HSP27 expression in the human peripheral blood mononuclear cells as an early prognostic biomarker in coronary artery disease patients

BackgroundCoronary artery disease (CAD), is one of the leading causes of death globally. CAD risk factors, such as smoking, dyslipidemia, and obesity, are mainly associated with increased oxidative stress. Heat Shock Protein-27 (HSP27) has a protective role in conditions of oxidative stress. The aim of the current study was to investigate the relationship between HSP27 mRNA copy numbers in the peripheral blood mononuclear cell (PBMCs) and the degree of CAD progression.MethodsA total of 103 subjects aged 49–71 years were recruited; Patients with CAD were categorized into two groups: patients having <50% stenosis (Angio^?) and ≥50% stenosis (Angio⁺). The mRNA copy numbers of HSP-27 in PBMCs, anthropometric-parameters, fasting blood glucose (FBG), and the fasted serum lipid profile were evaluated.ResultsAngio⁺ patients had a significantly higher level of TC and LDL-C values compared with Angio^? patients and the control group (p < 0.05). The HSP27 expression in PBMCs was significantly increased in Angio⁺ and Angio^? subjects, compared to the control group. Moreover, there was a significant association between the FBG, TC, LDL-C and TG among the groups (p < 0.05).ConclusionIt was shown that the increased expression of HSP27 in PBMCs of CAD patients is significantly correlated with CAD severity in Angio⁺ subjects, which can be used as an early prognostic biomarker, indicating the degree of overall oxidative stress in patients. In order to verify this statement, it is suggested to measure Pro-oxidant- Antioxidant Balance (PAB) test by the same design in subsequent studies.     

HDL cholesterol in cardiovascular diseases: The good,the bad,and the ugly?

Atherosclerotic cardiovascular diseases are the leading cause of death in developed and developing countries. HDL-raising therapeutic modalities (such as cholesterol ester transferase protein (CETP) inhibitors) are being developed to combat these diseases. However, recent setback of two CETP inhibitors (Torcetrapib and Dalcetrapib) has highlighted the importance of measuring qualitative functionality of HDL particles, rather than focusing quantitatively on HDL cholesterol serum concentrations. It has been known that, HDL from patients with coronary artery disease (CAD) (i.e., HDL^CAD) limits the anti-inflammatory and endothelial repair properties of normal HDL, due to the activation of lectin-like oxidized LDL receptor-1 (LOX-1), thereby causing failure in endothelial nitric oxide (NO) production. A more recent study (Immunity 2013; 38: 754–768) also demonstrates that HDL from patients with chronic kidney dysfunction (CKD) (i.e., HDL^CKD), unlike its healthy counterpart (i.e., HDL^Healthy), promotes superoxide production, reduces NO bioavailability and raises blood pressure via toll-like receptor-2 (TLR-2) activation. This study provides novel insights into understanding why HDL-raising agents failed to demonstrate beneficial effects on cardiovascular mortality in large clinical trials and why CKD accelerates the development of atherosclerosis in CAD patients. Further research is warranted to elucidate whether HDL^CKD and HDL^CAD participate in other cellular processes in atherosclerosis, such as foam cell formation, the proliferation and migration of smooth muscle cells, and most importantly, plaque destabilization.     

Can HDL cholesterol be replaced by paraoxonase 1 activity in the prediction of severe coronary artery disease in patients with type 2 diabetes?

