Explore the vast range of titles available.

Background:Patients with systemic sclerosis (SSc) may be burdened by increased cardiovascular (CV) risk due to accelerated atherosclerosis (ATS) due to systemic inflammation, and vascular impairment.Objectives:To evaluate CV risk in SSc patients SSc compared to healthy controls (HC) and to assess its association with disease-specific features.Methods:92 patients with SSc (81 females; mean age 52; mean disease duration 6.8 years; dcSSc: n=28, lcSSc: n=64) and 197 HC (147 females, mean age 56.7) were included, all with no history of CV disease (angina pectoris, myocardial infarction, cerebrovascular, and peripheral arterial vascular events). Disease activity and organ involvement were evaluated in SSc. In all participants comorbidities and current treatment were recorded, examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition (by densitometry (DXA) and bioelectrical impedance analysis (BIA)) were performed. The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE, charts for the European population) and its modifications: SCORE multiplied by the coefficient 1.5 (mSCORE), and SCORE2.Results:SSc patients had a trend to higher prevalence of dyslipidemia (p=0.063) and significantly more often prediabetes (p<0.001) than HC, but a comparable prevalence of arterial hypertension, diabetes mellitus, and current smoking to HC. Nevertheless, SSc used significantly more frequently antihypertensives HC (p<0.001), including calcium channel blockers (indicated for Raynaud’s phenomenon). SSc had significantly increased prevalence of carotid artery disease, more unfavorable CIMT and ABI (p<0.05), and only a trend to lower SCORE and overall CV risk based on SCORE but no significant difference in SCORE2 compared to HC.On the contrary, the overall CV risk based on US examination was significantly higher in SSc. A comparison of calculated CV risk with US examination showed inaccuracy of the CV risk scoring systems in SSc (Figure 1). Nevertheless, SCORE2 underestimated the real CV risk significantly less than SCORE (p=0.043), while SCORE2 vs. mSCORE and SCORE vs. mSCORE were comparable. In SSc, the CV risk and markers of subclinical ATS were associated especially with age, HbA1c, disease duration, and mean arterial pressure (p<0.05 for all).Conclusion:This cross-sectional case-control study in SSc patients demonstrated a significantly increased risk of subclinical ATS in SSc compared to HC, although there was an opposite trend in CV risk estimated by calculated SCORE. The CV risk in SSc was associated especially with age, disease duration, and HbA1c levels, among others. Scoring systems underestimated the CV risk (when compared to ultrasound findings), while SCORE2 was significantly more accurate than SCORE.REFERENCES:NIL.Acknowledgements:Supported by MHCR (023728; NV18-01-00161A; NU21-01-00146).Disclosure of Interests:None declared.

