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Background: The independent prognostic significance of the metabolic syndrome (MetS) in the elderly is not yet clear. We investigated the association between MetS and cardiovascular risk (composite endpoint of stroke and coronary events) in elderly treated hypertensive patients., Methods: Cardiovascular outcome was evaluated in 1,191 elderly treated hypertensive patients (≥60 years). Among them, 578 (48.5%) had MetS according to a modified joint interim statement definition (body mass index in place of waist circumference)., Results: During the follow-up (9.1±4.9 years, range 0.4-20 years), 139 strokes and 120 coronary events occurred. In univariate analysis, patients with MetS had higher risk of the composite endpoint (hazard ratio (HR) 1.322, 95% confidence interval (CI) 1.035-1.688, P < 0.05). Among the single components of MetS, only blood pressure (BP) level and impaired fasting glucose/diabetes were significantly associated with increased cardiovascular risk. After adjustment for age, previous events, estimated glomerular filtration rate (eGFR), left ventricular (LV) hypertrophy and left atrial (LA) enlargement, the prognostic relevance of MetS was attenuated (HR 1.245, 95% CI 0.974-1.591, P = 0.08). After further adjustment for the above-mentioned variables and ambulatory BP parameters and impaired fasting glucose/diabetes, Cox regression analysis showed that MetS was not independently associated with increased cardiovascular risk (HR 1.090, 95% CI 0.805-1.475, P = 0.58)., Conclusions: In elderly treated hypertensive patients, MetS is associated with increased cardiovascular risk, but not independently of BP and glucose levels and of organ damage., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The independent prognostic significance of morning surge (MS) of blood pressure (BP) is not yet clear. We investigated the association between MS of systolic BP and risk of coronary events in elderly treated hypertensive patients., Methods: The occurrence of coronary events was evaluated in 1,191 elderly treated hypertensive patients (age range 60-90 years). Subjects were divided according to tertiles of MS of systolic BP of the population as a whole, by dipping status and by group-specific tertiles of MS of systolic BP in dippers and nondippers., Results: During the follow-up (9.1 ± 4.9 years, range 0.4-20 years), 120 coronary events occurred. In the population as a whole, coronary event risk was not significantly associated with tertiles of MS of systolic BP, whereas nondippers were at higher risk than dippers. When nondippers and dippers were analyzed separately, by group-specific tertiles of MS of systolic BP, coronary event risk was associated with MS of systolic BP in dippers but not in nondippers. After adjustment for various covariates, Cox regression analysis showed that dippers in the third tertile (>23 mm Hg) of MS of systolic BP (hazard ratio 1.912, 95% confidence interval 1.048-3.488, P = 0.03) and nondippers (hazard ratio 1.739, 95% confidence interval 1.074-2.815, P = 0.02) were at higher coronary event risk than dippers with MS of systolic BP <23 mm Hg ., Conclusions: In elderly treated hypertensive patients, high MS of systolic BP predicts coronary events in dippers but not in nondippers. Nondippers, however, show higher risk of coronary events independently of MS in systolic BP., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The independent prognostic significance of left atrial enlargement is not yet completely clear. We investigated the association between left atrial enlargement and risk of ischemic stroke in elderly treated hypertensive patients., Methods: The occurrence of ischemic stroke was evaluated in 1,191 elderly treated hypertensive patients (age range = 60-90 years). Left atrium diameter (cm) was indexed by body surface area (m(2)) and subjects were divided into those with normal or enlarged (≥2.4cm/m(2)) left atrium., Results: During the follow-up (9.1±4.9 years; range = 0.4-20 years), 139 ischemic strokes occurred. The event rate per 100 patient-years was 1.28. There were 86 strokes in patients with normal (= 928) left atrium and 53 strokes in patients with enlarged (= 263) left atrium, respectively. Stroke-free survival curves were significantly different between the groups (P < 0.01). After adjustment for various covariables, including clinical variables, left ventricular hypertrophy, and ambulatory blood pressure parameters, Cox regression analysis showed that left atrial enlargement was significantly associated with increased risk of ischemic stroke (hazard ratio = 1.54; 95% confidence interval = 1.05-2.27; P = 0.03)., Conclusions: In elderly treated hypertensive patients, left atrial enlargement is an independent predictor of ischemic stroke., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The independent prognostic significance of morning surge (MS) in blood pressure (BP) is not yet clear. We investigated the association between MS in systolic BP (SBP) and risk of ischemic stroke in elderly patients treated for hypertension., Methods: Occurrence of ischemic stroke was evaluated in 1,191 elderly patients treated for hypertension (aged 60-90 years). Patients were divided according to tertiles of MS in SBP in the population as a whole, dipping status, and group-specific tertiles of MS in SBP in dippers and nondippers., Results: During follow-up (9.1±4.9 years, range 0.4-20 years), 139 ischemic strokes occurred. The event rate per 100 patient-years was 1.28. After adjustment for various covariates, Cox regression analysis showed that stroke risk was not significantly associated with tertiles of MS in SBP in the population as a whole. When nondippers and dippers were analyzed separately by group-specific tertiles of MS in SBP, stroke risk was not associated with MS in nondippers. Conversely, in dippers, stroke risk was significantly higher in the third tertile (>23mm Hg) of MS in SBP (hazard ratio, 2.08; 95% confidence interval, 1.03-4.23; P = 0.04). Additional analysis showed that stroke risk was significantly and similarly higher in dippers with MS >23mm Hg and in nondippers than in dippers with MS <23mm Hg., Conclusions: In elderly patients treated for hypertension, high MS in SBP predicts stroke in dippers but not in nondippers. Nondippers are at high stroke risk with or without MS >23mm Hg.

