Cause Of Atherosclerosis Research Articles

Relationship between high-sensitivity C-reactive protein and subclinical carotid atherosclerosis stratified by glucose metabolic status in Chinese adults.

Atherosclerosis is an inflammatory disease. Many studies demonstrated that hyperglycemia is not only increased inflammatory response, but also is a cause of atherosclerosis, implying that glucose metabolic status may be an important stratification factor when analyzing the relationship between inflammatory levels and subclinical carotid atherosclerosis. The aim of the present study is to assess the relationship between inflammatory levels and subclinical carotid atherosclerosis, stratified by different glucose metabolic status in a general population. An assessment was performed in 7975 participants living in Tianjin, China. In the present study, we examined subclinical carotid atherosclerosis, as defined by increased carotid intima-media thickness [IMT] and plaques. Measurements were performed using a carotid artery B-mode ultrasound system. The glucose metabolic status was defined by the criteria of the American Diabetes Association, and high-sensitivity C-reactive protein (hs-CRP) as an inflammatory indicator, was measured by immunoturbidimetric assay. Multiple logistic models were used to assess a stratified relationship between hs-CRP levels and subclinical carotid atherosclerosis. Strata were defined according to glucose metabolic status. The prevalence of increased IMT and plaques were 27.3% and 21.3%, respectively. The adjusted odds ratios (95% confidence interval) for IMT across hs-CRP quartiles were as follows: 1.00 (reference), 1.10(0.88-1.38), 1.08(0.86-1.35) and 1.32(1.06-1.66) in blood glucose-normal subjects; 1.00 (reference), 1.33(0.92-1.91), 1.33(0.93-1.91), and 1.59(1.10-2.30) in prediabetic subjects; 1.00 (reference), 0.94(0.54-1.62), 1.17(0.65-2.12) and 0.98(0.55-1.76) in diabetic subjects, respectively. Similar results were observed for plaques. Our results suggest that inflammatory levels are differently related to subclinical carotid atherosclerosis by the different glucose metabolic status.

Association of astragaloside IV-inhibited autophagy and mineralization in vascular smooth muscle cells with lncRNA H19 and DUSP5-mediated ERK signaling

Defective autophagy in vascular smooth muscle cells (VSMCs) is the principal cause of atherosclerosis. This study aimed to investigate the effect of astragaloside IV (AS-IV) on VSMCs autophagy. In vivo, ApoE−/− mice were fed with high-fat diet ad libitum for eight weeks, with or without AS-IV (25 mg/kg, daily). In vitro, human VSMCs were cultured and treated with β-Glycerophosphate (10 mmol/L) and AS-IV (50 μg/ml). VSMCs autophagy, mineralization, expression of p-ERK1/2, p-mTOR, and autophagy-related proteins (LC3 II/I, p62, and Beclin 1) were detected. Increased autophagy and mineralization was observed in VSMCs in thoracic aorta of mice and in in vitro VSMCs model of atherosclerosis. AS-IV administration attenuated the autophagy and mineralization in VSMCs. Reverse expression profiles of H19 and DUSP5 were observed. AS-IV inhibited DUSP5 and autophagy-related proteins and increased expression of H19, level of p-ERK1/2 and p-mTOR. Further, autophagy and mineralization level in VSMCs were in line with DUSP5 expression level, but in contrast to H19, p-ERK1/2, and p-mTOR profiles. We demonstrated that AS-IV could attenuate autophagy and mineralization of VSMCs in atherosclerosis, which may be associated with H19 overexpression and DUSP5 inhibition.

Rosuvastatin protects against oxidized low‑density lipoprotein‑induced endothelial cell injury of atherosclerosis invitro.

