The study provides preliminary stroke-specific error estimates for determining when a repeated measurement differs by more than ordinary measurement variation. Participants were eligible if they were 50 to 80 years old, had experienced their stroke at least 12 months earlier and could walk at least 10 meters independently, with or without an assistive device. The analyzed group had a mean age of 63.9 years, a mean body mass index of 31.2 kilograms per square meter and a mean time since stroke of 4.5 years.

Four participants were female. Median scores indicated mild stroke severity, mild cognitive impairment and reduced arm spasticity. Participants had mild neurological impairment and were generally able to follow the standardized procedures, so the results describe a relatively narrow chronic-stroke population rather than people in acute recovery or with severe disability.

Investigators measured pulse-wave velocity in the carotid-femoral, carotid-radial and femoral-dorsalis pedis arterial segments. The carotid-femoral segment was treated as the measure of central arterial stiffness, while the other two represented peripheral arterial sites. Noninvasive applanation tonometers recorded pressure waveforms at the proximal and distal sites, and pulse-wave velocity was calculated as the distance between those sites divided by the time delay between waveform arrival.

Each measurement was collected twice on both the paretic and non-paretic sides and averaged over 30 consecutive cardiac cycles. The surface-distance estimates used in the calculations were consistent across repeated measurements and between limbs, although the study did not establish that these distances caused or contributed to the observed reliability estimates. Carotid-femoral pulse-wave velocity had a standard error of measurement of 0.80 meters per second in paretic limbs and 0.61 meters per second in non-paretic limbs.

Its minimal detectable change at 95% confidence was 2.23 meters per second and 1.68 meters per second, respectively. By comparison, carotid-radial pulse-wave velocity had poor relative reliability, with intraclass correlation coefficients of 0.33 in paretic limbs and 0.24 in non-paretic limbs. Its 95% minimal detectable changes were 2.82 and 3.23 meters per second.

Femoral-dorsalis pedis pulse-wave velocity also performed poorly, with coefficients of 0.12 and 0.28 and minimal detectable changes of 4.71 and 4.09 meters per second. Confidence intervals for these estimates were wide, reflecting the small numbers of participants with usable site-specific data. Brachial artery flow-mediated dilation was evaluated with duplex ultrasound through a 30-second baseline recording, a five-minute ischemic-occlusion phase and three minutes of reactive hyperemia after rapid cuff deflation.

The cuff was inflated to 200 mmHg distal to the cubital fossa. Absolute dilation, expressed as the difference between peak and baseline artery diameter in millimeters, showed poor reliability: the intraclass correlation coefficient was 0.11 in paretic limbs and 0.44 in non-paretic limbs. Its 95% minimal detectable changes were 0.29 and 0.34 millimeters.

Relative dilation, calculated with allometric scaling, had moderate reliability, with coefficients of 0.50 in paretic limbs and 0.59 in non-paretic limbs. The corresponding 95% minimal detectable changes were 6.88% and 7.65%. The central finding was not a pronounced difference between paretic and non-paretic limbs.

Instead, the arterial site appeared more consequential: carotid-femoral pulse-wave velocity was much more reproducible than either peripheral pulse-wave measurement, while relative and absolute flow-mediated dilation showed similar broad patterns on the two sides. The investigators noted that peripheral arteries are smaller, more muscular and more responsive to vasodilatory stimuli than larger central arteries. They also considered post-stroke changes in sympathetic activity, muscle tone and spasticity, along with cardiovascular risk factors, as possible contributors to peripheral measurement variability.

Flow-mediated dilation displayed a different reliability pattern from central stiffness. Baseline and peak artery diameters were broadly similar between the two visits, yet the derived change score was not stable, especially when expressed in millimeters. The investigators suggested that variability in baseline measurements may have affected absolute dilation more than the scaled percentage measure, although this mechanism was not directly examined.

They also emphasized the use of experienced sonographers, stable probe positioning and automated edge-detection software when seeking greater precision. The sample’s relative dilation values of roughly 4% to 7% were consistent with the pooled estimate from a meta-analysis of post-stroke studies, but that broader literature showed extremely high heterogeneity and included values ranging from negative 4% to 13%. Minimal detectable change estimates provide a statistical way to distinguish measured physiological change from the error expected when an assessment is repeated.

