Showing papers by "Robert Fagard published in 2004"

Exercise and Hypertension

Abstract: SUMMARY Hypertension (HTN), one of the most common medical disorders, is associated with an increased incidence of all-cause and cardiovascular disease (CVD) mortality. Lifestyle modifications are advocated for the prevention, treatment, and control of HTN, with exercise being an integral component. Exercise programs that primarily involve endurance activity prevent the development of HTN and lower blood pressure (BP) in adults with normal BP and those with HTN. The BP lowering effects of exercise are most pronounced in people with HTN who engage in endurance exercise with BP decreasing approximately 5–7 mm Hg after an isolated exercise session (acute) or following exercise training (chronic). Moreover, BP is reduced for up to 22 h after an endurance exercise bout (e.g., postexercise hypotension), with the greatest decreases among those with the highest baseline BP. The proposed mechanisms for the BP lowering effects of exercise include neurohumoral, vascular, and structural adaptations. Decreases in catecholamines and total peripheral resistance, improved insulin sensitivity, and alterations in vasodilators and vasoconstrictors are some of the postulated explanations for the antihypertensive effects of exercise. Emerging data suggest genetic links to the BP reductions associated with acute and chronic endurance exercise. Nonetheless, definitive conclusions regarding the mechanisms for the BP reductions following endurance exercise cannot be made at this time. Individuals with controlled HTN and no CVD or renal complications may participate in an exercise program or competitive athletics, but should be evaluated, treated, and monitored closely. Preliminary peak or symptom-limited exercise testing may be warranted, especially for men over 45 and women over 55 yr planning a vigorous exercise program (i.e., 60% u VO2R, oxygen uptake reserve). In the interim, while formal evaluation and management are taking place, it is reasonable for the majority of patients to begin moderate intensity exercise training (40 –60% u VO2R) such as walking. When pharmacologic therapy is indicated in physically active people it should, ideally: a) lower BP at rest and during exertion; b) decrease total peripheral resistance; and, c) not adversely affect exercise capacity. For these reasons, angiotensin converting enzyme (ACE) inhibitors (or angiotensin II receptor blockers in case of ACE inhibitor intolerance) and calcium channel blockers are currently the drugs of choice for recreational exercisers and athletes who have HTN. Exercise remains a cornerstone therapy for the primary prevention, treatment, and control of HTN. The optimal training frequency, intensity, time, and type (FITT) need to be better defined to optimize the BP lowering capacities of exercise, particularly in children, women, older adults, and

Antihypertensive Treatment Based on Blood Pressure Measurement at Home or in the Physician's Office: A Randomized Controlled Trial

