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Background: It was suggested that depression and anxiety might be associated with increased cardiovascular risk in both primary and secondary prevention. In stable coronary heart disease (CHD) patients, we aimed to assess prevalence of depression and anxiety, its relations to conventional risk profile and mortality or morbidity and to quality of life (QoL). Methods: We examined 969 patients, at least 6 months after myocardial infarction or coronary revascularisation. Depression or anxiety was assessed using a standard HADS (Hospital Anxiety and Depression Scale), while QoL by SF-36 (Short-Form-36 Questions) questionnaires. Follow-up was done to assess mortality in incidence of non-fatal cardiovascular event. Results: Both mood disorders were rather frequent; borderline depression or anxiety (HADS score 8-10) had 14.8 or 10.9% of patients, respectively; moderate-to-severe depression or anxiety (HADS score ≥11) had another 8.2 or 6.7% of patients. After adjustment for potential covariates impaired QoL (SF-36 score <40) was independently associated with depressive mood [odds ratio (OR) 6.08 (95%CI: 2.92-12.7) or anxiety [OR 8.66 (95%CI: 3.77-19.89)], as well as with combination of both disorders [OR 33.58 (95%CI: 15.5-72.6)]. Conventional risk characteristics remained virtually unrelated to mood disorders (with exception of angina pectoris). We found significantly higher incidence of major cardiovascular events in patients with anxious mood and marginally significant inferior survival in patients with depression, but any cardiovascular risk disappeared if adjusted for potential covariates (conventional risk factors, natriuretic peptides, angina pectoris.) Conclusions: Mood disorders severely affected QoL of stable CHD patients, but not their global cardiovascular risk.

Background: Cardiovascular disease (CVD) followed by cancer are the two leading causes of death worldwide. SCORE charts have been recommended in Europe to identify individuals at increased CVD risk. However, the SCORE ability to identify individuals at increased risk of cancer has not yet been evaluated. The aim of this study was to determine the SCORE chart calibration in a country with changing CVD epidemiology, and its discrimination ability to identify individuals at increased risk of cancer over 20-years., Methods: The present analysis includes data from two cross-sectional independent surveys within the Czech post-MONICA study (randomly selected representative population samples of the Czech Republic, aged 25-64 years); 3209 individuals in 1997/98 and 3612 in 2006-2009., Results: The SCORE had reasonable discrimination to predict 10-year CVD mortality, but significantly overestimated the risk across all risk categories. During the 20-year follow up, high and very high-risk categories were associated with an increased risk of cancer morbidity (in particular colorectal, other gastrointestinal, lung and malignant skin) and cancer mortality, as compared to low risk category., Conclusions: The present study shows that periodical calibration testing of SCORE charts is needed in countries with changing CVD epidemiology. Furthermore, we show that in middle-aged individuals, identified by SCORE charts as being at high or very high risk for CVD, cancer morbidity and cancer mortality is increased. Rigorous cancer screening may be appropriate in this group, especially in countries with falling CVD mortality, where relative proportion of cancer mortality is increasing., Competing Interests: Declaration of Competing Interest The Authors declare that they have no conflict of interest., (Published by Elsevier B.V.)

Background: In stable coronary heart disease (CHD) patients we aimed to assess the predictive potential of only mild increase of brain natriuretic peptide (BNP) in subjects free from symptoms or diagnostic criteria of heart failure (HF). Methods: We examined 967 patients, at least 6 months after myocardial infarction or coronary revascularization and divided them into three categories: 'overt HF' (NYHA II-IV, objective signs of HF, chronic treatment with furosemide and/or spironolactone or history of hospitalisation for HF), 'subclinical HF (BNP over 150 ng/mL, but no criterion of overt HF)' and 'no HF' (no above mentioned criterion present). Follow-up was done to assess 5-years all-cause mortality. Results: Overt and subclinical HF (by definition) had 38.8% and 9.6% of patients, respectively. In analyses adjusted for classical risk factors and other possible covariates, both overt and subclinical HF were independently associated with increased mortality compared to no HF subjects [hazard risk ratio 1.99 (95%CI:1.02-3.91) and 3.01 (95%CI:1.90-4.78), respectively. The risk of total mortality was similar in overt and subclinical HF patients [HRR 1.30 (95%CI: 0.72-2.36)]. Within overt HF group, those with BNP >150 ng/mL had also higher mortality risk than those with low BNP levels [HRR 2.79 (95%CI: 1.67-4.68)]. The addition of left ventricle ejection fraction into definition of HF groups did not affect main results. Conclusions: Mild increase of BNP in generally stable and asymptomatic CHD patients identifies high individual mortality risk in the same extend that presence of clinically manifest HF.

Background: Compared with Western Europe, the decline in cardiovascular (CV) mortality has been delayed in former communist countries in Europe, including the Czech Republic. We have assessed longitudinal trends in major CV risk factors in the Czech Republic from 1985 to 2016/17, covering the transition from the totalitarian regime to democracy., Methods: There were 7 independent cross-sectional surveys for major CV risk factors conducted in the Czech Republic in the same 6 country districts within the WHO MONICA Project (1985, 1988, 1992) and the Czech post-MONICA study (1997/98, 2000/01, 2007/08 and 2016/2017), including a total of 7,606 males and 8,050 females. The population samples were randomly selected (1%, aged 25-64 years)., Results: Over the period of 31/32 years, there was a significant decrease in the prevalence of smoking in males (from 45.0% to 23.9%; p < 0.001) and no change in females. BMI increased only in males. Systolic and diastolic blood pressure decreased significantly in both genders, while the prevalence of hypertension declined only in females. Awareness of hypertension, the proportion of individuals treated by antihypertensive drugs and consequently hypertension control improved in both genders. A substantial decrease in total cholesterol was seen in both sexes (males: from 6.21 ± 1.29 to 5.30 ± 1.05 mmol/L; p < 0.001; females: from 6.18 ± 1.26 to 5.31 ± 1.00 mmol/L; p < 0.001)., Conclusions: The significant improvement in most CV risk factors between 1985 and 2016/17 substantially contributed to the remarkable decrease in CV mortality in the Czech Republic., Competing Interests: The authors have declared that no competing interests exist.

Our aim was to determine the serum uric acid (SUA) levels associated with an increased risk of cardiovascular (CV) and all-cause death in the general adult population. We analyzed data obtained in two independent cross-sectional surveys performed in the Czech Republic in 2006-09 and 2015-18, involving 1% population random samples in nine districts, aged 25-64 years, stratified by age and gender. Ten-year mortality data were obtained in a cohort with examination in 2006-09. Final analyses included 3542 individuals (48.2% men) examined in 2006-09, and 2304 (47.4% men) examined in 2015-18. From a cohort examined in 2006-09, 122 men and 60 women were reported dead (33% and 27% from CV disease). In men, there was no association of baseline SUA levels with baseline SCORE category or 10-year mortality rates. In women, each 10 µmol/L increase in baseline SUA levels was associated with an increase in baseline SCORE category (P < .001). Receiver operating characteristic curve analyses in women identified the baseline SUA cutoff values discriminating: 1. between low/intermediate and high/very high SCORE categories (309 µmol/L), 2. CV mortality (325 µmol/L), and 3. all-cause mortality (298 µmol/L). After adjusting for confounders including SCORE, Cox regression analysis confirmed that the baseline SUA cutoffs of 309 µmol/L and 325 µmol/L were associated with 4-times (P = .010) and 6-times (P = .036) greater risk of CV mortality, whereas the cutoff of 298 µmol/L was associated with 87% greater risk of all-cause mortality (P = .025). In conclusion, the SUA cutoff value of 309 µmol/L identified women at high/very high SCORE category and was associated with 4-times greater risk of observed CV mortality over 10 years., (© 2020 Wiley Periodicals, Inc.)

