G Mancia

Università degli Studi di Milano-Bicocca, Milano, Lombardy, Italy

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Publications (661)2605.73 Total impact

  • G. Mancia · G. Grassi · C. Borghi ·
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    ABSTRACT: Hyperuricemia is associated with hypertension, kidney disease, vascular and cardiovascular (CV) events. In experimental models, the inhibition of hepatic uricase induces hyperuricemia, hypertension and mild renal disease. Notably, the micro-and macrovascular changes observed in the experimental model of hyperuricemia resemble the histological changes of human hypertension.This paper presents and discusses the epidemiological correlation between high serum uric acid levels and hypertension, and reviews current evidence supporting the protective effects of the normalization of uric acid levels.This review is based on a PubMed/Embase database search for articles on hyperuricemia and its impact on cardiovascular and renal function.
    Current Medical Research and Opinion 09/2015; 31(sup2):15-19. DOI:10.1185/03007995.2015.1087981 · 2.65 Impact Factor
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    ABSTRACT: Reports detailing the response of hypertensive patients to renal denervation (RDN) in Asian patients are limited. We evaluated 6- and 12-month outcomes after RDN in an Asian population and compared outcomes to a primarily Caucasian population. The Global SYMPLICITY Registry (GSR) is a prospective, all-comer, worldwide registry that evaluates the safety and effectiveness of RDN and includes the Korean registry substudy (GSR Korea) and a Caucasian subset (GSR Caucasian). Given differences in baseline characteristics among GSR Korea (n=93) as compared with GSR Caucasian (n=169) patients, including lower baseline office systolic blood pressure (SBP), lower body mass index and differences in medications, propensity score adjustment was performed when comparing the change in SBP between subsets. The 6- and 12-month change in SBP in GSR Korea was -19.4±17.2 and -27.2±18.1 mm Hg, respectively (P<0.001 for both vs baseline). GSR Caucasian had a SBP change similar to GSR Korea at 6 months (-20.9±21.4 mm Hg, unadjusted P=0.547, adjusted P=0.998), whereas at 12 months the change was significantly less pronounced (-20.1±23.9 mm Hg, unadjusted P=0.004, adjusted P=0.002). There were no protocol-defined procedure-related adverse events and no chronic adverse events associated with the device in an Asian population. RDN provided a significant reduction in 6- and 12-month office SBP among Asian patients, with a favorable safety profile. The 12-month SBP reduction was larger than that observed in Caucasian patients.Journal of Human Hypertension advance online publication, 9 July 2015; doi:10.1038/jhh.2015.77.
    Journal of human hypertension 07/2015; DOI:10.1038/jhh.2015.77 · 2.70 Impact Factor
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    ABSTRACT: 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. 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+. 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). 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.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e22. DOI:10.1097/01.hjh.0000467406.56290.0a · 4.72 Impact Factor
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    ABSTRACT: 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. 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 Kienbaum's method). 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. 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.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e107. DOI:10.1097/01.hjh.0000467638.54870.a6 · 4.72 Impact Factor
