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Biomedical subjects

Robert H Fagard

Publications and source records attributed to Robert H Fagard.

At least 19 recordsLinked to original sources
PubMed2006

Progression to hypertension in the non-hypertensive participants in the Flemish Study on Environment, Genes and Health Outcomes.

OBJECTIVE: To evaluate the consistency between a randomly recruited Western European population and the participants of the Framingham Heart Study, with respect to the rates and determinants of progression to hypertension. METHODS: Among the non-hypertensive individuals enrolled in the Flemish Study on Environment, Genes and Health Outcomes, we assessed progression from optimal (< 120/80 mmHg), normal (120-129/80-84 mmHg) and high-normal (130-139/85-89 mmHg) blood pressure to hypertension (> or = 140/90 mmHg). Our analysis included 781 women and 675 men (age range 10-77 years) who were followed up for a median of 4.6 years (interquartile range 2.4-8.1 years). Our statistical methods included Kaplan-Meier survival function estimates, the log-rank test and multiple Cox regression. RESULTS: In individuals younger than 50 years, 4-year progression rates associated with optimal, normal and high-normal blood pressure were 7.4% [95% confidence interval (CI) 5.5-9.3], 17.9% (95% CI 14.3-21.6) and 24.5% (95% CI 18.7-30.2), respectively. Corresponding 4-year rates of progression for individuals aged 50 years or older were 16.4% (95% CI 11.2-22.5), 26.3% (95% CI 19.8-32.9) and 54.0% (95% CI 45.7-62.3), respectively. In multivariate Cox regression, blood pressure category and body mass index at baseline were strong predictors of hypertension. Before the age of 50 years, male sex and a fast heart rate were also forerunners of hypertension. CONCLUSIONS: The stepwise increase in incidence of hypertension across the three non-hypertensive blood pressure categories in our cohort was similar to that observed in the Framingham Heart Study. The Framingham findings, which have informed several guidelines, can be extrapolated to a Western European population.

Adolescent↗
PubMed2005

Effects of endurance training on blood pressure, blood pressure-regulating mechanisms, and cardiovascular risk factors.

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 > or =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<0.001) and 3.3/3.5 mm Hg (P<0.01). The reduction of resting blood pressure was more pronounced in the 30 hypertensive study groups (-6.9/-4.9) than in the others (-1.9/-1.6; P<0.001 for all). Systemic vascular resistance decreased by 7.1% (P<0.05), plasma norepinephrine by 29% (P<0.001), and plasma renin activity by 20% (P<0.05). Body weight decreased by 1.2 kg (P<0.001), waist circumference by 2.8 cm (P<0.001), percent body fat by 1.4% (P<0.001), and the homeostasis model assessment index of insulin resistance by 0.31 U (P<0.01); HDL cholesterol increased by 0.032 mmol/L(-1) (P<0.05). In conclusion, aerobic endurance training decreases blood pressure through a reduction of vascular resistance, in which the sympathetic nervous system and the renin-angiotensin system appear to be involved, and favorably affects concomitant cardiovascular risk factors.

Blood Pressure↗
PubMed2005

Endothelial function and outdoor temperature.

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 subjects (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 dysfunction increased by 58% (95% CI: 4-141%; p = 0.03) for each 10 degrees 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.

Adult↗
PubMed2005

Effect of resistance training on resting blood pressure: a meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the influence of resistance training on resting blood pressure in healthy sedentary adults. METHODS: A comprehensive literature search with the MEDLINE computerized database was conducted and reference lists of published articles and reviews on the topic were checked. Inclusion criteria were as follows: the study involved a randomized, controlled trial; resistance training was the sole intervention; participants were sedentary normotensive and/or hypertensive adults with no other concomitant disease; the article was published in a peer-reviewed journal up to December 2003. We identified nine randomized controlled trials, involving 12 study groups and 341 participants. A standard protocol was used to extract information on sample size, participant characteristics, study design, training method and duration, and study outcomes. Pooled blood pressure estimates were obtained, weighted by either the number of participants in the training group or the inverse of the variance for blood pressure change. RESULTS: The weighted net changes of blood pressure, after adjustment for control observations, averaged -3.2 [95% confidence limits (CL) -7.1 to +0.7]/-3.5 (95% CL -6.1 to -0.9) mmHg when weighted for the number of trained participants, and -6.0 (95% CL -10.4 to -1.6)/ -4.7 (95% CL -8.1 to -1.4) mmHg, when weighted by the reciprocal of the variance for the blood pressure change. CONCLUSIONS: Our 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.

