Progetto Ipertensione Umbria Monitoraggio Ambulatoriale Research Articles

The Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) Study.

The Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) Study is a prospective registry of morbidity and mortality in initially untreated patients with essential hypertension whose initial diagnostic evaluation included 24-hour ambulatory blood pressure (ABP) monitoring according to a standardized protocol. The present article summarizes the main results of the PIUMA Study. The PIUMA Study is conducted in three hospitals in Umbria, Italy. After their initial assessment at entry, patients are followed in the outpatient clinic of the referring hospital and in collaboration with their family doctors. Telephone interviews with patients and meetings with family doctors are periodically conducted to ascertain the incidence of major complications of hypertension. The PIUMA Study gave us a tremendous opportunity to investigate several aspects related to hypertension: 1) cross-sectional studies focused on the association between clinic and 24-hour ABP and organ damage; 2) longitudinal studies focused on the association between 24-hour ABP and hypertensive organ damage at cardiac level and other levels with the subsequent incidence of major cardiovascular events and mortality; 3) longitudinal studies exploring the prognostic impact of other risk factors in hypertensive patients (i.e. diabetes, dyslipidemia, atrial fibrillation, left ventricular dysfunction, etc.). The PIUMA Study provided the first ever evidence of the prognostic value of: 1) 24-hour ambulatory blood pressure monitoring; and 2) regression of echocardiographic left ventricular hypertrophy in hypertensive patients. The PIUMA Registry gave us an enormous opportunity for investigating several pathophysiologic, diagnostic and therapeutic aspects related to management of hypertensive patients. Some of our studies have been mentioned in several hypertension guidelines to support some specific statements.

Cardiovascular Risk Associated With White-Coat Hypertension: Con Side of the Argument.

Cardiovascular Risk Associated With White-Coat Hypertension: Con Side of the Argument.

Interpretation of Ambulatory Blood Pressure Profile: A Practical Approach for Clinicians

One of the first studies that addressed the prognostic value of ambulatory BP in hypertension was carried out by our group in 1994 [5]. We prospectively followed for up to 7.5 years, 1187 subjects with essential hypertension enrolled in the “Progetto Ipertensione Umbria Monitoraggio Ambulatoriale” (PIUMA) who had baseline off-therapy 24-hour noninvasive ABP monitoring. Our study demonstrated that ABP stratifies CV risk in essential hypertension independent of clinic BP and other traditional risk markers including echocardiographic left ventricular (LV) hypertrophy [5].

Response to Morning Surge, Dipping, and Sleep-Time Blood Pressure as Prognostic Markers of Cardiovascular Risk

We apologize to Hermida et al1 for not having appropriately discussed the results of the Monitorizacion Ambulatoria para Prediccion de Eventos Cardiovasculares (MAPEC)2 study. The Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA)3 and the MAPEC study2 differ under several aspects. The MAPEC study is a randomized intervention study that compares 2 different strategies: in 1 strategy, the initial monotherapy is given at bedtime; in the alternative strategy, the initial monotherapy is given in the morning.2 Randomization is stratified by agent given as initial monotherapy. Furthermore, antihypertensive treatment is adjusted not on the basis of clinic blood pressure (BP), but rather on the basis of ambulatory BP monitoring repeated after 3 months and, subsequently, at …

