AIMS:To evaluate prevalence, clinical predictors, brain lesions and cognitive test scores of high-risk carotid plaque features-namely intraplaque haemorrhage (IPH), lipid-rich necrotic core (LRNC), and plaque ulceration-in patients with asymptomatic, intermediate-degree carotid artery stenosis. METHODS AND RESULTS:The Carotid Artery Multi-modality imaging Prognostic (CAMP) study is a prospective, observational cohort study enrolling patients with 40-60% asymptomatic carotid artery stenosis assessed by Doppler ultrasound. The present study is a cross-sectional analysis of baseline data. High-risk plaque characteristics were evaluated with multimodal vascular imaging, including computed tomography and magnetic resonance angiography, while brain magnetic resonance imaging and neurocognitive testing assessed covert brain infarcts, cerebral small vessel disease, and cognitive functions. Among 155 patients (mean age: 72 years, 27% female, 29% with chronic coronary syndromes), at least one high-risk plaque feature (LRNC, IPH, or ulcer) was present in 51% of cases. IPH and LRNC were present in 23% for both, and ulceration in 38%. Patients with high-risk plaque features had higher high-sensitivity cardiac troponin T and 3-vessel coronary artery disease. Non-lacunar brain infarcts [cortical and large (>15 mm) subcortical brain infarcts] and markers of small vessel disease (lacunar infarcts or white matter hyperintensities) were observed in 11% and 71% of patients, respectively. In univariate analysis, homolateral IPH, LRNC, and ≥50% carotid stenosis were associated with non-lacunar brain infarcts. In multivariable models adjusted for cardiovascular risk factors and carotid stenosis, both IPH and LRNC remained significantly associated with non-lacunar brain infarcts. When high-risk plaque features (LRNC and/or IPH) and ≥50% stenosis were included in the same model, only high-risk plaque features remained significantly associated with non-lacunar brain infarcts. Low visuospatial and nonverbal memory test scores were common, with a tendency towards poorer performance in patients with high-risk features, although the differences were not statistically significant. CONCLUSION:High-risk plaque features are frequent in patients with asymptomatic intermediate carotid disease and are associated with non-lacunar covert brain infarcts. Cognitive impairment was common in the cohort, although not associated with high-risk carotid plaque. These findings support the use of a comprehensive plaque characterization beyond stenosis grading for cerebrovascular risk assessment in such patients.

Background: The impact of CYP2C19 loss-of-function (LOF) variants on clopidogrel efficacy in atrial fibrillation (AF) patients undergoing percutaneous coronary intervention (PCI) remains uncertain. While clopidogrel is the preferred P2Y12 inhibitor in combination with oral anticoagulants, approximately one-third of patients carry CYP2C19 LOF alleles, known to reduce platelet inhibition and increase ischemic risk. Methods: The WOEST-3 genetic substudy is an observational pharmacogenetic investigation embedded within the randomized WOEST-3 trial (NCT04436978). Patients with AF undergoing PCI and providing additional consent for genetic testing will be included. CYP2C19 *2, *3, *4, *8 and *35 genotypes will be determined using both Genedrive® (Genedrive Diagnostics Ltd, Manchester, UK) point-of-care and laboratory-based assays. Genetic results will remain blinded to investigators and clinicians to avoid treatment bias. The primary endpoint is a 6-month composite of death, myocardial infarction, stroke, systemic embolism, and stent thrombosis. Approximately 30% of patients are anticipated to carry CYP2C19 LOF alleles. The study will determine whether concomitant direct oral anticoagulants therapy mitigates the impact of reduced clopidogrel activation in these carriers or whether genetic variability continues to confer excess ischemic risk. Conclusions: This protocol paper describes the rationale and design of a genetic substudy aimed at clarifying the prognostic relevance of CYP2C19 genotype in AF patients undergoing PCI and informing the design of future genotype-guided antithrombotic trials.