Atherosclerosis-induced cardiovascular diseases (CVDs) are accompanied by substantial morbidity and mortality. The loss and injury of endothelial cells is the primary cause of atherosclerosis. Rosuvastatin is an alternative agent used to reduce the risk of cardiovascular disease. Subsequently, the present study aimed to investigate the protective effects of rosuvastatin on oxidized-low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cell (HUVEC) injury. The viability of ox-LDL-cultured HUVECs with or without rosuvastatin (0.01, 0.1 and 1 µmol/l) pretreatment, and pretreatment at different time points (3, 6, 12 and 24 h) was determined using an MTT assay. Morphological changes and the extent of apoptosis were detected; the anti-oxidase activity, including superoxide dismutase (SOD) and catalase (CAT), was examined, and the contents of malondiahdehyde (MDA) and nitric oxide (NO) were measured. The phosphorylation levels of endothelial nitric oxide synthase (eNOS), protein kinase B (Akt) and phosphoinositide 3 kinase (PI3K) were detected using western blot analysis. The results demonstrated that pretreatment with 0.01–1 µmol/l rosuvastatin decreased cell apoptosis caused by ox-LDL. Notably, pretreatment with 1 µmol/l rosuvastatin for >12 h increased cell viability. Additionally, DAPI staining revealed that rosuvastatin inhibited HUVEC apoptosis. Rosuvastatin treatment also resulted in increased SOD and CAT activities and decreased MDA content in ox-LDL-stimulated HUVECs. Furthermore, pretreatment with 0.01–1 µmol/l rosuvastatin significantly increased` the NO content compared with HUVECs treated with ox-LDL alone. Western blot analyses demonstrated that rosuvastatin upregulated the phosphorylation of eNOS, Akt and PI3K. These findings indicated that rosuvastatin could protect HUVECs against ox-LDL-induced injury through its anti-oxidant effect and its ability to upregulate the expression of vascular endotheliocyte-protecting factors.

Genetic variant at coronary artery disease and ischemic stroke locus 1p32.2 regulates endothelial responses to hemodynamics

Biomechanical cues dynamically control major cellular processes, but whether genetic variants actively participate in mechanosensing mechanisms remains unexplored. Vascular homeostasis is tightly regulated by hemodynamics. Exposure to disturbed blood flow at arterial sites of branching and bifurcation causes constitutive activation of vascular endothelium contributing to atherosclerosis, the major cause of coronary artery disease (CAD) and ischemic stroke (IS). Conversely, unidirectional flow promotes quiescent endothelium. Genome-wide association studies (GWAS) have identified chromosome 1p32.2 as strongly associated with CAD/IS; however, the causal mechanism related to this locus remains unknown. Using statistical analyses, assay of transposase accessible chromatin with whole-genome sequencing (ATAC-seq), H3K27ac/H3K4me2 ChIP with whole-genome sequencing (ChIP-seq), and CRISPR interference in human aortic endothelial cells (HAECs), our results demonstrate that rs17114036, a common noncoding polymorphism at 1p32.2, is located in an endothelial enhancer dynamically regulated by hemodynamics. CRISPR-Cas9-based genome editing shows that rs17114036-containing region promotes endothelial quiescence under unidirectional shear stress by regulating phospholipid phosphatase 3 (PLPP3). Chromatin accessibility quantitative trait locus (caQTL) mapping using HAECs from 56 donors, allelic imbalance assay from 7 donors, and luciferase assays demonstrate that CAD/IS-protective allele at rs17114036 in PLPP3 intron 5 confers increased endothelial enhancer activity. ChIP-PCR and luciferase assays show that CAD/IS-protective allele at rs17114036 creates a binding site for transcription factor Krüppel-like factor 2 (KLF2), which increases the enhancer activity under unidirectional flow. These results demonstrate that a human SNP contributes to critical endothelial mechanotransduction mechanisms and suggest that human haplotypes and related cis-regulatory elements provide a previously unappreciated layer of regulatory control in cellular mechanosensing mechanisms.

