The effect of an mRNA vaccine against COVID-19 on endothelial function and arterial stiffness.

To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine administration on endothelial function and arterial stiffness. Thirty-two participants (mean age 37 ± 8 years, 20 men) who received the BNT162b2 mRNA COVID-19 vaccine were studied in three sessions in a sequence-randomized, sham-controlled, assessor-blinded, crossover design. The primary outcome was endothelial function (assessed by brachial artery flow-mediated dilatation (FMD)), and the secondary outcomes were aortic stiffness (evaluated with carotid-femoral pulse wave velocity (PWV)) and inflammation (measured by high-sensitivity C-reactive protein (hsCRP) in blood samples). The outcomes were assessed prior to and at 8 h and 24 h after the 1st dose of vaccine and at 8 h, 24 h, and 48 h after the 2nd dose. There was an increase in hsCRP that was apparent at 24 h after both the 1st dose (-0.60 [95% confidence intervals [CI]: -1.60 to -0.20], p = 0.013) and the 2nd dose (maximum median difference at 48 h -6.60 [95% CI: -9.80 to -3.40], p < 0.001) compared to placebo. The vaccine did not change PWV. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p = 0.037) at 24 h after the 2nd dose. FMD values returned to baseline at 48 h. Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose, and a transient deterioration of endothelial function at 24 h that returns to baseline at 48 h. These results confirm the short-term cardiovascular safety of the vaccine.

Cardiovascular and cerebral vascular health in females with postacute sequelae of COVID-19.

Many individuals who had coronavirus disease 2019 (COVID-19) develop detrimental persistent symptoms, a condition known as postacute sequelae of COVID-19 (PASC). Despite the elevated risk of cardiovascular disease following COVID-19, limited studies have examined vascular function in PASC with equivocal results reported. Moreover, the role of PASC symptom burden on vascular health has not been examined. We tested the hypothesis that peripheral and cerebral vascular function would be blunted and central arterial stiffness would be elevated in patients with PASC compared with age-matched controls. Furthermore, we hypothesized that impairments in vascular health would be greater in those with higher PASC symptom burden. Resting blood pressure (BP; brachial and central), brachial artery flow-mediated dilation (FMD), forearm reactive hyperemia, carotid-femoral pulse wave velocity (PWV), and cerebral vasodilator function were measured in 12 females with PASC and 11 age-matched female controls without PASC. The severity of persistent symptoms in those with PASC was reported on a scale of 1-10 (higher score: greater severity). Brachial BP (e.g., systolic BP, 126 ± 19 vs.109 ± 8 mmHg; P = 0.010), central BP (P < 0.050), and PWV (7.1 ± 1.2 vs. 6.0 ± 0.8 m/s; P = 0.015) were higher in PASC group compared with controls. However, FMD, reactive hyperemia, and cerebral vasodilator function were not different between groups (P > 0.050 for all). Total symptom burden was not correlated with any measure of cardiovascular health (P > 0.050 for all). Collectively, these findings indicate that BP and central arterial stiffness are elevated in females with PASC, whereas peripheral and cerebral vascular function appear to be unaffected, effects that appear independent of symptom burden.NEW & NOTEWORTHY We demonstrate for the first time that resting blood pressure (BP) and central arterial stiffness are higher in females with PASC compared with controls. In contrast, peripheral and cerebral vascular functions appear unaffected. Moreover, there was no relationship between total PASC symptom burden and measures of BP, arterial stiffness, or vascular function. Collectively, these findings suggest that females with PASC could be at greater risk of developing hypertension, which appears independent of symptom burden.

The effect of SGLT2 inhibitors, GLP1 agonists, and their sequential combination on cardiometabolic parameters: A randomized, prospective, intervention study.

BACKGROUND: Pulse wave velocity (PWV) and augmentation index (AIx) are indices used to assess arterial stiffness. We aim to compare the effect of empagliflozin, liraglutide and their sequential combination on arterial stiffness indices in patients with type 2 diabetes (T2D). METHODS: This was a randomized single blind study evaluating the effect of empagliflozin vs liraglutide in adult patients with T2D. Patients were randomized to liraglutide titrated gradually to 1.8 mg or empagliflozin 25 mg in 1:1 ratio. Three months later empagliflozin was added to the liraglutide group, and liraglutide was added to the empagliflozin group. Patients were assessed with non-invasive tests for arterial stiffness (i.e., carotid-femoral PWV and AIx of aortic pressure) at baseline, 3-month and 9-month visits (final visit was extended for 3 months from the initial design due to Covid 19 pandemic). The primary outcome was the between-group difference of PWV change (ΔPWV) and ΔAIx at 3 months. Secondary outcomes included the between-group difference of ΔPWV and ΔAIx at 9 months, as well as the ΔPWV and ΔAIx between baseline and 9-month visit when total study population was assessed. RESULTS: A total of 62 patients with T2D (30 started liraglutide; 32 empagliflozin, mean age 63 years, 25 % with established cardiovascular disease) participated in the study. We failed to show any significant between-group differences of ΔPWV and ΔΑΙx at 3 and 9 months, as well as between-group difference of ΔPWV and ΔAIx for the total study population between baseline and 9-month visit. In contrast, systemic vascular resistance and lipoprotein(a) levels improved, showing better results with liraglutide than empagliflozin. Favorable effects were also observed on body weight, body mass index, body and visceral fat, blood pressure, HbA1c, and uric acid levels. CONCLUSION: No evidence of a favorable change in arterial stiffness indices was seen with empagliflozin or liraglutide or their combination in this study. Well-designed powerful studies are needed to address any potential effects on arterial stiffness in selected populations.

