Blood pressure variability within a single visit and all-cause mortality.

BACKGROUND: Within-visit variability of repeated sequential readings of blood pressure (BP) is an important phenomenon that may affect precision of BP measurement and thus decision making concerning BP-related risk and hypertension management. However, limited data exist concerning predictive ability of within-visit BP variability for clinical outcomes. Therefore, we aimed to investigate the association between the variability of three repeated office BP measurements and the risk of all-cause mortality, independent of BP levels. METHODS: Data collected through the National Health and Nutrition Examination Survey (NHANES) were analysed. NHANES is a program of studies designed to assess health and nutritional status of adults and children in the United States. A complete set of three sequential BP measurements, together with survival status, were available for 24969 individuals (age 46.8±;19.3 years, 49% males). Multivariable logistic regression models were used to determine the prognostic ability of the examined demographic, clinical, and haemodynamic indices. RESULTS: Among various examined indices of variability of systolic (SBP) and diastolic (DBP) blood pressure measurements, the standard deviation of DBP (DBPSD) was the stronger independent predictor of mortality (odds ratio 1.064, 95% Confidence Interval: 1.011-1.12) after adjustment for age, sex, body mass index, smoking, SBP, heart rate, history of hypertension, diabetes mellitus, hypercholesterolaemia, and cardiovascular events. CONCLUSION: Within-visit variability of three sequential office DBP readings may allow for the identification of high-risk patients better than mean SBP and DBP levels. The predictive value of within-visit BP variability and methods to improve its clinical application are worthy of further research.

Dietary patterns and cardiovascular risk in postmenopausal women: Protocol of a cross-sectional and prospective study.

OBJECTIVE: Aging and menopause are associated with an adverse cardiometabolic profile, predisposing to cardiovascular disease. Diet may also affect their cardiometabolic risk. The aim of this study is to assess dietary habits and patterns of postmenopausal women and their association with adiposity measures, cardiometabolic parameters and subclinical atherosclerosis. STUDY PROTOCOL: The study will include two parts. The first part consists of cross-sectional evaluation of 750 postmenopausal women recruited consecutively from the Menopause Unit of an academic hospital. Dietary intake will be assessed by a food frequency questionnaire. Nutrient and food group intake will be calculated and adherence to the Mediterranean diet and other dietary patterns will be evaluated. A-priori and a-posteriori defined dietary patterns will be tested for associations with major and minor outcome measures. The second part consists of a prospective follow-up of all women recruited at baseline and re-assessment of the same variables after 3 years. Adherence to predefined or a-posteriori defined dietary patterns over these 3 years will be evaluated in association with changes in obesity indices and lipid levels, as well as in the progression of subclinical atherosclerosis. MAJOR OUTCOME MEASURES: Body mass index, lipid profile, carotid and femoral artery intima-media thickness and plaques. MINOR OUTCOME MEASURES: Waist circumference, waist-to-hip ratio, abdominal fat layers, incident hypertension and diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), c-reactive protein and markers of subclinical arterial disease, including flow-mediated dilation, pulse wave velocity, augmentation index and ankle-brachial index. RESULTS: The study is expected to complete baseline enrolment by the end of 2018 and follow-up assessment by the end of 2021. The results of the study will address the question of whether dietary patterns and eating habits are associated with cardiometabolic risk as well as with accelerated subclinical arterial disease and arterial aging in postmenopausal women.

The effect of TNF-a antagonists on aortic stiffness and wave reflections: a meta-analysis.