They are not equivalent to minimally clinically important differences. A change can exceed measurement error without necessarily mattering to a patient, and this study did not establish stroke-specific clinical thresholds. The authors noted that epidemiological associations in non-stroke cohorts have linked each 1-meter-per-second increase in central pulse-wave velocity with an approximately 15% increase in cardiovascular-event risk, while a 1-percentage-point increase in brachial flow-mediated dilation has been associated with about 13% lower cardiovascular-event risk.

Those associations come from non-stroke populations and do not turn the study’s error estimates into clinical cutoffs for people after stroke. The principal limitations were the sample size and the narrowly defined cohort. Participants were mostly men, generally had mild strokes and were more than a year beyond onset, limiting generalization to acute stroke, more severe neurological impairment and more gender-balanced populations.

Site-specific analyses included only 10 to 14 participants, producing wide confidence intervals and imprecise reliability estimates, particularly for flow-mediated dilation. Measurement error was unavoidable, and operator skill may have contributed to variability between assessment protocols. Inter-rater reliability was not examined, so the results do not establish whether the same performance would hold when more than one assessor collects the measurements.

Overall, the preliminary findings identify carotid-femoral pulse-wave velocity as the most reproducible stiffness measurement examined in this group of adults with chronic stroke and provide error bounds for interpreting repeated central stiffness and flow-mediated dilation measurements, while the poorer performance of peripheral pulse-wave velocity and absolute flow-mediated dilation argues for caution in their use as precise outcome measures.

Subject of Research: Test–retest reliability and minimal detectable change of vascular measurements in paretic and non-paretic limbs of adults with chronic stroke

Article Title: Test–retest reliability and minimal detectable change of pulse wave velocity and flow‐mediated dilation in paretic and non‐paretic limbs of older adults post‐stroke

Article References: Abreu, J. A., D'Isabella, N., Stouth, D. W., MacDonald, M. J., Tang, A., & Moncion, K. (2026). Test–retest reliability and minimal detectable change of pulse wave velocity and flow‐mediated dilation in paretic and non‐paretic limbs of older adults post‐stroke. Physiological Reports, 14(20), Article e71138. https://doi.org/10.14814/phy2.71138

Image Credits: AI Generated

DOI: 10.14814/phy2.71138

Keywords: stroke, pulse-wave velocity, flow-mediated dilation, arterial stiffness, endothelial function, test–retest reliability, minimal detectable change, chronic stroke, older adults, vascular measurement, Test, retest

The study enrolled 391 adults aged 45 and older in China and compared three groups: 172 long-term Tai Chi practitioners, 72 conventional exercisers who regularly performed square dancing, jogging, or brisk walking, and 147 irregular exercisers. Regular exercise was strictly defined as at least three sessions per week of at least 30 minutes each, sustained for more than one year. By measuring a panel of vascular outcomes and blood biomarkers, the researchers set out to test whether Tai Chi, a mind-body exercise combining slow movement, balance, and breath control, would be associated with healthier arteries than simply being physically inactive or only occasionally active.

To capture vascular health, the team relied on several well-established noninvasive measures. Flow-mediated dilation, or FMD, reflects how well an artery widens in response to increased blood flow, a hallmark of endothelial function. Brachial-ankle pulse wave velocity, or baPWV, gauges arterial stiffness by timing how fast pressure waves travel between the arm and the ankle. The ankle-brachial index, or ABI, screens for peripheral artery disease by comparing blood pressure at the ankle with that in the arm. Carotid intima-media thickness, or IMT, measures the thickness of the inner layers of the carotid artery wall, a structural marker of early atherosclerosis. The researchers also recorded peak systolic velocity, wall shear stress, and resistance index, adding hemodynamic detail to the picture.

After adjusting for covariates and applying a modern statistical approach known as targeted maximum likelihood estimation, along with a Benjamini-Hochberg correction across the seven vascular outcomes, the results showed that Tai Chi practitioners had significantly better vascular measures than irregular exercisers. Compared with the irregular group, Tai Chi practice was associated with higher FMD by 1.39 percentage points, a meaningful gain in endothelial function. It was also linked to lower baPWV by roughly 103 centimeters per second, indicating less arterial stiffness, along with lower ABI, thinner carotid IMT by about 0.09 millimeters, and a lower resistance index, suggesting less resistance to blood flow in the peripheral circulation.

