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Biomedical subjects

Allan D Struthers

Publications and source records attributed to Allan D Struthers.

At least 19 recordsLinked to original sources
PubMed2007

Left ventricular hypertrophy is present in one-half of newly-diagnosed peripheral arterial disease patients.

OBJECTIVES: Peripheral arterial disease (PAD) patients are at high risk of cardiac death. Coincidental but silent coronary disease is obviously a major contributor but left ventricular hypertrophy (LVH) could be a second major contributor. METHODS: To investigate whether LVH could really be making a large contribution to cardiac death in PAD, we assessed the prevalence of LVH when PAD was first diagnosed. RESULTS: The prevalence of echo LVH when left ventricular mass was indexed to body surface area was 50%. Although office blood pressure and 24-h blood pressure were both significantly higher in those with LVH, in clinical practice, a contemporaneous blood pressure measurement (office or 24 h) at the time of PAD diagnosis would only partially identify those with LVH. For example, an office blood pressure cut-off of < 140/90 mmHg was found in 27% of all LVH cases and a 24-h blood pressure cut-off of < 125/80 mmHg was found in 24% of all LVH cases. CONCLUSION: In conclusion, there is already a high prevalence of LVH in patients at first diagnosis of PAD. LVH is therefore common enough in PAD patients to potentially make a major contribution to cardiac death, which means that future research should now investigate whether screening for and regressing LVH when present would actually reduce cardiac deaths over and above merely achieving target blood pressure.

Aged↗
PubMed2006

The influence of mode of delivery and ACE genotype on serum angiotensin converting enzyme (ACE) activity in the mother and infant at term.

OBJECTIVE: Angiotensin converting enzyme (ACE) and its genotype have been shown to play a role in the pathophysiology of pregnancy complications such as pre-eclampsia and intrauterine growth restriction and possibly in adult onset chronic diseases. The physiological changes of ACE and the influence of its genotype during the intrapartum period are not well known. Hence the aim of this study was to assess serum ACE activity and its genotype in mothers and infants at term in relation to labour and mode of delivery. STUDY DESIGN: A cross sectional study of 99 women who laboured and 27 women who delivered by elective caesarean section after 36 completed weeks gestation with uncomplicated pregnancies. Venous cord bloods were obtained immediately after delivery of the placenta for serum ACE activity, ACE genotype and acid-base status. Maternal venous samples were obtained just after delivery for analysis of ACE activity and ACE genotype. Univariate analyses were performed using parametric tests for normally distributed data and nonparametric tests for the data that were not normally distributed. A multiple regression model was developed to adjust for potential confounding factors. RESULTS: The umbilical venous ACE activity was similar for infants delivered following labour compared to those delivered by elective caesarean section, 47.2 U/L (35-64) versus 40.1 U/L (31-60) (adjusted p=0.21). Maternal ACE activities were 28.9 U/L (22-35) and 32.1 U/L (22-40) respectively (adjusted p=0.17). The ACE activity in infants was higher than that of mothers 46 U/L versus 22 U/L, respectively (p= or <0.001). Neither the mode of delivery nor the presence of suspected fetal compromise influenced maternal or infant ACE activity. There was no influence of the infants' genotype on ACE activity in relation to mode of delivery. The DD genotype was associated with higher ACE activity in mothers (p=0.001) but not in infants (p=0.56). CONCLUSIONS: This study shows that intrapartum events do not affect ACE activity. These results will enhance our ability to investigate the role of ACE and its genotype in abnormal fetal growth and in subsequent adult onset chronic disease.

Acidosis↗
PubMed2006

Effect of spironolactone on C-reactive protein levels in patients with heart disease.

