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Biomedical subjects

Ralph A H Stewart

Publications and source records attributed to Ralph A H Stewart.

At least 19 recordsLinked to original sources
PubMed2006

Longitudinal left ventricular contractile dysfunction after exercise in aortic stenosis.

OBJECTIVE: To determine whether longitudinal left ventricular systolic function measured by Doppler tissue imaging (DTI) after exercise can identify early left ventricular dysfunction in asymptomatic patients with moderate-severe aortic stenosis. DESIGN: Case-control study. SETTING: Outpatient cardiology departments. PATIENTS: 20 patients with aortic stenosis, with or without equivocal symptoms, a peak aortic valve velocity > or =3 m/s, and left ventricular ejection fraction >50% and 15 aged-matched normal controls. INTERVENTIONS: Echocardiogram performed at rest and immediately after treadmill exercise. MAIN OUTCOME MEASURES: The peak systolic velocity of the lateral mitral annulus (S') by DTI at rest and immediately after exercise, exercise capacity, exercise systolic blood pressure and the plasma level of B-type natriuretic peptide (BNP). RESULTS: For patients with aortic stenosis, mean (SD) aortic valve area was 0.95 (0.3) cm(2). At rest, S' was similar for patients with aortic stenosis and controls, respectively (8.5 (1.5) vs 9.1 (1.8) cm/s, p = 0.15). However, after exercise, S' (12.2 (3.2) vs 17 (2.8) cm/s, p<0.001) and the increase in S' between rest and exercise (4 (3) vs 7.9 (1.5) cm/s, p<0.001) were lower in patients with aortic stenosis. In patients with aortic stenosis, a smaller increase in S' after exercise was associated with lower exercise capacity (r = 0.5, p = 0.02), a smaller increase in exercise systolic blood pressure (r = 0.6, p = 0.005) and higher plasma level of BNP (r = 0.66, p = 0.002). CONCLUSION: In asymptomatic patients with moderate-severe aortic stenosis a lower than normal increase in peak systolic mitral annular velocity after treadmill exercise is a marker of early left ventricular systolic dysfunction.

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PubMed2006

Risk stratification of patients with acute anterior myocardial infarction and right bundle-branch block: importance of QRS duration and early ST-segment resolution after fibrinolytic therapy.

BACKGROUND: Patients with an acute anterior ST-segment elevation myocardial infarction and right bundle-branch block (RBBB) have a high mortality risk, which may be stratified by early ECG changes. METHODS AND RESULTS: In the Hirulog Early Reperfusion Occlusion (HERO-2) trial, 17 073 patients with acute myocardial infarction (AMI) within 6 hours of symptom onset were treated with streptokinase and randomized to receive bivalirudin or heparin. There was no difference in the primary end point of 30-day mortality. ECGs were recorded at randomization and 60 minutes after fibrinolytic therapy was begun. The 30-day mortality rate was 31.6% in the 415 patients with RBBB and anterior AMI at randomization and 33% in the 100 patients who developed new RBBB at 60 minutes from normal baseline conduction accompanying an anterior AMI. An increase in QRS duration by 20-ms increments was associated with increasing 30-day mortality rate in both RBBB groups on multivariable analyses with covariates of age, Killip class, systolic blood pressure, pulse, and prior infarction. Patients with QRS duration > or = 160 ms had higher 30-day mortality rate than those with QRS duration < 160 ms (37.2% versus 27.2%, P = 0.03, and 46.2% versus 24.5%, P = 0.025, in the 2 groups, respectively). For the patients with RBBB and anterior MI at randomization, RBBB resolved at 60 minutes in 40 patients, but 30-day mortality rate was unchanged. For those with persisting RBBB at 60 minutes, 30-day mortality rate was lower if ST-segment elevation had resolved by > or = 50% (20.4% versus 35.3%, P = 0.006). CONCLUSIONS: In patients with anterior AMI and RBBB, increasing QRS duration is associated with increasing 30-day mortality. Early ST-segment resolution after fibrinolytic therapy despite persisting RBBB is associated with lower mortality rate.

