Influence of chronic kidney disease and worsening renal function on clinical outcomes in patients undergoing primary percutaneous coronary intervention.

BACKGROUND: The combined influence of CKD and worsening renal function (WRF) on clinical outcomes in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) has not been fully understood. METHODS: We analyzed 443 patients diagnosed with AMI who underwent primary PCI. Based on their estimated glomerular filtration rate (eGFR), they were classified into two groups: a high eGFR group (eGFR ≥ 45 mL/min/1.73 m2, n = 381) and a low eGFR group (eGFR < 45 mL/min/1.73 m2, n = 63). WRF was defined as an increase in serum creatinine levels ≥ 0.3 mg/dL above the admission value during the course of hospitalization. The primary end-point was set as all-cause mortality. RESULTS: WRF was observed in 88 patients (19.8%). The median follow-up duration was 769 (interquartile range 397-1314) days. The all-cause mortality rate was significantly lower in the high eGFR than in the low eGFR group (5.5 vs. 28.6%, respectively, at 1500 days, P < 0.001). In patients with WRF, the all-cause and cardiac mortality rates were significantly higher than in patients without WRF, and these results were consistent between the high and low eGFR sub-groups. Multivariate Cox proportional hazards model analysis showed that low eGFR and WRF remained independent predictors of all-cause mortality [(hazard ratio 2.61, 95% confidence interval 1.27-5.36, P = 0.009) and (hazard ratio 2.59, 95% confidence interval 1.34-5.01, P = 0.005), respectively]. CONCLUSIONS: Both eGFR at baseline and WRF were observed to be important predictors of mortality in patients with AMI undergoing primary PCI. WRF showed a significant effect on mortality even in patients with high eGFR.

Impact of high-density lipoprotein 3 cholesterol subfraction on periprocedural myocardial injury in patients who underwent elective percutaneous coronary intervention.

BACKGROUND: Periprocedural myocardial injury (PMI) is a major complication of percutaneous coronary intervention (PCI) and is associated with atherosclerotic coronary plaque and worse clinical outcomes. High-density lipoprotein cholesterol (HDL-C) is a protective factor for cardiovascular disease. However, the role of HDL-C subfractions, such as HDL2 cholesterol (HDL2-C) or HDL3 cholesterol (HDL3-C), in cardiovascular disease remains unclear. The purpose of the study was to investigate the relationship between HDL2-C and HDL3-C subfractions and the incidence of PMI in patients who underwent elective PCI. METHODS: We enrolled 129 patients who underwent elective PCI for stable angina pectoris. PMI was defined as an increase in high-sensitivity troponin T levels > 5 times the upper normal limit (> 0.070 ng/mL) at 24 h after PCI. Serum HDL-C subfractions (HDL2-C and HDL3-C) were assessed using ultracentrifugation in patients with and those without PMI. RESULTS: HDL3-C levels were significantly lower in patients with PMI than in those without (15.1 ± 3.0 mg/dL vs. 16.4 ± 2.9 mg/dL, p = 0.016) and had an independent and inverse association with PMI (odds ratio, 0.86; 95% confidence interval, 0.74-0.99; p = 0.038). When divided by the cut-off value of HDL3-C for PMI (14.3 mg/dL), the incidence of PMI was significantly higher in low HDL3-C patients than in high HDL3-C patients (51.2% vs. 30.2%, p = 0.020). CONCLUSIONS: HDL3-C was an independent inverse predictor of PMI in patients who underwent elective PCI.

Clinical Impact of Circulating Irisin on Classified Coronary Plaque Characteristics.

