Peripheral BP Research Articles

Accuracy of methods to estimate central aortic SBP via upper arm cuff: a systematic review and meta-analysis.

Central aortic BP may predict cardiovascular outcomes better than upper arm brachial BP. In recent years, technology has enabled central BP estimation by recording a peripheral BP waveform from a standard upper arm cuff. The accuracy of these devices is not well documented, and this study aimed to address this issue. This study was a systematic review, conducted according to PRISMA guidelines, of observational studies published between 2008 and 2023 that reported accuracy testing of cuff-based central BP devices, compared with reference invasive aortic BP. The primary analysis was stratified according to each commercially available device. Pooled estimates were calculated using random-effects models based on mean differences and standard errors. Six thousand four hundred and fifteen studies were screened, and 27 studies met inclusion criteria (plus one unpublished study). This generated data for seven devices that are commercially available, which were tested among 2125 adult participants. There was very high heterogeneity when all devices were pooled ( I2 = 97.5%), and, when stratified by device, the accuracy of estimated central BP was highly device-dependent (range of accuracy across different devices -12.4 mmHg (-16.3 to -8.5) to 3.2 mmHg (0.2-6.1). Two of the seven commercially available devices had not undergone external validation testing. The accuracy of commercially available cuff-based central BP devices is highly device-specific and not all are accurate for the estimation of central SBP. These findings have major implications for the appropriate interpretation of studies that use cuff-based estimated central BP.

HYPERTENSION RELATED NETOSIS IS STRONGLY DEPENDENT ON NIGHTTIME BLOOD PRESSURE IN A COHORT OF NEWLY DIAGNOSED, TREATMENT NAÏVE HYPERTENSIVE PATIENTS

Objective: Over the last years, accumulating evidence has highlighted the key role of immunity in the inflammatory environment of essential hypertension (EH). Neutrophil extracellular traps (NETs) formation represents a protective innate immune mechanism of the neutrophils. However, excessive release of NETs (NETosis) has been shown to exert a potent pro-inflammatory and pro-thrombotic effect. Even though NETosis is increasingly implicated in the thrombo-inflammatory environment of cardiovascular disease, experimental and clinical data regarding the association between NETs and EH are scarce. Design and method: We recruited newly diagnosed, untreated hypertensives (UHTs) without overt cardiovascular disease and healthy, normotensive individuals (NTs). Office BP was measured according to guidelines. Ambulatory and central BP parameters were measured with the Mobil-O-Graph device. Plasma levels of NETs including myeloperoxidase (MPO)-DNA were determined by ELISA. Results: A total of 139 individuals including 99 UHTs and 40 NTs were included in the study. Levels of MPO-DNA were increased in UHTs compared to NTs (p<0.001). In multivariate analysis after adjustment for confounding variables (body mass index, hemoglobin, uric acid, high sensitivity c-reactive protein), hypertension was the strongest independent predictor of incident NETosis (p<0.001). Among the ambulatory BP indices, peripheral nighttime systolic BP (F:5.937; p=0.016) and central nighttime diastolic BP (F:4.751; p=0.031) were the strongest prognosticators of hypertension related NETosis (Optimal Scaling ANOVA; p=0.028). Conclusions: In a cohort of newly diagnosed, treatment-naïve hypertensive patients, nighttime BP indices are the strongest factors that can predict, independently, an increased NETosis, adding to the superior significance of nocturnal BP in cardiovascular prognosis. Further research is needed to clarify the association of NETs with hypertension as well as hypertension-mediated target organ damage.

Estimation of central blood pressure waveform from femoral blood pressure waveform by blind sources separation.

Central blood pressure (cBP) is a better indicator of cardiovascular morbidity and mortality than peripheral BP (pBP). However, direct cBP measurement requires invasive techniques and indirect cBP measurement is based on rigid and empirical transfer functions applied to pBP. Thus, development of a personalized and well-validated method for non-invasive derivation of cBP from pBP is necessary to facilitate the clinical routine. The purpose of the present study was to develop a novel blind source separation tool to separate a single recording of pBP into their pressure waveforms composing its dynamics, to identify the compounds that lead to pressure waveform distortion at the periphery, and to estimate the cBP. The approach is patient-specific and extracts the underlying blind pressure waveforms in pBP without additional brachial cuff calibration or any a priori assumption on the arterial model. The intra-arterial femoral BPfe and intra-aortic pressure BPao were anonymized digital recordings from previous routine cardiac catheterizations of eight patients at the German Heart Centre Berlin. The underlying pressure waveforms in BPfe were extracted by the single-channel independent component analysis (SCICA). The accuracy of the SCICA model to estimate the whole cBP waveform was evaluated by the mean absolute error (MAE), the root mean square error (RMSE), the relative RMSE (RRMSE), and the intraclass correlation coefficient (ICC). The agreement between the intra-aortic and estimated parameters including systolic (SBP), diastolic (DBP), mean arterial pressure (MAP), and pulse pressure (PP) was evaluated by the regression and Bland-Altman analyses. The SCICA tool estimated the cBP waveform non-invasively from the intra-arterial BPfe with an MAE of 0.159 ± 1.629, an RMSE of 5.153 ± 0.957 mmHg, an RRMSE of 5.424 ± 1.304%, and an ICC of 0.94, as well as two waveforms contributing to morphological distortion at the femoral artery. The regression analysis showed a strong linear trend between the estimated and intra-aortic SBP, DBP, MAP, and PP with high coefficient of determination R2 of 0.98, 0.99, 0.99, and 0.97 respectively. The Bland-Altman plots demonstrated good agreement between estimated and intra-aortic parameters with a mean error and a standard deviation of difference of -0.54 ± 2.42 mmHg [95% confidence interval (CI): -5.28 to 4.20] for SBP, -1.97 ± 1.62 mmHg (95% CI: -5.14 to 1.20) for DBP, -1.49 ± 1.40 mmHg (95% CI: -4.25 to 1.26) for MAP, and 1.43 ± 2.79 mmHg (95% CI: -4.03 to 6.90) for PP. The SCICA approach is a powerful tool that identifies sources contributing to morphological distortion at peripheral arteries and estimates cBP.

