Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals

The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at the individual patients level to capture the possible effect of ethnicity, gene—gene interaction, or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients’ data. The final collection consists of 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95% confidence interval (CI) 7–10%), with a higher effect in women, in patients taking acenocoumarol, and in white patients. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived

Snoring in a cohort of obese children: association with palate position and nocturnal desaturations

Purpose of the study: Frequency of habitual snoring is significantly higher in obese than in normal-weight subjects. Obesity and adeno-tonsillar size are risk factors of snoring. Other factors, such as fat distribution and upper airway collapsibility, could explain the relationship between obesity, snoring and obtructive sleep apneas. The aim of the study was to investigate clinical and instrumental significance of snoring in exogenous obese children referred to our department.Methodology: This preliminary study takes part of a larger prospective respiratory sleep study. In 36 consecutive obese children (18 males), bodymass index (BMI), BMI Z score and neck circumference were calculated according to age and sex. Nasal patency, tonsil size, palate position scoring were also recorded. An overnight polygraphy was performed using a portable ambulatory device. Statistical analysis was done using SPSS® Statistics 19.0 software for Windows®.Main findings: Snoring, objectively measured by polygraphy, was associated with palate position and with oxygen desaturation index (ODI). The correlation between snoring and ODI completely disappeared when adjusting for palate position scoring.Key conclusions: Low palate position can be identified as an adjunctive, although not unique, factor that can contribute to making snoring and increased desaturation events possibly related to increased risk of upper airway collapsibility during sleep in obese childre

Positive effects of tomato paste on vascular function after a fat meal in male healthy subjects

Tomato consumption has been recently associated with a reduced incidence of cardiovascular disease (CVD). The aim of this study was to test whether a seven-day period of tomato paste pur\ue8e (tomato paste, TP) supplementation could improve some haemodynamic parameters in healthy volunteers before and after a standardized fat meal (FM)

EARLY PREDICTION OF SUBCLINICAL VASCULAR DAMAGE IN RISKY POPULATIONS

Background. Atherosclerosis is a progressive disease that starts during adoles-cence and exerts its negative effects later in life. High blood pressure is one of the principal risk factors for cardiovascular disease. Central blood pressure is the pressure that directly insists and other major arteries and is linked to target organ damage and cardiovascular events. The aim of the thesis was to assess the role of traditional and novel risk factors (central blood pressure, cBP) on children and adolescents with type I diabetes (T1D; study number 1) and in children and ado-lescents with solitary functional kidney (SFK; study n.2). Methods. Carotid intima-media thickness (cIMT), carotid distensibility coeffi-cient (cDC), and carotid-femoral pulse wave velocity (PWV), were measured in children and adolescents with T1D and SFK. Blood Pressure (BP; both central and peripheral), echocardiographic measurements, biochemical data from blood and urine sample and other cardiovascular risk factors were evaluated in multi-variate linear regressions to assess the association with the measured indices of subclinical vascular damage. Results study 1. One hundred and twenty-six children and adolescents with T1D were included. cIMT was above the 95th percentile for age and height in 61% of the population. Bivariate correlations showed that cBP but not peripheral blood pressure (pBP) were positively associated with cIMT (r = 0.285; p = 0.001). In-dependent determinants of cIMT according to the regression models were only gender, type of glucose monitoring and central systolic BP (cSBP). PWV was as-sociated with age, sex, heart rate, and cSBP; cDC with age and both cSBP, and, alternatively, peripheral BP (pBP). Neither pBP nor any of the tested metabolic parameters, including glycated hemoglobin, were associated with PWV and cIMT. Results study 2. 48 SFK children and adolescents were included. Of them 50% had increased cIMT. cBP was correlated with all vascular indices measured and with the left ventricular mass (r = 0.417; p = 0.005) but not with RWT. pBP cor-related with distensibility, with PWV and with the LVMi. Daytime systolic blood pressure was found to be associated with all vascular indices but not with echo-cardiographic ones. BMI correlated with the variables indicative of organ dam-age and with many pressure variables. No correlation was found between the vas-cular or echocardiographic indices and either estimated glomerulaf filtration rate or urinary albumin to creatinine ratio. In linear regression pBP were not associat-ed with the above-mentioned vascular variables whereas cBP was positively as-sociated with cIMT (even when we consider z-score values). To the contrary, cDC and PWV were not associated with cBP. In binary logistic regression analy-sis, cBP was a predictor for increased cIMT. Conclusions: Taken together, our data show a high prevalence of increased cIMT in children and adolescents with T1D and SFK. cBP more than pBP or other tra-ditional risk factors associates with subclinical organ damage

