Increased Risk Of Atherosclerosis Research Articles

C92. Successful Percutaneous Coronary Intervention (PCI) in Rare Case of Anomalous Aortic Origin of the Right Coronary Artery from the Opposite Sinus (AAORCA) Presenting as Inferior ST Elevation Myocardial Infarction (STEMI)

Abstract Background AAORCA from opposite sinus is a rare congenital anomaly that can present with symptoms similar to coronary artery disease, even sudden cardiac death. AAORCA with Inferior STEMI is a rare combination situation. Management of acute myocardial infarction with AAORCA is not well established and still debatable. Case Summary We presented a case 61 years old aged male with STEMI and AAORCA. He admitted to our hospital with complaint of retrosternal chest pain with ST segment elevation in inferior lead thus we diagnosed as Inferior STEMI. He underwent an emergency coronary angiography (CAG) that showed anomalous of right coronary artery (RCA) and total occlusion of the proximal RCA with atherosclerotic lesion. Stent then implanted at proximal of RCA. Further work-up by Computed Tomography Angiography (CTA) revealed an AAORCA with interarterial course. Discussion AAORCA with interarterial course that presents as inferior STEMI is a rare case. Diagnosis requires CAG and coronary CTA to identify anatomy and physiology so revascularization can be carried out appropriately. It is still arguable whether atherosclerosis or the interarterial course of AAORCA that caused acute MI. There is evidence that anomalous coronary arteries doesn’t increase atherosclerosis risk than normal. Total occlusion located at the distal to interarterial course reinforce that atherosclerosis may be the possible cause of acute MI. PCI could be the preferred choice in patients with inferior STEMI accompanied by AAORCA with evidence of atherosclerotic lesion, because may result in complete reperfusion and good clinical outcome.

Abstract 10452: Exploring the Role of Mitochondrial Genetic Variants in Coronary Artery Disease

Introduction: Large-scale genome-wide association studies have identified >200 single-nucleotide variants (SNVs) significantly associated with coronary artery disease (CAD), collectively explaining <20% of the heritability. Hypothesis: Mitochondrial (MT) genetic variants presents an underexplored one potential source of the “missing heritability”. Methods: We analyzed 265 MT-SNVs in ∼500,000 UK Biobank individuals, exploring two different CAD definitions: including (SOFT=34,782) vs. excluding (HARD=20,405) angina, using the array, sex, birth year and first five principal components as covariates. Results: In SOFT cases, four MT-SNVs survived multiple testing correction (at FDR<5%), all conferring increased CAD risk: m.10400C>T (rs28358278, OR=1.28, MAF=0.02, T114T in MT-ND3), m.15301G>A (rs527236045, OR=1.03, MAF=0.04, L185L in MT-CYB), m.11251A>G (rs869096886, OR=1.03, MAF=0.2, L164L in MT-ND4) and m.15452C>A (rs193302994, OR=1.03, MAF=0.2, L236I in MT-CYB), the latter two previously associated with height in the UK Biobank. In HARD cases, no MT-SNVs survived multiple testing correction, the most significant nominal (P <0.05) findings being for four SNVs, whereof m.295C>T (rs41528348, OR=1.05, MAF=0.1, in the D-LOOP) and m.12612A>G (rs28359172, OR=1.05, MAF=0.04, V92V in MT-ND5) could potentially increase CAD risk, whereas m.12372G>A (rs2853499, OR=0.97, MAF=0.22, L12L in MT-ND5), m.11467A>G (rs2853493, OR=0.97, MAF=0.22, L236L in MT-ND4) and m.15301G>A (rs193302991, OR=0.97, MAF=0.04, L185L in MT-CYB) may confer protective effects. Previously, several of these variants have been associated with a number of blood cell traits in the UK Biobank, including the mean corpuscular hemoglobin levels (m.295C>T, m.12612A>G, m.12372G>A) and volume (m.295C>T and m.12612A>G). In addition, m.12372G>A was significantly association with five other blood cell traits, including the mean platelet volume and white/red blood cell count, as well as with several renal biomarkers, and m.12612A>G was associated with height. Conclusions: Our results indicated only spurious associations of the MT-SNV with the occurrence of CAD. More data in larger study cohorts may be needed to conclusively determine the role of MT-DNA in CAD.

