Group Of Coronary Artery Disease Patients Research Articles

LEPR isoform expression changes in local fat depots in coronary atherosclerosis and acquired heart defects

Aim. To evaluate the expression of leptin receptor isoforms in local fat depots in patients with coronary artery disease (CAD) and acquired heart defects (AHDs).Material and methods. The study included 120 patients with CAD. The comparison group consisted of 96 patients with degenerative aortic stenosis (AS). Expression of six leptin receptor isoforms (LEPR1, LEPR2, LEPR2/2, LEPR3, LEPR3/2, LEPR4) was assessed using quantitative real-time polymerase chain reaction in subcutaneous (SAT), epicardial (EAT) and perivascular (PVAT) adipose tissue. Statistical processing was carried out using the Statistica 10.0 and SPSS 17.0 for Windows software package.Results. In EAT, minimal expression of LEPR1, LEPR2, LEPR2/2, LEPR3, LEPR3/2, LEPR4 was detected relative to SAT and PVAT in the group of CAD patients. In patients with CAD, mRNA levels of six LEPR isoforms were lower than in patients with AS. In indi­viduals with AHDs, a decrease in the expression of LEPR1, LEPR2, LEPR2/2, LEPR3, LEPR3/2, LEPR4 in SAT relative to EAT and PVAT was recorded. However, only the LEPR1 and LEPR2 isoforms were significantly lower in SAT in patients with AS when com­pared with patients with CAD. In PVAT, the maximum mRNA levels of six LEPR isoforms were found in both groups. There were no significant differences in LEPR1, LEPR2, LEPR2/2, LEPR3, LEPR3/2, LEPR4 expression between patients with CAD and AHDs.Conclusion. Patients with CAD are characterized by a marked decrease in the expression of six LEPR isoforms in EAT. A decrease in the expression of studied LEPR isoforms in EAT is associated with impaired adipogenesis, adipocyte hypertrophy, insulin resistance, increased proinflammatory factors, hyperleptinemia, and progression of atherosclerosis. The identified features of EAT in patients with СФВ can probably have both local and systemic negative effects on the cardiovascular system.

Interrelation of growth/differentiation factor-15 level with laboratory and clinical and functional parameters of patients with coronary artery disease

Growth differentiation factor 15 (GDF-15) is a circulating protein that is associated with various pathological conditions.Aim. To study the relationship between the level of GDF-15 and labo­ratory, clinical and functional parameters of patients with coronary artery disease (CAD).Material and methods. All patients with coronary artery disease under­went a general clinical examination, coronary angiography, extrac­ranial artery ultrasound examination, echocardiography, deter­mi­nation of the serum level of GDF-15 (ng/ml) and matrix metal­lopro­teinase 9 (ng/ml). Statistical processing of the obtained results was carried out using the Statistica 10.0 software.Results. The study included 88 people (55 men and 33 women), 78 of whom were patients with an established diagnosis of CAD and 10 were healthy volunteers (control group). In the group of CAD patients, the median level of GDF-15 was 4,98 ng/ml [3,15; 8,24], while in the cont­rol group — 1,95 ng/ml [0,01; 2,45]. An association of GDF-15 con­centration with the age of patients was found (r=0,44; p<0,001). There was a direct correlation between the level of GDF-15 and interventricular septal thickness (r=0,33; p<0,05), heart failure stage (Strazhesko-Vasilenko classification) (r=0,23; p<0,05), the concentration of matrix metal­loproteinase 9 (r=0,24; p<0,05), carotid intima-media thickness (r=0,28; p<0,05), the number of coronary arteries that required revas­cularization during coronary artery bypass grafting (r=0,52; p<0,05), and multifocal atherosclerosis (r=0,23; p<0,05). In patients with athero­sclerotic lesions in 2 or 3 vascular beds, the level of GDF-15 was signifi­cantly higher than in patients with CAD (p<0,05).Conclusion. The results obtained demonstrate the value of GDF-15 as a potential marker of atherosclerotic vascular changes, the severity of myocardial hypertrophy, and the severity of heart failure.

Associations of non-HDL-C and triglyceride/HDL-C ratio with coronary plaque burden and plaque characteristics in young adults.

