ERRATUM: Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities.

According to the latest guidelines of European and American medical societies, genetic testing (GT) is essential in cardiovascular diseases for establishing diagnosis, predicting prognosis, enabling initiation of disease-modifying therapy, and preventing sudden cardiac death. The GT result may be relevant for cascade GT in the patient's relatives, for planning his/her profession and physical activity, and for procreative counseling. This position statement has been prepared due to the scarcity of GT in cardiovascular diseases in Poland and the need to expand its availability. We give a concise description of the genetic background of cardiomyopathies, channelopathies, aortopathies, familial hypercholesterolemia, pheochromocytomas, and paragangliomas. The article discusses various aspects of GT in specific populations, such as children or athletes, and also presents prenatal genetic diagnostics. We propose recommendations for GT and counselling, which take into account Polish needs and capabilities. We give an outline of legal regulations, good clinical practice in GT with respect for patient rights, the role of cardiologists and clinical geneticists in GT planning and post-test counseling, and the requirements for laboratories performing genetic tests. The Polish Cardiac Society and Polish Society of Human Genetics experts speak with one voice with cardiovascular patient communities to underline the need for a law on GT and increasing the availability of GT for cardiovascular patients.

The Impact of Haplotypes of the FTO Gene, Lifestyle, and Dietary Patterns on BMI and Metabolic Syndrome in Polish Young Adult Men.

BACKGROUND: Variants in fat mass and the obesity-associated protein (FTO) gene have long been recognized as the most significant genetic predictors of body fat mass and obesity. Nevertheless, despite the overall evidence, there are conflicting reports regarding the correlation between different polymorphisms of the FTO gene and body mass index (BMI). Additionally, it is unclear whether FTO influences metabolic syndrome (MetS) through mechanisms other than BMI's impact. In this work, we aimed to analyze the impact of the following FTO polymorphisms on the BMI as well as MetS components in a population of young adult men. METHODS: The patient group consisted of 279 Polish young adult men aged 28.92 (4.28) recruited for the MAGNETIC trial. The single-nucleotide polymorphisms (SNPs), located in the first intron of the FTO gene, were genotyped, and the results were used to identify "protective" and "risk" haplotypes and diplotypes based on the literature data. Laboratory, as well as anthropometric measurements regarding MetS, were performed. Measured MetS components included those used in the definition in accordance with the current guidelines. Data regarding dietary patterns were also collected, and principal components of the dietary patterns were identified. RESULTS: No statistically significant correlations were identified between the analyzed FTO diplotypes and BMI (p = 0.53) or other MetS components (waist circumference p = 0.55; triglycerides p = 0.72; HDL cholesterol p = 0.33; blood glucose p = 0.20; systolic blood pressure p = 0.06; diastolic blood pressure p = 0.21). Stratification by the level of physical activity or adherence to the dietary patterns also did not result in any statistically significant result. CONCLUSIONS: Some studies have shown that FTO SNPs such as rs1421085, rs1121980, rs8050136, rs9939609, and rs9930506 have an impact on the BMI or other MetS components; nevertheless, this was not replicated in this study of Polish young adult males.

Phenotypes of Polish primary care patients using hierarchical clustering: Exploring the risk of mortality in the LIPIDOGEN2015 study cohort.

