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International audience; Aortic valve stenosis (AS) shares similarities with the atherosclerotic process but little is known about the effect of the mechanical properties of large arteries on outcome in patients with AS. The aims of this study were (1) to determine the relationship between indexes of carotid stiffness/compliance and the severity of AS and (2) to identify whether local arterial stiffness is independently associated with mortality. 133 patients with moderate to severe isolated AS and preserved LV ejection fraction (LVEF) were included. All underwent transthoracic echocardiography and local carotid stiffness evaluation by means of high-definition echo-tracking ultrasound with the calculation of stiffness/compliance parameters included augmentation index (AIx). None of the carotid stiffness parameters were significantly associated with AS severity parameters. During a mean follow-up of 51.6 ± 39.4 months, 70 patients received aortic valve replacement, 45 died and 18 were alive with no surgery. Who died were older (79.2 ± 6.9 vs. 73 ± 8.8 years, p < 0.0001), had higher carotid AIx (21.3 ± 14 vs. 16 ± 12%, p = 0.028). In multivariate Cox regression analysis AIx was independently associated with mortality (HR 1.048, 95% CI 1.01-1.07, p = 0.001), also after inclusion of age and creatinine. There was a significant association between the level of AIx and mortality in those patients who did not have surgery (p = 0.016). In severe AS and a normal LVEF, carotid AIx measured by echo-tracking system was independently associated with death. No relationship between AS severity and local carotid stiffness was found. These data emphasize the importance of arterial stiffness has a hallmark of long-term atherosclerotic burden and impaired prognosis.

Since 1989, SIC Sport and a FMSI, in partnership with leading Italian Cardiological Scientific Associations (ANCE, ANMCO and SIC) have produced Cardiological Guidelines for Completive Sports Eligibility for athletes with heart disease (COCIS -- 1989, 1995, 2003, 2009 and 2017). The English version of the Italian Cardiological Guidelines for Competitive Sports Eligibility for athletes with heart disease was published in 2013 in this Journal. This publication is an update with respect to the document previously published in English in 2013. It includes the principal innovations that have emerged over recent years, and is divided into five main chapters: arrhythmias, ion channel disorders, congenital heart diseases, acquired valve diseases, cardiomyopathies, myocarditis and pericarditis and ischemic heart disease. Wherever no new data have been introduced with respect to the 2013 publication, please refer to the previous version. This document is intended to complement recent European and American guidelines but an important difference should be noted. The European and American guidelines indicate good practice for people engaging in physical activity at various levels, not only at the competitive level. In contrast, the COCIS guidelines refer specifically to competitive athletes in various sports including those with high cardiovascular stress. This explains why Italian guidelines are more restrictive than European and USA ones. COCIS guidelines address 'sports doctors' who, in Italy, must certify fitness to participate in competitive sports. In Italy, this certificate is essential for participating in any competition.

Background Whether blood pressure variability (BPV) measured with ambulatory monitoring (short-term BPV) or computed from office visits (long-term BPV) are related to each other and carry similar prognostic information is not well known. We investigated the independent determinants of short-term and long-term BPVs and their predictive capacity for the development of major adverse cardiovascular and renal events (MACEs) in a cohort of young hypertensive participants. Methods Long-term BPV was calculated as visit-to-visit SD and average real variability from office blood pressure (BP) measured during 7 visits, within 1 year. Short-term BPV was calculated as weighted 24-hour SD and coefficient of variation. Hazard ratios (HRs) for risk of MACE were computed from multivariable Cox regressions. Results 1,167 participants were examined; mean age was 33.1 ± 8.5 years. Variables independently associated with 24-hour systolic SD were 24-hour systolic BP, low physical activity, smoking, baseline office pulse pressure, systolic BP dipping, and diastolic white coat effect, while those associated with long-term BPV were mean systolic BP, age, female gender, and baseline office heart rate. During a median follow-up of 17.4 years 75 MACEs occurred. In Cox analysis only short-term BPV resulted a significant predictor of MACE (HR, 1.31 (1.07–1.59); P = 0.0086), while no index of long-term BPV was independently associated with outcome. Conclusions In young hypertensive subjects only short-term BPV resulted a significant predictor of MACE on top of traditional ambulatory BP monitoring parameters. Whether reduction of short-term BPV with therapy may reduce the cardiovascular risk independently from the effects on 24-hour BP is a matter for future research.

The clinical significance of isolated systolic hypertension (ISH) in youth is controversial. One main confounding factor is the strong white-coat effect often observed in ISH patients. The aim of this study was to investigate the risk of hypertension needing pharmacological treatment in ISH identified with ambulatory 24-h blood pressure (24-h BP).We examined 1206, 18-45-year-old participants from the Hypertension and Ambulatory Recording VEnetia STudy. Based on 24-h BP, 269 participants were normotensive, 209 had ISH, 277 had isolated diastolic hypertension, and 451 had systolic-diastolic hypertension. The predictive role of ISH for incident hypertension was evaluated in Cox survival analyses, adjusting for risk factors and confounders.ISH participants were more frequently young men active in sports, with lower heart rate and cholesterol. During a 6.9-year follow-up, 61.1% of participants developed hypertension. ISH participants had a nonsignificant increase in risk of hypertension compared with normotensive (reference group). In contrast, participants with diastolic hypertension (1.44; 1.13-1.85) or systolic-diastolic hypertension (2.04; 1.59-2.64) had a significant increase in risk. When the ISH participants were divided according to whether 24-h mean BP was normal (97 mmHg) or high, ISH patients with normal mean BP had no increase in risk (1.01; 0.73-1.40), whereas those with high mean BP had a significant increase in risk (1.70; 1.16-2.49).These data obtained with ambulatory BP monitoring show that in ISH people younger than 45 years, only mean BP is a predictor of future hypertension needing treatment, whereas the ISH status per se does not necessarily imply an increase in risk.

Objective The association of serum uric acid (SUA) with risk of hypertension is controversial and may be modulated by lifestyle factors. We did a prospective study to investigate whether SUA was an independent predictor of hypertension in the young and whether physical activity influences this association. Methods The study was conducted in a cohort of 1156 young to middle-age participants screened for stage 1 hypertension and followed for a median of 11.4 years. In multivariable Cox analyses, participants were stratified by tertiles of uric acid and physical activity habits. Results At follow-up end, 63.3% of the study participants developed hypertension needing treatment. In the whole group, SUA was an independent predictor of future hypertension (P = 0.005). Participants with SUA more than 5.60 mg/dl (top tertile) had a 31% increase in risk compared with those of the bottom tertile. However, the risk of hypertension related to SUA was increased only among the sedentary participants with a hazard ratio of 1.44 (95% confidence interval, 1.11-1.88) for the participants of the top SUA tertile. In contrast, among the active participants no association was found between SUA and risk of hypertension. Alcohol intake was another modulator of the SUA-hypertension relationship (hazard ratio, 95% confidence interval: 1.38, 1.02-1.87). Plasma renin activity, office and ambulatory heart rates, and metabolic variables were proportional to SUA level and were lower in active than sedentary participants. Conclusion These data confirm that SUA is a predictor of hypertension and suggest that exercise may counteract the pathophysiological mechanisms involved in the association between hyperuricemia and future hypertension.