Endothelial function, arterial stiffness and heart rate variability of patients with cardiovascular diseases hospitalized due to COVID-19.

BACKGROUND: The novel coronavirus disease (COVID-19) may cause vascular (e.g., endothelial dysfunction, and arterial stiffness), cardiac, autonomic (e.g., heart rate variability [HRV]), and systemic inflammatory response via direct viral attack, hypoxia-induced injury, or immunological dysregulation, especially in those patients with pre-existing cardiovascular diseases (CVD). However, to date, no study has shown prevalence of endothelial dysfunction, arterial stiffness and heart rate variability assessed by bedside peripheral arterial tonometry in patients with previous CVD hospitalized in the acute phase of COVID-19. OBJECTIVE: This study aimed to assess the prevalence of endothelial dysfunction, arterial stiffness, and altered HRV in patients with CVD hospitalized due to COVID-19. METHODS: This cross-sectional study was conducted from July 2020 to February 2021. Included male and female adult patients aged 40 to 60 years with previous CVD and diagnosed with COVID-19. Anthropometric data, comorbidities, and blood tests were analyzed. Endothelial function, arterial stiffness, and HRV were assessed using peripheral arterial tonometry (PAT), and the statistical significance was set at 5%. RESULTS: Fourteen (51.8%) patients presented endothelial dysfunction (reactive hyperemia index = 1.2 ± 0.3) and enhancement in the high-frequency component of HRV (p < 0.05). There was a high prevalence of endothelial dysfunction, especially in patients with chronic heart failure (10 (71.4%)). Patients with preserved endothelial function showed a high augmentation index normalized to a heart rate of 75 bpm (p < 0.01), suggesting arterial stiffness. CONCLUSION: Patients with CVD hospitalized due to COVID-19 presented endothelial dysfunction assessed using PAT, which could be used as a biomarker for arterial stiffness and altered HRV. The possibility of detecting vascular and autonomic changes during phase II of COVID-19 may help to prevent possible long-term complications.

Twenty-Four-Hour Central Hemodynamic Load in Adults With and Without a History of COVID-19.

BACKGROUND: Although hypertension is a risk factor for severe Coronavirus Disease 2019 (COVID-19) illness, little is known about the effects of COVID-19 on blood pressure (BP). Central BP measures taken over a 24-hour period using ambulatory blood pressure monitoring (ABPM) adds prognostic value in assessing cardiovascular disease (CVD) risk compared with brachial BP measures from a single time point. We assessed CVD risk between adults with and without a history of COVID-19 via appraisal of 24-hour brachial and central hemodynamic load from ABPM. METHODS: Cross-sectional analysis was performed on 32 adults who tested positive for COVID-19 (29 ± 13 years, 22 females) and 43 controls (28 ± 12 years, 26 females). Measures of 24-hour hemodynamic load included brachial and central systolic and diastolic BP, pulse pressure, augmentation index (AIx), pulse wave velocity (PWV), nocturnal BP dipping, the ambulatory arterial stiffness index (AASI), and the blood pressure variability ratio (BPVR). RESULTS: Participants who tested positive for COVID-19 experienced 6 ± 4 COVID-19 symptoms, were studied 122 ± 123 days after testing positive, and had mild-to-moderate COVID-19 illness. The results from independent samples t-tests showed no significant differences in 24-hour, daytime, or nighttime measures of central or peripheral hemodynamic load across those with and without a history of COVID-19 (P > 0.05 for all). CONCLUSIONS: No differences in 24-hour brachial or central ABPM measures were detected between adults recovering from mild-to-moderate COVID-19 and controls without a history of COVID-19. Adults recovering from mild-to-moderate COVID-19 do not have increased 24-hour central hemodynamic load.

Pulse wave velocity demonstrates increased aortic stiffness in newly diagnosed, antiretroviral naïve HIV infected adults: A case-control study.