Background: Cardiac outcome in patients with atherosclerotic renal artery stenosis (ARAS) undergoing percutaneous transluminal renal angioplasty (PTRA) or medical therapy is not yet completely clear. The aim of this study was to perform a meta-analysis of randomized controlled trials to compare the effect of PTRA and medical therapy on nonfatal myocardial infarction in patients with ARAS., Methods: We searched for articles reporting cardiovascular outcome, including nonfatal myocardial infarction, in patients with renal artery stenosis randomized to PTRA with/without stenting or medical therapy., Results: Five studies were identified. The pooled population consisted of 1,159 subjects who experienced 56 nonfatal myocardial infarctions. When compared with medical therapy, the overall relative risk (RR) was 0.85 (95% confidence interval (CI) 0.51-1.42), P = 0.55, for PTRA. There was no significant difference between PTRA and medical therapy according to procedural characteristics (with/without stent placement), mean serum creatinine at follow-up (higher or lower than 2.0 mg/dl), and maximum follow-up length (> or <2 years)., Conclusions: In patients with ARAS and hypertension, there is a lack of evidence supporting the superiority of PTRA over medical therapy in prevention of nonfatal myocardial infarction. Awaiting for results of ongoing trials, our data and previous data suggest that PTRA and drug therapy have a similar impact on cardiovascular risk reduction in patients with renal artery stenosis and hypertension.

Background: Metabolic syndrome (MetS) is a cluster of risk factors, related to visceral adiposity, which is frequently observed in overweight patients. However, it has also been reported in normal weight subjects. Epicardial adipose tissue (EAT) is a visceral fat. The aim of the study was to evaluate whether EAT is associated with MetS in hypertensive patients with normal weight and waist., Methods: We studied 174 Caucasian hypertensive patients, aged ≥40 years, with body mass index (BMI) <25 kg/m(2) and waist circumference <102 cm in men and 88 cm in women. MetS was defined according to NCEP ATP III criteria, not including waist circumference. EAT was measured by echocardiography above the free wall of the right ventricle, at end diastole., Results: MetS was present in 21 (12%) patients. EAT was significantly higher in patients with MetS than in those without MetS, 4.0 ± 0.8 vs 2.5 ± 0.9 mm, P < 0.01, respectively, but BMI and waist circumference were not. Multivariate analysis showed that EAT was independently associated with MetS. Receiver operating characteristic (ROC) curve analysis showed that EAT significantly improved prediction of MetS when added to BMI and waist circumference. Indeed, the area under the curve improved from 0.63 (0.50-0.76) to 0.91 (0.87-0.96), and resulted significantly higher (P < 0.01). ROC curve for EAT alone indicated that the cutoff value of 3.1 mm had the best performance in predicting MetS, that is, 100% sensitivity and 79% specificity., Conclusion: EAT thickness is associated with MetS in hypertensive patients with normal weight and waist.

