Background: Women usually have higher risk after receiving percutaneous coronary interventions (PCIs) than men with coronary artery disease (CAD). The aim of this study was to investigate the association of sex differences with future outcomes in CAD patients undergoing PCI, to assess the role of age, and to extend observed endpoints to stroke and congestive heart failure.Methods: Six thousand six hundred forty-seven patients with CAD who received successful PCIs. The associations between clinic outcomes and sex were analyzed. The primary outcome was major cardiovascular events (MACE), including cardiac death, nonfatal myocardial infraction, and nonfatal stroke. The secondary outcome was MACE and hospitalization for heart failure (total CV events).Results: During a mean of 52.7 months of follow-up, 4833 men and 1614 women received PCI. Univariate and multivariate analyses showed that women were independently associated with an increased risk of cardiac death (HR, 1.78; 95% CI, 1.32-2.41), hospitalization for heart failure (HR, 1.53; 95% CI, 1.23-1.89), MACE (HR, 1.34; 95% CI, 1.10-1.63), and total CV events (HR, 1.39; 95% CI, 1.20-1.62). In the subgroup analysis, women aged under 60 years had higher cardiovascular risks than men of the same age category.Conclusion: Women with CAD after successful PCI had poorer cardiovascular outcomes than men. Additionally, younger women (aged <60 years) were especially associated with a higher risk of developing future adverse cardiovascular outcomes.

Abstract Blood pressure variability (BPV) is independently associated with higher cardiovascular risks. However, whether BPV is associated with poor outcomes for coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) remained undetermined. We aimed to investigate the relationship between BPV and the outcomes of CAD patients undergoing PCI. Two thousand seven hundred and sixty‐two CAD patients (1938 males, mean age 69.6 ± 12.9) who received PCI at Taipei Veterans General Hospital from 2006 to 2015 with multiple blood pressure measurements before and after the index PCI were enrolled. We calculated the standard deviation of systolic blood pressure, diastolic blood pressure, and pulse pressure as parameters of BPV. The primary endpoint was the composite of major adverse cardiovascular events [MACE comprising of cardiovascular death, nonfatal myocardial infarction (MI), and non‐fatal stroke] and heart failure hospitalization (HHF). The key secondary endpoint was MACE. Both pre‐PCI and post‐PCI BPV were associated with CV events even after adjusting for co‐morbidities and mean blood pressure. In Cox analysis, for every 1 mmHg increase in systolic BPV, the hazard ratio for the MACE + HHF, MACE, HHF, and cardiovascular death was 1.04 (95%CI: 1.03–1.05), 1.04 (95%CI: 1.02–1.05), 1.05 (95%CI: 1.04–1.06), and 1.06 (95%CI: 1.03–1.09), respectively. The association between BPV and cardiovascular risk is independent of blood pressure control status. The prognostic value of BPV was superior to mean blood pressure in both pre‐PCI and post‐PCI period. BPV is independently associated with cardiovascular events after PCI and has a better prognostic value than mean blood pressure suggesting the importance of maintaining stable blood pressure for CAD patients.

BACKGROUND:Amplitude-integrated electroencephalography (aEEG) has been used as a tool to recognize brain activity in children with hypoxic encephalopathy.OBJECTIVES:To assess the prognostic value of aEEG during the post-resuscitation period of adult cardiogenic cardiac arrest, comatose survivors were monitored within 24 h of a return of spontaneous circulation using aEEG.METHODS:Forty-two consecutive patients experiencing cardiac arrest were retrospectively enrolled, and a return of spontaneous circulation was achieved in all cases. These patients were admitted to the Coronary Intensive Care Unit due to cardiogenic cardiac arrest. The primary outcome was the best neurologic outcome within 6 months after resuscitation, and the registered patients were divided into two groups based on the Cerebral Performance Category (CPC) scale (CPC 1-2, good neurologic function group; CPC 3-5, poor neurologic function group). All patients received an aEEG examination within 24 h after a return of spontaneous circulation, and the parameters and patterns of aEEG recordings were compared.RESULTS:Nineteen patients were in the good neurologic function group, and 23 were in the poor group. The four voltage parameters (minimum, maximum, span, average) of the aEEG recordings in the good neurologic function groups were significantly higher than in the poor group. Moreover, the continuous pattern, but not the status epilepticus or burst suppression patterns, could predict mid-term good neurologic function.CONCLUSIONS:aEEG can be used to predict neurologic outcomes based on the recordings' parameters and patterns in unconscious adults who have experienced a cardiac collapse, resuscitation, and return of spontaneous circulation.

