Pretransfer Aspirin Administration and Its Impact on Angiographic Outcomes for Patients with ST-Elevation Myocardial Infarction.

Although guidelines recommend early aspirin administration after diagnosis of ST-elevation myocardial infarction (STEMI), the decision of pretransfer aspirin administration is at the discretion of the primary physicians. Therefore, this study aimed to determine whether pretransfer aspirin administration was associated with better angiographical outcomes in patients with STEMI. This study compared the angiographic findings of thrombolysis in myocardial infarction (TIMI) flow grade in the infarct-related artery before percutaneous coronary intervention (PCI) between patients who received pretransfer aspirin and those who did not. In total, 28 patients (11.2%) were administered aspirin before transfer and 219 (88.8%) were administered aspirin upon arrival at the hospital. Propensity score matching yielded 135 patients [27 patients (20%) who were administered aspirin before transfer and 108 patients (80%) who were administered aspirin upon arrival at the hospital]. Patients who received pretransfer aspirin had a higher rate of TIMI-3 flow before PCI compared to those who did not receive pretransfer aspirin [8 (28.6%) versus 15 (6.8%), P < 0.01, in all study patients; 8 (26.6%) versus 7 (6.5%), P < 0.01, in propensity-score-matched patients]. Multivariable logistic regression analysis revealed that pretransfer aspirin administration was significantly associated with the presence of TIMI-3 flow before PCI, independent of age, gender, transfer time, and statin use (OR: 5.43, 95% CI: 1.94-15.2, P < 0.01, in all study patients; OR: 6.17, 95% CI: 1.86-20.46, P < 0.01, in propensity-score-matched patients). Pretransfer aspirin administration could lead to the early restoration of coronary blood flow in patients with STEMI, supporting its active use in STEMI care.

Prognostic Value of Novel Natriuretic Peptide Index After Percutaneous Coronary Intervention.

BACKGROUND: The predictive value of both atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) is well known. This study evaluated the prognostic value of a novel natriuretic peptide index (NPI) combining ANP and BNP. Methods and Results: This study included 849 consecutive patients with coronary artery disease who underwent successful percutaneous coronary intervention (PCI). Patients were followed up clinically for up to 3 years or until the occurrence of major adverse cardiac events (MACE). The primary endpoint was a composite of all-cause death and non-fatal myocardial infarction. The NPI (pg/mL) was defined as √ANP×BNP. MACE occurred in 73 patients (8.6%) during the follow-up period. Receiver operating characteristic curve analysis showed the highest area under the curve for NPI (0.779) compared with ANP and BNP (0.773 and 0.755, respectively). A risk analysis of MACE occurrence adjusted for the multivariable model showed the highest hazard ratio (HR) for NPI (1.33; 95% confidence interval [CI] 1.18-1.51; P<0.001) compared with ANP and BNP (HR 1.25 [95% CI 1.13-1.39] and 1.30 [95% CI 1.13-1.49], respectively; P<0.001). The NPI was a significant independent predictor of MACE, among other clinical parameters, in the multivariable analysis. CONCLUSIONS: Compared with ANP and BNP, the NPI was more effective in predicting future adverse events after PCI.

Predictive Value of CHADS2, CHA2DS2-VASc and R2-CHADS2 Scores for Short- and Long-Term Major Adverse Cardiac Events in Non-ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Non-ST-elevation myocardial infarction (NSTEMI) carries a poor prognosis, and accurately prognostication has significant clinical importance. In this study, we analyzed the predictive value of the CHADS2, CHA2DS2-VASc, and R2-CHADS2scores for major adverse cardiac events (MACE) following percutaneous coronary intervention (PCI) in patients with NSTEMI using data from a prospective multicenter registry.Methods and Results: The registry included 440 consecutive patients with NSTEMI and coronary artery disease who underwent successful PCI. Patients were clinically followed for up to 3 years or until the occurrence of MACE. MACE was defined as a composite of all-cause death and nonfatal MI. During the follow-up period, 55 patients (12.5%) experienced MACE. Risk analysis of MACE occurrence, adjusted for the multivariable model, demonstrated a significant increase in risk with higher CHADS2, CHA2DS2-VASc, and R2-CHADS2scores. Kaplan-Meier analysis showed a higher incidence of MACE in patients with higher CHADS2, CHA2DS2-VASc, and R2-CHADS2scores, both in the short- and long-term periods. CONCLUSIONS: Patients with NSTEMI and higher CHADS2, CHA2DS2-VASc, and R2-CHADS2scores displayed a greater incidence of MACE.