Background and aimsNovel biomarkers are required to improve cardiovascular disease prediction in patients with type 2 diabetes (T2D) as a high-risk population. This study was conducted to examine whether coronary artery disease (CAD) risk assessment can be improved by substituting high-density lipoprotein (HDL)-bound paraoxonase 1 (PON1) activity for HDL cholesterol (HDL-C) concentration in patients with T2D.Methods and resultsIn this study, we studied 139 patients with T2D (mean age 64.12 ± 8.17 years) who underwent coronary angiographic examination. The initial rate of substrate hydrolysis was spectrophotometrically assayed in kinetic mode for measuring PON1 activity. Receiver operating characteristic (ROC) graphs are created by plotting true positivity versus false positivity. In patients with HbA_1c ≥ 7%, PON1 (AUC = 0.7, p = 0.029) and nonHDL-C/PON1 (AUC = 0.75, p = 0.013) were significantly more capable of differentiating patients with CAD from those without CAD compared to HDL-C and nonHDL-C/HDL-C. Also, the predictive power of PON1 (AUC = 0.64, p = 0.029) and nonHDL-C/PON1 (AUC = 0.71, p = 0.004) were significantly higher in comparison with HDL-C and nonHDL-C/HDL-C for CAD characterization in patients aged ≥50 years. Moreover, PON1 and nonHDL-C/PON1 are associated with the incidence of CAD with an AUC of 0.7 (p = 0.026) and AUC of 0.64 (p = 0.087), respectively, among subjects with low HDL-C.ConclusionPON1 and the ratio of nonHDL-C/PON1 significantly improve the prediction of severe CAD in T2D patients and in patients with HbA_1c ≥ 7%, age ≥50 years, or low HDL-C. PON1 activity and lipid ratios using this enzyme may be valuable as substitutes of HDL-C for increasing clinical efficacies in cardiovascular risk assessment.     

Adiponectin receptor 1 and small ubiquitin-like modifier 4 polymorphisms are associated with risk of coronary artery disease without diabetes

Background The genes encoding adiponectin receptor 1 (ADIPOR1) and small ubiquitin-like modifier 4 (SUMO4) have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two genes, acting separately or interacting, affect risk of coronary artery disease (CAD) without diabetes. Methods We genotyped 200 CAD patients without diabetes and 200 controls without CAD or diabetes at three single-nucleotide polymorphisms (SNPs) in ADIPOR1 and one SNP in SUMO4, which were chosen based on previous studies. Potential associations were also explored between these SNPs and clinical characteristics of CAD without diabetes. Results Risk alleles at three SNPs in ADIPOR1 (rs7539542-G, rs7514221-C and rs3737884-G) and the G allele at SNP rs237025 in SUMO4 significantly increased risk of CAD without diabetes, with ORs ranging from 1.79 to 4.44. Carriers of any of these four risk alleles showed similar adverse clinical characteristics. Compared with individuals with a CC or GC genotype, those with a GG genotype at rs3737884 were at significantly higher risk of CAD that affected the left anterior descending coronary artery (OR: 6.77, P = 0.009), the right coronary artery (OR: 4.81, P = 0.028) or a relatively large number of vessels (P = 0.04). Individuals carrying a risk allele at one or more of the three SNPs in ADIPOR1 as well as a risk allele at the SNP in SUMO4 were at significantly higher risk of CAD without diabetes than individuals not carrying any risk alleles (OR: 5.82, 95% CI: 1.23?27.7, P = 0.013). Conclusions SNPs in ADIPOR1 and SUMO4 are associated with elevated risk of CAD without diabetes, and SNPs in the two genes may interact to jointly affect disease risk.     

Circulating Endothelial Progenitor Cells as Markers for Severity of Ischemic Chronic Heart Failure

IntroductionDespite a high potential of endothelial progenitor cells (EPCs) for diagnostic purposes, the EPC role in developing ischemic chronic heart failure (CHF) has not been determined obviously.The objective of this study was to assess the counts of CD45⁺CD34⁺, CD45⁻CD34⁺, CD14⁺CD309⁺, and CD14⁺CD309⁺Tie2⁺ phenotyped circulating EPCs of various subpopulations in patients with ischemic CHF.Methods and ResultsThe study involved 153 patients (86 male), aged 48–62 years, with angiographically proven coronary artery disease (CAD) and 25 healthy volunteers. CHF was diagnosed in 109 patients (71.2%). Mononuclear cell populations were phenotyped by flow cytofluorimetry. Cardiovascular risk factors, such as type 2 diabetes mellitus, hyperlipidemia, arterial hypertension, and adherence to smoking, may have a negative effect on circulating EPC counts in CAD patients regardless of the presence of CHF. The depletion of the CD14⁺CD309⁺- and CD14⁺CD309⁺Tie2⁺-phenotyped circulating EPC counts is associated with the severity of left ventricular dysfunction, whereas the CD45⁺CD34⁺- and CD45⁻CD34⁺-mononuclear cell counts are more representative of the severity of atherosclerotic coronary artery lesions.ConclusionThe authors found that New York Heart Association functional class of CHF, left ventricular ejection fraction <42%, the N-terminal pro–B-type natriuretic peptide level >554 pg/mL, and Е/Еm ratio >15 U had the highest predictive value for the depletion of the EPC count in CAD patients.     

