OBJECTIVE:The microneurographic technique has shown that sympathetic overactivity may characterize individuals with metabolic syndrome (MS). However, technical and methodological limitations of the ...published studies (small sample size, presence of comorbidities including sleep apnea, presence of multiple drug treatment) did not allow to draw definite conclusions. The present meta-analysis evaluated 10 microneurographic studies for a total of 432 MS patients and healthy controls. The analysis was primarily based on mucle sympathetic nerve traffic (MSNA) quantification in MS, excluding as concomitant conditions diabetes, sleep apnea, other comorbidities or drug treatment.
DESIGN AND METHODS:Assessment was extended to the relationships of MSNA with other neuroadrenergic markers, such as venous plasma norepinephrine and heart rate (NE and HR, respectively), anthropometric variables, as body mass index (BMI), waist-hip ratio (WHR), and metabolic profile.
RESULTS:Compared to controls MS individuals showed significantly greater MSNA values (40.5 ± 4.2 vs 53.8 ± 3.6 bursts/100 heart beats, P < 0.01). MSNA was directly and significantly related to clinic systolic blood pressure (r = 0.99, P < 0.01) but not to BMI and WHR (r = −0.05 and r = 0.41, P = NS for both). No significant relationship was also found between MSNA and metabolic variables included in the definition of MS, such as plasma glucose levels, plasma insulin, HOMA index, plasma triglycerides and plasma cholesterol (r = 0.44, r = −0.07, r = 0.19, r = 0.01 and r = 0.32, respectively, P = NS for all). No significant correlation was also detected between MSNA and HR and NE.
DESIGN AND METHOD:These data provide evidence that MS is characterized by a marked increase (about 25%) in MSNA. They also show that among the variables included in MS definition and related to the sympathetic overdrive blood pressure appears to be the most important one, at variance from what it has been described in obesity in which metabolic and anthropometric factors play a major role. Finally in MS neither HR nor NE appear to represent faithful mirrors of the occurring sympathetic activation.
OBJECTIVE:Pulse pressure (PP), is a simple measure of arterial stiffness. Several studies have shown that PP increases the risk of cardiovascular (CV) events but they were limited to clinic measure, ...mostly performed on individuals with high CV risk. Furthermore few studies reported PP-related risk of morbidity and mortality separately for genders.
DESIGN AND METHOD:3200 subjects, stratified for sex and decades of ages, were randomly selected to be representative of the general population of Monza (Northern Italy). In each subject we performed the following mesurements1) Clinic (C) Systolic (S) Blood Pressure (BP) and Diastolic (D) BP (sphygmomanometer), 2) Home SBP and DBP (Philips HP 5331), 3) Ambulatory (24 h) SBP and DBP (Spacelabs 90207), 4) Body Mass Index (BMI), 5) Blood Glucose and Serum Cholesterol. Each subject was followed for 12 years, during which all deaths were collected and classified by ICD-X codes as being a CV (ICD-X I-0 to I-99) or non CV death. Non-fatal CV events were identified by hospital diagnosis also using ICD-X codes and validated on the hospital clinical records.
RESULTS:The complete data set was obtained in 2045 subjects. PP was calculated as difference between SBP and DBP. Office, home and 24 h blood pressures were significantly higher in individuals who experienced a CV event or died during follow-up. Clinic, 24 h and Daytime PP were independent predictors of CV events after adjustment for main demographic and clinical parameters in the whole study population (HR 1.24, CI 1.03–1.49; HR 1.17, CI 1.01–1.36; HR 1.2, CI 1.03–1.39, respectively; p < 0.05 for all). Nighttime PP was an additional independent predictor in men (HR 1.23, CI 1.03–1.47, p < 0.05). None of measured PP (Clinic, Home, 24 h, Day- and Nighttime) was predictor of CV events in women. None of calculated PP was predictor of all-cause mortality in general population and in both genders.
CONCLUSIONS:Clinic and 24 h, but not home, PP represent a predictor of CV events in general population and in its male fraction. In females PP does not increase risk of CV events. All-cause death is not predicted by any of the PP measured.
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.
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).
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.
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.
OBJECTIVE:CAVI has been defined as a blood pressure (BP) independent index of arterial stiffness, when considering clinic BP values. Arterial stiffness measured with CAVI has also been shown to be a ...comprehensive indicator of arteriosclerosis, and it would thus be important to explore its relation with daily life BP patterns. Aim of our study was to assess this aspect in a group of treated essential hypertensive patients.
