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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. The 4 hypertensive groups did not differ by gender or 24-hour or daytime blood pressure. Muscle sympathetic nerve traffic was significantly higher in nondipper, dipper, and extreme dipper hypertensives than in normotensive controls (58.6+/-1.8, 55.6+/-0.9, and 53.3+/-0.8 versus 43.5+/-1.4 bursts/100 heartbeats, respectively; P<0.01 for all), a further significant increase being detected in reverse dippers (76.8+/-3.1 bursts/100 heartbeats; P<0.05). Compared with normotensives, baroreflex-heart rate control was similarly impaired in all the 4 hypertensive states, whereas baroreflex-sympathetic control was preserved. The day-night blood pressure difference correlated inversely with sympathetic nerve traffic (r=-0.76; P<0.0001) and homeostasis model assessment index (r=-0.32; P<0.005). Thus, the reverse dipping state is characterized by a sympathetic activation greater for magnitude than that seen in the other conditions displaying abnormalities in nighttime blood pressure pattern. The present data suggest that in hypertension, sympathetic activation represents a mechanism potentially responsible for the day-night blood pressure difference.

Objectives: Plasma norepinephrine displays a limited ability to reflect the enhanced sympathetic drive characterizing essential hypertension. Among the factors responsible, an important one is the reduced reproducibility of the norepinephrine approach. The present study aimed to determine whether increasing the number of blood samples on which norepinephrine assay is based improves norepinephrine reproducibility. This was done by taking muscle sympathetic nerve traffic recording as 'gold standard', which is characterized by an elevated short- and long-term reproducibility., Methods: In 14 untreated mild-to-moderate essential hypertensive patients, we evaluated, in two experimental sessions spaced each other by a 10-14-day interval, blood pressure (Finapres), heart rate (ECG), plasma norepinephrine (HPLC) and muscle sympathetic nerve traffic (microneurography, peroneal nerve). In the two sessions, three norepinephrine samples were obtained at 30-min intervals between each. Norepinephrine reproducibility between sessions was assessed on a single norepinephrine sample or averaging together the values obtained from second or third samples. Reproducibility of norepinephrine data was then compared with the microneurographic one., Results: Although muscle sympathetic nerve traffic values showed a highly significant correlation between sessions (r=0.79, P<0.001), norepinephrine values derived from a single blood sample did not correlate with each other (r=0.42, P=NS). Norepinephrine correlation coefficients were consistently improved and achieved statistical significance when average data from second or third blood samples were examined (r=0.63, P<0.03)., Conclusion: In essential hypertension, the reproducibility of plasma norepinephrine as an adrenergic marker can be substantially improved by performing a norepinephrine assay on multiple blood samples.

Aim: To re-evaluate the diagnostic criteria of insulin resistance hepatic iron overload based on clinical, biochemical and histopathological findings., Methods: We studied 81 patients with hepatic iron overload not explained by known genetic and acquired causes. The metabolic syndrome (MS) was defined according to ATPIII criteria. Iron overload was assessed by liver biopsy. Liver histology was evaluated by Ishak's score and iron accumulation by Deugnier's score; steatosis was diagnosed when present in >or=5% of hepatocytes., Results: According to transferrin saturation levels, we observed significant differences in the amount of hepatic iron overload and iron distribution, as well as the number of metabolic abnormalities. Using Receiving Operating Curve analysis, we found that the presence of two components of the MS differentiated two groups with a statistically significant different hepatic iron overload (P<0.0001). Patients with >or=2 metabolic alterations and steatosis had lower amount of hepatic iron, lower transferrin saturation and higher sinusoidal iron than patients with <2 MS components and absence of steatosis., Conclusion: In our patients, the presence of >or2 alterations of the MS and hepatic steatosis was associated with a moderate form of iron overload with a prevalent sinusoidal distribution and a normal transferrin saturation, suggesting the existence of a peculiar pathogenetic mechanism of iron accumulation. These patients may have the typical dysmetabolic iron overload syndrome. By contrast, patients with transferrin saturation>or=60% had more severe iron overload, few or no metabolic abnormalities and a hemochromatosis-like pattern of iron overload.