BACKGROUND: Comorbidities in primary care do not occur in isolation but tend to cluster together causing various clinically complex phenotypes. This study aimed to distinguish phenotype clusters and identify the risks of all-cause mortality in primary care. METHODS: The baseline cohort of the LIPIDOGEN2015 sub-study involved 1779 patients recruited by 438 primary care physicians. To identify different phenotype clusters, we used hierarchical clustering and investigated differences between clinical characteristics and mortality between clusters. We then performed causal analyses using causal mediation analysis to explore potential mediators between different clusters and all-cause mortality. RESULTS: A total of 1756 patients were included (mean age 51.2, SD 13.0; 60.3% female), with a median follow-up of 5.7 years. Three clusters were identified: Cluster 1 (n = 543) was characterised by overweight/obesity (body mass index ≥ 25 kg/m2), older (age ≥ 65 years), more comorbidities; Cluster 2 (n = 459) was characterised by non-overweight/obesity, younger, fewer comorbidities; Cluster 3 (n = 754) was characterised by overweight/obesity, younger, fewer comorbidities. Adjusted Cox regression showed that compared with Cluster 2, Cluster 1 had a significantly higher risk of all-cause mortality (HR 3.87, 95% CI: 1.24-15.91), whereas this was insignificantly different for Cluster 3. Causal mediation analyses showed that decreased protein thiol groups mediated the hazard effect of all-cause mortality in Cluster 1 compared with Cluster 2, but not between Clusters 1 and 3. CONCLUSION: Overweight/obesity older patients with more comorbidities had the highest risk of long-term all-cause mortality, and in the young group population overweight/obesity insignificantly increased the risk in the long-term follow-up, providing a basis for stratified phenotypic risk management.

Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities.

According to the latest guidelines of European and American medical societies, genetic testing (GT) is essential in cardiovascular diseases for establishing diagnosis, predicting prognosis, enabling initiation of disease-modifying therapy, and preventing sudden cardiac death. The GT result may be relevant for cascade GT in the patient's relatives, for planning his/her profession and physical activity, and for procreative counseling. This position statement has been prepared due to the scarcity of GT in cardiovascular diseases in Poland and the need to expand its availability. We give a concise description of the genetic background of cardiomyopathies, channelopathies, aortopathies, familial hypercholesterolemia, pheochromocytomas, and paragangliomas. The article discusses various aspects of GT in specific populations, such as children or athletes, and also presents prenatal genetic diagnostics. We propose recommendations for GT and counselling, which take into account Polish needs and capabilities. We give an outline of legal regulations, good clinical practice in GT with respect for patient rights, the role of cardiologists and clinical geneticists in GT planning and post-test counseling, and the requirements for laboratories performing genetic tests. The Polish Cardiac Society and Polish Society of Human Genetics experts speak with one voice with cardiovascular patient communities to underline the need for a law on GT and increasing the availability of GT for cardiovascular patients.

Recommendations of the Experts of the Polish Cardiac Society (PCS) and the Polish Lipid Association (PoLA) on the diagnosis and management of elevated lipoprotein(a) levels.

Lipoprotein(a) [Lp(a)] is made up of a low-density lipoprotein (LDL) particle and a specific apolipoprotein(a). The blood concentration of Lp(a) is approximately 90% genetically determined, and the main genetic factor determining Lp(a) levels is the size of the apo(a) isoform, which is determined by the number of KIV2 domain repeats. The size of the apo(a) isoform is inversely proportional to the blood concentration of Lp(a). Lp(a) is a strong and independent cardiovascular risk factor. Elevated Lp(a) levels ≥ 50 mg/dl (≥ 125 nmol/l) are estimated to occur in more than 1.5 billion people worldwide. However, determination of Lp(a) levels is performed far too rarely, including Poland, where, in fact, it is only since the 2021 guidelines of the Polish Lipid Association (PoLA) and five other scientific societies that Lp(a) measurements have begun to be performed. Determination of Lp(a) concentrations is not easy due to, among other things, the different sizes of the apo(a) isoforms; however, the currently available certified tests make it possible to distinguish between people with low and high cardiovascular risk with a high degree of precision. In 2022, the first guidelines for the management of patients with elevated lipoprotein(a) levels were published by the European Atherosclerosis Society (EAS) and the American Heart Association (AHA). The first Polish guidelines are the result of the work of experts from the two scientific societies and their aim is to provide clear, practical recommendations for the determination and management of elevated Lp(a) levels.

Association of body mass index and long-term mortality in patients from nationwide LIPIDOGRAM 2004-2015 cohort studies: no obesity paradox?

