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Biomedical subjects

J E Deanfield

Publications and source records attributed to J E Deanfield.

At least 37 records · Page 2Linked to original sources
PubMed2001

Subdiaphragmatic venous hemodynamics in the Fontan circulation.

OBJECTIVE: We investigated the subdiaphragmatic venous physiology in patients subjected to the Fontan operation to understand some of the early and late problems of this circulation. METHODS: Flows were evaluated by Doppler ultrasonography in the subhepatic inferior vena cava, hepatic vein, and portal vein during respiratory monitoring and with a tilt table. Twenty control subjects (group A) and 56 patients who had the Fontan operation, 27 in functional class I (group B) and 29 in class III or IV (group C), were studied. Inspiratory/expiratory flow ratio was calculated to reflect respiratory effects, and upright/supine flow ratio was calculated to assess gravity effects. Inferior vena caval, hepatic venous, and wedged hepatic venous pressures were measured during catheterization in 21 control subjects and 25 Fontan patients. The difference between wedged and hepatic venous pressures represents the transhepatic venous pressure gradient. RESULTS: Fontan hepatic venous flow depended more on inspiration than control, but without difference between groups B and C (inspiratory/expiratory flow ratios: 1.7, 2.9, and 2.9, respectively; P <.02). Normal portal venous flow was higher in expiration; this effect was lost in group B and reversed in group C (inspiratory/expiratory flow ratios: 0.8, 1.0, and 1.3; P <.0005). Gravity reduced portal venous flow in groups A and B, but progression to functional class III or IV (group C) exacerbated this effect (upright/supine flow ratios: 0.8, 0.7, and 0.5; P <.01). Inferior vena caval, hepatic venous, and wedged hepatic venous pressures (in millimeters of mercury) in the Fontan groups were all elevated compared with the control group (inferior vena cava, 14.4 +/- 4.4 vs 5.9 +/- 2.3; hepatic vein, 14.7 +/- 4.5 vs 5.9 +/- 1.9; wedged hepatic vein, 14.7 +/- 4.0 vs 8.3 +/- 2.6; P <.0001). However, transhepatic venous pressure gradient in the Fontan group was lower than in the control group (0.5 +/- 0.5 vs 2.4 +/- 2.0; P <.001). Univariate analysis of inferior vena caval pressure and transhepatic venous pressure gradient showed significant inverse correlation (r = 0.6, P <.002). CONCLUSIONS: In patients who are in functionally poorer condition after the Fontan operation, portal venous flow loses normal expiratory augmentation and adverse gravity influence is enhanced. These suboptimal flow dynamics, coupled with higher splanchnic venous pressures and lower transhepatic venous pressure gradients, suggest that hepatic sinusoids are congested, acting as "open tubes." Transhepatic gradient loss is incrementally worse with higher caval pressures. These observations may be responsible for late gastrointestinal problems in patients who have had the Fontan operation.

Adolescent↗
PubMed2001

Dialysis improves endothelial function in humans.

BACKGROUND: Circulating inhibitors of endothelial function have been implicated in the pathogenesis of vascular disease in chronic renal failure. The aim of this study was to determine if lowering the plasma concentration of these and other dialysable toxins improves endothelial function. To do this we compared the acute effects on endothelial function of single episodes of haemodialysis with automated peritoneal dialysis. We hypothesized that endothelial function would improve after dialysis, with a greater effect seen after haemodialysis due to more substantial clearance of endothelial toxins per-treatment. METHODS: Subjects with end-stage renal failure undergoing haemodialysis (n=16) or automated peritoneal dialysis (n=14) were investigated. Endothelial function was determined using vascular ultrasound to measure flow-mediated dilatation of the brachial artery and was compared with the dilatation caused by sublingual glyceryl trinitrate. Endothelial function was assessed before and after a single dialysis treatment. Plasma concentrations of the inhibitors of endothelial function, asymmetric dimethyl-l-arginine and homocysteine were measured. Flow-mediated dilatation was expressed as percentage change from basal diameter and analysed using Student's t test. RESULTS: The plasma concentration of circulating inhibitors of endothelial function was reduced after haemodialysis but not peritoneal dialysis. Haemodialysis increased flow-mediated dilatation from 4.0+/-1.0% to 5.8+/-1.2% (P<0.002). These changes persisted for 5 h but returned to baseline by 24 h. Automated peritoneal dialysis had no acute effect on flow-mediated dilatation (5.9+/-1.1% vs 5.4+/-0.8% after, P>0.5). There were no effects of either dialysis modality on dilatation to glyceryl trinitrate. CONCLUSIONS: Short-term reduction of circulating inhibitors of endothelial function by haemodialysis is associated with increased flow-mediated dilatation. These data suggest that dialysable endothelial toxins have deleterious effects on endothelial function that are rapidly reversible.