Patients with rheumatoid arthritis (RA) have higher aortic stiffness and cardiovascular risk. Tumor necrosis factor alpha (TNF-a) antagonists reduce inflammation in RA and are indicated for the treatment of patients with severe active rheumatoid disease. However, it is debatable if they have favorable effects on cardiovascular health. The present meta-analysis evaluates the effect of TNF-a antagonists on aortic stiffness and wave reflections, predictors of cardiovascular events and mortality, in RA patients. A search of PubMed, Cohrane, and Embase databases was conducted to identify studies into the effect of TNF-a antagonists on aortic stiffness in RA patients. Aortic stiffness and wave reflections were assessed by aortic (carotid-femoral [cf]) pulse wave velocity (PWV) and augmentation index (AIx), respectively. cfPWV significantly improved following TNF-a antagonist treatment (mean change: -0.53 m/s, 95% CI: -0.833 to -0.218, p = 0.001), independently of age and clinical response to treatment. A more prominent reduction in cfPWV was associated with etanercept/adalimumab (mean difference: -0.62 m/s, 95% CI: -0.968 to -0.272 m/s, p < 0.001) versus infliximab (mean difference: -0.193 m/s, 95% CI: -0.847 to 0.462 m/s, p = 0.564). TNF-a antagonist treatment induced a significant improvement in AIx (mean change: -1.48%, 95% CI: -2.89 to -0.078%, p = 0.039), but this reduction was influenced by age and clinical response to treatment. The balance of evidence suggests that TNF-a antagonists may have a beneficial effect on aortic stiffness and, therefore, on cardiovascular risk. However, larger, longitudinal studies are warranted to confirm such findings.

Eating frequency predicts changes in regional body fat distribution in healthy adults.

Background: Eating frequency (EF) has been associated with generalized obesity. Aim: We aimed to prospectively investigate potential associations of frequency of eating episodes with regional fat layers. Design: EF was evaluated at baseline in 115 subjects free of clinically overt cardiovascular disease (54 ± 9.1 years, 70 women) in a prospective, observational study. Methods: Metabolic parameters known to be associated with dietary factors and anthropometric markers including ultrasound assessment of subcutaneous (Smin) and pre-peritoneal (Pmax) fat and their ratio Smin/Pmax (AFI) were evaluated at baseline and at follow-up, 5 years later. Results: EF at baseline positively correlated with Pmax, even after adjustment for potential confounders. EF above median was also an independent predictor for Pmax (beta coefficient = -0.192, P = 0.037) and AFI (beta coefficient = 0.199, P = 0.049) at follow up. Multivariable linear mixed models analysis demonstrated that subjects with increased EF presented a lower progression rate of Pmax (beta = -0.452, P = 0.006) and a higher progression rate of AFI (beta = 0.563, P = 0.003) over time, independently of age, sex, progression of BMI, energy intake, smoking and changes in parameters of glucose metabolism. Conclusions: High EF is associated with lower progression rate of pre-peritoneal fat accumulation. Future interventional studies should further investigate the clinical utility of these findings.

Prolactin as a predictor of endothelial dysfunction and arterial stiffness progression in menopause.

Postmenopausal women are at increased risk for progression of arteriosclerosis and hypertension. Recent cross-sectional evidence suggests that high normal circulating prolactin levels may accelerate vascular ageing in menopause. Postmenopausal women (n=201) were consecutively recruited from a Menopause Clinic and re-evaluated in at least one follow-up visit within the next 3 years. Baseline circulating prolactin levels were measured while both baseline and follow-up vascular and biochemical measurements were performed. Endothelial function was assessed by flow-mediated dilation (FMD), aortic stiffness by pulse-wave velocity (PWV) and arterial wave reflections by applanation tonometry. Baseline prolactin significantly correlated with lower FMD at follow-up (P=0.005). After multivariable adjustment for age, follow-up time, blood pressure (BP), body mass index, smoking and medication, this correlation remained significant (P=0.003). In addition, baseline circulating prolactin levels were independently associated with changes in mean BP (ß=0.131, P=0.021), peripheral diastolic BP (ß=0.169, P=0.004) and new-onset hypertension (OR=1.235, P=0.001). Owing to significant interaction between baseline prolactin and age for changes in PWV over time (P=0.036), a subgroup analysis based on median age was performed. This analysis revealed that in women younger than 55 years, prolactin was an independent predictor of changes in PWV over time (P=0.008). In conclusion, high normal circulating prolactin levels predict changes in haemodynamic indices and worsening endothelial function in healthy postmenopausal women. Particularly in young postmenopausal women, prolactin predicts accelerated arterial stiffening.

Psychological but not vasomotor symptoms are associated with temperament and character traits.