Objectives: The aim of the study was to evaluate the role of central pulse pressure (PP) in carotid wall thickening and coronary artery calcification (CAC). Methods: In an asymptomatic general population ( N = 396, 163 men, 47–89 years), central PP was measured by applanation tonometry, CAC by computed tomography, and common carotid artery intima–media thickness (cIMT), pulse wave velocity (cPWV) and the power of the signal reflected from carotid media (cMP) by radiofrequency-based carotid ultrasound. High cIMT was defined as cIMT equal to or greater than the 75th percentile for given sex and age, and CAC presence as a CAC score greater than 0. Results: In the entire population, luminal diameter and cMP increased with increasing central PP ( r = 0.32 and 0.25; P < 0.0001). One hundred and ninety-seven individuals had high cIMT; individuals with high cIMT had higher central PP, luminal diameter, cMP and cPWV ( P = or <0.0001), but comparable wall tensile stress ( P = 0.23). In a logistic regression model, high cIMT was independently associated with luminal diameter and central PP. One hundred and fifty-two individuals had CAC score greater than 0; in a logistic regression model, CAC score greater than 0 was independently associated with sex, age, central PP, LDL-cholesterol, triglycerides and T2DM. Conclusion: Our findings indicate that high central PP contributes both to an increase in cIMT and the development of CAC. However, while central PP was the only risk factor linked to high cIMT, multiple atherosclerotic risk factors were associated with CAC. Therefore, both high cIMT and CAC reflect the adverse impact of high pulsatile load on the vascular system, yet only CAC can be considered a marker of atherosclerosis.

Abstract Background Patients admitted with an acute coronary syndrome (ACS) often have unknown cardiovascular risk factors, such as impaired glucose tolerance (IGT) or diabetes mellitus (DM). Detecting these conditions is crucial to intensify appropriate therapies. Increased aortic stiffness, assessed by aortic pulse wave velocity (PWV), is associated with higher mortality in patients at high cardiovascular risk. Purpose Estimating the prevalence of IGT and DM and their relationship with increased aortic stiffness in patients admitted with an ACS. Methods Seventy-five consecutive patients admitted for ACS (21% women, mean age 63.6±11.1 ys), with fasting plasma glucose (PG) and glycated hemoglobin (HbA1c) not diagnostic for diabetes mellitus, underwent a fully standardized oral glucose tolerance test. All patients were also evaluated with the Arteriograph device, which applies a brachial cuff-based oscillometric method for the estimation of aortic PWV and arterial pulse waveform features. The automated vascular studies and OGTTs were performed after patient stabilization, at least 96 hours after admission. Results Forty-one patients (55% of the total study population) showed an abnormal OGTT response: 14 patients had a 2-h PG-OGTT ≥ 200 mg/dL, uncovering a diagnosis of DM, and 27 patients had a 2-h PG-OGTT ≥ 140 mg/dL, uncovering a diagnosis of IGT. Patients with DM showed no differences in terms of age, cardiovascular risk factors, Framingham risk score, C-reactive protein values, whereas a significant difference was observed in the number of diseased coronary vessels (2.2±0.8 vs 1.6±0.9, p=0.016) and PWV values (10.0±1.3 vs 8.8±1.6 m/s, p=0.028). Similarly, when considering all patients with an abnormal OGTT, a significant difference was observed in PWV values compared to patients with a normal OGTT (9.5±1.5 vs 8.4±1.7 m/s, p=0.032), as well as in estimated glomerular filtration rate (78±18 vs 83±23 mL/min/1.73mq, p=0.05), and peak troponin values (3698±2905 vs 2124±2561 ng/ml, p=0.02). At follow-up (mean time 51.7 months), no patients had died, but 5 patients had a new major cardiovascular event. Aortic pulse wave velocity values were different between patients with and without events (10.6±2.3 vs 8.6±1.4 m/s, p=0.024), and PWV was a significant predictor of events at univariate regression analysis (hazard ratio 1.93; 95 confidence intervals 1.01-3.69, p=0.047). Conclusions An unknown diagnosis of DM and/or IGT is very frequent in patients with ACS. Undiagnosed dysglycemic conditions are linked to a higher prevalence of coronary multivessel disease and increased aortic stiffness, which is also predictive of future cardiovascular events. A systematic screening with OGTT may help identifying patients at even higher cardiovascular risk, and tailoring secondary prevention strategies through personalized aggressive therapeutic interventions.

