Renal effects of aspirin are clearly dose-dependent and are of clinical importance from a dose of 160 mg

BACKGROUND: High doses of aspirin counteract the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors. It is not known how low-dose aspirin, with concomitant ACE-inhibitor treatment, affects renal function. AIM: To study renal effects of different doses of aspirin in elderly healthy volunteers who had an activated renin-angiotensin system. METHODS: Sixteen subjects each received two different doses of aspirin (0 and160 mg or 80 and 320 mg) after pre-treatment with bendroflumethiazide and enalapril, in a randomised double-blind, cross-over fashion. RESULTS: Least square means of the observations 30 to 180 min after dosing, showed that urine flow, GFR, excretion rates of sodium, osmolality clearance and free water clearance were significantly decreased in a dose-dependent manner. Urine flow, sodium excretion rate and free water clearance were significantly lower with 320 mg aspirin vs. 0 mg and 80 mg, and GFR was significantly lower with 320 mg vs. 80 mg. Urine flow, sodium excretion rate, free water and osmolality clearance was significantly lower with aspirin 160 mg vs. 0 mg. CONCLUSION: The dose-dependent renal effects of aspirin are of clinical importance from a dose of 160 mg. The adverse influence of aspirin doses higher than 80 mg should be taken into consideration in patients with heart failure.     

Individual variability in response to renin angiotensin aldosterone system inhibition predicts cardiovascular outcome in patients with type 2 diabetes: A primary care cohort study

Aims

To assess variability in systolic blood pressure (SBP) and albuminuria (urinary albumin creatinine ratio [UACR]) responses in patients with type 2 diabetes mellitus initiating renin angiotensin aldosterone system (RAAS) inhibition, and to assess the association of response variability with cardiovascular outcomes.

Material and Methods

We performed an observational cohort study in patients with type 2 diabetes who started RAAS inhibition between 2007 and 2013 (n = 1600). Patients were identified from general practices in the Netherlands. Individual response in SBP and UACR was assessed during 15 months’ follow‐up. Patients were categorized as: good responders (?SBP <0 mm Hg and ?UACR <0%); intermediate responders (?SBP <0 mm Hg and ?UACR >0% or ?SBP >0 mm Hg and ?UACR <0%); or poor responders (?SBP >0 mm Hg and ?UACR >0%). Multivariable Cox regression was performed to test the association between initial RAAS inhibition response and subsequent cardiovascular outcomes.

Results

After starting RAAS inhibition, the mean SBP change was ?13.2 mm Hg and the median UACR was ?36.6%, with large between‐individual variability, both in SBP [5th to 95th percentile: 48.5‐20] and UACR [5th to 95th percentile: ?87.6 to 171.4]. In all, 812 patients (51%) were good responders, 353 (22%) had a good SBP but poor UACR response, 268 (17%) had a good UACR but poor SBP response, and 167 patients (10%) were poor responders. Good responders had a lower risk of cardiovascular events than poor responders (hazard ratio 0.51, 95% confidence interval 0.30‐0.86; P = .012).

Conclusions

SBP and UACR response after RAAS inhibition initiation varied between and within individual patients with type 2 diabetes treated in primary care. Poor responders had the highest risk of cardiovascular events, therefore, more efforts are needed to develop personalized treatment plans for these patients.     

SFE/SFHTA/AFCE Consensus on Primary Aldosteronism,part 2: First diagnostic steps

In patients with suspected primary aldosteronism (PA), the first diagnostic step, screening, must have high sensitivity and negative predictive value. The aldosterone-to-renin ratio (ARR) is used because it has higher sensitivity and lower variability than other measures (serum potassium, plasma aldosterone, urinary aldosterone). ARR is calculated from the plasma aldosterone (PA) and plasma renin activity (PRA) or direct plasma renin (DR) values. These measurements must be taken under standard conditions: in the morning, more than 2 hours after awakening, in sitting position after 5 to 15 minutes, with normal dietary salt intake, normal serum potassium level and without antihypertensive drugs significantly interfering with the renin-angiotensin-aldosterone system. To rule out ARR elevation due to very low renin values, ARR screening is applied only if aldosterone is > 240 pmol/l (90 pg/ml); DR values < 5 mIU/l are assimilated to 5 mIU/l and PRA values < 0.2 ng/ml/h to 0.2 ng/ml/h. We propose threshold ARR values depending on the units used and a conversion factor (pg to mIU) for DR. If ARR exceeds threshold, PA should be suspected and exploration continued. If ARR is below threshold or if plasma aldosterone is < 240 pmol/l (90 pg/ml) on two measurements, diagnosis of PA is excluded.     

The relationship between diuretic dose, and the haemodynamic response to captopril in patients with cardiac failure.

The effect of diuretic dose on the haemodynamic response to captopril was assessed in nine patients with chronic cardiac failure. Each patient was given an intravenous dose of captopril while maintained on (a) a low dose diuretic regime, and (b) a high dose diuretic regime. Activity of the renin angiotensin aldosterone system, as assessed by plasma concentrations of these hormones, was greater when patients were receiving the higher dose diuretic regime. The magnitude of haemodynamic response produced by intravenous captopril was greater when the patients were maintained on the high dose diuretic regime, although no significant correlation was found between resting plasma renin activity and resting plasma angiotensin II concentration and the change produced by captopril in any haemodynamic response on either diuretic regime. An increased dosage of loop diuretic potentiates the haemodynamic effects of captopril in patients with cardiac failure. Reduction of diuretic dose prior to introduction of captopril may protect against severe first dose hypotension.     

