Effects of metabolic syndrome on arterial function in different age groups: the Advanced Approach to Arterial Stiffness study

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 2 = 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

Geriatric care in European countries where geriatric medicine is still emerging

Purpose: Practicing geriatric medicine is a challenging task since it involves working together with other medical doctors while coordinating a multidisciplinary team. Global Europe Initiative (GEI) group within the European Geriatric Medicine Society gathers geriatricians from different regions where geriatrics is underrepresented or still developing to promote initiatives for the advancement of geriatric medicine within these countries. Methods: Here we present a first effort to describe several aspects that affect practicing geriatric medicine in five different countries: Greece, Portugal, Russia, Turkey, and Tunisia. Results: We can notice discrepancies between countries concerning all dimensions of geriatrics (recognition, training, educational and professional standards, academic representation, working context). Conclusions: These differences correspond to the specificities of each country and set the frame where geriatric medicine is going to be developed across Europe. EuGMS with GEI group can provide useful support

Gut Microbiota in Patients with Different Metabolic Statuses: Moscow Study

The aim of this paper was to study gut microbiota composition in patients with different metabolic statuses. Methods: 92 participants aged 25&ndash;76 years (26 of whom were men), with confirmed absence of cardiovascular and other chronic diseases (but with the possible presence of cardiovascular risk factors) were included. Carotid ultrasound examinations, 16S rRNA sequencing of stool samples and diet assessments were performed. Statistical analysis was performed using R programming language, 3.1.0. Results: Enterotyping yielded two clusters differentiated by alpha-diversity. Intima-media thickness was higher in the cluster with lower diversity (adj. p &lt; 0.001). Obesity was associated with higher Serratia (adj. p = 0.003) and Prevotella (adj. p &lt; 0.0003) in relative abundance. Abdominal obesity was associated with higher abundance of Serratia (adj. p = 0.004) and Prevotella (adj. p = 0.0008) and lower levels of Oscillospira (adj. p = 0.0005). Glucose metabolism disturbances were associated with higher Blautia (adj. p = 0.0007) and Serratia (adj. p = 0.003) prevalence. Arterial hypertension was associated with high Blautia levels (adj. p = 0.002). The Blautia genus strongly correlated with low resistant starch consumption (adj. p = 0.007). A combination of high-fat diet and elevated Blautia levels was very common for diabetes mellitus type 2 patients (adj. p = 0.0001). Conclusion: The results show that there is a relationship between metabolic changes and higher representation of opportunistic pathogens and low diversity of gut microbiota even in apparently healthy participants

Pharmacokinetics of serelaxin in patients with hepatic impairment: A single-dose, open-label, parallel-group study

Summary AIMS Serelaxin is a recombinant form of human relaxin-2 in development for the treatment of acute heart failure. The present study aimed to evaluate the pharmacokinetics (PK) of serelaxin in patients with hepatic impairment. Secondary objectives included the evaluation of immunogenicity, safety and tolerability of serelaxin. METHODS This was an open-label, parallel-group study (NCT01433458) comparing the PK of serelaxin following a single 24-hour intravenous infusion (30 μg/kg/day) between patients with mild, moderate or severe hepatic impairment (Child-Pugh Class A, B and C, respectively), and healthy matched controls. Blood sampling and standard safety assessments were conducted. The primary non-compartmental PK parameters [including area under the plasma concentration-time curve (AUC)0-48h and AUCinf, and serum concentration at 24 hours post-dose (C24h)] were compared between each hepatic impairment group and healthy controls. RESULTS A total of 49 subjects (including 25 patients with hepatic impairment) were enrolled, of which 48 subjects completed the study. In all groups, the serum concentration of serelaxin increased over the first few hours of infusion, reached steady-state at 12-24 hours and then declined following completion of the infusion with a mean terminal half-life of 7-8 hours. All PK parameter estimates were comparable between each group of patients with hepatic impairment and healthy controls. No serious adverse events, discontinuations due to an adverse event or deaths were reported. No serelaxin-treatment-related antibodies developed during this study. CONCLUSIONS The PK and safety profile of serelaxin were not affected by hepatic impairment, indicating that dose adjustments are unlikely to be required for such patients

