Biomedical subjects

Robert Fagard

Publications and source records attributed to Robert Fagard.

At least 37 records · Page 2Linked to original sources

PubMed2004

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

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.

Adult↗

PubMed2004

Antihypertensive treatment based on home or office blood pressure--the THOP trial.

OBJECTIVE AND METHODS: In this randomized clinical trial, conducted in 400 hypertensive patients [sitting diastolic blood pressure (DBP) >95 mmHg], blood pressure-lowering therapy was adjusted in a stepwise manner, either on the basis of the self-measured DBP at home or on the basis of conventional DBP measured at the doctor's office. RESULTS: Therapy guided by home blood pressure instead of office blood pressure led to less intensive drug treatment and marginally lower costs, but also to less blood pressure control with no differences in left ventricular mass. Self-measurement helped to identify patients with white-coat hypertension. CONCLUSIONS: The present findings support a stepwise strategy for the evaluation of blood pressure, in which self-measurement and ambulatory monitoring are complementary to conventional office blood pressure measurement.

Adult↗

PubMed2004

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

BACKGROUND: Benefits 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. DESIGN: Clinical association study. METHODS: Determinants 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. RESULTS: Improvements in peak VO2 and exercise duration averaged 26%. Eighteen per cent of the variance in absolute improvements of peak VO2 was explained, with age and training characteristics as the strongest determinants. Twenty-one per cent of the variation in relative improvements was explained, with baseline exercise performance and training characteristics being the strongest determinants. The intake of anti-arrhythmics (odds ratio=5.5; P<0.001) and the presence of ST-segment depression (> or =1 mm) at baseline exercise testing (odds ratio=1.6; P<0.001) were predictive for serious complications. The occurrence of events requiring resuscitation was higher at the sports club (1/16,533 versus 1/29,214 patient-hours). CONCLUSIONS: Age, baseline exercise performance and training characteristics were predictive for training effects in cardiac rehabilitation. Anti-arrhythmics and ST-segment depression at baseline exercise testing were predictive for complications.

Angioplasty, Balloon, Coronary↗

PubMed2004

American College of Sports Medicine position stand. Exercise and hypertension.

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 activities 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 greatest decreases among those with 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 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 participated 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. > or = 60% 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 (40-<60% VO2R) such as walking. When pharmacological therapy is indicated in physically active people it should be, 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 certain ethnic groups. based upon the current evidence, the following exercise prescription is recommended for those with high BP: Frequency: on most, preferably all, days of the week. Intensity: moderate-intensity (40-<60% VO2R). Time: > or = 30 min of continuous or accumulated physical activity per day. Type: primarily endurance physical activity supplemented by resistance exercise.

Adolescent↗

PubMed2004

The contribution of risk factors to blood pressure heritability estimates in young adults: the East flanders prospective twin study.

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.

Adolescent↗

PubMed2004

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

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 Dulbeccos modified Eagles 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 micromol/L), Ang II (100 nmol/L), Ang III (100 nmol/L) and bestatin (100 micromol/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: Ang I, II and III stimulated (p<0.05) collagen gel contraction by 30.4+/-4.8 (SEM)%, 27.1+/-3.1% and 15.4+/-3.6% respectively. Ang I- and II-induced stimulation of collagen gel contraction was of the same order but more pronounced (p<0.05) than Ang III- stimulated collagen gel contraction. The Ang I-, II- and III-stimulated collagen contraction was reduced by bestatin. Bestatin, however, did not affect basal collagen gel contraction in cardiac fibroblasts. Bestatin dose-dependently inhibited the hydrolysis of arginine- and alanine-p-nitroanilide in cardiac fibroblasts. When a neutralising antibody to transforming growth factor TGF-b1 was added to the collagen gel simultaneously with the angiotensins, the stimulated collagen contraction was not affected. Beta-aminoproprionitrile, an inhibitor of lysyl oxidase, completely abolished basal as well as Ang I-, II- and III-stimulated collagen contraction in cardiac fibroblasts. RESULTS: Our data suggest that aminopeptidases are involved in the Ang I-, II- and III-induced stimulation of collagen contraction in cardiac fibroblasts.