Abstract: ContextSelf-measurement of blood pressure is increasingly used in clinical practice, but how it affects the treatment of hypertension requires further study.ObjectiveTo compare use of blood pressure (BP) measurements taken in physicians' offices and at home in the treatment of patients with hypertension.Design, Setting, and ParticipantsBlinded randomized controlled trial conducted from March 1997 to April 2002 at 56 primary care practices and 3 hospital-based outpatient clinics in Belgium and 1 specialized hypertension clinic in Dublin, Ireland. Four hundred participants with a diastolic BP (DBP) of 95 mm Hg or more as measured at physicians' offices were enrolled and followed up for 1 year.InterventionsAntihypertensive drug treatment was adjusted in a stepwise fashion based on either the self-measured DBP at home (average of 6 measurements per day during 1 week; n = 203) or the average of 3 sitting DBP readings at the physician's office (n = 197). If the DBP guiding treatment was above (>89 mm Hg), at (80-89 mm Hg), or below (<80 mm Hg) target, a physician blinded to randomization intensified antihypertensive treatment, left it unchanged, or reduced it, respectively.Mean Outcome MeasuresOffice and home BP levels, 24-hour ambulatory BP, intensity of drug treatment, electrocardiographic and echocardiographic left ventricular mass, symptoms reported by questionnaire, and costs of treatment.ResultsAt the end of the study (median follow-up, 350 days; interquartile range, 326-409 days), more home BP than office BP patients had stopped antihypertensive drug treatment (25.6% vs 11.3%; P<.001) with no significant difference in the proportions of patients progressing to multiple-drug treatment (38.7% vs 45.1%; P = .14). The final office, home, and 24-hour ambulatory BP measurements were higher (P<.001) in the home BP group than in the office BP group. The mean baseline-adjusted systolic/diastolic differences between the home and office BP groups averaged 6.8/3.5 mm Hg, 4.9/2.9 mm Hg, and 4.9/2.9 mm Hg, respectively. Left ventricular mass and reported symptoms were similar in the 2 groups. Costs per 100 patients followed up for 1 month were only slightly lower in the home BP group (€3875 vs €3522 [$4921 vs $4473]; P = .04).ConclusionsAdjustment of antihypertensive treatment based on home BP instead of office BP led to less intensive drug treatment and marginally lower costs but also to less BP control, with no differences in general well-being or left ventricular mass. Self-measurement allowed identification of patients with white-coat hypertension. Our findings support a stepwise strategy for the evaluation of BP in which self-measurement and ambulatory monitoring are complementary to conventional office measurement and highlight the need for prospective outcome studies to establish the normal range of home-measured BP.

Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial

Abstract: Background To assess the impact of immediate versus delayed anti hypertensive treatment on the outcome of older patients with isolated systolic hypertension, we extended the double- blind placebo-controlled Systolic Hypertension in Europe (Syst- Eur) trial by an open-label follow-up study lasting 4 years. Methods The Syst-Eur trial included 4695 randomized patients with minimum age of 60 years and an untreated blood pressure of 160-219 mmHg systolic and below 95 mmHg diastolic. The double- blind trial ended after a median follow-up of 2.0 years (range 1-97 months). Of 4409 patients still alive, 3517 received open- label treatment consisting of nitrendipine (10-40 mg daily) with the possible addition of enalapril (5-20 mg daily), hydrochlorothiazide (12.5 - 25 mg daily), or both add-on drugs. Non-participants (n = 892) were also followed up. Results Median follow-up increased to 6.1 years. Systolic pressure decreased to below 150 mmHg (target level) in 2628 participants (75.0%). During the 4-year open-label follow-up, stroke and cardiovascular complications occurred at similar frequencies in patients formerly randomized to placebo and those continuing active treatment. These rates were similar to those previously observed in the active-treatment group during the double-blind trial. Considering the total follow-up of 4695 randomized patients, immediate compared with delayed anti hypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28% (P=0.01) and 15% (P=0.03), respectively, with a similar tendency for total mortality (13%, P = 0.09). In 492 diabetic patients, the corresponding estimates of long-term benefit (P < 0.02) were 60, 51 and 38%, respectively. Conclusions Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension. Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years. These findings underscore the necessity of early treatment of isolated systolic hypertension. J Hypertens 22:847 -857 (C) 2004 Lippincott Williams Wilkins.

Effect of exercise training in patients with an implantable cardioverter defibrillator.

Abstract: Aims Little research exists on exercise performance and training in patients with an implemented cardioverter defibrillator (ICD) and only in a limited number of patients. This study aims to investigate the effect of exercise training in ICD patients in comparison to the effects in other cardiac patients without an ICD. Methods and results 92 ICD patients were compared with a control group of 473 patients. A maximal cycle-spiroergometric test was performed until exhaustion before and after an ambulatory exercise training programme. Exercise training was offered 3 times a week for 3 months. The cut-off heart rate was set at (ICD detection rate −20 beats/min). At baseline, the ICD patients had a lower peak oxygen uptake (VO2) compared to the control group. Training effects were smaller for peak VO2 (mL/min/kg) and oxygen pulse in the ICD group (18 vs. 27%, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.006\) \end{document} and 11 vs. 17%, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.016\) \end{document}, respectively). Several appropriate shocks were delivered during (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n=5\) \end{document}), and in between (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(n=7\) \end{document}), testing or training and one inappropriate shock during training. Conclusions ICD patients can safely participate in an exercise training programme with favorable results. A randomised control study with evaluation of the physical and the psychosocial effects is warranted.