DESIGN AND METHOD:368 caucasian hypertensive patients aged 17–81, consecutively referred to our outpatients Hypertension Center, underwent a thorough clinical evaluation, 24 h ABPM (AND 2430) and CAVI assessment (VaSera Fukuda Denshi). The relation of CAVI with office BP and with 24 h, day and night ABP mean values and variability was investigated.
RESULTS:No relation was found between CAVI and all office BP parameters (p NS).Conversely CAVI in univariate analysis showed a significant relation with ambulatory PP (day R = 0,23 p < 0,01-night R = 0,23 p < 0,01- 24 h R = 0,22 p < 0,01) but not with the corresponding ambulatory DBP; a weak correlation was found between CAVI and ambulatory SBP (p < 0.05). The relation between CAVI and ambulatory PP lost significance (p = NS) after accounting for age, the strongest predictor of CAVI (r = 0,59; p < 0,0001). We also observed a relation between CAVI and daytime or 24 h heart rate (HR) (respectively R = 0.23 and R = 0.22; p < 0.01). These relationships remained significant even after accounting for age although not after correction for beta blocker therapy. Concerning short term BP variability we observed only a weak relation of CAVI with 24 h weighted systolic BP standard deviation (R = 0.12; p < 0.05) which lost significance after correction for age.
CONCLUSIONS:These data confirm the independence of CAVI from BP values obtained at the time of measurement and offer new information on its association with ABP parameters, suggesting its independence also from the daily blood pressure profile.This support the suggestion that CAVI could have a role in the evaluation of cardiovascular risk independently, at variance from other arterial stiffness indices, from BP levels.
OBJECTIVE:Neurogenic mechanims have been shown to regulate not only absolute blood pressure levels but also blood pressure variability during the short-term 24 hour period. No information are ...available on whether visit-to-visit blood pressure variability is related to sympathetic and baroreflex function.
DESIGN AND METHOD:61 untreated essential hypertensive patients aged 56.1 ± 2.5 years (mean ± SEM) underwent 3 clinic BP measurements on 3 occasions during a 6 weeks period. In each patient we assessed muscle sympathetic nerve traffic (MSNA, microneurography), spontaneous MSNA-baroreflex sensitivity according to Kienbaum method, and blood pressure variability of systolic and diastolic BP, quantified as coefficient of variation (CV) and as standard deviation (SD) of the BP values.
RESULTS:Patients were subdivided into CV and SD quartiles. Quartiles were matched for age and gender. For each quartile a relationship was sought with MSNA and baroreflex sensitivity. Compared with the patients in the lowest systolic BP CV quartile, patients in the highest quartile showed significantly greater MSNA (62.5 ± 4 vs 48.2 ± 3 bursts/100 heart beats, P < 0.02) and significantly lower baroreflex sensitivity values (1.23 ± 0.2 vs 2.09 ± 0.2 a.u., P < 0.03). This was the case also when BP variability was expressed as SD. When diastolic BP data were analyzed no significant difference between quartiles was found.
CONCLUSIONS:These data provide the first demonstration that in hypertension a greater visit-to-visit blood pressure variability is associated with greater levels of sympathetic activation and more pronounced baroreflex dysfunction. The relationship appears to be valid particularly for the systolic BP component. Thus sympathetic and reflex mechanisms contribute not only to the short-term but also to the long-term BP variability phenomenon.
OBJECTIVE:A recent hypothesis claims that iron metabolism directly or indirectly, i.e. throughout metabolic (insulin resistance) or inflammatory/autoimmune mechanisms, may be linked to the ...sympathetic nervous system. In the present study we tested this hypothesis by recording central sympathetic neural outflow in hypertensive patients characterized by normal or elevated circulating plasma levels of ferritin (FE), i.e. a marker of iron load.
DESIGN AND METHOD:In 8 untreated male essential hypertensives with elevated plasma FE (HTFE+, age 46.9 ± 2.6 yrs, mean ± SEM), we measured, along with Fe levels and transferrin saturation, body mass index clinic blood pressure (BP), heart rate (HR, EKG), muscle sympathetic nerve traffic (MSNA, microneurography), HOMA index, glucose, tryglicerides and cholesterol levels. Data were compared to those from 7 untreated male essential hypertensive patients with normal FE levels (HTFE-) age matched with HTFE+.
