Risk Marker For Coronary Artery Disease Research Articles

Genetic risk score for coronary artery calcification and its predictive ability for coronary artery disease

AimThe modest added predictive value of the existing genetic risk scores (GRSs) for coronary artery disease (CAD) could be partly due to missing genetic components, hidden in the genetic architecture of intermediate phenotypes such as coronary artery calcification (CAC). In this study, we investigated the predictive ability of CAC GRS for CAD. Materials and methodsWe investigated the association of CAC GRSs with CAD and coronary calcification among the participants in the Ludwigshafen Risk and Cardiovascular Health study (LURIC) (n = 2742), the Tampere Vascular Study (TVS) (n = 133), and the Tampere Sudden Death Study (TSDS) (n = 660) using summary data from the largest multi-ancestry GWAS meta-analysis of CAC to date. Added predictive value of the CAC GRS over the traditional CVD risk factors as well as metaGRS, a GRS for CAD constructed with 1.7 million genetic variants, was tested with standard train–test machine learning approach using the LURIC data, which had the largest sample size. ResultsCAC GRS was significantly associated with CAD in LURIC (OR=1.41, 95 % CI [1.28–1.55]), TVS (OR=1.79, 95 % CI [1.05–3.21]) as well as in TSDS (OR=4.20, 95 % CI [1.74–10.52]). CAC GRS showed strong association with calcification areas in left (OR=1.78, 95 % CI [1.16–2.74]) and right (OR=1.71, 95 % CI [1.98–2.67]) coronary arteries. There was statistically significant added predictive value of the CAC GRS for CAD over the used traditional CVD risk factors (AUC 0.734 vs 0.717, p-value = 0.02). Furthermore, CAC GRS improved the prediction accuracy for CAD when combined with metaGRS. ConclusionsThis study showed that CAC GRS is a new risk marker for CAD in three European cohorts, with added predictive value over the traditional CVD risk factors.

Temporal relationships between blood glucose, lipids and BMI, and their impacts on atherosclerosis: a prospective cohort study

ObjectivesThis study aimed to explore the temporal relationship between blood glucose, lipids and body mass index (BMI), and their impacts on atherosclerosis (AS).DesignA prospective cohort study was designed.Setting and participantsA...

The Effects of Curcumin Administration on Carotid Intima-Media Thickness and Pulse Wave Velocity in Diabetic Hemodialysis Patients: A Randomized, Double-Blinded, Placebo-Controlled Trial.

Prior studies have reported that curcumin is inversely associated with reduced markers of atherosclerosis risk, including carotid intima-media thickness (CIMT). This study was designed to assess the effects of curcumin on CIMT and pulse wave velocity (PWV) in diabetic hemodialysis (HD) patients. This randomized, double-blinded, placebo-controlled trial was conducted on 39 diabetic HD patients. People were assigned to receive curcumin or placebo (starch) for 24 weeks. Individuals in the curcumin group (n = 26) received 80 mg/day. CIMT and PWV levels were taken at baseline and after 24 weeks of intervention. After 24 weeks of intervention, curcumin intake did not affect mean levels of left (P = 0.83) and right (P = 0.47) CIMT and maximum levels of left (P = 0.84) and right (P = 0.11) CIMT, and PWV (P = 0.12) compared to the placebo. Furthermore, within-group difference demonstrated a significant reduction in mean levels of PWV (P = 0.01) in the curcumin group. We did not observe any significant change in C-reactive protein (CRP) concentrations after curcumin intake (P = 0.69). Curcumin intake did not affect mean levels of left and right CIMT and maximum levels of left and right CIMT, PWV, and CRP levels compared to the placebo. Additionally, within-group difference demonstrated a significant reduction in mean levels of PWV in the curcumin group.This trial was registered at www.irct.ir as http://www.irct.ir: IRCT20200527047584N1.

