Nonadherence to antihypertensive treatment is a critical contributor to suboptimal blood pressure control. There are limited and heterogeneous data on the risk factors for nonadherence because few ...studies used objective-direct diagnostic methods. We used high-performance liquid chromatography-tandem mass spectrometry of urine and serum to detect nonadherence and explored its association with the main demographic- and therapy-related factors in 1348 patients with hypertension from 2 European countries. The rates of nonadherence to antihypertensive treatment were 41.6% and 31.5% in the UK and Czech populations, respectively. Nonadherence was inversely related to age and male sex. Each increase in the number of antihypertensive medications led to 85% and 77% increase in nonadherence (
<0.001) in the UK and Czech populations, respectively. The odds of nonadherence to diuretics were the highest among 5 classes of antihypertensive medications (
≤0.005 in both populations). The predictive model for nonadherence, including age, sex, diuretics, and the number of prescribed antihypertensives, showed area under the curves of 0.758 and 0.710 in the UK and Czech populations, respectively. The area under the curves for the UK model tested on the Czech data and for the Czech model tested on UK data were calculated at 0.708 and 0.756, respectively. We demonstrate that the number and class of prescribed antihypertensives are modifiable risk factors for biochemically confirmed nonadherence to blood pressure-lowering therapy. Further development of discriminatory models incorporating these parameters might prove clinically useful in assessment of nonadherence in countries where biochemical analysis is unavailable.
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.Hypertension is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.
Abstract
Context
Impaired diurnal blood pressure (BP) variability is related to higher cardiovascular risk.
Objective
To assess diurnal variability of BP and its relation to target organ damage (TOD) ...and catecholamine phenotype in a consecutive sample of pheochromocytoma/paraganglioma (PPGL).
Design
We included 179 patients with PPGL All patients underwent 24 hours of ambulatory BP monitoring to determine dipping status. Differences in plasma metanephrine or urine adrenaline were used to distinguish catecholamine biochemical phenotype. To evaluate TOD, renal functions, presence of left ventricle hypertrophy (LVH), and the subgroup (n = 111) carotid-femoral pulse wave velocity (PWV) were assessed. Structural equation modeling was used to find the relationship among nocturnal dipping, catecholamine phenotype, and TOD parameters.
Results
According to the nocturnal dipping, patients were divided into the three groups: dippers (28%), nondippers (40%), and reverse dippers (32%). Reverse dippers were older (P < 0.05), with a higher proportion of noradrenergic (NA) phenotype (P < 0.05), a higher prevalence of diabetes mellitus (P < 0.05), and sustained arterial hypertension (P < 0.01) and its duration (P < 0.05), as opposed to the other groups. All parameters of TOD were more pronounced only in reverse dippers compared with nondippers and dippers. The presence of NA phenotype (=absence of adrenaline production) was associated with reverse dipping and TOD (LVH and PWV).
Conclusions
Patients with reverse dipping had more substantial TOD compared with other groups. The NA phenotype plays an important role, not only in impaired diurnal BP variability but also independently from dipping status in more pronounced TOD of heart and vessels.
Predominantly pure noradrenaline, without concomitant adrenaline overproduction, has a long-term effect on the cardiovascular system in pheochromocytoma/functional paraganglioma.
This prospective, randomized, open-label multicenter trial evaluated the efficacy of catheter-based renal denervation (Symplicity, Medtronic) versus intensified pharmacological treatment including ...spironolactone (if tolerated) in patients with true-resistant hypertension. This was confirmed by 24-hour ambulatory blood pressure monitoring after excluding secondary hypertension and confirmation of adherence to therapy by measurement of plasma antihypertensive drug levels before enrollment. One-hundred six patients were randomized to renal denervation (n=52), or intensified pharmacological treatment (n=54) with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. A significant reduction in 24-hour average systolic blood pressure after 6 months (−8.6 95% cofidence interval−11.8, −5.3 mm Hg; P<0.001 in renal denervation versus −8.1 95% cofidence interval−12.7, −3.4 mm Hg; P=0.001 in pharmacological group) was observed, which was comparable in both groups. Similarly, a significant reduction in systolic office blood pressure (−12.4 95% cofidence interval−17.0, −7.8 mm Hg; P<0.001 in renal denervation versus −14.3 95% cofidence interval−19.7, −8.9 mm Hg; P<0.001 in pharmacological group) was present. Between-group differences in change were not significant. The average number of antihypertensive drugs used after 6 months was significantly higher in the pharmacological group (+0.3 drugs; P<0.001). A significant increase in serum creatinine and a parallel decrease of creatinine clearance were observed in the pharmacological group; between-group difference were borderline significant. The 6-month results of this study confirmed the safety of renal denervation. In conclusion, renal denervation achieved reduction of blood pressure comparable with intensified pharmacotherapy.