Increased aortic stiffness is an important predictor of cardiovascular disease (CVD). It remains controversial whether HIV infected persons have increased aortic stiffness at the time of HIV diagnosis. An explorative, case-control study was performed using carotid-femoral pulse wave velocity (PWV) in a newly diagnosed, antiretroviral treatment (ART)-naïve cohort with modest baseline cardiovascular risk. We recruited 85 newly diagnosed adults without known CVD from health care facilities in South Africa (43 female; mean age 33). Median CD4 count was 285, IQR 156-393 cells/µL. Twenty two HIV uninfected controls were recruited from the same facilities (8 female; mean age 33). PWV was measured using the Vicorder module (Skidmore Medical, United Kingdom) using a corrective factor of 0.8. The HIV infected group's mean PWV measured 11% higher than controls (5.88 vs 5.28 m/s; P = .02). Median aortic distensibility in HIV infected persons was 18% lower than controls (0.37 vs 0.45 mm Hg-1; P = .009). Multivariate analysis revealed that the difference in PWV between groups remained significant when corrected for age, sex, mean blood pressure and kidney function (mean difference 0.52 m/s; P = .01). Mean blood pressure, estimated glomerular filtration rate, HIV infection per se, age and male sex were important associations with increased PWV. Our study provides evidence for increased aortic stiffness in ART naïve adults already demonstrable at the time of HIV diagnosis. The cohort's young age and recent HIV diagnosis makes atherosclerosis a less likely explanation for the difference. Alternative, potentially reversible, explanations that require further research include vasomotor tone abnormalities and endothelial dysfunction.

Effect of Empagliflozin and Dapagliflozin on Ambulatory Arterial Stiffness in Patients with Type 2 Diabetes Mellitus and Cardiovascular Co-Morbidities: A Prospective, Observational Study.

Background and Objectives: Individuals with type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular disease. Arterial stiffness is an independent prognostic marker for cardiovascular disease development. We aimed at determining the effect of two different sodium-glucose co-transporter-2 (SGLT-2) inhibitors on ambulatory arterial stiffness in individuals with T2DM. Materials and Methods: In this single-center, single-arm, prospective study performed from January 2020 to August 2021, we planned to enroll adult subjects with T2DM and stable antidiabetic and antihypertensive treatment, assigned either to empagliflozin or dapagliflozin for 6 months. All eligible subjects underwent ambulatory blood pressure monitoring. We set as the primary efficacy outcome the change in ambulatory pulse wave velocity (PWV) from baseline to week 24. Results: We finally enrolled 46 diabetic subjects, with a mean age of 62.89 (8.53) years and mean T2DM duration of 9.72 (6.37) years. Thirty patients received dapagliflozin, while sixteen patients received empagliflozin. Due to COVID-19 pandemic restrictive measures during the study, the mean follow-up period extended from 6 months to 9.98 (3.27) months. Regarding the prespecified primary efficacy outcome, we found that the SGLT-2 inhibitor treatment did not have a significant effect on PWV (p = 0.65). Prior history of cardiovascular disease did not significantly affect the observed effects. Other indices of arterial stiffness, such as augmentation index and central pulse pressure, were not significantly affected, neither by empagliflozin nor by dapagliflozin. Conclusions: SGLT-2 inhibitor treatment with empagliflozin or dapagliflozin in subjects with T2DM failed to improve ambulatory PWV over a mean follow-up of 10 months. Registration number: ISRCTN88851713.

Clinical implications of vascular dysfunction in acute and convalescent COVID-19: A systematic review.

BACKGROUND: Accumulating evidence suggests that endothelial dysfunction is implicated in the pathogenesis and severity of coronavirus disease 2019 (COVID-19). In this context, vascular impairment in COVID-19 might be associated with clinical manifestations and could refine risk stratification in these patients. METHODS: This systematic review aims to synthesize current evidence on the frequency and the prognostic value of vascular dysfunction during acute and post-recovery COVID-19. After systematically searching the MEDLINE, clinicaltrials.gov and the Cochrane Library from 1 December 2019 until 05 March 2022, we identified 24 eligible studies with laboratory confirmed COVID-19 and a thorough examination of vascular function. Flow-mediated dilation (FMD) was assessed in 5 and 12 studies in acute and post-recovery phase respectively; pulse wave velocity (PWV) was the marker of interest in three studies in the acute and four studies in the post-recovery phase. RESULTS: All studies except for one in the acute and in the post-recovery phase showed positive association between vascular dysfunction and COVID-19 infection. Endothelial dysfunction in two studies and increased arterial stiffness in three studies were related to inferior survival in COVID-19. DISCUSSION: Overall, a detrimental effect of COVID-19 on markers of endothelial function and arterial stiffness that could persist even for months after the resolution of the infection and provide prognostic value was congruent across published studies. Further research is warranted to elucidate clinical implications of this association.

