-day handgrip and squat exercise prevents endothelial ischemia-reperfusion injury in individuals with cardiovascular disease risk factors.

Whole body exercise provides protection against endothelial ischemia-reperfusion (IR) injury. In this crossover study, we examined the effects of 1) single bout of local exercise (handgrip, squats) on endothelial responses to IR, and 2) if 7 days of daily local exercise bolsters these effects in individuals with cardiovascular disease (CVD) risk factors. Fifteen participants (9 women, 58 ± 5 yr, ≥2 CVD risk factors) attended the laboratory for six visits. Subsequent to familiarization (visit 1), during visit 2 (control) brachial artery flow-mediated dilation (FMD) was measured before and after IR (15-min upper-arm ischemia, 15-min reperfusion). One week later, participants were randomized to 4 × 5-min unilateral handgrip (50% maximal voluntary contraction, 25 rpm) or squat exercises (15 rpm), followed by IR plus FMD measurements. Subsequently, home-based exercise was performed (6 days), followed by another visit to the laboratory for the IR protocol plus FMD measurements (18-24 h after the last exercise bout). After a 2-wk washout period, procedures were repeated with the alternative exercise mode. For a single exercise bout, we found a significant IR injury × exercise mode interaction (P < 0.01) but no main effect of injury (P = 0.08) or condition (P = 0.61). A lower post-IR FMD was evident after control (pre-IR: 4.3 ± 2.1% to post-IR: 2.9 ± 1.9%, P < 0.01) but not after handgrip (pre-IR: 3.8 ± 1.6% to post-IR: 3.4 ± 1.5%, P = 0.31) or squats (pre-IR: 3.9 ± 1.8% to post-IR: 4.0 ± 1.9%, P = 0.74). After 7 days of daily exercise, we found no change in FMD post-IR following handgrip (pre-IR: 4.3 ± 1.9% to post-IR: 4.7 ± 3.2%) or squats (pre-IR: 3.7 ± 2.1% to post-IR: 4.7 ± 3.0%, P > 0.05). Single bouts of dynamic, local exercise (handgrip, squats) provide remote protection against endothelial IR-induced injury in individuals with CVD risk factors, with 1-wk daily, home-based exercise preserving these effects for up to 24 h following the last exercise bout.NEW & NOTEWORTHY We show that single bouts of dynamic handgrip and squat exercise provide remote protection against endothelial ischemia-reperfusion (IR)-induced injury in individuals with cardiovascular disease (CVD) risk factors, with 1-wk daily, home-based exercise preserving these effects for up to 24 h following the last exercise bout.

Exercise-based cardiac rehabilitation in stable angina pectoris: a narrative review on current evidence and underlying physiological mechanisms.

Stable angina pectoris (SAP) is a prevalent condition characterised by a high disease burden. Based on recent evidence, the need for revascularisation in addition to optimal medical treatment to reduce mortality and re-events is heavily debated. These observations may be explained by the fact that revascularisation is targeted at the local flow-limiting coronary artery lesion, while the aetiology of SAP relates to the systemic, inflammatory process of atherosclerosis, causing generalised vascular dysfunction throughout the entire vascular system. Moreover, cardiovascular events are not solely caused by obstructive plaques but are also associated with plaque burden and high-risk plaque features. Therefore, to reduce the risk of cardiovascular events and angina, and thereby improve quality of life, alternative therapeutic approaches to revascularisation should be considered, preferably targeting the cardiovascular system as a whole with a physiological approach. Exercise-based cardiac rehabilitation fits this description and is a promising strategy as a first-line treatment in addition to optimal medical treatment. In this review, we discuss the role of exercise-based cardiac rehabilitation in SAP in relation to the underlying physiological mechanisms, we summarise the existing evidence and highlight future directions.

The Hypoxia Response Pathway: A Potential Intervention Target in Parkinson's Disease?

Parkinson's disease (PD) is a progressive neurodegenerative disorder for which only symptomatic treatments are available. Both preclinical and clinical studies suggest that moderate hypoxia induces evolutionarily conserved adaptive mechanisms that enhance neuronal viability and survival. Therefore, targeting the hypoxia response pathway might provide neuroprotection by ameliorating the deleterious effects of mitochondrial dysfunction and oxidative stress, which underlie neurodegeneration in PD. Here, we review experimental studies regarding the link between PD pathophysiology and neurophysiological adaptations to hypoxia. We highlight the mechanistic differences between the rescuing effects of chronic hypoxia in neurodegeneration and short-term moderate hypoxia to improve neuronal resilience, termed "hypoxic conditioning". Moreover, we interpret these preclinical observations regarding the pharmacological targeting of the hypoxia response pathway. Finally, we discuss controversies with respect to the differential effects of hypoxia response pathway activation across the PD spectrum, as well as intervention dosing in hypoxic conditioning and potential harmful effects of such interventions. We recommend that initial clinical studies in PD should focus on the safety, physiological responses, and mechanisms of hypoxic conditioning, as well as on repurposing of existing pharmacological compounds. © 2023 International Parkinson and Movement Disorder Society.