Relationship Between Stroke Subtypes and Morning Surge or Dipping Pattern

HomeHypertensionVol. 61, No. 2Relationship Between Stroke Subtypes and Morning Surge or Dipping Pattern Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBRelationship Between Stroke Subtypes and Morning Surge or Dipping Pattern Miki Hosaka Kei Asayama Yutaka Imai Takayoshi Ohkubo Miki HosakaMiki Hosaka Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan Search for more papers by this author Kei AsayamaKei Asayama Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan, Department of Cardiovascular Diseases Studies Coordinating Centre, Division of Hypertension and Cardiovascular Rehabilitation, University of Leuven, Leuven, Belgium Search for more papers by this author Yutaka ImaiYutaka Imai Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan Search for more papers by this author Takayoshi OhkuboTakayoshi Ohkubo Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan, Department of Health Science, Shiga University of Medical Science, Otsu, Japan Search for more papers by this author Originally published24 Dec 2012https://doi.org/10.1161/HYPERTENSIONAHA.111.00247Hypertension. 2013;61:e21Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2012: Previous Version 1 To the Editor:We read with interest the article by Verdecchia et al1 demonstrating that a blunted morning ambulatory blood pressure surge (MABPS) was an independent predictor of cardiovascular disease in the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study.1 Furthermore, cardiovascular risk was increased in reverse dippers and nondippers.1Kario2 reported that a high MABPS was a risk for stroke in their cohort of elderly hypertensive individuals who were older than those in the PIUMA study (72.2 versus 50.8 years). This might have resulted in the higher threshold of the top decile of MABPS among their patients (55 versus 44 mm Hg). However, Verdecchia et al1 further reported that the risk of cardiovascular events declined with higher levels of MABPS, regardless of age.In the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcome (IDACO; mean age, 53.0 years) study, the top decile of MABPS (≥37.0 mm Hg) was independently associated with cardiovascular risk only when the nocturnal decline of blood pressure was simultaneously included (P=0.01).3 The Ohasama study (mean age, 61.1 years) indicated that nondippers and risers had a significantly higher risk for cerebral infarction compared with dippers and extreme dippers (relative hazard, 1.59; P=0.04). An MABPS was not associated with cerebral infarction (P for trend=0.94), whereas an MABPS and a large nocturnal decline in blood pressure were associated with cerebral hemorrhage (P≤0.04), and the threshold for a high MABPS was similar to that in the PIUMA study (25.0 versus 27.5 mm Hg).4Exaggerated MABPS is likely to be a risk for cardiovascular disease in a specific population, but not in the general population. Nevertheless, the associations of each stroke subtype with MABPS or dipping pattern would be different. Therefore, we would like to understand the association of stroke subtypes with MABPS and the dipping pattern among the PIUMA patients. We would also like to know the association between cardiovascular risk and MABPS when the degree of nocturnal decline in blood pressure is simultaneously included as in the IDACO stuy.Miki HosakaDepartment of Planning for Drug Developmentand Clinical EvaluationTohoku University Graduate School of Pharmaceutical SciencesSendai, JapanKei AsayamaDepartment of Planning for Drug Developmentand Clinical EvaluationTohoku University Graduate School of Pharmaceutical SciencesSendai, JapanDepartment of Cardiovascular Diseases Studies Coordinating CentreDivision of Hypertension and Cardiovascular RehabilitationUniversity of LeuvenLeuven, BelgiumYutaka ImaiDepartment of Planning for Drug Developmentand Clinical EvaluationTohoku University Graduate School of Pharmaceutical SciencesSendai, JapanTakayoshi OhkuboDepartment of Planning for Drug Developmentand Clinical EvaluationTohoku University Graduate School of Pharmaceutical SciencesSendai, JapanDepartment of Health ScienceShiga University of Medical ScienceOtsu, JapanDisclosuresNone.FootnotesLetters to the Editor will be published, if suitable, as space permits. They should not exceed 500 words (typed double-spaced) plus 5 references in length and may be subject to editing or abridgment.

Echocardiographic left ventricular hypertrophy

Echocardiographic left ventricular hypertrophy

Clinical Implications

We apologize to Hermida et al1 for not having appropriately discussed the results of the Monitorizacion Ambulatoria para Prediccion de Eventos Cardiovasculares (MAPEC)2 study. The Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA)3 and the MAPEC study2 differ under several aspects. The MAPEC study is a randomized intervention study that compares 2 different strategies: in 1 strategy, the initial monotherapy is given at bedtime; in the alternative strategy, the initial monotherapy is given in the morning.2 Randomization is stratified by agent given as initial monotherapy. Furthermore, antihypertensive treatment is adjusted not on the basis of clinic blood pressure (BP), but rather on the basis of ambulatory BP monitoring repeated after 3 months and, subsequently, at …

Is Vascular Morning Blood Pressure Surge in the Elderly Resistant to Antihypertensives and More Risky?