Coronary artery disease (CAD) is uncommon in young adult patients. However, these patients have different risk factor profiles and high-risk coronary plaques are more common. The aim of this study was to examine the relations between the coronary plaque burden, plaque composition, serum non-high-density lipoprotein cholesterol (non-HDL-C) levels, and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio in young adults. We analyzed a total of 551 patients under age 45 who had undergone coronary computed tomography angiography (CCTA). Coronary plaque characteristics were analyzed using CCTA. Multivariate linear regression analysis was used to assess the predictors of non-calcified plaque (NCB) and calcified plaque (CB) burdens. Serum non-HDL-C levels and TG/HDL-C ratio were higher in the coronary atherosclerosis patient group. Serum non-HDL-C levels and the TG/HDL-C ratio were higher in the obstructive CAD patient group. The plaque burden was positively correlated with non-HDL-C (r = 0.30; p < 0.001), and TG/HDL-C ratio (r = 0.18; p < 0.001). NCB was positively correlated with age, gender, smoking status, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, serum triglycerides, hbA1c, non-HDL-C, and TG/HDL-C ratio. Non-HDL-C (β coefficient = 0.13; p = 0.023) and TG/HDL-C ratio (β = 0.10; p = 0.042) were independent predictors of NCB. Serum non-HDL-C levels and TG/HDL-C were significantly associated with the presence and burden of coronary plaques. Serum non-HDL-C and TG/HDL-C ratios were independently associated with NCB, suggesting their use as easy-to-compute markers for identifying high-risk groups in young adults.

Associations of Non-High-density Lipoprotein Cholesterol and Triglyceride/High-density Lipoprotein Cholesterol Ratio with Coronary Plaque Burden and Plaque Characteristics in Young Adults.

Coronary artery disease (CAD) is uncommon in young adult patients. However, these patients have different risk factor profiles and high-risk coronary plaques are more common. The aim of this study was to examine the relations between the coronary plaque burden, plaque composition, serum non-high-density lipoprotein cholesterol (non-HDL-C) levels, and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio in young adults. We analyzed a total of 551 patients under age 45 who had undergone coronary computed tomography angiography (CCTA). Coronary plaque characteristics were analyzed using CCTA. Multivariate linear regression analysis was used to assess the predictors of non-calcified plaque (NCB) and calcified plaque (CB) burdens. Serum non-HDL-C levels and TG/HDL-C ratio were higher in the coronary atherosclerosis patient group. Serum non-HDL-C levels and the TG/HDL-C ratio were higher in the obstructive CAD patient group. The plaque burden was positively correlated with non-HDL-C (r = 0.30; p < 0.001), and TG/HDL-C ratio (r = 0.18; p < 0.001). NCB was positively correlated with age, gender, smoking status, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, serum triglycerides, hbA1c, non-HDL-C, and TG/HDL-C ratio. Non-HDL-C (β coefficient = 0.13; p = 0.023) and TG/HDL-C ratio (β = 0.10; p = 0.042) were independent predictors of NCB. Serum non-HDL-C levels and TG/HDL-C were significantly associated with the presence and burden of coronary plaques. Serum non-HDL-C and TG/HDL-C ratios were independently associated with NCB, suggesting their use as easy-to-compute markers for identifying high-risk groups in young adults.

Expression levels of miR-22, miR-30c, miR-145, and miR-519d and their possible associations with inflammatory markers among patients with coronary artery disease.

Coronary artery disease (CAD) is a leading cause of death around the world. Micro-ribonucleic acid (miRNA) can be involved in forming of atherosclerotic plaques, inflammation, cholesterol metabolism, and other mechanisms involved in CAD development. This study aimed to evaluate the expression level of miR-22, miR-30c, miR-145, and miR-519d and their possible association with inflammatory markers among patients with CAD. The expression level of miR-22, miR-30c, miR-145, miR-519d, interleukin 6 (IL-6), and transforming growth factor beta (TGF-β) was determined in peripheral blood mononuclear cells (PBMCs) from 46 patients with CAD and 39 healthy controls using real-time quantitative polymerase chain reaction (qPCR) assay. 53.8% (n = 21) and 52.2% (n = 24) of controls and cases were men, respectively; the mean age was 59.8 ± 7.4 and 57.0 ± 9.8 years, respectively. The miRNA expression pattern of each group showed significantly different expression profiles. In the CAD patients group, miR-22, miR-30c, and miR-145 were down-regulated compared to the control group. On the opposite, miR-519d was up-regulated in patients with CAD compared to the control group. Our results also showed that the expression levels of IL-6 and TGF-β were up-regulated among patients with CAD compared to the control group. In addition, the expression of miR-145 and miR-519d had a significantly negative and positive correlation with TGF-β and IL-6, respectively. The change in expression levels of miR-22, miR-30c, miR-145, and miR-519d in PBMCs of patients with CAD could be considered as a potential biomarker for CAD.

Association of Sirtuin Gene Polymorphisms with Susceptibility to Coronary Artery Disease in a North Chinese Population.