Connections between serum Trimethylamine N-Oxide (TMAO), a gut-derived metabolite, and vascular biomarkers evaluating arterial stiffness and subclinical atherosclerosis in children with obesity.

Childhood obesity leads to early subclinical atherosclerosis and arterial stiffness. Studying biomarkers like trimethylamine N-oxide (TMAO), linked to cardio-metabolic disorders in adults, is crucial to prevent long-term cardiovascular issues. The study involved 70 children aged 4 to 18 (50 obese, 20 normal-weight). Clinical examination included BMI, waist measurements, puberty stage, the presence of acanthosis nigricans, and irregular menstrual cycles. Subclinical atherosclerosis was assessed by measuring the carotid intima-media thickness (CIMT), and the arterial stiffness was evaluated through surrogate markers like the pulse wave velocity (PWV), augmentation index (AIx), and peripheral and central blood pressures. The blood biomarkers included determining the values of TMAO, HOMA-IR, and other usual biomarkers investigating metabolism. The study detected significantly elevated levels of TMAO in obese children compared to controls. TMAO presented positive correlations to BMI, waist circumference and waist-to-height ratio and was also observed as an independent predictor of all three parameters. Significant correlations were observed between TMAO and vascular markers such as CIMT, PWV, and peripheral BP levels. TMAO independently predicts CIMT, PWV, peripheral BP, and central SBP levels, even after adding BMI, waist circumference, waist-to-height ratio, puberty development and age in the regression model. Obese children with high HOMA-IR presented a greater weight excess and significantly higher vascular markers, but TMAO levels did not differ significantly from the obese with HOMA-IR<cut-offs. TMAO did not correlate to HOMA-IR and insulin levels but presented a negative correlation to fasting glucose levels. An increase in TMAO was shown to be associated with an increase in the probability of the presence of acanthosis nigricans. TMAO levels are not influenced by other blood biomarkers. Our study provides compelling evidence supporting the link between serum TMAO, obesity, and vascular damage in children. These findings highlight the importance of further research to unravel the underlying mechanisms of this connection.

SUBCLINICAL TARGET ORGAN DAMAGE IN A SAMPLE OF CHILDREN WITH SOLITARY FUNCTIONING KIDNEY. A PRELIMINARY OBSERVATIONAL STUDY

Objective: Solitary Functioning Kidney (SFK) is a condition characterized by a single-functioning kidney. Children bearing this condition are exposed to an increased risk of subclinical organ damage (SOD) due to the compensatory hyperfiltration in the remaining kidney and increased peripheral blood pressure (pBP) values. The aim of the present study was to assess the impact of traditional (pBP) and novel (central systolic blood pressure, cSBP) cardiovascular risk factors on SOD in children and adolescents with solitary functional kidney. Design and method: Carotid ultrasonography was performed to measure carotid Intima-Media Thickness (cIMT), an index of subclinical atherosclerosis. Arterial stiffness was assessed by measuring carotid Distensibility Coefficient (cDC) and carotid-femoral Pulse Wave Velocity (PWV). Cardiac mass and remodeling were analyzed using transthoracic echocardiography. Central and peripheral (both office and ambulatory) BP measurements, as well as biochemical data from blood and urine samples were collected. Results: Forty-eight SFK children and adolescents were included, of whom 45.5% were hypertensive at the Ambulatory Blood Pressure Monitoring. Twenty-four patients had increased cIMT and RWT while 8.4% and 8.9% demonstrated a reduction of cDC and an increase of PWV. Two patients had a left ventricular mass index (LVMi) above the 95th percentile. cSBP correlated with all vascular indices measured (cIMT r = 0.43; cDC r = -0.33; PWV r = 0.42, p &lt; 0.05) and with LVMi (r = 0.41; p = 0.005). Office pSBP correlated with cDC (r = -0.31; p = 0.03), PWV (r = 0.42 and p = 0.004) and LVMi (r = 0.33; p = 0.02). Regarding ABPM measurements, daytime systolic BP correlated with all vascular indices (cIMT r = 0.34, cDC r = -0.31, PWV r = 0.39 p &lt; 0.005) but not with echocardiographic ones. No correlation was found between cardiovascular parameters and the estimated glomerular filtration rate or the urinary albumin to creatinine ratio. Conclusions: Our data show a high prevalence of subclinical atherosclerosis and cardiac remodeling in children and adolescents with SFK. A lesser proportion of patients presented an increased arterial stiffening. cSBP more than pBP (office or ambulatory) associates with SOD. Children with SFK could bear a greater cardiovascular risk pointing out the importance of early preventive efforts.

