Machine learning for classification of hypertension subtypes using multi-omics: A multi-centre, retrospective, data-driven study.

BACKGROUND: Arterial hypertension is a major cardiovascular risk factor. Identification of secondary hypertension in its various forms is key to preventing and targeting treatment of cardiovascular complications. Simplified diagnostic tests are urgently required to distinguish primary and secondary hypertension to address the current underdiagnosis of the latter. METHODS: This study uses Machine Learning (ML) to classify subtypes of endocrine hypertension (EHT) in a large cohort of hypertensive patients using multidimensional omics analysis of plasma and urine samples. We measured 409 multi-omics (MOmics) features including plasma miRNAs (PmiRNA: 173), plasma catechol O-methylated metabolites (PMetas: 4), plasma steroids (PSteroids: 16), urinary steroid metabolites (USteroids: 27), and plasma small metabolites (PSmallMB: 189) in primary hypertension (PHT) patients, EHT patients with either primary aldosteronism (PA), pheochromocytoma/functional paraganglioma (PPGL) or Cushing syndrome (CS) and normotensive volunteers (NV). Biomarker discovery involved selection of disease combination, outlier handling, feature reduction, 8 ML classifiers, class balancing and consideration of different age- and sex-based scenarios. Classifications were evaluated using balanced accuracy, sensitivity, specificity, AUC, F1, and Kappa score. FINDINGS: Complete clinical and biological datasets were generated from 307 subjects (PA=113, PPGL=88, CS=41 and PHT=112). The random forest classifier provided ∼92% balanced accuracy (∼11% improvement on the best mono-omics classifier), with 96% specificity and 0.95 AUC to distinguish one of the four conditions in multi-class ALL-ALL comparisons (PPGL vs PA vs CS vs PHT) on an unseen test set, using 57 MOmics features. For discrimination of EHT (PA + PPGL + CS) vs PHT, the simple logistic classifier achieved 0.96 AUC with 90% sensitivity, and ∼86% specificity, using 37 MOmics features. One PmiRNA (hsa-miR-15a-5p) and two PSmallMB (C9 and PC ae C38:1) features were found to be most discriminating for all disease combinations. Overall, the MOmics-based classifiers were able to provide better classification performance in comparison to mono-omics classifiers. INTERPRETATION: We have developed a ML pipeline to distinguish different EHT subtypes from PHT using multi-omics data. This innovative approach to stratification is an advancement towards the development of a diagnostic tool for EHT patients, significantly increasing testing throughput and accelerating administration of appropriate treatment. FUNDING: European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement No. 633983, Clinical Research Priority Program of the University of Zurich for the CRPP HYRENE (to Z.E. and F.B.), and Deutsche Forschungsgemeinschaft (CRC/Transregio 205/1).

Atherosclerotic cardiovascular disease burden in patients with familial hypercholesterolemia: interpretation of data on involvement of different vascular beds.

Familial hypercholesterolemia (FH) is a monogenic, autosomal dominant disorder that results in a rise of low­density lipoprotein cholesterol (LDL­C) and markedly increased risk of premature atherosclerotic cardiovascular disease. FH is relatively common, treatable, and its clinical course can be improved through early detection and timely initiation of lipid­lowering medications. The clinical picture of FH is highly variable, with a heterogeneous phenotype even within a single family, ranging from patients with very early onset of major cardiovascular events to those who do not develop overt cardiovascular disease even at an old age. We summarized studies indicating that atherosclerotic involvement in the coronary arteries and lower extremities is higher in FH patients than in the general population. There is a paucity of data regarding the relationship between FH and the incidence of atherosclerosis in other vascular beds. There are no studies systematically evaluating several vascular beds in asymptomatic patients with FH. Providing a systematic characteristic of patients with FH with respect to the presence and extent of atherosclerotic lesions in different vascular beds may have implications for daily practice not only for patients with FH but also for a larger number of patients with very high plasma LDL­C concentrations.

Fibrin clot properties and fibrinolysis in patients with endocrine hypertension due to aldosterone or catecholamines excess.