Reduced Population of CD36-/ABCA1+ Macrophages is Correlated with An Increase of Coronary Artery Disease Risk Markers in Type 2 Diabetes Mellitus

BACKGROUND: Cluster of differentiation (CD)36 and adenosine triphosphate-binding cassette transporter A1 (ABCA1) are 2 macrophages-expressed receptors that promote cholesterol uptake and efflux, in which their imbalance might be associated with the foam cell formation risk. Type 2 diabetes mellitus (T2DM) has been correlated with the increase of this plaque formation. Therefore, it is necessary to determine whether expression of CD36 and ABCA1 in macrophages are correlated with coronary artery disease (CAD) risk markers in T2DM cases.METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 13 diabetic patients and 11 healthy donors. Then, the PBMC-derived macrophages were cultured with supplement of oxidized low-density lipoprotein (ox-LDL) or lipopolysaccharide (LPS). Expression of CD36 and ABCA1 was measured using flowcytometry, meanwhile the supernatant concentration of interleukin (IL)-1b and IL-10 was measured by multiplex immunoassay.RESULTS: T2DM subjects more likely to have low proportion of CD36-ABCA+ macrophages compared to healthy donors (p=0.041) and it had negative correlation with glucose homeostasis and insulin resistance markers, including fasting blood glucose (FBG, r=-0.408, p=0.048), glycated hemoglobin (HbA1c, r=-0.380, p=0.049), triglyceride glucose index (r=-0,518, p=0.009), and high-sensitivity C-reactive protein (hs-CRP, r=-0.556, p=0.005). Moreover, it also had a negative correlation with atherogenic markers such as triglyceride (r=-0.417, p=0.043), triglyceride/HDL, and LDL/HDL, but had positive correlation with HDL (r=0.540, p=0.007). Most of T2DM subjects had high IL-1β/IL-10 ratio after ox-LDL and LPS stimulation (p=0.02 and p=0.05, respectively).CONCLUSION: Reduced proportion of CD36-ABCA1+ macrophages followed with high IL-1β/IL-10 can be a marker of CAD in T2DM.KEYWORDS: type 2 diabetes mellitus, coronary artery disease, macrophages, ABCA1, CD36

New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death.

Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.

Overnight changes in uric acid, xanthine oxidoreductase and oxidative stress levels and their relationships with sleep-disordered breathing in patients with coronary artery disease.

Serum uric acid (UA) level is associated with the high cumulative incidence or prevalence of coronary artery disease (CAD), and hyperuricemia is considered as an independent risk marker for CAD. Sleep-disordered breathing (SDB) is also associated with an increased risk of CAD. Several studies have shown that SDB is associated with hyperuricemia, but the mechanisms are unclear. We measured serum levels of UA and xanthine oxidoreductase (XOR) activity and urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), all of which were assessed at 6 p.m. and the following 6 a.m. in males with CAD. In addition, nocturnal pulse oximetry was performed for the night. Overall 32 eligible patients with CAD were enrolled. Serum UA levels significantly increased overnight. (5.32 ± 0.98 mg/dl to 5.46 ± 1.02 mg/dl, p < 0.001) Moreover, XOR activity and urinary 8-OHdG levels significantly increased from 6 p.m. to 6 a.m. Furthermore, 3% Oxygen desaturation index (ODI) was correlated with the overnight changes in XOR activity (r = 0.36, P = 0.047) and urinary 8-OHdG levels (r = 0.41, P = 0.02). In addition, 3%ODI was independently correlated with the changes in XOR activity (correlation coefficient, 0.36; P = 0.047) and 8-OHdG (partial correlation coefficient, 0.63; P = 0.004) in multivariable analyses. SDB severity was associated with the overnight changes in XOR activity and urinary 8-OHdG, suggesting that SDB may be associated with oxidative stress via UA production. This trial is registered at University Hospital Medical Information Network (UMIN), number: UMIN000021624.

Cardiac Alarmins as Residual Risk Markers of Atherosclerosis under Hypolipidemic Therapy.