Gender-specific differences in central blood pressure and optimal target blood pressure based on the prediction of cardiovascular events.

Hypertension (HBP) is a common disease among both men and women. Central blood pressure (CBP) is a method of evaluating aorta pressure that can assess the intrinsic BP of an individual patient that more closely correlates with cardiovascular disease (CVD) outcomes than peripheral BP parameters. We evaluated gender-specific differences in CBP and optimal target BP based on a composite outcome of CVD, heart failure (HF), and hypertensive complications in patients with HBP. Patients were enrolled from June 2011 to December 2015 and were followed through December 2019. CBP was measured using radial tonometry. The primary endpoint was a composite outcome. The median follow-up period for enrolled patients was 6.5 years. Out of a total of 2,115 patients with an average age of 57.9 ± 13.6 years, 266 patients (12.6%) had events of primary end points during the follow-up period. There was no difference in the lowest BP level between men and women in the incidence of CVD. Among the women (49.6%), 78.1% were postmenopausal. In a multivariable Cox proportional hazards model, CBP and systolic BP showed an increase in risk of 10 and 11%, respectively, with every 10 mmHg increase, and there was a similar trend of 12 and 13%, respectively, in postmenopausal women. However, PP showed an increase in risk of about 2% every 10 mmHg increase, but a tendency to increase risk by 19% in postmenopausal women. This study demonstrated that postmenopausal women will continue to show increased risk for CVD at BP higher than the optimal level. Conversely, there was no increase in CV risk due to menopause at BP values below the optimal level. Therefore, well-controlled BP is more important in postmenopausal women.

Age and sex related differences in orthostatic cerebral oxygenation: Findings from 2764 older adults in the Irish Longitudinal Study on Ageing (TILDA).

Cerebral hypoperfusion is implicated in the pathogenesis of associations between orthostatic hypotension and adverse outcome such as falls, cognitive impairment, depression, and mortality. Although the blood pressure response to orthostasis has been well studied there is a lack of information on orthostatic cerebrovascular responses in older populations. We measured cerebral hemodynamics, utilizing near infrared spectroscopy, coupled with peripheral blood pressure during an active stand in a large population of well-phenotyped older adults (N=2764). Multi-level mixed effect models were utilized to investigate associations with age and sex, as well as confounders including anti-hypertensive medications. Normative cerebral oxygenation responses were also modelled utilizing generalized additive models for location, scale, and shape (GAMLSS). Older age groups experienced larger initial drops in oxygenation and a slower recovery, and responses also differed by sex. The drop after standing ranged from -1.85% (95 % confidence interval (CI): -2.02 to -1.68) in the males aged 54-59years vs -1.15% (95 % CI: -1.31 to -1.00) in females aged 54-59years, to -2.67% (95 % CI: -3.01 to -2.33) in males aged ≥80years vs -1.97% (95 % CI: -2.32 to -1.62) females aged ≥80years. Reduced oxygenation levels were also evident in those taking anti-hypertensive medications. Cerebral autoregulation is impaired with age, particularly in older women and those taking anti-hypertensives. SBP during the stand explained some of the age gradient in the late recovery stage of the stand for the oldest age group. Reported orthostatic symptoms did not correlate with hypoperfusion. Therefore, measures of orthostatic cerebral flow should be assessed in addition to peripheral BP in older patients irrespective of symptoms. Further studies are required to investigate the relationship between NIRS measurements and clinical outcomes such as falls, cognitive impairment and depression.

The Oscillometric Pulse Wave Analysis Is Useful in Evaluating the Arterial Stiffness of Obese Children with Relevant Cardiometabolic Risks.

Early detection of all complications of childhood obesity is imperative in order to minimize effects. Obesity causes vascular disruptions, including early increased arterial stiffness and high blood pressure. This study’s aim is to assess the reliability of pulse wave analysis (PWA) in obese children and how additional risk factors influence the evaluated parameters. We analyzed 55 children aged 6–18 years old by measuring their pulse wave velocity (PWV), augmentation index (AIx), peripheral blood pressure (SBP, DBP), heart rate, central blood pressure (cSBP, cDBP) and central pulse pressure (cPP). We used the oscillometric IEM Mobil-O-Graph and performed a single-point brachial measurement. The subjects were divided into two groups: obese (n = 30) and normal-weight (n = 25) and were clinically and anamnestically assessed. BMI and waist circumference are significantly correlated to higher values for PWV, SBP, DBP, cSBP, and cDBP. Weight significantly predicts PWV, SBP, DBP and cPP. The risk factors that significantly influence the PWA and BP values are: a cardiometabolically risky pregnancy (higher PWV, AIx, SBP), active and passive smoking (higher PWV, SBP, cSBP, cDBP), sleep deprivation (higher PWV, SBP, cSBP) and sedentariness (higher PWV, AIx, peripheral and central BP). We conclude that obese children with specific additional cardiometabolic risk factors present increased arterial stiffness and higher blood pressure values.