OBJECTIVE: The aim of the study was to investigate a new possible background of increased risk of cardiovascular events in two forms of endocrine hypertension: in primary aldosteronism (PA) and pheochromocytoma/paraganglioma (PPGL) in comparison to essential hypertension (EHT). CONTEXT: Prothrombotic properties of the fibrin clot structure, impaired fibrinolysis and enhanced thrombin generation have been reported to be associated with increased cardiovascular risk. DESIGN: Patients with PA and PPGL were evaluated at baseline and re-evaluated 3 months after causative treatment. At baseline PA and PPGL patients were compared to matched EHT patients and to healthy controls. PATIENTS: The study included 35 patients with PA, 16 patients with PPGL and two reference groups of patients with EHT (32 and 22 patients) and healthy controls (35 and 23 subjects). MEASUREMENTS: All subjects underwent evaluation according to the study protocol that included plasma fibrin clot permeability (Ks), clot lysis time, endogenous thrombin potential. RESULTS: There were no differences in clot structure and fibrinolytic activity in PA and PPGL patients as compared to matched patients with EHT, whereas all hypertensive groups were characterized by more compact fibrin clot structure, faster clot formation and enhanced thrombin generation in comparison to healthy controls. Both in PA and PPGL patients, fibrin clot properties and fibrinolytic parameters remained stable after the causative treatment. CONCLUSIONS: Patients with PA and PPGL are at a prothrombic state comparable to patients with EHT. The results suggest the higher risk of cardiovascular events observed in hypertensive PA and PPGL as compared to EHT is not mediated through investigated prothrombic mechanisms.

Intrarenal hemodynamics and kidney function in pheochromocytoma and paraganglioma before and after surgical treatment.

PURPOSE: Current evidence regarding renal involvement in pheochromocytoma and paraganglioma (PPGL) is scant. More accurate diagnostic methods, such as renal Doppler ultrasound for intrarenal hemodynamic studies, may provide more detailed information on renal function. It might be postulated that renal function in PPGL patients might be altered by high blood pressure and excess secretion of catecholamines. The aim of this prospective study was to assess intrarenal blood flow parameters in PPGL patients included in the prospective monoamine-producing tumour (PMT) study and to evaluate the effects of normalisation of catecholamine production after surgical treatment on long-term renal function. MATERIALS AND METHODS: Seventy consecutive patients (aged 46.5 ± 14.0 years) with PPGL were included. Forty-eight patients from the PMT study cohort, matched for age, gender, blood pressure level and presence of hypertension, served as a control group. Renal artery doppler ultrasound spectral analysis included mean resistance index (RRI) and pulsatility index (PI). Forty-seven patients completed 12 months follow-up. RESULTS: There were no differences in renal parameters such as RRI, PI and kidney function between PPGL and non-PPGL patients as assessed by renal ultrasound, serum creatinine, eGFR and albumin excretion rate. No correlations between kidney function parameters, intrarenal doppler flow parameters and plasma catecholamines were observed in PPGL patients. At 12 months after surgery, no differences in creatinine level, eGFR, albumin excretion rate, RI and PI were found as compared to baseline results. CONCLUSIONS: In contrast to patients with other forms of secondary hypertension, our study did not show differences in intrarenal blood flow parameters and renal function between PPGL and non-PPGL subjects. Intrarenal hemodynamics and renal function did not change after normalisation of catecholamine levels by surgical treatment.

Primary aldosteronism is highly prevalent in patients with hypertension and moderate to severe obstructive sleep apnea.