Increased levels of low-density lipoproteins are the main risk factor in the initiation and progression of atherosclerosis. Although statin treatment can effectively lower these levels, there is still a residual risk of cardiovascular events. We hypothesize that a specific panel of stress-sensing molecules (alarmins) could indicate the persistence of silent atherosclerosis residual risk. New Zealand White rabbits were divided into: control group (C), a group that received a high-fat diet for twelve weeks (Au), and a treated hyperlipidemic group with a lipid diet for eight weeks followed by a standard diet and hypolipidemic treatment (atorvastatin and PCSK9 siRNA-inhibitor) for four weeks (Asi). Mass spectrometry experiments of left ventricle lysates were complemented by immunologic and genomic studies to corroborate the data. The hyperlipidemic diet determined a general alarmin up-regulation tendency over the C group. A significant spectral abundance increase was measured for specific heat shock proteins, S100 family members, HMGB1, and Annexin A1. The hypolipidemic treatment demonstrated a reversed regulation trend with non-significant spectral alteration over the C group for some of the identified alarmins. Our study highlights the discriminating potential of alarmins in hyperlipidemia or following hypolipidemic treatment. Data are available via ProteomeXchange with identifier PXD035692.

A Comparative Study of the Right and Left Carotid Arteries in Relation to Age for Patients With Diabetes and Hypertension

Introduction: Age, hypertension, and diabetes can cause significant alterations in arterial structure and function, including changes in lumen diameter (LD), intimal-medial thickness (IMT), flow velocities, and arterial compliance. These are also considered risk markers of atherosclerosis and cerebrovascular disease. A difference between right and left carotid artery blood flow and IMT has been reported by some researchers, and a difference in the incidence of nonlacunar stroke has been reported between the right and left brain hemispheres. The aim of this study was to determine whether there are differences between the right and left common carotid arteries and internal carotid arteries in patients with hypertension and diabetes for 2 age groups. Methods: We studied 250 patients with both diabetes and hypertension. Patients were divided into 2 age groups with the old age group being 56 to 75 years and the young age group 35 to 55 years. The bilateral common carotid and internal carotid arteries were evaluated with B-mode ultrasound and Doppler examinations. The LD and IMT were measured for both common carotid arteries, and spectral waveform parameters and indices were recorded for both internal carotid arteries. Results: The difference in LD between the left and right common carotid arteries for the old age group was 11.64% and for the young age group was 6.42%, with significant P values of &lt;.05 for both age groups. The difference in IMT between the left and right common carotid arteries was 18.27% in the old age group compared with 15.38% in the young age group, with significant P values of &lt;.05. There was a difference in peak systolic velocity between the left and right internal carotid arteries of 4.85% in the old age group which was not significant, compared with 14.28% in the young age group with a significant P value &lt;.05, whereas the difference in end-diastolic velocity between the left and right internal carotid arteries was not significant for both age groups. Differences between the right and left internal carotid arteries for resistive index, pulsatility index, and pressure gradient were significant only in the young age group. Conclusion: We found significant differences between the right and left common carotid and internal carotid arteries in patients with diabetes and hypertension which were more prominent in the young age group. Values for common carotid IMT and LD were significantly higher in the left common carotid artery versus the right common carotid artery in both age groups. Differences between the 2 carotid sides may be attributed to anatomic variations in the common carotid artery origins which lead to differences in stress between the 2 sides.

411-P: Potential to Utilize DNA Methylation as a Biomarker to Predict Major Coronary Artery Disease (CAD) Risk in Type 1 Diabetes (T1D)