Conventional exercise also outperformed irregular exercise on endothelial function, with a 0.79 percentage point higher FMD than the irregular group. However, when the researchers directly compared Tai Chi practitioners with conventional exercisers, no significant differences emerged after statistical correction. This suggests that the vascular benefits seen in Tai Chi practitioners may not be unique to the slow, meditative art itself, but could reflect the broader effects of sustained, regular physical activity on the cardiovascular system.

Beyond the vascular measures, the team explored whether inflammation and oxidative stress might indirectly link Tai Chi practice to vascular health. They measured blood levels of high-sensitivity C-reactive protein, or hs-CRP, a marker of systemic inflammation, along with tumor necrosis factor-alpha, interleukin-6, interleukin-10, and interleukin-33. On the oxidative stress side, they measured superoxide dismutase, or SOD, an antioxidant enzyme, malondialdehyde, or MDA, a marker of lipid damage from free radicals, and glutathione peroxidase, or GPx, another antioxidant defense molecule. Exploratory analyses pointed to nominal potential indirect associations involving hs-CRP, SOD, and combined inflammatory and oxidative-stress composites, hinting that Tai Chi might partly influence vascular health by dampening chronic inflammation and bolstering antioxidant capacity.

However, the researchers are careful to note that these biomarker findings are exploratory and were not adjusted for multiple comparisons, meaning they should be treated as hypothesis-generating rather than definitive. The cross-sectional design also means the study cannot establish causality; it is possible that people with healthier vasculature are simply more likely to sustain long-term Tai Chi practice, rather than the other way around. The authors emphasize that prospective cohort studies and randomized controlled trials are needed to determine whether Tai Chi truly causes these vascular improvements and whether the biomarker pathways hold up under more rigorous testing.

The study was registered with ClinicalTrials.gov under identifier NCT06307483 and received ethical approval from the Ethics Committee of Beijing Sport University. It was supported by funding from the Tai Chi Laboratory of the Chinese Intangible Cultural Heritage Association Tai Chi Committee, the Special Fund for Basic Scientific Research of Central Universities, the Science and Technology Commission of Shanghai Municipality, and Neil Shen’s SJTU Medical Research Fund. The work reflects a collaboration spanning Beijing Sport University, Shanghai Jiao Tong University, Henan Polytechnic University, and other institutions, with support from the Sports Bureau of Wenxian, Henan Province, and Wenxian People’s Hospital.

For the general public, the takeaway is nuanced. Tai Chi appears to be associated with better vascular function and structure than being irregularly active, and the magnitude of the differences, particularly in arterial stiffness and carotid wall thickness, is notable for a low-impact, accessible exercise. Yet the absence of significant differences from conventional exercise suggests that the key ingredient may be sustained, regular movement itself, whether slow and meditative or brisk and rhythmic. For older adults seeking a gentle, sustainable way to support cardiovascular health, Tai Chi remains a promising option, but the new study stops short of proving it superior to other forms of regular exercise. Larger, longer-term, and randomized studies will be needed to determine whether the ancient practice can truly reshape the arteries, and whether the quiet interplay of inflammation and oxidative stress holds the mechanistic key.

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Subject of Research: Tai Chi

Article Title: Associations of long-term Tai Chi practice with vascular health in middle-aged and older adults: potential indirect roles of inflammation and oxidative stress – a cross-sectional study

Article References: Luo, L., Wang, X., Huang, Z., Wang, Y., Zhou, H., Kong, Y., Yu, B., Liu, H., Ren, Y., Liu, L., Lu, H., Sun, J., Cheng, S., & He, H. (2026). Associations of long-term Tai Chi practice with vascular health in middle-aged and older adults: potential indirect roles of inflammation and oxidative stress – a cross-sectional study. BMC Complementary Medicine and Therapies. https://doi.org/10.1186/s12906-026-05645-3

Image Credits: AI Generated

DOI: 10.1186/s12906-026-05645-3

Keywords: Tai Chi, vascular health, inflammation, oxidative stress, aging, cross-sectional study, flow-mediated dilation, arterial stiffness, Associations, long-term, practice, vascular

The endothelium, the delicate single layer of cells lining the interior of every blood vessel, is far more than passive plumbing. It actively regulates vascular tone by releasing vasodilating and vasoconstricting compounds, controls oxidative processes, modulates cell adhesion, and influences arterial stiffness. When the endothelium falters, vessels stiffen, their dilatory responses weaken, and the earliest silent stages of cardiovascular disease take hold. Flow-mediated dilation of the brachial artery, measured with high-resolution ultrasound after a temporary ischemic stimulus, captures this dysfunction early and tracks closely with coronary artery function, which is why the research team led by Simon Iskra and Armin Paravlić of the University of Ljubljana centered their analysis on it.