The association of short-term blood pressure (BP) variability (BPV) with cardiovascular events (CVEs) is controversial. Aim of this study was to investigate whether BPV measured as weighted 24-h SD was associated with CVE in a prospective cohort study of young patients screened for stage 1 hypertension.We performed 24-h ambulatory BP monitoring in 1206 participants aged 33.1 ± 8.5 years, untreated at baseline examination. Participants were divided into two categories with low (12.8 mmHg) or high (≥12.8 mmHg) SBPV. Hazard ratios for CVE associated with BPV expressed either as continuous or categorical variable were computed from multivariable Cox models.During 15.4 ± 7.4 years of follow-up there were 69 fatal and nonfatal CVE. In multivariable Cox models, high SBPV was an independent predictors of CVE [2.75 (1.65-4.58); P = 0.0001] and of coronary events [3.84 (2.01-7.35), P 0.0001]. Inclusion in the model of development of hypertension requiring treatment during the follow-up, did not reduce the strength of the associations. Addition of SBPV to fully adjusted models had significant impact on risk reclassification and integrated discrimination (relative integrated discrimination improvement for BPV as continuous variable: 13.5%, P = 0.045, and for BPV as categorical variable: 26.6%, P = 0.001). When the coefficient of variation was used as BPV metric similar results were obtained. Of note, in all Cox models average 24-h BP was no longer an independent predictor of outcome after BPV was included.Short-term BPV adds to the risk stratification for cardiovascular events in young-to-middle-age patients screened for stage 1 hypertension over and above traditional 24-h ambulatory monitoring indexes.

Background : Takotsubo cardiomyopathy (TTC) is characterized by reversible left ventricular dysfunction, frequently precipitated by a stressful event. Despite the favorable course and good long-term prognosis, a variety of complications may occur in the acute phase of the disease. The aim of this study was to evaluate the in-hospital and long-term outcomes of a cohort of TTC patients. Methods : Fifty-five patients (mean age 68.1±12 years) were prospectively followed for a mean of 69.6±32.2 months (64,635 days). In-hospital (death, heart failure, arrhythmias) and long-term events (death and recurrences) were recorded. Results : Patients were predominantly women (87.3%) who experienced a recent stressful event (emotional or physical) and were admitted to hospital for chest pain. Eleven patients (20%) had a diagnosis of depressive disorder, and arterial hypertension was the most frequent cardiovascular risk factor. The ECG revealed ST-segment elevation in 43.6% of patients. At angiography, seven cases (12.7%) had at least one significant (≥50%) coronary artery stenosis and four patients (7.3%) had myocardial bridging of the left anterior descending artery. During hospitalization, three patients died (one from cardiac causes) and cardiovascular complications occurred in 12 patients. During follow-up, five patients died (none from cardiac causes), six patients had recurrences within the first year. Two patients had two recurrences: one after 114 days, triggered by an asthma attack as the first event, and the other after 1,850 days. Conclusions : In TTC patients, in-hospital and long-term mortality is primarily due to non-cardiovascular causes. Recurrences are not infrequent and coronary artery disease is not an uncommon finding. Keywords: coronary artery disease; follow-up study; recurrence; Takotsubo cardiomyopathy (Published: 6 July 2016) Citation: Journal of Community Hospital Internal Medicine Perspectives 2016, 6 : 31082 - http://dx.doi.org/10.3402/jchimp.v6.31082

Several studies have shown that the augmentation index (AIx) is negatively correlated with heart rate (HR). This led some authors to claim that the use of HR-lowering drugs may be detrimental in hypertension. The aim of this study was to assess the longitudinal and cross-sectional relationships of HR with AIx and central blood pressure (BP) in 346 subjects from the HARVEST (mean age 30.7 ± 8.5 years). At baseline, HR was measured with 24-h ambulatory recording. Central hemodynamics were evaluated with Specaway DAT system after a median of 8.0 years from baseline. In multivariate linear regression analyses, AIx and central systolic BP were used as dependent variables and night-time HR or office HR as predictors adjusting for several risk factors and confounders. In fully adjusted models, baseline night-time HR was a significant positive predictor of AIx (p

Summary Background Myocardial injury after non-cardiac surgery (MINS) increases the risk of cardiovascular events and deaths, which anticoagulation therapy could prevent. Dabigatran prevents perioperative venous thromboembolism, but whether this drug can prevent a broader range of vascular complications in patients with MINS is unknown. The MANAGE trial assessed the potential of dabigatran to prevent major vascular complications among such patients. Methods In this international, randomised, placebo-controlled trial, we recruited patients from 84 hospitals in 19 countries. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS. Patients were randomly assigned (1:1) to receive dabigatran 110 mg orally twice daily or matched placebo for a maximum of 2 years or until termination of the trial and, using a partial 2-by-2 factorial design, patients not taking a proton-pump inhibitor were also randomly assigned (1:1) to omeprazole 20 mg once daily, for which results will be reported elsewhere, or matched placebo to measure its effect on major upper gastrointestinal complications. Research personnel randomised patients through a central 24 h computerised randomisation system using block randomisation, stratified by centre. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary efficacy outcome was the occurrence of a major vascular complication, a composite of vascular mortality and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism. The primary safety outcome was a composite of life-threatening, major, and critical organ bleeding. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01661101. Findings Between Jan 10, 2013, and July 17, 2017, we randomly assigned 1754 patients to receive dabigatran (n=877) or placebo (n=877); 556 patients were also randomised in the omeprazole partial factorial component. Study drug was permanently discontinued in 401 (46%) of 877 patients allocated to dabigatran and 380 (43%) of 877 patients allocated to placebo. The composite primary efficacy outcome occurred in fewer patients randomised to dabigatran than placebo (97 [11%] of 877 patients assigned to dabigatran vs 133 [15%] of 877 patients assigned to placebo; hazard ratio [HR] 0·72, 95% CI 0·55–0·93; p=0·0115). The primary safety composite outcome occurred in 29 patients (3%) randomised to dabigatran and 31 patients (4%) randomised to placebo (HR 0·92, 95% CI 0·55–1·53; p=0·76). Interpretation Among patients who had MINS, dabigatran 110 mg twice daily lowered the risk of major vascular complications, with no significant increase in major bleeding. Patients with MINS have a poor prognosis; dabigatran 110 mg twice daily has the potential to help many of the 8 million adults globally who have MINS to reduce their risk of a major vascular complication. Funding Boehringer Ingelheim and Canadian Institutes of Health Research.