STUDY OBJECTIVES: It has been suggested that there might be a pathophysiological link and overlap between primary aldosteronism (PA) and obstructive sleep apnea (OSA). Therefore, in a prospective study, we evaluated the frequency of PA in hypertensive patients suspected of having OSA. METHODS: We included 207 consecutive hypertensive patients (mean age 53.2 ± 12.1 years, 133 M, 74 F) referred for polysomnography on the basis of one or more of the following clinical features: typical OSA symptoms, resistant or difficult-to-treat hypertension, diabetes, or cardiovascular disease. PA was diagnosed based on thew saline infusion test. RESULTS: Moderate-to-severe OSA was diagnosed in 94 patients (45.4% of the whole group). PA was diagnosed in 20 patients with OSA (21.3%) compared with 9 patients in the group without OSA (8.0%; P = .006). PA was also frequent in patients in whom symptoms of OSA were a sole indication for PA screening (15.4%) and in patients with and without resistant hypertension (24.5% and 17.8%, respectively). Most patients with PA and OSA were diagnosed with bilateral adrenal hyperplasia (18 patients, 90%). There were no major differences in clinical characteristics between patients with OSA with PA and those without PA. In multivariate models, moderate-to-severe OSA predicted the presence of PA (odds ratio 2.89, P = .018). CONCLUSIONS: Patients with clinically important moderate-to-severe OSA are characterized by a relatively high frequency of PA. Our results support the recommendations to screen patients with moderate-to-severe OSA for PA, regardless of the presence of other indications for PA screening.

Left Ventricular Structural and Functional Alterations in Patients With Pheochromocytoma/Paraganglioma Before and After Surgery.

OBJECTIVES: This study sought to evaluate left ventricular (LV) structure and function in pheochromocytoma and paraganglioma (PPGL) patients before and after curative surgery. BACKGROUND: Data on catecholamine-induced effects on LV structure and function in patients with PPGL are limited and conflicting. METHODS: The study evaluated 81 consecutive patients with a PPGL, among whom 66 were evaluated 12 months after tumor removal. Fifty patients matched for age, sex, hypertension presence, and blood pressure (BP) levels served as a control group (non-PPGL group). Echocardiography was employed to assess the LV mass index (LVMI), systolic function including speckle tracking echocardiography, and diastolic function. RESULTS: Patients with PPGL were characterized by higher LVMI (median 103 [interquartile range (IQR): 88 to 132] g/m2 vs. median 94 [IQR: 74 to 106] g/m2; p = 0.006) and frequency of LV hypertrophy (44.4% vs. 24.0%; p = 0.018) compared with the non-PPGL group. Patients with PPGLs were characterized by lower global longitudinal strain (GLS) and early diastolic mitral annular velocity compared with patients in the non-PPGL group (median -17.2% [IQR: 15.6% to 18.9%] vs. median -19.3% [IQR: 17.7% to 20.6%]; p < 0.001; and median 11.1 [IQR: 8.3 to 13.0] cm/s vs. median 12.3 [IQR: 10.6 to 14.6] cm/s; p = 0.018, respectively). Presence of LV hypertrophy and GLS were independently associated with plasma free metanephrine concentrations. In operated patients, there were lower frequencies of LV hypertrophy (39.4% vs. 22.7%; p = 0.003), LVMI (median 98 [IQR: 85 to 115] g/m2 vs. median 90 [IQR: 76 to 109] g/m2; p < 0.001), and the ratio of transmitral early diastolic velocity to early diastolic mitral annular velocity (median 6.8 [IQR: 5.5 to 8.6] vs. median 6.0 [IQR: 5.0 to 7.6]; p = 0.005) but higher values for GLS (median -17.4 [IQR: -15.8 to 19.1] vs. median -18.5 [IQR: -17.1 to 20.1] p < 0.001) after compared with before surgery. CONCLUSIONS: Catecholamine excess in patients with PPGLs can lead not only to LV hypertrophy, but also to impairment of systolic LV function and subclinical alterations of diastolic LV function, independently of BP levels. These structural and functional changes are reversible after surgical intervention.

Retinal arterial remodeling in patients with pheochromocytoma or paraganglioma and its reversibility following surgical treatment.