Background: The prognostic relevance of white-coat hypertension (WCH) and masked hypertension (MH) is controversial. The aim of this study was to perform an updated meta-analysis on the prognostic value of WCH and MH diagnosed by ambulatory monitoring in initially untreated subjects., Methods: We searched for articles evaluating cardiovascular outcome in WCH or MH or sustained hypertension (SH) in comparison with normotension, investigating untreated subjects at baseline or performing separate analysis for untreated or treated subjects, and reporting adjusted hazard ratio (HR) and 95% confidence interval (CI)., Results: Eight studies were identified. Five whole studies and untreated groups of three others were included in the meta-analysis. The pooled population consisted of 7,961 subjects who experienced 696 events. When compared with normotension, the overall adjusted HR was 0.96 (95% CI 0.65-1.42) for WCH (P = 0.85), 2.09 (1.55-2.81) for MH (P = 0.0001), and 2.59 (2.0-3.35) for SH (P = 0.0001). There was no significant difference between WCH and normotension according to normotensive subjects source (same or different study population) and follow-up length. Where reported, prevalence of drug therapy was higher in subjects with WCH than in those with normotension at follow-up., Conclusions: Cardiovascular risk is not significantly different between WCH and normotension, regardless of normotensive population type and follow-up length. However, at follow-up drug therapy was more frequent in WCH than in normotension and its possible impact on outcome should be evaluated in future studies. MH shows significantly higher risk than normotension, although the best way for its detection and treatment remains to be established.

Background: The prognostic relevance of echocardiographic left ventricular hypertrophy (LVH) regression in hypertension is uncertain. The aim of this study was to perform an updated meta-analysis about the impact of LVH regression on the occurrence of cardiovascular events in hypertensive patients., Methods: We searched for studies on echocardiographic LVH regression and prognosis in hypertension that compared patients with or without LVH regression or groups including subjects with or without LVH regression and reported adjusted hazard ratio (HR) for calculating the overall effect size., Results: Five studies were identified (3,149 patients, mean age range 48-66 years, 58% men). Follow-up echocardiography was performed after a mean period ranging from 1 to 5 years. Entire follow-up duration ranged from 3 to 9 years. Globally, 333 cardiovascular events occurred. Three whole studies and subgroups of two others were included in the meta-analysis, comprising 2,449 patients, 1,900 (78%) with baseline LVH and 969 (51%) with LVH regression, who experienced 304 events. The overall adjusted HR of total cardiovascular events was 0.54, 95% confidence interval (CI) 0.35-0.84, P = 0.007, for LVH regression/persistent normal left ventricular (LV) mass vs. LVH persistence/LVH development. Heterogeneity was found between studies. Higher baseline prevalence of comorbid conditions and Japanese ethnicity seemed to be associated with lower benefit from LVH regression., Conclusions: This meta-analysis indicates that regression of echocardiographic LVH in hypertension, even after adjustment for various confounders, is associated with reduction of cardiovascular events. However, future studies are needed to evaluate whether LVH regression is of benefit for all hypertensive patients and ethnic groups.

Background: The independent prognostic significance of different indices of blood pressure (BP) variability is not clear. We investigated the prognostic value of BP variability estimated as s.d. or average real variability (ARV) of daytime and night time BP, in hypertensive patients., Methods: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1,280 sequential hypertensive patients (550 initially untreated and 730 initially treated) aged > or =40 years. Subjects with s.d. or ARV of daytime or night time systolic or diastolic BP below or above the median were classified as having low or high BP variability., Results: During the follow-up (4.75 +/- 1.8 years), 104 cardiovascular events occurred. The event rate per 100 patient-years was 1.71 in the global population. After adjustment for other covariates, Cox regression analysis showed that cardiovascular risk was higher in subjects with high ARV of daytime systolic BP in initially untreated, initially treated, and all the subjects (high vs. low ARV, hazard ratio (HR) 2.29 (1.06-4.94), HR 1.90 (1.06-3.39), and HR 2.07 (1.31-3.28), respectively). ARV of daytime diastolic BP and night time BP, and s.d. of daytime and night time BP were not significantly associated with risk or were not independent predictors of outcome., Conclusions: In this study, high ARV of daytime systolic BP resulted in an independent predictor of cardiovascular risk in hypertensive patients, while high s.d. did not. Our data suggest that, in comparison to s.d., ARV could be a more appropriate index of BP variability and a more useful predictor of outcomes.

