Atrial Fibrillation and Early Vascular Aging: Clinical Implications, Methodology Issues and Open Questions-A Review from the VascAgeNet COST Action.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with adverse CV outcomes. Vascular aging (VA), which is defined as the progressive deterioration of arterial function and structure over a lifetime, is an independent predictor of both AF development and CV events. A timing identification and treatment of early VA has therefore the potential to reduce the risk of AF incidence and related CV events. A network of scientists and clinicians from the COST Action VascAgeNet identified five clinically and methodologically relevant questions regarding the relationship between AF and VA and conducted a narrative review of the literature to find potential answers. These are: (1) Are VA biomarkers associated with AF? (2) Does early VA predict AF occurrence better than chronological aging? (3) Is early VA a risk enhancer for the occurrence of CV events in AF patients? (4) Are devices measuring VA suitable to perform subclinical AF detection? (5) Does atrial-fibrillation-related rhythm irregularity have a negative impact on the measurement of vascular age? Results showed that VA is a powerful and independent predictor of AF incidence, however, its role as risk modifier for the occurrence of CV events in patients with AF is debatable. Limited and inconclusive data exist regarding the reliability of VA measurement in the presence of rhythm irregularities associated with AF. To date, no device is equipped with tools capable of detecting AF during VA measurements. This represents a missed opportunity to effectively perform CV prevention in people at high risk. Further advances are needed to fill knowledge gaps in this field.

Ring Opening Polymerization of Six- and Eight-Membered Racemic Cyclic Esters for Biodegradable Materials.

The low percentage of recyclability of the polymeric materials obtained by olefin transition metal (TM) polymerization catalysis has increased the interest in their substitution with more eco-friendly materials with reliable physical and mechanical properties. Among the variety of known biodegradable polymers, linear aliphatic polyesters produced by ring-opening polymerization (ROP) of cyclic esters occupy a prominent position. The polymer properties are highly dependent on the macromolecule microstructure, and the control of stereoselectivity is necessary for providing materials with precise and finely tuned properties. In this review, we aim to outline the main synthetic routes, the physical properties and also the applications of three commercially available biodegradable materials: Polylactic acid (PLA), Poly(Lactic-co-Glycolic Acid) (PLGA), and Poly(3-hydroxybutyrate) (P3HB), all of three easily accessible via ROP. In this framework, understanding the origin of enantioselectivity and the factors that determine it is then crucial for the development of materials with suitable thermal and mechanical properties.

Myocardial oxygen supply and demand imbalance predicts mortality in older nursing home residents: The PARTAGE study.

BACKGROUND: A mismatch between myocardial oxygen supply and demand is the most common cause of ischemic myocardial injury in older persons. The subendocardial viability ratio (SEVR) can usefully estimate the degree of myocardial perfusion relative to left-ventricular workload. The aim of the present study was to evaluate the ability of SEVR to predict long-term mortality in the older population. Additionally, we aimed to identify the SEVR cutoff value best predicting total mortality. METHODS: This is a multicenter, longitudinal study involving a large population of individuals older than 80 years living in nursing homes. Patients with cancer, severe dementia, and very low level of autonomy were excluded from the study. Participants were monitored for 10 years. Adverse outcomes were recorded every 3 months from inclusion to the end of the study. SEVR reflects the balance between subendocardial oxygen supply and demand, and was estimated non-invasively by analyzing the carotid pressure waveform recorded by applanation arterial tonometry. RESULTS: A total of 828 people were enrolled (mean age: 87.7 ± 4.7 years, 78% female). 735 patients died within 10 years and 24 were lost to follow-up. SEVR was inversely associated with mortality at univariate Cox-regression model (risk ratio, 0.683 per unit increase in SEVR; 95% confidence interval (CI) [0.502-0.930], p = 0.015) and in a model including age, sex, body mass index, Activity of Daily Living index and Mini-Mental State Examination score (risk ratio, 0.647; 95% CI [0.472-0.930]). The lowest tertile of SEVR was associated with higher 10-years total mortality than the middle (p < 0.001) and the highest (p < 0.004) tertile. A SEVR cutoff value of 83% was identified as the best predictor of total mortality. CONCLUSIONS: SEVR may be considered as a marker of "cardiovascular frailty." An accurate non-invasive estimation of SEVR could be a useful and independent parameter to assess survival probability in very old adults. TRIAL REGISTRATION: NCT00901355, registered on ClinicalTrials.gov website.

