Branislav Štrauch

Prevalence of primary hyperaldosteronism in moderate to severe hypertension in the Central Europe region.

Recently published studies from different parts of the world report significantly higher prevalence of primary hyperaldosteronism (PH) in hypertensives (ranging from 5 to 25%) than the previously accepted figures. There have been no data so far about the prevalence of PH in Central Europe. Therefore, we have undertaken this study to evaluate the prevalence of PH in patients with moderate to severe hypertension referred to a hypertension unit in the Czech Republic, together with the determination of the percentage of different subtypes of PH including familial forms. In addition to that, we have evaluated the prevalence of other types of secondary forms of hypertension.A total of 402 consecutive patients (230 females and 172 males) with hypertension, referred to our hypertension unit, were studied. Positive aldosterone/renin ratio (ARR, (ng/100 ml)/(ng/ml/h)) ⩾50 as a more strict marker of PH was found in 87 patients (21.6%), 30% of them were normokalaemic. The diagnosis of PH was later confirmed in 77 cases (89%); the total prevalence of PH was thus 19%. PH consisted of the following forms: idiopathic hyperaldosteronism 42%, unilateral aldosterone-producing adenoma 36%, unilateral hyperplasia 7%, nonclassifiable PH (refused operation/adrenal venous sampling) 13%, familial hyperaldosteronism type 1.2%. The prevalence of other types of secondary hypertension was as follows: pheochromocytoma 5%, renovascular 4.5%, hypercortisolism 2%, renal 0.75%.In conclusion, we have noted that PH in the Central Europe region (Czech Republic) is the most frequent form of endocrine hypertension with a considerably high prevalence in moderate to severe hypertension. Application of more strict criteria raises the probability of correct diagnosis of PH including the early normokalaemic stages of PH.

Randomized Comparison of Renal Denervation Versus Intensified Pharmacotherapy Including Spironolactone in True-Resistant Hypertension Six-Month Results From the Prague-15 Study

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.

Precise assessment of noncompliance with the antihypertensive therapy in patients with resistant hypertension using toxicological serum analysis

Background: The aim of our study was to assess the prevalence of pseudo-resistance caused by noncompliance with treatment among patients with severe resistant hypertension and to analyze the contributing factors. Method: Three hundred and thirty-nine patients (195 men) with resistant essential hypertension were studied. The first group consisted of 176 patients admitted for hospitalization for exclusion of a secondary cause to our hypertension centre (103 men); the second one consisted of 163 out-patients (92 men) investigated for the first time in an out-patient hypertension clinic. Unplanned blood sampling for assessment of serum antihypertensive drug concentrations by means of liquid chromatography–mass spectrometry was performed in all patients. Results: Our main finding is a surprisingly low compliance with drug treatment in out-patients with resistant hypertension (23% partially noncompliant and 24% totally noncompliant – in total, 47% prevalence of noncompliance). Eighty-one percent of hospitalized patients were positive, in 10% the results were partially positive and in 9% of the patients, the drugs were all negative. The compliance among hospitalized patients was probably better due to lower numbers of prescribed drugs and expected thorough investigation. More frequently, noncompliance was found in nonworking (potential purpose-built behaviour), younger and less well educated patients. The most frequent noncompliance was to doxazosine, spironolactone and hydrochlorothiazide. We have observed a surprisingly low compliance with treatment among out-patients with severe hypertension. Conclusion: We conclude that the evaluation of antihypertensive drugs concentrations is a useful and precise method for assessment of noncompliance in patients with resistant hypertension. This evaluation is useful before starting the diagnostic work-up of secondary forms of hypertension and before assignment patients into protocols with new therapy modalities such as renal denervation.

High incidence of cardiovascular complications in pheochromocytoma.

