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.

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.

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.

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.

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.

Oxidative Stress Markers in Hypertrophic Cardiomyopathy.

Background and Objectives: Hypertrophic cardiomyopathy (HCM) depends on the primary impairment of sarcomeres, but it can also be associated with secondary alterations in the heart related to oxidative stress. The present study aimed to examine oxidative-antioxidant disturbances in patients with HCM compared with control individuals. Materials and Methods: We enrolled 52 consecutive HCM patients and 97 controls without HCM. The groups were matched for age, body mass index, and sex. Peripheral blood was collected from all patients to determine the total antioxidant capacity (TAC), total oxidant status (TOS), lipid hydroperoxide (LPH), and malondialdehyde (MDA). The oxidative stress index (OSI) was defined as the ratio of the TOS level to the TAC level. Results: The median age was 52 years, and 58.4% were female. The area under the curve (AUC) indicated good predictive power for the TAC and TOS [AUC 0.77 (0.69-0.84) and 0.83 (0.76-0.90), respectively], as well as excellent predictive power for the OSI [AUC 0.87 (0.81-0.93)] for HCM detection. Lipid peroxidation markers also demonstrated good predictive power to detect HCM patients [AUCLPH = 0.73, AUCMDA = 0.79]. Conclusions: The TOS, the TAC, LPH levels, and MDA levels have good predictive power for HCM detection. The holistic assessment of oxidative stress by the OSI had excellent power and could identify patients with HCM.

Genetic and environmental factors associated with homocysteine concentrations in a population of healthy young adults. Analysis of the MAGNETIC study.

BACKGROUND AND AIMS: Elevated homocysteine concentration is associated with a higher risk of cardiovascular disease. The aim of our study was to determine the environmental and genetic factors associated with serum homocysteine concentration in healthy young adults. Moreover, we aimed to determine the cutoff value of homocysteine concentration for predicting unfavorable MTHFR genotype and to investigate whether this association is modified by dietary patterns and serum folate status. METHODS AND RESULTS: A total of 744 healthy individuals, aged 18-35 years, were included in the study. Diet quality was assessed by establishing diet quality scores and adherence to the pro-Healthy Diet Index (pHDI) and non-Healthy Diet Index (nHDI). Genotyping was performed using the TaqMan method. Multivariate analysis showed that pHDI, creatinine, folate concentrations, and the T/T genotype of the C677T polymorphism in MTHFR, as well as the interaction between the T/T genotype of MTHFR (C677T polymorphism) and folate level, were most strongly related to homocysteine concentrations. The specificity of a homocysteine >13.1 µmol/l in predicting T/T homozygous status was 76% (area under the curve 0.68). CONCLUSION: Healthy dietary patterns, folate, and creatinine levels, as well as the C677T polymorphism, proved to be the strongest predictors of homocysteine concentrations. T/T genotype of MTHFR modifies the relationship between folate and homocysteine.

Metabolically healthy obese and metabolic syndrome of the lean: the importance of diet quality. Analysis of MAGNETIC cohort.

