Showing papers by "Robert Fagard published in 2003"

Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension

Abstract: background It is uncertain whether ambulatory blood-pressure measurements recorded for 24 hours in patients with treated hypertension predict cardiovascular events independently of blood-pressure measurements obtained in the physician’s office and other cardiovascular risk factors. methods We assessed the association between base-line ambulatory blood pressures in treated patients and subsequent cardiovascular events among 1963 patients with a median follow-up of 5 years (range, 1 to 66 months). results We documented new cardiovascular events in 157 patients. In a Cox proportional-hazards model with adjustment for age, sex, smoking status, presence or absence of diabetes mellitus, serum cholesterol concentration, body-mass index, use or nonuse of lipidlowering drugs, and presence or absence of a history of cardiovascular events, as well as blood pressure measured at the physician’s office, higher mean values for 24-hour ambulatory systolic and diastolic blood pressure were independent risk factors for new cardiovascular events. The adjusted relative risk of cardiovascular events associated with a 1-SD increment in blood pressure was 1.34 (95 percent confidence interval, 1.11 to 1.62) for 24-hour ambulatory systolic blood pressure, 1.30 (95 percent confidence interval, 1.08 to 1.58) for ambulatory systolic blood pressure during the daytime, and 1.27 (95 percent confidence interval, 1.07 to 1.57) for ambulatory systolic blood pressure during the nighttime. For ambulatory diastolic blood pressure, the corresponding relative risks of cardiovascular events associated with a 1-SD increment were 1.21 (95 percent confidence interval, 1.01 to 1.46), 1.24 (95 percent confidence interval, 1.03 to 1.49), and 1.18 (95 percent confidence interval, 0.98 to 1.40). conclusions In patients with treated hypertension, a higher ambulatory systolic or diastolic blood pressure predicts cardiovascular events even after adjustment for classic risk factors including office measurements of blood pressure.

Practice guidelines for primary care physicians: 2003 ESH/ESC hypertension guidelines.

Abstract: R. Cifkova (Czech Republic) S. Erdine (Turkey) R. Fagard (Belgium) C. Farsang (Hungary) A.M. Heagerty (UK) W. Kiowski (Switzerland) S. Kjeldsen (Norway) T. Lüscher (Switzerland) J.M. Mallion (France) G. Mancia (Italy, Coordinator) N. Poulter (UK) K.H. Rahn (Germany) J.L. Rodicio (Spain) L.M. Ruilope (Spain) P. van Zwieten (Netherlands) B. Waeber (Switzerland) B. Williams (UK) A. Zanchetti (Italy, Coordinator)

High prevalence of right ventricular involvement in endurance athletes with ventricular arrhythmias. Role of an electrophysiologic study in risk stratification.

Abstract: 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.

Systolic blood pressure variability as a risk factor for stroke and cardiovascular mortality in the elderly hypertensive population.

Abstract: ObjectiveTo investigate whether baseline systolic blood pressure variability was a risk factor for stroke, cardiovascular mortality or cardiac events during the Syst-Eur trial.DesignThe Syst-Eur study was a randomized, double-blind, placebo-controlled trial, powered to detect differences in stroke r

Self-measured versus ambulatory blood pressure in the diagnosis of hypertension.

Abstract: ObjectiveWe examined to what extent self-measurement of blood pressure at home (HBP) can be an alternative to ambulatory monitoring (ABP) to diagnose white-coat hypertension.MethodsIn 247 untreated patients, we compared the white-coat effects obtained by HBP and ABP. The thresholds to diagnose hyper

Transforming growth factor-beta 1 promotes contraction of collagen gel by cardiac fibroblasts through their differentiation into myofibroblasts.