Combined cCTA and TAVR Planning for Ruling Out Significant CAD: Added Value of ML-Based CT-FFR

ObjectivesThe purpose of this study was to analyze the ability of machine-learning (ML)-based computed tomography (CT)-derived fractional flow reserve (CT-FFR) to further improve the diagnostic performance of coronary CT angiography (cCTA) for ruling out significant coronary artery disease (CAD) during pre-transcatheter aortic valve replacement (TAVR) evaluation in patients with a high pre-test probability for CAD.BackgroundCAD is a frequent comorbidity in patients undergoing TAVR. Current guidelines recommend its assessment before TAVR. If significant CAD can be excluded on cCTA, invasive coronary angiography (ICA) may be avoided. Although cCTA is a very sensitive test, it is limited by relatively low specificity and positive predictive value, particularly in high-risk patients.MethodsOverall, 460 patients (age 79.6 ± 7.4 years) undergoing pre-TAVR CT were included and examined with an electrocardiogram-gated CT scan of the heart and high-pitch scan of the vascular access route. Images were evaluated for significant CAD. Patients routinely underwent ICA (388/460), which was omitted at the discretion of the local Heart Team if CAD could be effectively ruled out on cCTA (72/460). CT examinations in which CAD could not be ruled out (CAD⁺) (n = 272) underwent additional ML-based CT-FFR.ResultsML-based CT-FFR was successfully performed in 79.4% (216/272) of all CAD⁺ patients and correctly reclassified 17 patients as CAD negative. CT-FFR was not feasible in 20.6% because of reduced image quality (37/56) or anatomic variants (19/56). Sensitivity, specificity, positive predictive value, and negative predictive value were 94.9%, 52.0%, 52.2%, and 94.9%, respectively. The additional evaluation with ML-based CT-FFR increased accuracy by Δ+3.4% (CAD⁺: Δ+6.0%) and raised the total number of examinations negative for CAD to 43.9% (202/460).ConclusionsML-based CT-FFR may further improve the diagnostic performance of cCTA by correctly reclassifying a considerable proportion of patients with morphological signs of obstructive CAD on cCTA during pre-TAVR evaluation. Thereby, CT-FFR has the potential to further reduce the need for ICA in this challenging elderly group of patients before TAVR.     

Undiagnosed coronary artery disease in long-term type 1 diabetes. The Dialong study

Aims

We studied the total prevalence of obstructive coronary artery disease (CAD), undiagnosed CAD and absent CAD in persons with ≥45-year duration of type 1 diabetes (T1D) versus controls, and associations with mean HbA_1c, LDL-cholesterol and blood pressure over 2–3 decades.

Improved risk assessment of coronary artery disease by substituting paraoxonase 1 activity for HDL-C: Novel cardiometabolic biomarkers based on HDL functionality

Background and aimsDeveloping laboratory assays to evaluate HDL functions and improve cardiovascular disease (CVD) risk assessment has recently emerged as a challenge. The present study was conducted to help predict the risk of coronary artery disease (CAD) by investigating new cardiometabolic risk factors based on substituting paraoxonase 1 (PON1) as a critical enzyme in the functionality of HDL for that of HDL-C.Methods and resultsThe present study recruited 274 subjects undergoing diagnostic coronary angiography, 92 without significant CAD (non-CAD), and 182 with a severe CAD. The diagnostic accuracy of the new biomarkers in non-CAD versus multi-vessel disease was obtained in descending order of AUC as 0.72 (P < 0.001) for log (TG/PON1), 0.70 (P < 0.001) for nonHDL-C/PON1, and 0.67 (P < 0.001) for LDL-C/PON1. After performing a multivariate adjustment for age, gender, BMI, statin therapy, and diabetes mellitus, the increased odds of CAD remained significant for the new cardiometabolic ratios as independent variables [adjusted OR = 1.47 (1.15–1.88), p = 0.002 for LDL-C/PON1; adjusted OR = 2.15 (1.41–3.5), p = 0.009 for nonHDL-C/PON1; adjusted OR = 5.03 (2.14–13.02), p = 0.004 for log (TG/PON1)]. CAD was diagnosed with an optimal discriminating cutoff of 1.84 for LDL-C/PON1, 2.8 for nonHDL-C/PON1, and 0.48 for log (TG/PON1).ConclusionsTo improve CAD's risk assessment, the PON1 activity was proposed as an alternative to HDL-C in the commonly used atherogenic lipid ratios. Substituting the PON1 activity for the HDL-C concentration can provide an index of the HDL activity. The present study sought to exploit the lipoprotein-related risk factors of CAD from a more effective perspective.     

