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Background: The carotid intima–media thickness (IMT) measurement may be carried out proximally (pIMT) or distally (dIMT) in relation to the bulb of the common carotid artery which has significant implications on the results and correlation with risk factors. The aim of the study was to compare the pIMT and dIMT in patients with familial hypercholesterolemia confirmed by genetic testing (FH group) and patients with severe non-familial hypercholesterolemia, with negative results of genetic testing (NFH group) and to determine the correlation of results with traditional atherosclerotic risk factors and calcium scores. Methods: A total of 86 FH and 50 NFH patients underwent pIMT and dIMT measurements of both carotid arteries as well as computed tomography (CT) with coronary and thoracic aorta calcium scoring. Results: The meanpIMT of both right and left common carotid artery were significantly higher in patients with FH compared to the NFH group (meanpRIMT 0.721 ± 0.152 vs. 0.644 ± 0.156, p < 0.01, meanpLIMT 0.758 ± 0.173 vs. 0.670 ± 0.110, p < 0.01). Patient age, pre-treatment lowdensity lipoprotein (LDL) cholesterol levels (LDLmax) at baseline and systolic blood pressure were independent predictors of pIMT increases in both carotid arteries. Smoking history, age and LDLmax were independent predictors of dIMT increase. There was a significant correlation between the calcium scores of the ascending aorta, coronary artery and aortic valve and all IMT parameters. Conclusions: The IMT measured proximally better between patients with familial and non-familial hypercholesterolemia. The association between IMT and traditional cardiovascular risk factors varies between measurement sites. IMT values correlate CT calcium scores in all patients with hypercholesterolaemia regardless of genetic etiology.

Background: Cardiovascular disease (CVD) is a leading cause of death globally. Recently, dipeptidyl peptidase‐4 inhibitors (DPP4i), glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) and sodium‐glucose co‐transporter‐2 inhibitors (SGLT2i) were approved for treating people with type 2 diabetes mellitus. Although metformin remains the first‐line pharmacotherapy for people with type 2 diabetes mellitus, a body of evidence has recently emerged indicating that DPP4i, GLP‐1RA and SGLT2i may exert positive effects on patients with known CVD. Objectives: To systematically review the available evidence on the benefits and harms of DPP4i, GLP‐1RA, and SGLT2i in people with established CVD, using network meta‐analysis. Search methods: We searched CENTRAL, MEDLINE, Embase, and the Conference Proceedings Citation Index on 16 July 2020. We also searched clinical trials registers on 22 August 2020. We did not restrict by language or publication status. Selection criteria: We searched for randomised controlled trials (RCTs) investigating DPP4i, GLP‐1RA, or SGLT2i that included participants with established CVD. Outcome measures of interest were CVD mortality, fatal and non‐fatal myocardial infarction, fatal and non‐fatal stroke, all‐cause mortality, hospitalisation for heart failure (HF), and safety outcomes. Data collection and analysis: Three review authors independently screened the results of searches to identify eligible studies and extracted study data. We used the GRADE approach to assess the certainty of the evidence. We conducted standard pairwise meta‐analyses and network meta‐analyses by pooling studies that we assessed to be of substantial homogeneity; subgroup and sensitivity analyses were also pursued to explore how study characteristics and potential effect modifiers could affect the robustness of our review findings. We analysed study data using the odds ratios (ORs) and log odds ratios (LORs) with their respective 95% confidence intervals (CIs) and credible intervals (Crls), where appropriate. We also performed narrative synthesis for included studies that were of substantial heterogeneity and that did not report quantitative data in a usable format, in order to discuss their individual findings and relevance to our review scope. Main results: We included 31 studies (287 records), of which we pooled data from 20 studies (129,465 participants) for our meta‐analysis. The majority of the included studies were at low risk of bias, using Cochrane's tool for assessing risk of bias. Among the 20 pooled studies, six investigated DPP4i, seven studied GLP‐1RA, and the remaining seven trials evaluated SGLT2i. All outcome data described below were reported at the longest follow‐up duration. 1. DPP4i versus placebo: Our review suggests that DPP4i do not reduce any risk of efficacy outcomes: CVD mortality (OR 1.00, 95% CI 0.91 to 1.09; high‐certainty evidence), myocardial infarction (OR 0.97, 95% CI 0.88 to 1.08; high‐certainty evidence), stroke (OR 1.00, 95% CI 0.87 to 1.14; high‐certainty evidence), and all‐cause mortality (OR 1.03, 95% CI 0.96 to 1.11; high‐certainty evidence). DPP4i probably do not reduce hospitalisation for HF (OR 0.99, 95% CI 0.80 to 1.23; moderate‐certainty evidence). DPP4i may not increase the likelihood of worsening renal function (OR 1.08, 95% CI 0.88 to 1.33; low‐certainty evidence) and probably do not increase the risk of bone fracture (OR 1.00, 95% CI 0.83 to 1.19; moderate‐certainty evidence) or hypoglycaemia (OR 1.11, 95% CI 0.95 to 1.29; moderate‐certainty evidence). They are likely to increase the risk of pancreatitis (OR 1.63, 95% CI 1.12 to 2.37; moderate‐certainty evidence). 2. GLP‐1RA versus placebo: Our findings indicate that GLP‐1RA reduce the risk of CV mortality (OR 0.87, 95% CI 0.79 to 0.95; high‐certainty evidence), all‐cause mortality (OR 0.88, 95% CI 0.82 to 0.95; high‐certainty evidence), and stroke (OR 0.87, 95% CI 0.77 to 0.98; high‐certainty evidence). GLP‐1RA probably do not reduce the risk of myocardial infarction (OR 0.89, 95% CI 0.78 to 1.01; moderate‐certainty evidence), and hospitalisation for HF (OR 0.95, 95% CI 0.85 to 1.06; high‐certainty evidence). GLP‐1RA may reduce the risk of worsening renal function (OR 0.61, 95% CI 0.44 to 0.84; low‐certainty evidence), but may have no impact on pancreatitis (OR 0.96, 95% CI 0.68 to 1.35; low‐certainty evidence). We are uncertain about the effect of GLP‐1RA on hypoglycaemia and bone fractures. 3. SGLT2i versus placebo: This review shows that SGLT2i probably reduce the risk of CV mortality (OR 0.82, 95% CI 0.70 to 0.95; moderate‐certainty evidence), all‐cause mortality (OR 0.84, 95% CI 0.74 to 0.96; moderate‐certainty evidence), and reduce the risk of HF hospitalisation (OR 0.65, 95% CI 0.59 to 0.71; high‐certainty evidence); they do not reduce the risk of myocardial infarction (OR 0.97, 95% CI 0.84 to 1.12; high‐certainty evidence) and probably do not reduce the risk of stroke (OR 1.12, 95% CI 0.92 to 1.36; moderate‐certainty evidence). In terms of treatment safety, SGLT2i probably reduce the incidence of worsening renal function (OR 0.59, 95% CI 0.43 to 0.82; moderate‐certainty evidence), and probably have no effect on hypoglycaemia (OR 0.90, 95% CI 0.75 to 1.07; moderate‐certainty evidence) or bone fracture (OR 1.02, 95% CI 0.88 to 1.18; high‐certainty evidence), and may have no impact on pancreatitis (OR 0.85, 95% CI 0.39 to 1.86; low‐certainty evidence). 4. Network meta‐analysis: Because we failed to identify direct comparisons between each class of the agents, findings from our network meta‐analysis provided limited novel insights. Almost all findings from our network meta‐analysis agree with those from the standard meta‐analysis. GLP‐1RA may not reduce the risk of stroke compared with placebo (OR 0.87, 95% CrI 0.75 to 1.0; moderate‐certainty evidence), which showed similar odds estimates and wider 95% Crl compared with standard pairwise meta‐analysis. Indirect estimates also supported comparison across all three classes. SGLT2i was ranked the best for CVD and all‐cause mortality. Authors' conclusions: Findings from both standard and network meta‐analyses of moderate‐ to high‐certainty evidence suggest that GLP‐1RA and SGLT2i are likely to reduce the risk of CVD mortality and all‐cause mortality in people with established CVD; high‐certainty evidence demonstrates that treatment with SGLT2i reduce the risk of hospitalisation for HF, while moderate‐certainty evidence likely supports the use of GLP‐1RA to reduce fatal and non‐fatal stroke. Future studies conducted in the non‐diabetic CVD population will reveal the mechanisms behind how these agents improve clinical outcomes irrespective of their glucose‐lowering effects.

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding Bill & Melinda Gates Foundation.

