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Background The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure. Methods We did a meta-analysis of individual participant-level data from 48 randomised trials of pharmacological blood pressure lowering medications versus placebo or other classes of blood pressure-lowering medications, or between more versus less intensive treatment regimens, which had at least 1000 persons-years of follow-up in each group. Trials exclusively done with participants with heart failure or short-term interventions in participants with acute myocardial infarction or other acute settings were excluded. Data from 51 studies published between 1972 and 2013 were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We pooled the data to investigate the stratified effects of blood pressure-lowering treatment in participants with and without prevalent cardiovascular disease (ie, any reports of stroke, myocardial infarction, or ischaemic heart disease before randomisation), overall and across seven systolic blood pressure categories (ranging from

This randomized, double-blind, parallel-group, multicenter study compared the efficacy of amlodipine and losartan in an older hypertensive population, focusing on therapeutic coverage in the case of missed doses. Following a 4-week, single-blind, placebo washout period, 211 patients were randomly assigned to receive either 5 mg of amlodipine once daily or 50 mg of losartan once daily. Doses were doubled after 6 weeks of treatment if the diastolic blood pressure exceeded 90 mm Hg. After the 12-week treatment period, patients received the placebo for 2 days (drug holiday) to simulate two missed doses of antihypertensive medication. Twenty-four-hour ambulatory blood pressure monitoring was conducted at the end of the placebo washout period (baseline), upon completion of the 12-week treatment period (steady state), and after the 2-day drug holiday. Amlodipine was more effective than losartan in reducing patients' 24-h ambulatory blood pressure at the steady-state sampling time. The increases in 24-h blood pressure during the drug holiday averaged 6±2/2±1 mm Hg (P

Abstract— Elevated systolic blood pressure (SBP) correlates to cognitive decline and incident dementia. The effects of heart rate (HR), visit to visit HR variation, and visit to visit SBP variation are less well established. Patients without preexisting cognitive dysfunction (N=24 593) were evaluated according to mean SBP, SBP visit to visit variation (coefficient of variation [standard deviation/mean×100%], CV), mean HR, and visit to visit HR variation (HR-CV) in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease. Cognitive function was assessed with mini mental state examination. Cognitive dysfunction (fall in mini mental state examination ≤24 points), important cognitive decline (drop of ≥5 points), and cognitive deterioration (drop of >1 point per year or decline to < 24 points) were assessed. SBP and HR were measured over 10.7±2.2 (mean±SD) visits. Mean SBP, mean HR, and SBP-CV were associated with cognitive decline, dysfunction, and deterioration (all P P =0.0030) and mean HR ( P =0.0008) remained predictors for cognitive dysfunction (odds ratios [95% confidence intervals], 1.32 [1.10–1.58] for 5th versus 1st quintile of SBP-CV and 1.40 [1.18–1.66] for 5th versus 1st quintile of mean HR). Similar effects were observed for cognitive decline and deterioration. SBP-CV and mean HR showed additive effects. In conclusion, SBP-CV and mean HR are independent predictors of cognitive decline and cognitive dysfunction in patients at high CV risk. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT 00153101.

A consensus document from the Study Group of Sports Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology.

Because of new evidence on several diagnostic and therapeutic aspects of hypertension, the present guidelines differ in many respects from the previous ones. Some of the most important differences are listed below: 1. Epidemiological data on hypertension and BP control in Europe. 2. Strengthening of the prognostic value of home blood pressure monitoring (HBPM) and of its role for diagnosis and management of hypertension, next to ambulatory blood pressure monitoring (ABPM). 3. Update of the prognostic significance of night-time BP, white-coat hypertension and masked hypertension. 4. Re-emphasis on integration of BP, cardiovascular (CV) risk factors, asymptomatic organ damage (OD) and clinical complications for total CV risk assessment. 5. Update of the prognostic significance of asymptomatic OD, including heart, blood vessels, kidney, eye and brain. 6. Reconsideration of the risk of overweight and target body mass index (BMI) in hypertension. 7. Hypertension in young people. 8. Initiation of antihypertensive treatment. More evidence-based criteria and no drug treatment of high normal BP. 9. Target BP for treatment. More evidence-based criteria and unified target systolic blood pressure (SBP) (

White coat hypertension is considered to be a benign condition that does not require antihypertensive treatment. Ambulatory blood pressure (ABP) was measured in 284 participants in the Hypertension in the Very Elderly Trial (HYVET), a double-blind randomized trial of indapamide sustained release 1.5 mg±perindopril 2 to 4 mg versus matching placebo in hypertensive subjects (systolic blood pressure 160–199 mm Hg) aged >80 years. ABP recordings (Diasys Integra II) were obtained in 112 participants at baseline and 186 after an average follow-up of 13 months. At baseline, clinic blood pressure (CBP) exceeded the morning ABP by 32/10 mm Hg. Fifty percent of participants fulfilled the established criteria for white coat hypertension. The highest ABP readings were in the morning (average 140/80 mm Hg), the average night-time pressure was low at 124/72 mm Hg, and the average 24-hour blood pressure was 133/77 mm Hg. During follow-up, the systolic/diastolic blood pressure placebo-active differences averaged 6/5 mm Hg for morning ABP, 8/5 mm Hg for 24-hour ABP, and 13/5 mm Hg for CBP. The lowering of blood pressure over 24 hours supports the reduction in blood pressure with indapamide sustained release±perindopril as the explanation for the reduction in total mortality and cardiovascular events observed in the main HYVET study. Because we estimate that 50% had white coat hypertension in the main study, this condition may benefit from treatment in the very elderly.