OBJECTIVE: Structural abnormalities in resistance arteries are a hallmark of patients with hypertension. In hypertensive patients with pheochromocytoma or paraganglioma (PPGL), it is still a matter of debate whether structural vascular changes are because of elevated blood pressure (BP) or to toxic effects of elevated circulating catecholamines. Hence, the aim of our study was to assess whether catecholamine excess and/or elevated BP affect the structure of small retinal arteries in patients with catecholamine-producing tumors. METHODS: The study included 27 patients with PPGL and 27 hypertensive patients. All patients underwent biochemical tests for catecholamine excess, echocardiography and analyses of scanning-laser-Doppler-flowmetry (SLDF) both at baseline and 12 months following surgical resection of PPGL. RESULTS: Baseline retinal arterial diameter, arterial wall thickness and wall cross sectional area (WCSA) were higher in patients with PPGL as compared with subjects without PPGL (arterial diameter: 110 ±â€Š16.5 vs. 99.5 ±â€Š10.8 µm, wall thickness: 16.3 ±â€Š6.0 vs. 13.5 ±â€Š4.0 µm, WCSA: 4953.9 ±â€Š2472.8 vs. 3784.1 ±â€Š1446.3 µm, P < 0.05). Significant correlations were noted between wall thickness and WCSA and echocardiographic parameters assessing diastolic and systolic function of left ventricle. No correlations between retinal parameters, BP level and plasma concentrations of metanephrines were observed. In patients with PPGL, there were postoperative decreases in wall thickness (16.4 ±â€Š15.8 vs. 14.8 ±â€Š4.7 µm; P = 0.011) and WLR (0.42 ±â€Š0.13 vs. 0.37 ±â€Š0.10; P = 0.003) at 12 months after surgical removal of tumors. CONCLUSION: This is the first study to demonstrate that catecholamine excess is related to thickening of retinal arteries independent of BP and reversible after surgical cure. These data support a role of catecholamines in vascular remodeling in PPGL patients.

Systematic and Multidisciplinary Evaluation of Fibromuscular Dysplasia Patients Reveals High Prevalence of Previously Undetected Fibromuscular Dysplasia Lesions and Affects Clinical Decisions: The ARCADIA-POL Study.

Fibromuscular dysplasia (FMD), regarded as a generalized vascular disease, may affect all vascular beds and may result in arterial stenosis, occlusion, aneurysm, or dissection. It has been proposed to systematically evaluate all vascular beds in patients with FMD, regardless of initial FMD involvement. However, the impact of this approach on clinical decisions and on management is unknown. Within the prospective ARCADIA-POL study (Assessment of Renal and Cervical Artery Dysplasia-Poland), we evaluated 232 patients with FMD lesions confirmed in at least one vascular bed, out of 343 patients included in the registry. All patients underwent a detailed clinical evaluation including computed tomography angiography of intracranial and cervical arteries, as well as computed tomography angiography of the abdominal aorta, its branches, and upper and lower extremity arteries. In the study group, FMD lesions were most frequently found in renal arteries (87.5%). FMD was also found in cerebrovascular (24.6%), mesenteric (13.8%), and upper (3.0%) and lower extremity (9.9 %) arteries. Newly diagnosed FMD lesions were found in 34.1% of the patients, and previously undetected vascular complications were found in 25% of the patients. Among all FMD patients included in the study, one out of every 4 evaluated patients qualified for interventional treatment due to newly diagnosed FMD lesions or vascular complications. The ARCADIA-POL study shows for the first time that the systematic and multidisciplinary evaluation of patients with FMD based on a whole-body computed tomography angiography scan has an impact on their clinical management. This proved the necessity of the systematic evaluation of all vascular beds in patients with FMD, regardless of initial FMD involvement.

Dissecting visceral fibromuscular dysplasia reveals a new vascular phenotype of the disease: a report from the ARCADIA-POL study.