Stratification Analysis of Statin Effect on Major Adverse Cardiac Events After Percutaneous Coronary Intervention in Patients on Hemodialysis.

ABSTRACT: The statin use in patients on hemodialysis remains controversial, and no beneficial effects of statin on the reduction of adverse cardiovascular events have been reported in these patients. This study used stratification analysis to examine the clinical factors in patients on hemodialysis who could benefit from statin for secondary prevention. This prospective multicenter study included 234 consecutive patients on hemodialysis with coronary artery disease who underwent successful reperfusion therapy with percutaneous coronary intervention. The patients were followed up for up to 3 years or until the occurrence of major adverse cardiac events (MACEs; defined as a composite of all-cause death and nonfatal myocardial infarction). Inverse probability of treatment weighting adjustment was used to remove the selection bias. During the median follow-up period of 30 months, MACEs occurred in 55 patients. Patients with MACEs had significantly lower statin therapy (P < 0.001). Multivariable Cox proportional hazards analysis showed that the patients on statins had a significantly reduced rate of MACE occurrence [adjusted hazard ratio 0.30 (0.11-0.81), P = 0.02]. The stratification analysis of outcomes according to the presence of clinical factors showed that beneficial effects of statin were associated with man, elderly, lower body mass index, lower abdominal circumference, hypertension, diabetes, higher C-reactive protein, symptomatic heart failure, lower left ventricular function, nonacute coronary syndrome, and shorter stent length. Statin was effective for the prevention of MACEs in patients on hemodialysis who underwent percutaneous coronary intervention. We identified specific clinical factors affecting statin effectiveness for secondary prevention.

Protein S-glutathionylation stimulate adipogenesis by stabilizing C/EBPß in 3T3L1 cells.

Reactive oxygen species (ROS) increase during adipogenesis and in obesity. Oxidants react with cysteine residues of proteins to form glutathione (GSH) adducts, S-glutathionylation, that are selectively removed by glutaredoxin-1 (Glrx). We have previously reported that Glrx knockout mice had increased protein S-glutathionylation and developed obesity by an unknown mechanism. In this study, we demonstrated that 3T3L1 adipocytes differentiation increased ROS and protein S-glutathionylation. Glrx ablation elevated protein S-glutathionylation and lipid content in 3T3L1 cells. Glrx replenishment decreased the lipid content of Glrx KO 3T3L1 cells. Glrx KO also increased protein expression and protein S-glutathionylation of the adipogenic transcription factor CCAAT enhancer-binding protein (C/EBP) ß. Protein S-glutathionylation decreased the interaction of C/EBPß and protein inhibitor of activated STAT (PIAS) 1, a small ubiquitin-related modifier E3 ligase that facilitates C/EBPß degradation. Experiments with truncated mutant C/EBPß demonstrated that PIAS1 interacted with the liver-enriched inhibitory protein (LIP) region of C/EBPß. Furthermore, mass spectrometry analysis identified protein S-glutathionylation of Cys201 and Cys296 in the LIP region of C/EBPß. The C201S, C296S double-mutant C/EBPß prevented protein S-glutathionylation and preserved the interaction with PIAS1. In summary, Glrx ablation stimulated 3T3L1 cell differentiation and adipogenesis via increased protein S-glutathionylation of C/EBPß, stabilizing and increasing C/EBPß protein levels.

Impact of persistent endothelial dysfunction in an infarct-related coronary artery on future major adverse cardiovascular event occurrence in STEMI survivors.