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    ABSTRACT: In the last two decades new drugs that oppose the effects of vascular endothelial growth factor receptor (VEGFR), and thus angiogenesis, have considerably improved treatment of solid tumors. These anti-VEGFR drugs, however, are burdened by several side effects, particularly relevant on heart and vessels. Aim of this study was to analyze the changes in cardiovascular structure and function associated with use of anti-VEGFR drugs. 29 patients (27 affected by renal and 2 by thyroid cancer), received treatment with antiVEGFR drugs. Hemodynamic, non invasive arterial investigation (Pulse Wave velocity -cfPWV-, Augmentation Index-Aix- and Aortic Pressure) and echocardiography with global longitudinal strain (gLS) were performed before starting therapy (T0), after 2 (T1) and 6 weeks (T2). Oncologic outcome was determined by the assessment of the neoplastic lesions at CT scans, according to Response Evaluation Criteria in Solid Tumors Guidelines. A significant increase of both peripheral and central blood pressure (BP) was observed. We documented a significant raise of cfPWV from T0 (9.9 ± 2.5m/sec) to T1 (10.6 ± 2.3m/sec); at T2 cfPWV still increased in patients who continued treatment (10.8 ± 2.3m/sec), while decreased in patients who stopped therapy (9.8 ± 1.9m/sec). At the on-treatment CT scan (available in 22 patients) 12 patients had a stable disease (StD), 5 showed a reduction of the lesions (responders -PR-) and 5 showed a disease progression (PD). PD patients showed a lower cfPWV at T2 than StD-PR patients (cfPWV: 9.3 ± 2.8 Vs 13.3 ± 1.5 m/sec; p value 0.02). Aix at T1 was higher in PD than in StD-PR (Aix: 36 ± 2.8% Vs 24.6 ± 9.2%; p value 0.02). Anti-VEGFR treatment is associated with a marked increase in both brachial and central BP. Moreover it early induces an aortic reversible stiffening. The evidence that cfPWV and AIx changes are early and sensitive cardio-vascular effects of anti-angiogenic treatment and that disease progression is associated with a concomitant come back to pre-treatment value of cfPWV and a further increase in augmentation index, suggests their possible role on oncologic outcome.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e111. DOI:10.1097/01.hjh.0000467649.08167.c3 · 4.72 Impact Factor
  • Article: PP.18.21
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    ABSTRACT: Objective: Radiotherapy (RT) of thoracic cancers exposes to late radiation induced complications, strengthened from pre-existing cardiovascular risk factors. The heart post-RT damage is a well known phenomenon and conformational RT has allowed its drastic reduction. However, prolonged life expectancy of cancer patients underlines the need to evaluate cardio-vascular risk for many years after therapy, also in attempt to prevent the increase cardiovascular mortality that it has been recently proposed in radio-treated subjects. An arterial structural or functional damage induced by RT might be one of mechanisms for increased atherosclerotic process in these subjects. Aim of our study was to evaluate arterial function by means of PWV and Aix in subjects treated by chest radiotherapy. Design and method: We enrolled 42 patients treated with radiotherapy 15 years ago for Mammary Cancer. We assessed traditional risk factors, atherosclerotic organ damage (Carotid Ultrasound) and functional arteries evaluation with carotid-radial PWV (Complior) and AIx (Sphygmocor). We divided patients in R (N = 26) (therapy on right mammary gland), and L (N = 18) (left mammary gland). Results: None of patients had story of cardiac artery disease. R and L had similar ages (70 +/- 8vs68 +/- 8 yrs,means+SD), BSA (1.68 +/- 0.16vs1.7 +/- 0.12 m2), distribution of hypercholesterolemia (40vs39%) and active smoking (8vs7%). R had higher prevalence of hypertension (60vs57%), instead L of diabetes (17vs12%). IMT was more frequently increased (>0.9 mm) in R than in L (38vs33%). R had a significantly increased cr-PWV on right arm compared with left arm (9.9 +/- 1.4vs8.9 +/- 1.2,p < 0.05); L had a significantly increased cr-PWV (9.5 +/- 1.5vs9 +/- 1.3,p < 0.05) and AIx on left arm (32.1 +/- 7.6vs28.3 +/- 6.8,p < 0.05). In both groups no significant differences were found on central blood pressure estimation between right and left arm. No correlations were found with hormone-therapy or chemotherapy. Conclusions: Our preliminary data suggest that arteries function reflects a possible local damage due to RT. This specific and local increased in arterial stiffness might be one of mechanisms under the increase atherosclerotic phenomenon and subsequent pathologies in RT patients. It could be useful to estimate the global cardio-vascular damage in patients subjected to chest radiotherapy and to access a complete cardio-vascular risk stratification in order to plan an optimized cardio-preventive strategy. Copyright