BACKGROUND: An obesity paradox has been described in relation to adverse clinical outcomes (e.g., mortality) with lower body mass index (BMI). AIMS: We sought to evaluate the association between BMI and weight loss with long-term all-cause mortality in adult populations under the care of family physicians. METHODS: LIPIDOGRAM studies were conducted in primary care in Poland in 2004, 2006, and 2015 and enrolled a total of 45,615 patients. The LIPIDOGRAM Plus study included 1627 patients recruited in the LIPIDOGRAM 2004 and repeated measurements in 2006 edition. Patients were classified by BMI categories as underweight, normal weight, overweight and class I, II, or III (obesity). Follow-up data up to December 2021 were obtained from the Central Statistical Office. Differences in all-cause mortality were analyzed using Kaplan‒Meier and Cox regression analyses. RESULTS: Of 45,615 patients, 10,987 (24.1%) were normal weight, 320 (0.7%) were underweight, 19,134 (41.9%) were overweight, and 15,174 (33.2%) lived with obesity. Follow-up was available for 44,620 patients (97.8%, median duration 15.3 years, 61.7% females). In the crude analysis, long-term all-cause mortality was lowest for the normal-weight group (14%) compared with other categories. After adjusting for comorbidities, the highest risk of death was observed for the class III obesity and underweight categories (hazard ratio, HR 1.79, 95% CI [1.55-2.05] and HR 1.57, 95% CI [1.22-2.04]), respectively. The LIPIDOGRAM Plus analysis revealed that a decrease in body weight (by 5 and 10%) over 2 years was associated with a significantly increased risk of death during long-term follow-up-HR 1.45 (95% CI 1.05-2.02, p = 0.03) and HR 1.67 (95% CI 1.02-2.74, p < 0.001). Patients who experienced weight loss were older and more burdened with comorbidities. CONCLUSIONS: Being underweight, overweight or obese is associated with a higher mortality risk in a population of patients in primary care. Patients who lost weight were older and more burdened with cardiometabolic diseases, which may suggest unintentional weight loss, and were at higher risk of death in the long-term follow-up. In nonsmoking patients without comorbidities, the lowest mortality was observed in those with a BMI < 25 kg/m2, and no U-curve relationship was observed.

Intensive Statin Therapy Versus Upfront Combination Therapy of Statin and Ezetimibe in Patients With Acute Coronary Syndrome: A Propensity Score Matching Analysis Based on the PL-ACS Data.

Background We aimed to compare statin monotherapy and upfront combination therapy of statin and ezetimibe in patients with acute coronary syndromes (ACSs). Methods and Results The study included consecutive patients with ACS included in the PL-ACS (Polish Registry of Acute Coronary Syndromes), which is a national, multicenter, ongoing, prospective observational registry that is mandatory for patients with ACS hospitalized in Poland. Data were matched using the Mahalanobis distance within propensity score matching calipers. Multivariable stepwise logistic regression analysis, including all variables, was next used in propensity score matching analysis. Finally, 38 023 consecutive patients with ACS who were discharged alive were included in the analysis. After propensity score matching, 2 groups were analyzed: statin monotherapy (atorvastatin or rosuvastatin; n=768) and upfront combination therapy of statin and ezetimibe (n=768 patients). The difference in mortality between groups was significant during the follow-up and was present at 1 (5.9% versus 3.5%; P=0.041), 2 (7.8% versus 4.3%; P=0.019), and 3 (10.2% versus 5.5%; P=0.024) years of follow-up in favor of the upfront combination therapy, as well as for the overall period. For the treatment, rosuvastatin significantly improved prognosis compared with atorvastatin (odds ratio [OR], 0.790 [95% CI, 0.732-0.853]). Upfront combination therapy was associated with a significant reduction of all-cause mortality in comparison with statin monotherapy (OR, 0.526 [95% CI, 0.378-0.733]), with absolute risk reduction of 4.7% after 3 years (number needed to treat=21). Conclusions The upfront combination lipid-lowering therapy is superior to statin monotherapy for all-cause mortality in patients with ACS. These results suggest that in high-risk patients, such an approach, rather than a stepwise therapy approach, should be recommended.