Although coronary endothelial vasomotor dysfunction predicts future coronary events, few human studies have shown the relationship between persistent endothelial vasomotor dysfunction and major adverse cardiovascular events (MACE) using serial assessments in the same coronary artery. This study examined whether persistent endothelial vasomotor dysfunction is related to MACE occurrence in the infarct-related coronary artery (IRA) of ST-segment elevation myocardial infarction (STEMI) survivors using serial assessments of the coronary vasomotor response to acetylcholine (ACh). This study included 169 consecutive patients with a first acute STEMI due to left anterior descending coronary artery (LAD) occlusion and successful reperfusion therapy with percutaneous coronary intervention. Vasomotor response to ACh in the LAD was measured within 2 weeks of acute myocardial infarction (AMI) (first test) and repeated 6 months (second test) after AMI under optimal anti-atherosclerotic therapy. MACE was defined as the composite of all-cause death, non-fatal MI, angina recurrence requiring percutaneous intervention or surgical bypass, and hospitalization for heart failure. We followed up 126 patients for a period of ≤ 60 months until MACE occurrence after second test. Nineteen MACEs occurred during the follow-up. The log-rank test, Kaplan-Meier curves and univariate Cox proportional hazards regression analysis showed that MACE occurrence was significantly associated with the persistent impairment of epicardial coronary artery dilation and coronary blood flow increases in response to ACh (log-rank test, p < 0.001 and p < 0.001, respectively) (Hazard ratio, p = 0.001 and p = 0.002, respectively). Persistent impairment of endothelial vasomotor function in the infarct-related conduit arterial segment and resistance arteriole were the significant predictor of future MACE occurrence in STEMI survivors.

Relationship of a thinned medial layer to the attenuated contractile response in atherosclerotic coronary arteries.

Coronary arteries with advanced atherosclerosis do not necessarily have greater contractile responses than those with early atherosclerosis. This study aimed to clarify the relationship between thickness of the medial layer and the contractile response to acetylcholine (ACh) in coronary artery using optical coherence tomography (OCT). The OCT and the vasomotor response to ACh in the left anterior descending coronary artery were assessed in 32 patients with previous myocardial infarction. The intimal and medial layer areas were measured by planimetric analysis of the OCT images. The coronary contractile response to ACh had a positive linear relationship with medial area (r = 0.61, P < 0.001). In contrast, the relationship between the coronary contractile response to ACh and intimal area was described by an inverted U-shaped curve that was fitted to a quadratic regression model (R2 = 0.35, P = 0.002, y-axis, contraction; x-axis, intimal area). The contractile response increased as the intimal layer thickened up to the inflection point; thereafter, the contractile response declined. The relationship between medial area and intimal area was also described by an inverted U-shaped curve that was fitted to a quadratic regression model (R2 = 0.41, P < 0.01, y-axis, medial area; x-axis, intimal area). The medial area increased as the intimal area thickened up to the inflection point; thereafter, the medial area thinned. In conclusion, the thinned medial layer was associated with the attenuated contractile response in a coronary artery with greater atherosclerosis.NEW & NOTEWORTHY This is the first clinical study to show the relationship between the contractile response and the thickness of medial smooth muscle layer in coronary artery of patients with previous myocardial infarction using OCT. The contractile response to acetylcholine was attenuated, and medial layer area was thinned in coronary artery with greater atherosclerosis compared with those in coronary artery with mild or moderate atherosclerosis. The coronary contractile response was positively correlated with thickness of the medial layer in coronary arteries with either mild or greater atherosclerosis. Thus, coronary arteries with advanced atherosclerosis do not necessarily have greater contractile responses than those with early atherosclerosis, which could be related to the thinned medial layer.

Persistent Myocardial Production of Follistatin-like 1 Is Associated With Left Ventricular Adverse Remodeling in Patients With Myocardial Infarction: Myocardial production of FSTL1 in AMI patients.

BACKGROUND: Although animal studies showed that Follistatin-like 1 (FSTL1) exerts cardioprotective effects against ischemic injury, little is known in humans. We examined whether FSTL1 is secreted in an infarcted myocardium and whether its production is associated with left ventricular (LV) remodeling in survivors of acute myocardial infarction. METHODS AND RESULTS: FSTL1 levels were measured by enzyme-linked immunosorbent assay in plasma collected from the aortic root and the anterior interventricular vein in 93 patients with anterior acute myocardial infarction. Measurement of FSTL1 levels and left ventriculography were repeated during the early phase (2 weeks) and the chronic phase (6 months) after MI. A persistent increment in FSTL1 levels from the aortic root to the anterior interventricular vein, reflecting FSTL1 production in the infarcted myocardium at both the early and chronic phases, was seen in 22 patients (24%). A linear regression analysis revealed that a persistent transmyocardial increment in FSTL1 levels was significantly associated with percent changes in LV end-diastolic volume index, LV end-systolic volume index, and LV ejection fraction from the early to the chronic phase (r = 0.44, 0.51, and -0.43, respectively, all P < .001). CONCLUSIONS: The persistent production of FSTL1 in the infarcted myocardium was associated with adverse LV remodeling in survivors of acute myocardial infarction.

