A structured physical activity program in an adolescent population with overweight or obesity: a prospective interventional study.

Obesity is a significant health problem, with increasing involvement of young population worldwide. The aim of this study was to evaluate the effects of 2 different types of physical exercise (resistance vs. combined aerobic-resistance) on cardiovascular and anthropometric profile of a sample of sedentary adolescents with overweight and obesity. After undergoing clinical, cardiovascular and anthropometric-metabolic evaluation (T0), subjects with overweight and obesity were randomized to a 6-month resistance or combined aerobic-resistance training program. Clinical, cardiovascular and anthropometric-metabolic evaluations were repeated after 6 months of training (T1) and after 3 months of detraining (T2). Thirty adolescents with overweight/obesity were enrolled and 20 subjects completed training program. A significant improvement in body composition was detected after 6 months, with a reduction of body mass index (32.1 [30.5 to 34.4] vs. 31.1 [29.6 to 33.4] kg/m2, p = 0.02) and adipose tissue (45.5 [41.1 to 49.7] vs. 41.6 [37.0 to 49.2] kg, p < 0.01). A reduction in diastolic blood pressure (75.5 ± 8.9 vs. 68.2 ± 6.4 mm Hg, p = 0.02) and pulse wave velocity (5.7 [5.1 to 5.9] vs. 5.2 [4.7 to 5.7] m/s, p = 0.04) was also observed. Persistence of the effect on the most important parameters was observed also after detraining period. In conclusion, regular physical exercise induces positive metabolic and cardiovascular effects, persisting even after brief discontinuation. Novelty: Physical exercise induces positive effect on cardiovascular risk profile. Positive effects persist also after brief discontinuation. Physical exercise reduces early signs of autonomic disfunction.

Current assessment of pulse wave velocity: comprehensive review of validation studies.

OBJECTIVE: Carotid-femoral pulse wave velocity (PWV) is considered the gold standard for arterial stiffness assessment in clinical practice. A large number of devices to measure PWV have been developed and validated. We reviewed different validation studies of PWV estimation techniques and assessed their conformity to the Artery Society Guidelines and the American Heart Association recommendations. METHODS: Pubmed and Medline (1995-2017) were searched to identify PWV validation studies. Of the 96 article retrieved, 26 met the inclusion criteria. RESULTS: Several devices had been developed and validated to noninvasively measure arterial stiffness, using applanation tonometry (SphygmoCor, PulsePen), piezoelectric mechanotransducers (Complior), cuff-based oscillometry (Arteriograph, Vicorder and Mobil-O-Graph), photodiode sensors (pOpmètre) and devices assessing brachial-ankle pulse wave velocity and cardiac-ankle PWV. Ultrasound technique and MRI remain confined to clinical research. Good agreement was found with the Artery Society Guidelines. Two studies (Complior, SphygmoCor Xcel) showed best adherence with the guidelines. In Arteriograph, MRI, ultrasound and SphygmoCor Xcel validation studies sample size was smaller than the minimum suggested by the guidelines. High discrepancies between devices were shown in distance estimation: in two studies (Arteriograph, Complior) path length was estimated in conformity to the guidelines. Transit time was calculated using the intersecting tangent method, but in two studies (Vicorder, pOpmètre) best agreement was found using the maximum of the second derivative. Six studies reached the accuracy level 'excellent' defined in the Artery guidelines. CONCLUSION: Method to assess transit time and path length need validation in larger populations. Further studies are required in different risk population to implement clinical applicability of every device.

Trisomy of the Short Arm of Chromosome 12 Associated with High Cardiovascular Risk: A Case Report.

Trisomy of the short arm of chromosome 12 is a rare genetic disease characterised by dysmorphic features, mental retardation, behavioural disorders, seizures predisposition and other congenital abnormalities. Arterial hypertension is not a characteristic feature of 12p trisomy, although congenital heart defects are reported. In this case report, we present a young patient with incomplete trisomy 12p, analysing some characteristics of this disease that have not been previously described in literature.

Arterial Hypertension and Multiple Myeloma: Physiopathology and Cardiovascular Risk and 'Practical' Indications in Patients Receiving Carfilzomib.