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, pINTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.FUNDING: Bayer AG.

Carcinoid syndrome is the constellation of symptoms mediated by humoral factors produced by some carcinoid tumors. It consists primarily of vasomotor symptoms, gastrointestinal hypermotility, hypotension, and bronchospasm, due to the production and release of vasoactive substances. Carcinoid heart disease occurs in more than 50% of patients with carcinoid syndrome; in some cases, it represents the initial manifestation of the disease. We report the case of a 75-year-old woman with a metastatic neuroendocrine tumor admitted to the emergency room for fatigue and heart failure. Transthoracic echocardiography showed severe tricuspid and pulmonic regurgitation suggesting carcinoid heart disease. A hypervascular retroperitoneal mass was found on abdominal computed tomography, which seemed to arise from the mesenteric artery, anteriorly to the abdominal aorta. Unfortunately, our patient was neither a candidate for mass resection nor for cardiac surgery due to advanced metastatic disease and poor clinical condition. Additionally, we performed a systematic literature review of carcinoid heart disease focusing on typical echocardiographic findings.

The role of pulse pressure in young individuals remains controversial. The aim of the present study was to investigate the clinical significance of elevated pulse pressure in young- to middle-aged subjects screened for stage 1 hypertension. We examined 1241 subjects (mean age, 33.1±8.4 years) from the HARVEST (Hypertension Ambulatory Recording Venetia Study), during a median follow-up of 12.1 years. To evaluate the predictive value of pulse pressure and mean blood pressure for future hypertension needing treatment and for cardiovascular events, participants were grouped into pressure tertiles. Significant determinants of pulse pressure were male sex ( P =0.029), younger age ( P P =0.003), heart rate ( P P P P =0.003). In contrast, participants in the top mean blood pressure tertile had an increase in risk (1.91; 1.57–2.33; P P =0.005) and those in the top mean blood pressure tertile had an increase in risk (3.06; 1.32–7.09; P =0.009). Our data show that in subjects

An interactive effect of tobacco and alcohol use has been described for cancer. The aim of this study was to investigate the joint effect of smoking and alcohol intake on major adverse cardiovascular and renal events (MACE) in young subjects screened for stage 1 hypertension.A total of 1204 untreated patients aged from 18 to 45 years (mean 33.1) were included in this prospective cohort study. Subjects were classified into 4 categories of cigarette smoking and 3 classes of alcohol use. Main outcome variable was risk for MACE.During a 12.6-year follow-up, there were 74 fatal and nonfatal MACE. In multivariable Cox models, current smoking and alcohol drinking were associated with risk of MACE. In a multivariable model also including follow-up changes in blood pressure and body weight, hazard ratio (HR) was 1.48 (95% confidence interval [CI], 1.20-1.83) for smoking and was 1.82 (95% CI, 1.05-3.15) for alcohol use. In addition, an interactive effect was found between smoking and alcohol on risk of MACE (P.001). Among the 142 smokers who also drank alcoholic beverages, the risk of MACE (HR 4.02; 95% CI, 1.98-8.15) was more than doubled compared with the 112 smokers who abstained from drinking (HR 1.64; 95% CI, 0.63-4.27). In the group of heavy smokers who also were alcohol drinkers (n = 51), the risk of MACE was even quadrupled (HR 7.79; 95% CI, 4.22-14.37).Alcohol use potentiates the deleterious cardiovascular effects of heavy smoking in stage 1 hypertensive subjects younger than 45 years. These results call for prompt intervention addressed to improve unhealthy behaviors in these subjects.

AIMS To describe the actual incidence, prevalence among acute coronary syndrome patients and rate of recurrences of tako-tsubo cardiomyopathy in an emergency department of a community hospital. METHODS We report the in-hospital and long-term clinical course (7.5 years follow-up) of 25 consecutive tako-tsubo cardiomyopathy patients (mean age 66.8 ± 11.76 years; F/M: 21/4) admitted to a community hospital (referring population: 97,000 inhabitants). RESULTS The incidence rate of tako-tsubo cardiomyopathy was 0.03 cases per 1000 person-years; the prevalence was 3.0% among those with acute coronary syndrome and 7.6% among ST elevation myocardial infarction patients. Clinical presentations included mainly chest pain (n = 16, 64%) and dyspnea (n = 3, 12%). Precipitating conditions were emotional (n = 10, 40%), physical stress (n = 5, 20%) or both (n = 1, 4%); no stressors were recorded in nine patients (36%). Two patients died during hospitalization (8%). At the end of follow-up (mean time: 960.24 ± 724.34 days), all patients (n = 23) were alive and no major cardiovascular events were observed. Five patients had recurrences (22%). The mean time of recurrence was 105.4 ± 82.92 days and the clinical presentation was less severe compared with the first event: ECG had less ST involvement, ejection fraction was higher and cardiac injury biomarkers were lower. CONCLUSIONS In our population incidence and prevalence of tako-tsubo cardiomyopathy among acute coronary syndrome patients, as well as the recurrence rate of tako-tsubo cardiomyopathy, were higher than previously reported, suggesting that probably this syndrome often passes undiagnosed.

Background Controversy still exists about the long-term cardiovascular effects of coffee consumption in hypertension. Methods The predictive capacity of coffee use for cardiovascular events (CVEs) was investigated in 1204 participants from the HARVEST, a prospective cohort study of non-diabetic subjects aged 18–45years, screened for stage 1 hypertension. Subjects were grouped into three categories of coffee drinking, non-drinkers (none), moderate drinkers (1 to 3cups/day) and heavy drinkers (4or more cups/day). Multivariate Cox proportional hazards models were developed adjusting for possible confounding variables and risk factors. Results During a median follow-up of 12.6years, CVEs were developed by 60 participants. CVEs were more common among coffee drinkers than abstainers (abstainers, 2.2%; moderate drinkers, 7.0%; heavy drinkers, 14.0%; p for trend=0.0003). In a multivariable Cox regression model, coffee use was a significant predictor of CVE in both coffee categories, with a hazard ratio of 2.8 (95% CI, 1.0–7.9) in moderate coffee drinkers and of 4.5 (1.4–14.2) in heavy drinkers compared to abstainers. After inclusion of change in body weight (p=ns), incident hypertension (p=0.027) and presence of diabetes/prediabetes (p=ns) at follow-up end, the association with CVE was attenuated but remained significant in heavy coffee drinkers (HR, 95% CI, 3.4, 1.04–11.3). Conclusions These data show that coffee consumption increases the risk of CVE in a linear fashion in hypertension. This association may be explained in part by the association between coffee and development of hypertension. Hypertensive patients should be discouraged from drinking coffee.

