Roberto Sega

Prognostic Value of Ambulatory and Home Blood Pressures Compared With Office Blood Pressure in the General Population Follow-Up Results From the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) Study

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.

Long-Term Risk of Mortality Associated With Selective and Combined Elevation in Office, Home, and Ambulatory Blood Pressure

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.

Ambulatory blood pressure normality : results from the PAMELA study

Objective To determine ambulatory and home blood pressure means and distributions in relation to clinic blood pressure in a general population. Methods We obtained a random sample of 2400 subjects stratified by sex and 10 year age groups to be representative of residents aged 25–64 years of the city of Monza. Participation rate was 69% (1651 subjects). Blood pressure measurements consisted of clinic blood pressure (average of three measurements, sphygmomanometry), home blood pressure (average of morning and evening measurements, semiautomatic device) and ambulatory blood pressure (automatic readings at 20 min intervals, Space labs 90207). Clinic blood pressure was obtained both before and after home and ambulatory blood pressures. Data analysis did not include 213 subjects receiving antihypertensive drug treatment and was therefore limited to 1438 participants. Results: In the 1438 subjects, clinic, home and ambulatory blood pressure showed a normal-like distribution, with a taller peak and a narrower base for ambulatory than for home and clinic values. Clinic, home and ambulatory blood pressures were significantly related to each other (P always < 0.001). The means of the two clinic blood pressures obtained on consecutive days were superimposable (127.4 ± 17.0/82.3 ± 9.8 and 128.2 ± 16.5/81.9 ± 9.9 mmHg) and both were markedly higher than home and 24 h average blood pressures (8.2 mmHg), which were similar to one another. The differences between clinic and home or 24 h average blood pressure were similar in both sexes but increased with increasing age and clinic blood pressure values. The influence of clinic blood pressure values on the clinic-ambulatory or clinic–home blood pressure differences was more important than age. Although higher than the 24 h average value, daytime average blood pressure was also lower than clinic blood pressure. Night-time blood pressure was markedly lower than the daytime value in both sexes and at all ages. Conclusion Data from a large and unbiased sample of a general population show that home and 24 h or daytime average blood pressures are much lower than clinic blood pressure. The relatively close correlation between blood pressure values measured with the different methods used has allowed calculation of home and ambulatory blood pressure values corresponding to the accepted upper limit of normality of clinic blood pressure (140/90 mmHg). The upper limit of normality for the population was for both home and ambulatory blood pressures in the range 120–130 and 75–81 mmHg for systolic and diastolic values, respectively, with slight differences depending on sex and age. Taking 140/90 mmHg as the upper normal limit of the population is therefore an error that leads to individuals whose home or ambulatory blood pressures are high being considered as normotensive.

Blood-pressure control in the hypertensive population

BACKGROUND In large-scale surveys of individuals with hypertension those whose clinic blood pressure is reduced to 140/90 mm Hg or less have been found to represent only a small fraction of the hypertensive population. We assessed whether these results arise because of a white-coat effect elevating clinic blood pressure. METHODS We randomly selected 2400 individuals from the town of Monza, Italy, and invited them to take part in our study. We measured clinic blood pressure as well as home (morning and evening measurements), and 24 h ambulatory blood pressure-ie, blood pressures largely devoid of a white-coat effect. Based on clinic blood pressure participants were then classified as normotensive, untreated hypertensive (clinic blood pressure > 140 mm Hg systolic and/or > 90 mm Hg diastolic), or treated hypertensive (having antihypertensive treatment). The mean blood pressures for each group were calculated. FINDINGS 1651 people took part in the study. The clinic blood pressure of treated hypertensives (n = 207; 146.9 [SD 18] mm Hg/90.2 [8.6] mm Hg) was only slightly less than in untreated hypertensives (n = 402; 148 [15.2] mm Hg/93.3 [8] mm Hg) and in both groups the blood pressure values were much greater than those of normotensive individuals (n = 1042; 119.5 [10.3] mm Hg/78.1 [6.6] mm Hg) p < 0.001. Averaged home and 24 h blood pressures were lower than clinic blood pressures but similarly higher in untreated and treated hypertensive individuals when compared with normotensive individuals. This was also the case for day and night average blood pressures. The number of treated hypertensive patients found to have blood pressures within the normal limits was small not only when based on clinic blood pressure values but also when based on ambulatory blood-pressure values. INTERPRETATION In the hypertensive population the number of patients with inadequate blood-pressure control is high not only when assessed in the clinic but also when assessed by ambulatory-blood-pressure monitoring or at home. The high blood-pressure values commonly found in treated hypertensive individuals cannot be accounted for by a white-coat effect but by a true lack of daily-life blood-pressure control.

Long-Term Prognostic Value of Blood Pressure Variability in the General Population. Results of the Pressioni Arteriose Monitorate e Loro Associazioni Study

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 (&bgr; coefficient=−0.040; P<0.02) and showed a significant positive relationship with residual diastolic blood pressure variability (&bgr; 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.

Metabolic Syndrome in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) Study: Daily Life Blood Pressure, Cardiac Damage, and Prognosis

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.