Objective: We assessed the prognostic value of electrocardiographic left ventricular hypertrophy (LVH) using Sokolow-Lyon (SL-LVH), Cornell Voltage (CV-LVH) or Cornell Product (CP-LVH) Criteria in 3043 hypertensive people aged 80 years and over enrolled in the Hypertension in the Very Elderly Trial. Methods: Multivariate Cox proportional hazard models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for all-cause mortality, cardiovascular diseases, stroke and heart failure in participants with and without LVH at baseline. The mean follow-up was 2.1 years. Results: LVH identified by CV- or CP-LVH Criteria was associated with a 1.6 to 1.9-fold risk of cardiovascular disease and stroke. The presence of CP-LVH was associated with an increased risk of heart failure (HR 2.38, 95% CL 1.16-4.86). In gender specific analyses, CV-LVH (HR 1.94, 95%Cl 1.06-3.55) and CP-LVH (HR 2.36, 95% CI 1.25-4.45) were associated with an increased risk of stroke in women and of heart failure in men, CV-LVH (HR 6.47, 95 % Cl 1.41-29.79) and CP-LVH (10.63, 95Cl % 3.58-31.57), respectively. There was no significant increase in the risk of any outcomes associated with SL LVH. LVH identified by these three methods was not a significant predictor of all-cause mortality. Conclusions: Use of Cornell Voltage and Cornell Product criteria for LVH predicted the risk of cardiovascular disease and stroke. Only Cornell Product was associated with an increased the risk of heart failure. This was particularly the case in men. The identification of electrocardiographic LVH proved to be important in very elderly hypertensive people.

Copyright © 2009 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved., The annual congress of the European Society of Cardiology (ESC) was held in Barcelona, Spain, August 29 to September 2, 2009. The total attendance was 31,323 participants from 136 different countries. Excellent congress facilities hosted 237 pre-arranged sessions in 30 meeting rooms running in parallel, including several joint sessions in collaboration with other societies (e.g., the American College of Cardiology, the American Heart Association, and the World Heart Federation). A total of 9,848 abstracts from 96 different countries was submitted, and 4,085 (42%) abstracts were selected for presentation.

The systemic arterial pressure is determined by 1) the cardiac output, 2) the blood volume, and 3) the total peripheral resistance. A triple antihypertensive therapy is therefore considered which interferes primarily with these three factors using 1) beta adrenergic blocking agents, 2) a low sodium diet and diuretics, and 3) vasodilating antihypertensive drugs. The hae-modynamic changes during this therapy are described. Since cardiac output, resistance and blood volume cannot be determined routinely in all hypertensive patients, a therapeutic regimen is discussed based on the determination of 1) rate, 2) body weight and 3) arterial blood pressure.

Background: Moderate alcohol consumption may reduce cardiovascular events, but little is known about its effect on atrial fibrillation in people at high risk of such events. We examined the association between moderate alcohol consumption and the risk of incident atrial fibrillation among older adults with existing cardiovascular disease or diabetes. Methods: We analyzed data for 30 433 adults who participated in 2 large antihypertensive drug treatment trials and who had no atrial fibrillation at baseline. The patients were 55 years or older and had a history of cardiovascular disease or diabetes with end-organ damage. We classified levels of alcohol consumption according to median cut-off values for low, moderate and high intake based on guidelines used in various countries, and we defined binge drinking as more than 5 drinks a day. The primary outcome measure was incident atrial fibrillation. Results: A total of 2093 patients had incident atrial fibrillation. The age- and sex-standardized incidence rate per 1000 person-years was 14.5 among those with a low level of alcohol consumption, 17.3 among those with a moderate level and 20.8 among those with a high level. Compared with participants who had a low level of consumption, those with higher levels had an increased risk of incident atrial fibrillation (adjusted hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.04–1.26, for moderate consumption; 1.32, 95% CI 0.97–1.80, for high consumption). Results were similar after we excluded binge drinkers. Among those with moderate alcohol consumption, binge drinkers had an increased risk of atrial fibrillation compared with non–binge drinkers (adjusted HR 1.29, 95% CI 1.02–1.62). Interpretation: Moderate to high alcohol intake was associated with an increased incidence of atrial fibrillation among people aged 55 or older with cardiovascular disease or diabetes. Among moderate drinkers, the effect of binge drinking on the risk of atrial fibrillation was similar to that of habitual heavy drinking.

We aimed to investigate the effect of exercise on endothelium-dependent vasodilator function assessed simultaneously in the brachial artery and in the distal arterial bed by flow-mediated dilation and the pulse amplitude tonometry method, respectively, in coronary artery disease patients. The study included 146 patients with stable coronary artery disease (123 men, mean age 62 ± 9 years) who participated in the Cardiac Rehabilitation and Genetics of Exercise performance study. All patients completed a 12-week supervised cardiac rehabilitation programme (three sessions per week at an intensity of 80% of the heart rate reserve). At baseline and upon completion of the training, we measured brachial artery diameters by means of ultrasound scanning (linear array transducer of 12 MHz) and simultaneously assessed pulse amplitudes in the fingertip using a pulse amplitude tonometry device both at rest and after reactive hyperaemia induced by a 5-min forearm cuff occlusion. Peak oxygen uptake significantly increased (+22%; p 0.0001) and flow-mediated dilation improved from 10.0% to 13.1% (+37%; p 0.0001), whereas the reactive hyperaemia index of the pulse amplitude tonometry method remained unchanged (p = 0.47) following exercise-based cardiac rehabilitation. However, the basal digital pulse amplitude (+58%; p 0.001) increased as a result of training, as did the digital pulse amplitude after reactive hyperaemia (+22%; p 0.05). Exercise-based cardiac rehabilitation is associated with an improvement in endothelial function, as can be measured by flow-mediated dilation but not by the reactive hyperaemia index of the pulse amplitude tonometry method.

2012 focused update of the ESC Guidelines for the management of atrial fibrillation : an update of the 2010 ESC Guidelines for the management of atrial fibrillation: developed with the special contribution of the European Heart Rhythm Association