The aim of this study was to investigate the effect of cigarette smoking on peripheral and central blood pressure (BP) in a group of young stage I hypertensives. A total of 344 untreated subjects from the HARVEST study were examined (mean age 37±10 years). Patients were divided into three groups based on smoking status: non-smokers, light smokers (⩽5 cigarettes/day) and moderate-to-heavy smokers (>5 cigarettes/day); and into three groups by age: 18–29, 30–39 and ⩾40 years. Central BP measurements and augmentation index (AIx) were calculated from brachial pressure waveform, with applanation tonometry, by means of the Specaway DAT System plus a Millar tonometer. The central waveform was derived from peripheral BP using the same software system of the SphygmoCor System pulse wave analysis. In addition, two indirect measurements of arterial stiffness were calculated: pulse pressure (PP) and systolic BP amplification. Central systolic BP and PP were higher in smokers than in non-smokers (systolic BP: 121.9±13.1 mmHg in non-smokers, 127.2±16.5 mmHg in light smokers, 126.7±15.3 mmHg in those who smoked >5 cigarettes/day, p=0.009; PP: 37.7±9.8 mmHg, 41.5±13.1 mmHg, 41.9±10.5 mmHg, respectively, p=0.005). Lower systolic BP amplification ( p

Background: The prion diseases are characterized by sleep disruption, with FFI typically characterized also by severe autonomic dysfunction and sympathetic hyperactivity. We report the results of an extensive neurophysiological and autonomic assessment in a CJD patient carrying the D178 mutation with the uncommon homozygosity for valine at codon 129, mutation with long disease duration. Results: A 47years old female presented with a memory impairment followed by progressive cognitive deficits and ataxia. The clinical picture slowly worsened to a state of akinetic mutism in about 2 years, and the patient died six years after the onset of symptoms. Repeated PSG and long-term actigraphic recordings, showed a peculiar, previously undescribed, pattern characterized by conservation of a rudimental circadian and ultradian rhythm, despite dramatic sleep micro-structure deterioration. We also observed a normal autonomic physiological response to orthostatic challenge and normal dynamic autonomic modulation during wake and sleep. The post-mortem brain pathology study, showed that neuronal loss was substantial in the cerebral cortex, diencephalon and thalami, but not in brainstem nuclei. Conclusions: We hypothesize that, despite a dramatic neurological picture (i.e. akinetic mutism) and a severe sleep micro-structural alteration, the persistence of an autonomic modulation and the persistence of a rudimental circadian and ultradian oscillation, are related to the relatively conserved anatomo-functional integrity of foundamental neuronal systems in the brainstem.

Glomerular hyperfiltration predicts development of nephropathy in hypertension but the factors responsible for increased glomerular filtration rate (GFR) are not well known. Aim of this study was to examine which clinical variables influence GFR in the early stage of hypertension.Participants were 1,106 young-to-middle-age hypertensive adults with creatinine clearance60 ml/min/1.73 m(2). Clinic and ambulatory blood pressures (BPs) were measured and the difference between clinic and 24-h systolic BP was defined as the white-coat effect (WCE). In 606 participants, 24-h urinary epinephrine and norepinephrine were also measured. Glomerular hyperfiltration, defined as a GFR ≥150 ml/min/1.73 m(2), was present in 201 subjects.Patients' mean age was 33.1 ± 8.5 years and office BP was 146 ± 10.5/94 ± 5.0 mm Hg. In multivariable linear regression, significant predictors of GFR were younger age (P0.0001), male gender (P0.0001), 24-h systolic BP (P = 0.0001), body mass (P0.0001), WCE (P = 0.02), log-epinephrine (P = 0.01), and coffee use (P0.01). In a logistic model, independent predictors of glomerular hyperfiltration were obesity (odds ratio, 95% confidence interval = 6.1, 3.8-9.8), male gender (2.9, 1.8-4.9), age33 years (2.1, 1.5-3.1), ambulatory hypertension (2.0, 1.4-3.0), WCE15 mm Hg (1.6, 1.1-2.3), heavy coffee use (2.0, 1.1-3.8), and epinephrine25 mcg/24 h (1.9, 1.2-3.1).The novel finding of this study is that hyper-reactivity to stress, as determined by urinary epinephrine level and WCE, and coffee use contribute to determining glomerular hyperfiltration in the early stage of hypertension. Our data may help to identify a subset of patients with glomerular hyperfiltration, who may be at increased risk of chronic kidney disease and may benefit from antihypertensive treatment.

Abnormal vascular reactivity contributes to the pathophysiology of hypertension and hypertension-related organ damage. As the dietary content of fatty acids may affect the vascular responses, we investigated the relationship of endothelium-independent and endothelium-dependent vasodilation with the fatty acid composition of red blood cell (RBC) membranes in hypertension.In 45 uncomplicated hypertensive patients, we measured the content of fatty acids in RBC membrane as a marker of dietary intake of fatty acids, and the vasodilatory response of the brachial artery to both nitrate-donor compound (nitrate-mediated vasodilation, NMD) and postischemic reactive hyperemia (flow-mediated vasodilation, FMD).Baseline diameter of the brachial artery was significantly lower and vasodilatory response to NMD was significantly greater in patients with RBC membrane polyunsaturated-to-saturated fatty acid (PUFA/SFA) ratio above the median of the distribution than in patients with PUFA/SFA ratio below the median, whereas no difference was observed in FMD. n-3 PUFA and n-6 PUFA content, and the PUFA/SFA ratio of RBC membranes were related inversely with brachial artery diameter and directly with maximal NMD, whereas no relationship of fatty acid components of RBC membrane with FMD was observed. Multivariate analysis that included demographic, anthropometric, clinical, and biochemical variables indicated that the RBC membrane PUFA/SFA ratio was an independent determinant of brachial artery diameter and NMD response.The endothelium-independent brachial artery vasodilation is independently related to the PUFA content of RBC membranes in patients with hypertension. This suggests the possible benefits of PUFA-enriched diets on the regulation of vascular tone and blood pressure in these patients.

Background Conflict still exists over whether patients with white-coat hypertension are at increased risk of developing target organ damage compared with normotensive individuals. Methods We studied vascular distensibility in 117 young-to-middle age patients with white-coat hypertension, 174 patients with sustained hypertension, and 51 normotensive controls. To obtain a measure of compliance, a model was used that divides the total systemic compliance into large artery (C 1 ) and small artery (C 2 ) compliance. With this aim, radial arterial pulse waves were recorded with a tonometer sensor array by means of an HDI CR2000 device (Eagan, Minnesota, USA). Moreover, pulse wave velocity and the augmentation index were measured using the Specaway DAT system (St Pauls, Sydney, Australia). Results Patients with sustained hypertension had a greater body mass index than patients with white-coat hypertension (P=0.04) or the normotensive individuals (P=0.01). C 1 and C 2 were decreased in the two hypertensive groups as compared with those in the normotensive group (P=0.0002 and 0.03, respectively, versus sustained hypertension; P=0.00007 and 0.0004, respectively, versus white-coat hypertension). Pulse wave velocity and aortic augmentation index were increased in the white-coat hypertension patients compared with the normotensive individuals (P= 0.02 and 0.004, respectively). Aortic augmentation index (P= 0.008) but not pulse wave velocity was increased in the sustained hypertensive patients compared with that in the normotensive individuals. All indexes of arterial distensibility were similar in the two hypertensive groups. Conclusions Indexes of arterial distensibility are impaired in the white-coat hypertensive group and similar to those in the sustained hypertensive group, indicating that early changes in the arterial wall can occur in white-coat hypertension. This may account for the higher risk of stroke that has been described in this condition.