Adult↗
PubMed2000

Mental stress induces transient endothelial dysfunction in humans.

BACKGROUND: Mental stress has been linked to increased morbidity and mortality in coronary artery disease and to atherosclerosis progression. Experimental studies have suggested that damage to the endothelium may be an important mechanism. METHODS AND RESULTS: Endothelial function was studied in 10 healthy men (aged 50. 4+/-9.6 years) and in 8 non-insulin-dependent diabetic men (aged 52. 0+/-7.2 years). Brachial artery flow-mediated dilation (FMD, endothelium dependent) and response to 50 microg of sublingual glyceryl trinitrate (GTN, endothelium independent) were measured noninvasively by use of high-resolution ultrasound before and after (30, 90, and 240 minutes) a standardized mental stress test. The same protocol without mental stress was repeated on a separate occasion in the healthy men. In healthy subjects, FMD (5.0+/-2.1%) was significantly (P:<0.01) reduced at 30 and 90 minutes after mental stress (2.8+/-2.3% and 2.3+/-2.4%, respectively) and returned toward normal after 4 hours (4.1+/-2.0%). Mental stress had no effect on the response to GTN. In the repeated studies without mental stress, FMD did not change. The diabetic subjects had lower FMD than did the control subjects (3.0+/-1.5% versus 5.0+/-2.1%, respectively; P:=0.02) but showed no changes in FMD (2.7+/-1.1% after 30 minutes, 2.8+/-1.9% after 90 minutes, and 3.1+/-2.3% after 240 minutes) or GTN responses after mental stress. CONCLUSIONS: These findings suggest that brief episodes of mental stress, similar to those encountered in everyday life, may cause transient (up to 4 hours) endothelial dysfunction in healthy young individuals. This might represent a mechanistic link between mental stress and atherogenesis.

Adult↗
PubMed2000

Effects of respiration and gravity on infradiaphragmatic venous flow in normal and Fontan patients.

BACKGROUND: In the Fontan circulation, pulmonary and systemic vascular resistances are in series. The implications of this unique arrangement on infradiaphragmatic venous physiology are poorly understood. METHODS AND RESULTS: We studied the effects of respiration and gravity on infradiaphragmatic venous flows in 20 normal healthy volunteers (control) and 48 Fontan patients (atriopulmonary connection [APC] n=15, total cavopulmonary connection [TCPC] n=30). Hepatic venous (HV), subhepatic inferior vena caval (IVC), and portal venous (PV) flow rates were measured with Doppler ultrasonography during inspiration and expiration in both the supine and upright positions. The inspiratory-to-expiratory flow rate ratio was calculated to reflect the effect of respiration, and the supine-to-upright flow rate ratio was calculated to assess the effect of gravity. HV flow depended heavily on inspiration in TCPC compared with both control and APC subjects (inspiratory-to-expiratory flow rate ratio 3.4, 1.7, and 1.6, respectively; P:<0.0001). Normal PV flow was higher in expiration, but this effect was lost in TCPC and APC patients (inspiratory-to-expiratory flow rate ratio 0.8, 1.0, and 1.1, respectively; P:=0.01). The respiratory influence on IVC flow was the same in all groups. Gravity decreased HV flow more in APC than in TCPC patients (supine-to-upright flow rate ratio 3.2 versus 2.1, respectively; P:<0.04) but reduced PV flow equally in all groups. CONCLUSIONS: Gravity and respiration have important influences on infradiaphragmatic venous return in Fontan patients. Although gravity exerts a significant detrimental effect on lower body venous return, which is more marked in APC than in TCPC patients, the beneficial effects of respiration in TCPC patients are mediated primarily by an increase in HV flow. These effects may have important short- and long-term implications for the hemodynamics of the Fontan circulation.