To assemble the evidence, the researchers searched six major databases from inception through multiple updated searches in 2023, 2025 and 2026, screening nearly 1,900 records against strict PICOS criteria. Only randomized controlled trials in adults that reported brachial artery flow-mediated dilation alongside at least one secondary outcome made the cut. The final pool spanned healthy volunteers and patients with cardiovascular disease, metabolic syndrome, diabetes, kidney disease, cancer, and even mental and neurological disorders. Participants ranged from about 20 to 78 years old, 43 percent were women, and interventions lasted from four to 26 weeks, with roughly two-thirds of study arms using continuous training and one-third using interval formats.

The headline result survived every robustness check the team threw at it. A random-effects model yielded a mean difference of 2.35 percent in flow-mediated dilation, a fixed-effects model produced 1.90 percent, and a trim-and-fill adjustment for publication bias still left a significant adjusted estimate of 1.74 percent. Sensitivity analysis removing the single largest study did not change the conclusion. Heterogeneity was high, as expected when pooling trials across such diverse populations and protocols, but the direction and clinical relevance of the effect were consistent. By the classification scheme the authors applied, the pooled gain qualifies as small but clinically meaningful, sitting above the 1 percent threshold considered the minimal clinically important difference.

The most novel contribution, however, lies in the meta-regression, which asked which physiological changes actually drive the vascular improvements. Four clusters emerged as significant moderators. Greater reductions in body weight and body fat were associated with larger gains in endothelial function, with regression coefficients of -4.021 and -1.721 respectively. Drops in systolic and diastolic blood pressure also tracked with better flow-mediated dilation, at coefficients of -0.525 and -0.484. On the positive side, improvements in maximal oxygen uptake, the classic index of cardiorespiratory fitness, showed a strong association with endothelial gains at a coefficient of 0.656, and changes in insulin levels moderated the effect as well. Notably, blood lipids, fasting glucose, HbA1c, and insulin resistance measured by HOMA-IR did not significantly moderate the vascular response, suggesting lipid and glucose improvements run on partly independent tracks.

Beneath these statistical associations lies a coherent mechanistic story. During aerobic exercise, blood flow to working muscles surges, subjecting the vessel walls to elevated shear stress. This mechanical signal activates endothelial nitric oxide synthase, boosting production of nitric oxide, the principal vasodilator of healthy arteries. The meta-analysis confirmed this biochemistry in blood: nitric oxide and its metabolites rose substantially, with standardized mean differences of 1.23 for both, while endothelin-1, the vessels’ chief constricting agent, fell moderately. Enhanced nitric oxide bioavailability combined with reduced endothelin-1 shifts vascular tone toward dilation, plausibly explaining much of the measured improvement in flow-mediated dilation, even though the biomarkers themselves did not reach statistical significance as moderators, likely because relatively few studies measured them.

The hemodynamic findings add another layer. Aerobic training produced small but significant reductions in systolic pressure, diastolic pressure, and mean arterial pressure, and the meta-regression tied these blood pressure drops directly to endothelial gains. The authors interpret this as evidence of a feedback loop: healthier endothelia dilate more readily, lowering vascular resistance and pressure, which in turn protects the vessel wall. Arterial stiffness told a subtler tale. Peripheral stiffness, measured at the brachial-ankle segment, decreased significantly, but central stiffness, measured at the carotid-femoral segment, and the augmentation index did not change. The researchers attribute this to the time course of vascular remodeling, since peripheral arteries adapt faster than the stiffer central vessels, and to the small number of trials that measured central outcomes alongside flow-mediated dilation.

Cardiorespiratory fitness emerged as perhaps the most intriguing partner in the adaptation. Maximal oxygen uptake rose moderately across trials, and the stronger the fitness gains, the stronger the endothelial improvements. The relationship is likely bidirectional. Repeated shear stress from training enhances nitric oxide signaling and vascular homeostasis, while preserved endothelial function optimizes skeletal muscle perfusion and oxygen delivery, supporting further fitness gains. The authors caution that because the meta-regression works at the study level, causality cannot be established; the pattern reflects interconnected adaptations rather than a simple cause-and-effect chain. Still, the convergence of fitness, body composition, blood pressure, and insulin changes as moderators paints exercise as a multi-front intervention rather than a single-target drug.