Background: Increased carotid intima media thickness (CIMT) is frequently associated with established modifiable and non-modifiable cardiovascular risk factors, and is thought to be an independent predictor of ischemic cerebrovascular and cardiac events. The presence of carotid plaque is considered an established feature of atherosclerosis. There exist few longitudinal data on the predictive role of CIMT in the occurrence of carotid plaque. Methods: We restudied the survivors of a cohort of the San Daniele Project, a large randomized general population study, investigated in 1990 regarding the prevalence and determinants of carotid atherosclerosis. Using ultrasonography, we determined in 1,193 subjects (548 men and 645 women), the common carotid IMT and the presence of non-stenotic and stenotic plaque. Results: In 795 subjects without plaques or previous ischemic events at baseline, we found in multivariate analysis that CIMT ≧1 mm, age, hypertension and history of smoking are significant predictive elements of the occurrence of a new carotid plaque. The incremental probability of plaque occurrence is greater in midlife. CIMT and age are the most predictive risk factors with ORs of 3.66 (95% CI 1.4–9.4) and 3.02 (95% CI 2.4–3.7), respectively. The ORs for hypertension and smoking account for 1.5 (95% CI 1.1–3.4) and 1.7 (95% CI 1.1–2.8), respectively. Conclusions: Age, hypertension, history of smoking and B-mode detection of CIMT increases in subjects without carotid atherosclerosis and free of previous vascular events predict the occurrence of carotid atherosclerotic plaque.

Introduction: The association of uric acid with risk of hypertension is controversial and may be modulated by other risk factors. We did a prospective study to investigate whether uric acid was an independent predictor of risk of hypertension in the young and whether an unhealthy lifestyle could favour this association. Design and methods: The study was conducted in a cohort of 1060 young to middle age subjects screened for stage 1 hypertension and followed for a median of 11 years. In multivariable Cox analyses, data were adjusted for age, gender, body mass index (BMI), parental hypertension, 24-hour systolic and diastolic blood pressure, serum creatinine, lifestyle factors and metabolic data. Results: At baseline uric acid showed an independent positive association with male gender, BMI, creatinine and metabolic data and a negative association with age and smoking. The uric acid level was 5.03 mg/dL in the sedentary subjects (n=659) and 5.00 mg/dL in the active subjects (p=n.s.). At follow-up end, 677 subjects developed hypertension needing treatment. In the whole group, uric acid was an independent predictor of future hypertension (p=0.004). Participants with uric acid > 5.60 mg/dL (lower limit of the top tertile) had a 31% increase in risk compared to those of the bottom tertile. However, the risk of hypertension related to uric acid was increased only among the sedentary subjects (p=0.0017) with a hazard ratio of 1.43 (95%CI, 1.10-1.88) for the subjects of the top uric acid tertile compared to those of the bottom tertile. In contrast, among the active subjects no association was found between uric acid and risk of hypertension (p=0.56). The association between uric acid and future hypertension remained virtually unchanged when baseline serum glucose, cholesterol and triglycerides were included in the regression models. Conclusions: Uric acid is an independent predictor of hypertension in young to middle age subjects. However, regular physical activity prevents the development of hypertension related to hyperuricemia. These data suggest that exercise can counteract the pathophysiological mechanisms involved in the association between hyperuricemia and development of hypertension.

The aim of the present study was to investigate the association of physical activity with small artery elasticity in the early stage of hypertension. We examined 366 young-to-middle-age stage 1 hypertensives (mean blood pressure 145.6±10.3/92.5±5.8 mmHg), divided into two categories of physical activity, sedentary ( n=264) and non-sedentary ( n=102) subjects. The augmentation index was measured using the Specaway DAT System. Small artery compliance (C2) was measured by applanation tonometry, at the radial artery, with an HDI CR2000 device. After 6 years of follow-up, arterial distensibility assessment was repeated in 151 subjects. Heart rate was lower in active than in sedentary subjects (71.2±8.9 vs 76.6±9.7 bpm, p

Little is known about the clinical significance of isolated ambulatory hypertension, a condition characterized by low office but elevated ambulatory blood pressure. This study aimed to investigate the prevalence and the predictive value of isolated ambulatory hypertension diagnosed after 3 months of observation for the development of sustained hypertension within a cohort of 871 never-treated stage-1 hypertensive subjects. The study end point was progression to more severe hypertension and need of antihypertensive medication. In 244 subjects (28%), clinic blood pressure declined to P P =0.02) increase in the risk of reaching the end point in comparison with the nonhypertensive subjects. Final ambulatory systolic blood pressure was also higher in the former than the latter ( P =0.03). Our results indicate that among subjects screened for stage 1 hypertension, individuals with isolated ambulatory hypertension after 3 months of observation have increased risk of developing sustained hypertension in later life compared with subjects in whom both clinic and ambulatory blood pressures are normal.

Whether and how coffee use influences glucose metabolism is still a matter for debate. We investigated whether baseline coffee consumption is longitudinally associated with risk of impaired fasting glucose in a cohort of 18-to-45 year old subjects screened for stage 1 hypertension and whether CYP1A2 polymorphism modulates this association. A total of 1,180 nondiabetic patients attending 17 hospital centers were included. Seventy-four percent of our subjects drank coffee. Among the coffee drinkers, 87 % drank 1–3 cups/day (moderate drinkers), and 13 % drank over 3 cups/day (heavy drinkers). Genotyping of CYP1A2 SNP was performed by real time PCR in 639 subjects. At the end of a median follow-up of 6.1 years, impaired fasting glucose was found in 24.0 % of the subjects. In a multivariable Cox regression coffee use was a predictor of impaired fasting glucose at study end, with a hazard ratio (HR) of 1.3 (95 % CI 0.97–1.8) in moderate coffee drinkers and of 2.3 (1.5–3.5) in heavy drinkers compared to abstainers. Among the subjects stratified by CYP1A2 genotype, heavy coffee drinkers carriers of the slow *1F allele (59 %) had a higher adjusted risk of impaired fasting glucose (HR 2.8, 95 % CI 1.3–5.9) compared to abstainers whereas this association was of borderline statistical significance among the homozygous for the A allele (HR 1.7, 95 % CI 0.8–3.8). These data show that coffee consumption increases the risk of impaired fasting glucose in hypertension particularly among carriers of the slow CYP1A2 *1F allele.

