Cholesterol associated genetic risk score and acute coronary syndrome in Czech males.

BACKGROUND: Despite a general decline in mean levels across populations, LDL-cholesterol levels remain a major risk factor for acute coronary syndrome (ACS). The APOB, LDL-R, CILP, and SORT-1 genes have been shown to contain variants that have significant effects on plasma cholesterol levels. METHODS AND RESULTS: We examined polymorphisms within these genes in 1191 controls and 929 patients with ACS. Only rs646776 within SORT-1 was significantly associated with a risk of ACS (P < 0.05, AA vs. + G comparison; OR 1.21; 95% CI 1.01-1.45). With regard to genetic risk score (GRS), the presence of at least 7 alleles associated with elevated cholesterol levels was connected with increased risk (P < 0.01) of ACS (OR 1.26; 95% CI 1.06-1.52). Neither total mortality nor CVD mortality in ACS subjects (follow up-9.84 ± 3.82 years) was associated with the SNPs analysed or cholesterol-associated GRS. CONCLUSIONS: We conclude that, based on only a few potent SNPs known to affect plasma cholesterol, GRS has the potential to predict ACS risk, but not ACS associated mortality.

Serum concentration of taurochenodeoxycholic acid predicts clinically significant portal hypertension.

BACKGROUND & AIMS: Severity of portal hypertension is usually quantified by measuring the hepatic venous pressure gradient (HVPG). However, due to its invasiveness, alternative markers are being sought. Bile acids (BA), being synthesized, metabolized, and transported by the liver, seem to have the potential to serve as endogenous markers. The aim of the present study was to determine whether serum BA reflect the severity of portal hypertension. METHODS: We correlated serum concentrations of individual BA with portal pressure (as HVPG) in an exploratory cohort of 21 cirrhotic patients with portal hypertension. The predictive potential of selected candidates was then confirmed in an independent validation cohort (n = 214). Additionally, nine previously published noninvasive markers were added to the stepwise logistic regression model to identify the most relevant ones, which were eventually used to create a prognostic index of portal hypertension. RESULTS: Serum levels of taurochenodeoxycholic acid (TCDCA) significantly correlated with HVPG and showed a high potential to predict clinically significant portal hypertension (HVPG ≥ 10 mm Hg: AUROC = 0.97 ± 0.06). This was confirmed in the validation cohort (AUROC = 0.96 ± 0.01). The predictive index (constructed based on AST/ALT, spleen diameter, and TCDCA concentration) was able to distinguish clinically significant portal hypertension with 95% sensitivity and 76% specificity. CONCLUSIONS: TCDCA seems to be a promising noninvasive marker of clinically significant portal hypertension. Its predictive potential may be further enhanced when it is combined with both the AST/ALT ratio and spleen diameter.

Significant Differences in IBD Care and Education across Europe: Results of the Pan-European VIPER Survey.

BACKGROUND: Inflammatory bowel disease (IBD) care and education might differ around Europe. Therefore, we conducted this European Variation In IBD PracticE suRvey (VIPER) to investigate potential differences between countries. METHODS: This trainee-initiated survey, run through SurveyMonkey®, consisted of 47 questions inquiring basic demographics, IBD training, and clinical care. Results were compared according to gross domestic product (GDP) per capita, for which countries were divided into 2 groups (low/high income, according to the World Bank). RESULTS: The online survey was completed by 1,285 participants from 40 European countries, with a majority of specialists (65.3%) working in academic institutions (50.4%). Significant differences in IBD-specific training (55.9% vs. 38.4%), as well as availability of IBD units (58.4% vs. 39.7%) and multidisciplinary meetings (73.2% vs. 40.1%), were observed between respondees from high and low GDP countries (p < 0.0001). In high GDP countries, IBD nurses are more common (85.9% vs. 36.0%), also mirrored by more nurse-led IBD clinics (40.6% vs. 13.7%; p < 0.0001). IBD dieticians (33.4% vs. 16.5%) and psychologists (16.8% vs. 7.5%) are mainly present in high GDP countries (p < 0.0001). In the current COVID era, telemedicine is available in 73.2% versus 54.1% of the high/low GDP countries, respectively (p < 0.0001). Treat-to-target approaches are implemented everywhere (85.0%), though access to biologicals and small molecules differs significantly. CONCLUSION: Much variability in IBD practice exists across Europe, with marked differences between high and low GDP countries. Further work is required to help address some of these inequalities, aiming to improve and standardize IBD care and training across Europe.

