Identification of coronary heart disease biomarkers with different severities of coronary stenosis in human urine using non-targeted metabolomics based on UPLC-Q-TOF/MS.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death worldwide, and its pathogenesis has attracted much attention. Metabolomics serves as an important tool for diagnosing diseases and exploring their pathogenesis in recent years. In this study, CHD patients were studied by comparing them with normal subjects to elucidate biomarkers that are linearly correlated with the severity of coronary stenosis. METHODS: An ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to analyze the urine metabolites of CHD patients and normal subjects. A total of 131 subjects included 27 patients who presented with 50-69% coronary stenosis, 22 with 70-89% stenosis, 29 with 90-99% stenosis, 24 with 100% stenosis, and 29 normal subjects. RESULTS: A total of 14 potential biomarkers associated with CHD were identified, and among them 4 biomarkers were linearly correlated with the severity of coronary stenosis in CHD patients. The metabolic pathways involved were amino acid metabolism, fatty acid metabolism, energy metabolism, and other pathways. CONCLUSION: This study identified the biomarkers and metabolic pathways that may be involved in the occurrence and development of CHD, laying a theoretical foundation for better diagnosis and treatment of CHD in the future.

Positive correlation between microalbuminuria and severity of coronary artery stenosis in patients with type 2 diabetes mellitus.

Diabetes mellitus (DM) is the most prevalent metabolic disease worldwide and is associated with coronary artery disease (CAD). Therefore it is very important to find a clue to diagnose the presence of CAD as early as possible in DM patients. The aim of this study was to find any correlation between microalbuminuria (MAU) and the severity of CAD in patients with DM type 2. This was a cross sectional study that included 77 DM type 2 patients with suspected CAD that all of whom were performed coronary angiography in our hospital (from 2010 to 2011). Patients were divided into two groups, the case group (group 1) that includes patients with MAU and the control group (group 2) that include patients without MAU. Severity of CAD was estimated by using Gensini score and MAU was defined as the ratio of urine albumin to urine creatinine.  Of 77 patients forty three (55.8%) were female, mean ± SD of their ages was 55.8 ± 10.3 and sixteen (21%) of them had MAU. Gensini score of case group was significantly higher than control group (94.94 ± 12 versus 33.25 ± 25.4, P<0.001). The linear regression analysis revealed urinary albumin to creatinine ratio (UA/CR) as an independent predictor for the severity of CAD (P<0.001). Based on the ROC curve, 10.25 was the best albumin level cut off point for differentiating Gensini score over and below 70. Area under curve was 0.9; sensitivity and specificity were 72% and 80%, respectively (P<0.001). According to this study, in patients with DM type2, MAU is an independent predictor of severity of coronary artery stenosis and reveals a positive correlation between MAU and the Gensini score.

Urinary bisphenol a concentration and angiography-defined coronary artery stenosis.

BACKGROUND: Bisphenol A is widely used in food and drinks packaging. There is evidence of associations between raised urinary bisphenol A (uBPA) and increased incidence of reported cardiovascular diagnoses. METHODOLOGY/PRINCIPAL FINDINGS: To estimate associations between BPA exposure and angiographically graded coronary atherosclerosis. 591 patients participating in The Metabonomics and Genomics in Coronary Artery Disease (MaGiCAD) study in Cambridgeshire UK, comparing urinary BPA (uBPA) with grades of severity of coronary artery disease (CAD) on angiography. Linear models were adjusted for BMI, occupational social class and diabetes status. Severe (one to three vessel) CAD was present in 385 patients, 86 had intermediate disease (n=86) and 120 had normal coronary arteries. The (unadjusted) median uBPA concentration was 1.28 ng/mL with normal coronary arteries, and 1.53 ng/mL with severe CAD. Compared to those with normal coronary arteries, uBPA concentration was significantly higher in those with severe CAD (OR per uBPA SD=5.96 ng/ml OR=1.43, CI 1.03 to 1.98, p=0.033), and near significant for intermediate disease (OR=1.69, CI 0.98 to 2.94, p=0.061). There was no significant uBPA difference between patients with severe CAD (needing surgery) and the remaining groups combined. CONCLUSIONS/SIGNIFICANCE: BPA exposure was higher in those with severe coronary artery stenoses compared to those with no vessel disease. Larger studies are needed to estimate true dose response relationships. The mechanisms underlying the association remain to be established.

Usefulness of periprocedural creatinine phosphokinase-MB release to predict adverse outcomes after intracoronary radiation therapy for in-stent restenosis.

We aimed to analyze periprocedural creatinine phosphokinase (CPK)-MB elevation in patients treated with intracoronary radiation therapy (IRT) for in-stent restenosis (ISR) to risk stratify these patients. The clinical significance of periprocedural CPK-MB elevation after IRT for ISR is unknown. An elevated CPK-MB has been associated with increased mortality after conventional angioplasty. We evaluated 1,326 patients who were enrolled in radiation trials for ISR at the Washington Hospital Center using gamma- and beta-emitters. Patients were analyzed according to degree of CPK-MB increase within 24 hours of the index IRT procedure (normal CPK-MB, CPK-MB 1 to 3 times the upper limit of normal, or CPK-MB >3 times the upper limit of normal). Patients with CPK-MB >3 times the upper limit of normal were older (64 +/- 12 years, p = 0.04), more likely to be smokers (64%, p = 0.04), hypertensive (85%, p <0.01), and diabetic (49%, p = 0.04). The cohort with the highest CPK-MB release (CPK-MB >3 times the upper limit of normal) had significantly higher rates of adverse clinical events at 12 months (major adverse cardiac events 40%, p <0.01), including death (9.3%, p <0.01) and late thrombosis (6.3%, p <0.01). Periprocedural CPK-MB elevation is of prognostic importance in patients treated with IRT for ISR, and its analysis appears to be mandatory to risk stratify these patients. The impact of glycoprotein IIb/IIIa antagonists in reducing periprocedural CPK-MB release awaits evaluation.