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Background: Whether and to what extent the reported blood pressure (BP) lowering effects of renal denervation (RDN) are associated with a central sympathoinhibition is controversial. We examined this issue by performing a meta-analysis of the microneurographic studies evaluating the BP and muscle sympathetic nerve activity (MSNA) responses to RDN in drug-resistant or uncontrolled hypertension (RHT). Methods: This analysis comprised 11 studies including a total of >400 RHT patients undergoing RDN and were followed up for 6 months. Evaluation was extended to the relationships of MSNA with clinic heart rate and BP changes associated with RDN. Results: MSNA showed a significant reduction after RDN (−4.78 bursts/100 heart beats; P P P =0.0001) BP decrease. No significant quantitative relationship was found between MSNA and systolic (r=−0.96, P =0.19) or diastolic BP (r=−0.97, P =0.23) responses to RDN. This was also the case for clinic heart rate (r=0.53, P =0.78, respectively), whose post RDN values were not significant different from the pre-RDN ones. More than 10 renal nerves ablations were found to be needed for obtaining a significant sympathoinhibition. Conclusions: This meta-analysis, the first ever done on the MSNA responses to RDN, shows that in a consistent number of RHT patients RDN is associated with a significant, although modest, central sympathoinhibition, which appears to be unrelated to the BP lowering effects of the procedure. Thus factors other than the central sympathetic outflow inhibition may concur at the BP lowering effects of RDN.

Purpose Renal denervation (RDN) exerts sympathoinhibitory effects. No information is available, however, on whether these effects have a regional or a more generalized behavior. Methods In 14 patients with resistant hypertension (RHT, age 58.3 ± 2.2 years, mean ± SEM), we recorded muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively) using the microneurographic technique, before, 1 month, and 3 months after RDN. Measurements included clinic blood pressure (BP), heart rate (HR), 24-h BP and HR, as well as routine laboratory and echocardiographic variables. Ten age-matched RHT patients who did not undergo RDN served as controls. Results MSNA, but not SSNA, was markedly higher in RHT. RDN caused a significant reduction in MSNA 1 month after RDN, with this reduction increasing after 3 months (from 68.1 ± 2.5 to 64.8 ± 2.4 and 63.1 ± 2.6 bursts/100 heartbeats, P P = NS). No quantitative or, in some cases, qualitative relationship was found between BP and the MSNA reduction induced by RDN. No significant changes in various sympathetic markers were detected in the control group who did not undergo RDN and were followed for 3-months observation. Conclusions These data provide the first evidence that RDN exerts heterogeneous effects on sympathetic cardiovascular drive, inducing a marked reduction in MSNA but not in SSNA, which appears to be within the normal range in this condition.These effects may depend on the different reflex modulation regulating neuroadrenergic drive in these cardiovascular districts.

Iron overload has been recently shown to be associated with a hyperadrenergic state in genetic hemochromatosis. Whether this is also the case in essential hypertension, characterized by sympathetic activation and frequently by body iron overload, is unknown. In 17 healthy normotensive controls (age 52.3±3.2 years, mean±SE), in 21 age-matched patients with hypertension with iron overload (HT+), defined by serum ferritin levels, and in 28 hypertensives without this condition, we measured efferent postganglionic muscle sympathetic nerve traffic (microneurography), heart rate and blood pressure variability (power spectral analysis), serum ferritin, and metabolic variables. Muscle sympathetic nerve traffic was significantly ( P r =0.51, P r =0.47, P r =0.76, P r =0.46, P

Findings regarding long-terms variations in blood pressure (BP) taken in different setting (ie, office, home, and ambulatory BP) in the community are scanty. We sought to assess this issue in members of the general population enrolled in the PAMELA (Pressioni Monitorate E Loro Associazioni) study. The study included 562 participants who attended the second and third survey of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, office, home, ambulatory BP, and standard blood examinations. Office, home, and 24-hour systolic BP over the 25-year interval between the first and third survey increased in a parallel way (ie, 12%, 10%, and 15.5%). The increments in office, home, and 24-hour diastolic BP were lower than the systolic BP ones (ie, 3.3%, 5.6%, and 6.1%). Thus, the combined changes in systolic BP and diastolic BP from the first to the third data collection resulted in a marked increase in pulse pressure (ie, 29%, 19%, and 30%). The prevalence of hypertension assessed at office visits and out-of-office either by self-BP measurements at home and ambulatory blood pressure monitoring increased ≈3 to 4× (3.1 office, 3.3 home, 3.9 ABPM, respectively). This trend was associated with adiposity indexes and worsening of the glucose profile. This community-based longitudinal study suggests that the progressive and marked increase in hypertension with age, consistently documented with different BP measurement methods, represents an epochal challenge for the prevention of cardiovascular diseases, due to the rapid growth the elderly population worldwide.

Aim:Little evidence is available on whether antihypertensive treatment lowers cardiovascular risk in white-coat hypertension (WCH). Protection might be indirectly inferred, however, from the blood pressure (BP) effects of treatment as in trials BP reduction is linearly related to outcome reduction. We analyzed the effect of antihypertensive treatment on office and ambulatory BP in WCH using data from the Plaque HYpertension Lipid-Lowering Italian Study (PHYLLIS).Methods: Office and ambulatory blood pressure were measured in 470 hypertensive patients randomized to fosinopril or hydrochlorothiazide alone or combined with a statin before treatment and at 6 month or yearly intervals during 2.6 years of follow-up. Patients were divided into two groups according to whether before randomization to treatment office and 24-h mean BP were elevated (sustained hypertension) or office BP was elevated but 24-h BP values were normal (WCH).Results: In both sustained hypertension and WCH antihypertensive treatment was associated with an early marked office BP reduction, which persisted virtually unchanged throughout the treatment period. In contrast, 24-h (and day and night) BP showed a marked and persistent treatment-related fall in sustained hypertension but no change in WCH. The results were similar when data were separately analyzed in patients under fosinopril or diuretic, with or without statin treatment.Conclusion: In WCH, antihypertensive treatment can effectively and durably reduce office BP. This reduction is accompanied by the inability to lower ambulatory BP from the normal values characterizing this condition at baseline. This appears to be unrelated to the type of treatment employed.

BACKGROUND Neuroadrenegic overdrive occurs in obstructive sleep apnoea syndrome (OSAS). However, the small sample size of the microneurographic studies, heterogeneity of the patients examined, presence of comorbidities, represented major weaknesses not allowing to precisely define the main features of the phenomenon, particularly in nonobese patients. OBJECTIVE This meta-analysis detected 14 microneurographic studies based on muscle sympathetic nerve activity (MSNA) quantification in uncomplicated OSAS of different clinical severity. METHODS The evaluation was extended to the relationships of MSNA with heart rate, anthropometric and blood pressure values, metabolic variables, apnoea-hypopnea index and oxygen saturation. RESULTS MSNA is activated markedly and almost homogeneously between studies, showing a progressive increase from the healthy state to mild, moderate and severe OSAS (46.03, 48.32, 71.84, 69.27 bursts/100 heart beats). Of special interest are the findings that MSNA is significantly related to the apnoea-hypopnea index, a marker of OSAS severity (r = 0.55, P = 0.04) but not to BMI, as it occurs in OSAS associated with obesity, and heart rate is significantly and directly related to MSNA and apnoea-hypopnea index (r = 0.68 and r = 0.60, respectively P = 0.03 and P = 0.02), thus representing a surrogate marker of the sympathetic overdrive. CONCLUSION OSAS, even when uncomplicated by other cardiometabolic disease, displays a marked sympathetic activation, reflected by the MSNA and heart rate behaviour, becoming a target of therapeutic interventions aimed at exerting sympathomoderating effects, such as continuous positive airway pressure.

