A proposal for the idea of a flexible-combination polypill in arterial hypertension

Objective: Modern pharmaceutical strategies in arterial hypertension, as well as in other fields, are directed toward two major apparently contrasting objectives: 1) sim- plification of treatment by grouping multiple drugs into single fixed-combination pharmaceutical units (including “polypill”) to improve patient adherence, and 2: personalization of therapy to tailor treatments according to specific individual aspects including pharmacogenomics. The combined fulfillment of these objectives would conceivably entail the unre- alistic development of a very great variety of fixed-combination polypills, each different for drug composition and dosage. An alternative view that could combine the need for both therapy simplification and personalization may be the concept of a flexible-combination polypill. Design and Methods: In order to test this approach, we are devising a preliminary study aimed to assess the feasibility and efficacy of shifting individual patients’ treatment from multiple daily administration (multi-administration) to a single once-a-day administration (mono-administration) of the same drugs. After approval of Ethical Committee, a cross-over randomized study will be carried out for 24 weeks in 52 well controlled non complicated hypertensive outpatients under multiple therapy with at least one hypotensive drug and/or a statin and/or aspirin. Each subject will remain for an 8 weeks period on multi-administration and for another 8 weeks period on mono-administration of the same therapy; the two peri- ods will be separated by 8 weeks to avoid a carry-over effect and their sequence will be randomized

Hypotensive and bradycardic effects of mouth opening: evidence in the human

Objective Previous studies in normotensive anesthetized rats (Lapi Arch.Ital.Biol 151:11-23,2013) showed that peripheral stimulation of the trigeminal nerve induced by submaximal mouth opening (mandibular extension, ME) caused prolonged (at least 80min) bradycardia, hypotension and cerebral hemodynamic changes (pial arterioles showed a characteristic response pattern consisting in a significant constriction during ME followed by a dilatation for the entire remaining observation time). Design and method In this study we assessed the in vivo effects of ME on HR, MABP and pial microcirculation in hypertensive rats. Experiments were performed in male Wistar rats weighing 250-300g (n = 8). Hypertension was induced by intraperitoneal daily injection of dexamethasone (0.03mg/kg/day) for 10 days. ME was obtained by inserting an ad hoc developed retractor between the dental arches. HR and MABP were recorded by ECG and a catheter placed in the left femoral artery and measured by a computer-assisted system. Pial arterioles were observed through a closed cranial window implanted above the left parietal cortex and visualized by an in vivo fluorescence microscopy technique to assess vessel diameter changes before (baseline), during 10min ME and thereafter until 160min. Arteriolar diameters were measured with a computer-assisted method (MIP Image program, frame by frame). Results In sham-treated (no ME) hypertensive rats (n=3) HR, MABP and pial microcirculation did not change during whole observation period. Hypertensive rats subjected to ME (n=5) showed a significant decrease of HR and MABP. HR declined by 42bpm, (p<0.01) starting from 60 min after ME up to 160min, while MABP by 18mmHg (p<0.05) starting from 20min after ME up to 100min, compared with baseline. Pial arterioles exhibited a biphasic response: the arteriolar diameter decreased by 2.94&#956;m (p<0.05) during ME, afterwards it significantly increased by 3.46&#956;m (p<0.01) starting from 20min after ME; this vasodilatation lasted for the whole observation period. Conclusions Our results suggest that ME is able to exert profound and prolonged regulatory effects on systemic arterial blood pressure and pial arteriolar tone in hypertensive rats

Repeated mandibular extension in rat: A procedure to modulate the cerebral arteriolar tone

Previous data have shown both in the rat and in the human that a single mandibular extension lasting 10 min induces a significant important and prolonged reduction in blood pressure and heart rate, affecting also rat pial microcirculation by the release of endothelial factors. In the present work, we assessed whether repeated mandibular extension could further prolong these effects. We performed two mandibular extensions, the second mandibular extension being applied 10 min after the first one. The second mandibular extension produced a reduction in blood pressure and heart rate for at least 240 min. As in the case of a single mandibular extension, pial arterioles dilated persisting up to 140 min after the second extension. Spectral analysis on 30 min recordings under baseline conditions and after repetitive mandibular extensions showed that the pial arterioles dilation was associated with rhythmic diameter changes sustained by an increase in the frequency components related to endothelial, neurogenic, and myogenic activity while a single mandibular extension caused, conversely, an increase only in the endothelial activity. In conclusion, repetitive mandibular extension prolonged the effects of a single mandibular extension on blood pressure, heart rate and vasodilation and induced a modulation of different frequency components responsible of the pial arteriolar tone, in particular increasing the endothelial activity

L'ipertensione renovascolare e la malattia aterosclerotica del distretto renale

rassegna su epidemiologia, eziologia, presentazione clinica, diagnosi e trattamento della malattia renovascolar

The importance of knowing the timing within the menstrual cycle in non-menopausal hypertensive women in the diagnostic workup for primary aldosteronism

