Form Of Secondary Hypertension Research Articles

ENDOVASCULAR RADIOFREQUENCY RENAL DENERVATION IN DIFFICULT TO TREAT ARTERIAL HYPERTENSION: A SINGLE CENTER EXPERIENCE

Objective: To assess safety and effectiveness of catheter-based renal denervation (RDN) for reduction of blood pressure (BP) in patients with difficult to treat arterial hypertension. Design and method: Thirtyfive patients selected with difficult to treat arterial hypertension, underwent RDN. Secondary forms of hypertension were excluded, and an appropriate renal artery anatomy was confirmed in all patients. Every patient underwent follow-up at 30 days, and then every 12 months, consisting in clinical examination, office BP measurements, ambulatory blood pressure monitoring, and biochemical analysis. At 12 months tansthoracic echocardiography and renal duplex sonography were performed. Results: The median value of systolic clinic BP decreased from 161 mmHg (25th-75th percentiles 158 - 191) at baseline to 144 mmHg (25th-75th percentiles 136 - 153) at follow up (p= 0.012), and the median value of diastolic clinic BP decreased from 102 mmHg (25th-75th percentiles 94 - 122) at baseline to 90 mmHg (25th-75th percentiles 78 - 99) at follow-up (p= 0.012). The number of medications changed from 5 (range 2-8) at baseline to 3.3 (range 0-6) at follow up. A significant decrease of left ventricular mass index from a median of 160 g/m2 (25th-75th percentiles 147 - 151) at baseline to 126 g/m2 (25th-75th percentiles 107 - 151) at follow-up (p= 0.043) was detected. The renal function did not demonstrate significant changes, however plasma renin activity and HOMA index were significantly reduced. No periprocedural or long term complications were observed. Conclusions: Our data confirm that RDN may constitute an effective and safe therapeutic choice for the treatment of difficult to treat hypertension.

Sex-related differences for uric acid in the prediction of cardiovascular events in essential hypertension. A population prospective study.

Uric acid (UA) is an independent prognostic factor for cardiovascular events, but there are no data demonstrating a different risk profile between women and men. Thus, we tested whether UA is associated with a possible sex-related difference in fatal and non-fatal cardiovascular events. In this prospective population-based study we enrolled 1,650 never-treated Caucasian hypertensive outpatients referred to Catanzaro University Hospital (Italy). Inclusion criteria were newly diagnosed hypertensive patients, aged 20years or more. Exclusion criteria were secondary form of hypertension, previous cardiovascular events, rheumatic and non-rheumatic valvular heart disease, prosthetic valves, cardiomyopathies, type-2 diabetes, chronic kidney disease, malignant diseases, gout arthritis and secondary forms of hyperuricemia, liver diseases, peripheral vascular diseases, and heart failure. Anthropometric, clinical, and biochemical parameters were measured. UA prognostic role was investigated by Cox regression analyses. Receiver-operating characteristic curve analyses and area under the curve were used to determine the predictive validity and the optimal cut-off point of UA. We investigated following endpoints: coronary events (fatal and nonfatal myocardial infarction, unstable angina, coronary revascularization procedures, coronary death); fatal and nonfatal stroke; all-cause mortality and major adverse cardiovascular events (MACE). We enrolled 830 males and 820 females aged 52.2 ± 11.3years. During 9.5 ± 3.1years follow-up, there were 424 new clinical events (2.71%): 250 coronary (1.59%), 118 (0.75%) cerebrovascular, and 56 (0.40%) deaths. Comparison between groups demonstrated a higher and significant difference in incidence rate in females for MACE (3.08 vs 2.33%, P = 0.001), coronary (1.82 vs 1.36%, P = 0.014) and cerebrovascular events (0.93 vs 0.57%, P = 0.006). UA at multiple Cox regression analysis resulted a strong and significant predictor of coronary events (HR = 1.493;95% CI 1.375-1.621), cerebrovascular events (HR = 1.256;95% CI 1.109-1.423), MACE (HR = 1.415;95% CI 1.328- 53 1.508), and all-cause mortality (HR = 1.469;95% CI 1.237-1.745) in the whole population and in both groups with a HR higher in females. The best estimated cut-off values of uric acid for males and females predicted these endpoints equally well, but it was always lower in females than males. We demonstrate, that UA operates with a sex-related impact and best cut-off value in predicting cardiovascular outcomes and all-cause mortality, reflecting a possible sex difference in disease pathophysiology.

