scispace - formally typeset
Search or ask a question

Showing papers by "Robert Fagard published in 2005"


Journal ArticleDOI
TL;DR: The results suggest that moderate intensity resistance training is not contraindicated and could become part of the non-pharmacological intervention strategy to prevent and combat high blood pressure, however, additional studies are needed, especially in the hypertensive population.
Abstract: ObjectiveTo assess the influence of resistance training on resting blood pressure in healthy sedentary adults.MethodsA comprehensive literature search with the MEDLINE computerized database was conducted and reference lists of published articles and reviews on the topic were checked. Inclusion crite

439 citations


Journal ArticleDOI
TL;DR: It is suggested that antihypertensive drug treatment improves outcome mainly through lowering of systolic blood pressure, and absolute benefit increased with age and with lower ratio of DBP to SBP lowering.
Abstract: Based on individual patient data, we performed a quantitative overview of trials in hypertension to investigate to what extent lowering of systolic blood pressure (SBP) and diastolic blood pressure (DBP) contributed to cardiovascular prevention. We selected trials that tested active antihypertensive drugs against placebo or no treatment. Our analyses included 12,903 young (30 to 49 years of age) patients randomized in 3 trials and 14,324 old (60 to 79 years of age) and 1209 very old (> or =80 years of age) patients enrolled in 8 trials. Antihypertensive treatment reduced SBP/DBP by 8.3/4.6 mm Hg in young patients, by 10.7/4.2 mm Hg in old patients, and by 9.4/3.2 mm Hg in very old patients, respectively, resulting in ratios of DBP to SBP lowering of 0.55, 0.39, and 0.32, respectively (P=0.004 for trend with age). In spite of the differential lowering of SBP and DBP, antihypertensive treatment reduced the risk of all cardiovascular events, stroke and myocardial infarction in the 3 age strata to a similar extent. Absolute benefit increased with age and with lower ratio of DBP to SBP lowering. Furthermore, in patients with a larger-than-median reduction in SBP, active treatment consistently reduced the risk of all outcomes irrespective of the decrease in DBP or the achieved DBP. These findings remained consistent if the achieved DBP averaged <70 mm Hg. In conclusion, our overview suggests that antihypertensive drug treatment improves outcome mainly through lowering of SBP.

264 citations


Journal ArticleDOI
TL;DR: In a meta-analysis of 44 randomized controlled intervention trials, the weighted net change in conventional systolic/diastolic blood pressure in response to dynamic aerobic training averaged −3.4/−2.4 mmHg (P<0.001), and exercise appears to be less effective than diet in lowering blood pressure.
Abstract: Epidemiological studies suggest an inverse relationship between physical activity or fitness and blood pressure. In a meta-analysis of 44 randomized controlled intervention trials, the weighted net change in conventional systolic/diastolic blood pressure in response to dynamic aerobic training averaged -3.4/-2.4 mmHg (P < 0.001). The effect on blood pressure was more pronounced in hypertensives than in normotensives. This type of training also lowered the blood pressure measured during ambulatory monitoring and during exercise. However, exercise appears to be less effective than diet in lowering blood pressure (P < 0.02), and adding exercise to diet does not seem to further reduce blood pressure.

86 citations


Journal ArticleDOI
TL;DR: There is overwhelming evidence from epidemiological prospective follow-up studies indicating that physical activity, assessed by questionnaire or interview, and physical fitness, measured on exercise testing, are inversely related to the incidence of cardiovascular disease and mortality.
Abstract: There is overwhelming evidence from epidemiological prospective follow-up studies indicating that physical activity, assessed by questionnaire or interview, and physical fitness, measured on exercise testing, are inversely related to the incidence of cardiovascular disease and mortality [1–3]. The relative risks of physical inactivity and low fitness are approximately 2. The benefits of moderately vigorous activity [4] and of greater fitness [5,6] have also been shown in hypertensive patients. It is currently not sufficiently known whether the beneficial effect of physical activity derives from the influence of physical activity itself or results from its effects on other risk factors or pathophysiological mechanisms, or all of these. There is evidence from randomized controlled trials and/or observational studies that exercise has favourable effects on blood pressure, glucose homeostasis, blood lipids, body fatness, smoking behaviour and endothelial function, amongst other factors [3]. With regard to blood pressure, many epidemiological studies have analysed the relationships between habitual physical activity or physical fitness and blood pressure. Although several studies did not observe significant independent relationships, others concluded that blood pressure is lower in fitter and more active subjects [7].