To the Editor: I have read the recent article on morning surge in blood pressure (BP; MSBP) in the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) Study.1 Surprisingly, the suppressed MSBP was a risk factor for poor long-term prognosis of cardiovascular disease (CVD) in hypertensives. In previous studies, including our Jichi Medical University Ambulatory Blood Pressure Monitoring (JMUABPM) Study and the International Database of Ambulatory Blood Pressure in Relation to Cardiovascular Outcome, exaggerated MSBP was found to be an independent risk factor of CVD.2,3 Why were these results so different? I would like to address this question from 3 standpoints. ### Elderly MSBP MSBP may be more risky in elderly than in younger individuals (Table). The mean age of …

Electrocardiographic abnormalities of left ventricular repolarization: Prognostic implications in hypertensive post-menopausal women

Background Although repolarization abnormalities on ECG are frequent in post-menopausal hypertensive women, their prognostic value in these women is uncertain. Methods We analyzed 908 hypertensive post-menopausal women consecutively included in the PIUMA (Progetto Ipertensione Umbria Monitoraggio Ambulatoriale) study. The median duration of follow-up was 8.6 years (range: 1–21). All women were untreated at entry. Drug treatment during follow-up was adjusted to single individuals. Standard 12-lead ECG was carried out at entry. The Minnesota Coding was used to define minor and major (“typical strain”) repolarization abnormalities. Design prospective observational study in essential hypertension. Results Mean age at entry was 60 years. At baseline, ECG was normal in 707 women, minor ST-T changes were noted in 152 women, and a typical strain pattern was present in 49 subjects. Predictors of typical strain were age, diabetes and systolic blood pressure (BP). During follow-up there were 119 new cardiovascular (CV) events and 75 all-cause deaths. Typical strain was associated with a threefold higher risk of CV disease (HR: 3.16; 95% CI: 1.59–6.31; p = 0.001) after adjustment for the significant influence of age, diabetes, serum creatinine, systolic BP and HDL-cholesterol. Women with minor LV repolarization abnormalities showed a non-significant excess risk of CV disease when compared with women with normal LV repolarization (HR: 1.25; 95% CI: 0.69–2.26; p = 0.467). Similar results were obtained for all-cause mortality. Conclusions Typical strain pattern, an easily detectable marker of altered LV repolarization, identifies post-menopausal hypertensive women at increased risk of CV disease and all-cause mortality.

Neutrophil Count for the Identification of Postmenopausal Hypertensive Women at Increased Cardiovascular Risk

High white blood cell and neutrophil counts identify patients at increased cardiovascular risk in various clinical settings. However, the prognostic value of white blood cell and neutrophil counts in hypertensive postmenopausal women is unknown. We tested the independent prognostic value of total white blood cell and neutrophil counts for cardiovascular events in hypertensive postmenopausal women. We examined 298 initially untreated postmenopausal women with essential hypertension who were part of Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA). Mean duration of follow-up was 8 years (range 1-20 years). Treatment was tailored to each individual. Mean age at entry was 59 years. Diabetic women comprised 9.1% of the group, and current smokers comprised 17.5% of the group. During follow-up, 31 new major cardiovascular events occurred. In univariable analyses, age, diabetes, serum creatinine, blood pressure, left ventricular hypertrophy, and neutrophil count showed an association with the risk of events (all P<.05). In a multivariable Cox analysis, after adjustment for traditional cardiovascular risk factors, for each 1.25x10 (1 standard deviation) increase in neutrophil count there was a 67% higher risk of cardiovascular events (hazard ratio 1.67, 95% confidence interval 1.32-2.07; P<.001). Furthermore, neutrophil count showed robust incremental predictive value for cardiovascular events, in addition to traditional risk factors. Total white blood cell count did not show any association with cardiovascular events. A high peripheral neutrophil count identifies postmenopausal hypertensive women at increased risk of cardiovascular disease. Such relation appears to be independent of traditional risk factors. III.

The emerging role of high-density lipoprotein cholesterol in hypertension trials

Population Health Research Institute,McMaster University, Hamilton Health Sciences, Hamilton, CanadaCorrespondence to Fabio Angeli, MD, Department of Cardiology, ClinicalResearch Unit ‘Preventive Cardiology’, Hospital Santa Maria della Misericordia,06156 Perugia, ItalyTel: +39 075 5782213; fax: +39 075 5782214; e-mail: fangeli@cardionet.it

Office and out of office heart rate measurements: which clinical value?

Office and out of office heart rate measurements: which clinical value?