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.
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.
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.
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.
Objective: Primary aldosteronism (PA) may present at younger age and may thus complicate pregnancy. Our aim was to identify female patients in whom PA was diagnosed after pregnancy complicated with ...hypertension and to analyze possible hypertension-related complications during pregnancy. Methods: We performed retrospective analysis of female patients with PA diagnosed and treated at our Department who were pregnant before the diagnosis of PA. Results: We found 14 patients with PA (age at diagnosis 32.2 ± 4.2 years, hypertension duration 5.4 ± 3.6 years) suffering from hypertension 3 (IQR 0, 4) years before pregnancy (6 patients had hypertension diagnosed during pregnancy). Three subjects were pregnant twice, and 1 patient had been pregnant three times before the final diagnosis of PA was made. Ten subjects delivered by Caesarean section (in 3 cases due to early-onset preeclampsia and 2 subjects due to significantly increased blood pressure), and 9 cases spontaneously (1 subject complicated twice due to late-onset preeclampsia). Preterm delivery occurred in 5 cases – the earliest one in the sixth month of gestation. Subsequent diagnosis of PA (sometimes with a long delay up to a maximum of 12 years) was made on the basis of significantly low potassium values (2.7 ± 0.4 mmol/L; 2 subjects even suffered from muscle cramps) and hypertension (mostly moderate), elevated plasma/serum aldosterone (54.1 ± 20.2 ng/dL) and suppressed plasma renin activity (0.4 ± 0.2 ng/mL/h) or plasma renin (1.9 ± 1.6 ng/L). Thirteen subjects underwent laparoscopic adrenalectomy (in all but 2 cases, diagnosis of a large cortical adenoma 16 ± 5.9 mm was made), and 1 subject was classified with bilateral hyperplasia according to adrenal venous sampling. Operation normalized BP in 10 subjects and improved BP control in the remaining 3 subjects. Two patients became pregnant after adrenalectomy, and their pregnancies were uneventful. Conclusion: PA is associated with a high rate of pregnancy-related complications. The most frequent complication is preeclampsia, in some cases leading to preterm delivery. The optimal prevention of these complications is early diagnosis of PA, and in these particular hypertensive cases, the awareness of hypokalemia.
This randomized, multicenter study compared the relative efficacy of renal denervation (RDN) versus pharmacotherapy alone in patients with true resistant hypertension and assessed the effect of ...spironolactone addition. We present here the 12-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. Twelve-month results are available in 101 patients. The intention-to-treat analysis found a comparable mean 24-hour systolic blood pressure decline of 6.4 mm Hg, P=0.001 in RDN versus 8.2 mm Hg, P=0.002 in the pharmacotherapy group. Per-protocol analysis revealed a significant difference of 24-hour systolic blood pressure decline between complete RDN (6.3 mm Hg, P=0.004) and the subgroup where spironolactone was added, and this continued within the 12 months (15 mm Hg, P= 0.003). Renal artery computed tomography angiograms before and after 1 year post-RDN did not reveal any relevant changes. This study shows that over a period of 12 months, RDN is safe, with no serious side effects and no major changes in the renal arteries. RDN in the settings of true resistant hypertension with confirmed compliance is not superior to intensified pharmacological treatment. Spironolactone addition (if tolerated) seems to be more effective in blood pressure reduction.