Objectives We sought to determine whether the blood pressure (BP) levels at which cardiovascular (CV) protection is achieved differ between diabetic and nondiabetic patients from the ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial). Background Greater absolute benefits of BP reductions have been claimed for diabetic as compared with nondiabetic patients. Methods A total of 25,584 patients (9,603 diabetic), older than 55 years, at high CV risk were randomized to ramipril, telmisartan, or both and observed for 4.6 years. We pooled the treatment arms to examine the relationships between BP and the primary composite outcome (CV death, nonfatal myocardial infarction or stroke, or hospitalized heart failure) and its components. Results The primary outcome occurred in 1,938 (20.2%) diabetic patients and in 2,276 (14.2%) nondiabetic patients. Compared with nondiabetic patients, diabetic patients had a significantly higher risk for the primary endpoint (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.38 to 1.57) and CV death (HR: 1.56; 95% CI: 1.42 to 1.71); myocardial infarction (HR: 1.30 (95% CI: 1.17 to 1.46); stroke (HR: 1.39; 95% CI: 1.23 to 1.56); and congestive heart failure hospitalization (HR: 2.06; 95% CI: 1.82 to 2.32). The CV risk was significantly higher in diabetic than in nondiabetic patients regardless of the systolic BP changes during treatment. In both diabetic and nondiabetic patients, progressively greater systolic BP reductions were accompanied by reduced risk for the primary outcome only if baseline systolic BP levels ranged from 143 to 155 mm Hg; except for stroke, there was no benefit in fatal or nonfatal CV outcomes by reducing systolic BP below 130 mm Hg. Conclusions The relationship between BP and overall CV risk had a similar pattern in diabetic and nondiabetic patients over a wide range of baseline and in-treatment BP values although, for the same systolic BP, a higher risk is observed in diabetic patients. (Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial [ONTARGET]; NCT00153101 )

We reviewed the effect of resistance training on blood pressure and other cardiovascular risk factors in adults. Randomized, controlled trials lasting ≥4 weeks investigating the effects of resistance training on blood pressure in healthy adults (age ≥18 years) and published in a peer-reviewed journal up to June 2010 were included. Random- and fixed-effects models were used for analyses, with data reported as weighted means and 95% confidence limits. We included 28 randomized, controlled trials, involving 33 study groups and 1012 participants. Overall, resistance training induced a significant blood pressure reduction in 28 normotensive or prehypertensive study groups [−3.9 (−6.4; −1.2)/−3.9 (−5.6; −2.2) mm Hg], whereas the reduction [−4.1 (−0.63; +1.4)/−1.5 (−3.4; +0.40) mm Hg] was not significant for the 5 hypertensive study groups. When study groups were divided according to the mode of training, isometric handgrip training in 3 groups resulted in a larger decrease in blood pressure [−13.5 (−16.5; −10.5)/−6.1(−8.3; −3.9) mm Hg] than dynamic resistance training in 30 groups [−2.8 (−4.3; −1.3)/−2.7 (−3.8; −1.7) mm Hg]. After dynamic resistance training, V o 2 peak increased by 10.6% ( P =0.01), whereas body fat and plasma triglycerides decreased by 0.6% ( P P

INTRODUCTION: : In a previous meta-analysis, we derived pooled estimates for the association of left ventricular mass (LVM) and hypertrophy (LVH), as diagnosed by electrocardiography or echocardiography, with the ACE D/I polymorphism. We updated this meta-analysis until May 2009 only considering echocardiographic phenotypes. METHODS: : We computed pooled estimates from a random-effects model. RESULTS: : Across 38 studies, both DD homozygotes (n = 2440) and DI heterozygotes ( n = 4310) had higher (p ≤ 0.002) LVM or LVM index than II homozygotes (n = 2229). Across 21 studies with available data, this was due to increased mean wall thickness (MWT) with no difference in left ventricular internal diameter (LVID). Standardised differences (DD versus II) were 0.39 (p < 0.001) for LVM, 0.34 (p = 0.009) for MWT, and 0.066 (p = 0.26) for LVID. Across 16 studies (4894 participants), the pooled odds ratios of LVH (versus II homozygotes) were 1.11 (p = 0.29) and 1.02 (p = 0.88) for the DD and DI genotypes, respectively. Sensitivity analyses were confirmatory. CONCLUSIONS: : Our meta-analysis supports the hypothesis that the enhanced ACE activity associated with the D allele is associated with higher LV mass. Smaller sample size might explain the lack of significant association with LVH. ispartof: Journal of the Renin-Angiotensin-Aldosterone System vol:12 issue:3 pages:243-253 ispartof: location:England status: published

Aims The aim of this study was to investigate the heritability as well as genetic and environmental correlations of left ventricular (LV) structural and functional traits in complex pedigrees of a Caucasian population. Methods and results We randomly recruited 459 white European subjects from 52 families (50% women; mean age 45 years). LV structure was measured by M-mode and 2D echocardiography and LV function was measured by conventional Doppler and tissue Doppler imaging (TDI). Other measurements included blood pressure, anthropometric, and biochemical measurements. We estimated the heritability of LV traits while adjusting for covariables, including sex, age, body height and weight, systolic and diastolic blood pressures, and heart rate. With full adjustment, heritability of LV mass was 0.23 ( P = 0.025). The TDI-derived mitral annular velocities Ea and Aa showed moderate heritability ( h 2= 0.36 and 0.53, respectively), whereas the mitral inflow A peak had weak heritability ( h 2 = 0.25) and the E peak was not heritable ( h 2 = 0.11). We partitioned the total phenotypic correlation when it reached significance, into a genetic and an environmental component. The genetic correlations were 0.61 between the E and Ea peaks and 0.90 between the A and Aa peaks. Conclusion Our study demonstrated moderate heritability for LV mass as well as the mitral annular Ea and Aa peaks. We also found significant genetic correlations between the E and Ea peaks and between the A and Aa peaks. Our current findings support the ongoing research to map and detect genetic variants that contribute to the variation in LV mass and other LV structural and functional phenotypes.

To report blood pressure control in the Hypertension in the Very Elderly Trial, a placebo-controlled trial of hypertensive (systolic blood pressure (SBP) 160-199 mm Hg, diastolic blood pressure (DBP)

We aimed to investigate the effects of endurance training intensity (1) on systolic blood pressure (SBP) and heart rate (HR) at rest before exercise, and during and after a maximal exercise test; and (2) on measures of HR variability at rest before exercise and during recovery from the exercise test, in at least 55-year-old healthy sedentary men and women. A randomized crossover study comprising three 10-week periods was performed. In the first and third period, participants exercised at lower or higher intensity (33% or 66% of HR reserve) in random order, with a sedentary period in between. Training programmes were identical except for intensity, and were performed under supervision thrice for 1 h per week. The results show that in the three conditions, that is, at rest before exercise, during exercise and during recovery, we found endurance training at lower and higher intensity to reduce SBP significantly (P