Reference values of retinal microcirculation parameters derived from a population random sample.

Retinal microcirculation reflects retinal perfusion abnormalities and retinal arterial structural changes at relatively early stages of various cardiovascular diseases. Our objective has been to establish reference values for major functional and structural parameters of retinal microcirculation in a randomly selected urban population sample. A total of 398 randomly selected individuals from an urban population aged 25 to 65 years, resident in Pilsen, Czech Republic, were screened for major cardiovascular risk factors. Retinal microcirculation was assessed using scanning laser Doppler flowmetry (SLDF), with data evaluable in 343 patients. Of this number, complete data were available for 256 individuals free from manifest cardiovascular disease, diabetes and drug treatment for hypertension and/or dyslipidemia, constituting the reference value population. Juxtapapillary retinal capillary blood flow has increased significantly with age whereas vessel and luminal diameters have decreased. No sex differences in retinal microcirculation parameters have been found. Therefore, reference values for retinal microcirculation parameters have been established by age groups. Unattended automated office systolic BP, after adjusting for age, correlated significantly with wall-to-lumen ratio (WLR) and wall thickness (WT). Moreover, after adjusting for age and mean BP, a positive relationship has been found between carotid femoral pulse wave velocity and WT, WLR and wall cross-sectional area, indicating the interaction between micro- and macro-vasculature. In conclusion, our study is the first to provide reference values of retinal microcirculation parameters in a random Caucasian population sample. Our results have shown that, at the population level, the first structural changes in retinal microcirculation are those in lumen diameters. Of note, a close relationship between BP and vascular remodeling of retinal arterioles and between aortic stiffness and WLR of retinal arterioles suggests an interaction between micro- and macro-vasculature.

The APOE4 allele is associated with a decreased risk of retinopathy in type 2 diabetics.

BACKGROUND: Common polymorphisms within the apolipoprotein E (APOE) gene are suggested to be associated with the development of type 2 diabetes mellitus (T2DM), but the potential association with T2DM complications (nephropathy, neuropathy and retinopathy) remains unclear. We perform the case-control study to analyse the association between the APOE polymorphism and risk of T2DM and to analysed the potential relationship between the APOE and T2DM complications. METHODS AND RESULTS: APOE variants (rs429358 and rs7412) were genotyped by TaqMan assay in T2DM patients (N = 1274; N = 829 with complications including retinopathy, neuropathy and nephropathy status) and with PCR-RFLP in healthy nondiabetic controls (N = 2055). The comparison of subjects with genotypes associated with low plasma cholesterol (APOE2/E2 and APOE2/E3 carriers vs. others) did not show an association with T2DM (OR [95% CI] = 0.88 [0.71-1.08). The differences remained insignificant after adjusting for diabetes duration, sex and BMI. Carriers of at least one APOE4 allele (rs429358) are protected against T2DM related retinopathy (OR [95% CI] = 0.65 [0.42-0.99]. Protection against retinopathy is driven mostly by females (OR [95% CI] = 0.50 [0.25-0.99]); and remains significant (P = 0.044) after adjustment for diabetes duration and BMI. CONCLUSION: Common APOE polymorphism was not associated with T2DM in the Czech population. Yet, APOE4 allele revealed an association with retinopathy. In particular, female T2DM patients with at least one APOE4 allele exhibit lower prevalence of retinopathy in our study subjects.

