Search

Cardiovascular (CV) events are the number one cause of lifetime disability and deaths worldwide. It is well known that traditional risk factors do not fully correlate with clinical outcomes; therefore, searching for other markers that would explain CV events’ occurrence seems essential. Of importance, one of the main factors at the origin of CV events is oxidative stress, causing inflammation and atherosclerotic plaque instability. Therefore, the present study was conducted to evaluate eight carefully selected genetic polymorphisms related to oxidative stress as risk modifiers for CV events. A cohort of 1020 patients with coronary atherosclerosis was analysed in a 7-year follow-up observational study. The following end points were assessed: CV death, myocardial infarction (MI) and a combined end point of CV death/MI/stroke. Our results show that single polymorphisms are not significant cardiovascular disease risk factors, but genetic risk score (GRS), defined as the accumulation of our eight studied polymorphisms, was significantly associated with the three. Specifically, low GRS was associated with a higher risk of CV death, MI and CV death/MI/stroke. In conclusion, when regarding CV events, GRS investigated here can become clinically meaningful and undoubtedly adds to the knowledge in stratifying the risk of CV events.

First described in 1990, Takotsubo cardiomyopathy (TC) is a medical condition defined by acute and transient left ventricular (LV) dysfunction with a diversity of wall-motion abnormalities. TC can be induced by emotional and physical stress, as well as direct administration of catecholamines or medications which can cause a catecholamine surge. Although recorded incidences of TC have been rising over the last decade (currently 15-30 cases per 100,000 per year), this is most likely due to increased awareness and recognition of the condition. Electrocardiogram (ECG), imaging modalities such as echocardiography, coronary computed tomography angiography, cardiac magnetic resonance, and coronary angiography are important tools in the diagnosis of TC. The in-hospital mortality rate for patients admitted with TC reaches 5%. In our report, we describe a case of TC in a 30-years old female with a medical history of episodes of focal atrial tachycardia (AT) after intravenous administration of a single, maximum dose of flecainide.

Myo-inositol is the most popular inositol in living organisms, where it is present as a sugar alcohol, in a free form, and can also be described as a lipid. The aim of this study was to check the concentration change of a myo-inositol solution from the time of oral administration and over a 48 h period in Wistar-type rats. All rats received 2 g/kg of inositol as a solution in distilled water by oral gavage. Estimated parameters were based on the serum concentration of myo-inositol observed in nine individual rats with regard to time. Observations were described as a one-compartment pharmacokinetic model with first-order absorption and zero-order endogenous input of checked inositol. The highest myo-inositol concentration was observed in the first hour after oral administration in the serum of all tested rats. Then, the concentration began decreasing immediately after the maximal peak. The inositol concentration continued to decrease, but after 24 h its level was still higher than before the administration. The plasma profile of the myo-inositol concentration showed a rapid decline over time, possibly due to the metabolism of this compound.

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.

Cardiovascular (CV) events are the number one cause of lifetime disability and deaths worldwide. It is well known that traditional risk factors do not fully correlate with clinical outcomes; therefore, searching for other markers that would explain CV events occurrence seems essential. Of importance, one of the main factors at the origin of CV events is oxidative stress, causing inflammation and atherosclerotic plaque instability. Therefore the present study was conducted to evaluate eight carefully selected genetic polymorphisms related to oxidative stress as risk modifiers for CV events. A cohort of 1020 patients with coronary atherosclerosis was analysed in a 7-year follow-up observational study. The following endpoints were assessed: CV death, myocardial infarction (MI) and a combined endpoint of CV death/MI/stroke. Our results show that single polymorphisms are not significant cardiovascular disease risk factors, but genetic risk score (GRS), defined as the accumulation of our eight studied polymorphisms, was significantly associated with the three studied follow-up endpoints. In conclusion, when regarding CV events, GRS investigated here can become clinically meaningful and undoubtedly adds to the knowledge in stratifying the risk of CV events.