Associations Between Plasma Kinin B1 Receptor Levels and the Presence and Severity of Coronary Artery Disease

Aim: Kinin B1 receptor (KB1R) was shown to be up-regulated in human carotid atherosclerotic lesions. Serum KB1R levels were also reported to be high in patients with stroke. However, KB1R deficiency increased atherosclerotic lesions. Therefore, the role of KB1R in atherosclerosis remains unclear. Moreover, no study has reported blood KB1R levels in patients with coronary artery disease (CAD). Methods: We measured plasma KB1R levels in 375 patients undergoing coronary angiography. The severity of CAD was represented as the numbers of ＞50% stenotic vessels and segments and the severity score. Results: CAD was found in 197 patients, of whom 89 had 1-vessel disease (1-VD), 62 had 2-VD, and 46 had 3-VD. Plasma KB1R levels were higher in 197 patients with CAD than in 178 without CAD (median 83.3 vs. 73.7 pg/mL, p ＜0.01). A stepwise increase in KB1R levels was found depending on the number of stenotic vessels: 77.1 in 1-VD, 87.8 in 2-VD, and 88.5 pg/mL in 3-VD ( p ＜0.025). A high KB1R level (＞90.0 pg/mL) was present in 30% of patients with CAD(-), 39% of 1-VD, 50% of 2-VD, and 48% of 3-VD ( p ＜0.025). KB1R levels correlated with the number of stenotic segments and the severity score (r=0.14 and r=0.17, p ＜0.01). In multivariate analysis, KB1R levels were an independent factor associated with CAD. Odds ratio for CAD was 1.62 (95%CI=1.02-2.58) for high KB1R level ＞90.0 pg/mL. Conclusion: Plasma KB1R levels in patients with CAD were high and were associated with the presence and severity of CAD independent of atherosclerotic risk factors.     

Ligation of RAGE with ligand S100B attenuates ABCA1 expression in monocytes

Hypothesis

ATP Binding Cassette Transporter (ABC) A1 is one of the key regulators of HDL synthesis and reverse cholesterol transport. Activation of Receptors for Advanced Glycation End products (RAGE) is involved in the pathogenesis of diabetes, and its complications. The aim of the present study is to examine the effect of RAGE ligand S100B on ABCA1 expression.

Methods

S100B mediated regulation of LXR target genes like ABCA1, ABCG1, ABCG8, LXR-α and LXR-β in THP-1 cells was analyzed by real-time PCR, RT-PCR and western blots. ABCA1 mRNA expression in monocytes from diabetic patients was studied. Effect of LXR ligand on S100B induced changes in LXR target genes was also studied. Luciferase reporter assay was used for S100B induced ABCA1 promoter regulation.

Results

S100B treatment resulted in a significant 2–3 fold reduction (p < 0.01) in ABCA1 and ABCG1 mRNA in dose and time dependent manner in THP1 cells. ABCA1 protein level was also significantly (p < 0.01) reduced. S100B-induced reduction on ABCA1 mRNA expression was blocked by treating THP-1 cell with anti-RAGE antibody. Reduced ABCA1 mRNA levels seen in peripheral blood monocytes from diabetes patients showed the in-vivo relevance of our in-vitro results. Effect of S100B on ABCA1 and ABCG1 expression was reversed by LXR ligand treatment. S100B treatment showed significant 2 fold (p < 0.01) decrease in T1317 induced ABCA1 promoter activation.

Conclusions

These results show for the first time that ligation of RAGE with S100B can attenuate the expression of ABCA1 and ABCG1 through the LXRs. This could reduce ApoA-I-mediated cholesterol efflux from monocytes.     

