Junqing Yang

Contrast medium volume to creatinine clearance ratio: a predictor of contrast-induced nephropathy in the first 72 hours following percutaneous coronary intervention.

Objectives: To investigate the predictive value of the contrast media volume to creatinine clearance (V/CrCl) ratio for the risk of contrast‐induced nephropathy (CIN) (i.e., within 48–72 hr) and to determine a relatively safe V/CrCl cut‐off value to avoid CIN in patients following percutaneous coronary intervention (PCI). Background: The V/CrCl ratio is a pharmacokinetic risk factor for an early abnormal increase in serum creatinine (i.e., within 24 hr) after PCI. Methods: V/CrCl ratios were obtained from 1,140 consecutive consenting patients after unselective PCI. Receiver‐operator characteristic (ROC) curves were used to identify the optimal sensitivity for the observed range of V/CrCl. The predictive value of V/CrCl for the risk of CIN was assessed using multivariate logistic regression. Results: Fifty‐five (4.8%) patients out of 1,140 developed CIN. There was a significant association between higher V/CrCl ratio values and risk of CIN in the overall population: 1.4%, 1.4%, 5.7%, and 10.9% for quartile 1 (Q1) of the V/CrCl value (<1.56, n = 283), Q2 (1.56–2.27, n = 289), Q3 (2.28–3.42, n = 282), and Q4 (>3.42, n = 285) of contrast, respectively (P < 0.001). ROC curve analysis indicated that a V/CrCl ratio of 2.62 was a fair discriminator for CIN (C‐statistic 0.73). After adjusting for other known predictors of CIN, V/CrCl ratios > 2.62 remained significantly associated with CIN (odds ratio: 2.20; 95% confidence interval: 1.00–4.81, P < 0.05). Conclusion: A V/CrCl ratio > 2.62 was a significant and independent predictor of CIN after PCI in unselected patients.

Clinical implications of three-vessel fractional flow reserve measurement in patients with coronary artery disease

Aims There are limited data on the clinical implications of total physiologic atherosclerotic burden assessed by invasive physiologic studies in patients with coronary artery disease. We investigated the prognostic implications of total physiologic atherosclerotic burden assessed by total sum of fractional flow reserve (FFR) in three vessels (3V-FFR). Methods and results A total of 1136 patients underwent FFR measurement in three vessels (3V FFR-FRIENDS study, NCT01621438). The patients were classified into high and low 3V-FFR groups according to the median value of 3V-FFR (2.72). The primary endpoint was major adverse cardiac events (MACE, a composite of cardiac death, myocardial infarction and ischaemia-driven revascularization) at 2 years. Mean angiographic percent diameter stenosis and FFR were 43.7 ± 19.3% and 0.90 ± 0.08, respectively. There was a negative correlation between 3V-FFR and estimated 2-year MACE rate (P < 0.001). The patients in low 3V-FFR group showed a higher risk of 2-year MACE than those in the high 3V-FFR group [(7.1% vs. 3.8%, hazard ratio (HR) 2.205, 95% confidence interval (CI) 1.201-4.048, P = 0.011]. The higher 2-year MACE rate was mainly driven by the higher rate of ischaemia-driven revascularization in the low 3V-FFR group (6.2% vs. 2.7%, HR 2.568, 95% CI 1.283-5.140, P = 0.008). In a multivariable adjusted model, low 3V-FFR was an independent predictor of MACE (HR 2.031, 95% CI 1.078-3.830, P = 0.029). Conclusion Patients with high total physiologic atherosclerotic burden assessed by 3V-FFR showed higher risk of 2-year clinical events than those with low total physiologic atherosclerotic burden. The difference was mainly driven by ischaemia-driven revascularization for both functionally significant and insignificant lesions at baseline. Three-vessel FFR might be used as a prognostic indicator in patients with coronary artery disease. Clinical trial registration 3V FFR-FRIENDS study (https://clinicaltrials.gov/ct2/show/NCT01621438, NCT01621438).

Safe Limits of Contrast Vary With Hydration Volume for Prevention of Contrast-Induced Nephropathy After Coronary Angiography Among Patients With a Relatively Low Risk of Contrast-Induced Nephropathy