Background Post-myocardial depression is a highly prevalent condition worsening the course and prognosis of coronary artery disease. One of the possible pathogenetic factors is dysregulation of the autonomous nervous system, resulting in heart rate variability reduction. Methods Twenty two patients hospitalised due to a first myocardial infarction were included. The Beck Depression Inventory (BDI) was used to rate the severity of their depressive symptoms. Results Depressive symptomatology, defined as BDI ≥10, was present in 36.3% of the patients. Increase in heart rate variability (HRV) was observed in both groups during the first 6 months after the myocardial infarction. The HRV was significantly lower in the depressed group compared to patients without depression. Conclusion Presence of depression after the myocardial infarction (MI) is associated with a significant decrease of the time domain HRV measure SDNN (standard deviation of all normal RR intervals) and with its slower increase during at least a three months period.

Oxidative stress is believed to play a critical role in atherosclerosis initiation and progression. In line with this, in a group of 1099 subjects, we determined eight single nucleotide polymorphisms (SNPs) related to oxidative stress (PON1 c.575A&gt, G, MPO c.&minus, 463G&gt, A, SOD2 c.47T&gt, C, GCLM c.&minus, 590C&gt, T, NOS3 c.894G&gt, T, NOS3 c.&minus, 786T&gt, C, CYBA c.214C&gt, T, and CYBA c.&minus, 932A&gt, G) and assessed the extent of atherosclerosis in coronary arteries based on Gensini score. An increased risk of having a Gensini score in the higher half of the distribution was observed for the PON1 c.575G allele (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.004&ndash, 1.617, p = 0.046). Next, the genetic risk score (GRS) for the additive effect of the total number of pro-oxidative alleles was assessed. We noted an increase in the risk of having a Gensini score above the median with the maximum number of risk alleles (OR = 2.47, 95% CI: 1.19&ndash, 5.23, p = 0.014). A univariate Spearman&rsquo, s test revealed significant correlation between the total number of pro-oxidant alleles (GRS) and the Gensini score (&rho, = 0.068, p = 0.03). In conclusion, the PON1 c.575A&gt, G variant and the high number of risk alleles (GRS) were independent risk factors for a high Gensini score. We suggest, however, that GRS might occur as a more valuable component in adding a predictive value to the genetic background of atherosclerosis.

The CYBA gene encodes the regulatory subunit of NADPH oxidase, which maintains the redox state within cells and in the blood vessels. That led us to investigate the course of coronary artery disease (CAD) with regards to CYBA polymorphisms. Thus, we recruited 1197 subjects with coronary atherosclerosis and observed them during 7-year follow-up. Three CYBA polymorphisms: c.214C&gt, T (rs4673), c.-932G&gt, A (rs9932581), and c.*24G&gt, A (1049255) were studied for an association with death, major adverse cardiovascular events (MACE) and an elective percutaneous coronary intervention or coronary artery bypass grafting (PCI/CABG). We found an association between the CYBA c.214C&gt, T polymorphism and two end points: death and PCI/CABG. CYBA c.214TT genotype was associated with a lower risk of death than C allele (9.5% vs. 21%, p &lt, 0.05) and a higher risk of PCI/CABG than C allele (69.3% vs. 51.7%, p &lt, 0.01). This suggests that the CYBA c.214TT genotype may be a protective factor against death OR = 0.47 (95%CI 0.28&ndash, 0.82, p &lt, 0.01), while also being a risk factor for an elective PCI/CABG OR = 2.36 (95%CI 1.15&ndash, 4.82, 0.05). Thus, we hypothesize that among patients with coronary atherosclerosis, the CYBA c.214TT genotype contributes to atherosclerotic plaque stability by altering the course of CAD towards chronic coronary syndrome, thereby lowering the incidence of fatal CAD-related events.

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention.METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months.RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; PCONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

Breakfast is considered to be the most important meal of the day, which significantly contributes to overall dietary quality. Global trends suggest a decline in breakfast consumption frequency in all age groups over the years. Breakfast skipping is associated with increased risk of weight gain, insulin resistance and type 2 diabetes, which are crucial risk factors of cardiovascular diseases (CVD). Regular breakfast consumption as a modifiable risk factor might be of great interest for cardiovascular prevention. Several prospective cohort studies showed contradictory findings on breakfast skipping and CVD risk. To the best knowledge of authors, this topic was not covered by any previous meta-analysis. Therefore, this review aimed to summarise the evidence on the association between breakfast skipping and CVD risk in prospective studies with particular emphasis on dose-response relationship and quality of existing evidence. A comprehensive search of the literature was performed using PubMed and Embase databases until February 2019, with no restriction to language and date. Inclusion criteria were as following: (1) participants aged ≥ 18 years, (2) prospective design, (3) information about breakfast consumption/skipping frequency and (4) outcome is the risk of CVD including coronary heart disease, stroke or heart failure. For high versus low comparison, random effects model was applied using the inverse variance method. Greenland-Longenecker method was used to conduct linear dose-response meta-analysis. Potential nonlinear association were examined using restricted cubic splines model. Heterogeneity was evaluated using the Cochrane Q test and I2 statistic with value > 50% indicating substantial heterogeneity. Quality of evidence was assessed using NutriGrade tool. Out of 877 records identified in the literature search, four prospective cohort studies with 7258 CVD cases were included. Comparing breakfast skipping to regular breakfast consumption, there was a positive association with CVD risk (RR = 1.17 95%CI: 1.02–1.34, I2 = 39%, pheterogenity = 0.14). In linear dose-response meta-analysis, each additional day of breakfast skipping was related to 2% higher risk of CVD (RR = 1.02 95%CI: 1.00–1.04, I2 = 15%, pheterogenity = 0.31, n = 3). No non-linear association was observed (pnon-linearity = 0.53, n = 3). The quality of evidence for these associations was rated as low. This review indicated that breakfast skipping is associated with increased risk of CVD. Potential implementation of these findings in cardiovascular prevention has to consider low trust in existing evidence. Further prospective studies on this topic have to focus on the type of foods and meals consumed during breakfast, as well as BMI mediation.

Background: Post-myocardial depression is a highly prevalent condition which worsens the course and prognosis of coronary artery disease. One possible pathogenetic factor is dysregulation of the hypothalamic-pituitary-adrenal axis, resulting in cortisol profile disturbances. Methods: Thirty seven patients hospitalized due to a first myocardial infarction (MI) were enrolled in this study. The Beck Depression Inventory (BDI) was used to rate the severity of their depressive symptoms. Morning and afternoon serum cortisol samples were taken on the fifth day of the MI. Results: Depression, defined as BDI ≥ 10, was present in 34.4% of the patients. A statistically significant difference was observed between the mean morning and the evening plasma concentrations in patients with depression compared to the no-depression group: F (1.29) = 5.0405, p = 0.0328. Conclusions: Patients with depressive symptoms directly after MI have a flattened diurnal serum cortisol profile. This is particularly expressed in patients with longer lasting symptoms.

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility and metabolic problems among women of reproductive age. The mechanism of PCOS is associated with concurrent alterations at the hormonal level. The diagnosis assumes the occurrence of three interrelated symptoms of varying severity, namely ovulation disorders, androgen excess, or polycystic ovarian morphology (PCOM), which all require a proper therapeutic approach. The main symptom seems to be an increased androgen concentration, which in turn may contribute to different metabolic disorders. A number of papers have demonstrated the significant role of inositol therapy in PCOS. However, there is a lack of detailed discussion about the importance of myo-inositol (MI) and d-chiro-inositol (DCI) in reference to particular symptoms. Thus, the aim of this review is to present the effectiveness of MI and DCI treatment for PCOS symptoms. Moreover, the review is focused on analyzing the use of inositols, taking into account their physiological properties, together with the mechanism of individual PCOS symptom formation.

Cyclitols play a particularly important role in cell functioning because they are involved in ion channel physiology, phosphate storage, signal transduction, cell wall formation, membrane biogenesis, osmoregulation and they have antioxidant activity. They are involved in the cell membranes as a phosphatidyl myo-inositol, an inositol triphosphate precursor, which acts as a transmitter that regulates the activity of several hormones, such as follicle-stimulating hormone, thyrotropin, and insulin. The aim of this paper is to characterize the selected cyclitols: myo-inositol, D-chiro-inositol, and D-pinitol in type-2 metabolic syndrome and diabetes treatment. Results and discussion: Cyclitols have certain clinical applications in the treatment of metabolic syndromes and are considered to be an option as a dietary supplement for the treatment or prevention of gestational diabetes mellitus and type-2 diabetes. Improved metabolic parameters observed after using cyclitols, like myo-inositol, in the treatment of polycystic ovary syndrome and type-2 diabetes suggest that they may have a protective effect on the cardiovascular system. Pinitol, together with myo-inositol,maybe responsible for improving lipid profiles by reducing serum triglyceride and total cholesterol. Pinitol is also well-researched and documented for insulin-like effects. Myo-inositol, D-chiro-inositol, and D-pinitol indicate a number of therapeutic and health-promoting properties.