Identification of potential therapeutic targets for coronary artery disease based on protein array and Mendelian Randomization analysis

Abstract Background Currently, coronary artery disease (CAD) is a main cause of mortality worldwide. Exposing the unknown pathogenic mechanism and exploring potential therapeutic targets of CAD is a critical issue in current CAD research. We aimed to identify potential therapeutic target for CAD using 2-sample Mendelian randomization (MR) approach among differential expression proteins between CAD and control group. Methods Serum samples from 16 first-onset CAD patients diagnosed by coronary angiography and 10 non-CAD controls were collected and detected using protein array. We identified differentially expressed proteins based on “DEseq2” R package and found the core module using MCODE plugin in Cytoscape. Proteins in core modules were used as candidate protein for causal inference. Genetic instrument variables (IV) of candidate proteins were extracted from Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS). Two-sample MR was performed to detect the causal association between the candidate proteins and CAD. For the identified protein causally associated with CAD, sensitivity analyses were used to confirm the finding, including using other MR approach, using more stringent instrument variables, and external cohorts for verification. Network MR was performed to explore whether metabolic risk factors for CAD mediated the risk of identified proteins, including indices of lipid metabolism, glucose metabolism, obesity and blood pressure. Mediation analysis was used to measure the effect of mediation. Results A total of 81 differentially expressed protein were found in CAD group compare to control group, among which 3 core functional modules were found. In five candidate proteins with available instrumental variables, only GP73 was causally associated with CAD risk. Per 1 SD increment in genetically determined GP73 level was associated with 12% increased CAD risk (odds ratio: 1.12; 95% confidence interval: 1.06–1.18, FDR<0.001). Sensitivity analysis yielded consistent results. Network MR analysis shows that across metabolic risk factors profiles for CAD, GP73 level was causally associated with low-density lipoprotein cholesterol (LDL-c), glycated hemoglobin (HbA1c) and waist-to-hip ratio (WHR). Besides, LDL-c, HbA1c and WHR serves as mediators in the causal pathway from GP73 to CAD and transmitted 40.4%, 1.4%, and 5.5% of the total effects, respectively. Conclusion Based on protein array and bioinformatics analysis, this study screened out 3 modules that play core functions in the differential expressed proteins. Among the 19 proteins in the core module, there was a causal relationship between circulating GP73 levels and incident CAD, and the causal effect is mainly mediated by lipid metabolism. The results suggest that GP73 can not only be used as a novel biomarker of CAD, but also may provide a new potential therapeutic target for the management of CAD. Funding Acknowledgement Type of funding sources: None. Figure 1

Electronic health records features associated to coronary artery disease in patients with chest pain

Abstract Introduction Cardiovascular diseases remain the main cause of death in most European countries and coronary artery disease (CAD) follows an ascendent tendency. Current guidelines on chronic coronary syndromes recommend to estimate the CAD pre-test probability based on age, sex and symptoms in patients with suspected CAD. Besides, they underline the importance of adapting this likelihood with the patient information, although the risk the physician attributes to the medical history might not be concordant among colleagues. Electronic health records (EHR) are the main patient-level data collection tools in clinical care and data capture systems compile this clinical information into research-oriented datasets. We can analyze which variables in EHR have stronger associations with CAD in this context to facilitate a more concise and personalized adjustment of the pre-test CAD risk. Purpose To analyze the association between features in EHR with the development of CAD in patients who attended the local public health system for thoracic pain in the 2016–2018 period. Methods We queried the system for patients who required medical attendance for thoracic pain or equivalent symptoms from 2016 to 2018 in the public health system. We extracted data within this subset of the potentially predictive features according to a literature review. We investigated whether patients developed CAD in the year following their attendance. A database cleaning process removed subjects without further diagnostic tests. We used parametric tests to assess the distribution differences of these features between patients who developed CAD and those who did not and we applied logistic regression to document their prediction potential. Results The EHR dataset extracted from the system contained information about 2,199,711 individuals, out of which 43,835 required medical attention for thoracic pain in the selected period. 10,463 patients had no further diagnostic tests, so were excluded. Among the remaining 33,372 patients, 5,379 (16.1%) developed CAD in the follow-up period. Heart failure and traditional cardiovascular risk factors were predominant in the CAD group, and so were related blood test features and therapies. Any history of CAD diagnostic test was significantly associated to CAD presentation. Ischemic etiology of the chest pain was more unlikely in patients with anxiety history and benzodiazepine prescription. Proton pump inhibitors use and hearth rhythm disorders did not increase CAD risk in adjusted models. Conclusions Medical history, basal blood tests and treatment information available in EHR are related to CAD risk in patients with chest pain. Considering this information seems valuable for a personalized risk adjustment of the CAD pre-test probability in symptomatic patients. Further studies with multivariable models and machine learning techniques applied to this dataset might entail more specific predictive algorithms. Funding Acknowledgement Type of funding sources: None.