Current concepts in atherosclerosis

Atherosclerosis is a complex disease process. It is increasingly recognised that both lipoprotein retention and inflammatory cellular components are intricately related in the initiation and development of atherosclerotic plaque. LDL-c (cholesterol) has been long established as a cause for atherosclerosis; additionally, inflammatory cells such as monocytes and subsequently foam cells have also been directly linked to the progression of atherosclerotic disease. Emerging data suggest that structures outside vascular intima and media are also closely related to atherosclerosis. Perivascular adipose tissue (PVAT) may be a determinant of the inflammatory status of the atherosclerotic plaque. All these features are becoming extremely relevant as therapies against atherosclerosis are targeting both lipid retention and inflammation. Recently, there has been some success in these novel therapies, such as the proprotein convertase subtilisin-kexin type 9 (PCSK-9) inhibitor evolocumab and the interleukin-1ß neutralising antibody, canakinumab, in reducing cardiovascular events when added to standard therapy such as statin. This review will discuss the pathogenesis of atherosclerosis, including some novel features, and its management using new anti-atherosclerotic drugs.

Dyslipidemia in pregnancy and maternal-fetal outcome.

Hyperlipidemia is a known cause of atherosclerosis and directly contributes to the current epidemic in cardio-vascular disease. Pregnancy is typified by an increase in serum levels of total cholesterol and triglycerides pushed by the rise in estrogen, progesterone and lactogen. Mobilization of stored fat depots in late pregnancy may provide a reservoir of fatty acids for fetal growth and placental tissue steroid synthesis. This physiologic increase in lipids performs an essential role during pregnancy; however, elevated levels of lipids in predisposed women or with familiar forms of hyperlipidemia can carry increased risk for maternal-fetal complications. The present treatment of pregnant women with hyperlipidemia is the suspension of medications. However, hyperlipidemia during pregnancy is associated with preeclampsia, preterm birth and gestational diabetes and offspring of these mothers show a propensity to enhanced fatty streak formation and an increased risk of progressive atherosclerosis. This current evidence may motivate the further study on the potential benefits of treatment of hyperlipidemia in pregnancy and its effects on maternal-fetal outcomes.

LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature

ABSTRACTIntroduction: For half a century, a high level of total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) has been considered to be the major cause of atherosclerosis and cardiovascular disease (CVD), and statin treatment has been widely promoted for cardiovascular prevention. However, there is an increasing understanding that the mechanisms are more complicated and that statin treatment, in particular when used as primary prevention, is of doubtful benefit.Areas covered: The authors of three large reviews recently published by statin advocates have attempted to validate the current dogma. This article delineates the serious errors in these three reviews as well as other obvious falsifications of the cholesterol hypothesis.Expert commentary: Our search for falsifications of the cholesterol hypothesis confirms that it is unable to satisfy any of the Bradford Hill criteria for causality and that the conclusions of the authors of the three reviews are based on misleading statistics, exclusion of unsuccessful trials and by ignoring numerous contradictory observations.

Identification of 26 novel loci that confer susceptibility to early-onset coronary artery disease in a Japanese population.