Aminopeptidases↗

PubMed2003

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

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 < or =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.

Adolescent↗

PubMed2003

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

OBJECTIVE: We 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. METHODS: In 247 untreated patients, we compared the white-coat effects obtained by HBP and ABP. The thresholds to diagnose hypertension were > or = 140/> or = 90 mmHg for conventional blood pressure (CBP) and > or = 135/> or = 85 mmHg for daytime ABP and HBP. RESULTS: Mean systolic/diastolic CBP, HBP and ABP were 155.4/100.0, 143.1/91.5 and 148.1/95.0 mmHg, respectively. The white-coat effect was 5.0/3.5 mmHg larger on HBP compared with ABP (12.3/8.6 versus 7.2/5.0 mmHg; P < 0.001). The correlation coefficients between the white-coat effects based on HBP and ABP were 0.74 systolic and 0.60 diastolic (P < 0.001). With ABP as a reference, the specificity of HBP to detect white-coat hypertension was 88.6%, and the sensitivity was 68.4%. CONCLUSION: Our findings are in line with the recommendations of the ASH Ad Hoc Panel that recommends HBP for screening while ABP has a better prognostic accuracy.

Adult↗

PubMed2003

Salt, endogenous ouabain and blood pressure interactions in the general population.

OBJECTIVE: Experimental data show that ouabain is a modulator of the sodium-potassium pump, which plays an important role in sodium homeostasis and blood pressure regulation. We investigated the distribution of plasma ouabain in the general population in relation to blood pressure and other determinants of sodium homeostasis. METHODS: In 379 subjects enrolled in a Belgian population study, we measured plasma ouabain, clinical characteristics including blood pressure, serum and urinary electrolytes, urinary aldosterone excretion, various lifestyle factors, and the Gly460Trp polymorphism of the alpha-adducin gene. Our statistical methods included analysis of covariance and multiple linear regression. RESULTS: Plasma ouabain (median, 140 pmol/l) correlated independently and positively with male gender (n = 182, P = 0.002), smoking (n = 116, P = 0.05), urinary potassium excretion (mean 69 mmol/day, P < 0.0001), and mutation of the alpha-adducin gene (n = 161, P < 0.0001). Both before and after adjustment for covariables, continuous as well as categorical analyses revealed a significant interaction (P < or = 0.02) between plasma ouabain and urinary sodium excretion (mean 194 mmol/day) in relation to blood pressure (mean systolic blood pressure/diastolic blood pressure, 123/76 mmHg). In individuals with plasma ouabain values below the median, blood pressure increased by 2.2 mmHg systolic and 1.4 mmHg diastolic for each 50 mmol/day increment in urinary sodium excretion (P < or = 0.01). No association between blood pressure and urinary sodium excretion was found when plasma ouabain exceeded the median. CONCLUSIONS: Plasma ouabain behaves as a blood pressure modulating factor, possibly released in response to potassium, either inhibiting the pressor effect of an excessive salt intake or counteracting the depressor action of sodium depletion.

Adult↗

PubMed2003

Athlete's heart.

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Electrocardiography↗

PubMed2003

Maternal and paternal influences on left ventricular mass of offspring.

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 (P=0.57) in 91 spouse-spouse pairs, 0.14 (P=0.002) in 500 parent-offspring pairs, and 0.32 (P<0.001) in 179 sib-sib pairs. Across the four parent-offspring relations, the intrafamilial correlations of left ventricular mass differed. The mother-son (n=140, r=0.27, P<0.001) and mother-daughter (n=161, r=0.28, P<0.001) correlations were significant, whereas the father-son (n=101, r=0.04, P=0.69) and father-daughter (n=98, r=-0.09, P=0.38) correlations were not different from zero. Overall, the mother-offspring correlation coefficient was significantly higher than the father-offspring correlation (r=0.28 versus r=-0.04; P=0.005). 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.

Adolescent↗

PubMed2003

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

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.