HIGH SALT INTAKE DID NOT DIMINISH BENEFICIAL EFFECT OF RENAL DENERVATION ON BLOOD PRESSURE, KIDNEY FUNCTION AND METABOLIC PROFILE - CROATIAN REAL-LIFE STUDY

Objective: Last trials clearly documented and confirmed the efficacy of renal denervation (RDN) on decrease of blood pressure (BP). Our aim was to analyze the effects of RDN beyond BP lowering in truly resistant hypertensive patients in real-life conditions. Design and method: Out of 31 truly resistant patients whose secondary forms of hypertension were ruled out and were enrolled into the Croatian Spyral RDN registry, 18(10 m, 8 w, average age 49.3) were eligible for analysis. Office BP, ABPM, central BP and PWV were measured with Omron M6, Mobilograph and Sphygmocor devices, respectively. Albuminuria and salt intake were determined from 24-h urine samples, eGFR using the CKD Epi equation. Sympathetic/parasympathetic activity was measured with an ANX-3.0 ANSAR device. All RDN procedures(Spyral Medtronic) were done by one physician (average number of ablation spots was 41/procedure). Patients were examined day before and that day, 1,3,6, and 12 months after the RDN. Reponse was drop of office systolic BP by 10 mmHg or more 6 months after RDN. There were no differences in the RDN procedure between responders and non-responders. Results: Office and ABPM values dropped the day after RDN and remained significantly lower at the end of the follow-up (6.5/-5.5 and -16.2/9 mmHg, respectively). The effect of RDN on BP was not abolished with high salt intake(15.5 g/day at the end of follow up). eGFR remained stable, and even slight improvement was observed at the end of follow-up(+8.4 ml/min/1.72m2); albuminuria significantly decreased (-115 mg/day). All metabolic parameters (lipids, uric acid) improved at the end of follow-up. LFa/RFa decreased the day after RDN and remained lower during the follow-up period. After RND central systolic BP and Aix decreased more in responders than in non-responders (-12.8 vs. -7.3; -7 vs. -2.6) while PP amplification was improved in responders (1.22 to 1.33) but decreased in non-responders (1.33 to 1.25). Conclusions: In real-life circumstances, BP significantly decreased after RDN despite large salt ingestion. eGFR and albuminuria improved as well as metabolic parameters at the end of follow-up and all of the beneficial changes run in parallel with observed decrease in sympathetic activity.

CHARACTERISTIC OF RESPONDERS TO RENAL DENERVATION - CROATIAN REAL-LIFE STUDY

Objective: Heterogeneity in response to renal denervation (RDN) is acknowledged phenomena and one of most important tasks in this field is to find reliable predictive biomarker for positive response. Our aim was to analyse characteristics of resistant hypertensive patients who were responders 6 months after RDN. Design and method: Out of 31 truly resistant patients whom secondary forms of hypertension were ruled out and were enrolled into the Croatian Spyral RDN registry, 18 (10 m, 8 w, average age 49.3) were eligible for analyses. Office BP, ABPM, central BP and PWV were measured with Omron M6, Molbilograph and Sphygmocor devices, respectively. Sympathetic/parasympathetic activity was measured with ANX-3.0 ANSAR device. Results: Responders were 6.7 years older, less obese with at basal slightly higher eGFR (88.6 vs. 79.8), uric acid (406.5 vs. 376.4), salt intake (12.6 g/day vs.9.8 g/day) and had significantly higher basal office BP (169.5/99.7 vs. 153.3/96.5) as well as ABPM values. Central aortic systolic BP and Aix were higher in responders (154.5 vs, 147.1; 31.5 vs 27.3) without difference in PWV (10.1 vs. 9.6). Responders had lower values of PP amplification (1.22 vs. 1.33). Significantly higher basal sympathetic activity (LFa/RFa) was determined in responders than in non-responders (6.68 vs. 1.25). Conclusions: Responders were older with higher basal office BP, ABPM but also higher central BP and Aix with lower pulse pressure amplification. They ingested more salt, had higher values of uric acid and importantly had more exaggerated sympathetic activity. Whether some of identified parameters could be considered as a biomarker for positive response in resistant hypertensive patients should be determined in larger cohort of patients.