Animal evidence shows that aldosterone is pro-inflammatory and that aldosterone blockade is anti-inflammatory. Therefore part of the beneficial effect of aldosterone blockade that might contribute to it reducing mortality could be an anti-inflammatory effect. However, there are no previous data on whether aldosterone blockade is anti-inflammatory in man. We performed 4 separate studies to investigate whether spironolactone treatment would reduce levels of C-reactive protein (CRP), a marker of inflammation, in serum samples taken from patients suffering from different degrees of heart failure. We found in all 4 studies that spironolactone had no significant effect compared with placebo, on CRP levels in these patients. These studies provide evidence against the hypothesis that the clinical benefits produced by aldosterone blockade are due to it having anti-inflammatory effects.

Biomarkers↗
PubMed2006

A critical re-appraisal of different ways of selecting ambulatory patients with suspected heart failure for echocardiography.

BACKGROUND: ECG and BNP have been assessed as screening tests for LVSD and heart failure. However, echocardiography also provides information about valvular disease and LVH. We assessed how good these screening tests are in identifying whether the subsequent echocardiogram will have any significant abnormality. AIMS: To re-appraise the ECG and BNP as screening tests for echocardiography since there are important practical deficiencies in our current knowledge in this area. METHODS: General practitioners referred suspected heart failure patients for clinical assessment, echocardiography, electrocardiography, and BNP measurement. The accuracy of each screening test and combinations of screening tests were calculated for LVSD, heart failure, valvular disease, and LVH. RESULTS: The sensitivities of the ECG for LVSD, heart failure, LVH and valvular disease were 97%, 95%, 76%, and 69%, respectively. The corresponding figures for BNP were 86%, 82%, 59%, and 48%, respectively. When patients with atrial fibrillation and murmurs were excluded, the values for ECG were 94%, 87%, 53%, and 55%, while for BNP they were 83%, 73%, 50%, and 32%. CONCLUSIONS: ECG interpretation and BNP are adequate screening tests to detect LVSD or heart failure but fail to screen for other echocardiographic abnormalities, like valvular disease and LVH. This remains the case even if patients with atrial fibrillation or heart murmurs are excluded on the basis that they require echocardiography anyway.

Adult↗
PubMed2006

Effects of an exercise intervention for older heart failure patients on caregiver burden and emotional distress.

BACKGROUND: The impact of exercise programmes for heart failure on those close to the patient is largely unknown. We examined the effect of a hospital and home-based exercise intervention on burden, anxiety and depression of informal caregivers. DESIGN: The study was a randomized, controlled trial. Heart failure patients were randomized to a seated 12-week hospital-based exercise programme. Caregiver measures were gathered at baseline, 3 months later and 6 months following baseline. METHODS: Sixty caregivers (mean age 63.4 years, 65% female) of heart failure patients (n = 82, mean age 80.5 years, 44% female) participating in a trial of an exercise intervention were recruited. Caregiver burden, anxiety and depression were assessed. RESULTS: There were no differences in caregiver burden, depression or anxiety between the two groups of caregivers at baseline (caregiver burden, patient control 33.1 versus patient exercise 34.1; anxiety 4.1 versus 5.5; depression 2.8 versus 3.8). At 3 months there were no differences between caregivers in the two groups on outcomes. At 6-month follow-up caregivers of heart failure patients in the exercise group had burden scores that were significantly worse than the control group. There were no differences between the carers of exercise and control groups in anxiety and depression. Levels of anxiety and depression in the entire carer sample were marginally higher than reference values in a healthy non-clinical sample. CONCLUSION: The present exercise interventions for frail older patients did not benefit caregivers and was associated with an increase in caregiver burden. We suggest that future exercise interventions for heart failure patients should actively incorporate informal caregivers into research designs.

Aged↗
PubMed2006

Sarcopenia--a potential target for Angiotensin-converting enzyme inhibition?