RESULTS:For similar BP, HR and BMI values, HTFE+ displayed FE values significantly greater than those seen in HTFE- (444.3 ± 101 vs 135.4 ± 98 μg/l, p < 0.05). This was the case also for transferrin saturation (38.9 ± 24 vs 24.2 ± 9.9 %). IN HTFE+ the increased iron load was accompanied by slightly, although not significantly, greater glucose, cholesterol and triglyceride plasma levels. More importantly, HOMA index values were significantly greater in HTFE+ than HTFE- (2.1 ± 0.4 vs 1.2 ± 0.2 au, P < 0.05). This was accompanied by significantly greater values of MSNA, both when expressed as bursts frequency over time (48.5 ± 4.3 vs 39.7 ± 3.5, <0.05) and when corrected for HR (66.4 ± 5.0 vs 50.9 ± 4.4, P < 0.05). In the group as a whole there was a significant relationship between MSNA and FE (r = 0.64,P < 0.01) whose level of significance was greater than the one related to the relationship MSNA and HOMA index (r = 0.53,P < 0.05). HOMA index and FE were also significantly and directly related each other (r = 0.56, P < 0.05).
CONCLUSIONS:These data provide the first evidence that in hypertensive males iron overload exerts marked sympathoexcitatory effects associated with a decrease in insulin sensitivity. It is likely that the iron overload directly or throughout the concomitant hyperinsulinemia may be responsible for this neuroadrenergic response.
OBJECTIVE:Stratification of cardiovascular (CV) risk is of fundamental importance in white coat hypertension (WCH) to identify individuals in need of closer follow up and perhaps antihypertensive ...drug treatment.
DESIGN AND METHOD:In subjects representative of the general population of Monza (Italy), the risk of CV and all-cause mortality was assessed over 16 years in stable and unstable WCH individuals, i.e, those in whom ambulatory BP normality was associated with a persistent or non persistent office BP elevation at two consecutive visits, respectively. Data were compared with those from an entire normotensive group, i.e ambulatory and persistent office BP normality.
RESULTS:Compared to the normotensive group, the risk of CV and all cause death was not significantly different in unstable WCH, whereas in stable WCH the risk was increased also when data were adjusted for baseline confounders, including ambulatory BP(hazard ratio 12.39 p = 0.0021 for CV, and 1.91 p = 0.0178 for all cause death). At a multivariable analysis, office BP was among the factors indipendently predicting death, and results were superimposable with use of Monza population-and guidelines-derived cutoff values for ambulatory BP normality (125/79 and 130/80 mmHg, respectively).
CONCLUSIONS:Thus, only when office BP is persistently elevated does WCH reflect the existence of an abnormal long term mortality risk. This means that in WCH office BP is prognostically relevant and that repeated collection of office BP values should be regarded as necessary.
OBJECTIVE:It is well known that congestive heart failure (CHF) is characterized by an increased adrenergic tone and by an impaired baroreflex sympathetic and vagal control. In recent years have been ...developed additional therapeutic options, baroreflex activation therapy (BAT), capable to antagonize the sympathetic overactivity. It has been reported in CHF patients a significant reduction in muscle sympathetic nerve activity (MSNA) after 6 months BAT. Whether the effects on sympathetic and clinical variables were maintained chronically is unknown.
DESIGN AND METHOD:Eleven CHF patients (NYHA class III, left ventricular ejection fraction < 40%, with optimized and stable medical therapy and no active resinchronization therapy) have been evaluated at baseline and after 6 and 24 months BAT follow-up. During each step we collected clinical parameters, HYHA class, six-minute hall walk distance (6MHW), quality of life from the Minnesota Living with Heart Failure Questionnaire score (QOL), LVEF (3D echo), B-type natriuretic peptide (BNP), estimated glomerular filtration rate (eGFR), MSNA by microneurography, and baro reflex sensitivity (variated Kienbaumʼs method).
RESULTS:Two patients died during long-term follow-up (pneumoniae and acute HF). In the surviving 9 the beneficial effects observed at 6 months (MSNA -28%; BRS +100%; 6MWD +22.7%; LVEF +10%; QOL +37.2%) were maintained 21.5 ± 4.2 months (MSNA -31.6%,p < 0.001; BRS +100%,p < 0.001; 6MWD +19%,p = 0.01; LVEF +2.4%,p < 0.01; QOL +42.7%p < 0.01). A slight but not significant reduction was observed in blood pressure, heart rate, BNP and eGFR values. Hospitalization was not necessary after BAT.