Left ventricular strain-volume loops and myocardial fibrosis in pediatric patients with Duchenne muscular dystrophy.

BACKGROUND: The left ventricular strain-volume loop (SVL) combines changes in global longitudinal strain (GLS) and LV volume across a cardiac cycle, providing insight into cardiac dynamics. This study explored the association between left ventricular SVL and presence of fibrosis, assessed with late gadolinium enhancement, in patients with Duchenne muscular dystrophy (DMD). METHODS AND RESULTS: 34 pediatric patients with DMD were included. Feature tracking analysis was used to assess endocardial GLS and volumetric measurements to construct the SVL. Mean age at the time of assessment was 14 ± 3 and 11 ± 2 years old (p < 0.01) in the group with (n = 18) versus without fibrosis (n = 16), respectively. Left ventricular ejection fraction was not significantly different between groups (fibrosis: 56.4 ± 3.8% versus without fibrosis: 54.0 ± 6.3%, p = 0.18). After adjusting for age, the late diastolic slope of the SVL was significantly associated with presence of fibrosis (OR 0.39 [95% CI 0.18-0.85]; area under the receiver operating characteristic curve: 0.83 [95% CI 0.70-0.97]) No significant association was observed for peak strain and fibrosis (OR 1.15 [95% CI 0.86-1.546]). CONCLUSION: A lower late diastolic slope of the left ventricular SVL, related to the interplay between longitudinal deformation and volume changes late in diastole, is associated with presence of myocardial fibrosis in pediatric patients with DMD.

Cerebrovascular CO2 reactivity and dynamic cerebral autoregulation through the eighth decade of life and their implications for cognitive decline.

Aging is accompanied by a decrease in cerebral blood flow (CBF), especially in the presence of preclinical cognitive decline. The role of cerebrovascular physiology including regulatory mechanisms of CBF in processes underlying aging and subclinical cognitive decline is, however, not fully understood. We explored changes in cerebrovascular CO2 reactivity and dynamic cerebral autoregulation (dCA) through the eighth decade of life, and their relation with early cognitive decline. After 10.9 years, twenty-eight (age, 80.0 ± 3.5 years; 46% female) out of forty-eight healthy older adults who had participated in a previous study (age at baseline, 70 ± 4 years; 42% female), underwent repeated transcranial Doppler assessments. Linear mixed-model analyses revealed small reductions in cerebrovascular CO2 reactivity with aging (-0.37%/mmHg, P = 0.041), whereas dCA was modestly enhanced (gain: -0.009 cm/s/mmHg, P = 0.038; phase: +8.9 degrees, P = 0.004). These changes were more pronounced in participants who had developed subjective memory complaints at follow-up. Our observations confirm that dCA is not impaired in aging, despite lower cerebral perfusion and cerebrovascular reactivity. Altogether, this unique longitudinal study highlights the involvement of cerebrovascular health in preclinical cognitive decline, which is of clinical relevance in the development of dementia management strategies.

The Effect of Remote Ischemic Postconditioning on Quality of Life and Clinical Events after an Ischemic Stroke.

OBJECTIVES: Repeated remote ischemic postconditioning (rIPostC) may be an easily applicable treatment following ischemic stroke to improve quality of life (QoL) and clinical outcomes. rIPostC consists of repeated, brief periods of limb ischemia (through inflation of a blood pressure cuff), followed by reperfusion. This study investigated the 1-year follow-up of rIPostC on QoL and clinical events. METHODS: As part of a randomized controlled trial, adult patients with an ischemic stroke within 24 hours after onset of symptoms were randomized to repeated rIPostC or sham-conditioning. rIPostC was applied twice daily during hospitalization (maximum of 4 days). QoL and patientreported outcome measures (PROMs) were assessed at 12-week and 1-year follow-ups. Additionally, we explored the effect of repeated rIPostC on clinical events (recurrent cerebrovascular events, hospitalization, and mortality). RESULTS: The trial was preliminarily stopped due to limitations in recruitment after the inclusion of 88 patients (rIPostC: 40; sham-conditioning: 48) (70 years, 68% male). Questionnaires were returned by 69 (78%) and 63 (72%) participants after 12 weeks and 1 year, respectively. The median difference of the stroke-specific QoL between rIPostC and sham-conditioning was 0.05 (p =0.986) and -0.16 (p =0.654) after 12 weeks and 1-year, respectively. No significant effect of rIPostC on the different domains of PROMs was detected. We observed no between-group differences in recurrent cerebrovascular events, hospitalization, or all-cause mortality (Hazard Ratios p >0.05). CONCLUSION: In this exploratory analysis, we observed no significant difference between repeated rIPostC and usual care on QoL and clinical outcomes at 12 weeks and 1 year in patients with an ischemic stroke. CLINICAL TRIAL REGISTRATION NUMBER: NTR6880.