OBJECTIVE: Visceral artery fibromuscular dysplasia (VA FMD) manifestations range from asymptomatic to life-threatening. The aim of the study is to evaluate the prevalence and clinical characteristics of VA FMD. METHODS: A total of 232 FMD patients enrolled into ongoing ARCADIA-POL study were included in this analysis. All patients underwent detailed clinical evaluation including ambulatory blood pressure monitoring, biobanking, duplex Doppler of carotid and abdominal arteries and whole body angio-computed tomography. Three control groups (patients with renal FMD without visceral involvement, healthy normotensive patients and resistant hypertensive patients) matched for age and sex were included. RESULTS: VA FMD was present in 32 patients (13.8%). Among these patients (women: 84.4%), FMD lesions were more frequent in celiac trunk (83.1%), 62.5% of patients showed at least one visceral aneurysm, and five patients presented with severe complications related to VA FMD. No demographic differences were found between patients with VA FMD and individuals from the three control groups, with the exception of lower weight (P < 0.001) and BMI (P < 0.001) in VA FMD patients. Patients with FMD (with or without visceral artery involvement) showed significantly smaller visceral arterial diameters compared with controls without FMD. CONCLUSION: Patients with FMD showed smaller visceral arterial diameters when compared with patients without FMD. This may reflect a new phenotype of FMD, as a generalized arteriopathy, what needs further investigation. Lower BMI in patients with VA FMD might be explained by chronic mesenteric ischemia resulting from FMD lesions. FMD visceral involvement and visceral arterial aneurysms in patients with renal FMD are far to be rare. This strengthens the need for a systematic evaluation of all vascular beds, including visceral arteries, regardless of initial FMD involvement.

Association of intrarenal blood flow with renal function and target organ damage in hypertensive patients with fibromuscular dysplasia: the ARCADIA-POL study.

INTRODUCTION Data on the assessment of intrarenal blood flow parameters in patients with renal fibromuscular dysplasia (FMD) are scarce. OBJECTIVES The aim of the study was to evaluate intrarenal blood flow parameters in patients with FMD and significant or nonsignificant renal artery stenosis (RAS). PATIENTS AND METHODS We evaluated intrarenal blood flow parameters by Doppler ultrasonography in 153 patients with renal FMD enrolled in the ARCADIA­POL study: 32 and 121 patients with and without significant RAS, respectively, compared with 60 matched patients with essential hypertension and 60 healthy controls. RESULTS Patients with FMD and significant RAS had a lower renal resistive index (RRI) compared with patients with FMD without significant RAS, patients with essential hypertension, and normotensive controls (mean [SD], 0.51 [0.08] vs 0.60 [0.07], 0.62 [0.06], and 0.61 [0.06], respectively; P <0.001). In patients with nonsignificant RAS, RRI correlated significantly with carotid intima-media thickness, 24­hour diastolic blood pressure, 24­hour pulse pressure, left ventricular diastolic function, known duration time of hypertension, and age. In patients with significant RAS, there was a significant correlation between RRI and known duration time of hypertension, left ventricular diastolic function, and age. In a separate, "per­kidney" analysis, renal arteries with FMD and significant RAS were characterized by lower RRI values, higher maximal blood flow velocity, higher renal aortic ratio, and longer acceleration time compared with renal arteries with FMD and nonsignificant RAS as well as renal arteries without FMD. CONCLUSIONS In contrast to atherosclerotic RAS, intrarenal blood flow in patients with FMD and RAS is preserved, confirming that renal vasculature is relatively intact in these patients.

Prevalence of smoking and clinical characteristics in fibromuscular dysplasia. The ARCADIA-POL study.

PURPOSE: Smoking was identified as a potential factor contributing to fibromuscular dysplasia (FMD). To evaluate the prevalence of smoking and clinical characteristics in FMD subjects. MATERIAL AND METHODS: We analysed 190 patients with confirmed FMD in at least one vascular bed. The rate of smokers in FMD patients was compared to that in two control groups selected from a nationwide survey. RESULTS: The rate of smokers in FMD patients was 42.6%. There were no differences in frequency of smokers between FMD patients and: a group of 994 matched control subjects from general population and a group of matched hypertensive subjects. There were no differences in the characteristics of FMD (including rates of multisite FMD and significant renal artery stenosis) and its complications (including rates of dissections and aneurysms) between smokers and non-smokers. Smokers as compared with non-smokers were characterized by higher left ventricle mass index. CONCLUSIONS: There is no difference in the rate of smokers between FMD patients and subjects from the general population. Moreover, we did not find any association between smoking and clinical characteristics of FMD patients nor its extent and vascular complications. Our results do not support the hypothesis that smoking is involved in the pathophysiology of FMD.