Society is ageing. There has been a steady increase in the number of people aged 65 years and over throughout the 20th century and this trend is predicted to continue worldwide. This has resulted in an increase in the incidence of sarcopenia, which is a loss of muscle mass and function with age. Maintenance of muscular function into old age is critical to sustaining normal daily activity and functional independence. Sarcopenia is associated with increased morbidity and mortality. Till now most efforts to counteract sarcopenia have met with limited success. We postulate that targeting the renin-angiotensin system through angiotensin-converting enzyme (ACE) inhibition could play a role in countering sarcopenia. ACE inhibitors could work by preventing mitochondrial decline and improving endothelial function and muscle metabolism. We describe the literature to support our hypothesis that sarcopenia may be a potential therapeutic target for ACE inhibitors.

Aging↗
PubMed2005

B-type natriuretic peptide as an alternative way of assessing total cardiovascular risk in patients with diabetes mellitus.

Cardiovascular risk scores are available but are often not calculated in busy clinics for numerous practical reasons. B-type natriuretic peptide (BNP) may be an alternative way of identifying subjects who have a high total cardiovascular risk score. We compared BNP level with Framingham 10-year Risk Scores for coronary heart disease and stroke and New Zealand Cardiovascular Risk Scores in 231 patients who had type 2 diabetes and no preexisting coronary heart disease or stroke. There was a significant correlation between log BNP and 10-year risk for coronary heart disease and stroke, and there were significantly higher BNP levels in those who had high cardiovascular risk as assessed by the New Zealand Risk Score. BNP may be a useful way of measuring total cardiovascular risk, thus having the potential to better target the most aggressive primary preventive therapies toward the most needy.

Adult↗
PubMed2005

Predictors of exercise capacity and everyday activity in older heart failure patients.

BACKGROUND: Exercise capacity and daily activity are key outcomes for older, frail heart failure patients. Little is known about the determinants of these outcomes in this patient group. AIMS: To explore predictors of exercise capacity and daily activity in older, frail heart failure patients. METHODS: Analysis of prospectively collected data from a cohort of 82 patients aged 70 years and over, enrolled in a randomised controlled trial of exercise in heart failure patients. Pathophysiological, demographic, psychological and social factors were analysed by multivariate regression to determine predictors of exercise capacity (6-min walk distance) and daily activity (daily accelerometer counts). RESULTS: Between 49% and 55% of the variance in 6-min walk distance was explained by variables including New York Heart Association class, depression score, attitude to ageing and use of walking aids. Only 11% to 26% of the variance in accelerometer scores was explained by the model; 6-min walk distance was the only consistent predictor of daily activity. CONCLUSIONS: Physical, psychological and attitudinal variables contribute to variance of the 6-min walk. Six-minute walk distance predicts a small amount of the variance in daily activity, but the majority of variance in daily activity remains unexplained and requires further investigation.

Activities of Daily Living↗
PubMed2005

Time course for recovery of atrial mechanical and endocrine function post DC cardioversion for persistent atrial fibrillation.

We prospectively determined the time course of recovery of atrial mechanical and endocrine function in patients following DC cardioversion for persistent atrial fibrillation (AF). Twenty-three consecutive patients underwent successful DC cardioversion (mean age 64 years, 20 male). By 28 days, nine had reverted to atrial fibrillation. Recovery of atrial mechanical (peak A wave velocity) and endocrine function (atrial natriuretic peptide, ANP) were assessed at four time points: immediately pre-cardioversion, and then 4 h, 7 and 28 days post. The 14 patients maintaining sinus rhythm formed the success group. In this group, peak A wave velocity increased significantly over time from 0.28+/-0.03 m/s (mean+/-S.E.M.) at 4 h to 0.50+/-0.03 m/s at day 7 and 0.67+/-0.05 m/s at day 28 (p<0.001). Plasma ANP was 150+/-34 pg/ml immediately prior to DC cardioversion in the success group. This showed an initial dip at 4 h to 44+/-9 pg/ml (p<0.001). By day 7, plasma ANP had increased to 105+/-21 pg/ml (p<0.05 vs. baseline and 4 h) and then appeared to remain constant, being 102+/-19 pg/ml at day 28 (p=0.06 vs. baseline). A similar early reduction in ANP levels was seen in the group who subsequently reverted to atrial fibrillation. Baseline ANP levels did not predict subsequent successful maintenance of sinus rhythm. Initial "stunning" in both atrial mechanical and endocrine function occurs in patients following DC cardioversion for atrial fibrillation. Whilst endocrine function appears to fully recover by day 7, mechanical function continues to improve beyond day 7.