DNA methylation (DNAme) has been associated with risk of future CAD in the general population and is a potential target for pharmacological intervention. In T1D, DNAme has been associated with microvascular complications but its association with CAD has not been examined in this high risk population. Thus, we performed an epigenome-wide association study (EWAS) of DNAme and 28-year major CAD (CAD death, nonfatal myocardial infarction) incidence in an observational T1D cohort. Whole blood DNAme was assayed via Illumina EPIC beadchip in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood onset (&amp;lt;17 years) T1D (n=400; mean age 29, T1D duration 21 yrs) . After quality control DNAme at 683,597 CpGs was analyzed in Cox models for time-to-CAD, adjusting for T1D duration, sex, smoking pack-years, estimated blood cell composition, and technical/batch covariates. Over 28 years 102 (25%) developed major CAD. DNAme at two CpGs was associated with lower CAD risk: cg06125996 (Chr 5, NLN; log HR per 5% DNAme= -1.10, p=6.0e-11) and cg051638 (Chr 9, CARD9; log HR= -0.97, p=1.2e-08) . Other associations with FDR&amp;lt;5% included CpGs in MRPS21, ZNF428, PCMTD1, and LYRM4. KEGG pathway analysis of all CpGs with FDR&amp;lt;10% (n=44) suggested enrichment for renin-angiotensin-aldosterone system, lipid metabolism, and immune system pathways. In GWAS we identified methylation quantitative trait loci (QTL) associated with DNAme at cg06125996 and cg05163804, three of which were annotated as expression QTLs in GTEx including SNPs in genes involved in insulin receptor signaling (SIK2) and cytokine activity (CMTM2, CMTM4) , and calcium ion binding (EFHB) . DNAme was not correlated with cross-sectional HbA1c at either CpG and adjusting for baseline HbA1c did not alter CpG-CAD associations. Our results demonstrate that DNAme may be an early marker of CAD risk in T1D, but the potential role of glycemic exposure in this association is unclear and warrants further study. Disclosure R.G.Miller: Stock/Shareholder; Becton, Dickinson and Company. J.Mychaleckyj: None. S.Onengut-gumuscu: None. T.J.Orchard: None. T.Costacou: None. Funding American Diabetes Association (1-19-JDF-109) ; NIH/NIDDK R01-DK034818, Rossi Memorial Fund

Improvement in cardiovascular risk markers by the combined effect of natural polyphenols and vitamins in patients after kidney transplantation.

The aim of this study was to evaluate the potential of supportive therapy by natural polyphenols combined with vitamins C and E on kidney function and risk factors of cardiovascular diseases in renal transplant recipients (RTR). Transplant patients have an altered lipid profile associated with the development of cardiovascular disease, which is a major cause of graft loss and mortality in patients. The study included 29 renal transplant recipients with mean graft function levels. The lipoprotein (atherogenic and non-atherogenic) subfractions were identified and quantified in plasma by polyacrylamide gel electrophoresis. After supplementation, glomerular filtration rate (GFR) was increased by 8 %, serum creatinine was decreased by 6.7 % and significant changes were found in atherogenic LDL subfractions. The effect of supplementation was observed in arylesterase and lactonase activities of paraoxonase 1 which increased by 9.3 % and 8.1 %, respectively. In addition, significantly decreased levels of neopterin (by 16 %) and asymmetric dimethylarginine (ADMA) (by 7.9 %) were found. We could summarize that supportive therapy improves the renal function (GFR, serum creatinine), and reduces the risk of cardiovascular disease by affecting important risk markers of atherosclerosis (lipid profile, paraoxonase 1 activity, neopterin and ADMA) in RTR (Tab. 4, Fig. 1, Ref. 53).

Fibrin clot properties in coronary artery disease: new determinants and prognostic markers.

Despite improved diagnosis and treatment options, coronary artery disease (CAD) is still the leading cause of mortality and morbidity worldwide. Established risk factors such as smoking, hypercholesterolemia, and hypertension only partly explain the pathophysiology of CAD. Besides the well-known role of platelets in atherosclerosis and arterial thrombus formation, reduced endogenous fibrinolytic activity may play a key role in CAD formation and progression. Thus, biomarkers of fibrinolysis may be future CAD risk markers. In this review, we provide an overview of regulators of fibrinolysis and the main factors of importance to fibrin clot formation including coagulation factor XIII, thrombin, and fibrinogen. We summarize markers of altered fibrinolysis and current laboratory methods applied in clinical practice and research. We present today’s evidence on fibrin clot properties in patients with stable CAD or acute coronary syndrome compared with healthy individuals and the significance of altered fibrinolysis as a risk for coronary thrombotic disease. In conclusion, we found evidence that altered fibrin clot properties and impaired fibrinolysis appear to contribute significantly to the thromboembolic risk in CAD patients. Therefore, more research is crucial in order to clarify whether modulation of the fibrinolytic system may pave the way for improved treatment of CAD.

