R. Fagard

Prognostic significance of blood pressure measured in the office, at home and during ambulatory monitoring in older patients in general practice

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⩽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.

Menopause and the characteristics of the large arteries in a population study.

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.

Geographical and temporal differences in the urinary excretion of inorganic arsenic: a Belgian population study.

OBJECTIVE: This Belgian study assessed the geographical and temporal differences in the exposure of the population to inorganic arsenic, a known carcinogen. METHODS: In the CadmiBel study (1985-9) the 24 h urinary arsenic excretion was measured, as an index of recent exposure, in industrialised cities (Liège: n = 664, Charleroi: n = 291), in a rural control area (Hechtel-Eksel: n = 397), and in rural districts in which the population had possibly been exposed through the drinking water or the emissions of nonferrous smelters (Wezel: n = 93, Lommel: n = 111, and Pelt: n = 133). In the PheeCad study, in 1991-5, the rural areas (n = 609) were re-examined together with an urban control area (Leuven: n = 152). RESULTS: The CadmiBel results showed that after adjustment for sex, age, and body mass index, the 24 h arsenic excretion was on average low in Liège (91 nmol), Charleroi (155 nmol), Hechtel-Eksel (144 nmol), and Wezel (158 nmol), whereas the highest excretions were found in Lommel (570 nmol) and Pelt (373 nmol). During the PheeCad study, the mean 24 h arsenic excretion in the rural areas ranged from 81 to 111 nmol. This was lower than six years earlier and similar to the excretion in the control town (108 nmol). Longitudinal studies in 529 people living in the rural areas confirmed that their 24 h arsenic excretion had decreased (P < 0.001) from 222 to 100 nmol. As well as the drinking water, industry was likely to be a source of the increased exposure in Lommel and Pelt in 1985-9, because at that time the urinary arsenic excretion did not follow the regional differences in the arsenic content of the drinking water, because the fall in the arsenic excretion over time coincided with the implementation by industry of stricter environmental regulations, because in individual subjects the urinary arsenic excretion was inversely correlated with the distance to the nearest smelter, and because an increased arsenic excretion was only found downwind from the main smelter. The official network that monitors the arsenic concentration in airborne and fall out dust did not detect the high exposure in Lommel and Pelt between 1985 and 1989. CONCLUSION: This study highlights the necessity to validate environmental monitoring programmes by directly estimating the internal exposure of the population.

Twenty-four hour blood pressure monitoring in the Syst-Eur trial

This article describes the objectives and protocol of a study on ambulatory blood pressure in elderly patients with isolated systolic hypertension. This study constitutes an optional side-project to the Syst-Eur trial.The multicentre Syst-Eur trial investigates whether antihypertensive treatment of elderly patients with isolated systolic hypertension will influence the incidence of stroke. Secondary endpoints include cardiovascular events, such as myocardial infarction.The main objective of the side-project is to investigate whether ambulatory blood pressure monitoring will improve the prediction of cardiovascular complications based on blood pressure measurement in the clinic. The side-project also provides the opportunity to evaluate the diurnal profile of blood pressure in elderly patients with isolated systolic hypertension randomized to placebo or active antihypertensive treatment.

Arterial properties in relation to genetic variation in α-adducin and the renin–angiotensin system in a White population

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 ⩽0.014), femoral cross-sectional compliance was significantly higher (0.74 vs 0.65 mm2 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 × 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⩽0.005) in AGT CG haplotype homozygotes compared with non-carriers, whereas the opposite was true for brachial distensibility (12.4 vs 14.4 × 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.

Intra-erythrocyte cation concentrations in relation to the C1797T |[beta]|-adducin polymorphism in a general population

Genetic variability in the ADD1 (Gly460Trp) and ADD2 (C1797T) subunits of the cytoskeleton protein adducin plays a role in the pathogenesis of hypertension, possibly via changes in intracellular cation concentrations. ADD2 1797CC homozygous men have decreased erythrocyte count and hematocrit. We investigated possible association between intra-erythrocyte cations and the adducin polymorphisms. In 259 subjects (mean age 47.7 years), we measured intra-erythrocyte Na+ [iNa], K+ [iK] and Mg2+ [iMg], serum cations and adducin genotypes. Genotype frequencies (ADD1: GlyGly 61.5%, Trp 38.5%; ADD2: CC 80.4%, T 19.6%) complied with Hardy–Weinberg proportions. In men, ADD2 CC homozygotes (n=100) compared to T-carriers (n=23) had slightly lower iK (85.8 versus 87.5 mmol/l cells; P=0.107), higher iMg (1.92 versus 1.80 mmol/l cells; P=0.012), but similar iNa (6.86 versus 6.88 mmol/l cells; P=0.93). In men, iK, iMg and iNa did not differ according to ADD1 genotypes. In men, iK (R2=0.128) increased with age and serum Na+, but decreased with serum total calcium and the daily intake of alcohol. iMg (R2=0.087) decreased with age, but increased with serum total calcium. After adjustment for these covariates (P⩽0.04 for all), findings in men for iK (CC versus T: 85.8 versus 87.3 mmol/l; P=0.14) and iMg (1.91 versus 1.82 mmol/l; P=0.03) remained consistent. In 136 women, none of the phenotype–genotype relations reached significance. Changes in intra-erythrocyte cations in ADD2 1797CC homozygous men might lead to osmotic fragility of erythrocytes, but to what extent they reflect systemic changes or are possibly involved in blood pressure regulation remains unknown.

