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We reported previously that two otherwise identical training programs at lower (LI) and higher intensity (HI) similarly reduced resting systolic blood pressure (BP) by approximately 4-6 mmHg. Here, we determined the effects of both programs on BP-regulating mechanisms, on biomarkers of systemic inflammation and prothrombotic state and on the heart. In this cross-over study (3 × 10 weeks), healthy participants exercised three times 1 h/week at, respectively, 33% and 66% of the heart rate (HR) reserve, in a random order, with a sedentary period in between. Measurements, performed at baseline and at the end of each period, involved blood sampling, HR variability, systolic BP variability (SBPV) and cardiac magnetic resonance imaging. Thirty-nine participants (18 men; mean age 59 years) completed the study. Responses were not different between both programs (P0.05). Pooled data from LI and HI showed a reduction in HR (-4.3 ± 8.1%) and an increase in stroke volume (+11 ± 23.1%). No significant effect was seen on SBPV, plasma renin activity, basal nitric oxide and left ventricular mass. Our results suggest that the BP reduction observed appears to be due to a decrease in systemic vascular resistance; training intensity does not significantly affect the results on mechanisms, biomarkers and the heart.

Earlier studies have demonstrated the interaction between ADD1 and ACE in relation to arterial properties. We investigated whether arterial characteristics might also be related to interactions of ADD1 with other renin-angiotensin system genes. Using a family-based sampling frame, we randomly recruited 1064 Flemish subjects (mean age, 43.6 years; 50.4% women). By means of a wall-tracking ultrasound system, we measured the properties of the carotid, femoral and brachial arteries. In multivariate-adjusted analyses, we assessed the multiple gene effects of ADD1 (Gly460Trp), AGT (C-532T and G-6A) and AT1R (A1166C). In ADD1 Trp allele carriers, but not in ADD1 GlyGly homozygotes (P-value for interaction < or =0.014), femoral cross-sectional compliance was significantly higher (0.74 vs 0.65 mm(2) kPa(-1); P=0.020) in carriers of the AT1R C allele than in AT1R AA homozygotes, with a similar trend for femoral distensibility (11.3 vs 10.2 x 10(-3) kPa(-1); P=0.055). These associations were independent of potential confounding factors, including age. Family-based analyses confirmed these results. Brachial diameter (4.35 vs 4.18 mm) and plasma renin activity (PRA) (0.23 vs 0.14 ng ml(-1) h(-1)) were increased (P< or =0.005) in AGT CG haplotype homozygotes compared with non-carriers, whereas the opposite was true for brachial distensibility (12.4 vs 14.4 x 10(-3) kPa(-1); P=0.011). There was no interaction between AGT and any other gene in relation to the measured phenotypes. ADD1 and AT1R interactively determine the elastic properties of the femoral artery. There is a single-gene effect of the AGT promoter haplotypes on brachial properties and PRA. ispartof: Journal of Human Hypertension vol:23 issue:1 pages:55-64 ispartof: location:England status: published

Vascular dementia (VD) is the second most common cause of dementia in the elderly after Alzheimer’s disease (AD). Prevalence estimates from community surveys indicate that, on average, 5% of persons over 65 and 15 to 20% of people over 80 suffer from “severe dementia”. Clinico-pathological studies have shown that AD accounts for 50 to 60% of the cases and VD for about 10 to 20%; 20% of the patients have both disorders. The incidence rate of VD ranges from 7 per 1,000 person-years in normal volunteers to 16 per 1,000 person-years in subjects with risk factors for strokes, particularly high blood pressure. The only effective therapeutic approach to VD is the prevention of strokes, mainly through the treatment of hypertension; however, none of the therapeutic trials has included VD prevention as one of its treatment goals. Syst-Eur Study is a European placebo controlled trial which aims to determine whether morbidity and mortality are changed when elderly patients (60 years and over) with isolated systolic hypertension are treated. In this trial, the incidence of VD will be carefully recorded during the five year follow-up of the expected 3,000 patients. The present side project to the Syst-Eur trial will specifically address the following questions: does antihypertensive treatment reduce the incidence of VD?, and how do the cognitive functions of elderly patients change when treated with active or placebo treatment? The protocol is based on the administration of the MMS (Folstein) once a year to all patients. If the MMS score is 23 or less, a set of criteria will be used to establish the diagnosis of vascular dementia. p]A pilot study has demonstrated the feasibility of the trial. The main study is in progress.

