COVID-19 pneumonia: relationship between inflammation assessed by whole-body FDG PET/CT and short-term clinical outcome.

PURPOSE: [18F]-2-Fluoro-2-deoxy-D-glucose PET/CT (FDG PET/CT) is a sensitive and quantitative technic for detecting inflammatory process. Glucose uptake is correlated with an increased anaerobic glycolysis seen in activated inflammatory cells such as monocytes, lymphocytes, and granulocytes. The aim of the study was to assess the inflammatory status at the presumed peak of the inflammatory phase in non-critically ill patients requiring admission for COVID-19. METHODS: Patients admitted with COVID-19 were prospectively enrolled. FDG PET/CT was performed from day 6 to day 14 of the onset of symptoms. Depending on FDG PET/CT findings, patients' profiles were classified as "inflammatory" or "low inflammatory." FDG PET/CT data were compared with chest CT evolution and short-term clinical outcome. All inflammatory sites were reported to screen potential extra-pulmonary tropism. RESULTS: Thirteen patients were included. Maximum standardized uptake values ranged from 4.7 to 16.3 in lungs. All patients demonstrated increased mediastinal lymph nodes glucose uptake. Three patients (23%) presented mild nasopharyngeal, two patients (15%) bone marrow, and five patients (38%) splenic mild increase in glucose uptake. No patient had significant digestive focal or segmental glucose uptake. There was no significant physiological myocardial glucose uptake in all patients except one. There was no correlation between PET lung inflammatory status and chest CT evolution or short-term clinical outcome. CONCLUSION: Inflammatory process at the presumed peak of the inflammatory phase in COVID-19 patients is obvious in FDG PET/CT scans. Glucose uptake is heterogeneous and typically focused on lungs. TRIAL REGISTRATION: NCT04441489. Registered 22 June 2020 (retrospectively registered).

Shear stress regulates endothelial microparticle release.

RATIONALE: Endothelial activation and apoptosis release membrane-shed microparticles (EMP) that emerge as important biological effectors. OBJECTIVE: Because laminar shear stress (SS) is a major physiological regulator of endothelial survival, we tested the hypothesis that SS regulates EMP release. METHODS AND RESULTS: EMP levels were quantified by flow cytometry in medium of endothelial cells subjected to low or high SS (2 and 20 dyne/cm(2)). EMP levels augmented with time in low SS conditions compared with high SS conditions. This effect was sensitive to extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and Rho kinases inhibitors but unaffected by caspase inhibitors. Low SS-stimulated EMP release was associated with increased endothelial Rho kinases and ERK1/2 activities and cytoskeletal reorganization. Overexpression of constitutively active RhoA stimulated EMP release under high SS. We also examined the effect of nitric oxide (NO) in mediating SS effects. L-NG-nitroarginine methyl ester (L-NAME), but not D-NG-nitroarginine methyl ester, increased high SS-induced EMP levels by 3-fold, whereas the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) decreased it. L-NAME and SNAP did not affect Rho kinases and ERK1/2 activities. Then, we investigated NO effect on membrane remodeling because microparticle release is abolished in ABCA1-deficient cells. ABCA1 expression, which was greater under low SS than under high SS, was augmented by L-NAME under high SS and decreased by SNAP under low SS conditions. CONCLUSIONS: Altogether, these results demonstrate that sustained atheroprone low SS stimulates EMP release through activation of Rho kinases and ERK1/2 pathways, whereas atheroprotective high SS limits EMP release in a NO-dependent regulation of ABCA1 expression and of cytoskeletal reorganization. These findings, therefore, identify endothelial SS as a physiological regulator of microparticle release.

Microparticles, vascular function, and atherothrombosis.