Adolescent↗
PubMed2000

Acute systemic inflammation impairs endothelium-dependent dilatation in humans.

BACKGROUND: We tested the hypothesis that endothelial dysfunction underlies the association between an acute inflammatory episode and the transiently increased risk of a cardiovascular event by examining the effects of an experimental inflammatory stimulus on endothelium-dependent vasodilation. METHODS AND RESULTS: Salmonella typhi vaccine was used to generate a systemic inflammatory response in healthy volunteers. In 12 subjects, dilatation of the brachial artery to flow and to sublingual nitroglycerin (NTG) was recorded (conduit vessel response), and in 6 subjects, venous occlusion plethysmography was used to measure forearm blood flow during intrabrachial infusion of the endothelium-dependent dilators acetylcholine (ACh) and bradykinin (BK) and the endothelium-independent dilators NTG and verapamil (resistance vessel response). Responses were assessed 16 hours before and 8 and 32 hours after vaccination. Vaccination resulted in elevations in white cell count and serum levels of interleukin-6 and interleukin-1 receptor antagonist. Eight hours after vaccination, resistance vessel responses to BK (P:=0.0099) and ACh (P:=0.0414) were markedly attenuated, and brachial artery flow-mediated dilatation was depressed. Resistance vessel responses to verapamil and NTG were unchanged, as was the conduit vessel response to NTG. Thirty-two hours after vaccination, resistance vessel responses to BK and ACh had returned to normal. CONCLUSIONS: S typhi vaccine generates a mild inflammatory reaction associated with temporary but profound dysfunction of the arterial endothelium in both resistance and conduit vessels to both physical and pharmacological dilator stimuli. This finding might explain the association between infection and inflammation and the enhanced risk of an acute cardiovascular event.

Acetylcholine↗
PubMed2000

Cholesterol and arterial distensibility in the first decade of life: a population-based study.

BACKGROUND: Blood cholesterol levels are a key determinant of coronary heart disease risk in adults, but the importance of lipid levels in the general population during childhood is less clear. We related arterial distensibility, a marker of vascular function known to be altered early in atherosclerosis, to the lipid profile of a population-based sample of children aged 9 to 11 years. METHODS AND RESULTS: A noninvasive ultrasound technique was used to measure arterial distension during the cardiac cycle in the brachial arteries of 361 children from 4 towns in the United Kingdom. This measure was related to their pulse pressure to assess arterial distensibility. All the children had previously had a comprehensive assessment of cardiovascular risk including a full lipid profile, cotinine-assessed smoke exposure, serum glucose, and questionnaire data on socioeconomic and dietary factors. Mean total cholesterol in the population was 4.72 [SD 0.75] mmol/L. There was a significant, inverse relation between cholesterol and distension of the artery across this range (linear regression coefficient -11.8 microm. mmol(-1). L(-1), P=0.003). Similar relationships were demonstrated with LDL and apolipoprotein B (-12.9 microm. mmol(-1). L(-1), P=0. 005 and -36.9 microm/mmol/L, P=0.01). HDL and triglyceride levels showed no consistent association with distensibility. CONCLUSIONS: LDL cholesterol levels had an impact on arterial distensibility in the first decade of life. Furthermore, the functional differences in the arterial wall were demonstrated within the lipid range found in normal children, a finding that raises the possibility that cholesterol levels in the general population during childhood may already be relevant to the development of vascular disease.