Determinants of the effects of physical training and of the complications requiring resuscitation during exercise in patients with cardiovascular disease.

Abstract: BackgroundBenefits of cardiac rehabilitation with exercise therapy are well-established, although individual reactions are heterogeneous. The identification of determinants of training effects is useful from a prognostic point of view, but data regarding this are scarce. Furthermore, limited data exist on the determinants of complications during exercise in cardiac patients. This study aimed to investigate the determinants (1) of training effects in cardiac rehabilitation and (2) of complications requiring resuscitation during exercise activities at the hospital and during continued exercise at a sports club for cardiac patients.DesignClinical association study.MethodsDeterminants of changes in peak oxygen uptake (VO2) after 3 months of cardiac rehabilitation were determined by multiple regression analysis (n = 1909). Determinants of events requiring resuscitation (n = 21) were assessed by logistic regression analysis.ResultsImprovements in peak VO2 and exercise duration averaged 26%. Eighteen per cent of...

Left Ventricular Mass in Relation to Genetic Variation in Angiotensin II Receptors, Renin System Genes, and Sodium Excretion

Abstract: Background— In the European Project On Genes in Hypertension (EPOGH), we investigated in 3 populations to what extent left ventricular mass (LVM) was associated with genetic variation in the angiotensin II receptors type 1 (AGTR1 A1166C) and type 2 (AGTR2 G1675A) while accounting for possible gene–gene interactions with the angiotensin-converting enzyme (ACE D/I) and angiotensinogen (AGT −532C/T) polymorphisms. Methods and Results— We randomly recruited 221 nuclear families (384 parents, 431 offspring) in Cracow (Poland), Novosibirsk (Russia), and Mirano (Italy). Echocardiographic LVM was indexed to body surface area, adjusted for covariates, and subjected to multivariate analyses using generalized estimating equations and quantitative transmission disequilibrium tests in a population-based and family-based approach, respectively. For AGTR1 and AGTR2, there was no heterogeneity in the phenotype–genotype relations across populations. LVM index was unrelated to the AGTR1 A1166C polymorphism. In men, in the ...

Prognostic Significance of Electrocardiographic Voltages and Their Serial Changes in Elderly With Systolic Hypertension

Abstract: 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 P ≤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 ≤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.

Blood pressure in relation to three candidate genes in a Chinese population.

Abstract: OBJECTIVE In a prospective analysis of a Caucasian population, we recently found that the genes encoding angiotensin-converting enzyme (ACE, I/D polymorphism), alpha-adducin (Gly460Trp) and aldosterone synthase (-344C/T) jointly influence the incidence of hypertension. We therefore investigated the association between blood pressure and these three genes in a Chinese population. METHODS We genotyped 479 Han Chinese from 125 nuclear families recruited in northern China via random sampling (approximately 75%) and at specialized hypertension clinics (approximately 25%). We performed population-based and family-based association analyses using generalized estimating equations (GEE) and the quantitative transmission disequilibrium test (QTDT), respectively, while controlling for covariables. RESULTS The participants included 239 (49.9%) women and 132 (27.6%) hypertensive patients, of whom 77 took antihypertensive drugs. The blood pressure, measured at the subjects' homes, averaged 126/80 mmHg. Mean values of urinary sodium, potassium and Na/K ratio were 226 mmol/day, 37 mmol/day and 6.31, respectively. In adjusted GEE analyses, systolic blood pressure was 9.3 mmHg (95% confidence interval 3.6-15.0 mmHg; P = 0.001) and 14.6 mmHg (95% confidence interval 3.4-25.8 mmHg; P = 0.01) higher in the ACE DD than II subjects among the alpha-adducin TrpTrp (n = 141) and aldosterone synthase CC (n = 33) homozygotes, respectively (P < or =0.05 for interactions of the ACE genotype with the alpha-adducin and aldosterone synthase polymorphisms). Among 40 informative offspring homozygous for the alpha-adducin Trp allele, systolic blood pressure was significantly associated with transmission of the ACE D allele (beta = 5.5 mmHg; P = 0.046). CONCLUSIONS The ACE I/D, alpha-adducin Gly460Trp and aldosterone synthase -344C/T polymorphisms interact to influence systolic blood pressure in Chinese, suggesting that these genes might indeed predispose to hypertension, especially in an ecogenetic context characterized by a high salt intake.