75 citations


Journal Article
TL;DR: National Institute of Sports Medicine, Italian National Olympic Committee, Via dei Campi Sportivi 46, 00197 Rome, Italy, and Department of Cardiology, Meander Medisch Centrum, Amersfoort, The Netherlands.
Abstract: National Institute of Sports Medicine, Italian National Olympic Committee, Via dei Campi Sportivi 46, 00197 Rome, Italy; Cardiovascular Rehabilitation Unit, KU Leuven, Leuven, Belgium; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway; Division of Inherited Cardiovascular Diseases, University of Athens, Athens, Greece; Department of Pathological Anatomy, University of Pavia, Pavia, Italy; Department of Cardiology, University of Brescia, Brescia, Italy; Department of Medicine, Sahlgrens University Hospital/Östra, Gothenburg, Sweden; Unité Biologie et Medicine du Sport, Hopital Pontchavillon, Rennes, France; Departments of Cardiology and Pathology, University of Padova, Padova, Italy; Department of Cardiology, Civil Hospital, Conegliano, Italy; Department of Cardiology, University Hospital, Munich, Germany; University Hospital Gasthuisberg, Leuven, Belgium; Department of Cardiology, Bad Oeynhausen, Germany; Department of Cardiology, Nijmegen, The Netherlands; Klinikk Ullevål Sykehus, Oslo, Norway; Department of Cardiology, University Hospital Uppsala, Uppsala, Sweden; Department of Sports Medicine, Aristotle University, Thessaloniki, Greece; Wellness Medical Center, Stockport, UK; Heart Institute, Sheba Medical Center, Tel Hashomer, Israel; Division of Cardiology, University Hospital, Basel, Switzerland; Children National Medical Center, Washington DC, USA; Cardiac Rehabilitation Center, Bronovo Hospital, Gravenhage, The Netherlands; Heart Hospital, University College London, London, UK; Department of Cardiology, University of L’Aquila, L’Aquila, Italy; Molecular Cardiology, Fondazione S. Maugeri, Pavia, Italy; and Department of Cardiology, Meander Medisch Centrum, Amersfoort, The Netherlands

56 citations


Journal ArticleDOI
TL;DR: The findings suggest that endothelial dysfunction might contribute to the increase in cardiovascular morbidity and mortality associated with hot weather.
Abstract: Studies within populations consistently showed that cardiovascular mortality increases with hot weather. However, the biological mechanisms underlying this association remain largely unknown. Endothelial function plays a pivotal role in the pathogenesis of cardiovascular disease. Therefore, we investigated the association between endothelial function and outdoor temperature. We measured flow-mediated vasodilatation (FMD) as index of endothelial function in 274 randomly recruited sub- jects (50% women, mean age 40.6 year). Both before (partial r = )0.14, p = 0.017) and after adjustment (partial r= )0.17, p= 0.006) for sex, age, body mass index, brachial artery diameter and current smoking, FMD was negatively associated with mean daily temperature. The odds of endothelial dysfunc- tion increased by 58% (95% CI: 4-141%; p = 0.03) for each 10 C increment in mean daily temperature during the week before the examination. Our findings suggest that endothelial dysfunction might contribute to the increase in cardiovascular morbidity and mortality associated with hot weather.

54 citations


Journal ArticleDOI
TL;DR: This poster presents a poster presented at the 2016 European Congress of Sports Medicine and Biologie et Médecine du Sport entitled “Sports Medicine Division, Aristotle University, Thessaloniki, Greece: Cardiovascular Rehabilitation and Hypertension.”
Abstract: Hypertension and Cardiovascular Rehabilitation Unit, KULeuven, Leuven, Belgium, Department of Heart Disease, Haukelund University Hospital, Bergen, Norway, Department of Medicine, Sahlgrens University Hospital/Östra, Gothenburg, Sweden, Unité Biologie et Médecine du Sport, Hôpital Pontchaillou, Rennes, France, Sports Medicine Division, Aristotle University, Thessaloniki, Greece and Department of Rehabilitation Sciences, KULeuven, Leuven, Belgium.