Background: The prognostic impact of masked hypertension is not yet completely clear. The aim of this study was to evaluate the prognostic relevance of masked hypertension in subjects with prehypertension., Methods: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 591 subjects with prehypertension defined as clinic blood pressure (BP) in the range of 120-139 mm Hg for systolic BP and 80-89 mm Hg for diastolic BP. Among them, 471 were classified as having true prehypertension (clinic BP <140/90 mm Hg and daytime BP <135/85 mm Hg) and 120 as having masked hypertension (clinic BP <140/90 mm Hg and daytime BP > or =135 or 85 mm Hg)., Results: During the follow-up (6.6 +/- 4.3 years, range 0.5-15.5 years), 29 cardiovascular events occurred. In subjects with true prehypertension and masked hypertension the event-rates per 100 patient-years were 0.57 and 1.51, respectively. Event-free survival was significantly different between the groups (P < 0.005). After adjustment for other covariates, including clinic BP (forced into the model), Cox regression analysis showed that cardiovascular risk was significantly higher in masked hypertension than in true prehypertension (masked vs. true prehypertension, relative risk 2.65, 95% confidence interval 1.18-5.98, P = 0.018)., Conclusions: Among subjects with prehypertension, those with masked hypertension are at higher cardiovascular risk than those with true prehypertension. Out-of-office BP should be known in individuals with prehypertension, preferably by ambulatory BP monitoring or alternatively by home BP measurement, to obtain a better prognostic stratification.

Background: There is still ambiguity about the prognostic relevance of regression of left ventricular hypertrophy (LVH) (as revealed by echocardiography) in a large population of subjects with hypertension, with and without evidence of LVH in their electrocardiograms (ECGs). This holds true even after adjusting for various confounders including in treatment ambulatory blood pressure (BP). The most suitable time point for a follow-up echocardiography also remains a matter for debate. In this study, we investigated the prognostic relevance of regression of LVH after 2 years of therapy, in a large population of subjects with hypertension, and possessing the aforesaid characteristics., Methods: The occurrence of adverse cardiovascular events was evaluated in 387 patients with LVH shown by echocardiography at baseline, and these patients were studied again after 2 years of therapy. At the second examination, 245 subjects showed regression of LVH, whereas 142 did not., Results: During the time period before the subsequent follow up (6.2 +/- 3 years, range 1.9-12.9 years), 59 first adverse events (26 cardiac and 33 cerebrovascular) had occurred among these subjects. The event rates per 100 patient-years in patients with and without LVH regression were 1.06 and 4.4, respectively. After adjusting for several covariates at the 2-year visit, including in treatment ambulatory BP, Cox regression analysis showed that cardiovascular risk was significantly lower in patients with LVH regression than in those without (RR 0.36, 95% CI 0.19-0.68, P = 0.002). When left ventricular (LV) mass index reduction was analyzed instead of LVH status, it was found to be significantly associated with reduced risk (RR 0.62 per 1-s.d. decrease, 95% CI 0.44-0.88, P = 0.01)., Conclusions: Regression of LVH, as revealed by echocardiography after 2 years of therapy, is associated with reduced cardiovascular risk in patients with hypertension, whether or not LVH was revealed in their ECGs. This holds true even after adjusting for various confounders including in treatment ambulatory BP.

Background: The prognostic impact of metabolic syndrome (MetS) in the hypertensive population at low-medium risk is unknown. In this study, we evaluated the prognostic relevance of MetS in hypertensive patients at low-medium risk., Methods: The occurrence of nonfatal and fatal cardiac and cerebrovascular events was evaluated in 802 patients with mild to moderate essential hypertension at low-medium risk according to the 2003 World Health Organization/International Society of Hypertension statement on the management of hypertension. Among these patients, 218 (27.2%) had MetS according to a modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definition (body mass index in place of waist circumference)., Results: During follow-up (6.9 +/- 3.1 years; range, 0.5 to 13.1 years, mean +/- SD), 58 first cardiovascular events occurred. The event rates per 100 patient-years in patients without and with MetS were 0.87 and 1.51, respectively. Event-free survival was significantly different between groups (P = .03). After adjustment for several covariates, Cox regression analysis showed that cardiovascular risk was significantly higher in patients with than in patients without MetS (relative risk, 2.64; 95% confidence interval, 1.52 to 4.58; P = .001). Other independent predictors of outcome were age, smoking habit, 24-h systolic BP, and LDL cholesterol., Conclusions: Hypertensive patients at low-medium risk with MetS are at higher cardiovascular risk than those without MetS. Metabolic syndrome may be a useful tool for clinicians to identify subjects who are at increased risk when traditional assessment may indicate low-medium risk.