OBJECTIVE: Recent evidence suggests that climacteric symptoms may be intensified by specific temperament and personality traits in postmenopausal women. In this study we investigate Cloninger's model of personality in relation to menopausal symptoms. METHODS: One-hundred and seventy peri- and postmenopausal women consecutively recruited from a menopause clinic of an academic hospital completed the Cloninger's Temperament and Character Inventory (TCI-140) which measures four dimensions of temperament: Harm avoidance, Novelty seeking, Reward dependence and Persistence, as well as three dimensions of character: Self-directedness, Cooperativeness, and Self-transcendence. Menopausal somatic, vasomotor and psychological symptoms were also assessed using the Greene Climacteric Scale. RESULTS: In comparison to the norms of the Greek general population, postmenopausal women presented lower scores in Novelty seeking and Reward dependence and higher scores in Persistence, Self-directedness, Cooperativeness and Self-transcendence. Higher harm avoidance (the inclination to avoid potential punishment, be shy and fearful of uncertainty) significantly correlated with anxiety and depressive symptoms while lower Self-directedness (the ability to have the willpower to adapt to or overcome any changes) correlated with depressive symptoms only. By multivariate regression analysis, higher Harm avoidance and lower Self-directedness were independently associated with the presence of depressive symptoms. No significant associations were observed between TCI-140 traits and somatic or vasomotor symptoms. CONCLUSIONS: Our findings indicate that most temperament and character traits according to Cloninger's model in peri- and postmenopausal women varied significantly as compared to the general population. Among several traits, high Harm avoidance and low Self-directedness were most strongly associated with psychological climacteric distress but not with somatic and vasomotor symptoms.

Pleiotropic effects of the acute and chronic inhibition of the renin-angiotensin system in hypertensives.

Renin-angiotensin system (RAS) inhibition may exert beneficiary pleiotropic effects on heart hemodynamics in hypertensive patients. We aimed to assess these effects on coronary flow reserve (CFR) and left ventricular (LV) filling pressure after acute and long-term treatment. Thirty-nine patients (48.4±6.8 years) with newly diagnosed, never-treated essential arterial hypertension were consecutively recruited from an outpatient hypertension clinic. CFR in the left anterior descending artery and the ratio of mitral inflow E wave to the averaged mitral annulus tissue velocity of the E waves (E/e' ratio), as an estimate of LV filling pressure, were assessed by Doppler echocardiography. In the acute phase of the study, consecutive eligible patients were assigned to receive po Quinapril (Q) 20 mg (n=15) or Losartan (L) 100 mg (n=14) or no treatment (n=10) and were reexamined 2 h post treatment. In the chronic phase of the study, the patients were reevaluated after 1 month on the assigned treatment. During the acute phase, CFR (P=0.005) was significantly improved in the RAS inhibition as compared with the control group, independently of blood pressure (BP) changes. The E/e' ratio was also marginally improved (P=0.053), but this effect was more pronounced in patients with E/e' ratio>8 (P=0.005). CFR and E/e' ratio were also improved after 1 month of treatment, particularly in responders after the acute phase. In hypertensive patients, RAS inhibition acutely improved CFR and E/e' ratio independently of BP changes. An acute positive response in these parameters was closely related to sustained improvement after 1 month of single-drug treatment.

Circulating levels of TNF-like cytokine 1A correlate with the progression of atheromatous lesions in patients with rheumatoid arthritis.

Interactions between TNF-like Cytokine 1A (TL1A) and its receptors, death receptor-3 (DR3) and decoy receptor-3 (DcR3) may be important in atherogenesis. We hypothesized that dysregulation of this system predicts formation of new atheromatic plaques in rheumatoid arthritis (RA). Forty-five patients were prospectively followed up for 40.5 ± 3.6 months. Serum concentrations of TL1A and DcR3 were measured at baseline and carotid and femoral arteries examined by ultrasound at baseline and at the end of follow-up. Individual serum levels of TL1A correlated with the progression of carotid atheromatic plaque height (Spearman rho = 0.550, p = 0.003). Patients with low TL1A and undetectable DcR3 serum levels at baseline showed significantly fewer newly formed carotid plaques during the next 3.5 years than the remaining patients (P = 0.016). Univariate analysis showed that a "low TL1A/DcR3" immunophenotype predicted a preserved atherosclerosis profile in carotid (P = 0.026), or carotid and/or femoral arteries (P = 0.022). Dysregulated TL1A-induced signaling may be associated with risk for accelerated atherosclerosis in RA.