Pulse Wave Velocity, a Predictor of Major Adverse Cardiovascular Events, and Its Correlation with the General Stress Level of Health Care Workers during the COVID-19 Pandemic.

Background and Objectives: In the COVID-19 epidemiological context, the health care workers who were treating patients with COVID-19 were exposed daily to additional stress. Pulse wave velocity (PWV) is a predictive parameter for possible major adverse cardiovascular events. The present study aimed to evaluate the correlation between the general stress levels and PWVs of medical workers during the COVID-19 pandemic. Materials and Methods: The study group was heterogeneous in terms of the medical profession. PWV was measured using a TendioMed arteriograph. Assessment of stress level was performed using a general stress questionnaire with questions grouped on the areas that contribute to stress: lifestyle, environment, symptoms, job, relationships and personality. PWV measurements and stress assessment were performed both during the period with many patients with COVID-19 and during the period with few patients with COVID-19. Results: The stress levels and PWVs of subjects were higher in the period when they cared for patients with COVID-19 than in the period when they did not have patients with COVID-19. Conclusions: The study shows a positive correlation between the PWV of each subject and his/her stress score (the higher the stress score, the higher the PWV).

Impact of breakthrough COVID-19 cases during the omicron wave on vascular health and cardiac autonomic function in young adults.

We and others have previously shown that COVID-19 results in vascular and autonomic impairments in young adults. However, the newest variant of COVID-19 (Omicron) appears to have less severe complications. Therefore, we investigated whether recent breakthrough infection with COVID-19 during the Omicron wave impacts cardiovascular health in young adults. We hypothesized that measures of vascular health and indices of cardiac autonomic function would be impaired in those who had the Omicron variant of COVID-19 when compared with controls who never had COVID-19. We studied 23 vaccinated adults who had COVID-19 after December 25, 2021 (Omicron; age, 23 ± 3 yr; 14 females) within 6 wk of diagnosis compared with 13 vaccinated adults who never had COVID-19 (age, 26 ± 4 yr; 7 females). Macro- and microvascular function were assessed using flow-mediated dilation (FMD) and reactive hyperemia, respectively. Arterial stiffness was determined as carotid-femoral pulse wave velocity (cfPWV) and augmentation index (AIx). Heart rate (HR) variability and cardiac baroreflex sensitivity (BRS) were assessed as indices of cardiac autonomic function. FMD was not different between control (5.9 ± 2.8%) and Omicron (6.1 ± 2.3%; P = 0.544). Similarly, reactive hyperemia (P = 0.884) and arterial stiffness were not different between groups (e.g., cfPWV; control, 5.9 ± 0.6 m/s and Omicron, 5.7 ± 0.8 m/s; P = 0.367). Finally, measures of HR variability and cardiac BRS were not different between groups (all, P > 0.05). Collectively, these data suggest preserved vascular health and cardiac autonomic function in young, otherwise healthy adults who had breakthrough cases of COVID-19 during the Omicron wave.NEW & NOTEWORTHY We show for the first time that breakthrough cases of COVID-19 during the Omicron wave does not impact vascular health and cardiac autonomic function in young adults. These are promising results considering earlier research showing impaired vascular and autonomic function following previous variants of COVID-19. Collectively, these data demonstrate that the recent Omicron variant is not detrimental to cardiovascular health in young, otherwise healthy, vaccinated adults.

Vascular Dysfunction of COVID-19 Is Partially Reverted in the Long-Term.

BACKGROUND: COVID-19 is characterized by severe inflammation during the acute phase and increased aortic stiffness in the early postacute phase. In other models, aortic stiffness is improved after the reduction of inflammation. We aimed to evaluate the mid- and long-term effects of COVID-19 on vascular and cardiac autonomic function. The primary outcome was aortic pulse wave velocity (aPWV). METHODS: The cross-sectional Study-1 included 90 individuals with a history of COVID-19 and 180 matched controls. The longitudinal Study-2 included 41 patients with COVID-19 randomly selected from Study-1 who were followed-up for 27 weeks. RESULTS: Study-1: Compared with controls, patients with COVID-19 had higher aPWV and brachial PWV 12 to 24 (but not 25-48) weeks after COVID-19 onset, and they had higher carotid Young's elastic modulus and lower distensibility 12 to 48 weeks after COVID-19 onset. In partial least squares structural equation modeling, the higher the hs-CRP (high-sensitivity C-reactive protein) at hospitalization was, the higher the aPWV 12 to 48 weeks from COVID-19 onset (path coefficient: 0.184; P=0.04). Moreover, aPWV (path coefficient: -0.186; P=0.003) decreased with time. Study-2: mean blood pressure and carotid intima-media thickness were comparable at the end of follow-up, whereas aPWV (-9%; P=0.01), incremental Young's elastic modulus (-17%; P=0.03), baroreflex sensitivity (+28%; P=0.049), heart rate variability triangular index (+15%; P=0.01), and subendocardial viability ratio (+12%; P=0.01×10-4) were significantly improved. There was a trend toward improvement in brachial PWV (-6%; P=0.14) and carotid distensibility (+18%; P=0.05). Finally, at the end of follow-up (48 weeks after the onset of COVID-19) aPWV (+6%; P=0.04) remained significantly higher in patients with COVID-19 than in control subjects. CONCLUSIONS: COVID-19-related arterial stiffening involves several arterial tree portions and is partially resolved in the long-term.