Background: The independent prognostic value of blood pressure (BP) variability in treated hypertension is not yet clear. We investigated the relationship between BP variability, evaluated by noninvasive monitoring, and cardiovascular outcome in treated hypertensive patients., Methods: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1472 treated patients. Subjects with the standard deviation of daytime or night-time systolic BP below or above the median of the population were classified as having low or high BP variability. Specifically, 738 and 734 patients had low and high daytime BP variability, respectively, and 739 and 733 subjects had low and high night-time BP variability, respectively., Results: During follow-up (4.88 +/- 2.9 years, range 0.2-11.6 years) there were 119 events. The event rates per 100 patient-years in subjects with low and high BP variability according to daytime BP were 1.18 and 2.01, respectively, and in those with low and high BP variability according to night-time BP were 1.2 and 2.05, respectively. Event-free survival was significantly different between the low and high BP variability groups (P = .006 for both daytime and night-time BP). However, after adjustment for other covariates in a Cox multivariate analysis, the adverse prognostic relevance of high BP variability was no longer detectable, whereas age, smoking habit, LDL cholesterol, diabetes, previous events, LV hypertrophy, and daytime or night-time systolic BP resulted independent predictors of risk., Conclusions: Increased BP variability is associated with higher incidence of cardiovascular events, but also with other relevant prognostic factors. Indeed, in multivariate analysis the possible adverse prognostic impact of BP variability is no longer evident. Thus, in treated hypertension, BP variability evaluated by noninvasive monitoring is not an independent predictor of outcome.

Background: The aim of this study was to evaluate the cardiovascular outcome in apparently responder hypertensive patients with responder and masked hypertension, and in apparently resistant hypertensive patients with false and true resistant hypertension., Methods: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 340 patients with responder hypertension (clinic blood pressure [BP] <140/90 mm Hg and daytime BP <135/85 mm Hg), 126 with masked hypertension (clinic BP <140/90 mm Hg and daytime BP >135 or 85 mm Hg), 146 with false resistant hypertension (clinic BP >or=140 or 90 mm Hg and daytime BP <135/85 mm Hg), and 130 with true resistant hypertension (clinic BP >or=140 or 90 mm Hg and daytime BP >135 or 85 mm Hg)., Results: During follow-up period (4.98 +/- 2.9 years), the event-rate per 100 patient-years was 0.87, 2.42, 1.2, and 4.1 in patients with responder, masked, false resistant, and true resistant hypertension, respectively. After adjustment for several covariates, including clinic BP (forced into the model), Cox regression analysis showed that cardiovascular risk was significantly higher in masked hypertension (masked versus responder hypertension, relative risk [RR] 2.28, 95% confidence interval [CI] 1.1-4.7, P < .05) and in true resistant hypertension (true resistant versus responder hypertension, RR 2.94, 95% CI 1.02-8.41, P < .05), whereas there was no significant difference between false resistant and responder hypertension., Conclusions: This study shows that patients with masked hypertension are at higher risk than those with responder hypertension, and that those with false resistant hypertension are at lower risk than those with true resistant hypertension. Ambulatory BP monitoring should be performed in treated hypertensive patients to obtain a better prognostic stratification.

Background: The prognostic value of left ventricular (LV) concentric remodeling in essential hypertension, and particularly in uncomplicated mild hypertension, is not yet completely clear. We investigated cardiovascular outcome in uncomplicated mild hypertensive patients with normal LV geometry and LV concentric remodeling., Methods: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1088 uncomplicated mild hypertensive patients, 751 with normal LV geometry (LV mass index <125 g/m(2) in men and <110 g/m(2) in women and relative wall thickness <0.45) and 337 with LV concentric remodeling (LV mass index <125 g/m(2) in men and <110 g/m(2) in women and relative wall thickness >/=0.45)., Results: During follow-up (4.74 +/- 2.4 years, range 0.5 to 9.7 years) the event rates per 100 patient-years in subjects with normal LV geometry and LV concentric remodeling were 0.69 and 1.87, respectively. After adjustment for other covariates, Cox regression analysis showed that LV concentric remodeling (LV concentric remodeling versus normal LV geometry, RR 1.78, 95% CI 1.02 to 3.1, P < .05) was an independent predictor of cardiovascular events., Conclusion: In a population with uncomplicated mild hypertension, patients with LV concentric remodeling have a worse prognosis than those with normal LV geometry.