Body composition results carried their own surprise. Even though the analysis excluded trials that combined exercise with dieting, aerobic training alone significantly reduced body weight, body mass index, and body fat percentage, with no change in skeletal muscle mass. The regression confirmed that fat loss amplified the vascular benefit, and the authors suggest that shrinking adipose tissue dampens chronic low-grade inflammation, a process tightly linked to endothelial health. Inflammation markers moved in the expected direction, with a small significant fall in C-reactive protein and a moderate, near-significant decrease in TNF-alpha. Lipid changes were real but modest, with small rises in HDL cholesterol and small falls in LDL and triglycerides, while glucose metabolism improved through fasting glucose, HbA1c, and insulin resistance, even without significant changes in insulin itself.

The authors are candid about limitations. The restriction to trials reporting brachial artery flow-mediated dilation means conclusions may not generalize to other endothelial assessments. Flow-mediated dilation tends to normalize over longer interventions as structural remodeling proceeds, so pooled changes may understate peak functional adaptation. Pooling healthy and clinical populations yields general tendencies rather than disease-specific prescriptions, and the use of standardized mean differences for secondary outcomes, while necessary given heterogeneous measurement methods, obscures absolute changes. Publication bias was detected for the primary outcome and several secondary markers, though corrections preserved the core finding. Even so, the message is hard to dismiss: aerobic exercise acts simultaneously on fat mass, fitness, blood pressure, insulin regulation, nitric oxide signaling, and inflammation, and these converging pathways collectively rebuild endothelial function. For clinicians and the public alike, the analysis reinforces aerobic training as one of the most powerful non-pharmacological tools available for protecting the vascular system, with benefits that compound across nearly every measurable dimension of cardiovascular health.

Subject of Research: Effects of aerobic exercise on endothelial function and cardiovascular disease markers

Article Title: Impact of Aerobic Exercise on Endothelial Function and Other Cardiovascular Disease Markers in Health and Disease: A Systematic Review and Meta-analysis with Meta-regression of Randomized Controlled Trials

Article References: Iskra, S., Turnšek, G., Drole, K., & Paravlić, A. (2026). Impact of Aerobic Exercise on Endothelial Function and Other Cardiovascular Disease Markers in Health and Disease: A Systematic Review and Meta-analysis with Meta-regression of Randomized Controlled Trials. Sports Medicine – Open, 12(1), Article 150. https://doi.org/10.1186/s40798-026-01110-0

Image Credits: AI Generated

DOI: 10.1186/s40798-026-01110-0

Keywords: aerobic exercise, endothelial function, flow-mediated dilation, cardiovascular disease, meta-analysis, nitric oxide, blood pressure, cardiorespiratory fitness, body composition, insulin, arterial stiffness, vascular health

The research team recruited 21 adults aged 35 to 68, dividing them into 11 controls and 10 individuals with long COVID. Every participant had a documented history of SARS-CoV-2 infection, but the two groups differed sharply in the severity of the acute illness and in their recovery. The controls had all experienced asymptomatic or mild infections and reported no lingering symptoms. The long COVID group, by contrast, had suffered moderate-to-critical disease: 60 percent required hospitalization, 60 percent needed oxygen therapy, and one person required mechanical ventilation. At the time of testing, roughly three years after infection, they continued to report fatigue, exercise intolerance, breathlessness, and headaches, and their scores on the Post-COVID-19 Functional Status Scale indicated substantially greater functional limitation than the controls.

To disentangle the possible mechanisms behind this persistent limitation, the investigators designed a three-visit protocol that separated each measurement from the others. On the first visit, participants completed a symptom-limited cardiopulmonary exercise test on a cycle ergometer, with breath-by-breath gas exchange analysis, continuous electrocardiography, and blood pressure monitoring. The second visit was devoted to transthoracic echocardiography, including advanced speckle-tracking analyses of myocardial work. The third visit assessed endothelial function using brachial artery flow-mediated dilation, a noninvasive ultrasound technique in which a blood pressure cuff is inflated for five minutes to induce ischemia and the subsequent surge of blood upon release is used to probe how well the artery dilates. Participants abstained from caffeine, alcohol, and strenuous activity before each session to prevent interference between measurements.