BLOOD PRESSURE VARIABILITY AND CIRCADIAN PATTERN AFTER RENAL DENERVATION - CROATIAN REAL-LIFE STUDY

Objective: Recent trials confirmed the lowering effect of renal denervation (RDN) on blood pressure (BP). We aimed to analyze the impact of RDN on BP variability and circadian rhythm. Design and method: Out of 31 truly resistant patients whose secondary forms of hypertension were ruled out and were enrolled into the Croatian Spyral RDN registry, 18 (10 m, 8 w, average age 49.3) were eligible for analyses. Office BP, ABPM, central BP, and PWV were measured with Omron M6, Mobilograph, and Sphygmocor devices. Sympathetic/parasympathetic activity was measured with ANX-3.0 ANSAR device. All RDN procedures (Spyral Medtronic) were done by one physician (average number of ablation spots was 41/procedure). Patients were examined the day before and that day, 1,3,6, and 12 months after the RDN. The response was a drop of office systolic BP by 10 mmHg or more 6 months after RDN. There were no differences in the RDN procedure between responders and non-responders. Results: Office and ABPM values dropped the day after RDN and remained significantly lower at the end of the follow-up (6.5/-5.5 and -16.2/9 mmHg, respectively). We failed to find changes in BP variability (SD) after RDN. However, a significant decrease in morning BP surge was observed immediately the day after RDN (-12.4) and was even lower at the end of the follow-up (-18.8 mmHg). Substantial number of patients who had an abnormal nocturnal BP pattern became dippers. Central systolic BP and PWV decreased (-6.3 mmHg and -0.72 m/s, respectively). LFa/RFa decreased the day after RDN and reminded lower during the follow-up period. After RDN morning BP surge remained stable and normal in responders; however, in non-responders, it decreased immediately after RDN (-21.2) and remained lower during the follow-up till the last visit (-33.3). Conclusions: Significant improvements in circadian rhythm and several parameters of central hemodynamics were observed after RDN indicating that RDN might be considered as a pathway to the complete, so-called perfect 24-hour BP control. Observed beneficial effects run in parallel with the observed decrease in sympathetic activity. Importantly, even in non-responders, RDN had a beneficial effect on morning BP surge.

Rates of Pheochromocytoma/Paraganglioma Screening in At-Risk Populations.

Pheochromocytomas and paragangliomas (PPGL) are rare causes of secondary hypertension, but when unrecognized, they can lead to serious complications. Data regarding PPGL screening are lacking. This study aimed to assess the rates and patterns of PPGL screening among eligible patients. We conducted a retrospective review of adults with hypertension seen in outpatient clinics of a large academic center between January 1, 2017, and June 30, 2020. We included patients with treatment-resistant hypertension, hypertension at age < 35 years, and/or adrenal mass(es). Of 203 535 patients with hypertension identified, 71 088 (35%) met ≥ 1 inclusion criteria, and 2013 (2.83%) were screened for PPGL. Patients screened were younger (56.2 ± 17.4 vs 64.0 ± 17.1 years), more often women (54.1% vs 44.2%), and never-smokers (54.6% vs 47.5%, P < 0.001 for all). The rate of screening was highest in patients with hypertension and adrenal mass(es) (51.7%, vs 3.9% in patients with early-onset hypertension, and 2.4% in those with treatment-resistant hypertension). Multivariable logistic regression showed higher odds ratio (OR) of PPGL screening in women (OR [95% CI]: 1.48 [1.34-1.63]); Black vs White patients (1.35 [1.19-1.53]); patients with adrenal mass(es) (55.1 [44.53-68.15]), stroke (1.34 [1.16-1.54]), dyslipidemia (1.41 [1.26-1.58]), chronic kidney disease (1.40 [1.26-1.56]), and obstructive sleep apnea (1.96 [1.76-2.19]). PPGL screening is pursued in roughly half of patients with adrenal nodules and hypertension, but rarely in patients with treatment-resistant or early-onset hypertension. Similar to screening for other forms of secondary hypertension, PPGL screening occurs more often after serious complications develop.

A systematic review of Tuina for cervical hypertension: A protocol for systematic review and meta-analysis.

