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Introduction and Objective: The relationship between either paraoxonase 1 (PON1) gene promoter DNA methylation or genetic variations and bleeding or major adverse cardiac events after dual antiplatelet therapy has been incompletely characterized. We aimed to systematically investigate the role of genetic variations and DNA methylation of the PON1 CpG island promoter on the clinical outcomes of dual antiplatelet therapy for patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI).Methods: This study included 653 patients with CAD undergoing PCI and receiving dual antiplatelet therapy. Genomic DNAs were isolated from whole blood and were genotyped for the three single nucleotide polymorphisms (SNPs) of the PON1 gene. The DNA methylation levels in the PON1 promoter region were determined by bisulfite sequencing or pyrosequencing at five CpG sites (positions -142, -161, -163, -170, and -184 from the transcription start site). Clopidogrel and its metabolites in plasma were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and platelet function analysis was performed using the VerifyNow assay.Results: Statistically significant associations between methylation levels at five PON1 CpG sites and bleeding were observed: -184 [odds ratio (OR) 0.98, 95% confidence interval (CI) 0.96-1.00, p = 0.028]; -170 (OR 0.99, 95% CI 0.97-1.00, p = 0.048); -163 (OR 0.98, 95% CI 0.96-1.00, p = 0.029); -161 (OR 0.98, 95% CI 0.97-1.00, p = 0.026); and -142 (OR 0.98, 95% CI 0.97-1.00, p = 0.042) at a false discovery rate of <5%. Statistical analysis also revealed that aspirin reaction units (ARUs) were significantly associated with PON1 methylation level at CpG site -163 (p = 0.0342). The ARUs of patients with the PON1 126 CC genotype was 527 ± 94, which was higher than the ARUs (473 ± 89) of patients with the 126 CG genotype (p = 0.0163). Multivariate logistic regression analysis indicated that the PON1 methylation level at CpG site -161 (OR 0.95, 95% CI 0.92-0.98, p = 0.002) and the use of angiotensin-converting enzyme inhibitors (OR 0.48, 95% CI 0.26-0.89, p = 0.021) were associated with a decreased risk of bleeding events.Conclusions: Hypomethylation of CpGs in the PON1 promoter may be a weak, albeit statistically significant, risk factor of bleeding after dual antiplatelet therapy. Further large-scale studies are needed to verify our results. [ABSTRACT FROM AUTHOR]

Objectives: Previous studies have suggested that prolonged electrocardiogram QTc duration was independent risk factor for both increased cardiovascular and all-cause mortality, but there was no dating about the relationship between central aortic systolic blood pressure (CASP) and QTc duration. The aim of this study was to analyze the relationship between CASP and QTc duration, and assess whether CASP can predict prolonged QTc duration more than BSBP. Methods: A total of 500 patients were enrolled in this study, central and brachial aortic blood pressure and electrocardiogram QTc duration were measured. Pearson correlation was assessed for determining the associations of QTc duration with clinical conditions. Multivariate logistic regression analyses were performed to determine the independent predictor of prolonged QTc duration. Receiver operating characteristic (ROC) curve was used to evaluate the utility of blood pressure for prolonged QTc duration. Results: We found QTc durations were significantly positive with CASP (r = 0.308, p < 0.001), BSBP (r = 0.227, p < 0.001), and age (r = 0.154, p = 0.010), but negatively related to heart rate (r = −440, p < 0.001). A multiple logistic regression analysis demonstrated that the CASP was an independent determinant of prolonged QTc (OR = 1.648; 95%CI: 1.032, 2.101; p < 0.001). CASP had a better predictive value for prolonged QTc duration than (AUC: 0.771 vs. 0.646, p < 0.001) BSBP. Conclusion: Our results suggested that the non-invasive CASP is independently correlated with QTc duration, and CASP can predict prolonged QTc duration more than BSBP. [ABSTRACT FROM AUTHOR]