Early-onset coronary artery disease (CAD) has a strong genetic component. Although genome-wide association studies have identified various genes and loci significantly associated with CAD mainly in European populations, genetic variants that contribute toward susceptibility to this condition in Japanese patients remain to be definitively identified. In the present study, exome-wide association studies (EWASs) were performed to identify genetic variants that confer susceptibility to early-onset CAD in Japanese. A total of 7,256 individuals aged ≤65 years were enrolled in the present study. EWAS were conducted on 1,482 patients with CAD and 5,774 healthy controls. Genotyping of single nucleotide polymorphisms (SNPs) was performed using Illumina Human Exome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The association between allele frequencies for 31,465 SNPs that passed quality control and CAD was examined using Fisher's exact test. To compensate for multiple comparisons of allele frequencies with CAD, a false discovery rate (FDR) of <0.05 was applied for statistically significant associations. The association between allele frequencies for 31,465 SNPs and CAD, as determined by Fisher's exact test, demonstrated that 170 SNPs were significantly (FDR <0.05) associated with CAD. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of hypertension, diabetes mellitus and dyslipidemia revealed that 162 SNPs were significantly (P<0.05) associated with CAD. A stepwise forward selection procedure was performed to examine the effects of genotypes for the 162 SNPs on CAD. The 54 SNPs were significant (P<0.05) and independent [coefficient of determination (R2), 0.0008 to 0.0297] determinants of CAD. These SNPs together accounted for 15.5% of the cause of CAD. Following examination of results from previous genome-wide association studies and linkage disequilibrium of the identified SNPs, 21 genes (RNF2, YEATS2, USP45, ITGB8, TNS3, FAM170B-AS1, PRKG1, BTRC, MKI67, STIM1, OR52E4, KIAA1551, MON2, PLUT, LINC00354, TRPM1, ADAT1, KRT27, LIPE, GFY and EIF3L) and five chromosomal regions (2p13, 4q31.2, 5q12, 13q34 and 20q13.2) that were significantly associated with CAD were newly identified in the present study. Gene ontology analysis demonstrated that various biological functions were predicted in the 18 genes identified in the present study. The network analysis revealed that the 18 genes had potential direct or indirect interactions with the 30 genes previously revealed to be associated with CAD or with the 228 genes identified in previous genome-wide association studies. The present study newly identified 26 loci that confer susceptibility to CAD. Determination of genotypes for the SNPs at these loci may prove informative for assessment of the genetic risk for CAD in Japanese patients.

Association of pentraxin 3 with atherosclerotic cardiovascular diseases — general knowledge in 2018

Pentraxin 3 (PTX3), an acute phase protein, contrary to C-reactive protein (CRP), is produced locally, where the inflammation takes place, for example in the endothelium. It is not clearly known whether the inflammatory factors are the cause of atherosclerosis or only indicators of vascular inflammation. It is still not known what is the role of PTX in the natural history of atherosclerosis — protection or promotion. It was established that the elevated plasma concentration of PTX is related to the occurrence of cardiovascular events caused by atherosclerosis, including myocardial infarction (MI), decreased 3-months survival after MI, unstable angina or heart failure. On the other hand, PTX is suspected to play a protective role in the ischemic cardiac muscle. Therefore, if confirmed in trials, PTX3 could be administered during acute coronary syndrome. PTX3 might in the future become useful in assessing prognosis for patients with cardiovascular diseases and choosing the best therapeutic option for them.

Spontaneous coronary artery dissections

Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic coronary artery pathology and an important cause of coronary artery disease in young women with an average age of 40 to 50 years with few or no cardiovascular risk factors. There has been a surge in the diagnosis of SCAD due to an increased use of coronary angiography and the clinical availability and application of high-resolution intracoronary imaging. SCAD is due to the separation of coronary wall layers with the formation of intramural hematoma, compression of the true lumen and secondary myocardial ischemia. Coronary angiography is the first-line imaging, also useful are intravascular ultrasound and optical coherence tomography. Therapy is conservative in most cases because of the high percentage of spontaneous healing of the vascular wall. The prognosis is good, although the disease is burdened by a high prevalence of major adverse coronary events, including recurrence of coronary dissection, thus making careful follow-up essential in survivors of the acute event. Given that the presence of SCAD may be associated with aneurysm formation and dissections of other arteries, screening of the arterial tree may be useful, especially of the supra-aortic trunks and splanchnic circulation.

Association between Polymorphisms of Antioxidant Gene (MnSOD, CAT, and GPx1) and Risk of Coronary Artery Disease.