CONCLUSIONS:BAT provides long-term reduction in sympathetic activity and improvement in baroreflex sensitivity. This is accompanied by an improvement in clinical status, quality of life and functional capacity and by a reduction in rates of hospitalization.
OBJECTIVE:Plasma concentrations of the endogenous inhibitor of nitric oxide synthase asymmetric dimethyl arginine (ADMA) are associated with sympathetic activity in patients with chronic disease. The ...driver of this association remains unknown. To solve the question it has been used the renal denervation of resistant hypertensive patients due to the marked reduction in whole-body norepinephrine spillover and sustained decrease in sympathetic nerve traffic (MSNA), thus representing an unique model to examine the hypothesis that sympathetic activity modulates circulating ADMA and its symmetric enantiomer (SDMA).
DESIGN AND METHOD:14 true resistant hypertensives (ESH/ESC guidelines definition) were evaluated at baseline and 15, 30, 90, 180 days after renal denervation. In each session blood samples were taken and then we measured beat-to-beat finger blood pressure (BP, Finapres), heart rate (HR), MSNA (microneurography). The global relationship between MSNA vs ADMA and SDMA was based on the calculation of the areas under the curves of these variables after renal denervation. Regression analyses were then performed.
RESULTS:After renal denervation we observed a reduction in MSNA of -17% (rangefrom -66% to +10%). Changes in MSNA were strongly associated with the corrisponding changes in plasma ADMA (r = 0.69, p = 0.005) and SDMA (r = 0.87, p < 0.001). Furthermore, changes in MSNA went along with simultaneous changes in systolic (r = 0.79, p = 0.001) and diastolic BP (r = 0.82, p < 0.001) and HR (r = 0.68, p < 0.01). All these relationships were largerly independent of renal dysfunction.
CONCLUSIONS:These observations are compatible with the hypothesis that the sympathetic nervous system exerts an important role in modulating circulating levels of ADMA and SDMA in this condition.
OBJECTIVE:According to the 2013 ESH/ESC guidelines combination drug treatment is recommended in the treatment of isolated systolic hypertension (ISH) to improve blood pressure (BP) control. The ...present study was aimed at comparing the antihypertensive effects, tolerability and side effects profile of nebivolol/hydrochlorothiazide vs irbesartan/hydrochlorothiazide combination in elderly patients with ISH.
DESIGN AND METHOD:124 ISH patients aged 69.1 ± 3.1 (mean ± SEM) followed by 13 general practictioners in Netherlands and Belgium were enrolled and randomized in a double blind fashion to Nebivolol 5 mg/Hydrochlorothiazide 12.5 mg (NH, n = 62) or Irbesartan 150 mg/Hydrochlorothaizide 12.5 (IH,N = 62) once daily for a 12 week period on sitting office BP, ambulatory BP, 24 hour BP variability, pulse pressure, tolerability and safety profile.
RESULTS:9 pts were withdrawn after randomization. After 12 weeks NH caused a significant greater reduction than IH in sitting SBP (-25.8 ± 1.6 vs -20.6 ± 1.7 mmHg, P < 0.03) and heart rate (HR, -7.0 ± 1.0 vs 2.5 ± 1 b/min, P < 0.01), while the decrease in diastolic and pulse BP showed a non significant tendency to be greater in NH than in IH (-7.4 ± 1.0 and -18.3 ± 1.5 vs -5.0 ± 0.09 and -15.7 ± 1.7 mmHg, P = NS for both). The magnitude of the 24-h, day-time and night-time SBP reduction was almost superimposable in the 2 groups, while HR reduction induced by NH was significantly (P < 0.001) greater during the 24-h, the daytime as well as the nighttime period than that induced by IH. NH caused a significantly greater reduction than IH in 24-h SBP variability, both when expressed as standard deviation (-4.4 ± 2.7 ± vs -2.2 ± 5.1 mmHg, P < 0.02) or as coefficient of variation (-2.0 ± 2.6 vs -0.3 ± 3.4, P < 0.01). This was the case also for pulse pressure and mean BP. Both the 2 drug combinations were well tolerated.
CONCLUSIONS:These data provide evidence that NH induces an office BP reduction greater than IN but similar effects throughout the 24 hours. NH, however, reduces, at variance from IH, 24-h systolic, mean and pulse BP variability, suggesting a greater protection against a variable known to adversely affect morbidity and mortality in hypertensive patients.
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