Hematological parameters and early-onset coronary artery disease: a retrospective case-control study based on 3366 participants.

Background: Thrombosis and inflammation are crucial elements in the pathogenesis of cardiovascular disease. Hematological parameters elucidate information involving the inflammatory and blood coagulation processes. Objectives: The current study explored the association of hematological parameters with EOCAD to identify specific risk factors. Design: A single-center retrospective case-control study was conducted with 1693 coronary artery disease patients and 1693 controls. Methods: Hematological parameters were examined through an automated analyzer. Results: The basophil percentage was significantly reduced in EOCAD (0.43 ± 0.26, p < 0.001) and MI (0.33 ± 0.24, p < 0.001) groups compared with controls (0.54 ± 0.28). The eosinophil percentage was also significantly lower in EOCAD (2.21 ± 1.71, p < 0.001) and MI (1.71 ± 2.44, p < 0.001) groups compared with controls (2.41 ± 1.75). The lymphocyte percentage in patients of EOCAD and MI and controls was 31.65 ± 7.93, 25.48 ± 9.43, and 34.82 ± 7.28, respectively. A significant difference was observed among the groups (p < 0.001). Except for the mean corpuscular hemoglobin (MCH), other red blood cell (RBC) parameters significantly differed between EOCAD patients and controls. The red blood cell distribution width (RDW), hematocrit (HCT), RBC count, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), and hemoglobin level were associated with EOCAD prevalence after adjusting for baseline differences. Platelet volume distribution width (PDW) also correlated with EOCAD prevalence (ORadjust = 1.087, 95% CI: 1.044-1.131). Conclusions: Hematological parameters are closely associated with EOCAD. Moreover, leukocyte parameters correlated with the presence and severity of the disease. In addition, erythrocyte parameters were associated with the disease presence but not with the disease severity. Among the platelet parameters, only PDW was related to the disease presence.

Serum fatty acids profile and association with early-onset coronary artery disease.

BACKGROUND: Fatty acids (FAs) play crucial roles in modulating and preventing diseases in humans, including early-onset coronary artery disease (EOCAD). In this study, we aimed to provide a profile of FAs in the serum of EOCAD patients and identify potential EOCAD-associated FAs. METHODS: In the first stage, we analyzed the FAs profiles in pooled samples of patients with EOCAD using gas chromatography-mass spectrometry. In the second stage, the serum levels of the candidate FAs were validated in EOCAD patients. RESULTS: A total of 128 EOCAD patients and 64 controls were included in the study. Forty-nine serum FAs were quantified in pooled samples; three ω-3 FAs were identified to be associated with EOCAD. Moreover, results from the validation stage indicated that serum levels of docosahexaenoic acid (DHA) were significantly lower in EOCAD patients (55.43 ± 33.86 µg/ml) and myocardial infarction (MI) patients (47.49 ± 28.44 µg/ml) than those in the controls (70.65 ± 43.56 µg/ml). Multivariate regression analysis revealed that elevated serum DHA level was an independent protective factor for EOCAD [odds ratio (OR) = 0.8917, 95% confidence interval (CI): 0.879-0.957] and MI (OR = 0.835, 95% CI: 0.799-0.862). Decreased serum levels of docosapentaenoic acid (DPA) and eicosapentaenoic acid (EPA) were observed in the early-onset MI group. CONCLUSION: The study provided the serum FAs profile of EOCAD and confirmed that the decrease in serum levels of DHA, DPA, and EPA was associated with EOCAD. These findings might contribute to understanding the cardiovascular effects of FAs, particularly the protective effects of ω-3 polyunsaturated FAs.

Quantitative Assessment of Serum Amino Acids and Association with Early-Onset Coronary Artery Disease.