Adult↗
PubMed2000

Atorvastatin but not L-arginine improves endothelial function in type I diabetes mellitus: a double-blind study.

OBJECTIVES: We sought to determine the effects of oral L-arginine and the hexamethylglutaryl coenzyme A reductase inhibitor atorvastatin on endothelial function in young patients with type I diabetes mellitus (DM). BACKGROUND: Endothelial dysfunction, a key early event in atherosclerosis, occurs in young patients with type I DM, and its reversal may benefit the progression of vascular disease. Cholesterol reduction in L-arginine improve endothelial function in nondiabetic subjects, but their effect in patients with type I DM is unknown. METHODS: In a double-blind, 2x2 factorial study, we investigated the effect of L-arginine (7 g twice daily) and atorvastatin (40 mg/day) on conduit artery vascular function in 84 normocholesterolemic young adults (mean+/-SD: age 34 years [range 18 to 46], low density lipoprotein [LDL] cholesterol 2.96+/-0.89 mmol/liter) with type I DM. Brachial artery dilation to flow (flow-mediated dilation [FMD]) and to the direct smooth muscle dilator glyceryl trinitrate (GTN) were assessed noninvasively using high resolution ultrasound at baseline and after six weeks of treatment. RESULTS: Atorvastatin resulted in a 48+/-10% decrease in serum LDL cholesterol levels, whereas L-arginine levels increased by 247+/-141% after L-arginine therapy. By analysis of covariance, treatment with atorvastatin resulted in a significant increase in FMD (p = 0.018. L-Arginine therapy had no significant effect on endothelial function, and there was no significant change in dilation to GTN after either intervention. CONCLUSIONS: In young patients with type I DM, improvement in endothelial dysfunction can be demonstrated after just six weeks of treatment with atorvastatin. In contrast to studies of hypercholesterolemia, however, L-arginine had no benefit. Treatment with atorvastatin at an early stage may have an impact on the progression of atherosclerosis in these high risk patients.

Adolescent↗
PubMed1999

Exercise training enhances endothelial function in young men.

OBJECTIVES: The present study was designed to assess whether exercise training can enhance endothelium-dependent dilatation in healthy young men. BACKGROUND: Exercise has been shown to reduce cardiovascular morbidity and mortality, but the mechanisms for this benefit are unclear. Endothelial dysfunction is an early event in atherogenesis, and animal studies have shown that exercise training can enhance endothelial function. METHODS: We have examined the effect of a standardized, 10-week, aerobic and anaerobic exercise training program on arterial physiology in 25 healthy male military recruits, aged 17 to 24 (mean 20) years, of average fitness levels. Each subject was studied before starting, and after completing the exercise program. Baseline vascular reactivity was compared with that of 20 matched civilian controls. At each visit, the diameter of the right brachial artery was measured at rest, during reactive hyperemia (increased flow causing endothelium-dependent dilation) and after sublingual glyceryltrinitrate (GTN; an endothelium-independent dilator), using high-resolution external vascular ultrasound. RESULTS: At baseline, flow-mediated dilatation (FMD) and GTN-mediated dilatation were similar in the exercise and control groups (FMD 2.2+/-2.4% and 2.4+/-2.8%, respectively, p = 0.33; GTN 13.4+/-6.2 vs. 16.7+/-5.9, respectively, p = 0.53). In the military recruits, FMD improved from 2.2+/-2.4% to 3.9+/-2.5% (p = 0.01), with no change in the GTN-mediated dilation (13.4+/-6.2% vs. 13.9+/-5.8%, p = 0.31) following the exercise program. CONCLUSION: Exercise training enhances endothelium-dependent dilation in young men of average fitness. This may contribute to the benefit of regular exercise in preventing cardiovascular disease.