Sirolimus vs mycophenolate mofetil (MMF) in primary combined pancreas and kidney transplantation. Results of a long-term prospective randomized study.

The study was intended to compare pancreas graft survival rates in two groups of pancreas and kidney transplant recipients prospectively randomized to treatment either with sirolimus or MMF. From 2002 to 2013, 238 type 1 diabetic recipients with end-stage kidney disease were randomized 1:1 to sirolimus or MMF treatment. Noncensored pancreas survival at 5 years was 76.4 and 71.6% for sirolimus and MMF groups, respectively (P > .05). Death-censored pancreas survival was better in the sirolimus group (P = .037). After removal of early graft losses pancreas survival did not differ between groups (MMF 83.1% vs sirolimus 91.6%, P = .11). Nonsignificantly more grafts were lost due to rejection in the MMF group (10 vs 5; P = .19). Cumulative patient 5-year survival was 96% in the MMF group and 91% in the sirolimus group (P > .05). Five-year cumulative noncensored kidney graft survival rates did not statistically differ (85.6% in the sirolimus group and 88.8% in MMF group). Recipients treated with MMF had significantly more episodes of gastrointestinal bleeding (7 vs 0, P = .007). More recipients in the sirolimus group required corrective surgery due to incisional hernias (21 vs 12, P = .019). ClinicalTrials No.: NCT03582878.

Serum Bilirubin in the Czech Population　- Relationship to the Risk of Myocardial Infarction in Males.

BACKGROUND: The potential antiatherogenic role of bilirubin is generally acknowledged, so the aim of this study was to determine serum bilirubin concentrations and the prevalence of Gilbert syndrome (GS) in the Czech general population with particular reference to its relationship to the risk of myocardial infarction (MI).Methods and Results:Biochemical markers were analyzed in 2 independent Czech post-MONICA studies (in total, n=3,311), and in 741 male MI patients. TheUGT1A1promoter gene variant (rs81753472) was analyzed in these MI patients and in the first control population cohort (n=717). Medians of serum bilirubin concentrations in the 2 Czech general population cohorts were 9.6 and 9.8 µmol/L (10.7 and 11.3 µmol/L in males, and 8.3 and 8.8 µmol/L in females; P<0.01). The prevalence of GS was 8.9%, twice as high in males compared with females (11.6 vs. 6.1%; P<0.01). TheUGT1A1(TA)7/7promoter repeats significantly influenced serum bilirubin concentrations in the controls, but not in the MI patients. Serum bilirubin concentrations were significantly lower in MI patients (7.7 vs. 10.7 µmol/L; P<0.01), with almost 5-fold lower prevalence of GS. CONCLUSIONS: Serum bilirubin concentrations and the prevalence of GS were determined in the Czech general population. Significantly lower serum bilirubin concentrations were observed in male MI patients.

Spironolactone-furosemide combination therapy and acid-base disorders in liver cirrhosis patients
.

OBJECTIVE: Respiratory alkalosis (RA) and dilutional hyperchloremic acidosis (DHA) are the most common acid-base balance (ABB) disorders in patients with liver cirrhosis. The aims of this study were to clarify whether RA develops in relation to DHA via respiratory compensation of metabolic acidosis and whether spironolactone in combination with low-dose furosemide - diuretics known to ameliorate DHA - positively affects RA in liver cirrhosis patients. MATERIALS AND METHODS: 59 patients with advanced cirrhosis were divided into two groups. Group D consisted of individuals (urine sodium concentration (UNa+) > 20 mmol/L) who responded to combination therapy consisting of spironolactone and low-dose furosemide. The non-D group consisted of individuals (UNa+ ≤ 20 mmol/L) who either did not respond to the treatment or who were not administered it. In both groups, we examined serum and urine concentrations of electrolytes and ABB parameters, including SNa+-SCl- and SNa+/SCl- values. RESULTS: In group D, we found a statistically significant relationship between pCO2 and SHCO3-: r = 0.756 (p < 0.001) and between pCO2 and SNa+-SCl-: r = 0.522 (p = 0.001). Neither Salb nor the corrected anion gap were associated with changes in SHCO3- or pCO2 values. Although SHCO3- values were normal, abnormal pCO2 values were observed in one third of group D patients. Based on multivariable analysis, SHCO3- proved to be a statistically significant influencing factor on pCO2 values. CONCLUSION: DHA contributes to the development of RA in individuals with liver cirrhosis. Reducing DHA by means of effective diuretic therapy comprising spironolactone and furosemide has a beneficial effect on RA in such patients.