Impact of vitamin D receptor polymorphisms in selected metabolic disorders.

PURPOSE OF REVIEW: Vitamin D (vitD) can regulate metabolic pathways in adipose tissue and pancreatic ß cells by interacting with its vitamin D receptor (VDR). The aim of this study was to review original publications published in the last months and verify the relationship between genetic variants in the VDR gene and type 2 diabetes (T2D), metabolic syndrome (MetS), overweight, and obesity. RECENT FINDINGS: The recent studies concern genetic variants located in the coding and noncoding regions of the VDR gene. Some of the described genetic variants may affect VDR expression or posttranslational processing altered functionality or vitD binding capacity of VDR. Nevertheless, the data collected in recent months on the assessment of the relationship between VDR genetic variants and the risk of T2D, MetS, overweight, and obesity still do not give a clear answer to whether they have a direct impact on these metabolic disorders. SUMMARY: Analysis of the potential association between VDR genetic variants and parameters such as glycemia, body mass index, body fat, and lipid levels improves the current understanding of the pathogenesis of T2D, MetS, overweight, and obesity. A thorough understanding of this relationship may provide important information for individuals with pathogenic variants and enable the implementation of appropriate prevention against the development of these disorders.

Metabolic syndrome is associated with similar long-term prognosis in those living with and without obesity: an analysis of 45 615 patients from the nationwide LIPIDOGRAM 2004-2015 studies.

AIMS: We aimed to evaluate the association between metabolic syndrome (MetS) and long-term all-cause mortality. METHODS AND RESULTS: The LIPIDOGRAM studies were carried out in the primary care in Poland in 2004, 2006, and 2015. MetS was diagnosed based on the National Cholesterol Education Program, Adult Treatment Panel III (NCEP/ATP III), and Joint Interim Statement (JIS) criteria. The cohort was divided into four groups: non-obese patients without MetS, obese patients without MetS, non-obese patients with MetS, and obese patients with MetS. Differences in all-cause mortality were analysed using Kaplan-Meier and Cox regression analyses. A total of 45 615 participants were enrolled (mean age 56.3, standard deviation: 11.8 years; 61.7% female). MetS was diagnosed in 14 202 (31%) by NCEP/ATP III criteria and 17 216 (37.7%) by JIS criteria. Follow-up was available for 44 620 (97.8%, median duration 15.3 years) patients. MetS was associated with increased mortality risk among the obese {hazard ratio, HR: 1.88 [95% confidence interval (CI) 1.79-1.99] and HR: 1.93 [95% CI 1.82-2.04], according to NCEP/ATP III and JIS criteria, respectively} and non-obese individuals [HR: 2.11 (95% CI 1.85-2.40) and 1.7 (95% CI 1.56-1.85) according to NCEP/ATP III and JIS criteria, respectively]. Obese patients without MetS had a higher mortality risk than non-obese patients without MetS [HR: 1.16 (95% CI 1.10-1.23) and HR: 1.22 (95% CI 1.15-1.30), respectively in subgroups with NCEP/ATP III and JIS criteria applied]. CONCLUSIONS: MetS is associated with increased all-cause mortality risk in non-obese and obese patients. In patients without MetS, obesity remains significantly associated with mortality. The concept of metabolically healthy obesity should be revised.

Metabolic syndrome (MetS) is used to describe a constellation of metabolic disturbances such as elevated blood glucose, increased levels of triglycerides and decreased level of high density lipoprotein cholesterol. They are often accompanied by elevated blood pressure and central obesity, defined as increased waist circumference. Usually, those metabolic disturbances occur in obese individuals, but sometimes, they can also occur in lean subjects. This relatively recent concept is often referred to as lean MetS. A key conclusion from our paper is that MetS, when it occurs in lean patients, is associated with similarly unfavourable long-term prognosis as in obese patients. Additionally, our analysis shows that lean patients with MetS are less often treated with lipid-lowering drugs despite having higher low density lipoprotein cholesterol levels (LDL-C). An additional finding, which is important from a public health perspective, is that obese patients who do not fulfil MetS criteria have higher long-term all-cause mortality than their lean counterparts without MetS. This finding should be an argument to encourage maintenance of normal body weight.

