Abstract Background The cardiovascular death rate significantly declined last decades. But premature atherosclerosis burden remains an unresolved problem. Purpose The study aimed to assess the association of clinical factors with types of premature atherosclerosis onset. Methods Date of 702 patients (pts) (523 men and 179 women) with premature atherosclerosis (men ≤55 (48.6±6.2), women ≤60 (52.7±7.0) years of age) were analyzed with decision tree method using SPSS 23.0 program with the Python GUI module. Clinical and instrumental variables (n=109) were used. The test sample was formed by the cross-validation method. Results Myocardial infarction at the onset of atherosclerosis (n=542, 77.2%) was associated with the presence of peripheral atherosclerosis (1st order node, p<0.0001, F=93.174). The 2nd order node was a uric acid level (p<0.0001, F=26.493) in pts without peripheral atherosclerosis. In pts with uric acid level, less than 225 mmol/L-the left ventricle posterior wall thickness more than 10 mm was a 3d order node (p<0.0001, F=30.143). Area under the ROC-curve 0.916, p=0.011. Multivessel lesion according to coronary angiography data (102 patients) was associated with family history of cardiovascular disease (p=0.001, F=13.238), the area under the ROC-curve was 0.667, p=0.041. For pts. with peripheral atherosclerosis (n=66, 9,4%) the aortic root diameter obtained by an echo was the 1st order node (p<0.0001, F=36.057). In pts with aortic root diameter over 27 mm, a 2nd order node was creatinine level above 90 mmol/L (p=0.036, F=9.945) and in pts with a smaller diameter of aortic root was the history of hypertension emergency (p=0.001, F=13.897). Area under the ROC-curve 0.676, p=0.02. For pts. with ischemic stroke (n=26, 3,7%) as atherosclerosis onset 1st order node was brachiocephalic atherosclerosis lesion (p<0.0001, F=30.259). Among them, untarget BP level was 2nd order node (p=0.033, F=4.958). For pts without atherosclerosis age over 46.7 yrs was a 2nd order node (p<0.0001, F=24.515), and for pts younger than 46.7 yrs admission glucose higher than 11.06 mmol/L was a 3rd order node (p=0.026, F=12.382). This model had high predictive accuracy (area under the ROC-curve 0.963, p<0.0001). Conclusion Thus multiple clinical variants of premature atherosclerotic cardiovascular disease onset appeal to develop an individualized approach to early diagnosis and management of this kind of patient. Funding Acknowledgement Type of funding sources: None.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease which plays an important role in the regulation of LDL receptor (LDLR) expression and apolipoprotein B (apoB) lipoprotein cholesterol metabolism. It is well known that hepatic PCSK9 expression, its activity and secretion influence cholesterol homeostasis. An upregulation of PCSK9 causes an increase of LDLR degradation, which results in decrease of apoB lipoprotein uptake, and a consequent increase in plasma lipoprotein concentration, including LDL. Therefore, PCSK9 has become a new target for lipid lowering therapy. The aim of this review is to consider current data on metabolic and dietary regulation of PCSK9 and its effect on cholesterol and apoB lipoproteins metabolism and risk of cardiovascular disease.