Six-month longitudinal tracking of arterial stiffness and blood pressure in young adults following SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can increase arterial stiffness 3-4 wk following infection, even among young, healthy adults. However, the long-term impacts of SARS-CoV-2 infection on cardiovascular health and the duration of recovery remain unknown. The purpose of this study was to elucidate potential long-lasting effects of SARS-CoV-2 infection on markers of arterial stiffness among young adults during the 6 mo following infection. Assessments were performed at months 1, 2, 3, 4, and ∼6 following SARS-CoV-2 infection. Doppler ultrasound was used to measure carotid-femoral pulse wave velocity (cfPWV) and carotid stiffness, and arterial tonometry was used to measure central blood pressures and aortic augmentation index at a heart rate of 75 beats·min-1 (AIx@HR75). Vascular (VCAM-1) and intracellular (ICAM-1) adhesion molecules were analyzed as circulating markers of arterial stiffness. From months 1-6, a significant reduction in cfPWV was observed (month 1: 5.70 ± 0.73 m·s-1; month 6: 4.88 ± 0.65 m·s-1; P < 0.05) without any change in carotid stiffness measures. Reductions in systolic blood pressure (month 1: 123 ± 8 mmHg; month 6: 112 ± 11 mmHg) and mean arterial pressure (MAP; month 1: 97 ± 6 mmHg; month 6: 86 ± 7 mmHg) were observed (P < 0.05), although AIx@HR75 did not change over time. The month 1-6 change in cfPWV and MAP were correlated (r = 0.894; P < 0.001). A reduction in VCAM-1 was observed at month 3 compared with month 1 (month 1: 5,575 ± 2,242 pg·mL-1; month 3: 4,636 ± 1,621 pg·mL-1; P < 0.05) without a change in ICAM-1. A reduction in cfPWV was related with MAP, and some indicators of arterial stiffness remain elevated for several months following SARS-CoV-2 infection, possibly contributing to prolonged recovery and increased cardiovascular health risks.NEW & NOTEWORTHY We sought to investigate potential long-lasting effects of SARS-CoV-2 infection on markers of arterial stiffness among young adults for 6 mo following infection. Carotid femoral pulse wave velocity was significantly reduced while carotid stiffness measures remained unaltered over the 6-mo period. These findings suggest several months of recovery from infection may be necessary for young adults to improve various markers of arterial stiffness, possibly contributing to cardiovascular health and recovery among those infected with SARS-CoV-2.

Evaluation of Aortic Elasticity Parameters in Survivors of COVID-19 Using Echocardiography Imaging.

OBJECTIVE: While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects lung tissue, it may cause direct or indirect damage to the cardiovascular system, and permanent damage may occur. Arterial stiffness is an early indicator of cardiovascular disease risk. The aim of our study was to establish the potential effects of SARS-CoV-2 on the vascular system evaluated by transthoracic echocardiographic examination. SUBJECTS AND METHODS: This study compared arterial stiffness between the survivors of COVID-19 and those without a history of COVID-19 infection. The difference in aortic diameter was examined using echocardiography. RESULTS: The study included 50 patients who survived COVID-19 in the last 3-6 months and 50 age- and gender-matched healthy volunteers. In surviving COVID-19 patients, aortic diastolic diameter in cm ([3.1 ± 0.2] vs. [2.9 ± 0.1], p < 0.001), pulse pressure (PP) ([43.02 ± 14.05] vs. [35.74 ± 9.86], p = 0.004), aortic distensibility ([5.61 ± 3.57] vs. [8.31 ± 3.82], p < 0.001), aortic strain ([10.56 ± 4.91] vs. [13.88 ± 5.86], p = 0.003), PP/stroke volume index ([1.25 ± 0.47] vs. [0.98 ± 0.28], p = 0.001), and aortic stiffness index ([2.82 ± 0.47] vs. [2.46 ± 0.45], p < 0.001) were statistically significant compared to the control group. CONCLUSION: SARS-CoV-2 may cause reduced or impaired aortic elasticity parameters linked to impaired arterial wall function in COVID-19 survivors compared with controls.

Evaluation of the cardio-ankle vascular index in COVID-19 patients.