53 citations


Journal ArticleDOI
TL;DR: There was no significant difference in creatinine clearance between twins who both had LBW as compared with twins whoBoth had a high birth weight, which may suggest that maternal factors, which influence the relation between LBW and renal function, are less important.
Abstract: Previous studies have shown that low birth weight (LBW) is a risk factor for renal impairment in adult life. The effects of LBW and renal function were studied by using twins, which allows distinguishing among fetoplacental, maternal, and genetic influences. Perinatal data were obtained at birth, and absolute creatinine clearance (not corrected for body surface area) was measured at a mean age of 25.6 yr in 653 individuals. Twins were considered both as individuals and as members of twin pairs. Statistical analyses were performed with and without adjusting for gestational age, zygosity, gender, age, body mass index, glucose level, BP, and smoking status. Creatinine clearance was 4 ml/min lower in twins with LBW (<2500 g) than in twins with a high birth weight (P < 0.04, adjusted). Intrapair birth weight difference correlated positively with the intrapair difference in creatinine clearance equally in monozygotic and dizygotic twins (r = 0.35, P < 0.0001; r = 0.43, P < 0.0001, respectively). This suggests that fetoplacental factors are related to renal function and that genetic factors are less important. There was no significant difference in creatinine clearance between twins who both had LBW as compared with twins who both had a high birth weight. This may suggest that maternal factors, which influence the relation between LBW and renal function, are less important. LBW is related to a lower creatinine clearance at adult age. This relationship is probably due to fetoplacental factors. Surprising, genetic and maternal factors seem less important.

35 citations



Journal ArticleDOI
TL;DR: The result suggests that the apparent effect on blood pressure is not the only cause of stroke risk reduction in hypertensive subjects submitted to an antihypertensive medicine, and that the mechanism of risk reduction obtained by blood pressure‐lowering pharmacological treatment remains unclear.
Abstract: The mechanism of risk reduction obtained by blood pressure-lowering pharmacological treatment remains unclear. We explored the amount of risk reduction attributable to the apparent effect of antihypertensive medicines on blood pressure by using the capture approach. Five randomized, placebo or nil controlled trials with a total of 28,997 subjects and 1,935 cardiovascular fatal or non-fatal events from the INDANA database met the eligibility criteria. Computations were performed on the original individual records using multiple Cox's proportional hazard regression models designed for meeting the assumed treatment mode of action and comparing relevant assumptions. For coronary event, the results are inconclusive essentially because the risk reduction is mild. However, for stroke the risk reduction adjusted for baseline risk factors is 34% (P<0.0001). The part explained by the effect of treatment on systolic blood pressure is 49% of this reduction, with 95% confidence interval not including 100%. This result suggests that the apparent effect on blood pressure is not the only cause of stroke risk reduction in hypertensive subjects submitted to an antihypertensive medicine.

25 citations



Journal ArticleDOI
TL;DR: The results pave the way for studies looking for the influence of NOS3 on blood pressure in high-risk subsets such as diabetic or hypertensive patients, and indicate the importance of ambulatory blood pressure and haplotype analysis in revealing the moderate effect of polymorphisms onBlood pressure.
Abstract: BACKGROUND: Nitric oxide is involved in the regulation of vascular basal tone and blood pressure. Polymorphisms of NOS3, the gene that codes for endothelial nitric oxide synthase, have been associated with essential hypertension. OBJECTIVE: To look for linkage and association of three di-allelic polymorphisms (Glu298Asp, intron 4 VNTR and T-786C) and the intron 13 CA-repeat of NOS3 with blood pressure as a continuous trait. METHODS: Genotyping was performed in 110 dizygotic white twin pairs from Flanders, Belgium. The influence of NOS3 polymorphisms on conventional and ambulatory blood pressure was assessed by sib-pair analysis and haplotype association analysis. RESULTS: Genotype frequencies were similar to those previously reported in white populations. Sib-pair analysis did not show a significant influence of either polymorphism on blood pressure. Haplotype analysis disclosed a significant association between NOS3 haplotypes and daytime ambulatory diastolic (P = 0.02) and systolic (P < 0.0001) blood pressure, the latter remaining significant after multiple testing was taken into account (P = 0.032). The association between daytime ambulatory systolic blood pressure and NOS3 haplotypes was mainly attributable to four haplotypes accounting for 11.9% of all represented haplotypes. CONCLUSION: We show for the first time a highly significant association of ambulatory blood pressure with NOS3 haplotypes in well-characterized white individuals from Flanders. These results pave the way for studies looking for the influence of NOS3 on blood pressure in high-risk subsets such as diabetic or hypertensive patients. They indicate the importance of ambulatory blood pressure and haplotype analysis in revealing the moderate effect of polymorphisms on blood pressure.