Objectives: There is an ongoing controversy about the magnitude of the difference between unattended automated office blood pressure (AOBP) and conventional office blood pressure (BP). The aim of our study was to compare unattended AOBP with both auscultatory BP and oscillometric attended AOBP in an epidemiological setting., Methods: In 2588 participants of the Czech post-MoNItoring of CArdiovascular Disease study (a randomly selected 1% representative population sample aged 25-64 years, mean age 48 ± 11 years, 47.5% males), BP was measured using an AOBP device unattended, auscultatory mercury sphygmomanometer and an oscillometric attended AOBP device., Results: On average, auscultatory BP was 10.6/5.6 mmHg higher than unattended AOBP. Similarly, oscillometric attended AOBP was 9.9/3.4 mmHg higher than unattended AOBP, while the mean difference between attended oscillometric AOBP and auscultatory BP was 0.8/2.1 mmHg. Unattended systolic AOBP of 127 mmHg corresponded to SBP of 140 mmHg measured by a conventional sphygmomanometer. The prevalence of hypertension varied depending on the measurement technique and ranged from 31.5 to 40.1%. Reasonable agreement in hypertension diagnosis was observed with unattended AOBP cut-off at least 130/85 mmHg when compared with both auscultatory (McNemar P = 0.07, kappa 0.819) and attended oscillometric AOBP (McNemar P = 0.46, kappa 0.852) thresholds of at least 140/90 mmHg., Conclusion: Unattended automated office SBP is on average 10 mmHg lower than the office auscultatory or attended AOBP values. In epidemiological settings, a threshold of unattended AOBP at least 130/85 mmHg should make comparison of hypertension prevalence possible with studies using auscultatory techniques and cut-off values of 140/90 mmHg.

Purpose: Advanced glycation end products (AGEs) are a heterogeneous group of highly oxidant compounds which can potentiate microvascular and macrovascular complications through the formation of irreversible cross-links between molecules in the basal membrane and also by engaging the receptor for AGEs (RAGE). Soluble receptor for AGEs (sRAGE) is suggested to have a protective role neutralizing the toxic action of AGEs. We aimed to investigate differences in plasma levels of sRAGE alongside with classic cardiovascular risk factors between offspring of patients with early onset of coronary heart disease (CHD) and healthy controls. Materials and methods: In a cross-sectional design, we examined 114 adult offspring of patients with premature CHD and 194 controls. Concentrations of soluble RAGE were quantified by ELISA methods. Aortic PWV was measured using Sphygmocor device. Multivariate logistic regressions were used to compare differences between the offspring and controls. Results: In the offspring group there were more men ( p  = 0.023), both groups had similar age (28.5 vs. 28.9 years; p  = 0.51). After adjustment for covariates, we observed significantly higher aPWV (6.17 vs. 5.82 m s -1 ; p  = 0.001) and lower sRAGE (1308.11 vs. 1475.59; p  = 0.009) in the offspring group compared to controls. The significant determinants of the intergroup difference were sRAGE ( p  = 0.0017), aPWV ( p  = 0.011) and current smoking ( p  = 0.0053). Conclusion: Offspring of patients with early onset of CHD compared to age-matched healthy controls had significantly lower sRAGE levels suggesting a shift in the oxidative balance between stressors and defence mechanisms that may influence a higher cardiovascular risk in the future. The measurement of sRAGE might be a valuable predictor for more precise stratification of cardiovascular risk.

Background: Asymptomatic high-risk individuals represent one of the highest priorities of cardiovascular prevention, in clinical practice frequently overlooked. We analyzed the real adherence to recommended principles of cardiovascular prevention in primary care subjects., Methods: Our analysis is based on random general population sample, examined in the frame of post-MONICA survey in 2016/17. Each subject was categorized with regard to its individual cardiovascular risk (based on Sixth Joint European Guidelines) and the real adherence to recommended targets was ascertained., Results: In total 898 subjects aged 25-75 years (47% males) were analyzed. Of them, 16.7% were classified into &#8220;very high risk&#8220; and 36.8% into &#8220;high risk&#8220; subgroup; remaining 46.5% were only at moderate or low risk. Regarding adherence to recommended principles, in &#8220;very high risk&#8220; category only 58.7% abstain from any form of tobacco, 38% reported appropriate physical activity (150 minutes of at least moderate activity weekly), 16.7% had recommended body constitution (BMI 20-25 kg/m2 ), 39.3% appropriate blood pressure (.

Circulating levels of soluble receptor for advanced glycation end-products (sRAGE) have been suggested to have a protective role in neutralizing advanced glycation end-products (AGEs) and their pathological effects on vessel walls. We aimed to investigate the association between the circulating concentration of sRAGE and the dynamics of arterial wall stiffening as a manifestation of vascular aging in the general population. In a prospective cohort study, we longitudinally followed 530 general-population-based subjects (subsample of Czech post-MONICA study). Aortic pulse wave velocity (PWV) was measured twice (at baseline and after ~8 years of follow-up) using a SphygmoCor device (AtCor Medical Ltd), and the intraindividual change in PWV per year (∆PWV/year) was calculated. Concentrations of sRAGE were assessed at baseline by ELISA (R&D Systems). The average ∆PWV/year significantly decreased across the sRAGE quintiles (p = 0.048), and a drop by one sRAGE quintile was associated with an ~21% increase in the relative risk of accelerated age-dependent stiffening (∆PWV/year ≥ 0.2 m/s). Subjects in the bottom quintile of sRAGE (<889.74 pg/mL) had a fully adjusted odds ratio of accelerated stiffening of 1.72 (95% CI: 1.06-2.79), p = 0.028, while those with high sRAGE concentrations (≥1695.2 pg/mL) showed the opposite effect [odds ratio 0.55 (95% CI: 0.33-0.90), p = 0.017]. In conclusion, the circulating status of sRAGE independently influenced the individual progression of arterial stiffness over time. This finding strongly supports the hypothesis that high sRAGE has a protective role against vascular aging.

Aim: We aimed to establish the association between sclerostin (a glycoprotein involved in bone metabolism) and development of pulse wave velocity (PWV) in the general population. Methods: A prospective cohort study with a total of 522 subjects. Aortic PWV was measured twice (at baseline and after approximately 8 years of follow-up) and intraindividual change in PWV per year (ΔPWV/year) was calculated. Results: ΔPWV/year increased across the sclerostin quintiles, but generally in a strong age-dependent manner. However, a significant independent positive association between sclerostin and ΔPWV/year was observed exclusively in C allele carriers of rs5186 polymorphism for the angiotensin II receptor 1 (n = 246). Conclusion: Sclerostin concentrations were associated with an accelerated natural course of arterial stiffening, but only in interaction with renin-angiotension system.

Background: In December 2016, nusinersen gained FDA approval as the first pharmacologic treatment for spinal muscular atrophy (SMA), a disorder of motor neurons and the leading genetic cause of infant mortality. Nusinersen's intrathecal delivery requirement, strict dosage protocol, and accelerated FDA approval presented a challenge to health care centers hoping to implement treatment of patients with SMA. Scheduling logistics, combined with the specific ventilatory, anesthetic, and spinal access needs of this patient population, requires extensive coordination of care. This complexity, in addition to the high cost of treatment, may lead to overburdening of an institution's dosing resources, causing delays in treatment initiation and limiting patients' access to therapy and may result in barriers to coverage., Methods: We initiated a comprehensive stepwise protocol to maximize patient inclusion, as well as safety and efficiency outcome measures. This retrospective cohort study reviews the dosing process., Results: As a result of immense collaborative efforts involving care coordination of patients and families, in addition to health providers in the divisions of neurology, anesthesiology, pulmonology, orthopedics, interventional radiology, physical therapy, and neurosurgery, we have successfully dosed 62 SMA patients. Throughout this process, we have improved anesthetic techniques, as well as minimized procedural complications and missed scheduled doses., Conclusion: We present here recommendations for safe and effective implementation of nusinersen utilizing a multidisciplinary approach, based on our 1 and a half year experience at a tertiary care children's hospital., (© 2019 American Academy of Neurology.)

Background: Hypertension is the most prevalent major independent risk factor for developing coronary heart disease (CHD). The present analysis aimed to assess blood pressure (BP) distribution and factors associated with insufficient BP control in coronary patients from 24 countries participating in the European Society of Cardiology (ESC) EURoObservational Research Programme (EORP) EUROASPIRE IV survey., Methods: EUROASPIRE IV is a cross-sectional study conducted in 2012-2013 in patients aged 80 years or less hospitalized for CHD with a follow-up visit at a median of 16 months later. Logistic regression analysis was applied to confirm factors associated with BP control defined as less than 140/90 mmHg for nondiabetic patients and less than 140/85 mmHg for diabetic patients., Results: A total of 7998 patients (response rate, 48.7%) attended the follow-up visit. Complete data were available in 7653 participants (mean age 62.5 ± 9.6 years). The BP goal was achieved in 57.6%. Patients failing to achieve the BP goal were older, had higher BMI, had more often a history of coronary artery bypass grafting (CABG) and reported diabetes more frequently. Logistic regression confirmed the following independent significant predictors of not achieving the BP goal: a history of diabetes [odds ratio (OR) 1.75], obesity (OR 1.70 vs. normal BMI), overweight (OR 1.28 vs. normal BMI), age at least 65 years (OR 1.53) and CABG as the index event (OR 1.26 vs. acute MI)., Conclusion: EUROASPIRE IV found insufficient BP control in a large proportion of patients with stable CHD, with diabetes, increased BMI, older age and CABG as the index event being independent predictors of poor BP control.