Aged↗

PubMed2003

Transforming growth factor-beta 1-mediated collagen gel contraction by cardiac fibroblasts.

OBJECTIVE: 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. METHODS: Cardiac fibroblasts (from male adult Wistar rats) from passage two were cultured to confluency and incubated on a hydrated collagen gel with and without TGF-beta(1) (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. RESULTS: TGF-beta(1) dose-dependently increased the contraction of collagen gel mediated by cardiac fibroblasts, reaching a maximal effect at 100 pmol/L TGF-beta(1). TGF-beta(1) also stimulated 3(H)-thymidine incorporation and total protein content in cardiac fibroblasts in the collagen gel lattice. TGF-beta(1) dose-dependently induced an increase in beta-smooth muscle actin, a marker of myofibroblasts. The TGF-beta(1)-induced reduction of area of the collagen gel was negatively correlated to the TGF-beta(1)-evoked appearance of a-smooth muscle actin in the collagen gel matrix. CONCLUSION: Our data demonstrate that 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 might depend on the promotion of myofibroblast differentiation.

Actins↗

PubMed2002

The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study.

BACKGROUND: After the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial ended in February 1997, randomized patients were offered active study medication for a further period of observation. OBJECTIVE: To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia. METHODS: Eligible patients had no dementia and were at least 60 years old. Their systolic blood pressure at entry was 160 to 219 mm Hg, with diastolic blood pressure below 95 mm Hg. Antihypertensive therapy was started immediately after randomization in the active treatment group, but only after termination of the double-blind trial in the control patients. Treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d), hydrochlorothiazide (12.5-25 mg/d), or both add-on drugs. RESULTS: Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall. The incidence of dementia doubled from 32 to 64 cases, 41 of whom had Alzheimer disease. Throughout follow-up, systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects randomized to active treatment. At the last examination, the blood pressure difference was still 4.2/2.9 mm Hg; 48.1%, 26.4%, and 11.4% of the control patients were taking nitrendipine, enalapril, and/or hydrochlorothiazide, whereas in the active treatment group these proportions were 70.2%, 35.4%, and 18.4%, respectively. Compared with the controls, long-term antihypertensive therapy reduced the risk of dementia by 55%, from 7.4 to 3.3 cases per 1000 patient-years (43 vs 21 cases, P<.001). After adjustment for sex, age, education, and entry blood pressure, the relative hazard rate associated with the use of nitrendipine was 0.38 (95% confidence interval, 0.23-0.64; P<.001). Treatment of 1000 patients for 5 years can prevent 20 cases of dementia (95% confidence interval, 7-33). CONCLUSION: The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure-lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.

Aged↗

PubMed2002

J-shaped relationship between blood pressure and mortality in hypertensive patients: new insights from a meta-analysis of individual-patient data.

BACKGROUND: Population-based longitudinal studies of hypertension have usually shown a continuous and positive relationship between blood pressure and mortality. However, several studies in hypertensive patients receiving treatment have described this relationship as J-shaped, with an increased risk for events in patients with low blood pressure. OBJECTIVE: To assess the evidence for a J-shaped relationship between blood pressure and mortality and its relation to treatment. DESIGN: Meta-analysis of individual-patient data. SETTING: Seven randomized clinical trials from the INDANA (INdividual Data ANalysis of Antihypertensive intervention) database. PATIENTS: 40 233 persons with hypertension (mean follow-up, 3.9 years). INTERVENTION: Primarily beta-blockers or thiazide diuretics versus placebo or no treatment. MEASUREMENTS: Diastolic and systolic blood pressure and number of cardiovascular, noncardiovascular, and all-cause deaths in yearly periods of follow-up. RESULTS: The analysis included data on 1655 deaths (56% cardiovascular). A J-shaped relationship between diastolic blood pressure and risk for death was observed for total and cardiovascular mortality in treated patients (nadir, 84 and 80 mm Hg, respectively) and untreated patients (nadir, 90 and 85 mm Hg, respectively). For noncardiovascular deaths, the relationship was J-shaped in the treated group (nadir, 84 mm Hg) and negative in the control group. Similar results were observed for systolic blood pressure. The presence of patients with wide pulse pressure did not explain these findings. CONCLUSIONS: The increased risk for events observed in patients with low blood pressure was not related to antihypertensive treatment and was not specific to blood pressure-related events. Poor health conditions leading to low blood pressure and an increased risk for death probably explain the J-shaped curve.

