Allan Struthers

..We ascertained whether high-dose allopurinol prolongs exercise capability in patients with chronic stable angina...

..To assess the accuracy of findings from the clinical history, symptoms, signs and diagnostic tests (ECG, CXR and natriuretic peptides) in relation to the diagnosis of left ventricular systolic dysfunction (LVSD) in a primary care setting...

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..87. The reduction in the risk of sudden death from cardiac causes was statistically significant. In conclusion, aldosterone blockade should form part of optimal therapy for patients with heart failure...

..4. Once individuals are identified as being at high risk, a range of interventions is possible (e.g. intensive statin therapy or angiotensin-converting enzyme inhibitors if LV abnormalities or autonomic imbalance are found)...

..The increased understanding of the mechanistic role of aldosterone in cardiovascular disease provides a rationale for the positive results that have been seen in clinical trials of aldosterone blockade...

..The term "aldosterone vasculopathy" has been coined to describe that the fundamentally adverse effect of aldosterone may well be on endothelial nitric oxide...

..Aldosterone blockade should become a regular third neuroendocrine-blocking drug in patients with chronic heart failure...

..We review the evidence for this new prospect, which has the potential to reduce cardiac deaths by using a simple blood test to better target cardioprotective strategies to those who most need them...

..Clinicians should now assess these various arguments to select what they believe would be best for their patients...

..BNP/N-BNP could become to the heart what microalbuminuria is to the kidneys, i.e. an indicator of early, silent TOD...

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..Choice of a specific agent should be based on individual patient issues, such as the nature of heart failure and patient concerns about adverse events...

..Inhibition of aldosterone's effect on mineralocorticoid receptors should now be considered standard therapy in these patient populations...

..This hypothesis is based on previous data that a high urate concentration is independently associated with mortality with a risk ratio of 4.23 in CHF...

..However, because of aldosterone "escape," the effectiveness of this blockade decreases over time...

..On the other hand, allopurinol did reduce BNP, which is the best available surrogate marker for prognosis in CHF...

..We therefore assessed the full effects of aldosterone blockade in poorly controlled hypertensive patients with type 2 diabetes, focussing on blood pressure, endothelial function, glycaemic control and key hormones...

..The reduction in vascular oxidative stress was profound because high-dose allopurinol totally abolished the oxidative stress that was sensitive to the high-dose vitamin C that was used in this study...

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..Finally, aldosterone blockade has been shown to reduce atherosclerosis in animal studies of atherosclerosis without heart failure, which are analogous to CAD patients...

..Therefore, amiloride has fewer beneficial mechanistic effects than spironolactone, but it does share with spironolactone the ability to shorten the QT interval and reduce ventricular extrasystoles...

..The mechanism could be either that lisinopril limits the angiotensin II-induced production of superoxide radicals which would normally inactivate NO, or that lisinopril may increase bradykinin-mediated NO release...

..However, it remains unknown whether the same overall phenomenon occurs in other patients taking chronic ACE inhibitor therapy, such as patients with type 2 diabetes mellitus...

..Allopurinol improves endothelial function in chronic heart failure by reducing oxidative stress. We wished to explore if such an effect would attenuate autonomic dysfunction in CHF in line with many other effective therapies in CHF...

..CONCLUSIONS: Spironolactone reduced heart rate and improved HRV and QT dispersion in CHF. Its effects were particularly prominent during the morning hours...

..Endothelial independent vasodilator responses (to nitroprusside and verapamil) were unaltered in smokers. A defect in the vasoconstrictor response to angiotensin I was also seen...

..We aimed to investigate if this was the case with losartan when compared to atenolol. We also investigated the differential effect of losartan and atenolol on the prognostic marker, brain type natriuretic peptide (BNP)...

..Since inhibition of the RAAS at the level of ACE is now seen to be an important therapy in diabetes; the purpose of this article is to explore the potential benefits of additional aldosterone inhibition in Type 2 diabetes mellitus...

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..The aim of this study was to assess the effect of ovarian hormones on vascular tone, vascular ACE activity and vasoconstriction to angiotensin II in males...