LIPID INDICES, ARTERIAL DAMAGE AND ALBUMINURIA IN PEDIATRIC PATIENTS WITH UNTREATED PRIMARY HYPERTENSION

Objective: Adult data proved that dyslipidemia is associated with cardiovascular risk. Our study aimed to analyze the relation between lipid indices, arterial damage and urinary albumin excretion (UAE) in children with primary hypertension (PH). Design and method: In 87 pediatric patients (15.10 ± 2.68 years, 60 boys, 27 girls) with untreated PH, we nalysed total, high-density, and low-density lipoprotein cholesterol (T-C, LDL-C, HDL-C), triglycerides (TG), and lipid indices: TG/HDL-C, Non-HDL-C, T-C/HDL-C, LDL-C/HDL-C, atherogenic index of plasma (AIP), atherogenic index (AI), lipoprotein combine index (LCI), and CHOLIndex (LDL-C - HDL-C). Additionally, we assessed 24 h ABPM, central and peripheral office BP, and arterial damage: aortic PWV, AIx75HR, cIMT, carotid arterial stiffness estimated by ultrasonic wall tracking (E-tracking - ET) and UAE [mg/24 h]. Lipid reference values were taken from the American Academy of Paediatrics 2011 Guidelines. Results: In the study group, borderline/high T-C was found in 22 (25.3%), LDL-C in 10 (11.5%), TG in 45 (51.7%), and borderline/low HDL-C in 28 (32.2%) patients; overall, 60 (69.0%) patients had dyslipidemia. Children with borderline/high LDL-C had significantly higher aPWV (5.83 ± 1.78 vs. 5.26 ± 0.78 [m/s], p = 0.047) and UAE (16 [8–122] vs. 8 [5–22] [mg/24], p = 0.034) compared to patients with normal LDL-C. In 87 studied children, UAE correlated with T-C and LDL-C (R = 0.269, p = 0.017; R = 0.245, p = 0.030) and AIx75HR with T-C (R = 0.228, p = 0.035). Also, ET augmentation index (ET AIx) correlated with HDL-C, T-C/HDL-C and AI (R = -0.245, p = 0.023; R = 0.233, p = 0.031; R = 0.233, p = 0.031), and maximal diameter of common carotid artery (D_max) with HDL-C, TG/HDL-C, T-C/HDL-C, LDL-C/HDL-C, AIP, and AI (R = -0.332, p = 0.002; R = 0.220, p = 0.042; R = 0.255, p = 0.018; R = 0.223, p = 0.039; R = 0.220, p = 0.042; R = 0.255; p = 0.018). Logistic regression revealed that the rise in CHOLIndex increased risk of elevated (&gt;30 mg/24 h) UAE (OR: 1.035 95CI: 1.008–1.070). Conclusions: 1. Lipid disturbances are common in pediatric patients with PH 2. Elevated lipid indices are associated with common carotid artery diameter and stiffness in hypertensive children and adolescents. 3. Pediatric patients with PH and abnormal LDL cholesterol are at risk of increased aortic stiffness. 4. CHOLIndex may serve as a marker of risk of hypertensive nephropathy in pediatric patients with PH.

Effect of Amlodipine/Nebivolol combination therapy on central BP and PWV compared to Amlodipine/Valsartan combination therapy

BackgroundPulse wave velocity (PWV) and central blood pressure (CBP) have been intoduced into managment of hypertensive patients. PWV is positively correlated with arterial wall stiffness while central aortic pressure becomes better predictor of cardiovascular outcome than peripheral pressure. Reduction in CBP provides protective properties against subclinical organ damage. This work aims to investigate the effect of a new combination therapy of Amlodipine/Nebivolol (A/N) on central BP, peripheral BP and PWV. The results of using this combination will be compared to the well-established fixed-dose combination of Amlodipine/Valsartan (A/V). The study conducted between October 2018 and August 2020. One hundred and two hypertensive patients were assigned for Amlodipine 10 mg/Valsartan 160 mg combination therapy (A/V, n = 52) or Amlodipine 10 mg/Nebivolol 5 mg combination therapy (A/N, n = 50) by simple 1:1 randomization. Office, central blood pressure and PWV were measured on first (0 week), second (4–8 weeks) and third visit (10–12). Difference in BP (in each arm and between arms) was calculated along all visits.ResultsNo statistical significant difference was found between A/V and A/N regarding age, gender, BMI and CV history. OBP, CBP and PWV were significantly reduced in each arm, but no differences were found when comparing both arm results to each other. Recorded side effects were insignificant.ConclusionsThe new combination therapy Amlodipine/Nebivolol (A/N) affords a significant reduction in CBP, PBP and PWV with minor and tolerable side effects. It has provided comparable results to Amlodipine/Valsartan (A/V) combination therapy.

Importance of central BP assessment in ISH of the young. Which devices are best suited for practical use?