Longitudinal trends in the prevalence of hyperuricaemia and chronic kidney disease in hypertensive and normotensive adults.

The purpose: To evaluate longitudinal trends in the prevalence of hyperuricaemia and chronic kidney disease (CKD) in Czech adults with and without arterial hypertension (HT).Materials and methods: Two independent cross-sectional surveys were performed in 2006-2009 and 2015-2018, each screening involving 1% population random sample of the general population of nine districts of the Czech Republic aged 25-64 years, stratified by age and gender. Hyperuricaemia was defined as serum uric acid ≥ 420 µmol/l in men, and ≥ 360 µmol/l in women. CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2 and/or albumin/creatinine ratio ≥ 3 mg/mmol.Results: Final analyses included 3504 individuals examined in 2006-2009, and 2309 in 2015-2018. The overall prevalence of hyperuricaemia increased from 16.4% to 25.2% in men (p < 0.001), and from 7.6% to 10.9% in women (p < 0.001), whereas the overall prevalence of CKD declined from 6.8% to 3.6% in men (p = 0.001), and from 7.6% to 4.8% in women (p < 0.001). There was no interaction between HT and hyperuricaemia in either gender; the increase in hyperuricaemia prevalence was observed both in hypertensive and normotensive adults and was accompanied by the increased prevalence of abdominal obesity. Contrarily, there was an interaction between HT and CKD in both men (p < 0.001) and women (p = 0.011); the CKD prevalence declined only in hypertensive individuals, specifically in those using antihypertensive medication and was accompanied by the increased use of renin-angiotensin-aldosterone system (RAS) inhibitors and calcium channel blockers (CCBs).Conclusions: Over the period of 10 years, the overall prevalence of hyperuricaemia increased, while the prevalence of CKD decreased. An increase in the prevalence of hyperuricaemia was observed both in hypertensive and normotensive individuals and was accompanied by an increase in the prevalence of abdominal obesity. A decline in the prevalence of CKD was only observed in hypertensive individuals and was accompanied by the increased use of RAS inhibitors and CCBs.

Primary aldosteronism in a general population sample. The Czech post-MONICA study.

Purpose: Primary aldosteronism (PA) is considered the most common form of secondary hypertension, however, its prevalence, particularly in a general population, is still a matter of debate. The aim of our study was to evaluate the prevalence of PA in a randomly selected general population sample.Materials and methods: A total of 1940 individuals (1% population random sample) aged 25-64 years were screened for major cardiovascular risk factors in six districts of the Czech Republic. Hypertension was defined as a mean of two blood pressure readings ≥140/90 mmHg at one visit or taking antihypertensive medication. Within this population, 740 individuals were labelled as hypertensives and 650 of them sampled for the analysis of direct plasma renin and serum aldosterone. The diagnosis of PA was based on elevated serum aldosterone, low plasma renin and high aldosterone/renin (ARR) ratio and was also verified by a confirmatory test with saline infusion.Results: Positive ARR was found in 52 (8%) individuals (64% women, 36% men, however, due to substatntial proportion of reluctatnt participants to undergo a further work-up (27%), we could confirm the diagnosis of PA only in 13 of them (2%). Aldosterone-producing adenoma was found in one case only, seven patients had idiopathic type and five individuals refused potential surgical treatment therefore, adrenal venous sampling was not performed.Conclusion: Elevated serum aldosterone together with low renin and high ARR were found in 52 (8%) of hypertensives selected from a general population sample, however, the diagnosis of PA was confirmed only in 13 of them (2%). This study based on a general population survey highlighted the difficulty of conducting epidemiological studies on primary aldosteronism in a relatively healthy cohort part of whom did not provide the level of collaboration that is necessary to assess the true prevalence of this condition.

