AimsCarotid–femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population.Methods and resultsWe gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors.ConclusionThe present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

Large-artery properties are altered in OFF/HT compared with OFF/NT. The findings from this cross-sectional study suggest that the alterations in arterial function in subjects with a family history of hypertension are determined mainly by an increased BP and age-related hemodynamic changes.

There is accumulating evidence that vitamin D exerts important pathophysiological effects on cardiovascular system. Low vitamin D was associated with increased cardiovascular risk in several reports. We studied the association between vitamin D and arterial stiffness in a random sample of 560 subjects selected from general population. Arterial stiffness was measured as aortic pulse-wave velocity (PWV) using Sphygmocor device. Serum 25-hydroxyvitamin D (25(OH)D) was measured using commercial kits. We found a clear negative trend in aortic PWV among 25(OH)D quartiles. Subjects in the bottom 25(OH)D quartile (o20 ng ml À1 ) showed the highest aortic PWV (9.04 m s À1 ), compared with 2nd-4th quartile (8.07 m s À1 , 7.93 m s À1 and 7.70 m s À1 , respectively; P for trend o0.0001). The association between 25(OH)D and aortic PWV remained significant after adjustment for age, gender and other potential confounders; subjects in the first 25(OH)D quartile had adjusted odds ratio 2.04 (1.26-3.30) for having aortic PWV X9 m s À1 (top quartile) in multiple regression. In conclusion, we found a clear significant and independent negative association between 25(OH)D and aortic PWV. Subjects with lowest vitamin D status showed the highest arterial stiffness.

Total homocysteine (tHcy) level was identified as a strong and independent predictor of cardiovascular events. We investigated the association between tHcy and mechanical properties of large arteries in a random, general population-based sample of 251 subjects (mean age 48 years). Large artery properties, such as aortic and peripheral (lower-limb) pulse wave velocity (PWV), and augmentation index of radial artery were measured using semi-automatic Sphygmocor s device. Aortic PWV (APWV) positively correlated with tHcy (r ¼ 0.28, Po0.0001), and a significant increasing trend of APWV was found by tHcy quartiles (P ¼ 0.0003 by ANOVA). This association remained significant after adjustment for conventional cardiovascular risk factors (age, gender, smoking, overweight, hypertension, dyslipidaemia and impaired glucose metabolism) and for usual homocysteine confounders (folate, B 12 , renal function). Subjects with mild hyperhomocysteinaemia (i.e. with tHcy X15 lmol/l) had 2.74 times higher risk of having their APWV over 8.42 m/s (i.e. in the top quartile). No such association was found either for PWV measured at lower extremity or for radial augmentation index. In conclusion, in our series of subjects from general population, we found a strong and independent relationship between homocysteine concentration and APWV, a parameter of stiffness of central arteries.

Background: Treatment with mesenchymal stem cells (MSCs) has elicited considerable interest as an adjunctive therapy in sepsis. However, the encouraging effects of experiments with MSC in rodents have not been adequately studied in large-animal models with better relevance to human sepsis. Objectives: Here, we aimed to assess safety and efficacy of bone marrow-derived MSCs in a clinically relevant porcine model of progressive peritonitis-induced sepsis. Methods: Thirty-two anesthetized, mechanically ventilated, and instrumented pigs were randomly assigned into four groups (n = 8 per group): (1) sham-operated group (CONTROL); (2) sham-operated group treated with MSCs (MSC-CONTROL); (3) sepsis group with standard supportive care (SEPSIS); and (4) sepsis group treated with MSCs (MSC-SEPSIS). Peritoneal sepsis was induced by inoculating cultivated autologous feces. MSCs (1 × 10 6 /kg) were administered intravenously at 6 h after sepsis induction. Results: Before, 12, 18, and 24 h after the induction of peritonitis, we measured systemic, regional, and microvascular hemodynamics, multiple-organ functions, mitochondrial energy metabolism, systemic immune-inflammatory response, and oxidative stress. Administration of MSCs in the MSC-CONTROL group did not elicit any measurable acute effects. Treatment of septic animals with MSCs failed to mitigate sepsis-induced hemodynamic alterations or the gradual rise in Sepsis-related organ failure assessment scores. MSCs did not confer any protection against sepsis-mediated cellular myocardial depression and mitochondrial dysfunction. MSCs also failed to modulate the deregulated immune-inflammatory response. Horak et al. Stem Cell Therapy for Sepsis Conclusion: Intravenous administration of bone marrow-derived MSCs to healthy animals was well-tolerated. However, in this large-animal, clinically relevant peritonitis-induced sepsis model, MSCs were not capable of reversing any of the sepsis-induced disturbances in multiple biological, organ, and cellular systems.

The observation of significant intrafamilial concordance and heritability of various indexes of arterial stiffness as well as the genetic correlations among arterial phenotypes strongly support the search for shared genetic determinants underlying these traits.

Chromatin remodeling, including histone post-translational modifications, during spermatogenesis can affect sperm quality and fertility, and epigenetic marks may therefore be useful for clinical evaluations of sperm. Together with histone hyperacetylation, the dimethylation of histone H3 on lysine K4 (H3K4me2) is also required during protamination. Accordingly, we evaluated the utilization of this epigenetic mark for the identification of sperm with decrease quality and immature chromatin. In this study, 99 semen samples, including 22 normozoospermic (N), 63 asthenozoospermic (A), and 14 oligoasthenozoospermic (OA) samples, were comprehensively analyzed with respect to H3K4me2 levels, DNA damage (DNA fragmentation index, DFI), and sperm immaturity (high DNA stainability, %HDS), as determined by a sperm chromatin structure assay using flow cytometry. We detected a significant relationship between H3K4me2 and %HDS (r = 0.47; p < 0.001). Furthermore, we observed negative correlations between H3K4me2 and sperm concentration, motility, and mitochondrial activity (p < 0.05). The increase in immaturity as semen quality decreased (N > A > OA) indicates the importance of chromatin immaturity and histone code deviations in sperm evaluations. Using various approaches, our study elucidated H3K4me2 as a molecular marker of sperm quality with potential use in reproductive medicine.

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