Aged↗
PubMed2005

Autonomic effects of spironolactone and MR blockers in heart failure.

Neurohormonal dysfunction is an important and potentially modifiable part of the disease process of heart failure. In this review we will discuss the ways in which the autonomic system is deranged in congestive cardiac failure and the different ways we have of monitoring these abnormalities i.e.: heart rate variability, plasma norephinephrine activity, MIBG scanning, heart rate turbulence, baroreceptor function and briefly, microneurographic techniques and QT interval analysis. We will then discuss the direct effects of aldosterone and of aldosterone blockade on some of these parameters. We conclude that neurohormonal dysfunction is an important component of chronic heart failure, which is affected by aldosterone and can be modified by the use of aldosterone receptor blockade.

Aldosterone↗
PubMed2005

B-type natriuretic Peptide is associated with both augmentation index and left ventricular mass in diabetic patients without heart failure.

BACKGROUND: B-type natriuretic peptide (BNP) increases the risk of death and cardiovascular events in patients without heart failure, even at BNP values within the "normal" range. The reasons for this are unclear. METHODS: We performed two separate studies (n = 33 and n = 129) on subjects with type 2 diabetes mellitus in whom frank left ventricular systolic dysfunction had been excluded to ascertain whether a high-normal BNP could be identifying either greater augmentation of the ascending aortic pressure wave, increased left ventricular mass, or a subtly lower left ventricular ejection fraction (but within the normal range). RESULTS: Our results demonstrate that an increased augmentation index is an independent predictor of BNP levels even when BNP levels are within the normal range (P = .006 in study one and P = .007 in study two). A high-normal BNP also correlated with increased left ventricular mass and (P = .021) with a subtly lower left ventricular ejection fraction (P < .001). CONCLUSIONS: We found that high-normal BNP levels identified increased augmentation of the ascending aortic pressure wave as well as subtle left ventricular abnormalities.

Aged↗
PubMed2005

Elevated levels of natriuretic peptides in patients with pulmonary thromboembolism.

BACKGROUND: Pulmonary thromboembolism (PTE) occurs in a wide variety of clinical settings and presents a diagnostic challenge to clinicians, often requiring extensive imaging of the vascular bed. Management increasingly requires accurate risk stratification to rapidly identify those with massive and submassive PTE requiring different therapeutic strategies such as thrombolysis. Provision of a rapid blood test that improves diagnostic certainty and helps stratify risk could therefore bridge the gap between uncertainty and delivery of immediate early life-saving treatment. METHODS AND RESULTS: One hundred and fourteen consecutive patients with suspected PTE underwent prospective evaluation. Venous blood samples were obtained from an unselected group referred for ventilation-perfusion scintigraphy. B-type natriuretic peptide (BNP), atrial natriuretic peptide (ANP) and N-terminal pro-ANP (N-ANP) were measured by radioimmunoassay using commercially available kits. The scans were classified into three groups according to standard criteria (PIOPED); normal scan (N) (n=20), low/intermediate probability (L/I) of PTE (n=77) and high probability (H) of PTE (n=17). Comparisons were also made between patients with high probability scans who died (n=3) and those who survived (n=14). Values are quoted for the median and interquartile ranges. There were statistically significant differences between groups for levels of (a) BNP (P<0.001): N=6.7 pmol/l (5.6-11.9), L/I=12.5 pmol/l (6.7-28.2) and H=18.5 pmol/l (12.6-74.6); (b) ANP (P<0.005): N=12.6 pmol/l (7.1-16.0), L/I=19.51 pmol/l (12.5-28.2) and H=19.1 pmol/l (15.7-31.7) and (c) N-ANP (P<0.05): N=177 pmol/l (119-200), L/I=302 pmol/l (152-576) and H=322 pmol/l (223-563). Levels of BNP and ANP were significantly (P<0.05) higher in patients with high probability scans and a diagnosis of PTE who died (n=3) than in those who survived (n=14); BNP: 91.6 pmol/l (77.5-336.2) vs. 14.4 pmol/l (11.9-27.4) and ANP 32.5 pmol/l (21.7-105.5) vs. 17.6 pmol/l (15.2-19.3), respectively. CONCLUSIONS: PTE is associated with significantly elevated levels of the natriuretic peptides ANP, BNP and N-ANP. Increasing ventilation-perfusion mismatch on scintigraphy corresponds to incremental increases in the levels of ANP, BNP and N-ANP found. These peptides, and in particular BNP, may add to the diagnosis by rapidly providing a probability of PE before dedicated imaging studies can be performed. Natriuretic peptides require further study to establish their role in identifying a high-risk group who may benefit from early treatments such as thrombolysis.