Four dipping categories have been described, based on the night-day blood pressure ratio from 24-h ambulatory blood pressure recordings: extreme dippers (night-day blood pressure ratioor = 0.8), dippers (0.8ratioor = 0.9), nondippers (0.9ratioor = 1.0) and reverse dippers (ratio1.0). The main purpose of this article is to discuss the prognostic significance of these four dipping categories in hypertension, mainly based on a large meta-analysis of individual patient data. In hypertensive patients without cardiovascular disease at baseline and with statistical adjustment for confounders and 24-h blood pressure, mortality was lower in extreme dippers than in dippers, whereas the incidence of cardiovascular events was higher in reverse dippers. The worst prognosis for reverse dippers was also observed in hypertensive patients with major cardiovascular disease at baseline. Higher incidences of cardiovascular events and mortality were also found in reverse dippers in comparison with dippers in a comprehensive meta-analysis of population-based studies but outcome was not significantly different between extreme dippers and dippers. Based on these findings, there appears to be little doubt that reverse dipping is associated with a worse prognosis. Some studies suggest that prognosis is similar in nondippers and extreme dippers in comparison with dippers, but other studies suggest a somewhat worse prognosis in nondippers, or a better or worse prognosis in extreme dippers.

Previous studies reported on the association of left ventricular mass index (LVMI) with urinary sodium or with circulating or urinary aldosterone. We investigated the independent associations of LVMI with the urinary excretion of both sodium and aldosterone. We randomly recruited 317 untreated subjects from a white population (45.1% women; mean age 48.2 years). Measurements included echocardiographic left ventricular (LV) properties, the 24-hour urinary excretion of sodium and aldosterone, plasma renin activity (PRA), and proximal (RNa prox ) and distal (RNa dist ) renal sodium reabsorption, assessed from the endogenous lithium clearance. In multivariable-adjusted models, we expressed changes in LVMI per 1-SD increase in the explanatory variables, while accounting for sex, age, systolic blood pressure, and the waist-to-hip ratio. LVMI increased independently with the urinary excretion of both sodium (+2.48 g/m 2 ; P =0.005) and aldosterone (+2.63 g/m 2 ; P =0.004). Higher sodium excretion was associated with increased mean wall thickness (MWT: +0.126 mm, P =0.054), but with no change in LV end-diastolic diameter (LVID: +0.12 mm, P =0.64). In contrast, higher aldosterone excretion was associated with higher LVID (+0.54 mm; P =0.017), but with no change in MWT (+0.070 mm; P =0.28). Higher RNa dist was associated with lower relative wall thickness (−0.81×10 −2 , P =0.017), because of opposite trends in LVID (+0.33 mm; P =0.13) and MWT (−0.130 mm; P =0.040). LVMI was not associated with PRA or RNa prox. In conclusion, LVMI independently increased with both urinary sodium and aldosterone excretion. Increased MWT explained the association of LVMI with urinary sodium and increased LVID the association of LVMI with urinary aldosterone.

The prognostic importance of the nocturnal systolic blood pressure (SBP) fall, adjusted for average 24-hour SBP levels, is unclear. The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) examined this issue in a meta-analysis of 17 312 hypertensives from 3 continents. Risks were computed for the systolic night-to-day ratio and for different dipping patterns (extreme, reduced, and reverse dippers) relative to normal dippers. ABC-H investigators provided multivariate adjusted hazard ratios (HRs), with and without adjustment for 24-hour SBP, for total cardiovascular events (CVEs), coronary events, strokes, cardiovascular mortality, and total mortality. Average 24-hour SBP varied from 131 to 140 mm Hg and systolic night-to-day ratio from 0.88 to 0.93. There were 1769 total CVEs, 916 coronary events, 698 strokes, 450 cardiovascular deaths, and 903 total deaths. After adjustment for 24-hour SBP, the systolic night-to-day ratio predicted all outcomes: from a 1-SD increase, summary HRs were 1.12 to 1.23. Reverse dipping also predicted all end points: HRs were 1.57 to 1.89. Reduced dippers, relative to normal dippers, had a significant 27% higher risk for total CVEs. Risks for extreme dippers were significantly influenced by antihypertensive treatment ( P

Several large epidemiological studies have reported an inverse relationship between blood pressure and physical activity. However, longitudinal intervention studies are more appropriate for assessing the effects of physical activity. We performed meta-analyses of randomized controlled trials involving dynamic aerobic endurance training or resistance training. The meta-analysis on endurance training involved 72 trials and 105 study groups. After weighting for the number of trained participants, training induced significant net reductions in resting and daytime ambulatory blood pressure of, respectively, 3.0/2.4 mmHg (P

Previous meta-analyses of randomized controlled trials on the effects of chronic dynamic aerobic endurance training on blood pressure reported on resting blood pressure only. Our aim was to perform a comprehensive meta-analysis including resting and ambulatory blood pressure, blood pressure–regulating mechanisms, and concomitant cardiovascular risk factors. Inclusion criteria of studies were: random allocation to intervention and control; endurance training as the sole intervention; inclusion of healthy sedentary normotensive or hypertensive adults; intervention duration of ≥4 weeks; availability of systolic or diastolic blood pressure; and publication in a peer-reviewed journal up to December 2003. The meta-analysis involved 72 trials, 105 study groups, and 3936 participants. After weighting for the number of trained participants and using a random-effects model, training induced significant net reductions of resting and daytime ambulatory blood pressure of, respectively, 3.0/2.4 mm Hg ( P P P P P P P P P P −1 ( P

The 1996 American Heart Association consensus panel recommendations stated that pre-participation cardiovascular screening for young competitive athletes is justifiable and compelling on ethical, legal, and medical grounds. The present article represents the consensus statement of the Study Group on Sports Cardiology of the Working Group on Cardiac Rehabilitation and Exercise Physiology and the Working Group on Myocardial and Pericardial diseases of the European Society of Cardiology, which comprises cardiovascular specialists and other physicians from different European countries with extensive clinical experience with young competitive athletes, as well as with pathological substrates of sudden death. The document takes note of the 25-year Italian experience on systematic pre-participation screening of competitive athletes and focuses on relevant issues, mostly regarding the relative risk, causes, and prevalence of sudden death in athletes; the efficacy, feasibility, and cost-effectiveness of population-based pre-participation cardiovascular screening; the key role of 12-lead ECG for identification of cardiovascular diseases such as cardiomyopathies and channelopathies at risk of sudden death during sports; and the potential of preventing fatal events. The main purpose of the consensus document is to reinforce the principle of the need for pre-participation medical clearance of all young athletes involved in organized sports programmes, on the basis of (i) the proven efficacy of systematic screening by 12-lead ECG (in addition to history and physical examination) to identify hypertrophic cardiomyopathy-the leading cause of sports-related sudden death-and to prevent athletic field fatalities; (ii) the potential screening ability in detecting other lethal cardiovascular diseases presenting with ECG abnormalities. The consensus document recommends the implementation of a common European screening protocol essentially based on 12-lead ECG.