Background Studies on fish oil effects on ambulatory blood pressure (ABP) are inconclusive. We evaluated fish effects on fatty acid composition of red blood cell (RBC) membrane and ABP values and tested the hypothesis that the starting membrane fatty acid composition affects the ability to incorporate additional polyunsaturated fatty acids (PUFA) and decrease blood pressure. Methods In 55 hypertensive patients, we measured RBC membrane fatty acid by gas chromatography and performed ABP monitoring. Patients received nutritional counseling and 3 weekly meals of trout rich in PUFA. In 42 patients, RBC membrane fatty acid and ABP were reassessed after 6 months. Results At baseline, the PUFA/saturated fatty acid (SFA) ratio of RBC membrane (PUFA/SFA) was inversely related to 24-hour, daytime, and nighttime systolic and pulse pressure, a relationship that was independent of covariables. At follow-up, the PUFA/SFA ratio increased in 20 (48%) of 42 patients. Patients with increased PUFA/SFA ratio at follow-up had lower baseline PUFA/SFA ratio than patients without such increase. Fish meal supplementation decreased 24-hour systolic and diastolic pressure only in patients who had increased PUFA/SFA ratio, a change that was more prominent during the nighttime. The change in PUFA/SFA was inversely and independently related to the change in 24-hour systolic and pulse pressure, and a logistic regression analysis indicated low baseline PUFA/SFA ratio as the only independent predictor of PUFA/SFA increase and blood pressure decrease. Conclusions The ability of fish meals to increase membrane PUFA content and decrease blood pressure in hypertensive patients depends upon the starting membrane fatty acid composition.

Objective To determine whether the prediction of target-organ damage varies according to the reproducibility of 24 h blood pressure. Setting Seventeen hypertension clinics in northeast Italy. Main outcome measures Correlations of left ventricular mass index and albumin excretion rate with 24 h and office blood pressures in relation to tertiles of ambulatory blood pressure reproducibility. Patients and methods In 716 consecutive, stage I, hypertensives enrolled in the Hypertension and Ambulatory Recording Venetia Study (HARVEST), ambulatory blood pressure monitoring was performed twice, 3 months apart. In all subjects, the albumin excretion rate was measured by radioimmunoassay, and in 567, the left ventricular mass index was assessed by echocardiography. Results The subjects were divided into tertiles of ambulatory blood pressure consistency (between-monitoring differences, regardless of the sign). In the tertile of subjects with good reproducibility, correlation coefficients of systolic and diastolic ambulatory blood pressure with left ventricular mass and urinary albumin excretion were significant and higher than those of office blood pressure. In contrast, in the two tertiles with poorer reproducibility, the coefficients were barely or not significant for both pressures. The advantage of ambulatory blood pressure over office blood pressure in predicting target-organ damage was no longer present for systolic blood pressure differences greater than 3.8 mmHg and diastolic blood pressure differences greater than 3.1 mmHg. Conclusions These data indicate that ambulatory blood pressure is a better predictor of left ventricular mass and urinary albumin excretion than office blood pressure, but only in subjects with good pressure reproducibility. Therefore, the assessment of hypertensive patients should be based on duplicate blood pressure monitorings. Recordings with 24 h systolic and diastolic blood presssure differences greater than 4 and 3 mmHg, respectively, should be considered with caution.

The aim of the present study was to evaluate the association of central blood pressure (BP) with organ damage and risk of future hypertension in a cohort of young to middle-aged patients.We studied 305 subjects screened for stage 1 hypertension to determine which subjects developed hypertension needing therapy according to current guidelines. Central BP was obtained from radial artery tonometry. Organ damage was the presence of left ventricular hypertrophy and/or microalbuminuria.In a multiple logistic regression including ambulatory 24-h BP, central mean BP was associated with presence of end-organ damage (p = 0.003). In the subjects divided according to whether their central mean BP was above or below the median, subjects with high central mean BP presented an earlier impairment of arterial distensibility and developed sustained hypertension more frequently compared with those with low central mean BP (p0.001). In logistic analyses, central mean BP was an independent predictor of future hypertension (p0.001) and remained associated with outcome when 24-h BP was included in the same model (p = 0.006).In young to middle-aged subjects in the early stage of hypertension, central mean BP is a useful adjunct to brachial BPs to better define the individual risk profile.

The impact of high blood pressure (BP) on target organs (TO) in premenopausal women is not well known. The purpose of this study was to describe gender differences in TO involvement in a cohort of young-to-middle-aged subjects screened for stage 1 hypertension and followed for 8.2 years.Participants were 175 women and 451 men with similar age (range 18-45 years). Ambulatory BP at entry was 127.5±12.5/83.7±7.2 mm Hg in women and 131.9±10.3/81.0±7.9 mm Hg in men. Ambulatory BP, albumin excretion rate (AER), and echocardiographic data (n=489) were obtained at entry, every 5 years, and before starting antihypertensive treatment.Female gender was an independent predictor of final AER (p=0.01) and left ventricular mass index (LVMI) (p0.001). At follow-up end, both microalbuminuria (13.7% vs. 6.2%, p=0.002) and left ventricular hypertrophy (LVH) (26.4% vs. 8.8%, p0.0001) were more common among women than men. In a multivariable Cox analysis, after adjusting for age, lifestyle factors, body mass, ambulatory BP, heart rate, and parental hypertension, female gender was a significant predictor of time to development of microalbuminuria (p=0.002), with a hazard ratio (HR) of 3.06, (95% confidence interval [CI] 1.48-6.34) and of LVH (p=0.004), with an HR of 2.50 (1.33-4.70). Inclusion of systolic and diastolic BP changes over time in the models only marginally affected these associations, with HRs of 3.13 (1.50-6.55) and 3.43 (1.75-6.70), respectively.These data indicate that premenopausal women have an increased risk of hypertensive TO damage (TOD) and raise the question about whether early antihypertensive treatment should be considered in these patients.