BACKGROUND: Myokines are hormones secreted by skeletal muscles during physical activity. Low myokine levels may contribute to metabolic dysfunction and cardiovascular disorders. Irisin, a newly identified myokine, has been the focus of recent research. The aim of the present study was to analyze the association between circulating irisin levels and tissue characteristics of nonculprit left main coronary artery (LMCA) plaques with the use of integrated backscatter (IB) intravascular ultrasound (IVUS). METHODS: This observational study enrolled 55 Japanese patients following successful percutaneous coronary intervention for lesions in the left anterior descending arteries or left circumflex arteries. Circulating myokine levels, including myostatin, brain-derived neurotrophic factor, and irisin, were measured by an enzyme-linked immunosorbent assay. Tissue characteristics of LMCA plaque were evaluated by IB-IVUS. RESULTS: Circulating irisin levels were negatively associated with percent lipid volume (%LV) [r = -0.31 (95% CI, -2.52 to -0.21), P = 0.02] and positively associated with percent fibrous volume (%FV) [r = 0.32 (95% CI, 0.22-2.20), P = 0.02]. The optimal cutoff value of circulating irisin for the prediction of lipid-rich LMCA plaques was 6.02 µg/mL [area under the curve = 0.713, P < 0.01 (95% CI, 0.58-0.85)]. Multivariate linear regression analysis identified circulating irisin levels as independent predictors for %LV and %FV of the LMCA [ß = -0.29 (95% CI, -2.53 to -0.07), P = 0.04 and ß = 0.30 (95% CI, 0.10-2.23), P = 0.03, respectively]. CONCLUSIONS: Circulating irisin levels are significantly associated with tissue characteristics of nonculprit LMCA plaques.

Impact of post-dilatation on longitudinal stent elongation: An in vitro study.

OBJECTIVES: To evaluate whether balloon inflation for post-dilatation causes longitudinal stent deformation (LSD). METHODS AND RESULTS: Two stents, sized 2.5mm×28mm and 3.5mm×28mm (Nobori®, biodegradable polymer biolimus-eluting stent; Ultimaster®, biodegradable polymer sirolimus-eluting stent; Terumo Co., Tokyo, Japan), were deployed at nominal pressure in straight and tapered silicon vessel models. Then, post-dilatation was performed in two ways: dilatation from the distal (D-P group) or proximal (P-D group) side of the stent. Microscopic findings showed that the stents were elongated during every step of the procedure regardless of the post-dilatation method and type of vessel model. The D-P group showed linear elongation during each step of post-dilatation (straight model: 28.7±0.3mm vs. 29.9±0.3mm, p=0.002; tapered model: 28.0±0.1mm vs. 29.9±0.1mm, p<0.001). In contrast, in the P-D group, the most significant change was observed in the first step of post-dilatation and only slight changes were observed thereafter (straight model: 28.6±0.1mm vs. 29.5±0.1mm, p<0.001; tapered model: 28.2±0.1mm vs. 29.5±0.1mm, p<0.001). Optical frequency domain imaging analysis showed that the frequency of stent strut malapposition was positively correlated with the percentage change in stent length (r=0.74, p<0.0001). CONCLUSION: LSD was observed during every step of post-dilatation in both the straight and tapered vessel models. However, some differences were observed between the D-P and P-D groups. Minimizing stent strut malapposition may reduce the risk of LSD.

Impact of Coronary Stent Fracture on Restenotic Neointimal Tissue Characterization After Drug-Eluting Stent Implantation.

Although drug-eluting stents (DESs) reduce the rates of in-stent restenosis (ISR) and subsequent target lesion revascularization, stent fracture (SF) after DES implantation has become an important concern because of its potential association with restenosis and stent thrombosis. We aimed to assess the pathogenic impact of SF on in-stent restenotic neointimal tissue components after DES implantation. We analyzed 43 consecutive patients (14 with SF and 29 without SF) with ISR requiring revascularization after DES implantation between January 2008 and March 2014. For evaluation of in-stent tissue components, integrated backscatter intravascular ultrasound (IB-IVUS) was performed. SF was defined as complete or partial separation of stent segments observed using plain fluoroscopy or intravascular ultrasound. On volumetric IB-IVUS analyses, patients with SF had a significantly higher percentage of lipid tissue volume within the neointima and a significantly lower percentage of fibrous tissue volume than those without (37.3 ± 18.9% versus 24.9 ± 12.4%, P = 0.02, and 61.2 ± 18.3 versus 72.6 ± 12.1%, P = 0.04, respectively). Moreover, SF was positively correlated with the percentage of lipid volume on multiple linear regression analysis after adjustment for confounding factors (ß = 0.36, P = 0.03). The interval from stent implantation was similar in both groups (47.0 ± 28.7 versus 37.7 ± 33.3 months; P = 0.39). In conclusion, SF is associated with larger lipid tissue volume within the neointima after DES placement, suggesting a contribution to the development of neoatherosclerosis and vulnerable neointima. Thus SF might lead to future adverse coronary events.