Background: Secondary prevention of atherosclerotic vascular diseases represents a cascade of procedures to reduce the risk of future fatal and non-fatal cardiovascular events. We sought to determine whether the expression of selected microRNAs influenced mortality of stable chronic cardiovascular patients., Methods: The plasma concentrations of five selected microRNAs (miR-1, miR-19, miR-126, miR-133 and miR-223) were quantified in 826 patients (mean age 65.2 years) with stable vascular disease (6-36 months after acute coronary syndrome, coronary revascularization or first-ever ischemic stroke). All-cause and cardiovascular mortality rates were followed during our prospective study., Results: Low expression (bottom quartile) of all five miRNAs was associated with a significant increase in five-year all-cause death, even when adjusted for conventional risk factors, treatment, raised troponin I and brain natriuretic protein levels [hazard risk ratios (HRRs) were as follows: miR-1, 1.65 (95% CI: 1.16-2.35); miR-19a, 2.27 (95% CI: 1.59-3.23); miR-126, 1.64 (95% CI: 1.15-2.33); miR-133a, 1.46 (95% CI: 1.01-2.12) and miR-223, 2.05 (95% CI: 1.45-2.91)]. Nearly similar results were found if using five-year cardiovascular mortality as the outcome. However, if entering all five miRNAs (along with other covariates) into a single regression model, only low miR-19a remained a significant mortality predictor; and only in patients with coronary artery disease [3.00 (95% CI: 1.77-5.08)], but not in post-stroke patients [1.63 (95% CI: 0.94-2.86)]., Conclusions: In stable chronic coronary artery disease patients, low miR-19a expression was associated with a substantial increase in mortality risk independently of other conventional cardiovascular risk factors., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: We analyzed to what extent measurement protocol influenced individual blood pressure (BP) and achievement of treatment target in patients with coronary heart disease. Methods: In a subsample of Czech EUROASPIRE III-V survey participants (n = 913), we compared the per-protocol BP measurement (by automated oscillometric device OMRON at the beginning of survey procedure) with control auscultatory measurement (by physician during interview). Results: Per-protocol approach produced significantly (p < 0.0001) higher BP values (by 9/6 mmHg in median) than auscultatory measurements and led to markedly higher proportion of patients over target BP (less than 140/90 mmHg; 59.3 vs 34.9% [p < 0.0001], per-protocol vs auscultatory technique, respectively). Conclusion: Per-protocol oscillometric technique was not equivalent to conventional auscultatory measurement and seriously over-rated the real nonachievement of BP target in observational surveys.

Introduction: Ozone is a ubiquitous and irritant gas. We questioned whether an acute exposure to 0.2 ppm ozone impaired olfactory functioning., Methods: Healthy, normosmic subjects were exposed according to a parallel group design either to 0.2 ppm ozone (n = 15) or to sham (n = 13) in an exposure chamber for two hours. Possible irritating effects were assessed by questionnaire (range 0-5). The detection threshold of n-butanol was measured with the Sniffin' Sticks test before and after exposure. Olfactory thresholds were logarithmized and a two-way analysis of variance (ANOVA) with repeated measurements was carried out to test the effects of exposure (ozone vs. sham) and time (before vs. after exposure). Additionally, nasal secretions were taken at a preliminary examination and after exposure to determine interleukins 1ß and 8., Results: No irritating effects to the upper airways were observed. In the ozone group, the median score for cough increased from 0 to 2 at the end of exposure (sham group 0 and 0, respectively, p < 0.001). The ANOVA showed a main effect for ozone exposure (F (1, 26) = 27.6, p = 0.0002), indicating higher olfactory thresholds in the ozone group. Concentrations of interleukins in nasal secretions did not increase following ozone exposure., Conclusions: This study shows a clear impairment of olfactory functioning following an acute exposure to 0.2 ppm ozone., (Copyright © 2018. Published by Elsevier Inc.)

Low vitamin D status has been frequently associated with impaired glucose metabolism. We examined associations between 25-hydroxyvitamin D (25-OH-D) and several parameters of glucose homeostasis in virtually healthy subjects, and explored possible interaction with vitamin D receptor (VDR) polymorphism. Nondiabetic subjects without chronic medication or any known significant manifest disease were selected from large general-population based population survey. Insulin sensitivity and β cell secretion were calculated by homeostasis model assessment (HOMA) and soluble isoform of receptor for advanced glycation end-products (sRAGE) using commercial ELISA. Subjects were also genotyped for rs2228570 polymorphism of VDR. After adjustment for potential confounders, we observed a significant relationship between 25-OH-D and fasting glycemia (β coefficient=-5.904; p=0.002) or insulin sensitivity (β=0.042; p=0.001), but not with β cell secretion or sRAGE. We found also an interaction with VDR polymorphism. Subjects with low 25-OH-D and AA genotype had significantly lower insulin sensitivity than those with GG genotype plus highest 25-OH-D concentrations (107.3% vs. 183.9%, p=0.021). In conclusion, low vitamin D status was in virtually healthy subjects associated with decreased insulin sensitivity, namely in those with GG genotype of rs2228570 VDR polymorphism., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: We aimed to clarify the impact of metabolic syndrome (MetS) as assessed by different definitions on the cardiovascular mortality in patients with coronary heart disease (CHD)., Methods: A total of 1692 patients, 6-24months after myocardial infarction and/or coronary revascularization at baseline, were followed in a prospective cohort study. MetS was identified using four different definitions: standard National Cholesterol Education Program definition (NCEP-ATPIII) based on the presence of ≥3 of the following factors: increased waist circumference, raised blood pressure, hypetriglyceridemia, low high-density lipoprotein cholesterol, and increased fasting glycemia; modified NCEP-ATPIII definition (similar, but omitting antihypertensive treatment as an alternative criterion); presence of "atherogenic dyslipidemia"; or "hypertriglyceridemic waist". The primary outcome was a fatal cardiovascular event at 5years., Results: During 5-year follow-up, 117 patients (6.9%) died from a cardiovascular cause. Patients with MetS by modified NCEP-ATPIII (n=1066, 63.0% of the whole sample) had significantly higher 5-year cardiovascular mortality [adjusted hazard risk ratio (HRR) 2.01 [95%CI:1.26-3.22]; p=0.003] than subjects without MetS. However, when testing single MetS component factors, the majority of attributable mortality risk was driven by increased fasting glycemia (≥5.6mmol/L) [HRR 2.69 (95%CI:1.29-5.62), p=0.009] and the significance of MetS disappeared. None of the other MetS definitions, i.e., standard NCEP-ATPIII (n=1210; 71.5%), "hypertriglyceridemic waist" (n=455; 26.9%) or "atherogenic dyslipidemia" (n=223; 13.2%) were associated with any significant mortality risk., Conclusions: The co-incidence of MetS has a limited mortality impact in CHD patients, while an increase in fasting glycemia seems to be more a specific marker of mortality risk., (Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Both vitamins K and D are nutrients with pleiotropic functions in human tissues. The metabolic role of these vitamins overlaps considerably in calcium homeostasis. We analyzed their potential synergetic effect on arterial stiffness. In a cross-sectional study, we analyzed aortic pulse wave velocity (aPWV) in 1023 subjects from the Czech post-MONICA study. Desphospho-uncarboxylated matrix γ-carboxyglutamate protein (dp-ucMGP), a biomarker of vitamin K status, was measured by sandwich ELISA and 25-hydroxyvitamin D 3 (25-OH-D 3 ) by a commercial immunochemical assay. In a subsample of 431 subjects without chronic disease or pharmacotherapy, we detected rs2228570 polymorphism for the vitamin D receptor. After adjustment for confounders, aPWV was independently associated with both factors: dp-ucMGP [β-coefficient(S.E.M.)=13.91(4.87); P=.004] and 25-OH-D 3 [0.624(0.28); P=.027]. In a further analysis, we divided subjects according to dp-ucMGP and 25-OH-D 3 quartiles, resulting in 16 subgroups. The highest aPWV had subjects in the top quartile of dp-ucMGP plus bottom quartile of 25-OH-D 3 (i.e., in those with insufficient status of both vitamin K and vitamin D), while the lowest aPVW had subjects in the bottom quartile of dp-ucMGP plus top quartile of 25-OH-D 3 [9.8 (SD2.6) versus 6.6 (SD1.6) m/s; P<.0001]. When we compared these extreme groups of vitamin K and D status, the adjusted odds ratio for aPWV≥9.3 m/s was 6.83 (95% CI:1.95-20.9). The aPWV was also significantly higher among subjects bearing the GG genotype of rs2228570, but only in those with a concomitantly poor vitamin K status. In conclusion, we confirmed substantial interaction of insufficient K and D vitamin status in terms of increased aortic stiffness., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Goal: The cardiovascular diseases (CVDs) developing as the result of atherosclerosis are among the most frequent causes of morbidity and mortality within the Czech Republic and elsewhere. Genetic predisposition for cardiovascular diseases is amplified in the presence of routine risk factors which can be influenced. Our aim was to establish whether the level of the risk factors for ICHS already differs in the population of healthy descendants of the patients after early myocardial infarction, as opposed to the control group of examined individuals., Methodology: We approached adult children (n = 127; age 28.7 ± 6.5 years) of the patients with early manifestation of ICHS, who were examined within the study EUROASPIRE IV. The examination of both the descendants and the control group (n = 199; age 28.9 ± 5.3 years) focused on identifying the risk factors for ICHS., Results: Descendants presented arterial hypertension more often (18.9 vs 8.0 %, p = 0.003) and there were more smokers among them compared to the control group (37 vs 24.1 %, p = 0.01). The levels of triglycerides (1.13 vs 0.99 mmol/l, p = 0.05) and LDL-cholesterol (2.7 vs 2.45 mmol/l, p = 0.01) were higher in the descendant group, HDL-cholesterol was similar in both groups (1.6 vs 1.67 mmol/l, p = 0.17). Increased fasting glycemia occurred more frequent in the descendant group (5.5 vs 1.5 %, p = 0.05). None of the examined participants met the criteria for the diagnosis of diabetes mellitus. Aortic stiffness was higher in the descendant group as opposed to the control group (6.2 vs 5.8 m/s, p = 0.001). The total calculated cardiovascular risk based on the SCORE system was also higher in the descendant group as compared to the control group - the current risk related to the age of 40 years: 0.35 (0.19-0.64) vs 0.20 (0.13-0.47), p < 0.0001 and the risk related to the age of 60 years: 3.35 (2.23-5.36) vs 2.40 (1.58-4.11), p < 0.0001., Conclusion: The population of the descendants includes, based on our results, a greater number of smokers and hypertensive patients. They also have higher levels of LDL-cholesterol, triglycerides and impaired fasting glycemia more frequently. Unfavourable genetic predisposition along with unfitting lifestyle contributes to a higher likelihood of accumulation of risk factors, and therefore to a higher risk of a cardiovascular disease manifestation. In practice we should try, with regard to these predisposed individuals, to lower their cardiovascular risk and implement a healthy lifestyle.Key words: atherosclerosis - cardiovascular disease - lifestyle - myocardial infarction - primary prevention - risk factors for CVD.