INTRODUCTION Among the observational studies performed in the area of blood pressure measurements in the population the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) investigation represents an unique research for a number of reasons. EVIDENCE ACQUISITION AND SYNTHESIS The PAMELA study combines clinic, home and 24-hour blood pressure measurements in all partiicipants, which were representative of the general population. Examination included metabolic variables, allowing us to determine the interrelationships between bood pressure and metabolic profile. The protocol also included evaluation of organ damage, such as left ventricular hypertrophy, left ventricular diastolic dysfunction, left atrial dimensions and aortic root diameters. Finally, PAMELA represents one of the few studies with a prolonged follow-up, the last survey being completed three years ago and data collected are actually under analysis. This will allow to update the information related to cardiovascular morbidity and mortality in the study cohort. CONCLUSIONS The present paper will provide an overview of the various scientific contributions of the PAMELA study to the epidemiology, pathophysiology and clinical aspects of hypertension and hypertension related cardiovascular risk.

AIM We sought to assess the long-term changes in aortic root diameter in a population-based sample, focusing on new-onset aortic root dilatation, as well as on the demographic and clinical variables independently related to this dynamic process. METHODS A total of 1122 participants with measurable echocardiographic parameters at baseline and after a 10-year follow-up were included in the analysis. Sex-specific upper limits of normality for absolute aortic root diameter, aortic root diameter indexed to body surface area (BSA) and to height were derived from 712 healthy normotensive PAMELA participants. RESULTS Over the 10-year follow-up, new aortic root dilatation occurred in 3.4% (aortic root /BSA), 4.4% (aortic root /height) and 7.3% (absolute aortic root), respectively. No substantial relationship was observed between baseline office and ambulatory blood pressure (BP) or their changes over time and incident aortic root /BSA and aortic root /height dilatation. Baseline aortic root diameter and left ventricular mass index (LVMI) emerged as important predictors of aortic root dilation, regardless of the diagnostic criteria used. This was also the case for the 10-year change in LVMI. The strength of association between nonhemodynamic variables and new-onset aortic root dilatation was variable, depending on the definition of the aortic phenotype. CONCLUSION The incidence of aortic root dilatation in a general middle-aged population is a relatively infrequent but not so rare event and scarcely influenced by both office and out-office BP. On the contrary, it is strongly related to LVMI (and its variations over time). From a clinical perspective, this underlines that LVH prevention and regression can reduce the risk of aortic root dilatation in the community.

Masked hypertension (MH) is defined as normal office blood pressure (BP) and elevated ambulatory BP (ABP) or home BP or both. This study assessed the association of MH (ie, isolated home, isolated ABP and dual MH) with echocardiographic left ventricular hypertrophy (LVH). The present analysis of the PAMELA study included 1087 untreated and treated participants with normal office BP and a measurable LV mass (LVM). A total of 193 individuals (17.7%) had any MH (ie, normal office BP, elevated ABP or home BP or both), 48 had dual MH (25%), 62 isolated ambulatory MH (32%), and 83 isolated home MH (43%). Average LVM indexed to body surface area was superimposable in the three MH phenotypes (being the largest difference between groups

True drug-resistant hypertension (RHT) is characterized by a marked neuroadrenergic activation and reflex alterations compared with the nonresistant hypertensive state. It is unknown however, whether this behavior is specific for the RHT state or is also shared by apparent RHT (ARHT). In 38 middle-age patients with RHT, 44 treated essential controlled hypertensives (HT) and 32 ARHT; we evaluated sphygmomanometric, beat-to-beat (Finapres) and 24-hour (Spacelabs) blood pressure, heart rate and muscle sympathetic nerve traffic (microneurography). Measurements included plasma aldosterone, plasma norepinephrine, homeostasis model assessment index, and spontaneous baroreflex-muscle sympathetic nerve traffic sensitivity. All the various above-mentioned blood pressure values were significantly greater in both RHT and ARHT as compared with HT, while 24-hour blood pressure was significantly lower in ARHT as compared with RHT. In ARHT, muscle sympathetic nerve traffic was significantly lower than RHT (74.8±5.2 versus 89.2±4.8 bursts/100 hb, P P =NS). RHT showed, at variance from the other 2 groups, greater plasma aldosterone and homeostasis model assessment index values and an impaired baroreflex function. In RHT, but not in ARHT and HT, muscle sympathetic nerve traffic was significantly and inversely related to baroreflex function ( r =−0.40, P r =0.34–0.36, P

BACKGROUND AND OBJECTIVES Sympathetic neural activation occurs in congestive heart failure (CHF). However, the small sample size of the microneurographic studies, heterogeneity of the patients examined, presence of comorbidities as well as confounders (including treatment) represented major weaknesses not allowing to identify the major features of the phoenomenon, particularly in mild CHF. This meta-analysis evaluated 2530 heart failure (CHF) patients recruited in 106 microneurographic studies. It was based on muscle sympathetic nerve activity (MSNA) quantification in CHF of different clinical severity, but data from less widely addressed conditions, such as ischemic vs. idiopathic, were also considered. METHODS Assessment was extended to the relationships of MSNA with venous plasma norepinephrine, heart rate (HR) and echocardiographic parameters of cardiac morphology [left ventricular (LV) end-diastolic diameter] and function (LV ejection fraction) as well. RESULTS MSNA was significantly greater (1.9 times, P

Nerve traffic recordings (muscle sympathetic nerve traffic [MSNA]) have shown that sympathetic activation may occur in obesity. However, the small sample size of the available studies, presence of comorbidities, heterogeneity of the subjects examined represented major weaknesses not allowing to draw definite conclusions. This is the case for the overweight state. The present meta-analysis evaluated 1438 obese or overweight subjects recruited in 45 microneurographic studies. The analysis was primarily based on MSNA quantification in obesity and overweight, excluding as concomitant conditions hypertension, metabolic syndrome, and other comorbidities. Assessment was extended to the relationships of MSNA with other neuroadrenergic markers, such as plasma norepinephrine and heart rate, anthropometric variables, as body mass index, waist-to-hip ratio, presence/absence of obstructive sleep apnea, and metabolic profile. Compared with normoweights MSNA was significantly greater in overweight and more in obese individuals (37.0±4.1 versus 43.2±3.5 and 50.4±5.0 burts/100 heartbeats, P r =0.41 and r =0.64, P r =0.68, P r =0.91, r =0.94, and r =0.80, respectively, P

Purpose of Review To review the results of studies of the effects of dialysis and kidney transplantation on the autonomic nervous system alterations that occur in chronic kidney disease. Recent Findings Vagal control of the heart mediated by arterial baroreceptors is altered early in the course of the renal disease. Sympathetic activation occurs, with increases in resting heart rate, venous plasma norepinephrine levels, muscle sympathetic nerve traffic, and other indirect indices of adrenergic drive. The magnitude of the changes reflects the clinical severity of the kidney disease. Both the sympathetic and parasympathetic alterations have a reflex origin, depending on the impairment in baroreflex and cardiopulmonary reflex control of the cardiovascular system. These alterations are partially reversed during acute hemodialysis, but the responses are variable depending on the specific type of dialytic treatment that is employed. Renal transplantation improves reflex cardiovascular control, resulting in sympathoinhibition following renal transplantation if the native kidneys are removed. Sympathoinhibitory effects have been also reported in renal failure patients after bilateral renal denervation. Summary Assessment of autonomic nervous system responses to dialysis and renal transplantation provides information of clinical interest, given the evidence that autonomic alterations are involved in the development and progression of cardiovascular complications, as well as in the prognosis of chronic kidney disease.