Background:Cervical hypertension is a secondary form of hypertension with a high incidence rate. As the main etiology of cervical hypertension is related to cervical spondylosis, commonly used antihypertensive drugs have poor efficacy in the treatment of cervical spondylosis, and improving the symptoms of cervical spondylosis can effectively reduce blood pressure. Massage can effectively improve the symptoms of patients with cervical hypertension, but there has been no systematic review of massage treatment for cervical hypertension. This study aimed to evaluate the efficacy and safety of massage in patients with cervical hypertension.Methods:Before February 10, 2022, a systematic literature search was conducted using the following databases: Embase, SinoMed (previously called the Chinese Biomedical Database), China Science and Technology Journal Database for Chinese Technical Periodicals, Chinese National Knowledge Infrastructure, and Wanfang Data. Review Manager software (version 5.3) will be used for statistical analysis. Quality and risk assessments of the included studies were performed, and the outcome indicators of the trials were observed.Results:This meta-analysis further confirmed the beneficial effects of massage in patients with cervical hypertension.Conclusion:This study investigated the efficacy and safety of massage therapy in patients with cervical hypertension, providing clinicians and patients with additional options for the treatment of this disease.

Spontaneous, independent, single-center renal denervation registry of a resistant hypertension multidisciplinary team

Abstract Background Uncontrolled resistant hypertension (URH) is defined as PAS ≥140mmHg despite the adherence to at least 3 maximally tolerated doses of antihypertensive medications. In the adult population URH is a common condition with a prevalence that ranges between 10–15% and is related with poor prognosis and higher risk of major adverse cardiovascular events. Renal sympathetic denervation (RDN) has recently proved efficacy in different hypertensive subsets of patients. However, patients with chronic kidney disease (CKD) IIIB-V stages (i.e. glomerular filtrate rate &amp;lt;45 ml/min) have been systematically excluded from randomized clinical trials (RCT). Purpose To evaluate the safety and the efficacy of RDN in a daily practice population of patients with URH on top of medical therapy, including patients with renal function impairment (GFR&amp;lt;45ml/min). Methods Consecutive unselected patients with URH undergoing RDN were enrolled. Indication of RDN was assessed in a multidisciplinary team involving cardiologist, nephrologist and hypertension specialists, after secondary forms of hypertension had been excluded. Efficacy was defined as the inter-individual change of office (OBP) and ambulatory blood pressure monitoring (ABPM) at 3, 6 and 12 months after RDN. Safety as the absence of any device-related major complication (BARC classification), end-stage renal disease, stroke, acute myocardial infarction and any cause of death within 1 month of the procedure. Safety and efficacy profile was assessed in patients with an estimated GFR below 45 ml/min/1.73 m2. Results Seventy-two patients underwent RDN for URH from 2012 to 2022. The population presented with multiple comorbidities and target organ damage: almost 50% were smoker, 43% diabetic, 33% PAD, 25% CAD and 60% CKD. Isolated systolic hypertension prevalence was 53%. The average number of antihypertensive medications at baseline was 5.3±1.1. Baseline OBP and ABPM were 158.8/86.6±23.4/15.3 mmHg and 151.4/87.6±18.8/14.2 mmHg, respectively. The vast majority of the procedures were performed with tetrapolar radio-frequency catheter (91.7%), with 37.3±14.3 number of ablations per procedure. The average amount of contrast medium was 72.1±38.1 ml. At 12-month follow-up a significant reduction of office and ambulatory systolic BP, respectively by −15.66±29.73 mmHg (P&amp;lt;0.01) and by −11.3±23.1mmHg (P&amp;lt;0.05), was noticed. BP reduction at 12-month follow-up among patients with eGFR &amp;lt;45 ml/min was similar to that obtained in patients with higher eGFR. No major complications were observed and renal function was stable up to 12 months, even in patients with lowest eGFR at baseline. Conclusion(s) RDN is safe and feasible in patients with URH on top of medical therapy, even in a high-risk CKD population with multiple comorbidities. Our experience underlines the central role of multidisciplinary team evaluation for the targeted management of uncontrolled resistant hypertension. Funding Acknowledgement Type of funding sources: None.

Thrombophilia: An Amalgam of Never Ending Clinical Manifestations

Abstract Thrombophilia is a blood coagulation disorder, in which blood has an increased tendency to clot, with both arterial and venous localization, being responsible for multiple manifestations: secondary arterial hypertension, stroke, acute pancreatitis or intracardiac masses. We are presenting the case of a 21-year-old male patient, hypertensive, known with thrombophilia, who was sent for the echocardiographic evaluation of an intracardiac mass attached to the posterior leaflet of the mitral valve. The echocardiography and transesophageal echocardiogram showed a hyperechogenic, homogeneous intracardiac mass, attached to the posterior leaflet of the mitral valve, the clinical context and the echocardiographic appearance being suggestive for a thrombus. Given the context of thrombophilia and the hypertension’s characteristics, we considered a secondary form of hypertension, the incriminated mechanism being represented by microthrombosis in the renal arterial circulation. There were two complications in the evolution of the patient: stroke and the recurrent acute pancreatitis, both being explained in the context of thrombophilia. The discharge echocardiography showed a favorable evolution, with a complete resolution of the thrombus under the anticoagulant treatment.