    Journal of Hypertension 06/2015; 33:e296. DOI:10.1097/01.hjh.0000468275.71224.9d · 4.72 Impact Factor
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    ABSTRACT: 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. 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. 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). 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.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e37. DOI:10.1097/01.hjh.0000467445.30741.70 · 4.72 Impact Factor
  • Article: PP.21.31
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    ABSTRACT: Objective: Isolated systolic hypertension (ISH) is a major risk factor for cardiovascular disease and results primarily from elastic artery stiffening. Whether and to what extent the vascular abnormalities decribed in ISH can be affected by antihypertensive combination drug therapy is still debated Design and method: 24 ISH patients, aged > 65yrs recruited in the randomised, double blind, parallel group NEHIS study were randomized in a double blind fashion to Nebivolol 5 mg/Hydrochlorothiazide 12.5 mg (NH, n = 12) or Irbesartan 150 mg/Hydrochlorothiazide 12.5 (IH,N = 12) once daily for a 12 week period. Measurements included, along with clinic and ambulatory blood pressure (BP), carotid and femoral arterial pulse waves (VP-2000 Omron Healthcare) allowing to obtain an index of arterial stiffness, i.e. pulse wave velocity. Other vascular indices included carotid and femoral artery distensibility coefficient as well compliance coefficient. Results: NH and IH induced similar significant (p < 0.01) reduction in ambulatory SBP and DBP values, which were coupled in the case of NH with a slightly greater, although not significant, office SBP decrease. IH caused a slight, not significant, increase in carotid distensibility coefficient (from 0.011 +/- 0.003 to 0.015 +/- 0.04 10-3 mmHg-1, P = NS) and in carotid compliance coefficient (from 0.091 +/- 0.023 to 0.123 +/- 0.026 mm2/kPa, mean +/- SD, P = NS). Similar results were obtained by NH (distensibility 0.008 +/- 0.002 to 0.010 +/- 0.004 10-3 mmHg-1, P = NS, compliance 0.091 +/- 0.02 to 0.123 +/- 0.02 mm2/kPa, P = NS). Similar effects were also seen for femoral artery distensibility and compliance. Pulse wave velocity was only slightly and not significantly reduced by combination drug treatment both in the NH (from 13.6 +/- 3.o to 11.5 +/- 2.7 cm/sec) and in IH (from 16.9 +/- 4.4 to 15.6 +/- 3.7 cm/sec) group (P = NS). Conclusions: These data provide evidence that in ISH the vascular functional alterations are not reversed by two different drug treatments capable to exert similar antihypertensive effects. Because nebivolol and irbesartan, alone or in combination treatment, have been shown in systodiastolic hypertension to improve arterial distensibility and compliance, well as arterial stiffness, these findings may suggest that the vascular alterations observed in ISH are not reversible, at least in the short-term period, even by a combination drug treatment capable to effectively reduce elevated BP values. Copyright
    Journal of Hypertension 06/2015; 33:e327. DOI:10.1097/01.hjh.0000468383.47938.56 · 4.72 Impact Factor
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    ABSTRACT: 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). 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. After renal denervation we observed a reduction in MSNA of -17% (range: from -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. 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.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e50. DOI:10.1097/01.hjh.0000467478.51825.50 · 4.72 Impact Factor