Preliminary Study on the Effect of a Night Shift on Blood Pressure and Clock Gene Expression.

Night shift work has been found to be associated with a higher risk of cardiovascular and cerebrovascular disease. One of the underlying mechanisms seems to be that shift work promotes hypertension, but results have been variable. This cross-sectional study was carried out in a group of internists with the aim of performing a paired analysis of 24 h blood pressure in the same physicians working a day shift and then a night shift, and a paired analysis of clock gene expression after a night of rest and a night of work. Each participant wore an ambulatory blood pressure monitor (ABPM) twice. The first time was for a 24 h period that included a 12 h day shift (08.00-20.00) and a night of rest. The second time was for a 30 h period that included a day of rest, a night shift (20.00-08.00), and a subsequent period of rest (08.00-14.00). Subjects underwent fasting blood sampling twice: after the night of rest and after the night shift. Night shift work significantly increased night systolic blood pressure (SBP), night diastolic blood pressure (DBP), and heart rate (HR) and decreased their respective nocturnal decline. Clock gene expression increased after the night shift. There was a direct association between night blood pressure and clock gene expression. Night shifts lead to an increase in blood pressure, non-dipping status, and circadian rhythm misalignment. Blood pressure is associated with clock genes and circadian rhythm misalignement.

Microcirculatory and Rheological Adaptive Mechanisms at High Altitude in European Lowlander Hikers and Nepalese Highlanders.

BACKGROUND: Physical activity at high-altitudes is increasingly widespread, both for tourist trekking and for the growing tendency to carry out sports and training activities at high-altitudes. Acute exposure to this hypobaric-hypoxic condition induces several complex adaptive mechanisms involving the cardiovascular, respiratory and endocrine systems. A lack of these adaptive mechanisms in microcirculation may cause the onset of symptoms of acute mountain sickness, a frequent disturbance after acute exposure at high altitudes. The aim of our study was to evaluate the microcirculatory adaptive mechanisms at different altitudes, from 1350 to 5050 m a.s.l., during a scientific expedition in the Himalayas. METHODS: The main haematological parameters, blood viscosity and erythrocyte deformability were assessed at different altitudes on eight European lowlanders and on a group of eleven Nepalese highlanders. The microcirculation network was evaluated in vivo by conjunctival and periungual biomicroscopy. RESULTS: Europeans showed a progressive and significant reduction of blood filterability and an increase of whole blood viscosity which correlate with the increase of altitude (p < 0.02). In the Nepalese highlanders, haemorheological changes were already present at their residence altitude, 3400 m a.s.l. (p < 0.001 vs. Europeans). With the increase in altitude, a massive interstitial oedema appeared in all participants, associated with erythrocyte aggregation phenomena and slowing of the flow rate in the microcirculation. CONCLUSIONS: High altitude causes important and significant microcirculatory adaptations. These changes in microcirculation induced by hypobaric-hypoxic conditions should be considered when planning training and physical activity at altitude.

Vascular ageing: moving from bench towards bedside.

Prevention of cardiovascular disease (CVD) remains one of the largest public health challenges of our time. Identifying individuals at increased cardiovascular risk at an asymptomatic, sub-clinical stage is of paramount importance for minimizing disease progression as well as the substantial health and economic burden associated with overt CVD. Vascular ageing (VA) involves the deterioration in vascular structure and function over time and ultimately leads to damage in the heart, brain, kidney, and other organs. Vascular ageing encompasses the cumulative effect of all cardiovascular risk factors on the arterial wall over the life course and thus may help identify those at elevated cardiovascular risk, early in disease development. Although the concept of VA is gaining interest clinically, it is seldom measured in routine clinical practice due to lack of consensus on how to characterize VA as physiological vs. pathological and various practical issues. In this state-of-the-art review and as a network of scientists, clinicians, engineers, and industry partners with expertise in VA, we address six questions related to VA in an attempt to increase knowledge among the broader medical community and move the routine measurement of VA a little closer from bench towards bedside.

Blood pressure variability: methodological aspects, clinical relevance and practical indications for management - a European Society of Hypertension position paper ∗.