A network meta-analysis on the comparative effect of nutraceuticals on lipid profile in adults.

It is estimated that 2.6 million deaths worldwide can be attributed to hypercholesterolemia. The main reason for non-adherence to statin therapy are the statin-associated muscle symptoms (including nocebo/drucebo effect). In this case, apart from ezetimibe, nutraceuticals are prescribed. We aimed to assess the comparative efficacy of different nutraceuticals in terms of lowering low density lipoprotein cholesterol (LDL-C) and improving lipid profile. Electronic and hand searches were performed until February 2021. The inclusion criteria were the following: (1) randomized trial with any of the reportedly LDL-C lowering nutraceutical: artichoke, berberine, bergamot, garlic, green tea extract, plant sterols/stanols, policosanols, red yeast rice (RYR), silymarin or spirulina. (2) outcome either LDL-C (primary outcome), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) or serum triglycerides (TG). Random effects network meta-analysis (NMA) was performed to rank the effect of each intervention using frequentist approach. Finally, a total of 131 trials enrolling 13,062 participants were included. All analysed nutraceuticals except for policosanols were more effective in lowering LDL-C (-1.21 [-46.8 mg/dL] to -0.17 [-6.6 mg/dL] mmol/l reduction) and TC (-1.75 [-67.7 mg/dL] to -0.18 [7 mg/dL] mmol/l reduction) than placebo/no intervention. The most effective approaches in terms of LDL-C- and TC-lowering were bergamot and RYR (-1.21 [-46.8 mg/dl] and -0.94 [-36.4 mg/dl] mmol/l) reduction respectively. In conclusion, bergamot and RYR appear to be the most effective nutraceuticals in terms of LDL-C and TC reduction. Evidence for bergamot effect was based on relatively small study group and may require further investigations. Policosanols have no effect on the lipid profile.

Design and rationale of a nationwide screening analysis from the LIPIDOGRAM2015 and LIPIDOGEN2015 studies.

Introduction: Cardiovascular disease (CVD) is a major cause of morbidity and mortality throughout the world. The LIPIDOGRAM2015 study was performed to estimate the prevalence of risk factors for atherosclerotic diseases as well as cardiovascular and related disorders in the primary care setting in Poland. The LIPIDOGEN2015 sub-study was designed to include a random cohort of patients in order to analyse parameters related to lipid metabolism, oxidative stress, inflammatory responses, autoimmune disorders, and gene variants that confer susceptibility to cardiometabolic and atherosclerotic diseases. Material and methods: The recruitment was carried out by 438 primary care physicians in Poland. The expected number of patients recruited for the LIPIDOGRAM2015 study was 13,000-14,000 with 13-15% (1700-2000) also participating in the LIPIDOGEN2015 sub-study. Each patient had to complete a questionnaire concerning medical and family history, concomitant diseases, and pharmacotherapy. Anthropometric measurements were performed at the doctor's office. For the LIPIDOGEN2015 sub-study, saliva samples for DNA isolation and blood samples for measurement of glycated haemoglobin, oxidative stress parameters, autoantibody levels, and inflammatory cytokine profile and apolipoprotein profile were collected. Follow-up data will be obtained from the National Health Fund in Poland. Results: The LIPIDOGRAM2015 and LIPIDOGEN2015 study cohort reflects the prevalence of cardiovascular risk factors and concomitant diseases, markers of oxidative stress, the presence of autoantibodies, inflammatory cytokine profile, and apolipoprotein profile, as well as genetic variants potentially conferring susceptibility to cardiometabolic and atherosclerotic diseases. Conclusions: This study presents the prevalence of different CV risk factors, with special emphasis on lipid disorders, and it assesses the relationship between inflammation, oxidative stress, and mutations in genes encoding proteins regulating lipid metabolism, as well as genes conferring susceptibility to cardiovascular, cardiometabolic, and related diseases.