Membrane-shed submicron microparticles (MPs) are released after cell activation or apoptosis. High levels of MPs circulate in the blood of patients with atherothrombotic diseases, where they could serve as a useful biomarker of vascular injury and a potential predictor of cardiovascular mortality and major adverse cardiovascular events. Atherosclerotic lesions also accumulate large numbers of MPs of leukocyte, smooth muscle cell, endothelial, and erythrocyte origin. A large body of evidence supports the role of MPs at different steps of atherosclerosis development, progression, and complications. Circulating MPs impair the atheroprotective function of the vascular endothelium, at least partly, by decreased nitric oxide synthesis. Plaque MPs favor local inflammation by augmenting the expression of adhesion molecule, such as intercellular adhesion molecule -1 at the surface of endothelial cell, and monocyte recruitment within the lesion. In addition, plaque MPs stimulate angiogenesis, a key event in the transition from stable to unstable lesions. MPs also may promote local cell apoptosis, leading to the release and accumulation of new MPs, and thus creating a vicious circle. Furthermore, highly thrombogenic plaque MPs could increase thrombus formation at the time of rupture, together with circulating MPs released in this context by activated platelets and leukocytes. Finally, MPs also could participate in repairing the consequences of arterial occlusion and tissue ischemia by promoting postischemic neovascularization.

Carotid circumferential wall stress homeostasis in early remodeling: theoretical approach and clinical application.

PURPOSE: To assess the influence of cardiovascular risk factors on arterial wall growth and the remodeling process. METHODS: In a theoretical part, we used a well-established relationship linking the rate of thickening of the arterial wall to the circumferential wall stress (CWS) increase. In a clinical part, we measured the intima-media thickness (IMT) in 166 subjects with increased cardiovascular risk score but no treatment for hypertension or hypercholesterolemia, no diabetes, and no cardiovascular disease. Far wall IMT and lumen diameter were measured along the right carotid artery by high-resolution ultrasonography and computerized image analysis. RESULTS: A decreasing linear relationship between IMT and CWS was deduced from the theoretical model, implying that an increase in CWS would result in an IMT increase, and that the higher the IMT-CWS slope, the higher the thickening response. Subjects with advanced age, renal insufficiency, high 10-year Framingham risk, carotid atherosclerosis, and advanced atherosclerosis at other sites had sharper IMT-CWS slope (p < 0.05), in agreement with the homeostasis of CWS hypothesis. CONCLUSIONS: The IMT increase responding to a CWS increase was greater in high-risk patients.

[Cardiovascular risk as assessed by traditional risk factors]. / Diagnostic du risque cardiovasculaire par les facteurs de risque traditionnels.

Although traditional cardiovascular risk factors play a proven aetiologic role in atherosclerosis-related cardiovascular disease, they fail to predict the occurrence of future clinical events, and, taken separately, they provide useful therapeutic target rather than diagnostic tools. Apart from the situation of severe monorisk, more frequent is the presentation of one individual with numerous moderate risk factors, the resulting global risk of whom being estimated by risk scores, such as the Framingham risk score or its derivatives. These models suffer various limitations, including the lack of applicability depending on geographic zones, and the lack of discrimination in the intermediate risk category, as compared to a better predictive value in the low risk and high risk categories. This lack is partially overcome by models that include complementary risk factors, requiring the need for other tools of reclassification, including the detection of subclinical atherosclerosis.

[New biomarkers for cardiovascular risk evaluation]. / Nouveaux biomarqueurs d'évaluation du risque cardiovasculaire.

Biomarkers aim at refining risk prediction and at better identifying individuals at high cardiovascular risk. To be recommended in clinical practice, a novel biomarker should be simple to measure, non-invasive, cost-effective, reproducible, and should provide a predictive and discriminative value independently of, and beyond existing risk scores. In addition, it should offer a favourable impact on morbidity, mortality and disability of the disease. Among the hundreds of candidate circulating biomarkers, certain have shown solid statistical associations with the incidence of future events, as is the case for high-sensitivity C-reactive protein. However, contrary to subclinical atherosclerosis assessment, they offer only a modest increase in the predictive value of current scores. To date, the main interest of cardiovascular biomarkers in primary prevention is to better understand pathophysiological mechanisms of atherosclerosis in the research setting.

Microvascular injuries, secondary edema, and inconsistencies in lung vascularization between affected and nonaffected pulmonary segments of non-critically ill hospitalized COVID-19 patients presenting with clinical deterioration.