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    ABSTRACT: Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by an elevated cardiovascular morbidity and mortality, but detailed informations on the risk score profile using different approaches, as well as on the major determinant(s) of the cardiovascular risk of these patients are scanty. The present study reports data collected in a cohort of RA patients with CV risk score calculators Framingham and SCORE uncorrected or corrected according to European League against Rheumatism (EULAR) recommendations. Cardiovascular events were recorded during the 3 yrs follow-up, to determine the burden of CV morbidity and the relative impact of traditional CV risk factors and disease activity/severity.We enrolled in the study 198 pts, 77% females, age 65.0 ± 11.6 yrs (means ± SD), disease duration 13 ± 9 yrs. 76% of pts were RF +, 68% ACPA+ and 46% with erosive disease. 3% were smokers and 32% ex smokers. Mean BMI (24.6 ± 4.4), plasma levels of cholesterol (total,HDL,LDL), triglycerides and glucose and prevalence of smokers were comparable with those detected in the local general population, while the prevalence of hypertension and diabetes were significantly higher in both males and females. Risk scores with Framingham were lower than in general population and comparable using SCORE, but the application of 1.5x correction factor for RA, as recommended by EULAR, modified these figures. The number of hypertensive and diabetic pts increased significantly (P<.0001/ .019) during the follow-up as well as the mean values of Framingham and SCORE (p < .015/.011). The MI and stroke prevalence were 5% and 2% respectively: the incidence rate/1000 person/year were 8.8 and 3.7 versus 2.7 and 2.6 in the general population. No relation was detectable between disease activity indices and CV events or risk scores. The present study provides evidence that 1) RA is associated with an increased CV morbidity even in the medium follow-up period, 2) risk score needs to be adjusted as by EULAR indications to obtain sensitive assessment of risk and 3) that hypertension represents a major CV risk factor in this population.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book(Suppl 2):e118. DOI:10.1097/01.hjh.0000467667.84403.7d · 4.72 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e124-e125. DOI:10.1097/01.hjh.0000467688.85296.90 · 4.72 Impact Factor
  • Article: 4C.07
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    ABSTRACT: The relation between blood pressure (BP) and cognitive function has received growing interest in recent years. Some cross-sectional studies have shown an inverse association between BP and cognitive dysfunction, while longitudinal studies yield mixed results. In the PAMELA study cognitive function was assessed via minimental test at the evaluation performed in 2001-2002, taking as reference clinic data collected at the 1st PAMELA examination carried out 10 yrs before. 471 subjects participated at this substudy. Measurements included clinic and 24-hour BP (Spacelabs 90207). BP variability was obtained by calculating 1) the SD of 24-hour, day, and night mean values, 2) the day/night BP difference and (3) the residual or erratic BP variability (Fourier spectral analysis). Mean age of the subjects enrolled was 63.0 ± 5.7 yrs (mean ± SD) at the 1St examination. At the 2nd evaluation performed 10 yrs later 26 subjects had a minimental score < 23, indicative of a cognitive dysfunction (CD), the remaining 445 showing normal scores (C, 24-30). For similar heart rate, office and home systolic (but not diastolic) BP were, although not significantly, greater in CD than in C (148.0 ± 22.5 vs 143.5 ± 19.9 and 139.5 ± 15.14 vs 133.3 ± 17.9 mmHg, P = NS). 24hour BP was similar in CD and C, this being the case also for 24 hour BP variability, expressed as SD systolic (15.3 ± 4.1 vs 14.8 ± 3.7 mmHg, P = NS) and diastolic (12.9 ± 3.47 vs 12.2 ± 2.9 mmHg, P = NS) or day/night BP difference. In contrast, residual BP variability was significantly greater in CD than in C for both systolic (11.2 ± 2.2 vs 10.6 ± 2.5 mmHg, P < 0.05) and diastolic (9.3 ± 2.1 vs 8.7 ± 2.3 mmHg, P < 0.05), the difference between groups being greater when the grading of minimental responses was based on 3 score categories (0-20,21-24 and >24). This was particularly the case in males. Our data show that the most sensitive prognostic variable for the development of cognitive alterations does not appear to be absolute BP load or absolute BP variability but rather its short-term erratic component, which has been previously shown to represent the part of BP variability with major impact on cardiovascular mortality.