Long-Term Risk of Sustained Hypertension in White-Coat or Masked Hypertension

It is debated whether white-coat (WCHT) and masked hypertension (MHT) are at greater risk of developing a sustained hypertensive state (SHT). In 1412 subjects of the Pressioni Arteriose Monitorate e Loro Associazioni Study, we measured office blood pressure (BP), 24-hour ambulatory BP, and home BP. The condition of WCHT was identified as office BP >140/90 mm Hg and 24-hour BP mean <125/79 mm Hg or home BP <132/82 mm Hg. Corresponding values for MHT diagnosis were office BP <140/90 mm Hg, 24-hour BP ≥125/79 mm Hg, and home BP ≥132/82 mm Hg. SHT was identified when both office and 24-hour BP means or home BP were over threshold values and normotension was under the threshold value. Subjects were reassessed 10 years later to evaluate the BP status of the various conditions defined previously. At the first examination, 758 (54.1%), 225 (16.1%), 124 (8.9%), and 293 (20.9%) subjects were normotensive, WCHT, MHT, and SHT subjects, respectively. At the second examination, 136 normotensives (18.2%), 95 WCHT (42.6%), and 56 MHT (47.1%) subjects became SHT. As compared with normotensives, adjusting for age and sex, the risk of becoming SHT was significantly higher for WCHT and MHT subjects (odds ratio: 2.51 and 1.78, respectively; P<0.0001). Similar results were obtained when the definition of the various conditions was based on home BP. Independent contributors of worsening of hypertension status were not only baseline BP, but also, although to a lesser extent, metabolic variables and age. Subjects with WCHT and MHT are at increased risk of developing SHT. This may contribute to their prognosis that appears to be worse as compared with that of normotensive subjects.

Ambulatory and Home Blood Pressure Normality in the Elderly Data From the PAMELA Population

To determine ambulatory blood pressure (BP) means and distributions in an elderly population, we studied a random sample of 800 subjects stratified by sex and representative of residents aged 65 to 74 years of the city of Monza. Participation was 50%. Measurements consisted of clinic BP (average of three measurements with mercury sphygmomanometry), home BP (average of morning and evening measurements with a semiautomatic device), and ambulatory BP (SpaceLabs 90207). Clinic BP was obtained before and after home and ambulatory BP measurements. In normotensive and untreated hypertensive subjects (n=248), clinic, home, and ambulatory BPs were significantly related (P<.001). The means of the clinic BPs obtained on consecutive days were very similar and markedly higher than 24-hour average BP (+25 mm Hg systolic and + 10 mm Hg diastolic, P<.001). Nighttime BP was markedly less than daytime BP (-14 and -13 mm Hg, P<.001), whereas home BP values occurred approximately midway between clinic and 24-hour average BP values. Only minor differences existed between data in men and women, and the differences in clinic, home, and ambulatory BP values occurred in both normotensive and untreated hypertensive subjects. All BPs were similar in the untreated and treated hypertensive groups. Thus, as previously reported in subjects younger than 65 years, in the elderly fraction of the population, 24-hour average BP is much lower than clinic BP. The upper limit of normality for 24-hour average BP (calculated as the value corresponding to 140/90 mm Hg clinic BP) is about 120 mm Hg systolic and 76 mm Hg diastolic. At variance with data from younger subjects, home BP in the elderly is higher than 24-hour average BP. However, similar to data from younger subjects, clinic, home, and ambulatory BPs are higher in treated hypertensive than normotensive elderly subjects, indicating that in hypertensive elderly subjects, antihypertensive treatment does not commonly achieve full BP control both inside and outside the clinic environment.

Left ventricular hypertrophy increases cardiovascular risk independently of in-office and out-of-office blood pressure values

Objectives Previous studies have shown that left ventricular hypertrophy (LVH) represents a cardiovascular risk factor independently of clinic blood pressure (BP). The present study was aimed at determining the impact of LVH on the incidence of cardiovascular morbid and fatal events taking into account not only classical risk factors but also home and ambulatory BP values, which have been shown to have an important independent prognostic impact. Methods In 1716 patients belonging to the ‘Pressioni Arteriose Monitorate E Loro Associazioni’ population of Monza, we quantified left ventricular mass index and identified LVH by standard cutoff values. We also measured clinic, home and 24-h ambulatory BPs together with serum glucose and lipids. Results During a follow-up of 148 months, the rate of fatal and nonfatal (hospitalizations) cardiovascular events as well as of all-cause death was markedly greater (four-fold to five-fold) in patients as compared with those without LVH. In LVH individuals, the increased risk remained significant even when data were adjusted for a large number of other confounding factors including home BP, 24-h mean BP and ambulatory BP. Results were similar when left ventricular mass was indexed by height and body surface area. A 10% increase in left ventricular mass index was associated with a significant increase in cardiovascular risk or all-cause deaths. In multivariate analysis, left ventricular mass index was always an independent predictor of cardiovascular events and death for any cause. Conclusion Our data provide evidence that LVH is an important risk factor even when the contribution of different BPs to risk is fully taken into account.

HIV and metabolic syndrome - A comparison with the general population

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.