Administration, Sublingual↗
PubMed1998

Recurrence risks in offspring of adults with major heart defects: results from first cohort of British collaborative study.

BACKGROUND: Congenital heart defects are generally assumed to have a multifactorial aetiology. We have tested this hypothesis by studying adults with heart defects and their families. METHODS: We identified 1094 patients who survived surgery for major cardiac defects before 1970. We chose individuals with disturbance of situs or segmental connection, with atrioventricular septal defect or with tetralogy of Fallot. After exclusion and non-participation, 727 individuals were traced. Each was visited by an investigator and completed a detailed questionnaire. If possible, all "normal" offspring were examined by a paediatric cardiologist. FINDINGS: The 727 individuals had 393 live offspring. There were 71 miscarriages and five terminated pregnancies. Overall, we found recurrent heart defects in 16 liveborn offspring--a recurrence risk of 4.1%. This result differed significantly from sibling risk (2.1%; p=0.021). More congenital heart defects occurred in the offspring of affected women than in those of affected men (p=0.047); when all malformations (cardiac and non-cardiac) in the offspring were taken into account the excess was more significant (p=0.032). We found an excess of miscarriages in the offspring of affected women (p=0.001). In tetralogy of Fallot, heart defects occurred in seven (3.1%) of 223 offspring, 12 (2.2%) of 539 siblings, five (0.3%) of 1575 second-degree relatives, and eight (0.3%) of 2728 third-degree relatives. INTERPRETATION: Our findings do not support a polygenic basis for all heart defects. Atrioventricular septal defect seems to be a single-gene defect and tetralogy of Fallot a polygenic disorder with a small number of interacting genes. Our data suggest that isolated transposition of the great arteries is a sporadic defect.

Adult↗
PubMed1998

Effect of enalapril on endothelial function in young insulin-dependent diabetic patients: a randomized, double-blind study.

OBJECTIVES: We sought to determine whether 6 months of treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril can improve conduit artery endothelial function in young subjects with insulin-dependent diabetes mellitus (IDDM). BACKGROUND: Endothelial dysfunction is an early event in atherogenesis and has been demonstrated in young subjects with IDDM. ACE inhibitors have been shown to enhance conduit artery endothelial function in animal experiments and in patients with established coronary atherosclerosis, although their effect in IDDM is not known. METHODS: Ninety-one subjects (mean age 30.9 years, range 18 to 44) with stable IDDM but no clinical evidence of vascular disease were randomized to receive enalapril (20 mg once daily) (46 subjects) or placebo (45 subjects) in a randomized, double-blind, parallel-group study. Brachial artery flow-mediated dilation (FMD), an endothelium-dependent stimulus, and response to glyceryl trinitrate (GTN), which acts directly on vascular smooth muscle, were assessed noninvasively by means of high resolution external vascular ultrasound at baseline and after 12 and 24 weeks of treatment. RESULTS: FMD was inversely correlated with total cholesterol (r=0.22, p=0.041) but not with any diabetic variables. Treatment with enalapril had no significant effect on FMD (p=0.67) or response to the endothelial-independent dilator GTN (p=0.45). CONCLUSIONS: These data suggest that impairment of endothelial-dependent dilation in young subjects with IDDM is not improved by treatment with the ACE inhibitor enalapril. This lack of improvement may reflect the complex nature of vascular disease in IDDM, which can affect both endothelial and smooth muscle function.

Adolescent↗
PubMed1998

Smooth muscle dysfunction occurs independently of impaired endothelium-dependent dilation in adults at risk of atherosclerosis.