Blood pressure is not a static parameter, but rather undergoes continuous fluctuations over time, as a result of the interaction between environmental and behavioural factors on one side and intrinsic cardiovascular regulatory mechanisms on the other side. Increased blood pressure variability (BPV) may indicate an impaired cardiovascular regulation and may represent a cardiovascular risk factor itself, having been associated with increased all-cause and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease, and dementia incidence. Nonetheless, BPV was considered only a research issue in previous hypertension management guidelines, because the available evidence on its clinical relevance presents several gaps and is based on heterogeneous studies with limited standardization of methods for BPV assessment. The aim of this position paper, with contributions from members of the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability and from a number of international experts, is to summarize the available evidence in the field of BPV assessment methodology and clinical applications and to provide practical indications on how to measure and interpret BPV in research and clinical settings based on currently available data. Pending issues and clinical and methodological recommendations supported by available evidence are also reported. The information provided by this paper should contribute to a better standardization of future studies on BPV, but should also provide clinicians with some indications on how BPV can be managed based on currently available data.

Dietary habits, lifestyle, and gestational diabetes in immigrant women: a survey in Northwestern Tuscany (Central Italy).

BACKGROUND: immigrant women diagnosed with gestational diabetes mellitus (GDM) have additional language and cultural obstacles in following lifestyle and dietary recommendations within a Western health care setting. OBJECTIVES: to describe: • sociodemographic characteristics and dietary and lifestyle behaviours in Italian and immigrant pregnant women who underwent a GDM screening; • any differences in these aspects among GDM Italian and immigrant women; • any differences in terms of primary maternal-neonatal outcomes among GDM and normal glucose tolerance (NGT) cohorts. DESIGN: survey. SETTING AND PARTICIPANTS: this survey was conducted in three hospitals located in Tuscany Region (Central Italy). According to a convenience sampling, an ad hoc questionnaire was administered both to Italian and immigrant women who underwent an oral glucose tolerance test. MAIN OUTCOME MEASURES: information about nutrition and lifestyle, medical and obstetric history, clinical and therapy data, maternal and neonatal primary outcomes was analysed. Eating habits have been investigated referring to the prudent diet, in order to also include those foods specifically consumed by the immigrant women, in addition to the Mediterranean Diet which is more widespread among Italians. RESULTS: a total of 117 Italian women (42 diagnosed with GDM) and 95 immigrant women (36 with GDM) were enrolled. Immigrant women showed lower adherence to the prudent diet compared to Italian women (p<0.05) and a broader use of unhealthy food preparation (e.g., frying; p<0.05). Primary maternal and neonatal outcomes (preterm birth, caesarean section, macrosomia) showed no statistical differences among GDM and NGT cohorts. CONCLUSIONS: even if immigrant and Italian women gained similar pregnancy outcomes, immigrant women showed lower adherence to the prudent diet at the time of GDM screening. An ethnic and tailored meal plan is needed to overcome cultural barriers in dietary recommendations during pregnancy in immigrant women.

Estimation of Aortic Stiffness with Bramwell-Hill Equation: A Comparative Analysis with Carotid-Femoral Pulse Wave Velocity.

Aortic stiffness is an important clinical parameter for predicting cardiovascular events. Carotid-femoral pulse wave velocity (cf-PWV) has been proposed for performing this evaluation non-invasively; however, it requires dedicated equipment and experienced operators. We explored the possibility of measuring aortic stiffness using ultrasound scans of the abdominal aorta coupled with the Bramwell-Hill equation. Healthy subjects were investigated; measurements of cf-PWV were taken by arterial tonometry and aortic systo-diastolic pressure difference was estimated using a validated model. Pulsatility of an abdominal tract of aorta was assessed by automated processing of ultrasound scans. Through a Bland-Altmann analysis, we found large biases when estimating each parameter by applying the Bramwell-Hill equation to the measured values of the other two paramters (bias, ± 1.96 SD; PWV, about 2.1 ± 2.5 m/s; pulsatility, 12 ± 14%; pressure jump, 47 ± 55 mmHg). These results indicate that the two measures are not interchangeable, and that a large part of the bias is attributable to blood pressure estimation. Further studies are needed to identify the possible sources of bias between cf-PWV and aortic pulsatility.

Haemodynamic Adaptive Mechanisms at High Altitude: Comparison between European Lowlanders and Nepalese Highlanders.