Pharmacodynamic and Pharmacokinetic Profiles of Sacubitril/Valsartan (LCZ696) in Patients with Heart Failure and Reduced Ejection Fraction

Aims: Concomitant renin–angiotensin–aldosterone system blockade and natriuretic peptide system enhancement may provide unique therapeutic benefits to patients with heart failure and reduced ejection fraction (HFrEF). This study assessed the pharmacodynamics and pharmacokinetics of LCZ696 in patients with HFrEF. Methods: This was an open-label, noncontrolled single-sequence study. After a 24-h run-in period, patients (n = 30) with HFrEF (EF ≤ 40%; NYHA class II–IV) received LCZ696 100 mg twice daily (bid) for 7 days and 200 mg bid for 14 days, along with standard treatment for heart failure (HF) (except angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers [ARBs]). Results: On Day 21, significant increases were observed in the plasma biomarkers indicative of neprilysin and RAAS inhibition (ratio-to-baseline: cyclic guanosine monophosphate [cGMP], 1.38; renin concentration and activity, 3.50 and 2.27, respectively; all, P < 0.05). Plasma NT-proBNP levels significantly decreased at all the time points on Days 7 and 21; plasma aldosterone and endothelin-1 levels significantly decreased on Day 21 (all, P < 0.05). Following administration of LCZ696, the Cmax of sacubitril (neprilysin inhibitor prodrug), LBQ657 (active neprilysin inhibitor), and valsartan were reached within 0.5, 2.5, and 2 h. Between 100- and 200-mg doses, the Cmax and AUC0–12 h for sacubitril and LBQ657 were approximately dose-proportional while that of valsartan was less than dose-proportional. Conclusions: Treatment with LCZ696 for 21 days was well tolerated and resulted in plasma biomarker changes indicative of neprilysin and RAAS inhibition in patients with HF. The pharmacokinetic exposure of the LCZ696 analytes in patients with HF observed in this study is comparable to that observed in the pivotal Phase III study

Metagenomic Profiles of the Intestinal Virome of Long-Livers

The microbial community of the human intestine is important for maintaining human health. It has been reported that the gut microbiome changes with age, and it can be enrichedwith certain beneficial bacteria while also losing certain commensal bacteria.Little is known about the gut virome of long-livers. Our research aimed to extract, sequence and analyze the viral fraction of long-livers’ gut microbiota in comparison with those of young adults and the elderly. We were thereby able to characterize the gut virome profiles and viral diversity of three age groups. Keywords: aging, gut microbiome, viral metagenomics, bacteriophage

Metagenomic Profiles of the Intestinal Virome of Long-Livers

The microbial community of the human intestine is important for maintaining human health. It has been reported that the gut microbiome changes with age, and it can be enrichedwith certain beneficial bacteria while also losing certain commensal bacteria.Little is known about the gut virome of long-livers. Our research aimed to extract, sequence and analyze the viral fraction of long-livers' gut microbiota in comparison with those of young adults and the elderly. We were thereby able to characterize the gut virome profiles and viral diversity of three age groups. Keywords: aging, gut microbiome, viral metagenomics, bacteriophage

Vascular Health Assessment of The Hypertensive Patients (VASOTENS) Registry: Study Protocol of an International, Web-Based Telemonitoring Registry for Ambulatory Blood Pressure and Arterial Stiffness

Hypertension guidelines recommend ambulatory blood pressure (ABP), central aortic pressure (CAP), and pulse wave velocity (PWV) as parameters for estimating blood pressure (BP) control and vascular impairment. Recent advances in technology have enabled devices to combine non-invasive estimation of these parameters over the 24-hour ABP monitoring. However, currently there is limited evidence on the usefulness of such an approach for routine hypertension management