Background: The prognostic value of white coat hypertension (WCH) in uncomplicated patients with mild hypertension is not yet completely clear. We investigated cardiovascular outcomes in patients with mild hypertension and without left ventricular hypertrophy, diabetes mellitus, and associated cardiovascular and renal disease, with sustained hypertension (SH) and WCH., Methods: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1038 patients with mild hypertension and 241 normotensive subjects. The presence of WCH was defined as clinic hypertension and daytime blood pressure <135/85 mm Hg., Results: During follow-up (4.5 +/- 2.3 years, range 0.5 to 9.2 years) the event rates per 100 patient-years in subjects with normotension, WCH, and SH were 0.27, 0.38, and 1.39, respectively. After adjustment for other covariates, Cox regression analysis showed that SH was an independent predictor of cardiovascular events (SH versus WCH, RR 5.17, 95% CI 2.04 to 13.1, P = 0 .001), whereas there was no significant difference between normotension and WCH (normotension versus WCH, RR 0.93, 95% CI 0.22 to 3.98, P = .92). At the end of follow-up, drug therapy was less frequent and intensive in WCH than in SH., Conclusions: In this study of individuals with mild hypertension and without left ventricular hypertrophy, diabetes mellitus, and associated cardiovascular and renal disease, subjects with WCH, despite less frequent and intensive drug therapy, had a significantly better prognosis than those with sustained hypertension.

Background: Endothelial dysfunction is a frequent finding in essential hypertension. The aim of this study was to assess endothelial function, by evaluating circulating nitric oxide metabolites, nitrate plus nitrite (NOx), and endothelium-dependent vasodilation (EDD), in white coat hypertension in comparison with sustained hypertension and normotension., Methods: We selected 22 sustained hypertensive, 22 white coat hypertensive, and 22 normotensive subjects matched for age, gender, body mass index, and occupation. Women were also matched for menopausal status. Subjects with smoking habit, dyslipidemia, and diabetes mellitus were excluded from the study. White coat hypertension was defined as clinical hypertension and daytime ambulatory blood pressure (BP) <135/85 mm Hg. Groups received for 2 days a low-nitrate diet before obtaining blood samples for laboratory measurements. The NOx levels were measured by using the Griess reagent after enzymatic conversion of all nitrate to nitrite. Subjects also underwent brachial artery study by ultrasonography to evaluate EDD and endothelium-independent vasodilation., Results: White coat hypertensive subjects had significantly higher levels of NOx than sustained hypertensive patients (30.8 +/- 12 v 22 +/- 8.5 micromol/L, P <.05) and significantly higher EDD (7.8% +/- 3.1% v 4.6% +/- 3.0%, P <.05). No significant difference was observed between white coat hypertensive and normotensive subjects regarding these parameters. Endothelium-independent vasodilation was not significantly different among sustained hypertensives, white coat hypertensives, and normotensives (18% +/- 4.2% v 18.3% +/- 3.9% v 18.6% +/- 4.8%, respectively, P = not significant)., Conclusions: Our data suggest that middle-aged white coat hypertensive subjects without other cardiovascular risk factors do not show endothelial dysfunction in contrast with sustained hypertensive patients.