A polymorphism in the ABCG1 promoter is functionally associated with coronary artery disease in a Chinese Han population

Objective

In this study, we examine the association of single nucleotide polymorphisms (SNPs) of the human ATP binding cassette transporter G1 (ABCG1) gene with atherosclerotic coronary artery disease (CAD) in a Chinese Han population.

Methods

1021 patients with CAD and 1013 unaffected control subjects were enrolled. PCR-based ligation detection reaction (PCR-LDR) method was used to genotype four SNPs of ABCG1, three (rs2234714, rs2234715 and rs57137919) in the promoter region and one (rs1044317) in the 3′-untranslated region (UTR).

Results

The human ABCG1 −367G>A polymorphism (rs57137919) showed a significantly decreased risk for CAD and myocardial infarction (MI) in a dominant model (adjusted OR = 0.73, p = 0.033 for CAD, and adjusted OR = 0.65, p = 0.014 for MI, respectively). The rs57137919 also showed an association with angiographic severity of CAD (multi-vessel vs. single-vessel CAD, adjusted OR = 0.40, p = 0.005). The findings were further supported by luciferase reporter assay, in which the polymorphism impaired reporter gene expression. The ABCG1 −768G>A polymorphism (rs2234714) showed an association with CAD in a recessive model (adjusted OR = 0.64, p = 0.015), but did not demonstrate a functional influence on reporter gene expression in the luciferase reporter assay.

Conclusions

The SNP rs57137919 in the ABCG1 promoter region is functionally associated with a reduced risk of CAD in a Chinese Han population.     

Periodontal disease,smoking, cardiovascular complications and mortality in type 1 diabetes

AimTo assess the role of periodontal disease (PD) as a predictor of coronary artery disease (CAD) and mortality in a prospective type 1 diabetes (T1D) cohort and to evaluate the role of smoking in this relationship.MethodsData were based on 320 participants of the Pittsburgh Epidemiology of Diabetes Complications study of T1D who, during 1992–94, received a partial mouth periodontal exam, and who were followed for up to 19 years to ascertain complication incidence. PD was defined as clinical attachment loss of ≥4 mm for at least 10% of the examined sites. Predictors of all-cause mortality; Hard CAD (CAD death, myocardial infarction or revascularization), and Total CAD (Hard CAD, angina, ischemic ECG) were assessed using Cox models.ResultsDuring 19 years of follow-up, 33.7% (97/288) developed CAD, 27.3% (83/304) developed Hard CAD, and 16.9% (54/320) died. Among current smokers, 46.4% (26/56) developed CAD, 42.7% (24/56) developed Hard CAD and 29.5% (18/61) died. PD was not associated with all-cause mortality, although it was a significant predictor of both CAD (HR = 1.12, CI = 1.01–1.23) and Hard CAD (HR = 1.30, CI = 1.11–1.51). As smoking modified the PD-CAD and PD-Hard CAD associations, analyses were stratified by smoking status. PD was associated with an increased risk of CAD (HR = 1.25, CI = 1.03–1.50) and Hard CAD (HR = 1.85, CI = 1.17–2.93) only among smokers.ConclusionPD was a significant predictor of CAD and Hard CAD among current smokers with T1D.     

rs629301 CELSR2 polymorphism confers a ten-year equivalent risk of critical stenosis assessed by coronary angiography

Background and aimsNovel genetic determinants associated with coronary artery disease (CAD) have been discovered by genome wide association studies. Variants encompassing the CELSR2- PSRC1-SORT1 gene cluster have been associated with CAD. This study is aimed to investigate the rs629301 polymorphism association with the extent of CAD evaluated by coronary angiography (CAG), and to evaluate its associations with an extensive panel of lipid and lipoprotein measurements in a large Italian cohort of 2429 patients.Methods and resultsThe patients were collected by four Intensive Care Units located in Palermo and Verona (Italy). Clinical Records were filed, blood samples were collected, lipids and apolipoproteins (apo) were measured in separate laboratories. CAD was defined by the presence of stenotic arteries (>50% lumen diameter) by CAG.The presence of CAD was associated with the rs629301 genotype. Patients with CAD were 78% and 73% (p = 0.007) of the T/T vs. T/G + G/G genotype carriers respectively. T/T genotype was also correlated with the number of stenotic arteries, with a 1.29 (1.04–1.61) risk to have a three-arteries disease. T/T genotype correlated with higher levels of LDL-, non-HDL cholesterol, apoB, apoE and apoCIII, and lower HDL-cholesterol. Logistic Regression confirmed that rs629301was associated with CAD independently from the common risk factors, with a risk similar to that conferred by ten years of age [odds ratios were 1.43 (1.04–1.96) and 1.39 (1.22–1.58) respectively].Conclusionsrs629301 risk allele was independently associated with the extension and severity of CAD and positively with apoE and apoB containing lipoproteins.     

