Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40–69 years in Europe. Methods and results  We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65–0.68) to 0.81 (0.76–0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low-risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries. Conclusion  SCORE2—a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations—enhances the identification of individuals at higher risk of developing CVD across Europe.

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 agematched 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.

Abstract-Direct and indirect indices of neuroadrenergic function have shown that end-stage renal disease is characterized by a marked sympathetic overdrive. It is unknown, however, whether this phenomenon represents a peculiar feature of end-stage renal disease or whether it is also detectable in the early clinical phases of the disease. The study has been performed in 73 hypertensive patients, of which there were 42 (age: 60.7Ϯ1.8 years, meanϮSEM) with a stable moderate chronic renal failure (mean estimated glomerular filtration rate: 40.7 mL/min per 1.73 m 2 , MDRD formula) and 31 age-matched controls with a preserved renal function. Measurements included anthropometric variables, sphygmomanometric and beat-to-beat blood pressure, heart rate (ECG), venous plasma norepinephrine (highperformance liquid chromatography), and efferent postganglionic muscle sympathetic nerve activity (microneurography, peroneal nerve). For similar anthropometric and hemodynamic values, renal failure patients displayed muscle sympathetic nerve activity values significantly and markedly greater than controls (60.0Ϯ2.1 versus 45.7Ϯ2.0 bursts per 100 heartbeats; PϽ0.001). Muscle sympathetic nerve activity showed a progressive and significant increase from the first to the fourth quartile of the estimated glomerular filtration rate values (first: 41.0Ϯ2.7; second: 51.9Ϯ1.7; third: 59.8Ϯ3.0; fourth: 61.9Ϯ3.3 bursts per 100 heartbeats), the statistical significance (PϽ0.05) between groups being maintained after adjustment for confounders. In the population as a whole, muscle sympathetic nerve activity was significantly and inversely correlated with the estimated glomerular filtration rate (rϭϪ0.59; PϽ0.0001). Thus, adrenergic activation is a phenomenon not confined to advanced renal failure but already detectable in the initial phases of the disease. The sympathetic overdrive parallels the severity of the renal failure, state and, thus, it might participate, in conjunction with other factors, at the disease progression. (Hypertension. 2011;57:846-851.) Key Words: chronic renal failure Ⅲ microneurography Ⅲ sympathetic nervous system A dvanced renal failure is accompanied by a marked activation of sympathetic cardiovascular influences, as documented by the increase in the circulating plasma levels of norepinephrine, the elevated number of sympathetic neural bursts recorded in the peroneal nerve via the microneurographic technique, and the augmented oscillations in the high-frequency band of the heart rate power spectra. [1][2][3][4][5][6][7][8][9][10][11][12][13] Whether the sympathetic activation also characterizes the earlier clinical phases of the renal failure state is not clear, however. This is because in the few studies performed so far in patients with mild renal disease, the population sample was small, and the plasma levels of norepinephrine showed inconsistent changes. 11,12 Furthermore, in the 2 previously published studies that assessed sympathetic nerve traffic via microneurography, approximately half of the patients evaluated ...