Renal Denervation in Resistant Hypertension and Obstructive Sleep Apnea: Randomized Proof-of-Concept Phase II Trial.

It has been postulated that catheter-based renal denervation (RDN) may lower blood pressure (BP) and improve severity of obstructive sleep apnea (OSA) in resistant hypertensive patients. The aim of our study (NCT01366625) was to investigate in a prospective randomized trial the effect of RDN on BP and clinical course of OSA. Sixty patients with true resistant hypertension coexisting with moderate-to-severe OSA (apnea/hypopnea index, ≥15) were randomly allocated to RDN group (30 patients) and to control group (30 patients). The primary end point was reduction in office systolic BP at 3 months. Secondary end points included reduction in diastolic office and ambulatory BP, change in apnea/hypopnea index and biochemical measurements at 3 months, and change in echocardiographic measurements at 6 months. There were no differences in clinical characteristics between the groups. At 3 months in the RDN group, both office and ambulatory BP were significantly reduced, and a significant decrease in OSA severity (apnea/hypopnea index, 39.4 versus 31.2 events per hour; P=0.015) was observed. Between-group difference in apnea/hypopnea index change was significant at 0.05. At 6 months in the RDN group, reductions in office and ambulatory BP were sustained and were accompanied by significant improvement in echocardiographic measures of global longitudinal strain. There were no differences in metabolic variables in follow-up in both groups. In a randomized controlled trial, RDN lowered both office and ambulatory BP in patients with resistant hypertension and OSA. This was accompanied by improvement of the clinical severity of OSA. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01366625.

Echocardiographic assessment of left ventricular morphology and function in patients with fibromuscular dysplasia: the ARCADIA-POL study.

OBJECTIVE: To provide a comprehensive assessment of left ventricle (LV) structure, and function and to detect alterations in cardiac properties in relationship to presence, subtypes and extent of fibromuscular dysplasia (FMD). METHODS: We studied 144 patients with FMD. The control group consisted of 50 matched individuals. Office and ambulatory blood pressure levels were evaluated. Echocardiography was employed to assess: left ventricular mass index (LVMI), systolic function including speckle tracking echocardiography and diastolic function assessed by mitral flow and tissue Doppler imaging. RESULTS: There were no differences in LV morphology and function between patients with FMD and the control group. Among 128 patients with renal FMD, there were no differences in LVMI and LV systolic function between patients with unifocal and multifocal FMD. The patients with multifocal FMD were characterized by lower early diastolic velocity (e') as compared with unifocal FMD and control groups. However, in a multivariate regression model, e' was not independently correlated with FMD. There were no associations between echocardiographic indexes and vascular involvement of FMD. Also, there were no differences in LV morphology and function in patients with significant renal artery stenosis (RAS) compared with patients with history of significant RAS and patients with nonsignificant RAS. CONCLUSION: Our study in contrast to those with atherosclerotic RAS, did not show differences in LV morphology and function between FMD patients and matched controls. Although FMD can result in hypertension and serious vascular complications, there is no proof that it can alter LV regardless of FMD type and its extent.

Narcolepsy type 1 and hypersomnia associated with a psychiatric disorder show different slow wave activity dynamics.

