Combination antihypertensive therapy in clinical practice. The analysis of 1254 consecutive patients with uncontrolled hypertension.

The aim of the study was to analyze the clinical use of different types of combination therapy in a large sample of consecutive patients with uncontrolled hypertension referred to Hypertension Centre. We performed a retrospective analysis of combination antihypertensive therapy in 1254 consecutive patients with uncontrolled hypertension receiving at least triple-combination antihypertensive therapy. Among the most prescribed antihypertensive classes were renin-angiotensin blockers (96.8%), calcium channel blockers (82.5%), diuretics (82.0%), beta-blockers (73.0%), centrally acting drugs (56.0%) and urapidil (24.1%). Least prescribed were spironolactone (22.2%) and alpha-1-blockers (17.1%). Thiazide/thiazide-like diuretics were underdosed in more than two-thirds of patients. Furosemide was prescribed in 14.3% of patients treated with diuretics, while only indicated in 3.9%. Inappropriate combination therapy was found in 40.4% of patients. Controversial dual and higher blockade of renin-angiotensin system occurred in 25.2%. Incorrect use of a combination of two antihypertensive drugs with the similar mechanism of action was found in 28.1%, most commonly a combination of two drugs with central mechanism (13.5%). In conclusion, use of controversial or incorrect combinations of drugs in uncontrolled hypertension is common. Diuretics are frequently underdosed and spironolactone remains neglected in general practice. The improper combination of antihypertensive drugs may contribute to uncontrolled hypertension.

Inflammatory markers in primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. The unfavorable cardiometabolic profile may be due to aldosterone-mediated activation of inflammatory cells, circulatory cytokines and activation of collagen synthesis in the vessel wall. Aim of our study was to evaluate differences in the levels of hsCRP, IL-6, TNF-alpha and N-terminal propeptide of collagen I (PINP) in patients with PA and essential hypertension (EH) as a control group, and between the subtypes of PA (aldosterone producing adenoma - APA, idiopathic hyperaldosteronism - IHA). We studied 28 patients with PA (IHA - 10 patients, APA - 12 patients, 6 unclassified) and 28 matched patients with EH. There were no differences in the levels of inflammatory markers between the followed groups [EH vs. PA: TNF-alpha (5.09 [3.68-6.32] vs. 4.84 [3.62-6.50] pg/ml), IL-6 (0.94 [0.70-1.13] vs. 0.97 [0.71-1.28] pg/ml), hsCRP (0.53 [0.25-1.54] vs. 0.37 [0.31-0.61] mg/l), leukocytes (6.35+/-1.42 vs. 5.97+/-1.29 10(9) l); APA vs. IHA: TNF-alpha (4.54 [3.62-7.03] vs. 5.19 [4.23-5.27] pg/ml), IL-6 (0.96 [0.63-1.21] vs. 0.90 [0.65-1.06] pg/ml), hsCRP (0.34 [0.29-0.47] vs. 0.75 [0.36-1.11] mg/l), leukocytes (6.37+/-1.41 vs. 5.71+/-1.21 10(9) l)]. Significant differences in the levels of PINP between PA and EH group were observed (35.18 [28.46-41.16] vs. 45.21 [36.95-62.81] microg/l, p

Biochemical Testing After Pheochromocytoma Removal: How Early?

Pheochromocytomas are catecholamine-producing tumors with typical clinical presentation. Tumor resection is considered as an appropriate treatment strategy. Due to its unpredictable clinical behavior, biochemical testing is mandatory to confirm the success of tumor removal after surgery. The aim of the study was to investigate the feasibility of a shorter interval of postoperative testing (earlier than the recommended 2-4 weeks according to recently published Guidelines). We investigated 81 patients with pheochromocytoma before and after surgery. Postoperative examination was performed of stable subjects after their transport from the surgical to the internal ward (7.1±2.2 days after surgery). Plasma metanephrines were used for the diagnosis of pheochromocytoma and confirmation of successful tumor removal. All subjects with pheochromocytoma had markedly elevated plasma metanephrines before surgery. No correlation between postoperative interval (the shortest being 3 days) and plasma metanephrine levels was found. Postoperative plasma metanephrine levels did not differ significantly from those taken at the one-year follow-up. In conclusion, we have shown that early postoperative diagnostic workup of subjects with pheochromocytoma is possible and may thus simplify early postoperative management of this clinical condition.

Importance of thorough investigation of resistant hypertension before renal denervation: should compliance to treatment be evaluated systematically?

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.

Peripheral arterial stiffness in primary aldosteronism.

Aldosterone overproduction increases arterial wall stiffness by accumulation of different types of collagen fibres and growth factors. Our previous studies showed that central (aortic) arterial stiffness is increased in primary aldosteronism (PA) independently of concomitant hypertension and that these changes might be reversible after successful adrenalectomy. There is limited data available on the potential impact of mineralocorticoid overproduction on the deterioration of peripheral arterial stiffness. The current study was thus aimed at investigating the effect of aldosterone overproduction on peripheral arterial stiffness assessed by peripheral (femoral-ankle) pulse wave velocity (PWV) in PA patients compared with essential hypertension (EH) patients. Forty-nine patients with confirmed PA and 49 patients with EH were matched for age, blood pressure, body mass index, lipid profile, and fasting glucose. PWV was obtained using the Sphygmocor applanation tonometer. Both peripheral and central PWV were significantly higher in PA patients compared to EH patients, while clinical blood pressures were similar. Plasma aldosterone level was the main predictor of peripheral PWV in PA. Our data indicate aldosterone overproduction in PA does not preferentially affect central arterial system. Fibroproliferative effect of higher aldosterone levels lead to alteration of central-elastic as well as peripheral-muscular arteries with subsequent increase in its stiffness.

