Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study

<p>Background: High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT[1]study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study.</p> <p>The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting.</p> <p>Methods/design: The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios.</p> <p>Primary Objective – To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios.</p> <p>Secondary Objectives – To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement predicts the antihypertensive response to spironolactone and/or bendrofluazide.</p> <p>Discussion: The numerous deleterious effects of hypertension dictate the need for a systematic approach for its treatment. In spite of various therapies, resistant hypertension is widely prevalent. Among various factors, primary aldosteronism is an important cause of resistant hypertension and is now more commonly recognised. More significantly, hypertensives with primary aldosteronism are also exposed to various other deleterious effects of excess aldosterone. Hence treating hypertension with specific aldosterone antagonists may be a better approach in this group of patients. It may lead on to better blood pressures with fewer medications.</p&gt

Investigating the evolution of undergraduate medical students' perception and performance in relation to an innovative curriculum-based research module: A convergent mixed methods study launching the 8A-Model.

BackgroundEmbedding into undergraduate medical programs experiential research curricula, based on holistic theories of education which emphasize participation in the social world, remains uncommon. The purpose of this study was to investigate the journey of undergraduate medical students in relation to an innovative compulsory curriculum-based research module, which has a prominent experiential learning component.MethodsA convergent mixed methods study design was adapted to develop a systemic understanding of the experience of the undergraduate medical students throughout the respective research module. As such, the students' perception of the experience was qualitatively explored using thematic analysis (n = 15). In parallel, the students' performance data were quantitatively analyzed using multi-repeated ANOVA (n = 158). The findings from both types of analyses (i.e., qualitative and quantitative study components) were then mapped onto each using joint display analysis.FindingsThe exploration generated four themes that correspond to sequential steps that the students go through to effectively integrate the scientific research method. These themes include: 1- Attend-Acquire, 2- Accumulate-Assimilate, 3- Apply-Appreciate, and 4-Articulate-Affect. Quantitatively, two distinct clusters of mean Grade Point Average were revealed (pConclusionThe evidence-driven 8A-Model, generated by this study, highlights that medical students' understanding of the true value of research seems to increase as they progress in the module. They begin expressing appreciation of the significance of the experience when they start implementing what they are learning as part of their own research studies. It is recommended for such a research module, with a firm experiential learning component, to be integral to undergraduate medical programs. This is expected to improve the future physicians' research competences, and in turn add value in terms of quality of care and patient outcomes

Estimation of Salt Intake and its Relation to Knowledge and Attitude Regarding the Dangers of High Salt Intake Among an Urban Omani Population: A pilot study

Objectives: High salt consumption is a major risk factor for hypertension. Studies have shown dietary salt intake to be high in many parts of the world. The aim of this study was to assess the daily salt consumption by the urban population in Oman and to assess their knowledge and attitudes towards dietary salt. Methods: This was a cross-sectional questionnaire-based study conducted between September to December 2017 in Muscat. We used previously validated questionnaires to assess salt intake and the knowledge and attitudes to salt intake. Results: 345 responses were received out of 500 distributed questionnaires (response rate 69%) of which 300 responses (27.88 + 7.9 years, 53.3% male) were included for analysis. 94% of the participants agreed that lowering salt in diet is important and nearly half the participants said that they were taking measures to reduce salt intake. However, the median salt intake was high at 10.5(7.3-15.1) gm salt/day. 90% of those questioned consume more than the maximum recommended amount of salt per day. Salt intake was significantly higher in females and older age group (>40 years of age), There did not appear to be any correlation between awareness of the dangers of salt intake and the amount consumed. Conclusion: The salt intake in our sampled population in Oman is high and does not depend on knowledge. Strategies should be designed to reduce salt intake by health education and increasing knowledge about complications of high salt intake among the urban population. Keywords: dietaray sodium chloride; knowledge attitudes and practices

Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study

Abstract Background High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT1study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study. The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting. Methods/design The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios. Primary Objective – To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios. Secondary Objectives – To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement predicts the antihypertensive response to spironolactone and/or bendrofluazide Discussion The numerous deleterious effects of hypertension dictate the need for a systematic approach for its treatment. In spite of various therapies, resistant hypertension is widely prevalent. Among various factors, primary aldosteronism is an important cause of resistant hypertension and is now more commonly recognised. More significantly, hypertensives with primary aldosteronism are also exposed to various other deleterious effects of excess aldosterone. Hence treating hypertension with specific aldosterone antagonists may be a better approach in this group of patients. It may lead on to better blood pressures with fewer medications.</p

Does the ratio of serum aldosterone to plasma renin activity predict the efficacy of diuretics in hypertension?:Results of RENALDO

&lt;b&gt;Objectives:&lt;/b&gt; We hypothesized that the aldosterone: renin ratio (ARR) predicts the antihypertensive response to mineralocorticoid receptor antagonist, spironolactone (SPIRO), when compared with bendroflumethiazide (BFZ).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods:&lt;/b&gt; We conducted a randomized, crossover, trial on hypertensive patients with either high ARR (HARR defined as &gt;750 and plasma aldosterone &gt;250 pmol/l) or low ARR (LARR defined as &lt;300 and plasma renin activity &lt;10 ng/ml per h). Each group took SPIRO 50 mg once daily for 12 weeks and BFZ 2.5 mg once daily for 12 weeks in random order separated by 2-week washout. Patients with mean 24-h systolic ambulatory blood pressure (SABP) at least 140 mmHg were included. Primary endpoint was difference in SABP between SPIRO and BFZ in patients with HARR compared with those with LARR.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results:&lt;/b&gt; One hundred and eleven patients (60 HARR and 51 LARR) completed the study. SABP at 12 weeks in the HARR group was 129.4 mmHg on SPIRO and 134.4 mmHg on BFZ [difference −5.01; 95% confidence interval (CI) −7.51, −2.52; P &lt; 0.0002]. In the LARR group, SABP was 129.7 mmHg on SPIRO and 133.1 mmHg on BFZ [difference −3.43 (95% CI −6.18, −0.68) P &lt; 0.01]. Difference between groups (HARR vs. LARR) was −1.58 mmHg (95% CI 5.25, −2.08; not significant, P = 0.394). In a secondary analysis of the overall study population of 111 patients, SABP reduction with SPIRO 50 mg was superior to BFZ 2.5 mg [SPIRO −14.8 mmHg, BFZ −10.5 mmHg, difference −4.29 mmHg (95% CI −6.12, −2.46)].&lt;p&gt;&lt;/p&gt; Results were similar for secondary endpoints. Plasma renin activity or aldosterone did not predict blood pressure response to SPIRO. Results were independent of concomitant angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion:&lt;/b&gt; The ARR did not predict the blood pressure response to SPIRO. SPIRO 50 mg was significantly more effective than BFZ 2.5 mg in lowering SABP irrespective of baseline ARR, plasma renin activity or aldosterone.&lt;p&gt;&lt;/p&gt