BackgroundCardiovascular (CV) risk due to accelerated atherosclerosis and impaired metabolism can be increased in idiopathic inflammatory myopathies (IIM) on behalf of systemic inflammation, limited mobility, and glucocorticoid therapy.ObjectivesThis study aimed to evaluate CV risk in patients with IIM in comparison to healthy controls (HC) and to assess its association with disease-specific features.Methods90 patients with IIM (70 females; mean age 56.6; mean disease duration 5.95 years; dermatomyositis: n=29, polymyositis: n=12, immune-mediated necrotizing myopathy (IMNM): n=20, anti-synthetase syndrome: n=29) and 180 HC (130 females, mean age 54.3) were included. In both groups, subjects with a history of CV disease (angina pectoris, myocardial infarction, cerebrovascular, and peripheral arterial vascular events) were excluded. Muscle involvement, disease activity, and tissue damage were evaluated (by MMT-8, MITAX, MDI, respectively). Comorbidities and current treatment were recorded. All participants underwent examinations of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), ankle-brachial index (ABI), and body composition (by densitometry (DXA) and bioelectrical impedance analysis (BIA)). The risk of fatal CV events was evaluated by the Systematic COronary Risk Evaluation (SCORE, charts for the European population) and its modifications: SCORE multiplied by the coefficient 1.5 (mSCORE), and SCORE2.ResultsCompared to HC, IIM patients had a significantly higher prevalence of traditional CV risk factors, carotid artery disease (CARD), abnormal ABI, and PWV (p<0.05 for all). After propensity score matching (PSM) using traditional CV risk factors, the prevalence of CARD and pathologic PWV remained significantly higher in IIM than HC (p<0.05 for all), but no significant difference in SCORE was observed. Overall CV risk based on calculated risk (modifications of SCORE) and ultrasound (US) examinations was comparable between IIM ad HC after PSM (CVR-SCORE p=0.457, CVR-SCORE2 p=0.130, CVR-US p=0.126). IMNM patients had the most unfavorable CV risk profile among IIM subtypes. The calculated CV risk scores by SCORE and SCORE2 (in both IIM and HC), and mSCORE (in IIM only) were reclassified according to CIMT and the presence of carotid plaques. SCORE was demonstrated to be the most inaccurate in predicting CV risk in IIM, while there was a significantly higher proportion of reclassified patients with underestimated CV risk evaluated by SCORE compared to SCORE2 and mSCORE (p=0.020). Age, disease activity, lipid profile, body composition parameters, and blood pressure were the most significant predictors of CV risk in IIM patients (p<0.05 for all variables in bivariate analysis). Moreover, the length of glucocorticoid therapy was positively associated with an increased count of carotid plaques and overall CV risk estimated by US examination (p<0.05 for both).ConclusionThis cross-sectional cohort study in IIM patients demonstrated a significantly increased risk of subclinical atherosclerosis and CV risk, and also an increased prevalence of traditional CV risk factors compared to HC with comparable age and gender distribution. The most unfavorable findings were seen in patients with IMNM. All scoring systems for CV risk screening underestimated the CV risk in IIM when using the CV risk according to ultrasound findings. SCORE2 appeared to be the most accurate tool in IIM.AcknowledgementsSupported by MHCR (023728; NV18-01-00161A; NU21-01-00146).Disclosure of InterestsNone Declared.

Objectives: There is some controversy as to whether there is a benefit from the use of a centrifugal pump compared with a roller pump during cardiopulmonary bypass to facilitate cardiac surgery. We compared the two pumps, with the primary aim of determining any difference in the effects on inflammation after pulmonary endarterectomy surgery which required prolonged cardiopulmonary bypass and deep hypothermic circulatory arrest. Methods: Between September 2010 and July 2013, 58 elective patients undergoing pulmonary endarterectomy were included in this prospective, randomised, controlled study; 30 patients were randomly allocated to the control group, which used a roller pump, and 28 patients to the treatment group, which used a centrifugal pump. Interleukin-6, procalcitonin, C-reactive protein, thromboelastographic parameters, P-selectin, international normalised ratio, activated prothrombin time, free haemoglobin, haematocrit, red blood cell count, white blood cell count, platelet count and protein S100β were recorded during and after the procedure. We also recorded the length of intensive care unit stay, blood loss and transfusion, neurological outcomes and respiratory and renal failure. Results: There was a significant difference in the primary outcome measure: Interleukin-6 was significantly higher in the roller pump group (587±38 ng·l-1 vs. 327±37 ng·l-1; p<0.001) 24 hours after surgery, which we interpreted as an increased inflammatory response. This was confirmed by a significant rise in the procalcitonin level in the roller pump group 48 hours following surgery (0.79 (0.08-25.25) ng·ml-1 vs. 0.36 (0.02-5.83) ng·ml-1; p<0.05). There were, however, no significant differences in clinical outcome data. Conclusions: We have shown that the use of a centrifugal pump during prolonged cardiopulmonary bypass and deep hypothermic circulatory arrest is associated with a reduced inflammatory response compared to the standard roller pump. Larger multi-centre trials in this area of practice are required.