Background Cangrelor, an intravenous, reversible P2Y12 antagonist, is approved for use in patients undergoing percutaneous coronary intervention (PCI). Objectives This study sought to evaluate the efficacy and safety of cangrelor compared with clopidogrel in subgroups that did and did not receive glycoprotein IIb/IIIa inhibitors (GPIs). Methods This pooled, patient-level analysis of the 3 CHAMPION (Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition) trials analyzed all randomized patients who underwent PCI and received the study drug (n = 24,902). Only bailout/rescue GPI use was permitted, except in CHAMPION PCI, in which routine or bailout/rescue GPI use was at the site investigator’s discretion. The primary efficacy endpoint was the composite of all-cause mortality, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 h after randomization. Results Overall, 3,173 patients (12.7%) received a GPI, most commonly eptifibatide (69.4%). Despite variation in indications for GPIs, baseline characteristics were well balanced between the cangrelor and clopidogrel arms in subsets receiving and not receiving GPIs. Rates of the primary composite endpoint were lower with cangrelor compared with clopidogrel in patients who did (4.9% vs. 6.5%; odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.55 to 1.01) or did not receive a GPI (3.6% vs. 4.4%; OR: 0.82; 95% CI: 0.72 to 0.94; Pint = 0.55). Cangrelor did not increase the primary safety endpoint, GUSTO-defined severe/life-threatening bleeding, in patients who did (0.4% vs. 0.5%; OR: 0.71; 95% CI: 0.25 to 1.99) or did not receive GPIs (0.2% vs. 0.1%; OR: 1.56; 95% CI: 0.80 to 3.04; Pint = 0.21). GPI use was associated with increased risk of bleeding in both treatment arms. Conclusions Cangrelor’s efficacy in reducing ischemic complications in patients undergoing PCI was maintained irrespective of GPI administration. GPI use was associated with substantially higher bleeding rates, regardless of the randomization to cangrelor or clopidogrel. (A Clinical Trial to Demonstrate the Efficacy of Cangrelor [PCI]: NCT00305162 ; Cangrelor Versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition [PLATFORM]: NCT00385138 ; A Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [PCI] [CHAMPION PHOENIX] [CHAMPION]: NCT01156571 )

Uvod: I přes velký pokrok v nedavne době je familiarni hypercholesterolemie (FH) stale jestě celosvětově podceňovane, nedostatecně diagnostikovane, a tedy i nedostatecně lecene onemocněni. O přesne prevalenci pacientů postižených familiarni hypercholesterolemii v regionu středni, východni a jižni Evropy (CESE) mame jen velmi malo informaci. Cilem studie bylo popsat na zakladě dostupných udajů epidemiologickou situaci v regionu CESE. Metody: Vsichni vedouci představitele projektu ScreenPro FH v jednotlivých oblastech byli požadani o poskytnuti lokalnich udajů, ktere se týkaji (a) expertniho odhadu prevalence FH, (b) již fungujicich zdravotnických zařizeni, (c) použitých diagnostických kriterii, (d) poctu pacientů již zavedených v mistni databazi a konecně (e) dostupnosti možnosti lecby (zejmena plazmaferezy). Výsledky: Vzhledem k odhadovane prevalenci FH přibližně 1 : 500 odhadujeme, že celkova populace FH heterozygotů v regionu CESE zahrnuje 588 363 osob. V mistnich databazich se vsak zobrazilo pouze 14 108 osob (2,4 %), přicemž mira zobrazeni se lisila v rozmezi od 0,1 % až 31,6 %. Pouze 4 země oznamily dostupnost LDL aferezy. Zavěr: Nase udaje svědci o velke populaci pacientů postižených heterozygotni formou FH v regionu CESE a zaroveň o nizkých podilech jejich zobrazeni. V ramci projektu ScreenPro FH jsou vsak nyni vytvařeny potřebne struktury a můžeme tak doufat v dosaženi přiznivějsich výsledků.

The severe hypercholesterolaemia can be recognised when low density lipoprotein cholesterol (LDL-C) serum levels are equal to or above 5 mmol/L (≥ 190 mg/dL). The prevalence of LDL-C ≥ 5 mmol/L is 3.8% in Polish population aged 18-79 years. Among these adults there are patients with familial hypercholesterolaemia (FH). According to meta-analysis of 6 Polish population surveys prevalence of heterozygous FH (HeFH) diagnosed using Dutch Lipid Clinic criteria is 0.4% (95% Cl 0.28-0.53%) in men and women aged 20-74 years, i.e. one in every 250 people. As HeFH is a wellknown cause of premature coronary heart disease the rigorous treatment targets for LDL-C have been established in clinical guidelines. Their achievements, even with a high dose of high efficacy statin therapy is difficult or even impossible. New strong hypolipidaemic drugs i.e. PCSK9 inhibitors have been initiated against this chalange. Both drugs, evolocumab and alirocumab, have been extensively studied in numerous phase 2 and phase 3 trials. Fewer studies with bococizumab are available until now. The PCSK9 inhibitors, as monotherapy as well in combination with statins were associated with mean LDL-C reduction about 60%. It means that the majority of patients (70-90%) with severe hypercholesterolaemia (including HeFH), treated with statins, after addition of PCSK9 inhibitors were able to achieve an LDL-C < 2.5 mmol/L (< 100 mg/dL) or < 1.8 mmol/L (< 70 mg/dL) level. Another group of patients who may benefit from PCSK9 inhibitors include those who need lipid lowering therapy, but who are statin intolerant, especially because of statin-associated muscle symptoms (SAMS). In our statement we have accepted the diagnosis of SAMS proposed recently by European Atherosclerosis Society. Today the longest clinical trial with evolocumab (11 months) was the open OSLER study, and with alirocumab ODYSSEY LONG TERM (78 weeks). In the first one the reduction of cardiovascular events by 53% (95% Cl 22-72%) was observed, and in the second one by 48% (10-69%). Neurocognitive events were reported more frequently with both drugs than with placebo. This adverse effect will be the subject of observation in ongoing studies. We still await the results of 4 ongoing large placebo controlled phase 3 trials investigating whether PCSK9 inhibitors on background of statin therapy reduce cardiovascular events. Meanwhile evolocumab, as well as alirocumab have been accepted to use in clinical practice by European Medicine Agency. In this situation the experts of Polish Society of Cardiology have prepared the statement on the use PCSK9 inhibitors with indication in the first place for HeFH patients, statin intolerant and those at high risk who are not able to reach LDL-C target level with a high potent high dose statin.

Familial hypercholesterolemia (FH) is the most common monogenic autosomal dominant disorder. FH results in an increased cardiovascular mortality rate. However, cardiovascular risk control factors enable the avoidance of approximately 80% of strokes and cardiovascular diseases. Therefore, early detection and implementation of lipid-lowering treatment is essential. In the present study, 57 pediatric patients aged 9.57 &plusmn, 3.26 years with FH were enrolled in the study. Researchers checked the lipid profile and performed the ultrasound imaging including intima-media thickness (IMT) measurement and echo (e)-tracking in the study group. Patients were treated with a low-cholesterol diet solely or along with pharmacological treatment with statins. Subsequently, patients were monitored for 12 months. The positive results of dietary treatment were observed in 40 patients. The efficacy of 12 months of nutritional therapy along with pharmacological treatment was reported in 27 patients. We observed a significant decrease in the carotid beta index stiffness and an insignificant decrease in the IMT in the group of patients treated with statins. The obtained data show that statin therapy in children with FH allow for the reduction of the degree of atherosclerotic vessel changes.

Background Physical inactivity and resultant lower energy expenditure contribute unequivocally to cardiovascular diseases, such as coronary artery disease and stroke, which are considered major causes of disability and mortality worldwide. Aim The aim of the study was to investigate the influence of physical activity (PA) and exercise on different aspects of health - genetics, endothelium function, blood pressure, lipid concentrations, glucose intolerance, thrombosis, and self - satisfaction. Materials and. Methods In this article, we conducted a narrative review of the influence PA and exercise have on the cardiovascular system, risk factors of cardiovascular diseases, searching the online databases; Web of Science, PubMed and Google Scholar, and, subsequently, discuss possible mechanisms of this action. Results and Discussion Based on our narrative review of literature, discussed the effects of PA on telomere length, nitric oxide synthesis, thrombosis risk, blood pressure, serum glucose, cholesterol and triglycerides levels, and indicated possible mechanisms by which physical training may lead to improvement in chronic cardiovascular diseases. Conclusion PA is effective for the improvement of exercise tolerance, lipid concentrations, blood pressure, it may also reduce the serum glucose level and risk of thrombosis, thus should be advocated concomitant to, or in some cases instead of, traditional drug-therapy.