OBJECTIVE: This study aimed to investigate the relationship and prognostic significance of cardio-ankle vascular index, which is a measure of arterial stiffness that can lead to endothelial dysfunction and poor cardiovascular issues in COVID-19 patients, with COVID-19. METHODS: The study included 115 patients, of which 65 patients in the case group with Real time reversetranscription-polymerasechainreaction test positive and diagnosed for COVID-19 and 50 volunteers in the control group. Patients with COVID-19 were classified as moderate/severe or mild COVID-19 in the subgroup analysis based on the severity of the disease. We investigated the relationship between cardio-ankle vascular index and COVID-19 by using the VaSera VS-1000 device to automatically measure each patient's cardio-ankle vascular index and ankle-brachial pressure index. RESULTS: The mean age of participants included in the study was 65.7±10.7 years. Patients and volunteers were statistically similar in terms of age, gender, comorbidities, Charlson comorbidity index scores, and body mass index values (p>0.05). The right-cardio-ankle vascular index value was 9.6±2.4 in the case group and 8.5±1.1 in the control group (p=0.004). The left-cardio-ankle vascular index value was 9.4±2.7 in the case group and 8.5±1.2 in the control group (p=0.01). The right-cardio-ankle vascular index value was 10.8±3.4 in the moderate/severe disease group and 8.8±0.9 in the mild disease group (p=0.008). The left-cardio-ankle vascular index value was 10.7±3.6 in the moderate/severe disease group and 8.5±1.5 in the mild disease group (p<0.001). The right-cardio-ankle vascular index and left-cardio-ankle vascular index values were found to be significantly higher in COVID-19 patients in our study. When receiver operating characteristic analysis was performed to distinguish moderate/severe COVID-19 patients from mild patients, right-cardio-ankle vascular index was area under the curve 0.757 (0.630-0.884), and left-cardio-ankle vascular index was area under the curve 0.782 (0.661-0.902). CONCLUSION: The right-cardio-ankle vascular index and left-cardio-ankle vascular index values increased in COVID-19 patients in our study, and this was thought to be prognostically significant.

Blood Pressure and Arterial Stiffness in Association With Aircraft Noise Exposure:Long-Term Observation and Potential Effect of COVID-19 Lockdown.

In a cross-sectional analysis of a case-control study in 2015, we revealed the association between increased arterial stiffness (pulse wave velocity) and aircraft noise exposure. In June 2020, we evaluated the long-term effects, and the impact of a sudden decline in noise exposure during the coronavirus disease 2019 (COVID-19) lockdown, on blood pressure and pulse wave velocity, comparing 74 participants exposed to long-term day-evening-night aircraft noise level >60 dB and 75 unexposed individuals. During the 5-year follow-up, the prevalence of hypertension increased in the exposed (42% versus 59%, P=0.048) but not in the unexposed group. The decline in noise exposure since April 2020 was accompanied with a significant decrease of noise annoyance, 24-hour systolic (121.2 versus 117.9 mm Hg; P=0.034) and diastolic (75.1 versus 72.0 mm Hg; P=0.003) blood pressure, and pulse wave velocity (10.2 versus 8.8 m/s; P=0.001) in the exposed group. Less profound decreases of these parameters were noticed in the unexposed group. Significant between group differences were observed for declines in office and night-time diastolic blood pressure and pulse wave velocity. Importantly, the difference in the reduction of pulse wave velocity between exposed and unexposed participants remained significant after adjustment for covariates (-1.49 versus -0.35 m/s; P=0.017). The observed difference in insomnia prevalence between exposed and unexposed individuals at baseline was no more significant at follow-up. Thus, long-term aircraft noise exposure may increase the prevalence of hypertension and accelerate arterial stiffening. However, even short-term noise reduction, as experienced during the COVID-19 lockdown, may reverse those unfavorable effects.

Estimated pulse wave velocity improves risk stratification for all-cause mortality in patients with COVID-19.

Accurate risk stratification in COVID-19 patients consists a major clinical need to guide therapeutic strategies. We sought to evaluate the prognostic role of estimated pulse wave velocity (ePWV), a marker of arterial stiffness which reflects overall arterial integrity and aging, in risk stratification of hospitalized patients with COVID-19. This retrospective, longitudinal cohort study, analyzed a total population of 1671 subjects consisting of 737 hospitalized COVID-19 patients consecutively recruited from two tertiary centers (Newcastle cohort: n = 471 and Pisa cohort: n = 266) and a non-COVID control cohort (n = 934). Arterial stiffness was calculated using validated formulae for ePWV. ePWV progressively increased across the control group, COVID-19 survivors and deceased patients (adjusted mean increase per group 1.89 m/s, P < 0.001). Using a machine learning approach, ePWV provided incremental prognostic value and improved reclassification for mortality over the core model including age, sex and comorbidities [AUC (core model + ePWV vs. core model) = 0.864 vs. 0.755]. ePWV provided similar prognostic value when pulse pressure or hs-Troponin were added to the core model or over its components including age and mean blood pressure (p < 0.05 for all). The optimal prognostic ePWV value was 13.0 m/s. ePWV conferred additive discrimination (AUC: 0.817 versus 0.779, P < 0.001) and reclassification value (NRI = 0.381, P < 0.001) over the 4C Mortality score, a validated score for predicting mortality in COVID-19 and the Charlson comorbidity index. We suggest that calculation of ePWV, a readily applicable estimation of arterial stiffness, may serve as an additional clinical tool to refine risk stratification of hospitalized patients with COVID-19 beyond established risk factors and scores.