Markers for cardiovascular disease in monozygotic twins discordant for the use of third-generation oral contraceptives

Oral contraceptives (OC) modulate the risk for developing cardiovascular (CV) diseases. The aim of this study was to determine whether the use of third-generation OC has an impact on markers of CV disease in genetically identical women. We performed an intrapair comparison in 27 monozygotic twin pairs, one of whom was taking third-generation OC, whereas the other was not using OC. Biometric parameters were ascertained and conventional and 24-h ambulatory blood pressure (BP) was recorded. A fasting blood sample was taken for the measurement of glucose, insulin, proinsulin, lipids, and insulin-like growth factor binding protein-1 (IGFBP-1). Insulin resistance and β-cell function were calculated by homeostasis model assessment (HOMA). A 24-h urine sample for cortisol was obtained. Third-generation OC use increased 24-h ambulatory systolic and diastolic BP by 5.2 and 3.9 mmHg, respectively (both P=0.0003). There was no effect on glucose, insulin and proinsulin levels, and on HOMA parameters, but the IGFBP-1 levels were markedly raised (P=0.0009). The lipid profile showed a 34% increase in triglyceride levels (P<0.0001), but also a 7% increase in HDL-cholesterol levels (P=0.037). Use of third-generation OC impacts on CV disease markers in young-adult genetically identical women. Some changes are beneficial (increased HDL-cholesterol), whereas others may be deleterious (increased BP and triglyceride levels) or have unknown effects at this time (increased IGFBP-1 levels).

MORBIDITY AND MORTALITY ON COMBINATION VERSUS MONOTHERAPY IN THE SYSTOLIC HYPERTENSION IN EUROPE TRIAL: 2B.02

Objective: The current literature supports the immediate use of combinations of antihypertensive drugs in terms of ease of use and adherence, but the key issue whether combination therapy is more effective than monotherapy in the prevention of cardiovascular complications remains unproven. Design and Method: We analysed the double-blind (median follow-up: 2.0 years) and open follow-up (6.0 years) phases of the Systolic Hypertension in Europe trial. Patients were >60 years with an entry systolic/diastolic blood pressure (BP) of 160–219/<95 mmHg. Antihypertensive treatment started immediately after randomisation in the active-treatment group, but only after completion of the double-blind trial in control patients. Treatment consisted of nitrendipine (10–40 mg/day) with the possible addition of enalapril (5–20 mg/day). We adjusted our analyses for sex, age, history of cardiovascular complications, baseline systolic blood pressure and previous antihypertensive treatment. Results: During the double-blind trial, adding enalapril to nitrendipine (n = 515), compared to the equivalent placebos (n = 559), decreased systolic BP by a further 9.5 mmHg and reduced all cardiovascular events by 51% (P = 0.0035) and heart failure by 66% (P = 0.032) with similar trends for stroke (–51%; P = 0.066) and cardiac events (–44%; P = 0.075). Over the whole duration of follow-up, combination therapy (n = 871), compared to nitrendipine monotherapy (n = 1552) decreased systolic BP by 3.1 mmHg and reduced total mortality (–32%; P = 0.023, Figure), with similar trends for all cardiovascular events (–23%; P = 0.081) and stroke (–42%; P = 0.054). Conclusions: Congruent with the stronger blood pressure reduction, our results suggest that combination therapy with nitrendipine plus enalapril might improve outcome over and beyond the benefits seen with nitrendipine monotherapy. Figure 1. No caption available.

ASSOCIATION OF ECHOCARDIOGRAPHIC LEFT VENTRICULAR STRUCTURE WITH THE ACE D/I POLYMORPHISM: A META-ANALYSIS: PP.22.364

Introduction: In a meta-analysis published in 2000, we derived pooled estimates for the association of left ventricular mass (LVM) and hypertrophy (LVH), as diagnosed by electrocardiography or echocardiography, with the deletion/insertion polymorphism in the angiotensin-converting enzyme gene (ACE D/I). Design: We updated the meta-analysis until May 2009, but we only considered echocardiographically phenotypes. Methods: We used random effects models to compute pooled estimates. Results: Of 831 screened studies, we reviewed 43 studies (10320 participants, 17.5% Asians, 82.4% Whites, 0.1%Blacks). 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 vs II) were 0.39 (95% confidence interval 0.20 to 0.59, p < 0.001) for LVM, 0.34 (0.085 to 0.59, p = 0.009) for MWT, and 0.066 (–0.049 to 0.18; p = 0.26) for LVID. Across 16 studies (4894 participants), the pooled odds ratios of LVH (vs II homozygotes) were 1.11 (0.91 to 1.36, p = 0.29) and 1.02 (CI 0.75 to 1.39, p = 0.88) for the DD and DI genotypes, respectively. For LVM, there was a deficit of small studies with null results, but for LVH we did not find publication bias. 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.

De nieuwste richtlijnen (2007) voor de aanpak van hypertensie volgens de Europese verenigingen voor hypertensie en cardiologie

De laatste jaren werden door het Belgisch Hypertensie Comite de richtlijnen ondersteund die in 1999 uitgevaardigd werden door het Guidelines Subcommittee van de Wereldgezondheidsorganisatie (WGO) en de Internationale Vereniging voor Hypertensie (ISH) (1). Onlangs werden deze richtlijnen aangepast door de Europese Verenigingen voor Hypertensie en Cardiologie (2, 3), teneinde te beantwoorden aan de meer specifieke en homogene Europese situatie en om de richtlijnen aan te vullen met de meest recente wetenschappelijke informatie. Het is belangrijk te onderstrepen dat deze richtlijnen voortbouwen op de WGO-ISH-richtlijnen zodat de artsen er zich gemakkelijk in kunnen terugvinden. De kern van het document bestaat uit de classificatie van hypertensie, de evaluatie en de risicostratificatie van de patient en de daaraan gekoppelde richtlijnen voor aanpak en behandeling. Deze tekst is geen letterlijke vertaling van de richtlijnen, maar een zo getrouw mogelijke weergave van de belangrijkste aspecten.