Reduced L-Arginine and L-Arginine-ADMA-Ratio, and Increased SDMA after Norseman Xtreme Triathlon.

Endothelial vasodilatory function is dependent on the NO synthesis from L-arginine by endothelial NO-synthetase (eNOS). eNOS can be inhibited by asymmetric dimethylarginine (ADMA) by competitive inhibition on the binding site, and symmetric dimethylarginine (SDMA) can reduce the L-arginine availability intracellularly through competing for transport over the cellular membrane. To study the NO synthesis after prolonged exercise, we assessed circulatory L-arginine, the L-arginine/ADMA ratio, and SDMA before, after, and on the day after the Norseman Xtreme triathlon, an Ironman distance triathlon. We found significantly reduced levels of L-arginine and the L-arginine/ADMA ratio and increased levels of SDMA after the race (all p < 0.05). L-arginine rose toward baseline levels the day after the race, but ADMA increased beyond baseline levels, and SDMA remained above baseline the day after the race. The reduced levels of L-arginine and the L-arginine/ADMA ratio, and increased SDMA, after the race indicate a state of reduced capability of NO production. Increased levels of ADMA and SDMA, and reduced L-arginine/ADMA ratio, as seen the day after the race, are known risk markers of atherosclerosis and warrant further studies.

Proportions of long-chain ω-3 fatty acids in erythrocyte membranes of Canadian adults: Results from the Canadian Health Measures Survey 2012–2015

The Omega-3 Index (OI) is a proposed marker of coronary artery disease (CAD) risk. Another index, the EPA/arachidonic acid (AA) ratio has also been proposed as a possible risk marker for CAD. Our primary objective was to characterize the Canadian population subgroups that have an undesirable OI (<4%, associated with high CAD risk) and to identify the participants' characteristics most strongly associated with the OI. Our secondary objective was to identify the characteristics most strongly associated with the EPA/AA ratio. Data from 4025 adult participants of cycles 3 and 4 (2012-2015) of the cross-sectional Canadian Health Measures Survey were pooled. Adjusted mean proportions of erythrocyte membrane ω-3 (n-3) fatty acids, total ω-6 fatty acids, and ratios were analyzed by sociodemographic, health, and lifestyle characteristics using covariate-adjusted models. The mean OI was 4.5%. Almost 40% of Canadians had an undesirable (<4%) OI. ω-3 supplement use, fish intake, and race were the variables most strongly associated with OI scores. The prevalence of undesirable OI was significantly higher among participants consuming fish less than twice a week (43.8%; 95% CI: 39.0%, 48.6%) than among those consuming more fish (12.7%; 95% CI: 7.8%, 19.9%), among smokers (62.7%; 95% CI: 52.9%, 71.7%) than nonsmokers (33.4%; 95% CI: 29.4%, 37.7%), in whites (42.7%; 95% CI: 38.2%, 47.4%) than in Asians (23.0%; 95% CI: 15.4%, 33.0%), and in adults aged 20-39 y (49.6%; 95% CI: 42.3%, 56.9%) than in those aged 60-79 y (24.4%; 95% CI: 21.0%, 28.1%). ω-3 supplement intake and fish intake were the characteristics most strongly associated with EPA/AA. All P≤0.05. An important proportion of Canadian adults has an undesirable (<4%) OI, with higher prevalence in some subgroups. Further assessment is required to determine the value and feasibility of an increase in the population's OI to the currently proposed target of≥8% as a potential public health objective.

Effect of essential fatty acid blend on circadian variations of ambulatory blood pressure in patients with essential hypertension and coronary artery disease risk markers.