Cardiovascular (CV) mortality was reduced more than 50 % in the Czech population at the turn of the century, due to an improvement of major CV risk factors in the general population, interventional procedures implemented into the treatment of acute coronary events, and new drugs (ACE inhibitors, statins etc.) for CV prevention (Czech MONICA and post-MONICA studies, 1985-2008). An insufficient level of preventive efforts is described in the Czech patients after acute coronary syndrome (Czech part of the EUROASPIRE studies, 1995-2013). Drug underdosing and wrong patients' compliance to life style and drug therapy recommendations represent two main reasons of this unsatisfactory situation. The residual vascular risk of patients with stable coronary heart disease (CHD) is still high due to a poor control of conventional risk factors on the one hand, and due to increasing weight and glucose metabolism abnormalities on the other hand. Patients with insulin resistance and glucose disorders have more frequently non LDL C dyslipidemia (atherogenic dyslipidemia), hypertriglyceridemic waist and high atherogenic index of plasma (AIP>0.24), i.e. markers of residual CV risk. Among others increased dose of statins and combined lipid modifying therapy should be implemented in patients with CHD, diabetes or metabolic syndrome.

Short bowel syndrome is a potentially devastating morbidity for the very low birth weight infant and family with a high risk for mortality. Prevention of injury to the intestine is the ideal, but, if and when the problem arises, it is important to have a systematic approach to manage nutrition, use pharmaceutical strategies and tools to maximize the outcome potential. Safely maximizing parenteral nutrition support by providing adequate macronutrients and micronutrients while minimizing its hepatotoxic effects is the initial postoperative strategy. As the infant stabilizes and starts to recover from that initial injury and/or surgery, a slow and closely monitored enteral nutrition approach should be initiated. Enteral feeds can be complemented with medications and supplements emerging as valuable clinical tools. Engaging a multidisciplinary team of neonatologists, gastroenterologists, pharmacists, skilled clinical nutrition support staff including registered dietitians and nutrition support nurses will facilitate optimizing each and every infant's long term result. Promoting intestinal rehabilitation and adaptation through evidence-based practice where it is found, and ongoing pursuit of research in this rare and devastating disease, is paramount in achieving optimal outcomes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Mycobacteriophage DS6A is unique among the more than 8,000 isolated mycobacteriophages due to its ability to form plaques exclusively on mycobacteria belonging to the Mycobacterium tuberculosis complex (MTBC). Speculation surrounding this specificity has led to unsupported assertions in published studies and patents that nontuberculous mycobacteria (NTM) are wholly resistant to DS6A infection. In this study, we identified two independent nonessential regions in the DS6A genome and replaced them with an mVenus-expressing plasmid to generate fluorescent reporter phages Φ 2 GFP12 and Φ 2 GFP13. We show that even though DS6A is able to form plaques only on MTBC bacteria, infection of various NTM results in mVenus expression in transduced cells. The efficiency of DS6A in delivering DNA varied between NTM species. Additionally, we saw a striking difference in the efficiency of DNA delivery between the closely related members of the Mycobacterium abscessus complex, M. abscessus and Mycobacterium massiliense We also demonstrated that TM4 and DS6A, two phages that do not form plaques on M. massiliense, differ in their ability to deliver DNA, suggesting that there is a phage-specific restriction between mycobacterial species. Phylogenetic analysis reveals that the DS6A genome has a characteristically mosaic structure but provided few insights into the basis for the specificity for MTBC hosts. This study demonstrates that the inability of the MTBC-specific phage DS6A to form plaques on NTM is more complex than previously thought. Moreover, the DS6A-derived fluorophages provide important new tools for the study of mycobacterial biology., Importance: The coevolution of bacteria and their infecting phages involves a constant arms race for bacteria to prevent phage infection and phage to overcome these preventions. Although a diverse array of phage defense systems is well characterized in bacteria, very few phage restriction systems are known in mycobacteria. The DS6A mycobacteriophage is unique in the mycobacterial world in that it forms plaques only on members of the Mycobacterium tuberculosis complex. However, the novel DS6A reporter phages developed in this work demonstrate that DS6A can infect nontuberculous mycobacteria at various efficiencies. By comparing the abilities of DS6A and another phage, TM4, to infect and form plaques on various mycobacterial species, we can begin to discern new phage restriction systems employed within the genus., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Background: The tumor microenvironment plays a critical role in tumor growth and spreading. Tumor-associated macrophages (TAM) make up a large proportion of the tumor mass and are one of the main producers of CC-chemokine ligand 18 (CCL18), which is believed to carry out important functions in the immunological interactions that promote tumor progression., Materials and Methods: Cytokines/chemokines were measured in bronchoalveolar lavage (BAL) from the tumor site and serum before and after resection in patients with proven non-small cell lung cancer (NSCLC)., Results: CCL18 concentrations in BAL positively correlated with the radiologically determined tumor volume (r=0.72, p=0.0003) in NSCLC. In addition, tumors with lymph-node metastasis exhibited significantly higher CCL18 concentrations in BAL (p=0.049) than those without. Serum CCL18 concentrations did not differ significantly before and after tumor resection., Conclusion: The increased release of CCL18 with greater tumor size is most likely due to the accompanied growth of leukocyte infiltrate. With previous findings taken into account, this could be one factor contributing to tumor invasiveness and particularly lymphatic spread in patients with larger tumors., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objectives: It is evident that patients with atherosclerotic vascular disease (AVD) benefit from appropriate secondary prevention. In clinical reality, the secondary prevention in AVD patients other than those with coronary heart disease (CHD) is often overlooked. Therefore, we compared the adherence to secondary prevention principles between poststroke and CHD patients., Study Design: Descriptive (cross-sectional) study with prospective mortality follow-up., Methods: We examined 1729 chronic patients with AVD (mean age 65.9 (±SD 9.6) years), 964 with CHD, and 765 poststroke (pooled data of Czech samples of EUROASPIRE III, IV, and the ESH stroke survey). The interview was performed 6-36 months after the coronary event/revascularization or the first ischemic stroke, while the mortality follow-up 5 years after this interview., Results: Poststroke patients had a significantly higher risk of persistent smoking, blood pressure ≥140/90 mmHg and LDL ≥2.5 mmol/L than CHD patients [odds ratios adjusted for age, gender and survey were 1.63 (95% CI: 1.13-2.33), 1.38 (95% CI: 1.13-1.69) and 2.26 (95% CI: 1.84-2.78), respectively]. In contrast, poststroke patients showed a lower risk of inappropriate glucose control and hypertriglyceridemia [0.66 (95%CI: 0.54-0.82) and 0.74 (95%CI: 0.61-0.91), respectively]. The prescription rates of antiplatelets/anticoagulants, antihypertensives and statins were also significantly lower in poststroke than in CHD patients (89.4 vs 93.7, 85.9 vs 97.5, and 57.7 vs 89.8, respectively). Mortality analysis was performed in a subsample of 815 subjects interviewed in 2006/07. The 5-year all-cause mortality rates were 25.8% and 13.3% in poststroke and coronary patients, respectively (P = 0.0023); the hazard ratio for stroke adjusted for major risk factors was 1.85 (95% CI: 1.31-2.63)., Conclusions: Compared to CHD patients, poststroke patients are strongly handicapped in terms of poor adherence to secondary prevention target, prescription of basic pharmacotherapies and mortality risk., (Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