The heart is a major site of natriuretic peptides (NP). Atrial and brain natriuretic peptide (ANP and BNP) are predominantly produced by atria and ventricles. C-Natriuretic peptide (CNP) is also found in heart tissue. ANP and BNP are produced by cardiomyocytes and fibroblasts. Cardiac fibroblasts also secrete CNP. Three NP-receptors (NPR-A, NPRB, NPR-C) are expressed in heart atria and ventricles. Baseline plasma BNP is a sensitive predictor of morbidity and mortality in heart failure and changes in BNP over time are associated with corresponding changes in subsequent mortality and morbidity. Plasma BNP, and to a lesser extent ANP, is also a strong cardiovascular risk marker in patients with essential hypertension and left ventricular hypertrophy without left ventricle dysfunction or overt renal disease. However, evidence to date suggests that plasma BNP levels should not be viewed as a diagnostic test for chronic heart failure and sequential assays of BNP have not been shown to be useful in the follow-up or the initiation of appropriate therapy. However, patients who present with dyspnea with unclear but suspected cardiac etiologies may be considered to have venous blood taken for the measurement of BNP level to assist with diagnostic decision and therefore appropriate management of the dyspnea. BNP level is however not a stand-alone test and must be used in conjunction with careful clinical evaluation and in patients with an intermediate pre-test likelihood of heart failure.

White-coat hypertension (WCHT), also called 'isolated office or clinic hypertension', is defined as the occurrence of blood pressure (BP) values higher than normal when measured in the medical environment, but within the normal range during daily life, usually defined as average daytime ambulatory BP (ABP) or home BP values (

The aim of the present study was to assess the prognostic value of ECG voltages at baseline and their serial changes during follow-up in a large prospective study with standardized follow-up and strictly defined end points. Patients who were 60 years old or older, with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure P ≤0.01 for all). A 1-mV decrease in electrocardiographic voltages during follow-up independently predicted a lower incidence of cardiac events (relative hazard rate: 0.86; P ≤0.05), but not of stroke or mortality. In conclusion, electrocardiographic voltages at baseline and their serial changes during follow-up predict subsequent events in older patients with systolic hypertension.

Background To assess the impact of immediate versus delayed anti hypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double- blind placebo-controlled Systolic Hypertension in Europe (Syst- Eur) trial by an open-label follow-up study lasting 4 years. Methods The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double- blind trial ended after a median follow-up of 2.0 years (range 1-97 months). Of 4409 patients still alive, 3517 received open- label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5 - 25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up. Results Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed anti hypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P=0.01) and 15% (P=0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively. Conclusions Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension. J Hypertens 22:847 -857 (C) 2004 Lippincott Williams Wilkins.

SUMMARY Hypertension (HTN), one of the most common medical disorders, is associated with an increased incidence of all-cause and cardiovascular disease (CVD) mortality. Lifestyle modifications are advocated for the prevention, treatment, and control of HTN, with exercise being an integral component. Exercise programs that primarily involve endurance activity prevent the development of HTN and lower blood pressure (BP) in adults with normal BP and those with HTN. The BP lowering effects of exercise are most pronounced in people with HTN who engage in endurance exercise with BP decreasing approximately 5–7 mm Hg after an isolated exercise session (acute) or following exercise training (chronic). Moreover, BP is reduced for up to 22 h after an endurance exercise bout (e.g., postexercise hypotension), with the greatest decreases among those with the highest baseline BP. The proposed mechanisms for the BP lowering effects of exercise include neurohumoral, vascular, and structural adaptations. Decreases in catecholamines and total peripheral resistance, improved insulin sensitivity, and alterations in vasodilators and vasoconstrictors are some of the postulated explanations for the antihypertensive effects of exercise. Emerging data suggest genetic links to the BP reductions associated with acute and chronic endurance exercise. Nonetheless, definitive conclusions regarding the mechanisms for the BP reductions following endurance exercise cannot be made at this time. Individuals with controlled HTN and no CVD or renal complications may participate in an exercise program or competitive athletics, but should be evaluated, treated, and monitored closely. Preliminary peak or symptom-limited exercise testing may be warranted, especially for men over 45 and women over 55 yr planning a vigorous exercise program (i.e., 60% u VO2R, oxygen uptake reserve). In the interim, while formal evaluation and management are taking place, it is reasonable for the majority of patients to begin moderate intensity exercise training (40 –60% u VO2R) such as walking. When pharmacologic therapy is indicated in physically active people it should, ideally: a) lower BP at rest and during exertion; b) decrease total peripheral resistance; and, c) not adversely affect exercise capacity. For these reasons, angiotensin converting enzyme (ACE) inhibitors (or angiotensin II receptor blockers in case of ACE inhibitor intolerance) and calcium channel blockers are currently the drugs of choice for recreational exercisers and athletes who have HTN. Exercise remains a cornerstone therapy for the primary prevention, treatment, and control of HTN. The optimal training frequency, intensity, time, and type (FITT) need to be better defined to optimize the BP lowering capacities of exercise, particularly in children, women, older adults, and