Analysis of incidence and prevalence of cardiovascular risk factors and evaluation of their control in epidemiological survey in the Czech Republic.

OBJECTIVE: The aim of this analysis was to analyze the presence of the most important cardiovascular (CV) risk factors and to discuss patterns of LDL cholesterol management in the population studied. METHODS: We enrolled 961 males, average age of 42.9 ± 4.7, and 851 females, average age of 51.2 ± 3.6. Data on personal, pharmacological and family history, and laboratory examinations were collected. Cardiovascular (CV) risk was calculated using the Systematic Coronary Risk Evaluation (SCORE) algorithm with modifications according to the guidelines. RESULTS: The distribution of CV risk in the observed cohort was as follows: 24% of the subjects had low, 51% moderate, 17% high and 8% very high risk. The percentage of patients who reached target values of LDL cholesterol was dramatically lower in the groups with very high (1%) and high (3%) risk than in the groups with moderate (14%) or low risk (59%). Dyslipidemia was newly identified in 20% of both sexes. Arterial hypertension was newly diagnosed in 8% of males and 5% of females, and type 2 diabetes mellitus was newly diagnosed in 3% of both the males and females. Dyslipidemia was present in 39% of males and 41% of females; arterial hypertension in 43% of males and 45% of females, and type 2 diabetes mellitus was diagnosed in 11% of the subjects of both sexes. 49% of males and 31% of females were overweight and 32% of both genders were obese. There were 36% of male smokers and 22% of female smokers. 48% of the participants were pharmacologically treated. Non-pharmacological treatment was recommended to 62% of male and to 65% of female participants. Pharmacological intervention was started in 53% of males and 51% of females. In both gender antihypertensive treatment with angiotensin-converting enzyme (ACE) inhibitors (29% of males and 27% of females) and lipid lowering therapy with a statin (28% of males, 27% of females) were the most commonly initiated treatments. In the subgroup of the 101 patients with LDL cholesterol levels > 5 mmol/L 56% were not treated with a statin. The analysis of relationship between the positive family history of any of the followed CV risks showed significant increases of the risk for arterial hypertension, type 2 diabetes mellitus and dyslipidemia. CONCLUSION: European guidelines suggest general screening for risk factors, including analysis of lipid profiles in the population of 40-year-old males and 50-year-old or postmenopausal women. Our study documents high prevalence and incidence of CV risk factors together with insufficient control of the risk factors in Czech patients of this age range. This finding suggests that preventive examinations should be undertaken earlier (e.g., in 30-year-old males and 40-year-old women). Exact timing of the preventive check-ups to yield the best cost-benefit ratio needs to be verified.

The fat mass and obesity related gene polymorphism influences the risk of rejection in heart transplant patients.

Heart transplantation is a relatively common treatment for end-stage heart failure. The major complication of heart transplantation is organ rejection. Epigenetic could play a role in the pathogenesis of organ rejection, and the FTO gene is a mediator of DNA methylation. We analyzed a tagging FTO SNP rs17817449 in both donor and recipient DNA obtained through 370 heart transplantations. Recipient FTO genotypes were not associated with either type of rejection or with the general increase in the risk of rejection. When compared with patients without a history of rejection, carriers of transplanted hearts with the FTO TT genotype exhibited a significantly increased risk (P = 0.02) of suffering from both types of rejection in comparison to carriers of hearts with at least one G allele (OR; 95% CI = 2.56; 1.15-5.69). Our results suggest that the donor, but not the recipient, FTO genotype could be a significant predictor of acute rejection in heart transplant patients.