Aims The longitudinal relationship between aerobic exercise and left ventricular (LV) mass in hypertension is not well known. We did a prospective study to investigate the long-term effect of regular physical activity on development of LV hypertrophy (LVH) in a cohort of young subjects screened for Stage 1 hypertension. Methods and results We assessed 454 subjects whose physical activity status was consistent during the follow-up. Echocardiographic LV mass was measured at entry, every 5 years, and/or at the time of hypertension development before starting treatment. LVH was defined as an LV mass ≥50 g/m2.7 in men and ≥47 g/m2.7 in women. During a median follow-up of 8.3 years, 32 subjects developed LVH (sedentary, 10.3%; active, 1.7%, P = 0.000). In a logistic regression, physically active groups combined ( n = 173) were less likely to develop LVH than sedentary group with a crude OR = 0.15 (CI, 0.05–0.52). After controlling for sex, age, family history for hypertension, hypertension duration, body mass, blood pressure, baseline LV mass, lifestyle factors, and follow-up length, the OR was 0.24 (CI, 0.07–0.85). Blood pressure declined over time in physically active subjects (−5.1 ± 17.0/−0.5 ± 10.2 mmHg) and slightly increased in their sedentary peers (0.0 ± 15.3/0.9 ± 9.7 mmHg, adjusted P vs. active = 0.04/0.06). Inclusion of changes in blood pressure over time into the logistic model slightly decreased the strength of the association between physical activity status and LVH development (OR = 0.25, CI, 0.07–0.87). Conclusion Regular physical activity prevents the development of LVH in young stage 1 hypertensive subjects. This effect is independent from the reduction in blood pressure caused by exercise.

The longitudinal relationship between coffee use and hypertension is still controversial. Cytochrome P450 1A2 (CYP1A2) is the main responsible enzyme for the metabolism of caffeine. The aim of the present study was to investigate the effect of coffee intake on the risk of developing hypertension needing antihypertensive treatment in individuals stratified by CYP1A2 genotype.We assessed prospectively 553 young White individuals screened for stage 1 hypertension. Coffee intake was ascertained from regularly administered questionnaires. Incident physician-diagnosed hypertension was the outcome measure. Genotyping of CYP1A2 SNP was performed by real time PCR.During a median follow-up of 8.2 years, 323 individuals developed hypertension. For carriers of the slow *1F allele (59%), hazard ratios of hypertension from multivariable Cox analysis were 1.00 in abstainers (reference), 1.72 (95%CI, 1.21-2.44) in moderate coffee drinkers (P = 0.03), and 3.00 (1.53-5.90) in heavy drinkers (P = 0.001). In contrast, hazard ratios for coffee drinkers with the rapid *1A/*1A genotype were 0.80 (0.52-1.23, P = 0.29) for moderate drinkers and 0.36 (0.14-0.89, P = 0.026) for heavy drinkers. In a two-way ANCOVA, a gene x coffee interactive effect was found on follow-up changes in systolic (P = 0.000) and diastolic (P = 0.007) blood pressure. Urinary epinephrine was higher in coffee drinkers than abstainers but only among individuals with slow *1F allele (P = 0.001).These data show that the risk of hypertension associated with coffee intake varies according to CYP1A2 genotype. Carriers of slow *1F allele are at increased risk and should thus abstain from coffee, whereas individuals with *1A/*1A genotype can safely drink coffee.

BACKGROUND The aim of the study was to investigate the effect of polymorphism A1166C for AGTR1 and -1332G/A for AGTR2 on the incidence of sustained hypertension (HT) and metabolic syndrome in a cohort of young patients screened for stage 1 HT. METHODS We assessed 420 white hypertensive subjects never treated for HT and followed up for 7.3 years in the HT and Ambulatory Recording Venetia Study (HARVEST). Incident physician-diagnosed HT, increase in ambulatory blood pressure (BP), and new onset metabolic syndrome were the outcome measures. RESULTS For AGTR1, 37.2% of the subjects in the group with AA genotype, 47.5% in the group with AC genotype, and 66.7% in the group with CC genotype developed HT during follow-up (P = 0.001). Ambulatory systolic (P = 0.007) and diastolic (P < 0.001) BPs increased largely in the patients with CC genotype than in the rest of the group. New onset metabolic syndrome during follow-up (n = 30, P = 0.008), and the frequency of the metabolic syndrome at the end of follow-up (n = 65, P = 0.002) were also more common among the patients with CC and AC genotype. In a Cox analysis, subjects with CC genotype had an increased risk of developing HT (hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.2-2.0, P = 0.000) and metabolic syndrome (HR 2.8, 1.5-5.2, P = 0.002) than AA subjects. No association was found between the AGTR2 polymorphism and any outcome measure. CONCLUSIONS The AGTR1 A1166C polymorphism may be considered a genetic marker predisposing to an increase in BP and the development of the metabolic syndrome in subjects screened for stage 1 HT.

RGS2 is a negative regulator of Galpha protein signaling and promotes adipocyte differentiation. Recently, we described a polymorphism at the C1114G locus with the G allele associated with hypertension in a cross-sectional study. The aim of the present study was to assess whether the RGS2 C1114G is predictive of overweight in young subjects with grade I hypertension. We genotyped at the RGS2 C1114G locus 406 (male, n = 294; female, n = 112) white hypertensive subjects (age, 33 +/- 9 years) never treated for hypertension and at low cardiovascular risk. Median follow-up was 7.85 years. At baseline, male patients carrying the RGS2 1114G allele had higher body mass index (BMI) than patients with CC genotype (26.1 +/- 0.3 vs 25.3 +/- 0.3 kg/m2, P.05). The frequency of male patients with BMIor = 25 was similar between the patients with G allele and those with CC genotype (55.1% vs 47.8%, P = not significant). No significant difference between the 2 groups was observed with regard to physical activity, blood pressure, and heart rate. At the end of follow-up, BMI was higher in male patients with G allele compared with patients with CC genotype (26.8 +/- 0.3 vs 25.8 +/- 0.2 kg/m2, P.01); and the frequency of male patients with BMI25 kg/m2 was greater in the former (69.0% vs 52.2%, P.01). According to Cox regression, allele G was a significant predictor of developing overweight or obesity during follow-up. These epidemiologic relations were not significant in female patients. In young male patients with grade I hypertension, RGS2 1114G allele is associated with increased BMI and with greater risk of developing overweight or obesity. The RGS2 1114G allele may be considered a genetic marker that predicts an individual's predisposition to gaining weight.

The longitudinal relationship between coffee use and hypertension is not well known. Aim. We did a prospective study to investigate if there is a temporal relationship between coffee consumption and development of sustained hypertension.We assessed 1107 white subjects with elevated blood pressure who were followed up for 6.4 years. Coffee intake and other life-style factors were ascertained from regularly administered questionnaires. Incident physician-diagnosed hypertension was the outcome measure.During the follow-up, 561 subjects developed sustained hypertension, whereas 546 subjects did not meet the criteria for treatment. Coffee drinkers developed sustained hypertension more frequently than abstainers (53.1% versus 43.9%, P = 0.007). The incidence of hypertension did not differ between moderate and heavy coffee drinkers. Kaplan-Meier analysis confirmed that sustained hypertension was developed more frequently by coffee drinkers compared with nondrinkers (P0.001). The adjusted relative risk of hypertension was greater in both categories of coffee drinking than in abstainers (hazard ratio, 95% confidence limit (CL) = 1.24, 1.06-1.44). The risk of hypertension associated with coffee drinking increased gradually with increasing level of alcohol use (adjusted P for interaction = 0.005).In subjects screened for stage 1 hypertension a nonlinear association was found between coffee consumption and development of sustained hypertension.