Abstract Hypertension is a frequent manifestation of chronic kidney disease but the ideal blood pressure (BP) target in patients with coronary artery disease (CAD) with end‐stage renal disease (ESRD) (eGFR < 15 ml/min/1.73m2) still unclear. The authors aimed to investigate the ideal achieved BP in ESRD patients with CAD after coronary intervention. Five hundred and seventy‐five ESRD patients who had undergone percutaneous coronary interventions (PCIs) were enrolled and their clinical outcomes were analyzed according to the category of systolic BP (SBP) and diastolic BP (DBP) achieved. The clinical outcomes included major cardiovascular events (MACE) and MACE plus hospitalization for congestive heart failure (total cardiovascular (CV) event).The mean systolic BP was 135.0 ± 24.7 mm Hg and the mean diastolic BP was 70.7 ± 13.1 mm Hg. Systolic BP 140–149 mm Hg and diastolic BP 80–89 mm Hg had the lowest MACE (11.0%; 13.2%) and total CV event (23.3%; 21.1%). Patients with systolic BP < 120 mm Hg had a higher risk of MACE (HR: 2.01; 95% CI: 1.17–3.46, p = .008) than those with systolic BP 140–149 mm Hg. Patients with systolic BP ≥ 160 mm Hg (HR: 1.84; 95% CI, 3.27–1.04, p = .04) and diastolic blood BP ≥ 90 mm Hg (HR: 2.19; 95% CI: 1.15–4.16, p = .02) had a higher risk of total CV event rate when compared to those with systolic BP 140–149 mm Hg and diastolic BP 80–89 mm Hg. A J‐shaped association between systolic (140–149 mm Hg) and diastolic (80–89 mm Hg) BP and decreased cardiovascular events for CAD was found in patients with ESRD after undergoing PCI in non‐Western population.

Phosphate has been linked to higher cardiovascular (CV) risk. However, whether phosphate is associated with poor outcomes for patients with coronary artery disease (CAD) after percutaneous coronary interventions (PCIs) remained undetermined. 2,894 CAD patients (2,220 male, aged 71.6 ± 12.2), who received PCI at TVGH from 2006 to 2015, with phosphate measurement, were enrolled. The primary outcome was the composite of major adverse CV events [MACE, comprising of CV death, nonfatal MI, and nonfatal stroke] and heart failure hospitalization (HHF). The key secondary outcome was MACE. There was a J-curve association between phosphate and CV events after adjusted for comorbidities and renal function. Phosphate around 3.2 ± 0.1 mg/dL was associated with the lowest CV risk. In Cox analysis, each 1 mg/dL increases in phosphate was associated with a higher risk of MACE + HHF (HR: 1.12, 95% CI: 1.05–1.21): CV death (HR: 1.37, 95% CI: 1.22–1.55) and HHF (HR: 1.12, 95% CI: 1.02–1.23). Subgroup analyses showed more prominent association between phosphate and MACE + HHF in male, age > 65, bare-metal stents (BMSs), LVEF < 50%, eGFR < 60, LDL > 70 mg/dL, and emergent PCI. Phosphate has a significant association with the risk of CV events in CAD patients undergoing PCI that was independent of comorbidities and renal function.

