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Background: The cardio-ankle vascular index (CAVI) measure of arterial stiffness is associated with prevalent cardiovascular risk factors, while its predictive value for cardiovascular events remains to be established. The aim was to determine associations of CAVI with cardiovascular morbimortality (primary outcome) and all-cause mortality (secondary outcome), and to establish the determinants of CAVI progression., Methods: TRIPLE-A-Stiffness, an international multicentre prospective longitudinal study, enrolled >2000 subjects ≥40 years old at 32 centres from 18 European countries. Of these, 1250 subjects (55% women) were followed for a median of 3.82 (2.81-4.69) years., Findings: Unadjusted cumulative incidence rates of outcomes according to CAVI stratification were higher in highest stratum (CAVI > 9). Cox regression with adjustment for age, sex, and cardiovascular risk factors revealed that CAVI was associated with increased cardiovascular morbimortality (HR 1.25 per 1 increase; 95% confidence interval, CI: 1.03-1.51) and all-cause mortality (HR 1.37 per 1 increase; 95% CI: 1.10-1.70) risk in subjects ≥60 years. In ROC analyses, CAVI optimal threshold was 9.25 (c-index 0.598; 0.542-0.654) and 8.30 (c-index 0.565; 0.512-0.618) in subjects ≥ or <60 years, respectively, to predict increased CV morbimortality. Finally, age, mean arterial blood pressure, anti-diabetic and lipid-lowering treatment were independent predictors of yearly CAVI progression adjusted for baseline CAVI., Interpretation: The present study identified additional value for CAVI to predict outcomes after adjustment for CV risk factors, in particular for subjects ≥60 years. CAVI progression may represent a modifiable risk factor by treatments., Funding: International Society of Vascular Health (ISVH) and Fukuda Denshi, Japan., Competing Interests: Declaration of interests AdlS reports support from Sanofi and Viatris. JB reports support from AstraZeneca, Bayer, Elkendi, Hikma, Leurquin, Omron, Organon, Sanofi, and Vivactis. AK reports honoraria for lecturing from Servier, KRKA, and Novartis, and travel support from Servier. PW reports support from Ministry of Health of the Czech Republic, grant nr. NV 19-09-00125, National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, Project No. LX22NPO5104)–Funded by the European Union–Next Generation EU, Servier, and ProMED. The remaining authors have nothing to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Acute genital ulcers can affect females of all ages. In children, they often appear as an emergency and remain a diagnostic challenge for pediatricians, gynecologists and dermatologists. Prompt diagnosis and identification of disease- related factors help to implement appropriate treatment. Firstly, it is crucial to properly compile the past medical history of the patient. Past infectious, autoimmune, malignant or traumatic conditions, as well as vaccinations may contribute to the occurrence of acute genital ulcers. Moreover, new infectious agents, such as severe acute respiratory syndrome coronavirus 2 and vaccinations against Coronavirus disease of 2019, may play a significant role in the development of atypical clinical symptoms. Here we present a case of a 12-year-old girl with acute genital ulcers. Additional symptoms accompanying the ulcer included: abdominal pain, nausea, vomiting, dysuria, vulvar pain and fever. Blood test showed leukocytosis, especially neutrophilia and monocytosis and increased levels of c-reactive protein and procalcitonin. Serological tests for the most common infections were negative. Moreover, the patient had a history of autoimmune diseases. She had periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome, and IgA vasculitis, also known as Henoch-Schönlein purpura in her past medical history. Additionally, she was vaccinated against SARS-CoV-2 shortly before the lesions appeared., (© 2024. The Author(s).)

Background: Numerous studies based on assessment of lithium clearance demonstrated higher sodium reabsorption in renal proximal tubules in individuals with hypertension, overweight, obesity, metabolic syndrome, or diabetes., Aims: We aimed to assess the influence of angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin-II-receptor antagonists (ARB) treatment on sodium handling., Methods: In a sample of 351Caucasian subjects without diuretic treatment with prevailing sodium consumption, we studied associations between renal sodium reabsorption in proximal (FPRNa) and distal (FDRNa) tubules assessed by endogenous lithium clearance and daily sodium intake measured by 24-hour excretion of sodium (UNaV), in the context of obesity and long-term treatment with ACE-I or ARB., Results: In the entire study population, we found a strong negative association between FPRNa and ACE-I/ARB treatment (b = -19.5; SE = 4.9; P <0.001). Subjects with FPRNa above the median value showed a significant adverse association between FPRNa and age (b = -0.06; SE = 0.02; P = 0.003), with no association with ACE-I/ARB treatment (P = 0.68). In contrast, in subjects with FPRNa below the median value, we found a strongly significant adverse relationship between FPRNa and ACE-I/ARB treatment (b = -30.4; SE = 8.60; P <0.001), with no association with age (P = 0.32)., Conclusions: ACE-I/ARB long-term treatment modulates FPRNa in the group with lower reabsorption, but not in that with higher than median value for the entire study population.