Decreased Serum Albumin Predicts Bleeding Events in Patients on Antiplatelet Therapy After Percutaneous Coronary Intervention.

BACKGROUND: Antiplatelet therapy (APT) after percutaneous coronary intervention (PCI) prevents ischemic events with increased risk of bleeding. Little is known about the relationship between hypoalbuminemia and bleeding risk in patients receiving APT after PCI. This study investigated the association between serum albumin level and bleeding events in this population.Methods and Results:We enrolled 438 consecutive patients who were prescribed dual APT (DAPT; aspirin and thienopyridine) beyond 1 month after successful PCI without adverse events. The patients were divided into 3 groups according to serum albumin tertile: tertile 1, ≤3.7 g/dL; tertile 2, 3.8-4.1 g/dL; and tertile 3, ≥4.2 g/dL. Adverse bleeding events were defined as Bleeding Academic Research Consortium criteria types 2, 3, and 5. During the median follow-up of 29.5 months, a total of 30 adverse bleeding events were observed. Median duration of DAPT was 14 months. The tertile 1 group had the highest risk of adverse bleeding events (event-free rate, 83.1%, 94.3% and 95.8%, respectively; P<0.001). On Cox proportional hazards modeling, serum albumin independently predicted adverse bleeding events (HR, 0.10, 95% CI: 0.027-0.39, P=0.001, for tertile 3 vs. tertile 1). CONCLUSIONS: Decreased serum albumin predicted bleeding events in patients with APT after PCI.

Impact of Skeletal Muscle Mass on Long-Term Adverse Cardiovascular Outcomes in Patients With Chronic Kidney Disease.

Sarcopenia, defined as skeletal muscle loss and dysfunction, is attracting considerable attention as a novel risk factor for cardiovascular events. Although the loss of skeletal muscle is common in chronic kidney disease (CKD) patients, the relation between sarcopenia and cardiovascular events in CKD patients is not well defined. Therefore, we aimed to investigate the relation between skeletal muscle mass and major adverse cardiovascular events (MACE) in CKD patients. We enrolled 266 asymptomatic CKD patients (median estimated glomerular filtration rate: 36.7 ml/min/1.73 m2). To evaluate skeletal muscle mass, we used the psoas muscle mass index (PMI) calculated from noncontrast computed tomography. The patients were divided into 2 groups according to the cut-off value of PMI for MACE. There were significant differences in age and body mass index between the low and high PMI groups (median age: 73.5 vs 69.0 years, p = 0.002; median body mass index: 22.6 vs 24.2 kg/m2, p <0.001, respectively). During the follow-up period (median: 3.2 years), patients with low PMI had significantly higher risk of MACE than those with high PMI (31.7% and 11.2%, log-rank test, p <0.001). The Cox proportional hazard model showed that low PMI is an independent predictor of MACE in CKD patients (hazard ratio 3.98, 95% confidence interval 1.65 to 9.63, p = 0.0022). In conclusion, low skeletal muscle mass is an independent predictor of MACE in CKD patients. The assessment of skeletal muscle mass may be a valuable screening tool for predicting MACE in clinical practice.

Nutrition Status Predicts Severity of Vascular Calcification in Non-Dialyzed Chronic Kidney Disease.

