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Biomedical subjects

A D Struthers

Publications and source records attributed to A D Struthers.

At least 91 records · Page 5Linked to original sources
PubMed1997

Cross sectional study of contribution of clinical assessment and simple cardiac investigations to diagnosis of left ventricular systolic dysfunction in patients admitted with acute dyspnoea.

OBJECTIVE: To assess the comparative contribution of clinical assessment, electrocardiography, and chest radiography to the diagnosis of left ventricular systolic dysfunction in patients admitted to a general medical ward with acute dyspnoea. DESIGN: Prospective cross sectional study. SETTING: Acute medical admissions ward of a teaching hospital. SUBJECTS: 71 randomly selected patients admitted with acute dyspnoea. MAIN OUTCOME MEASURES: Sensitivity and specificity of each investigation and logistic regression analysis of each variable in identifying left ventricular systolic dysfunction. RESULTS: Clinical assessment in this cohort of patients with severe dyspnoea was generally sensitive (sensitivity 81%). Patients were divided into three groups on the basis of clinical assessment. In the first group (37 patients) the diagnosis of systolic dysfunction was clear, in the second (22) it was in doubt, and in the third (12) it was unlikely. The sensitivity of clinical assessment in identifying left ventricular systolic dysfunction was 81% and the specificity was 47%. The specificity of diagnosis was improved by electrocardiography (69%) and chest radiography (92%). Logistic regression analysis showed that isolated pulmonary crepitations were a comparatively poor predictor of left ventricular systolic dysfunction chi 2 = 10.215, P = 0.0014) but that a full clinical examination had reasonable predictive value (chi 2 = 24.82, P < 0.00001). The combination of clinical assessment and chest radiography improved the accuracy of diagnosis (chi 2 = 28.08, P < 0.00001), as did the combination of clinical assessment and electrocardiography (chi 2 = 32.41, P < 0.00001). CONCLUSION: Clinical assessment in patients admitted with acute dyspnoea is comparatively accurate. Patients with abnormal results on chest radiography, electrocardiography, and clinical examination have a high likelihood of having left ventricular systolic dysfunction. Echocardiography contributes little more to the diagnosis in these patients and may be more efficiently directed towards patients in whom the diagnosis is still in doubt after clinical assessment, chest radiography, and electrocardiography.

Acute Disease↗
PubMed1997

Enalapril reduces QTc dispersion in mild congestive heart failure secondary to coronary artery disease.

This study was designed to investigate the possible mechanisms whereby enalapril improves cardiac function and mortality in chronic heart failure. We explored potential mechanisms by following 41 patients with early heart failure over the course of 1 year. These patients were randomized in a prospective triple-blind manner to receive either enalapril or placebo. Over the 1 year, repeated measurements were obtained of echocardiographic parameters, glomerular filtration rate, renal blood flow, hematocrit, plasma neurohormones, and QTc dispersion. Echocardiographic parameters improved with enalapril but deteriorated with placebo (cardiac output 4.6 +/- 1.6 to 3.7 +/- 1.5 L/min with placebo, and 4.5 +/- 1.3 to 5.8 +/- 2.0 L/min with enalapril; p <0.01). In contrast, there were no significant changes in renal blood flow (518 +/- 185 to 509 +/- 180 ml/min/1.73 m2 with placebo, and 541 +/- 142 to 504 +/- 162 ml/min/1.73 m2 with enalapril). Glomerular filtration rate changed from 79 +/- 20 to 78 +/- 19 ml/min/1.73 m2 with placebo, and from 85 +/- 21 to 73 +/- 27 ml/min/1.73 m2 with enalapril (p = 0.051). Enalapril reduced hematocrit (0.414 +/- 0.041 to 0.377 +/- 0.040%) significantly more than placebo (0.420 +/- 0.029 to 0.411 +/- 0.023 l/l; p <0.01). In addition, enalapril produced a marked reduction in QTc dispersion (93 +/- 36 to 88 +/- 28 ms with placebo and 93 +/- 35 to 60 +/- 22 ms with enalapril; p <0.05). Thus, enalapril significantly reduced hematocrit and reduced QTc dispersion in early heart failure. Both of these effects, but especially the latter, could be an important mechanism for the reduced mortality seen with angiotensin-converting enzyme inhibitors in heart failure. In contrast, renal hemodynamics did not parallel either the placebo-induced deterioration in cardiac function or the enalapril-induced improvements in cardiac function.