Isolated systolic hypertension (ISH), defined as brachial systolic blood pressure (bSBP) ≥140 mmHg and diastolic blood pressure (DBP) <90 mmHg, is highly prevalent among young subjects and in the elderly. The prognostic significance of ISH in young individuals remains the object of large debate which might be solved, at least in part, if considering the prognostic role of central BP. For any given value of pBP, the cardiovascular (CV) risk is better defined by central BP (cBP). Young individuals with ISH have long been considered at low CV risk, given the assumption that a "spurious hypertension" phenotype characterized by elevated peripheral (brachial) BP (pBP), normal cBP, and elevated BP amplification was often found in this population. However, this remains to be proven, because many other studies found no differences in BP amplification between ISH and sisto-diastolic hypertension. Despite numerous attempts, methodologies for cBP assessment by non-invasive devices are currently not standardized. As a result, different devices could provide different cBP values despite using the same biological signals. Devices providing accurate estimates of BP amplification as a dimensionless ratio between amplitudes of central and peripheral arterial waveforms might be well suited for clinical purposes in young individuals with ISH. There is urgent need of well-designed prospective studies aiming at longitudinally evaluating the amount of CV risk associated with elevated cBP in young subjects with ISH and their related incremental prognostic value.

The effect of non-invasively obtained central blood pressure on cardiovascular outcome in diabetic patients in Assiut University Hospitals

BackgroundThe major cause of morbidity and mortality in diabetes is cardiovascular disease, which is exacerbated by the presence of hypertension. Therefore, proper control of BP in diabetic hypertensive patients is essential. Few studies have specifically investigated the prognostic significance of central BP in Egyptian populations with diabetes and hypertension and its relation with cardiovascular outcome. This study aims to evaluate relation between central BP and diabetic composite cardiovascular complications.ResultsDiabetic patients with CVD were significantly older (p value < 0.01), obese (p value < 0.01) with long duration of diabetes (p value < 0.001) and had significantly higher peripheral and central systolic and diastolic BP and higher AIx@75(p values < 0.01) than those without CVD. Regarding the metabolic parameters, they had significantly higher fasting blood glucose, HbA1c, and higher blood cholesterol levels (p values < 0.001), higher LDL (p value < 0.01), triglycerides levels (p value = 0.014), and microalbuminuria (p value = 0.028). Logistic regression analysis found increased BMI, central systolic BP, and AIx@75 were independent predictors of composite CVD (p values < 0.05).ConclusionsThere is a pattern of favorability towards central rather than peripheral BP indices to predict the occurrence of CVD in diabetic patients.

Study of central aortic blood pressure in hypertensive patients & its relation with blood pressure-lowering drugs.

In clinical settings, peripheral blood pressure (PBP) is measured routinely. It is thought that central blood pressure (CBP) which reflects aortic BP, may be more predictive of outcomes in specific populations. Hence, this study was carried out to measure CBP in patients with hypertension and to see the effect of antihypertensive drugs on CBP. This cross-sectional study was conducted on 134 hypertensive patients and 134 normotensive healthy individuals as controls. Peripheral BPs and CBPs were measured of all patients and controls. The data were correlated and the effect of antihypertensive drugs on CBP was also evaluated. Of the 134 hypertensive patients, 44 (32.84%) were newly diagnosed and the rest 90 (67.16%) had a history of hypertension and were on treatment. Of these 90 patients on treatment, 37 (41.11%) had uncontrolled peripheral BP and 53 (58.89%) had normal peripheral BP. Of the 134 hypertensive patients, 45 (33.58%) had controlled CBP. In 90 patients, who were on antihypertensive treatment, 45 (50%) had controlled CBP and 45 (50%) had uncontrolled CBP. Patients on calcium channel blockers (CCBs) had better control of CBP. Hypertension is diagnosed mainly by measuring peripheral BP. CBP, which correlates better with the incidence of cardiovascular events, is not routinely measured. Patients with a history of hypertension and on treatment had normal office peripheral BP, but a few of them had high CBP and may require modification in treatment for control of CBP. Control of CBP was better in patients taking CCB.

Abstract 11634: Sympathetic Neural Overdrive, Endothelial Dysfunction and Aortic Stiffness in Coronavirus Disease 2019 Survivors: A Short-Term Study of Cardiovascular Sequelae