Abstract: Myofibroblasts and transforming growth factor-beta 1 (TGF-beta 1) are key elements of cardiac tissue fibrosis development. The aim of this study was to determine whether the ability of TGF-beta 1 to affect the contractile activity of cardiac fibroblasts depends on their differentiation into myofibroblasts. Cardiac fibroblasts (from male adult Wistar rats) from passage 2 were therefore cultured to confluency and incubated on a hydrated collagen gel, both with and without TGF-beta 1 (0, 20, 40, 100, 200, 400 or 600 pmol/l), for 1, 2 and 3 days in a Dulbecco's Modified Eagle's Medium (DMEM) without fetal bovine serum (FBS). Growing cultures of cardiac fibroblasts were obtained by incubating second-passage fibroblasts in DMEM with 10% FBS with or without TGF-beta 1 (0 to 600 pmol/l) for 6 days. These fibroblasts were then further incubated on the collagen gel for 1, 2 and 3 days in DMEM without FBS. TGF-beta 1 dose-dependently increased the contraction of collagen gel mediated by cardiac fibroblasts, either added directly to the gel or after growing of the cardiac fibroblasts in the presence of TGF-beta 1 for 6 days, reaching a maximal effect at 100 pmol/l TGF-beta 1. In both culturing conditions, TGF-beta 1 also stimulated the [3H]-thymidine incorporation and the total protein content in the cardiac fibroblasts in the collagen gel lattice. TGF-beta 1 dose-dependently induced an increase in alpha-smooth muscle actin, a marker of myofibroblasts, in both culturing conditions. The TGF-beta 1-induced reduction of area of the collagen gel was negatively correlated to the TGF-beta 1-evoked appearance of alpha-smooth muscle actin in the collagen gel matrix. TGF-beta 1 increased the contractile activity of adult rat cardiac fibroblasts and their ability to differentiate into myofibroblasts. Because contractile activity was correlated with differentiation, the influence of TGF-beta 1 on cardiac fibroblast-induced collagen gel contraction may depend on the promotion of myofibroblast differentiation.

Host and environmental determinants of heart rate and heart rate variability in four European populations.

Abstract: Objective In a population-based sample of nuclear families recruited in the framework of the European Project on Genes in Hypertension (EPOGH), we investigated the association between heart rate (HR) and its variability (HRV), and gender, age, posture, breathing frequency, body mass index, systolic blood pressure, family history of hypertension and various lifestyle factors, such as smoking, alcohol and coffee consumption and physical activity. Methods RR interval and respiration were registered in the supine and standing positions (15 min each) in 1208 subjects in Bucharest (Romania, n = 267), Cracow (Poland, n = 323), Mirano (Italy, n = 323) and Novosibirsk (Russian Federation, n = 295). After exclusion of 199 participants on antihypertensive treatment and/or patients with diabetes mellitus (n = 40) or myocardial infarction (n = 4), 993 subjects were eligible for analysis. We evaluated 858 participants with high-quality recordings. Using fast Fourier transform, we decomposed HRV into low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF: 0.15-0.40 Hz) components, which were expressed in normalized units. Results Mean values were 35.3 years for age, 24.3 kg/m 2 for body mass index (BMI) and 121.0/77.2 mmHg for blood pressure. The group included 462 (53.8%) women. Across four centres, HR and HRV were similarly and independently associated with gender, age and postural position (P <0.001).In the supine position, HR was higher in women than men (67.2 versus 63.7 bpm). Men had higher normalized LF power than women (48.8 versus 41.5), but lower HF power (40.6 versus 47.4). The normalized HF power decreased with age (r= -0.43), whereas LF power increased (r= 0.32). On standing, HR increased (83.3 versus 65.6 bpm), normalized HF power declined (19.2 versus 44.3) and LF power increased (67.4 versus 44.9). The independent effects of respiration frequency, systolic blood pressure, family history of hypertension, body mass index and lifestyle factors on HRV differed between populations, and explained no more than 8% of the total variance. Conclusions Across four European populations, gender, age and posture were consistent and independent correlates of HR and HRV. Lifestyle seems to have small but varying influences on HR and/or HRV, probably depending on the environmental and cultural background of the population under study.