We investigated whether high-sensitivity C-reactive protein (hsCRP) levels were associated with contrast-induced nephropathy (CIN) and long-term mortality after coronary angiography (CAG). Patients (N = 2133) undergoing CAG with preprocedural hsCRP were consecutively enrolled. High-sensitivity C-reactive protein was measured before angiography. Median follow-up was 2.3 years. The overall incidence of CIN was 2.77% (59 of 2133). There was a positive trend of hsCRP quartiles (Q) with rates of CIN: 0.9% for Q1 (<1.6 mg/L), 0.9% for Q2 (1.6-3.9 mg/L), 2.4% for Q3 (4.0-11.3mg/L), and 6.8% for Q4 (>11.3 mg/L; P < .05). The receiver operating characteristic (ROC) analysis showed that the cutoff point of hsCRP was 7.3 mg/L for predicting CIN with a 72.7% sensitivity and a 67.0% specificity (area under the curve [AUC] = 0.742, 95% confidence interval [CI] 0.672-0.810; P < .05). The predictive value of hsCRP was similar to the Mehran score for CIN (AUChsCRP = 0.742 vs AUCMehran = 0.801; P = .228). After adjustment for other potential risk factors, hsCRP >7.3 mg/L still was an independent predictor of CIN (odds ratio [OR] = 2.83, 95% CI: 1.44-5.58; P = .003). Furthermore, hsCRP >7.3 mg/L was associated with higher mortality (OR = 2.04, 95% CI: 1.30-3.19; P = .002). [ABSTRACT FROM AUTHOR]

Background: Left ventricular ejection fraction (LVEF) is the most widely used parameter to evaluate the cardiac function in patients with heart failure (HF). However, the association between LVEF and contrast-induced nephropathy (CIN) is still controversial. Therefore, the aim of this study is to evaluate the association of LVEF with CIN and long-term mortality following coronary angiography (CAG) or intervention in patients with HF.Methods: We analyzed 1,647 patients with HF (New York Heart Association [NYHA] or Killip class >1) undergoing CAG or intervention, including 207 (12.57%) patients with reduced LVEF (HFrEF), 238 (14.45%) with mid-range LVEF (HFmrEF) and 1,202 (72.98%) with preserved LVEF (HFpEF). CIN was defined as an absolute increase of ≥0.5 mg/dL or a relative increase of ≥25% from baseline serum creatinine within 48-72 h after contrast medium exposure. Multivariable logistic regression and Cox proportional hazards regression analyses were performed to identify the association between LVEF, CIN and long-term mortality, respectively.Results: Overall, 225 patients (13.7%) developed CIN. Individuals with lower LVEF were more likely to develop CIN (HFrEF, HFmrEF and HFpEF: 18.4%, 21.8% and 11.2%, respectively; P<0.001), but without a significant trend after adjusting for the confounding factors (HFrEF vs HFpEF: odds ratio [OR] =1.01; HFmrEF vs HFpEF: OR =1.31; all P>0.05). However, advanced HF (NYHA class >2 or Killip class >1) was an independent predictor of CIN (adjusted OR =1.54, 95% confidence interval [CI], 1.07-2.22; P=0.019). During the mean follow-up of 2.3 years, reduced LVEF (HFrEF group) was significantly associated with increased mortality (HFrEF vs HFpEF: adjusted hazard ratio =2.88, 95% CI, 1.77-4.69; P<0.001).Conclusion: In patients with HF undergoing CAG or intervention, not worsened LVEF but advanced HF was associated with an increased risk of CIN. In addition, reduced LVEF was an independent predictor of long-term mortality following cardiac catheterization. [ABSTRACT FROM AUTHOR]