OBJECTIVES: We sought to assess smooth muscle function in adults at risk for atherosclerosis. BACKGROUND: Previous studies in subjects at risk for atherosclerosis have demonstrated arterial endothelial dysfunction, with reduced vasodilator responses after pharmacologic or physiologic stimulation of endothelial nitric oxide (NO). Most have also shown a slight but nonsignificant impairment of vasodilation in response to exogenous sources of NO, such as nitroglycerin (NTG). We hypothesized that NTG responses might be reduced in a large number of consecutively studied adults at risk for atherosclerosis, independent of any impaired endothelium-dependent responses, consistent with concomitant smooth muscle dysfunction. METHODS: Using high resolution ultrasound, the dilator response of the brachial artery to 400 microg of sublingual NTG was measured in 800 asymptomatic subjects. Subjects were also assessed for a history of vascular risk factors, blood pressure, total serum cholesterol and flow-mediated endothelium-dependent dilation (EDD). RESULTS: We studied 317 men and 483 women, 38 +/- 17 years old (mean +/- SD, range 15 to 76). The mean cholesterol level was 5.2 +/- 1.3 mmol/liter, and there were 126 smokers and ex-smokers (16 +/- 9 mean pack-years) and 105 diabetic subjects. On univariate analysis, a reduced vasodilator response to NTG was associated with high cholesterol, cigarette smoking, diabetes mellitus, increasing age, male gender, larger vessel size and reduced EDD (p < or = 0.01 for all). On multivariate analysis, diabetes, larger vessel size and reduced EDD were all independently associated with impaired NTG-related vasodilation (p < or = 0.001 for all). In the 574 nondiabetic subjects who had never smoked cigarettes, the independent relation between EDD and NTG responses was still observed (r = 0.24, p = 0.01). CONCLUSIONS: The vasodilator response to exogenous NO is impaired in asymptomatic subjects with reduced EDD, consistent with smooth muscle dysfunction in adults at risk for atherosclerosis.

Administration, Sublingual↗
PubMed1998

Early endothelial dysfunction in adults at risk from atherosclerosis: different responses to L-arginine.

OBJECTIVES: We sought to examine endothelial responses to L-arginine in three groups with isolated risk factors: hypercholesterolemia, smoking and insulin-dependent diabetes mellitus (IDDM). BACKGROUND: Endothelial dysfunction occurs early in atherosclerosis, predating clinical disease. We hypothesized that the nature of endothelial injury associated with individual cardiovascular risk factors might be different and that this might affect the response to L-arginine, the substrate for endothelial nitric oxide synthase. METHODS: We studied the effects of intravenous L-arginine on brachial artery flow-mediated dilation (FMD) and glyceryl trinitrate (GTN)-mediated dilation in 36 young subjects (18 to 40 years old) without clinical atherosclerosis: 9 each of normal control subjects, hypercholesterolemic subjects, cigarette smokers and subjects with IDDM. RESULTS: Baseline FMD was significantly impaired in hypercholesterolemic subjects (mean +/- SD 1.7 +/- 2.3%), smokers (1.6 +/- 1.8%) and diabetic subjects (1.8 +/- 1.5%) compared with that in control subjects (6.9 +/- 3.3%, p = 0.001). The response to GTN was not significantly different between the subjects with risk factors and control subjects, apart from those with IDDM, in whom it was significantly impaired (p = 0.026). After infusion of L-arginine, there was no change in FMD in control or diabetic subjects. In hypercholesterolemic subjects and smokers, FMD improved from 1.9 +/- 1.9% to 4.1 +/- 2.1% (p = 0.01) and from 2.0 +/- 1.71% to 3.1 +/- 2.5% (p = 0.02), respectively. CONCLUSIONS: FMD was impaired in all three risk factor groups; however, they responded differently to L-arginine, FMD being improved in hypercholesterolemic subjects and smokers but unchanged in diabetic subjects. These results indicate differing underlying pathophysiologies that may facilitate the design of treatment strategies for subjects with different risk factors.

Adolescent↗
PubMed1998

Amlodipine versus diltiazem CR in the reduction of the total ischemic burden: the Circadian Anti-Ischemia Program in Europe (CAPE) II trial--clinical rationale and methodology.