Background Lower extremity arterial disease (LEAD) and increased aortic stiffness are associated with higher mortality in patients with chronic coronary syndrome, while their prognostic significance after an acute coronary syndrome (ACS) is less known. Methods We analyzed prevalence, clinical phenotypes and association of LEAD – assessed by the ankle-brachial index (ABI) – and increased aortic stiffness – assessed by the aortic pulse wave velocity (PWV) – with all-cause mortality and major adverse cardiovascular events (MACE) in patients admitted with an ACS. Results Among 270 patients admitted for ACS (mean age 67 years, 80% males), 41 (15%) had an ABI ≤0.9, with 14 of them (34%) presenting with intermittent claudication (symptomatic LEAD). Patients with symptomatic LEAD, compared with those with asymptomatic LEAD or without LEAD, had higher prevalence of cardiovascular risk factors, lower estimated glomerular filtration rate and higher high-sensitivity C-reactive protein. Patients with LEAD, either symptomatic or asymptomatic, more frequently presented with non-ST-elevation myocardial infarction and more frequently had multivessel coronary artery disease. Both symptomatic and asymptomatic LEAD were significantly associated with all-cause mortality after adjustment for confounders, including multivessel disease or carotid artery disease (hazard ratio 4.03, 95% confidence interval 1.61–10.08, P < 0.01), whereas PWV was not associated with the outcome in the univariable model. LEAD and PWV were not associated with a higher risk of MACE (myocardial infarction or unstable angina, stroke, or transient ischemic attack). Conclusions LEAD, either clinical or subclinical, but not increased aortic stiffness, is an independent predictor of all-cause mortality in patients admitted for ACS.

Background/Objectives: This study compares the power of the radiofrequency (RF) signal reflected from the media layer (media power) of the common carotid artery (CCA) and the CCA stiffness between individuals with and without type 2 diabetes mellitus (T2DM). It also evaluates the associations of CCA media power with plasma glucose and lipid levels, as well as carotid stiffness. Methods: A total of 540 individuals, 115 with and 425 without T2DM (273 males, mean age = 64 ± 8 years) were studied using RF-based tracking of the right CCA. The following parameters were measured: CCA media thickness, luminal diameter, wall tensile stress (WTS), local pulse wave velocity (PWV), and media power. Results: Compared to the non-diabetic individuals, the T2DM patients had significantly higher CCA media thickness (652 ± 122 vs. 721 ± 138 microns, p < 0.005), luminal diameter (6.12 ± 0.78 vs. 6.86 ± 0.96 mm, p < 0.0005), media power (36.1 ± 4.8 vs. 39.3 ± 4.6, p < 0.0001), and PWV (7.65 ± 1.32 vs. 8.40 ± 1.89 m/s; p < 0.01), but comparable WTS (32.7 ± 10.4 vs. 33.1 ± 10.7 kPa; p = 0.25). In the entire population, CCA media power was independently associated with male sex, pulse pressure, current smoking, and T2DM; when T2DM was not included in the model, triglycerides emerged as an independent determinant of media power. The CCA PWV was independently associated with age, pulse pressure, media power, and T2DM. Conclusions: Our findings suggest the presence of structural changes in the arterial media of T2DM patients, leading to carotid stiffening and remodeling, aiming to preserve WTS. T2DM-related changes in arterial wall composition may be driven by high plasma triglyceride levels, which have previously been associated with both arterial stiffening and the incidence of CV events.