Aims Coronary artery disease (CAD) represents the leading cause of death worldwide. Accumulating evidence also suggests that sirtuins (SIRTS) have been associated with CAD. The present study was aimed at investigating the association between 12 gene polymorphisms for SIRTs and the development of CAD in a Chinese population. Materials and Methods 12 SNPs (rs12778366 (T > C), rs3758391 (T > C), rs3740051 (A > G), rs4746720 (C > T), rs7895833 (G > A), rs932658 (A > C) for SIRT1, rs2015 (G > T) for SIRT2, rs28365927 (G > A), rs11246020 (C > T) for SIRT3, rs350844 (G > A), rs350846 (G > C), and rs107251 (C > T) for SIRT6) were selected and assessed in a cohort of 509 CAD patients and 552 matched healthy controls for this study. Genomic DNA from whole blood was extracted, and the SNPs were assessed using MassARRAY method. Results TT genotype for rs3758391 and GG genotype for rs7895833 of SIRT1 were at higher risk of CAD, whereas the CC genotype for rs4746720 of SIRT1 was associated with a significantly decreased risk of CAD. The A allele of the rs28365927 of SIRT3 showed a significant decreased risk association with CAD patient group (P = 0.014). Significant difference in genotypes rs350844 (G > A) (P = 0.004), rs350846 (G > C) (P = 0.002), and rs107251 (C > T) (P ≤ 0.01) for SIRT6 was also found between the CAD patients and the healthy controls. Haplotype CTA significantly increased the risk of CAD (P = 0.000118, OR = 1.497, 95%CI = 1.218–1.840), while haplotype GCG significantly decreases the risk of CAD (P = 0.000414, OR = 1.131, 95%CI = 0.791–1.619). Conclusions The SNP rs28365927 in the SIRT3 gene and SNP rs350844, rs350846, and rs107251 in the SIRT6 gene present significant associations with CAD in a north Chinese population. Haplotype CTA and GCG generated by rs350846/rs107251/rs350844 in the SIRT6 might also increase and decrease the risk of CAD, respectively.

Differential polarization and the expression of efferocytosis receptor MerTK on M1 and M2 macrophages isolated from coronary artery disease patients

BackgroundDifferential polarization of macrophage into M1 and M2 mediates atherosclerotic plaque clearance through efferocytosis. Higher expression of Mer proto-oncogene tyrosine kinase (MerTK) on M2 macrophage helps in maintaining macrophage efferocytic efficiency. In healthy individuals, macrophage polarization into M1 and M2 occurs in tissues in concomitance with the acquisition of functional phenotypes depending on specific microenvironment stimuli. However, whether the macrophage differential polarization and MerTK expression vary in coronary artery disease (CAD) patients remain unknown.ObjectiveThis study aimed to elucidate the polarization of M1 and M2 macrophage from CAD patients as well as to investigate the expression of MerTK in these macrophage phenotypes.MethodsA total of 14 (n) CAD patients were recruited and subsequently grouped into “no apparent CAD”, “non-obstructive CAD” and “obstructive CAD” according to the degree of stenosis. Thirty ml of venous blood was withdrawn to obtain monocyte from the patients. The M1 macrophage was generated by treating the monocyte with GMCSF, LPS and IFN-γ while MCSF, IL-4 and IL-13 were employed to differentiate monocyte into M2 macrophage. After 7 days of polarization, analysis of cell surface differentiation markers (CD86+/CD80+ for M1 and CD206+/CD200R+ for M2) and measurement of MerTK expression were performed using flow cytometry.ResultsBoth M1 and M2 macrophage expressed similar level of CD86, CD80 and CD206 in all groups of CAD patients. MerTK expression in no apparent CAD patients was significantly higher in M2 macrophage compared to M1 macrophage [12.58 ± 4.40 vs. 6.58 ± 1.37, p = 0.040].ConclusionDifferential polarization of macrophage into M1 and M2 was highly dynamic and can be varied due to the microenvironment stimuli in atherosclerotic plaque. Besides, higher expression of MerTK in patients with the least coronary obstructive suggest its vital involvement in efferocytosis.

Abstract P571: Effects of Renal Insufficiency on Congestive Heart Failure and Coronary Artery Disease Burden in Patients Undergoing Elective Percutaneous Coronary Intervention