Background: Chronic kidney disease (CKD) is characterized by a pronounced sympathetic overactivity as documented by the marked increase in muscle sympathetic nerve traffic (MSNA) and in plasma norepinephrine reported in this condition. Whether and to what extent in CKD heart rate (HR) reflects the adrenergic overdrive remains undefined. It is also undefined the relative validity of the different adrenergic markers in reflecting renal dysfunction. Materials and methods: In 82 CKD patients, aged 58.4 ± 1.1 years (mean ± SEM), we measured resting clinic blood pressure, HR (EKG), venous NE (HPLC) and MSNA (microneurography). The same measurements were made in 24 age-matched healthy controls. Results: HR was significantly greater in CKD than in controls (74.0 ± 1.1 versus 68.2 ± 1.8 bpm, P < 0.02) and significantly directly related to the elevated plasma norepinephrine and MSNA values (r = 0.22 and 0.39, P < 0.05 and

In 1722 hypertensives recruited for the European Lacidipine Study on Atherosclerosis and treated with atenolol or lacidipine (±additional drugs) during 4 years, we evaluated the long-term reproducibility of dipping, nondipping, extreme dipping, and reverse dipping, an information of key relevance for defining the prognostic impact of these blood pressure (BP) phenotypes. Ambulatory BP was measured at baseline and every year during treatment, allowing repeated classifications of these conditions. Based on systolic BP, at baseline 50.1%, 37.5 %, 4.5 %, and 7.9 % were dippers, nondippers, extreme dippers, and reverse dippers, respectively. Antihypertensive drug treatment reduced the number of dippers and extreme dippers in favor of nondippers and reverse dippers. During treatment, the dipping and nondipping phenotypes were markedly unstable and shifts from one to other phenotypes were even more common in reverse and extreme dippers In only a very small fraction of patients, a given nighttime BP phenotype was persistently found throughout the 4 years. Data were similar for diastolic BP and in subgroups differing for the type of treatment, the treatment complexity, and the achieved on-treatment BP value Poor reproducibility characterized also the absolute nighttime BP reduction as measured by the nighttime BP fall and the night/day BP ratio. Thus nighttime BP phenotypes are all largely inconsistent, their detection over the entire treatment period involving just a minute fraction of the entire patients’ cohort.

AIM: Available evidence on regression of left ventricular (LV) hypertrophy in patients with primary aldosteronism after unilateral adrenalectomy is scanty. We performed a systematic meta-analysis of echocardiographic studies to provide an updated and comprehensive information on this issue. METHODS: The PubMed, OVID-MEDLINE and Cochrane library databases were analyzed to search English-language articles published from 1 January 1990 up to 30 June 2020. Studies were identified by using MeSH terms and crossing the following search items: 'primary aldosteronism' 'Conn's syndrome' 'adrenalectomy', with 'cardiac damage', 'hypertensive heart disease' 'left ventricular mass', 'left ventricular hypertrophy', 'left ventricular hypertrophy regression', 'echocardiography'. RESULTS: A total of 629 hypertensive patients with primary aldosteronism (mean age 49 years, 45% men) were included in 14 studies. Baseline and postintervention pooled mean LV mass/BSA values were 134 ± 4 and 108 ± 3 g/m2 [standard means difference (SMD) -0.42 ± 0.05, confidence interval (CI) -0.52/-0.32, P

We examined in 11 young subjects (age 29.7±3.6 years, mean±SEM) whether carotid baroreceptor stimulation via the neck chamber device may affect central venous pressure (CVP), thus potentially involving other reflexogenic areas in the examined responses. Application of progressively greater neck chamber subatmospheric pressures caused a progressive lengthening in RR interval, which reached a peak at the maximal value of negative neck chamber pressure applied. This was accompanied by significant and progressively greater reduction in CVP values when the data were calculated considering the early changes occurring within the first 2 seconds of the stimulus. There was a weak correlation between the early changes in CVP and the RR interval responses when all stimuli were pooled together (r=0.32, P&nbsp

BACKGROUND: Neuroadrenergic overdrive occurs in obstructive sleep apnea syndrome (OSAS). However, the small sample size of the microneurographic studies, heterogeneity of the patients examined, presence of comorbidities, represented major weaknesses not allowing to precisely define the main features of the phenomenon, particularly in nonobese patients. OBJECTIVE: This meta-analysis evaluated 850 participants recruited in 26 microneurographic studies, based on muscle sympathetic nerve activity (MSNA) quantification in uncomplicated OSAS of different clinical severity. METHODS: The evaluation was extended to the relationships of MSNA with heart rate (HR), anthropometric and blood pressure (BP) values, metabolic variables, apnea-hypopnea index (AHI) and oxygen saturation. RESULTS: MSNA is activated markedly and almost homogeneously between studies, showing a progressive increase from the healthy state to mild, moderate and severe OSAS (41.6, 48.3, 65.5 and 70.7 bursts/100 heart beats, respectively, P

Whether blood pressure (BP) values differ when BP is measured with or without the presence of a doctor (attended and unattended BP measurements) is controversial, and no information exists on whether and to what extent neurogenic mechanisms participate at the possible BP differences between these measurements. In this study, we assessed continuous beat-to-beat finger systolic BP and diastolic BP, heart rate, muscle, and skin sympathetic nerve traffic (microneurography) before and during BP measurement by an automatic device in the presence or absence of a doctor. This was done in 18 untreated mild-to-moderate essential hypertensive patients (age, 40.2±2.8 years, mean±SEM). During attended BP measurement, there was an increase in systolic BP, diastolic BP, heart rate, and skin sympathetic nerve traffic and a muscle sympathetic nerve traffic decrease, the peak changes being +5.3%,+8.4%,+9.4%,+30.9%, and −15.2%, respectively ( P

The recent European Society of Cardiology/European Society of Hypertension hypertension guidelines identify resting heart rate (HR) values >80 bpm as predictors of cardiovascular risk, with the unproven assumption that this might reflect the presence of a sympathetic overdrive. In the present study, we tested this hypothesis throughout the use of direct and indirect sympathetic markers. In 193 untreated moderate essential hypertensives aged 50.4±0.6 years (mean±SEM), we measured clinic and ambulatory blood pressure and corresponding HR, venous plasma norepinephrine (high performance liquid chromatography), and muscle sympathetic nerve traffic (microneurography). We then subdivided the study population into 2 groups according to HR < or >80 bpm. Eighty-four patients displayed resting HR >80 bpm, which was this cutoff value in the remaining 109 patients, the 2 groups showing superimposable age, and sex distribution. Clinic and ambulatory blood pressure were similar in the 2 groups, whereas left ventricular mass index was significantly greater in the group with HR >80 bpm. Muscle sympathetic nerve traffic values were also significantly greater in this latter group (72.77±0.9 versus vs 36.83±1.3 bursts/min, P P 80 bpm are characterized by a marked sympathetic overdrive, particularly when direct adrenergic markers are used. This finding suggests that cardiac and peripheral sympathetic activation are involved in the increased cardiovascular risk detected in this group of patients.