Transforming growth factor-β1-mediated collagen gel contraction by cardiac fibroblasts

Abstract: ObjectiveMyofibroblasts and transforming growth factor-β1 (TGF-β1) are key elements of cardiac tissue fibrosis development. The aim of this study was to determine whether the ability of TGF-β1 to affect the contractile activity of cardiac fibroblasts depends on their differentiation into myofibroblasts.MethodsCardiac fibroblasts (from male adult Wistar rats) from passage two were cultured to confluency and incubated on a hydrated collagen gel with and without TGF-β1 (0, 20, 40, 100, 200, 400 or 600 pmol/L) for one, two and three days in a Dulbecco's Modified Eagle's Medium without foetal bovine serum.ResultsTGF-β1 dose-dependently increased the contraction of collagen gel mediated by cardiac fibroblasts, reaching a maximal effect at 100 pmol/L TGF-β1. TGF-β 1 also stimulated 3H-thymidine incorporation and total protein content in cardiac fibroblasts in the collagen gel lattice . TGF-β 1 dose-dependently induced an increase in αsmooth muscle actin, a marker of myofibroblasts. The TGF-β1-induced reduction o...

Are low dehydroepiandrosterone sulphate levels predictive for cardiovascular diseases? A review of prospective and retrospective studies.

Abstract: Study objective It has been suggested that low levels of dehydroepiandrosterone sulphate (DHEAS) are predictive for cardiovascular diseases in men. We aimed to review the available evidence from prospective cohort studies and retrospective case-control studies. Methods We extracted summary statistics from 4 case-control studies and 8 cohort studies, and calculated the pooled relative risk associated with a 2 micromol/l increase in DHEAS. Main results The number of subjects included in each of the individual studies ranged from 94 to 2134, mean age from 48 to 83 years and mean DHEAS levels from 1.2 to 7.3 pmol/l. In men, coronary mortality was available as outcome in 3 cohort studies and 1 case-control study. Combining data from these 4 studies showed a 15% (95% CI: 4%-28%, p = 0.008) increase in fatal coronary heart disease associated with a 2 micromol/l decrease in DHEAS. However, statistical significance was lost when the retrospective study causing significant heterogeneity (p = 0.02) was excluded. Fatal and non-fatal coronary events were reported in 1 cohort study and 3 case-control studies. The average increase in fatal plus non-fatal coronary heart disease associated with a 2 micromol/l decrease in DHEAS amounted to 13% (2%-26%, p = 0.02). The available data did not allow drawing any conclusions on the prognostic value of DHEAS in women, nor on the relationship between DHEAS and total or cardiovascular mortality or stroke in men. Conclusions The present findings suggest that, in men, low serum levels of DHEAS may be associated with coronary heart disease. However, whether DHEA supplementation has any cardiovascular benefit is not clear. Data from prospective randomised trials are needed.

Influence of chorionicity on the heritability estimates of blood pressure: a study in twins.

Abstract: BackgroundA basic assumption of the twin design is that environmental influences including prenatal experiences are equal across twin types. However, the intra-uterine environment may differ according to the chorionicity of the monozygotic twins, which may have biased previous heritability estimates

Maternal and Paternal Influences on Left Ventricular Mass of Offspring

Abstract: Significant intrafamilial correlations of left ventricular mass exist in first-degree relatives. However, the specific maternal and paternal influences on left ventricular mass of offspring remain unknown. We therefore evaluated familial aggregation of left ventricular mass by type of familial relation in two European populations. A random sample of 159 nuclear families (250 parents and 321 offspring) was investigated in Cracow, Poland, and Novosibirsk, Russia. The mean age of parents and offspring was 51.4 years and 25.1 years, respectively. Two-dimensionally guided M-mode echocardiography was performed, and left ventricular mass was calculated. As a measure of concordance, we computed correlation coefficients for left ventricular mass between first-degree relatives and between spouse pairs. After adjustment for center, gender, age, height, body weight, systolic blood pressure, antihypertensive treatment, smoking, alcohol intake, and physical activity, the intrafamilial correlations for left ventricular mass were 0.06 ( P0.57) in 91 spouse-spouse pairs, 0.14 (P0.002) in 500 parent-offspring pairs, and 0.32 (P0.001) in 179 sib-sib pairs. Across the four parent-offspring relations, the intrafamilial correlations of left ventricular mass differed. The mother-son ( n140, r0.27, P0.001) and mother-daughter (n161, r0.28, P0.001) correlations were significant, whereas the father-son (n101, r0.04, P0.69) and father-daughter (n98, r0.09, P0.38) correlations were not different from zero. Overall, the mother-offspring correlation coefficient was significantly higher than the father-offspring correlation (r0.28 versus r0.04; P0.005). Thus, maternal factors appear to have more impact on left ventricular mass of offspring than do paternal influences. Further studies are required to elucidate the genetic, epigenetic, and ecogenetic mechanisms underlying these divergent parent-offspring correlations. (Hypertension. 2003;41:69-74.)