Background: Transforming growth factor-beta1 (TGF-beta1) has been demonstrated to be overexpressed in hypertension. Leptin, an adipocyte product, has been shown to play a role in obesity-related hypertension and in vitro studies demonstrated a biologic interaction between leptin and TGF-beta1. Thus, we evaluate a possible in vivo association between TGF-beta1, body mass index (BMI), and leptin circulating levels in hypertensive subjects., Methods: Blood samples for fasting leptin and TGF-beta1, were evaluated in 29 overweight, 46 obese, and 29 nonobese hypertensive patients before and after a 12-week calorie-restricted diet. Monocyte cultures were used for in vitro experiments., Results: Transforming growth factor-beta1 was significantly elevated in hypertensive obese patients (n = 46) as compared with TGF-beta1 levels of hypertensive patients with normal BMI (n = 29) (8. 9 +/- 3 ng/mL v 4.4 +/- 2; P < .001). The circulating levels of TGF-beta1 were associated with BMI and leptin levels in an univariate analysis (r = 0.59, P < .0001; r = 0.62, P < .0001, respectively) and these associations were still present after stepwise multivariate analysis. Weight loss of 10% produced a parallel decrease in TGF-beta1 (from 8.9 +/- 3 ng/mL to 5.3 +/- 2.8 ng/mL; P < .01) and leptin levels (from 30 +/- 24 ng/mL to 17 +/- 14; P < .05). In vitro experiments showed that leptin is able to induce a dose-dependent increase in TGF-beta1 production and mRNA expression in human monocyte cultures., Conclusions: Our data indicate that TGF-beta1 levels are positively associated with BMI and leptin levels in hypertensive patients and suggest that adipose tissue may be an important determinant of TGF-beta1 levels possibly by a leptin-dependent pathway.

We sought to evaluate the relationships among circulating levels of an endogenous ouabain-like factor (EO) and systemic hemodynamics and left ventricular (LV) geometry in patients with recently diagnosed essential hypertension. We selected 92 never-treated patients with essential hypertension. Blood samples were drawn for estimation of plasma EO (radioimmunoassay) and subjects underwent echocardiographic examination to evaluate LV end-systolic and end-diastolic wall thickness and internal dimensions. LV volumes, stroke volume, cardiac output, total peripheral resistance, LV mass, and relative wall thickness were calculated, and all except the last parameter were indexed by body surface area. LV mass also was indexed by height. On the basis of the values of LV mass index (body surface area or height) and relative wall thickness, subjects were divided into groups with either normal geometry, concentric remodeling, concentric hypertrophy, or eccentric nondilated hypertrophy. In the study population as a whole, circulating EO levels were significantly and directly correlated with mean blood pressure (r = 0.21, P = .048), relative wall thickness (r = 0.34, P = .001), and total peripheral resistance index (r = 0.37, P = .0003). Plasma EO also was significantly and inversely correlated with LV end-diastolic volume index (r = -0.32, P = .002), stroke index (r = -0.34, P = .0009), and cardiac index (r = -0.35, P = .0007). In multiple regression analysis, plasma EO was an independent correlate of total peripheral resistance index, cardiac index, and relative wall thickness. Regardless of the indexation method used for LV mass, plasma EO was higher in patients with concentric remodeling than in those with either normal geometry or concentric hypertrophy. Plasma EO tended to be higher (indexation by body surface area) or was significantly higher (indexation by height) in subjects with concentric remodeling than in those with eccentric nondilated hypertrophy. Patients with concentric remodeling showed the highest total peripheral resistance index and the lowest cardiac index. Our data suggest that EO plays a role in regulating systemic hemodynamics and LV geometry in patients with essential hypertension.

Low-density lipoprotein oxidation and antioxidant vitamins E and C were investigated in dipper (nocturnal blood pressure fall > 10%) and nondipper (nocturnal blood pressure fall < 10%) hypertensives. We studied 40 dippers and 28 nondippers balanced for gender, age, and body mass index. Blood samples were drawn for lipid profile determination, assessment of thiobarbituric acid-reactive substances, and fluorescent products of lipid peroxidation in native low-density lipoprotein, evaluation of susceptibility to low-density lipoprotein oxidation in vitro (lag phase and propagation rate), and determination of low-density lipoprotein vitamin E and plasma vitamins E and C contents. Compared with dippers, nondippers had significantly higher thiobarbituric acid-reactive substances and fluorescent products of lipid peroxidation (0.63 +/- 0.1 v 0.77 +/- 0.08 nmol malondialdehyde/mg low-density lipoprotein protein, and 14.5 +/- 6 v 17.9 +/- 4 units of relative fluorescence/mg low-density lipoprotein protein, respectively, both P < .05), shorter lag phase (56 +/- 13 v 49 +/- 9 min, P < .05), and lower plasma vitamin C content (42 +/- 9 v 35 +/- 10 micromol/L, P < .05). When gender was taken into account, differences were not significant between dipper and nondipper men, whereas, compared with dipper women, nondipper women showed significantly higher thiobarbituric acid-reactive substances and fluorescent products of lipid peroxidation (0.56 +/- 0.1 v 0.77 +/- 0.07 nmol malondialdehyde/mg low-density lipoprotein protein, and 12.5 +/- 4 v 17.5 +/- 4.6 units of relative fluorescence/mg low-density lipoprotein protein, respectively, both P < .05), shorter lag phase (62.5 +/- 11 v 49 +/- 9.5 min, P < .05), and lower plasma vitamin C content (44.9 +/- 10 v 34.7 +/- 10.8 micromol/L, P < .05). Given the role of low-density lipoprotein oxidation in the pathogenesis of atherosclerosis and that of vitamin C in protecting against it, our data suggest that nondippers, especially among women, show higher atherogenic risk than dippers.