Background: Exposure to high altitudes determines several adaptive mechanisms affecting in a complex way the whole cardiovascular, respiratory, endocrine systems because of the hypobaric hypoxic condition. The aim of our study was to evaluate the circulatory adaptive mechanisms at high altitudes, during a scientific expedition in the Himalayas. Methods: Arterial distensibility was assessed measuring carotid-radial and carotid-femoral pulse wave velocity. Tests were carried out at several altitudes, from 1350 to 5050 m above sea level, on 8 lowlander European researchers and 11 highlander Nepalese porters. Results: In Europeans, systolic blood pressure and pulse pressure increased slightly but significantly with altitude (p < 0.05 and p < 0.001, respectively). Norepinephrine showed a significant increase after the lowlanders had spent some time at high altitude (p < 0.001). With increasing altitude, a progressive increase in carotid-radial and carotid-femoral pulse wave velocity values was observed in lowlanders, showing a particularly significant increase (p < 0.001) after staying at high altitude (carotid-radial pulse wave velocity, median value (interquartile range) from 9.2 (7.9−10.0) to 11.2 (10.9−11.8) m/s and carotid-femoral pulse wave velocity from 8.5 (7.9−9.0) to 11.3 (10.9−11.8) m/s). At high altitudes (3400 and 5050 m above sea level), no significant differences were observed between highlanders and lowlanders in hemodynamic parameters (blood pressure, carotid-radial and carotid-femoral pulse wave velocity). Conclusions: The progressive arterial stiffening with altitude observed in European lowlanders could explain the increase in systolic and pulse pressure values observed at high altitudes in this ethnic group. Further studies are needed to evaluate the role of aortic stiffening in the pathogenesis of acute mountain sickness.

Arterial Stiffness in Thyroid and Parathyroid Disease: A Review of Clinical Studies.

Growing evidence shows that arterial stiffness measurement provides important prognostic information and improves clinical stratification of cardiovascular risk. Thyroid and parathyroid diseases are endocrine diseases with a relevant cardiovascular burden. The objective of this review was to consider the relationship between arterial stiffness and thyroid and parathyroid diseases in human clinical studies. We performed a systematic literature review of articles published in PubMed/MEDLINE from inception to December 2021, restricted to English languages and to human adults. We selected relevant articles about the relationship between arterial stiffness and thyroid and parathyroid diseases. For each selected article, data on arterial stiffness were extracted and factors that may have an impact on arterial stiffness were identified. We considered 24 papers concerning hypothyroidism, 9 hyperthyroidism and 16 primary hyperparathyroidism and hypoparathyroidism. Most studies evidenced an increase in arterial stiffness biomarkers in hypothyroidism, hyperthyroidism and primary hyperparathyroidism, even in subclinical and mild forms, although heterogeneity of measurement methods and of study designs prevented a definitive conclusion, suggesting that the assessment of arterial stiffness may be considered in the clinical evaluation of cardiovascular risk in these diseases.

Non-Invasive Assessment of Arterial Stiffness: Pulse Wave Velocity, Pulse Wave Analysis and Carotid Cross-Sectional Distensibility: Comparison between Methods.

Background: The stiffening of large elastic arteries is currently estimated in research and clinical practice by propagative and non-propagative models, as well as parameters derived from aortic pulse waveform analysis. Methods: Common carotid compliance and distensibility were measured by simultaneously recording the diameter and pressure changes during the cardiac cycle. The aortic and upper arm arterial distensibility was estimated by measuring carotid−femoral and carotid−radial pulse wave velocity (PWV), respectively. The augmentation index and blood pressure amplification were derived from the analysis of central pulse waveforms, recorded by applanation tonometry directly from the common carotid artery. Results: 75 volunteers were enrolled in this study (50 females, average age 53.5 years). A significant inverse correlation was found between carotid distensibility and carotid−femoral PWV (r = −0.75; p < 0.001), augmentation index (r = −0.63; p < 0.001) and central pulse pressure (r = −0.59; p < 0.001). A strong correlation was found also between the total slope of the diameter/pressure rate carotid curves and aortic distensibility, quantified from the inverse of the square of carotid−femoral PWV (r = 0.67). No correlation was found between carotid distensibility and carotid−radial PWV. Conclusions: This study showed a close correlation between carotid−femoral PWV, evaluating aortic stiffness by using the propagative method, and local carotid cross-sectional distensibility.

Meta-analysis on the Association Between Thyroid Hormone Disorders and Arterial Stiffness.