The aim of the study was to compare electrophysiological parameters of night sleep in narcolepsy type 1 and hypersomnia associated with a psychiatric disorder. Fortyfour patients: 15 with narcolepsy type 1, 14 with hypersomnia associated with a psychiatric disorder and 15 age- and sex-matched controls participated in the study. The study subjects filled in the Athens Insomnia Scale (AIS) and the Beck Depression Inventory (BDI). The severity of daytime sleepiness was quantified subjectively using the Epworth Sleepiness Scale (ESS) and the Stanford Sleepiness Scale (SSS), and objectively using the Multiple Sleep Latency Test (MSLT). All subjects underwent polysomnography (PSG) on the two consecutive nights. The data from the second night was analysed. The slow wave activity (SWA, 1-4 Hz) was calculated for the three consecutive sleep cycles, and topographic delta power maps were plotted. In contrast to narcoleptics, psychiatric hypersomniacs had undisturbed nocturnal sleep, high sleep efficiency, normal non-rapid eye movement (NREM) and rapid eye movement (REM) sleep proportions, normal REM latency and sleep latencies on MSLT and PSG. The subjective and objective sleepiness was significantly higher in narcolepsy group than in psychiatric hypersomnia group. In all the study groups SWA was the most prominent in frontal areas, while the greatest between-group differences were found in the central areas. There were significant differences between the groups in SWA in the second NREM episode. The highest SWA was observed in the hypersomnia group, while the lowest in the narcolepsy group. Psychiatric hypersomniacs and controls did not differ in the SWA exponential decline over consecutive NREM episodes, whereas narcoleptics exhibited a steeper dissipation of sleep pressure from the first to the second NREM episode. In conclusion, narcolepsy type1 and hypersomnia associated with psychiatric disorder differ in the SWA dynamics. Narcoleptics presented with the altered dynamics of sleep homeostasis, whereas psychiatric hypersomniacs showed normal nocturnal sleep and normal sleep homeostasis.

Relationship between gender and clinical characteristics, associated factors, and hypertension treatment in patients with resistant hypertension.

BACKGROUND AND AIM: Recent meta-analyses indicate that the pooled prevalence of resistant hypertension (RHT) barely differs between the sexes. However, differences between women and men with RHT in patient characteristics, associated factors, and hypertension (HT) management are still not well-described. METHODS: In the cross-sectional questionnaire-based observational study we included 7306 hypertensive females and 5069 hypertensive males, ≥ 18 years old, and treated for at least 12 months with antihypertensive drugs. We defined HT control as blood pressure (BP) levels both < 140 mm Hg/< 90 mm Hg. Patients were divided into three groups: controlled HT, uncontrolled HT (not fulfilling the criteria of RHT), and RHT (uncontrolled HT despite using three antihypertensive drugs including diuretic). Cardiovascular (CV) risk was evaluated according to 2013 ESH/ESC guidelines. RESULTS: There were no differences in the rates of controlled HT (47.6% vs. 47.0%), uncontrolled HT (27.3% vs. 28.8%), and RHT (25.1% vs. 24.2%) between women and men, respectively (p = 0.17). Among patients with RHT, women were older than men and had lower diastolic BP and estimated glomerular filtration rate (eGFR) as well as higher pulse pressure (PP). Cerebro-vascular diseases (16.9% vs. 14.3%; p = 0.062), abdominal obesity, and metabolic syndrome (MS, 70.5% vs. 60.1%; p < 0.001) were more frequent among women than men with RHT. Women with RHT had higher rate of high/very high added CV risk in comparison to men. In a multivariate model higher PP, presence of MS, CV disease, and eGFR < 60 mL/min/1.73 m² were related to the presence of RHT both in males and females. In women RHT was also related to abdominal obesity, cerebro-vascular diseases, and diseases causing disability. In men, RHT was additionally related to diseases requiring treatment with non-steroidal anti-inflammatory drugs. CONCLUSIONS: Although there were no differences in the rate of RHT between women and men, we identified gender-related differences in CV risk profiles in RHT patients and in factors related with the presence of RHT. When divided into age groups, RHT was less frequent in women aged less than 40 years and aged between 40 and 65 years, and among patients 65 years and older there was a tendency towards a higher rate of HT in women.

Altered plasma fibrin clot properties in hypertensive patients with obstructive sleep apnoea are improved by continuous positive airway pressure treatment.