PURPOSE: We aimed to better understand the pathophysiology of SARS-CoV-2 pneumonia in non-critically ill hospitalized patients secondarily presenting with clinical deterioration and increase in oxygen requirement without any identified worsening factors. METHODS: We consecutively enrolled patients without clinical or biological evidence for superinfection, without left ventricular dysfunction and for whom a pulmonary embolism was discarded by computed tomography (CT) pulmonary angiography. We investigated lung ventilation and perfusion (LVP) by LVP scintigraphy, and, 24 h later, left and right ventricular function by Tc-99m-labeled albumin-gated blood-pool scintigraphy with late (60 mn) tomographic albumin images on the lungs to evaluate lung albumin retention that could indicate microvascular injuries with secondary edema. RESULTS: We included 20 patients with confirmed SARS-CoV-2 pneumonia. All had CT evidence of organizing pneumonia and normal left ventricular ejection fraction. No patient demonstrated preserved ventilation with perfusion defect (mismatch), which may discard a distal lung thrombosis. Patterns of ventilation and perfusion were heterogeneous in seven patients (35%) with healthy lung segments presenting a relative paradoxical hypoperfusion and hypoventilation compared with segments with organizing pneumonia presenting a relative enhancement in perfusion and preserved ventilation. Lung albumin retention in area of organizing pneumonia was observed in 12 patients (60%), indicating microvascular injuries, increase in vessel permeability, and secondary edema. CONCLUSION: In hospitalized non-critically ill patients without evidence of superinfection, pulmonary embolism, or cardiac dysfunction, various types of damage may contribute to clinical deterioration including microvascular injuries and secondary edema, inconsistencies in lung segments vascularization suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others. SUMMARY STATEMENT: Microvascular injuries and dysregulation of the balance in perfusion between segments affected by COVID-19 and others are present in non-critically ill patients without other known aggravating factors. KEY RESULTS: In non-critically ill patients without evidence of superinfection, pulmonary embolism, macroscopic distal thrombosis or cardiac dysfunction, various types of damage may contribute to clinical deterioration including 1/ microvascular injuries and secondary edema, 2/ inconsistencies in lung segments vascularization with hypervascularization of consolidated segments contrasting with hypoperfusion of not affected segments, suggesting a dysregulation of the balance in perfusion between segments affected by COVID-19 and others.

The value of carotid intima-media thickness for predicting cardiovascular risk.

We reviewed prospective epidemiological data in the general population, mostly middle-aged to older persons, to determine the association of carotid intima-media thickness (CIMT) (assessed by B-mode ultrasonography) with cardiovascular risk. Reported risks were expressed as absolute (event risk per persons-years in subjects with a high CIMT) and relative (hazard ratio of high vs low CIMT). They were hardly comparable as the result of differences between the analyzed studies, including the site and procedure of CIMT measurement, the report of adjusted or unadjusted models, and the arbitrary cutoff point to evaluate the CIMTAEs ability to predict risk. Despite these heterogeneities, the following four main conclusions emerged: (1) CIMT was an independent but relatively modest (as judged by absolute risk) predictor of coronary heart disease (CHD); (2) CIMT was an independent predictor for stroke, slightly better than for CHD as judged by the relative risks of both events; (3) CIMT added little to the CHD prediction by risk factors, as judged by c statistic and receiver operating characteristic curve analysis (however, appropriate data for stroke on this important issue were lacking); and (4) the CHD prediction by CIMT was inferior to that by ultrasonography-assessed carotid plaque because plaque may be more representative of atherosclerosis than CIMT.

Self-Illusion and Medical Expertise in the Era of COVID-19.

The Dunning-Kruger premise assumes that unqualified people are unaware of their limited skills. We tested this hypothesis in the context of the coronavirus disease 2019 (COVID-19) pandemic. In this cross-sectional study, 2487 participants had to self-estimate their knowledge about COVID-19 in a questionnaire on the topic. Poor performers were more likely to use mass media and social networks as sources of information and had lower levels of education. The mean self-assessment (SD) was 6.88 (2.06) and was not linked to actual level of knowledge. This observation should prompt regulatory agencies and media to apply rules that limit dissemination of "infodemics" during global health crises.