Subclinical Organ Damage in Children and Adolescents with Hypertension: Current Guidelines and Beyond

High blood pressure (BP) is becoming a growing health issue even in children and adolescents. Moreover, BP elevation in youth frequently translates into children and adult hypertension contributing to the development of cardiovascular disease. The detection of early markers of vascular damage, potentially leading to overt cardiovascular disease, is important for clinical decisions about if and how to treat hypertension and can be useful in monitoring the effectiveness of the treatment. The purpose of this review is to summarize the actual knowledge about subclinical organ damage (SOD) in hypertensive children and adolescents and its association with cardiovascular disease in children and young adults. Our focus is especially put on left ventricular mass, pulse wave velocity, carotid intima-media thickness and microalbuminuria. We also want to address the scientific evidence about possible regression of SOD and cardiovascular risk with the use of behavioural and specific anti-hypertensive therapy. Indications from current guidelines are critically discussed

THE INTAKE OF OMEGA-3 PUFA IS NOT ASSOCIATED WITH SUBSTANTIAL CHANGES OF BLOOD PRESSURE EVEN CONSIDERING THE INTERACTION WITH SOME GENE POLYMORPHISMS.

Background. A higher intake of polyunsaturated fatty acids (PUFA) omega-3 has been associated with lower blood pressure (BP). Their antihypertensive properties could be due to the reduction of the omega-6/omega-3 ratio and consequent competitive effect of omega-3 compared to arachidonic acid (the main omega-6 PUFA). In fact both act as substrate of cytochrome P450 (CYP450), enzymes involved in the production of vasoactive mediators such as 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs). Some polymorphisms (SNPs) in genes that encode for these CYPs were associated with the development of hypertension and ischemic stroke in a Swedish population. The aim of this study was to evaluate if food intake of omega-3 and omega-6 PUFA has a favorable effect on blood pressure, also considering the interaction with different SNPs in genes involved in their metabolism.Methods. We analyzed the change in BP over time (mean follow-up 16.7 ± 1.5 years) in a subset of subjects enrolled in the Malmö Diet and Cancer Study (n = 3632) in relation to PUFA intake, detected by a validated questionnaire, and the their possible interaction with some functional polymorphisms in the CYP4F2, CYP4A11, CYP2J2, CYP2C8 and EPHX2 genes. We repeated the analysis after excluding subjects under antihypertensive therapy (leaving n = 2272 available for the analysis) and in different genders.Results. We did not find any association between the intake of omega-3, omega-6 or their ratio and longitudinal change of BP. After adjustment for the number of statistical tests, we did not observe any effect on blood pressure by the interaction of different assumption of PUFAs and and different genotypes. Neither the exclusion of subjects under chronic antihypertensive therapy or the analysis of males and females separately changed the results.Conclusion. In a Swedish population followed longitudinally, intake of PUFA showed no detectable effect on BP, also after considering a possible interaction with functional SNPs in genes involved in their metabolism. Further studies will be needed to clarify whether and in which individuals PUFA have a beneficial effect on BP

Onset of Addison Disease appeared during the first trimester of a twin pregnancy: A case report

Key Clinical MessageAddison Disease is an uncommon, life-threatening condition affecting people at any age, including women during pregnancy. If left untreated, the disease can be rapidly fatal, but the prognosis is good if promptly recognized and hormones are replaced

[OP.6A.07] SLEEP DISORDERED BREATHING IS ASSOCIATED WITH BLOOD PRESSURE AND CAROTID ARTERIAL STIFFNESS IN A SAMPLE OF OBESE CHILDREN

Sleep disordered breathing (SDB) and high blood pressure (BP) are more frequent among obese with respect to normal weight children and this may be due to endothelial dysfunction and a worsened arterial stiffness. The aim of this study was to evaluate the possible association between SDB and BP and the possible role of endothelial function and local and systemic arterial stiffness in a sample of obese children asymptomatic for sleep disturbances