The aim of this study was to evaluate whether sustained hypertensives with high clinic blood pressure, despite multiple drug treatment, show a true resistant hypertension or a "white-coat effect," and whether the pretreatment white-coat effect is maintained despite pharmacological therapy. The occurrence of resistant hypertension was determined in 250 consecutive essential hypertensives who had had an ambulatory blood pressure monitoring before treatment assignment. Twenty-seven of 250 hypertensives with persistently high clinic blood pressure despite 3 months of adequate pharmacological therapy underwent further ambulatory blood pressure monitoring. Using our internal standards, seven patients had a true resistant hypertension whereas 20 subjects showed a large white-coat effect (white-coat resistant hypertension), ie, high clinic blood pressure (> 140/90) but "normal" ambulatory daytime (< 139/90 mm Hg) and 24 h (135/85 mm Hg) blood pressure. Using other cutoff points for ambulatory blood pressure, 134/90 and 135/85 mm Hg for daytime blood pressure, 10 and 13 patients, respectively, were reclassified as true resistant hypertensives and 17 and 14, respectively, were white-coat resistant hypertensives. Interestingly, in white-coat resistant hypertensives the large differences between clinic and ambulatory daytime blood pressure (white-coat effect), recorded before treatment assignment, were not affected by drugs and remained constant over time. Left ventricular mass index in white-coat resistant hypertensives was significantly lower than in truly resistant hypertensives, suggesting that prognosis could differ between these groups. In this study, using either our internal standards or some other cutoffs reported in the literature, the white-coat phenomenon was an important cause of resistant hypertension. The use of ambulatory blood pressure monitoring in these patients may avoid misdiagnosis of resistant hypertension, unnecessary overtreatment, and expensive procedures to look for possible secondary hypertension.

Carotid artery and small vessel structural changes were evaluated in 45 dipper and 45 nondipper hypertensive subjects matched for sex, age, body mass index, smoking habit, and serum lipids. Patients underwent carotid ultrasonography to evaluate lumen diameter, intima-media thickness, cross-sectional area, and atherosclerotic plaques, and plethysmographic examination to record minimum forearm vascular resistance. In the whole study population, carotid cross-sectional area and prevalence of atherosclerotic plaques tended to be higher in nondippers than in dippers (19.9 +/- 6.0 v 17.5 +/- 6.1 mm2, P = .07, and 40% v 26%, P = .18), whereas intima-media thickness and minimum forearm vascular resistance were significantly higher in nondippers than in dippers (0.89 +/- 0.12 v 0.8 +/- 0.15 mm, P < .02, and 2.53 +/- 0.3 v 2.34 +/- 0.3 arbitrary resistance units (RU), P < .02). When gender was taken into account, different results were obtained in men and women. In men, vascular characteristics were not significantly different between dippers and nondippers. In women, carotid cross-sectional area and prevalence of atherosclerotic plaques tended to be higher in nondippers than in dippers (18.3 +/- 4.9 v 15.5 +/- 4.5 mm2, P = .06, and 40% v 15%, P = .15), and intima-media thickness and minimum forearm vascular resistance were significantly higher in nondippers than in dippers both before (0.84 +/- 0.1 v 0.73 +/- 0.1 mm, P < .01, and 2.38 +/- 0.3 v 2.16 +/- 0.2 RU, P < .01) and after adjustment for 24-h blood pressure. In conclusion, our data suggest that the progression of vascular disease may be differently affected in the two sexes by a different circadian blood pressure profile.