Cardiac enlargement in athletes was already recognised by the end of the 19th century through percussion of the chest in cross country skiers, and was later confirmed by use of radiography and evidence from necropsy. The advent of echocardiography allowed investigators to gain a better insight into the heart of athletes, and these findings were in general confirmed by other techniques such as magnetic resonance imaging. The present review will focus on the impact of different sports and training on cardiac structure and function, and on electrocardiographic alterations associated with athlete’s heart. ### Left ventricle #### Cross sectional studies Physical exercise is associated with haemodynamic changes and alters the loading conditions of the heart. In dynamic exercise the emphasis is on movement with no or minimal development of force. The main haemodynamic features are increases in heart rate and stroke volume, the two components of cardiac output. Systemic vascular resistance drops but the net result is a slight to moderate rise in blood pressure. The load on the heart is predominantly that of volume. In static exercise force is developed with no or minimal movement. The haemodynamic consequences involve a slight elevation of cardiac output, caused by the increase of heart rate, and a more pronounced rise of blood pressure, resulting in a pressure load on the heart. From a theoretical point of view the haemodynamic alterations and the ventricular loading conditions during exercise could, in the long run, lead to left ventricular hypertrophy (LVH). Volume load would lead to enlargement of the left ventricular internal diameter and a proportional increase of wall thickness; this type of adaptation is termed eccentric LVH. The pressure load would induce thickening of the ventricular wall with unchanged internal dimension, or concentric LVH. It was suggested that these cardiac adaptations serve to normalise wall stress. Individual studies showed that cardiac adaptations …

OBJECTIVE: To investigate whether baseline systolic blood pressure variability was a risk factor for stroke, cardiovascular mortality or cardiac events during the Syst-Eur trial. DESIGN: The Syst-Eur study was a randomized, double-blind, placebo-controlled trial, powered to detect differences in stroke rate between participants on active antihypertensive treatment and placebo. Systolic blood pressure variability measurements were made on 744 participants at the start of the trial. Systolic blood pressure variability was calculated over three time frames: 24 h, daytime and night-time. The placebo and active treatment subgroups were analysed separately using an intention-to-treat principle, adjusting for confounding factors using a multiple Cox regression model. PARTICIPANTS: An elderly hypertensive European population. MAIN OUTCOME MEASURES: Stroke, cardiac events (fatal and non-fatal heart failure, fatal and non-fatal myocardial infarction and sudden death) and cardiovascular mortality (death attributed to stroke, heart failure, myocardial infarction, sudden death, pulmonary embolus, peripheral vascular disease and aortic dissection). RESULTS: The risk of stroke increased by 80% (95% confidence interval: 17-176%) for every 5 mmHg increase in night-time systolic blood pressure variability in the placebo group. Risk of cardiovascular mortality and cardiac events was not significantly altered. Daytime variability readings did not predict outcome. Antihypertensive treatment did not affect systolic blood pressure variability over the median 4.4-year follow-up. CONCLUSION: In the placebo group, but not the active treatment group, increased night-time systolic blood pressure variability on admission to the Syst-Eur trial was an independent risk factor for stroke during the trial. ispartof: Journal of hypertension vol:21 issue:12 pages:2251-7 ispartof: location:Netherlands status: published

Background Electrocardiographic abnormalities and premature ventricular contractions are common in athletes and are generally benign. However, the specific outcome of high-level endurance athletes with frequent and complex ventricular arrhythmias is unclear. Also, information on the predictive accuracy of different investigations in this subgroup is unknown. Results We report on 46 high-level endurance athletes with ventricular arrhythmias (45 male; median age 31 years) followed-up for a median of 4.7 years. Eighty percent were cyclists. Hypertrophic cardiomyopathy or coronary abnormalities were present in ≤5%. Eighty percent of the arrhythmias had a left bundle branch morphology. Right ventricular (RV) arrhythmogenic involvement (based on a combination of multiple criteria) was manifest in 59% of the athletes, and suggestive in another 30%. Eighteen athletes developed a major arrhythmic event (sudden death in nine, all cyclists). They were significantly younger than those without event (median 23 years vs 38 years; P =0.01). Outcome could not be predicted by presenting symptoms, non-invasive arrhythmia evaluation or morphological findings at baseline. Only the induction of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) during invasive electrophysiological testing was significantly related to outcome (RR 3.4; P =0.02). Focal arrhythmias were associated with a better prognosis than those due to reentry ( P =0.02) but the mechanism could be determined in only 22 (48%). Conclusions Complex ventricular arrhythmias do not necessarily represent a benign finding in endurance athletes. An electrophysiological study is indicated for risk evaluation, both by defining inducibility and identifying the arrhythmogenic mechanism. Endurance athletes with arrhythmias have a high prevalence of right ventricular structural and/or arrhythmic involvement. Endurance sports seems to be related to the development and/or progression of the underlying arrhythmogenic substrate.

The Syst-Eur trial investigated whether active treatment starting with the dihydropyridine calcium channel blocker (CCB) nitrendipine, could reduce the cardiovascular complications of isolated systolic hypertension (ISH) in the elderly. The intention-to-treat analysis showed that active treatment improved outcome. The per-protocol analysis largely confirmed these results. The effect of treatment on total and cardiovascular mortality might be attenuated in very old patients. Further analysis also suggested benefit in those patients who remained on nitrendipine monotherapy. Active treatment was more beneficial in patients with diabetes as compared with those without diabetes at entry and reduced the incidence of dementia by 50%. Analyses of data from the Ambulatory Blood Pressure Monitoring (ABPM) Side Project suggested that most of the benefit of treatment was seen in patients with a daytime systolic BP > or = 160 mm Hg. Finally, a meta-analysis partly based on Syst-Eur data showed that in older hypertensive patients pulse pressure and not mean pressure is the major determinant of cardiovascular risk. ispartof: Current Opinion in Cardiology vol:16 issue:6 pages:342-348 ispartof: location:United States status: published

Background The intrauterine environment may be a critical period for the development of hypertension in later life. In the present study, we applied the twin approach to estimate the contribution of genetic and environmental causes that may underlie the birth weight–adult blood pressure association. Methods and Results Birth weights of 418 twin pairs were obtained prospectively, and resting and 24-hour ambulatory blood pressures were obtained at the age of 18 to 34 years. In women, resting systolic blood pressure decreased 4.27 mm Hg ( P P =0.02) per kilogram increase in birth weight. Similar associations were found for ambulatory measurements, although these were somewhat less pronounced. Pair-wise analysis confirmed these findings: twin pairs of whom both members had a low birth weight (P =0.02) higher and of the heaviest ≥2.4 mm Hg higher ( P =0.2) than similar measurements in high-birth-weight pairs. Intrapair differences in blood pressure between the lightest and the heaviest at birth were only present in low-birth-weight pairs. The results were similar for monozygotic and dizygotic twin pairs. In men, no associations were found between birth weight and adult blood pressure. Conclusions These findings suggest that prenatal programming of adult blood pressure occurs at least in female twins. We suggest that particularly maternal influences, experienced by both twin members, may underlie the association between birth weight and blood pressure. The fetoplacental unit seems to influence blood pressure only when both fetuses had low birth weight.