Antihypertensive Agents↗

PubMed2002

Depression and the heart: a systematic overview of definition, measurement, consequences and treatment of depression in cardiovascular disease.

Depression is an independent risk factor in the pathogenesis of cardiovascular disease and it is a prevalent disorder after cardiovascular disease associated with negative outcome in terms of mortality and morbidity. It is a dangerous condition requiring adequate screening and treatment, however, it often remains undiagnosed and thus untreated. Non-psychiatric healthcare workers, like nurses, general practitioners, physiotherapists and cardiologists are the health providers most closely involved in the management of patients with cardiovascular disease. They can play an important role in screening cardiovascular patients for depressive symptoms and in referring them for treatment. The purpose of this article therefore is to provide an evidence-based framework, aiming to educate non-psychiatric healthcare providers on depressive disorder in the context of chronic cardiovascular disease. In this paper, an overview of the definition, prevalence and consequences of depression will be discussed. Moreover, an overview of measurement methods and treatment modalities for depression will be provided. In addition, a step-by-step guide is provided in order to help non-psychiatric healthcare providers in dealing with depressed patients.

Algorithms↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed2002

Association between hypertension and variation in the alpha- and beta-adducin genes in a white population.

BACKGROUND: The substitution of tryptophan for glycine at amino acid 460 (Gly460Trp polymorphism) of the alpha-subunit of the heterodimeric cytoskeleton protein adducin increases renal sodium reabsorption and may be involved in the pathophysiology of essential hypertension. In the present study, we investigated in multivariate analyses whether the risk of hypertension was associated with the C1797T polymorphism of the beta-adducin gene. METHODS: A total of 1848 subjects randomly selected from a white population were genotyped. Study nurses measured blood pressure at the participants' homes. RESULTS: The frequencies of the alpha-adducin Trp and beta-adducin T alleles were 0.23 and 0.11, respectively. In men (N = 904), the beta-adducin T allele was not associated with hypertension [adjusted relative risk (RR) vs. CC homozygotes 0.94, P = 0.77], but T allele carriers had lower plasma renin activity (PRA) and 24-hour urinary aldosterone excretion (P < 0.04). In all women (N = 944), beta-adducin T allele carriers had a higher risk of hypertension than CC homozygotes (RR 1.81, CI 1.18-2.77, P = 0.007), but similar PRA and 24-hour urinary aldosterone excretion (P> 0.29). In 345 post-menopausal women and 190 users of oral contraceptives, the RRs of hypertension were 2.47 (CI 1.34-4.64, P = 0.003) and 2.56 (CI 0.83-7.86, P = 0.10), respectively. For systolic pressure in women, there was a significant interaction (P = 0.02) between the alpha- and beta-adducin polymorphisms. Only in female carriers of the mutated alpha-adducin Trp allele was the systolic pressure significantly higher in beta-adducin T allele carriers compared with CC homozygotes (+3.8 mm Hg, P = 0.02). Furthermore, in the presence of the mutated alpha-adducin Trp allele, the RRs associated with the beta-adducin T allele were 2.35 (P = 0.01) in all women, 2.92 (P = 0.03) in post-menopausal subjects, and 3.79 (P = 0.09) in users of oral contraceptives. CONCLUSIONS: The 1797T allele of the beta-adducin gene is associated with increased risk of hypertension in post-menopausal women and in users of oral contraceptives, particularly in the presence of the mutated alpha-adducin Trp allele. We hypothesize that inhibition of the renin-aldosterone system in men and absence of such a compensatory mechanism in women may explain, at least to some extent, the sexual dimorphism of the blood pressure phenotype in relation to the C1797T beta-adducin polymorphism.

Adolescent↗