BACKGROUND: Obesity is considered as an indispensable component of metabolic health assessment and metabolic syndrome diagnosis. The associations between diet quality and metabolic health in lean, young adults have not been yet established whilst data addressing this issue in overweight and obese subjects is scarce. Our analysis aimed to establish the link between diet quality (measured with data-driven dietary patterns and diet quality scores) and metabolic syndrome (MS) in young adults, regardless of their adiposity status. METHODS: A total of 797 participants aged 18-35 years old were included in the study. Participants were assigned into metabolic syndrome (MS) group if at least two abnormalities within the following parameters were present: blood pressure, triglycerides, total cholesterol, HDL cholesterol, blood glucose. Participants with one or none abnormalities were considered as metabolically healthy subjects (MH), Diet quality was assessed with two approaches: 1) a posteriori by drawing dietary patterns (DPs) with principal component analysis (PCA) and 2) a priori by establishing diet quality scores and the adherence to pro-Healthy-Diet-Index (pHDI) and non-Healthy-Diet-Index (nHDI). Logistic regression with backward selection based on Akaike information criterion was carried out, to identify factors independently associated with metabolic health. RESULTS: Within the MS group, 31% were of normal weight. Three PCA-driven DPs were identified, in total explaining 30.0% of the variance: "Western" (11.8%), "Prudent" (11.2%) and "Dairy, breakfast cereals & treats" (7.0%). In the multivariate models which included PCA-driven DPs, higher adherence to middle and upper tertiles of "Western" DP (Odds Ratios [OR] and 95% Confidence Intervals [95% CI]: 1.72, 1.07-2.79 and 1.74, 1.07-2.84, respectively), was associated with MS independently of clinical characteristics including BMI and waist-hip ratio (WHR). Similar results were obtained in the multivariate model with diet quality scores - MS was independently associated with higher scores within nHDI (2.2, 0.92-5.28). CONCLUSIONS: Individuals with MS were more likely to adhere to the western dietary pattern and have a poor diet quality in comparison to metabolically healthy peers, independently of BMI and WHR. It may imply that diet composition, as independent factor, plays a pivotal role in increasing metabolic risk. Professional dietary advice should be offered to all metabolically unhealthy patients, regardless of their body mass status.

Characteristics of lipid profile and effectiveness of management of dyslipidaemia in patients with acute coronary syndromes - Data from the TERCET registry with 19,287 patients.

Despite well-defined therapeutic low-density lipoprotein cholesterol (LDL-C) target in the highest-risk population, low percentage of patients is administered with intensive lipid-lowering therapy and achieves recommended levels. Therefore, based on the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) Registry data we investigated the characteristics of lipid profile and management of dyslipidemia in acute coronary syndrome (ACS) patients. 19,287 consecutive patients hospitalized between 2006 and 2016 have been included in the study. The lipid profile on admission and long-term laboratory effects (namely the efficacy of achievement of the therapeutic target of LDL-C <70 mg/dl [1.8 mmol/L]) after follow-up of twelve months were assessed. Acute coronary syndromes occurred in 36.1% of the Registry patients including 14.3% with ST-elevated myocardial infarction (STEMI), 10.2% with NSTEMI and 9,9% with unstable angina (UA). The highest LDL-C concentration on admission was observed in the STEMI subgroup (mean level: 127.0 mg/dL [3.28 mmol/L]). In 76.6% of the Registry patients LDL-C concentration was lower than 130 mg/dL and in 20.7% was lower than 70 mg/dL at baseline. The patients with baseline LDL < 70 mg/dL were usually presented with the worst clinical profile. In 91,6% of the patients admitted due to acute coronary syndrome, statin treatment was administered at discharge. Among them, 37.6% received intensive statin therapy. In the 12-month follow-up, in 32.4% of patients admitted due to STEMI, LDL-C concentration was lower than 70 mg/dL, compared to 29.9% in patients with NSTEMI and 27.8% in patients with UA. In conclusion, STEMI patients are less clinically burdened with concomitant risk factors and comorbidities, but present significantly worse baseline lipid profile values. Among the patients already treated with statins, patients with ACS regardless of its type have significantly higher LDL-C than patients with SA. Despite discrepancies in the clinical profile on admission, achievement of the therapeutic target equalizes the outcomes in 12-month follow-up, however with the best results for STEMI patients.

Evaluation of dyslipidaemia and the impact of hypolipidemic therapy on prognosis in high and very high risk patients through the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) Registry.