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PubMed2006

Coronary sinus and ascending aortic levels of aldosterone, angiotensin II, and B-type natriuretic peptide in patients with aortic stenosis and in patients with coronary heart disease.

Demonstration that aldosterone synthesis occurs in the myocardium would suggest that the clinical benefits of aldosterone receptor antagonists may extend to patients with normal circulating plasma levels of aldosterone. Previous studies have reported myocardial aldosterone synthesis in patients with heart failure. This study determined whether myocardial aldosterone and angiotensin II release occurs in patients with aortic stenosis (AS) and/or coronary heart disease (CHD) with normal left ventricular ejection fractions and no clinical heart failure. In 19 patients with severe AS and 18 patients with stable CHD, plasma levels of aldosterone, angiotensin II, B-type natriuretic peptide (BNP), and procollagen type III amino terminal peptide (PIIINP) were measured in blood samples taken from the coronary sinus and aortic root before diagnostic coronary angiography. Plasma aldosterone was approximately 20% greater in the coronary sinus than the aorta, respectively, in the 2 patient groups (AS: 120 vs 102 pmol/L, p <0.001; CHD: 94 vs 77 pmol/L, p <0.001). Plasma angiotensin II was also greater in the coronary sinus (AS: 16 vs 11 pmol/L, p <0.001; CHD: 12 vs 9 pmol/L, p <0.001). Plasma levels of BNP in the coronary sinus were approximately double those in the aorta in the 2 groups of patients (p <0.001). In contrast, there was no transmyocardial gradient in the plasma level of PIIINP for either AS or CHD. In conclusion, these results indicate that aldosterone, angiotensin II, and BNP are released into the coronary sinus in severe AS and in stable CHD, even when the left ventricular ejection fraction is normal and there is no clinical heart failure.

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PubMed2006

Frequency of recurrent ST-elevation myocardial infarction after fibrinolytic therapy in a different territory as a manifestation of multiple unstable coronary arterial plaques.

Multiple unstable plaques have been demonstrated by various imaging techniques in culprit and nonculprit arteries in patients with acute coronary syndromes, but the frequency with which clinical manifestations of multiple unstable plaques occur is unclear. To estimate this frequency in patients who present within 6 hours with ST-elevation myocardial infarction, we studied electrocardiograms and cardiac marker levels of 722 patients with suspected reinfarction in the HERO-2 trial of 17,073 patients; this trial compared intravenous bivalirudin with unfractionated heparin before administration of streptokinase. Twenty-six patients (3.6%) developed recurrent ST elevation in a different territory. Of all the patients who developed ST elevation in a different territory, 50% (13 of 26) did so during the 48 hours of randomized antithrombin therapy compared with 29% (140 of 487) of those who developed recurrent ST elevation in the index territory (p = 0.046). Recurrent index territory ST elevation occurred in 392 of 552 patients (71%) with confirmed reinfarction, and ST elevation in a new territory occurred in 21 patients (3.8%) with confirmed reinfarction (2.3% and 0.12% of all HERO-2 enrollees, respectively). These data suggest that clinical manifestation of multiple unstable plaques of recurrent ST elevation and reinfarction in a territory different from that of the index ST elevation myocardial infarction after intravenous fibrinolytic and antithrombin therapies is rare.

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PubMed2006

Effects of exercise training on 5 inflammatory markers associated with cardiovascular risk.