We studied the relationships of automated blood pressure (BP), measured in the healthcare centre, with manual office BP and home BP. Stable outpatients treated for hypertension were measured automatically, seated alone in a quiet room, six times after a 5 min rest with the BpTRU device, and immediately afterwards using the auscultatory method. Home BP was measured in a subgroup during 7 days preceding the visit. The automated, office and home BP values were 131.2 ± 21.8/77.8 ± 12.1 mmHg, 146.9 ± 20.8/85.8 ± 12.4 mmHg and 137.7 ± 17.7/79.4 ± 8.2 mmHg, respectively. Limits of agreement between office and automated BP (2 SDs in Bland-Altman plots) were +42.6 to -12.6/+22.6 to -6.6 mmHg for systolic/diastolic BP; for home and automated BP they were +45.8 to -25.8/+20.8 to -12.6 mmHg. For patients with two visits, intraclass correlation coefficients of BP values measured during the first and second visits were 0.66/0.72 for systolic/diastolic automated BP and 0.68/0.74 for systolic/diastolic office BP. Automated BP was lower than home BP and no more closely related to home BP than to office BP. It did not show better repeatability than office BP. Whether automated BP and the "white-coat effect", calculated cas the office BP-automated BP difference, have clinical and prognostic importance deserves further studies.

Matrix Gla protein (MGP), a natural inhibitor of calcification, strongly correlates with the extent of coronary calcification. Vitamin K is the essential cofactor for the activation of MGP. The nonphosphorylated-uncarboxylated isoform of MGP (dp-ucMGP) reflects the status of this vitamin. We investigated whether there is an association between dp-ucMGP and stiffness of elastic and muscular-type large arteries in a random sample from the general population. In a cross-sectional design, we analyzed 1087 subjects from the Czech post-MONICA study. Aortic and femoro-popliteal pulse wave velocities (PWVs) were measured using a Sphygmocor device. Dp-ucMGP concentrations were assessed in freshly frozen samples by enzyme-linked immunosorbent assay methods using the InaKtif MGP iSYS pre-commercial kit developed by IDS and VitaK. Aortic PWV significantly (P<0.0001) increased across the dp-ucMGP quartiles. After adjustment for all potential confounders, aortic PWV independently correlated with dp-ucMGP (with beta coefficient (s.d.) 11.61 (5.38) and P-value=0.031). In a categorized manner, subjects in the top quartile of dp-ucMGP (⩾ 671 pmol l(-1)) had a higher risk of elevated aortic PWV, with corresponding adjusted odds ratio (95% confidence interval) 1.73 (1.17-2.5). In contrast, no relation between dp-ucMGP and femoro-popliteal PWV was found. In conclusion, increased dp-ucMGP, which is a circulating biomarker of vitamin K status and vascular calcification, is independently associated with aortic stiffness, but not with stiffness of distal muscular-type arteries.

Background: The purpose of this study was to ascertain way in which conventional risk factors, readiness to modify behaviour and to comply with recommended medication, and the effect of this medication were associated with education in patients with established coronary heart disease (CHD)., Methods: The EUROASPIRE IV (EUROpean Action on Secondary Prevention by Intervention to Reduce Events) study was a cross-sectional survey undertaken in 24 European countries to ascertain how recommendations on secondary CHD prevention are being followed in clinical practice. Consecutive patients, men and women ≤80 years of age who had been hospitalized for an acute coronary syndrome or revascularization procedure, were identified retrospectively. Data were collected through an interview with examinations at least six months and no later than three years after hospitalization., Results: A total of 7937 patients (1934 (24.37%) women) were evaluated. Patients with primary education were older, with a larger proportion of women. Control of risk factors, as defined by Joint European Societies 4 and 5 guidelines, was significantly better with higher education for current smoking (p = 0.001), overweight and obesity (p = 0.047 and p = 0.029, respectively), low physical activity (p < 0.001) and low high-density lipoprotein (HDL)-cholesterol (p = 0.011) in men, and for obesity (p = 0.005), high blood pressure (p < 0.005 and p < 0.001), low physical activity (p = 0.001), diabetes (p < 0.001) and low HDL-cholesterol (p = 0.023) in women. Patients with primary and secondary education were more often treated with diuretics and antidiabetic drugs. Better control of hypertension was achieved in patients with higher education., Conclusion: Particular risk communication and control are needed in secondary CHD prevention for patients with lower educational status., (© The European Society of Cardiology 2015.)

It has been suggested that accumulation of advanced glycation end products (AGEs) is involved in several pathophysiological processes in the vessel wall. We hypothesized that low levels of the soluble receptor for AGEs (sRAGE) might be associated with increased arterial stiffness, a manifestation of vascular ageing in the general population. Using a cross-sectional design, we analyzed 1077 subjects from the Czech post-MONICA study. The aortic pulse wave velocity (aPWV) was measured using a Sphygmocor device. sRAGE concentrations were assessed in frozen samples using enzyme-linked immunosorbent assay methods (R&D Systems). aPWV significantly (P<0.0001) increased across the sRAGE quartiles. An aPWV of 1 m s(-1) was associated with a 37% increase in the risk of low sRAGE (<918 pg ml(-1), bottom quartile; P-value=0.018). In a categorized manner, subjects in the bottom sRAGE quartile had an odds ratio of an increased aPWV (⩾9.3 m s(-1)), adjusted for all potential confounders of 2.05 (95% confidence interval: 1.26-3.32; P=0.004), but this was only the case for non-diabetic hypertensive patients. In contrast, a low sRAGE was rejected as an independent predictor of an increased aPWV in normotensive or diabetic subjects using similar regression models. In conclusion, low circulating sRAGE was independently associated with increased arterial stiffness in a general population-based sample, but this was only observed in hypertensive non-diabetic patients.