Aged↗
PubMed1997

Cardiopulmonary effects of endothelin-1 in man.

OBJECTIVES: Endothelin-1 levels are elevated in a number of conditions characterised by impaired cardiovascular performance and abnormal vasoconstriction such as congestive cardiac failure and primary and secondary pulmonary hypertension. The aim of the present study was to assess the effects of the vasoconstrictor peptide endothelin-1 on pulmonary and systemic haemodynamics and cardiovascular performance in normal man. METHODS: Ten healthy male volunteers were studied on two occasions in a randomised, double-blind, placebo-controlled, cross-over study and received systemic infusions of either endothelin-1 (0.75, 1.5 and 3 pmol.kg-1.min-1 for 30 min each) or saline placebo. Systemic and pulmonary haemodynamic parameters were monitored non-invasively by pulsed-wave Doppler, as were parameters of left and right ventricular diastolic filling and inotropic state. Effects on renin-angiotensin and natriuretic peptide system activity were also measured. RESULTS: Endothelin-1 infusion produced dose-related falls in heart rate, stroke volume and cardiac output. Systemic vascular resistance (SVR) increased from 1156 +/- 57 to 1738 +/- 115 dyn.s.cm-5, and total pulmonary vascular resistance (TPR) increased from 142 +/- 12 to 329 +/- 22 dyn.s.cm-5. Endothelin-1 caused significant impairment of left and right ventricular diastolic filling, even at a low dose which had no pulmonary or systemic pressor effects. Electromechanical and Doppler acceleration indices of inotropic state were also significantly impaired. Activity of the renin-angiotensin system was suppressed by endothelin-1 whilst plasma levels of atrial natriuretic peptide (ANP) were unchanged. CONCLUSIONS: Thus, in addition to systemic and pulmonary pressor effects our results suggest that endothelin-1 impairs overall cardiovascular performance by causing diastolic dysfunction and acting as a negatively inotropic agent. These effects were associated with compensatory changes in the renin-angiotensin system.

Adult↗
PubMed1997

Aldosterone blockade reduces vascular collagen turnover, improves heart rate variability and reduces early morning rise in heart rate in heart failure patients.

BACKGROUND: Experimental data suggest that aldosterone has harmful effects promoting myocardial fibrosis and disturbing autonomic balance. There has been no evidence of these potential effects in intact man. METHODS AND RESULTS: We report the findings in 31 patients with stable chronic heart failure (CHF) who were treated with spironolactone (50-100 mg/day) or placebo in addition to diuretics and angiotensin converting enzyme (ACE) inhibition. In a controlled randomised double-blind study, we found that spironolactone treatment reduced circulating levels of procollagen type III N-terminal amino peptide, a marker of vascular collagen turnover, and in addition increased time-domain parameters of heart rate variability (n = 24). These latter parameters suggest a parasympathomimetic effect for additional spironolactone. Spironolactone significantly reduced heart rate (prolonged RR interval) particularly during the dawn hours (06.00-09.00 h). In this unbalanced study it was not possible to provide a detailed diurnal assessment of the impact of spironolactone on heart rate variability, but the preliminary data suggest that there may be an interaction with the autonomic nervous system which varies in time. CONCLUSIONS: These are the first human data to show that use of the aldosterone antagonist, spironolactone, can positively improve time-domain heart rate variability and reduce myocardial collagen turnover, as reflected by further reductions in serum procollagen peptide, despite concurrent ACE inhibitor treatment. Residual aldosterone after ACE inhibitor treatment may therefore have a role promoting arrhythmia and cardiac death by two mechanisms. Effects of additional spironolactone on slowing heart rate (and potentially the detrimental effect of aldosterone) were most prominent between 6 a.m. and 10 a.m. when cardiac death is also known to be most prominent.

Aged↗
PubMed1997

Rationalizing the heart failure trials: from theory to practice.

It is 10 years since the CONSENSUS I study showed that ACE inhibitors improved mortality in heart failure. This finding has been confirmed in numerous trials, for example SOLVD, SAVE. Indeed, in the intervening 10 years, many other potential therapies have been examined in mortality trials, but so far no other therapy has had as good effect on mortality as ACE inhibitors. The other therapies which have been examined are digoxin, amlodipine, beta-blockers, amiodarone, etc. Despite ACE inhibitors being a very effective therapy for heart failure, there is still remarkable under-use of them in clinical practice. The reason for this needs to be explained further, but fear of hypothermia and renal dysfunction appear to be major factors.