Background: Metabolic syndrome is characterized by a pronounced sympathetic overactivity as documented by the marked increase in muscle sympathetic nerve traffic (MSNA) as well as in plasma norepinephrine values reported in this condition. Whether and to what extent heart rate (HR) reflects the abovementioned adrenergic alterations in metabolic syndrome remains largely undefined. It is also undefined the validity of the abovementioned adrenergic markers in reflecting the main features of the metabolic syndrome. Methods: In 65 metabolic syndrome patients, aged 56.5 ± 1.3 years (mean ± SEM), we measured over a 30-min resting period blood pressure, HR (ECG), venous plasma norepinephrine (HPLC) and MSNA (microneurography). We also evaluated anthropometric and metabolic variables including HOMA index, correlating them with the adrenergic markers. The same measurements were also made in 48 age-matched healthy controls. Results: HR was significantly greater in the metabolic syndrome patients than in controls (74.6 ± 1.5 versus 67.5 ± 1.5 bpm, P < 0.001) and significantly and directly correlated with the elevated norepinephrine and MSNA values (r = 0.25 and 0.33, P < 0.05 and 0.01, respectively). MSNA was significantly and directly related to blood pressure (r = 0.27 and 0.31 SBP and DBP, respectively, P < 0.05 for both), BMI (r = 0.36, P < 0.01), waist circumference (r = 0.34, P < 0.01), waist-to-hip ratio (r = 0.49, P < 0.01) and plasma insulin (r = 0.57, P < 0.01). In contrast, no significant correlation was detectable between HR or norepinephrine and the abovementioned anthropometric and metabolic variables. Conclusion: Our data show that in the metabolic syndrome not only peripheral but also cardiac sympathetic drive is markedly potentiated and HR can be regarded as a marker of adrenergic overdrive characterizing this clinical condition. The reliability of HR (and of plasma norepinephrine) as sympathetic marker appears to be limited, however, this variable being unable to reflect, at variance from MSNA, the main metabolic and anthropometric abnormalities characterizing the metabolic syndrome.

Aim Information regarding the association of hypertension-mediated organ damage (HMOD) with extreme dipping pattern is scanty and not univocal. We sought to assess the clinical correlates of this blood pressure (BP) phenotype and its relationship with cardiac HMOD in the general population belonging to Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study. Methods The present analysis included all participants with good-quality ABPM recordings with reliable echocardiography at entry. Results A total of 792 out of 1597 patients (49.6%) exhibited an extreme dipping pattern (155 had a night-time reduction in both SBP and DBP at least 20% compared with daytime values and 637 a night-time reduction in DBP at least 20%); 34.2% were dippers and 16.2% nondippers. Left ventricular mass (LVM) indexed to height and LV hypertrophy (LVH) prevalence rates increased progressively from diastolic extreme dipping (14%), dipper (17%), systolic/diastolic extreme dipping (21%) to nondipper group (27%). However, after adjusting for confounders, statistical differences in both LVMI and LVH rates among the four groups disappeared. Similar results were obtained for LVM indexed to body surface area and absolute/indexed left atrial diameter. Conclusion Extreme dipping pattern is a BP phenotype highly frequent in the general population largely consisting of middle-aged individuals without prevalent cardiovascular disease. In this population, the extreme dipping pattern is not associated with an increased risk of cardiac HMOD, which suggests that the mechanisms invoked for the potential adverse cardiovascular effects of this condition (i.e. nocturnal hypoxemia, low-grade myocardial inflammation, coronary hypoperfusion, sympathetic activation at early morning, etc.) are not operative.

AIM: Findings regarding the association of left ventricular mass (LVM) and new-onset hypertension are based on blood pressure measured in the office. We sought to assess the value of LVM in predicting in-office and out-of-office incident hypertension in members of the general population enrolled in the Pressioni Monitorate E Loro Associazioni study. METHODS: The study included participants with normal office (n = 792), home (n = 714) and 24-h (n = 825) ambulatory blood pressure (ABP) at baseline evaluation who had a readable echocardiogram at entry and at the end of follow-up. Each normotensive group was divided into quartiles of LVM indexed (LVMI) to height. RESULTS: Over a follow-up of 148 months cumulative incidence of new office, home and 24-h ABP hypertension were 35.9, 30.7 and 36.1%, respectively. In fully adjusted models (including age, sex, BMI change during follow-up, baseline serum glucose, creatinine, total cholesterol office, home and 24-h SBP and DBP). higher LVMI values (i.e. the highest vs. the lowest quartile) were independently associated with an increased risk of home [odds ratio (OR) = 2.14, 95% confidence interval (CI) 1.21-3.77, P = 0.008] and 24-h ABP hypertension (OR = 1.70, 95% CI 1.05-2.76, P = 0.03). This was not the case for new-onset office hypertension (OR = 1.61, 95% CI 0.94-2.74, P = 0.07). CONCLUSION: Our study provides the first evidence that in normotensive individuals the magnitude of LVMI is independently associated with the risk of incident out-of-office hypertension.

Objective We aimed to investigate left atrial phasic function in the recently diagnosed hypertensive patients and determine association between circadian blood pressure (BP) patterns and left atrial function. Methods The present study involved 256 untreated hypertensive patients who underwent 24-h ambulatory BP monitoring and comprehensive echocardiographic examination. All patients were divided into four groups according to the percentage of nocturnal BP drop (dippers, extreme dippers, nondippers and reverse dippers). Results There was no significant difference in daytime BPs between the observed groups, whereas night-time BPs significantly and gradually increased from extreme dippers and dippers, across nondippers, to reverse dippers. Total, passive and active left atrial emptying fractions that correspond with left atrial reservoir, conduit and contractile function were lower in nondippers and reverse dippers than in dippers and extreme dippers. Reservoir and contractile left atrial strains were lower in reverse dippers than in dippers and extreme dippers, whereas conduit left atrial strain was lower in reverse dippers in comparison with extreme dippers. Nondipping and reverse dipping BP patterns were, independently of age, sex, nocturnal BPs, left ventricular mass index, E/e', associated with reduced reservoir function. Nevertheless, only reverse dipping profile was independently of other circadian BP profiles, nocturnal BP, demographic and echocardiographic parameters related with reduced conduit and contractile functions. Conclusion Nondipping and reverse dipping BP patterns were related with impaired left atrial phasic function. However, reverse pattern was the only circadian profile that was independently of other clinical parameters, including night-time BP, associated with decreased reservoir, conduit and contractile function.

OBJECTIVE: The microneurographic technique has shown that sympathetic overactivity may characterize patients with the metabolic syndrome. However, technical and methodological limitations of the studies prevented to draw definite conclusions. The present meta-analysis evaluated 16 microneurographic studies including 650 individuals, 444 metabolic syndrome patients and 206 healthy controls, respectively. The analysis was primarily based on muscle sympathetic nerve traffic (MSNA) quantified by microneurography in metabolic syndrome. METHODS: Assessment was extended to the relationships of MSNA with an indirect neuroadrenergic marker, such as heart rate (HR), anthropometric variables, as BMI, waist-hip ratio and metabolic profile. RESULTS: Metabolic syndrome individuals displayed MSNA values (means ± SEM) significantly greater than controls (58.6 ± 4.8 versus 41.6 ± 4.1 bursts/100 heart beats, P

Purpose of Review: The present paper will review the results of experimental and clinical studies aimed at defining the functional behavior of the central and peripheral nervous system in adrenal pheochromocytoma. Recent Findings: The contribution of sympathetic neural influences to the development of high blood pressure values in pheochromocytoma is complex. Studies performed in experimental animal models have shown that hypertension and the concomitant high circulating levels of catecholamines can lead to inhibition of central sympathetic neural outflow by reflex mechanisms and direct stimulation of central adrenergic receptors, respectively. However, these studies have also shown that high circulating levels of catecholamines favor a downregulation of alpha- and beta-adrenergic receptors, lessening their response to endogenous and exogenous adrenergic stimulation. The present paper reviews results of human studies performed by our group and others on the behavior of the central and peripheral nervous system in human pheochromocytoma. We discuss data collected in patients with different levels of peripheral sympathetic drive, i.e., before and after surgical removal of the adrenal pheochromocytoma. Summary: In the presence of elevated plasma catecholamine level, such as that characterizing adrenal pheochromocytoma, microneurography shows that central sympathetic neural activity is normal or even inhibited. At the peripheral vascular level, pheochromocytoma is characterized by a reduced vascular reactivity to exogenous sympathetic stimulation but a normal response by the vessels to endogenous adrenergic stimulation.