BACKGROUND: Vascular calcification is a major complication in chronic kidney disease (CKD) that increases the risk of adverse clinical outcomes. Geriatric nutritional risk index (GNRI) is a simple nutritional assessment tool that predicts poor prognosis in elderly subjects. The purpose of the present study was to evaluate the correlation between GNRI and severity of vascular calcification in non-dialyzed CKD patients.Methods and Results:We enrolled 323 asymptomatic CKD patients. To evaluate abdominal aortic calcification (AAC), we used aortic calcification index (ACI) determined on non-contrast computed tomography. The patients were divided into three groups according to GNRI tertile. Median ACI significantly decreased with increasing GNRI tertile (15.5%, 13.6%, and 7.9%, respectively; P=0.001). On multivariate regression analysis GNRI was significantly correlated with ACI (ß=-0.15, P=0.009). We also investigated the combination of GNRI and C-reactive-protein (CRP) for predicting the severity of AAC. Low GNRI and high CRP were significantly associated with severe AAC, compared with high GNRI and low CRP (OR, 4.07; P=0.004). CONCLUSIONS: GNRI was significantly associated with AAC in non-dialyzed CKD patients.

The combination assessment of lipid pool and thrombus by optical coherence tomography can predict the filter no-reflow in primary PCI for ST elevated myocardial infarction.

The usefulness of distal protection devices is still controversial. Moreover, there is no report on thrombus evaluation by using optical coherence tomography (OCT) for determining whether to use a distal protection device. The aim of the present study was to investigate the predictor of filter no-reflow (FNR) by using OCT in primary percutaneous coronary intervention (PCI) for ST-elevated acute myocardial infarction (STEMI).We performed preinterventional OCT in 25 patients with STEMI who were undergoing primary PCI with Filtrap. FNR was defined as coronary flow decreasing to TIMI flow grade 0 after mechanical dilatation.FNR was observed in 13 cases (52%). In the comparisons between cases with or without the FNR, the stent length, lipid pool length, lipid pool + thrombus length, and lipid pool + thrombus index showed significant differences. In multivariate analysis, lipid pool + thrombus length was the only independent predictor of FNR (OR 1.438, 95% CI 1.001 - 2.064, P < .05). The optimal cut-off value of lipid pool + thrombus length for predicting FNR was 13.1 mm (AUC = 0.840, sensitivity 76.9%, specificity 75.0%). Moreover, when adding the evaluation of thrombus length to that of lipid pool length, the prediction accuracy of FNR further increased (IDI 0.14: 0.019-0.25, P = .023).The longitudinal length of the lipid pool plus thrombus was an independent predictor of FNR and the prediction accuracy improved by adding the thrombus to the lipid pool. These results might be useful for making intraoperative judgment about whether filter devices should be applied in primary PCI for STEMI.

Predictors of abdominal aortic calcification progression in patients with chronic kidney disease without hemodialysis.

BACKGROUND AND AIMS: Abdominal aortic calcification (AAC) is an important predictor of cardiovascular mortality in patients with chronic kidney disease (CKD). However, little is known regarding AAC progression in these patients. This study aimed to identify risk factors associated with AAC progression in patients with CKD without hemodialysis. METHODS: We recruited 141 asymptomatic patients with CKD without hemodialysis [median estimated glomerular filtration rate (eGFR), 40.3 mL/min/1.73 m2] and evaluated the progression of the abdominal aortic calcification index (ACI) over 3 years. To identify risk factors contributing to the rate of ACI progression, the associations between baseline clinical characteristics and annual change in ACI for each CKD category were analyzed. The annual change of ACI (ΔACI/year) was calculated as follows: (second ACI - first ACI)/duration between the two evaluations. RESULTS: Median ΔACI/year values significantly increased in advanced CKD stages (0.73%, 0.87%, and 2.24%/year for CKD stages G1-2, G3, and G4-5, respectively; p for trend = 0.041). The only independent risk factor for AAC progression in mild to moderate CKD (G1-3, eGFR ≥ 30 mL/min/1.73 m2) was pulse pressure level (ß = 0.258, p = 0.012). In contrast, parathyroid hormone (PTH) level was significantly correlated with ΔACI/year (ß = 0.426, p = 0.007) among patients with advanced CKD (G4-5, eGFR < 30 mL/min/1.73 m2). CONCLUSIONS: This study suggests that the AAC progression rate was significantly accelerated in patients with advanced CKD. In addition, measuring PTH is useful to evaluate both bone turnover and AAC progression in patients with advanced CKD.