The introduction of carfilzomib in the treatment of relapsing and refractory multiple myeloma has allowed a significant increase in survival. The most frequent adverse effect of Carfilzomib treatment is arterial hypertension, even though the exact physiopathological mechanism are still unclear. MM patients, on the other hand, often present significant cardiovascular risk factors and comorbidities. Uncontrolled hypertension is frequently the cause of cardiovascular complications. It has been estimated that up to 50% of subjects in the general population are unaware of their hypertensive condition and only half of those who are aware of this risk factor present good control of blood pressure. Although the management of arterial hypertension is clearly important in reducing the risk of cardiovascular events, and is well described by the current guidelines, no clear indications are provided on how to approach and treat specifically MM patients undergoing treatment with proteasome inhibitors. The aim of our work is to summarize a practical approach to the stratification of cardiovascular risk of hypertensive in patients who are candidates for or actively treated with carfilzomib for refractory multiple myeloma (MMR). MM patients eligible for carfilzomib treatment should preliminary undergo a careful cardiovascular risk stratification. Perspective studies will help to better identify the specific risk factors that should be considered and treated in these patients.

Issues in the Diagnosis and Treatment of Primary Aldosteronism.

Primary aldosteronism (PA) is associated with a high rate of cardio- and cerebrovascular complications and metabolic alterations. PA is also recognized as the most frequent, although often unrecognized, secondary form of hypertension. Guidelines have been released to assist clinicians in the diagnostic work-up and subtype differentiation of PA. In this review we discuss and compare the available guidelines in the context of our professional experience and evaluate diagnostic and therapeutic aspects that are still a matter of debate.

18-hydroxycorticosterone, 18-hydroxycortisol, and 18-oxocortisol in the diagnosis of primary aldosteronism and its subtypes.

CONTEXT: Diagnosis of primary aldosteronism (PA) is made by screening, confirmation testing, and subtype diagnosis (computed tomography scan and adrenal vein sampling). However, some tests are costly and unavailable in most hospitals. OBJECTIVE: The aim of the study was to evaluate the role of serum 18-hydroxycorticosterone (s18OHB), urinary and serum 18-hydroxycortisol (u- and s18OHF), and urinary and serum 18-oxocortisol (u- and s18oxoF) in the diagnosis of PA and its subtypes, aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH). PATIENTS: The study included 62 patients with low-renin essential hypertension (EH), 81 patients with PA (20 APA, 61 BAH), 24 patients with glucocorticoid-remediable aldosteronism, 16 patients with adrenal incidentaloma, and 30 normotensives. INTERVENTION AND MAIN OUTCOME MEASURES: We measured s18OHB, s18OHF, and s18oxoF before and after saline load test (SLT) and 24-h u18OHF and u18oxoF. RESULTS: PA patients displayed significantly higher levels of s18OHB, u18OHF, and u18oxoF compared to EH and normal subjects; APA patients displayed s18OHB, u18OHF, and u18oxoF levels significantly higher than BAH patients. Similar results were obtained for s18OHF and s18oxoF. SLT significantly reduced s18OHB, s18OHF, and s18oxoF in all groups, but steroid reduction was much less for APA patients compared to BAH and EH. The s18OHB/aldosterone ratio after SLT more than doubled in EH but remained unchanged in APA patients. CONCLUSIONS: u18OHF, u18oxoF, and s18OHB measurements in patients with a positive aldosterone/plasma renin activity ratio correlate with confirmatory tests and adrenal vein sampling in PA patients. If verified, these steroid assays would refine the diagnostic workup for PA.

Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study (Primary Aldosteronism in TOrino-GENetic forms).