Introduction: The present study was aimed at comparing the antihypertensive efficacy, tolerability, and side effects profile of nebivolol/hydrochlorothiazide (NH) vs irbesartan/hydrochlorothiazide (IH) combination in elderly patients with isolated systolic hypertension (ISH). Methods: 124 ISH patients aged 69.1 ± 5.1 years (mean ± SD) were enrolled by 13 general practitioners in Netherlands and Belgium and randomized in a double-blind fashion to receive either NH (5/12.5 mg day, n = 62) or IH (150/12.5 mg day, n = 62) for a 12-week period. The primary efficacy endpoint of the study was the comparison of the two combinations in terms of sitting office systolic blood pressure (BP) reduction after 12 weeks of treatment. In addition ambulatory BP, 24-h BP variability, tolerability, and safety profile were also investigated. Results: 122 patients were included in the intention-to-treat analysis. After 12 weeks of treatment the reduction of systolic BP with NH was significantly greater than IH (−25.8 ± 12 vs −21.2 ± 14 mm Hg, P

In the PAMELA study (Pressioni Arteriose Monitorate e Loro Associazioni), clinical variables, an echocardiogram, as well as office and ambulatory blood pressure (ABP) were simultaneously measured at baseline and after a 10-year follow-up. The study design allowed us to assess the value of masked hypertension (MH) as a predictor of new-onset left ventricular hypertrophy (LVH). The present analysis included 803 participants without LVH at baseline (left ventricular mass index 2 in men and 2 in women). Based on office and 24-hour mean ABP values, subjects were divided into 3 groups: normal subjects (normotensive, office blood pressure [BP] P =0.0250) after adjustment for potential confounders. This was also the case for the absolute increase of left ventricular mass index. Our study provides a new piece of evidence that MH, identified by office and ABP values, is associated with an increased risk of new-onset LVH. Moreover, our findings convey the notion that office BP may inaccurately estimate the risk of incident LVH in the general population.

AIM: Although abnormalities in reflex sympathetic neural function represent a hallmark of heart failure, no information is available on the neuroadrenergic and baroreflex function in heart failure with preserved, midrange and reduced ejection fraction. The current study was designed to assess muscle sympathetic nerve traffic (MSNA) and baroreflex function in the clinical classes of heart failure defined by the new European Society of Cardiology/American College of Cardiology Foundation/American Heart Association guidelines. METHODS: In 32 treated heart failure patients aged 69.3 ± 1.1 (mean ± SEM) classified according to new heart failure guidelines, we measured MSNA (microneurography), spontaneous baroreflex sensitivity and venous plasma norepinephrine (HPLC). Fourteen age-matched healthy individuals represented the control group. RESULTS: MSNA was progressively and significantly increased from controls to heart failure conditions characterized by preserved, midrange and reduced ejection fraction (40.4 ± 2.5, 55.6 ± 2.1, 70.4 ± 3 and 78.6 ± 2.6 bursts/100 heart beats, P

Background: Although several data suggest that serum uric acid (SUA) predicts future development of metabolic abnormalities, the evidence is not conclusive in Mediterranean populations. Methods: A total of 3200 individuals were randomly selected from the residents of Monza (North Italy) to be representative of its general population for sex and age (25-74 years). The participation rate was 64%. At baseline and 10 years later, we measured waist circumference, office blood pressure, fasting blood glucose, serum triglycerides, serum HDL cholesterol and SUA. Results: The analysis was carried out in individuals without metabolic syndrome at baseline (N=1192) when looking for incidence of metabolic syndrome, without impaired fasting glucose (IFG) at baseline (N=1320) when looking for incidence of IFG and without diabetes mellitus at baseline (N=1352) when looking for incidence of diabetes mellitus. Adjusting for confounders, a 1-SD increase of baseline SUA was not associated with and increased risk of new-onset metabolic syndrome, but with new-onset IFG [relative risk (RR)=1.26, confidence interval (CI) 1.06-1.5, P=0.01]. It was associated with a 29% increased risk of new-onset diabetes mellitus, that was more than twice in the highest as compared with the lowest quartile of baseline SUA (RR=1.29, CI 0.98-1.7, P=0.07, and RR=2.16, CI 0.95-4.88, P=0.07). Focusing the analysis on the individuals with age above the median value, SUA increase was significantly associated with an increased risk of new-onset metabolic syndrome, IFG and diabetes mellitus. Conclusion: SUA increase is associated with an increased risk of developing IFG and, in the population fraction with age above the median value, also metabolic syndrome and diabetes mellitus

Objective: Adrenergic activation and baroreflex dysfunction are common in established essential hypertension, elderly hypertension, masked and white-coat hypertension, resistant hypertension, and obesity-related hypertension. Whether this autonomic behavior is peculiar to established hypertension or is also detectable in the earlier clinical phases of the disease, that is, the high-normal blood pressure (BP) state, is still largely undefined, however. Methods: In 24 individuals with optimal BP (age: 37.1 ± 2.1 years, mean ± SEM) and in 27 with normal BP and 38 with high-normal BP, age matched with optimal BP, we measured clinic, 24-h and beat-to-beat BP, heart rate (HR), and muscle sympathetic nerve activity (MSNA) at rest and during baroreceptor stimulation and deactivation. Measurements also included anthropometric as well as echocardiographic and homeostasis model assessment (HOMA) index. Results: For similar anthropometric values, clinic, 24-h ambulatory, and beat-to-beat BPs were significantly greater in normal BP than in optimal BP. This was the case when the high-normal BP group was compared to the normal and optimal BP groups. MSNA (but not HR) was also significantly greater in high-normal BP than in normal BP and optimal BP (51.3 ± 2.0 vs. 40.3 ± 2.3 and 41.1 ± 2.6 bursts per 100 heartbeats, respectively, P < 0.01). The sympathetic activation seen in high-normal BP was coupled with an impairment of baroreflex HR control (but not MSNA) and with a significant increase in HOMA Index, which showed a significant direct relationship with MSNA. Conclusion: Thus, independently of which BP the diagnosis is based, high-normal BP is a condition characterized by a sympathetic activation. This neurogenic alteration, which is likely to be triggered by metabolic rather than reflex alterations, might be involved, together with other factors, in the progression of the condition to established hypertension.