Vascular alterations among young adults with SARS-CoV-2.

While SARS-CoV-2 primarily affects the lungs, the virus may be inflicting detriments to the cardiovascular system, both directly through angiotensin-converting enzyme 2 receptor and initiating systemic inflammation. Persistent systemic inflammation may be provoking vascular dysfunction, an early indication of cardiovascular disease risk. To establish the potential effects of SARS-CoV-2 on the systemic vasculature in the arms and legs, we performed a cross-sectional analysis of young healthy adults (control: 5 M/15 F, 23.0 ± 1.3 y, 167 ± 9 cm, 63.0 ± 7.4 kg) and young adults who, 3-4 wk prior to testing, had tested positive for SARS-CoV-2 (SARS-CoV-2: 4 M/7 F, 20.2 ± 1.1 y, 172 ± 12 cm, 69.5 ± 12.4 kg) (means ± SD). Using Doppler ultrasound, brachial artery flow-mediated dilation (FMD) in the arm and single passive limb movement (sPLM) in the leg were assessed as markers of vascular function. Carotid-femoral pulse wave velocity (PWVcf) was asvsessed as a marker of arterial stiffness. FMD was lower in the SARS-CoV-2 group (2.71 ± 1.21%) compared with the control group (8.81 ± 2.96%) (P < 0.01) and when made relative to the shear stimulus (SARS-CoV-2: 0.04 ± 0.02 AU, control: 0.13 ± 0.06 AU, P < 0.01). The femoral artery blood flow response, as evidenced by the area under the curve, from the sPLM was lower in the SARS-CoV-2 group (-3 ± 91 mL) compared with the control group (118 ± 114 mL) (P < 0.01). PWVcf was higher in the SARS-CoV-2 group (5.83 ± 0.62 m/s) compared with the control group (5.17 ± 0.66 m/s) (P < 0.01). Significantly lower systemic vascular function and higher arterial stiffness are evident weeks after testing positive for SARS-CoV-2 among young adults compared with controls.NEW & NOTEWORTHY This study was the first to investigate the vascular implications of contracting SARS-CoV-2 among young, otherwise healthy adults. Using a cross-sectional design, this study assessed vascular function 3-4 wk after young adults tested positive for SARS-CoV-2. The main findings from this study were a strikingly lower vascular function and a higher arterial stiffness compared with healthy controls. Together, these results suggest rampant vascular effects seen weeks after contracting SARS-CoV-2 in young adults.

Association of COVID-19 with impaired endothelial glycocalyx, vascular function and myocardial deformation 4 months after infection.

AIMS: SARS-CoV-2 infection may lead to endothelial and vascular dysfunction. We investigated alterations of arterial stiffness, endothelial coronary and myocardial function markers 4 months after COVID-19 infection. METHODS AND RESULTS: In a case-control prospective study, we included 70 patients 4 months after COVID-19 infection, 70 age- and sex-matched untreated hypertensive patients (positive control) and 70 healthy individuals. We measured (i) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV), (v) global left and right ventricular longitudinal strain (GLS), and (vi) malondialdehyde (MDA), an oxidative stress marker, thrombomodulin and von Willebrand factor as endothelial biomarkers. COVID-19 patients had similar CFR and FMD as hypertensives (2.48 ± 0.41 vs. 2.58 ± 0.88, P = 0.562, and 5.86 ± 2.82% vs. 5.80 ± 2.07%, P = 0.872, respectively) but lower values than controls (3.42 ± 0.65, P = 0.0135, and 9.06 ± 2.11%, P = 0.002, respectively). Compared to controls, both COVID-19 and hypertensives had greater PBR5-25 (2.07 ± 0.15 µm and 2.07 ± 0.26 µm, P = 0.8 vs. 1.89 ± 0.17 µm, P = 0.001), higher PWV (carotid-femoral PWV 12.09 ± 2.50 vs. 11.92 ± 2.94, P = 0.7 vs. 10.04 ± 1.80 m/s, P = 0.036) and impaired left and right ventricular GLS (-19.50 ± 2.56% vs. -19.23 ± 2.67%, P = 0.864 vs. -21.98 ± 1.51%, P = 0.020 and -16.99 ± 3.17% vs. -18.63 ± 3.20%, P = 0.002 vs. -20.51 ± 2.28%, P < 0.001). MDA and thrombomodulin were higher in COVID-19 patients than both hypertensives and controls (10.67 ± 0.32 vs 1.76 ± 0.03, P = 0.003 vs. 1.01 ± 0.05 nmol/L, P = 0.001 and 3716.63 ± 188.36 vs. 3114.46 ± 179.18 pg/mL, P = 0.017 vs. 2590.02 ± 156.51 pg/mL, P < 0.001). Residual cardiovascular symptoms at 4 months were associated with oxidative stress and endothelial dysfunction markers. CONCLUSIONS: SARS-CoV-2 may cause endothelial and vascular dysfunction linked to impaired cardiac performance 4 months after infection.