BACKGROUND: Amino acids play essential roles in protein construction and metabolism. Our study aims to provide a profile of amino acid changes in the serum of patients with early-onset coronary artery disease (EOCAD) and identify potential disease biomarkers. METHODS: Ultra-performance liquid chromatography-multiple reaction monitoring-multistage/mass spectrometry (UPLC-MRM-MS/MS) was used to determine the amino acid profile of patients with EOCAD in sample pools. In the validation stage, the serum levels of candidate amino acids of interest are determined for each sample. RESULTS: A total of 128 EOCAD patients and 64 healthy controls were included in the study. Eight serum amino acids associated with disease state were identified. Compared with the control group, serum levels of seven amino acids (L-Arginine, L-Methionine, L-Tyrosine, L-Serine, L-Aspartic acid, L-Phenylalanine, and L-Glutamic acid) increased and one (4-Hydroxyproline) decreased in the patient group. Results from the validation stage demonstrate that serum levels of 4-Hydroxyproline were significantly lower in myocardial infarction (MI) patients (9.889 ± 3.635 µg/mL) than those in the controls (16.433 ± 4.562 µmol/L, p < 0.001). Elevated serum 4-Hydroxyproline levels were shown to be an independent protective factor for MI (OR = 0.863, 95% CI: 0.822-0.901). The significant negative correlation was seen between serum 4-Hydroxyproline levels and cardiac troponin I (r = -0.667) in MI patients. CONCLUSION: We have provided a serum amino acid profile for EOCAD patients and screened eight disease state-related amino acids, and we have also shown that 4-Hydroxyproline is a promising target for further biomarker studies in early-onset MI.

Association between ALMS 1 variants and early-onset coronary artery disease: a case-control study in Chinese population.

BACKGROUND: Genome-wide linkage analysis revealed the polymorphism of rs6748040 and glutamic acid repeat are potential pathogenic factors of early-onset myocardial infarction (MI). The present study was designed to investigate the associations of Alström syndrome 1 (ALMS 1) gene in Chinese populations with early-onset coronary artery disease (CAD). METHODS: The two variants of the ALMS 1 gene were genotyped in 1252 early-onset CAD patients and 1378 controls using PCR, followed by Sml I restriction enzyme digestion or direct sequencing of the PCR product. The associations were estimated using the odds ratio (OR) and the 95% confidence interval (CI). RESULTS: A significant association between the ALMS 1 G/A variant and the risk of early-onset MI was detected in G vs.A (OR = 1.371, 95% CI: 1.183-1.589), GG vs. AA (OR = 2.037, 95% CI: 1.408-2.948), dominant genetic model (OR = 1.794, 95% CI: 1.254-2.567), and recessive genetic model (OR = 1.421, 95% CI: 1.177-1.716). 14 glutamic acid repeat (A14) is risk factor for early-onset MI (OR = 1.605, 95% CI: 1.313-1.962) and 17 glutamic acid repeat (A17) is protective factor for the disease (OR = 0.684, 95% CI: 0.601-0.827). These associations were not detected in early-onset CAD patients. CONCLUSIONS: Our findings indicated that G/A variant (rs6748040) and glutamic acid repeat polymorphism of the ALMS 1 gene associated with the risk of early-onset MI in the Chinese population.

Association Between MTHFR Gene Common Variants, Serum Homocysteine, and Risk of Early-Onset Coronary Artery Disease: A Case-Control Study.

The common variants of the methylenetetrahydrofolate reductase (MTHFR) gene are related to the activity of the MTHFR enzyme and the concentrations of blood homocysteine (Hcy). This study was designed to investigate the associations of MTHFR in Chinese populations with early-onset coronary artery disease (EOCAD). The two common variants of the MTHFR gene were genotyped in 875 EOCAD patients and 956 controls using PCR, followed by direct sequencing of the PCR product. Serum levels of Hcy were measured using an automatic biochemistry analyzer. A significant association between the MTHFR-677C/T variant and the risk of EOCAD was detected in CC versus TT (odds ratio (OR) 1.456, 95% confidence interval (CI) 1.120-1.892), dominant genetic model (OR 1.266, 95% CI 1.027-1.546), and recessive genetic model (OR 1.306, 95% CI 1.040-1.639). Hcy was most abundant in TT genotype (18.31 ± 7.22 µmol/L), least abundant in CC genotype (11.37 ± 5.23 µmol/L), and detectable at intermediate levels in heterozygotes (15.25 ± 6.58 µmol/L). Elevated serum Hcy levels were an independent risk factor for EOCAD (ORadjust 1.431, 95% CI 1.135-1.763). Our findings indicated that the T allele of -677C/T MTHFR variant predisposes to high levels of Hcy, and that the T allele is an important risk factor for EOCAD in the Chinese population.

Serum adenosine deaminase activity and coronary artery disease: a retrospective case-control study based on 9929 participants.