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e58. DOI:10.1097/01.hjh.0000467501.75589.73 · 4.72 Impact Factor
  • Article: 3D.01
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    ABSTRACT: High blood pressure variability has been associated with an increased risk of cardiovascular events. We aimed to assess if increased visit-to-visit variability in systolic blood pressure increases the risk of stroke or cardiac events (fatal/non-fatal coronary or heart failure events) in the VALUE population. The VALUE trial was a randomised-controlled, double-masked investigation of valsartan versus amlodipine in patients 50 years or older with hypertension and high risk of cardiovascular events. Mean follow-up time was 4.2 years. We calculated the standard deviation (SD) of mean systolic blood pressure from visits from 6 months onward, excluding patients with less than 2 visits, or stroke or cardiac events during the first 6 months. In the pooled treatment arms, we grouped SD in quintiles and compared the risk of stroke or cardiac events in the highest and the lowest quintile, using a Cox regression model, adjusting for a number of prognostic variables, including randomised treatment and mean BP from 6 months onwards. Of 14.146 patients included, 1278 (9.0%) experienced a cardiac event and 473 (3.3%) experienced a stroke. Compared to patients with the lowest variability, those in the highest quintile had an increased risk of stroke or cardiac events (HR 1.4, 95% CI 1.0-1.8, p = 0.045 and HR 1.9, 95% CI 1.6-2.3, p < 0.0001, respectively, Figure). Visit-to-visit systolic BP variability predicts stroke and cardiac events in high risk hypertensive patients receiving valsartan or amlodipine, and independent of mean BP. Systolic blood pressure variability was a stronger predictor of cardiac events than of stroke.(Figure is included in full-text article.).
    Journal of Hypertension 06/2015; 33 Suppl 1 - ESH 2015 Abstract Book:e40. DOI:10.1097/01.hjh.0000467454.55397.ea · 4.72 Impact Factor
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    ABSTRACT: This analysis is aimed to determine blood pressure (BP) levels and BP control rates in a large population of hypertensive patients in Italy. Data were taken from two large and inclusive cross-sectional surveys, which covered two distinct and subsequent time periods (2000-2005 and 2005-2011, respectively). Observational clinical studies and surveys, which reported average systolic/diastolic clinic BP levels, proportions of treated/untreated and controlled/uncontrolled patients, and prevalence of cardiovascular risk factors in hypertensive patients followed in either outpatient clinics, hypertension centres or general practice, were considered for the analyses. The overall sample included 211 591 hypertensive patients (119 997 (56.7%) women, age 57.0±10.0 years, body mass index 26.9±4.0 kg m(-2), BP levels 146.9±16.7/88.7±9.6 mm Hg). BP levels were 148.2±15.4/87.5±9.3 mm Hg in patients followed by general practitioners (n=168 313, 79.5%), 148.1±17.3/90.1±9.7 mm Hg in those followed by hypertension centres (n=28 180, 13.3%), and 142.4±17.6/86.6±9.8 mm Hg in those followed by outpatient clinics and hospital divisions (n=15 098, 7.1%). Among treated hypertensive patients (n=128 079; 60.5%), 43 008 (33.6%) were reported to have controlled BP levels. Over one decade of observation, we reported that ~60% of hypertensive patients were treated and among these only 33% achieved effective BP control. These findings highlight the need for more effective interventions to improve management of hypertension in Italy.Journal of Human Hypertension advance online publication, 12 February 2015; doi:10.1038/jhh.2015.4.
    Journal of Human Hypertension 02/2015; 29(11). DOI:10.1038/jhh.2015.4 · 2.70 Impact Factor
  • G. Seravalle · G. Grassi · G. Mancia ·
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    ABSTRACT: Several metabolic, humoral, local, and neural influences contribute to the homeostatic control of the cardiovascular system. All these factors physiologically interact with each other and participate in the regulation of cardiac as well as vascular function. Both endothelial and sympathetic functions seem to be the main important regulatory mechanisms involved in maintaining the homeostatic balance and participating in the cardiovascular responses to environmental needs. The alterations of these mechanisms represent the key factor for the cardiovascular modifications typical of several clinical conditions, such as heart, kidney, lung, and liver diseases as well as obesity and diabetes and represent the target for non-pharmacologic and pharmacologic interventions.