Blood pressure, serum total cholesterol and contraceptive pill use in 17-year-old girls.

Abstract: BACKGROUND Many studies have analysed the relation between cardiovascular risk factors and oral contraceptive use in adult women, whereas information on the possible health effects of oral contraceptive use during adolescence is lacking. DESIGN The effect of current contraceptive pill use on blood pressure and serum total cholesterol concentration was studied in a cross-sectional sample of 120 adolescent girls with a mean age of 17.4 years. METHODS After the girls had rested for 5 minutes in the sitting position, trained study nurses measured blood pressure three times consecutively using a mercury sphygmomanometer. The nurses also administered a questionnaire gathering information on the use of oral contraceptives, smoking and parental social class. In the morning blood samples were taken for the measurement of serum total cholesterol. RESULTS Mean age (+/-SD) was 17.4+/-0.8 years. Blood pressure averaged (+/-SD) 108.7+/-9.9 systolic and 68.0+/-8.2 mmHg diastolic. Serum total cholesterol was 4.5+/-0.7 mmol/l. Forty-nine girls (41%) were taking the contraceptive pill. Of these, 44 (90%) were on a combination of ethinyloestradiol (20-35 microg) and a progestogen, four (8%) on anti-androgens (35 microg) and one (2%) only on a progestogen. After adjustment for age, body mass index, smoking and alcohol status systolic blood pressure was 4.6 mmHg higher (95% CI 1.2-8.1; P<0.001) in current pill users than in girls not currently on the pill (111.4 versus 106.8 mmHg). Adjusted for the aforementioned covariates, diastolic blood pressure was not related to pill use (68.2 versus 67.8 mmHg; P=0.7). Serum total cholesterol was 0.43 mmol/l (95% CI 0.18-0.60; P=0.001) higher among girls using oral contraceptives (4.7 versus 4.3 mmol/l), irrespective of whether or not the model was adjusted for age, body mass index, smoking and alcohol status. CONCLUSIONS In 17-year-old girls, the use of oral contraceptives was associated with a nearly 5 mmHg higher systolic blood pressure and a 0.4 mmol/l higher level of serum total cholesterol. The long-term prognostic implications of our findings remain to be elucidated.

The ALLHAT trial: strengths and limitations.

Abstract: It is well-known that high blood pressure increases the incidence of fatal and non-fatal cardiovascular events such as stroke, coronary heart disease (CHD) and heart failure (CHF). However, effective and tolerable antihypertensive agents have only become available in the second half of the last century. These drugs have then been used as tools in randomized controlled outcome trials investigating whether treatment of hypertension would reduce the incidence of cardiovascular complications and of mortality. A large number of individual studies have been performed, first in patients with systolic-diastolic hypertension [1–14] and subsequently in patients with isolated systolic hypertension [15–17]. Meta-analyses of these studies clearly showed that allcause and cardiovascular mortality, non-fatal and fatal stroke and CHD, and aggregate cardiovascular events were significantly reduced in both types of hypertension [18–21]. Diuretics have been used as first-line treatment in most of these trials [1–11,13–15] and are undoubtedly the best studied of the older drug classes. Some trials used a beta-blocker [10,12–14] or a dihydropyridine calcium channel blocker (CCB) [16,17] as initial therapy. No outcome trials have currently been published in patients with uncomplicated mild (grade 1) systolic hypertension or in the very elderly, but a meta-analysis revealed a cardiovascular benefit in patients with hypertension who were aged at least 80 years [22].