Flaxseed oil is an excellent source of alpha-linolenic acid ALA known for its antihypertensive action. Flaxseed oil is unstable and its dose is not achievable in our conventional diet hence blending of natural flaxseed oil with palm oil, containing high flavonoids may be a better strategy, to stabilize the blend and provide proper balance of essential fatty acids and potential antioxidant effects. Aim of this study was to access the effect of blended flaxseed oil on 24 h 7-day circadian variations of blood pressure in subjects with essential hypertension. Assessment of CHAT (circadian hyper amplitude tension) using ABPM is the best marker for cardiovascular function. We registered 50 subjects with CAD (Group 1) and 50 subjects with Essential hypertension HT (Group 2) and 52 control subjects with CAD/Hypertension. Group 1 and 2 participant was supplemented with blended flaxseed oil (BFO) (30 ml/day) for the period of 24 weeks, while control group administered available oils sunflower in identical containers, for a follow-up period of 24 weeks. Twenty four hour seven days continuous ambulatory blood pressure monitoring was done initially and after six months of BFO supplementation. There were significant changes noted in lipid profile along with Ambulatory blood pressure parameters like MESOR, ACROPHASE, Hyperbaric Indexes, and CHAT. Circadian hyper amplitude tension (CHAT) incidence decreased after BFO supplementation. Study results suggest that blended flaxseed oil administration can be a potent natural vegetarian antihypertensive supplement which helps in synchronization of cardiac rhythms, and can be used as a preventive treatment of hypertension and as effective vegetarian source of maintaining Omega 3 and omega 6 ratios of essential fatty acids in the body.

Combined past preeclampsia and gestational diabetes is associated with a very high frequency of coronary microvascular dysfunction

BackgroundA history of preeclampsia (pPE) and gestational diabetes (pGDM) are female-specific risk markers for atherosclerosis and future cardiovascular risk. In addition to increasing the risk of established risk factors for atherosclerosis, such as hypertension or diabetes, evidence suggests that pregnancy-related complications can also directly accelerate atherosclerosis by inducing endothelial dysfunction. A combination of both conditions is seen in a subset of patients with pregnancy, though it is not known whether this combination increases the overall risk for cardiovascular events. AimsPresent study aimed to find the impact of combined pPE/pGDM on the prevalence of coronary microvascular dysfunction (CMD). MethodsA total of 24 patients with combined pPE/pGDM, 19 patients with isolated pPE and 63 patients with pGDM were included to the present study and a further 36 healthy women with no previous pregnancy-related complications served as controls. Coronary flow reserve was measured using echocardiography and CMD was defined as a coronary flow reserve ≤2.5. ResultsPatients with combined pPE/pGDM had a high prevalence of CMD (91%), which was significantly higher than controls (5.6%, p < 0.001) and patients with pGDM (55%, p = 0.01). A history of pPE on top of pGDM was associated with an increased risk of CMD (HR:6.28, 95%CI:1.69–23.37, p = 0.006) after multivariate adjustment, but pGDM did not increase the odds for CMD in those with pPE. ConclusionsCombined pPE/pDM is associated with a very high prevalence of CMD, which may indicate an increased risk for future cardiovascular events.

Dab2 gene variant is associated with increased coronary artery disease risk in Chinese Han population.

Disabled-2 (Dab2) is a clathrin and cargo-binding endocytic adaptor protein that plays a role in cellular trafficking of low-density lipoprotein receptor (LDLR). However, little is known about its involvement in coronary artery disease (CAD). Here, we aimed to investigate the association between Dab2 single-nucleotide polymorphisms (SNPs) and CAD in Chinese Han and Uyghur populations.We performed a case-control study in CAD group that consisted of 621 Han and 346 Uygurs, and the age and gender matched control group consisted of 611 Han and 405 Uygurs. The clinicopathological characteristics of these subjects were analyzed. Genotyping of 4 SNPs (rs1050903, rs2855512, rs11959928, and rs2255280) of the Dab2 gene was performed in all subjects with an improved multiplex ligase detection reaction method.The distribution of the genotype, dominant model (AA vs. AC + CC), as well as allele frequencies of both rs2855512 and rs2255280, was significantly different between CAD patients and control subjects in Han population but not in Uyghur population. AA genotype may be a risk factor for CAD. For Han population, statistical significant correlation between dominant model for both SNPs (AA) and CAD was found after multivariate adjustment. After multivariate adjustment in the Han population, we speculate that rs285512 A allele and rs2255280 A allele may be potentially associated with the onset of coronary heart disease. Individuals with the AA genotype had an OR of 1.44 (95% CI: 1.10–1.88, P = .01, rs2855512) and 1.41 (95% CI: 1.08–1.85, P = .01, rs2255280) for CAD compared with individuals with the AC or CC genotype, respectively.Our data indicates that the AA genotype of rs2855512 and rs2255280 in the Dab2 gene may be a genetic marker of CAD risk in Chinese Han population.

