Clinician perception of a novel cardiovascular lifestyle prescription form in the primary and secondary care setting in Wales, UK.

ISSUES ADDRESSED: To establish the views of clinicians on the feasibility and effectiveness of using a novel lifestyle prescription form (LRx) which requires co-signing by clinician and patient and is uniquely based on the design of the standard drug prescription form, in the primary and secondary health care settings. METHODS: Thirty-six participants were issued with a "prescription" pad, of 20 LRx scripts, for 1 month and requested to issue an LRx prescription to patients they deemed suitable during their consultation, recording their reason for use of the LRx. Each clinician was then asked to complete a comprehensive feedback questionnaire. RESULTS: Feedback of the LRx was overwhelmingly positive. The script was viewed as a more effective way to convey and support cardiovascular lifestyle advice, than usual care. Forty per cent (196 of 480) of the LRx scripts that were provided to primary and secondary care clinicians during the study period were issued. In most consultations, the LRx script was issued to reaffirm dietary advice. Nurses and health care assistants were more likely than doctors to use the LRx in response to a request for lifestyle advice from a patient. CONCLUSIONS: The LRx may be a useful addition to the clinician's communication toolkit to stimulate lifestyle behaviour changes in their patients. The main barrier to use in the study was lack of consultation time. SO WHAT?: Issuing the LRx is a method of solidifying lifestyle advice that clinicians could utilise, providing them with another tool in their behaviour change arsenal, particularly with familiarity with the tool.

Platelet nitrate responsiveness in fasting and postprandial type 2 diabetes.

Vascular responsiveness to exogenous nitrates in type 2 diabetes (T2DM) is attenuated in brachial and coronary vessels. We determined platelet responsiveness to nitric oxide (NO) in T2DM and control subjects. We examined whether the postprandial (PP) state affected platelet sensitivity to NO donors in T2DM patients and the extent of correlation between this and measures of oxidative stress, compared to changes in endothelial function. Twelve T2DM subjects were studied fasting and four hours after a test meal and compared with 15 healthy controls. We assessed the inhibitory effects of NO donors on adenosine 5'-diphosphate (ADP)-induced platelet aggregation. Oxidative stress was assessed by lipid-derived free radicals, ex vivo by electron paramagnetic resonance spectroscopy and markers of lipid peroxidation. Endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery. Results are expressed as (mean +/- SEM). Fasting platelet aggregation was increased in diabetics versus controls (14.86 +/- 1.1 Ohms vs. 10.76 +/- 1.1 Ohms, p < 0.05). Sodium nitroprusside (SNP) and glyceryl trinitrate (GTN) inhibited ADP-induced aggregation by 73.1 +/- 5.9% and 50.3 +/- 7.7% in healthy controls compared to 15.4 +/- 7% and 19.5 +/- 8.2% in T2DM (p < 0.05). Fasting and postprandial inhibition of platelet aggregation with NO donors in T2DM was similar. T2DM patients had higher levels of oxidative stress in the fasting state and postprandially. There were no PP correlations with platelet NO resistance. In conclusion, there is platelet hyporesponsiveness to NO donors (SNP/GTN) in T2DM compared to controls, with increased ADP-induced platelet aggregation. Platelet abnormalities were associated with increased oxidative stress.

Role of nitric oxide and oxidative stress in baroreceptor dysfunction in patients with chronic heart failure.

Abnormalities of autonomic control of the cardiovascular system are seen in chronic heart failure (CHF) and confer a poor prognosis. Nitric oxide appears to be important in the regulation of baroreflex control in health and in disease states. The antioxidant vitamin C increases nitric oxide bioavailability in CHF. We evaluated the effects of vitamin C on baroreceptor sensitivity (BRS) by sequence analysis in 100 CHF patients and 44 control subjects. Groups of 55 CHF patients and 22 controls were randomly allocated to receive a single intravenous injection of vitamin C (2 g) or placebo. In addition, 45 CHF patients were randomly allocated to receive a 4-week course of oral vitamin C (4 g/day) or placebo. An age-related reference range for BRS was developed in 22 healthy controls matched for age and gender to the CHF group. BRS was significantly impaired in the CHF group compared with age-matched older controls and young controls (6.9 +/- 3.1, 12.5 +/- 4.9 and 21.7 +/- 9.1 mmHg/ms respectively; P < 0.001 between groups). Intravenous vitamin C acutely improved BRS in CHF patients by 24% (by 1.8 +/- 4.1 mmHg/ms; P < 0.05), but not in controls. There was no improvement in BRS in CHF patients given chronic oral vitamin C. Thus acute intravenous, but not chronic oral, vitamin C improved BRS in CHF patients. There was no effect of intravenous vitamin C in healthy subjects, suggesting that the mechanism was either by free radical scavenging or due to central effects.