Cardiovascular disease (CVD) is the most significant prognostic factor in individuals with type 2 diabetes (T2D). However, a significant number of individuals may develop CVD that does not present with the classic angina-related or heart failure symptoms. In these cases, CVD may seem to be ‘silent’ or ‘asymptomatic’, but may be more accurately characterised as unrecognised diabetic cardiac impairment. An initial step to raise awareness of unrecognised CVD in individuals with T2D would be to reach a consensus regarding the terminology used to describe this phenomenon. By standardising the terminologies, and agreeing on the implementation of an efficient screening program, it is anticipated that patients will receive an earlier diagnosis and appropriate and timely treatment. Given the availability of anti-diabetic medications that have been shown to concomitantly reduce CV risk and mortality, it is imperative to improve early identification and initiate treatment as soon as possible in order to enable as many patients with T2D as possible to benefit.

Background: The MacNew health-related quality of life questionnaire was designed to assess feelings about how heart disease affects their daily physical, emotional and social functioning in patients with 1 of the 3 major coronary artery diagnoses, stable coronary artery disease (CAD) with angina, ST-elevation myocardial infarction (STEMI), and ischemic heart failure (HF). The aim of this study was to determine the reliability and validity of the Polish version of the MacNew in patients with CAD. Methods: Patients with CAD completed a self-report sociodemographic and clinical ques­tionnaire: the MacNew, the Short-Form 36 Health Survey, and HADS at baseline; 10% of the patients completed each questionnaire 2 weeks later. Results: We studied patients with stable CAD with angina (n = 115), with STEMI (n = 112), and with ischemic HF (n = 105). Internal consistency reliability was demonstrated with Cronbach’s a from 0.86 to 0.95 for the MacNew global scale and subscales. The original 3-factor structure was confirmed for the Polish version of the MacNew explaining 53.5% of the variance. Convergent validity of similar MacNew and SF-36 subscales was confirmed in the total group and in each diagnosis. Discriminant validity with the SF-36 health transition was fully confirmed in the total group and in patients with HF and partially confirmed in patients with stable CAD with angina or myocardial infarction. Conclusions: The Polish MacNew health-related quality of life questionnaire can be recommended in patients with stable CAD with angina, myocardial infarction and HF.

Background: Red cell distribution width (RDW) in acute heart failure (AHF) is accepted as a prognostic indicator with unclear pathophysiological ties. The aim of this study was to evaluate the prognostic value of RDW in AHF patients in relation to clinical and echocardiographic data. Methods: 170 patients with AHF were retrospectively studied. All patients had laboratory testing and an echocardiogram performed within 24 h of admission to the Cardiology Department. Results: During the mean 193 ± 111 days of follow-up, 33 patients died. More advanced age, high RDW and low peak early diastolic velocity of the lateral mitral annulus (MVe’) were independent predictors of all-cause mortality with hazard ratios of: 1.05 (95% CI 1.02–1.09), p < 0.005, 1.40 (95% CI 1.22–1.60), p < 0.001, and 0.77 (95% CI 0.63–0.93), p < 0.007, respectively. In a stepwise multiple linear regression model, RDW was correlated with hemoglobin concentration (standardized b = –0.233, p < 0.001), mean corpuscular volum (standardized b = –0.230, p < 0.001), mean corpuscular hemoglobin concentration (standardized b = –0.207, p < 0.007), the natural logarithm of C-reactive protein (CRP) (standardized b = 0.184, p < 0.004) and tricuspid regurgitation peak gradient (TRPG) values (standardized b = 0.179, p < 0.006), whereas MVe’ was correlated with atrial fibrillation (standardized b = 0.269, p < 0.001). Conclusions: The present data demonstrates a novel relation between higher levels of RDW and elevated TRPG and high sensitivity CRP values in patients with AHF. These findings suggest that RDW, the most important mortality predictor, is independently associated with elevated pulmonary pressure and systemic inflammation in patients with AHF. Moreover, in AHF patients, more advanced age and decreased MVe’ are also independently associated with total mortality risk.

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, pINTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.FUNDING: Bayer AG.

Aims The effectiveness of revascularization of chronic total occlusion (CTO) remains intriguing. Thus, we sought to investigate whether a successful PCI for single CTO improves outcomes in a setting of stable angina and chronic occlusion of single coronary artery. Methods and Results Of 11 957 consecutive patients referred for nonurgent PCI between 2003 and 2010, 1110 displayed single CTO and were enrolled to the central CTO-registry database. The primary end-point included all-cause mortality, the secondary end-point a composite of safety outcome measure of all-cause death, nonfatal-MI, the need for urgent revascularization and stroke. The major adverse cardiovascular event (MACE) records were extracted from the national administrative database and all patients were linked to the long-term follow-up. Since the patient assignment was not random, we performed the propensity scoring to minimize selection bias; 734 patients (66%) had a successful PCI-CTO. Compared with successful procedures, unsuccessful procedures had similar rates of all-cause death both in crude (HR, 0.78; 95%CI, 0.49–1.25; P = 0.30) and adjusted analysis (HR, 0.80; 95%CI, 0.50-1.28; P = 0.34). A similar, significant reduction in overall MACE was noted with successful PCI-CTO compared with unsuccessful procedure in unadjusted (HR, 0.74; 95%CI, 0.56–0.96; P = 0.020) and adjusted calculation (HR, 0.73; 95%CI, 0.56–0.96; P = 0.019). Patients after successful PCI-CTO as compared with failed recanalization less frequently underwent surgical revascularization. The benefit was sustained at 3 years follow-up. Conclusions Successful PCI for single CTO does not improve long-term survival, nonetheless, is associated with reduced overall MACE and the need for surgical revascularization. © 2015 Wiley Periodicals, Inc.

Introduction Quality of life measures are useful when interventions or treatments are indicated for several reasons such as improvement of physical functioning, pain relief, to estimate the effectiveness of therapies or to predict mortality. The aim of the current study was to describe quality of life in patients with stable coronary artery disease, myocardial infarction and heart failure and to evaluate the relationship between depression and health-related quality of life. Material and methods Patients after STEMI, with stable coronary artery disease, and heart failure (n = 332) completed the MacNew Heart Disease Health-related Quality of Life Questionnaire and the Hospital Anxiety and Depression Scale. Results Patients with myocardial infarction had significantly higher scores than patients with stable coronary artery disease or heart failure on the MacNew global scale (p < 0.001) and the physical (p < 0.001), emotional (p < 0.001) and social (p < 0.001) subscales. The anxiety scores were significantly higher in the group of patients with stable coronary artery disease than in patients with myocardial infarction (p < 0.05). The depression scores were significantly higher in patients with heart failure (p < 0.01). Conclusions In patients with stable CAD, anxiety correlated mainly with symptoms, i.e. angina, than with the history of MI. Patients with symptoms of angina react to the illness with anxiety more than depression, whereas patients with heart failure with dyspnea react to the illness with depressive symptoms more than anxiety. In patients after MI and with stable CAD, cognitive-behavioral techniques could be useful to quickly reduce the level of anxiety, while patients with heart failure require long-term support therapy to reduce the risk of depressive symptoms.

Objectives The objective of this study was to assess the prognostic significance of exercise capacity in patients with ischemic left ventricular (LV) dysfunction eligible for coronary artery bypass graft surgery (CABG). Background Poor exercise capacity is associated with mortality, but it is not known how this influences the benefits and risks of CABG compared with medical therapy. Methods In an exploratory analysis, physical activity was assessed by questionnaire and 6-min walk test in 1,212 patients before randomization to CABG (n = 610) or medical management (n = 602) in the STICH (Surgical Treatment for Ischemic Heart Failure) trial. Mortality (n = 462) was compared by treatment allocation during 56 months (interquartile range: 48 to 68 months) of follow-up for subjects able (n = 682) and unable (n = 530) to walk 300 m in 6 min and with less (Physical Ability Score [PAS] >55, n = 749) and more (PAS ≤55, n = 433) limitation by dyspnea or fatigue. Results Compared with medical therapy, mortality was lower for patients randomized to CABG who walked ≥300 m (hazard ratio [HR]: 0.77; 95% confidence interval [CI]: 0.59 to 0.99; p = 0.038) and those with a PAS >55 (HR: 0.79; 95% CI: 0.62 to 1.01; p = 0.061). Patients unable to walk 300 m or with a PAS ≤55 had higher mortality during the first 60 days with CABG (HR: 3.24; 95% CI: 1.64 to 6.83; p = 0.002) and no significant benefit from CABG during total follow-up (HR: 0.95; 95% CI: 0.75 to 1.19; p = 0.626; interaction p = 0.167). Conclusions These observations suggest that patients with ischemic left ventricular dysfunction and poor exercise capacity have increased early risk and similar 5-year mortality with CABG compared with medical therapy, whereas those with better exercise capacity have improved survival with CABG. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595 )

Familial hypercholesterolemia (FH) is a genetic disease that causes accelerated atherosclerosis and a high risk of occurrence of cardiovascular events. Atherosclerosis in the course of FH develops insidiously and reaches an advanced stage before the onset of clinical symptoms. Homozygous form of FH occurs in the Caucasian population with a frequency of one per million, while the heterozygous form of FH in European countries applies on average in 1 person per 500. FH diagnosis is an indication to take the whole family under medical care, education, and to introduce dietary and pharmacological treatment. The aim of treatment in children with FH is to achieve more than 50% reduction in LDL level or to achieve LDL-cholesterol concentrations below 130 mg/dl and below 100 mg/dl in diabetic children. The effectiveness of low fat diet in the treatment of FH is limited. The medicaments of first choice in the treatment of FH are statins. After initiation of therapy in children, cholesterol levels and the side effects of therapy and its impact on children's development, nutritional status, degree of sexual maturity should be routinely evaluated. Familial hypercholesterolemia is a relatively common metabolic disorder, but still quite rarely recognized and not properly treated. Early diagnosis and appropriate treatment of FH in children and adolescents can significantly reduce the risk of cardiovascular disease and sudden death in adults. The purpose of these recommendations is to describe the current epidemiological situation in Poland, to establish the guidelines for identifying FH in children and adolescents and to enable the introduction of effective treatment. This document is a supplement to the position of Lipid Expert Forum on FH in adults.