Exercised-based cardiac rehabilitation associates with lower all-cause mortality in patients with primary pulmonary hypertension.

Background: Despite pharmacological therapies to improve outcomes of pulmonary hypertension (PH), poor long-term survival remains. Exercised-based cardiac rehabilitation (ExCR) may be an alternative strategy to improve prognosis. Therefore, using an electronic medical record (EMR) database, the objective of this study was to compare mortality between patients with primary PH with ExCR vs. propensity-matched PH patients without ExCR. Methods: The retrospective analysis was conducted on February 15, 2023 using anonymized data within TriNetX, a global federated health research network. All patients were aged ≥18 years with primary PH recorded in EMRs with at least 1-year follow-up from ExCR. Using logistic regression models, patients with PH with an EMR of ExCR were 1:1 propensity score-matched with PH patients without ExCR for age, sex, race, and comorbidities, and cardiovascular care. Results: In total, 109,736 patients with primary PH met the inclusion criteria for the control group and 784 patients with primary PH met the inclusion criteria for the ExCR cohort. Using the propensity score-matched cohorts, 1-year mortality from ExCR was proportionally lower with 13.6% (n = 101 of 744 patients) in the ExCR cohort compared to 23.3% (n = 174 of 747 patients) in the controls (OR 0.52, 95% CI 0.40-0.68). Conclusion: The present study of 1,514 patients with primary PH suggests that ExCR is associated with 48% lower odds of 1-year mortality, when compared to propensity score-matched patients without ExCR.

Baroreflex sensitivity is impaired in survivors of mild COVID-19 at 3-6 months of clinical recovery; association with carotid artery stiffness.

The association between the stiffening of barosensitive regions of central arteries and the derangements in baroreflex functions remains unexplored in COVID-19 survivors. Fifty-seven survivors of mild COVID-19 (defined as presence of upper respiratory tract symptoms and/or fever without shortness of breath or hypoxia; SpO2 > 93%), with an age range of 22-66 years (27 females) participated at 3-6 months of recovering from the acute phase of RT-PCR positive COVID-19. Healthy volunteers whose baroreflex sensitivity (BRS) and arterial stiffness data were acquired prior to the onset of the pandemic constituted the control group. BRS was found to be significantly lower in the COVID survivor group for the systolic blood pressure-based sequences (BRSSBP ) [9.78 (7.16-17.74) ms/mmHg vs 16.5 (11.25-23.78) ms/mmHg; p = 0.0253]. The COVID survivor group showed significantly higher carotid ß stiffness index [7.16 (5.75-8.18) vs 5.64 (4.34-6.96); (p = 0.0004)], and pulse wave velocity ß (PWVß ) [5.67 (4.96-6.32) m/s vs 5.12 (4.37-5.41) m/s; p = 0.0002]. BRS quantified by both the sequence and spectral methods showed an inverse correlation with PWVß in the male survivors. Impairment of BRS in the male survivors of mild COVID-19 at 3-6 months of clinical recovery shows association with carotid artery stiffness.

Relationship of Daily Step Counts to All-Cause Mortality and Cardiovascular Events.

BACKGROUND: The minimal and optimal daily step counts for health improvements remain unclear. OBJECTIVES: A meta-analysis was performed to quantify dose-response associations of objectively measured step count metrics in the general population. METHODS: Electronic databases were searched from inception to October 2022. Primary outcomes included all-cause mortality and incident cardiovascular disease (CVD). Study results were analyzed using generalized least squares and random-effects models. RESULTS: In total, 111,309 individuals from 12 studies were included. Significant risk reductions were observed at 2,517 steps/d for all-cause mortality (adjusted HR [aHR]: 0.92; 95% CI: 0.84-0.999) and 2,735 steps/d for incident CVD (aHR: 0.89; 95% CI: 0.79-0.999) compared with 2,000 steps/d (reference). Additional steps resulted in nonlinear risk reductions of all-cause mortality and incident CVD with an optimal dose at 8,763 (aHR: 0.40; 95% CI: 0.38-0.43) and 7,126 steps/d (aHR: 0.49; 95% CI: 0.45-0.55), respectively. Increments from a low to an intermediate or a high cadence were independently associated with risk reductions of all-cause mortality. Sex did not influence the dose-response associations, but after stratification for assessment device and wear location, pronounced risk reductions were observed for hip-worn accelerometers compared with pedometers and wrist-worn accelerometers. CONCLUSIONS: As few as about 2,600 and about 2,800 steps/d yield significant mortality and CVD benefits, with progressive risk reductions up to about 8,800 and about 7,200 steps/d, respectively. Additional mortality benefits were found at a moderate to high vs a low step cadence. These findings can extend contemporary physical activity prescriptions given the easy-to-understand concept of step count. (Dose-Response Relationship Between Daily Step Count and Health Outcomes: A Systematic Review and Meta-Analyses; CRD42021244747).