Pulmonary Vascular Resistance Is Associated With Brachial-Ankle Pulse-Wave Velocity and Adverse Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: The precise mechanisms underlying the high prevalence of pulmonary hypertension (PH) with increased pulmonary vascular resistance (PVR) in heart failure with preserved ejection fraction (HFpEF) remain largely unknown. Measurements of brachial-ankle pulse wave velocity (baPWV) have been shown to be useful for risk assessment in HF patients. Thus, this study sought to define the association of PVR with baPWV and clinical outcomes in HFpEF. METHODS AND RESULTS: Patients with HFpEF (n = 198) had measurements of baPWV and PVR by right heart catheterization, and were prospectively followed-up for <96 months or until the occurrence of a composite of all-cause death, hospitalization with worsening HF, and nonfatal acute coronary syndrome. RESULTS: Multivariate logistic analysis showed that baPWV was independently associated with PH with increased PVR (P < .001). During the follow-up period, 46 clinical events occurred. Multivariate Cox proportional hazards analysis showed that PH with increased PVR was a significant predictor of adverse outcomes after adjustment for conventional risk factors (HR 1.96, 95% CI 1.03-3.76, P = .04). CONCLUSIONS: PH with increased PVR was associated with increased baPWV and adverse clinical outcomes in HFpEF. Thus, increased arterial stiffness may contribute to increased risk predictability of PVR for patients with HFpEF.

Remnant Lipoproteins Are Residual Risk Factor for Future Cardiovascular Events in Patients With Stable Coronary Artery Disease and On-Statin Low-Density Lipoprotein Cholesterol Levels <70 mg/dL.

BACKGROUND: This study examined the predictive value of remnant lipoprotein levels for cardiovascular events (CVEs) in patients with stable coronary artery disease (CAD) and low-density lipoprotein cholesterol (LDL-C) levels <70 mg/dL on statin treatment.Methods and Results:Serum levels of remnant lipoproteins (remnant-like lipoprotein particles cholesterol: RLP-C) were measured by an immunoseparation method in 247 consecutive patients with CAD who had on-statin LDL-C levels <70 mg/dL. All the patients were followed prospectively for a period of ≤60 months or until the occurrence of the primary composite endpoint of cardiac death, nonfatal myocardial infarction, unstable angina requiring coronary revascularization, worsening heart failure, peripheral artery disease, aortic event, and ischemic stroke. During a mean follow-up period of 38 months, 33 CVEs occurred. Kaplan-Meier analysis demonstrated that higher RLP-C levels (≥3.9 mg/dL, determined by ROC curve) resulted in a significantly higher probability for the primary endpoint than did lower RLP-C levels (<3.9 mg/dL) (P<0.01 by log-rank test). Stepwise multivariate Cox proportional hazard analysis showed that RLP-C was a significant predictor of the primary endpoint after adjustment for known risk factors and lipid variables including triglycerides, and total apolipoprotein B (hazard ratio 1.62, 95% confidence interval 1.26-2.07, P<0.01). CONCLUSIONS: RLP-C levels are a residual risk factor for future CVEs in patients with CAD and on-statin LDL-C <70 mg/dL.

High levels of stromal cell-derived factor-1α predict short-term progression of renal dysfunction in patients with coronary artery disease.

BACKGROUND: Stromal cell-derived factor-1α (SDF-1α) is an inflammatory chemokine that plays a critical role in cardiovascular disease. Although persistent inflammation causes renal dysfunction, it remains unclear whether SDF-1α is related to progression of chronic kidney disease. This study examined whether high levels of SDF-1α are associated with future declines in renal function in patients with coronary artery disease (CAD). METHODS: Plasma levels of SDF-1α in the peripheral blood were measured by enzyme-linked immunosorbent assay in 344 patients with CAD. All patients were followed for 24 months or until the occurrence of renal dysfunction, defined as ≥ 25% decrease in estimated glomerular filtration rate (eGFR) from baseline. RESULTS: During the follow-up period, 36 patients developed renal dysfunction. Multivariate logistic regression analysis showed that high plasma levels of SDF-1α were significantly associated with progression of renal dysfunction (odds ratio 1.65; 95% confidence intervals 1.07-2.35, p = 0.03). In addition, high plasma levels of SDF-1α had a significant incremental effect on the predictive value of known risk factors for renal dysfunction in analyses using net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.58 [0.07-1.02], p < 0.01; and IDI 0.030 [0.001-0.085], p = 0.02). CONCLUSION: High plasma levels of SDF-1α were associated with the short-term decline of eGFR in patients with CAD. Thus, SDF-1α may be useful for predicting the progression of renal dysfunction in patients with CAD.