Background: We investigated coronary artery disease (CAD) burden and rates of death and stroke in stable patients with renal insufficiency undergoing elective percutaneous coronary intervention (PCI). Methods: Data from 2015 NY state Angioplasty registry was utilized. There were 33,508 PCI recipients (65+/-11 years old; 32% females, 40% with diabetes, 6.4% with COPD, 6.9% with history of CHF, and 8.25% with peripheral artery disease) without history of recent myocardial infarction (MI in less than 24 hours), shock, or prior coronary artery bypass surgery. Patients were divided according to the glomerular filtration rate (GFR) status consistent with the National Kidney Foundation classification: 24% had a GFR more than 90 ml/min (group G1) , 49% GFR of 60-89 (G2), 15% GFR of 45-49 (G3a), 6.9% GFR 30-44 (G3b), 2% GFR of 15-29 (G4), and 4% with GFR of less than 15 ml/min (G5). Results: With decline in GFR, prevalence of CHF increased significantly. CHF was present in 3.6% of G1 patients undergoing elective PCI, 4.49% of G2, 10.20% of G3a, 17% of G3b, 22.26% of G4 and 22.20% of G5 patients (P&lt;0.0001). With decline in GFR, CAD burden was also significantly increased. Left main or three vessel CAD was present in 19.39% of G1 patients undergoing elective PCI, 19.13% of G2, 22.62% of G3a, 25.83% of G3b, 29% of G4 and 27.8% of G5 patients (p&lt;0.001). Furthermore, advanced kidney disease was associated with increased rates of post elective PCI stroke and death. Specifically, post PCI stroke occurred in 0.11% of G1 patients, 0.13% of G2, 0.33% of G3a, 0.27% of G3b, 0.7% of G4, and 0.6% of G5 patients (p&lt;0.001). Similarly, post elective PCI mortality occurred in 0.16% in G1 patients, 0.19% in G2, 0.41% in G3a, 1.04% in G3b, 1.22% in G4 and 1.49% in G5 patients (p&lt;0.0001). After adjustment for co-morbidities such as diabetes, CVD, and COPD, risk of post PCI stroke and death was significantly increased by 3.528 (95%CI 1.866-6.671, p&lt;0.0001) in patients with GFR less than 15 ml/min. Conclusion: In patients undergoing elective PCI, renal insufficiency is associated with increased rates of post-procedural death and stroke as well as increased prevalence of CHF. Additional research is needed to decrease risk of elective interventions in this vulnerable group of CAD patients.

Influence of single nucleotide polymorphisms among cigarette smoking and non-smoking patients with coronary artery disease, urinary bladder cancer and lung cancer.

IntroductionCigarette smoke is suggested to be a risk factor for coronary artery disease (CAD), urinary bladder cancer (UBCa) or lung cancer (LCa). However, not all heavy smokers develop these diseases and elevated cancer risk among first-degree relatives suggests an important role of genetic factor.MethodsThree hundred and ten healthy blood donors (controls), 98 CAD, 74 UBCa and 38 LCa patients were included in this pilot study. The influence of 92 single nucleotide polymorphisms (SNPs) and impact of cigarette smoking were analysed.ResultsOut of 92 SNPs tested, differences in distribution of 14 SNPs were detected between controls and patient groups. Only CTLA4 rs3087243 showed difference in both CAD and UBCa patient group compared to control group. Stratified by smoking status, the impact of smoking was associated to frequencies of 8, 3 and 4 SNPs in CAD, UBCa, LCa patients, respectively. None of these 92 SNPs showed a statistically significant difference to more than one type of disease among smoking patients. In non-smoking patients, 7, 3 and 6 SNPs were associated to CAD, UBCa, LCa, respectively. Out of these 92 SNPs, CTLA4 rs3087243 was associated to both non-smoking CAD and UBCa. The XRCC1 rs25487 was associated to both non-smoking UBCa and LCa.ConclusionSNPs might be important risk factors for CAD, UBCa and LCa. Distribution of the SNPs was specific for each patient group, not a random event. Impact of cigarette smoking on the disease was associated to the specific SNP sequences. Thus, smoking individuals with SNPs associated to risk of these serious diseases is an important target group for smoking cessation programs.

External applicability of the ISCHEMIA trial: an analysis of a prospective, nationwide registry of patients with stable coronary artery disease.

We sought to assess the proportion of patients eligible for the ISCHEMIA trial and to compare the characteristics and outcomes of these patients with those without ISCHEMIA inclusion or with ISCHEMIA exclusion criteria in a contemporary, nationwide cohort of patients with stable coronary artery disease (CAD). Among the 5,070 consecutive patients enrolled in the START registry, 4,295 (84.7%) did not fulfil the inclusion criteria (ISCHEMIA-Not Included or ISCHEMIA-Unclassifiable), 582 (11.5%) had exclusion criteria (ISCHEMIA-Excluded), and the remaining 193 (3.8%) were classified as ISCHEMIA-Like. At one year, the incidence of the primary outcome, a composite of death from cardiovascular (CV) causes, myocardial infarction (MI), or hospitalisation for unstable angina and heart failure, was 0.5% in the ISCHEMIA-Like versus 3.3% in other patients (p=0.03). The composite secondary outcome of CV mortality and MI occurred in 0.5% of the ISCHEMIA-Like patients and in 1.4% of the remaining patients (p=0.1). In a contemporary real-world cohort of stable CAD patients, only 4% resulted in being eligible for the ISCHEMIA trial. These patients presented an extremely low annual risk of adverse events, especially when compared with other groups of stable CAD patients.

