Frequency of Iatrogenic Sexual Dysfunction Associated with Antihypertensive Compounds

Iatrogenic sexual dysfunction (SD) caused by antihypertensive (AH) compounds, provoking sexual desire, orgasm or arousal dysfunction, is a common clinical adverse event. Unfortunately, it is often underestimated and underreported by clinicians and prescribers in clinical practice, deteriorating the adherence and patient quality of life. The objective of this study was to investigate the frequency of SD in patients treated with different antihypertensive compounds; a real-life naturalistic and cross-sectional study in patients receiving AH treatment was carried out. Method: A total of 256 patients were included in the study (188 males and 68 females who met the inclusion and exclusion criteria). The validated Psychotropic-Related Sexual Dysfunction Questionnaire (PRSexDQ-SALSEX) was transversally applied once at least every two months following the onset of the treatment in order to measure possible AH-related SD. Although the spontaneous reporting of SD was very low (6.81% females/24.8% males), 66.40% of the patients reported impaired sexual function through the SALSEX questionnaire after the treatment onset, as follows: decreased desire (55.8% females/54.2% males), delayed orgasm (42.6%/45.7%), anorgasmia (42.6%/43.6%) and arousal difficulties (53%/59.6%). The average frequency of moderate to severe iatrogenic SD was 66.4% with AH in monotherapy as follows: angiotensin II receptor antagonists (ARBs), 29.8%; calcium antagonists, 40%; diuretics, 42.9%; beta blockers, 43.8%; and angiotensin-converting enzyme (ACE) inhibitors, 77.8%. Combined treatments showed a higher percentage of main SD (70.3%): diuretic + ACE inhibitor, 42.3%; ARB + calcium antagonist, 55.6%; diuretic + calcium antagonist, 68.8%; and diuretic + ARB, 74.2%. The greatest risk factors associated with SD were poor general health, age over 60 with a comorbid coronary or musculoskeletal disease, mood disorder and diuretic +ARB combined therapy. Conclusion: SD is common in patients treated with antihypertensive drugs, and it is still underreported. The most harmful treatment deteriorating sexual function was the combination of diuretic +ARB, while the least harmful was monotherapy with ARBs. More research is needed on the clinical management of this problem to preserve the quality of life of patients and their partners.

Biomarkers of Uremic Cardiotoxicity

Cardiovascular (CV) morbidity and mortality increase along with the progression of chronic kidney disease (CKD). The potential novel biomarkers of cardiotoxicity have been tested with the aim of the early detection of patients at high CV risk, and among them are markers of inflammation, oxidative stress, acute renal injury, and microRNAs. The study analyzed biomarkers in non-dialysis-dependent (NDD; stage 3a–4 CKD) and dialysis-dependent (DD) CKD patients. The prospective cohort study included 87 patients who were followed for 18 months, during which period newly occurred CV events were recorded. Cox regression analysis confirmed serum albumin, urea, interventricular septum thickness diameter (IVST), the use of calcium antagonist, and erythropoiesis-stimulating agent to be significant predictors of CV outcome. No significant difference was observed in biomarkers of inflammation, oxidative stress, acute kidney injury (IL-18, CRP, ferritin, IMA, SOD, NGAL, and KIM-1), and miR-133a, in regards to the presence/absence of CV event, CV death, and left ventricular hypertrophy. Serum albumin, urea, IVST, and the use of calcium antagonist and erythropoiesis-stimulating agents were confirmed to be factors associated with CV events in CKD patients. Apart from traditional risk factors, new research is needed to define novel and reliable biomarkers of cardiotoxicity in CKD patients.