Acute carotid stent thrombosis after carotid artery stenting.

BACKGROUND: Carotid artery stenting (CAS) is a reasonable alternative to carotid endarterectomy (CEA), especially in patients at high risk for surgery. Carotid artery thrombosis of the treated segment is a rare, early but potentially devastating complication of this endovascular procedure. The aim of this article is to identify and critically review cases of acute stent thrombosis reported in the literature. MATERIALS AND METHODS: Previous trials that compared CEA with CAS were rather heterogeneous and not large enough to allow reliable conclusions. Furthermore, because there is limited follow-up information to date, the long-term effect of CAS remains unclear. Acute carotid thrombosis after angioplasty and stenting is a very rare but potentially fatal complication, and there are very few reports in the literature. This article reviews twelve cases of acute carotid thrombosis published in the English literature from eight different Vascular and Radiology Departments around the world. RESULTS: The different ways of immediate treatment of this rare complication of acute carotid thrombosis after CAS are, open surgical procedure with thrombus removal and thromboendarterectomy with or without removing of the stent, selective local or facilitated thrombolysis with the rescue use of GPIs (glycoprotein IIb/IIIa receptor inhibitors), recanalization by instent percutaneous transluminal angioplasty with distal protection and additional stent placement on the stented portion of the internal carotid artery (ICA) in conjunction with the intravenous administration of recombinant tissue plasminogen activator (rtPA: 1300,000 IU). CONCLUSION: Carotid artery stenting has to be performed under specific pro- and post procedure protocol from experienced endovascular specialists. The treatment of acute carotid thrombosis after CAS must be urgent and immediate in order to regain restoration of blood flow and avoid major neurological adverse events.

Estradiol levels predict short-term adverse health outcomes in postmenopausal acute stroke women.

BACKGROUND: Data on the role of endogenous sex steroids in cerebrovascular disease are sparse. Estradiol is a hormone with diverse actions on the central nervous system. Our aim was to investigate the role of circulating estradiol levels in a postmenopausal acute stroke population. METHODS: During a time-period of 2 years, we prospectively studied 302 postmenopausal female patients hospitalized for an acute stroke in two tertiary hospitals. We addressed the question whether endogenous estradiol is associated with stroke severity on admission and functional outcome 1 month after stroke, as assessed by the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS), respectively. RESULTS: Estradiol levels were significantly related to stroke severity on admission, as expressed by NIHSS, even after correcting for confounding factors in the multivariate analysis (beta 0.353, P < 0.001). Estradiol was an independent determinant of 1-month mortality and adverse functional outcome (mRS ≥ 4), [odds ratio (OR) with 95% confidence intervals (CI): 3.341 (1.617-6.902), P = 0.001 and 2.277 (1.273-4.074), P = 0.006, respectively]. CONCLUSIONS: We identified an independent association of endogenous estradiol levels with stroke severity and short-term mortality and outcome. These findings suggest challenging the role of estradiol as a neuroprotective agent.

Expression of platelet-bound stromal cell-derived factor-1 in patients with non-valvular atrial fibrillation and ischemic heart disease.

AIMS: Blood cell infiltration and inflammation are involved in atrial remodelling during atrial fibrillation (AF) although the exact mechanisms of inflammatory cell recruitment remain poorly understood. Platelet-bound stromal cell-derived factor-1 (SDF-1) is increased in cases of ischemic myocardium and regulates recruitment of CXCR4(+) cells on the vascular wall. Whether platelet-bound SDF-1 expression is differentially influenced by non-valvular paroxysmal or permanent atrial fibrillation (AF) in patients with stable angina pectoris (SAP) or acute coronary syndrome (ACS) has not been reported so far. METHODS AND RESULTS: A total of 1291 consecutive patients with coronary artery disease (CAD) undergoing coronary angiography were recruited. Among the patients with SAP, platelet-bound-SDF-1 is increased in patients with paroxysmal AF compared with SR or to persistent/permanent AF (P < 0.05 for both). Platelet-bound SDF-1 correlated with plasma SDF-1 (r = 0.488, P = 0.013) in patients with AF and ACS, which was more pronounced among patients with persistent AF (r = 0.842, P = 0.009). Plasma SDF-1 was increased in persistent/permanent AF compared with SR. Patients with ACS presented with enhanced platelet-bound-SDF-1 compared with SAP. Interestingly, among patients with ACS, patients with paroxysmal or persistent/permanent AF presented with an impaired platelet-bound SDF-1 expression compared with patients with SR. CONCLUSIONS: Differential expression of platelet-bound and plasma SDF-1 was observed in patients with AF compared with SR which may be involved in progenitor cell mobilization and inflammatory cell recruitment in patients with AF and ischemic heart disease. Further in vivo studies are required to elucidate the role of SDF-1 in atrial remodeling and the atrial fibrillation course.