Objective Reactive oxygen species (ROS) been cited as one of the major causes of atherosclerosis and coronary artery disease which are possible agents inducing DNA damage. Manganese superoxide dismutase (MnSOD), catalase (CAT), and glutathione peroxidase-1 (GPx1) have evolved to address primary defense against free radical mediated damage in mitochondria. The aim of this study was to delineate the association of MnSOD, CAT, and GPx1 polymorphisms and risk of CAD in Taiwan. Methods We conducted a case-control study with 657 participants recruited at a medical center. All subjects were evaluated by noninvasive stress test and then quantitative coronary angiography to confirm the diagnosis of CAD. 447 CAD cases were defined as >50% stenosis of coronary artery and 210 controls were stenosed below 50%. Polymorphisms of MnSOD (Val16Ala), CAT (C-262T), and GPx1 (Pro198Leu) genes were determined by polymerase chain reaction methods. Multivariate logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Results The MnSOD Val/Ala+Ala/Ala genotype was significantly associated with an increased risk of CAD compared to the Val/Val genotype (OR = 1.86, 95% CI = 1.15-3.01). This polymorphism was also associated with the severity of CAD of single and two vessel diseases. The corresponding ORs were 2.31 (95% CI = 1.32-4.03) and 1.92 (95% CI = 1.02-3.61), respectively. Among cigarette smokers, the harmful genetic effect of MnSOD Ala allele on CAD risk was much higher (OR = 2.23, 95% CI = 1.02-4.88). However, the interaction between MnSOD genotype and cigarette smoking on CAD risk was not significant. No significant association between CAT and GPx1 polymorphisms and CAD risk was observed. Conclusion Our results suggest that MnSOD polymorphism is an independent risk factor for susceptibility to CAD in the Chinese population.

Adiponectin and coronary artery disease risk: A bi-directional Mendelian randomization study

BackgroundObservational studies have found adiponectin inversely associated with cardiovascular disease thereby indicating a potential target of intervention, but genetically higher adiponectin appears unrelated to coronary artery disease (CAD). To clarify, we examined the role of genetically predicted adiponectin in CAD in a larger study and additionally examined the role of genetically predicted CAD in adiponectin using a bi-directional Mendelian randomization study. MethodsWe obtained estimates using inverse variance weighting (IVW) with multiplicative random effects, based on 21 single nucleotide polymorphism (SNPs) to predict adiponectin and 28 SNPs for CAD, using two large genome wide association studies of adiponectin (ADIPOGen Consortium (n = 39,883)) and CAD CARDIoGRAMplusC4D 1000 Genomes based GWAS (n = 60,801 CAD cases; n = 123,504 controls). Sensitivity analyses included using MR-Egger, weighted median method, and exclusion of potentially invalid (pleiotropic) SNPs. ResultsAdiponectin was inversely associated with CAD (odds ratio 0.82 per unit increase log transformed adiponectin, 95% confidence interval (CI) 0.71 to 0.94) using IVW. However, the association was null using a weighted median method or MR-Egger, or after exclusion of pleiotropic SNPs acting on obesity related traits. CAD was not associated with adiponectin (−0.011 log transformed adiponectin unit per log odds CAD, 95% CI −0.039 to 0.017), with similar findings from MR-Egger, weighted median method or exclusion of pleiotropic SNPs. ConclusionAdiponectin is unlikely a cause of CAD although we cannot completely rule out the possibility. Previous observational studies are likely driven by factors driving both adiponectin and CAD, whose elucidation might provide new insights concerning interventions for CAD.

Oxidant and antioxidant status in coronary artery disease.