The purpose of the study was to assess the prognostic significance of out-of-the-office blood pressure (BP) measurement in older patients in general practice, and to compare the results for BP measured in the office, at home and during 24-h ambulatory monitoring. All registerd patients who were 60 years or older were eligible for the study, except when bedridden, demented or admitted in a home for sick elderly people, or when they had suffered a myocardial infarction or stroke. After baseline measurements in 1990-1993, incidence of major cardiovascular events (cardiovascular death, myocardial infarction and stroke) was ascertained in 2002-2003 and related to the BPs by use of multivariate Cox regression analysis. Age of the 391 patients averaged 71+/-9 years; 40% were men. During median follow-up of 10.9 years, 86 patients (22%) suffered a cardiovascular event. The adjusted relative hazard rate, associated with a 1 s.d. increment in systolic BP was 1.13 for office BP (NS), and, respectively, 1.32, 1.33 and 1.42, for home, daytime and night time BP (P< or =0.01 for all). Results were similar for diastolic BP. The prognostic significance of all out-of-the-office BPs was independent of office BP. The prognostic value of home BP was equal to (systolic) or even better (diastolic) than that of daytime BP. Night time BP predicted cardiovascular events independent of all other BPs. Prognosis of white-coat hypertension was similar to that of true normotension, but better than in sustained hypertension. In conclusion, the prognostic value of home BP is better than that of office BP in older patients in primary care, and is at least equal to that of daytime ambulatory BP. The prognosis of patients with white-coat hypertension is similar to that of true normotensives.

OBJECTIVE AND METHODS: In this randomized clinical trial, conducted in 400 hypertensive patients [sitting diastolic blood pressure (DBP) >95 mmHg], blood pressure-lowering therapy was adjusted in a stepwise manner, either on the basis of the self-measured DBP at home or on the basis of conventional DBP measured at the doctor's office. RESULTS: Therapy guided by home blood pressure instead of office blood pressure led to less intensive drug treatment and marginally lower costs, but also to less blood pressure control with no differences in left ventricular mass. Self-measurement helped to identify patients with white-coat hypertension. CONCLUSIONS: The present findings support a stepwise strategy for the evaluation of blood pressure, in which self-measurement and ambulatory monitoring are complementary to conventional office blood pressure measurement. ispartof: pages:311-4 ispartof: Blood pressure monitoring vol:9 issue:6 pages:311-4 ispartof: Workshop on Whats New in Blood Pressure Measurement location:FRANCE, Paris date:Jun 2004 status: published

The Syst-Eur study investigated whether active antihypertensive treatment could reduce cardiovascular complications in elderly patients with isolated systolic hypertension.Randomised, placebo-controlled, double-blind outcome trial.Hypertension clinics or general practitioners' surgeries in 198 centres in 23 Western and Eastern European countries.Patients agedor = 60 years with sitting systolic blood pressure (BP) 160-219 mmHg and sitting diastolic BP95 mmHg during run-in phase.Four thousand, six hundred and ninety-five patients were randomly assigned to active treatment (N = 2,398), i.e. nitrendipine, with the possible addition of enalapril and hydrochlorothiazide, or to matching placebos (N = 2,297). In the intention-to-treat analysis, the between-group difference in blood pressure (BP) amounted to 10.1/4.5 mmHg (P0.001). Active treatment reduced the incidence of fatal and non-fatal stroke (primary endpoint) by 42% (P = 0.003). On active treatment all cardiac endpoints decreased by 26% (P = 0.03) and all cardiovascular endpoints by 31% (P0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, P = 0.07), but all-cause mortality was not influenced (-14%, P = 0.22). For total (P = 0.009) and cardiovascular mortality (P = 0.09), the benefit of antihypertensive treatment weakened with advancing age, and for total mortality it decreased with lower systolic BP at entry (P = 0.05). The benefits of active treatment were not independently related to sex or to the presence of cardiovascular complications at entry. The antihypertensive regimen was more effective in patients with diabetes than in those without diabetes at entry. Further analyses also suggested benefit in patients who were taking nitrendipine as the sole therapy. The per-protocol analysis largely confirmed the intention-to-treat results. Active treatment reduced all strokes by 44% (P = 0.004), all cardiac endpoints by 26% (P = 0.05) and all cardiovascular endpoints by 32% (P0.001). Total mortality was reduced by 26% (P = 0.05), but a similar reduction in cardiovascular mortality did not reach statistical significance in this analysis. Compared with placebo, active treatment also reduced the incidence of dementia by 50%.Stepwise antihypertensive drug treatment, starting with the dihydropiridine calcium-channel blocker nitrendipine, improves prognosis in elderly patients with isolated systolic hypertension.