Adult↗
PubMed2005

B-type natriuretic peptide is associated with mortality in older functionally impaired patients.

OBJECTIVES: To determine the predictive power of B-type natriuretic peptide (BNP) regarding death in older, functionally impaired patients with multiple comorbidity. DESIGN: Prospective cohort study. SETTING: Specialist geriatric assessment clinic and day hospital. PARTICIPANTS: Two hundred ninety-nine older, functionally impaired patients, mean age 79 at enrollment. MEASUREMENTS: Full clinical history and examination, baseline BNP, and echocardiography. Date and cause of death were ascertained from Scottish death records. Kaplan-Meier survival curves were constructed for quartiles of log (BNP), and the contribution of BNP to prediction of death was investigated. RESULTS: The follow-up period ranged from 3.9 to 5.2 years (mean 4.4 years). BNP was a powerful independent predictor of all-cause and cardiovascular mortality. BNP was a more powerful predictor than blood pressure, diabetes mellitus, smoking, echocardiographic left ventricular hypertrophy, left ventricular systolic dysfunction, or age. BNP predicted death in those with and without a previous cardiovascular event at baseline. CONCLUSION: BNP has significant predictive power for death in older, functionally impaired patients.

Activities of Daily Living↗
PubMed2004

Age is not a significant risk factor for failed trial of beta-blocker therapy in older patients with chronic heart failure.

OBJECTIVES: To evaluate how well older heart failure patients tolerate beta-blockers in everyday clinical practice. DESIGN: Retrospective casenote analysis. SETTING: Specialist heart failure clinic in a large teaching hospital. PARTICIPANTS: 226 patients with a clinical diagnosis of heart failure and evidence of left ventricular systolic dysfunction. MEASUREMENTS: Data on age, sex, comorbid illness, other medications, duration of beta-blocker therapy, side-effects and reasons for discontinuation. RESULTS: Patients aged 75 years and over had a higher level of comorbid disease and worse New York Heart Association status. Despite this, 60.4% of those aged 75 or over had been tried on a beta-blocker (versus 69% of those aged <75), and of those tried, 80% of those aged 75 or over were still taking a beta-blocker at the time of survey (versus 86% of those aged <75). Forty-seven percent of those aged 75 or over had at least one side-effect recorded (versus 48% of those aged <75). Significant risk factors for failing a trial of beta-blocker therapy were worse New York Heart Association status and worse left ventricular function, but importantly not age. CONCLUSIONS: A high proportion of older heart failure patients tolerate beta-blockers. Side-effects and failure rates are comparable to younger patients. Left ventricular function and worse New York Heart Association class, rather than age, predict low tolerability of therapy. Further studies are warranted to evaluate whether frail patients with heart failure can improve their quality of life by taking beta-blockers.

Adrenergic beta-Antagonists↗