Background: Neurogenic abnormalities characterize overt diabetic state. However, how early is their appearance in the clinical course of the disease is unclear. Methods: In 26 normotensive and normoweight prediabetic patients, aged 45.2 ± 3.2 years (mean ± SEM), we assessed efferent postganglionic muscle sympathetic nerve traffic (MSNA, microneurography), spontaneous baroreflex sensitivity, and a number of hemodynamic and metabolic variables, including homeostatic model assessment (HOMA) index. Measurements were compared with those obtained in a group of 30 healthy controls of similar age. Results: For similar clinic and ambulatory blood pressure and BMI values, prediabetic patients displayed significantly greater MSNA values than controls, both when expressed as bursts incidence over time (33.3 ± 2.0 vs. 25.6 ± 1.2 bursts/min, P < 0.01) and when corrected for heart rate values (49.6 ± 1.9 vs. 36.7 ± 1.4 bursts/100 heart beats, P < 0.01). This neurogenic abnormality was associated with a reduced spontaneous baroreflex MSNA sensitivity (-3.20 ± 0.2 vs. -4.72 ± 0.2 a.u., P < 0.01) and significantly greater HOMA index values (3.73 ± 0.1 vs. 1.65 ± 0.1 a.u., P < 0.01). In the multivariate analysis, performed in prediabetic patients, MSNA values were directly and significantly related to HOMA index and inversely and significantly to baroreflex-MSNA sensitivity. Conclusion: These data provide evidence that sympathetic and reflex abnormalities are of early appearance in the clinical course of the diabetic disease. The adrenergic overdrive and the baroreflex impairment may thus participate at the disease progression, favoring the development of the hypertensive state and adversely affecting the disease prognosis

Muscle sympathetic nerve activity (MSNA) has shown that sympathetic activation may occur in essential hypertension (EHT). However, the small sample size of the studies, the heterogeneity of the patients examined, and the presence of confounders represented major weaknesses not allowing to draw definite conclusions. Among the 432 studies identified providing information in EHT on MSNA, 63 were eligible (1216 patients) and meta-analyzed grouping them on the basis of clinically relevant questions: (1) Is MSNA increased in hypertension of mild/moderate-to-severe degree? (2) Does sympathetic activation occur in borderline, white-coat, and masked EHT? (3) Is MSNA related to clinic and ambulatory blood pressure and target organ damage? (4) Are heart rate and venous plasma norepinephrine valuable surrogate markers of MSNA in clinical practice? The results show that MSNA was significantly greater (1.5×; P P r =0.67 and r =0.83; P r =−0.38; P r =0.28; P r =0.27; P

Vascular inflammation plays an important role in the pathophysiology of hypertension and high levels of endocan may reflect ongoing vascular inflammation in hypertensive patients. In the present hypothesis-generating study, we aimed at investigating the comparative effects of amlodipine and valsartan on endocan levels in newly diagnosed hypertensive patients. The study population consisted of 37 untreated hypertensive patients who were randomized to the two treatment arms. After baseline assessment, each patient was randomly allocated to either 10 mg daily of amlodipine (n = 18, 7 males) or 160 mg daily of valsartan (n = 19, 3 males) and treated for a 3-month period. Sphygmomanometric blood pressure (BP) and serum endocan were measured before and every 2 weeks during drug treatment. There was no statistically significant difference between the two treatment arms as far as baseline socio-demographic and clinical characteristics are concerned. After a 3-month treatment period, systolic and diastolic BP values significantly reduced by antihypertensive treatment (p < 0.001). Furthermore, endocan levels were significantly decreased in both treatment arms (p < 0.05). However, amlodipine caused a greater percent decrease in circulating endocan levels compared with valsartan at the end of the treatment period. Both drugs reduced high sensitivity C-reactive protein values. However, the statistical significant difference vs baseline was achieved only in the group treated with amlodipine. No correlation was found between endocan plasma levels and BP reduction. The results of this hypothesis-generating study suggest that amlodipine and valsartan decrease endocan levels in newly diagnosed hypertensive patients. The effects, which are more evident with amlodipine, may contribute to the anti-inflammatory effects exerted by the two drugs on the vascular target.

OBJECTIVE: Previous studies have shown that blood pressure assessment by a nurse markedly attenuates the pressor and tachicardic responses triggered by the physician blood pressure measurement. Whether and to what extent this attenuation reflects a different pattern of the neuroadrenergic responses to doctor or nurse blood pressure evaluation is unknown. METHODS: In 19 lean untreated mild essential hypertensive patients (age 39.1 ± 2.4 years, mean ± SEM), we measured beat-to-beat mean arterial pressure (Finapres), heart rate (ECG), and efferent postganglionic muscle and skin sympathetic nerve traffic [muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve activity (SSNA), respectively, by microneurography], before, during, and following a 10-min sphygmomanometric BP measurement by a doctor or by a nurse unfamiliar to the patients. Measurements were repeated at a 30-min interval to obtain, in separate periods, muscle and skin sympathetic nerve traffic recordings. Both the sequences (doctor vs. nurse and muscle vs. skin sympathetic nerve traffic) were randomized. RESULTS: A doctor visit induced sudden, marked, and prolonged blood pressure and heart rate increases, accompanied by a muscle sympathetic nerve traffic inhibition (average response: -18.1 ± 4.3%, P

Introduction: Although improved during the past few years, blood pressure control remains sub optimal. Aim: The impact of follow-up assessment on blood pressure control was evaluated in a group of patients of the HYT (HYperTension survey), treated with a combination of different dihydropyridine calcium-channel blockers (CCBs regimen) and inhibitors of renin-angiotensin-aldosterone system (RAAS) and with uncontrolled blood pressure. This was obtained assessing (a) the rate of blood pressure control at 3 and 6 months of follow-up in the whole group of patients, (b) the rate of blood pressure control and the average blood pressure values in subjects treated with different DHP-CCBs regimen. Methods: From the 4993 patients with uncontrolled blood pressure, (BP ? 140/90 or ?140/85 in patients with diabetes), 3729 (mean age 61.2 ± 11.5 years), maintained CCBs regimen combined wih RAAS blockers and were evaluated at 3 and 6 months follow-up. At each visit BP (semiautomatic device, Omron-M6, 3 measurements), heart rate, adverse events and treatment persistence were collected. Results: At 1st and 2nd follow-up the rate of controlled BP was 63.5 and 72.8% respectively (p < 0.05 vs 35.3% at baseline), whereas in diabetes was 32.5 and 37.9% respectively (p < 0.05 vs 20% at baseline). No differences in heart rate were observed. No differences in control rate were observed between the different CCBs regimen. The incidence of drugs related adverse events was 3.6%. Conclusions: These findings provide evidence that: (a) the follow-up of hypertensive patients under therapy increase the rate of blood pressure control; (b) there is no significant difference in the antihypertensive effect between different CCBs regimen; (c) lipophilic CCBs induce less ankle edema. © 2017, Springer International Publishing Switzerland.

Purpose of Review: Detection of elevated blood pressure values in elderly patients represents a common clinical condition associated with an increased cardiovascular risk. This has been shown to be the case in both systodiastolic and isolated systolic hypertension as well. However, despite the evidence of the benefits of the blood pressure lowering intervention in terms of reduction of cardiovascular morbidity and mortality, at least two issues related to antihypertensive drug treatment in aged individuals are still undefined: (1) the blood pressure threshold at which antihypertensive drug should be initiated and (2) the blood pressure goals of the therapeutic intervention. Recent Findings: The present paper will critically review the evidence available so far on these two issues as well as the position of current guidelines and consensus statements. Emphasis will be given to the analysis of the new data of the Systolic Blood Pressure Interventional Trial (SPRINT), which have recently demonstrated the benefits, even in individuals aged more than 75years, of a tight blood pressure reduction to systolic blood pressure to 120mmHg or less. The potential limitations of the trial will be also critically addressed and the expectations of ongoing clinical studies investigating the issue in elderly patients properly emphasized. Summary: Although of interest, the results of the SPRINT trial encompass a number of limitations which limit their applicability to the general elderly hypertensive population. A prudent approach will be to adopt in clinical practice the less intensive and more conservative targets recommended by current guidelines.