Background: Malnutrition is associated with poor outcomes in patients with cancer, heart failure and chronic kidney disease. This study aimed to investigate the predictive value of the Controlling Nutritional Status (CONUT) score in coronary artery disease (CAD) patients. Methods: We recruited a cohort of 3118 patients with CAD undergoing percutaneous coronary intervention (PCI) from 2005 to 2015. Nutritional status was evaluated using the CONUT score, with higher scores reflecting worse nutritional status. Results: After adjustment for comorbidities and medication, an increased CONUT score was independently associated with a higher risk of acute myocardial infarction (AMI) (HR: 1.13; 95% CI: 1.03–1.24), cardiovascular (CV) death (HR: 1.18; 95% CI: 1.07–1.30), congestive heart failure (CHF) (HR: 1.11; 95% CI: 1.04–1.18), a major adverse cardiovascular event (MACE) (HR: 1.14; 95% CI: 1.07–1.22), and total CV events (HR: 1.11; 95% CI: 1.07–1.15). The subgroup analyses demonstrated that the association of the CONUT score existed independently of other established cardiovascular risk factors. In addition, CONUT significantly improved risk stratification for myocardial infarction (MI), cardiac death, CHF, MACEs and total CV events compared to conventional risk factors in CAD patients by the significant increase in the C-index (p < 0.05) and reclassification risk categories in cardiac death and MACEs. Conclusions The CONUT score improved the risk prediction of adverse events compared to traditional risk factors in CAD patients after percutaneous coronary intervention (PCI).

Background and aims: Hyperuricemia is independently associated with cardiovascular disease (CVD) and is considered to be one of the major risk factors for CVD. However, the impact of inter-visit uric acid (UA) variability on cardiovascular risk remains undetermined. Methods: We enrolled 3202 patients with coronary artery disease (CAD), who received successful coronary intervention, in a cohort from Taipei Veterans General Hospital from 2006 to 2015. All post-baseline visits UA measurements using standard deviation (SD) were analyzed to correlate with long-term outcome. The primary outcome was the composite of cardiac death, nonfatal MI, nonfatal stroke (MACE). The secondary event was MACE and hospitalization for heart failure. Results: During an average 65.06 +/- 32.1-month follow-up, there were 66 cardiovascular deaths, 175 nonfatal myocardial infarctions, 64 nonfatal strokes, 287 hospitalizations for heart failure, and 683 revascularization procedures. There was a linear association between high UA SD and future adverse events. Compared to the lowest quartile SD, subjects in the highest quartile SD had a higher risk of MACE (HR: 2.53, 95% CI: 1.78-3.59), myocardial infarction (HR: 2.43, 95% CI: 1.53-3.86), cardiovascular death (HR: 6.45, 95% CI: 2.52-16.55), heart failure-related hospitalization (HR: 3.43, 95% CI: 2.32-5.05), and total major CV events (HR: 2.72, 95% CI: 2.09-3.56). Furthermore, compared to the average achieved on-treatment UA value, increasing UA SD had a stronger association of higher risk of developing MACE (HR: 1.51, 95% CI: 1.36-1.68), myocardial infarction (HR: 1.37, 95% CI: 1.38-1.68), ischemic stroke (HR: 1.43, 95% CI: 1.13-1.82), CV death (HR: 1.77, 95% CI: 1.50-2.11), HF (HR: 1.43, 95% CI: 1.29-1.58), and total major CV events (HR: 1.46, 95% CI: 1.34-1.58). Conclusions: High UA variability is associated with a higher risk of developing future cardiovascular events, suggesting the importance of maintaining stable serum UA levels and avoiding large fluctuations in CAD patients after percutaneous coronary intervention (PCI).