Adrenergic beta-Antagonists↗
PubMed1997

Angiotensin-converting enzyme gene polymorphism and cardiovascular disease.

1. The crucial role played by the renin-angiotensin-aldosterone system in the cardiovascular system and the immense therapeutic potential of angiotensin-converting enzyme inhibitors and, more recently, angiotensin II receptor blocking agents, in both heart failure and post-myocardial infarction is becoming increasingly evident. Polymorphisms within the genes controlling this enzyme system are candidates for the elucidation of the pathogenesis of cardiovascular disease and this link is both intriguing and provocative. Recently, an association between a polymorphism of the angiotensin-converting enzyme gene and phenotypic expression of cardiovascular disease, namely myocardial infarction, was reported. Since then, several small case-controlled studies have confirmed an association with manifestations of ischaemic heart disease or various other cardiac end-points. However, in a large prospective study the angiotensin-converting enzyme gene conferred no appreciable risk. 2. Our aim was to review the evidence that links polymorphisms of the angiotensin-converting enzyme gene with cardiovascular disease. We searched the Medline database (1990-1997) using the key words myocardial infarction, ischaemic heart disease, angiotensin-converting enzyme and polymorphisms and performed a search of the reference citation of relevant articles. We selected clinical studies on cardiovascular disease related to the angiotensin-converting enzyme genotype. 3. Taken together, the available evidence supports the notion that the DD-angiotensin-converting enzyme genotype adversely influences specific cardiovascular diseases but appears to do so in specific geographical areas and in particular patient subgroups. It is not yet known whether it does this through an interaction with other genes or by as yet unexplained biochemical mechanisms. 4. We should regard the current data with the angiotensin-converting enzyme genotype as an intriguing clue in the pathogenesis of cardiovascular disease. However, the main factor against this potential benefit is that the impact of the DD genotype appears to be small and its clinical manifestations rather heterogeneous.

Cardiovascular Diseases↗
PubMed1997

The effect of the neutral endopeptidase inhibitor drug, candoxatril, on circulating levels of two of the most potent vasoactive peptides.

AIMS: Candoxatril is a specific neutral endopeptidase (NEP) 24.11 inhibitor, and previous work has documented the effect of NEP inhibition on atrial and brain natriuretic peptides (ANP, BNP). The aim of the present study was to ascertain the effect of NEP inhibition on circulating levels of vasoactive peptides. METHODS: We studied seven patients with chronic heart failure who were randomized to receive candoxatril, candoxatril/captopril, captopril and placebo in a four way cross over, double-blind pattern. RESULTS: The mean circulating level of endothelin (ET) was increased 2 h after placebo (10 to 20 pg ml-1) and also calcitonin gene-related peptide (CGRP) (27 to 51 pg ml-1), but ANP levels changed little during this time (73 to 75 pg ml-1). Following candoxatril, however, ET (10 to 39 pg ml-1, P < 0.05), CGRP (34 to 99 pg ml-1, P < 0.05) and ANP (72 to 108 pg ml-1, P < 0.05) increased further. A similar result was observed following combined treatment with candoxatril and captopril. CONCLUSIONS: We conclude that neutral endopeptidase inhibition increases circulating plasma levels of ET and CGRP in addition to the natriuretic peptides.

Aged↗
PubMed1997

Further evidence that chronic perindopril treatment maintains neurohormonal suppression but does not lower blood pressure in chronic cardiac failure.