Adult↗
PubMed2005

Reversal of angiotensin II-stimulated collagen gel contraction in cardiac fibroblasts by aminopeptidase inhibition.

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.

Aminopeptidases↗
PubMed2005

Influence of the endothelial nitric oxide synthase gene on conventional and ambulatory blood pressure: sib-pair analysis and haplotype study.

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.

Adult↗
PubMed2005

Collagen production in cardiac fibroblasts during inhibition of aminopeptidase B.

OBJECTIVE: To determine whether the aminopeptidase B inhibitor, arphamenine A, could affect collagen production and expression in control and TGF-ss1-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-ss1 for 2 days in serum-free Dulbecco's modified Eagle's medium and then incubated with 100 mol/l arphamenine A for 1 day in this medium with added ascorbic acid, ss-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 type I and III. RESULTS: Arphamenine A dose-dependently inhibited basal and TGF-ss1-stimulated aminopeptidase activity. Arphamenine A reduced soluble and non-soluble collagen production in control and TGF-ss1-treated cardiac fibroblasts, while it decreased collagen type I and III expression only in TGF-ss1-treated fibroblasts. Lysyl oxidase, MMP-1 and MMP-2 activity were inhibited by arphamenine A in the conditioned media of control and TGF-ss1-treated cardiac fibroblasts. CONCLUSIONS: Our 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.

Alanine↗
PubMed2004

Prognostic significance of electrocardiographic voltages and their serial changes in elderly with systolic hypertension.

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 <95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe trial. Active treatment consisted of nitrendipine, which could be combined with or replaced by enalapril, hydrochlorothiazide, or both. At the end of the double-blind part of the trial (median follow-up, 2.0 years), follow-up was extended and all patients received active study drugs (median total follow-up, 6.1 years). Electrocardiography was performed at baseline and yearly thereafter. Electrocardiographic left ventricular mass was prospectively defined as the sum of 3 voltages (RaVL+SV1+RV5), which averaged 3.1+/-1.0 mV. The adjusted relative hazard rate, associated with a 1 mV higher sum at baseline, amounted to 1.10 and 1.15 for all-cause and cardiovascular mortality and to 1.21 and 1.18 for strokes and cardiac events, respectively (P< or =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< or =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.

Aged↗
PubMed2004

White-coat hypertension: a clinical review.

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 (<135 mm Hg systolic and <85 mm Hg diastolic). The prevalence of WCHT varies from 15% to over 50% of all patients with mildly elevated office BP (OBP) values. In untreated hypertensive patients, the probability of WCHT especially increases with female gender and a mildly elevated OBP level. The value of other possible determinants such as (non) smoking status, duration of hypertension, left ventricular mass, number of OBP measurements, educational level, etc. is less consistently shown. Although, for various reasons, studies evaluating the long-term effects of WCHT are not always easy to interpret, most data indicate that persons with WCHT have a worse or equal cardiovascular prognosis than normotensives, but a better one than those with sustained hypertension. WCHT is sometimes considered a prehypertensive state, but data on the long-term evolution of subjects with WCHT are scarce. Patients with WCHT and a high cardiovascular risk or proven target organ damage should be pharmacologically treated. Subjects with uncomplicated WCHT should probably not receive medical therapy, but a close follow-up, including regular assessment of other risk factors and measurement of OBP (every 6 months) and ABP (every 1 or 2 years), is warranted.