Menopausal symptoms are associated with subclinical atherosclerosis in healthy recently postmenopausal women.

OBJECTIVES: To determine whether menopausal symptoms are associated with changes in arterial structure and function in healthy, recently postmenopausal women. METHODS: One hundred and ten postmenopausal women aged 45-55 years were included in the present cross-sectional study. Menopausal symptoms were recorded by the Greene Climacteric Scale. Anthropometric measures, blood pressure, serum lipids, glucose, insulin, sex and thyroid hormones were determined in each individual. Arterial structure, function and stiffness were assessed by intima-media thickness (IMT), flow-mediated dilation and pulse-wave velocity, respectively. RESULTS: Women with moderate to severe hot flushes had increased IMT compared to women with no or mild hot flushes (IMT in women with no hot flushes 0.61±0.08 mm, IMT in women with mild hot flushes 0.62±0.11 mm, IMT in women with moderate to severe hot flushes 0.67±0.11 mm; p = 0.034). This difference was independent of cardiovascular risk factors like age, menopausal age, smoking, blood pressure, adiposity, lipid levels, insulin resistance or hormone levels. No association was detected between psychological or psychosomatic symptoms and arterial indices. Furthermore, menopausal symptoms were not associated with serum sex steroids or thyroid hormone levels. CONCLUSIONS: Carotid IMT, a surrogate marker of subclinical atherosclerosis and cardiovascular risk, was found to be increased in women with vasomotor symptoms as compared to asymptomatic women. This association was independent of cardiovascular risk factors or endogenous hormone levels. It remains to be elucidated whether the presence of menopausal symptoms is an additional cardiovascular risk factor requiring preventive intervention.

A pilot study of endothelial dysfunction and aortic stiffness after interleukin-6 receptor inhibition in rheumatoid arthritis.

Interleukin (IL)-6 is a pleiotropic proinflammatory cytokine involved in the pathogenesis of both atherosclerosis and rheumatoid arthritis. The role of the IL-6/IL-6 receptor pathway in the documented acceleration of atherosclerosis in rheumatoid arthritis has not been examined. In a non-randomized prospective pilot study we asked whether endothelial dysfunction, defined as impaired flow mediated dilatation (FMD), and aortic stiffness, assessed by pulse wave velocity (PWV) improve after 3 and 6 monthly therapeutic infusions of the anti-IL-6 receptor antibody tocilizumab for active rheumatoid arthritis. We found that FMD increased from 3.3 ± 0.8 to 4.4 ± 1.2 to 5.2 ± 1.9% (p = 0.003), whereas PWV decreased from 8.2 ± 1.2 to 7.7 ± 1.3 to 7.0 ± 1.0m/s (p < 0.001). Whether these beneficial arterial changes are direct effects of the IL-6/IL-6 receptor pathway inhibition, maintained over time and translate into better clinical outcome warrants further studies.

Diurnal variation of endothelial function and arterial stiffness in hypertension.