The main objective of the present study was to identify the determinants of heart rate (HR) and of the low-frequency (LF) and high-frequency (HF) components of short-term heart rate variability (HRV) in the population. HF power represents vagal modulation of HRV and LF power predominantly sympathetic modulation. Data were collected in a population-based sample of 614 men and women, aged 25-89 years. Because of the uncertainty on the optimal methodology for power spectral analysis of HRV, we first compared the results obtained with the two most frequently used methods. We found that autoregressive modelling and fast Fourier transform yielded similar overall qualitative results, but that within subject differences between methods could be considerable. Results could also differ according to whether they were expressed in absolute (ms2) or in normalized (%) units. Age and gender significantly influenced HR and various components of HRV. Furthermore we observed significant interactions between age and gender regarding several components of HRV, indicating that men and women differ at younger age, but not after the age of about 50 yrs. Parasympathetic modulation appeared to be greater in women than in men at younger age, but not after the age of menopause. The changes of HR and HRV on standing were attenuated with increasing age. Influences of body mass index, smoking, alcohol consumption and habitual physical activity were small to negligible. In conclusion, the employed methodology and several demographic, anthropometric and/or lifestyle characteristics should be taken into account for the interpretation of HRV in cardiovascular disease.

International Society of Hypertension Low and Middle Income Countries Committee Review of the Goals of the Committee and of 5 years of ISH activities in Low and Middle Income Countries

The goal of the present study was to assess the effect of antihypertensive therapy on clinic (CBP) and ambulatory (ABP) blood pressures, on ECG voltages, and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension.Patients who were/=60 years old, with systolic CBP of 160 to 219 mm Hg and diastolic CBP of95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both. Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups: nonsustained hypertension (140 mm Hg), mild sustained hypertension (140 to 159 mm Hg), and moderate sustained hypertension (/=160 mm Hg). At baseline, patients with nonsustained hypertension had smaller ECG voltages (P0.001) and, during follow-up, a lower incidence of stroke (P0.05) and of cardiovascular complications (P=0.01) than other groups. Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension (P0.001). The influence of active treatment on ECG voltages (P0.05) and on the incidence of stroke (P0.05) and cardiovascular events (P=0.06) was more favorable than that of placebo only in patients with moderate sustained hypertension.Patients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension. The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension.