Introduction: Coronavirus disease 2019 (COVID-19) has become one of the more dramatic health problems in the century. This disease has enormous consequence for the health care worldwide. In addition to high mortality rate, patients recovered from COVID-19 present short and long-term cardiovascular sequelae including chest pain, myocardial dysfunction, arrhythmia, dyspnea, breathlessness, postural tachycardia syndrome, and thrombotic complications. The explanations for these clinical manifestations are still uncertain but can involve a constellation of physiological alterations. Hypothesis: To test if COVID-19 survivors have augmented sympathetic outflow, diminished endothelial function, elevated aortic stiffness, and reduced physical capacity compared to healthy individuals. Methods: Nineteen COVID-19 survivors [age: 47.0±2.3 years, BMI: 30.1±1.2 Kg/m 2 ] and eighteen well-matched healthy controls (age: 44.0±2.0 years, BMI: 28.4 ±1.2 Kg.m 2 ] were included in study. COVID-19 survivors were evaluated within 6 months of original diagnosis by RT-PCR. Muscle sympathetic nerve activity (MSNA) from fibular nerve (Microneurography), brachial artery flow-mediated dilation (BAFMD; Doppler-Ultrasound), carotid-femoral pulse wave velocity (cf-PWV; Complior), beat-to-beat blood pressure (Peripheral BP; Finometer), heart rate (HR; Electrocardiography) and peak oxygen uptake (VO 2peak , Cardiopulmonary exercise testing) were measured in both groups. Results: MSNA was higher in COVID-19 survivors compared to controls (33.0±1.0 vs. 22.0±1.0 bursts/min, p =0.001). Both BAFMD and VO 2peak were lower in COVID-19 survivors compared to controls (4.6±0.7 vs. 8.2 ±0.8%, p =0.005 and 22.2±1.5 vs. 29.7±1.6 mL/Kg/min p =0.001, respectively). Although COVID-19 survivors had greater cf-PWV than controls (8.6±0.5 m/s vs. 7.4±0.4 m/s, p =0.03), BP and HR were not different between groups. Conclusions: Our study revealed that patients recently recovered from COVID-19 have abnormal neurovascular control, vascular alterations and reduced physical capacity. These findings strongly indicate the need of further long-term investigations to uncover cardiovascular sequelae provoked by COVID-19.

Peripheral vascular involvement in transthyretin cardiac amyloidosis. A comparative analysis with AL amyloidosis

Abstract Background The pattern of peripheral vascular involvement in the wild type transthyretin-related cardiac amyloidosis (ATTRwt) and its diagnostic utility in differentiating this infiltrating cardiomyopathy from light chain (AL) cardiac amyloidosis (AL-CA) and heart failure with preserved ejection fraction (HFpEF) of different origin have not been explored. Aims To characterize the pattern of peripheral vascular involvement in ATTRwt and evaluate its value in differentiating ATTRwt from AL-CA and HFpEF. Methods Newly diagnosed patients with ATTRwt (n=42) were consecutively recruited from our amyloidosis center. These patients were matched 1:1 for age and sex to patients with AL-CA (n=32) and subjects without amyloidosis (n=32) and also matched 2:1 to HFpEF patients (n=16). All subjects underwent a series of non-invasive vascular examinations for the assessment of: 1. subclinical carotid atherosclerosis with B-mode ultrasonography, 2. Arterial stiffness with measurement of carotid-femoral pulse wave velocity, 3. Reactive vasodilation with flow-mediated dilation (FMD) and 4. Aortic blood pressures and arterial wave reflections with augmentation index (AI) and return time of reflected wave (Tr). Results ATTRwt patients had lower peripheral (pBP) and aortic blood pressure (aBP) markers compared to non-AL controls (p&amp;lt;0.05 for all). ATTRwt grouping was an independent determinant of these markers, after adjustment for cardiovascular risk factors (CVRF), including history of hypertension, hyperlipidemia and diabetes, glomerular filtration rate, body mass index and smoking status (core model). ATTRwt had lower aDBP and increased Tr compared to AL subjects. In a comparison between ATTRwt and AL patients with cardiac involvement, AI and Tr were higher and FMD lower in ATTRwt patients. ATTRwt was an independent determinant of these markers, after adjustment for the core model (p&amp;lt;0.05 for all). Compared to HFpEF, patients with ATTRwt had lower peripheral and central BP and higher Tr (p&amp;lt;0.05 for all). By ROC analysis, Tr provided high diagnostic value for ATTRwt vs. AL-CA (Area Under the Curve, AUC=0.809, CI: 0.65–0.96) and for ATTRwt vs combined AL-CA and HFpEF (AUC=0.880, CI: 0.79–0.97). Finally, AI was closely correlated with posterior (Spearman's Rho=−0.30) and intraventricular wall thickness (Rho=−0.329) and left ventricular global longitudinal strain (Rho=−0.4) and lower cDBP with higher Gilmore and New York Heart Association stage (p&amp;lt;0.05). Conclusion ATTRwt patients present differential characteristics of peripheral vascular function and aortic hemodynamics as compared to AL, HFpEF and healthy controls. The clinical value of these characteristics merit further investigation since differential diagnosis among amyloidosis types is clinically challenging, while it may have prognostic implications. Funding Acknowledgement Type of funding sources: None.

Central Systolic Blood Pressure Is Associated With Early Vascular Damage in Children and Adolescents With Type 1 Diabetes.

Objective of the study: This study aimed to test the effect of multiple cardiovascular risk factors on subclinical indices of atherosclerosis in children and adolescents with type 1 diabetes (T1D).Methods: Carotid intima-media thickness (cIMT), carotid distensibility coefficient (cDC), and carotid–femoral pulse wave velocity (PWV) were measured in children and adolescents with T1D, in a follow-up at the outpatient clinics of Verona. Blood pressure (BP; both central and peripheral), metabolic and other cardiovascular risk factors were evaluated in multivariate linear regressions to assess the association with the measured indices of subclinical vascular damage.Results: One hundred and twenty-six children and adolescents were included. cIMT was above the 95th percentile for age and height in 60.8% of the population, whereas 26% of the sample had cDC impairment (less than the 5th percentile) and 4.8% had an elevated PWV. Independent determinants of cIMT according to the regression models were only gender type of glucose monitoring and central systolic BP (cSBP). PWV was associated with age, sex, heart rate, and cSBP; cDC with age and both cSBP and, alternatively, peripheral BP (pBP). Neither pBP nor any of the tested metabolic parameters, including glycated hemoglobin, was associated with PWV and cIMT.Conclusions: A high proportion of early vascular damage, especially an increased cIMT, is present in children and adolescents with T1D in whom cSBP seems to be a common determinant. In children and adolescents with T1DM, a special focus should be on hemodynamic risk factors beyond metabolic ones.