Vascular disturbances in primary aldosteronism: clinical evidence.

Primary aldosteronism (PA) is a common form of arterial hypertension with a high prevalence of cardiovascular complications. In patients with PA, complex mechanisms may lead to functional and/or structural abnormalities of the blood vessel wall. Clinical evidence indicates that patients with PA may have immune cell activation, increased oxidative stress, impaired endothelial function and vascular remodeling. Activation of fibroproliferation has been found in resistant arteries of patients with PA. Subjects with PA compared to essential hypertensives with similar blood pressure levels have increased intima-media thickness and arterial stiffness as measured by pulse wave velocity. These functional and morphological changes can be modified by an increased sodium intake. Vascular remodeling in PA may indicate a poor response to specific therapy with lower probability of cure and/or normalization of blood pressure. Early diagnosis of PA before blood vessel wall disturbances develop is of utmost importance.

Have main types of primary aldosteronism different phenotype?

Primary aldosteronism (PA) is the most common cause of endocrine hypertension with a high frequency of cardiovascular complications. We found in our previous study higher occurrence of metabolic disturbances in patients with idiopathic hyperaldosteronism (IHA) compared to subjects with aldosterone-producing adenoma (APA). The aim of our present study is to evaluate potential differences in the frequency of end-organ damage (arterial stiffness and microalbuminuria) between two main types of PA. The diagnosis of the particular form of PA was based on adrenal venous sampling and/or histopathological examination. We analyzed clinical and laboratory data from 72 patients with PA (36 with IHA, 36 with APA). The arterial stiffness was expressed as the carotid-femoral pulse wave velocity (PWV) and the renal damage as urinary albumin excretion levels (UAE). Patients with IHA had significantly (p<0.03) higher prevalence of metabolic syndrome (17 % in APA, 35 % in IHA), higher triglycerides (1.37+/-0.71 mmol/l in APA, 1.85+/-0.87 mmol/l in IHA), lower HDL cholesterol (1.25+/-0.28 mmol/l in APA, 1.06+/-0.25 mmol/l in IHA), higher PWV (7.91+/-1.61 m/s in APA, 8.99+/-1.77 m/s in IHA) and higher UAE (12.93+/-2.21 mg/l in APA, 28.09+/-6.66 mg/l in IHA). It seems that patients with IHA may have a slightly different phenotype compared to APA.

[Diagnostic of secondary hypertension in clinical practice]. / Diagnostika sekundární hypertenze v ambulantní praxi.

Arterial hypertension is a common worldwide disease with a prevalence of approximately 26%. Secondary cause is known in 5-10% of patients with hypertension. We should think of secondary hypertension in all patients with resistant hypertension, in patients with sudden deterioration in the control of hypertension and in patients with laboratory and clinical signs of diseases associated with secondary hypertension. It is important to distinguish between secondary hypertension and pseudo-resistance (noncompliance to treatment, white coat syndrome). Secondary causes of hypertension can be divided into endocrine (primary aldosteronism, pheochromocytoma, hypercortisolism, hyperparathyreoidism), renal - renovascular and renal parenchymal hypertension, and other causes as sleep apnoe syndrome, hypertension in pregnancy, coarctation of the aorta and intracranial tumors.

The prevalence of metabolic syndrome and its components in two main types of primary aldosteronism.

Metabolic syndrome (MS) is frequent clinical condition in patients with hypertension. Primary aldosteronism (PA) is a common form of secondary hypertension. This study was aimed at investigating the prevalence of the MS and its components in the two major forms of PA, in unilateral aldosterone-producing adenoma (APA) and bilateral aldosterone overproduction because of idiopathic hyperaldosteronism (IHA). The diagnosis of the particular form of PA was based on adrenal venous sampling and/or successful surgery confirmed by histopathological examination. We analyzed clinical and laboratory data from 100 patients with PA (50 patients with IHA and 50 patients with APA) and from 90 patients with essential hypertension (EH). Metabolic profiles of patients with bilateral form of PA (because of IHA) were similar to EH, but differed from those in patients with unilateral form of PA (APA). The prevalence of the MS (62% in IHA, 34% in APA and 56% in EH), the body mass index value (30±4 kg m(-2) in IHA, 27±5 kg m(-2) in APA and 29±5 kg m(-2) in EH) and triglycerides levels (1.9±0.9 mmol l(-1) in IHA,1.4±0.8 mmol l(-1) in APA and 2.01±1.39 mmol l(-1) in EH) were all significantly (P<0.05) higher in IHA compared with APA patients. Metabolic profile of patients with bilateral form of PA (because of IHA) is similar to EH in contrast to unilateral form of PA (APA).