Diagnosis and Treatment of Secondary Hypertension

Secondary hypertension, which refers to arterial hypertension caused by an identifiable medical condition, accounts for 5-10% of all hypertensive diagnoses; however, this is thought to be an underestimate. If diagnosed promptly, secondary hypertension can be treated, and proper blood pressure restored. This review focuses on the screening, diagnosis, and management of the most common forms of secondary hypertension, including primary aldosteronism, renovascular hypertension, pheochromocytoma, Cushing’s syndrome, and renal parenchymal disease.

Screening for hypertension-mediated organ damage and aetiology: Still of value after 65 years of age?

Pathophysiological aspects and the consequences of hypertension may differ between younger and older patients. The aim of the present study was to explore the specificity of hypertension-mediated organ damage (HMOD) and secondary forms in patients ≥ 65 years in comparison to younger ones in a contemporary cohort. A total of 938 hypertensive patients who had at baseline HMOD and secondary forms screening were included among them 190 were ≥ 65 years. The mean ± SD number (2.1 ± 0.8 vs. 1.2 ± 0.9, P < 0.001) and frequency of HMOD (96.3% vs. 72.9%, P < 0.001) was higher in patients ≥ 65 years than younger ones. Carotid femoral pulse wave velocity > 10 m/s was the most frequent HMOD in patients ≥ 65 years (90.1%), while echocardiographic left ventricular hypertrophy was the most common in the younger patients (45.0%). Among ECG left ventricular ECG indexes, only R wave in aVL lead was significantly more frequently observed in patients ≥ 65 years (32.6%) than in younger ones (19.0%, P < 0.001). The frequency of secondary hypertension was not significantly different between younger and older patients (respectively; 30.5% vs. 27.8%, P = 0.487). The most frequent aetiology was primary aldosteronism regardless of age. The frequency of renovascular hypertension was higher in patients ≥ 65 years (6.3% vs. 3.3%, P = 0.038). Among older patients, 3.2% were treated with adrenalectomy (primary aldosteronism or Cushing syndrome) and 6.3% with percutaneous transluminal renal angioplasty. In a tertiary centre, secondary forms of hypertension have a similar frequency in both subgroups. Extensive screening of HMOD in patients aged ≥ 65 years may be questionable because of its very high frequency.

Plasma aldosterone concentration is associated with white matter lesions in patients with primary aldosteronism.

Primary aldosteronism (PA) is the most frequent form of secondary hypertension. Hypertension is a risk factor for cognitive decline and dementia. White matter lesions (WMLs) are linked to vascular risk factors, which increase the risk of dementia. We aimed to analyze the association of PA-related parameters and WMLs in patients with PA. We conducted a retrospective analysis of all patients with PA in the Hypertension Center of the People's Hospital of Xinjiang Uygur Autonomous Region from January 1, 2011 to April 1, 2021. We analyzed the relationship between plasma aldosterone concentration (PAC), plasma renin activity (PRA), aldosterone-renin ratio (ARR), serum potassium, and WMLs. We enrolled 138 patients with WMLs and matched these to controls without WMLs at a 1:4 ratio. Among the analytic sample (N = 711) with ages ranging from 30 to 64 years, 69% were male. In the logistic regression analysis, PAC, PRA and serum potassium were treated as continuous variables. The results showed that PAC (OR 1.04, 95% CI 1.01, 1.06, P = 0.008) was positively associated with the risk of WMLs, and serum potassium (OR 0.26, 95% CI 0.16, 0.44, P < 0.001) was inversely associated with the risk of WMLs. PRA (OR 0.86, 95% CI 0.68, 1.08, P = 0.384) was not associated with the risk of WMLs after adjusting for confounders. The results of restricted cubic splines showed the dose-response association between increasing PAC, ARR, decreasing serum potassium, and the risk of WMLs. We also divided PAC, ARR and serum potassium into two groups according to the result of restricted cubic splines. After adjusting for confounders, patients who were in Q2 (≥23.12 ng/dl) of PAC (OR 2.07, 95% CI 1.36, 3.15), Q2 (≥56.81 (ng/dl per ng/ml*h) of ARR (OR 1.82, 95% CI 1.22, 2.72) and Q2 (≤3.58 mmol/l) of serum potassium (OR 2.99, 95% CI 1.95, 4.50) had a significantly higher risk of WMLs than their counterparts. In stratified analyses, there was no evidence of subgroup heterogeneity regarding the change in the risk of WMLs (P > 0.05 for interaction for all). Our results suggested that the PAC and serum potassium were related to the risk of WMLs in patients with PA. In particular, PAC ≥23.12 ng/dl significantly increased the risk of WMLs in patients with PA.

