We hypothesized that screening for nonadherence to antihypertensive treatment using liquid chromatography-tandem mass spectrometry-based biochemical analysis of urine/serum has therapeutic applications in nonadherent hypertensive patients. A retrospective analysis of hypertensive patients attending specialist tertiary care centers was conducted in 2 European countries (United Kingdom and Czech Republic). Nonadherence to antihypertensive treatment was diagnosed using biochemical analysis of urine (United Kingdom) or serum (Czech Republic). These results were subsequently discussed with each patient, and data on follow-up clinic blood pressure (BP) measurements were collected from clinical files. Of 238 UK patients who underwent biochemical urine analysis, 73 were nonadherent to antihypertensive treatment. Their initial urinary adherence ratio (the ratio of detected to prescribed antihypertensive medications) increased from 0.33 (0-0.67) to 1 (0.67-1) between the first and the last clinic appointments. The observed increase in the urinary adherence ratio in initially nonadherent UK patients was associated with the improved BP control; by the last clinic appointment, systolic and diastolic BPs were ≈19.5 and 7.5 mm Hg lower than at baseline (P=0.001 and 0.009, respectively). These findings were further corroborated in 93 nonadherent hypertensive patients from Czech Republic-their average systolic and diastolic BPs dropped by ≈32.6 and 17.4 mm Hg, respectively (P<0.001), on appointments after the biochemical analysis. Our data show that nonadherent hypertensive patients respond to liquid chromatography-tandem mass spectrometry-based biochemical analysis with improved adherence and significant BP drop. Such repeated biochemical analyses should be considered as a therapeutic approach in nonadherent hypertensive patients.

• Klíčová slova
• adherence, antihypertensive agents, blood pressure, chromatography, liquid, hypertension,
• MeSH
• adherence k farmakoterapii psychologie   MeSH
• antihypertenziva * analýza   terapeutické užití   MeSH
• biologické markery * krev   moč   MeSH
• chromatografie kapalinová metody   MeSH
• dospělí MeSH
• hypertenze * diagnóza   farmakoterapie   epidemiologie   psychologie   MeSH
• krevní tlak účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• management farmakoterapie normy   MeSH
• měření krevního tlaku metody   psychologie   MeSH
• senioři MeSH
• výsledky a postupy - zhodnocení (zdravotní péče) MeSH
• zlepšení kvality MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Spojené království epidemiologie   MeSH
• Názvy látek
• antihypertenziva * MeSH
• biologické markery * MeSH

Background Although measurement of drug serum levels is an objective direct method for testing compliance, it can be distorted by "white-coat compliance" or by variations in drug elimination. Objective The aim of this prospective study was to evaluate the prevalence of noncompliance with perindopril therapy in adult out-patients using pharmacokinetic simulations. The additional aim was to compare the predictive performance of two glomerular filtration rate markers-creatinine and cystatin C. Setting Department of Cardiology, Tomas Bata Regional Hospital in Zlín, Czech Republic. Method Perindoprilat pharmacokinetic models individualized according to patient characteristics were compared with measured perindoprilat serum concentrations to document compliance. Linear regression was used to evaluate the relations between perindoprilat clearance and glomerular filtration rate estimated using creatinine and cystatin C. Main outcome measure Assessment of non-compliance with medication using drug concentration measurements reinforced with therapeutic drug monitoring. Results Non-detectable perindoprilat levels were observed in 26.1% of patients. Another 21.7% were classified as non-compliant based on therapeutic drug monitoring pharmacokinetic simulations. Volume of distribution, clearance and half-life median value (interquarti°range) for perindoprilat were 408.3 (360.4-456.8) L, 10.1 (4.9-17.0) L h-1 and 24.7 (19.4-62.7) h, respectively. Linear regression models showed tight relationship between cystatin C and perindoprilat clearance. Conclusions Assessment of adherence with medication reinforced with therapeutic drug monitoring and pharmacokinetic simulations is proposed as an optimal method reducing disadvantages of simple drug concentration measurements. Cystatin C proves to be better surrogate marker for perindoprilat elimination than creatinine.

• Klíčová slova
• ACE inhibitors, Compliance, Creatinine, Cystatin C, Perindopril, Therapeutic drug monitoring,
• MeSH
• adherence k farmakoterapii * MeSH
• cystatin C metabolismus   MeSH
• hodnoty glomerulární filtrace účinky léků   fyziologie   MeSH
• inhibitory ACE metabolismus   farmakologie   MeSH
• kreatinin metabolismus   MeSH
• lidé MeSH
• metabolická clearance účinky léků   fyziologie   MeSH
• monitorování léčiv metody   MeSH
• perindopril metabolismus   farmakologie   MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• Názvy látek
• cystatin C MeSH
• inhibitory ACE MeSH
• kreatinin MeSH
• perindopril MeSH

PURPOSE OF REVIEW: Resistant hypertension is a common clinical situation. Identification of true resistant hypertension (using 24-h ambulatory blood pressure monitoring to exclude white coat phenomenon, excluding secondary causes and non-adherence to treatment) is important mostly because of the application of a proper therapeutic approach and the higher cardiovascular risk of these patients. This review surveys recent studies, with a focus on mineralocorticoid receptor antagonists, including spironolactone, in the treatment of resistant hypertension. RECENT FINDINGS: A range of randomized and non-randomized studies have proved the efficacy of mineralocorticoid receptor antagonists, including spironolactone. However, long-term mortality studies are still missing for the hypertensive population. In the case of spironolactone side effects, higher doses of amiloride or eplerenone might be used. Based on available data and our own experience, spironolactone (mineralocorticoid receptor antagonists) should be involved, if tolerated, in combination therapy in true resistant hypertensive patients. Spironolactone still represents primary therapeutic modality under specific conditions of primary aldosteronism.