Background—Few studies have investigated the safe limits of contrast to prevent contrast-induced nephropathy (CIN) based on hydration data. We aimed to investigate the relative safe maximum contrast volume adjusted for hydration volume in a population with a relatively low risk of CIN. Methods and Results—The ratios of contrast volume-to-creatinine clearance (V/CrCl) and hydration volume to body weight (HV/W) were determined in patients undergoing cardiac catheterization. Receiver–operator characteristic curve analysis based on the maximum Youden index was used to identify the optimal cutoff for V/CrCl in all patients and in HV/W subgroups. Eighty-six of 3273 (2.6%) patients with mean CrCl 71.89±27.02 mL/min developed CIN. Receiver–operator characteristic curve analysis indicated that a V/CrCl ratio of 2.44 was a fair discriminator for CIN in all patients (sensitivity, 73.3%; specificity, 70.4%). After adjustment for other confounders, V/CrCl >2.44 continued to be significantly associated with CIN (adjusted odds ratio, 4.12; P<0.001) and the risk of death (adjusted hazard ratio, 2.62; P<0.001). The mean HV/W was 12.18±7.40. We divided the patients into 2 groups (HV/W ⩽12 and >12 mL/kg). The best cutoff value for V/CrCl was 1.87 (sensitivity, 67.9%; specificity, 64.4%; adjusted odds ratio, 3.24; P=0.011) in the insufficient hydration subgroup (HV/W, ⩽12 mL/kg; CIN, 1.32%) and 2.93 (sensitivity, 69.0%; specificity, 65.0%; adjusted odds ratio, 3.04; P=0.004) in the sufficient hydration subgroup (HV/W, >12 mL/kg; CIN, 5.00%). Conclusions—The V/CrCl ratio adjusted for HV/W may be a more reliable predictor of CIN and even long-term outcomes after cardiac catheterization. We also found a higher best cutoff value for V/CrCl to predict CIN in patients with a relatively sufficient hydration status, which may be beneficial during decision-making about contrast dose limits in relatively low-risk patients with different hydration statuses.

Development of contrast-induced acute kidney injury after elective contrast media exposure in patients with type 2 diabetes mellitus: effect of albuminuria.

Background The influence of albuminuria and urinary pH on the development of contrast-induced acute kidney disease (CI-AKI) in patients with type 2 diabetes mellitus (T2DM) after elective coronary angiography (CAG) or percutaneous coronary intervention (PCI) is unknown. Methods CI-AKI was defined as an increase in serum creatinine >26.4 µmol/L or ≥50% of baseline value within 48 hours after contrast media exposure. Demographics, traditional risk factors, clinical outcomes and CI-AKI incidence were compared between groups. Univariate analysis and multivariate logistic regression were performed to assess risk factors of CI-AKI. Results We observed 597 patients with T2DM after CAG or PCI. Patients were divided into 3 groups based on early morning urinary albumin: negative group (urine dipstick negative, n = 483), trace group (urine dipstick trace, n = 60), and positive group (urine dipstick ≥1+, n = 54). CI-AKI occurred in 33 (5.5%) patients, including 19 (3.9%) in the negativealbuminuria group, 4 (6.7%) in the trace group, and 10 (18.5%) in the positive group (p< 0.001), respectively. After adjusting for potential confounding risk factors, positive albuminuria (OR = 3.8, 95% CI: 1.5 to 9.2, p = 0.004) and urinary pH<6 (OR = 2.4, 95% CI: 1.1 to 5.1, p = 0.020) remained significantly associated with CI-AKI. Conclusion Preprocedural albuminuria and urinary pH <6 are independent risk factors of CI-AKI in patients with T2DM undergoing elective cardiac catheterization, and may be used to identify patients at high risk of post-procedural CI-AKI.

Atorvastatin protects against contrast-induced nephropathy via anti-apoptosis by the upregulation of Hsp27 in vivo and in vitro

Contrast-induced nephropathy (CIN) is an iatrogenic acute renal failure occurring following the intravascular injection of iodinated radiographic contrast medium. However, the regulatory mechanisms for CIN remain to be fully elucidated. The present study aimed to investigate whether atorvastatin protects against CIN via anti-apoptotic effects by the upregulation of Hsp27 in vivo and in vitro. To determine whether atorvastatin attenuated CIN, the inflammatory response and apoptosis in vivo and in vitro, a rat model of iopamidol-induced CIN was used, and human embryonic proximal tubule (HK2) cell damage was assessed. The rats were assigned into four groups (n=10 per group), as follows: Control rats; rats+atorvastatin; rats + iopamidol; rats+iopamidol+atorvastatin. In vitro, the HK2 cells were treated with iopamidol in the presence or absence of atorvastatin, heat shock protein (Hsp)27 small interfering (si)RNA or pcDNA3.1-Hsp27. The renal tissues were examined histopathologically and collected for western blot analysis. The results showed that atorvastatin ameliorated the apoptosis and deterioration of renal function (P<0.05). Furthermore, atorvastatin reduced the iopamidol-induced activity of B cell lymphoma-2 (Bcl-2)-associated X protein (Bax)/caspase-3 and increased the expression of Bcl-2 in vivo and in vitro. Notably, following treatment with Hsp27 siRNA or pcDNA3.1-Hsp27, it was found that iopamidol enhanced or weakened the upregulation of Bax/caspase-3 and downregulation of Bcl-2 in the HK2 cells, respectively. The results of the present study suggested that atorvastatin protected against contrast-induced renal tubular cell apoptosis through the upregulation of Hsp27 in vivo and in vitro.

Preprocedural High-Sensitivity C-Reactive Protein Predicts Contrast-Induced Nephropathy and Long-Term Outcome After Coronary Angiography:

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).