BACKGROUND: Cross-sectional studies suggest that regular exercise has anti-inflammatory effects, leading to lower levels of several proatherogenic inflammatory markers. However, this has yet to be confirmed by randomized prospective trials. We performed a randomized controlled trial to assess whether exercise training decreases levels of 5 inflammatory markers linked to future cardiovascular risk: white blood cell count, fibrinogen, C-reactive protein, soluble intercellular adhesion molecule 1, and soluble CD40 ligand. METHODS: One hundred fifty-two healthy female smokers were randomized to either 12 weeks of exercise training or health education as part of a smoking cessation program. Smoking was held steady for the first 6 weeks, and thereafter, smoking cessation was actively attempted. One hundred four participants completed 6 weeks, and 88 completed 12 weeks. Fitness and circulating inflammatory marker levels were measured at baseline, 6 weeks, and 12 weeks. To avoid potential confounding from changes in smoking exposure during the second 6 weeks of the trial, the primary end point was change in inflammatory marker levels from baseline to 6 weeks. Change in inflammatory markers from baseline to 12 weeks was a secondary end point. RESULTS: At baseline, greater physical fitness was associated with lower white blood cell, fibrinogen, and C-reactive protein levels, but these associations were not statistically significant after adjusting for body mass index (P > .1 for all). Fitness improved significantly in the exercise group at both 6 and 12 weeks. However, there were no differences in levels of any inflammatory marker between the exercise and control groups at either 6 weeks (primary end point) or 12 weeks (secondary end point) (P > .05 for all comparisons). CONCLUSION: In female smokers, baseline associations between fitness and inflammatory markers were largely attributable to differences in body fat; regular exercise did not reduce levels of any of the inflammatory markers studied despite a significant improvement in fitness at both 6 and 12 weeks.

Adult↗
PubMed2005

Prognostic differences between different types of bundle branch block during the early phase of acute myocardial infarction: insights from the Hirulog and Early Reperfusion or Occlusion (HERO)-2 trial.

AIMS: Bundle branch block (BBB) early during acute myocardial infarction (AMI) is often considered high risk for mortality. Little is known about how different BBB types influence prognosis. METHODS AND RESULTS: The HERO-2 trial recruited 17 073 patients with ischaemic symptoms lasting >30 min and either ST elevation with or without right bundle branch block (RBBB) or presumed-new left bundle branch block (LBBB). Electrocardiograms were performed before and 60 min after the start of fibrinolytic therapy. Using patients with normal intraventricular conduction as a reference, odds ratios (ORs) for 30-day mortality were calculated for different BBB types (LBBB, RBBB with anterior AMI, and RBBB with inferior AMI) present at randomization and/or 60 min, with adjustment for recruitment region, pre-infarction characteristics, time to randomization, hemodynamics, and Killip class. At randomization, the 873 patients (5.11%) with BBB had worse baseline characteristics than patients without BBB. In patients presenting with LBBB (n=300), the ORs for 30-day mortality were 1.90 (95% CI 1.39-2.59) before and 0.68 (0.48-0.99) after adjustment for other prognosticators. In patients presenting with RBBB (n=415) and anterior AMI, the ORs were 3.52 (2.82-4.38) before and 2.48 (1.93-3.19) after adjustment. In patients presenting with RBBB and inferior AMI (n=158), the ORs were 1.74 (1.06-2.86) before and 1.22 (0.71-2.08) after adjustment. Within 60 min, 143 patients (0.92%) developed new BBB. The adjusted ORs for 30-day mortality were 2.97 (1.16-7.57) in the 25 patients with new LBBB, 3.84 (2.38-6.22) in the 100 with new RBBB and anterior AMI, and 2.23 (0.54-9.21) in the 18 with new RBBB and inferior AMI. CONCLUSION: RBBB accompanying anterior AMI at presentation and new BBB (including LBBB) early after fibrinolytic therapy are independent predictors of high 30-day mortality. These electrocardiographic features should be considered in risk stratification to identify high-risk patients.

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PubMed2005

Patients with prolonged ischemic chest pain and presumed-new left bundle branch block have heterogeneous outcomes depending on the presence of ST-segment changes.