Abstract-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. Key Words: masked hypertension Ⅲ white-coat hypertension Ⅲ ambulatory blood pressure monitoring Ⅲ prognosis N o conclusive evidence exists as to whether isolated office or white-coat hypertension (HT; WCHT) and masked HT (MHT), ie, the conditions in which, respectively, only office or out-of-office blood pressure (BP) is elevated, are clinically innocent or rather associated with an increase in cardiovascular (CV) risk. [1][2][3] This is because in white-coat and masked hypertensive individuals, the prevalence of structural organ damage has not invariably been found to be greater than in "truly" normotensive individuals. [3][4][5][6][7] It is also because the longitudinal studies that have addressed this issue by assessing the incidence of morbidity and mortality have been based on a small number of CV events and/or a relatively short observation period. 8 -14 Information on the clinical significance of WCHT and MHT can also be obtained by investigating whether, compared with "true" normotension, these conditions are accompanied by a greater rate of development of a "sustained" hypertensive state, ie, HT both in and outside the clinical environment. We have addressed this issue in the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) population by identifying subjects with WCHT and MHT through in-office and out-of-office BP measurements and by detecting the development of sustained HT (SHT) over a 10-year time interval, ie, a long follow-up that allowed a large number of cases to occur. A peculiar aspect of the study was that out-of-office BP was measured both at home and over 24 hours, which allowed us to obtain 2 separate identifications of WCHT and MHT. MethodsThe methodology used in the PAMELA Study has been reported in detail elsewhere. 12,15 Briefly, 3200 individuals were randomly selected from the white residents of Monza (a town in the northeast outskirts of Milan), to be representative of its residents for sex, age (25 to 74 years), and socioeconomic characteristics, according to the criteria used by the World Health Organization Monitoring Diseases Project 16 conducted in the same geographic area. 6 Data were collected in 2051 subjects (64% of the original sample), and survivors were contacted 10 years later to be re-examined. All of the subjects agreed to participate in the study after explanation of its nature and purpose the study, and protocol was approved by the ethics committee of the institutions involved.Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz.

Abstract-Limited information is available on whether and to what extent the different patterns of the nocturnal blood pressure profile reported in hypertension are characterized by differences in sympathetic drive that may relate to, and account for, the different day-night blood pressure changes. In 34 untreated middle-aged essential hypertensive dippers, 17 extreme dippers, 18 nondippers, and 10 reverse dippers, we assessed muscle sympathetic nerve traffic, heart rate, and beat-to-beat arterial blood pressure at rest and during baroreceptor deactivation and stimulation. Measurements were also performed in 17 age-matched dipper normotensives. All patients displayed reproducible blood pressure patterns at 2 different monitoring sessions. Key Words: reverse dipping Ⅲ extreme dipping Ⅲ ambulatory blood pressure Ⅲ sympathetic activity Ⅲ baroreflex Ⅲ hypertension U se of ambulatory blood pressure (BP) monitoring allowed identification of 4 different patterns of the nocturnal BP profile (ie, the dipping, nondipping, extreme dipping, and reverse dipping type), each with a prevalence that makes it a rather common phenomenon to be seen in clinical practice. 1-3 It also has been shown that these different BP patterns are associated with different rates of target organ damage and clinical outcome. 2-12 However, information is limited and contradictory on whether individuals with these different BP patterns display differences in the factors involved in cardiovascular control that may relate to and account for the different day-night BP changes. [13][14][15][16][17][18] This is particularly the case for a fundamental mechanism participating in day and night cardiovascular modulation such as the adrenergic nervous system. 19 The present study was aimed at addressing the above issue by using direct measurement of muscle sympathetic nerve activity (MSNA) via microneurography in untreated hypertensive patients whose belonging to the dipping, nondipping, extreme dipping, and reverse dipping pattern was confirmed by repeated ambulatory BP monitorings. Microneurographic measurements were coupled with assessment of baroreflex function and insulin sensitivity to determine the relative contribution of reflex and metabolic alterations to the sympathetic abnormalities. Methods PopulationOur study was performed from a population of males and females referred to the outpatient cardiovascular risk and hypertension clinic of our Hospital (San Gerardo, Monza). Inclusion criteria were: (1) an elevated office (Ͼ140/90 mm Hg) and 24-hour (Ͼ125/79 mm Hg) BP; (2) no obesity (body mass index Յ30 kg/m 2 ); (3) no history of smoking, excessive alcohol consumption, and major cardiovascular or noncardiovascular disease, including diabetes mellitus; (4) no use of antihypertensive and other cardiovascular or metabolic drugs; (5) no echocardiographic evidence of left ventricular hypertrophy, alteration in renal function, or ultrasonographic evidence of carotid artery thickening or plaques; (6) no evidence of disease or conditions responsible for second...