Background and aim: The long-term benefit of percutaneous recanalisation of chronic total occlusion (CTO) is still unclear. Given advances in interventional cardiology over the last two decades, we sought to investigate whether a successful percutaneous coronary intervention for CTO (PCI-CTO) improves outcomes in an age- and gender-matched single-centre cohort of stable angina patients. Methods: Out of 401 consecutive patients enrolled to the CTO-Registry database, 276 patients were included in the final analysis. Patients with unsuccessful PCI-CTO (n = 138) were age- and gender-matched in a 1:1 ratio with patients who underwent a successful procedure. The primary end-points included hard end-points comprising death and nonfatal myocardial infarction (MI) and a composite safety outcome measure of death, nonfatal MI and ischaemia-driven revascularisation. The secondary end-point was improvement in angina status or complete resolution of angina symptoms. Patients were followed up for six months and at two years. Results: Patients who underwent a successful recanalisation of CTO, compared to those who underwent an unsuccessful procedure, revealed similar rates of composite death and MI at six months (0.7% vs. 1.4%; hazard ratio [HR], 0.50; 95% confidence interval ratio [CI], 0.05–4.80; p = 0.56) and two years (1.4% vs. 5.8%; HR 0.24; 95% CI 0.07–0.85; p = 0.053). A significant difference in composite safety end-points between subsets, although not recorded after six months of observation (8.7% vs. 15.2%; HR 0.54; 95% CI 0.27–1.07; p = 0.095), was noted at two years follow-up (15.2% vs. 29.7%; HR 0.47; 95% CI 0.29–0.77; p = 0.004). A greater improvement in symptom burden or resolution of angina symptoms was documented after a successful PCI at both six months (68.1% vs. 23.2%, p < 0.001; 80.4% vs. 34.8%, p < 0.001, respectively) and two years (52.2% and 8.0%, p < 0.001; 68.1% vs. 22.5%, p < 0.001, respectively). Conclusions: Successful recanalisation of CTO improves outcomes in long-term observation.

1Katedra i Klinika Pediatrii, Diabetologii i Endokrynologii, Gdanski Uniwersytet Medyczny, Gdansk 2Klinika Pediatrii, Endokrynologii, Diabetologii, Chorob Metabolicznych i Kardiologii Wieku Rozwojowego, Pomorski Uniwersytet Medyczny, Szczecin 3Klinika Pediatrii, Endokrynologii i Diabetologii Dzieciecej, Śląski Uniwersytet Medyczny, Katowice 4Klinika Patologii Noworodka, Instytut Pediatrii, Centrum Zdrowia Dziecka, Warszawa 5Instytut Żywności i Żywienia, Warszawa 6I Katedra i Klinika Kardiologii, Warszawski Uniwersytet Medyczny, Warszawa 7Wydzial Medyczny, Uniwersytet Rzeszowski, Rzeszow 8Klinika Pediatrii, Hematologii, Onkologii i Diabetologii, Łodzki Uniwersytet Medyczny, Łodź 9I Katedra i Klinika Kardiologii, Gdanski Uniwersytet Medyczny, Gdansk 10Katedra i Klinika Transplantacji Szpiku, Onkologii i Hematologii Dzieciecej, Wroclawski Uniwersytet Medyczny, Wroclaw 11Klinika Gastroenterologii, Hepatologii i Żywienia Dzieci, Centrum Zdrowia Dziecka, Warszawa 12Zaklad Genetyki, Instytut Psychiatrii i Neurologii, Warszawa 13Zaklad Prewencji i Dydaktyki, Katedra Nadciśnienia Tetniczego i Diabetologii, Gdanski Uniwersytet Medyczny, Gdansk 14Katedra i Zaklad Biologii i Genetyki, Gdanski Uniwersytet Medyczny, Gdansk 15Katedra Nefrologii i Nadciśnienia Tetniczego, Łodzki Uniwersytet Medyczny, Łodź

Background.High blood pressure is a substantial risk factor for cardiovascular disease.Design & Methods.The Physicians' Observational Work on patient Education according to their vascular Risk (POWER) survey was an open-label investigation of eprosartan-based therapy (EBT) for control of high blood pressure in primary care centers in 16 countries. A prespecified element of this research was appraisal of the impact of EBT on estimated 10-year risk of a fatal cardiovascular event as determined by the Systematic Coronary Risk Evaluation (SCORE) model.Results.SCORE estimates of CVD risk were obtained at baseline from 12,718 patients in 15 countries (6504 men) and from 9577 patients at 6 months. During EBT mean (±SD) systolic/diastolic blood pressures declined from 160.2 ± 13.7/94.1 ± 9.1 mmHg to 134.5 ± 11.2/81.4 ± 7.4 mmHg. This was accompanied by a 38% reduction in mean SCORE-estimated CVD risk and an improvement in SCORE risk classification of one category or more in 3506 patients (36.6%).Conclusion.Experience in POWER affirms that (a) effective pharmacological control of blood pressure is feasible in the primary care setting and is accompanied by a reduction in total CVD risk and (b) the SCORE instrument is effective in this setting for the monitoring of total CVD risk.

Background. The prognostic value of cardiopulmonary exercise testing (CPET) is known, but the predictive value of 6MWT in patients with heart failure (HF) and patients undergoing coronary artery bypass grafting (CABG) is not established yet.Objective. We conducted a systematic review exploring the prognostic value of 6MWT in HF patients undergoing cardiac surgery. The aim was to find out whether the change in the distance walked during follow-up visits was associated with prognosis.Data Source. We searched “PubMed” from January 1990 to December 2012 for any review articles or experimental studies investigating the prognostic value of 6MWT in HF patients and patients undergoing cardiac surgery.Results. 53 studies were included in the review, and they explored the role of 6MWT in cardiology, cardiac surgery, and rehabilitation. The results did not show the relation between the six-minute walk distance and adverse events after CABG. The predictive power of the distance walked for death in HF patients undergoing cardiac surgery was not found. It is not yet proved if the change in the six-minute walk distance is associated with prognosis. The predictive power of the six-minute walk distance for death in HF patients undergoing cardiac surgery remains unclear.

Background: Heart failure (HF) is a growing cause of hospitalisation worldwide, and despite significant progress in its treat­ment it is still associated with high mortality. Aim: The aim of this study was to find factors predicting in-hospital death in acute decompensated HF by analysis of basic laboratory data and echocardiography, routinely collected on admission to the hospital. Methods: To this single-centre retrospective study we involved 638 consecutive patients hospitalised in the years 2007–2008 due to acute decompensated HF. To the initial univariate analysis we included the results of echocardiography and 36 basic laboratory tests performed at hospital admission. Parameters significantly associated with in-hospital death in univariate analysis were taken to multivariate regression analysis. Results: In-hospital death occurred in 119 cases (median age 75 years; 40.3% females). The multivariate analysis revealed sig­nificant association between in-hospital death and: higher leukocyte count (death [D]: 13.5 vs. survival [S]: 8.8 G/L, p < 0.01), higher neutrophil count (D: 10.5 vs. S: 5.9 G/L, p < 0.01), lower lymphocyte count (D: 1.3 vs. S: 1.7 G/L, p < 0.05), higher C-reactive protein concentration (D: 20.8 vs. S: 6.7 mg/dL, p < 0.01), higher serum glucose concentration (D: 167.0 vs. S: 116.0 mg/dL, p < 0.00001), higher serum creatinine concentration (D: 1.5 vs. S: 1.2 mg/dL, p < 0.0001), higher blood urea nitrogen concentration (D: 29.0 vs. S: 22.0 mg/dL, p < 0.00001), and higher aspartate aminotransferase (D: 72.0 vs. S: 27.0 U/L, p < 0.0001). Surprisingly, there was no significant association with echocardiographic parameters. Conclusions: Analysis of basic laboratory data collected on admission to the hospital may help to identify patients with acute decompensated HF, who are at high risk of in-hospital death.