Late-onset renal failure from angiotensin blockade (LORFFAB) in 100 CKD patients

Introduction Notwithstanding proven renoprotection from RAAS blockade (AB) with ACE inhibitors and ARBs, and despite increasing utilization of AB in the US, we have continued to experience a CKD/ESRD epidemic. Given concerns for iatrogenic CKD/ESRD, we designed a prospective study to analyze the course of eGFR following withdrawal of AB in such patients. Patients Between September 2002 and February 2005, all consecutive CKD patients on AB presenting with >25% increase in baseline serum creatinine were enrolled. eGFR following withdrawal of AB was monitored. The main outcome measures were serum creatinine, MDRD eGFR, and UA/Cr. Results 100 Caucasians, M:F = 52:48, mean age 71.5 years were enrolled. Mean follow up was 26 months. Sixteen patients progressed to ESRD, of whom seven died. In 74, eGFR improved from 23.9 ± 9 (7–47) to 39.2 ± 15.4 (17–89) ml/min/1.73 m² BSA, 26.5 (3–46) months after stopping AB (P = 0.001). The majority of the cohort, 95 patients, had known risk factors: 26 with RAS, 12 hypovolemia, 11 sepsis, 10 NSAIDs/cox II inhibtor use/abuse, 7 CIN, 2 congestive heart failure, 2 obstructive uropathy, and 27 with other medical and surgical causes, including malignancies, postoperative states, and infections. In the 26 with RAS, 5 with higher baseline creatinine −2.1 ± 0.6 versus 1.5 ± 0.4 mg/dL, P = 0.013, progressed to ESRD; 4/5 ESRD patients died after 6.3 months. The remaining five patients (one male and four females), mean age 68 (44–83) years, demonstrated sustained improved eGFR with discontinuation (four) or reduction (one) of RAAS blockade, despite normal renal arteries and the absence of known traditional risk factors. UA/Cr generally increased following withdrawal of AB. Conclusions Worsening azotemia in older susceptible CKD patients on AB, often but not always associated with known precipitating risk factors, remains under-recognized. Sustained improved eGFR often follows the discontinuation of AB. The practising physician should be well aware of these syndromes. Our observations call for further study. No external funding was involved in this study. Institutional review board (IRB) approval was obtained. This work is dedicated to the memory of a pleasant unnamed 74-year-old white woman, with ESRD, who died suddenly at home watching television, probably from a malignant arrhythmia.     

Cardiovascular protection using beta-blockers: a critical review of the evidence

For more than 3 decades, beta-blockers have been widely used in the treatment of hypertension and are still recommended as first-line agents by national and international guidelines. Recent meta-analyses indicate that, in patients with uncomplicated hypertension, compared with other antihypertensive agents, first-line therapy with beta-blockers was associated with an increased risk of stroke, especially in the elderly cohort with no benefit for the end points of all-cause mortality, cardiovascular morbidity, and mortality. In this review, we critically analyze the evidence supporting the use of beta-blockers in patients with hypertension and evaluate evidence for its role in other indications. The review of the currently available literature shows that in patients with uncomplicated hypertension, there is a paucity of data or absence of evidence to support use of beta-blockers as monotherapy or as first-line agents. Given the increased risk of stroke, their "pseudo-antihypertensive" efficacy (failure to lower central aortic pressure), lack of effect on regression of target end organ effects like left ventricular hypertrophy and endothelial dysfunction, and numerous adverse effects, the risk benefit ratio for beta-blockers is not acceptable for this indication. However, beta-blockers remain very efficacious agents for the treatment of heart failure, certain types of arrhythmia, hypertropic obstructive cardiomyopathy, and in patients with prior myocardial infarction.     

Clinical experiences with drospirenone: from reproductive to postmenopausal years

OBJECTIVE: To review the scientific publications concerning the clinical use of drospirenone (DRSP) as the progestin in combined oral contraceptives (OCs), and as hormone treatment for menopause. METHODS: This is a retrospective study of published information concerning DRSP retrieved from both a PubMed and a personal search. RESULTS AND DISCUSSION: DRSP is a progestin with antimineralocorticoid and antiandrogenic activities that confer special clinical relevance. The OC containing ethinyl estradiol (either 30 or 20 microg/day) and DRSP (3 mg) has been shown to be highly efficacious and to provide safety equivalent to that of other OC formulations. These OCs appear to improve many of the symptoms associated with premenstrual complaints and dysphoric disorders, including negative mood, water retention and increased appetite. The comparative safety and efficacy of newer OC formulations is difficult to establish since only a few randomized controlled trials have compared newer OCs in a head-to-head manner, and because pregnancy rates with today's OCs are so low that demonstrating a significant difference in efficacy would require very large sample sizes. The combined daily administration of DRSP and estradiol valerate has been reported to reduce most of the frequent climacteric symptoms and to provide a slight reduction in blood pressure, preventing fluid retention and hypertension. The unwanted effects related with DRSP are minor and not medically serious. Therefore, the follow-up rate is high in both OC and menopause treatments.     

The Association Between Gastric Achlorhydria and Subacute Combined Degeneration of the Spinal Cord

The following address briefly outlines the basic differences between traditional bronchial asthma and so-called “cardiac asthma.” It attempts to show that the fundamental differences have been confused by the use of the common word “asthma.” Further, these differences are of conspicuous importance, not only as to etiology, but also as to prognosis and therapy.     

针灸调节血压与血管的细胞通路关系

高血压近年来发病率有逐步上升的趋向.中医针灸对本病的调效已得到广泛的认同,近年来在细胞通路调机制方面的研究亦逐渐增加.探讨针灸产生的通路效应,并通过一氧化氮、肾素-血管紧张素-醛固酮系统、钙离子通道3种通路机制,进一步了解他们对血管的调节以及血压的控制.调节针对血管平滑肌细胞,及其内皮依赖性收缩、舒张因子,通过细胞化学反应及膜离子通道作为靶向目标,调降血压.