The exercise testing revealed clear and quantifiable deficits. Compared with controls, the long COVID group achieved a lower peak oxygen uptake, a lower predicted peak oxygen uptake relative to reference values, and a lower oxygen uptake at the first ventilatory threshold, the point during incremental exercise where metabolism begins to shift toward anaerobic contribution. These differences carried large effect sizes, indicating that the impairment was not marginal. Because both maximal and submaximal aerobic capacity were reduced, the results suggest that everyday activities, not just athletic performance, demand more physiological effort from these individuals than from their fully recovered counterparts.

The vascular findings were even more striking. Flow-mediated dilation was dramatically lower in the long COVID group, with a Cohen’s d of 2.30, an effect size that is exceptionally large for a between-group comparison in human vascular physiology. Crucially, the team also measured the shear-rate stimulus, the frictional force that flowing blood exerts on the vessel wall and that normally triggers the endothelium to release nitric oxide and other vasodilators. Peak shear rate, the area under the shear-rate curve during the hyperemic period, and the area under the curve up to maximal vasodilation were all significantly reduced in the long COVID participants. This means the problem involves not only a blunted vasodilatory response but also a diminished hyperemic signal, a double hit to the mechanisms that normally match blood flow to metabolic demand.

The researchers took care to ensure that the difference in flow-mediated dilation was not an artifact of differing artery sizes. Allometric scaling of log-transformed baseline and peak diameters showed no significant group-by-diameter interaction, and the between-group difference remained significant after adjustment for baseline diameter. The difference also persisted after statistical adjustment for age, sex, body composition, and comorbidities, strengthening the conclusion that the vascular impairment is a genuine feature of the long COVID phenotype rather than a byproduct of the higher body mass index and obesity prevalence observed in this group.

Perhaps the most informative result came from the correlation analyses. Within the long COVID group, flow-mediated dilation was positively and significantly associated with both peak oxygen uptake and predicted peak oxygen uptake, meaning that individuals with better endothelial function tended to have better aerobic capacity. No such association appeared among the controls, whose vascular function was uniformly good. This pattern supports the idea that, in long COVID, the state of the peripheral vasculature becomes a rate-limiting factor for exercise performance, constraining oxygen delivery to skeletal muscle in a way that does not occur in healthy vasculature with reserve capacity to spare.

The heart, meanwhile, told a different story. Conventional echocardiographic measures, including left ventricular ejection fraction, volumes, and global longitudinal strain, were indistinguishable between groups, as were the myocardial work indices derived from pressure-strain analysis: global work index, global constructive work, global wasted work, and global work efficiency. Myocardial work integrates ventricular deformation with afterload and can detect subtle dysfunction that conventional parameters miss, yet even this sensitive approach found no group differences. Exploratory analyses did reveal intriguing internal patterns: in the long COVID group, lower global work index was associated with greater ventilatory drive and poorer ventilatory efficiency during exercise, and with higher body mass index, hinting at interactions between metabolic status, breathing mechanics, and cardiac mechanics that deserve further study in larger cohorts.

Taken together, the data sketch a coherent physiological account of long COVID exercise intolerance. Persistent endothelial injury after SARS-CoV-2 infection, plausibly driven by chronic inflammation, oxidative stress, and reduced nitric oxide bioavailability, compromises the ability of conduit and resistance vessels to dilate appropriately during exercise. The result is a peripheral limit on oxygen delivery that manifests as reduced aerobic capacity, while the central pump continues to function within normal limits. This peripheral mechanism aligns with earlier studies conducted one and two years after infection, but the present work extends the timeline considerably, showing that these abnormalities persist well into the third year after the acute illness.

The authors are careful to note the limitations of their study. It was observational, cross-sectional, and single-center, with a modest sample size, so the findings are hypothesis-generating rather than definitive. The long COVID cohort consisted predominantly of people with previous moderate-to-critical illness, and the controls all had prior asymptomatic or mild infection, so the results may not generalize to the full spectrum of post-COVID conditions. The cohort was also predominantly composed of individuals with overweight or obesity, and the study was not powered to detect sex or race differences. Even so, the large effect sizes and the a priori power calculation lend credibility to the central conclusion. Clinically, the work argues for evaluating vascular health, not just cardiac function, in patients with persistent post-COVID exercise intolerance, and for cardiometabolic risk management alongside structured rehabilitation. Whether improving endothelial function can restore exercise tolerance remains a critical question for future interventional trials.