Journal ArticleDOI
TL;DR: In this article, the authors investigated in three populations to what extent in a family-based study, left ventricular mass (LVM) was associated with the C-532T and G-6A polymorphisms in the angiotensinogen (AGT) gene.
Abstract: In the European Project on Genes in Hypertension (EPOGH), we investigated in three populations to what extent in a family-based study, left ventricular mass (LVM) was associated with the C-532T and G-6A polymorphisms in the angiotensinogen (AGT) gene. We randomly recruited 221 nuclear families (384 parents and 440 offspring) in Cracow (Poland), Novosibirsk (Russia), and Mirano (Italy). Echocardiographic LVM was indexed to body surface area, adjusted for covariables, and subjected to multivariate analyses, using generalized estimating equations and quantitative transmission disequilibrium tests in a population-based and family-based approach, respectively. We found significant differences between the two Slavic centres and Mirano in left ventricular mass index (LVMI) (94.9 vs 80.4 g/m2), sodium excretion (229 vs 186 mmol/day), and the prevalence of the AGT -6A (55.7 vs 40.6%) and -532T (16.8 vs 9.4%) alleles. In population-based as well as in family-based analyses, we observed positive associations of LVMI and mean wall thickness (MWT) with the -532T allele in Slavic, but not in Italian male offspring. Furthermore, in Slavic male offspring, LVMI and MWT were significantly higher in carriers of the -532T/-6A haplotype than in those with the -532C/-6G or -532C/-6A allele combinations. In women, LVMI was neither associated with single AGT gene variants nor with the haplotypes (0.19 < P <0.98). In Slavic offspring carrying the AGT -532C/-6G or -532C/-6A haplotypes, LVMI significantly increased with higher sodium excretion (+3.5 g/m2/100 mmol; P=0.003), whereas such association was not present in -532T/-6A haplotype carriers (P-value for interaction 0.04). We found a positive association between LVMI and the AGT -532T allele due to increased MWT. This relation was observed in Slavic male offspring. It was therefore dependent on gender, age and ecogenetic context, and in addition it appeared to be modulated by the trophic effects of salt intake on LVM.

Journal ArticleDOI
TL;DR: The primary efficacy outcome, which included all-cause mortality, myocardial infarction, refractory angina, new overt heart failure, debilitating stroke and peripheral revascularization, was not significantly different between the two groups.
Abstract: The ACTION trial was a multicentre, double-blind, randomized, placebo-controlled trial in which the effect of long-acting nifedipine GITS (Gastrointestinal Therapeutic System) on mortality and cardiovascular morbidity was evaluated in patients with stable angina [1]. The trial was designed in response to the debate in the 1990s concerning the safety of calcium antagonists, in particular in patients with coronary artery disease [2]. Patients who were aged 35 years or older, and who had stable angina pectoris and needed oral or transdermal anti-anginal treatment, were eligible for the study if they had a history of myocardial infarction, angiographic coronary artery disease but no history of myocardial infarction, or just a positive exercise test or perfusion defect. Leftventricular ejection fraction had to be at least 40%. Patients with orthostatic hypotension or a systolic blood pressure of 90 mmHg or less were excluded, as well as those patients with a systolic blood pressure of at least 200 mmHg or a diastolic blood pressure of at least 105 mmHg, or both. The main results have been published elsewhere [3]. Seven thousand, six hundred and sixty-five patients were randomly allocated to addition of either nifedipine GITS (30–60 mg daily), or matching placebo, to the basic regimen they were taking, and followed up for an average of 4.9 years. The primary efficacy outcome, which included all-cause mortality, myocardial infarction, refractory angina, new overt heart failure, debilitating stroke and peripheral revascularization, was not significantly different between the two groups (P 1⁄4 0.54). When the components of the primary combined endpoint were analysed separately, nifedipine treatment was associated with a 29% reduction in new overt heart failure (P 1⁄4 0.015), which was the only significant difference among these endpoints. With regard to secondary endpoints, coronary angiography ( 18%; P < 0.001) and coronary bypass surgery ( 21%; P 1⁄4 0.002) were performed less frequently in the nifedipinetreated patients. Finally, blood pressure was lower in the nifedipine group by approximately 5/3 mmHg throughout the trial.