Aims We sought to determine the degree of anticoagulation reversal required to mitigate bleeding, and assess the feasibility of using pegnivacogin to prevent ischaemic events in acute coronary syndrome (ACS) patients managed with an early invasive approach. REG1 consists of pegnivacogin, an RNA aptamer selective factor IXa inhibitor, and its complementary controlling agent, anivamersen. REG1 has not been studied in invasively managed patients with ACS nor has an optimal level of reversal allowing safe sheath removal been defined. Methods and results Non-ST-elevation ACS patients ( n = 640) with planned early cardiac catheterization via femoral access were randomized 2:1:1:2:2 to pegnivacogin with 25, 50, 75, or 100% anivamersen reversal or heparin. The primary endpoint was total ACUITY bleeding through 30 days. Secondary endpoints included major bleeding and the composite of death, myocardial infarction, urgent target vessel revascularization, or recurrent ischaemia. Enrolment in the 25% reversal arm was suspended after 41 patients. Enrolment was stopped after three patients experienced allergic-like reactions. Bleeding occurred in 65, 34, 35, 30, and 31% of REG1 patients with 25, 50, 75, and 100% reversal and heparin. Major bleeding occurred in 20, 11, 8, 7, and 10% of patients. Ischaemic events occurred in 3.0 and 5.7% of REG1 and heparin patients, respectively. Conclusion At least 50% reversal is required to allow safe sheath removal after cardiac catheterization. REG1 appears a safe strategy to anticoagulate ACS patients managed invasively and warrants further investigation in adequately powered clinical trials of patients who require short-term high-intensity anticoagulation. Clinical Trials Registration: ClinicalTrials.gov [NCT00932100][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00932100&atom=%2Fehj%2Fearly%2F2012%2F08%2F01%2Feurheartj.ehs232.atom

This article describes the design and methodology of the POWER study (Physicians' Observational Work on Patient Education According to their Vascular Risk). POWER is an open-label multinational postmarketing study of the angiotensin II-receptor blocker eprosartan. The Systemic Coronary Risk Evaluation (SCORE) model has been used to estimate total cardiovascular risk and changes in total cardiovascular risk status during treatment for patients recruited in all countries other than Canada. Framingham Heart Study equations have been used to estimate risk in the Canadian contingent of POWER. Observations from POWER will provide insights into how clinicians try to achieve blood pressure goals within the framework of total cardiovascular risk management and how they integrate their treatment of blood pressure with other interventions. Experience during the POWER study may also help to affirm the utility, practicability and perhaps limitations of the SCORE system for estimating total cardiovascular risk and identify ways to improve the acceptance and implementation of risk estimation methods in cardiovascular primary prevention.

The aim of this study was a comparison of aortic valve calcium score (AVCS) between patients with hypercholesterolemia and genetic diagnosis of familial hypercholesterolemia with low-density lipoprotein receptor gene mutation (LDLR-M group), versus patients with hypercholesterolemia without LDLR gene mutation (LDLR-WT group). A total of 72 LDLR-M patients and 50 LDLR-WT patients were enrolled in the study and underwent CT as a part of an assessment of coronary calcium scoring. AVCS was determined and compared between the two patient groups. AVCS was significantly higher in the LDLR-M group in comparison to the LDLR-WT group (13.8 ± 37.9 vs. 0.94 ± 3.1, p = 0.03). The Yates' chi-squared test for independence revealed that LDLR mutation and AVCS were significantly dependable (Chi^2 = 6.106, p = 0.013). The LDLR mutation was a strong predictor of a high AVCS (OR 7.83, 95% CI 2.08-29.50, p = 0.002) on multivariate regression analysis. Among the traditional risk factors, age (odds ratio 1.12, 95% CI 1.05-1.18, p

Background Aortic stenosis leads to left ventricular hypertrophy and accumulation of fibrillar collagens. The analysis of integrated backscatter (IBS) parameters provides information on ultrasonic myocardial properties. Methods The study population consisted of 58 patients with aortic stenosis. They were followed up for an average 18 ± 5 months after aortic valve replacement (AVR). Traditional transthoracic echocardiography and analysis of IBS reflectivity were performed before AVR and during the control visit after AVR. Results A significant reduction in left ventricular mass index, a significant increase in the mean cyclic variation of IBS, and a decrease in absolute end-diastolic IBS intensity were observed after AVR. Conclusions These data suggest improvements in ultrasonic myocardial properties after AVR. Preoperative analysis of IBS parameters might provide additional information for predicting left ventricular reverse remodeling in patients a mean of 1.5 years after AVR for aortic stenosis.

in hypertrophic cardiomyopathy (HCM), the following five risk factors have a major role in the primary prevention of sudden death (SD): family history of SD (FHSD), syncope, massive wall thickness (MWTh)30 mm, non-sustained ventricular tachycardia (nsVT) in Holter monitoring of electrocardiography, and abnormal blood pressure response to exercise (aBPRE). In HCM, as a genetic cardiac disease, the risk for SD may also exist from birth. The aim of the study was to compare the survival curves constructed for each of the five risk factors in a traditional follow-up model (started at the first presentation of a patient at the institution) and in a novel follow-up model (started at the date of birth). In an additional analysis, we compared the survival rate in three subgroups (without FHSD, with one SD, and with two or more SDs in a family).a total of 1306 consecutive HCM patients (705 males, 601 females, mean age of 47 years, and 193 patients were18 years) evaluated at 15 referral centres in Poland were enrolled in the study. In a novel method of follow-up, all the five risk factors confirmed its prognostic power (FHSD: P = 0.0007; nsVT: P0.0001; aBPRE: P = 0.0081; syncope: P0.0001; MWTh P0.0001), whereas in a traditional method, only four factors predicted SD (except aBPRE). In a novel model of follow-up, FHSD in a single episode starts to influence the prognosis with a delay to the fifth decade of life (P = 0.0007). Multiple FHSD appears to be a very powerful risk factor (P0.0001), predicting frequent SDs in childhood and adolescence.the proposed concept of a lifelong calculated follow-up is a useful strategy in the risk stratification of SD. Multiple FHSD is a very ominous risk factor with strong impact, predicting frequent SD episodes in the early period of life.

Objectives The aim of this study was to confirm the generalizability of the conclusions of the STICH (Surgical Treatment for Ischemic Heart Failure) trial. Background Surgical ventricular reconstruction (SVR) added to coronary artery bypass grafting (CABG) did not decrease death or cardiac hospitalization in STICH patients randomized to CABG with (n = 501) or without (n = 499) SVR. Methods Baseline clinical characteristics of 1,000 STICH SVR hypothesis patients and 1,036 STICH-eligible Society of Thoracic Surgeons (STS) National Cardiac Database patients undergoing CABG plus SVR were entered into a multivariate model equation to predict a mortality that placed these 2,036 patients in 1 of 32 risk at randomization (RAR) groups. The number of patients in each RAR group profiled the risk of STICH treatment arms and of STICH and STS STICH-eligible patients. Results That 85% of the 1,000 STICH patients known to have no significant differences in baseline characteristics between the 2 treatment arms shared the same RAR group suggests that the RAR methodology has sufficient accuracy to compare RAR profiles of STICH and STS patients. RAR group was shared by 1,522 of 2,036 STICH and STS STICH-eligible patients (75%) who underwent CABG plus SVR. Differences in baseline characteristics responsible for more low-risk STICH patients and more high-risk STS patients were modest. Cox proportional hazard ratios of 1,000 STICH patients in 3 RAR groups suggested by STICH and STS RAR differences showed no differential treatment effect on survival across the low-, intermediate-, and high-risk groups. Conclusions The STICH conclusion of no benefit from adding SVR to CABG applies to a broad spectrum of CABG-eligible patients with ischemic cardiomyopathy. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease; NCT00023595)

The group of experts representing the Polish Cardiologic Society, the Polish Gynecological Society and the Polish Menopause and Andropause Society has issued this Joint Position Statement based on the review of available literature on the effect of postmenopausal hormone replacement therapy on the cardiovascular system. The results of older clinical and epidemiological studies are confronted with the most recently published data. The importance of type, doses and delivery route of hormones is discussed with respect to the cardiovascular safety of HRT.