BACKGROUND: Adenosine deaminase (ADA) regulates purine metabolism through the conversion of adenosine to uric acid (UA). Adenosine and UA are closely associated with cardiovascular events, but the correlation between serum ADA activity and coronary artery disease (CAD) has not been defined. METHODS: We performed a hospital-based retrospective case-control study that included a total of 5212 patients with CAD and 4717 sex- and age-matched controls. The serum activity of ADA was determined by peroxidase assays in an automatic biochemistry analyzer. RESULTS: Serum ADA activity in the CAD group (10.08 ± 3.57 U/l) was significantly lower than that of the control group (11.71 ± 4.20 U/l, p < 0.001). After adjusting for conventional factors, serum ADA activity negatively correlated with the presence of CAD (odds ratio = 0.852, 95% confidence interval: 0.839-0.865, p < 0.001). Among the patients with CAD, serum ADA activity was lowest in patients with myocardial infarction (MI; 9.77 ± 3.80 U/l). Diabetes mellitus and hypertension increased the serum ADA activity in CAD patients. CONCLUSIONS: Serum ADA activity is significantly attenuated in patients with CAD, particularly in MI. We propose a mechanism by which the body maintains adenosine levels to protect the cardiovascular system in the event of CAD.

Screening and Identification of Pregnancy Zone Protein and Leucine-Rich Alpha-2-Glycoprotein as Potential Serum Biomarkers for Early-Onset Myocardial Infarction using Protein Profile Analysis.

PURPOSE: The present study aims to discover novel serum biomarkers of early-onset myocardial infarction (MI) using proteomic analysis. EXPERIMENTAL DESIGN: In the first stage, the iTRAQ-coupled LC-MS/MS technique is utilized to investigate protein profiles of patients with early-onset MI. In the second stage, these candidate proteins are validated using ELISA. RESULTS: A total of 538 proteins are quantified, with pregnancy zone protein (PZP), leucine-rich α-2-glycoprotein (LRG) and Apolipoprotein C-I (Apo C-I) being upregulated and Apolipoprotein A-I (Apo A-I) and Apolipoprotein A-IV (Apo A-IV) downregulated in early-onset MI patients. Results from the validation stage demonstrate that the serum concentrations of PZP and LRG are significantly increased in the early-onset MI group. The correlation between the concentrations of C-reactive protein (CRP) and the two candidate biomarkers is positive. Area under the curve values used to diagnose early-onset MI for LRG and PZP are 0.939 and 0.874, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Five differential serum proteins are identified in early-onset MI using proteomic analysis. Lipoprotein-related biomarkers further demonstrate the close relationship between lipid metabolism and the disease. Inflammation-associated LRG and PZP may be novel biomarkers of the disease. In addition, changes in these proteins may partly reveal the possible mechanisms in the pathogenesis and pathophysiology of early-onset MI.

Serum Uric Acid as an Independent Risk Factor for the Presence and Severity of Early-Onset Coronary Artery Disease: A Case-Control Study.

Serum uric acid (UA) is the final product of purine metabolism in humans. The present study is aimed at identifying the potential association between serum UA and early-onset coronary artery disease (EOCAD). The study population consisted of 1093 EOCAD patients aged ≤50 years, and 1117 age- and sex-matched apparently healthy people served as controls. The concentrations of UA were measured by uricase method. The severity of CAD was evaluated by Gensini score. The mean serum level of UA was 5.843 ± 1.479 mg/dl in EOCAD patients and 5.433 ± 1.529 mg/dl in controls. Serum UA levels were significantly higher in the EOCAD group than those in the control group (P < 0.001) and was an independent risk factor for EOCAD (OR = 1.100, 95% CI: 1.022-1.185). The early-onset myocardial infarction patients with 3-vessel disease had higher serum UA levels than those with 1- or 2-vessel disease. The serum UA levels of EOCAD patients with acute coronary syndrome were significantly higher than those with chronic coronary artery disease. EOCAD patients with hyperuricemia had higher Gensini scores than those without hyperuricemia. In addition, the serum UA levels were affected by drinking (P < 0.01) and were positively correlated with serum creatinine (r = 0.323) and weight (r = 0.327). Our results show that serum UA was an independent risk factor for EOCAD. The serum UA levels were associated with the presence and severity of EOCAD and suggested that UA may be involved in the progression of EOCAD.

Dimethylarginine Dimethylaminohydrolase 2 (DDAH 2) Gene Polymorphism, Asymmetric Dimethylarginine (ADMA) Concentrations, and Risk of Coronary Artery Disease: A Case-Control Study.