Addition of candesartan to angiotensin converting enzyme inhibitor therapy in patients with chronic heart failure does not reduce levels of oxidative stress.

BACKGROUND: Angiotensin II exerts a number of harmful effects in patients with chronic heart failure (CHF) and, through an increase in oxidative stress, is thought to be critical in the development of endothelial dysfunction. Angiotensin II may be elevated in CHF despite treatment with angiotensin converting enzyme (ACE) inhibitors, producing a rationale for adjunctive angiotensin receptor blockade. We investigated whether the addition of angiotensin antagonism to ACE inhibition would reduce oxidative stress and improve endothelial function and exercise tolerance in patients with chronic heart failure. METHODS AND RESULTS: Twenty-eight heart failure patients, who were on stable ACE inhibitor therapy, were randomised to receive adjunctive therapy with candesartan or placebo. Plasma lipid-derived free radicals, TBARS and neutrophil O2-generation, markers of oxidative stress, were measured in venous blood. Arterial endothelial function was assessed as the response of the brachial artery to flow-related shear stress. Exercise capacity was determined by cardiopulmonary exercise testing. Compared with placebo, candesartan had no effect on changes in lipid derived free radicals (-0.1+/-1.2 vs. -0.1+/-1.0 units, respectively, P=NS), TBARS (-2.2+/-1.1 vs. -2.6+/-2.2 micromol/l, respectively, P=NS) or neutrophil O2-generating capacity (-7.3+/-5.1 vs. -8.4+/-7.9 mV/5x10(5) neutrophils, respectively, P=NS). There was no effect on changes in brachial artery flow-mediated dilatation (0.5+/-1.0 vs. 0.8+/-1.3%, respectively, P=NS) nor peak VO2 (1.6+/-0.7 ml/kg per min vs. 1.8+/-0.6 ml/kg per min; P=NS). CONCLUSION: The addition of the candesartan to ACE inhibitor therapy had no effect on oxidative stress and did not improve endothelial function or exercise capacity in patients with CHF.

Racial differences in responses to drug treatment: implications for pharmacotherapy of heart failure.

Chronic heart failure (CHF) is a common disease with high associated morbidity and mortality, and the outcome appears to be worse in black compared with white patients. There is currently no clear consensus for basing the pharmacological treatment of CHF on racial differences. Most studies that have investigated the potential effects of racial differences on pharmacological responses in heart failure have been based on African Americans and white participants. Using these data, this review will discuss the current understanding of the effects of racial differences in response to pharmacotherapy in heart failure, possible mechanisms for these observed differences, and how this may impact on patient management. Diuretics have favorable symptomatic benefits in both black and white patients with heart failure with evidence of fluid retention. ACE inhibitors seem to be less effective in the treatment of black patients with heart failure compared with white patients. This may be due to low pre-existing activity of the renin-angiotensin system in blacks. The role of angiotensin receptor blockers (ARBs) in the management of all patients with heart failure is incompletely defined and there are no clear trial data to show any difference in effect between black and white patients with heart failure. There is good evidence for the use of spironolactone in all patients with heart failure, but no evidence for a different effect in black patients. Similarly, there is no conclusive data to suggest a difference in effect of digoxin in different racial groups. The evidence available would suggest that certain beta-adrenoceptor antagonists (certainly carvedilol but not bucindolol) are effective in both black and white patients with CHF. The combination of hydralazine and nitrates would appear to be particularly effective in black patients with CHF though the African American Heart Failure Trial (A-HeFT) trial should provide clearer evidence for the potentially greater beneficial effects of these two drugs in the black population. It is important to accept that racial categorization acts as only a surrogate marker for genetic or other factors responsible for individual responses to drug therapy and that any identified differences will not apply to all members of each stratified group. Nonetheless, in managing a complex, common and often fatal condition such as heart failure, recognizing potential individual differences in drug responses should enable the responsible clinician to provide a tailored and evidence-based approach to patient treatment.