Prognostic significance of various characteristics of out-of-the-office blood pressure.

Abstract: After the initial investigations by Perloff et al. [1,2], our knowledge on the prognostic significance of out-of-theoffice blood pressure measurements has tremendously increased in the last decade [3–27]. Blood pressure was most often assessed by use of ambulatory blood pressure monitoring [1–7,9–25,27], although in some reports blood pressure was measured at the patients’ home [8,26,27]. Studies have been performed in the general population [5,6,8,9,14,19], in elderly [16,22], in hypertensive patients in general, with or without treatment [1–4,7,11,17,18,21,23,24,26,27], in older patients with systolic–diastolic or isolated systolic hypertension [12,13,15,20,25] and in refractory hypertension [10]. In the current issue of the journal, Björklund et al. [28] extend our knowledge by assessing the prognostic significance of ambulatory blood pressure in 70-year-old men who participated in a prospective longitudinal population-based follow-up study in Uppsala, Sweden.

Genetic variation in CYP11B2 and AT1R influences heart rate variability conditional on sodium excretion

Abstract: Sympathetic tone increases with stimulation of the renin-angiotensin system and is under the influence of salt intake. In the European Project On Genes in Hypertension (EPOGH), we investigated whether polymorphisms in the genes encoding aldosterone synthase (CYP11B2 C-344T) and the type-1 angiotensin II receptor (AT1R A1166C) affect the autonomic modulation of heart rate at varying levels of salt intake. We measured the low frequency (LF) and high frequency (HF) components of heart rate variability and their ratio (LF:HF) in the supine and standing positions in 1797 participants (401 families and 320 unrelated subjects) randomly selected from 6 European populations, whose average urinary sodium excretion ranged from 163 to 245 mmol/d. In multivariate analyses with sodium excretion analyzed as a continuous variable, we explored the phenotype-genotype associations using generalized estimating equations and quantitative transmission disequilibrium tests. Across populations, there was no heterogeneity in the phenotype-genotype relations. The genotypic effects differed according to sodium excretion. In subjects with sodium excretion 190 mmol/d, these associations with the CYP11B2 and AT1R polymorphisms were nonsignificant or in the opposite direction, respectively. Thus, CYP11B2 C-344T and AT1R A1166C polymorphisms affect the autonomic modulation of heart rate, but these genetic effects depend on sodium excretion.

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.

Exercise intensity and postexercise hypotension.

Abstract: Lifestyle modifications are advocated for the prevention, treatment and control of hypertension, with exercise being an integral component. Higher levels of physical activity and greater fitness are associated with a reduced incidence of hypertension [1]. Furthermore, a number of studies with well-controlled randomized experimental designs, examining the effects of aerobic endurance training programmes in hypertension, generally demonstrate training to exert a significant antihypertensive effect [2,3]. Recent guidelines therefore recommend that everybody who is able should engage in regular aerobic physical activity, such as brisk walking, for at least 30 min per day most days of the week, as a means to lower blood pressure [1,4].

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

Abstract: 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.