Body Adiposity Changes After Lifestyle Interventions in Children/Adolescents and the NYD-SP18 and TMEM18 Variants.

BACKGROUND This study was carried out to determine the relationship between the common TMEM-18 (rs4854344, G>T) and NYD-SP18 (rs6971091, G>A) gene variants and weight loss after lifestyle interventions (increased physical activity in conjunction with optimal dietary intake) in overweight/obese children/adolescents. MATERIAL AND METHODS We genotyped 684 unrelated, white, non-diabetic children (age 12.7±2.1 years, average BMI at baseline 30.66±4.80 kg/m²). Anthropometric and biochemical examinations were performed before and after 4 weeks of an intensive lifestyle intervention. RESULTS The mean weight loss achieved was 5.20±2.02 kg (P<0.001). NYDSP-18 AA homozygotes had significantly higher abdominal skinfold value before and after the intervention (both, P=0.001). No significant associations between BMI decrease and the NYD-SP18 and TMEM18 variants were found. Associations between all anthropometrical and biochemical changes and genes remained non-significant after data were adjusted for sex, age, and baseline values. CONCLUSIONS Decreased body weight in overweight/obese children is not significantly influenced by the NYD-SP18 rs6971091 or TMEM18 rs4854344 polymorphisms.

Falsely elevated human epididymis protein 4 results and Risk of Ovarian Malignancy Algorithm in polymorbid women after solid organ transplantation: A pilot and case-control study.

BACKGROUND: Cancer prevention is essential after transplantation (Tx). The use of HE4 and Risk of Ovarian Malignancy Algorithm (ROMA) is recommended as a tool for selective ovarian cancer screening; however, creatinine is a known confounder. This study assessed the reliability of HE4, CA125, and ROMA after Tx. METHODS: We matched a total of 202 women without gynecological malignancies and 236 men by age and serum creatinine. Each pair consisted of a patient after Tx (kidney, liver, heart, and pancreas) and a diseased but non-Tx consecutive patient. Serum HE4, CA125 (Roche Cobas 6000), and creatinine (enzymatic, Abbott Architect) were measured in all patients. RESULTS: Creatinine correlated with HE4 (women: r = .864, P < .0001; men: r = .848, P < .0001). Age correlated slightly with HE4 in women (r = .250, P < .005) and men (r = .240, P < .0005). HE4 in women after Tx (median of 84.8 pmol/L) was significantly higher than non-Tx women (53.7 pmol/L, P < .0001) in the reference range of serum creatinine. Neither HE4 nor CA125 correlated with tacrolimus concentration, but anemia, hyperparathyroidism, kidney, liver, and lung diseases were possible confounders for HE4 after transplantation (P < .05). CONCLUSION: Human epididymis protein 4 (HE4) was significantly increased in women after solid organ transplantation compared to levels without transplants matched by age and serum creatinine. HE4 results may be misleading in these patients.

Prevalence and risk factors of steatosis after liver transplantation and patient outcomes.