High prevalence of non-dipping patterns among black Africans with uncontrolled hypertension: a secondary analysis of the CREOLE trial

Abstract Background Dipping of blood pressure (BP) at night is a normal physiological phenomenon. However, a non-dipping pattern is associated with hypertension mediated organ damage, secondary forms of hypertension and poorer long-term outcome. Identifying a non-dipping pattern may be useful in assessing risk, aiding the decision to investigate for secondary causes, initiating treatment, assisting decisions on choice and timing of anti-hypertensive therapy, and intensifying salt restriction. Objectives To estimate the prevalence and factors associated with non-dipping pattern and determine the effect of three 6-months anti-hypertensive regimens on the dipping pattern among Black African hypertensive patients. Methods This was a secondary analysis of the CREOLE Study which was a randomized, single blind, three-group trial conducted in 10 sites in 6 Sub-Saharan African countries. The participants were 721 Black African patients, aged between 30 and 79 years, with uncontrolled hypertension and a baseline 24-hour ambulatory blood pressure monitoring (ABPM). Dipping was calculated from the average day and average night systolic blood pressure measures. Results The prevalence of non-dipping pattern was 78% (564 of 721). Factors that were independently associated with non-dipping were: serum sodium &amp;gt;140mmol/l (OR=1.72, 95% CI: 1.17–2.51, p-value 0.005), a higher office systolic BP (OR=1.03, 95% CI: 1.01–1.05, p-value 0.003) and a lower office diastolic BP (OR=0.97, 95% CI: 0.95–0.99, p-value 0.03). Treatment allocation did not change dipping status at 6 months (McNemar's χ2 0.71, p-value 0.40). Conclusion There was a high prevalence of non-dipping among Black Africans with uncontrolled hypertension. ABPM should be considered more routinely in Black Africans with uncontrolled hypertension, if resources permit, to help personalise therapy. Further research is needed to understand the mechanisms and causes of non-dipping pattern and if targeting night-time BP improves clinical outcomes. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Fogarty International Center and the National Institutes of Health of the United States of America Figure 1

In Silico Analysis of the Gene Expression Patterns between Aldosterone-Producing Adenoma and Nonfunctional Adrenocortical Adenoma.

Primary aldosteronism is the most common form of secondary hypertension, and aldosteronoma makes up a significant proportion of primary aldosteronism cases. Aldosteronoma is also called aldosterone-producing adenoma (APA). Although there have been many studies about APA, the pathogenesis of this disease is not yet fully understood. In this study, we aimed to find out the difference of gene expression patterns between APA and nonfunctional adrenocortical adenoma (NFAA) using a weighted gene coexpression network (WGCNA) and differentially expressed gene (DEG) analysis; only the genes that meet the corresponding standards of both methods were defined as real hub genes and then used for further analysis. Twenty-nine real hub genes were found out, most of which were enriched in the phospholipid metabolic process. WISP2, S100A10, SSTR5-AS1, SLC29A1, APOC1, and SLITRK4 are six real hub genes with the same gene expression pattern between the combined and validation datasets, three of which indirectly or directly participate in lipid metabolism including WISP2, S100A10, and APOC1. According to the gene expression pattern of DEGs, we speculated five candidate drugs with potential therapeutic value for APA, one of which is cycloheximide, an inhibitor for phospholipid biosynthesis. All the evidence suggests that phospholipid metabolism may be an important pathophysiological mechanism for APA. Our study provides a new perspective regarding the pathophysiological mechanism of APA and offers some small molecules that may possibly be effective drugs against APA.