Current data indicate that heart failure (HF) is associated with inflammation and microvascular dysfunction and remodeling. These mechanisms could be involved in HF development and progression, especially in HF with preserved ejection fraction (HFpEF). We aimed to compare structural changes in retinal arterioles and carotid arteries between HF patients and patients without heart failure. This preliminary, retrospective, case-control study included 28 participants (14 patients with HFpEF and 14 age- and sex-matched healthy controls). Carotid intima-media thickness to lumen ratio (cIMTLR) was assessed using B-mode ultrasonography. Retinal arterioles wall- to-lumen ratio (rWLR) was assessed by adaptive optics camera rtx1. The HF patients had higher IMTLR (Δmedian [HFpEF–control group] 0.07, p = 0.01) and eWLR (Δmedian 0.03, p = 0.001) in comparison to patients without HF. In the whole study group, rWLR correlated significantly with IMTLR (r = 0.739, p = 0.001). Prevalence of arterial hypertension was similar in both groups, however, patients with HF had a significantly lower office, central and 24-h ambulatory blood pressure (systolic Δmedian −21 to −18 mmHg; diastolic Δmedian −23 to −10 mmHg). Our data suggests gradual and simultaneous progression of vascular remodeling in both retinal arterioles and carotid arteries in HFpEF patients. This process could be a marker of HF development. Significantly lower blood pressure values in HF group may indicate that vascular remodeling could be independent of BP control. Nevertheless, further and larger prospective studies allowing to reduce the impact of confounding and address temporality are warranted.

Oxidative stress induces functional changes in arteries. Therefore, the effect of myo-inositol, a possible anti-inflammatory/antioxidant agent was studied on human plasma and rat thoracic arteries. Aortic rings from male Wistar rats (3 months of age) were incubated with myo-inositol (1, 10 and 100 μM, 120 min) and analyzed using the gas chromatography (GC) method. In another experiment, aortic rings were protected first with myo-inositol (1 µM, 60 min) and then subjected to a thromboxane receptor agonist (U-46619, 0.1 nM, 60 min). Therefore, these four groups under the following conditions were studied: (i) the control in the vehicle; (ii) myo-inositol; (iii) the vehicle plus U-46619; (iv) myo-inositol plus U-46619. The hemostatic parameters of human plasma and an H2O2/Fe2+ challenge for lipid and protein peroxidation were also performed. Myo-inositol was not absorbed into the pre-incubated aortic rings as measured by the GC method (0.040 µg/mg, p ≥ 0.8688). The effect of myo-inositol was more significant in the impaired arteries due to U-46619 incubation, which resulted in an improved response to acetylcholine (% Emax: 58.47 vs. 86.69), sodium nitroprusside (logEC50: −7.478 vs. −8.076), CORM-2 (% Emax: 44.08 vs. 83.29), pinacidil (logEC50: −6.489 vs. −6.988) and noradrenaline (logEC50: −7.264 vs. −6.525). This was most likely a possible response to increased nitric oxide release (×2.6-fold, p < 0001), and decreased hydrogen peroxide production (×0.7-fold, p = 0.0012). KCl-induced membrane depolarization was not modified (p ≥ 0.4768). Both the plasma protein carbonylation (×0.7-fold, p = 0.0006), and the level of thiol groups (×3.2-fold, p = 0.0462) were also improved, which was not significant for TBARS (×0.8-fold, p = 0.0872). The hemostatic parameters were also not modified (p ≥ 0.8171). A protective effect of myo-inositol was demonstrated against prooxidant damage to human plasma and rat thoracic arteries, suggesting a strong role of this nutraceutical agent on vasculature which may be of benefit against harmful environmental effects.