Context: Aortic stiffness is an emerging predictor of cardiovascular morbidity and mortality. Current data about the effect of subclinical and overt thyroid hormone disorders on aortic stiffness are often conflicting. Objective: Primary outcome was to investigate if subclinical and overt thyroid hormone disorders were associated with aortic stiffness. Secondary outcome was to identify disease effect modifiers. Methods: Data sources were PubMed, Google Scholar, SCOPUS, Web of Sciences, and the Cochrane Library. Eligible studies included reports of pulse wave velocity (PWV), which is the gold standard method for measuring aortic stiffness, in patients with subclinical and overt thyroid disorders. Two investigators independently identified eligible studies and extracted data. Pooled mean difference was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Univariate meta-regression analysis was used to identify effect modifiers. Results: Eleven observational studies were selected, including 1239 patients with subclinical hypothyroidism, 81 patients with overt hypothyroidism, 338 patients with thyrotoxicosis, and 12 715 controls. PWV was significantly higher in subclinical (P < .001) and overt hypothyroidism (P < .001), as well as in patients with thyrotoxicosis (P = .027) compared with controls. Age was an effect modifier in hypothyroid patients. Conclusion: This study shows that both overt and subclinical hypothyroidism as well as thyrotoxicosis were associated with an increase of aortic stiffness. The impact of treatment of these conditions on aortic stiffness should be assessed in clinical trials.

Postoperative and mid-term hemodynamic changes after replacement of the ascending aorta.

OBJECTIVES: To evaluate aortic distensibility and pulse waveform patterns associated with the ascending aortic aneurysm, and to analyze the postoperative and mid-term hemodynamic changes induced by prosthetic replacement of the ascending aorta. METHODS: Central blood pressure waves were recorded at the carotid artery level by means of a validated transcutaneous arterial tonometer in 30 patients undergoing prosthetic replacement of ascending aortic aneurysm and in 30 control patients. Measurements were obtained the day before surgery and 5 to 7 days and 16 to 20 months after surgery. RESULTS: The ascending aortic aneurysm was associated with a less steep slope of early systolic phase of the pressure curve (pulsus tardus) compared with a control group (0.54 ± 0.18 mm Hg/ms vs 0.69 ± 0.26 mm Hg/ms; P = .011). Replacing the ascending aorta with a noncompliant vascular prosthesis steepened the pulse pressure slope during the early systolic phase in the postoperative period (0.77 ± .29 mm Hg/ms), providing values comparable with those of the control group in the mid-term (0.67 ± .20 mm Hg/ms). No change in aortic stiffness was found either postoperatively or in the mid-term after ascending aorta surgical replacement (carotid-femoral pulse wave velocity: preoperative, 9.0 ± 2.6 m/s; postoperative, 9.0 ± 2.9 m/s; mid-term postoperative, 9.3 ± 2.8 m/s). CONCLUSIONS: This study does not confirm the assumption that substitution of the viscoelastic ascending aorta with a rigid prosthesis can cause serious hemodynamic alterations downstream, because we did not observe a worsening of global aortic distensibility after insertion of a rigid prosthetic aorta. The ascending aortic aneurysm is associated with a pulsus tardus.

Comparison Between Invasive and Noninvasive Methods to Estimate Subendocardial Oxygen Supply and Demand Imbalance.

Background Estimation of the balance between subendocardial oxygen supply and demand could be a useful parameter to assess the risk of myocardial ischemia. Evaluation of the subendocardial viability ratio (SEVR, also known as Buckberg index) by invasive recording of left ventricular and aortic pressure curves represents a valid method to estimate the degree of myocardial perfusion relative to left ventricular workload. However, routine clinical use of this parameter requires its noninvasive estimation and the demonstration of its reliability. Methods and Results Arterial applanation tonometry allows a noninvasive estimation of SEVR as the ratio of the areas directly beneath the central aortic pressure curves obtained during diastole (myocardial oxygen supply) and during systole (myocardial oxygen demand). However, this "traditional" method does not account for the intra-ventricular diastolic pressure and proper allocation to systole and diastole of left ventricular isometric contraction and relaxation, respectively, resulting in an overestimation of the SEVR values. These issues are considered in the novel method for SEVR assessment tested in this study. SEVR values estimated with carotid tonometry by "traditional" and "new" method were compared with those evaluated invasively by cardiac catheterization. The "traditional" method provided significantly higher SEVR values than the reference invasive SEVR: average of differences±SD= 44±11% (limits of agreement: 23% - 65%). The noninvasive "new" method showed a much better agreement with the invasive determination of SEVR: average of differences±SD= 0±8% (limits of agreement: -15% to 16%). Conclusions Carotid applanation tonometry provides valid noninvasive SEVR values only when all the main factors determining myocardial supply and demand flow are considered.

Meta-analysis on the Effect of Mild Primary Hyperparathyroidism and Parathyroidectomy Upon Arterial Stiffness.