Association of ApoCIII common variants with risk of coronary artery disease: A Mendelian randomization study

Background and Aims: Bold Hypertriglyceridemia has emerged as an important coronary artery disease (CAD) risk factor. Rare loss of function (LOF) variants in apolipoprotein CIII have been reported to reduce triglycerides (TG) and decrease the risk of CAD in American Indians and Europeans. However, there is a paucity of data on whether these variants are cardioprotective in other European and non-European populations. Also, whether genetically increased TG due to ApoCIII is causally associated with increased CAD risk is still unclear and inconsistent.

Can Subclinical Atherosclerosis Be Assessed More Precisely in Behçet Syndrome Patients by Using a Particular Cutoff Value for Carotid Intima Media Thickness?

Behçet syndrome (BS) is a multisystemic chronic vasculitic disease. Among previous studies, although there are some that showed increased risk of subclinical atherosclerosis in BS, there are also others that showed the opposite. The objective of this study is to evaluate subclinical atherosclerosis in BS by using the cutoff value for intima-media thickness in the 2013 European Society of Cardiology/European Society of Hypertension guideline. We conducted a cross-sectional analysis of 100 BS patients and 30 healthy volunteers at a single center in a 4-month period. All ultrasound scans were performed in a blind manner to the clinical assessment, and they were carried out by the same researcher by a B-mode ultrasonography. When we grouped the patients based on the presence of subclinical atherosclerosis, the frequency of subclinical atherosclerosis in the BS patients was found to be higher than that in the healthy controls (32% and 7%, respectively; p = 0.006). When a cutoff is used for carotid intima-media thickness, increased atherosclerosis risk is observed in BS patients with vascular involvement (p = 0.043). Although higher inflammation and increased atherosclerosis in vascular BS patients were expected, this situation was not supported much in previous studies. We think that this may have been caused by mere comparison of numerical data, and usage of a cutoff value could be more significant in distinguishing what is normal and what is abnormal as in several medical parameters.

Investigating the relationships between unfavourable habitual sleep and metabolomic traits: evidence from multi-cohort multivariable regression and Mendelian randomization analyses

BackgroundSleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic traits to investigate possible biochemical mechanisms linking sleep to cardiovascular disease.MethodsWe used AMV (N = 17,368) combined with two-sample MR (N = 38,618) to examine effects of self-reported insomnia symptoms, total habitual sleep duration, and chronotype on 113 metabolomic traits. The AMV analyses were conducted on data from 10 cohorts of mostly Europeans, adjusted for age, sex, and body mass index. For the MR analyses, we used summary results from published European-ancestry genome-wide association studies of self-reported sleep traits and of nuclear magnetic resonance (NMR) serum metabolites. We used the inverse-variance weighted (IVW) method and complemented this with sensitivity analyses to assess MR assumptions.ResultsWe found consistent evidence from AMV and MR analyses for associations of usual vs. sometimes/rare/never insomnia symptoms with lower citrate (− 0.08 standard deviation (SD)[95% confidence interval (CI) − 0.12, − 0.03] in AMV and − 0.03SD [− 0.07, − 0.003] in MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] in AMV and 0.06SD [0.03, 0.10) in MR]), lower total very large HDL particles (− 0.04SD [− 0.08, 0.00] in AMV and − 0.05SD [− 0.09, − 0.02] in MR), and lower phospholipids in very large HDL particles (− 0.04SD [− 0.08, 0.002] in AMV and − 0.05SD [− 0.08, − 0.02] in MR). Longer total sleep duration associated with higher creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.03] in AMV and 0.15SD [0.02, 0.29] in MR) and with isoleucine in MR analyses (0.22SD [0.08, 0.35]). No consistent evidence was observed for effects of chronotype on metabolomic measures.ConclusionsWhilst our results suggested that unfavourable sleep traits may not cause widespread metabolic disruption, some notable effects were observed. The evidence for possible effects of insomnia symptoms on glycoprotein acetyls and citrate and longer total sleep duration on creatinine and isoleucine might explain some of the effects, found in MR analyses of these sleep traits on coronary heart disease, which warrant further investigation.