VERY LOW-CARBOHYDRATE KETOGENIC DIET FOR THE TREATMENT OF SEVERE OBESITY AND ASSOCIATED NON-ALCOHOLIC FATTY LIVER DISEASE: THE ROLE OF SEX DIFFERENCES

Very low-carbohydrate ketogenic diets (VLCKDs) are a new type of weight loss (WL) intervention for severe obesity and are associated with a significant improvement in non-alcoholic fatty liver disease (NAFLD).Little is known about the effect of sex differences on weight loss induced by following a VLCKD.The aim of this study was to investigate the effects of sex differences on weight loss and NAFLD improvement in patients with severe obesity undergoing a VLCKD. Seventy-three patients (42 females and 28males) with morbid obesity (BMI 40kg/m2 or 35 kg/m2+comorbidity) eligible for sleeve gastrectomy underwent a 25-day-long VLCKD.Anthropometric parameters, peripheral BP, bioimpedentiometry, degree of liver steatosis measured by ultrasonography, liver function tests, and glucose homeostasis were measured before and after the VLCKD. Males experienced a significantly larger excess body weight loss (EBWL, 14.5 vs11.7% respectively,p=0.018) and a greater reduction in y-glutamyl transferase (ϒ-GT, 17 vs6 IU/L respectively,p=0.003) than females. Dividing the female group by menopausal status, a significant difference between males and pre-menopausal females was found for both EBWL (14.5 vs10.8% respectively,p=0.017) and ϒ-GT (17 vs3 IU/L respectively,p<0.001). No significant difference was observed for EBWL and ϒ-GT between males and post-menopausal women and between sexes for improvement in the Edmonton stage or in the degree of steatosis. The efficacy of VLCKD in severe obesity is influenced by sex differences and, for females, by menopausal status. Males seem to experience larger benefits than females in terms of EBWL and NAFLD improvement. These differences seems attenuated after menopause, probably because of changes in hormonal profile and body composition.

EFFECTS OF FIXED DOSE COMBINATION AZILSARTAN MEDOXOMIL/CHLORTALIDONE ON THE CENTRAL BP IN HYPERTENSIVE PATIENTS WITH HFPEF

Objective: We aimed to study the effects of a fixed AZL-M/CLD combination on central BP in patients with AH and HFpEF. Design and method: This 12-week study evaluated effects of a fixed-dose combination AZL-M/CLD (n = 30) vs non-fixed-dose combinations of iACE/ARB and thiazide/ thiazide-like diuretics (n = 30) on central BP (cBP), arterial stiffness and pulse wave velocity (PWV) in patients with AH and HFpEF. Patients with EF &lt; 50%, significant valvular disease, ACS, permanent AF, neoplasm, eGFR &lt; 30 ml/min/1.73 m2, BMI &gt; 40 kg/m2 were not included. The initial doses could be titrated to meet BP targets during weeks 4 to 12: in 1 group to 40/25 mg, in the control group up to the maximum daily dose. Results: The mean age in the study group was 67 ± 11 years (M ± SD), 36% (10 /30) males, SBP/DBP 140 ± 12/84 ± 9 mmHg (M ± SD), DM 30% (9/30), obesity 61,2% (18/30), paroxysmal AF 20% (6/30), CKD 57% (16/30), eGFR 63 [44.1;72.8]. In the control group: 66 ± 10 years (M ± SD), 40% (12 /30) males, SBP/DBP was 141 ± 11/82 ± 10 mmHg (M ± SD), DM 30% (9/30), obesity 55 % (16/30), paroxysmal AF 26% (7/30), CKD 61% (18/30), eGFR 65 [46.3;76.1]. During observation, the level of pBP in the study group decreased from 140 ± 12/84 ± 9 mmHg to 120 ± 15/71 ± 12 mmHg (p &lt; 0.05); cBP from 131 ± 15/84 ± 10 to 117 ± 14/78 ± 9 mmHg (p &lt; 0.05) and PWV from 11.7 (9.4;13.4) to 10.1 (8.7;12.3) m/s (p &lt; 0.05). The levels of pBP in the control group decreased from 141 ± 11/82 ± 11 mmHg to 128 ± 16/79 ± 9 mmHg (p &lt; 0.05), cBP from 132 ± 14/85 ± 9 to 127 ± 16/82 ± 13 mmHg (p &lt; 0.05), PWV from 11.5 (9.5; 13.6) to 10.2 (9.2.;12.8) m/s p &lt; 0.05. The t-test indicated significant differences between this two groups in peripheral BP, cBP and PWV (p = 0.004, p &lt; 0.01, p &lt; 0,05 respectively). Conclusions: There is significant antihypertensive effect and reduction of arterial stiffness in patients with AH and HFpEF treated with AZL-M/CLD.