CONTEXT: Current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold standard for assessing aortic stiffness, and it predicts cardiovascular morbidity and mortality. OBJECTIVE: Primary outcomes were to investigate if mild pHPT was associated with higher PWV and if parathyroidectomy (PTX) reduced PWV in mild pHPT. Secondary outcome was to investigate blood pressure changes after PTX. METHODS: Sources were PubMed, Google Scholar, SCOPUS, Web of Science, and the Cochrane Library. Eligible studies included reports of PWV in patients with mild pHPT and controls, or in patients with mild pHPT before and after PTX. Two investigators independently identified eligible studies and extracted data. Pooled mean difference (MD) was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Nine observational studies and one randomized clinical trial were selected, including 433 patients with mild pHPT, 171 of whom underwent PTX, and 407 controls. PWV was significantly higher in mild pHPT than in controls (MD = 1.18, 0.67 to 1.68, P < .0001). Seven studies evaluated the effect of PTX on PWV. PTX significantly reduced PWV (MD = -0.48, -0.88 to -0.07, P = .022). CONCLUSION: Aortic stiffness is increased in patients with mild pHPT, supporting the notion that mild pHPT is also associated with adverse cardiovascular manifestations. PTX significantly reduced arterial stiffness in mild pHPT, indicating that the benefit of PTX over cardiovascular manifestations should not be dismissed but it deserves further studies.

Assessment of Phasic Changes of Vascular Size by Automated Edge Tracking-State of the Art and Clinical Perspectives.

Assessment of vascular size and of its phasic changes by ultrasound is important for the management of many clinical conditions. For example, a dilated and stiff inferior vena cava reflects increased intravascular volume and identifies patients with heart failure at greater risk of an early death. However, lack of standardization and sub-optimal intra- and inter- operator reproducibility limit the use of these techniques. To overcome these limitations, we developed two image-processing algorithms that quantify phasic vascular deformation by tracking wall movements, either in long or in short axis. Prospective studies will verify the clinical applicability and utility of these methods in different settings, vessels and medical conditions.

Mean arterial pressure estimated by brachial pulse wave analysis and comparison with currently used algorithms.

OBJECTIVE: Mean arterial pressure (MAP) is usually calculated by adding one-third of pulse pressure (PP) to DBP. This formula assumes that the average value of pulse waveform is constant in all individuals and coincides with 33.3% of PP amplitude (MAP = DBP + PP × 0.333). Other formulas were lately proposed to improve the MAP estimation, adding to DBP an established percentage of PP: MAP = DBP + PP × 0.40; MAP = DBP + PP × 0.412; MAP = DBP + PP × 0.333 + 5 mmHg. METHODS: The current study evaluated the integral of brachial pulse waveform recorded by applanation tonometry in 1526 patients belonging to three distinct cohorts: normotensive or hypertensive elderly, hypertensive adults, and normotensive adults. RESULTS: The percentage of PP to be added to DBP to obtain MAP was extremely variable among individuals, ranging from 23 to 58% (mean: 42.2 ±â€Š5.5%), higher in women (42.9 ±â€Š5.6%) than men (41.2 ±â€Š5.1%, P < 0.001), lower in the elderly cohort (40.9 ±â€Š5.3%) than in the general population cohort (42.8 ±â€Š6.0%, P < 0.001) and in the hypertensive patients (42.4 ±â€Š4.8%, P < 0.001). This percentage was significantly associated with DBP (ß = 0.357, P < 0.001) and sex (ß = 0.203, P < 0.001) and significantly increased after mental stress test in 19 healthy volunteers (from 39.9 ±â€Š3.2 at baseline, to 43.0 ±â€Š4.0, P < 0.0001). The average difference between MAP values estimated by formulas, compared with MAP assessed on the brachial tonometric curve, was (mean ±â€Š1.96 × SD): -5.0 ±â€Š6.7 mmHg when MAP = DBP + PP × 0333; -1.2 ±â€Š6.1 mmHg when MAP = DBP + PP × 0.40; -0.6 ±â€Š6.1 mmHg when MAP = DBP + PP × 0.412; -0.4 ±â€Š6.7 mmHg when MAP = DBP + PP × 0.333 + 5. CONCLUSION: Due to high interindividual and intraindividual variability of pulse waveform, the estimation of MAP based on fixed formulas derived from SBP and DBP is unreliable. Conversely, a more accurate estimation of MAP should be based on the pulse waveform analysis.