The Clinical Significance of New-Onset Diabetes Mellitus in Hypertension

Several intervention trials found that some antihypertensive drugs, mostly ACE inhibitors, calcium-channel blockers and angiotensin II receptor blockers, are associated to a lesser risk of developing diabetes mellitus in comparison with other drug classes, including diuretics and β-blockers. This finding is clinically relevant because it has been demonstrated that patients who develop new-onset diabetes during therapy rapidly become a high-risk population, not dissimilar from patients with prior diagnosis of diabetes. In a recent analysis of the PIUMA (Progetto Ipertensione Umbria Monitoraggio Ambulatoriale) study, pre-treatment glucose levels and use of diuretic drugs were independent predictors of new-onset diabetes. Although there is some controversy on this topic, prevention of new-onset diabetes could contribute to explain at least part of the benefit attributed to ACE inhibitors, calcium-channel blockers and angiotensin II receptor blockers in some intervention trials. In clinical practice, when faced with subjects at high risk of diabetes, it is important to implement nonpharmacological strategies whenever appropriate (diet, physical activity, weight loss). In these subjects, ACE inhibitors, calcium-channel blockers and angiotensin II receptor blockers could be considered first-line drugs.

Why Is Nondipping in Ambulatory Blood Pressure Monitoring Not Prognostic in Poor Sleepers?

To the Editor: In another analysis of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale cohort, Verdecchia et al1 demonstrated that nighttime blood pressure (BP) was higher in poor sleepers and that, in this subset of participants, the incidence of cardiovascular events did not differ between dippers and nondippers. Poor sleep quality was a plausible reason presented by the authors …

Estimate of white-coat effect and arterial stiffness

Blood pressure (BP) measured in the office is usually higher than the average ambulatory BP, a difference generally taken as an estimate of the white-coat effect. This study was designed to assess whether such a difference is associated with impairment of the conduit arterial system. We calculated the difference between office and average daytime peak systolic blood pressure (DeltaSBP) in 2778 hypertensive participants (1240 women) of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale cohort. Arterial stiffness was evaluated using an adjusted office pulse pressure to stroke volume ratio (PP/SV), measured at rest, which has previously been shown to predict cardiovascular outcome independent of echocardiographic left ventricular hypertrophy. Effective arterial elastance was also estimated. Across quintiles of PP/SV, significant linear, positive trends were found with age, the proportion of women, plasma glucose and triglyceride levels (0.05 > P < 0.0001). Heart rate measured in the office increased mildly with quintiles of PP/SV (P < 0.05). After adjusting for age, sex, body weight and office heart rate, DeltaSBP progressively increased with increasing quintiles of PP/SV (P for trend < 0.0001), whereas stroke volume decreased, paralleling the increase in left ventricular relative wall thickness (both P < 0.0001) and left ventricular mass index (P < 0.05). The significant increase in effective arterial elastance with quintiles of PP/SV was also independent of peak systolic BP, in addition to age, sex, heart rate and body weight. The difference between office BP and ambulatory BP, an estimate of the white-coat effect, is strongly associated with increased arterial stiffness, evaluated by a two-element fluid system accumulator.

Prognostic Value of Elevated White Blood Cell Count in Hypertension

Chronic low-grade inflammation may contribute to vascular injury and atherogenesis, and has been described in association to high blood pressure (BP). However, as yet the prognostic significance of white blood cell (WBC) count in the setting of uncomplicated hypertension has not been investigated. In the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study, 1617 white patients with essential hypertension (aged 49 +/- 12 years, 55% men) without prevalent cardiovascular or renal disease underwent off-treatment baseline clinical evaluation and were then followed up for 11 years (average 4.9 years). The WBC count had a direct association with smoking status, serum triglycerides, body mass index, and 24-h BP, and an inverse one with age (all P < .05). During follow-up, 146 patients developed a major fatal or nonfatal cardiovascular event (1.9 events per 100 patient-years). Patients who will develop a cardiovascular event had a higher WBC count (7.08 +/- 1.6 v 6.68 +/- 1.6 x 10(9) cells/L, P = .004). Event rate increased progressively from the first to the fourth quartile of WBC count distribution (1.2, 1.8, 1.9, and 2.3 events per 100 patient-years; P < .01 by log-rank test). After adjustment (Cox model) for the effect of age, gender, diabetes, serum cholesterol, glomerular filtration rate, smoking, left ventricular hypertrophy, and 24-h systolic BP, cardiovascular event risk increased by 24% (95% confidence interval +4% to +48%; P = .019) for each 2 x 10(9) cells/L increase in WBC. After adjustment for average 24-h BP, established risk factors and target organ damage, an elevated WBC count remains an independent predictor of cardiovascular morbidity in hypertensive patients.