The use of statins in the treatment of hyperlipidaemia leads to a significant decrease in cardiovascular (CV) endpoints, and therapy effects are proportional to the reduction of cholesterol levels. In Poland, information about the effects of statin therapy is scarcely available. The information gathered in the Hyperlipidaemia Therapy in the tERtiary Cardiological cEnTer (TERCET) Registry on high-risk and very high-risk patients might improve our knowledge on this issue and help to introduce suitable activities. The main aim of the TERCET Registry is to achieve the target value of low density lipoprotein cholesterol (LDL-C) during a 1-year follow-up: LDL-C <70 mg/dL in very high-risk patients and LDL-C <100 mg/dL in high-risk patients. All consecutive patients with either stable coronary artery disease (sCAD) or acute coronary syndrome (ACS) have been included in the Registry, and the information on all-cause mortality, nonfatal myocardial infarction (MI), and planned or ACS-caused revascularisation have been being gathered within 12-month follow-up. At the moment, the TERCET Registry includes 14,873 patients (66.8% male) at an average age of 64.8 ±â€¯10.2 with a significantly higher age of women (67.5 ±â€¯10.3 vs. 63.5 ±â€¯9.7; p < .001). The causes of hospitalisation were as the following: sCAD (n = 9375 patients, 63% of the investigated population), ST-elevated myocardial infarction (n = 2328 [15.6%]), non-ST-elevated myocardial infarction (n = 1700 [11.4%]), and unstable coronary artery disease (n = 1466 [10%]). 62,7% (n = 9144) of the patients were diagnosed with hyperlipidaemia before hospital admission, with no significant difference between male and female patients. The TERCET registry will allow unveiling real lipid profiles of the high- and very-high risk patients treated in the tertiary hospital. The results may play an essential role in establishing the patients' future clinical outcomes and help to assess if the lipid lowering therapy modifications changed the occurrence of CV endpoints. The registry data will summarize the number of patients unable to reach their LDL-C goals, and who in the future might become candidates suitable for new hypolipidemic therapies (ID: NCT03065543).

The association of functional polymorphisms in genes encoding growth factors for endothelial cells and smooth muscle cells with the severity of coronary artery disease.

BACKGROUND: Despite the important roles of vascular smooth muscle cells and endothelial cells in atherosclerotic lesion formation, data regarding the associations of functional polymorphisms in the genes encoding growth factors with the severity of coronary artery disease (CAD) are lacking. The aim of the present study is to analyze the relationships between functional polymorphisms in genes encoding basic fibroblast growth factor (bFGF, FGF2), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), platelet derived growth factor-B (PDGFB), transforming growth factor-ß1 (TGF-ß1) and vascular endothelial growth factor A (VEGF-A) and the severity of coronary atherosclerosis in patients with stable CAD undergoing their first coronary angiography. METHODS: In total, 319 patients with stable CAD who underwent their first coronary angiography at the Silesian Centre for Heart Diseases in Zabrze, Poland were included in the analysis. CAD burden was assessed using the Gensini score. The TaqMan method was used for genotyping of selected functional polymorphisms in the FGF2, PDGFB, TGFB1, IGF1 and VEGFA genes, while rs4444903 in the EGF gene was genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The associations between the selected polymorphisms and the Gensini were calculated both for the whole cohort and for a subgroup of patients without previous myocardial infarction (MI). RESULTS: There were no differences in the distribution of the Gensini score between the genotypes of the analyzed polymorphisms in FGF2, EGF, IGF1, PDFGB, and TGFB1 in the whole cohort and in the subgroup of patients without previous MI. The Gensini score for VEGFA rs699947 single-nucleotide polymorphism (SNP) in patients without previous myocardial infarction, after correction for multiple testing, was highest in patients with the A/A genotype, lower in heterozygotes and lowest in patients with the C/C genotype, (p value for trend = 0.013, false discovery rate (FDR) = 0.02). After adjustment for clinical variables, and correction for multiple comparisons the association between the VEGFA genotype and Gensini score remained only nominally significant (p = 0.04, FDR = 0.19) under the dominant genetic model in patients without previous MI. CONCLUSIONS: We were unable to find strong association between analyzed polymorphisms in growth factors and the severity of coronary artery disease, although there was a trend toward association between rs699947 and the severity of CAD in patients without previous MI.

Prognostic implications of mean platelet volume on short- and long-term outcomes among patients with non-ST-segment elevation myocardial infarction treated with percutaneous coronary intervention: A single-center large observational study.