Serum discrimination and phenotype assessment of coronary artery disease patents with and without type 2 diabetes prior to coronary artery bypass graft surgery.

Diabetes Mellitus (DM) accelerates coronary artery disease (CAD) and atherosclerosis, the causes of most heart attacks. The biomolecules involved in these inter-related disease processes are not well understood. This study analyzes biomolecules in the sera of patients with CAD, with and without type (T) 2DM, who are about to undergo coronary artery bypass graft (CABG) surgery. The goal is to develop methodology to help identify and monitor CAD patients with and without T2DM, in order to better understand these phenotypes and to glean relationships through analysis of serum biomolecules. Aorta, fat, muscle, and vein tissues from CAD T2DM patients display diabetic-related histologic changes (e.g., lipid accumulation, fibrosis, loss of cellularity) when compared to non-diabetic CAD patients. The patient discriminatory methodology utilized is serum biomolecule mass profiling. This mass spectrometry (MS) approach is able to distinguish the sera of a group of CAD patients from controls (p value 10−15), with the CAD group containing both T2DM and non-diabetic patients. This result indicates the T2DM phenotype does not interfere appreciably with the CAD determination versus control individuals. Sera from a group of T2DM CAD patients however are distinguishable from non-T2DM CAD patients (p value 10−8), indicating it may be possible to examine the T2DM phenotype within the CAD disease state with this MS methodology. The same serum samples used in the CAD T2DM versus non-T2DM binary group comparison were subjected to MS/MS peptide structure analysis to help identify potential biochemical and phenotypic changes associated with CAD and T2DM. Such peptide/protein identifications could lead to improved understanding of underlying mechanisms, additional biomarkers for discriminating and monitoring these disease conditions, and potential therapeutic targets. Bioinformatics/systems biology analysis of the peptide/protein changes associated with CAD and T2DM suggested cell pathways/systems affected include atherosclerosis, DM, fibrosis, lipogenesis, loss of cellularity (apoptosis), and inflammation.

Association of leptin and leptin receptor polymorphisms with coronary artery disease in a North Chinese Han population.

INTRODUCTION: Leptin (LEP) is a peptide hormone that acts via leptin receptor (LEPR) binding. Genetic evidence from different human populations has implicated LEP/LEPR in the pathogenesis of coronary artery disease (CAD), and suggests that certain LEP/LEPR gene polymorphisms may increase the risk of CAD. The aim of this study was to assess two single nucleotide polymorphisms (SNPs) in LEP genes (rs2167270 and rs7799039) and two in LEPR genes (rs6588147, rs1137100) for association with CAD.METHODS: We enrolled 271 North Chinese Han CAD patients, and 113 healthy age- and sex-matched controls. Genomic DNA was extracted from whole blood, and the four SNPs were assessed using a MassArray system.RESULTS: The G allele frequency at rs2167270 was significantly higher among CAD cases than among controls. The AG genotype at rs7799039 was associated with a significantly decreased risk of CAD unlike the AA genotype used as the reference. The A allele was significantly associated with the CAD patient group. Interestingly, statistically significant differences in genotype and allele frequency at LEP rs2167270 and rs7799039 existed among females but not among males. CONCLUSIONS: The current study detected a significant association between genetic variations at LEP rs7799039 and rs2167270 and the risk of CAD in a north Chinese population, and revealed that LEP rs2167270 and rs7799039 gene polymorphisms might act as predisposing factors for CAD.

265Amyloid beta 1-40 and its upstream regulatory pathway BACE1-AS long noncoding RNA/BACE1 are associated with presence and severity of human atherosclerotic disease