Journal ArticleDOI
TL;DR: The data show that the specific aminopeptidase B inhibitor, arphamenine A, reduces collagen production in cardiac fibroblasts and that this reduction is accompanied by a pronounced inhibition of lysyl oxidase.
Abstract: Objective. To determine whether the aminopeptidase B inhibitor, arphamenine A, could affect collagen production and expression in control and TGF-s1-treated cardiac fibroblasts.Design and Methods. Cardiac fibroblasts from passage 2 from normal male adult rats were cultured to confluency and incubated with and without 600 pmol/l TGF-s1 for 2 days in serum-free Dulbecco's modified Eagle's medium and then incubated with 100 µmol/l arphamenine A for 1 day in this medium added ascorbic acid, s-aminopropionitrile and titriated proline. Soluble collagen was measured in the conditioned medium and non-soluble collagen in the cell layer. Aminopeptidase activity was estimated by spectrophotometric determination of the liberation of p-nitroaniline from alanine- or arginine-p-nitroanilide. Matrix metalloproteinase (MMP) and lysyl oxidase activity were assayed in the conditioned medium. A semi-quantitative reverse transcriptase- polymerase chain reaction was used to examine the expression of lysyl oxidase and collagen ...


Journal ArticleDOI
TL;DR: The data suggest that both alanine and arginine aminopeptidases are involved in the reversal of the angiotensin II-stimulated collagen gel contraction in control and TGF-beta1-treated cardiac fibroblasts or myofibroblast.
Abstract: The purpose of this investigation was to determine whether aminopeptidase inhibition could affect the angiotensin II-stimulated collagen gel contraction in basal (control) and TGF-beta1-treated cardiac fibroblasts (or myofibroblasts). The tested aminopeptidase inhibitors were the broad range aminopeptidase inhibitor bestatin, the specific inhibitor of alanine aminopeptidase leuhistin, and the specific inhibitor of arginine aminopeptidase arphamenine A. Cardiac fibroblasts (from normal male adult rats) from passage 2 were cultured to confluency and incubated with(out) 400 pmol/L TGF-beta1 in Dulbecco Modified Eagle Medium (DMEM) with 10% fetal bovine serum (FBS). These fibroblasts were then further incubated in a floating collagen gel lattice with the tested products (angiotensin II, bestatin, leuhistin, or arphamenine A) for 3 days in DMEM without FBS. The contraction of the collagen gel lattice by cardiac fibroblasts was determined by measuring the gel volume with tritiated water. Aminopeptidase activity was estimated by spectrophotometric determination of the liberation of p-nitroaniline from alanine- or arginine-p-nitroanilide. Angiotensin II (100 nmol/L) reduced the gel volume in control and TGF-beta1-treated cardiac fibroblasts. The angiotensin II-stimulated collagen gel contraction in control and TGF-beta1-treated fibroblasts was almost completely reversed by leuhistin and arphamenine A (100 micromol/L). Bestatin (100 micromol/L) only partially inhibited the angiotensin II-stimulated collagen gel contraction in control fibroblasts, although it did not affect the angiotensin II-induced contraction in TGF-beta1-treated fibroblasts. In control and TGF-beta1-treated cardiac fibroblasts, 100 micromol/L leuhistin or arphamenine A only partially inhibited alanine aminopeptidase activity, whereas bestatin (100 micromol/L) completely inhibited the alanine aminopeptidase activity. Arginine aminopeptidase activity was only partially inhibited by leuhistin and arphamenine A at 100 micromol/L in control and TGF-beta1-treated fibroblasts. Bestatin, however, completely blocked the arginine aminopeptidase activity in control fibroblasts and only partially in TGF-beta1-treated fibroblasts at 100 micromol/L. Our data suggest that both alanine and arginine aminopeptidases are involved in the reversal of the angiotensin II-stimulated collagen gel contraction in control and TGF-beta1-treated cardiac fibroblasts or myofibroblasts.


Journal ArticleDOI
TL;DR: There was a significant synergistic effects of eNOS 894T allele and GNB3 825T allele in EH, which should be a risk factor for EH in chinese Han nationality.


Journal ArticleDOI
TL;DR: In this paper, the influence of resistance training on resting blood pressure in healthy sedentary adults was assessed using a comprehensive literature search with the MEDLINE computerized database and reference lists of published articles and reviews on the topic were checked.
Abstract: ObjectiveTo assess the influence of resistance training on resting blood pressure in healthy sedentary adults.MethodsA comprehensive literature search with the MEDLINE computerized database was conducted and reference lists of published articles and reviews on the topic were checked. Inclusion crite