• Klíčová slova
• Mineralocorticoid receptor antagonists, Resistant hypertension, Spironolactone,
• MeSH
• diuretika terapeutické užití   MeSH
• hypertenze farmakoterapie   MeSH
• léková rezistence MeSH
• lidé MeSH
• metaanalýza jako téma MeSH
• randomizované kontrolované studie jako téma MeSH
• spironolakton terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• diuretika MeSH
• spironolakton MeSH

BACKGROUND: Aldosterone has been shown to substantially contribute to the accumulation of different types of collagen fibres and growth factors in the arterial wall, thus increasing wall thickness. A previous study showed reduction of increased common carotid intima-media thickness (IMT) in patients with primary aldosteronism 1 year after adrenalectomy. Our study in patients with primary aldosteronism was aimed at comparing the long-term effect of adrenalectomy vs. spironolactone therapy on common carotid IMT regression. METHOD: Forty-two patients with confirmed primary aldosteronism (21 with aldosterone-producing adenoma treated by unilateral laparoscopic adrenalectomy, 21 treated with spironolactone) were investigated by carotid ultrasound at baseline and 1 and 6 years after the specific treatment. RESULTS: There was a decrease in common carotid IMT from 0.956 ± 0.140 to 0.900 ± 0.127 mm (-5.9%; P < 0.05) at 1 year and to 0.866 ± 0.130 mm (-9.4%; P < 0.01) at 6 years after adrenalectomy; in the spironolactone group, common carotid IMT decreased from 0.917 ± 0.151 to 0.900 ± 0.165 mm (-1.8%; NS) at 1 year and to 0.854 ± 0.176 mm (-6.8%; P < 0.01) at 6 years of treatment. The magnitude of improvement at 1 year was significantly higher (by 70%; P < 0.05) in the adrenalectomy group; however, the difference (by 27%) became nonsignificant at 6 years. Comparing the adrenalectomy and spironolactone groups, there was no significant difference in blood pressure decrease after treatment. CONCLUSION: In the long term, spironolactone therapy in patients with primary aldosteronism had significant effect on regression of IMT, which was comparable to surgical treatment in patients with unilateral forms of primary aldosteronism.

• MeSH
• adenom komplikace   chirurgie   MeSH
• adrenalektomie * MeSH
• aldosteron krev   MeSH
• antagonisté mineralokortikoidních receptorů terapeutické užití   MeSH
• dospělí MeSH
• hyperaldosteronismus farmakoterapie   etiologie   chirurgie   MeSH
• intimomediální šíře tepenné stěny * MeSH
• krevní tlak MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory nadledvin komplikace   chirurgie   MeSH
• následné studie MeSH
• prospektivní studie MeSH
• senioři MeSH
• spironolakton terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• aldosteron MeSH
• antagonisté mineralokortikoidních receptorů MeSH
• spironolakton MeSH

Catheter-based renal denervation (RD) has been introduced recently as a potentially effective invasive treatment of refractory hypertension. The proportion of patients with severe hypertension suitable for RD is not clear. The aim of this study was to identify what percentage of patients has truly resistant essential hypertension and are thus potentially eligible for RD. We investigated 205 consecutive patients referred to a university hypertension center for severe hypertension within 12 months. Ambulatory 24-h blood pressure (BP) monitoring (24 h ABPM), secondary hypertension screening and compliance to treatment testing (by use of plasma drug level measurements) were performed in all patients. Fifty-seven patients (27.8%) did not have truly resistant hypertension (RH) based on clinical BP. Among the remaining 122 patients (59.5%) with RH confirmed by 24 h ABPM, 50 patients (24.4% of the original cohort) had a secondary cause of hypertension and in 27 (13.2%) non-compliance to treatment was confirmed. Thus, only 45 patients (22%) had truly resistant essential hypertension and were considered for RD. Only one-third (n=15, 7.3% of the original cohort) was, however, finally referred for RD (14 were excluded due to contraindications for RD and 16 refused the invasive treatment). In conclusion, thorough examination of severe hypertension including 24 h ABPM, secondary hypertension exclusion and drug compliance testing before considering RD reveals that majority of these patients are not suitable for RD. Specifically, compliance to treatment testing should be mandatory in order to identify eligible candidates for RD.

• MeSH
• adherence k farmakoterapii * MeSH
• ambulantní monitorování krevního tlaku MeSH
• antihypertenziva terapeutické užití   MeSH
• autonomní denervace metody   MeSH
• dospělí MeSH
• hypertenze diagnóza   farmakoterapie   patofyziologie   chirurgie   MeSH
• konziliární vyšetření a konzultace MeSH
• krevní tlak účinky léků   MeSH
• ledviny inervace   MeSH
• léková rezistence * MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování léčiv MeSH
• nemocnice univerzitní MeSH
• prediktivní hodnota testů MeSH
• retrospektivní studie MeSH
• senioři MeSH
• určení vhodnosti pacienta MeSH
• výběr pacientů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antihypertenziva MeSH