The onset of cardiovascular events presents a circadian variation that may be mediated by similar temporal patterns of vascular function. Blood pressure also follows circadian variation. We investigated the possible diurnal variation of endothelial function and arterial stiffness in patients with hypertension. Thirty-five individuals with recently diagnosed hypertension (mean age 48.3 years, range 30-60 years, 14 men) were examined. Flow-mediated vasodilatation (FMD), nitrate-mediated vasodilatation (NMD) and carotid-femoral (cf) pulse wave velocity (PWV) were measured at three different occasions: at 0700 hours immediately after awaking, at 1200 hours and at 2100 hours. FMD was markedly lower in the morning (0700 hours, 2.22+/-1.58%; 1200 hours, 4.37+/-2.25%; 2100 hours, 4.28+/-2.12%; P<0.001), whereas NMD was similar at the same time points. This difference remained significant after adjustment for baseline brachial artery diameter and reactive hyperaemia. PWVcf progressively increased from morning to evening (0700 hours, 9.8+/-1.9 m s(-1); 1200 hours, 10.2+/-2.2 m s(-1); 0900 hours, 10.5+/-1.9 m s(-1); P=0.013 for linear trend). Similar temporal patterns were observed in systolic and diastolic blood pressures peaking in the evening. PWVcf changes lost significance after adjustment for changes in mean blood pressure. Endothelial function is decreased in the early morning in hypertensive patients, whereas arterial stiffness is increased in the evening. Changes in BP-dependent passive artery distension may be involved in this phenomenon.

Incremental value of arterial wave reflections in the determination of left ventricular diastolic dysfunction in untreated patients with essential hypertension.

Systemic arterial stiffness is an indicator of cardiovascular disease and an independent marker of morbidity and cardiovascular mortality. We investigated the association of arterial wave reflections with left ventricular (LV) diastolic dysfunction and their incremental value to other determinants of LV diastolic dysfunction in patients with essential hypertension. In total 143 patients and 20 controls with similar atherosclerotic risk factors were examined by applanation tonometry of the radial artery (Sphygmocor) and echocardiography. Central augmentation index (CAI%) of reflected arterial waves as well as aortic strain (AoS) assessed by echocardiography were estimated. Doppler diastolic abnormalities were defined as proposed by the European Study Group on diastolic heart failure by measurement of E/A ratio (the ratio of the mitral inflow velocities), isovolumic relaxation time, deceleration time and flow propagation velocity. AoS and CAI were impaired in patients compared with controls (4.67 +/- 2.94 vs 6.06 +/- 4.91% and 145.8 +/- 22.7 vs. 135.7 +/- 20.3%, P < 0.01) as well as in patients with LV diastolic dysfunction compared to patients without, (5.52 +/- 4.29 vs. 10.73 +/- 5.77% and 139.5 +/- 21.7 vs. 124.5 +/- 17.0%, P < 0.05). The odds ratio (OR) of AoS and CAI for diastolic dysfunction was OR:0.918, 95% confidence interval (CI):0.837-0.99, P = 0.04 and OR:1.023, 95% CI: 1.023-1.040 P = 0.010, respectively. The addition of CAI to the multivariable model including age, LV mass index, AoS and mean arterial pressure increased the power of the model for determination of LV diastolic dysfunction (-2 log likelihood = 139.368, change of chi2 = 4.2, P-value for change=0.04). In untreated patients with newly diagnosed essential hypertension, wave reflections are independent and additive determinants of LV diastolic dysfunction.

Improvement of vascular endothelial function using the oral endothelin receptor antagonist bosentan in patients with systemic sclerosis.

OBJECTIVE: Increased endothelin activity may play a role in the pathogenesis of vascular injury, a primary feature of systemic sclerosis (SSc; scleroderma). Our goal was to test the hypothesis that treatment with the oral endothelin receptor antagonist bosentan might improve vascular endothelial function in SSc patients. METHODS: A 4-week, prospective, parallel-group study compared 12 SSc patients who did not receive bosentan treatment with 12 patients who did receive treatment (125 mg/day) for pulmonary hypertension and/or digital ulcers. There were no differences in demographic and clinical characteristics or medications between the 2 groups. Baseline endothelial dysfunction was documented by decreased brachial artery ultrasound-derived flow-mediated dilation (FMD%; <5.5). Pulse wave analysis, venous occlusion plethysmography, and measurement of serum vascular markers were performed in parallel. RESULTS: FMD%, the main end point, increased significantly from a mean +/- SD of 3.1 +/- 1.3% to 8.4 +/- 2.6% after 4 weeks of bosentan treatment (P < 0.001, compared with a change from 2.4 +/- 1.6% to 2.4 +/- 2.2% in control patients). Arterial blood pressure, endothelium-independent vascular function, augmentation index, peripheral flow reserve, as well as circulating intercellular adhesion molecule 1, E-selectin, vascular endothelial growth factor, and endothelin 1 were not significantly affected by bosentan treatment. In patients continuously treated for 4 months, during which the dosage of bosentan remained at 125 mg/day (n = 5) or increased to 250 mg/day (n = 5), the 4-week results remained unchanged. CONCLUSION: Small doses of bosentan improve endothelial function without affecting hemodynamic parameters or endothelial activation-related processes, thus supporting a direct, reversible effect of endothelin in SSc-associated vascular injury. A long-term, controlled trial to examine the potentially global clinical benefit of endothelin receptor blockade in patients with early SSc may be warranted.