The aim of this preliminary study was to compare exercise performance and the effect of exercise training in cardiac patients with and without an implantable cardioverter-defibrillator (ICD). There are few data on exercise performance and on the effect of exercise training in patients with an ICD. Data in patients with an ICD (n = 8) were compared with those from a matched control group (n = 16). Patients performed maximal cycle-ergometer testing before and after 3 months of exercise training. All patients had to stop the exercise test for reasons of exhaustion. The predetermined heart rate threshold in ICD patients, set at the detection rate of the ICD minus 30 beats/min, was not reached. Before training, peak oxygen uptake was not different in the ICD patients compared with the control group (21.0 +/- 6.9 vs 21.9 +/- 5.0 ml oxygen standard temperature pressure dry/min/kg). Exercise training increased peak oxygen uptake to a similar extent in both groups, 20% and 24%, respectively. One ICD patient developed uneventful ventricular tachycardia at the end of the post-training exercise test, and another during training. Thus, exercise performance and the favorable response to a 3-month exercise training program are comparable in patients with ICD and matched control patients. However, tachyarrhythmias may occur during exercise testing or training and require special attention. Selected patients with ICD can be encouraged to participate in medically supervised exercise training programs. The results of this study should be confirmed with additional studies on larger numbers of subjects.

The aim of the present study was to investigate the reproducibility of the exponential method of CO2 rebreathing with the use of automated curve fitting and to determine whether this method is superior to the equilibrium method in terms of reproducibility and clinical practicability.Repeated measurements of cardiac output were performed using the automated equilibrium and exponential methods. These measurements were compared in 12 healthy male subjects at rest and during incremental exercise tests.Estimated cardiac output was not significantly different between duplicate measurements at rest nor at any level of exercise with either method. At rest the exponential method showed a tendency toward larger variability than the equilibrium method. The exponential method produced significantly higher (Por = 0.001) estimates at rest (averaging up to 9.8 L x min(-1)) compared with the equilibrium method (averaging up to 6.5 L x min(-1)). Reproducibility improved for both methods with increasing workloads, and a second measurement at rest also seemed more reproducible and valid than the first. During exercise, both methods produced comparable values for cardiac output, and highly significant relations between cardiac output and oxygen uptake were observed for both methods (ranging from r2 = 0.79 to r2 = 0.88, Por = 0.001). The equilibrium method produced unpleasant side effects more frequently (75% vs 21%, Por = 0.001) compared with the exponential method and lead more subjects to premature interruption of the exercise test because of the rebreathing maneuver (42% vs 17%, P = 0.058).Automated curve fitting for the exponential method gave reproducible and valid results during submaximal and maximal exercise but not at rest. The equilibrium method on the other hand interfered with exercise. Therefore, the equilibrium method is recommended at rest and at lower levels of exercise and the exponential method at higher intensities.

The objective was to assess the influence of a cardiac rehabilitation training session on blood pressure measured shortly after exercise and during the subsequent 24 h in patients with stable coronary artery disease. Blood pressure was measured conventionally and by use of 24-h ambulatory blood pressure monitoring in seven men, mean age 53+/-8 (s.d.) years, after participation in a cardiac rehabilitation session and, in randomised order, on a non-exercise control day. Conventional blood pressure averaged 112+/-7/77+/-5 mm Hg in the sitting position on the control day and was not different at the same time of the day shortly after the patients had participated in a cardiac rehabilitation training session. Standing systolic pressure was lower by 7.8+/-4.3 mm Hg (P < 0.005) after exercise compared to the control situation, but this was not associated with orthostatic symptoms. However, ambulatory monitoring showed no differences in blood pressure with the non-exercise day during the subsequent 24-h period. In conclusion, standing but not sitting blood pressure was slightly lower shortly after a cardiac rehabilitation session, but the postexercise orthostatic hypotension was not sustained during normal activities of daily living.

Background —Many studies have focused on the prognostic power of peak oxygen uptake (V̇ o 2 ) in patients with chronic heart failure, but maximal exercise testing is not without risk. The purpose of the present study was, therefore, to assess the prognostic significance of the steepness of changes in ventilation and carbon dioxide output (V̇ co 2 ) during submaximal exercise in comparison with V̇ o 2 . Methods and Results —The study population consisted of 284 adult heart transplant candidates who performed a graded maximal bicycle ergometer test with respiratory gas analysis. Using the respiratory data up to a gas exchange ratio of 1.0, 3 submaximal slopes were calculated in each patient. During follow-up (median, 1.33 years), 57 patients died and 149 had ≥1 cardiovascular event. When using Cox proportional hazards analysis, both peak V̇ o 2 and submaximal respiratory slopes predicted outcome before and after accounting for age, sex, and body mass index. However, whereas the prognostic power of peak V̇ o 2 was independent of submaximal respiratory data, the prognostic significance of the slopes was lost after controlling for peak V̇ o 2 . Stepwise regression analysis even selected peak V̇ o 2 as an independent prognostic index among the following factors: cause of heart failure, ejection fraction, pulmonary vascular resistance, natremia, and the forced expiratory volume in 1 s. Conclusions —Respiratory data during submaximal exercise are significant predictors of outcome in patients with chronic heart failure, but their prognostic power is inferior to that of peak V̇ o 2 . However, these data may be useful when maximal exercise is contraindicated or not achievable.