: Pheochromocytomas (PHEO) are tumors arising from chromaffin cells from the adrenal medulla, having the ability to produce, metabolize and secrete catecholamines. The overproduction of ...catecholamines leads by many mechanisms to the impairment in the left ventricle (LV) function, however, endocardial measurement of systolic function did not find any differences between patients with PHEO and essential hypertension (EH). The aim of the study was to investigate whether global longitudinal strain (GLS) derived from speckle-tracking echocardiography can detect catecholamine-induced subclinical impairments in systolic function.
: We analyzed 17 patients (10 females and seven males) with PHEO and 18 patients (nine females and nine males) with EH. The groups did not differ in age or in 24-h blood pressure values.
: The patients with PHEO did not differ in echocardiographic parameters including LV ejection fraction compared to the EH patients (0.69 ± 0.04 vs. 0.71 ± 0.05; NS), nevertheless, in spackle-tracking analysis, the patients with PHEO displayed significantly lower GLS than the EH patients (-14.8 ± 1.5 vs. -17.8 ± 1.7;
< 0.001).
: Patients with PHEO have a lower magnitude of GLS than the patients with EH, suggesting that catecholamines induce a subclinical decline in LV systolic function.
Context:Catecholamines may contribute to the accumulation of collagen fibers and extracellular matrix in the arterial and myocardial wall due to various mechanisms. Reversibility of this process has ...not been studied on both structures simultaneously.Objective:This study aimed to clarify the long-term effect of catecholamines’ excess normalization on carotid and myocardial wall changes in patients with pheochromocytoma or functional paraganglioma (PHEO) after tumor removal.Design, Settings and Patients:Carotid intima-media thickness (IMT) and left ventricle (LV) mass index were studied in 50 patients with PHEO before tumor removal and 5 years after tumor removal and in 50 blood pressure- and age-matched essential hypertensive patients (EH) before follow-up and after 5 years of follow-up.Main outcome measures:Common carotid IMT (CCA-IMT) and LV mass indexed to the lean body mass (LBM).Results:Elimination of catecholamine excess in the PHEO group resulted in a significant decrease in CCA-IMT and LV mass index from 0.86 ± 0.17 to 0.83 ± 0.18 mm (P <0.05) and from 3.2 ± 0.9 to 2.9 ± 0.9 g/LBM (P <0.001), respectively. In contrast, CCA-IMT and LV mass index increased significantly from 0.78 ± 0.14 to 0.81 ± 0.15 mm (P <0.05) and from 3.1 ± 0.7 to 3.2 ± 0.6 g/LBM (P <0.05), respectively, in patients with essential hypertension.Conclusion:In patients with PHEO, carotid IMT and LV mass index can significantly regress after the tumor removal, in contrast to the impairment of these parameters in patients with EH during the same long-term period.
OBJECTIVES:The randomized, multicentre study compared the efficacy of renal denervation (RDN) versus spironolactone addition in patients with true resistant hypertension. We present the 24-month ...data.
METHODS:A total of 106 patients with true resistant hypertension were enrolled in this study52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline SBP of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Two-year data are available in 86 patients. Spironolactone addition, as crossover after 1 year, was performed in 23 patients after RDN, and spironolactone addition followed by RDN was performed in five patients.
RESULTS:Similar and comparable reduction of 24-h SBP after RDN or spironolactone addition after randomization was observed, 9.1 mmHg (P = 0.001) and 10.9 mmHg (P = 0.001), respectively. Similar decrease of office blood pressure (BP) was observed, 17.7 mmHg (P < 0.001) versus 14.1 mmHg (P < 0.001), whereas the number of antihypertensive drugs did not differ significantly between groups. Crossover analysis showed nonsignificantly better efficacy of spironolactone addition in 24-h SBP and office SBP reduction than RDN (3.7 mmHg, P = 0.27 and 4.6 mmHg, P = 0.28 in favour of spironolactone addition, respectively). Meanwhile, the number of antihypertensive drugs was significantly increased after spironolactone addition (+0.7, P = 0.001).
CONCLUSION:In the settings of true resistant hypertension, spironolactone addition (if tolerated) seems to be of better efficacy than RDN in BP reduction over a period of 24 months. However, by contrast to the 12-month results, BP changes were not significantly greater.
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