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    ABSTRACT: Background In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) factorial trial, the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes, but intensive glucose control, targeting a glycated hemoglobin level of less than 6.5%, did not. We now report results of the 6-year post-trial follow-up. Methods We invited surviving participants, who had previously been assigned to perindopril-indapamide or placebo and to intensive or standard glucose control (with the glucose-control comparison extending for an additional 6 months), to participate in a post-trial follow-up evaluation. The primary end points were death from any cause and major macrovascular events. Results The baseline characteristics were similar among the 11,140 patients who originally underwent randomization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years (blood-pressure-lowering comparison) or 5.4 years (glucose-control comparison). Between-group differences in blood pressure and glycated hemoglobin levels during the trial were no longer evident by the first post-trial visit. The reductions in the risk of death from any cause and of death from cardiovascular causes that had been observed in the group receiving active blood-pressure-lowering treatment during the trial were attenuated but significant at the end of the post-trial follow-up; the hazard ratios were 0.91 (95% confidence interval [CI], 0.84 to 0.99; P=0.03) and 0.88 (95% CI, 0.77 to 0.99; P=0.04), respectively. No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the standard-glucose-control group; the hazard ratios were 1.00 (95% CI, 0.92 to 1.08) and 1.00 (95% CI, 0.92 to 1.08), respectively. Conclusions The benefits with respect to mortality that had been observed among patients originally assigned to blood-pressure-lowering therapy were attenuated but still evident at the end of follow-up. There was no evidence that intensive glucose control during the trial led to long-term benefits with respect to mortality or macrovascular events. (Funded by the National Health and Medical Research Council of Australia and others; ADVANCE-ON ClinicalTrials.gov number, NCT00949286 .).
    New England Journal of Medicine 09/2014; DOI:10.1056/NEJMoa1407963 · 55.87 Impact Factor
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    ABSTRACT: To assess associations between patient characteristics, intensification of blood glucose-lowering treatment through oral glucose lowering therapy and/or insulin, and effective glycaemic control in type 2 diabetes. 11,140 patients from the ADVANCE trial who were randomised to intensive glucose control or standard glucose control and followed for a median of 5 years were categorised into 2 groups: effective glycaemic control (HbA1c ≤7.0% or a proportionate reduction in HbA1c over 10%) or ineffective glycaemic control (HbA1c >7.0% and a proportionate reduction in HbA1c less than or equal to 10%). Therapeutic intensification was defined as addition of an oral glucose-lowering agent or commencement of insulin. Pooled logistic regression models examined the associations between patient factors, intensification and effective glycaemic control. 7768 patients (69.7%), including 3198 in the standard treatment group achieved effective glycaemic control. Compared to patients with ineffective control, patients with effective glycaemic control had shorter duration of diabetes and lower HbA1c at baseline and at the time of treatment intensification. Treatment intensification with addition of an oral agent or commencement of insulin was associated with a 107% (OR: 2.07 [95% CI: 1.95-2.20]) and 152% (OR: 2.52 [95% CI: 2.30-2.77]) greater chance of achieving effective glycaemic control, respectively. These associations were robust after adjustment for several baseline characteristics and not modified by the number of oral medications taken at the time of treatment intensification. Effective glycaemic control was associated with treatment intensification at lower HbA1c levels at all stages of the disease course and in both arms of the ADVANCE trial.