Endothelial microparticles in diseases.

Microparticles are submicron vesicles shed from plasma membranes in response to cell activation, injury, and/or apoptosis. The measurement of the phospholipid content (mainly phosphatidylserine; PSer) of microparticles and the detection of proteins specific for the cells from which they are derived has allowed their quantification and characterization. Microparticles of various cellular origin (platelets, leukocytes, endothelial cells) are found in the plasma of healthy subjects, and their amount increases under pathological conditions. Endothelial microparticles (EMP) not only constitute an emerging marker of endothelial dysfunction, but are also considered to play a major biological role in inflammation, vascular injury, angiogenesis, and thrombosis. Although the mechanisms leading to their in vivo formation remain obscure, the release of EMP from cultured cells can be caused in vitro by a number of cytokines and apoptotic stimuli. Recent studies indicate that EMP are able to decrease nitric-oxide-dependent vasodilation, increase arterial stiffness, promote inflammation, and initiate thrombosis at their PSer-rich membrane, which highly co-expresses tissue factor. EMP are known to be elevated in acute coronary syndromes, in severe hypertension with end organ damage, and in thrombotic thrombocytopenic purpura, all conditions associated with endothelial injury and pro-thrombotic state. The release of EMP has also been associated with endothelial dysfunction of patients with multiple sclerosis and lupus anticoagulant. More recent studies have focused on the role of low shear stress leading to endothelial cell apoptosis and subsequent EMP release in end-stage renal disease. Improved knowledge of EMP composition, their biological effects, and the mechanisms leading to their clearance will probably open new therapeutic approaches in the treatment of atherothrombosis.

Correction of carotid intima-media thickness for adaptive dependence on tensile stress: implication for cardiovascular risk assessment.

PURPOSE: Early artery wall-thickening detected by ultrasound-assessed increased carotid intima-media thickness (IMT) may reflect atherosclerosis or represent an adaptive response to keep homeostasis tensile stress that is related inversely to wall thickness by Laplace's equation. We attempted to discriminate between both mechanisms by correcting IMT for its inverse association with tensile stress. METHODS: Common carotid IMT and lumen diameter (D) where determined in 40 healthy controls and 119 never-treated asymptomatic patients with >or=1 traditional cardiovascular risk factor. The cross-sectional area (CSA) was calculated as pi x IMT x (IMT + D). Tensile stress was approximated by [mean blood pressure x (D/2 x IMT)], and wall shear stress by [(blood viscosity) x 4 x (mean blood velocity/D)]. Inverse regression line relating IMT and tensile stress in controls (p < 0.001) was used as a reference to determine in an individual at-risk patient the IMT deviation, defining DeltaIMT from the regression line of controls at the measured patient's tensile stress. RESULTS: DeltaIMT correlated positively with age (p < 0.05), body mass index (p < 0.05), blood pressure (p < 0.001), and glucose (p < 0.001). In multivariate analysis, DeltaIMT was independently associated with age (p < 0.01), male gender (p < 0.001), and blood pressure (p < 0.001). IMT showed positive association with age (p < 0.001) but not with other risk factors. Also, DeltaIMT, like CSA, correlated positively with tensile stress (p < 0.001) and negatively with wall shear stress (p < 0.05, p < 0.01), whereas IMT correlated negatively with tensile stress (p < 0.001) but not with wall shear stress. CONCLUSION: Correcting IMT for adaptive association with tensile stress may give more strength to carotid evaluation for assessing cardiovascular risk.

Impact of shear stimulus, risk factor burden and early atherosclerosis on the time-course of brachial artery flow-mediated vasodilation.