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension, and patients display an increased prevalence of cardiovascular events compared with essential hypertensives. To date, 3 familial forms of PA have been described and termed familial hyperaldosteronism types I, II, and III (FH-I to -III). The aim of this study was to investigate the prevalence and clinical characteristics of the 3 forms of FH in a large population of PA patients. Three-hundred consecutive PA patients diagnosed in our unit were tested by long-PCR of the CYP11B1/CYP11B2 hybrid gene that causes FH-I, and all of the available relatives of PA patients were screened to confirm or exclude PA and, thus, FH-II. Urinary 18-hydroxycortisol and 18-oxocortisol were measured in all of the familial PA patients. Two patients were diagnosed with FH-I (prevalence: 0.66%), as well as 21 of their relatives, and clinical phenotypes of the 2 affected families varied markedly. After exclusion of families who refused testing and those who were not informative, 199 families were investigated, of which 12 were diagnosed with FH-II (6%) and an additional 15 individuals had confirmed PA; clinical and biochemical phenotypes of FH-II families were not significantly different from sporadic PA patients. None of the families displayed a phenotype compatible with FH-III diagnosis. Our study demonstrates that familial forms of hyperaldosteronism are more frequent than previously expected and reinforces the recommendation of the Endocrine Society Guidelines to screen all first-degree hypertensive relatives of PA patients.

LXR-activating oxysterols induce the expression of inflammatory markers in endothelial cells through LXR-independent mechanisms.

AIMS: Liver X receptors alpha and beta (LXRalpha, LXRbeta) are key regulators of cholesterol homeostasis. The effects of LXR ligands on endothelial cells are largely unknown. While oxysterol LXR agonists can increase the endothelial-leukocyte interaction, synthetic LXR agonists are anti-atherogenic and anti-inflammatory. Mechanistic differences may underlie such findings. METHODS AND RESULTS: LXRalpha and LXRbeta were found to be expressed in human endothelial cells. While synthetic LXR agonists could blunt the LPS-induced up-regulation of adhesion molecules (ICAM-1, VCAM-1, E-Selectin), 22-hydroxycholesterol and 24,25-epoxycholesterol enhanced such response. Microarray profiling further showed that the endothelial gene expression fingerprints of 22-hydroxycholesterol and T0901317 largely differed and unexpectedly shared only a restricted number of genes. Indeed, 22-hydroxycholesterol down-regulated eNOS and up-regulated a vast cohort of inflammatory mediators such as adhesion molecules, cytokines, enzymes and transcription factors. Other LXR-activating oxysterols such as 24,25-epoxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol could also stimulate the endothelial expression of inflammatory markers, although significant differences were observed. These effects persisted in LXR-silenced cells, confirming the mechanistic dissociation of oxysterol and LXR pathways. Furthermore, the oxysterol-induced expression of inflammatory markers was not secondary to cell apoptosis and may relate to oxidative stress. CONCLUSIONS: LXR-activating oxysterols comprehensively activate the expression of endothelial inflammation markers independently from LXRs. At proper dosage, synthetic LXR agonists are safe on endothelial cells and may even transrepress inflammatory reactions.

Aldosterone as an independent factor in cerebrovascular damage.

Aldosterone is produced not only in the adrenal gland but also in other tissues, including the brain, where it plays an important role in the control of blood pressure and water and electrolyte homeostasis. Aldosterone has also been demonstrated to be a major factor in target organ damage independent of its effects on blood pressure. Herein we review the pathophysiology of aldosterone action in the brain and the clinical and experimental studies on the detrimental effects of aldosterone in the brain.

Bradykinin B2 receptor gene (-58T/C) polymorphism influences baroreflex sensitivity in never-treated hypertensive patients.

BACKGROUND: Most evidence currently favours a fundamental role of the autonomic nervous system in the pathogenesis of essential hypertension. Recent studies suggest that about 40% of baroreflex variation, an index of cardiac autonomic control, is influenced by genetic factors. METHODS AND RESULTS: The aim of this study was to investigate the effect of a common polymorphic variant of the bradykinin B2 receptor gene (B2R; -58T/C) on the autonomic regulation of baroreflex sensitivity (BRS) in 129 mild-moderate never-treated hypertensive patients. No significant differences were found for clinical and biochemical parameters among genotypes. BRS increased with the number of B2R T alleles. B2R genotype was a strong independent predictor of BRS, accounting for 12% of its variation. We suggest that a decrease in the transcription of the bradykinin B2R gene in the presence of the B2R -58C allele could reduce BRS via the diminished effect of bradykinin. CONCLUSIONS: B2R genotype can explain part of the BRS variation that is unaccounted for by simple anthropometric variables and common risk factors.