The Synergistic Effect of Plasminogen Activator Inhibitor-1 (PAI-1) Polymorphisms and Metabolic Syndrome on Coronary Artery Disease in the Korean Population.

The most common type of cardiovascular disease is coronary artery disease (CAD), in which a plaque builds up inside the coronary arteries that can lead to a complete blockage of blood flow to the heart, resulting in a heart attack. The CAD may be affected by various factors including age, gender, and lipoprotein disposition as well as genetic factors and metabolic syndrome. In this study, we investigated whether three PAI-1 polymorphisms (−844 G > A, −675 4G > 5G, and +43 G > A) and CAD-related clinical parameters are associated with CAD susceptibility. Genotyping of 463 CAD patients and 401 controls was performed using polymerase chain reaction restriction fragment length polymorphism analysis. We report that the 4G5G genotype (crude odds ratio(COR), 1.392; 95% confidence interval (CI), 1.036–1.871; p = 0.028) and dominant model (4G4G vs. 4G5G + 5G5G; COR, 1.401; 95% CI, 1.060–1.850; p = 0.018; adjust odds ratio, 1.371; 95% CI, 1.027–1.831; p = 0.032) of PAI-1 −675 polymorphisms were associated with increased CAD risk. Haplotype and genotype combinations of PAI-1 −675 and +43 polymorphisms show an increased risk of CAD according to alterations of the −675 polymorphism allele or genotype. Moreover, the PAI-1 -675 polymorphisms show a synergistic effect with the metabolic syndrome component of CAD risk. This study suggests that polymorphisms in the PAI-1 genes along with the metabolic syndrome component of CAD can be useful biomarkers for CAD diagnosis and treatment.

Phosphate and Oxysterols May Mediate an Inverse Relationship Between Atherosclerosis and Cancer

The peer-reviewed literature has reported an inverse relationship between atherosclerosis and cancer for almost 100 years, but no causative mechanism has been established to explain this puzzling relationship. More recent research has reported an association between tumourigenesis and phosphate toxicity from dysregulated phosphate metabolism, and an association has also been reported between atherosclerosis and cholesterol oxidation products or oxysterols. The present review article synthesises these research findings and proposes that an inverse relationship between the associated risk of cancer and atherosclerosis may be mediated by tumourigenic and atherogenic dietary patterns containing inverse proportions of dietary phosphate and oxysterols. Low-fat animal-based foods generally have reduced cholesterol and oxysterol levels and relatively higher protein and phosphate levels, and dietary patterns containing these foods are associated with reduced atherosclerosis risk and increased cancer risk. By comparison, full-fat animal-based foods are higher in cholesterol and oxysterols and relatively lower in protein and phosphate, and dietary patterns containing these foods are associated with increased atherosclerosis risk and reduced cancer risk. Fruits, vegetables, and plant-based fats generally have lower phosphate levels and no cholesterol, and dietary patterns associated with increased amounts of these foods, such as the Mediterranean diet, reduce risk for both cancer and cardiovascular disease.

Effect of plasma polyunsaturated fatty acid levels on leukocyte telomere lengths in the Singaporean Chinese population

BackgroundShorter telomere length (TL) has been associated with poor health behaviors, increased risks of chronic diseases and early mortality. Excessive shortening of telomere is a marker of accelerated aging and can be influenced by oxidative stress and nutritional deficiency. Plasma n6:n3 polyunsaturated fatty acid (PUFA) ratio may impact cell aging. Increased dietary intake of marine n-3 PUFA is associated with reduced telomere attrition. However, the effect of plasma PUFA on leukocyte telomere length (LTL) and its interaction with genetic variants are not well established.MethodsA nested coronary artery disease (CAD) case-control study comprising 711 cases and 638 controls was conducted within the Singapore Chinese Health Study (SCHS). Samples genotyped with the Illumina ZhongHua-8 array. Plasma n-3 and n-6 PUFA were quantified using mass spectrometry (MS). LTL was measured with quantitative PCR method. Linear regression was used to test the association between PUFA and LTL. The interaction between plasma PUFAs and genetic variants was assessed by introducing an additional term (PUFA×genetic variant) in the regression model. Analysis was carried out in cases and controls separately and subsequently meta-analyzed using the inverse-variance weighted method. We further assessed the association of PUFA and LTL with CAD risk by Cox Proportional-Hazards model and whether the effect of PUFA on CAD was mediated through LTL by using structural equation modeling.ResultsHigher n6:n3 ratio was significantly associated with shorter LTL (p = 0.018) and increased CAD risk (p = 0.005). These associations were mainly driven by elevated plasma total n-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (p < 0.05). There was a statistically significant interaction for an intergenic single nucleotide polymorphism (SNP) rs529143 with plasma total n-3 PUFA and DHA on LTL beyond the genome-wide threshold (p < 5 × 10− 8). Mediation analysis showed that PUFA and LTL affected CAD risk independently.ConclusionsHigher plasma n6:n3 PUFA ratio, and lower EPA and DHA n-3 PUFAs were associated with shorter LTL and increased CAD risk in this Chinese population. Furthermore, genetic variants may modify the effect of PUFAs on LTL. PUFA and LTL had independent effect on CAD risk in our study population.

Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells.

Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. Recent genome-wide association studies revealed 163 loci associated with CAD. However, the precise molecular mechanisms by which the majority of these loci increase CAD risk are not known. Vascular smooth muscle cells (VSMCs) are critical in the development of CAD. They can play either beneficial or detrimental roles in lesion pathogenesis, depending on the nature of their phenotypic changes. To identify genetic variants associated with atherosclerosis-relevant phenotypes in VSMCs. We quantified 12 atherosclerosis-relevant phenotypes related to calcification, proliferation, and migration in VSMCs isolated from 151 multiethnic heart transplant donors. After genotyping and imputation, we performed association mapping using 6.3 million genetic variants. We demonstrated significant variations in calcification, proliferation, and migration. These phenotypes were not correlated with each other. We performed genome-wide association studies for 12 atherosclerosis-relevant phenotypes and identified 4 genome-wide significant loci associated with at least one VSMC phenotype. We overlapped the previously identified CAD loci with our data set and found nominally significant associations at 79 loci. One of them was the chromosome 1q41 locus, which harbors MIA3. The G allele of the lead risk single nucleotide polymorphism (SNP) rs67180937 was associated with lower VSMC MIA3 expression and lower proliferation. Lentivirus-mediated silencing of MIA3 (melanoma inhibitory activity protein 3) in VSMCs resulted in lower proliferation, consistent with human genetics findings. Furthermore, we observed a significant reduction of MIA3 protein in VSMCs in thin fibrous caps of late-stage atherosclerotic plaques compared to early fibroatheroma with thick and protective fibrous caps in mice and humans. Our data demonstrate that genetic variants have significant influences on VSMC function relevant to the development of atherosclerosis. Furthermore, high MIA3 expression may promote atheroprotective VSMC phenotypic transitions, including increased proliferation, which is essential in the formation or maintenance of a protective fibrous cap.

Osteoprotegerin SNP associations with coronary artery disease and ischemic stroke risk: a meta-analysis.

Osteoprotegerin (OPG) is involved in the development of atherosclerosis and cardio-cerebrovascular disease. The goal of this meta-analysis was to evaluate the association of OPG single nucleotide polymorphisms (SNPs) with coronary artery disease (CAD) and ischemic stroke. A total of 15 eligible studies were extracted from electronic databases. Odds ratios (ORs) were presented, with 95% confidence intervals (CIs), to assess the associations. Meta-analysis was conducted using MetaGenyo, STATA, and Comprehensive Meta-Analysis. Meta-analysis of our data showed that the OPG SNP T950C was significantly associated with increased CAD risk among Asians via recessive (OR 1.55, 95% CI 1.18–2.04, P=0.002), CC vs TT (OR 1.57, 95% CI 1.16–2.11, P=0.003) and allelic (OR 1.21, 95% CI 1.05–1.38, P=0.007) models. No strong associations were observed for the OPG SNP G1181C, T245G and G209A with CAD risk. When evaluating the OPG SNP T245G and T950C associations with ischemic stroke, we found the OPG SNP T245G to be significantly associated with increased risk of ischemic stroke among Chinese via recessive (OR 1.53, 95% CI 1.02–2.29, P=0.039) and CC vs AA (OR 1.61, 95% CI 1.07–2.42, P=0.021) models. Our results suggested that the OPG SNP T950C was associated with increased risk of CAD among Asians, and the OPG SNP T245G was associated with enhanced ischemic stroke risk among Chinese.