AIM The aim of this study was to compare coronary calcium scores and aortic calcium scores between patients with severe hypercholesterolemia having a DNA-based diagnosis of FH (FH group) versus patients with severe hypercholesterolemia without the FH gene mutation (NFH group). METHOD A total of 89 FH and 50 NFH patients underwent CT with coronary and thoracic aorta calcium scoring. Their CCS and TCS in ascending aorta (TCSasc) and descending aorta (TCSdesc) were determined and compared between the two patient groups. RESULTS TCSasc was significantly higher in the FH group when compared to the NFH group (30.6± 59 vs 4.7±13.4, p＜0.001. After adjusting for age, sex, smoking, blood pressure, history of diabetes mellitus and LDL cholesterol levels, FH gene mutation was an independent risk factor of having non-zero TCSasc 3.6 (95% CI, 1.4-9.5, p＜0.01), high TCSasc 9.6 (95% CI, 2.4-38.2, p＜0.01) and high CCS of 4.1 (95% CI, 1.2-13.2. p＜0.05). CONCLUSION We found that when computed tomography calcium scores were used as an assessment, patients with familial hypercholesterolemia displayed an increased burden of ascending aorta atherosclerosis when compared to patients with nonfamilial severe hypercholesterolemia. This phenomenon appears to be more dependent on the presence of FH genotype than hypercholesterolemia itself.

Familial hypercholesterolemia (FH), which leads to premature cardiovascular events, still remains underrecognized and undertreated in most countries. Untreated FH individuals aged 20-39 years are at 100-fold higher risk of mortality from coronary heart disease compared to those of a general population. Therefore, special efforts should be implemented to diagnose FH patients at early stages of life. The aim of this study was to evaluate the efficacy of the revised Dutch Lipid Clinic Network (DLCN) criteria proposed by the Polish Lipid Experts Forum to select index FH patients for DNA mutational analysis in Poland.The study included 193 unrelated adult patients (mean age 48 ± 13 years) with clinical diagnosis of FH based on the revised DLCN score, tested sequentially for mutations in LDLR and APOB genes using bidirectional Sanger sequencing and MLPA techniques. The cut-off points of the clinical FH criteria score were assessed by ROC statistics to identify patients with the highest probability of carrying an FH-causing mutation.The causal heterozygous LDLR or APOB mutation was identified in 41% (80/193) of probands. Adults aged40 years were more likely to carry an FH-causing mutation compared to subjects aged ≥40 years (65% vs. 33%; p 0.001). LDL-C thresholds for the molecular diagnosis of FH were 5.79 mmol/l for individuals aged40 and 6.7 mmol/l for subjects ≥40 years old. The threshold values of the clinical diagnostic score for efficient selection of patients for genetic testing were 5 and 7 points for individuals aged40 and ≥40 years, respectively.The study validated the efficacy of proposed clinical FH criteria for the disease diagnosis in Poland. The clinical criteria score thresholds for positive FH molecular diagnosis differ depending on age (40 and ≥40 years). We propose that in the healthcare systems with limited genetic testing resources individuals younger than 40 years, who fulfill the clinical criteria for possible, probable or definite FH should qualify for the FH mutation testing. The index patients aged ≥40 years with clinical diagnosis of probable or definite FH should also qualify for the genetic testing.

BACKGROUND: The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS: The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS: Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P

CelCelem badania było oznaczenie stężenia czterech cytokin prozapalnych (IL17a, IL6, TNFα i IL12p70 ) w osoczu pacjentów z zawałem mięśnia sercowego i ocena ich związku z wystąpieniem depresji w ciągu 6 miesięcy od zawału serca.MetodaU 40 pacjentów z pierwszym zawałem mięśnia sercowego z uniesieniem odcinka ST dokonano pomiaru stężeń IL17a, IL6, TNFα i IL12p70 w osoczu w trzecim i piątym dniu zawału, następnie dokonano analizy wyników w zależności od obecności depresji w okresie 6 miesięcy obserwacji.WynikiNie stwierdzono istotnych różnic pomiędzy badanymi grupami pacjentów po zawale m. sercowego pod względem stężenia badanych cytokin. Porównując badane grupy z osobami zdrowymi zaobserwowano miedzy nimi pewne różnice. W porównaniu z grupą osób zdrowych grupa z depresją cechowała się podwyższonymi stężeniami wszystkich badanych cytokin w 3 dni po zawale, w dniu piątym – dwóch z nich: IL17a i IL6, w grupie bez depresji w 3 dniu podwyższone były tylko dwie z czterech badanych cytokin, w dniu 5 jedynie IL6.WnioskiNie stwierdzono istotnych różnic pomiędzy badanymi grupami osób po zawale m. sercowego pod względem stężenia badanych cytokin. Przeprowadzona analiza porównawcza tych grup z osobami zdrowymi może sugerować obecność nieco większej aktywacji badanych cytokin, szczególnie IL17a w grupie pacjentów z obecnością depresji.

Whether the C-344T polymorphism of the aldosterone synthase gene is important for blood pressure control remains controversial. It has been proposed that an association between this polymorphism and blood pressure might be evident in elderly subjects. The aim of the present study was to test this hypothesis in an epidemiological context.A cross-sectional epidemiological evaluation of a highly homogeneous unselected general population of elderly Caucasians.Lifestyle, medical history, anthropometrics, skinfold thickness, supine blood pressure, heart rate and biochemical measures were recorded in 437 subjects agedor = 65 years living in a secluded valley. All were genotyped for C-344T allele status and underwent measurements of plasma aldosterone and renin.The C-344T genotypic frequency did not deviate from Hardy-Weinberg equilibrium. The aldosterone to renin ratio was 19% lower in the CC than in the TT genotype. Systolic blood pressure was significantly lower in subjects with the CC genotype, higher in the TT (+9.6 mmHg versus CC) and intermediate in the CT (+7.9 mmHg versus CC). Adjustment for age, gender, smoking and antihypertensive treatment did not affect this association. Diastolic blood pressure did not differ across genotypes. A significant increase of systolic blood pressure with increasing age and with increasing skinfold thickness was observed in the TT homozygotes but not in the C-carriers.These data support the concept that the C-344T polymorphism plays a role in controlling systolic blood pressure and the age-related increase in systolic blood pressure in response to age and to body fat, possibly through differences in modulation of aldosterone synthesis.

Sirs: Takotsubo cardiomyopathy (TTC) was first described by Sato et al. [1] in 1990. According to the clinical features, TTC usually affects postmenopausal women and is preceded by a psychical or physical stress. Characteristics of TTC contain ST-segment elevation or T wave inversion in ECG, modest biomarker release (troponin, CK, CK-MB) and almost always complete wall-motion resolution. However, the clinical spectrum of the TTC patients could be heterogeneous and occurs extremely rarely in the male population [2]. Here we present a case on a 56-year-old male with no past cardiovascular history who was admitted to the emergency room due to sudden chest pain and dyspnoea. Symptoms followed an acute emotional stress event caused by the defeat of his favorite soccer team, he watched at the fan zone during the Euro 2012 cup. Initial ECG revealed sinus rhythm of 76 bpm, RBBB with negative T waves in V3–V6 and heart rate-corrected QT interval (QTc) was 447 ms. Blood pressure was 145/85 mmHg, troponin I level of 0.21 ng/dl and elevated BNP (243 pg/ml). With subsequent diagnosis of acute coronary syndrome, the patient was referred for urgent coronary angiography, which documented no coronary artery disease (Fig. 1a top). Ventriculography revealed an apical ballooning pattern with contrast retention in the apex (Fig. 1a lower). Bedside echocardiogram revealed akinesis of apical and midventricular segments of left ventricle with ejection fraction (LVEF) of 30 % and diminished average global longitudinal peak systolic strain (GLPS −10.3 %) (Fig. 1b). Cardiac magnetic resonance T2-weighted sequence did not record any pathological regional increase of the myocardial signal intensity (Fig. 1c); delayed postcontrast hyperenhancement was absent, consistent with viable myocardium (Fig. 1D). Four days later an ECG showed deep negative T waves in V3–V6, II, III, aVF. The patient was initially treated for STEMI and received β-blockers, aspirin and ACE inhibitor after the final diagnosis had been made. The patient’s recovery was uneventful and the patient was discharged after 5-day hospitalization. Fig. 1 Left and right coronary artery (a top), cardiac ventriculography at diastole at systole (a lower), left ventricular average global longitudinal peak systolic strain (GLPS) at acute phase (b), cardiac magnetic resonance T2-weighted sequence (c), cardiac ... Three weeks later echocardiography recorded no signs of left ventricle apical ballooning with RBBB wall motion pattern, estimated LVEF of 65 % and GLPS improvement to −14, 9 % (Fig. 1e). It has been proved that great and important sport events such as the European Championships are associated with physical stress and emotional strain especially after a favorite team’s loss [3]. Incidences of sudden cardiac death or other cardiovascular events are suggested to be increased during an important football match due to increased sympathetic tone and catecholamine levels. Interestingly, the impact of adrenergic stimulation increasing the risk of cardiovascular events may persist for several days after the game [4]. Stressful events and elevated catecholamine plasma levels in the acute course of TTC indicate a possible involvement of the sympathetic nervous system in this cardiomyopathy as well [5]. A minor size of the LV and hormonal disruption in the female subset may play a key-role in the pathology of TTC [6]. The small LV size observed in women could potentially predispose the LV-outflow tract obstruction raising the intraventricular pressure gradient and an oxygen mismatch in the region of the apex. The studies on animals have shown the important protective roles of estrogen in myocardial damage including through stimulating transcription of cardioprotective substances such as atrial natriuretic peptide [7]. Among the male population TTC, however, is triggered more often by physical stress [8]. Therefore, we present a particular case of a man with the TTC-event after participating in football match at the Fan Zone Euro 2012 Cup in the Host City of Gdansk, Poland. Bill Shankly, the former F.C. Liverpool manager, could be right in saying: “Some people believe football is a matter of life and death… I can assure you it is much, much more important than that.”