Subject of Research: Persistent endothelial dysfunction and exercise intolerance in long COVID three years after SARS-CoV-2 infection

Article Title: Persistent endothelial dysfunction is associated with exercise intolerance in adults despite preserved myocardial work 3 years after SARS‐CoV‐2 infection

Article References: de Araújo Alves, C. C., Goulart, C. D. L., D'Ávila, L., de Souza Silva, B. H. E., Alves, I. M., Aguiar, B. V. S., Conde, C., Stein, R., & Cipriano, G., Jr. (2026). Persistent endothelial dysfunction is associated with exercise intolerance in adults despite preserved myocardial work 3 years after SARS‐CoV‐2 infection. Physiological Reports, 14(19), Article e71103. https://doi.org/10.14814/phy2.71103

Image Credits: AI Generated

DOI: 10.14814/phy2.71103

Keywords: long COVID, endothelial dysfunction, flow-mediated dilation, exercise intolerance, myocardial work, cardiopulmonary exercise testing, SARS-CoV-2, vascular function, peak oxygen uptake, echocardiography, nitric oxide, post-COVID condition

The research, led by Leandro C. Brito and colleagues at Oregon Health & Science University, set out to answer a deceptively simple question: does the baroreflex system itself follow a circadian rhythm, and if so, does that rhythm line up with the circadian rhythm of blood pressure? Previous studies had hinted at a daily pattern in baroreflex function, with sensitivity appearing greatest around three in the morning in both normotensive and hypertensive individuals. But those studies measured people during their normal sleep-wake cycles, meaning the results were hopelessly entangled with behavior. Sleep, posture, meals, and physical activity all influence blood pressure and autonomic function, making it impossible to separate the effect of the internal clock from the effect of simply being asleep.

To untangle this knot, the team turned to one of the most powerful tools in human circadian physiology: the forced desynchrony protocol. In this design, volunteers live on a behavioral schedule that is too short for their internal circadian pacemaker to follow. Because the human circadian clock runs on an intrinsic period of roughly 24.1 hours and cannot entrain to cycles far outside its entrainment range, the internal rhythm is forced to free-run at its own pace while the behavioral cycle marches to a different drummer. When physiological measurements are later plotted against circadian phase rather than clock time, any rhythm that emerges must be driven by the endogenous circadian system rather than by sleep, meals, or activity.

Eleven healthy young adults, aged 20 to 39, completed a 30-hour laboratory stay built around five consecutive six-hour cycles, each containing four hours of wakefulness followed by a two-hour sleep opportunity. Every aspect of their environment was tightly controlled. Wake periods took place in dim light below eight lux, sleep occurred in total darkness, and no time cues were provided. Identical isocaloric meals of roughly 322 kilocalories, composed of about 35 percent fat, 50 percent carbohydrate, and 15 percent protein, were delivered every three hours. Participants remained supine except during meals, scheduled restroom visits, and supervised exercise. Polysomnography confirmed that they slept an average of 114 minutes during each two-hour window, with no significant differences in sleep duration across the protocol. Circadian phase was anchored to the dim light melatonin onset, the gold-standard marker of the biological clock, determined from hourly salivary samples.

During each wake period, the researchers recorded beat-to-beat blood pressure with finger photoplethysmography and cardiac electrical activity with a standard three-lead electrocardiogram. From these continuous signals they extracted two distinct measures of baroreflex function. The first, baroreflex sensitivity, quantifies how strongly the heart rate responds to a given change in systolic pressure, expressed as the slope of the relationship between the two. The second, the baroreflex effectiveness index, counts how often the baroreflex actually intervenes: it is the ratio of validated baroreflex sequences, in which pressure and heart interval change in the appropriate opposing directions across at least three consecutive cardiac cycles, to the total number of spontaneous systolic pressure sequences observed. Sensitivity measures the strength of the reflex when it fires; effectiveness measures how frequently it fires at all.