Abstract Background [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a valid technique to quantify carotid plaque inflammation and can improve identification of patients at high risk for stroke. There are few data on the inflammatory plaque activity in asymptomatic patients and of its association with other characteristics of plaque vulnerability. Purpose To assess the inflammatory carotid plaque activity and its correlations with patient characteristics and features of plaque vulnerability detected by other imaging techniques in a population of patients with asymptomatic mild/moderate degree of stenosis. Methods Seventy-five asymptomatic patients with 40-60% unilateral carotid stenosis at Doppler ultrasound (DUS) were prospectively evaluated with [18F]FDG-PET, computed tomography angiography (CTA), and magnetic resonance angiography (MRA). Regions of interests were drawn using fused PET/CT slices on the most diseased segment (MDS), defined as the single hottest slice of [18F]FDG uptake. Background blood pool activity was obtained from regions of interests placed in the lumen of the jugular vein. The target-to-background ratio (TBR) was calculated by dividing maximum standardized uptake value (SUVmax) of the MDS to SUVmax of ipsilateral blood pool activity. Plaque vulnerability was defined as the presence of an echolucent plaque at DUS, plaque ulceration at CTA, intraplaque hemorrhage, and lipid-rich necrotic core at MRA. Results Patients with a TBR ≥median (1.75), compared with those below the median, were significantly more frequently male and on statin therapy, had higher prevalence of ulcerated plaque at CTA (61% vs 35%, p=0.03) and intraplaque hemorrhage at MRA (33% vs 10%, p=0.03), while the prevalence of a lipid-rich necrotic core at MRA was not significantly different (p=0.16). TBR and SUVmax of the MDS were similar in those with or without a ≥50% stenosis, and peak velocities indices at DUS were not significantly correlated with TBR or SUVmax. Log(TBR) was significantly higher in ulcerated, rather than non-ulcerated, plaque (0.27 vs 0.21, p=0.03) and numerically higher in plaques with an intraplaque hemorrhage (0.22 vs 0.30, p=0.06). Log(TBR) and Log(SUVmax) were similar in plaques with and without a lipid-rich necrotic core (p=0.86 for both). Conclusions Higher TBR or SUVmax, indicating a high inflammatory activity, are associated with an ulcerated plaque and the presence of intraplaque hemorrhage but not with either the degree of stenosis or the presence of a lipid-rich necrotic core.

Several noninvasive vascular biomarkers have been proposed to improve risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and without diabetes and lipid-lowering treatment. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score = 0 (OR 0.67; 95%CI 0.48-0.92, p = 0.01), CAC score > 100 (1.59; 1.08-2.39, p = 0.01) and high common femoral artery (CFA) IMT (1.89; 1.19-3.06, p < 0.01), but not with other biomarkers. Our data confirm that in individuals at intermediate risk, lipid-lowering treatment can be avoided in the presence of a CAC score = 0, while it should be used with a CAC score > 100. CFA IMT could represent a useful biomarker for decisions regarding lipid-lowering treatment. However, sex- and age-specific reference values should be established in a large healthy population.

Pulse wave velocity (PWV) is a powerful predictor of cardiovascular events. However, its intrinsic blood pressure (BP)-dependency complicates distinguishing between acute and chronic effects of increased BP on arterial stiffness. Based on the assumption that arteries exhibit a nearly exponential pressure-area (P-A) relationship, this study proposes a method to assess intersubject differences in local PWV independently from BP. The method was then used to analyze differences in local carotid PWV (cPWV) between hypertensive and healthy normotensive people before and after BP-normalization. Pressure (P) and diameter (D) waveforms were simultaneously acquired via tonometer at the left and ultrasound scanning at right common carotid artery (CCA), respectively, in 22 patients with Grade 1 or 2 hypertension and 22 age- and sex-matched controls. cPWV was determined using the D2P-loop method. Then, the exponential modeling of the P-area (A = πD2/4) relationships allowed defining a mathematical formulation to compute subject-specific changes in cPWV associated with BP changes, thus enabling the normalization of cPWV against intersubject differences in BP at the time of measurement. Carotid systolic BP (SBP) and diastolic BP (DBP) were, on average, 17.7 (p < 0.001) and 8.9 mmHg (p < 0.01) higher in hypertensives than controls, respectively. cPWV was 5.56 ± 0.86 m/s in controls and 6.24 ± 1.22 m/s in hypertensives. BP alone accounted for 68% of the cPWV difference between the two groups: 5.80 ± 0.84 vs. 6.03 ± 1.07 m/s after BP-normalization (p = 0.47). The mechanistic normalization of cPWV was in agreement with that estimated by analysis of covariance (ANCOVA). In conclusion, the proposed method, which could be easily implemented in the clinical setting, allows to assess the intersubject differences in PWV independently of BP. Our results suggested that mild hypertension in middle-aged subjects without target organ damage does not significantly alter the stiffness of the CCA wall independently of acute differences in BP. The results warrant further clinical investigations to establish the potential clinical utility of the method.