Thoracic insufficiency syndrome (TIS) is a broad grouping of disorders that have a substantial impact on the chest wall, spine, and in many situations, both. While the conditions are varied, they share a potentially substantial impact on respiratory capacity and development over time and a presentation and need for intervention that is often in early childhood. Addressing these conditions has required a new paradigm that involves both deformity correction and a preservation of growth capacity. While there are now a number of options to treat severe spinal deformity early in life, when the deformity causes or is caused by a chest wall deformity, the Vertical Expandable Prosthetic Titanium Rib(VEPTR) is able to support surgical correction of both. The skeletal correction is often quite dramatic, but the functional measurements of quality of life and pulmonary function often do not show as dramatic and improvement, but consistently show a stabilization indicating control of the progressive thoracospinal disorder that produced TIS., (Copyright © 2016 Mosby, Inc. All rights reserved.)

Background: Matrix Gla protein (MGP) is a natural inhibitor of tissue calcification. In a previous study, we observed the positive association between abnormal concentrations of uncarboxylated MGP species and increased mortality risk in stable vascular patients. We explore whether co-incidence of abnormal status of uncarboxylated MPG and heart failure (HF) affects the mortality risk., Methods: We examined 799 patients (mean age 65.1 years) with stable vascular disease and followed them in a prospective study. Both, desphospho-uncarboxylated and total uncarboxylated MGP (dp-ucMGP or t-ucMGP) were quantified by pre-commercial ELISA assays., Results: Elevated (>100 ng/L) circulating brain natriuretic peptide (BNP) and abnormal status of plasma uncarboxylated MGP species (i.e.: dp-ucMGP ≥ 977 pmol/L or t-ucMGP ≤ 2825 nmol/L) were all identified as robust predictors of all-cause 5-year mortality. However, their co-incidence represented a substantial additional risk. We observed the highest mortality risk in patients with elevated BNP plus high dp-ucMGP compared to those with normal BNP plus low dp-ucMGP; fully adjusted HRR's were 4.86 (3.15-7.49). Likewise, the risk was increased when compared with patients with elevated BNP plus low dp-ucMGP; HRR 2.57 (1.60-4.10). Similar result we observed when co-incidence of elevated BNP and low t-ucMGP was analyzed [corresponding HRR's were 4.16 (2.62-6.61) and 1.96 (1.24-3.12)]., Conclusions: The concomitant abnormality of uncarboxylated MGP and mild elevation of BNP leads in chronic patients with vascular disease to about two-fold increase of the relative mortality risk. We hypothesize that abnormal homeostasis of MGP is involved in the pathophysiology of HF., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Vascular calcification was once regarded as an advanced stage of atherosclerosis only. However, calcification is currently considered as highly regulated and potentially reversible process.Matrix Gla protein (MGP) represents natural inhibitor of vascular calcification, whereas vitamin K is key co-factor of its maturation to the active form. There is accumulating evidence that vitamin K status and corresponding MGP activity may influence cardiovascular risk. This review summarizes pathophysiological mechanism and recent evidence relative to MGP. Moreover, available data concerning vitamin K supplementation are depicted.

Purpose: The German MAK value of methyl methacrylate has been fixed at 50 ppm. The aim of this study was to evaluate possible acute effects of an exposure to 50 ppm methyl methacrylate on the upper airways of human subjects., Methods: Twenty healthy subjects were exposed to 50 ppm methyl methacrylate and to air (sham) in an exposure chamber for 4 h according to a crossover design. Symptoms were assessed by the SPES questionnaire. Olfactory thresholds for n-butanol and mucociliary transport time were measured before and after exposure. Concentrations of interleukin 1ß and interleukin 8 were determined in nasal secretions taken after exposure. mRNA levels of interleukins 1ß, 6 and 8, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1, and cyclooxygenases 1 and 2 were measured in nasal epithelial cells, obtained after exposure. Possible effects were investigated by semiparametric and parametric crossover analyses., Results: The score of the item "irritation to the nose" was slightly elevated following exposure to methyl methacrylate (p ≤ 0.01). Olfactory functioning was not impaired. Mucociliary transport time did not change. Neither concentrations of interleukins in nasal secretions nor mRNA levels were elevated., Conclusion: Only minor irritating effects on the nose were observed. The acute exposure to 50 ppm methyl methacrylate did not cause any adverse effects. However, the results cannot be extrapolated to chronic exposure.

Perceived quality of life (QoL) and psychological well-being represents an important target of secondary prevention practice in post-stroke patients. We aimed to identify the major covariates of impaired QoL in stable post-stroke patients and whether impaired QoL itself represents independent mortality predictor.The study consisted of a cross-sectional and a prospective part. Three hundred forty-one patients [mean age 69.0 (SD 9.1)] were interviewed at least 6 months after discharge from hospital for their first-ever ischemic stroke. QoL was objectivized using 36-Item Short-Form Health Survey (SF-36) scoring. Standard health-related questionnaires, including Hospital Anxiety and Depression Scale (HADS), risk factors, and biochemical markers, were assessed. To estimate the 5-year all-cause and cardiovascular mortality, we ascertained the vital status and declared cause of death.Anxiety, depression (HADS score ≥11), brain natriuretic peptide levels ≥100 ng/mL, residual motor impairment at interview, Rankin Scale ≥4 at discharge from hospitalization, and raised blood pressure were identified as main determinants of impaired QoL in the cross-sectional part. The 5-year all-cause and cardiovascular mortality rates were 25.8 and 19.9 %, respectively. After adjustment for potential covariates, patients with an SF-36 score ≤40 at baseline had more than a twofold higher risk of all-cause and cardiovascular mortality (with HRRs 2.01 (95 % CI 1.21-3.32), p < 0.007 and 2.32 (95 % CI 1.32-4.09), p < 0.003, respectively) during the 5 years of follow-up.In conclusion, anxiety, depression, and raised brain natriuretic peptide levels were the most important covariates of impaired QoL in post-stroke patients. Moreover, a decreased SF-36 score (≤40) represents an independent surrogate of increased additive mortality risk.

Background: Previous cross-sectional surveys in different European countries within the EUROASPIRE programme demonstrated a high prevalence of modifiable risk factors, unhealthy lifestyles and inadequate drug treatment in coronary heart disease patients. Comparable data for ischaemic stroke patients is lacking., Methods: A stroke-specific study module was added to the EUROASPIRE III core survey. This cross-sectional multicentre survey included consecutive patients with first-ever ischaemic stroke from four European countries. Data were obtained from medical records, patient interviews and patient examinations within 6-36 months after the stroke event. Control of modifiable risk factors after stroke was evaluated against contemporary European guidelines., Results: A total of 881 patients was recruited. Median age was 66 years, 37.5% were female; average time from the stroke event to interview was 550 days. At the time of the interview, 17.6% of stroke patients smoked cigarettes, 35.5% had a body mass index ≥30 kg/m(2), 62.4% showed elevated blood pressure and 75.7% exhibited elevated LDL cholesterol levels. Antiplatelet drugs or oral anticoagulants were used by 87.2%, antihypertensive medication by 84.4% and statins by 56.8% of stroke patients. Among patients using antihypertensive drugs and lipid-lowering medication at the time of the interview, 34.3% and 34.4%, respectively, achieved target blood pressure and total cholesterol values according to current European guidelines., Conclusion: The EUROASPIRE III stroke-specific module shows that secondary prevention and risk factor control in patients after ischaemic stroke need to be improved in four European centres at the time of the study since about half of patients are not achieving risk factor targets defined in European guidelines., (© The European Society of Cardiology 2014.)

Objective: Recurrent strokes are associated with higher mortality, greater disability, and increased healthcare costs compared with first-ever stroke. Lifestyle measures and drug treatment in secondary prevention decrease the risk of recurrence while improving the quality of life of patients. The objective of this study was to determine the prevalence of hypertension and other cardiovascular risk factors in stroke survivors and population controls., Methods and Results: A total of 424 poststroke survivors (aged 66.0 ± 10.4 years) were examined 6-36 months after their first ischemic stroke. Controls of similar age and from the same geographic region were selected from the database of the Czech post-Multinational MONItoring of trends and determinants in CArdiovascular disease Study. Hypertension was found to be the most prevalent risk factor affecting 91.5% of stroke survivors and 71.8% of controls. Use of antihypertensive drugs was reported in 79.5% of stroke survivors and 56.7% of controls. However, blood pressure lower than 140/90 mmHg was achieved in only 49.5% of hypertensive stroke survivors. More than 60% of stroke survivors used statins but low-density lipoprotein-cholesterol lower than 2.5 mmol/l was achieved in only 47.4 and 37% of male and female poststroke survivors, respectively. About a third of poststroke patients continue to smoke, and obesity is a major problem, particularly in women (prevalence 47%), who also have a high prevalence of diabetes., Conclusion: We found a high prevalence and poor control of major cardiovascular risk factors in patients surviving their first-ever ischemic stroke, thus showing poor implementation of guidelines for secondary prevention in clinical practice.