BACKGROUND Due to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is warranted. PURPOSE To conduct an updated systematic review and meta-analysis of plasma, serum, and urine metabolite markers and incident type 2 diabetes. DATA SOURCES We searched PubMed and Embase until 6 March 2021. STUDY SELECTION We selected prospective observational studies where investigators used high-throughput techniques to investigate the relationship between plasma, serum, or urine metabolites and incident type 2 diabetes. DATA EXTRACTION Baseline metabolites per-SD risk estimates and 95% CIs for incident type 2 diabetes were extracted from all eligible studies. DATA SYNTHESIS A total of 61 reports with 71,196 participants and 11,771 type 2 diabetes cases/events were included in the updated review. Meta-analysis was performed for 412 metabolites, of which 123 were statistically significantly associated (false discovery rate–corrected P < 0.05) with type 2 diabetes risk. Higher plasma and serum levels of certain amino acids (branched-chain, aromatic, alanine, glutamate, lysine, and methionine), carbohydrates and energy-related metabolites (mannose, trehalose, and pyruvate), acylcarnitines (C4-DC, C4-OH, C5, C5-OH, and C8:1), the majority of glycerolipids (di- and triacylglycerols), (lyso)phosphatidylethanolamines, and ceramides included in meta-analysis were associated with higher risk of type 2 diabetes (hazard ratio 1.07–2.58). Higher levels of glycine, glutamine, betaine, indolepropionate, and (lyso)phosphatidylcholines were associated with lower type 2 diabetes risk (hazard ratio 0.69–0.90). LIMITATIONS Substantial heterogeneity (I2 > 50%, τ2 > 0.1) was observed for some of the metabolites. CONCLUSIONS Several plasma and serum metabolites, including amino acids, lipids, and carbohydrates, are associated with type 2 diabetes risk.

Neuromodulatory electroceuticals such as vagus nerve stimulation have been recently gaining traction as potential rehabilitation tools for disorders of consciousness (DoC). We present a longitudinal case study of non-invasive auricular vagus nerve stimulation (taVNS) in a patient diagnosed with chronic unresponsive wakefulness syndrome (previously known as vegetative state). Over a period of 6 months we applied taVNS daily and regularly evaluated the patient’s behavioral outcomes using Coma Recovery Scale – Revised. We also took electrophysiological measures: resting state electroencephalography (EEG), heart rate (HR) and heart rate variability (HRV). All these methods revealed signs of improvement in the patient’s condition. The total CRS-R scores fluctuated but rose from 4 and 6 at initial stages to the heights of 12 and 13 in the 3rd and 5th month, which would warrant a change in diagnosis to a Minimally Conscious State. Scores obtained in a 2 months follow-up period, though, suggest this may not have been a lasting improvement. Behavioral signs of recovery are triangulated by EEG frequency spectrum profiles with re-emergence of a second oscillatory peak in the alpha range, which has been shown to characterize aware people. However, sustained spontaneous theta oscillations did not predictably diminish, which most likely reflects structural brain damage. ECG measures revealed a steady decrease in pre-stimulation HR combined with an increase in HRV-HR. This suggests a gradual withdrawal of sympathetic and an increase in parasympathetic control of the heart, which the previous literature has also linked with DoC improvements. Together, this study suggests that taVNS stimulation holds promise as a DoC treatment.

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.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To systematically review the available evidence on the effects (benefits and harms) of DPP‐4 inhibitors, GLP‐1 receptor agonists, and SGLT‐2 inhibitors in people with established CVD, using network meta‐analysis.

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.

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: Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.METHODS: This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.FINDINGS: Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).INTERPRETATION: Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.FUNDING: Bayer AG.