BACKGROUND: Mean platelet volume (MPV) is a simple and reliable indicator of platelet size that correlates with platelet activation and their ability to aggregate. We studied the predictive value of MPV in patients with non-ST-segment elevation myocardial infarction (NSTEMI) treated with percutaneous coronary intervention (PCI). METHODS: We analyzed the consecutive records of 1001 patients who were hospitalized due to NSTEMI at our center. The primary end point was a composite end point that included the rates of all-cause death, non-fatal myocardial infarction, and acute coronary syndrome (ACS) driven revascularization at 12 months. The enrolled patients were stratified according to the quartile of the MPV level at admission. RESULTS: Along with the increasing quartile of MPV, the 12-month composite end point increased significantly (p = 0.010), and this association remained significant after the risk-adjusted analyses (per 1 fL higher MPV; adjusted hazard ratio [HR] 1.13; 95% confidence interval [CI] 1.02-1.27; p = 0.026). In the multivariate analysis, the MPV was also an independent factor of all-cause mortality (per 1 fL increase; adjusted HR 1.34; 95% CI 1.12-1.61; p = 0.0014) and death or non-fatal myocardial infarction (per 1 fL increase; adjusted HR 1.16; 95% CI 1.03-1.31; p = 0.017). CONCLUSION: In patients with NSTEMI treated with PCI, a high MPV value was associated with a significantly increased incidence of long-term adverse events, particularly for all-cause mortality.

The role of septal perforators and "myocardial bridging effect" in atherosclerotic plaque distribution in the coronary artery disease.

The distribution of atherosclerotic plaque burden in the human coronary arteries is not uniform. Plaques are located mostly in the left anterior descending artery (LAD), then in the right coronary artery (RCA), circumflex branch (LCx) and the left main coronary artery (LM) in a decreasing order of frequency. In the LAD and LCx, plaques tend to cluster within the proximal segment, while in the RCA their distribution is more uniform. Several factors have been involved in this phenomenon, particularly flow patterns in the left and right coronary artery. Nevertheless, it does not explain the difference in lesion frequency between the LAD and the LCx as these are both parts of the left coronary artery. Branching points are considered to be the risk points of atherosclerosis. In the LCx, the number of side branches is lower than in the LAD or RCA and there are no septal perforators with intramuscular courses like in the proximal third of the LAD and the posterior descending artery (PDA). We hypothesized that septal branches generate disturbed flow in the LAD and PDA in a similar fashion to the myocardial bridge (myocardial bridging effect). This coronary architecture determines the non-uniform plaque distribution in coronary arteries and LAD predisposition to plaque formation.

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.

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.

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.

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.

Red cell distribution width is associated with long-term prognosis in patients with stable coronary artery disease.

BACKGROUND: Data regarding the association between red cell distribution width (RDW) values and mortality in patients with stable coronary artery disease are scarce. We aimed to investigate the link between mortality and RDW in patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI). METHODS: We analyzed 2550 consecutive patients with stable coronary artery disease who underwent PCI between 2007 and 2011 at our institution. The patients were divided into four groups according to RDW quartiles. The association between the RDW values and the outcomes was assessed using Cox proportional regression analysis after adjusting for clinical, echocardiographic, hemodynamic and laboratory data in the whole population and in subgroups stratified by gender, presence of diabetes, anemia or heart failure. RESULTS: In the entire population, there was a stepwise relationship between RDW intervals and comorbidities. Patients with the highest RDW values were older and more often burdened with diabetes, heart failure and chronic kidney disease. There was an almost 4-fold increase in mortality during an average of 2.5 years of follow-up between the group of patients with RDW values lower than 13.1% (25th percentile) and the group with RDW values higher than 14.1% (75th percentile), (4.3% vs. 17.1%, p < 0.0001). After adjusting for the covariates, RDW remained significantly associated with mortality in the whole cohort (HR-1.23 [95% CI (1.13-1.35), p < 0.0001]) and in the subgroups stratified by gender, age (over and under 75 years), presence of anemia, diabetes, heart failure and chronic kidney disease. CONCLUSION: Higher RDW values correspond to higher comorbidity burdens and higher mortality. RDW is an independent predictor of mortality in patients with stable coronary artery disease.

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.

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.