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.

Objective: Blood pressure (BP) 'Cardiette BP one' system (BP one) is an oscillometric ambulatory BP monitor manufactured in Italy in conformity to current regulations for medical devices. We decided to determine the accuracy of measures made with BP one, using the protocol of the British Hypertension Society published in 1990, and revised in 1993, for evaluating the accuracy of BP measurement devices., Methods: The evaluation included before-use calibration, in-use assessment, after-use calibration, and static device validation that involved 85 participants., Results: The mean difference between manual readings with sphygmomanometer and automatic ones with the device were -0.36+/-5.74 (mean+/-SD) for systolic values and 2.52+/-4.87 for diastolic values. On the basis of the percentages of measurements differing from the mercury sphygmomanometer standard by

The primary objective is to verify the relation between job strain and clinic blood pressure in a working population from the Milan municipality (1,909 men, 3,786 women) enrolled from 1992 to 1996. Job strain was investigated through the Karasek model. Clinic blood pressure was evaluated using standard procedures from the MONICA project. The association between the two was calculated controlling for age, education, smoking, body mass index, total and high-density lipoprotein (HDL) cholesterol. Significantly, associations were found for systolic blood pressure in men and for both systolic and diastolic blood pressure in women. However, these results do not reflect biological plausibility. The relationship between job strain and blood pressure is an unfinished business: sample characteristics and measurement methods should be carefully considered.

Objective: To compare the prevalence of metabolic syndrome (MS) in HIV-positive patients with that from a sample of a general Italian population., Design: Cross-sectional study., Methods: A total of 1263 HIV-infected patients 18 years of age or older were recruited in 18 centers for infectious diseases in northern and central Italy. Controls were 2051 subjects aged 25 to 74 years representative of the residents of Monza, a town in Milan province, who were enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni study., Results: The prevalence of MS in the HIV group was 20.8%, whereas in the control group, it was only 15.8%, with the difference being statistically significant. The age- and gender-adjusted risk of having MS in HIV-infected patients was twice as great as that in controls. Compared with controls, HIV-infected patients had a greater prevalence of the impaired fasting glucose, increased plasma triglycerides, and reduced high-density lipoprotein cholesterol components. MS prevalence was similar in treated and never-treated HIV-infected patients, and so were the various MS components., Conclusions: The risk of MS is greater in HIV-infected patients compared with the general population because of a greater prevalence of lipid and glucose abnormalities. The prevalence of MS and its components is similar in treated and untreated HIV-positive patients.

The hypothesis has been advanced that cardiovascular prognosis is related not only to 24-hour mean blood pressure but also to blood pressure variability. Data, however, are inconsistent, and no long-term prognostic study is available. In 2012 individuals randomly selected from the population of Monza (Milan), 24-hour ambulatory blood pressure (Spacelabs 90207) was measured via readings spaced by 20 minutes. Systolic and diastolic blood pressure variability was obtained by calculating the following: (1) the SD of 24-hour, day, and night mean values; (2) the day-night blood pressure difference; and (3) the residual or erratic blood pressure variability (Fourier spectral analysis). Fatal cardiovascular and noncardiovascular events were registered for 148 months. When adjusted for age, sex, 24-hour mean blood pressure, and other risk factors, there was no relationship between the risk of death and 24-hour, day, and night blood pressure SDs. In contrast, the adjusted risk of cardiovascular death was inversely related to day-night diastolic BP difference (beta coefficient=-0.040; P<0.02) and showed a significant positive relationship with residual diastolic blood pressure variability (beta coefficient=0.175; P<0.002). Twenty-four-hour mean blood pressure attenuation of nocturnal hypotension and erratic diastolic blood pressure variability all independently predicted the mortality risk, with the erratic variability being the most important factor. Our data show that the relationship of blood pressure to prognosis is complex and that phenomena other than 24-hour mean values are involved. They also provide the first evidence that short-term erratic components of blood pressure variability play a prognostic role, with their increase being accompanied by an increased cardiovascular risk.