Formation of atherosclerotic plaques is the major cause of coronary artery disease (CAD). Several lines of study have revealed the role of oxidative stress in CAD pathogenesis. In the present study the aim was to investigate the oxidative and antioxidative markers in CAD patients and a control population. The study sample comprised of acute coronary syndrome (ACS) patients, chronic CAD patients and healthy controls (n=30/group). Blood samples of patients and control subjects were collected to measure the concentrations of reduced glutathione (GSH), malondialdehyde (MDA) and the percentage of MDA release as well as the activity of erythrocyte glutathione peroxidase (GPx) and total antioxidant capacity (TAC) of plasma. All parameters were measured by spectrophotometric methods. Additionally, oxidant/antioxidant status was compared between CAD patients with single, double or triple-vessel stenosis and in comparison with controls. The results indicated a significant increase in MDA level and the percentage of MDA release (P<0.05), and a marked decrease in GSH concentration (P<0.0001), TAC (P<0.0001) and the activity of erythrocyte GPx (P<0.0001) in the patient groups compared controls. ACS patients exhibited a similar pattern of data when compared with the chronic CAD group. Similar results were also observed when chronic CAD patients with single, double or triple vessel stenosis and controls were compared. The present study indicates that the acute form of CAD is more susceptible to oxidative damage, suggesting that use of antioxidant therapy may be warranted to ameliorate oxidative stress in this condition.

Inverse association of ApoB and HSP60 antibodies with coronary artery disease in Indian population

ObjectiveAtherosclerosis is an autoimmune condition and the underlying cause of coronary artery disease (CAD). Circulating antibodies to self-antigens can have a pathogenic or protective function in atherosclerosis. The objective of...

Study of atherosclerosis in abdominal aortic aneurysms of autopsied patients

BackgroundAny kind of change in the arterial wall as atherosclerosis, may be the etiologic agent of the formation of aneurysm in an artery. The aim of this study was to describe the morphological and morphometric characteristics of the aorta with aneurysm in autopsied patients in relation to age, gender, white and non-white patients and the aortic segment. Methods22 samples of aorta were evaluated, from patients autopsied, grouped in 11 patients with aneurysm and 11 patients without aneurysm. Macroscopic evaluation of the intensity of atherosclerosis has been described quantitatively in centimeters. Staining were made by Picrosirius for quantification of collagen fibers. The analysis of captured images was performed by software Leica QWin Plus®. For statistical, the data were analyzed with the software GraphPad Prism®. ResultsThere was a positive and non significant correlation between the intensity of atherosclerosis and age of the total group (rS = 0.352; p = 0.29).There was a greater intensity of atherosclerosis in relation to age in the group with aortic aneurysm (PA) (U = 26.50; p = 0.03) and higher percentage of collagen fibers (U = 31,950; p < 0.0001)when compared to the NA group. A negative correlation was observed between the percentage of collagen fibers and the intensity of atherosclerosis (rS = −0.109; p = 0.02) (PA). ConclusionsThe intensity of atherosclerosis presented a relation with age, feminine gender, white patients and abdominal aortic segment. The aging process is the cause of atherosclerosis, causing alterations in the arterial walls as an increase of the collagen fibers, thus favoring the appearance of vascular aneurysms.

Abstract 211: MKL1 Affects Proliferation/Survival Property of Pro-Atherogenic Macrophages