Post-prandial dylipidemia and elevated serum ferritin levels in type 2 diabetes mellitus patients: A risk marker for accelerated atherosclerotic cardiovascular events

Aims and Objectives of the Study: The type 2 diabetes mellitus (T2DM) prevalence is increasing worldwide at alarming rates. The prevalence of T2DM is expected to be more than 350 million people worldwide in next 20 yrs. The risk of coronary and peripheral artery disease increases by 2 to 4 fold, while the risk of stroke is increased by 10 fold in type 2 diabetes mellitus patients. In type 2 diabetes mellitus, dyslipidemia plays an important role in the pathogenesis of accelerated atherosclerosis. Hyperlipidemia in postprandial state is thought to play an important role in atherosclerosis, and concentrations of triglycerides(TG) in post prandial state are superior to those of fasting TG for predicting cardiovascular disease. Increase in serum ferritin levels are associated with insulin resistance(IR), systemic inflammation, metabolic syndrome(MetS), type 2 diabetes mellitus and cardiovascular disease. Elevated body iron stores may contribute to insulin resistance through chronic inflammation and oxidative stress. The present study is under taken to assess the implication of post prandial dyslipidemia in comparison to fasting dyslipidemia in the pathogenesis of cardiovascular disease and to show the importance of increased serum ferritin levels in type 2 diabetes patients which acts as a potential risk marker for coronary artery disease. Materials and Methods: Fifty type 2 diabetes mellitus patients and fifty normal adults between age group 30-75yrs attending Medicine OPD, Rajarajeswari Medical College and Hospital, Bangalore were scree ned for lipid profile using enzymatic method by ERBA 360 autoanalyzer and serum ferritin levels by chemiluminiscence method. The statistical analysis was done by students unpaired t-test. Results: Serum lipid profile including TGs, LDL-C, VLDL-C were significantly increased in the postprandial state as compared to the fasting state in cases with p elevated in cases, compared to controls with p state compared to fasting state in cases w

Administration of eicosapentaenoic acid may alter high-density lipoprotein heterogeneity in statin-treated patients with stable coronary artery disease: A 6-month randomized trial

BackgroundCombined statin plus eicosapentaenoic acid (EPA) therapy might be a potentially effective treatment option to prevent coronary artery disease (CAD). The serum EPA/arachidonic acid (AA) ratio has been identified as a potential new risk marker for CAD. Few data exist whether administration of EPA could affect high-density lipoprotein (HDL) particle size. We hypothesized that the addition of EPA to ongoing statin therapy may result in altered HDL heterogeneity. MethodsWe conducted this 6-month, single-center, prospective, randomized open-label clinical trial to investigate the effect of the additional administration of EPA on the HDL heterogeneity (HDL2, HDL3, and HDL2/HDL3 ratio) in stable CAD patients receiving treatment with statins. We assigned stable CAD patients already receiving statin therapy to the EPA group (1800mg/day: n=50) or the control group (n=50). ResultsA significant decrease in the serum HDL3 level (−4.7% vs. −0.5%, p=0.037), but not of the serum HDL2 level, and a significant increase in the HDL2/HDL3 ratio (5.5% vs. −5.1%, p=0.032) were observed in the EPA group as compared to the control group. Multiple regression analysis with adjustments for coronary risk factors identified the achieved EPA/ AA ratio as an independent and significant predictor of an increase of the HDL2/HDL3 ratio (β=0.295, p=0.001). Furthermore, the change in the serum cholesterol ester transfer protein mass was positively correlated with the change in the EPA/AA ratio in the EPA group (r=0.286, p=0.044), but not in the control group (r=0.121, p=0.401). ConclusionAdministration of EPA might decrease the serum HDL3 level, resulting in an increase in the HDL2/HDL3 ratio. Furthermore, increased EPA/AA ratio by the addition of EPA to ongoing statin therapy might be an indicator of an increase in the HDL2/HDL3 ratio, thereby regulating HDL particle size.Clinical Trial Registration: UMIN (http://www.umin.ac.jp/) Study ID: UMIN000010452