Assessment of calcium antagonist therapy protective effect on the thickness of the intima-media complex in patients with arterial hypertension

Aim. To evaluate the connection of calcium antagonist (amlodipine) therapy with the dynamics of the intima-media complex thickness in patients with arterial hypertension (AH), depending on genetic polymorphism.Methods. The study included representatives of the indigenous nationality (the Shors) – 901 people, of which a group of 367 people with hypertension was identified. The prospective stage of observation included 234 people who did not receive antihypertensive therapy. Based on the prescription of calcium antagonists, patients with hypertension were divided into two groups. Gene polymorphism was tested by polymerase chain reaction.Results. In the Shor cohort, the regression of the intima-media complex thickness of the carotid arteries was observed more often in hypertensive patients who received calcium antagonists if to compare them with those who did not take the drug [OR = 2.30]. In addition, the decrease in the atherosclerotic process is associated with the genotype carriage: I/I of the ACE gene [OR = 9.42], T/C of the AGT gene [OR = 3.52], 4b/4b and 4b/4a of the eNOS gene [OR = 2.26 and OR = 3.75], C/C of the MTHFR gene [OR = 2.62].Conclusion. Pharmacogenetic aspects are valuable from the point of view of an individual approach and obtaining the most pronounced pharmacological response in order to slow down the processes of vascular wall remodeling in patients with hypertension.

Masked uncontrolled hypertension: risk factors and ways of influence

According to the current Guidelines, the effectiveness of antihypertensive therapy is assessed mainly by achieving target levels of office blood pressure (BP). However, masked uncontrolled hypertension (MUCH) increases the risk of cardiovascular events, therefore deserves timely diagnosis and correction. Objective — to establish the prevalence and risk factors of MUCH and to clarify how the use of fixed combinations can affect the control of office and out‑of‑office BP. Materials and methods. We examined 70 patients with arterial hypertension (AH) of 1 — 2 degrees. The initial assessment of the effectiveness of antihypertensive therapy was carried out 3 months after its appointment. Of the 70 patients initially enrolled in the study, 63 were able to reach essential office BP reduction point (< 140/90 mm Hg, according to 2020 ISH Guidelines). Patients who reached essential point of office BP reduction were additionally provided 24 hour ambulatory BP monitoring (ABPM) to detect possible MUCH. Results. It was found that among 63 patients in whom AH was controlled according to office BP data, 37 patients (58.7 %) had insufficient hypertension control according to ABPM data (they had MUCH). An assessment of possible factors for the development of MUCH showed that elderly age occurred in 29 (78.4 %) patients with MUCH, male sex — in 22 (59.5 %) patients, smoking — in 26 (70.3 %) patients, stress — in 29 (78.4 %) patients, various sleep disorders — in 17 (45.9 %) patients, diabetes mellitus (DM) — in 21 (56.8 %) patients, obesity — in 25 (67.6 %) patients, insulin resistance (IR) — in 27 (73 %) patients, chronic kidney disease (CKD) — in 13 (35.1 %) patients. Analysis of patient therapy showed that out of 37 patients with MUCH, 7 patients received monotherapy, 9 patients received free dual combinations (ACE inhibitor/sartan + calcium antagonist/diuretic), and 21 patients received fixed dual combinations. In accordance with 2018 ESC/ESH Guidelines, antihypertensive therapy was strengthened for patients with MUCH: those patients who had previously received monotherapy or free combinations were transferred to double fixed combinations (ACE inhibitors/sartans + calcium antagonist/diuretic), in which both drugs acted for 24 hours, and those patients with MUCH who received double fixed combinations were transferred to triple fixed combinations. Evaluation of antihypertensive therapy after 3 months showed that of 37 patients with initially established MUCH, complete BP control was achieved in 32 (86.5 %) patients (in the remaining 5 patients, despite sufficient control of office BP, MUCH was maintained according to ABPM data). Conclusions. In inadequate control of out‑of‑office BP, various disturbances of the circadian rhythm (with a predominance of the non‑dipper rhythm) are more common than with complete BP control. MUCH is associated with such risk factors as elderly age, male gender, smoking, stress, sleep disturbances, DM, obesity, IR, and CKD. Strengthening antihypertensive therapy contributed to the achievement of both office and out‑of‑office BP in 86.5 % of patients with previously established MUCH.