Haematological phenotypes in relation to the C1797T β-adducin polymorphism in a Caucasian population

Abstract: b-Adducin plays a role in maintaining the structural integrity of the red blood cell (erythrocyte) membrane. Moreover, b-adducin-deficient knock-out mice show a phenotype characterized by mild anaemia and compensated haemolysis. We therefore investigated whether, in humans, common haematological phenotypes of red blood cells were associated with a polymorphism in exon 15 of the human b-adducin gene (C1797T). We studied 802 unrelated individuals and 294 families (459 parents and 609 ospring) randomly selected from a Caucasian population. We employed generalized estimating equations to allow for the non-independence of the observations within families, while controlling for co-variables. In 917 men, with adjustments applied for age, body mass index, serum total cholesterol, smoking and alcohol intake, CC homozygotes had significantly (Pv 0.02) lower values for red blood cell count (4.93x10 12 /l compared with 4.86x10 12 /l), haemoglobin level (9.30 compared with 9.18 mmol/l) and haematocrit (45.0% compared with 44.4%) than T allele carriers. In the 329 men who consumed alcohol, the dierences between CC homozygotes and T allele carriers were 0.13x10 12 /l (Pv 0.02) for red blood cell count, 0.23 mmol/l (Pv 0.005) for haemoglobin and 1.08% (Pv 0.02) for haematocrit. In 953 women, none of these associations was significant (P & 0.06), regardless of alcohol intake [13.3% of women (nv 127) consmued alcohol]. In conclusion, in men consuming alcohol, the b-adducin CC genotype was associated with lower red blood cell count, haemoglobin level and haematocrit. We hypothesize that, in CC homozygotes, alcohol consumption may unveil the greater fragility of the red blood cell membrane. This genotype may slightly potentiate the structural and functional haematological disturbances associated with alcohol intake.

Relationship between left ventricular mass and the ace D/I polymorphism varies according to sodium intake

Abstract: Background In the European Project on Genes in Hypertension (EPOGH), we investigated to what extent left ventricular mass (LVM) in populations and families relates to the angiotensin-converting enzyme (ACE D/I) and aldosterone synthase (CYP11B2 −344C/T) polymorphisms and urinary sodium excretion. Methods We recruited 219 nuclear families (382 parents and 436 offspring) randomly in Cracow (Poland), Novosibirsk (Russia) and Mirano (Italy). Echocardiographical 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. Results We found significant differences between the two Slavic centres and Mirano in left ventricular mass index (LVMI) (94.9 versus 80.3 g/m2), sodium excretion (229 versus 186 mmol/day), and the prevalence of the ACE D allele (52.1 versus 58.5%). There was significant heterogeneity between Slavic and Italian subjects in the phenotype–genotype relationships with the ACE gene, but not with the aldosterone synthase gene. In the two Slavic centres, ACE II homozygosity was significantly associated with higher LVMI, in population-based as well as in family-based analyses. By contrast, in Mirano, LVMI was slightly higher in DD homozygotes (P = 0.05), but only in the population-based approach. LVMI increased with higher sodium excretion in ACE II homozygous offspring of both Slavic and Italian extraction (+4.2 ± 2.1 g/m2 per 100 mmol; P = 0.04) and in Slavic (+2.6 ± 1.1 g/m2 per 100 mmol; P = 0.02), but not Italian (−3.3 ± 3.2 g/m2 per 100 mmol; P = 0.29) D allele carriers. We did not find any association between LVMI and the aldosterone synthase −344C/T polymorphism. Conclusions The relationship between LVMI and the ACE D/I polymorphism differs across populations, possibly as a consequence of intermediate regulatory mechanisms responsive to varying levels of salt intake.

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

Abstract: 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).