AIMS: Previous studies in heart failure (CHF) after temporary diuretic withdrawal have suggested that perindopril is associated with no first dose hypotension in comparison with other ACE inhibitors (ACEI) or placebo. The aim of this study was to explore further the profile of perindopril during chronic dosing. METHODS: We report the effects of acute and chronic (8 weeks) treatment with the ACE inhibitor perindopril (Per, 2-->4 mg daily) or placebo (P) in a double-blind parallel group study of 24 diuretic treated patients (17M; 67 +/- 8 years, 80 +/- 17 kg) with ischaemic cardiomyopathy (fractional shortening, 19 +/- 5%; radionuclide ejection fraction, 31 +/- 3%). Baseline biochemical, hormonal (ACE, Ang I, Ang II), isotopic renal function (GFR, ERPF, ECFV), pretreatment diuretic dose and heart failure scores were similar between groups. Concomitant cardiac treatments remained unchanged and diuretic withdrawal was not used to introduce treatment. RESULTS: There were no significant effects on electrolytes, liver function tests, serum or erythrocyte magnesium. There was no significant first dose fall in SBP over 6 h) (P, baseline 137 +/- 18; min 115 +/- 16 mmHg; Per, baseline 137 +/- 15; min 118 +/- 17 mmHg). Neither supine nor erect BP was significantly affected by chronic treatment (P, erect baseline 134 +/- 23/76 +/- 10 to 124 +/- 41/74 +/- 10 mmHg; Per, baseline 135 +/- 21/76 +/- 14 to 128 +/- 22/70 +/- 12 mmHg, P=NS). Active treatment was associated with significant ACE inhibition (P, baseline 47 +/- 17 to 43 +/- 17; Per baseline 49 +/- 15 to 14 +/- 7); aldosterone (P, baseline 337 +/- 179 to 375 +/- 306; Per, baseline 335 +/- 357 to 293 +/- 155 pg ml(-1)) and Ang II suppression (P, baseline 9 +/- 9 to 20 +/- 39; Per baseline 10 +/- 9 to 3 +/- 3 pM). Isotopic renal function was unaffected by either treatment. CONCLUSIONS: At this dose (2-4 mg orally) chronic perindopril therapy has no significant effect on blood pressure or renal function. Sustained neurohormonal suppression of ACE and AII occurred without evidence of AII reactivation. A lack of effect on BP at these doses may make perindopril suitable for study in unstable patients with acute HF or useful in those patients where there are concerns over ACEI induced hypotension.

Aged↗
PubMed1997

Right coronary artery stenosis is associated with impaired cardiac endocrine function during exercise.

AIMS: Resting plasma levels of atrial natriuretic peptide and B-type natriuretic peptide rise with left ventricular dysfunction, but little is known about effects of cardiac ischaemia on atrial natriuretic peptide and B-type natriuretic peptide levels during exercise. We investigated exercise levels of atrial natriuretic peptide and B-type natriuretic peptide in patients with suspected angina to determine whether these measurements could improve non-invasive assessment of coronary disease severity. METHODS AND RESULTS: One hundred patients performed an exercise test (Bruce protocol) within 2 weeks of coronary angiography. Plasma levels of atrial natriuretic peptide and B-type natriuretic peptide were measured at rest and at peak exercise. Multivariate regression analysis was used to assess effects of age, sex, coronary anatomy, exercise time and ventricular function on atrial natriuretic peptide and B-type natriuretic peptide levels. Increasing age and female sex were significantly associated with higher resting atrial natriuretic peptide levels; age alone was associated with higher exercise atrial natriuretic peptide levels. As expected, left ventricular end-diastolic pressure and disease of left anterior descending and circumflex coronary arteries were associated with increased resting B-type natriuretic peptide levels. However, the usual rise in B-type natriuretic peptide levels during exercise was independently reduced by disease of the right coronary artery. CONCLUSION: This paradoxical effect of right coronary artery disease limits the value of natriuretic peptide measurements as predictors of coronary disease severity. Impaired release of B-type natriuretic peptide may reduce exercise tolerance in patients with right coronary artery disease.

Age Factors↗
PubMed1997

Can drug effects on mortality in heart failure be predicted by any surrogate measure?

Clearly at present, the one perfect surrogate marker for mortality remains elusive. Chronic heart failure is a complex syndrome: as such it may perhaps be too simplistic to expect any single parameter to be universally predictive of drug effects on mortality, especially when each drug works by different mechanisms. Nevertheless, neurohormonal antagonists, such as ACE inhibitors and beta-blockers, seem to benefit both mortality and all surrogate markers of mortality. Equally, inotropic drugs and Class I antiarrhythmics appear to worsen both mortality and many surrogates. This is encouraging. However, significant discrepancies exist, particularly for digoxin, ibopamine and hydralazine-nitrates, although it is only with the latter two that diametrically opposite effects occurred, whereby favourable surrogate effects turned into unfavourable mortality effects (or vice versa). It appears appropriate to have guarded optimism about the potential use of these surrogates to predict drug effects in chronic heart failure. Given our current understanding, none of the parameters discussed above is perfect when used alone. Perhaps a battery of surrogates would be more appropriate rather than there being any single surrogate. The most promising surrogates are heart rate variability, QT dispersion and plasma neurohormones, the first two for sudden death and the last one for death from progressive disease.