Abstract Background Amyloid-beta (1-40) (Aβ1–40), a proinflammatory and pro-atherosclerotic peptide, is associated with accelerated atherosclerosis and major adverse cardiac events. Abeta1–40 production is mainly dependent on the cleavage of amyloid precursor protein by β-amyloid cleaving enzyme-1 (BACE1), known as beta-secretase. BACE1 antisense (BACE1-AS) is a long noncoding RNA that enhances BACE1 stability. Objectives To evaluate the clinical value of plasma amyloid-beta levels and its upstream regulatory pathway BACE1/BACE1-AS in patients with subclinical and established atherosclerotic cardiovascular disease. Methods Plasma levels of Aβ40 were measured in 642 consecutively recruited patients with and without clinically overt coronary artery disease (CAD). BACE1-AS lncRNA and BACE1 mRNA expression were measured in peripheral blood mononuclear cells derived from 214 study participants. Intima-media thickness and atheromatous plaques by ultrasonography, markers of arterial wave reflections and pulse wave velocity were used as surrogate markers of subclinical CVD. Cardiovascular risk factors (CVRFs), including impaired glomerular filtration rate (&lt;60 ml/min), smoking, hypertension, hyperlipidemia, diabetes, obesity and increased hsCRP (&gt;2 mg/l) were assessed as a measure of CVRF burden. Results Both in non-CAD (n=369) and CAD (n=273) patients, Aβ1–40 was associated with age, aortic and peripheral systolic and pulse pressure, and low GFR (p&lt;0.05 for all). In non-CAD subjects Aβ1–40 also correlated with diabetes and low HDL. Importantly, Aβ1–40 was associated with the presence of any plaque in subjects without CAD (p=0.035) and with increased number of diseased coronary arteries (p=0.022) independently of age, gender and CVRFs. Aβ1–40 plasma levels were increased in the highest tertile of BACE1 and BACE1AS (p&lt;0.05) while their expression levels were highly intercorrelated (r=0.825, P&lt;0.001). BACE1 and BACE1-AS levels progressively increased across the 3 groups of non-CAD (n=145), stable CAD (n=43) and acute myocardial infarction (n=26) patients (p for trend&lt;0.001). Among non-CAD subjects, both BACE1 and BACE1-AS were increased in individuals with &gt;2 CVRFs. Among CAD patients, BACE1-AS was associated with decreased LVEF (&lt;50%) (adjusted OR=1.92 per 1-SD increase, p=0.047) while BACE1 in the highest tertile was associated with 5-fold higher odds for coronary multi-vessel disease (p=0.004) after adjustment for age, gender and CVRFs. Conclusions Circulating Aβ1–40 and increased expression of its upstream regulators BACE1/BACE1-AS are intercorrelated and associated with the presence and severity of subclinical and clinically overt atherosclerosis. These findings suggest that BACE1-AS/BACE1-mediated increased availability of Aβ1–40 may play a pivotal role in its adverse cardiovascular effects.

Impact of coronary artery disease and percutaneous coronary intervention in women undergoing transcatheter aortic valve replacement: From the WIN-TAVI registry.

To evaluate the impact of coronary artery disease (CAD) with or without recent (≤ 30 days) percutaneous coronary intervention (PCI) in women undergoing transcatheter aortic valve replacement (TAVR). Although women display a specific risk-profile for both PCI and TAVR, the impact of CAD and PCI in the setting of TAVR in women is unclear. The multinational Women's International Transcatheter Aortic Valve implantation registry enrolled consecutive female patients undergoing contemporary TAVR in 19 centers between 2013 and 2015. Patients with available coronary angiography or CT scan in the pre-operative assessment of TAVR were categorized as without CAD, with CAD but no recent PCI and CAD and recent PCI (≤30 days). All events were adjudicated according to the VARC-2 criteria. A total of 787 patients were included in this analysis, among whom 459 (58.3%) had no CAD, 247 (31.4%) had CAD without recent PCI and 81 (10.3%) underwent recent PCI (≤ 30 days before TAVR). After multivariable adjustment, both groups of CAD patients, without and with recent PCI, presented with higher risk of death, myocardial infarction or stroke, compared with patients without CAD (adj HR 1.56, 95%CI 1.03-2.39, P = 0.038 and adj HR 1.96, 95% CI 1.1-3.5, P = .021, respectively). Patients with recent PCI had increased risk of all-cause death (adj HR 1.89, 95% CI 1.0-3.5, P = 0.04) and stroke (adj HR 3.7, 95% CI 1.0-13.5, P = 0.046) compared with patients without CAD. The presence of CAD in women undergoing TAVR, with or without recent PCI, was associated with long-term poorer outcomes.

Genetic and Environmental Dispositions for Cardiovascular Variability: A Pilot Study