OBJECTIVES: Our aim was to analyze flow-mediated dilation (FMD) time-course in response to forearm occlusion in the clinical setting. METHODS AND RESULTS: In 50 asymptomatic subjects, monitoring software measuring continuous beat-to-beat change in brachial artery diameter was used to determine FMD magnitude in percentage change in peak diameter from baseline (FMD-DeltaD), time to peak diameter after occlusion release (FMD-t(peak)), integrated FMD response calculated as area under dilation curve (FMD-AUC), maximum FMD rate calculated as maximal slope of dilation (FMD-MDR). FMD-DeltaD and FMD-MDR correlated positively with peak wall shear stress (P < 0.05, P < 0.01). FMD-MDR correlated negatively with age (P < 0.001), Framingham risk score (P < 0.01) and carotid intima-media thickness (P < 0.05), while FMD-DeltaD correlated negatively with Framingham risk score only (P < 0.01). After adjustment, all these correlations were independent of antihypertensive, lipid-lowering and antidiabetic therapies. All but that of FMD-MDR with intima-media thickness were also found in a subgroup of 29 untreated subjects and in a subgroup of 24 untreated and low-risk (FRS < 10%) subjects. FMD-t(peak) and FMD-AUC were not associated with shear stimulus, Framingham risk score, and intima-media thickness. CONCLUSION: The kinetics of dilation (maximum rate) seem more sensitive than their magnitude in assessing FMD performance and its determinants.

New assessment of endothelium-dependent flow-mediated vasodilation to characterize endothelium dysfunction.

The vascular endothelium plays an important role in the regulation of vascular tone, cell growth, inflammation, and thrombogenicity. Endothelium dysfunction, then, is considered to promote several disorders that initiate the atherosclerosis process. Vascular tone dysfunction can be determined by high-resolution ultrasonographic imaging of the brachial artery, enabling one to assess endothelium-dependent flow-mediated dilation (FMD). It is based on the principle that an increase in blood flow, specifically in shear stress, provokes the release of nitric oxide and then a vasodilation that can be quantified. In this study, brachial artery diameter evolution was continuously followed during baseline and hyperemia after forearm occlusion using a custom designed software. Some techniques used to measure FMD are limited by operator dependence. We present a new, automated, and versatile method of FMD quantification based on B-mode echographic images and edge detection algorithms. Edges for each image in the acquired sequences are recognized as interfaces based on the grey-level profiles of the averaged pixel values. Within-reading and within-subject FMD% coefficients of variation were 7% and 10%, respectively. This technique largely improves manual measurements and was shown to be appropriate for wide clinical use.

Decreased number of circulating CD34+KDR+ cells in asymptomatic subjects with preclinical atherosclerosis.

OBJECTIVES: To assess whether circulating endothelial progenitor cells (CEPCs) can be considered as a cardiovascular risk marker before event has occurred, that is less firmly established than in clinically overt atherosclerosis. METHODS: Number of CD34+KDR+ cell number per ml blood was measured by flow cytometry in 84 untreated subjects without cardiovascular disease. Atherosclerotic plaque was detected by ultrasound in carotid, abdominal aortic and femoral sites and the number of sites affected by plaque among these three sites was counted as 0, 1, 2 or 3. Additionally, intima-media thickness (IMT) was measured by computerized ultrasound imaging of both common carotid segments. RESULTS: CD34+KDR+ cell number decreased by 48, 29 or 30% in the presence of carotid, aortic or femoral plaque (p<0.001, 0.05, 0.05, respectively) as compared to the absence of plaque and by 70% in the presence of three sites affected with plaque as compared with 0 site with plaque (p<0.01) but did not change with increasing IMT tertiles. Adjustment for Framingham risk score, that was also associated with decreased CD34+KDR+ cell number (p<0.001), made CD34+KDR+ cell number associations with plaque insignificant, except at the carotid site (p<0.01). CONCLUSIONS: Reduced CEPC number may participate to preclinical stage of atherosclerosis and provide additional information to traditional risk factors as regards global risk assessment.

New monitoring software for larger clinical application of brachial artery flow-mediated vasodilatation measurements.