Objective: Arterial stiffening is associated with an increased risk of cardiovascular disease. However, limited evidence exists on whether it also relates to subclinical atherosclerosis, thereby providing a non-invasive marker of the overall cardiovascular status. The aim of the present study was to provide information on arterial stiffening in angina patients in whom angiographic evaluation allowed quantification of coronary atherosclerosis., Methods: We studied 101 patients with angina from a large number admitted to our hospital for coronary angiography. In each patient, radial (RA), subdiaphragmatic aorta (AO) and carotid (CA) distensibility (Dist) were measured by an ultrasonic device, following ultrasonic exclusion of atherosclerotic lesions at these specific sites. Patients were classified into three groups according to the angiographic findings: (i) no significant coronary lesions (lumen obstruction < 50%, group A); (ii) one (group B); and (iii) two or three (group C) coronary vessels with hemodynamic significant plaques (lumen obstruction > 50%)., Results: Age, male prevalence, previous cardiovascular disease and interventions were progressively greater or more common from group A to C, whereas several other risk factors (plasma glucose, serum cholesterol, smoking, history of hypertension, etc.) did not differ between the three groups or between the group with single vessel (B) versus the group with multivessel disease (C). CA and AO Dist decreased progressively from group A to C with a significant relationship in the group as a whole between distensibility values and the number of diseased vessels. The progressive decrease in AO Dist from group A to C remained significant after adjustment for variables that showed between-group differences (such as gender, age and systolic blood pressure) and the ROC curve showed it to be a more sensitive and specific marker of coronary atherosclerosis than CA Dist. RA Dist was similar in the three groups and showed no relationship with the number of diseased vessels in the group as a whole., Conclusion: In patients with angina, AO and CA Dist are related to the severity of coronary atherosclerosis, with the relationship being better for alterations in aortic than in carotid mechanical properties. Large elastic artery (and in particular aortic) stiffening can thus be considered as a marker of the severity of coronary atherosclerosis, providing non-invasive obtainable information on the need to proceed with further clinical examinations.

The prevalence of the metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III criteria) and its relationships with daily life blood pressures, cardiac damage, and prognosis were determined in 2013 subjects from a Northern Italian population aged 25 to 74 years. Home blood pressure, 24-hour blood pressure, and left ventricular mass index (echocardiography) were also measured. Cardiovascular and noncardiovascular deaths were registered over 148 months. Metabolic syndrome was found in 16.2% of the sample, an office blood pressure elevation being the most frequent (95.4%) and the blood glucose abnormality the least frequent (31.5%) component. There was in metabolic syndrome a frequent elevation in home and/or 24-hour average blood pressure, as well as a greater left ventricular mass index and prevalence of left ventricular hypertrophy, which was manifest even when data were adjusted for between-group differences, including blood pressure. The adjusted risk of cardiovascular and all-cause mortality was greater in metabolic syndrome subjects (+71.0% and +37.0%; P<0.05), a further marked increase being observed with left ventricular hypertrophy or "in-office" and "out-of-office" blood pressure elevations. The increased risk was related to the blood pressure and the blood glucose component of metabolic syndrome, with no contribution of the remaining components. Thus, metabolic syndrome is common in a Mediterranean population in which it significantly increases the long-term risk of death. Cardiac abnormalities and increases in home and 24-hour blood pressure are common in metabolic syndrome, and their occurrence further enhances the risk. The contribution of metabolic syndrome components to the risk, however, is unbalanced and mainly related to blood pressure and glucose abnormalities.