Association of Metabolically Healthy and Unhealthy Obesity Phenotype with Markers Related to Obesity, Diabetes among Young, Healthy Adult Men. Analysis of MAGNETIC Study.

Adipose tissue secretes many regulatory factors called adipokines. Adipokines affect the metabolism of lipids and carbohydrates. They also influence the regulation of the immune system and inflammation. The current study aimed to evaluate the association between markers related to obesity, diabesity and adipokines and metabolically healthy and unhealthy obesity in young men. The study included 98 healthy participants. We divided participants into three subgroups based on body mass index and metabolic health definition: 49 metabolically healthy normal-weight patients, 27 metabolically healthy obese patients and 22 metabolically unhealthy obese patients. The 14 metabolic markers selected were measured in serum or plasma. The analysis showed associations between markers related to obesity, diabesity and adipokines in metabolically healthy and unhealthy obese participants. The decreased level of adipsin (p < 0.05) was only associated with metabolically healthy obesity, not with metabolically unhealthy obesity. The decreased level of ghrelin (p < 0.001) and increased level of plasminogen activator inhibitor-1 (p < 0.01) were only associated with metabolically unhealthy obesity, not with metabolically healthy obesity. The decreased level of adiponectin and increased levels of leptin, c-peptide, insulin and angiopoietin-like 3 protein were associated with metabolically healthy and unhealthy obesity. In conclusion, our data show that metabolically healthy obesity was more similar to metabolically unhealthy obesity in terms of the analyzed markers related to obesity and diabesity.

New Variants of the Cytochrome P450 2R1 (CYP2R1) Gene in Individuals with Severe Vitamin D-Activating Enzyme 25(OH)D Deficiency.

BACKGROUND: Vitamin D is a fat-soluble cholesterol derivative found in two forms, vitamin D2, and vitamin D3. Cytochrome P450 2R1 (CYP2R1) encoded by the CYP2R1 gene is the major hydroxylase that activates vitamin D by catalyzing the formation of 25-hydroxyvitamin D (25(OH)D). METHODS: We collected 89 (100%) subjects, 46 of which (51.69%) had a documented severe deficiency of 25(OH)D (<10 ng/mL) and 43 (48.31%) in the control group with documented optimum levels of 25(OH)D (>30 ng/mL). We performed Sanger sequencing of three selected fragments of the CYP2R1 gene (Ch11: 14878000-14878499; Ch11: 14880058-14880883 and Ch11: 14885321-14886113) that affect the binding of substrates to this enzyme and analyzed the possible involvement of genetic variation in these regions with an increased risk of vitamin D deficiency in healthy Polish individuals. RESULTS: Two substitutions were found within the three fragments. Bioinformatic analysis suggested that one of these (NC_000011.10: g.14878291G>A) may influence the structure and function of CYP2R1. CONCLUSIONS: Variant NC_000011.10: g.14878291G>A may have a perturbing effect on heme binding in the active site of CYP2R1 and on the function of 25-hydroxylase and probably affects the concentration of 25(OH)D in vivo. We intend to perform functional verification in a larger patient population to confirm and extend these results.

Risk-factors associated with extremely high cardiovascular risk of mid- and long-term mortality following myocardial infarction: Analysis of the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) registry.