Regression of left ventricular hypertroiphy and risk of stroke in hypertension

Left ventricular hypertrophy (LVH) is a risk marker for stroke and LVH regression confers protection from a composite of cardiovascular events. It is unknown whether LVH regression confers specific protection from stroke independently of ambulatory blood pressure (BP). In the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale study, 880 initially untreated hypertensive subjects (mean age 48, office BP 155/98 mmHg; 24-h ambulatory BP 137/87 mmHg) underwent diagnostic tests including echocardiography and 24-h ambulatory BP monitoring at entry and after a median of 3.5 years, still in the absence of cardiovascular events. Months or years after the follow-up study, 34 of these subjects developed a first cerebrovascular event (stroke in 21, transient ischemic in 13). Event rate (x 100 patients per year) was 0.25 among the subjects who never developed echocardiographic LVH or with regression of LVH, Vs 1,16 among the subjects with lack of regression or new development of LVH (log-rank test: p = 0.00001). The serial changes in the electrocardiographic features of LVH failed to define subgroups at different risk. In a Cox analysis, the risk of cerebrovascular events was 2.8 times higher (95% CI: 1-18-6.69) in the subset with lack of regression or new development of LVH than in that with LVH regression or persistently normal LV mass. Such effect was independent of age (p=0.001) and 24-h systolic BP (p=0.003) (figure). In conclusion, regression of LVH by itself confers an improvement in risk for cerebrovascular complications in hypertensive patients. Such effect is independent of ambulatory BP and other individual risk factors. Open in new tabDownload slide

Does the reduction in systolic blood pressure alone explain the regression of left ventricular hypertrophy?

Systolic blood pressure (SBP) is an important determinant of the development and regression of left ventricular hypertrophy (LVH) in hypertensive humans. However, comparative assessments with other BP components are scarce and generally limited in size. As part of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA), 743 hypertensive subjects underwent echocardiography and 24-h ambulatory BP monitoring before and after an average of 3.9 years of treatment. The changes in left ventricular mass showed a significant direct association with the changes in 24-h SBP (r=0.40), diastolic blood pressure (DBP) (r=0.33) and pulse pressure (PP) (r=0.35). Weaker associations were found with the changes in clinic BP (r=0.32, 0.31 and 0.16, respectively). In a multivariate linear regression analysis, the changes in 24-h SBP were the sole independent determinants of the changes in left ventricular mass (LVM) according to the following equation: percentage changes in LVM=0.73 x (percentage changes in 24-h SBP) -0.48 (P<0.0001). For any given reduction in 24-h SBP, the reduction in LVM did not show any association with the changes in DBP and PP, either clinic or ambulatory. These data indicate that SBP is the principal determinant of LVH regression in hypertensive humans.

Asymptomatic left ventricular dysfunction: a potent predictor of cardiac complications in hypertension

OR-61 Key Words: Systolic Dysfunction, Left Ventricular Hypertrophy, Prognosis

Prognostic value of treatment-induced changes in twenty-four-hour mean and pulse pressures in adult hypertensive patients

Antihypertensive therapy may lead to a decrease in pulse pressure (PP), which does not necessarily parallel that of systolic and diastolic blood pressure (BP).1 A spontaneous increase in PP over time has been associated with subsequent cardiovascular events.2,3 However, the prognostic benefits of treatment-induced PP reduction compared with the reduction in steady BP components (systolic, diastolic, and mean) remain to be determined in prospective outcome studies. In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study,4,5 we undertook the present analysis to assess the prognostic significance of changes in PP and mean BP induced by antihypertensive treatment in subjects who attended the pretreatment and follow-up visits and were free of cardiovascular disease. We measured 24-hour ambulatory BP, which is superior to office BP for cardiovascular risk stratification in subjects with essential hypertension.4,6,7 In particular, ambulatory PP is a stronger risk marker than office PP.7