Previous studies on aggressiveness and impulsiveness in women with polycystic ovary syndrome (PCOS) are ambiguous. Furthermore, no biochemical or clinical factors related to these variables have been definitively confirmed. The aim of the study was to clarify whether, in women with phenotype A of PCOS, variables such as body mass index and clinical and biochemical hyperandrogenism have an impact on either the intensity of impulsivity or aggression or on other selected behavioral manifestations of these variables. The study included 95 patients diagnosed with PCOS phenotype A. The criterion for recruitment into the study group and the control group was body mass index. The study was conducted with the use of a closed-format questionnaire and calibrated clinical scales. Higher body mass index (BMI) values in women with PCOS phenotype A are associated with poor eating habits. The severity of impulsivity and aggression syndrome, as well as the tendency to engage in risky sexual behavior and patterns of alcohol consumption among patients diagnosed with PCOS phenotype A, are not dependent on BMI. The severity of impulsiveness and the syndrome of aggression in women with phenotype A PCOS are not associated with clinical symptoms of hyperandrogenism or with androgen levels., Competing Interests: The authors declare no conflict of interest.

Insulin resistance is documented in clamp studies in 75% of women with polycystic ovary syndrome (PCOS). Although it is not included in the diagnostic criteria of PCOS, there is a crucial role of this metabolic impairment, which along with hormonal abnormalities, increase each other in a vicious circle of PCOS pathogenesis. Insulin resistance in this group of patients results from defects at the molecular level, including impaired insulin receptor-related signaling pathways enhanced by obesity and its features: Excess visceral fat, chronic inflammation, and reactive oxygen species. While lifestyle intervention has a first-line role in the prevention and management of excess weight in PCOS, the role of anti-obesity pharmacological agents in achieving and maintaining weight loss is being increasingly recognized. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) not only act by reducing body weight but also can affect the mechanisms involved in insulin resistance, like an increasing expression of glucose transporters in insulin-dependent tissues, decreasing inflammation, reducing oxidative stress, and modulating lipid metabolism. They also tend to improve fertility either by increasing LH surge in hypothalamus-pituitary inhibition due to estrogen excess connected with obesity or decreasing too high LH levels accompanying hyperinsulinemia. GLP1-RAs seem promising for effective treatment of obese PCOS patients, acting on one of the primary causes of PCOS at the molecular level.

Purpose: The parameters of cerebral blood flow are modulated by many factors. The aim of the study was to prospectively assess the relationship between the number of the established cardiovascular risk factors and hemodynamic parameters of cerebral blood flow. Material and methods: The study was cross-sectional baseline and 6-year follow-up data analysis. We analyzed data regarding cardiovascular risk factors, medications use, and ultrasonographically (transcranial Doppler) obtained mean cerebral blood flow velocity (mCBFV), pulsatility (PI), resistance (RI) indexes of middle cerebral artery. Results: After 6.0 ± 0.6 years of follow-up, there was increase in systolic ( p  = .047), and decrease in diastolic ( p  = .005) blood pressure, resulting in greater pulse pressure ( p  < .001). Although intima-media thickness increased during follow-up ( p  = .019), PI, RI and mCBFV did not differ between baseline and follow-up. In the cohort without follow-up ( n  = 112), we observed strong association between number of studied cardiovascular risk factors and lower mCBFV, and higher PI and RI (all p  < .001), in the cohort with 6 year follow-up ( n  = 53), we confirmed similar association for mCBFV and PI ( p  = .002) at baseline, and mCBFV ( p  = .024) after follow-up. During follow-up, more patients were treated with vasoactive medications ( p  < .05). Also the median (interquartile range) of total number of taken drugs at follow-up 2 (1-3) was greater than at baseline 1 (0-2), ( p  < .001). The addition of vasoactive medications during follow-up was associated with increase of the mCBFV (0.012 ± 0.02 m/s, p  = .013). Conclusion: The parameters of the cerebral blood flow are adversely influenced by accretion of cardiovascular risk factors, both at baseline and after 6 years of follow-up. The addition of a vasoactive medication during follow-up is associated with an increase of the mCBFV, a possibly beneficial effect.