    Diabetes Obesity and Metabolism 11/2013; 16(5). DOI:10.1111/dom.12238 · 6.36 Impact Factor
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    ABSTRACT: IMPORTANCE Type 2 diabetes mellitus and associated chronic kidney disease (CKD) have become major public health problems. Little is known about the influence of diet on the incidence or progression of CKD among individuals with type 2 diabetes. OBJECTIVE To examine the association between (healthy) diet, alcohol, protein, and sodium intake, and incidence or progression of CKD among individuals with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS All 6213 individuals with type 2 diabetes without macroalbuminuria from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) were included in this observational study. Recruitment spanned from January 2002 to July 2003, with prospective follow-up through January 2008. MAIN OUTCOMES AND MEASURES Chronic kidney disease was defined as new microalbuminuria or macroalbuminuria or glomerular filtration rate decline of more than 5% per year at 5.5 years of follow-up. We assessed diet using the modified Alternate Healthy Eating Index (mAHEI). The analyses were adjusted for known risk factors, and competing risk of death was considered. RESULTS After 5.5 years of follow-up, 31.7% of participants had developed CKD and 8.3% had died. Compared with participants in the least healthy tertile of mAHEI score, participants in the healthiest tertile had a lower risk of CKD (adjusted odds ratio [OR], 0.74; 95% CI, 0.64-0.84) and lower risk of mortality (OR, 0.61; 95% CI, 0.48-0.78). Participants consuming more than 3 servings of fruits per week had a lower risk of CKD compared with participants consuming these food items less frequently. Participants in the lowest tertile of total and animal protein intake had an increased risk of CKD compared with participants in the highest tertile (total protein OR, 1.16; 95% CI, 1.05-1.30). Sodium intake was not associated with CKD. Moderate alcohol intake reduced the risk of CKD (OR, 0.75; 95% CI, 0.65-0.87) and mortality (OR, 0.69; 95% CI, 0.53-0.89). CONCLUSIONS AND RELEVANCE A healthy diet and moderate intake of alcohol may decrease the incidence or progression of CKD among individuals with type 2 diabetes. Sodium intake, within a wide range, and normal protein intake are not associated with CKD. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00153101.
    JAMA Internal Medicine 08/2013; 173(18). DOI:10.1001/jamainternmed.2013.9051 · 13.12 Impact Factor
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    ABSTRACT: Erectile dysfunction (ED) is associated with cardiovascular risk factors as elevated systolic blood pressure (SBP), resting high heart rate (HR), and endothelial dysfunction and predicts cardiovascular events. However, the interaction between high HR and SBP and the development of ED remains unclear. We evaluated 1015 male patients enrolled in the ED substudy of ONTARGET and TRANSCEND, examining the influence of mean HR and mean SBP obtained over all study visits (mean 10.9±1.4 study visits) and their interaction with ED. In patients without pre-existing ED, new onset ED was detected in 29% of patients below, and 41% of patients above, the median of mean HR (OR 1.72, 95% CI 1.8-2.5, p = 0.0047). In patients with pre-existing ED, high HR had no add-on effect. With or without pre-existing ED, high SBP had no influence after adjustment for covariates (OR 1.03, 95% CI 0.66-1.59, p = 0.91). In a continuous model, it was shown that effects of high HR were prominent at low Kölner (Cologne) Evaluation of Erectile Function (KEED) score baseline values and in the presence of SBP above the median. In patients at risk for cardiovascular events, high HR is associated with ED, whereas the effect of high SBP was not significant. High resting HR might represent a cardiovascular risk indicator. Whether HR represents a potential treatment target to improve ED in high-risk individuals must be scrutinized in prospective trials.