A study of associations between CUBN, HNF1A, and LIPC gene polymorphisms and coronary artery disease

The aim of this study was to identify novel genetic markers related to coronary artery disease (CAD) using a whole-exome sequencing (WES) approach and determine any associations between the selected gene polymorphisms and CAD prevalence. CUBN, HNF1A and LIPC gene polymorphisms related to CAD susceptibility were identified using WES screening. Possible associations between the five gene polymorphisms and CAD susceptibility were examined in 452 CAD patients and 421 control subjects. Multivariate logistic regression analyses indicated that the CUBN rs2291521GA and HNF1A rs55783344CT genotypes were associated with CAD (GG vs. GA; adjusted odds ratio [AOR] = 1.530; 95% confidence interval [CI] 1.113–2.103; P = 0.002 and CC vs. CT; AOR = 1.512; 95% CI 1.119–2.045; P = 0.007, respectively). The CUBN rs2291521GA and HNF1A rs55783344CT genotype combinations exhibited a stronger association with CAD risk (AOR = 2.622; 95% CI 1.518–4.526; P = 0.001). Gene-environment combinatorial analyses indicated that the CUBN rs2291521GA, HNF1A rs55783344CT, and LIPC rs17269397AA genotype combination and several clinical factors (fasting blood sugar (FBS), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels) were associated with increased CAD risk. The CUBN rs2291521GA, HNF1A rs55783344CT, and LIPC rs17269397AA genotypes in conjunction with abnormally elevated cholesterol levels increase the risk of developing CAD. This exploratory study suggests that polymorphisms in the CUBN, HNF1A, and LIPC genes can be useful biomarkers for CAD diagnosis and treatment.

A study of acute coronary syndrome in post-menopausal women

Background: Ischemic heart disease (IHD) is the most common, serious, chronic, life-threatening illness. Account for around half of the global burden from these conditions, i.e. around 17.9 million lives each year, 2020 WHO. Although many factors can influence an individual’s risk for coronary artery disease (CAD), some factors are unique to women, including reproductive status. Menopause is associated with significant elevations in serum cholesterol levels and a threefold increase in risk of CAD. It has been suggested that these changes result from a reduction in the level of estrogen. One in every two women will die of heart disease and stroke, compared with only 1 in 28 who will die of breast cancer. Contrary to the belief that CAD is a man’s disease. So, this study was undertaken to study the risk factors, clinical profile and Complications (in hospital) of Acute coronary syndrome in post-menopausal women. Methods: An observational study conducted in 100 patients with post-menopausal women admitted in Basaveshwar hospital, Kalaburgi, for a period of 6 months. Study subjects selected after applying inclusion and exclusion criteria.Results: 100 post-menopausal women, 80% were above 50 years, mean age was 59.05 years (±9.97 years). The following risk factors were noted, Hypertension (52%), diabetes (36%), obesity (20%), dyslipidaemia (10%), family history of IHD. Chest pain was the most common presenting complaint in 92%. 39% of the patients were admitted after 12 hours of onset of chest pain.Conclusion: Acute myocardial infarction (MI) is common in post-menopausal women and they generally present late. Because of the late presentation, the beneficial effects of thrombolytic therapy are denied.

Heterozygous ABCG5 Gene Deficiency and Risk of Coronary Artery Disease.

Familial sitosterolemia is a rare Mendelian disorder characterized by hyperabsorption and decreased biliary excretion of dietary sterols. Affected individuals typically have complete genetic deficiency-homozygous loss-of-function (LoF) variants-in the ABCG5 or ABCG8 genes and have substantially elevated plasma sitosterol and LDL (low-density lipoprotein) cholesterol (LDL-C) levels. The impact of partial genetic deficiency of ABCG5 or ABCG8-as occurs in heterozygous carriers of LoF variants-on LDL-C and risk of coronary artery disease (CAD) has remained uncertain. We first recruited 9 sitosterolemia families, identified causative LoF variants in ABCG5 or ABCG8, and evaluated the associations of these ABCG5 or ABCG8 LoF variants with plasma phytosterols and lipid levels. We next assessed for LoF variants in ABCG5 or ABCG8 in CAD cases (n=29 321) versus controls (n=357 326). We tested the association of rare LoF variants in ABCG5 or ABCG8 with blood lipids and risk for CAD. Rare LoF variants were defined as protein-truncating variants with minor allele frequency <0.1% in ABCG5 or ABCG8. In sitosterolemia families, 7 pedigrees harbored causative LoF variants in ABCG5 and 2 pedigrees in ABCG8. Homozygous LoF variants in either ABCG5 or ABCG8 led to marked elevations in sitosterol and LDL-C. Of those sitosterolemia families, heterozygous carriers of ABCG5 LoF variants exhibited increased sitosterol and LDL-C levels compared with noncarriers. Within large-scale CAD case-control cohorts, prevalence of rare LoF variants in ABCG5 and in ABCG8 was ≈0.1% each. ABCG5 heterozygous LoF variant carriers had significantly elevated LDL-C levels (25 mg/dL [95% CI, 14-35]; P=1.1×10-6) and were at 2-fold increased risk of CAD (odds ratio, 2.06 [95% CI, 1.27-3.35]; P=0.004). By contrast, ABCG8 heterozygous LoF carrier status was not associated with increased LDL-C or risk of CAD. Although familial sitosterolemia is traditionally considered as a recessive disorder, we observed that heterozygous carriers of an LoF variant in ABCG5 had significantly increased sitosterol and LDL-C levels and a 2-fold increase in risk of CAD.