Human soluble phospholipase A2 receptor is an inhibitor of the integrin-mediated cell migratory response to collagen-I.

Murine membrane-bound phospholipase A2 receptor 1 (PLA2R) is shed and released into plasma in a soluble form that retains all of the extracellular domains. Relatively little is known about human PLA2R. This study examined whether human soluble PLA2R has biological functions and whether soluble PLA2R exists in human plasma. Here, we showed that human recombinant soluble PLA2R (rsPLA2R) bound to collagen-I and inhibited interaction of collagen-I with the extracellular domain of integrin ß1 on the cell surface of human embryonic kidney 293 (HEK293) cells. As a result, rsPLA2R suppressed integrin ß1-mediated migratory responses of HEK293 cells to collagen-I in Boyden chamber experiments. Inhibition of phosphorylation of FAK Tyr397 was also observed. Similar results were obtained with experiments using soluble PLA2R released from HEK293 cells transfected with a construct encoding human soluble PLA2R. rsPLA2R lacking the fibronectin-like type II (FNII) domain had no inhibitory effects on cell responses to collagen-I, suggesting an important role of the FNII domain in the interaction of rsPLA2R with collagen-I. In addition, rsPLA2R suppressed the migratory response to collagen-IV and binding of collagen-IV to the cell surface of human podocytes that endogenously express membrane-bound, full-length PLA2R. Immunoprecipitation and Western blotting showed the existence of immunoreactive PLA2R in human plasma. In conclusion, human recombinant soluble PLA2R inhibits integrin ß1-mediated cell responses to collagens. Further studies are warranted to elucidate whether immunoreactive PLA2R in human plasma has the same properties as rsPLA2R.

Lack of phospholipase A2 receptor increases susceptibility to cardiac rupture after myocardial infarction.

RATIONALE: Recent evidence indicates that the biological effects of secretory phospholipase A2 (sPLA2) cannot be fully explained by its catalytic activity. A cell surface receptor for sPLA2 (PLA2 receptor 1 [PLA2R]) and its high-affinity ligands (including sPLA2-IB, sPLA2-IIE, and sPLA2-X) are expressed in the infarcted myocardium. OBJECTIVE: This study asked whether PLA2R might play a pathogenic role in myocardial infarction (MI) using mice lacking PLA2R (PLA2R(-/-)). METHODS AND RESULTS: MI was induced by permanent ligation of the left coronary artery. PLA2R(-/-) mice exhibited higher rates of cardiac rupture after MI compared with PLA2R wild-type (PLA2R(+/+)) mice (46% versus 21%, respectively; P=0.015). PLA2R(-/-) mice had a 31% decrease in collagen content and a 45% decrease in the number of α-smooth muscle actin-positive fibroblasts in the infarcted region compared with PLA2R(+/+) mice. PLA2R was primarily found in myofibroblasts in the infarcted region. PLA2R(-/-) myofibroblasts were impaired in collagen-dependent migration, proliferation, and activation of focal adhesion kinase in response to sPLA2-IB. Binding of sPLA2-IB to PLA2R promoted migration and proliferation of myofibroblasts through functional interaction with integrin ß1, independent of the catalytic activity of sPLA2-IB. In rescue experiments, the injection of PLA2R(+/+) myofibroblasts into the infarcted myocardium prevented post-MI cardiac rupture and reversed the decrease in collagen content in the infarcted region in PLA2R(-/-) mice. CONCLUSIONS: PLA2R deficiency increased the susceptibility to post-MI cardiac rupture through impaired healing of the infarcted region. This might be partly explained by a reduction in integrin ß1-mediated migratory and proliferative responses of PLA2R(-/-) myofibroblasts.

Sustained myocardial production of stromal cell-derived factor-1α was associated with left ventricular adverse remodeling in patients with myocardial infarction.