Background: Insulin resistance and renal tubular sodium handling influence arterial structure and function and play an essential role in salt-sensitive forms of hypertension., Methods: In a population with prevailing sodium consumption, we assessed the relationship between cardiovascular phenotypes (peripheral and central blood pressures, elastic properties of large arteries, the left ventricular structure) and sodium handling parameters (daily urinary sodium excretion, fractional urinary lithium excretion in proximal-FELi and distal tubules), as a function of insulin sensitivity-measured by homeostasis model assessment-insulin resistance (HOMA-IR), leptin-to-adiponectin (L/A) ratio, and homeostasis model assessment-adiponectin (HOMA-AD)., Results: In patients with FELi below the median value (corresponding to the group with increased proximal sodium reabsorption) and higher insulin resistance as measured by HOMA-IR, pulse wave augmentation indexes were significantly higher-AIxP (99.4% vs. 86.2%; P = 0.007), AIxC1 (159.4% vs. 144.2%; P = 0.04), and AIxC2 (36.1% vs. 28.3%; P = 0.02), than in patients with lower insulin resistance. The same trend was observed in relation to L/A ratio-AIxP (98.7% vs. 87.1%; P = 0.005), AIxC1 (158.6% vs. 144.5%; P = 0.02), and AIxC2 (35.6% vs. 28.5%; P = 0.01) and HOMA-AD-AIxP (99.7% vs. 83.8%; P = 0.001), AIxC1 (160.5% vs. 140.3%; P = 0.007), and AIxC2 (36.6% vs. 26.3%; P = 0.003). Such relationships were not observed in patients with FELi above the median value., Conclusions: In the hypertensive population with prevailing sodium intake, insulin resistance and increased sodium reabsorption in proximal tubules may affect arterial wall function., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: The aim of the Advanced Approach to Arterial Stiffness study was to compare arterial stiffness measured simultaneously with two different methods in different age groups of middle-aged and older adults with or without metabolic syndrome (MetS). The specific effects of the different MetS components on arterial stiffness were also studied., Methods: This prospective, multicentre, international study included 2224 patients aged 40 years and older, 1664 with and 560 without MetS. Patients were enrolled in 32 centres from 18 European countries affiliated to the International Society of Vascular Health & Aging. Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI) and the carotid-femoral pulse wave velocity (CF-PWV) in four prespecified age groups: 40-49, 50-59, 60-74, 75-90 years. In this report, we present the baseline data of this study., Results: Both CF-PWV and CAVI increased with age, with a higher correlation coefficient for CAVI (comparison of coefficients P < 0.001). Age-adjusted and sex-adjusted values of CF-PWV and CAVI were weakly intercorrelated (r = 0.06, P < 0.001). Age-adjusted and sex-adjusted values for CF-PWV but not CAVI were higher in presence of MetS (CF-PWV: 9.57 ± 0.06 vs. 8.65 ± 0.10, P < 0.001; CAVI: 8.34 ± 0.03 vs. 8.29 ± 0.04, P = 0.40; mean ± SEM; MetS vs. no MetS). The absence of an overall effect of MetS on CAVI was related to the heterogeneous effects of the components of MetS on this parameter: CAVI was positively associated with the high glycaemia and high blood pressure components, whereas lacked significant associations with the HDL and triglycerides components while exhibiting a negative association with the overweight component. In contrast, all five MetS components showed positive associations with CF-PWV., Conclusion: This large European multicentre study reveals a differential impact of MetS and age on CAVI and CF-PWV and suggests that age may have a more pronounced effect on CAVI, whereas MetS increases CF-PWV but not CAVI. This important finding may be due to heterogeneous effects of MetS components on CAVI. The clinical significance of these original results will be assessed during the longitudinal phase of the study.

Purpose: The high prevalence of cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD) is observed especially in those undergoing dialysis. Osteoprotegerin (OPG) and its ligands, receptor activator of nuclear factor kappa-B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been associated with cardiovascular complications. Our aim was to study their role as cardiovascular risk factors in stage 5 CKD patients., Patients and Methods: OPG, RANKL and TRAIL concentrations were measured in 69 hemodialyzed CKD patients and 35 healthy volunteers. In CKD patients, cardiovascular dysfunction was assessed with aortic pulse wave velocity (AoPWV), carotid artery intima-media thickness (CCA-IMT), coronary artery calcium score (CACS) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentrations. Cardiovascular and overall mortality data were collected during a 7-years follow-up., Results: OPG plasma concentrations were higher in CKD patients comparing to controls. Total soluble RANKL was lower and OPG/RANKL ratio higher in patients. Soluble TRAIL concentrations did not differ between the groups and OPG/TRAIL ratio was higher in CKD patients. OPG and OPG/TRAIL positively predicted long-term mortality (all-cause and cardiovascular) in CKD patients. OPG positively correlated with AoPWV, CCA-IMT and NT-proBNP whereas OPG/TRAIL with AoPWV and NT-proBNP. Described relationships were independent of classical and non-classical cardiovascular risk factors, with exception of age., Conclusions: Our study confirmed the role of OPG as a biomarker of cardiovascular dysfunction and a predictor of mortality in stage 5 CKD. OPG/TRAIL ratio can be proposed as a predictor of cardiovascular dysfunction and mortality., (Copyright © 2016 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)