Role of ankle-brachial pressure index as a predictor of coronary artery disease severity in patients with diabetes mellitus

BACKGROUND:

Previous studies have reported a close correlation between low ankle-brachial pressure index (ABPI) and various cardiovascular risk factors. However, despite the well-established potential hazards of consequent coronary artery disease (CAD), no data exist on the relationship between ABPI and the severity of CAD, particularly in patients with diabetes mellitus (DM).

METHODS:

A total of 840 patients ranging from 35 to 87 years of age (mean [± SD] 63.9±10.2 years) with suspected CAD in a clinical practice were enrolled. All patients underwent ABPI measurements and coronary angiography. Patients were divided into four groups according to the results of ABPI measurements and the presence or absence of DM: group A had an ABPI value of at least 0.9 but no DM (A⁻/D⁻); group B had an ABPI value of at least 0.9 and DM (A⁻/D⁺); group C had an ABPI of less than 0.9 but no DM (A⁺/D⁻); and group D had an ABPI value of less than 0.9 and DM (A⁺/D⁺).

RESULTS:

Age was significantly higher in the A⁺ (groups C and D) than the A⁻ patients (groups A and B). Moreover, men predominated in all four groups. Comparisons of sex distribution among the four groups revealed that group D had the highest percentage of women, while group A had the lowest. Total cholesterol level did not differ among the four groups, although group D tended to have the highest result. Patients in group D had the highest percentages of hypertension, hypercholesterol, hypertriglyceride, low high-density lipoprotein cholesterol and high low-density lipoprotein cholesterol among the four groups. Group D exhibited the highest triglyceride and uric acid levels, the lowest high-density lipoprotein cholesterol level, and the highest metabolic syndrome criteria number and percentage of metabolic syndrome. Furthermore, group D had the highest mean lesion numbers, mean numbers of target vessel involvement, stenoses with type C classification and complex morphology lesions (chronic total occlusion, diffuse or calcified lesions) among the four groups. There were still significant differences in lesion numbers (P<0.001) and numbers of target vessel involvement (P<0.001) for ABPI predicting CAD severity after controlling for the effects of DM and age. The sensitivity, specificity, positive predictive value and negative predictive value of using an ABPI of less than 0.9 to predict CAD differed significantly between patients with and without DM.

CONCLUSIONS:

ABPI is a useful noninvasive tool for predicting CAD severity, even in patients with DM.     

Serum lipid profile in diabetic macular edema

PurposeTo evaluate the correlation of lipid profile and clinical presentation of macular edema in Type 2 diabetes mellitus (DM) patients.Materials and MethodsThe study included 20 patients with chronic diabetic macular edema and plaque-like hard exudates (Group 1), 20 patients with diabetic macular edema (Group 2), and 20 DM patients but without retinopathy (Group 3). Diabetic retinopathy was classified according to the Early Treatment Diabetic Retinopathy Study grading system. Sample t test was used to evaluate the association between the fasting serum lipid [total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL)], glycosylated hemoglobin (HbA1c), fasting blood glucose, creatinine levels, and the clinical findings. P values <.05 were considered statistically significant.ResultsThere was no difference between fasting serum lipids and HbA1c levels. Duration of diabetes was shorter in Group 3 than in Groups 1 and 2. Patients in Group 1 had longer duration of diabetes than others (P<.05). Creatinine levels in Group 1 were higher than in other groups (P<.05). Although there was no correlation between fasting blood glucose and HbA1c levels, HbA1c was higher in all three groups from the baseline-normal limits (P<.05).ConclusionNo correlation was found between serum lipid levels and macular edema severity, but the duration of diabetes was demonstrated as a significant factor in the progression of macular edema. High HbA1c levels in all patients highlight the importance of intense glycemic control in diabetic patients.     