Background This study examines the predictive value of a novel systemic immune-inflammation index (SII, platelet x neutrophil/lymphocyte ratio) in coronary artery disease (CAD) patients. Methods A total of 5602 CAD patients who had undergone a percutaneous coronary intervention (PCI) were enrolled. They were divided into two groups by baseline SII score (high SII vs low SII) to analyse the relationship between SII groups and the long-term outcome. The primary outcomes were major cardiovascular events (MACE) which includes nonfatal myocardial infarction (MI), nonfatal stroke and cardiac death. Secondary outcomes included a composite of MACE and hospitalization for congestive heart failure. Results An optimal SII cut-off point of 694.3 x 10(9) was identified for MACE in the CAD training cohort (n = 373) and then verified in the second larger CAD cohort (n = 5602). Univariate and multivariate analyses showed that a higher SII score (>= 694.3) was independently associated with increased risk of developing cardiac death (HR: 2.02; 95% CI: 1.43-2.86), nonfatal MI (HR: 1.42; 95% CI: 1.09-1.85), nonfatal stroke (HR: 1.96; 95% CI: 1.28-2.99), MACE (HR: 1.65; 95% CI: 1.36-2.01) and total major events (HR: 1.53; 95% CI: 1.32-1.77). In addition, the SII significantly improved risk stratification of MI, cardiac death, heart failure, MACE and total major events than conventional risk factors in CAD patients by the significant increase in the C-index (P < .001) and reclassification risk categories by significant NRI (P < .05) and IDI (P < .05). Conclusions SII had a better prediction of major cardiovascular events than traditional risk factors in CAD patients after coronary intervention.

To evaluate the use of plasma haptoglobin (Hp) levels and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in predicting survival in patients with severe acute decompensated heart failure (AHF). Management of AHF is challenging. Identifying markers associated with patient prognosis in this disease is clinically important. In this prospective observational study, plasma Hp and NT-proBNP levels were measured. Receiver operating characteristic (ROC) curves were used to identify cut-offs of Hp and NT-proBNP with the greatest specificity and sensitivity for predicting overall survival and cardiovascular-related survival. The cut-off values were tested in patients with AHF (n=41). The cut-off value with the greatest specificity and sensitivity with respect to overall survival and for cardiovascular-related survival for Hp was 177. 1 ng/mL for both outcomes and for NT-proBNP was 34 246.0 pg/mL and 11 848.5 ng/mL, respectively. Using these cut-off values, this study found that patients with lower baseline Hp levels (<177. 1 ng/mL) or higher baseline NT-proBNP (≥34 246 pg/mL) were more likely to have shorter overall survival. Similarly, patients with <177. 1 ng/mL of Hp and ≥11 848.5 pg/mL of NT-proBNP had the highest risk of death related to cardiovascular disease. Our findings indicate that Hp and NT-proBNP using specific cut-off values for AHF can be used to determine risk of survival in these patients.

OBJECTIVES:The purpose of this study was to assess the long-term clinical impact of revascularization of coronary concomitant coronary chronic total occlusion (CTO) in patients with Non-ST-segment elevation myocardial infarction (NSTEMI).BACKGROUND:CTO is associated with poorer prognosis in patients with NSTEMI. The evidence of revascularization of CTO in patients with NSTEMI is still conflicting.METHODS:Consecutive patients with NSTEMI and CTO who underwent percutaneous coronary intervention (PCI) within 72 h of admission from 2006 to 2015 were retrospectively recruited and analyzed. A total of 967 patients underwent PCI for NSTEMI. Among them, 106 (11%) patients had concomitant CTO and were recruited for analysis. CTO lesions were revascularized successfully in 67 (63.2%) patients (successful CTO PCI group), while the CTO in the remaining 39 patients were either not attempted or failed (No/failed CTO PCI group).RESULTS:The 30-day cardiac death and major adverse cardiac events (MACE) were significantly lower in the successful CTO PCI group (both cardiac death and MACE were 3% vs 30%, P < 0.001, respectively). A landmark analysis set at 30th day for 30-day survivals was performed. After a mean of 2.5-year follow-up, the long-term cardiac death was still significantly lower (16.9% vs 42.3%, P < 0.001), whereas the MACE showed a trend toward lower incidence (26.2% vs 40.7%, P = 0.051) in the successful CTO PCI group. In multivariate Cox regression analysis, successful revascularization of CTO is an independent protective predictor for long-term cardiac death (HR 0.310, 95% CI, 0.109-0.881, P = 0.028) in all population and in propensity-score matched cohort (P = 0.007).CONCLUSIONS:Successful revascularization of CTO was associated with reduced risk of long-term cardiac death in patients with NSTEMI and concomitant CTO.