Concomitant coronary and renal revascularization improves left ventricular hypertrophy more than coronary stenting alone in patients with ischemic heart and renal disease

Percutaneous transluminal renal artery stenting (PTRAS) has been proved to have no more benefit than medication alone in treating atherosclerotic renal artery stenosis (ARAS). Whether PTRAS could improve left ventricular hypertrophy (LVH) and reduce adverse events when based on percutaneous coronary intervention (PCI) for patients with coronary artery disease (CAD) and ARAS is still unclear. A retrospective study was conducted, which explored the effect of concomitant PCI and PTRAS versus PCI alone for patients with CAD and ARAS complicated by heart failure with preserved ejection fraction (HFpEF). A total of 228 patients meeting inclusion criteria were divided into two groups: (1) the HFpEF-I group, with PCI and PTRAS; (2) the HFpEF-II group, with PCI alone. Both groups had a two-year follow-up. The left ventricular mass index (LVMI) and other clinical characteristics were compared between groups. During the follow-up period, a substantial decrease in systolic blood pressure (SBP) was observed in the HFpEF-I group, but not in the HFpEF-II group. There was marked decrease in LVMI in both groups, but the HFpEF-I group showed a greater decrease than the HFpEF-II group. Regression analysis demonstrated that PTRAS was significantly associated with LVMI reduction and fewer adverse events after adjusting for other factors. In HFpEF patients with both CAD and ARAS, concomitant PCI and PTRAS can improve LVH and decrease the incidence of adverse events more than PCI alone. This study highlights the beneficial effect of ARAS revascularization, as a new and more aggressive revascularization strategy for such high-risk patients.中文概要目 的研究经皮肾动脉支架术(PTRAS)能否在冠脉介入(PCI)基础上进一步改善冠心病合并肾动脉狭窄患者的左室肥厚(LVH)及减少主要心血管不良事件的发生。创新点本研究对集中入选全身动脉粥样硬化这类高危患者(冠心病合并肾动脉狭窄(CAD & ARAS))临床诊治进行研究,有别于既往对单纯的肾动脉狭窄(RAS)人群的研究,且入选标准使用选择性动脉造影以排除其他诊断手段可能带来的假阴性或假阳性,并对冠脉狭窄进行血运重建以解决心肌灌注问题,再对PTRAS 进行评价;有别于既往对PTRAS 较为保守的建议,本研究发现对于CAD & ARAS 患者,肾动脉狭窄的血运重建应该更加积极,RAS 的介入治疗可能是该类患者一个重要的治疗靶点。方 法将入选的228 名CAD & ARAS 患者,分为收缩功能保留性心衰-I(HFpEF-I)组(PCI & PTRAS)以及HFpEF-II 组(单纯PCI),术后随访至少两年。随访发现,两组的左室重量指数(LVMI)均较基线明显下降,且HFpEF-I 组下降幅达大于HFpEF-II 组(Δ=(32.80±12.62) g/m2 vs. Δ=(18.52±8.17) g/m2, P<0.001),回归分析发现PTRAS 与LVMI 的下降及不良事件的发生减少密切相关。结 论对于CAD & ARAS 并HFpEF 患者,同期行PCI及PTRAS 可较单纯PCI 进一步减轻LVH 及降低心血管不良事件发生。对该类高危患者,可予以积极的肾动脉狭窄血运重建治疗。

Decrease of Glomerular Filtration Rate may be Attributed to the Microcirculation Damage in Renal Artery Stenosis

Background:The decrease of glomerular filtration rate has been theoretically supposed to be the result of low perfusion in renal artery stenosis (RAS). But the gap between artery stenosis and the glomerular filtration ability is still unclear. Methods:Patients with selective renal artery angiogram were divided by the degree of renal artery narrowing, level of estimated glomerular filtration rate (eGFR), respectively. The different levels of eGFR, renal microcirculation markers, and RAS severity were compared with each other, to determine the relationships among them. Results:A total of 215 consecutive patients were enrolled in the prospective cohort study. Concentrations of microcirculation markers had no significant difference between RAS group (RAS ≥ 50%) and no RAS group (RAS < 50%) or did not change correspondingly to RAS severity. The value of eGFR in RAS group was lower than that in the no RAS group, but it did not decline parallel to the progressive severity of RAS. The microcirculation markers presented integral difference if grouped by different eGFR level with negative tendency, especially that plasma cystatin C (cysC) and urinary microalbumin to creatinine ratio (mACR) increased with the deterioration of eGFR, with strong (r = −0.713, P < 0.001) and moderate (r = −0.580, P < 0.001) correlations. In the subgroup analysis of severe RAS (RAS ≥ 80%), the levels of plasma cysC and urinary mACR demonstrated stronger negative associations with eGFR, (r = −0.827, P < 0.001) and (r = −0.672, P < 0.001) correlations, respectively. Conclusions:Severity of RAS could not accurately predict the value of eGFR, whereas microcirculation impairment may substantially contribute to the glomerular filtration loss in patients with RAS.