The triglyceride-glucose index predicts peripheral artery disease complexity

Background/aimHigh levels of triglyceride (TG) and fasting blood glucose (FBG) values increase atherosclerosis risk. This study evaluates the relationship between peripheral artery disease (PAD) severity and complexity, as assessed by TransAtlantic InterSociety Consensus-II (TASC-II) classification and the triglyceride-glucose (TyG) index.Materials and methodsA total of 71 consecutive patients with PAD (males 93%, mean age 63.3 ± 9.7), who underwent percutaneous peripheral intervention were included retrospectively. The patients were divided into two groups according to the angiographically detected lesions. Those with TASC A-B lesions were included in Group 1, and those with TASC C-D lesions were included in Group 2. TyG index was calculated as formula: ln[fasting TG (mg/dL) × fasting plasma glucose (mg/dL)/2].ResultsThere were 40 patients in Group 1 (90.3% men, with a mean age of 63.6 ± 9.3 years) and 31 patients in Group 2 (96.8% men, with a mean age of 62.0 ± 8.6 years). In the majority of patients in both groups, the target vessels are iliac arteries and femoral arteries. In Group 2, platelet count and TyG index were significantly high, according to Group 1. The TyG index was significantly correlated with TASC-II, Rutherford category, HbA1c, and HDL-C.ConclusionIn this present study, we showed that the TyG index was an independent predictor of peripheral artery disease complexity, according to TASC-II classification, for the first time in the literature.

Detection of ADTRP in circulation and its role as a novel biomarker for coronary artery disease.

Androgen dependent tissue factor pathway inhibitor regulating protein (ADTRP) is a novel protein associated with coronary artery disease (CAD) susceptibility, and reduced mRNA expression of ADTRP was shown to be associated with increased CAD risk. This study aimed to determine and compare circulating ADTRP levels between CAD patients and controls, and to test the performance of plasma ADTRP as a biomarker for CAD. We measured plasma ADTRP, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and high sensitivity-C reactive protein (hs-CRP) levels in 362 CAD patients, 150 angiographically negative CAD controls, and 83 healthy adults with no known clinical or medical conditions using commercial ELISA. Statistical analyses were performed using receiver operator characteristic (ROC) curves, quantile regression and logistic regression, with adjustments for age, gender, ethnicity and BMI. CAD patients had significantly lower plasma ADTRP levels 1,545 (1,087–2,408) pg/ml as compared to CAD controls 2,259 (1,533–3,778) pg/ml and healthy adults 3,904 (2,732–5,463) pg/ml. Plasma ADTRP outperformed the other three inflammatory biomarkers (TNF-α, IL-6 and hs-CRP) for CAD (Area under ROC curve: 0.67, Odds ratio (OR): 0.907). Our study has shown for the first time that ADTRP is present in circulation, and that plasma ADTRP may be a novel independent biomarker for CAD.

Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease.