ASSOCIATION OF CARDIOVASCULAR ENDPOINTS AND MORTALITY WITH CENTRAL AND PERIPHERAL PULSATILE BLOOD PRESSURE COMPONENTS

Objective: Pulsatile blood pressure (pBP) confers cardiovascular risk. Whether associations of cardiovascular endpoints are tighter for central than peripheral systolic or pulse pressure (cSBP, pSBP, cPP, pPP) is uncertain. Design and method: We constructed the International Database of Central Arterial Properties for Risk Stratification (IDCARS), allowing a subject-level meta-analysis. IDCARS cohorts qualified for inclusion in the present analysis, if peripheral and central BP and cardiovascular risk factors had been measured at baseline, and if follow-up included both fatal and non-fatal outcomes. Results: Among 5608 participants (54.1% women; mean age, 54.2 years) enrolled in nine studies, median follow-up was 4.1 years. pSBP and pPP averaged 134.1 and 53.9 mmHg, and cSBP and cPP, estimated tonometrically from the radial waveform, 123.7 and 42.5 mmHg. The primary composite cardiovascular endpoint occurred in 317 participants (5.7%). Across fourths of the cPP distribution, rates increased exponentially (2.9, 5.7, 9.7, and 26.1 per 1000 person-years) with comparable estimates for cSBP, pSBP and pPP. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in blood pressure (HR), were 1.33 (95% confidence interval, 1.19–1.50) for cPP, 1.47 (1.31–1.64) for cSBP, 1.31 (1.17–1.46) for pPP, and 1.45 (1.30–1.62) for pSBP (P &lt; 0.001). Further adjustment of cPP and cSBP, respectively for pPP and pSBP, and vice versa, removed the significance of all HRs. Adding cPP, cSBP, pSBP, pPP to a base model including covariables increased model fit (P &lt; 0.001) with generalised R2 increments ranging from 0.40 to 0.77%, but adding a second pBP to a model including already one did not. Analyses of total mortality (204 deaths) and 106 cerebrovascular endpoints and sensitivity analyses across various subgroups produced consistent results. Conclusions: In this subject-level meta-analysis, the primary endpoint, mortality and cerebrovascular events were similarly associated with central than peripheral pBP.

MICROVASCULAR ANGINA IS ASSOCIATED WITH SYSTEMIC DYSFUNCTION OF PERIPHERAL RESISTANCE ARTERIES

Objective: Microvascular angina (MVA) is characterized by functional and structural alterations of resistance coronary arteries without any significant alterations of epicardial coronary arteries. Whether MVA patients present also dysfunction of peripheral resistance arteries is still a matter of debate. We sought to evaluate whether MVA is associated with parameters of systemic microvascular dysfunction. Design and method: Thirteen patients with MVA and 13 healthy control subjects were enrolled in this study. The diagnosis of MVA was based on the presence of typical symptoms of ischemic heart disease, evidence of myocardial ischemia on exercise stress testing and normal epicardial coronary arteries at angiography. Parameters of peripheral microvascualar alterations, arterial stiffness (Pulse Wave Velocity, PWV), and central blood pressure (cBP) and Subendocardial Viability Ratio (SEVR, and index of subendocardial microvascular dysfunction), were evaluated by applanation tonometry. Results: Patients and controls were similar with respect to metabolic parameters, BMI, and renal function. MVA patients were on therapy with beta-blockers (50%), calcium channel blockers (37%), nitrates (12%), renin-angiotensin-blockers (44%), and statins (25%). MVA patients were slightly older than controls (63.6 ± 1.9 vs 53.1 ± 2.0 years, p &lt; 0.05). Albeit in the normal range, peripheral (pSBP) and central (cSBP) systolic BP were significantly higher in MVA patients as compared to controls (pSBP:134.3 ± 2.9 vs 118.5 ± 3.5 mmHg, p &lt; 0.002; and cSBP:124.8 ± 2.9 vs 109.7 ± 2.9 mmHg, p &lt; 0.001). Diastolic BP was similarly preserved in both groups. SEVR, an index of subendocardial microvascular dysfunction, was lower in MVA patients as compared to controls (139.7 ± 4.1 vs 160.4 ± 8.5 %, p &lt; 0.05). Augmentation index (AI), reflected (RPH), and forward (FPH) pulse height, all parameters of peripheral microvascular dysfunction, were also altered in MVA patients as compared to controls (AI:29.0 ± 1.0 vs 19.9 ± 2.4%, p &lt; 0.003; RPH:22.3 ± 1.4 vs 15.3 ± 0.9 mmHg, p &lt; 0.001; FPH:31.0 ± 1.4 vs 24.2 ± 1.4 mmHg p &lt; 0.005). The index of aortic stiffness PWV was similar in both groups (7.20 ± 07 vs 6.6 ± 0.2 m/sec, NS). Conclusions: Patients with MVA on optimal anti-schemic therapy exhibit alterations of parameters of both subendocardial and peripheral microvascular dysfunction, suggesting that coronary microvascular dysfunction is part of a more generalized disorder also involving peripheral resistance arteries.