Amiodarone↗
PubMed1997

Diagnosing left ventricular dysfunction after myocardial infarction: the Dundee algorithm.

Large-scale trials of angiotensin converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) suggest that the benefits are greatest in patients with left ventricular (LV) dysfunction. However, early evaluation of LV function in all patients after AMI by current methods can be difficult due to a lack of resources and skilled personnel. Thus a clinical algorithm that could be used at the bedside to reliably identify patients with a left ventricular ejection fraction (LVEF) < or = 40% would be helpful as an occasional alternative to echocardiography. We have devised such an algorithm based on the presence of one of: (i) clinical signs of heart failure; (ii) an index Q-wave anterior myocardial infarction; (iii) lack of thrombolytic therapy when there is a history of two or more previous myocardial infarctions and a CK rise > 1000 U/l. We tested this new algorithm prospectively in the coronary care units of two hospitals (one UK and one USA). In the UK centre, the sensitivity and specificity of the algorithm at identifying patients with a LVEF < or = 40% were 82% and 72%, respectively. In the US centre, the sensitivity of the algorithm was 91% and the specificity 78% at identifying patients with LV dysfunction. We have validated a simple clinical algorithm which can be used at the bedside for identifying patients who would benefit from an ACE inhibitor after AMI.

Aged↗
PubMed1997

The practical assessment of compliance with ACE-inhibitor therapy--a novel approach.

Poor compliance may be responsible for symptomatic decompensation or neurohormonal "escape" in patients with heart failure treated over the long term with angiotensin-converting enzyme-1 (ACEI) drugs. Serum ACE activity is a poor index of neurohormonal suppression or haemodynamic effect after ACE-inhibitor treatment. Serum ACE activity may, however, be a useful index of compliance with treatment, as serum ACE is sensitive to the presence of an ACE inhibitor in the blood. Sixteen normotensive male volunteers of known ACE genotype received 7 days of randomised, double-blind therapy on four occasions 2 weeks apart with lisinopril 20 mg (L) or matched placebo (P) to simulate (A) noncompliance (all P), (B) full compliance (all L), (C) partial compliance (L days, 1, 3, 6; P days, 2, 4, 5, 7), or (D) single dose (L day 7; P, 1-6). Supine (30 min) blood pressure (BP)/heart rate (HR), ACE, and angiotensins were measured on d7 before dose and 4-6 h after dose. Results are mean +/- 1 SD. BP showed the expected small decrease with active treatment on d7 (B or D) but not with placebo (A) or partial compliance (C). Prestudy serum ACE, despite a wide range (16-124 U/L), was reproducible within subjects [coefficient of variation (CV), 1.7%]. Serum ACE activity, before (41.9 +/- 30) and after (41 +/- 30) angiotensin (A) I or II, were unaffected by treatment (placebo A). Active treatment (B) resulted in very low serum ACE activity and d7 and a small further suppression after dosing (before, 3.9 +/- 4; after, 1.8 +/- 4). AI was elevated in this group with further elevation after dosing (before, 234 +/- 116; after, 551 +/- 250). AII was only modestly reduced from baseline and showed little further suppression after dosing (before, 7.8 +/- 4; after, 6.3 +/- 5). Partial compliance (C) showed low ACE but no reduction after treatment (before, 7 +/- 3; after, 7 +/- 4), an elevated AI but no dosing effect (before, 187 +/- 198; after, 200 +/- 151) and reduced AII but with no further dose suppression (before, 6.4 +/- 3.4; after, 7 +/- 4) induced increase in peptide (compared with B). Single-dose treatment (D) showed ACE inhibition as expected (before, 47 +/- 30; after, 2.2 +/- 3). There was a dosing-related increase of AI but to a lesser extent than seen with chronic active dosing (B) (before, 39 +/- 10; after, 240 +/- 200). In contrast to long-term dosing, there was marked ANG II suppression (before, 8.8 +/- 4; after, 2.9 +/- 3). With this long-acting ACEI in a dose relevant to congestive heart failure management, we suggest that 4-6 h after-dosing serum ACE (< 5 EU/L) and elevated ANG I (> 300 pg/ml) can be used to confirm compliance with treatment. These absolute values may be altered in patients treated concomitant with loop diuretics. In principle, however, this may be a useful tool in clinical trials or in clinical practice after further work has been done to assess the limits in patients across the doses and across the range of available drugs used.