BACKGROUND AND AIMS: Risk-factor identification and risk stratification are prerequisites to the effective primary and secondary prevention of cardiovascular disease (CVD). Patients at the highest risk benefit the most from the intensive risk-factor reduction. However, the high-risk patients' group is heterogeneous, and it is increasingly recognised that there is an 'extreme-risk' category of patients who may require particularly close attention and intensive therapeutic approach. The aim of this study was to identify subgroups of patients at the highest risk of death following myocardial infarction (MI) that might be considered as those at extremely high CVD risk. METHODS: We used data from 19,582 participants of the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) Registry (NCT03065543) of patients with ischaemic heart disease in Poland from 2006 to present. Characteristics of 13,052 patients with chronic coronary syndromes (CCS) were compared with those of 4295 patients with myocardial infarction (STEMI and NSTEMI). Multivariable logistic regression with stepwise backward elimination was used to identify risk factors associated with mortality in the 12-36 months following the index hospitalisation. RESULTS: The mortality rates were significantly higher in patients after MI than in patients with CCS. In the multivariable analysis, the risk factors most strongly associated with 12-month mortality in patients after MI were left ventricular ejection fraction (LVEF) lower than 35% (hazard ratio [HR] 3.83, 95% confidence interval [CI] 3.14-4.67), age >75 years (HR 1.91, 95%CI 1.55-2.35), multivessel coronary artery disease (HR 1.61, 95%CI 1.30-1.99), atrial fibrillation (HR 1.53, 95%CI 1.21-1.94) diabetes mellitus (HR 1.35, 95%CI 1.11-1.64) and increased LDL-C (HR per 1 mmol/l 1.09, 95%CI 1.01-1.19) or creatinine levels (HR per 10 µmol/L 1.04, 95% CI 1.04-1.05). The risk factors that influenced mortality after 24-36 months were consistent with those after 12 months, with additional low haemoglobin (20-25% risk increase per 1 mmol reduction) and chronic obstructive pulmonary disease (65% risk increase after 36 months). CONCLUSIONS: In our large, single-center real-world analysis, we identified the patients with the highest risk of death who could probably benefit the most from the most intensive therapy, and hence should be considered to be an 'extreme risk' population.

Oxidative Stress in Association with Metabolic Health and Obesity in Young Adults.

INTRODUCTION: Obesity is one of the most important public health problems in the world. Among obese people, there are those who, apart from excessive body weight, do not exhibit other metabolic dysfunctions, have a lower risk of developing cardiovascular diseases (CVDs), and show lower mortality. According to the theory, they are referred as metabolically healthy obese (MHO), in contrast to metabolically unhealthy obese (MUO). Metabolic disturbances occurring with obesity have been well established to be associated with oxidative stress. AIM: The purpose of this study was to analyse the association between selected anthropometric and biochemical parameters with oxidative stress in MHO, MUO, and normal weight young adults. Material and Methods. Individuals with age between 18 and 36 years with no history of chronic diseases and use of medicaments, with or without obesity, participated in the study. Complete blood counts, biochemical measurements, and parameters of oxidative stress such as total antioxidant capacity (TAC), total oxidative status (TOS), oxidative stress index (OSI), serum concentration of malondialdehyde (MDA), ceruloplasmin, thiol groups and lipid hydroperoxides (LPH), concentration of lipofuscin (LPS) in erythrocytes, and the activity of superoxide dismutase (SOD) were measured. RESULTS: 422 patients who met the inclusion criteria were enrolled in the study. Among the study participants, 208 people (49.29%) were offspring of patients with angiographically confirmed coronary artery disease. Among the participants, 16 patients have been included in the group of metabolically healthy obese (MHO) people and 61 patients in the group of metabolically unhealthy obese (MUO) people and 345 patients had normal body weight. Significant differences between metabolically unhealthy obese and normal weight patients, as well as between women and men, have been found. CONCLUSIONS: We showed significant differences in the selected parameters of oxidative stress between metabolically unhealthy obese (MUO) individuals and young volunteers with normal body weight as well as without significant medical history.

VDR Gene Polymorphisms in Healthy Individuals with Family History of Premature Coronary Artery Disease.