BACKGROUND Carotid artery disease is highly prevalent and a main cause of ischemic stroke and vascular dementia. There is a paucity of information on predictors of serious vascular events. Besides percentage diameter stenosis, international guidelines also recommend the evaluation of qualitative characteristics of carotid artery disease as a guide to treatment, but with no agreement on which qualitative features to assess. This inadequate knowledge leads to a poor ability to identify patients at risk, dispersion of medical resources, and unproven use of expensive and resource-consuming techniques, such as magnetic resonance imaging, positron emission tomography, and computed tomography. OBJECTIVES The Carotid Artery Multimodality imaging Prognostic (CAMP) study will: prospectively determine the best predictors of silent and overt ischemic stroke and vascular dementia in patients with asymptomatic subcritical carotid artery disease by identifying the noninvasive diagnostic features of the 'vulnerable carotid plaque'; assess whether 'smart' use of low-cost diagnostic methods such as ultrasound-based evaluations may yield at least the same level of prospective information as more expensive techniques. STUDY DESIGN We will compare the prognostic/predictive value of all proposed techniques with regard to silent or clinically manifest ischemic stroke and vascular dementia. The study will include ≥300 patients with asymptomatic, unilateral, intermediate degree (40-60% diameter) common or internal carotid artery stenosis detected at carotid ultrasound, with a 2-year follow-up. The study design has been registered on Clinicaltrial.gov on December 17, 2020 (ID number NCT04679727).

BackgroundThe arterial pressure waveform reflects the interaction between the heart and the arterial system and carries potentially relevant information about circulatory status. According to the commonly accepted ‘wave transmission model’, the net BP waveform results from the super-position of discrete forward and backward pressure waves, with the forward wave in systole determined mainly by the left ventricular (LV) ejection function and the backward by the wave reflection from the periphery, the timing and amplitude of which depend on arterial stiffness, the wave propagation speed and the extent of downstream admittance mismatching. However, this approach obscures the ‘Windkessel function’ of the elastic arteries. Recently, a ‘reservoir-excess pressure’ model has been proposed, which interprets the arterial BP waveform as a composite of a volume-related ‘reservoir’ pressure and a wave-related ‘excess’ pressure.MethodsIn this study we applied the reservoir-excess pressure approach to the analysis of carotid arterial pressure waveforms (applanation tonometry) in 10 young healthy volunteers before and after a 5-week head down tilt bed rest which induced a significant reduction in stroke volume (SV), end-diastolic LV volume and LV longitudinal function without significant changes in central blood pressure, cardiac output, total peripheral resistance and aortic stiffness. Forward and backward pressure components were also determined by wave separation analysis.ResultsCompared to the baseline state, bed rest induced a significant reduction in LV ejection time (LVET), diastolic time (DT), backward pressure amplitude (bP) and pressure reservoir integral (INTPR). INTPR correlated directly with LVET, DT, time to the peak of backward wave (bT) and stroke volume, while excess pressure integral (INTXSP) correlated directly with central pressure. Furthermore, Δ.INTPR correlated directly with Δ.LVET, and Δ.DT, and in multivariate analysis INTPR was independently related to LVET and DT and INTXSP to central systolic BP.ConclusionThis is an hypothesis generating paper which adds support to the idea that the reservoir-wave hypothesis applied to non-invasively obtained carotid pressure waveforms is of potential clinical usefulness.