Objectives: We compared definitions of metabolic syndrome performed by ATPIII [the National Cholesterol Education Program Adult Treatment Panel III; three criteria of the following: systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg, fasting serum glucose ≥110 mg/dl, high-density lipoprotein plasma cholesterol ≤40 mg/dl (men) or ≤50 mg/dl (women), plasma triglycerides ≥150 mg/dl, waist circumference ≥102 cm (men) or 88 cm (women)], AHA (the American Heart Association; same cut-off of ATPIII except serum glucose ≥ 100 mg/dl) and IDF [the International Diabetes Federation; mandatory criteria of visceral obesity with reduced cut-off of 94 cm (men) or 80 cm (women), and at least two criteria with the same cut-off as in AHA] for their impact on metabolic syndrome prevalence, cardiac organ damage, long-term risk of cardiovascular events and death for any cause and risk of developing diabetes mellitus, in-office and out-of-office hypertension and left ventricular hypertrophy (LVH). Methods: In 2051 participants, we measured office, home and ambulatory blood pressure as well as metabolic, anthropometric and echocardiographic variables. Measurements were performed between 1990 and 1992 and repeated 10 years later. Information on long-term incidence of cardiovascular events and all-cause deaths was also collected. Results: Prevalence of metabolic syndrome was significantly greater when using the AHA and IDF as compared to the ATPIII definition. Prevalence of LVH was higher in participants with than without metabolic syndrome and similar for the three definitions. Over 12-year follow-up, there were 179 cardiovascular events and 233 deaths for any cause. The risk of cardiovascular events and death was markedly greater for participants with as compared with those without metabolic syndrome, regardless of the definition of metabolic syndrome. This was the case also for the risk of new-onset diabetes mellitus, office, home and ambulatory hypertension and new-onset LVH. Conclusion: Risks of fatal and nonfatal cardiovascular events, diabetes mellitus, hypertension and LVH were similar for the three definitions of metabolic syndrome. However, the AHA and IDF definitions are more sensitive than that of ATPIII in identifying metabolic syndrome condition. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Blood pressure changes occurring over a 24-h period are under behavioral, humoral and reflex regulation. The sympathetic nervous system modulates blood pressure variation by affecting cardiac output and peripheral vascular resistance. This paper reviews evidence for the relationship between adrenergic neural drive and blood pressure as measured by direct and indirect approaches. This paper also reviews the sympathetic activity associated with increased in-office and out-of-office blood pressure, that is, the white-coat and the masked-hypertensive states. Finally, this paper examines altered neuroadrenergic influences on nocturnal blood pressure reduction and blood pressure variability. © 2010 The Japanese Society of Hypertension All rights reserved.

Objective - Screening and educational campaigns on cardiovascular (CV) risk factors are important for primary and secondary prevention of CV disease.The CardioLab project is an observational cross-sectional study aimed at determining the prevalence of CV risk factors in a large unselected sample of the Italian population leaving in northern, central and southern Italy. Methods and results - Data collection included family and clinical history, anthropometric data, blood pressure, blood glucose and total cholesterol values. Individual CV risk profile was assessed throughout by the risk charts of both the Progetto Cuore and the Score Project. In 36,161 participants (56.3% men) with a mean age of 60 years a complete assessment of the above mentioned variables was obtained. 44.4% of the screened subjects was overweight, while approximately 20% of the population displayed an obese state with a body mass index > 30 kg/m 2 . Alterations in blood glucose levels indicating the presence of glucose intolerance were identified in 11.5% of the population while 9.3% displayed overt diabetes. 36. 1% and 42.3% had elevated total cholesterol levels ( > 200 mg/dl) and blood pressure values (≥140/90 mmHg), respectively. New diagnosis of diabetes, hypercholesterolaemia and hypertension was obtained in 5.3%, 23.6% and 19.6%, respectively. Global assessment of the CV risk showed that approximately 12.6% of the population is at a high risk of CV events over a 10-year period. Gonclusions - This large-scale observational study provides important information on the CV risk profile of an unselected Italian population and underlines the need for a more aggressive identification and appropriate correction of CV risk factors.

White coat hypertension, which should be more descriptively termed “isolated clinic hypertension” (1), consists of a condition in which clinic (or office) blood pressure is repeatedly ≥140 mmHg systolic or 90 mmHg diastolic, whereas 24-h mean blood pressure is below its generally accepted upper limit of normality, i.e.

The present study was designed to determine whether and to what extent the activation of the sympathetic nervous system reported in the metabolic syndrome is generalized to the whole cardiovascular system or if it is rather confined to selected vascular districts. In 16 untreated patients with metabolic syndrome, 12 essential hypertensive subjects, 12 obese subjects, and 14 lean healthy normotensive controls, we measured blood pressure (Finapres, Englewood, CO), heart rate (electrocardiogram), venous plasma norepinephrine (high-performance liquid chromatography), and postganglionic sympathetic nerve traffic in the skeletal muscle and in the skin districts (microneurography). The muscle and skin nerve traffic measurements were obtained in a randomized sequence. Measurements also included skin sympathetic nerve responses to an arousal (acoustic stimulus). The 4 groups of subjects had superimposable ages. Muscle sympathetic nerve traffic values were significantly higher in subjects with hypertension and in those with obesity than in controls (51.2 ± 2.8 and 52.0 ± 3.0 vs 37.2 ± 3.3 bursts per 100 heart beats, respectively; P < .01 for all). A further significant increase in muscle sympathetic nerve traffic was detected in subjects with the metabolic syndrome (61.0 ± 3.2 bursts per 100 heart beats, P < .05). In contrast, skin sympathetic nerve traffic was not significantly different in the 4 groups of individuals (13.0 ± 0.7, 14.3 ± 1.3, 12.5 ± 0.8 vs 15.4 ± 1.0 bursts per minute, respectively; P = not significant). The skin sympathetic responses to an acoustic stimulus were also similar in the different groups. The present data provide the first direct evidence that in the metabolic syndrome the sympathetic activation is not uniformly distributed over the cardiovascular system. This may depend on the fact that muscle and skin sympathetic nerve activities are regulated by mechanisms that are affected in a different fashion by the various components of the disease. © 2009 Elsevier Inc. All rights reserved.