Steatosis occurs frequently after liver transplantation (LT). We aimed to determine the prevalence of steatosis in adult LT recipients, to determine the effects of significant (>33%; grades 2-3) steatosis on patient survival, and to identify risk factors for the development of significant steatosis and its effect on fibrosis progression. We retrospectively examined 2360 posttransplant biopsies of 548 LT recipients. Survival was compared between patients with significant steatosis and those with grades 0-1 steatosis. Patients with significant steatosis were compared to controls without steatosis (grade 0) for clinical and laboratory factors and fibrosis progression. Steatosis was found in 309 (56.4%) patients, including 93 (17.0%) patients with significant steatosis. Steatohepatitis (nonalcoholic fatty liver disease activity score ≥ 5) was diagnosed in 57 (10.4%) patients. The prevalence of steatosis increased from 30.3% at 1 year to 47.6% at 10 years after LT (P < 0.001). Survival times did not differ between groups (P = 0.29). On multivariate analysis of pretransplant factors and initial immunosuppression (IS), alcohol-induced cirrhosis (P < 0.001) and high body mass index (BMI; P = 0.002) were associated with the development of significant steatosis, whereas increased levels of alkaline phosphatase (P = 0.01) and mycophenolate mofetil given initially (P = 0.009) appeared to protect against significant steatosis. On multivariate analysis of posttransplant factors, high BMI (P < 0.001), serum triglycerides (P < 0.001), alcohol consumption (P = 0.005), and type 2 diabetes mellitus (P = 0.048) were associated with significant steatosis, whereas high creatinine (P = 0.02) appeared to protect against significant steatosis. Significant steatosis was not associated with a higher fibrosis stage (P = 0.62). Posttransplant steatosis affects 56.4% of LT recipients, and the prevalence increases with time after LT. Recipient factors and types of IS affect the risk for significant steatosis, which is not associated with a higher fibrosis stage or worse patient survival. Liver Transplantation 22 644-655 2016 AASLD.

Novel insights into pretransplant allosensitization in heart transplant recipients in the contemporary era of immunosuppression and rejection surveillance.

Solid-phase assays (SPA) have facilitated detection and definition of antibodies to human leukocyte antigens (HLA) and major histocompatibility complex class I chain-related antigen A (MICA). However, clinical consequences of pretransplant SPA results in heart transplantation have been studied insufficiently in the current era of immunosuppression and rejection surveillance. Pretransplant sera, panel-reactive antibodies (PRA), pretransplant crossmatch, and clinical data were retrospectively analyzed in 264 adult heart transplant recipients. The specificity of HLA and MICA antibodies and C1q-binding activity of donor-specific antibodies (DSA) were defined using SPA. Pretransplant HLA antibodies were detected in 57 (22%) individuals, in 28 individuals (11%); these antibodies were DSA after transplant. Preformed DSA and elevated peak PRA were independent predictors of pathologic AMR, which occurred in 19 individuals (7%). The increasing number of DSA and the cumulative mean fluorescence intensity of DSA were associated with AMR. C1q-binding assay was a suboptimal predictor of AMR in our cohort. Pretransplant allosensitization and MICA antibodies were related neither to impaired graft survival nor to other adverse clinical events during a median follow-up of 39 months. Identification of preformed DSA by SPA, in addition to PRA monitoring, may predict AMR in the contemporary era of heart transplantation.

Diurnal variation in cholesterol 7α-hydroxylase activity is determined by the -203A>C polymorphism of the CYP7A1 gene.

AIM: To determine whether the promoter polymorphism -203A>C of cholesterol-7α-hydroxylase encoding gene (CYP7A1) affects diurnal variation in CYP7A1 enzyme activity. METHODS: The study included 16 healthy male volunteers - 8 homozygous for -203A and 8 homozygous for the -203C allele of CYP7A1. Three 15-hour examinations (from 7am to 10pm) were carried out for each of the participants: after one-day treatment with cholestyramine; after one-day treatment with chenodeoxycholic acid (CDCA); and a control examination without any treatment. The plasma concentration of 7α-hydroxy-4-cholesten-3-one (C4), a marker of CYP7A1 activity, was determined in all the experiments at 90-min intervals. RESULTS: CYP7A1 activity was up-regulated after treatment with cholestyramine and suppressed after treatment with CDCA. There were no differences between -203A and -203C allele carriers in the response of enzyme activity to both drugs. In the control experiment, -203A allele carriers displayed diurnal variation in enzyme activity, whereas CYP7A1 activity did not change in -203C allele carriers. These results were confirmed by modeling the dynamics of C4 using polynomial regression. CONCLUSION: The promoter polymorphism of the CYP7A1 gene has a pronounced impact on diurnal variation in CYP7A1 activity.