The concept of vascular age (VA) was proposed to provide patients with an understandable explanation of cardiovascular (CV) risk and to improve the performance of prediction models. The present study compared risk-based VA derived from Framingham Risk Score (FRS) and Systematic Coronary Risk Estimation (SCORE) models with value-based VA derived from the measurement of the common carotid artery (CCA) distensibility coefficient (DC), and it assessed the impact of DC-based VA on risk reclassification. In 528 middle-aged individuals apparently free of CV disease, DC was measured by radiofrequency-based arterial wall tracking that was previously utilised to establish sex- and age-specific reference values in a healthy population. DC-based VA represented the median value (50th percentile) for given sex in the reference population. FRS-based and SCORE-based VA was calculated as recommended. We observed a good agreement between DC-based and FRS-based VA, with a mean difference of 0.46 ± 12.2 years (p = 0.29), while the mean difference between DC-based and SCORE-based VA was higher (3.07 ± 12.7 years, p < 0.0001). When only nondiabetic individuals free of antihypertensive therapy were considered (n = 341), the mean difference dropped to 0.70 ± 12.8 years (p = 0.24). Substitution of chronological age with DC-based VA in FRS and SCORE models led to a reclassification of 28% and 49% of individuals, respectively, to the higher risk category. Our data suggest that the SCORE prediction model, in which diabetes and antihypertensive treatment are not considered, should be used as a screening tool only in healthy individuals. The use of VA derived from CCA distensibility measurements could improve the performance of risk prediction models, even that of the FRS model, as it might integrate risk prediction with additional risk factors participating in vascular ageing, unique to each individual. Prospective studies are needed to validate the role of DC-based VA in risk prediction.

Blood flow velocity profile in large arteries, although commonly assumed parabolic, quite often shows more complex patterns. The aim of this study was to investigate possible correlations between the different flow patterns and their potential determinants like systemic hemodynamic factors as well as local vessel geometry, distensibility and wave reflections. The study focuses on carotid (common, CCA, and internal, ICA) and femoral (common, CFA) arteries in normal subjects. The velocity profiles were obtained through the Multi Line Vector Doppler (MLVD) approach implemented in the ULA-OP 256 scanner, and their shape was quantified through the Bluntness Index (BI), i.e. the ratio between peak and cross-section averaged velocity. Possible correlations among BI and the other systemic and local parameters were investigated. We found that in healthy subjects, plaque free, the profile shape in the CCA is almost parabolic, but it is not in ICA and CFA. Moreover, the profile shape in the carotid is mainly affected by systemic hemodynamic factors, while local factors are more relevant for the profile in CFA.

Objectives: Arterial stiffness as pulse wave velocity (PWV) predicts cardiovascular events independently of blood pressure (BP). PWV does not distinguish between stiffness in systole and diastole. This cross-sectional study aimed to test the hypothesis that viscous and elastic carotid wall properties differ between systole and diastole, distinguishing effects of ageing, hypertension and T2 diabetes (T2DM). Methods: We examined carotid visco-elasticity in 307 people (180 men), with hypertension alone (n = 69), combined hypertension/T2DM (H-T2DM, n = 99), normotensive (N-T2DM, n = 25) and healthy controls (n = 114). Diameter (D)/pressure (P) waveforms were measured at right /left common carotid arteries, respectively. Local carotid PWV and distensibility in systole and diastole were evaluated by the D 2 P-loop method, and wall viscosity from hysteresis, the area (H A) within the P--D loop, as a dynamic measure of systolic loading and diastolic unloading. Results: Controls’ hysteresis fell quadratically with age (R 2 = 0.23, P < 0.001). Yet mean H A in hypertensive patients (0.95, 95% CI 0.65–1.23) was six-fold higher than in age-matched controls (0.14, −0.20 to 0.49, P < 0.001) with a 2.5× difference between diastolic (d Ds) to systolic (s Ds) distensibility (P < 0.05) in hypertensive patients. H A was higher in hypertensive patients and H-T2DMs (0.80, 0.58–1.04) than N-T2DMs (0.20, −0.17 to 0.54, P < 0.05), but similar between controls and N-T2DMs. BP-adjusted carotid diameters in all T2DM were significantly greater compared with controls and hypertensive patients. Conclusion: Higher BP increased wall viscosity, hysteresis and relative difference between systolic and diastolic distensibility across groups. Carotid diameters were increased in all T2DMs, more in H-T2DM, probably altering BP-flow dynamics in T2DM.