BACKGROUND: The reproducibility of brachial artery flow-mediated vasodilatation (FMD) is limited by the operator dependence of most measurement methods. METHODS: A new automated computerized analysis of brachial artery ultrasound scan providing a continuous evolution of the diameter during acute hyperemia, reactive to short hyperemia of the forearm and hand, was tested in 10 normal volunteers and 26 asymptomatic patients with cardiovascular risk factors such as hypertension, hypercholesterolemia, heavy smoking, history of premature coronary heart disease and the metabolic syndrome. FMD was the percentage of the maximum hyperemic diastolic diameter from baseline. Within-reading variations in FMD and diameters were assessed by reading one scan from the same subject twice by two observers. The within-subject variability of FMD was assessed by analysing two repeated measurements in the same subject by the same operator 1 h, 1 week or 1 month apart. RESULTS: Coefficients of variation (CV) of repeated FMD readings were 7.5% in normal volunteers and 6.9% in patients with risk factors. CV of repeated FMD measurements 1 h apart were 7.8% in normal volunteers and 16.5% in patients with risk factors. In normal volunteers, CV of repeated FMD measurements 1 week apart was 9.6%, and in patients with risk factors CV of repeated FMD measurement 1 month apart was 18.1%. CONCLUSION: This method overcomes the variability of FMD measurement seen with conventional manual analysis in normal volunteers, and to a lesser extent in patients with major cardiovascular risk factors, thus supporting its clinical applicability to patients with disease conditions.

Atherosclerosis in ANCA-associated vasculitides.

It is currently accepted that atherosclerosis is rather, or also, an inflammatory disease and, indeed, vasculitis is defined by inflammatory infiltrates in blood vessel walls, albeit initially by different predominant cell populations and in arteries of different calibers. As for other chronic systemic inflammatory diseases, premature and accelerated atherosclerosis has emerged during the last 5-10 years as an important facet of vasculitides, independently of the other risk factors of cardiovascular disease and also, apparently, corticosteroids. Chronic systemic inflammation, like persistently active vasculitis, might play a role in early atherosclerosis, through the actions of C-reactive protein (CRP), some adhesion molecules, and/or cytokines, as well as local inflammation, perhaps through locally secreted TNF-alpha and/or upregulation of matrix metalloproteinases and oxidative stress. Endothelial cell dysfunction and increased arterial stiffness have also been found in vasculitis patients. Notably, some vasculitis treatments were able to reverse some of these endothelial cell anomalies. Unlike antineutrophil cytoplasm autoantibodies (ANCA), which were not shown to correlate with a higher risk of atherosclerosis or cardiovascular events, autoantibodies to endothelial cells, heat-shock proteins, or oxidized-LDL may also be implicated, although these latter are now thought to protect against atherosclerosis. It is likely that other, as yet unidentified, factors facilitating atherosclerosis may play more important roles in vasculitides. Until their precise identification, it remains important to take into consideration and treat, every time it is necessary and possible, the other well-known cardiovascular risk factors.

Circulating leukocyte-derived microparticles predict subclinical atherosclerosis burden in asymptomatic subjects.

OBJECTIVE: To clarify circulating microparticles (MP) relationships with preclinical atherosclerosis. METHODS AND RESULTS: In 216 subjects without cardiovascular disease, we assessed: (1) annexin V-positive, platelet-derived, endothelium-derived and leukocyte-derived circulating MP by capture on annexin V, anti-GPIb, anti-CD105, and anti-CD11a antibody-coated wells, respectively; (2) Framingham risk, metabolic syndrome, and low-grade inflammation by risk factors measurement including hsCRP; and (3) subclinical atherosclerosis by ultrasound examination of carotid, abdominal aorta, and femoral arteries. Number of sites with plaque ranged from 0 to 3 and plaque burden was classified into 0 to 1 or 2 to 3 sites disease. Leukocyte-derived MP level was higher in the presence than in the absence of moderate to high Framingham risk (P<0.05), metabolic syndrome (P<0.01), high C-reactive protein (CRP) (P<0.05), or 2- to 3-sites disease (P<0.01), and correlated positively with number of metabolic syndrome components (P<0.001), tertiles of fibrinogen (P<0.001), and number of diseased sites (P<0.01). In multivariate analysis, 2- to 3-sites disease was independently associated with leukocyte-derived MP level (P<0.05), Framingham risk (P<0.001), and metabolic syndrome (P<0.01). None of the other MP types correlated with risk markers or atherosclerosis. CONCLUSIONS: Leukocyte-derived MP, identified by affinity for CD11a, are increased in subjects with ultrasound evidence of subclinical atherosclerosis, unveiling new directions for atherosclerosis research.