Aim: We speculated whether DRD2 or CHRN subunit polymorphisms might be associated with the risk of smoking cessation failure in subjects after coronary heart disease (CHD) manifestation., Methods: A total of 964 patients with CHD, mean age 64.3 years (standard deviation [SD] 9.0), examined in the EUROASPIRE III and IV surveys were genotyped for rs1800497 (DRD2/ANKK1 Taq1A), rs578776 (CHRNA5-A3-B4), rs16969968 (CHRNA5) and rs1051730 (CHRNA3) SNPs., Results: The presence of DRD2/ANKK1 Taq1A minor T allele was independently associated with increased relative risk of smoking persistence (odds ratio: 1.79; 95% CI: 1.13-4.35). We observed no association between CHRN SNPs and smoking habit., Conclusion: DRD2/ANKK1 Taq1A polymorphism is associated with a decreased likelihood of smoking cessation in patients after CHD manifestation.

The indication for vena cava filters (VCF) in treatment of venous thromboembolism is still controversial. The presented overview should support the practical decisions. Beside of large volume of observational date there is only one study - PREPIC 1 - fulfilling requirements of prospective randomized design. During 8 years of follow up, pulmonary embolism (PE) was less frequent in the group with VCF than in the group without VCF, but at the cost of more frequent deep vein thrombosis (DVT). Other, but observational studies, showed similar results. Since last 10 years retrievable VCF are available. PREPIC 2 study was settled to prove, if use of retrievable VCF and their early removal will decrease the frequency of late complications observed in PREPIC 1. The results are available as conference abstract only, but it was presented that recurrence of DVT and PE was less frequent in group without IVC than with inserted VCF. Evaluation of impact of VCF insertion on mortality from RIETE registry showed only a trend which was in favour of VCF. On the other hand, a protective effect of VCF was demonstrated in hemodynamically unstable patients with PE (cardiogenic shock, massive embolism) with or without thrombolytic therapy evaluating cases from US NIS registry. Metaanalysis of studies in patients with polytrauma showed VCF protection mainly in patients where anticoagulation was contraindicated. Data gained from literature are discussed with existing guidelines. 2014 Recommendations of European Cardiologic Society is thatVC filters may be used when there are absolute contraindications to anticoagulation and a high risk of VTE recurrence. The routine use of IVC filters in patients with PE is not recommended.

Objective: Due to contradictory results of previous studies evaluating the association between ischemic stroke (IS) and thrombophilic polymorphisms, their routine screening in IS patients, particularly those older than 60 years, is not recommended. We evaluated the differences in the distribution of rs6025 and rs1799963 polymorphisms according to IS subtypes and their interaction with smoking., Methods: We conducted a case-control study of 423 hospital-based consecutive survivors of their first-ever IS and 614 population-based controls. Survivors (18-81 years) with IS documented by brain imagining were examined at a median of 16 months after the index event. The stroke subtype was categorized using the Causative Classification of Stroke System. Controls (50-75 years) were free of a history of stroke/TIA, coronary heart disease, and venous thromboembolism., Results: Age- and gender-adjusted prevalence of individuals carrying at least one copy of the rs1799963A minor allele was 5.3% among stroke survivors (by subtypes: 3.1% in large artery atherosclerosis, 2.0% in cardio-aortic embolism, 2.4% in small artery occlusion, and 10.3% in undetermined stroke) vs. 2.4% among controls. In multinomial multivariate adjusted analysis, rs1799963 was exclusively associated with undetermined stroke (OR: 3.67; 95% CI: 1.52-8.85; p = 0.004). There was strong evidence of rs1799963 × smoking synergistic interaction (OR: 5.14; 95% CI: 1.65-16.01; p = 0.005). There was no association of rs6025 with IS in general, or with any subtype., Conclusions: In our consecutive IS survivors, carriage of the rs1799963A allele is associated with undetermined stroke. This effect appears to be confined to smokers., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Although obesity is a risk factor for stroke and achieving normal weight is advocated to decrease stroke risk, the risk associated with obesity and weight loss after stroke has not been well established. The aim of this study was to assess the association of obesity at the time of stroke admission and weight loss after stroke with total mortality., Methods: We analyzed 736 consecutive patients (mean age, 66 ± 11 years; 58% men) hospitalized for their first ischemic stroke. Body weight at hospital admission and at the outpatient visit during follow-up was used in the analysis., Results: After multivariate adjustment, obesity at admission was associated with lower mortality risk as compared with normal weight (hazard ratio [HR], .50, P = .03). At the outpatient visit, with a median follow-up time of 16 months, 21% of patients had lost more than 3 kg of weight. Stroke severity, heart failure, transient ischemic attack, and depression after stroke were independently associated with significant weight loss. Weight loss of more than 3 kg was associated with increased mortality risk (HR, 5.87; P = .001) independently of other factors. Similar results were seen when weight loss was defined as losing more than 3% of baseline weight (HR, 4.97; P = .004). Weight gain of more than 5% of the baseline weight tended to be associated with better survival when compared with no weight change (log-rank test, P = .07)., Conclusions: Normal weight at hospital admission and weight loss after ischemic stroke are independently associated with increased mortality. Overweight and obesity at baseline do not decrease the risk associated with weight loss., (Copyright © 2015 National Stroke Association. All rights reserved.)

Background: A number of clinical trials have shown that patients with overt atherovascular disease may benefit from more aggressive dosage of statins. We aimed to determined the usual dosage of statin in clinical practice and the adherence to recommended target concentration of LDL-cholesterol., Methods and Results: We analyzed 948 patients with mean age 64.5 years (SD ± 9.0) after acute coronary syndrome and/or coronary revascularization (Czech samples of EUROASPIRE III and IV). In spite that more than 93 % of patients were in 2012/2013 treated with statin, only 2.4 % with the highest dose (atorvastatin 80 mg or equivalent). On the other hand, medium-dosed statin (atorvastatin 40 mg) was more often prescribed, in comparison to 2006/2007. We observed mild improvement in adherence to former LDL-cholesterol target < 2.5 mmol/l (from 54 % to 65 %), but the recent target < 1.8 mmol/l was reached only in less than one quarter of patients in 2012/2013. It can be approximate (using individual LDL-cholesterol values), that after maximal possible up-titration of statin, the adherence to recent LDL-cholesterol target may improve up to 43 %., Conclusions: Although the majority of CHD patients are currently being treated with statin, the usual dosage regimen and adherence to the recommended target values were not consistent with current therapeutic standards for secondary prevention of CHD.

Objectives: Due to improved analytical performance of the newest generation of troponin assays, several patients have mild elevations of this parameter. Nevertheless, they do not show any signs of acute coronary syndrome. We speculated whether non-acute cardiac troponin I (cTnI) concentrations may improve prediction of residual mortality risk in clinically stable outpatients with chronic vascular disease., Design and Methods: We followed 830 patients (mean age 65.2years) after myocardial infarction, coronary revascularization or first ischemic stroke (pooled Czech samples of EUROASPIRE III and EUROASPIRE-stroke surveys, interviewed in 2006/2007) in a prospective cohort study. In addition to standard protocol, troponin I and brain natriuretic peptide (BNP) was estimated from frozen samples. Vital status and declared cause of death from death certificates was registered to ascertain a 5-year all-cause and cardiovascular mortality., Results: During a median follow up of 2050days (5.6years) 168 patients died. In the multivariate Cox proportional hazard model, cTnI≥0.03ng/mL independently predicted an all-cause 5-year mortality with HRR 1.76 (95% CI: 1.09-2.83). In the Cox model, the better predictor of mortality was BNP >150ng/L [HRR 3.47 (95% CI: 2.23-5.41)]. However, the combination of BNP with cTnI did not substantially improve its sensitivity or predictive power., Conclusion: We cannot confirm the utility of asymptomatic mild cTnI elevation as a tool to detect residual risk of stable patients with vascular disease. On the other hand, BNP seems to be more appropriate for this purpose., (Copyright © 2014. Published by Elsevier Inc.)