The estimation of central aortic blood pressure is a cardinal measurement, carrying effective physiological, and prognostic data beyond routine peripheral blood pressure. Transfer function-based devices effectively estimate aortic systolic and diastolic blood pressure from peripheral pressure waveforms, but the reconstructed pressure waveform seems to preserve features of the peripheral waveform. We sought to develop a new method for converting the local diameter distension waveform into a pressure waveform, through an exponential function whose parameters depend on the local wave speed. The proposed method was then tested at the common carotid artery. Diameter and blood velocity waveforms were acquired via ultrasound at the right common carotid artery while simultaneously recording pressure at the left common carotid artery via tonometer in 203 people (122 men, 50 +/- 18 years). The wave speed was noninvasively estimated via the lnDU-loop method and then used to define the exponential function to convert the diameter into pressure. Noninvasive systolic and mean pressures estimated by the new technique were 3.8 +/- 21.8 (p = 0.015) and 2.3 +/- 9.6 mmHg (p = 0.011) higher than those obtained using tonometery. However, differences were much reduced and not significant in people >35 years (0.6 +/- 18.7 and 0.8 +/- 8.3 mmHg, respectively). This proof of concept study demonstrated that local wave speed, estimated from noninvasive local measurement of diameter and flow velocity, can be used to determine an exponential function that describes the relationship between local pressure and diameter. This pressure-diameter function can then be used for the noninvasive estimation of local arterial pressure.

Purpose Obesity clearly increases cardiovascular risk, often inducing high blood pressure (BP), impaired left ventricular (LV) function, and increased arterial stiffness. Intensive weight loss and bariatric surgery induce improvement in hypertension and diabetes for morbid obesity. Carotid artery haemodynamics is a powerful prognostic indicator for stroke and cognitive decline independent of BP. The aim of this study was to evaluate the impact of a 3-stage bariatric strategy of diet, bariatric surgery, and consequent weight loss on carotid haemodynamics and cardiac diastolic function. Material and Methods This prospective study included 26 patients (45 ± 10 years, 4 men) with severe obesity undergoing bariatric surgery without comorbidities (hypertension, diabetes, etc.). Anthropometry, BP, Doppler echocardiography, and common carotid haemodynamics by ultrasound were measured at three times: (1) baseline, (2) after 1-month diet (post-diet), and (3) 8 months after surgery (post-surgery). The lnDU-loop method was used to estimate local carotid pulse wave velocity ( nc PWV). Results Baseline BMI was 47.9 ± 7.1 kg/m 2 and reduced by 5% and 30% post-diet and post-surgery, respectively. BP decreased only post-diet, without pulse pressure change. However, nc PWV, 6.27 ± 1.35 m/s at baseline, was significantly reduced by 10% and 23% post-diet and post-surgery, respectively, also adjusted for BP changes. The E/A ratio rose from 0.95 ± 0.20 to 1.27 ± 0.31 ( p < 0.005), without change in LV geometry or mass, while heart rate and cardiac output fell substantially. Conclusion Weight loss following diet and bariatric surgery is associated with reduced carotid arterial stiffness and improved LV diastolic function. Diet and bariatric surgery are effective treatments for morbid obesity with its concomitant adverse cardiovascular effects.

INTRODUCTION:The effect of metabolic syndrome (MS) on carotid stiffness (CS) in the context of gender is under research.OBJECTIVE:We examined the relationship between the MS and CS in men (M) and women (W) and investigated if the impact of cardiovascular risk factors on CS is modulated by gender.PATIENTS AND METHODS:The study included 419 subjects (mean age 54.3 years): 215 (51%) with MS (109 W and 106 M) and 204 (49%) without MS (98 W and 106 M). Carotid intima-media thickness (IMT) and CS parameters (beta stiffness index (beta), Peterson's elastic modulus (Ep), arterial compliance (AC) and one-point pulse wave velocity (PWV-beta)) were measured with the echo-tracking (eT) system.RESULTS:ANCOVA demonstrated that MS was associated with elevated CS indices (p = 0.003 for beta and 0.025 for PWV-beta), although further sex-specific analysis revealed that this relationship was significant only in W (p = 0.021 for beta). Age was associated with CS in both M and W, pulse pressure (PP) and body mass index turned out to be determinants of CS solely in W, while the effect of mean arterial pressure (MAP) and heart rate was more pronounced in M. MANOVA performed in subjects with MS revealed that age and diabetes mellitus type 2 were determinants of CS in both sexes, diastolic blood pressure and MAP - solely in M and systolic blood pressure, PP and waist circumference - solely in W (the relationship between the waist circumference and AC was paradoxical).CONCLUSION:The relationship between MS and CS is stronger in W than in M. In subjects with MS, various components of arterial pressure exert different sex-specific effects on CS - with the impact of the pulsative component of arterial pressure (PP) observed in W and the impact of the steady component (MAP) observed in M.