Whether heart rate predicts the development of sustained hypertension in individuals with hypertension is not well known. We carried out a prospective study to investigate whether clinic and ambulatory heart rates assessed at baseline and changes in clinic heart rate during 6 months of follow-up were independent predictors of subsequent blood pressure (BP).The study was conducted in a cohort of 1103 white, stage 1 hypertensive individuals from the HARVEST study, never treated for hypertension and followed-up for an average of 6.4 years. Data were adjusted for baseline BP, age, sex, body fatness, physical activity habits, parental hypertension, duration of hypertension, cigarette smoking, alcohol consumption, and change of body weight from baseline.Clinic heart rate and heart rate changes during the first 6 months of follow-up were independent predictors of subsequent systolic blood pressure (SBP) and diastolic blood pressure (DBP) regardless of initial BP and other confounders (all P0.01). A significant interaction was found between sex (male) and baseline resting heart rate on final SBP (P = 0.017) and DBP (P0.001). The ambulatory heart rate and the heart rate white-coat effect did not add prognostic information to that provided by the clinic heart rate. Patients whose heart rate was persistently elevated during the study had a doubled fully adjusted risk (95% confidence interval 1.4-2.9) of developing sustained hypertension in comparison with subjects with a normal heart rate.Baseline clinic heart rate and heart rate changes during the first few months of follow-up are independent predictors of the development of sustained hypertension in young persons screened for stage 1 hypertension.

OBJECTIVE Microalbuminuria (MA) is a marker of adverse outcome in hypertension. The aim of this study was to investigate the association of MA with cardiovascular risk factors and glomerular hyperfiltration in the early stage of hypertension and to assess its predictive value for the development of sustained hypertension requiring antihypertensive treatment. DESIGN AND PARTICIPANTS We studied 1041 young stage 1 hypertensive subjects. Study variables were 24-h ambulatory blood pressure and heart rate, anthropometric measures, metabolic variables, creatinine clearance and lifestyle factors analyzed as a function of ascending urinary albumin measured from 24-h collections. Subjects were followed until they developed sustained hypertension and were eligible for antihypertensive medication according to current guidelines. SETTING Seventeen outpatient clinics in Italy. RESULTS Eighty-five percent of the subjects were normoalbuminuric, 9% had borderline MA, and 6% had overt MA. No between-group differences were found for age, body mass index, heart rate, lifestyle factors and biochemistry in both genders. Creatinine clearance was greater in the subjects with overt MA and borderline MA than in the normoalbuminuric subjects (P = 0.003 and 0.011, respectively). In a two-way ANCOVA, microalbuminuric subjects both with hyperfiltration (P < 0.001) and with normal filtration (P = 0.04) had higher 24-h systolic blood pressure than subjects with normoalbuminuria and normal filtration. In a Cox analysis, neither MA nor hyperfiltration were significant predictors of development of sustained hypertension. CONCLUSION MA is not associated with an adverse metabolic risk profile in the early stage of hypertension. MA is associated with greater hemodynamic load and with glomerular hyperfiltration in this clinical setting, but does not help in predicting those subjects destined to develop sustained hypertension requiring antihypertensive therapy.

The 825T allele of the GNB3 gene has been associated with essential hypertension and obesity in cross-sectional studies. We have therefore planned a longitudinal cohort study to assess whether the GNB3 825T allele is predictive of blood pressure increase in young subjects with grade I hypertension. We genotyped at the GNB3 825 locus 461 participants of the Hypertension and Ambulatory Recording Venetia Study (HARVEST) study (age, 18 to 45 years) at low cardiovascular risk, according to 1999 ISH/WHO criteria. The study end point was eligibility for antihypertensive medication, that is, progression to grade II hypertension during the first year of observation or office systolic blood pressure ≥150 mm Hg and/or office diastolic blood pressure ≥95 mm Hg in two later consecutive visits during follow-up. At baseline, there was no statistically significant difference among genotypes with respect to body mass index, blood pressure, and heart rate. During follow-up (mean, 4.7 years), 113 (51.1%) patients with CC genotype and 145 (60.4%) patients with TT/TC genotype reached the end point. According to survival analysis, the patients carrying the 825T allele had an increased risk of reaching the blood pressure end point (CI, 1.108 to 1.843; P =0.006). In young patients with grade I hypertension, the 825T allele is associated with increased risk of progression to more severe hypertension requiring antihypertensive therapy. The GNB3 825T allele may be considered a genetic marker of predisposition for hypertension.

The main purpose of this study was to compare efficacy, tolerability and influence on quality of life (QOL) of nifedipine gastrointestinal therapeutic system (NI) 30-60 mg once a day vs amlodipine (AM) 5-10 mg once a day in elderly patients with mild-moderate hypertension.This was a randomized, double-blind, parallel-group, multicenter study. After a 2-week single-blind placebo run-in, patients were randomized to either NI 30 mg or AM 5 mg. Responders continued on the same dosage for 16 additional weeks, while non-responders were titrated to 60 mg NI or 10 mg AM.Blood pressure was measured by mercury sphygmomanometer and efficacy equivalence of NI and AM tested by covariance analysis. Diastolic blood pressure (DBP) was the primary efficacy parameter, its baseline value being taken as covariate while centers effect and treatment interaction were included as fixed effects in the analysis model. The secondary efficacy variables systolic blood pressure (SBP) and scores for QOL were analyzed according to the same model.At the end of the study, overall mean DBPs, calculated as least-square means (LSMEANS), in the "by protocol" population were 87.5 mmHg for NI and 86.7 for AM (difference 0.8 mmHg with 90% CI -1.2 to 2.8 mmHg). In the "by intention to treat" (ITT) population LSMEANS were 87.6 mmHg for NI and 86.4 mmHg for AM (difference 1.2 mmHg with 90% CI -0.6 to 3.1 mmHg). SBP LSMEANS in the "by protocol" population were 147.7 mmHg for NI and 147.3 mmHg for AM (difference 0.3 mmHg, with 90% CI -3.7 to 4.3); corresponding values in the "by ITT" population were 148.0 mmHg for NI and 147.2 for AM (difference 0.8 mmHg, with 90% CI -2.8 to 4.6). Mean values for QOL parameters were not significantly different. A total of 173 episodes of adverse events were documented in 54 patients (26 NI and 28 AM), dropouts were 15 (20% of group) on NI and 21 (28%) on AM.NI 30-60 mg was shown to be as efficacious and safe as AM 5-10 mg in elderly patients with mild-moderate hypertension. QOL improved compared to baseline with no significant difference between the two drugs, thus confirming a positive class effect for calcium antagonists.