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

Abstract: 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 25.0 kg/m 2 ). Twenty (17%) girls and seven (9%) boys had hypercholesterolemia (total serum cholesterol ≥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.

Arginine–aminopeptidase in rat cardiac fibroblastic cells participates in angiotensin peptide turnover

Abstract: Objective: The aim of the present study was to elucidate the presence in rat cardiac fibroblastic cells of arginine–aminopeptidase and its involvement in the hydrolysis of angiotensin peptides. Methods: Peptidase activity was measured as hydrolysis of the synthetic substrates, aryl- p -nitroanilides. Immunoblottings were performed with antibodies to aminopeptidase B and Glyceraldehyde-3-phosphate dehydrogenase. Results: Arginine–aminopeptidase found in cardiac fibroblasts (Fb) was arginine and lysine specific, sensitive to various aminopeptidase (AP) inhibitors and to the inhibitor of metalloproteases, 1.10-phenatroline. Experiments with arphamenine A, a specific inhibitor of aminopeptidase B, have shown the presence of two Arginine–aminopeptidase activities: arphamenine-sensitive: chloride-stimulated Arginine–aminopeptidase, and arphamenine-insensitive: chloride-insensitive Arginine–aminopeptidase. Transforming growth factor-β1 stimulated both Arginine–aminopeptidase activities by approximately threefold. Immunoblot with an antibody specific to rat aminopeptidase B has revealed that arphamenine-sensitive: chloride stimulated aminopeptidase is aminopeptidase B. Arginine- p -nitroanilide hydrolysis was significantly inhibited by angiotensin peptides such as angiotensin (1–10), (1–8), (1–7), (1–4), (5–8), (4–8), (3–8), and (2–8) at the concentration of 50 μmol/l which was fourfold less than the Arginine- p -nitroanilide concentration. Conclusions: Our data show that chloride-insensitive Arginine–aminopeptidase could contribute to the hydrolysis of all studied angiotensin peptides in concert with other peptidases present in fibroblasts. Some of the peptides could probably not be hydrolyzed by Arginine–aminopeptidase. Instead, they could be first hydrolyzed by another peptidase in fibroblasts and the product of this hydrolysis could be a substrate for Arginine–aminopeptidase. The data obtained suggest that Arginine–aminopeptidase could perform processing of angiotensin peptides in the myocardium and participate in processes regulated by angiotensins such as fibrosis.

The caregene study: muscle-specific creatine kinase gene and aerobic power in coronary artery disease.

Abstract: In 927 biologically unrelated Caucasian patients with coronary artery disease it was investigated whether the NcoI restriction fragment length polymorphism of the muscle-specific creatine kinase (CKMM) gene is associated with aerobic power and with the response to physical training. Physical training significantly (P<0.001) increased peak oxygen consumption in the GG, AG and AA NcoI genotypes. Covariate-adjusted peak oxygen consumption at baseline, after training and the response to training were not different across CKMM NcoI genotypes.

The Contribution of Risk Factors to Blood Pressure Heritability Estimates in Young Adults: The East Flanders Prospective Twin Study

Abstract: The contribution of risk factors to blood pressure heritability estimates in young adults: the East flanders prospective twin study. Zeegers MP, Rijsdijk F, Sham P, Fagard R, Gielen M, De Leeuw PW, Vlietinck R. Maastricht University, Department of Epidemiology, Maastricht, the Netherlands. mpa.zeegers@epid.unimaas.nl The heritability of blood pressure estimated in previous studies may be confounded by the influence of potential blood pressure risk factors. We applied the classical twin design to estimate the contribution of these covariates to blood pressure heritability. The study consisted of 173 dizygotic and 251 monozygotic twin pairs aged 18-34 years, randomly selected from the East Flanders Prospective Twin Survey. In a standardized examination, blood pressure and anthropometry was measured, a questionnaire was completed, and a fasting blood sample was taken. In univariate and bivariate modeling, diastolic and systolic heritability were estimated both unadjusted and adjusted for potential risk factors. Also, covariate interaction was modeled. Bivariate analysis gave heritability estimates of 0.63 (95%CI 0.55-0.59), 0.74 (95%CI: 0.68-0.79), and 0.78 (95%CI: 0.70-0.84) for diastolic, systolic, and cross-trait heritability, respectively. The remaining variances could be attributed to unique environmental influences. These heritability estimates did not change substantially in univariate analyses or after adjustment for risk factors. A sex-limitation model showed that the heritability estimates for women were significantly higher than for men, but the same genetic factors were operating across sexes. Sex and cigarette smoking appeared to be statistically significant interaction terms. The heritability of blood pressure is relatively high in young adults. Potential risk factors of blood pressure do not appear to confound the heritability estimates. However, gene by sex by smoking interaction is indicated