Background: The aim of our study was to evaluate the degree of genetic homozygosity in the group of patients with coronary artery disease (CAD), as well as to evaluate morphogenetic variability in CAD patients regarding the presence of investigated risk factors (RF) compared to a control sample of individuals. Additionally, we aimed to evaluate the distribution of ABO blood type frequencies between tested samples of individuals. Methods: This study analyzed individual phenotype and morphogenetic variability of 17 homozygously-recessive characteristics (HRC), by using HRC test in a sample of 148 individuals in CAD patients group and 156 individuals in the control group. The following RF were analyzed: hypertension, diabetes mellitus, hyperlipidemia, and smoking. Results: The mean value of HRC in CAD patients is significantly higher, while variability decreases compared to the control sample (CAD patients: 4.24 ± 1.59, control sample: 3.75 ± 1.69; VCAD-patients = 37.50%, VC = 45.07%). There is a significant difference in individual variations of 17 HRC between control sample and CAD patients (χ2 = 169.144; p < 0.01), which points out to different variability for tested genes. Mean values of HRC significantly differed in CAD patients in regard to the number of RF present. A blood type (OR = 1.75) is significant predictor for CAD, while O blood type (OR = 0.43) was significantly associated with controls. Conclusion: There is a higher degree of recessive homozygosity in CAD patients versus individuals in the control sample, and the presence of significant variations in the degree of recessive homozygosity as the number of tested RF increases.

Neutrophyl to lymphocyte ratio and c reactive protein are indipendent predictors of severe coronary artery disease: comparison with hydroperoxides and consolidated inflammatory markers.

Several inflammatory factors have been determined as indicators of coronary artery disease (CAD) and recently some studies showed neutrophyl to lymphocyte ratio (NLR) as a powerful predictor. The aim of this study was to evaluate NLR, comparing it with the consolidate inflammatory and oxidative stress marker in a group of control and CAD patients. Twenty healthy subjects and 47 patients, that were affected by 1-4 compromised coronary arteries, were enrolled in the study. All subjects were classified into 3 groups on the base of NLR tertile. The efficacy of NLR as indicator of the severity of CAD and its association with inflammatory markers were analyzed. According to the tertile of NLR, patients in the high NLR value had higher % of males, number of compromise coronary arteries, CRP levels, neutrophyl count, and low lymphocyte count. Moreover NLR and CRP levels showed to be independent predictors of 3-4 compromised coronary arteries. The ROC curve analysis showed that CRP and NLR markers had the largest area under the curve (AUC = 0,85, 95% CI: 0,74-0,96, p = 0,000; AUC = 0,81, 95% CI: 0,66-0,96, p = 0,001). In conclusion our data indicate that only NLR and CRP are independent predictors for 3-4 compromised coronary arteries.

Impact of coronary artery disease on augmentation index as measured by estimated central blood pressure: A case control study in Asian Indians

AimsWe compared various components of blood pressure and arterial stiffness of healthy control with those of coronary artery disease (CAD) patients using BP+ machine™. MethodsIn this prospective, case-control study, total 585 individuals of both the genders were enrolled. The study population consisted of 277 controls (healthy siblings of diseased subjects not having CAD – group A) and 308 CAD patients (group B). Age and sex adjusted regression and receiver operative curve (ROC) analysis was performed to assess the strength of association of these parameters. ResultsWe found that mean systolic blood pressure (SBP) (137.14±22.49 vs. 129.26±19.86), central systolic blood pressure (CSBP) (130.78±21.89 vs. 117.53±17.98), augmentation index (AI) (108.55±44.98 vs. 49.38±21.03) and pulse rate variability (98.82±231.09 vs. 82.86±208.77) were significantly (p<0.05) higher in CAD population as compared to healthy counterparts. Left ventricular contractibility as measured by dP/dt was significantly lower in CAD patients. All these parameters were significantly abnormal in CAD as compared to healthy control population irrespective of the gender of the patient except for SBP in females. Both – odds ratio (1.108; 95% CI: 1.081–1.135; p<0.0001) and ROC analysis (AUC: 0.937; 95% CI: 0.919–0.956; p<0.0001) showed AI as the strongest predictor of CAD, closely followed by CSBP. ConclusionCentral aortic blood pressure parameters such as AI and CSBP measured noninvasively with BP+ machine could be the effective predictors of CAD in Asian Indians.

Impaired Left Atrial Conduit Function in Coronary Artery Disease Patients With Poorly Controlled Diabetes: Two-Dimensional Speckle-Tracking Echocardiographic Study.

The myocardium can be affected by diabetes mellitus. The effects of blood glucose control on some organs such as the kidney and eye have been previously reported. The aim of our study was to evaluate left atrial function via 2-dimensional (2D) speckle-tracking echocardiography in a group of coronary artery disease (CAD) patients with well-controlled diabetes (hemoglobin A1c [HbA1c] < 7%) and to compare it with that in a group of CAD patients with poorly controlled diabetes. This cross-sectional study included 110 CAD patients, comprising 44 euglycemic control patients, 33 patients with well-controlled diabetes (HbA1c < 7%), and 33 patients with poorly controlled diabetes. The study population thereafter underwent 2D speckle-tracking echocardiography for an evaluation of their left atrial function. Our findings showed that the absolute values of early diastolic strain and early diastolic strain rate were lower in the CAD patients with poorly controlled diabetes than in the euglycemic control patients with CAD. Moreover, early diastolic strain in the CAD patients with poorly controlled diabetes was lower than that in the CAD patients with well-controlled diabetes. Multivariable analysis revealed that poorly controlled diabetes was an independent determinant of early diastolic strain and strain rate. The conduit function of the left atrium was impaired in the CAD patients with poorly controlled diabetes compared with that in the euglycemic control patients with CAD and the CAD patients with well-controlled diabetes.