Abstract P136: Reference Ranges And Cut-Off Values For Simultaneous Monitoring Of RAS-Blocker Efficacy And Screening For Secondary Hypertension Using RAAS Triple-A Profiling

Uncontrolled hypertension is caused by various factors including compliance issues, patient specific drug uptake and elimination profiles or secondary forms of hypertension, resulting in blood pressure control rates of less that 50%. RAAS Triple-A profiling is a high-throughput mass-spectrometry based assay for Angiotensin I (Ang I), Angiotensin II (Ang II) and Aldosterone in serum samples. Hormone levels are used to calculate markers for plasma-renin-activity (PRA-S), plasma angiotensin-converting-enzyme activity (ACE-S) and adrenal aldosterone secretion (AA2-Ratio). The integrated analysis of these molecular markers together with drug prescription information allows to identify the underlying cause of uncontrolled hypertension, including primary aldosteronism and insufficiency in drug adherence or dosing for ACE inhibitors (ACEi) and angiotensin receptor blockers (ARBs). 500 participants with prescribed antihypertensive drugs were selected from the “Cooperative Health Research in South Tyrol” (CHRIS) study, a population-based study from an Alpine rural environment. Five age- and sex-matched groups (N=100 each) selected were individuals on single therapy with ARBs, ACEi or beta blockers, and on single pill dual therapy of ACEi or ARBs in combination with diuretics. Three age and sex-matched control groups of 100 participants each were included, being normotensive, hypertensive (treated with non-antihypertensive drugs) and hypertensive participants without any prescribed medication. RAAS Triple-A analysis was performed in all individuals and reference values for Ang I, Ang II, Aldosterone, PRA-S, ACE-S and AA2-Ratio were established in appropriate sub-populations. Drug monitoring by LC-MS/MS based quantification of anti-hypertensive drugs in serum was used as a gold standard to determine cut-off values for compliance with ARB and ACEi therapy and ROC analysis was performed using angiotensin-based biomarkers.

High prevalence of non-dipping patterns among Black Africans with uncontrolled hypertension: a secondary analysis of the CREOLE trial

BackgroundDipping of blood pressure (BP) at night is a normal physiological phenomenon. However, a non-dipping pattern is associated with hypertension mediated organ damage, secondary forms of hypertension and poorer long-term outcome. Identifying a non-dipping pattern may be useful in assessing risk, aiding the decision to investigate for secondary causes, initiating treatment, assisting decisions on choice and timing of antihypertensive therapy, and intensifying salt restriction.ObjectivesTo estimate the prevalence and factors associated with non-dipping pattern and determine the effect of 6 months of three antihypertensive regimens on the dipping pattern among Black African hypertensive patients.MethodsThis was a secondary analysis of the CREOLE Study which was a randomized, single blind, three-group trial conducted in 10 sites in 6 Sub-Saharan African countries. The participants were 721 Black African patients, aged between 30 and 79 years, with uncontrolled hypertension and a baseline 24-h ambulatory blood pressure monitoring (ABPM). Dipping was calculated from the average day and average night systolic blood pressure measures.ResultsThe prevalence of non-dipping pattern was 78% (564 of 721). Factors that were independently associated with non-dipping were: serum sodium > 140 mmol/l (OR = 1.72, 95% CI 1.17–2.51, p-value 0.005), a higher office systolic BP (OR = 1.03, 95% CI 1.01–1.05, p-value 0.003) and a lower office diastolic BP (OR = 0.97, 95% CI 0.95–0.99, p-value 0.03). Treatment allocation did not change dipping status at 6 months (McNemar’s Chi2 0.71, p-value 0.40).ConclusionThere was a high prevalence of non-dipping among Black Africans with uncontrolled hypertension. ABPM should be considered more routinely in Black Africans with uncontrolled hypertension, if resources permit, to help personalise therapy. Further research is needed to understand the mechanisms and causes of non-dipping pattern and if targeting night-time BP improves clinical outcomes.Trial registration ClinicalTrials.gov (NCT02742467).