Factors determining drug choice in patients with hypertension and carbohydrate metabolism disorders considering ethnicity

Aim: to evaluate the antihypertensive efficacy of two drug combinations, RAAS inhibitor plus calcium antagonist or RAAS inhibitor plus a diuretic, in hypertension and carbohydrate metabolism disorders using a small population of the Shoria people as an example. Patients and Methods: this study included 901 indigenous inhabitants of the Mountain Shoria over 18 years. 40.7% were diagnosed with hypertension according to the Guidelines of the Russian Scientific Society of Cardiologists/Russian Medical Society on Hypertension (2010). The prospective study enrolled 320 treatment-naive patients with hypertension. Participants were randomized into two groups using envelopes. Group 1 patients (n=160) received RAAS inhibitor plus calcium antagonist. Group 2 patients (n=160) received RAAS inhibitor plus thiazide-like diuretic. Each group was divided into two subgroups, i.e., patients with isolated hypertension or patients with hypertension and carbohydrate metabolism disorders (impaired fasting glycemia, impaired glucose tolerance, diabetes). Blood pressure (BP) <140/90 mm Hg was considered the target level. Results: drug class choice and accompanying risk factors determined the efficacy of hypertension in the indigenous population of the Mountain Shoria. Both combinations (RAAS inhibitor plus calcium antagonist or RAAS inhibitor plus diuretic) were equally effective in patients with isolated hypertension or hypertension and carbohydrate metabolism disorders (56.4% and 43.9%, respectively, р=0.121). However, when prescribing RAAS inhibitor plus a diuretic, group 1 patients achieved the target BP more often than group 2 patients (59.2% vs. 38.7%, р=0.012). Moreover, in the Shoria inhabitants with hypertension, carbohydrate metabolism disorders, and obesity (particularly abdominal obesity), RAAS inhibitor plus calcium antagonist were more effective than RAAS inhibitor plus diuretic (59.3% vs. 44.0%, р=0.037). Similar findings were reported in participants with other disorders, e.g., left ventricular hypertrophy and increased intima-media thickness. Conclusions: the sensitivity of patients with hypertension to various classes of antihypertensives and its effective treatment is determined by numerous recognized factors. However, ethnicity is also to be considered. Conclusions: the sensitivity of patients with hypertension to various classes of antihypertensives and its effective treatment is determined by numerous recognized factors. However, ethnicity is also to be considered. KEYWORDS: treatment efficacy, antihypertensive combination, hypertension, carbohydrate metabolism disorders, ethnicity. FOR CITATION: Mulerova T.A., Ogarkov M.Yu. Factors determining drug choice in patients with hypertension and carbohydrate metabolism disorders considering ethnicity. Russian Medical Inquiry. 2021;5(9):568–574 (in Russ.). DOI: 10.32364/2587-6821-2021-5-9-568-574.

Mixed Connective Tissue Disease

AbstrakMixed Connective Tissue Disease (MCTD) adalah penyakit yang gejala klinisnya tumpang tindih antara Lupus Eritematosus Sistemik (LES), Skleroderma, dan Polimiositis. Tidak ada obat khusus untuk MCTD. Rekomendasi untuk pengelolaan didasarkan pada perawatan konvensional untuk LES, polimyositis, RA dan skleroderma. Dilaporkan pasien wanita berusia 33 tahun, dirawat di Penyakit Dalam RSUP Dr M Djamil Padang dengan keluhan utama tangan dan kaki semakin kaku sejak 1 bulan yang lalu. Rambut rontok dan pada kulit terdapat Indurasi, skuama coklat kehitaman, hiperpigmentasi kedua tungkai dan wajah serta teleangiektasis. Laboratorium didapatkan albumin 1,8 mg/dl, ureum 60 mg/dl, kreatinin 1,3 mg/dl. Urinalisis: protein +++. Analisis cairan asites kesan transudat, rontgen thoraks dengan kesan fibrosis paru dan rontgen manus tampak kontraktur dari phalang media dan proximal. USG Ginjal kesan sesuai dengan gambaran akut di kedua ginjal. Pemeriksaan ANA Profil (RNP/Sm +, Sm +, Ro-52 Recombinant ++, Scl-70 +++, dsDNA +, Nucleosomes +, Ribosomal-P-Protein +++ ), ANA IF Positif Titer 1>1000. Biopsi kulit kesan skleroderma. Pasien didiagnosis dengan MCTD & Nefritis Lupus. Pasien diterapi methotrexate (MTX), kortikosteroid, dihydropyridine-type calcium antagonist dan dorner, teknik rehabilitasi seperti stretching dan peningkatan gerak yang berpengaruh terhadap kesembuhan dari sklerosis sistemik.