Background: It is uncertain whether remote ischemic conditioning (RIC) has a protective effect on contrast-induced acute kidney injury (CI-AKI) after percutaneous coronary intervention (PCI)/coronary artery angiography (CAG). We performed a meta-analysis of randomized controlled trials (RCTs) to assess the effect of RIC on CI-AKI in such patients.Methods: PubMed, MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials databases were searched for RCTs that assessed the effect of RIC on CI-AKI in patients undergoing PCI/CAG.Results: Ten RCTs with 1389 patients (RIC group, 757 and control, 632) were included. The RIC group significantly exerted a lower risk of CI-AKI compared to the controls (odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.34-0.77, P = .001), and they had the similar effect on major adverse cardiovascular events within 1 year (OR = 0.36, 95% CI = 0.20-0.66, P < .001). The RIC reduced the rates of death within 30 days, but this was not significant (OR = 0.16, 95% CI = 0.02-1.34, P = .091). The RIC was associated with a significantly lower incidence of CI-AKI in patients following elective PCI/CAG (OR = 0.54, 95% CI = 0.33-0.87, P = .011). The RIC before not after the intervention was effective in reducing the occurrence of CI-AKI (OR: 0.37 vs 1.05, P = .022). The RIC of the upper arm has statistically significant effect on protecting CI-AKI but not that of the lower limb (OR: 0.41 vs 1.41, P = .004). The effect of RIC on CI-AKI was similar between patients with a mean estimated glomerular filtration rate <60 mL/min/1.73 m(2) and those with mean rates ≥60 (OR: 0.23 vs 0.41, P = .333).Conclusion: The RIC reduced the incidence of CI-AKI in those receiving PCI/CAG. And RIC of the upper arm significantly reduced the risk of CI-AKI but not RIC of the lower limb in patients undergoing PCI/CAG. [ABSTRACT FROM AUTHOR]

Objectives: We prospectively compared the preventive effects of rosuvastatin and atorvastatin on contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI). Methods: We enrolled 1078 consecutive patients with CKD undergoing elective PCI. Patients in Group 1 (n = 273) received rosuvastatin (10 mg), and those in group 2 (n = 805) received atorvastatin (20 mg). The primary end-point was the development of CIN, defined as an absolute increase in serum creatinine ≥0.5 mg/dL, or an increase ≥25% from baseline within 48–72 h after contrast medium exposure. Results: CIN was observed in 58 (5.4%) patients. The incidence of CIN was similar in patients pretreated with either rosuvastatin or atorvastatin (5.9% vs. 5.2%, p = 0.684). The same results were also observed when using other definitions of CIN. Clinical and procedural characteristics did not show significant differences between the two groups (p>0.05). Additionally, there were no significant inter-group differences with respect to in-hospital mortality rates (0.4% vs. 1.5%, p = 0.141), or other in-hospital complications. Multivariate logistic regression analysis revealed that rosuvastatin and atorvastatin demonstrated similar efficacies for preventing CIN, after adjusting for potential confounding risk factors (odds ratio = 1.17, 95% confidence interval, 0.62–2.20, p = 0.623). A Kaplan–Meier survival analysis showed that patients taking either rosuvastatin or atorvastatin had similar incidences of all-cause mortality (9.4% vs. 7.1%, respectively; p = 0.290) and major adverse cardiovascular events (29.32% vs. 23.14%, respectively; p = 0.135) during follow-up. Conclusions: Rosuvastatin and atorvastatin have similar efficacies for preventing CIN in patients with CKD undergoing PCI. [ABSTRACT FROM AUTHOR]

High-risk patients with rheumatic heart disease (RHD) who were undergoing valve replacement surgery (VRS) were not identified entirely. This study included 1782 consecutive patients with RHD who were undergoing VRS to explore the relationship between hypoalbuminemia and adverse outcomes and to confirm whether hypoalbuminemia plays a role in risk evaluation. A total of 27.3% of the RHD patients had hypoalbuminemia. In-hospital deaths were significantly higher in the hypoalbuminemic group than in the non-hypoalbuminemic group (6.6% vs 3.1%, P = 0.001). Hypoalbuminemia was an independent predictor of in-hospital death (OR = 1.89, P = 0.014), even after adjusting for the Euro score. The addition of hypoalbuminemia to Euro score enhanced net reclassification improvement (0.346 for in-hospital death, P = 0.004; 0.306 for 1-year death, p = 0.005). A Kaplan-Meier curve analysis revealed that the cumulative rate of 1-year mortality after the operation was higher in patients with a new Euro score ≥6. These findings indicated that hypoalbuminemia was an independent risk factor for in-hospital and 1-year mortality after VRS in patients with RHD, which might have additive prognostic value to Euro score.