Abstract Background Genetic predisposition makes a considerable contribution to premature acute coronary syndrome (ACS) development. Tumour necrosis factor (TNF) is an important proinflammatory cytokine influencing intravascular inflammation. Annexin A2 (ANXA2) is an endogenous PCSK9 inhibitor. Higher LDL level is associated with AA genotype of ANXA2 gene SNP rs17845226. Aim The aim of the study was to elucidate the association of TNF and ANXA2 gene polymorphism with coronary angiography features and outcome in patients (pts) with early ACS. Methods We analyzed data from two prospective observational trials (2004–2007; 2014–2016) - 672 pts (498 men and 174 women) with premature ACS (men≤55, women≤60 years of age). Coronary angiography (CAG) data were analyzed in 225 pts. Genotyping of SNP rs1800629 of TNF (502 pts) and rs17845226 of ANXA2 gene (235 pts) was performed by RT-PCR with allele-specific primers. The primary endpoint was calculated as a combination of all-cause mortality, recurrent ACS, stroke, and peripheral vascular disease. We also analyzed recurrent coronary events (CE) (coronary deaths & recurrent ACS). The mean follow-up time: 414±347.6 days. Results Mean age was 48.6±5.8 (M), 52.7±6.3 (F) years. 298 (44.3%) pts had STEMI, 362 (53.9%) pts – history of CAD, 500 (74.4%) – arterial hypertension, 32 (4.8%) – history of stroke, 81 (12.1%) – diabetes mellitus, 241 (37.1%) – heart failure (HF). The genotype distribution did not differ from the expected Hardy–Weinberg equilibrium: GG/AG/AA=0.557/0.191/0.006 (χ2=3.34, p=0.07) for TNF and CC/AC/AA=0.86/0.136/0.004 (χ2=0.05, p=0.82) for ANXA2. Carriers of allele A of TNF gene SNP had higher frequency of no significant coronary lesion (17.6% vs 5.9%; p=0.021) and NSTEMI (69.5% vs 50.8%, p<0.001). Carriers of allele A of ANXA2 gene SNP had higher frequency of coronary calcinosis (39.3% vs 19.6%; p=0.019) and HF (39.4% vs 22.3%, p=0.034). Carriers of A allele of TNF had higher frequency of CE (30.5% vs 19.5%, p=0.01, log-rank χ2=7.29, p=0.007). HF (OR, 2.686; 95% CI, 1.769–4.077; p<0.001), creatinine level (OR, 1.009; 95% CI, 1.001–1.017; p=0.025) and carrying of A allele of TNF gene SNP (OR, 1.836; 95% CI, 1.163–2.898; p=0.007) and STEMI at admission (OR, 1.009; 95% CI, 1.001–1.017; p=0.025) were independent predictors of any unfavorable outcome and CE in a multivariable Cox regression model. LAD and left main coronary artery involvement (OR, 1.836; 95% CI, 1.163–2.898; p=0.007) was an independent predictor of any unfavorable outcome. Identified relationship was independent of invasive treatment of ACS. Conclusion Thus, in patients with early ACS TNF mediated inflammation is associated with NSTEMI, no significant coronary lesion and could play a significant role in the development of unfavourable outcome. Carrying of A allele of ANXA2 gene may accelerate coronary atherosclerosis in these patients and is associated with HF.
To use quality indicators to study the management of ST-segment elevation myocardial infarction (STEMI) in different regions.Prospective cohort study of STEMI within 24 h of symptom onset (11 462 patients, 196 centres, 26 European Society of Cardiology members, and 3 affiliated countries). The median delay between arrival at a percutaneous cardiovascular intervention (PCI) centre and primary PCI was 40 min (interquartile range 20-74) with 65.8% receiving PCI within guideline recommendation of 60 min. A third of patients (33.2%) required transfer from their initial hospital to one that could perform emergency PCI for whom only 27.2% were treated within the quality indicator recommendation of 120 min. Radial access was used in 56.6% of all primary PCI, but with large geographic variation, from 76.4 to 9.1%. Statins were prescribed at discharge to 98.7% of patients, with little geographic variation. Of patients with a history of heart failure or a documented left ventricular ejection fraction ≤40%, 84.0% were discharged on an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and 88.7% were discharged on beta-blockers.Care for STEMI shows wide geographic variation in the receipt of timely primary PCI, and is in contrast with the more uniform delivery of guideline-recommended pharmacotherapies at time of hospital discharge.
BACKGROUND: Genetic factors are essential for the pathogenesis of coronary heart disease (CHD). This study presents the role of genetic factors in a prematurely developing disease in males under 55 years old and females under 60 years old. Additionally, genetic risk factors may also be significant for CHD development in other age groups although specific genetic factors may differ.
AIM: The work aimed to analyze the prevalence of hereditary genetic factors in different age groups in patients with coronary heart disease.
MATERIALS AND METHODS: The study was conducted as part of the analysis of data from two observational multicenter Russian studies of acute coronary syndrome (ACS) ORACUL I (1193 patients) and ORACUL II (1803 patients) (the study was registered on ClinicalTrials.gov with an ID number NCT04068909). The average age of patients was 63.512.45 years (1875 men and 1121 women). The study of a panel of candidate genes was performed using the polymerase chain reaction method.