High-Density Lipoprotein Cholesterol Efflux Capacity as a Novel Prognostic Surrogate for Coronary Artery Disease

Aim: We examined the impact of baseline high-density lipoprotein cholesterol efflux capacity (CEC) on major cardiac adverse events (MACE) in patients with coronary artery disease (CAD) during a long-term secondary prevention. Method: CEC was measured using a cell-based efflux system in (3)[H]-cholesterol-labeled J774 macrophages in apolipoprotein B-depleted plasma between January 2011 and January 2013. Patients with CAD were divided into 2 groups as a boundary CEC value of 1: 0.19 ≤ CEC ＜1 (impaired CEC group, mean CEC of 0.76±0.16, n =136), and 1 ≤ CEC ≤ 2.08 (enhanced CEC group, 1.20±0.19, n =44). MACE, comprised the incidence of cardiac death, non-fatal myocardial infarction, and any revascularizations (RV) without restenosis approximately 1 year after vascularization, was retrospectively investigated at September 2019. Impact of enhanced CEC on MACE among 22 variables was examined by applying a Cox proportional hazard model. Result: The frequency of MACE in impaired CEC group (16.9%, mean observational interval of 2111±888 days) was significantly higher than that in enhanced CEC group (2.3%, 2,252±685, p =0.013), largely driven by the significantly higher RV incidence (14.0 % versus 2.3 %, p =0.032). Enhancement of CEC was the significant predictor of MACE (hazard ratio: 0.11; 95% CI: 0.013-0.879; p =0.038). Conclusion: A baseline CEC level of more than 1 in patients with CAD brought favorable long-term clinical outcomes, suggesting that CEC is a useful prognostic and therapeutic surrogate for secondary prevention of CAD.     

Role of cytochrome epoxygenase (CYP2J2) in the pathophysiology of coronary artery disease in South Indian population

Background

The cytochrome P-450 2J2 (CYP2J2) is known to be one of the major enzymes of epoxygenase pathway of arachidonic acid in extrahepatic tissues, which produces series of regioisomeric cis-epoxyeicosatrienoic acids (EETs) such as 5,6-, 8,9-, 11,12-, and 14,15-EETs. In the present study, we analyzed the impact of a genetic variant in CYP2J2 on coronary artery disease (CAD) in the Telangana region of Indian population.

Monocyte subsets in coronary artery disease and their associations with markers of inflammation and fibrinolysis

Aims

The multiple roles of monocytes in atherogenesis, including inflammation, angiogenesis and repair are attributed to the existence of different monocyte sub-populations. Scarce data are available on changes in phenotype and functional status of human monocyte subsets in patients with coronary artery disease (CAD), especially when monocytes are evaluated as three distinct subsets.

Methods and results

Surface expression of receptors implicated in inflammation, repair and activation status (intracellular IKKβ) of monocyte subsets was assessed by flow cytometry in 53 patients with CAD and compared to 50 age- and sex-matched healthy controls. Monocyte subsets were defined as CD14++CD16−CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2− (Mon3). Plasma levels of inflammatory cytokines (FACSArray) and fibrinolytic factors (ELISA) were measured in CAD. CAD was associated with reduced expression of CD14 on Mon1 (p = 0.02) and Mon3 (p = 0.036), higher expression of IL6 receptor on Mon1 (p = 0.025) and Mon2 (p = 0.015), CXCR4 on Mon1 (p = 0.035) and Mon3 (p = 0.003), and CD34 on all subsets (all p < 0.007). Monocyte CD163 expression correlated negatively with interleukin (IL)-6 levels (p < 0.01 for all subsets). Expression of vascular endothelial growth factor receptor-1 correlated positively with plasminogen activator inhibitor (PAI)-1 antigen levels (r = 0.47, p = 0.006). In vitro, monocyte subsets derived from CAD patients showed significantly altered responses to endotoxin stimulation compared to monocytes from healthy controls.

Conclusions

There is a complex interplay between phenotype and activity of monocytes and plasma cytokines and fibrinolytic factors. These findings support the presence of unique roles for the three human monocyte subsets in atherogenesis and CAD pathogenesis.