The results were striking in their asymmetry. Systolic blood pressure showed a clear circadian rhythm with a peak-to-trough amplitude of ten millimeters of mercury, bottoming out at a circadian phase corresponding to roughly 1:40 in the morning and peaking near 11:40 in the morning. Diastolic pressure showed no significant rhythm. Baroreflex sensitivity, perhaps surprisingly, also showed no significant circadian variation. But the baroreflex effectiveness index told a different story entirely. It peaked at a circadian phase corresponding to about one in the morning, averaging 34 percent above its overall mean, and fell to its lowest value, 48 percent below the mean, at around nine in the morning. In other words, the reflex was most active precisely when systolic pressure was at its circadian minimum.

Deeper analysis of the directionality of the reflex added an important nuance. When the researchers separated the data into up-up sequences, in which the reflex slows the heart in response to rising pressure, and down-down sequences, in which it accelerates the heart as pressure falls, they found that the nocturnal advantage came almost entirely from the up-up responses. During the circadian night, the baroreflex was 110 percent more effective at correcting increases in blood pressure than during the circadian morning. This asymmetry carries real clinical weight. Prior work has shown that in women with a family history of hypertension, the ability to correct pressure rises is selectively impaired, and in people with established hypertension, a deficient baroreflex response to pressure increases independently predicts death and adverse cardiovascular events.

The study also mapped the circadian rhythms of the vasculature. Brachial artery vascular conductance, an index of skeletal muscle vasodilation, peaked around two in the morning at 27 percent above its mean, immediately preceding the systolic pressure trough, and fell to its lowest point around six in the evening. Vascular endothelial function, measured as flow-mediated dilation of the brachial artery, peaked later, at around ten in the morning, 34 percent above the mean, and was lowest at six in the evening. Notably, this morning peak in endothelial function occurred about five hours earlier than previously reported in middle-aged adults studied with the same technique, raising the possibility that aging shifts the circadian phase of vascular protection. The authors suggest this morning peak may help explain why, paradoxically, adverse cardiovascular events cluster between six in the morning and noon in epidemiological studies.

Why did sensitivity fail to rhythm while effectiveness did? The authors offer several possibilities. Their participants were exceptionally healthy, young, and recreationally active, conditions that may have created a ceiling effect masking a true rhythm in sensitivity. Alternatively, sensitivity and effectiveness may act in counterphase, as earlier work by di Rienzo and colleagues proposed when the effectiveness index was first introduced. It is also possible that the circadian system exerts a stronger influence on the spontaneous engagement of the reflex than on its gain. Importantly, the findings held up when the total number of pressure sequences and validated baroreflex sequences were included as covariates, ruling out the trivial explanation that more opportunities to detect sequences arose at night.

The implications extend well beyond basic physiology. No currently available antihypertensive medication acts directly on the baroreflex, but non-pharmacological interventions, including exercise training, respiratory muscle training, and non-invasive vagal nerve stimulation, are known to improve baroreflex function. If the circadian system genuinely gates baroreflex effectiveness, these therapies might be timed to exploit that rhythm, opening a chronotherapy-based avenue for treating non-dipping blood pressure. The authors are careful to note the limits of their work: the sample was small and predominantly young and healthy, the 30-hour protocol offers only six-hour phase resolution, and the findings must be reproduced in older adults and in people with hypertension before they can inform clinical practice. Still, by rigorously isolating the internal clock from the noise of daily behavior, the study elevates the baroreflex from a passive bystander to a leading suspect in the mystery of nocturnal blood pressure regulation, and it hands researchers a concrete, testable target in the search for why some hearts fail to dip when night falls.

Subject of Research: Circadian variation in cardiac baroreflex effectiveness and its alignment with the nocturnal trough in systolic blood pressure in young healthy adults

Article Title: Nocturnal peak in cardiac baroreflex effectiveness aligns with nocturnal trough in systolic blood pressure in young healthy adults: Possible circadian effects

Article References: Brito, L. C., Jones, M. L., Chaudhary, N., Shea, S. A., & Thosar, S. S. (2026). Nocturnal peak in cardiac baroreflex effectiveness aligns with nocturnal trough in systolic blood pressure in young healthy adults: Possible circadian effects. Physiological Reports, 14(17), Article e71092. https://doi.org/10.14814/phy2.71092

Image Credits: AI Generated

DOI: 10.14814/phy2.71092

Keywords: circadian rhythm, baroreflex, blood pressure, nocturnal dipping, forced desynchrony, autonomic nervous system, vascular function, hypertension, melatonin, flow-mediated dilation, cardiovascular physiology, chronotherapy