Journal Article↗
PubMed2004

Prevalence of hypertension, hypercholesterolemia, smoking and overweight in older Belgian adolescents.

BACKGROUND: Risk factors in young adulthood may persist into later life and eventually lead to cardiovascular (CV) disease. The purpose of this study was to describe the prevalence of hypertension and other established CV risk factors in older adolescents. METHODS: Study nurses examined 120 girls and 80 boys with a mean age of 17.4 (SD, 0.8; range 15.8-19.6 years). After 5 minutes of sitting rest, resting blood pressure (BP) of the participants was measured in triplicate by sphygmomanometry. Body height and weight were measured and body mass index (BMI) was calculated. Serum lipids, smoking and drinking status were assessed. Hypertension was diagnosed according to the criteria specified in the 1996 update of the Task Force on BP treatment in Children and Adolescents (Pediatrics 1996;98:649-58). RESULTS: Almost 25% of the subjects currently smoked with a median daily consumption of 6 (Interquartile 4-9) and 11 (6-16) cigarettes in girls and boys, respectively. Fourty-nine (41%) girls used oral contraceptives. Systolic (118 versus 109 mm Hg, p<0.001) and diastolic BPs (70.5 versus 68.0 mm Hg, p=0.033) were significantly higher in boys than in girls. Two (2%) girls and four (5%) boys had systolic hypertension; diastolic hypertension was found in six (5%) girls and one (1%) boy. Twelve (10%) girls and six (8%) boys were overweight (>25.0 kg/m2). Twenty (17%) girls and seven (9%) boys had hypercholesterolemia (total serum cholesterol > or =5.2 mmol/L). Overall, 50 (42%) girls and 31 (39%) boys had at least one CV risk factor, 12 (10%) girls and four (5%) boys had two risk factors, and three (3%) girls and one (1%) boy had more than two risk factors. CONCLUSIONS: In 17-year-olds living in an affluent society the prevalence of CV risk factors was high. These findings underscore the importance of health education and prevention at this age.

Adolescent↗
PubMed2004

Relationship between ambulatory blood pressure and follow-up clinic blood pressure in elderly patients with systolic hypertension.

BACKGROUND: Patients with elevated clinic blood pressure and normal ambulatory blood pressure have a better prognosis than patients with sustained ambulatory hypertension, and may not have to be treated with antihypertensive drugs. On the contrary, current guidelines emphasize repeated clinic blood pressure measurements for the initiation of antihypertensive therapy. OBJECTIVE: To examine the relationship between ambulatory blood pressure at baseline and clinic blood pressure after 6 months of follow-up in untreated hypertensive patients, and the relationships of these pressures with the subsequent incidence of cardiovascular events. METHODS: Patients who were > or = 60 years old, with systolic clinic blood pressure of 160-219 mmHg and diastolic pressure < 95 mmHg, participated in the Systolic Hypertension in Europe trial. The relationship between ambulatory blood pressure at baseline and clinic blood pressure after 6 months of follow-up was examined in 295 patients enrolled in the Ambulatory Blood Pressure Monitoring substudy and randomized to the placebo arm, and who were still on double-blind treatment and not taking other antihypertensive drugs after 6 months follow-up. RESULTS: Age averaged 70 +/- 6 years, 41% were men, and baseline daytime ambulatory blood pressure was 152 +/- 16/84 +/- 10 mmHg; clinic blood pressure decreased from 173 +/- 10/86 +/- 6 mmHg at baseline to 163 +/- 20/85 +/- 9 mmHg at month 6. Systolic daytime ambulatory blood pressure at baseline and systolic clinic blood pressure at month 6 were considered normal if < 140 mmHg. Of the 74 patients with normal systolic daytime ambulatory blood pressure at baseline, only seven (9.5%) had a normal systolic clinic blood pressure during follow-up. Conversely, of the 24 patients with normal follow-up clinic blood pressure, only seven (29%) had a normal systolic daytime ambulatory blood pressure at baseline. The incidence of cardiovascular events beyond the 6-month visit was significantly related to baseline ambulatory blood pressure but not to follow-up clinic pressure. CONCLUSIONS: Baseline daytime ambulatory blood pressure and follow-up clinic blood pressure do not identify the same patients for antihypertensive treatment. Baseline ambulatory pressure is a better predictor of cardiovascular events than follow-up clinic pressure.