Summary Background Previous meta-analysis of outcome trials in hypertension have not specifically focused on isolated systolic hypertension or they have explained treatment benefit mainly in function of the achieved diastolic blood pressure reduction. We therefore undertook a quantitative overview of the trials to further evaluate the risks associated with systolic blood pressure in treated and untreated older patients with isolated systolic hypertension Methods Patients were 60 years old or more. Systolic blood pressure was 160 mm Hg or greater and diastolic blood pressure was less than 95 mm Hg. We used non-parametric methods and Cox regression to model the risks associated with blood pressure and to correct for regression dilution bias. We calculated pooled effects of treatment from stratified 2 X 2 contingency tables after application of Zelen's test of heterogeneity. Findings In eight trials 15 693 patients with isolated systolic hypertension were followed up for 3.8 years (median). After correction for regression dilution bias, sex, age, and diastolic blood pressure, the relative hazard rates associated with a 10 mm Hg higher initial systolic blood pressure were 1.26 (p=0.0001) for total mortality, 1.22 (p=0.02) for stroke, but only 1.07 (p=0.37) for coronary events. Independent of systolic blood pressure, diastolic blood pressure was inversely correlated with total mortality, highlighting the role of pulse pressure as risk factor. Active treatment reduced total mortality by 13% (95% Cl 2–22, p=0.02), cardiovascular mortality by 18%, all cardiovascular complications by 26%, stroke by 30%, and coronary events by 23%. The number of patients to treat for 5 years to prevent one major cardiovascular event was lower in men (18 vs 38), at or above age 70 (19 vs 39), and in patients with previous cardiovascular complications (16 vs 37). Interpretation Drug treatment is justified in older patients with isolated systolic hypertension whose systolic blood pressure is 160 mm Hg or higher. Absolute benefit is larger in men, in patients aged 70 or more and in those with previous cardiovascular complications or wider pulse pressure. Treatment prevented stroke more effectively than coronary events. However, the absence of a relation between coronary events and systolic blood pressure in untreated patients suggests that the coronary protection may have been underestimated.

This prospective population study investigated in a random sample of 692 subjects (age 20-83 years) how changing environmental exposure to cadmium influenced blood pressure (BP) and the incidence of hypertension. At baseline (1985 to 1989; participation rate, 78%) and follow-up (1991 to 1995; re-examination rate, 81%), blood pressure was measured by conventional sphygmomanometry (CBP; 15 readings in total) and, at follow-up, also by 24-h ambulatory blood pressure monitoring (ABP). Systolic/diastolic CBP at baseline averaged 128.4/77.3 mm Hg. At baseline, blood cadmium concentration (B-Cd) and urinary cadmium excretion (U-Cd) averaged (geometric means) 11.1 nmol/L and 10.2 nmol/24 h. Over 5.2 years (median follow-up), B-Cd fell by 29.6% and U-Cd by 15.2%. B-Cd fell less in subjects living closer to three zinc smelters and in premenopausal women. During follow-up, systolic CBP decreased by 2.2 mm Hg in men and remained unchanged in women, and diastolic CBP increased by 1.8 mm Hg in both sexes. No relationship could be demonstrated between the secular trends in CBP and B-Cd or U-Cd or between B-Cd or U-Cd at baseline and the incidence of hypertension. In addition, in cross-sectional analyses involving the average of all available CBP measurements in each participant or 24-h ABP at follow-up (mean, 119.1/71.4 mm Hg), blood pressure was not correlated with B-Cd or U-Cd. In conclusion, environmental exposure to cadmium was not associated with higher CBP or 24-h ABP or with increased risk for hypertension. The lesser fall in B-Cd in the residents living closer to the zinc smelters or in premenopausal women underscores the necessity to sanitize cadmium-polluted areas and to systematically reinforce the preventive measures to be adopted by exposed communities to reduce cadmium uptake. (C) 2000 American Journal of Hypertension, Ltd.

Background Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension. We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events. In this post hoc analysis, we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients. Methods After stratification according to center, sex, and presence or absence of previous cardiovascular complications, 4695 patients (age, ≥60 years) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were randomly assigned to receive active treatment or placebo. Active treatment consisted of nitrendipine (10 to 40 mg per day) with the possible addition or substitution of enalapril (5 to 20 mg per day) or hydrochlorothiazide (12.5 to 25 mg per day) or both, titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg. In the control group, matching placeb...

The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Ci: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P < 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.

Sudden death is a tragic fact, unexpectedly arising in all age groups. Ventricular arrhythmias are the main cause. At the end of a maximal exercise test more ventricular premature beats were noted in a group of well trained triathletes compared with a similar control group. The etiology is multifactorial. When these ventricular premature beats are associated with specific structural and functional heart adaptations, echocardiographically and electrocardiographically well-documented, then those ‘banal’ ventricular premature beats cannot longer be considered as a physiological phenomenon. In these circumstances the involved subject is a candidate for dangerous arrhythmias and ‘sudden cardiac death’. Purpose: The principal cause of ‘Sudden cardiac death’ is ventricular arrhythmias. We explore the incidence of ventricular premature beats (VPB) in triathletes, who engage in enforced endurance sports. Methods: Fifty-two triathletes were compared with twenty-two control subjects with comparable anthropometric parameters in function of structural and functional cardiac adaptations. Maximal exercise tests were conducted on a stationary bicycle and a treadmill. During the last two minutes of each test, the VPB were registered. Results: Statistically significant differences emerged in the cardiac structure and function between the triathletes and the controls. There were signs of cardiac hypertrophy and arguments for a supernormally diastolic left ventricular function in the triathletes. The performance capacity was also significantly higher in the triathletes. The maximal heart rate was significantly higher in the control group. The number of VPB was significantly higher in the triathletes. The increased risk of VPB in the triathlon group is caused by several factors: the degree of cardiac hypertrophy, the increased diastolic reserve, the duration of the exercise, the existence of an aortic insufficiency jet and some specific electrocardiographic findings. Conclusions: The triathlete has an increased risk of VPB during maximal efforts. We doubt the traditionally accepted view of the physiological nature of those VPB and suspect that the limit of physiological cardiac adaptations to sport efforts is exceeded with the appearance of VPB. The triathlete with VPB and with specific electrocardiographic and echocardiographic findings is a candidate for ‘sudden cardiac death’.

A pulse pressure (PP) below 35-40 mm Hg has been shown to carry a worse prognosis in patients with chronic heart failure (CHF), but its non-dependence on peak oxygen uptake, which is a major if not the major prognostic factor in these patients, has not been studied. We assessed whether PP adds prognostic precision to peak oxygen uptake in 284 patients with advanced CHF, in whom blood pressure (BP) was measured at rest and who performed a graded symptom-limited bicycle exercise test with respiratory gas analysis. The results confirm that a low PP rather than a high PP predicts cardiovascular (CV) mortality in patients with CHF and that PP adds prognostic value to peak oxygen uptake, which is the strongest predictor of outcome.