Effects of enhanced external counterpulsation on carotid circulation in patients with coronary artery disease.

BACKGROUND: Enhanced external counterpulsation (EECP) is a noninvasive method previously shown to improve measures of myocardial ischemia in patients with coronary artery disease. However, the concomitant effects of EECP on large and small arterial properties have been poorly examined. In a randomized controlled study, we investigated whether arterial stiffness and resistance of the carotid circulation are altered by EECP. METHODS: Thirty patients with angiographically demonstrated coronary artery disease were randomized into two groups to receive either 'sham' or active EECP therapy for 35 1-hour sessions. The beta stiffness index was calculated by the ln(Ps/Pd)/DD equation where Ps and Pd = systolic and diastolic blood pressure, and DD = the ratio between carotid pulse and diastolic diameter, measured by ultrasound sequential frames during the cardiac cycle. Carotid vascular resistance was calculated as the ratio between mean arterial pressure and mean common carotid blood flow. RESULTS: No significant between-group differences were seen in clinical characteristics or carotid hemodynamics at baseline. The beta stiffness index and carotid vascular resistance were significantly reduced after 35 h of active EECP (p < 0.01), and the decrease was significantly different when compared with controls (p < 0.05 for beta stiffness index and p < 0.001 for carotid vascular resistance). These reductions persisted after multiple covariate adjustment. CONCLUSIONS: This study suggests that EECP exerts clear arterial effects on large and small vessels of the carotid circulation. The combined effects on arterial stiffness and vascular resistance are of particular interest in cardiovascular disease involving reduction in blood flow, in which techniques that increase regional blood flow may be beneficial.

Relationship of circulating biomarkers of inflammation and hemostasis with preclinical atherosclerotic burden in nonsmoking hypercholesterolemic men.

BACKGROUND: Relations of mediators of inflammation and hemostasis with preclinical atherosclerosis have been poorly analyzed. The aim of this study was to test potential associations of these blood markers with indicators of cardiovascular risk and atherosclerotic burden in asymptomatic, nonsmoking, hypercholesterolemic men. METHODS: A total of 87 men underwent cardiovascular risk assessment by means of 10-year Framingham risk calculation (median 9%) and atherosclerotic burden evaluation by means of ultrasonographic measurement of common carotid intima-media thickness and assessment of atherosclerotic plaques at three arterial sites (three-site plaques). RESULTS: Of the markers C-reactive protein, tumor necrosis factor-alpha, interleukin-10, factor VIIc, fibrinogen, plasminogen activator inhibitor-activator, soluble intercellular adhesion molecule-1, soluble P-selectin (sP-selectin), and von Willebrand factor, only sP-selectin was positively and independently associated with high Framingham risk score (>9%) (71.7 +/- 3.6 ng/mL, n = 33 v 59.6 +/- 2.8, n = 54; mean +/- SEM; P < .05) and with three-site plaques (75.4 +/- 5.7 ng/mL, n = 14 v 62.0 +/- 2.5, n = 73; P < .05). After adjustment for all of the above markers and for cardiovascular risk factors, odd ratios of having high Framingham risk and three-site plaques were 3.38 (1.43 to 10.21) and 5.23 (1.74 to 23.52) respectively, per 1-standard deviation increase in sP-selectin. CONCLUSIONS: These results confirm that among several hemostasis and inflammation mediators, only sP-selectin blood level was associated with preclinical atherosclerosis. It might confer to sP-selectin measurement a clinical usefulness for detecting and managing high cardiovascular risk in primary prevention.