RESULTS: In order to analyze the significance of hereditary factors in patients of different ages, groups of patients with early development of CHD (men under 55 years old, women under 60 years old) were formed (n=828). The middle-aged group included men aged 5574 years and women aged 6074 years (n=1410). The older age group consisted of patients aged 75 years and older (n=602). In the group of patients with early onset coronary heart disease, the proportion of patients with aggravated heredity was higher. In the older age group, the proportion of patients with non-burdened or unknown heredity was higher. Significant differences in the frequencies of alleles and genotypes of the polymorphic variants studied by us were revealed only for the G-2667C variant of the CRP gene (the frequency of the GG genotype was 87.3% in young patients and 77.2% in the elderly and old patients (p=0.007) and for the C804A variant of the LTA gene (frequency of the CC genotype was 52 0% in young patients, 49.4% in middle-aged patients, and 34.2% in elderly and old patients, p=0.026).
CONCLUSIONS: A burdened family history is more common among patients with early onset coronary artery disease. The differences revealed in the frequencies of genetic variants of genes encoding anti-inflammatory cytokines may indicate their role in the pathogenesis of coronary heart disease in older individuals.
Abstract Introduction Familial hypercholesterolemia (FH) is the most common genetically inherited disease in the world, which leads to a significant increase in blood cholesterol and an increased risk of early atherosclerosis and, consequently, an increase in mortality from ischemic heart disease (IHD). The actual prevalence of genetic variants causing FH in every population remains unknown. Purpose To compare the frequency of mutations in patients with FH who underwent acute coronary syndrome (ACS) and patients with stable IHD. Material and methods We included 120 patients (male-79, female-41) who had a clinical diagnosis of FH based on the Dutch Lipid Clinic Network (DLCN) score and Simon Broome criteria. The men and women included in the study were ≤55 and ≤60 years of age, respectively. 40 of them were patients with ACS; the remaining 80 were patients with stable IHD. Genetic studies were performed using a multiple approach based on targeted Next Generation Sequencing (NGS) in the Health in code and the ReadSense laboratories. Results Variants of the three “classic” genes implicated in FH were detected in 46 patients (38,3%). The frequency of mutations was detected in 32.5% of cases, and in patients with stable IHD in 41.25% of cases (p=0.35). In the group of participants with stable IHD, a mutation in the LDLR gene was obtained in 85% of cases; mutations in the APOB, PCSK9 genes were detected in 15% of cases. The same rate of mutations in the APOB and LDLR genes (38.5% each) was detected in patients with ACS. One patient had a mutation in the PCSK9 gene. In two patients there were mutations at once in two genes responsible for the development of FH: in one case, mutations were determined in the APOB and LDLR genes, in the other - LDLR and PCSK9. All patients who carried variants of the studied genes were heterozygous. Patients with clinically established FH had mutations in other genes involved in lipid metabolism, such as APOE, which turned to be mutant in 20 participants (16,6%). This variant defines the apoE4 isoform (also called ε4 allele), which is one of the three common genetic isoforms (apoE2, apoE3, and apoE4) of the APOE gene. It has been shown that the choice of apoE4 isoform have TC and LDL levels and increased risk of cardiovascular events related to atherosclerosis. Two patients had LPA mutations. This variant is a genetic polymorphism that has been previously published in association with elevated lipoprotein (a) (Lp(a)) levels and increased risk of IHD. Three patients were found to have ABCG8 mutations thought to be associated with sitosterolemia: two were pathogenic and another one of uncertain significance. Conclusion Thus, the frequency of mutations in patients with FH does not depend on the presence or absence of ACS. Both groups of patients are patients of a very high risk of developing both primary and repeated cardiovascular events.
The search for causal factors that can influence the prognosis after an acute coronary syndrome in elderly patients is a critical task. This study aimed to assess the correlation between increased uric acid levels with the incidence of adverse outcomes in patients over 75 years of age with history of acute coronary syndrome. Medical Records of 343 patients over 75 years old with history of acute coronary syndrome were retrospectively reviewed. Clinical characteristics and laboratory data upon admission, whether deceased or survived, were also analyzed. When carrying out multivariate analysis, following factors independently associated with total mortality were analyzed: aortic stenosis, atrial fibrillation, hyperglycemia, and acute heart failure at the moment of the index event, hyperuricemia, and percutaneous coronary intervention at the time of hospitalization caused by the index event. Thus, an increase in the level of uric acid is an independent predictor of lethality in the senior age group patients.
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