OBJECTIVES: The purpose of this research was to examine the prognostic value of ST-segment changes (concordant ST-segment elevation and/or precordial V1 to V3 ST-segment depression) during presumed-new left bundle branch block (LBBB) in patients receiving fibrinolytic therapy. BACKGROUND: These patients are often considered high-risk, but their outcome is not well-defined. METHODS: The Hirulog and Early Reperfusion or Occlusion (HERO)-2 trial compared bivalirudin with heparin in patients receiving streptokinase for ST-segment elevation or presumed-new LBBB. Each patient with LBBB was matched with a control (with normal intraventricular conduction) for age, gender, pulse rate, systolic blood pressure, Killip class, and region. RESULTS: A total of 300 patients had LBBB (92 with and 208 without ST-segment changes) and 15,340 had normal conduction. Acute myocardial infarction (AMI) occurred in 80.7% of LBBB patients and 88.7% of controls (p = 0.006). ST-segment changes were specific (96.6%) but not sensitive (37.8%) for enzymatic diagnosis of AMI. Mortality at 30 days was similar in LBBB patients with ST-segment changes (21.7%) and controls (25.0%, p = 0.563), but lower in LBBB patients without ST-segment changes than in controls (13.5% vs. 21.6%, p = 0.022). In the whole HERO-2 cohort, the LBBB patients with ST-segment changes had higher mortality than patients with normal conduction (odds ratio [OR] 1.37, 95% confidence interval [CI] 0.78 to 2.42). The LBBB patients without ST-segment changes had lower mortality than patients with normal conduction (OR 0.52, 95% CI 0.33 to 0.80). CONCLUSIONS: ST-segment changes during LBBB are specific for the diagnosis of AMI and predict 30-day mortality; LBBB patients without ST-segment changes have lower adjusted 30-day mortality than those with normal conduction. Trials are required to determine the best treatment for high-risk and low-risk patients with LBBB.

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PubMed2005

White blood cell count predicts reduction in coronary heart disease mortality with pravastatin.

BACKGROUND: Elevated serum inflammatory marker levels are associated with a greater long-term risk of cardiovascular events. Because 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) may have an antiinflammatory action, it has been suggested that patients with elevated inflammatory marker levels may have a greater reduction in cardiovascular risk with statin treatment. METHODS AND RESULTS: We evaluated the association between the white blood cell count (WBC) and coronary heart disease mortality during a mean follow-up of 6.0 years in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Study, a clinical trial comparing pravastatin (40 mg/d) with a placebo in 9014 stable patients with previous myocardial infarction or unstable angina. An increase in baseline WBC was associated with greater coronary heart disease mortality in patients randomized to placebo (hazard ratio for 1x10(9)/L increase in WBC, 1.18; 95% CI, 1.12 to 1.25; P<0.001) but not pravastatin (hazard ratio, 1.02; 95% CI, 0.96 to 1.09; P=0.56; P for interaction=0.004). The numbers of coronary heart disease deaths prevented per 1000 patients treated with pravastatin were 0, 9, 30, and 38 for baseline WBC quartiles of <5.9, 6.0 to 6.9, 7.0 to 8.1, and >8.2x10(9)/L, respectively. WBC was a stronger predictor of this treatment benefit than the ratio of total to high-density lipoprotein cholesterol and a global measure of cardiac risk. There was also a greater reduction (P=0.052) in the combined incidence of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin as baseline WBC increased (by quartile: 3, 41, 61, and 60 events prevented per 1000 patients treated, respectively). CONCLUSIONS: These data support the hypothesis that individuals with evidence of inflammation may obtain a greater benefit from statin therapy.

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PubMed2005

Usefulness of serial measurement of N-terminal pro-brain natriuretic peptide plasma levels in asymptomatic patients with aortic stenosis to predict symptomatic deterioration.

In 29 initially asymptomatic patients with aortic stenosis followed for an average of 18 months, patients with a N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level above the normal range at baseline were more likely to develop symptoms during follow-up compared with patients with NT-pro-BNP within normal limits. The average increase in NT-pro-BNP per year was greater for patients who developed symptoms compared with patients who remained asymptomatic. Aortic valve area, peak aortic velocity, and the ejection fraction were less reliable predictors of symptom onset. Measurement of NT-pro-BNP in addition to clinical assessment and echocardiography may allow more reliable follow-up and timing of valve replacement for aortic stenosis.

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PubMed2003

Effect of aortic valve replacement on c-reactive protein in nonrheumatic aortic stenosis.

Plasma levels of C-reactive protein were higher in 20 patients with bicuspid or trileaflet degenerative aortic stenosis than in 31 normal controls and in 19 patients with pure aortic regurgitation. C-reactive protein decreased from before to 6 months after aortic valve replacement for aortic stenosis. These observations suggest that aortic stenosis is an inflammatory disease.