Plasma gamma-glutamyltransferase (GGT) was suggested to reflect the level of systemic oxidative stress. Oxidative stress induces changes in arterial structure and function and contributes to the development of hypertension. Therefore, GGT may be associated with arterial remodeling and blood pressure (BP) increment, even in absence of disease. To test this hypothesis, we evaluated, in 825 healthy subjects at low cardiometabolic risk, the associations of plasma GGT with carotid artery intima-media thickness (IMT), luminal diameter and prehypertension; in 154 subjects was evaluated also the association with aortic stiffness (cfPWV). Associations were controlled for insulin sensitivity, C-reactive protein, and life-style habits. In the main population, BP was remeasured after 3 years. Carotid diameter and cfPWV, but not IMT, were directly and independently related to plasma GGT. Subjects with prehypertension (N = 330) had higher GGT as compared with subjects with normal BP (22 [14] vs 17 [11] IU/L; adjusted P = 0.001), and within prehypertensive subjects, those who developed hypertension during 3 years had higher GGT than those without incident hypertension (27 [16] vs 21 [14] IU/L; adjusted P < 0.05). Within subjects with arterial stiffness measurement, those with prehypertension (N = 79) had higher both GGT and arterial stiffness (25 [14] vs 16 [20] IU/L and 9.11 ± 1.24 vs 7.90 ± 0.94 m/s; adjusted P < 0.01 and <0.05). In the view of previous evidence linking plasma GGT concentration to the level of systemic oxidative stress, our findings suggest a role of oxidative stress in subclinical arterial damage and in prehypertension, even in healthy subjects free of cardiometabolic risk. Arterial organ damage may represent the link between GGT and hypertension.

Purpose: It is unclear whether plasma homocysteine (Hcy) has a direct noxious impact on the cardiovascular (CV) system or whether its association with cardiovascular events (CVEs) is mediated by established risk factors. To explore the role of Hcy in CV impairment, the study evaluated cross-sectional relationships between plasma Hcy and indices of CV organ damage together with the associations of these indices with the history of CVEs. Methods: In 269 patients with a high prevalence of diabetes, dyslipidemia, and hypertension, the carotid intima-media thickness, ankle-brachial index (ABI), reactive hyperemic index, carotid-femoral pulse wave velocity (cfPWV), left ventricular (LV) mass, and cardiac index were measured. Results: 132 patients had carotid plaque, 31 ABI < 0.90, 126 endothelial dysfunction, 66 increased cfPWV, 125 LV hypertrophy (LVH), 153 decreased cardiac index, and 115 a history of CVEs. Plasma Hcy levels were related to LV mass and ABI, after adjustment for covariates and creatinine. Significantly higher Hcy levels were found in patients with LVH (8.5 [4.4] vs 7.6 [2.8] mu mol/L; adjusted P = .001) and ABI < 0.9 (10.4 [3.8] vs 7.9 [3.4] mu mol/L; adjusted P = .001) than in those with LV mass and ABI within limits. Hcy levels were comparable between patients with and without carotid plaques, increased arterial stiffness, impaired endothelial, and LV pump function. Within markers of CV organ damage, only LVH was associated with a history of CVEs. Conclusion: This study demonstrated an independent association between Hcy and LV mass as well as between LVH and a history of CVEs and suggests that LVH may represent 1 of the pathophysiologic links between Hcy and CV risk.