In previous cross-sectional and longitudinal population studies, we found that the slope of systolic pressure on age was steeper in postmenopausal than in premenopausal women. We hypothesised that this observation could be due to a specific effect of menopause on the elasticity of the large arteries. We investigated 315 randomly selected women, aged 30 to 70 years. Based on 5.2 years of follow-up, 166 women were premenopausal and 149 menopausal (44 reaching menopause and 105 postmenopausal). These women were matched on age and body mass index with 315 men. We used a wall-tracking ultrasound system to measure the diameter, compliance and distensibility of the brachial and the common carotid and femoral arteries as well as carotid-femoral pulse wave velocity. Pulse pressure was determined from 24-h blood pressure recordings. Both in menopausal women (r = 0.37; P < 0.001) and in matching male controls (r = 0.16; P = 0.04), pulse pressure widened with increasing age. The slope of the 24-h pulse pressure on age was steeper in menopausal women than in their premenopausal counterparts (0.428 vs -0.066 mm Hg per year; P = 0.003) and than in the male controls (0.428 vs 0.188 mm Hg per year; P = 0.06). After adjustment for age, 24-h mean pressure, body mass index, antihypertensive drug treatment, smoking and the use of oral contraceptives or hormonal replacement therapy, postmenopausal women showed a higher carotid-femoral pulse wave velocity (7.77 vs 6.71 m/s; P = 0.02) and had a slightly greater diameter of the common carotid artery (7.09 vs 6.79 mm; P = 0.07) than their premenopausal counterparts. After similar adjustments, menopausal class was not significantly associated with other vascular measurements in women or with any vascular measurement in control men. In conclusion, menopause per se may increase aortic stiffness. We hypothesise that this phenomenon may contribute to the rise in systolic pressure and pulse pressure in women beyond age 50 and, in turn, may lead to a slight dilatation of the common carotid artery.

Peak oxygen uptake (VO2) is a powerful prognostic index, but maximal exercise testing in heart transplant candidates has a number of disadvantages. It is unknown whether it is possible to predict peak VO2 from a comprehensive dataset with parameters of heart and lung function at rest.One hundred adult patients in sinus rhythm and with either idiopathic or ischaemic heart failure performed a graded cycle ergometer test until volitional fatigue and underwent radionuclide ventriculography, heart catheterization, and lung function measurements at rest.Weight, height, age, gender and aetiology of heart failure explained 48% of the variance of peak VO2. On top of these anthropometric, demographic and clinical patient characteristics, 12% of the variance of peak VO2 was additionally explained by all resting measurements combined, i.e. radionuclide left ventricular ejection fraction, peak ejection rate, peak filling rate, cardiac frequency, mean right atrial pressure, pulmonary capillary wedge pressure, pulmonary artery pressures, cardiac output, forced vital capacity, forced expiratory volume in one second, and pulmonary diffusing capacity (cumulative R2 = 0.60); among these, pulmonary vascular resistance was the most important predictor (+6%; P0.001). Analyses in a subset of 43 male patients pointed out that systemic pressures and vascular resistance were not related to peak VO2.On the basis of resting left ventricular function, haemodynamics, and routine pulmonary measurements, it is unlikely to accurately predict exercise tolerance in the majority of heart transplant candidates, i.e. patients with either idiopathic or ischaemic heart failure and able to exercise until exhaustion.

The Syst-Eur study investigated whether active antihypertensive treatment could reduce cardiovascular complications in elderly patients with isolated systolic hypertension. Patients (or = 60 years) were randomly assigned to active treatment (n = 2398), i.e. nitrendipine, with the possible addition of enalapril and hydrochlorothiazide, or matching placebos (n= 2297). In the intention-to-treat analysis, the between-group difference in blood pressure amounted to 10.1/4.5 mm Hg (P0.001). Active treatment reduced the total incidence of stroke (primary endpoint) by 42% (P = 0.003), of all cardiac endpoints by 26% (P = 0.03), and of all cardiovascular endpoints combined by 31% (P0.001). Cardiovascular mortality was slightly lower on active treatment (-27%; P = 0.07), but all-cause mortality was not influenced (-14%; P = 0.22). For total (P = 0.009) and cardiovascular mortality (P = 0.09), the benefit of antihypertensive treatment weakened with advancing age and for total mortality it decreased with higher systolic blood pressure at entry (P = 0.05). The benefits of active treatment were not independently related to gender or to the presence of cardiovascular complications at entry. Further analyses also suggested benefit in patients who were taking nitrendipine as the sole therapy. The per-protocol analysis largely confirmed the intention-to-treat results. It can be concluded that stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis in elderly patients with isolated systolic hypertension.

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 BPor = 160 mm Hg and diastolic BP95 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; P0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P0.001). 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.

Scientific evidence suggests that there is a mutual relationship between blood pressure and physical activity. On one hand, a high blood pressure may adversely affect exercise performance, on the other dynamic exercise training seems to contribute to the control of blood pressure. These relationships between pressure and activity will be explored in this review.