Adult↗
PubMed2003

Associations between plasma natriuretic peptide levels, symptoms, and left ventricular function in patients with chronic aortic regurgitation.

In 40 patients with chronic moderate to severe aortic regurgitation, brain natriuretic peptide, N-brain natriuretic peptide, and atrial natriuretic peptide were higher in symptomatic patients compared with asymptomatic patients after adjustment for age, gender, and ejection fraction, but each natriuretic peptide correlated weakly with echocardiographic measures of left ventricular size and function. In patients with chronic aortic regurgitation, measurement of natriuretic peptide levels may provide information on left ventricular function in addition to echocardiography.

Adult↗
PubMed2003

Plasma natriuretic peptide levels increase with symptoms and severity of mitral regurgitation.

OBJECTIVES: This paper will describe associations between plasma natriuretic peptide levels and the severity and symptoms of mitral regurgitation (MR). BACKGROUND: A biochemical test that assisted grading of the severity of MR and the interpretation of symptoms would be of clinical value. METHODS: Forty-nine patients with isolated MR and left ventricular (LV) ejection fractions (EFs) of >55% underwent transthoracic echocardiography, assessment of symptoms, and measurement of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and its amino-terminal portion, N-BNP. RESULTS: The level of each natriuretic peptide rose with increasing severity of MR and with increases in left atrial (LA) dimensions (p < 0.001 for all comparisons), but no significant correlation existed between any natriuretic peptide and the LV dimensions or EF. Natriuretic peptide levels were higher in symptomatic MR (n = 16, BNP geometric mean 16.9 [95% confidence interval (CI) 13.3 to 21.4] pmol/l) compared with asymptomatic MR (n = 33, BNP 7.1 [95% CI 6.0 to 8.4] pmol/l, p < 0.001), and higher in asymptomatic MR than in normal controls (n = 100, BNP 5.3 [95% CI 4.8 to 5.8] pmol/l, p < 0.0001). These differences were similar for N-BNP and ANP and remained statistically significant (p < 0.05) after adjustment for echocardiographic measures of LV function and severity of MR. Both the sensitivity and the specificity for symptoms for the natriuretic peptides (area under receiver-operator characteristic curve for BNP = 0.90, N-BNP = 0.89, ANP = 0.89) were similar to the MR score (0.88) and greater than for LA dimension (0.81), vena contracta width (0.82), and LV end-systolic dimension (0.63). CONCLUSIONS: Plasma natriuretic peptides levels increase with the severity of MR and are higher in symptomatic compared to asymptomatic patients, even when LV EF is normal.

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PubMed2003

Increased plasma natriuretic peptide levels reflect symptom onset in aortic stenosis.

BACKGROUND: The onset of symptoms is a critical point in the natural history of aortic stenosis and the cardinal indication for valve replacement. This study assessed the associations between natriuretic peptide levels, disease severity, and cardiac symptoms in aortic stenosis. METHODS AND RESULTS: Seventy-four patients with isolated aortic stenosis underwent independent assessment of symptoms, transthoracic echocardiography, and measurement of plasma levels of atrial natriuretic peptide, brain natriuretic peptide (BNP), and N-BNP. Natriuretic peptide levels were also measured in 100 clinically normal control subjects. The aortic valve area was smaller in symptomatic patients (n=45) than in asymptomatic patients (n=29; mean, 0.71+/-0.23 cm2 and 0.99+/-0.31 cm2, respectively; P<0.0001). Plasma natriuretic peptide levels were higher in symptomatic patients than in asymptomatic patients (for N-BNP: median, 112 versus 33 pmol/L; interquartile range, 70 to 193 versus 16 to 58 pmol/L, respectively; P=0.0002). After adjustment for age, sex, serum creatinine, aortic valve area, and left ventricular ejection fraction, N-BNP levels were 1.74 times higher (95% confidence interval, 1.12 to 2.69) for symptomatic than asymptomatic patients with aortic stenosis (P=0.014). Natriuretic peptide levels increased with the New York Heart Association class (for N-BNP median values were 13, 34, 105, and 202 pmol/L for normal control subjects, class I, class II, and class III/IV patients, respectively; interquartile ranges for the same patients were 8 to 21, 16 to 58, 57 to 159, and 87 to 394 pmol/L; P<0.0001). Similar associations were observed for BNP and atrial natriuretic peptide. CONCLUSIONS: Plasma natriuretic peptide levels are elevated in symptomatic patients with aortic stenosis. Measurement of natriuretic peptides may complement clinical and echocardiographic evaluation of patients with aortic stenosis.