Asymmetric dimethylarginine (ADMA) has been shown to be an independent predictor of cardiovascular diseases. Dimethylarginine dimethylaminohydrolase 2 (DDAH 2) promotes the metabolism of ADMA and plays a key role in the regulation of acute inflammatory response. With the present study, we investigated the relationship between DDAH 2 polymorphisms and risk of coronary artery disease (CAD) and its association to plasma ADMA concentrations. We used the haplotype-tagging SNP approach to identify tag SNPs in DDAH 2. The SNPs were genotyped by PCR and sequenced in 385 CAD patients and 353 healthy controls. Plasma concentrations of ADMA were determined using enzyme-linked immunosorbent assay (ELISA). A promoter polymorphism -449C/G (rs805305) in DDAH 2 was identified. Compared with the ADMA concentrations in CC genotype (0.328 ± 0.077 µmol/l), ADMA concentrations in CG + GG genotype were significantly increased (0.517 ± 0.090 µmol/l, P < 0.001). No significant associations between the -449C/G and risk of CAD were detected in the genetic models. The results of this study suggest that Genetic -499C/G polymorphism in DDAH 2 gene may affect the plasma ADMA concentrations in patients with CAD. However, it does not indicate a novel genetic risk marker for CAD.

Histone demethylases and their roles in cancer epigenetics.

The genetic abnormalities that drive tumorigenesis are usually coupled with epigenetic alterations, such as DNA methylation and aberrant histone modifications, which may help oncogenic drivers accelerate cancer progression, metastasis, and therapy resistance. The discovery of histone demethylases has provided us new insight for understanding the epigenetic landscape of the chromatin environment of cancer cells. This review aims to summarize the current knowledge on the human histone lysine demethylases and their functions in cancers, and recent advances in development of small molecule inhibitors to target histone demethylases in cancer treatment.

Levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, and risk of coronary artery disease: A meta-analysis based on 4713 participants.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase by competing with L-arginine. As a result, the expression of nitric oxide decreases and endothelial dysfunction occurs. Studies have evaluated the association between the serum ADMA level and risk of coronary artery disease. However, conflicting results have been obtained. METHODS: Pubmed, Web of Science, Embase, Ovid, Cochrane databases were searched to identify eligible studies published in English until December 2014. Association was assessed on the basis of weighted mean differences (WMD) with 95% confidence intervals (CIs). Publication bias was analysed using Begg's and Egger's tests. Sensitivity analysis was performed to evaluate result stability. RESULTS: A total of 16 case-control studies with 2939 patients and 1774 controls were included in the meta-analysis. Pooled result indicated that patients with coronary artery disease yielded a higher ADMA level than healthy controls (WMD: 0.248, 95% CI: 0.156-0.340; p = 1.16 e-7). Sensitivity analysis suggested that our meta-analysis result was stable. Subgroup analysis found a similar pattern in patients with myocardial infarction (WMD: 0.397, 95% CI: 0.112-0.683; p = 0.0106), stable angina pectoris (WMD: 0.197, 95% CI: 0.031-0.364; p = 0.02) and unstable angina pectoris (WMD: 0.857, 95% CI: 0.293-1.420; p = 0.003). CONCLUSIONS: Meta-analysis results indicated that an increased ADMA level is associated with an increased risk of coronary artery disease.

Diagnostic accuracy of glycosylated hemoglobin in chinese patients with gestational diabetes mellitus: a meta-analysis based on 2,812 patients and 5,918 controls.

BACKGROUND AND AIMS: The accuracy of glycosylated hemoglobin (HBA1c) detection for the diagnosis of gestational diabetes mellitus (GDM) has been extensively studied in the Chinese population, but the exact role of these detections remains controversial. The present meta-analysis was performed to establish the overall accuracy of HBA1c for the diagnosis of Chinese patients with GDM. METHODS: After a systematic review of related studies, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and other measures about the accuracy of HBA1c in the diagnosis of GDM were pooled using random-effects models. The summary receiver operating characteristic (SROC) curve analysis was used to summarize the overall test performance. RESULTS: Forty-one studies included 2812 Chinese patients with GDM and 5918 controls were included in our meta-analysis. The summary estimates for HBA1c in the diagnosis of GDM in the studies included were as follows: sensitivity 0.762 (95% confidence interval [CI]: 0.746-0.777), specificity 0.917 (95% CI: 0.910-0.924), PLR 8.21 (95% CI: 3.77-17.89), NLR 0.20 (95% CI: 0.09-0.44), and DOR 41.40 (95% CI: 11.47-149.38). Our data showed that the SROC curve is positioned near the desirable upper left corner of the SROC curve, while the area under curve (AUC) was 0.93 with a Q* value of 0.865. CONCLUSIONS: Measurement of HBA1c is likely to be a useful diagnostic tool for confirming GDM. The results of HBA1c should be interpreted in parallel with clinical findings and the results of conventional tests.