The primary aim was to determine frequencies of mutations related to risk of venous thrombosis in healthy Caucasians in Central Bohemia. In a cohort of 1527 healthy individuals the frequency of risk alleles for the mutations FV Leiden and FII 20210G>A was 4.5 % and 1.3 %, respectively. Frequency of 4G PAI-1 allele was 55.5 %. Genotype frequencies were: GG 91.03 %, GA 8.91 %, and AA 0.07 % for FV Leiden; GG 97.45 %, GA 2.49 %, and AA 0.07 % for FII 20210G>A; 4G/4G 30.26 %, 4G/5G 50.56 %, and 5G/5G 19.19 % for PAI-1. Frequency of the risk allele A in polymorphism SERPINC1 (IVS +141G >A) was 11.3 %, and frequencies of genotypes were as follows: GG 78.36 %, GA 20.66 %, and AA 0.98 %. Frequency of the risk allele T for polymorphism GP6 13254T>C was 87.7 %, and frequencies of genotypes were as follows: TT 77.14 %, TC 21.15 %, and CC 1.70 %. Frequency of the risk allele A in polymorphism CYP4V2 (Lys259Gln) was 65.2 %, and frequencies of genotypes were: CC 12.25 %, CA 45.12 %, and AA 42.63 %. All observed genotypes and alleles frequencies were without gender differences. Their occurrences confirm a relatively high prevalence of hereditary thrombophilia predisposition in the Czech Republic.

Advanced glycation end-products (AGEs) are key players in pathogenesis of long-term vascular diabetes complications. Several enzymes such as fructosamine 3-kinase (FN3K) and glyoxalase I (GLO I) are crucial in preventing glycation processes. The aim of our study was to evaluate an association of FN3K (rs1056534, rs3848403) and GLO1 rs4746 polymorphisms with parameters of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in 595 diabetic and non-diabetic subjects. Genotypic and allelic frequencies of mentioned polymorphisms did not differ between subgroups. In diabetic patients significant differences were observed in sRAGE concentrations according to their rs1056534 and rs3848403 genotype. While GG and CG genotypes of rs1056534 with mutated G allele were associated with significant decrease of sRAGE (GG: 1055±458 and CG: 983±363 vs. CC: 1796±987 ng/l, p<0.0001), in rs3848403 polymorphism TT genotype with mutated T allele was related with significant sRAGE increase (TT: 1365±852 vs. CT: 1016±401 and CC: 1087±508 ng/l, p=0.05). Significant differences in adhesion molecules were observed in genotype subgroups of GLO1 rs4746 polymorphism. In conclusion, this is the first study describing significant relationship of FN3K (rs1056534) and (rs3848403) polymorphisms with concentration of sRAGE in patients with diabetes.

In this trial, 27,564 patients with cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter or higher on statin therapy were assigned to either evolocumab or placebo. At 2.2 years, the evolocumab group had a significantly lower rate of major adverse cardiovascular events. Low-density lipoprotein (LDL) cholesterol is a well-established and modifiable risk factor for cardiovascular disease. Monoclonal antibodies that inhibit proprotein convertase subtilisin–kexin type 9 (PCSK9) have emerged as a new class of drugs that effectively lower LDL cholesterol levels. 1 Evolocumab, a member of this class, is a fully human monoclonal antibody that reduces LDL cholesterol levels by approximately 60%. 2 – 6 Genetic studies have shown that carriage of PCSK9 loss-of-function alleles is associated with lower LDL cholesterol levels and a reduced risk of myocardial infarction. 7 , 8 Moreover, exploratory data from longer-term follow-up in phase 2 and phase 3 trials of PCSK9 inhibitors . . .

Edoxaban, an oral factor Xa inhibitor, was noninferior to warfarin in the prevention of stroke or systemic embolism in patients with atrial fibrillation. There was less bleeding with edoxaban than with warfarin. Edoxaban is an oral, reversible, direct factor Xa inhibitor with a linear and predictable pharmacokinetic profile and 62% oral bioavailability. 1 It achieves maximum concentrations within 1 to 2 hours, and 50% is excreted by the kidney. 2 A randomized, dose-ranging, warfarin-controlled, phase 2 study involving 1146 patients with atrial fibrillation showed that once-daily doses of edoxaban (60 mg or 30 mg) were safer than twice-daily doses. 3 Pharmacokinetic modeling and simulation showed that patients with low body weight, moderate-to-severe renal dysfunction, or concomitant use of a potent P-glycoprotein inhibitor should have the edoxaban dose reduced by 50%. 4 A phase 3 study involving . . .