It is debated whether white-coat (WCHT) and masked hypertension (MHT) are at greater risk of developing a sustained hypertensive state (SHT). In 1412 subjects of the Pressioni Arteriose Monitorate e Loro Associazioni Study, we measured office blood pressure (BP), 24-hour ambulatory BP, and home BP. The condition of WCHT was identified as office BP >140/90 mm Hg and 24-hour BP mean P

OBJECTIVE: A sustained blood pressure elevation is associated with an increased risk of new-onset diabetes mellitus. Whether this is the case also in white-coat and masked hypertension is unknown. METHODS: In 1412 individuals of the Pressioni Arteriose Monitorate E Loro Associazioni study stratified for sex and age decades, we measured office, home and 24-h ambulatory blood pressure together with fasting plasma glucose and other metabolic variables. This allowed to identify patients with white-coat, masked, sustained hypertension and true normotension. RESULTS: Over a 10-year period, the increase in plasma glucose and the incidence of new-onset diabetes (plasma glucose ≤126 mg/dl or use of antidiabetic drugs) was significantly greater in individuals with white-coat and masked hypertension than in those with 'true' normotension (age and sex-adjusted risk 2.9 and 2.7, respectively), the increase being similar to that of sustained hypertensive individuals. The adjusted risk showed a marked increase when development of an impaired fasting glucose condition was also considered, and the results were similar when individuals reporting antihypertensive drug treatment were excluded or white-coat and masked hypertension were identified by office versus home blood pressure. The increased risk of new-onset diabetes become no more significant when data were adjusted for initial blood glucose and BMI, which, at a multivariate analysis, were the most significant predictors of this condition, with only a small although significant contribution of the initial blood pressure. CONCLUSION: Thus, white-coat and masked hypertension are associated with a long-term greater progression of blood glucose abnormalities and an increased risk of developing diabetes. This is largely accounted for by the metabolic abnormalities that are frequent components of these conditions. © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.

OBJECTIVES: Metabolic syndrome is accompanied by an increased risk of developing diabetes mellitus. Limited or no evidence exists on whether and to what extent metabolic syndrome increases the risk of developing office hypertension, daily-life hypertension and left ventricular hypertrophy. METHODS: In 1412 individuals representative of the population of Monza, plasma glucose, office, home and ambulatory blood pressure, and echocardiographic left ventricular mass index were measured between 1990 and 1992 and 10 years later. New onset diabetes mellitus, new onset office, home and ambulatory hypertension as well as new onset left ventricular hypertrophy were assessed in individuals with and without metabolic syndrome (Adult Treatment Panel criteria) at the first examination. RESULTS: New onset diabetes mellitus, hypertension and left ventricular hypertrophy were all much more frequent in individuals with metabolic syndrome than in those without. In patients with metabolic syndrome, the adjusted risk of new onset diabetes mellitus was five to six times greater (P < 0.001), that of new onset office, home or ambulatory hypertension 3.5, 2.9 and 3.2 times greater (P < 0.001), respectively, and that of new onset left ventricular hypertrophy 2.6 times greater (P < 0.001). The most important predictors of new onset diabetes mellitus, hypertension and left ventricular hypertrophy were the baseline blood glucose, blood pressure and left ventricular mass index, respectively, with an independent contribution, in each condition, from other metabolic syndrome components. The metabolic syndrome as such did not have an additional predictive value. CONCLUSION: In the general population, metabolic syndrome is associated with a marked increase in the risk not only of new onset diabetes mellitus but also of new onset office and daily-life hypertension, and left ventricular hypertrophy. This may account for the increased rate of cardiovascular morbidity and mortality exhibited with this condition in long-term studies. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.

High blood pressure represents one of the leading risk factors for the development of stroke and its recurrence. This explains why blood pressure control is a major objective of antihypertensive treatment, both in primary and secondary prevention of this cerebrovascular disease. This paper reviews the evidence provided by randomized clinical trials on the favorable effects exerted by blood pressure reduction on this end point. Emphasis is given to the results of recently published clinical trials documenting that drugs acting on the renin-angiotensin system may exert cerebrovascular protective effects additive to the ones associated with blood pressure reduction.

The PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study represents a major research project aimed at investigating the normality values, prognostic significance and relationships of ambulatory and home blood pressure with end-organ damage and metabolic alterations. This article reviews the background, rationale and main results of the various PAMELA studies published to date. These include studies focused on (i) the normal values of ambulatory and home blood pressure in different age decades; (ii) the relevance of the different blood pressures in predicting the occurrence of end-organ damage; (iii) the prognostic significance of 'white-coat' and 'masked' hypertension; (iv) the 'power' of different blood pressures in predicting cardiovascular and all-cause death; and (v) the main features of the blood pressure control in the population. Altogether, the findings reported in this review emphasise the clinical relevance of ambulatory and home blood pressure and the importance of obtaining information on different blood pressures both in treated and untreated hypertensive patients. © 2007 Adis Data Information BV. All rights reserved

Introduction: Although improved during the past few years, high blood pressure control still remains an unmet goal of antihypertensive drug treatment. Among different antihypertensive agents, calcium channel blockers (CCBs), either as monotherapy or in combination with other drugs are recommended by several guidelines for initiation and maintenance of antihypertensive treatment. Aim: The HYT-HYperTension survey, carried out in Turkey was aimed to assess (a) blood pressure control in hypertensive patients under treatment with dihydropyridine CCBs, either as monotherapy or in combination with other drugs and (b) the prevalence of blood pressure control in subgroups of patients with cardiovascular risk factors (previous cardiovascular disease, diabetes, renal disease, isolated systolic hypertension, visceral obesity, overweight, current smoking habit). Methods: More than 7000 hypertensive patients (60.0 % men, mean age 61.2 ± 11.5 years), routinely visited by either a specialist or a non-specialist physician in the Primary Care Units of 26 cities across Turkey, were enrolled in the survey. Only patients treated with dihydropyridine-type CCBs, as mono- or combination therapy were included in the study, whereas individuals treated with non-dihydropyridine-type CCBs or with other drug classes (as monotherapy or combination therapy), were excluded. Demographic data (age, gender, height, weight, waist circumference, current smoker habit), clinical data and drug treatments were collected at each visit. Blood pressure was measured with a semiautomatic device (Omron-M6) with the patient in sitting position and after at least 5 min of rest. Measurements were repeated three times, at intervals of 5 min each other. Results: In the overall survey population blood pressure control (blood pressure

Aims/hypothesis: Previous studies have shown that alterations in vascular, metabolic, inflammatory and haemocoagulative functions characterise the metabolic syndrome. Whether this is also the case for sympathetic function is not clear. We therefore aimed to clarify this issue and to determine whether metabolic or reflex mechanisms might be responsible for the possible adrenergic dysfunction. Methods: In 43 healthy control subjects ( age 48.2 +/- 1.0 years, mean +/- SEM) and in 48 untreated age-matched subjects with metabolic syndrome ( National Cholesterol Education Program's Adult Treatment Panel III Report criteria) we measured, along with anthropometric and metabolic variables, blood pressure ( Finapres), heart rate ( ECG) and efferent postganglionic muscle sympathetic nerve activity ( microneurography) at rest and during baroreceptor manipulation ( vasoactive drug infusion technique). Results: Compared with control subjects, subjects with metabolic syndrome had higher BMI, waist circumference, blood pressure, cholesterol, triglycerides, insulin and homeostasis model assessment ( HOMA) index values but lower HDL cholesterol values. Sympathetic nerve traffic was significantly greater in subjects with metabolic syndrome than in control subjects ( 61.1 +/- 2.6 vs 43.8 +/- 2.8 bursts/100 heartbeats, p < 0.01), the presence of sympathetic activation also being detectable when the metabolic syndrome did not include hypertension as a component. Muscle sympathetic nerve traffic correlated directly and significantly with waist circumference ( r=0.46, p < 0.001) and HOMA index ( r=0.49, p < 0.001) and was inversely related to baroreflex sensitivity ( r=-0.44, p < 0.001), which was impaired in the metabolic syndrome. Conclusions/interpretation: These data provide evidence that the metabolic syndrome is characterised by sympathetic activation and that this abnormality ( 1) is also detectable when blood pressure is normal and ( 2) depends on insulin resistance as well as on reflex alterations.