Supplemental Digital Content is available in the text., Background: Thrombotic events are reduced with cangrelor, an intravenous P2Y12 inhibitor. We sought to characterize the timing, number, and type of early events (within 2 hours of randomization) in CHAMPION PHOENIX (A Clinical Trial Comparing Cangrelor to Clopidogrel Standard of Care Therapy in Subjects Who Require Percutaneous Coronary Intervention). Methods: CHAMPION PHOENIX was a double-blind, placebo-controlled trial that randomized patients undergoing percutaneous coronary intervention to cangrelor or clopidogrel. For this analysis, we evaluated the efficacy of cangrelor in the first 2 hours postrandomization with regards to the primary end point (death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis). Sensitivity analyses were performed evaluating a secondary, post hoc end point (death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium definite stent thrombosis). Results: The majority of events (63%) that occurred in the trial occurred within 2 hours of randomization. The most common early event was myocardial infarction; next were stent thrombosis, ischemia driven revascularization, and death. In the first 2 hours after randomization, cangrelor significantly decreased the primary composite end point compared with clopidogrel (4.1% versus 5.4%; hazard ratio, 0.76 [95% CI, 0.64–0.90], P=0.002). Similar findings were seen for the composite end point of death, Society of Coronary Angiography and Intervention myocardial infarction, ischemia-driven revascularization, or Academic Research Consortium stent thrombosis at 2 hours (0.9% versus 1.6%; hazard ratio, 0.57 [95% CI, 0.40–0.80], P=0.001). Between 2 and 48 hours, there was no difference in the primary composite end point (0.6% versus 0.5%; odds ratio, 1.17 [95% CI, 0.71–1.93]; P=0.53). Early (≤2 hours of randomization) GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) moderate or severe bleeding events were infrequent, and there was no significant difference with cangrelor compared with clopidogrel (0.2% [n=10] versus 0.1% [n=4]; adjusted odds ratio, 1.41 [95% CI, 0.37–5.40]; P=0.62). Conclusions: The reductions in ischemic events and overall efficacy seen with cangrelor in CHAMPION PHOENIX occurred early and during the period of time in which patients were being actively treated with cangrelor. These findings provide evidence that supports the importance of potent platelet inhibition during percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01156571.

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 .).

It is known that solving mental tasks leads to tonic increase in cardiovascular activity. Our previous research showed that tasks involving rule application (RA) caused greater tonic increase in cardiovascular activity than tasks requiring rule discovery (RD). However, it is not clear what brain mechanisms are responsible for this difference. The aim of two experimental studies was to compare the patterns of brain and cardiovascular activity while both RD and the RA numeric tasks were being solved. The fMRI study revealed greater brain activation while solving RD tasks than while solving RA tasks. In particular, RD tasks evoked greater activation of the left inferior frontal gyrus and selected areas in the parietal, and temporal cortices, including the precuneus, supramarginal gyrus, angular gyrus, inferior parietal lobule, and the superior temporal gyrus, and the cingulate cortex. In addition, RA tasks caused larger increases in HR than RD tasks. The second study, carried out in a cardiovascular laboratory, showed greater increases in heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) while solving RA tasks than while solving RD tasks. The results support the hypothesis that RD and RA tasks involve different modes of information processing, but the neuronal mechanism responsible for the observed greater cardiovascular response to RA tasks than to RD tasks is not completely clear.

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.

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 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.

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.

In the present simultaneous EEG/ECG-fMRI study we compared the temporal and spatial characteristics of the brain responses and the cardiac activity during fear picture processing between spider, blood-injection-injury (BII) and social fearful as well as healthy (non-fearful) volunteers. All participants were presented with two neutral and six fear-related blocks of pictures: two social, two spider and two blood/injection fear blocks. In a social fear block neutral images were occasionally interspersed with photographs of angry faces and social exposure scenes. In spider and blood/injection fear blocks neutral pictures were interspersed with spider fear-relevant and blood/injection pictures, respectively. When compared to healthy controls the social fear group responded with increased activations in the anterior orbital, middle/anterior cingulate and middle/superior temporal areas for pictures depicting angry faces and with a few elevated superior frontal activations for social exposure scenes. In the blood/injection fear group, heart rate was decreased and the activity in the middle/inferior frontal and visual processing regions was increased for blood/injection pictures. The HR decrease for blood/injection pictures correlated with increased frontal responses. In the spider fear group, spider fear-relevant pictures triggered increased activations within a broad subcortical and cortical neural fear network. The HR response for spider fear-relevant stimuli was increased and correlated with an increased insula and hippocampus activity. When compared to healthy controls, all fear groups showed higher LPP amplitudes for their feared cues and an overall greater P1 hypervigilance effect. Contrasts against the fear control groups showed that the increased responses for fear-specific stimuli are mostly related to specific fears and not to general anxiety proneness. The results suggest different engagement of cognitive evaluation and down-regulation strategies and an overall increased sensitization of the fear system in the three fear groups.

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.

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: 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.

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.

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.