AGTR1 rs3772622 gene polymorphism increase the risk of nonalcoholic fatty liver disease patients suffer coronary artery disease in Northern Chinese Han population.

BackgroundCardiovascular disease (CAD) responsible and nonalcoholic fatty liver disease (NAFLD) are both metabolic diseases, and they are mostly influenced by genetic factors. The aim of our study is to evaluate the relationship between angiotensin II type-1 receptor (AGTR1) gene rs3772622 polymorphisms and the risk of developing coronary artery disease (CAD) in Chinese patients with NAFLD.MethodsGenotype for AGTR1 rs3772622 in 574 NAFLD patients with CAD or 589 NAFLD patients without CAD, 332 CAD patients exclude NAFLD and 338 health control subjects were determined by sequencing and polymerase chain reaction analysis. Relevant statistical methods were employed to analyze the genotypes, alleles and the clinical date. Inter-group differences and associations were assessed statistically using t-tests and Chi square and logistic analyses. The relative risk of AGTR1 rs3772622 for NAFLD was estimated by logistic regression analysis.ResultsNo significant difference in genotype and allele frequency of AGTR1 rs3772622 was found between the NAFLD without CAD population and the controls (P > 0.05). However, makeable difference was found when compared the CAD in patients with NAFLD and CAD free NAFLD patients (P < 0.001 OR = 2.09). Similarly, significant difference was found in AGTR1 rs3772622 genotype distribution between the groups of CAD patients and control (P = 0.046 OR = 1.71).ConclusionsAGTR1 rs3772622 gene polymorphism was not associated with the risk of NAFLD, but could increase the risk of NAFLD patients suffering from CAD in the Chinese Han population. Deeply mechanisms underlying the association between AGTR1 rs3772622 gene polymorphism and the risk of CAD in NAFLD patients need more research.

Endothelial nitric oxide gene polymorphisms and their association with coronary artery disease in Tunisian population

Objective:By releasing mediators, like nitric oxide (NO), vascular endothelium is considered so significant in the process of atherosclerotic. In fact, the major functions of NO consist in inhibiting the activation of platelet, relaxing the muscles (vascular and smooth ones), and modulating the growth and the migration of cells (vascular and smooth ones). Therefore, this process makes the endothelial nitric oxide synthase (NOS3) considerably important because it possesses atheroprotective activity. Polymophisms, rs1808593 (10G/T) as well as rs891512 (G24943A) within NOS3 gene, play major role in the coronary artery disease (CAD) development. The aim of the study is to evaluate the relationship between the 10G/T and G24943A polymorphisms and the CAD among Tunisian individuals.Methods:We included, in this survey, a set of 274 patients suffering from CAD together with 162 normotensive subjects. The PCR-RFLP was app- lied to analyze the polymorphism of intron 23 (10G/T) gene, while the ASA-PCR was used to analyze the intronic G24943A gene polymorphism. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association bet- ween NOS3 10G/T and G24943A polymorphisms as well as CAD risk. Statistical analysis was performed with SPSS V.10.Results:The genotype frequencies for G24943A polymorphism differed significantly between the CAD patients and the controls. The former had a frequency of 11.4% for the AA genotype, 34.7% for the GA genotype and 53.9% for the GG genotype. The latter had a frequency of only 2.5% for the AA genotype, 29.7% for the GA genotype and 67.7% for the GG genotype (χ2=7.62; OR=1.79; p=0.006). The CAD patient group showed a significantly-higher frequency of the A allele compared to the controls (0.28 vs. 0.16; χ2=15.20; p<0.001). The odds ratio of CAD for A vs. G allele frequency was statistically significant 1.99 (1.4–2.82) at 95% CI. The genotype distribution for the 3 investigated variants of 10G/T were not significantly different between CAD and control subjects (χ2=1.46; OR=1.72; p=0.22). Whereas, 10G/T has revealed barely allelic (χ2=4.45; OR=2.3; p=0.034) correlation with coronary artery diseaseConclusion:The present study was designed so that there would be an association between the CAD and NOS3 polymorphism (G24943A). Howe- ver, these results have proven that the polymorphism of 10G/T is not associated with CAD in the Tunisian population.