Objectives: There is no agreement on optimal blood pressure (BP) level during the acute phase of stroke, because studies on the relation between BP and stroke outcome have shown contradicting results. The aim of this study was to compare the relationship of admission, maximal, discharge BP and its components during hospitalization for the first-ever acute ischemic stroke with total mortality after stroke., Methods: In 532 consecutive patients (mean age 66 ± 10 years, 59% of men) hospitalized for their first-ever ischemic stroke, the association between BP and total mortality during a median follow-up of 66 weeks (interquartile range 33-119 weeks) was analyzed., Results: In multivariate analysis, both admission mean BP (MBP) and discharge SBP quartiles were independent predictors of mortality and outperformed other parameters of BP. After multivariate adjustments, patients with admission MBP below 100 mmHg had a higher risk of death than those with MBP between 100-110 and 110-121 mmHg, whereas the risk of mortality did not differ from the group with admission MBP above 122 mmHg. Similarly, patients with discharge SBP below 120 mmHg had an increased risk of death as compared to groups with SBP between 120-130 and 130-141 mmHg, whereas the risk of death was similar to that with discharge SBP above 141 mmHg., Conclusion: Among patients hospitalized for their first-ever ischemic stroke, the risk of all-cause death is significantly increased in those with admission MBP below 100 mmHg and discharge SBP below 120 mmHg, even after adjustments for other confounders.

Objective: Nitric oxide plays an important role in vascular biology. Several single nucleotide polymorphisms (SNP) in the endothelial nitric oxide gene (NOS3) have been previously associated with arterial hypertension. We investigated whether these SNPs might be associated with arterial phenotypes in the Czech general population., Methods: We genotyped three NOS3 SNPs in 426 subjects not treated for arterial hypertension (mean age, 49.1 years; 55.9% women). Arterial properties were measured using applanation tonometry. In multivariate-adjusted analyses, we assessed the gene effects of rs3918226 (-665 C>T), rs1799983 (glu298asp G>T) and rs2070744 (786 T>C) on augmentation index (AIx), central augmentation pressure (AP) and aortic pulse wave velocity (PWV)., Results: Carriers of rs3918226 mutated T allele had marginally higher AIx (145.3 ± 2.5 vs. 140.2 ± 1.1%; P = 0.064) and significantly higher AP (12.7 ± 0.7 vs. 11.1 ± 0.3 mm Hg; P = 0.033). These associations were independent of potential confounding factors. Aortic PWV was not different in the two rs39182226 genotypes groups (P = 0.35). In single gene analyses, we did not observe any association between measured phenotypes and rs1799983 or rs2070744 (P ≥ 0.11). In haplotype analysis, we observed trend for higher PWV in haplotypes containing rs3918226 mutated T allele compared with other allelic combination (P ≤ 0.079)., Conclusion: Mutated T allele of rs3918226 polymorphism in NOS3 gene was associated with parameters reflecting central arterial stiffness and wave reflection. We hypothesize that genetic modulation of intermediate arterial phenotypes might lead to higher blood pressure., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Metabolic syndrome (MetSy) is associated with a high risk of cardiovascular complications. Arterial stiffness is an independent predictor of cardiovascular morbidity and mortality. This study investigated the effect of individual MetSy risk factors on central and peripheral parameters of aortic stiffness. In the Czech post-MONICA study, we measured aortic pulse-wave velocity (aPWV), lower extremity pulse-wave velocity (lePWV), augmentation index (AIx) and central augmentation pressure (cAP) in 936 subjects. Based on the definition of MetSy, we divided subjects according to number of risk factors. We used univariate and multivariate linear regression analysis to assess the association between number of risk factors and aPWV, lePWV, AIx and cAP. In analyses adjusted for age, gender, heart rate and mean arterial pressure, aPWV was higher in subjects with MetSy (MetSy+ group) than in those without (MetSy + group) (8.3 vs. 7.7 m/s; p < 0.0001), but lePWV was not significantly different between the groups (11.0 vs. 11.2 m/s; p = 0.2037). After adjustment for covariates, AIx in MetSy+ was lower than in MetSy- respondents (143.2 vs. 146.8; p = 0.014). In adjusted analysis, aPWV rose with increasing number of MetSy risk factors (7.3 ± 0.1 vs. 9.0 ± 0.1 m/s; p for trend < 0.0001). The number of MetSy risk factors did not affect lePWV (p = 0.11). AIx decreased with higher number of MetSy risk factors (148.3 vs. 141.5; p = 0.020). This finding confirms the fact that PWV and AIx may have different associations with risk factors and AIx should not be used as an isolated parameter of arterial stiffness. The individual MetSy risk factors have only a small effect on lower extremity arterial stiffness.

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is independently associated with cardiovascular risk, probably via inflammatory activity in sclerotic plaque. We speculated whether Lp-PLA2 has a role in the aetiology of vascular calcifications, estimated from circulating uncarboxylated matrix Gla protein (MGP) species and whether we could find a potential interaction of Lp-PLA2 and MGP in terms of mortality., Materials and Methods: We examined 798 patients (mean age 65.1 years) with stable vascular disease and followed them in a prospective study. Both, desphospho-uncarboxylated and total MGP (dp-ucMGP or t-ucMGP) were quantified by pre-commercial ELISA assays, developed by VitaK (Maastricht, The Netherland), Results: Lp-PLA2 activity was independently positively associated with desphospho-uncarboxylated MGP (dp-ucMGP) [β coeff = 0.098, p=0.006]. 1SD of Lp-PLA2 activity was associated with 37% increased risk (p=0.001) of elevated dp-ucMGP (≥977 pmol/L, top quartile). In the Cox proportional hazard model adjusted for conventional risk factors, the patients in the highest quartile of dp-ucMGP or lowest quintile of total-uncarboxylated ucMGP (<2660 nmol/L) had higher risk of all-cause mortality [HRR 2.79 (95% CI 1.97-3.94) and HRR 1.69 (95% CI 1.18-2.42), respectively]. We observed no effect of high Lp-PLA2 activity (≥195 nmol/min/mL) on total mortality., Conclusions: We assume that Lp-PLA2 is involved in vascular calcification and that dp-ucMGP is a more appropriate biomarker of residual risk than Lp-PLA2 itself., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Vitamin K is the essential co-factor for activation of matrix Gla-protein (MGP), the natural inhibitor of tissue calcification. Biologically inactive, desphospho-uncarboxylated MGP (dp-ucMGP) is a marker of vascular vitamin K status and is described to predict mortality in patients with heart failure and aortic stenosis. We hypothesized that increased dp-ucMGP might be associated with mortality risk in clinically stable patients with chronic vascular disease., Materials and Methods: We examined 799 patients (mean age 65.1 ± 9.3 years) who suffered from myocardial infarction, coronary revascularization or first ischemic stroke (pooled Czech samples of EUROASPIRE III and EUROASPIRE-stroke surveys), and followed them in a prospective cohort study. To estimate the 5-year all-cause and cardiovascular mortality we ascertained vital status and declared cause of death. Circulating dp-ucMGP and desphospho-carboxylated MGP (dp-cMGP) were measured by ELISA methods (IDS and VitaK)., Results: During a median follow-up of 2050 days (5.6 years) 159 patients died. In the fully adjusted multivariate Cox proportional hazard model, the patients in the highest quartile of dp-ucMGP (≥ 977 pmol/L) had higher risk of all-cause and cardiovascular 5-year mortality [HRR 1.89 (95% CI, 1.32-2.72) and 1.88 (95% CI, 1.22-2.90)], respectively. Corresponding HRR for dp-cMGP were 1.76 (95% CI, 1.18-2.61) and 1.79 (95% CI, 1.12-2.57)., Conclusions: In patients with overt vascular disease, circulating dp-ucMGP and dp-cMGP were independently associated with the risk of all-cause and cardiovascular mortality. Since published results are conflicting regarding the dp-cMGP, we propose only circulating dp-ucMGP as a potential biomarker for assessment of additive cardiovascular risk., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)