In the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study, office, home, and ambulatory blood pressure (BP) values were measured contemporaneously between 1990 and 1993 in a large population sample (n=2051). Cardiovascular (CV) and non-CV death certificates were collected over the next 148 months, which allowed us to assess the prognostic value of selective and combined elevation in these 3 BPs over a long follow-up. There were 69 CV and 233 all-cause deaths. Compared with subjects with normal office and 24-hour BP, the hazard ratio for CV death showed a progressive increase in those with a selective office BP elevation (white-coat hypertension), a selective 24-hour BP elevation (masked hypertension), and elevation in both office and 24-hour BP. This was the case also when the above conditions were identified by office versus home BP values. Selective elevation in home versus ambulatory BP or vice versa also carried an increased risk. There was indeed a progressive increase in both CV and all-cause mortality risk from subjects in whom office, home, and ambulatory BP were all normal to those in whom 1, 2, or all 3 BPs were elevated, regardless of which BP was considered. The trends remained significant after adjustment for age and gender, as well as, in most instances, after further adjustment for other cardiovascular risk factors. Thus, white-coat hypertension and masked hypertension, both when identified by office and ambulatory or by office and home BPs, are not prognostically innocent. Indeed, each BP elevation (office, home, or ambulatory) carries an increase in risk mortality that adds to that of the other BP elevations.

Background: Menopause is commonly associated with some blood pressure (BP) rise, but cross-sectional or longitudinal studies completed so far were often too small and were unable to indicate whether this BP increase is really dependent on menopause, or was caused by age or changes in body mass index (BMI)., Methods and Results: The SIMONA study (Study on Hypertension Prevalence in Menopause in the Italian population) was a large cross-sectional study on 18 326 women of age range 46-59 years, consecutively seen by 302 practitioners all over Italy, and representing 60% of the women of that age in the National Health care list of those doctors. BP was measured three times in the seated position by the same automatic machine, and demographic and clinical data were taken. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were slightly but significantly higher in postmenopausal than premenopausal and perimenopausal women, but so were age and BMI. Within seven biannual strata, differences in age and BMI were minimized, but SBP/DBP remained significantly higher (by 3.4/3.1 mmHg) in postmenopausal than in premenopausal subjects in the youngest stratum (46-47 years), and was also significantly higher in the stratum 48-49 years. The differences remained significant after the exclusion of 1809 women with surgical menopause or 695 women with cardiovascular disease. Even when the confounding effects of age, BMI, smoking and contraceptive or replacement therapies were excluded by analysis of covariance, menopause was significantly and positively associated with SBP and DBP (approximately 2 mmHg difference in the age range 46-49 years)., Conclusion: Menopause is associated with a slightly but significantly higher BP, even after adjustment for age and BMI, as well as other confounding factors, but the association is evident only in the younger end of the age range related to menopause.

Alterations in blood glucose and cholesterol are more frequently detectable in hypertensive than in normotensive conditions. However, no information exists as to whether this phenomenon involves only office or also home and 24-hour ambulatory blood pressure (ie, when values are representative of daily life). In 2045 subjects enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, we measured home, 24-hour, and office blood pressure. Measurements also included fasting blood glucose and serum total and HDL cholesterol values. Prevalence of diabetes (> or =126 mg/dL or use of antidiabetic drugs), impaired fasting blood glucose (> or =110 to <126 mg/dL), and hypercholesterolemia (serum total cholesterol > or =240 mg/dL or 200 mg/dL) increased progressively from "optimal" to "normal," "high-normal," and "elevated" office systolic or diastolic blood pressure. Fasting blood glucose and total serum cholesterol also increased progressively from the first to the fourth group, with HDL cholesterol values showing a concomitant progressive decrease. This was also the case for quartiles of office, home, and 24-hour blood pressure. In the whole population, there was a positive correlation between serum cholesterol or blood glucose and all blood pressure values (P always <0.0001), with a much smaller and less consistent relationship with heart rate. In a multivariate analysis that included gender, body mass index, age, and antihypertensive treatment, all blood pressure values remained highly significantly related to values of either metabolic variables. Thus, in the PAMELA population, glucose and lipid values are independently related to blood pressure. This is also the case when daily life blood pressure values are considered.