The aim of the study was to evaluate skin microvascular reactivity (MVR) and possible influencing factors (fibrinolysis, oxidative stress, and endothelial function) in patients with Cushing’s syndrome. Twenty-nine patients with active Cushing’s syndrome (ten of them also examined after a successful operation) and 16 control subjects were studied. Skin MVR was measured by laser Doppler flowmetry during post-occlusive (PORH) and thermal hyperemia (TH). Malondialdehyde and Cu,Zn-superoxide dismutase were used as markers of oxidative stress. Fibrinolysis was estimated by tissue plasminogen activator (tPA) and its inhibitor (PAI-1). N-acetyl-β-glucosaminidase, E-selectin, P-selectin, and ICAM-1 were used as markers of endothelial function. Oxidative stress and endothelial dysfunction was present in patients with hypercortisolism, however, increased concentration of ICAM-1 was also found in patients after the operation as compared to controls (290.8±74.2 vs. 210.9±56.3 ng.ml-1, p<0.05). Maximal perfusion was significantly lower in patients with arterial hypertension during PORH and TH (36.3±13.0 vs. 63.3±32.4 PU, p<0.01, and 90.4±36.6 vs. 159.2±95.3 PU, p<0.05, respectively) and similarly the velocity of perfusion increase during PORH and TH was lower (3.2±1.5 vs. 5.2±3.4 PU.s-1, p<0.05, and 0.95±0.6 vs. 1.8±1.1 PU.s-1, p<0.05, respectively). The most pronounced impairment of microvascular reactivity was present in patients with combination of arterial hypertension and diabetes mellitus.

The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Willebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P < 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P < 0.05). Three-month treatment of hypertensive patients with quinapril led to a significant decrease in the levels of endothelin-1 (5.76 vs 5.28 fmol/ml, P < 0.01). We did not observe significant changes in the levels of adhesion molecules and vWf after ACE inhibitor treatment, although a trend toward a decrease was apparent with all these parameters. Patients with uncomplicated hypertension with no other risk factors of atherosclerosis had significantly elevated levels of ICAM-1, vWf, and endothelin-1. Our data suggest that these factors may serve as markers of endothelial damage even in uncomplicated hypertension. In hypertensive patients, treatment with the ACE inhibitor quinapril resulted in a significant decrease in endothelin-1 levels. These findings indicate a beneficial effect of ACE inhibitors on endothelial dysfunction in hypertensive patients.

The aim of our study was to evaluate potential differences in the concentration of biochemical markers of endothelial dysfunction between essential hypertension, endocrine hypertension (pheochromocytoma, primary hyperaldosteronism) and control healthy group and to assess a potential relationship between these markers of endothelial dysfunction and vasopressor substances overproduced in endocrine hypertension. We have investigated 21 patients with moderate essential hypertension, 29 patients with primary hyperaldosteronism, 24 subjects with pheochromocytoma and 26 healthy volunteers. Following parameters of endothelial dysfunction were measured, von Willebrand factor (vWf), plasminogen activator (t-PA) and E-selectin (E-sel). Clinical blood pressure was measured according to the European Society of Hypertension recommendations. We found significantly higher levels of the von Willebrand factor in patients with essential hypertension in comparison with a control group (114+/-20 IU/dl vs 90+/-47 IU/dl; P=0.04) and patients with primary hyperaldosteronism (114+/-20 IU/dl vs 99+/-11 IU/dl; P=0.01). Patients with endocrine hypertension revealed increased levels of vWF compared to the control group, but these differences did not reach statistical significance. Levels of t-PA were increased in patients with pheochromocytoma in comparison with the control group (4.6+/-1.9 ng/ml vs 3.4+/-0.9 ng/ml; P=0.01) and with primary hyperaldosteronism (4.6+/-1.9 ng/ml vs 3.4+/-1.1 ng/ml; P<0.01). In case of E-selectin we found lower levels in patients with pheochromocytoma in comparison with other groups, but they differed significantly only with primary hyperaldosteronism (40.2+/-15.0 ng/ml vs 51.3+/-23.0 ng/ml; P=0.05). Our study did not reveal any convincing evidence of differences in the levels of biochemical markers of endothelial dysfunction between essential and endocrine hypertension. No correlation between the biochemical markers of endothelial dysfunction and vasopressor substances activated in endocrine hypertension was found.