..These data demonstrate that the DD ACE genotype in a young population is associated with a blunting of stimulated endothelial NO and donated NO responses but not to non-NO vasodilators or vasoconstrictors...

..CONCLUSIONS: Patients in whom bradycardia and hypotension develop with induction of positive-pressure capnoperitoneum have cardiovascular autonomic dysfunction, which is identifiable by bedside stress tests of autonomic function...

..The prevalence of echocardiographic LVH in patients with high cardiovascular risk appears to be high, even in patients currently considered normotensive...

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..To test whether a single large dose of vitamin D2 can improve endothelial function in patients with Type 2 diabetes mellitus and low serum 25-hydroxyvitamin D levels...

..This will enable intensified efforts to ensure LVH regression, which is associated with reduction in both cardiovascular morbidity and mortality...

..We postulated that aldosterone blockade with spironolactone might also have beneficial effects on the prognostic markers of endothelial function and heart rate variability in diabetic patients...

..We compared the effect of 100,000 and 200,000 IU doses of vitamin D(3) on endothelial function, blood pressure and markers of glycaemic control in patients with type 2 diabetes...

..Although it is widely acknowledged that diabetes is a risk factor for coronary artery disease, the increased prevalence of potentially lethal left ventricular abnormalities in this population is less well appreciated...

..To find out what spectrum of cardiac abnormalities are found in those stroke survivors who can be deemed to be at high cardiac risk by their having long QT...

..CONCLUSION: BNP is of value in predicting silent ischaemia on exercise testing in asymptomatic patients with type 2 diabetes...

..start of QRS to peak of T wave) is easier to measure. Therefore, we tested the hypothesis that long QT peak was associated with left ventricular hypertrophy and assessed its cost-effectiveness at diagnosing left ventricular hypertrophy...

..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...

..To compare QT dispersion in patients with impaired left ventricular systolic function and in matched control patients with normal left ventricular systolic function...

..In conclusion, irbesartan improved QT dispersion, and this effect may be important in preventing sudden cardiac death in at-risk hypertensive subjects...

..We tested the hypothesis that this benefit was partially due to improvement in endothelial function and/or to amplified suppression of the vascular renin-angiotensin axis...

..This raises the possibility that salt may have BP-independent adverse cardiac effects in susceptible hypertensive subjects...

..It remains uncertain whether angiotensin converting enzyme (ACE) inhibitors benefit all heart failure patients or just those with renin-angiotensin-aldosterone system (RAAS) activation...

..One patient treated with placebo developed new heart failure. These results show that xamoterol can be administered safely to selected patients following myocardial infarction, including those treated for mild heart failure...

..Third, the authors assessed whether the prognostic utility of hs-TnT is independent of various echocardiographic abnormalities...

..The results of the present study allude to a potential direct or indirect relationship between adiponectin and BNP post-ACS which requires further investigation...

..To test the hypothesis that B-type natriuretic peptide (BNP) predicts reversible myocardial ischaemia in stroke survivors who do not have chest pain or previous myocardial infarction...

..Diagnosing suspected left ventricular systolic dysfunction (LVSD) in the community is a challenge for GPs. We developed and validated a clinical prediction rule (CPR) for LVSD based on history, examination and electrocardiogram (ECG)...

..In congestive heart failure (CHF) such failure of hormonal suppression is associated with increased mortality. This study examined how common AII and aldosterone increases are observed during routine clinical practice...

..This highlights the need to resolve co-existing vascular risk factors in patients with hypertension...

..The aim of the study was to explore the long-term effect of allopurinol on mortality and cardiovascular hospitalisations in heart failure (HF) patients...

..CONCLUSIONS: Elevated serum urate concentration may be used to stratify risk of future cardiac death after stroke. This appeared to be true even in stroke survivors who were not on diuretic therapy...

..These workflows provide the ability to robustly exploit ever more common clinical samples yielding extremely low cell numbers and RNA yields for global transcriptomics...