Blunted peripheral but not cerebral vasodilator function in young otherwise healthy adults with persistent symptoms following COVID-19.

Recent findings suggest that COVID-19 causes vascular dysfunction during the acute phase of the illness in otherwise healthy young adults. To date, to our knowledge, no studies have investigated the longer-term effects of COVID-19 on vascular function. Herein, we hypothesized that young, otherwise healthy adults who are past the acute phase of COVID-19 would exhibit blunted peripheral [brachial artery flow-mediated dilation (FMD) and reactive hyperemia] and cerebral vasodilator function (cerebral vasomotor reactivity to hypercapnia; CVMR) and increased central arterial stiffness. Sixteen young adults who were at least 4 wk past a COVID-19 diagnosis and 12 controls who never had COVID-19 were studied. Eight subjects with COVID-19 were symptomatic (SYM) and eight were asymptomatic (ASYM) at the time of testing. FMD and reactive hyperemia were not different between COVID and control groups. However, FMD was lower in SYM (3.8 ± 0.6%) compared with ASYM (6.8 ± 0.9%; P = 0.007) and control (6.8 ± 0.6%; P = 0.003) with no difference between ASYM and control. Similarly, peak blood velocity following cuff release was lower in SYM (47 ± 8 cm/s) compared with ASYM (64 ± 19 cm/s; P = 0.025) and control (61 ± 14 cm/s; P = 0.036). CVMR and arterial stiffness were not different between any groups. In summary, peripheral macrovascular and microvascular function, but not cerebral vascular function or central arterial stiffness were blunted in young adults symptomatic beyond the acute phase of COVID-19. In contrast, those who were asymptomatic had similar vascular function compared with controls who never had COVID-19.NEW & NOTEWORTHY This study was the first to investigate the persistent effects of COVID-19 on vascular function in otherwise healthy young adults. We demonstrated that peripheral macrovascular and microvascular vasodilation was significantly blunted in young adults still symptomatic from COVID-19 beyond the acute phase (>4 wk from diagnosis), whereas those who become asymptomatic have similar vascular function compared with controls who never had COVID-19. In contrast, cerebral vascular function and central arterial stiffness were unaffected irrespective of COVID-19 symptomology.

Investigation of endothelial dysfunction and arterial stiffness in multisystem inflammatory syndrome in children.

Severe acute respiratory syndrome coronavirus 2 infection can result in multisystem inflammatory syndrome in children (MIS-C). MIS-C can lead to myocardial dysfunction, heart failure, and multiorgan failure; the primary finding is hyperinflammation. Endothelial dysfunction has not been evaluated in patients with MIS-C. We investigated endothelial dysfunction and arterial stiffness parameters in patients with MIS-C. The study included 38 pediatric patients (20 males and 18 females aged 4-17 years, mean age 8.89 years) with MIS-C. Thirty-eight age- and sex-matched healthy individuals were enrolled as the control group. Systolic and diastolic ventricular measurements and systolic and diastolic measurements of ascending aorta diameter were performed by M-mode echocardiography. Endothelial dysfunction was evaluated using flow-mediated dilation by measuring the brachial artery diameter with a high-resolution probe. The MIS-C group had lower flow-mediated dilation than did the controls. The MIS-C group had decreased aortic strain and aortic distensibility values and correlations between decreased flow-mediated dilation and reduced aortic strain, aortic distensibility, and reduced ejection fraction.Conclusion: The results show that patients with MIS-C had endothelial dysfunction and arterial stiffness. Furthermore, the degree of endothelial dysfunction correlated with reduced ejection fractions.What is Known:•Endothelial dysfunction and arterial stiffness are unknown in patients with MIS-C.•The effect of endothelial dysfunction and arterial stiffness on decreased cardiac function is unknown.What is New:•MIS-C patients have endothelial dysfunction and arterial stiffness.•There is a link between left ventricular dysfunction and reduced endothelial dysfunction in patients with MIS-C.