Coronary artery disease (CAD) is one of the leading causes of death in the most countries. Atherosclerosis of coronary arteries often results in high incidence of vascular occlusion and is recognized as the major cause of CAD. We have previously reported from a genome-wide association study that a promoter SNP in megakaryoblastic leukemia 1 gene ( MKL1 ), which conferred higher transcriptional activity, was significantly associated with the susceptibility to CAD as well as coronary atherosclerosis. MKL1 is a Rho-Rock signaling-responsive co-activator of serum response factor, and regulates a variety of cellular functions. We found that MKL1 was highly expressed in activated macrophages in the neointima of atherosclerotic lesions from human and ApoE-knockout (KO) mouse. In addition, the expression level of MKL1 in lesional macrophages was increased during the development of atherosclerosis in ApoE-KO mice. We have established a transgenic mouse line, MKL1-TgM, in which human MKL1 was specifically overexpressed in monocyte/macrophage lineage cells. In this study, MKL1-TgM was crossbred onto ApoE-KO background. ApoE-KO/MKL1-TgM fed with normal chow developed severer atherosclerosis and showed poorer survival rate than ApoE-KO mice. Serum level of pro-inflammatory cytokines was increased in ApoE-KO/MKL1-TgM. Interestingly, ApoE-KO/MKL1-TgM also developed hypertriglyceridemia, which was associated with severe lipodystrophy. We also investigated how MKL1 regulated macrophages function. Recently, local proliferation/accumulation of lesional macrophages was reported to be a crucial event in atherosclerosis. We treated bone marrow-derived macrophages (BMDMs) with stimuli, such as M-CSF or OxLDL, and found that proliferation property of BMDMs from MKL1-TgM was elevated. On the other hand, BMDMs from MKL1-TgM were more resistant to apoptosis. Furthermore, immunohistochemistry analyses of lesional macrophages in ApoE-KO/MKL1-TgM showed enhanced proliferation and mitigated apoptosis. Taken together, our data indicated that MKL1 would contribute to the development of atherosclerosis by modulating pro-atherogenic functions of macrophages, providing a potential molecular target for the therapy and prevention of atherosclerosis.

Abstract 412: Dietary Lectins Cause Coronary Artery Disease via an Autoimmune Endothelial Attack Mediated by Interleukin 16

Interleukin 16 (IL-16) is a chemoattractant released by endothelial and other cells to attract activated T cells. It has previously been shown to have expression in many autoimmune diseases (AI). Based on our previous reports using elevated adiponectin levels of 16 ug/mL to predict lectin sensitivity, and showing an association between lectins and AI causation, we have treated a large pt population with known autoimmune disease (as confirmed by markers). We recently began using the PULS Cardiac Test (GD Biosciences Lab, Irvine, CA) a validated blood test for predicting 5 year risk of acute coronary syndrome (ACS) to examine which measured biomarkers predominate in these patients. 325 consecutive pts aged 25-89 had PULS tested as part of a comprehensive blood panel, which also screens for 14 autoimmune disease markers. The PULS tests ranks 9 biomarkers, including IL-16, MCP-3, Eotaxin, CTACK, sFas, Fas Ligand, HGF for ACS risk, ranking each biomarker from lowest to highest level contributing to risk. 241 pts (74%) were positive for elevated adiponectin, hx of AI, and/or markers for AI. Of these pts, 223 (93%) were positive for IL-16 as the highest PULS risk factor. In contrast, of the other 84 pts without AI or adiponectin elevation, only 5 (6%) had IL-16 recorded as a risk. We conclude that based on IL-16 testing via PULS, that this provides further evidence to support an autoimmune cause of coronary artery disease at the endothelial level via T cell activation and attraction in patients with gluten and lectin sensitivity or known autoimmune disease. It also explains the known high association of autoimmune disease and ACS.

Abstract 174: Lipid Levels after Acute Coronary Syndromes: a Perspective from a General Hospital