AimsTo explore whether variability in dietary cholesterol and phytosterol absorption impacts the risk of coronary artery disease (CAD) using as instruments sequence variants in the ABCG5/8 genes, key regulators of intestinal absorption of dietary sterols.Methods and resultsWe examined the effects of ABCG5/8 variants on non-high-density lipoprotein (non-HDL) cholesterol (N up to 610 532) and phytosterol levels (N = 3039) and the risk of CAD in Iceland, Denmark, and the UK Biobank (105 490 cases and 844 025 controls). We used genetic scores for non-HDL cholesterol to determine whether ABCG5/8 variants confer greater risk of CAD than predicted by their effect on non-HDL cholesterol. We identified nine rare ABCG5/8 coding variants with substantial impact on non-HDL cholesterol. Carriers have elevated phytosterol levels and are at increased risk of CAD. Consistent with impact on ABCG5/8 transporter function in hepatocytes, eight rare ABCG5/8 variants associate with gallstones. A genetic score of ABCG5/8 variants predicting 1 mmol/L increase in non-HDL cholesterol associates with two-fold increase in CAD risk [odds ratio (OR) = 2.01, 95% confidence interval (CI) 1.75–2.31, P = 9.8 × 10−23] compared with a 54% increase in CAD risk (OR = 1.54, 95% CI 1.49–1.59, P = 1.1 × 10−154) associated with a score of other non-HDL cholesterol variants predicting the same increase in non-HDL cholesterol (P for difference in effects = 2.4 × 10−4).ConclusionsGenetic variation in cholesterol absorption affects levels of circulating non-HDL cholesterol and risk of CAD. Our results indicate that both dietary cholesterol and phytosterols contribute directly to atherogenesis.

CircFOXO3 rs12196996, a polymorphism at the gene flanking intron, is associated with circFOXO3 levels and the risk of coronary artery disease.

CircFOXO3 plays an important role in the pathogenesis of coronary artery disease (CAD). Single nucleotide polymorphisms (SNPs) at circRNA flanking introns may change its back-splicing and influence circRNA formation. Here, we aimed to investigate the influence of the polymorphisms at the circFOXO3 flanking introns on individual susceptibility to CAD. A total of 1185 individuals were included in the case-control study. In a multivariate logistic regression analysis, we determined that the rs12196996 G variant was significantly associated with increased CAD risk (OR = 1.36, P = 0.014). A similar trend of the association was observed in the recessive model (OR = 2.57, P = 0.003). Stratified analysis revealed a more significant association with CAD risk among younger subjects and non-smokers. Consistent with these results, the haplotype rs12196996G-rs9398171C containing rs12196996G allele was also associated with increased CAD risk (OR = 1.31, P = 0.013). Further investigation revealed that the rs12196996 GG genotype was associated with decreased circFOXO3 expression, but not linear FOXO3 levels. Taken together, our data provide the first evidence that the rs12196996 polymorphism at the circFOXO3 gene flanking intron is associated with CAD risk in the Chinese Han population, which is probably due to influence circFOXO3 levels.

Is it possible to predict the complexity of peripheral artery disease with atherogenic index?

Lower extremity peripheral artery disease develops mainly due to atherosclerosis and occurs as a result of the systemic atherosclerotic process. Increased triglyceride (TG) and decreased high density lipoprotein cholesterol (HDL-C) values increase atherosclerosis risk. With regard to this information, TG/HDL-C ratio is used as the atherogenic index. The aim of the present study was to evaluate the role of TG/HDL-C ratio to predict the complexity of disease in patients with peripheral artery disease. Patients who were diagnosed with peripheral artery disease and admitted to our clinic between August 2013 and August 2019 were included in this study retrospectively. Patients were divided into two groups based on angiographic evaluations with TransAtlantic Inter-Society Consensus-II classification. Those with TASC A-B lesions were included in Group 1 and those with TASC C-D lesions constituted Group 2. The mean ages of Group 1 (n = 314) and Group 2 (n = 98) patients were 56.1 ± 9.3 and 58.4.1 ± 8.1 years, respectively. The frequency of male gender and coronary artery disease was significantly higher in Group 2 (p = 0.043, p = 0.001, respectively). In Group 2, triglyceride and TG/HDL-C ratios were significantly high, while HDL-C was significantly low (p = 0.022, p < 0.001, p = 0.010, respectively). The multivariate logistic regression analysis performed to evaluate the parameters in predicting the angiographic complexity of peripheral artery disease showed that coronary artery disease (OR: 1.009 CI 95%: 1.003-1.021 p = 0.016) and TG/HDL-C ratio (OR: 5.385 CI 95%: 2.553-9.357 p = 0.001) were independent predictors for complexity. ROC analysis revealed that the cut-off value of TG/HDL-C was 2.9 (AUC = 0.670, p < 0.001) with 75.5% sensitivity and 56.7% specificity. It is possible to predict the angiographic complexity of peripheral artery disease with TG/HDL-C ratio, also known as atherogenic index, which is easily obtained by routine biochemical parameters.