Renal function in relation to three candidate genes in a Chinese population.

Abstract: We recently found in a white population that the genes encoding angiotensin-converting enzyme (ACE, I/D polymorphism), α-adducin (Gly460Trp), and aldosterone synthase (−344C/T) jointly influence renal function. We therefore investigated in a Chinese population the associations between the serum concentrations of creatinine and uric acid and these three genetic polymorphisms. We genotyped 471 ethnic Han Chinese subjects from 125 nuclear families recruited in northern China via random population sampling (75%) and at specialized hypertension clinics (25%). We performed population-based and family-based association analyses using generalized estimating equations (GEE) and quantitative transmission disequilibrium test (QTDT), respectively, while controlling for covariables. The participants were 39.7 years old and included 235 women (49.9%). The blood pressure measured at the subjects’ homes averaged 126/80 mmHg. Mean values were 71 µmol/l for serum creatinine, 111 ml min−1 1.73 m−2 for calculated creatinine clearance, and 236 µmol/l for serum uric acid. With adjustment for covariables, GEE analyses of single genes demonstrated that serum uric acid, but not serum creatinine, was positively associated with the ACE D allele. Serum uric acid concentrations were 15.8 µmol/l (95% confidence interval 3.3–28.2) and 25.7 µmol/l (11.1–40.2) higher in DD homozygotes than in ID and II subjects, respectively. Further GEE analyses of the three genes combined showed that the association between serum uric acid and the ACE polymorphism was confined to carriers of the α-adducin Gly and/or aldosterone synthase C alleles. Sensitivity analyses in parents and offspring separately as well as QTDT analyses were confirmatory. Among 114 informative offspring carrying the α-adducin Gly allele serum uric acid was significantly and positively associated with the transmission of the ACE D allele (β=20.7 µmol/l). In conclusion, the present study extends our previous findings on the combined effects of the three candidate genes and supports the concept that these genetic polymorphisms jointly influence renal function.

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

Abstract: 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.

Effect of bestatin on angiotensin I-, II- and III-induced collagen gel contraction in cardiac fibroblasts.

Abstract: Objective The purpose of this investigation was to determine whether the aminopeptidase inhibitor with broad specificity, bestatin, affects angiotensin I (Ang I)-, angiotensin II (Ang II)- or angiotensin III (Ang III)stimulated collagen gel contraction in cardiac fibroblasts. Design and methods Cardiac fibroblasts (from normal male adult rats) were cultured to confluency in Dulbecco’s modified Eagle’s medium (DMEM) with 10% foetal bovine serum (FBS). These fibroblasts (100,000 cells) were then further incubated in a floating collagen gel lattice with the test products Ang I (1 µmol/L), Ang II (100 nmol/L), Ang III (100 nmol/L) and bestatin (100 µmol/L) for three days in DMEM without FBS. The area of the collagen gels embedded with cardiac fibroblasts was determined by a densitometric analysis. Aminopeptidase activity was estimated by spectrophotometric determination of the liberation of p-nitroaniline from alanine- or arginine-p-nitroanilide. Results