Aged↗
PubMed2004

Collagen production in cardiac fibroblasts during inhibition of angiotensin-converting enzyme and aminopeptidases.

OBJECTIVE: To determine whether lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, and bestatin, an aminopeptidase inhibitor with broad specificity, could affect collagen production in control and transforming growth factor (TGF)-beta1-treated cardiac fibroblasts. DESIGN AND METHODS: Cardiac fibroblasts from passage 2 from normal male adult rats were cultured to confluency, incubated with or without 600 pmol/l TGF-beta1 for 2 days in serum-free Dulbecco's modified Eagle's medium and then incubated with the test products (lisinopril or bestatin) for 1 day in this medium with added ascorbic acid, beta-aminoproprionitrile and tritiated proline. Soluble collagen was measured in the conditioned medium and non-soluble collagen in the cell layer. ACE activity was measured fluorimetrically with hippuryl-histidyl-leucine as substrate, and DNA with the bisbenzimide dye, Hoechst 33,258. Aminopeptidase activity was estimated by spectrophotometric determination of the liberation of p-nitroaniline from alanine-p-nitroanilide. RESULTS: Lisinopril dose-dependently reduced ACE activity in control and TGF-beta1-treated cardiac fibroblasts. Bestatin inhibited the basal and TGF-beta1-stimulated aminopeptidase activity in a concentration-dependent manner. Lisinopril (10 micromol/l) decreased (P < 0.05) the production of soluble and non-soluble collagen in control cardiac fibroblasts. TGF-beta1 (600 pmol/l) increased (P < 0.05) the production of soluble and non-soluble collagen, and this effect was decreased (P < 0.05) by lisinopril. Bestatin (100 micromol/l) reduced (P < 0.01) the production of soluble collagen in control and TGF-beta1-treated cardiac fibroblasts, but did not affect the production of non-soluble collagen in these cells. CONCLUSIONS: Our data suggest that ACE and aminopeptidases are involved in the basal and TGF-beta1-stimulated production of collagen in adult rat cardiac fibroblasts in culture.

Aminopeptidases↗
PubMed2004

Do we need drug therapy to manage mild hypertension in the elderly?

Mild hypertension (grade 1 or stage 1 hypertension) is defined as a systolic blood pressure of 140-159 mm Hg or a diastolic pressure of 90-99 mm Hg. According to current guidelines, patients with mild hypertension can be at low, medium, high or very high risk depending on the presence of other risk factors, target organ damage and associated cardiovascular or renal conditions. Guidelines recommend prompt initiation of antihypertensive treatment in patients at very high risk because of associated clinical conditions and this recommendation is strongly supported by the literature. Also patients at high risk must be treated without much delay, but it should be mentioned that the evidence is stronger for patients who are at high risk because of diabetes mellitus, than for patients at high risk because of left ventricular hypertrophy or the accumulation of >or = 3 other risk factors. Patients at low and medium risk should be followed up and given advice on nonpharmacological measures and treatment should only be initiated in cases of persistently elevated blood pressure. However, this advice is based on indirect evidence and is currently not supported by randomised controlled trials. A survey on treatment of hypertension and implementation of World Health Organization/International Society of Hypertension (WHO/ISH) guidelines in primary care revealed that, respectively, only 20% and 33% of elderly men with mild hypertension at medium and high risk were treated with antihypertensive drugs and that this prevalence amounted to 67% in patients at very high risk; the prevalence was higher in patients with higher levels of blood pressure in each risk category.

Aged↗