We read with interest the paper by Ahmed el al (1), which demonstrates the importance of knowing the timing within the menstrual cycle when a diagnostic test is done for primary aldosteronism in non-menopausal women, reporting greater percentages of positive fludrocortisone suppression tests in the luteal compared to the follicular phase. Interestingly, a positive fludrocortisone test in the luteal phase was less likely to predict subsequent positive adrenal vein sampling than in the follicular phase, suggesting a lesser diagnostic accuracy of the test in the luteal phase. In their paper, the Authors focused on a late step of the diagnostic workup for hyperaldosteronism, that generally consists of performing a confirmatory test (such as the fludrocortisone test) after an initial laboratory positive screening test by means of determination of plasma aldosterone and renin levels. As also mentioned by Ahmed et al, some years ago we provided evidence that the menstrual cycle may affect the diagnostic performance for primary aldosteronism even in the early laboratory screening phase in hypertensive female patients (2) in a way similar to that observed by Ahmed, i.e. a higher "positivity" for suspected hyperaldosteronism when the test was done in the same women in the luteal compared to the follicular phase. We also recently confirmed this finding in an extended series of patients (3) (Fig 1). This article is protected by copyright. All rights reserved

CARDIORENAL SCINTIGRAPHY WITH 99mTc-TETROFOSMIN AS AN IMAGING TOOL TO STUDY CARDIORENAL DISEASE IN ARTERIAL HYPERTENSION

Background. Renal function is a strong predictor of cardiovascular prognosis and cardiorenal disease is increasingly investigated. Cardiorenal Scintigraphy with the perfusion tracer 99mTc-Tetrofosmin was proposed as a single combined examination allowing the simultaneous investigation of heart and kidney in cardiovascular patients, including hypertensives at risk of both cardiac and renal disease (Fommei, 2009). The renal uptake index (UI) of Tetrofosmin as a percent of the injected dose was used as a renal diagnostic parameter and found to be related to clinical and scintigraphic (99mTc-DTPA) indexes of cardiorenal severity. Aim of the study. Here we tested 99mTc-Tetrofosmin renal diagnostic validity in hypertensive patients in a comparison with 123 I-Hippuran scintigraphy as a gold standard for renal function. Patients and Methods. 22 hypertensive patients (5 F, 17 M, age range 46-79 yrs) were scheduled for both 99mTc-Tetrofosmin cardiac G-SPECT and 123-I Hippuran scintigraphy in their diagnostic workup. As previously described, cardiorenal scintigraphy consisted in a dynamic renal acquisition after Tetrofosmin bolus injection, followed by standard cardiac G-SPECT. Hippuran scintigraphy was performed in a separate day following standard procedures. Renal images and renograms were obtained and renal uptake was calculated for each kidney both in Tetrofosmin and Hippuran scintigraphies. Results. Tetrofosmin UI (mean 13.13±6.9 SD%) resulted lower than Hippuran UI (23.24±12.80 % (p<0.001) reflecting different intrarenal kinetics. Positive correlations were observed between the two tracers clearances and UI (either as total or separate kidney uptake) (p<.01) and between Tetrofosmin UI and age, serum creatinine, creatinine clearance and the Doppler-renal resistive index (p<.01). Five patients with angiographically confirmed renal artery stenosis showed corresponding renographic and scintigraphic abnormalities with both tracers. Conclusions. 99mTc-Tetrofosmin cardiorenal scintigraphy may be used to obtain simultaneous renal and cardiac functional information which may be relevant for diagnosis and prognosis in states of cardiorenal diseases, with no study lenghtening nor an increase in the radiation burden to the patient compared to a standard cardiac study

INDEXES OF PERCEIVED STRESS AND ANXIETY: AN OBSERVATIONAL STUDY IN NEWLY EVALUATED HYPERTENSIVE PATIENTS

Background. Chronic stress and anxiety are frequently associated with arterial hypertension (Greenage et al, Curr Atheroscler Rep, 2010) and related to sympathetic activation and hypothalamic, hypophyseal and adrenal activation. A link between plasma aldosterone and stress/anxiety has also been recently suggested both in animals and humans, particularly in women (Jezova and Hlavacova, Ann. N.Y.Acad.Sci, 2008). Objective. To investigate in hypertensive subjects the relationships between emotional stress and anxiety with endocrine or hemodynamic parameters as assessed in a routine diagnostic workup for arterial hypertension. Design and Methods. An observational study was started in day-hospital hypertensive patients (n= 74 up to date, 38M, 36F; mean age±SD 53±14), including two questionnaires for self-perceived stress (PSS10) and anxiety (TAS-20)respectively, which were administered on first-evaluation day, soon after (9.00-9:30am) blood pressure and heart rate measurements (by automatic device) and blood samples withdrawal for PRA, aldosterone and cortisol determinations according to standardized procedures. Results. The scores of the two tests were directly related with each other (p <.0001). For both, a positive association was found with heart rate and a negative one with cortisol levels, more significantly (p <.05 and p<0.01 respectively) after the exclusion of cases (n=14) who had positive screening criteria for primary aldosteronism. Anxiety scores were negatively related to cortisol levels particularly in women. No other significant differences or relationships were observed. Conclusions. These preliminary up-to-date results were unable to confirm a significant association between plasma aldosterone and anxiety/stress profiles in hypertensive patients as previously suggested by others. The relationship of anxiety and perceived stress scores with heart rate but not blood pressure levels may be explained by an higher sensitivity of heart rate as an index of sympathetic activation, suggesting it as a sensitive marker of anxiety level in the diagnostic evaluation and follow up of hypertensive patients. Interestingly, in our patients cortisol levels appeared unexpectedly to be negatively related to stress profiles, suggesting a possible primary defect in coping with emotional stress and anxiety in arterial hypertension