REFERENCE RANGES AND CUT-OFF VALUES FOR SIMULTANEOUS MONITORING OF RAS BLOCKER EFFICACY AND SCREENING FOR SECONDARY HYPERTENSION USING RAAS TRIPLE-A PROFILING

Objective: Uncontrolled hypertension is caused by various factors including compliance issues, patient specific drug uptake and elimination profiles or secondary forms of hypertension, resulting in blood pressure control rates of less that 50%. RAAS Triple-A profiling is based on a high-throughput mass-spectrometry assay for Angiotensin I (Ang I), Angiotensin II (Ang II) and Aldosterone in serum samples. Quantified hormone levels are used to calculate markers for plasma-renin-activity (PRA-S), plasma angiotensin-converting-enzyme activity (ACE-S) and adrenal aldosterone secretion (AA2-Ratio). The integrated analysis of these molecular markers together with drug prescription information allows to identify the underlying cause of uncontrolled hypertension, including primary aldosteronism and insufficiency in drug adherence or dosing for ACE inhibitors (ACEi) and angiotensin receptor blockers (ARBs). Design and method: 500 participants with prescribed antihypertensive drugs were selected from the “Cooperative Health Research in South Tyrol” (CHRIS) study, a population-based study from an Alpine rural environment. Five age- and sex-matched groups (N = 100 each) selected were individuals on single therapy with ARBs, ACEi or beta blockers, and on single pill dual therapy of ACEi or ARBs in combination with diuretics. Three age and sex-matched control groups of 100 participants each were included, being normotensive, hypertensive (treated with non-antihypertensive drugs) and hypertensive participants without any prescribed medication. Results: RAAS Triple-A analysis was performed in all individuals and reference values for Ang I, Ang II, Aldosterone, PRA-S, ACE-S and AA2-Ratio were established in appropriate sub-populations. Drug monitoring by LC-MS/MS based quantification of anti-hypertensive drugs in serum was used as a gold standard to determine cut-off values for compliance with ARB and ACEi therapy and ROC analysis was performed using angiotensin-based biomarkers. Conclusions: RAAS Triple-A profiling for the first time provides an interpretation of blood pressure regulating effector hormone levels under consideration of individual drug prescriptions and its dynamic molecular impact on a patient's physiology. The resulting model for patient stratification paves the way for personalized treatment of hypertension, simultaneously screening for secondary hypertension and drug adherence/dosing based on a single high throughput routine blood test applied to patients while being on their standard therapy.

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.

Malignant hypertension and hyperreninemia: primary or secondary hypertension? A case report

Malignant hypertension is a rare condition characterized by severe hypertension and multi-organ ischemic damage. Marked activation of the renin-angiotensin system is observed in many patients, but its persistence over time is not known. We report a case of a 42-year-old woman who presented with severe hypertension and multi-organ damage. Initial evaluation showed an elevated value of direct renin concentration with normal plasma aldosterone concentration and a nodular lesion in the left adrenal gland. The differential diagnosis between the primary and secondary form of hypertension had to be questioned. Consequently, the patient was followed up for 20 months. Repeated checks showed a significant increase in renin levels with a normal aldosterone concentration and regression of organ damage. After 20 months, renin values returned within normal range. Hyperreninemia persisting over a long period of time has not been fully explained. Long-term follow-up allowed us to attribute malignant hypertension to de novo essential hypertension.

What Is the Most Common Cause of Secondary Hypertension?: An Interdisciplinary Discussion

Traditional statements in medical textbooks pointed that 90 to 95% of cases of hypertension is essential or primary. However, secondary hypertension seems to be common in those patients with resistant forms of hypertension. Appropriate investigation and treatment may have prognostic impact but frequently hypertension remission did not occur raising concerns about the real meaning of secondary hypertension. Here, we provided an interdisciplinary and critical discussion comprising an endocrinologist, a nephrologist, and a cardiologist with expertise in resistant hypertension. We reviewed the literature approaching each one of the recognizable cause of hypertension. Recent studies pointed that the most common causes of secondary hypertension are those who overall responses to their treatments do not promote hypertension remission including obstructive sleep apnea (OSA), chronic kidney disease, renovascular hypertension and primary aldosteronism. The authors raised concerns regarding the lack of inclusion of obesity by several societies as a formal cause of hypertension considering not only the biologic plausibility but also the huge impact of weight loss therapies such as bariatric surgery on hypertension remission. In contrast, there is no discussion that a very rare condition-namely pheochromocytoma-is the most "typical" cause of hypertension by promoting hypertension remission in the majority of patients after surgical procedure. Hypertension is a complex condition with multiple environmental and genetics interactions. In clinical practice, it is challenging to prove causality in hypertension. Common conditions largely acceptable as causes of hypertension (OSA, chronic kidney disease, renovascular hypertension, and primary aldosteronism) frequently occur in a setting of an established hypertension background and therefore do not promote hypertension remission in a significant proportion of patients. If obesity becomes largely accepted by several societies as a secondary form of hypertension, this pandemic condition will be certainly the most common cause of hypertension.