Background: The Pl A2 allele of the gene encoding for GPIIIa subunit of the platelet membrane receptor glycoprotein (GP) IIb/IIIa has been suggested as a significant risk factor for thrombotic complications of coronary artery disease (CAD). The aim of the current investigation was to investigate the association between Pl A GPIIIa polymorphism and the extent of angiographically confirmed CAD in patients from the north region of Poland. Methods: The study was performed in 397 male Caucasian patients. All subjects had significant coronary artery stenosis confirmed by elective coronary angiography. Screening for the Pl A GPIIIa genotypes was performed by polymerase chain reaction of genomic DNA, followed by Nci I digestion and agarose gel electrophoresis. Results: The genotype distribution of the Pl A GPIIIa polymorphism in our study group was Pl A1/A1 —75%, Pl A1/A2 —24% and Pl A2/A2 —1% with Pl A1 and Pl A2 allele frequencies of 0.87 and 0.13, respectively. The prevalence of the homozygous Pl A1/A1 genotype among subjects with multiple-vessel CAD (two or three vessels with at least 50% stenosis) was significantly higher than in patients with single-vessel disease; the odds ratio of Pl A2/A2 or Pl A1/A2 patients for having multiple-vessel CAD was 0.46 (95% CI 0.27–0.77, P Pl A1/A1 patients was significantly higher in comparison to Pl A2/A2 and Pl A1/A2 patients (7.58±2.20 and 6.98±2.37, respectively, P Conclusions: Our results suggest, that the Pl A1/A1 genotype of Pl A GPIIIa polymorphism is associated with more severe CAD in male Caucasian patients from the north region of Poland.

A 61-year-old woman was admitted to our hospital due to recurrent, atypical angina pain. The medical documentation of the patient contained 15 years history of Crohn's disease, malabsorption syndrome (BMI: 15 kg/m2), chronic anemia and the inflammatory intestine tumor.

IntroductIon Endothelial dysfunction is one of the markers of atherosclerosis. oBjectIves The aim of the study was to evaluate endothelial function by assessing flow‑mediated dilation (FMD) and to measure the parameters of brachial arterial stiffness in patients with familial hypercholesterolemia (FH) and those with high low‑density lipoprotein (LDL) cholesterol levels without FH mutations (nonfamilial hypercholesterolemia – non‑FH). PAtIents And methods The study involved 60 patients (mean age, 41.9 ±7.7 y) without documented cardiovascular events and clinical symptoms of cardiovascular diseases: 21 patients with elevated plasma LDL cholesterol levels and genetically confirmed FH, 19 patients with elevated LDL cholesterol levels and without FH mutations, and 20 healthy controls. In each patient, ultrasound imaging was used to assess endothelium‑dependent FMD and nitroglycerin‑induced endothelium‑independent dilation (EID) in the brachial artery. In addition, echo‑tracking and photoplethysmography were used to assess the parameters of arterial stiffness. results FMD was significantly lower in patients with FH (11.0% ±9.9% vs. 21.0% ±14.3%, P

IMPORTANCE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been hypothesized to be involved in atherogenesis through pathways related to inflammation. Darapladib is an oral, selective inhibitor of the Lp-PLA2 enzyme. OBJECTIVE: To evaluate the efficacy and safety of darapladib in patients after an acute coronary syndrome (ACS) event. DESIGN, SETTING, AND PARTICIPANTS: SOLID-TIMI 52 was a multinational, double-blind, placebo-controlled trial that randomized 13,026 participants within 30 days of hospitalization with an ACS (non-ST-elevation or ST-elevation myocardial infarction [MI]) at 868 sites in 36 countries. INTERVENTIONS: Patients were randomized to either once-daily darapladib (160 mg) or placebo on a background of guideline-recommended therapy. Patients were followed up for a median of 2.5 years between December 7, 2009, and December 6, 2013. MAIN OUTCOMES AND MEASURES: The primary end point (major coronary events) was the composite of coronary heart disease (CHD) death, MI, or urgent coronary revascularization for myocardial ischemia. Kaplan-Meier event rates are reported at 3 years. RESULTS: During a median duration of 2.5 years, the primary end point occurred in 903 patients in the darapladib group and 910 in the placebo group (16.3% vs 15.6% at 3 years; hazard ratio [HR], 1.00 [95% CI, 0.91-1.09]; P = .93). The composite of cardiovascular death, MI, or stroke occurred in 824 in the darapladib group and 838 in the placebo group (15.0% vs 15.0% at 3 years; HR, 0.99 [95% CI, 0.90-1.09]; P = .78). There were no differences between the treatment groups for additional secondary end points, for individual components of the primary end point, or in all-cause mortality (371 events in the darapladib group and 395 in the placebo group [7.3% vs 7.1% at 3 years; HR, 0.94 [95% CI, 0.82-1.08]; P = .40). Patients were more likely to report an odor-related concern in the darapladib group vs the placebo group (11.5% vs 2.5%) and also more likely to report diarrhea (10.6% vs 5.6%). CONCLUSIONS AND RELEVANCE: In patients who experienced an ACS event, direct inhibition of Lp-PLA2 with darapladib added to optimal medical therapy and initiated within 30 days of hospitalization did not reduce the risk of major coronary events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01000727.

A 61-year-old male with no previous cardiovascular history was admitted to the coronary care unit suffering from acute angina. On presentation the patient was conscious, the heart rate was 100 bpm, and the blood pressure was 80/60 mm Hg. Standard electrocardiogram displayed prominent ST-segment elevation in the anterolateral leads. The initial treatment was 300 mg of aspirin, 600 mg of clopidogrel, and intravenous bolus of unfractioned heparin, all given in the ambulance. In the catheterisation laboratory, sudden cardiac arrest occurred and the patient was subsequently defibrillated. The patient needed defibrillation because of ventricular fibrillation followed by pulseless electrical activity. A cardiopulmonary resuscitation (CPR) was started. Through the left femoral artery a balloon for intra-aortic balloon counterpulsation (IABP) was introduced. The coronary angiogram of the left coronary artery (LCA) selectively engaged with a 6 French EBU-4 guiding catheter revealed an acute total occlusion of the left main stem (LMS) (Fig. 1A). During the CPR, a manual thrombectomy was performed and the blood flow in left anterior descending artery was restored (Fig. 1B). The left circumflex artery (LCX) was opened after a second thrombectomy (Fig. 1C). The patient received a subsequent intracoronary bolus of abciximab. Finally, the culprit lesion localised in the distal portion of the LMS was treated with a second-generation everolimus eluting stent 3.5/18 mm deployed at 20 atmospheres (Fig. 1D), and post dilated with a 4.0/15 mm non-compliant balloon. The final kissing-balloon inflation was complicated with a dissection of the ostial portion of the LCX (Fig. 1E). It was subsequently covered with a 3.0/18 mm drug eluting stent using a “T and protrusion” technique (Fig. 1E, inset). As percutaneous coronary intervention of the LCA was accomplished, the angiography of the right coronary artery showed no significant disease. After the procedure, the patient was transferred to the coronary care with catecholamine infusion and IABP 1:1 support. On the third day of hospitalisation, the patient received a red blood cell transfusion due to the large local haematoma and severe anaemia. IABP was removed 6 days after baseline; the patient was weaned from the respirator and extubated. In 4-month follow-up the patient remained asymptomatic with New York Heart Association class II. The control angiography revealed a good result in both left main and left circumflex arteries with no signs of in-stent restenosis (Fig. 1F). Figure 1. A. Acute occlusion of the left main coronary artery; B. The angiographic result after manual thrombectomy in left anterior descending artery; C. The angiographic result after manual thrombectomy in left circumflex artery (LCX); D. The angiographic result after implantation of drug eluting stent to the left main; E. Ostial dissection in LCX after kissing balloons and the final angiographic result; F. The angiographic follow-up after 4 months A C

Familial hypercholesterolemia (FH) is an under-recognized and undertreated common lipid metabolism disorder [1, 2]. Early and intensive treatment reduces consequent mortality from coronary heart disease [3, 4]. A promising tool for retarding or arresting the atherosclerotic process in hypercholesterolemic patients refractory to maximally tolerated pharmacotherapy is LDL apheresis [5, 6].