The role of stromal cell-derived factor-1α (SDF-1α) expressed in infarcted myocardium is unknown in humans. We examined whether SDF-1α produced in an infarcted myocardial lesion may play a role in left ventricle (LV) remodeling and dysfunction in patients with acute myocardial infarction (AMI). We measured SDF-1α levels in plasma obtained from aortic root (AO) and anterior interventricular vein (AIV) in the early phase (2 wk after MI) and the chronic phase (6 mo after MI) in 80 patients with anterior MI. An increment in SDF-1α level from AO to AIV, reflecting SDF-1α release from infarcted myocardium, was more frequent in patients with MI in the early phase of MI [n = 52 (65%), P = 0.03] but not in the chronic phase of MI [n = 46 (58%), P = 0.11] compared with that in control patients [n = 6/17 (35%)]. On linear regression analysis, the transmyocardial gradient in SDF-1α level in the chronic phase of MI was correlated with percentage changes in LV end-diastolic volume index (r = 0.39, P < 0.001), LV end-systolic volume index (r = 0.38, P < 0.001), and LV ejection fraction (r = -0.26, P = 0.01) 6 mo after AMI. By contrast, the transmyocardial gradient of SDF-1α in the early phase of MI had no significant correlations. In conclusion, the production of SDF-1α in infarcted myocardium in the chronic phase of MI was associated with LV adverse remodeling and progressive dysfunction in AMI survivors.

Deficiency of phospholipase A2 receptor exacerbates ovalbumin-induced lung inflammation.

Secretory phospholipase A2 (sPLA2) plays a critical role in the genesis of lung inflammation through proinflammatory eicosanoids. A previous in vitro experiment showed a possible role of cell surface receptor for sPLA2 (PLA2R) in the clearance of extracellular sPLA2. PLA2R and groups IB and X sPLA2 are expressed in the lung. This study examined a pathogenic role of PLA2R in airway inflammation using PLA2R-deficient (PLA2R(-/-)) mice. Airway inflammation was induced by immunosensitization with OVA. Compared with wild-type (PLA2R(+/+)) mice, PLA2R(-/-) mice had a significantly greater infiltration of inflammatory cells around the airways, higher levels of groups IB and X sPLA2, eicosanoids, and Th2 cytokines, and higher numbers of eosinophils and neutrophils in bronchoalveolar lavage fluid after OVA treatment. In PLA2R(-/-) mice, intratracheally instilled [(125)I]-labeled sPLA2-IB was cleared much more slowly from bronchoalveolar lavage fluid compared with PLA2R(+/+) mice. The degradation of the instilled [(125)I]-labeled sPLA2-IB, as assessed by trichloroacetic acid-soluble radioactivity in bronchoalveolar lavage fluid after instillation, was lower in PLA2R(-/-) mice than in PLA2R(+/+) mice. In conclusion, PLA2R deficiency increased sPLA2-IB and -X levels in the lung through their impaired clearance from the lung, leading to exaggeration of lung inflammation induced by OVA treatment in a murine model.

High remnant lipoprotein predicts recurrent cardiovascular events on statin treatment after acute coronary syndrome.

BACKGROUND: After acute coronary syndrome (ACS), there is a high risk of recurrent cardiovascular events. Triglyceride-rich lipoproteins influence residual cardiovascular risk in patients taking statin. This study examined the predictive value of remnant lipoprotein level for secondary cardiovascular events in patients treated with statins after ACS. METHODS AND RESULTS: A total of 190 patients treated with statins after ACS were enrolled in the study. The serum level of remnant lipoproteins (remnant-like lipoprotein particle cholesterol; RLP-C) was measured using an immunoseparation method. All the patients were followed prospectively for a maximum period of 70 months or until the occurrence of one of the following events: cardiac death, non-fatal myocardial infarction, unstable angina requiring unplanned coronary revascularization, or ischemic stroke. During the follow-up period, 42 patients had a secondary event. Multivariate Cox analysis showed that a high level of RLP-C (≥5.4 mg/dl; determined on receiver operating characteristic curve analysis) was a significant risk factor for secondary events, independent of conventional risk factors (hazard ratio, 2.94; 95% confidence interval: 1.40-6.18; P<0.01). The addition of high RLP-C to traditional risk factors enhanced net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI, 0.66, P=0.0003; and IDI, 0.08, P=0.0002). CONCLUSIONS: RLP-C is useful for risk assessment of secondary cardiovascular events in patients treated with statins after ACS.