AIM: We investigated plasma fibrin clot properties in high-risk hypertensive patients with obstructive sleep apnoea (OSA) and assessed the impact of continuous positive airway pressure (CPAP) treatment on clot phenotype. METHODS: We studied 50 hypertensive patients with clinically significant OSA (age 50.0 ±â€Š8.8 years, 39 M, 11 F). In total, 38 hypertensive patients without OSA balanced for age, sex, blood pressure, cardiovascular risk factors, and metabolic status served as controls. Plasma fibrin clot properties, including clot permeability coefficient, clot lysis time (CLT), and turbidimetric parameters of clot formation were determined. Patients underwent transthoracic echocardiography, carotid ultrasonography, evaluation of endothelial function and calcium score index of coronary arteries, and Doppler imaging of renal arteries. RESULTS: Compared with controls, OSA patients were characterized by more compact fibrin structure (lower median clot permeability coefficient, 6.00 vs. 7.25 10 cm; P < 0.001), impaired fibrinolysis (longer median CLT, 108.00 vs. 92.50 min; P < 0.001), and by faster clot formation (shorter median lag phase, 40.50 vs. 42.50 s; P = 0.041), and higher median maximum clot absorbency indicating denser fibrin networks (0.87 vs. 0.81; P = 0.028). Clot permeability coefficient and CLT correlated with apnoea-hypopnoea index (r = -0.46; P < 0.001 and r = 0.44; P < 0.001, respectively) as well with mean (r = 0.31; P = 0.003; r = -0.36; P = 0.001, respectively) and minimal oxygen saturation (r = 0.46; P < 0.001; r = -0.49; P < 0.001, respectively). After 3 months of CPAP treatment we observed an increase in clot permeability coefficient (5.95 vs. 7.60 10 cm; P = 0,001), shortened CLT (107.00 vs. 87.00; P = 0.006), a longer lag phase of fibrin formation (40.00 vs. 43.50 s; P = 0.013), and a trend toward lower maximum clot absorbency (0.86 vs. 0.81; P = 0.058). CONCLUSION: In hypertensive patients at high cardiovascular risk, OSA was associated with unfavourable prothrombotic fibrin clot characteristics, including hypofibrinolysis, which significantly improve as early as after 3 months of CPAP treatment.

A single-centre experience of the implementation of adrenal vein sampling procedure: the impact on the diagnostic work-up in primary aldosteronism.

BACKGROUND: Primary aldosteronism is one of the most common causes of secondary hypertension. Adrenal vein sampling (AVS) remains a "gold standard" procedure in differentiation between unilateral (adenoma) and bilateral (hyperplasia) disease. AIM: The aim of this study was to present our single-centre experience in establishing and implementating the AVS procedure. METHODS: All patients had primary aldosteronism confirmed in a salt-infusion test. AVS was performed sequentially during a continuous intravenous infusion of cosyntropin and was preceded by multislice contrast-enhanced computed tomography (CT) examination of adrenal glands performed a few weeks before AVS in the majority of patients. AVS was regarded as successful if the ratio of each adrenal vein cortisol to inferior vena cava cortisol levels (selectivity index [SI]) was higher than 3.0. In the case of failure, a second attempt was considered in a few weeks. Patients were divided into four groups according to the order of the procedure by quartiles. RESULTS: Between 31 May, 2012 and 5 May, 2016, AVS was performed in 124 patients (69% males, aged 55.3 ± 10.3 years) and was successful in 120 (96.8%) patients. All failed cases were due to the failure of cannulation of the right adrenal vein. The first-attempt success rate was 94.3% (117 of 124 patients) and increased from 83.9% in the first 31 patients to 100% in the last 31 patients. Similarly, the overall success rate increased from 93.5% to 100%. The right SI was significantly higher than the left one (26.4 vs. 11.0, p < 0.0001). Both indices did not differ across quartiles of patients. No complications occurred during the procedure. CONCLUSIONS: The AVS procedure, preceded by adrenal CT, may be implemented into daily diagnostic practice safely with an excellent success rate.