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PubMed2003

Depression and cardiovascular morbidity and mortality: cause or consequence?

BACKGROUND: Depression after myocardial infarction has been associated with increased cardiovascular mortality. This study assessed whether depressive symptoms were associated with adverse outcomes in people with a history of an acute coronary syndrome, and evaluated possible explanations for such an association. METHODS AND RESULTS: Depressive symptoms were assessed using the General Health Questionnaire at least 5 months after hospital admission for acute myocardial infarction or unstable angina in 1130 participants of the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study, a multicentre, placebo-controlled, clinical trial of cholesterol-lowering treatment. Cardiovascular symptoms, self-rated general health, cardiovascular risk factors, employment status, social support and life events were also assessed at the baseline visit. Cardiovascular death (n=114), non-fatal myocardial infarction (n=108), non-fatal stroke (n=53) and unstable angina (n=274) were documented during a median follow-up period of 8.1 years. Individuals with depressive symptoms (General Health Questionnaire score >/=5; 22% of participants) were more likely to report angina, dyspnoea, claudication, poorer general health, not being in paid employment, few social contacts and/or adverse life events (P<0.05 for all). There was a modest association between depressive symptoms and cardiovascular events (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.13-1.77), but not cardiovascular death (HR 1.12. 95% CI 0.71-1.77). After adjustment for symptoms related to cardiovascular disease, the HR for cardiovascular events was 1.22 (95% CI 0.97-1.53). After further adjustment for employment status, social support and life events, the HR was 1.13 (95% confidence interval 0.87-1.47). CONCLUSIONS: There was no significant association between depressive symptoms and fatal or non-fatal cardiovascular events after adjustment for cardiovascular symptoms associated with poorer prognosis. Previously observed associations between depression and cardiovascular mortality may not be causal.

Adult↗
PubMed2002

Relationship between lipid levels and clinical outcomes in the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Trial: to what extent is the reduction in coronary events with pravastatin explained by on-study lipid levels?

BACKGROUND: The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial showed that pravastatin significantly reduced mortality and coronary heart disease (CHD) events in 9014 patients with known CHD and total cholesterol 4.0 to 7.0 mmol/L at baseline. Secondary objectives included assessment of CHD event reduction according to lipid levels. METHODS AND RESULTS: We investigated the relationships of baseline and on-study lipids with subsequent CHD events in separate Cox models. Treatment effect on CHD event reduction was examined by baseline lipids and after adjustment for on-study lipid levels. Baseline lipids were significant predictors of CHD events. The adjusted relative risk per mmol/L (on placebo) was 1.24 (P=0.004) for total cholesterol, 1.28 (P=0.002) for low-density lipoprotein cholesterol, and 0.52 (P=0.004) for high-density lipoprotein cholesterol. Apolipoproteins A1 and B were strong predictors (each P=0.001). Pravastatin reduced the risk of the composite outcome of fatal CHD or nonfatal myocardial infarction by 24% (95% confidence interval [CI], 15% to 32%) and the expanded end point of fatal CHD, nonfatal myocardial infarction, unstable angina, or coronary revascularization by 17% (95% CI, 10% to 24%). Similar relative effects were observed for different categories of baseline lipids. The proportion of treatment effect explained by on-study lipid levels was 67% (95% CI, 27% to 106%) for the composite and 97% (95% CI, 49% to 145%) for the expanded end point. The most important lipids associated with event reduction were apolipoprotein B, low-density lipoprotein cholesterol, and the combination of total and high-density lipoprotein cholesterol. CONCLUSIONS: Changes in lipid levels can explain all or most of the observed benefit of pravastatin. Some treatment effect may also be mediated through nonlipid changes.

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