Echolucency of carotid plaque is useful for assessment of residual cardiovascular risk in patients with chronic coronary artery disease who achieve LDL-C goals on statin therapy.

BACKGROUND: Ultrasound assessment of either intima-media thickness (IMT) or plaque echolucency of the carotid artery provides prognostic information on coronary events. This study examined the hypothesis that IMT and plaque echolucency of the carotid artery may remain useful for prediction of coronary events in patients with coronary artery disease (CAD) after achievement of LDL-C goals on statin therapy. METHODS AND RESULTS: Ultrasound assessment of carotid maximum IMT (maxIMT) and plaque echolucency with integrated backscatter (IBS) analysis was performed in 357 chronic CAD patients with LDL-C <100mg/dl on statin therapy. All patients were prospectively followed up until the occurrence of one of the following coronary events: cardiac death, non-fatal myocardial infarction, or unstable angina pectoris requiring unplanned revascularization. During a mean follow-up of 32±18 months, 33 coronary events occurred. On multivariate Cox proportional hazards analysis, plaque echolucency (lower IBS value) was a significant predictor of coronary events (HR, 0.44; 95% CI: 0.29-0.73; P=0.009), whereas maxIMT was not. The addition of plaque echolucency to traditional risk factors improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI; NRI, 0.59; P=0.0013; and IDI, 0.075; P=0.0009). CONCLUSIONS: Measurement of echolucency of the carotid artery was useful for assessment of residual coronary risk in CAD patients after LDL-C goal attainment on statin treatment.

Water quality monitoring and risk assessment by simultaneous multipathogen quantification.

Water quality monitoring and microbial risk assessment are important to ensure safe water for drinking, recreational, and agricultural purposes. In this study, we applied a microfluidic quantitative PCR (MFQPCR) approach to simultaneously quantify multiple waterborne pathogens in a natural freshwater lake in Hokkaido, Japan, from April to November, 2012. Tens of thousands of geese stopped over at this lake during their migration in spring and fall. Because lake water is used for irrigation of the surrounding agricultural area, we assessed infection risks through irrigation water usage based on pathogen concentrations directly measured by MFQPCR. We detected various pathogens in the lake water, particularly during the bird migration seasons, suggesting that migratory birds were the main source of the pathogens. However, neither counts of geese nor fecal indicator bacteria were good predictors of pathogen concentrations. On the basis of quantitative microbial risk assessment, concentrations of Campylobacter jejuni and Shigella spp. in water samples were above the concentrations that can potentially cause 10(-4) infections per person per year when water is used to grow fresh vegetables. These results suggest that direct and simultaneous multipathogen quantification can provide more reliable and comprehensive information for risk assessment than the current fecal indicator-based approach.

Impact of atherothrombotic risk stratification in patients with heavily calcified lesions following rotational atherectomy.

BACKGROUND: Patients who undergo percutaneous coronary intervention (PCI) with rotational atherectomy (RA) are at high risk of adverse clinical outcomes, and there are few clinical risk stratification tools for these patients. METHODS: We conducted a study with 196 patients who underwent PCI with RA out of 7391 patients who underwent PCI using a multicenter, prospective cohort registry. Patients were divided into three groups according to the tertiles of the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS 2°P): 65 patients in the T1 group (TRS 2°P < 3), 66 patients in the T2 group (TRS 2°P = 3), and 65 patients in the T3 group (TRS 2°P > 3). The primary endpoint was the cumulative 2-year incidence of major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of cardiac death, acute coronary syndrome, and ischemic stroke. RESULTS: Cumulative 2-year MACCE occurred in 41 patients (24 %) during the follow-up period. The cumulative incidence of MACCE was significantly higher in the T3 group than in the T1 group (log-rank test, p = 0.02). Multivariate Cox analyses revealed that the T3 group was associated with an increased risk of MACCE compared to that of the T1 group (adjusted hazard ratio, 2.66; 95 % confidence interval, 1.04-6.77; p = 0.04). The addition of TRS 2°P to conventional risk factors, including male sex, number of diseased vessels, and low-density lipoprotein cholesterol levels, improved the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.39, p = 0.027; IDI 0.072, p < 0.001). CONCLUSIONS: Atherothrombotic risk stratification using TRS 2°P was useful in identifying high-risk patients with heavily calcified lesions following RA.