Acute effects of renin-angiotensin system blockade on arterial function in hypertensive patients.

The acute effects of the renin-angiotensin system (RAS) blockers may be important in some clinical settings. To assess the acute impact of such drugs on arterial function, we studied the effects of captopril 25 mg, quinapril 20 mg and telmisartan 80 mg on 100 hypertensive patients, according to a randomized, double-blind, placebo-controlled study. Central (aortic) blood pressure (BP) and augmentation index (AIx, a measure of wave reflections), as well as flow-mediated dilatation (FMD) of the brachial artery and forearm blood flow (FBF) (measures of conduit and resistance artery endothelial function, respectively), were evaluated before and 2 h after oral drug administration. Compared to placebo, captopril and quinapril decreased central systolic (by 7.5 mm Hg, P<0.05 and by 12.3 mm Hg, P<0.001) and diastolic BP (by 4.9 mm Hg, P<0.01 and by 8.4 mm Hg, P<0.001), whereas telmisartan had no significant effect (P=NS). Additionally, AIx was reduced after quinapril (absolute decrease of 7.2%, P<0.01) and marginally after captopril (decrease of 4.7%, P=0.07). Only quinapril led to a beneficial change of FMD (absolute increase of 2.7%, P<0.001). No treatment was related to significant changes of peak hyperaemic or 3-min hyperaemic FBF. In adjusted analyses, all the favourable alterations induced by quinapril were independent of potential confounding haemodynamic factors. Our data show that acute RAS inhibition with quinapril (20 mg) may be more beneficial in terms of arterial function and central haemodynamics compared to captopril (25 mg) or telmisartan (80 mg). Further studies are needed to investigate whether these acute arterial effects of quinapril are clinically significant.

The combined effect of augmentation index and carotid intima-media thickness on cardiovascular risk in young and middle-aged men without cardiovascular disease.

Carotid artery intima-media thickness (IMT) has been used as a surrogate marker of atherosclerosis and is related to cardiovascular risk. Indices of arterial stiffness are also associated with cardiovascular risk and atherosclerosis. The aim of this study was to assess the prognostic value of the combination of surrogate markers of cardiovascular disease measured non-invasively in subjects without cardiovascular disease. In this cross-sectional study, 81 young and middle aged males (39.2+/-6.3 years) without evidence of overt cardiovascular disease or diabetes mellitus were enrolled. High-resolution B-mode ultrasonography and pulse wave analysis were used to measure carotid artery IMT and augmentation index (AI), a measure of arterial stiffness. Framingham risk score (FRS) was used as an estimate of the risk for development of cardiovascular disease. Regional differences were observed in the carotid arteries' IMT regarding their relationship with FRS: combined (average from all sites) IMT and IMT in the carotid bulb (CB), but not in the common (CC) and internal carotid artery (IC), and AI showed significant increases of FRS by their tertiles. However, subjects with both AI and IMT at any site in the highest tertile (AI>15%, CC>0.65 mm, CB>0.8 mm, IC>0.65 mm) had an increased FRS compared to subjects with one or none of these parameters in the highest tertile. In conclusion, young and middle-aged men without overt cardiovascular disease with both high IMT and AI are in high cardiovascular risk, as assessed by FRS. Epidemiological studies are needed to further validate this combination.