The Circadian Anti-ischemia Program in Europe (CAPE) trial was a large, 10-week, double-blind study of the antiischemic effects of the third-generation calcium antagonist, amlodipine, in patients with chronic stable angina. The study showed that, compared with the addition of placebo to conventional medical therapy (if any), the addition of amlodipine significantly reduced the total ischemic burden. Both symptomatic and asymptomatic ischemic events were reduced, over 24 hours, with no change in the heart rate profile. The next logical step is to compare amlodipine with other agents, as monotherapy and in combination therapy, which is the basis for the CAPE II trial. This European multicenter project will recruit patients with coronary artery disease and chronic stable angina in order to compare the efficacy of the intrinsically long-acting amlodipine with an artificially extended-release formulation of diltiazem, a calcium antagonist with a short plasma half-life. The impact of these agents will also be compared during irregular dosing periods. An agent with an intrinsically long half-life, such as amlodipine, may maintain better clinical efficacy than a short-acting drug with a prolonged delivery system in these circumstances. The CAPE II trial will investigate whether this results in improved management of the circadian pattern of transient myocardial ischemia. In addition, basic therapy will be augmented by the addition of a beta-blocker to amlodipine and the addition of a nitrate to diltiazem to evaluate which of these frequently prescribed treatment approaches results in optimal ischemia suppression. Both the subjective endpoints of angina and patient well-being, as well as the objective measures of myocardial ischemia in exercise testing and ambulatory electrocardiography (ECG) monitoring, will be employed. Answers to these issues will help to define the optimal medical approach to ischemia suppression in patients with coronary artery disease and will complement the findings from large-scale prognosis trials currently being performed.

Adult↗
PubMed1997

Prognostic significance of myocardial ischemia detected by ambulatory electrocardiography, exercise treadmill testing, and electrocardiogram at rest to predict cardiac events by one year (the Asymptomatic Cardiac Ischemia Pilot [ACIP] study)

Myocardial ischemia identified by ambulatory electrocardiography (AECG), exercising treadmill testing, (ETT), or 12-lead electrocardiogram at rest is associated with an adverse prognosis, but the effect of improving these ischemic manifestations by treatment on outcome is unknown. The Asymptomatic Cardiac Ischemia Pilot (ACIP) study was a National Heart, Lung, and Blood Institute funded study to determine the feasibility of conducting a large-scale prognosis study and to assess the effect of 3 treatment strategies (angina-guided strategy, AECG ischemia-guided strategy, and revascularization strategy) in reducing the manifestations of ischemia as indicated by AECG and ETT. The study cohort for this database study consisted of 496 randomized patients who performed the AECG, ETT, and 12-lead electrocardiogram at rest at both the qualifying and week 12 visits. The effect of modifying ischemia by treatment on the incidence of cardiac events (death, myocardial infarction, coronary revascularization procedure, or hospitalization for an ischemic event) at 1 year was examined. In the 2 medical treatment groups (n = 328) there was an association between the number of ambulatory electrocardiographic ischemic episodes at the qualifying visit and combined cardiac events at 1 year (p = 0.003). In the AECG ischemia-guided patients there was a trend associating greater reduction in the number of ambulatory electrocardiographic ischemia episodes with a reduced incidence of combined cardiac events (r = -0.15, p = 0.06). In the revascularization strategy patients this association was absent. In the medical treatment patients the exercise duration on the baseline ETT was inversely associated with an adverse prognosis (p = 0.02). The medical treatment strategies only slightly improved the exercise time and the exercise duration remained of prognostic significance. In the revascularization group strategy patients this association was absent. Thus, myocardial ischemia detected by AECG and an abnormal ETT are each independently associated with an adverse cardiac outcome in patients subsequently treated medically.

Electrocardiography↗
PubMed1997

Endothelium-dependent dilatation is impaired in young healthy subjects with a family history of premature coronary disease.