Adult↗
PubMed1997

Cutaneous vascular responses to acetylcholine are mediated by a prostanoid-dependent mechanism in man.

Approximately 50% of the forearm vasodilatation to intra-arterial infusions of acetylcholine is mediated by endothelium-derived nitric oxide. These conclusions have been derived from venous occlusion plethysmographic measurements of total forearm blood flow during co-infusions of acetylcholine and NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthase. Since venous occlusion plethysmography measures total limb blood flow, the relative proportion of the measurement from skin cannot be determined precisely. To determine the effects of acetylcholine on skin specifically, we have used laser Doppler flowmetry to measure vascular responses to local iontophoresis of acetylcholine in the forearm of normal male volunteers. To elucidate the possible mechanisms of cutaneous vasodilatation to acetylcholine, vascular responses were measured before and after systemic inhibition of prostanoid production and nitric oxide synthesis by oral aspirin (600 mg daily for 3 days) and intravenous L-NMMA (3 mg/kg for 60 min), respectively. After aspirin administration, dose-dependent vascular responses to acetylcholine were reduced significantly by approximately 53% (p < 0.005, ANOVA). In contrast, intravenous L-NMMA appeared to have no significant effect on cutaneous vascular responses to acetylcholine. While the role of nitric oxide is uncertain, vasodilatation to acetylcholine in the forearm skin is mediated largely by a prostanoid-dependent mechanism. Assessment of cutaneous vascular responses to iontophoresis of acetylcholine may, therefore, be useful in diseases where abnormal endothelium-dependent prostanoid function has been implicated.

Acetylcholine↗
PubMed1996

Diagnostic value of B-type natriuretic peptide concentrations in patients with acute myocardial infarction.

Although elevations of plasma atrial natriuretic peptide (ANP) concentrations have been shown to have prognostic significance in patients after acute myocardial infarction (AMI), the relation between plasma levels of B-type natriuretic peptide (BNP) and cardiovascular mortality remains unknown. To test the prognostic value of plasma ANP and BNP after AMI, plasma concentrations were measured a mean of 3 days after infarction in 75 patients. During a median follow-up of 19.7 months, 14 patients (18.4%) died of cardiovascular causes. On univariate analysis, plasma ANP and BNP, Killip class, modified Peel index, left ventricular ejection fraction, and presence of left ventricular failure were all associated with cardiovascular mortality. In contrast, plasma ANP was the only variable that correlated with the development of symptomatic heart failure and hospitalization. For the combined end point of cardiovascular mortality, symptomatic heart failure, and hospitalization, plasma neurohormones were the only variables of predictive value. By stepwise regression analysis, plasma BNP was the only significant independent predictor of cardiovascular mortality (p = 0.001), whereas plasma ANP identified patients at risk of symptomatic heart failure and hospitalization (p = 0.002 and 0.019, respectively). This study indicates that plasma BNP measured after AMI is a powerful neurohormonal predictor of subsequent cardiovascular mortality, whereas plasma ANP correlates better with the development of symptomatic heart failure and hospitalization. Routine measurement of both of these peptides in the period immediately after an AMI may provide a simple means of risk stratification with different information gained from each peptide.

Adult↗
PubMed1996

Comparison of atrial natriuretic peptide B-type natriuretic peptide, and N-terminal proatrial natriuretic peptide as indicators of left ventricular systolic dysfunction.