Excess of catecholamines in pheochromocytoma is usually accompanied with classical symptoms and signs. In some cases, severe cardiovascular complications (e. g., heart failure, myocardial infarction) may occur. We performed a retrospective analysis focused on the incidence of cardiovascular complications (classified as follows: arrhythmias, myocardial involvement or ischemia and atherosclerosis, cerebrovascular impairment) before the establishment of diagnosis of pheochromocytoma among 145 subjects treated in our hospital. Cardiovascular complications occurred in 28 subjects, but these subjects did not differ significantly from subjects without complications in age, gender, body mass index, paroxysmal symptoms, symptom duration, tumor dimension, catecholamine secretory phenotype, and incidence of hypertension or diabetes mellitus. Arrhythmias occurred in 15 subjects (2 arrhythmia types in 2 subjects): atrial fibrillation in 9 subjects, supraventricular tachycardia in 3 cases, and ventricular tachycardia in 2 patients. Significant bradycardia was noted in 3 cases. Five subjects presented with heart failure with decreased systolic function (takotsubo-like cardiomyopathy found in 2 cases). One subject suffered from hypertrophic obstructive cardiomyopathy. Seven subjects presented with non-ST-segment elevation myocardial infarction, 2 patients with ST-segment myocardial infarction, and 1 subject underwent coronary artery bypass grafting. Two subjects suffered from significant peripheral atherosclerosis. Among cerebrovascular complications, transient ischemic attack was found in 3 cases, 2 subjects suffered from stroke, and subarachnoidal bleeding occurred in 1 patient. One subject suffered from diffuse neurological impairment due to multiple ischemic white matter lesions. These data show relatively high incidence of cardiovascular complications (19.3%) in subjects with pheochromocytoma. Early diagnosis is mandatory to prevent severe complications in pheochromocytoma.

Adrenalectomy Improves Arterial Stiffness in Primary Aldosteronism

BackgroundAldosterone has been shown to substantially contribute to the accumulation of different types of collagen fibers and growth factors in the arterial wall, which increase wall stiffness. We previously showed that arterial wall stiffness is increased in primary aldosteronism (PA) independently of concomitant hypertension. This study was aimed at assessing the effects of specific treatment of PA on the arterial stiffness.MethodsTwenty-nine patients with confirmed PA (15 with aldosterone-producing adenoma treated by unilateral laparoscopic adrenalectomy, 14 treated with spironolactone (mainly idiopathic aldosteronism) were investigated by Sphygmocor applanation tonometer (using measurement of carotid-femoral pulse wave velocity (PWV) and augmentation index (AI)) at the time of the diagnosis and then approximately 1 year after the specific treatment.ResultsThe office blood pressure (BP) decreased from 167 +/- 18/96 +/- 9 to 136 +/- 12/80 +/- 7 mm Hg after adrenalectomy (P = 0.001), and from 165 +/- 21/91 +/- 13 to 151 +/- 22/88 +/- 8 mm Hg (not significant (n.s.)) on spironolactone. The mean 24-h BP decreased from 150 +/- 18/93 +/- 11 mm Hg to 126 +/- 17/80 +/- 10 mm Hg after adrenalectomy (P < 0.01), and from 155 +/- 16/94 +/- 12 to 139 +/- 18/88 +/- 8 mm Hg (n.s.) on spironolactone. The PWV significantly decreased after surgery from 9.5 +/- 2.7 m/s to 7.6 +/- 2 m/s (P = 0.001), and the AI (recalculated for heart rate 75/min) decreased significantly from 27 +/- 10 to 19 +/- 9% (P < 0.01). On the other hand, we did not find significant change of arterial stiffness indices in patients treated with spironolactone (PWV: 9.3 +/- 1.6 m/s vs. 8.8 +/- 1.3 m/s (n.s.); AI: 25 +/- 9% vs. 25 +/- 8% (n.s.)).ConclusionsSurgical but not conservative treatment of PA led to a significant decrease of BP and arterial stiffness parameters.American Journal of Hypertension (2008). doi:10.1038/ajh.2008.243American Journal of Hypertension (2008); 21, 10, 1086-1092. doi 10.1038/ajh.2008.243.

Diurnal blood pressure variation in pheochromocytoma, primary aldosteronism and Cushing's syndrome

We examined circadian blood pressure (BP) variation (expressed as a relative night-time BP decline) in subjects with primary aldosteronism (78 patients), pheochromocytoma (n=45) and Cushings syndrome (n=18). Subjects with aldosterone-producing adenoma (n=21) and pheochromocytoma (n=27) were also investigated after the tumour removal. In all, 65 patients with essential hypertension served as a control group. The night-time BP decline was significantly attenuated in all three forms of endocrine hypertension compared to the control group (primary aldosteronism P<0.0001, pheochromocytoma P<0.0001 for systolic and diastolic BP and Cushings syndrome P<0.0001/<0.001 vs essential hypertension). In the case of pheochromocytoma, the absence of the night-time BP decrease was more prominent compared to the primary aldosteronism group (P=0.003/0.001) and for the diastolic BP also in comparison with the Cushings syndrome group (P=0.03). Tumour removal led in both groups to the restoration of the previously altered circadian rhythm (aldosterone-producing adenoma: P=0.0005/0.0009; pheochromocytoma: P=0.001/0.0007). Our study demonstrates a blunted circadian BP variation in all forms of adrenal hypertension in comparison with essential hypertension. This reduction of the night-time BP decrease was more prominent in pheochromocytoma than in primary aldosteronism or Cushings syndrome.