..CONCLUSIONS: Despite the infrequent use of statin during the study period, good adherence to statin treatment was associated with lower risk of recurrent MI...

..CONCLUSIONS: Stroke patients living in more socially deprived areas had their strokes at an earlier age but were not at a greater risk of dying or longer hospital stay once they had been admitted to hospital...

..Regression of LVH reduces risk. Patients with blood pressure in the normal range and LVH are common. We investigated whether further reduction in blood pressure would further regress LVH...

..CONCLUSIONS: Six minute walking distance is improved considerably by treatment with perindopril in older patients with heart failure caused by left ventricular systolic dysfunction...

..These findings may be important in the prevention of a potentially dangerous interaction in susceptible patients taking this combination of drugs...

..We conclude that xamoterol does not cause deleterious neuroendocrine changes in patients with AMI even in those treated for heart failure...

..05). This reversed association and the weaker relationships between methods in post-infarction as compared to chronic heart failure patients may be related to interference by thrombolytic or aspirin treatments...

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..Supplementation with potassium and magnesium had no effect on electrocardiographic changes, and the addition of triamterene to bendrofluazide only attenuated electrocardiographic responses in some subjects...

..To test the hypothesis that the QTc of any lead of the ECG predicts death after stroke, and to determine which lead of the ECG carries the greatest risk of cardiac death when its QTc is measured...

..Larger studies are needed to confirm the observation from this pilot study...

..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...

..However, it is unknown how BNP compares with GRACE and how their combination performs in ACS...

..6 m/month in nonattenders; P=.03). Similar results were seen for other outcomes. Only a small proportion of the variance in change of any of the outcomes was explained by differences in baseline variables...

..The possible mechanisms are that aldosterone promotes myocardial fibrosis and lengthens the QTc interval as well as decreasing potassium in CAD patients without heart failure...

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..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...

..This article reviews the pathophysiology of aldosterone and critically reviews the present evidence for the efficacy and potential role for the new selective aldosterone-receptor antagonist, eplerenone...

..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...

..Pre-echocardiography screening with electrocardiograms (ECGs) is recommended as a means of targeting this scarce resource. There are data to support this policy when ECGs are interpreted by cardiologists but not by GPs...

..We sought to examine the effect of the angiotensin-converting-enzyme (ACE) inhibitor perindopril on physical function in elderly people with functional impairment who had no heart failure or left ventricular systolic dysfunction...

..However, LVH will only have a large impact overall in CAD if it is highly prevalent. Therefore we aimed to assess the prevalence of LVH in patients with stable, treated angina and its relationship with blood pressure (BP)...

..02). Salt loading impaired vascular endothelial function, left ventricular mechanical relaxation, and electric repolarization in young healthy normotensives...

..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...

..These studies provide evidence against the hypothesis that the clinical benefits produced by aldosterone blockade are due to it having anti-inflammatory effects...

..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...

..To assess how well heart failure patients tolerate spironolactone in routine clinical practice...

..In Conclusion, BNP may potentially act as a homeostatic mechanism that helps to limit exercise incapacity in hypertension irrespective of LVH...

..We assessed the hypothesis that CNP is produced by the heart in patients with CHF...

..CONCLUSIONS: Losartan improves basal NO bioactivity in healthy salt-replete volunteers. Even in salt-replete man, basal Ang II levels exert a tonic effect, which reduces basal NO...

..To evaluate how well older heart failure patients tolerate beta-blockers in everyday clinical practice...

..We sought to determine how many cases of echo LVH would be missed by applying the ECG criteria for LVH used in the LIFE study...

..Importantly, use of the technique of applanation tonometry to derive the central waveform from non-invasively acquired peripheral data needs to be validated prospectively...

..quot;Aldosterone-induced vasculopathy" may be the main mechanism why aldosterone promotes widespread tissue injury and ultimately cardiac death...

..It has been shown to be accurate when data obtained invasively are used, but has not been tested prospectively using data obtained non-invasively...

..Patients' clinical outcome was stable and not hospitalized (Group 0); alive but hospitalized (Group 1); or dead during follow up (Group 2)...