We have directly compared atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and N-terminal pro-ANP (N-ANP) as markers of patients with left ventricular ejection fraction (LVEF) < or = 35%, as measured by radionuclide ventriculography. Venous blood samples were obtained from an unselected group of 87 patients who had been referred for assessment of ventricular function. ANP, BNP, and N-ANP were measured by radioimmunoassay using commercial kits. Receiver-operating characteristic analysis was used for the objective assessment of the diagnostic performance of each assay. There was a weak negative correlation between LVEF and plasma levels of ANP-li (r = -0.50,), BNP-li (r = -0.57), and N-ANP-li (r = -0.49) (p <0.01 for each peptide). Areas under the receiver-operating characteristic curves for BNP (0.880) and N-ANP (0.832) were not significantly different from each other, but were both significantly greater than the value for ANP (0.761): BNP versus ANP, p <0.01; and N-ANP versus ANP, p <0.05. The optimal sensitivity and specificity of each assay for the detection of patients with LVEF < or = 35% were: BNP > 4 pmol/L-sensitivity 1.0, specificity 0.58; N-ANP >200 pmol/L-sensitivity 0.95, specificity 0.35; and ANP >10 pmol/L-sensitivity 0.90, specificity 0.30. Plasma concentrations of BNP and N-ANP provide sensitive indicators of moderate to severe LV dysfunction; both peptides, are objectively superior to ANP for identifying patients with LVEF < or = 35%. These simple tests could be used to screen patients with suspected ventricular dysfunction to reduce the demand for further cardiac investigations.

Aged↗
PubMed1996

Sensitivity and specificity of QTc dispersion for identification of risk of cardiac death in patients with peripheral vascular disease.

OBJECTIVE: To determine whether QTc dispersion, which is easily obtained from a standard electrocardiogram, can predict those patients with peripheral vascular disease who will subsequently suffer a cardiac death, despite having no cardiac symptoms or signs. DESIGN: Patients with peripheral vascular disease were followed up for five years after they had had coronary angiography, radionuclide ventriculography, and their QTc dispersion calculated from their 12 lead electrocardiogram. SUBJECTS: 49 such patients were then divided into three groups: survivors (34), cardiac death (12), and non-cardiac death (3). MAIN OUTCOME MEASURE: Survival. RESULTS: The mean (SD; range) ejection fractions were similar in all three groups: survivors 45.9 (11.0; 27.0-52.0), cardiac death 44.0 (7.90; 28.5-59.0), and non-cardiac death 45.3 (4.55; 39.0-50.0). QTc dispersion was significantly prolonged in the cardiac death group compared with in the survivors (86.3(23.9; 41.0-139) v 56.5 (25.4; 25.0-164); P = 0.002). A QTc dispersion > or = 60 ms had a 92% sensitivity and 81% specificity in predicting cardiac death, QTc dispersion in patients with diffuse coronary artery disease was significantly (P < 0.05) greater than in those with no disease or disease affecting one, two, or three vessels. CONCLUSIONS: There is a strong link between QTc dispersion and cardiac death in patients with peripheral vascular disease. QTc dispersion may therefore be a cheap and non-invasive way of assessing the risk of cardiac death in patients with peripheral vascular disease.

Aged↗
PubMed1996

C-type natriuretic peptide. An endogenous inhibitor of vascular angiotensin-converting enzyme activity.

BACKGROUND: Atrial and B-type natriuretic peptide are both known to be antagonists of the renin-angiotensin system. C-type natriuretic peptide (CNP) is a new member of this family except that its principal source is the vascular endothelium. This study tested the hypothesis that CNP is a local inhibitor of vascular angiotensin-converting enzyme (ACE) activity. METHODS AND RESULTS: Vascular ACE activity was assessed by the differential vascular response to angiotensin I and angiotensin II. Healthy male volunteers were studied with the use of brachial artery infusions of angiotensin I and angiotensin II at two doses, with and without coinfusion of CNP at 500 pmol/min (n=8) and hydralazine at 10 microgram/min (n=8) (as a nonspecific vasodilator control). CNP alone and hydralazine alone caused similar increases in forearm blood flow (CNP+, 93.0+/-14.8%; hydralazine+, 84.2+/-22.6%). CNP inhibited the vasoconstrictive effect of angiotensin I (reduction in overall effect with CNP, 56.8+/-12.9%, P<.001) but not that of angiotensin II. Hydralazine did not significantly inhibit the effect of either angiotensin I or angiotensin II. CONCLUSIONS: This evidence of a differential effect of CNP on the vascular response to angiotensin I but not to angiotensin II suggest that CNP acts as a local endogenous regulator of vascular ACE activity in the human forearm resistance vessels.

Adult↗