    07/2013; 21(3). DOI:10.1177/2047487313494835
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    ABSTRACT: Background: ARTEMIS is the first International Ambulatory Blood Pressure Monitoring (ABPM) Registry aiming at assessing the actual degree of blood pressure (BP) and cardiovascular risk control of treated or untreated hypertensive patients followed by Hypertension (HT) Clinics in different countries over the world. A previous data analysis showed a higher prevalence of masked hypertension in the studied population and indicated a lack of BP dip among the important determinants of such a condition. Thus, we settled the present analysis in order to better investigate the dipping (D) status and its determinants among the study participants. Methods: As with previous analyses data have been provided by existing databases including subjects performing an ABPM for clinical or research purposes. Sitting clinic BP was measured in all subjects before being submitted to 24h ABPM. A non-dipper (ND) was defined as a subject displaying a mean BP drop at night as respect to day-time <=10%. A logistic regression analysis was used to assess the determinants of dipping. Categorical variables previously verified in univariate tests were entered in the multivariate model as covariates. Results: 14,143 subjects were included in the analysis (73% from Europe, 14% from Asia, 9% from America, 3% from Asia and 1% from Oceania). Mean participants’ age was 57±14 years, 51% were males, 46% treated for HT, 14% had a previous cardiovascular disease, 14% diabetes, 33% dyslipidemia, 19% were smokers. We also ran a safety analysis on comparable numbers of patients from each continent. The overall proportion of NDs was 37%, with a larger prevalence of this phenomenon in people living in America (39%), Asia (37%) and Europe (37%) than in Oceania (31%) and Africa (24%). NDs showed average day-time BP values very similar to those of dippers (134±16 / 80±11 vs. 136±15 / 84±10 mmHg, p=0.0001 between-groups), while night-time average BPs were consistently higher in ND (130±16 / 76±11 vs. 116±14 / 68±10 mmHg, p=0.0001). The strongest determinant of a ND pattern was an advanced age [OR: 1.66 (95% confidence interval: 1.53, 1.79), p=0.0001], followed in decreasing order by current antihypertensive treatment [1.48 (1.37, 1.59), p=0.0001], residency in an Asian, European or American country [1.40 (1.15, 1.70), p=0.001], previous diagnosis of diabetes [1.25 (1.13, 1.39), p=0.0001] or of a cardiovascular disease [1.15 (1.04, 1.28), p=0.0001], and male gender [1.10 (1.02, 1.18), p=0.009]. Conversely, alcohol drinking [0.89 (0.80, 0.98), p=0.023] and an isolated clinic hypertension [0.76 (0.70, 0.83), p=0.0001] were both less likely associated with the risk of ND at night. Conclusions: A loss of the normal diurnal BP pattern is a quite common feature of HT worldwide and is more likely observed in elderly, male, treated hypertensive individuals, with cardiovascular comorbidities. Significant differences among continents were observed, possibly depending on ethnic and/or environmental factors. Interestingly the presence of masked hypertension increased the chance of displaying such a condition.
    23rd European Meeting on Hypertension and Cardiovascular Protection; 06/2013

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19k Citations
2,605.73 Total Impact Points


  • 1999-2015
    • Università degli Studi di Milano-Bicocca
      • Department of Statistics and Quantitative Methods
      Milano, Lombardy, Italy
    • Associazione Nazionale Medici Cardiologi
      Florens, Tuscany, Italy
  • 1994-2015
    • Azienda Ospedaliera San Gerardo
      Monza, Lombardy, Italy
    • University of Bonn - Medical Center
      Bonn, North Rhine-Westphalia, Germany
  • 1968-2015
    • University of Milan
      • • Department of Internal Medicine
      • • Istituto di Patologia Generale
      Milano, Lombardy, Italy
  • 1990-2013
    • I.R.C.C.S. Istituto Auxologico Italiano
      • Department of Neurology and Laboratory of Neuroscience
      Milano, Lombardy, Italy
  • 2008
    • Policlinico di Monza
      Monza, Lombardy, Italy
  • 2007
    • Jagiellonian University
      Cracovia, Lesser Poland Voivodeship, Poland
    • Mascara Universit
  • 2004
    • Universitair Ziekenhuis Ghent
      Gand, Flanders, Belgium
  • 2000-2003
    • University of Sydney
      Sydney, New South Wales, Australia
    • New York Presbyterian Hospital
      New York City, New York, United States
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
  • 2002
    • Oslo University Hospital
      • Department of Cardiology
      Oslo, Oslo, Norway
  • 1998-2001
    • Politecnico di Milano
      • Department of Bioengineering
      Milano, Lombardy, Italy
    • IRCCS Multimedica
      Milano, Lombardy, Italy
  • 1997
    • Foundation of the Carlo Besta Neurological Institute
      Milano, Lombardy, Italy
  • 1992
    • Ospedale Maggiore Carlo Alberto Pizzardi di Bologna
      Bolonia, Emilia-Romagna, Italy
  • 1980
    • University of Adelaide
      Tarndarnya, South Australia, Australia