Objectives: Contrast-induced acute kidney injury (CI-AKI) is a well-known serious complication of percutaneous coronary intervention (PCI) and may cause increased morbidity and mortality. We aim to identify the predictive value of Global Registry for Acute Coronary Events (GRACE) risk scores for CI-AKI in patients with ST-segment elevation myocardial infarction (STEMI) before primary PCI, allowing pre-procedural decisions regarding prevention therapy for CI-AKI. Methods: We enrolled 251 consecutive patients with STEMI undergoing primary PCI. Receiver operating characteristic curves were used to identify the optimal sensitivity for the observed range of GRACE risk scores. CI-AKI was defined as any of the following: absolute increase in serum creatinine (SCr) of ≥ 0.3 or ≥ 0.5 mg/dL within 48-72 h after contrast exposure, or a percentage increase in SCr level of ≥ 50 %. Results: Forty-three patients (17.1 %) developed CI-AKI0.3, 22 (8.8 %) CI-AKI0.5, and 19 (7.6 %) CI-AKI50. The GRACE quartiles were as follows: Q1 (<136), Q2 (136-159), Q3 (159-180), and Q4 (>180). Patients with high GRACE risk scores had higher risk for CI-AKI0.3, 0.5, and 50 (6.6, 6.6, 23.4, 31.7 %, respectively, p < 0.001; 1.6, 1.6, 9.4, 22.2 %, respectively, p < 0.001; and 3.3, 3.2, 9.4, 14.3 %, respectively, p = 0.009). ROC showed that a GRACE risk score >160 was a fair discriminator for CI-AKI0.3, 0.5, and 50 ( C statistic = 0.723, 0.788, 0.668, respectively). After adjusting for potential confounding predictors, GRACE risk score >160 remained significantly associated with CI-AKI0.3 or 0.5 (OR 3.84; 95 % CI 1.61-9.17; p = 0.002, or OR 5.54; 95 % CI 1.42-21.66; p = 0.014), and high-sensitivity C-reactive protein (Hs-CRP) >15.5 mg/L was a highly significant predictor of CI-AKI0.3, 0.5, and CI-AKI50. Conclusions: GRACE risk score (>160) and post-procedural Hs-CRP >15.5 mg/L are independent and significant predictors of CI-AKI in patients with STEMI before primary PCI. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the association of PON1 genetic variants with the susceptibility to coronary artery disease (CAD) and with the clinical endpoints in aspirin and clopidogrel (dual antiplatelet therapy)-treated Han Chinese patients with CAD after percutaneous coronary intervention (PCI). Methods: A total of 538 Han Chinese patients undergoing PCI and receiving dual-antiplatelet therapy were sequentially recruited to the study and followed for up to 1 year. Healthy controls ( n = 539) were enrolled during the same period. All study participants were genotyped for five genetic variants in PON1 and the cytochrome P450 2C19*2 mutation ( CYP2C19*2). The effect of genetic variants on disease risk and clinical outcome of major adverse cardiac events (MACE) within 1 year or bleeding within 6 months was assessed. Results: CYP2C19*2 was associated with a higher risk of MACE (adjusted P = 0.0098), but a lower risk of bleeding events (adjusted P = 0.0016). The PON1 Q192R polymorphism was significantly associated with a lower risk of bleeding events [odds ratio (OR) 0.61, 95% confidence interval (CI) 0.43-0.87, adjusted P = 0.0066). The haplotype bearing the PON1 -126C allele was associated with a higher risk to CAD (OR 1.48, 95% CI 1.04-2.09, P = 0.029) and a higher risk of bleeding events (OR 1.68, 95% CI 1.10-2.56, P = 0.017) compared to the most frequent haplotype. The transcription activity of haplotype p-162A-126C-108C in the PON1 promoter was 2.6-fold higher than that of the most frequent haplotype (p-162G-126G-108T). Conclusions: Based on these results, we suggest that the haplotype-bearing PON1 -126C allele contributes to the disease risk and the risk of bleeding events in dual antiplatelet-treated CAD patients after PCI. [ABSTRACT FROM AUTHOR]