AIM: The gene encoding the vitamin D receptor (VDR) is considered in many studies to be a good candidate responsible for susceptibility to several diseases such as coronary artery disease (CAD). Epidemiological data show that cardiovascular disease is one of the major health problems in Polish society. Basic studies show that genetic factors play a significant role in the pathogenesis of CAD. We conducted this clinical study to determine if the VDR gene polymorphisms TaqI (rs731236), ApaI (rs7975232), and FokI (rs2228570) could predispose healthy individuals to an increased risk of premature CAD (P-CAD) incidents. METHODS: We genotyped 845 subjects in a cohort consisting of 386 healthy volunteers with a documented P-CAD incident in their first-degree relatives and 459 healthy volunteers without family history (FH) of P-CAD. TaqI, ApaI, and FokI polymorphisms in VDR were genotyped using TaqMan assays and the endpoint genotyping method (qPCR). Statistical analyses were performed using the Power Analysis Software STATISTICA v.13.3. RESULTS: Although no statistical significance was found for TaqI and ApaI genotype frequencies, the AA genotype of FokI polymorphism was significantly more frequent in the study group compared to the control group (24.61% vs. 16.99%). The results of logistic regression analysis suggested a significant association between FokI polymorphism and FH of P-CAD in heathy people under the recessive model (OR: 1.26 (1.07-1.49, p = 0.007)); however, the frequency of VDR haplotypes did not differ significantly between the control and study populations. CONCLUSIONS: FokI polymorphism is may be associated with FH of P-CAD. FokI polymorphism may predispose to the development of P-CAD among healthy people over the next years.

Association of Metabolically Healthy and Unhealthy Obesity Phenotypes with Oxidative Stress Parameters and Telomere Length in Healthy Young Adult Men. Analysis of the MAGNETIC Study.

Obesity is a significant factor related to metabolic disturbances that can lead to metabolic syndrome (MetS). Metabolic dysregulation causes oxidative stress, which affects telomere structure. The current study aimed to evaluate the relationships between telomere length, oxidative stress and the metabolically healthy and unhealthy phenotypes in healthy young men. Ninety-eight participants were included in the study (49 healthy slim and 49 obese patients). Study participants were divided into three subgroups according to body mass index and metabolic health. Selected oxidative stress markers were measured in serum. Relative telomere length (rTL) was measured using quantitative polymerase chain reaction. The analysis showed associations between laboratory markers, oxidative stress markers and rTL in metabolically healthy and unhealthy participants. Total oxidation status (TOS), total antioxidant capacity (TAC) and rTL were significantly connected with metabolically unhealthy obesity. TAC was associated with metabolically healthy obesity. Telomeres shorten in patients with metabolic dysregulation related to oxidative stress and obesity linked to MetS. Further studies among young metabolically healthy and unhealthy individuals are needed to determine the pathways related to metabolic disturbances that cause oxidative stress that leads to MetS.

The CTGF gene -945 G/C polymorphism is associated with target lesion revascularization for in-stent restenosis.

BACKGROUND AND AIMS: Previous studies have shown that transforming growth factor ß (TGF-ß) and vascular endothelial growth factor A (VEGF-A) pathways are involved in the in-stent restenosis (ISR) process. The present study aimed to assess the relationship between single-nucleotide polymorphisms (SNPs) in genes encoding downstream proteins of TGF-ß and VEGF-A pathways and the risk of target lesion revascularization (TLR) for in-stent restenosis. METHODS: A total of 657 patients (with 781 treated lesions) who underwent percutaneous coronary intervention (PCI) with stent implantation at our center between 2007 and 2012 and completed a 4-year follow-up for clinically-driven TLR, were included. SNPs in CTGF (rs6918698), TGFBR2 (rs2228048), SMAD3 (rs17293632), KDR (rs2071559), CCL2 (rs1024610) were genotyped using TaqMan assay. RESULTS: Major allele carriers of CTGF gene -945 G/C polymorphism (rs6918698) were significantly less likely to underwent clinically-driven TLR during follow-up than minor allele carriers. After adjustment for clinical, angiographic, and procedural covariates, CTGF polymorphism was significantly associated with TLR, and minor allele (C) carriers had nearly two times higher risk of developing ISR requiring TLR (HR of 1.93, 95%CI 1.15-3.24) compared to patients with major (GG) genotype. No significant relationship was found between other analyzed polymorphisms and cumulative incidence of TLR at 4-years. CONCLUSIONS: Our results suggest that functional -945 G/C polymorphism in the gene encoding connective tissue growth factor is associated with the need for TLR in patients who underwent PCI for stable coronary artery disease.