BACKGROUND: A family history of premature coronary artery disease (CAD) in a first-degree relative is an independent risk factor for coronary disease. Both genetic and environmental influences are likely to be responsible and may interact, but their relative importance is unclear. METHODS AND RESULTS: We studied endothelial function in 50 first-degree relatives (31 men, 19 women; mean age, 25+/-8 years) of patients (men < or = 45 years, women < or = 55 years) with proven CAD. All subjects were well, lifelong nonsmokers, not diabetic, and not hypertensive and took no medications. Using high-resolution external vascular ultrasound, we measured brachial artery diameter at rest and in response to reactive hyperemia (with increased flow causing an endothelium-dependent vasodilatation) and to sublingual glyceryltrinitrate (GTN, an endothelium-independent dilator). Vascular responses were compared with those of 50 healthy control subjects matched for age and sex. Flow-mediated dilatation (FMD) was impaired in the family history group (4.9+/-4.6% versus 8.3+/-3.5% in control subjects, P<.005). In contrast, GTN caused dilatation in all subjects (family history, 17.1+/-8.8%; control subjects, 19.0+/-6.3%; P=NS), suggesting that reduced FMD was due to endothelial dysfunction. When the family history subjects were subdivided, those found to have a serum cholesterol > 4.2 mmol/L (group A, n=10) had mildly impaired FMD compared with control subjects (5.5+/-5.1% versus 8.3+/-3.5%). In others whose affected relative had coronary risk factors (group B, n=24), FMD was also only slightly reduced (6.2+/-4.8% versus 8.3+/-3.5%). In contrast, subjects with no risk factors and whose affected relative had a normal cardiovascular risk factor profile (group C, n=16) had markedly impaired FMD (2.9+/-3.7% versus 8.3+/-3.5%). Although ANOVA of the three family history subgroups did not reach statistical significance (F=2.55, P=.09), pairwise analysis showed that FMD in group C was significantly impaired compared with group B (P=.026). CONCLUSIONS: Healthy young adults with a family history of premature coronary disease may have impaired endothelium-dependent dilatation, even in the absence of other cardiovascular risk factors. Those subjects, who were free of risk factors and whose affected first-degree relative was free of risk factors, had the most impaired endothelial function, suggesting a genetic influence on early arterial physiology that may be relevant to later clinical disease.

Adult↗
PubMed1997

Flow-mediated dilation in 9- to 11-year-old children: the influence of intrauterine and childhood factors.

BACKGROUND: Early life factors, particularly size at birth, may influence later risk of cardiovascular disease, but a mechanism for this influence has not been established. We have examined the relation between birth weight and endothelial function (a key event in atherosclerosis) in a population-based study of children, taking into account classic cardiovascular risk factors in childhood. METHODS AND RESULTS: We studied 333 British children aged 9 to 11 years in whom information on birth weight, maternal factors, and risk factors (including blood pressure, lipid fractions, preload and postload glucose levels, smoking exposure, and socioeconomic status) was available. A noninvasive ultrasound technique was used to assess the ability of the brachial artery to dilate in response to increased blood flow (induced by forearm cuff occlusion and release), an endothelium-dependent response. Birth weight showed a significant, graded, positive association with flow-mediated dilation (0.027 mm/kg; 95% CI, 0.003 to 0.051 mm/kg; P=.02). Childhood cardiovascular risk factors (blood pressure, total and LDL cholesterol, and salivary cotinine level) showed no relation with flow-mediated dilation, but HDL cholesterol level was inversely related (-0.067 mm/mmol; 95% CI, -0.021 to -0.113 mm/mmol; P=.005). The relation between birth weight and flow-mediated dilation was not affected by adjustment for childhood body build, parity, cardiovascular risk factors, social class, or ethnicity. CONCLUSIONS: Low birth weight is associated with impaired endothelial function in childhood, a key early event in atherogenesis. Growth in utero may be associated with long-term changes in vascular function that are manifest by the first decade of life and that may influence the long-term risk of cardiovascular disease.

Birth Weight↗