B-type natriuretic peptide: powerful predictor of end-stage chronic heart failure in individuals with systolic dysfunction of the systemic right ventricle.

AIM: To assess whether B-type natriuretic peptide (BNP) can serve as a predictor of end-stage chronic heart failure (CHF) in patients with severe systolic dysfunction of the systemic right ventricle (SRV). METHODS: We performed a retrospective analysis in 28 patients with severe systolic dysfunction of the SRV (ejection fraction 23 ± 6%) who were evaluated as heart transplant (HTx) candidates between May 2007 and October 2014. The primary endpoints of the study (end-stage CHF) were progressive CHF, urgent HTx, and ventricular assist device (VAD) implantation. Plasma BNP levels were measured using a chemiluminescent immunoassay. RESULTS: During median follow-up of 29 months (interquartile range, 9-50), 3 patients died of progressive CHF, 5 patients required an urgent HTx, and 6 patients underwent VAD implantation. BNP was a strong predictor of end-stage CHF (hazard ratio per 100 ng/L: 1.079, 95% confidence interval, 1.042-1.117, P<0.001). The following variables with corresponding areas under the curve (AUC) were identified as the most significant predictors of end-stage CHF: BNP (AUC 1.00), New York Heart Association functional class class III or IV (AUC 0.98), decompensated CHF in the last year (AUC 0.96), and systolic dysfunction of the subpulmonal ventricle (AUC 0.96). CONCLUSION: BNP is a powerful predictor of end-stage CHF in individuals with systolic dysfunction of the SRV.

Genetic and biochemical characteristics in the Roma minority in the South Bohemia Region.

OBJECTIVE: At present, health characteristics of Roma minority within the Czech Republic are generally unknown. Therefore we examined a Roma population for some anthropometrical, biochemical and genetic parameters. DESIGN: Groups include Roma aged above 18 years (men, women), with permanent residence in the South Bohemia Region. The Roma group (302 individuals) was selected using the snowball sampling method--the same method was used to select the non-Roma control group (78 individuals) for total cholesterol and blood sugar reference values. The main non-Roma control group was selected using the quota selection method (298 individuals). All participants completed a life style questionnaire, had their body measurements taken, were weighed, had their blood pressure and heart rates measured, had a capillary blood sample taken. RESULTS: The non-Roma population had a lower Body Mass Index (BMI) (25.86 ± 4.23 vs. 27.45 ± 6.48 kg/m², p = 0.0004). The difference in BMI and weight was found to be associated with the MC4R gene. The values of systolic and diastolic blood pressure, total cholesterol, blood sugar did not differ with regard to the tested polymorphisms. We did not find any difference in the prevalence of MC4R or TMEM18 between groups. CONCLUSION: Despite educational efforts to introduce healthier life styles into the Roma population, there has been only limited success; as a result, Roma are very likely to suffer from premature complications of atherosclerotic processes, mostly due to theirs life style. Intensive further research is needed to improve the health conditions of the Roma minority, while still respecting their cultural differences.

Body Composition Changes in Adult Females after Lifestyle Intervention Are Influenced by the NYD-SP18 Variant.

AIM: The study focuses on the analysis of the possible relationship between a common NYD-SP18 (rs6971091, G>A) gene polymorphism and weight loss after lifestyle intervention (combined dietary intake and physical activity) in overweight/obese females. METHODS: We genotyped 139 unrelated non-diabetic Czech females (49.5 ± 13.3 years, average BMI at baseline 32.2 ± 4.6 kg/m². Biochemical and anthropometrical measurements were performed before and after ten weeks of lifestyle intervention. CONCLUSION: Overweight/obese female carriers of the NYD-SP18 rs6971091 GG genotype exhibited a more beneficial response to the intensive lifestyle intervention than others.