Background: Contrast-induced nephropathy (CIN) is a serious complication in percutaneous coronary intervention (PCI) patients, which may be related to the contrast dose used during cardiac catheterization. Methods: We prospectively investigated 277 consecutive consenting patients with acute ST-segment elevation myocardial infarction (STEMI) who were given primary PCI, and we calculated their ratio of volume of contrast media to estimated glomerular filtration rate (V/eGFR). Receiver-operator characteristic methods were used to identify the optimal sensitivity for the observed range of V/eGFR for CIN (i.e., within 48-72 h). The predictive value of V/eGFR for the risk of CIN was assessed using multivariable logistic regression. Results: Twenty-five (9%) patients developed CIN. The baseline mean and median V/eGFR values were significantly greater among patients with CIN (mean 3.22 ± 1.53, median 2.97, and interquartile range 1.90-4.17) than among those without CIN (mean 1.80 ± 1.00, median 1.52, and interquartile range 1.12-2.21, P < 0.001). The receiver-operator characteristic curve analysis indicated that a V/eGFR ratio of 2.39 was a fair discriminator for CIN (C statistic 0.81). After adjusting for other known predictors of CIN, a V/eGFR ratio ≥ 2.39 remained significantly associated with CIN (odds ratio 4.24, 95% confidence interval 1.23-14.66, P < 0.05). Conclusion: A V/eGFR ratio ≥ 2.39 was a significant and independent predictor of CIN after primary PCI in patients with STEMI. [ABSTRACT FROM AUTHOR]

Background: It remained lack of a kind of contrast-induced acute kidney injury (CI-AKI) model which was widely used in clinical practice and comparable to CI-AKI in humans.Methods: Fifty Sprague-Dawley rats were divided into five groups of 10 rats each: (1) sham group (normal saline [NS] + NS); (2) NS plus low osmolality contrast medium (CM15) (NS + CM15); (3) furosemide (FM) plus NS (FM + NS); (4) FM + CM10; and (5) FM + CM15.We measured the levels of serum creatinine (SCr), cystatin C (cys-C) and histopathological scores of kidney tissues.Results: SCr level in the FM + CM15 group were significantly increased after CM exposure compared with baseline levels (32.9 ± 4.57 vs. 158.7 ± 14.48 μmol/L, p < 0.001). Minor changes were found about the SCr levels between the pre- and post-exposure CM or NS treatment in the other groups. Additionally, the cys-C levels after CM exposure were increased compared with pretreatment levels in the FM + CM15 group (0.08 ± 0.03 vs. 0.18 ± 0.05 mg/L, p < 0.001). Minor changes were noted in the FM + NS group before and after NS administration. Only rats in the FM + CM15 group developed CI-AKI with the definitions of SCr or cys-C. Comparing to the FM + NS group, the histopathological scores were significantly increased in the FM + CM15 group.Conclusions: A simple and reliable animal model for low osmolality contrast medium-induced AKI was established, which is similar to clinical CI-AKI based on different definitions for AKI. [ABSTRACT FROM AUTHOR]

Background: Contrast-induced acute kidney injury (CI-AKI) contributes toward unfavorable clinical outcomes. Oral hydration with water is inexpensive and it may be effective in the prevention of CI-AKI, but its efficacy among patients undergoing primary percutaneous coronary intervention (PCI) remains unknown.Methods/design: Our study is a secondary analysis on the database from the ATTEMPT study. We enrolled ST-elevation myocardial infarction (STEMI) patients undergoing primary PCI. Eligible patients received peri-procedural aggressive (left ventricular end-diastolic pressure-guided) or routine (≤ 500 mL) intravenous hydration with an isotonic solution (0.9% NaCl) with randomization. The primary endpoint was CI-AKI, defined as a > 25% or 0.5 mg/dL increase in serum creatinine from baseline during the first 48-72 h post-procedurally. All patients drank unrestricted amounts of fluids freely, the volume of which was recorded until 24 h following primary PCI. Oral hydration volume/weight (OHV/W) ratios were calculated. The association between post-procedural oral hydration (quartiles) and CI-AKI was assessed using multivariable analysis controlling for confounders, including intravenous hydration strategies.Discussion: Our study determined the effects of post-procedural oral hydration on CI-AKI following primary PCI, which is a potential strategy for CI-AKI prevention among patients with STEMI at very high risk.Trial Registration: ClinicalTrials.gov, NCT02067195 . Registered on 21 February 2014. [ABSTRACT FROM AUTHOR]