Background: Low-density lipoprotein cholesterol (LDL-C) is a risk factor and even cause of atherosclerosis. High dose statins early in all Acute Coronary Syndrome (ACS) patients are now recommended. . Mean serum LDL-C vary relatively little over the early days of ACS and lipid therapy generally is not considered a priority during ACS . Initiation of statin is strongly associated with their use after discharge Purpose: To evaluate our data on lipids after ACS and compare with current standards of therapy. Methods: 100 patients were analyzed during 6 months in 2016 in a step-down unit with ACS -unstable angina (UA), myocardial infarction with ST elevation (STEMI) and without ST elevation (NonSTEMI). Data regarded age, gender, type of ACS, coronary angiogram , medical therapy, lipid levels. Symmetric variables are described by mean and standard deviation(sd) and asymetric by the median and interquartile range. Categorical variables are described by frequencies and percentages . 95% confidence intervals for percentages are presented for main results. Results: 56 men, 44 women, mean ages 64 years old (sd 12.5); 36 with diabetes; 42 UA, 35 NonSTEMI and 23 STEMI. Coronary angiograms in 98 patients, 4 without lesions . Medical therapy with aspirin in 100, clopidogrel 92,beta blockers 96, ACE inhibitors 63, angiotensin receptor blockers 12, calcium channel blockers 7, diuretics 20 , nitrates 9. Previous statin use in 32 and statin use during hospital stay and discharge in 99. The range of TC was 90 to 291 mg/dL (mean: 167,1; sd 40.8), LDL-C: 39 to 194mg/dL (mean 98.0; sd: 34.1); HDL-C from 20 to 68 mg/dL (mean :34.8; sd: 99.2); Triglycerides from 55 to 615 mg/dl ( median 151.5; interquartile range : 114.5 to 197.0) . Patients with LDL-C ≤ 70 mg/dL : 25% ( CI 95% : 16.9- 34.7); HDL-C ≥40 : 24% (CI 95% : 16.0 - 33.6). Lipid levels were measured in only 12 patients at arrival (CI 95% : 6.4 - 20.0), in 70 during hospital stay (CI 95% : 60.0 - 78.8); in 30 patients no measure at all (CI95% : 21.2 - 40.0). Conclusion: Knowledge of serum lipid levels early after ACS is very relevant and should facilitate initiation of lipid lowering therapy. There is still a large gap between current recommendations and clinical practice concerning lipids in ACS, as shown with our data.

Psycho-emotional stress - A cause of coronary artery disease

Psycho-emotional stress is one of the risk factors for metabolic syndrome and related diseases. Hence, this study has designed to the effect of psycho-emotional stress in the form of immobilization stress in rabbits. In this study, we used 12 m ale New Zealand White rabbits (2.5 -3 kg body weight), Six animals for hanging fixation and another six as control. Blood samples were taken before hanging (0 minute) and at 60, 120 minutes. Serum was separated and used for the estimation of various biochemical parameters. Hanging fixation appears to produce significant increase in malondialdehyde and lipid profile levels. The non-enzymatic antioxidants like reduced glutathione, vitamin E and ceruloplasmin were found to be decrease and the level of enzymatic antioxidant like glutathione peroxidase was increased significantly. The results reveal that the hanging fixation may develop coronary artery disease. This is the area, which should be evaluated further by carrying out chronic studies in hun g stress and by histopathological studies.

Analyzing the association between aortic regurgitation and atherosclerosis: is pulse pressure a cause of atherosclerosis?

ABSTRACTIf pulse pressure, one of the mechanical stresses, is a risk factor for atherosclerotic cardiovascular disease, then atherosclerosis should be progressive in aortic regurgitation which is a representative disease with increased pulse pressure. This cross-sectional study included 1,149 patients. We examined the influence of aortic regurgitation on maximum intima-media thickness or brachial-ankle pulse wave velocity. The degree of aortic regurgitation was classified into 4 grades by color Doppler examination. There were 177 patients with aortic regurgitation. Pulse pressure was significantly higher in patients with aortic regurgitation than in those without it. On multiple regression analysis, aortic regurgitation was not found to be a significant independent variable for maximum intima-media thickness [standard partial regression coefficient: aortic regurgitation = grade 1, 0.011, P = 0.7635; aortic regurgitation ≥ grade 2, −0.034, P = 0.3289] and brachial-ankle pulse wave velocity [standard partial regression coefficient: aortic regurgitation = grade1, −0.043, P = 0.1197; aortic regurgitation ≥ grade2, 0.002, P = 0.9358] after adjusting for age, sex, body mass index, presence or absence of cardiovascular disease, antihypertensive treatment, diabetes, dyslipidemia, and smoking. These results found no causal association between aortic regurgitation and atherosclerosis, and were a contradiction to the opinion that pulse pressure was a risk factor of atherosclerosis.