462-P: Diabetes Is Associated with Progression of Coronary Arterial Calcification in Patients New to Dialysis

Background and Objective: Coronary artery calcification is a risk marker of atherosclerosis. Recently, a large multicenter, prospective observational study showed the CAC density was inversely related to the occurrence of cardiac vascular events. The proposed hypothesis is that low density area is more prone to rupture due to large lipid core and a marker of plaque instability. However, high CAC density in 125 chronic hemodialysis patients was associated with increased mortality. Our aim was to determine CAC density in new dialysis patients, and the role of DM in the progression of CAC density. Design, Setting, Participants, and Measurements: Ninety-eight initial dialysis patients were enrolled. CAC density was calculated by Agatson score divided by calcium volume score. CAC density progression was measured by the difference in score between CT/time. Sixty-seven study participants had repeat CAC measures at one year. Results: The mean age of study participants was 50.1 ± 12.7 years. A third were women, and 64.7% were black. The baseline CAC density for DM group was 85.2 (interquartile range (IQR), 10.3-452) compared to 0(IQR, 0-90.3) for non-DM group was (P=0.01). Seventy percent of diabetes patients had progression of calcium density while forty one percent of nondiabetic patients had progression of calcium density score. (P=0.02). Hazard ratio for DM after adjust for age and smoke is 2.0 (1.05-72.6). Conclusions: Our results indicate that DM is a risk factor for high calcium density of individuals new to dialysis patients and is a risk factor for progression of calcium density score. Increased calcium density in new dialysis patient is a risk factor for CAC progression, rather than a marker of plaque stabilization. Disclosure N. Roy: None. D. Yang: None. S. Rosas: Research Support; Self; Bayer US, Ironwood Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.

Rare SCARB1 mutations associate with high-density lipoprotein cholesterol but not with coronary artery disease.

AimsScavenger receptor Class B Type 1 (SR-BI) is a major receptor for high-density lipoprotein (HDL) that promotes hepatic uptake of cholesterol from HDL. A rare mutation p.P376L, in the gene encoding SR-BI, SCARB1, was recently reported to associate with elevated HDL cholesterol (HDL-C) and increased risk of coronary artery disease (CAD), suggesting that increased HDL-C caused by SR-BI impairment might be an independent marker of cardiovascular risk. We tested the hypothesis that alleles in or close to SCARB1 that associate with elevated levels of HDL-C also associate with increased risk of CAD in the relatively homogeneous population of Iceland.Methods and resultsUsing a large resource of whole-genome sequenced Icelanders, we identified thirteen SCARB1 coding mutations that we examined for association with HDL-C (n = 136 672). Three rare SCARB1 mutations, encoding p.G319V, p.V111M, and p.V32M (combined allelic frequency = 0.2%) associate with elevated levels of HDL-C (p.G319V: β = 11.1 mg/dL, P = 8.0 × 10−7; p.V111M: β = 8.3 mg/dL, P = 1.1 × 10−6; p.V32M: β = 10.2 mg/dL, P = 8.1 × 10−4). These mutations do not associate with CAD (36 886 cases/306 268 controls) (odds ratio = 0.90, 95% confidence interval 0.67–1.22, P = 0.49), despite effects on HDL-C comparable to that reported for p.P376L, both in terms of direction and magnitude. Furthermore, HDL-C raising alleles of three common SCARB1 non-coding variants, including one previously unreported (rs61941676-C: β = 1.25 mg/dL, P = 1.7 × 10−18), and of one low frequency coding variant (p.V135I) that independently associate with higher HDL-C, do not confer increased risk of CAD.ConclusionElevated HDL-C due to genetically compromised SR-BI function is not a marker of CAD risk.