Increased blood pressure variability in pheochromocytoma compared to essential hypertension patients

Objective Catecholamines are responsible for short and long-lasting blood pressure (BP) elevations in pheochromocytoma. We investigated whether in patients with pheochromocytoma this catecholamine excess would result in higher BP variability in comparison with patients suffering from essential hypertension (EH). Design We examined retrospectively 54 (26 treated with α1-blockers) patients with pheochromocytoma (30 patients also investigated after tumour removal) and 108 (42 treated with α1-blockers) patients with EH. They all underwent 24-h ambulatory BP monitoring. To assess the BP variability, coefficient of BP variability (SD of average BP/average BP) was used. Results In subjects with pheochromocytoma, a higher coefficient of BP variability was shown compared with EH during the 24-h period (0.12 ± 0.03 versus 0.10 ± 0.02, P = 0.003 for systolic BP in the treated group) and mainly during the daytime (0.11/0.13 ± 0.04/0.03 versus 0.09/0.11 ± 0.03/0.04, P = 0.007/0.06 for systolic/diastolic BP in the untreated group and 0.12/0.13 ± 0.04/0.04 versus 0.09/0.12 ± 0.04/0.02, P < 0.001/0.01 in the treated group). Tumour removal resulted in a decrease of the previously increased 24-h (0.11 ± 0.03 versus 0.10 ± 0.03, P = 0.04) and daytime (0.11 ± 0.03 versus 0.09 ± 0.03, P = 0.03) coefficient of systolic BP variation. Twenty-seven subjects with pheochromocytoma and inverted circadian BP rhythm (night-time BP > daytime BP) had a significantly higher 24-h (0.13 ± 0.03 versus 0.10 ± 0.03, P < 0.001 for systolic BP) and daytime coefficient of BP variation (0.13/0.15 ± 0.04/0.03 versus 0.09/0.12 ± 0.02/0.02, P < 0.001/<0.001) and also a higher occurrence of the isolated excretion of norepinephrine (14 versus seven subjects, P = 0.05) compared with the 27 subjects with pheochromocytoma without inverted circadian BP rhythm. Conclusion The excess of catecholamines in patients with pheochromocytoma is associated with higher long-term BP variability in comparison with patients suffering from EH especially in subjects with inverted circadian BP rhythm. Tumour removal resulted in the amelioration of the previously increased BP variability.

Role of Adding Spironolactone and Renal Denervation in True Resistant Hypertension: One-Year Outcomes of Randomized PRAGUE-15 Study.

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.

Pulse wave velocity in primary hyperparathyroidism and effect of surgical therapy

The study was aimed at investigating the arterial stiffness assessed by aortic pulse wave velocity (PWV) in the presence of primary hyperparathyroidism (PH), with and without concomitant hypertension. Subsequently, we examined the effect of parathyroidectomy (PTX) on arterial stiffness. A total of 28 patients with PH and concomitant hypertension, and 16 with PH without hypertension were investigated in comparison with 28 essential hypertensive patients and 18 healthy controls, respectively. Patients were matched for age, blood pressure (BP), body mass index, lipid profile and fasting glucose. Six months after PTX, 15 patients were examined again (hypertensive as well as normotensive). PWV was obtained using the SphygmoCor applanation tonometer (AtCor Medical, West Ryde, Australia). PWV was significantly higher in patients with PH and hypertension when compared with patients with essential hypertension (10.1 vs. 8.5 m s−1, P=0.013). PWV remained significant even after adjustment for age and BP (P=0.02). Similarly, PWV was significantly higher in PH patients without hypertension in comparison with healthy controls (7.6 vs. 5.8 m s−1, P<0.001). Six months after surgery, in addition to a normalization of calcium metabolism, a significant decrease in systolic BP (131 vs. 123 mm Hg, P=0.004) and PWV (9.1 vs. 8.5 m s−1, P=0.024) was observed. After adjusting for BP reduction, the decrease in PWV appeared non-significant. Our data indicate that PH increases PWV as a marker of arterial stiffness, in both hypertensive and non-hypertensive patients. However, neither the calcium serum level nor the parathyroid hormone level has been associated with PWV. Specific treatment by PTX significantly decreases PWV, which may be determined primarily by improved BP control after surgery.

Risk Factors for Nonadherence to Antihypertensive Treatment

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 (P<0.001) in the UK and Czech populations, respectively. The odds of nonadherence to diuretics were the highest among 5 classes of antihypertensive medications (P⩽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.