Background: Studies in hypertensive patients suggest that ambulatory blood pressure (BP) is prognostically superior to office BP. Much less information is available in the general population, however. Obtaining this information was the purpose of the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study., Methods and Results: Office, home, and 24-hour ambulatory BP values were obtained in 2051 subjects between 25 and 74 years of age who were representative of the general population of Monza (Milan, Italy). Subjects were followed up for an average of 131 months, during which time cardiovascular and noncardiovascular fatal events were recorded (n=186). Office, home, and ambulatory BP values showed a significant exponential direct relationship with risk of cardiovascular or all-cause death. The goodness of fit of the relationship was greater for systolic than for diastolic BP and for night than for day BP, but its overall value was not better for home or ambulatory than for office BP. The slope of the relationship, however, was progressively greater from office to home and ambulatory BP. Home and night BP modestly improved the goodness of fit of the risk model when added to office BP., Conclusions: In the PAMELA population, risk of death increased more with a given increase in home or ambulatory than in office BP. The overall ability to predict death, however, was not greater for home and ambulatory than for office BP, although it was somewhat increased by the combination of office and outside-of-office values. Systolic BP was almost invariably superior to diastolic BP, and night BP was superior to day BP.

Background: Attention has recently been directed to a condition termed 'reversed white coat' because of an average 24 h ambulatory blood pressure (BP) uncharacteristically greater than office BP. No data are available, however, on the prevalence of this condition in the general population, as well as on its relationship to BP, age, gender, antihypertensive treatment and cardiac organ damage., Methods: In 3200 individuals (participation rate 64%), randomly selected to be representative of the residents of Monza (Milan, Italy) for sex and decades of age (25 to 74 years), we measured office BP (average of three measurements, sphygmomanometry), ambulatory BP (automatic readings every 20 min, Spacelabs 90207) and left ventricular mass (echocardiography)., Results: A 'reversed white coat' condition (identified when 24-h average ambulatory systolic, diastolic or mean were higher than the corresponding office values) was seen in 15% (diastolic) to 26% (systolic) of the population as a whole. Prevalence was greater (34-40%) when the difference between office and daytime BP was considered but in both instances it remained less than the prevalence of the white-coat phenomenon. A reversed white-coat condition was similarly frequent in males and females and showed a steep reduction with age and increasing office BP values. Prevalence was greater in hypertensive subjects in whom treatment achieved BP control than in untreated or unsatisfactorily treated individuals. Within each quartile of 24-h or office BP, left ventricular mass index adjusted for demographic and biochemical values was similar in reversed white coat versus the remaining subjects. The absence of any association with left ventricular hypertrophy scores against the clinical significance of this phenomenon.

In hypertensive patients, 24-hour blood pressure (BP) variability (V) shows a positive relationship with organ damage, organ damage progression, and cardiovascular morbidity. The clinical relevance of BPV in the population has never been investigated. In a sample of 3200 individuals, randomly selected from the general population of Monza (Milan, Italy), we evaluated BP by an automatic oscillometric device every 20 minutes for 24 hours and left ventricular mass index (LVMI) by echocardiography. In each subject, individual systolic and diastolic BP readings were averaged to obtain a 24-hour mean. Systolic BPV was obtained by calculating (1) the standard deviation of the 24-hour mean, which was taken as the overall BPV, (2) the cyclic components (Fourier spectral analysis) that in the population as a whole explained >95% of the overall BPV, and (3) the fraction of the overall BPV that in each subject was not accounted for by the 2 cyclic components, termed individual residual BPV. A similar procedure was used for diastolic BP and heart rate. Participation rate was 64.1%. Patients receiving antihypertensive therapy (n=403) were excluded from the analysis, which was therefore limited to 1648 participants. In the population as a whole, LVMI significantly related to 24-hour systolic and diastolic BP mean (beta=0.40 and beta=0.37, respectively, P<0.001 for both) but not to the 2 cyclic components that accounted for most of the BPV. On the other hand, the individual residual BPV (which accounts on average for about 50% of overall BPV) showed a significant positive relationship with LVMI (beta =0.38 and beta=0.88 for systolic and diastolic BP, respectively, P<0.05 and P<0.01). No relationship was found between LVMI and heart rate values. These findings provide evidence that there is a relationship between LVMI and 24-hour average BP values in the population. They also provide the first demonstration that in the population there is also a positive independent association between LVMI and BPV. This association, however, can be exclusively seen with the BPV component that has an erratic rather than a cyclic nature.