Coronary artery disease is the leading cause death all over the world. Dysfunction of the endothelial cells in blood vessels is one of the major events in the development of atherosclerosis. Inflammation involve in the initiative of atherosclerotic lesion process. In the progression, monocytes recruitment contributes to the early stage of atherosclerosis. Oxidation stress is another remarkable proinflammatory factor will induce endothelial cell inflammation and stimulate monocytes recruitment and differentiated to resident macrophages in vascular wall.In this study, we estimate that haptoglobin have strong anti‐oxidant activity and decrease the differentiated adhesive monocytes amount in vitro. In addition, we find haptoglobin inhibit monocyte adhesion molecular vascular cell adhesion molecule 1 (VCAM‐1) and Intercellular Adhesion Molecule 1 (ICAM‐1) expression in PMA‐induced inflammation endothelial cells. According, haptoglobin has the abilities to prevent LDL oxidation to mm‐LDL and ox‐LDL and decrease inflammation driven monocyte recruitment and differentiate into resident macrophages in vascular wall intimal space. Furthermore, we find haptoglobin enhance human umbilical vein endothelial cells (HUVECs) proliferation, migration, and angiogenesis in vitro. The abilities can accelerate wound healing process in the oxidative and inflammation initiated atherosclerotic lesion and improve cardiomyocyte function in ischemic damaged lesion.Currently, anti‐oxidant, anti‐inflammation, and angiogenesis enhance agents are the major studies trend for coronary artery diseases therapeutic application. In this study, we find haptoglobin has the activities to prevent atherosclerotic process and to improve functional activities in damaged atherosclerotic lesion. In conclusion, haptoglobin has strong potential as a protein drug for atherosclerosis prevention and therapeutic application.Support or Funding InformationThis work was supported by the grants MOST 105‐2314‐B‐038‐016 and MOST 105‐2119‐M‐038‐001 from Ministry of Science and Technology, Taiwan.

Aim: To evaluate the association of post-acute myocardial infarction (AMI) plasma haptoglobin (Hp) levels with long-term overall survival in AMI patients.Methods and results: Patients who were diagnosed of AMI were recruited and their Hp phenotypes and plasma levels were determined. According to previously reported cutoff point for Hp level (288.4 ng/ml), patients were classified as higher Hp group (N288.4 ng/ml) and lower Hp group (<= 288.4 ng/ml). The primary outcome was overall survival. This study recruited and followed a total of 117 patients for a median of 11.0 (3.2-17.6) years. Higher Hp group had 46 patients (39.3%) and lower Hp group had 71 patients (60.7%). Twelve patients had Hp 1-1 (10.3%), 50 with Hp 2-1 (42.7%), and 55 with Hp 2-2 (47.0%). The lower Hp group had significantly better overall survival (174.1 [51.6-212.5] vs. 106.5 [22.2-209.1], P = 0.037). There was no significant difference in overall survival between the three phenotype groups (P = 0.477). Multivariate regression analysis revealed that increased age (adjusted HR = 1.06, 95% CI: 1.03-1.10, P < 0.001) and higher Hp level (adjusted HR = 1.65, 95% = 1.02-2.67, P = 0.040) were significantly associated with poor overall survival.Conclusion: Higher post-AMI plasma Hp level was independently associated with poor overall survival in AMI patients. No significant difference in overall survival was noted between three Hp phenotype groups. Acute phase Hp level might reflect the severity of oxidative stress during inflammation process. (C) 2016 Published by Elsevier Ireland Ltd.

Fixed-dose combinations (FDCs) are one of the options for improving blood pressure (BP) goal attainment. We enrolled 141 patients and evaluated the efficacy and safety between a fixed dose of olmesartan/amlodipine (OA) and a double dose of amlodipine (DA) for treating mild to moderate hypertension after amlodipine monotherapy failure. After at least 2 weeks of monotherapy failure, the patients were randomized to receive either OA or DA for 8 weeks. We compared the systolic blood pressure (SBP)-lowering efficacy of the OA and DA using both an office BP and an ambulatory blood pressure monitoring (ABPM) device. The intent-to-treat analysis found that the early (2nd week) and final visit (8th week) SBP reductions were significantly greater in those patients receiving OA (n = 70) than DA (n = 71) (17.57 ± 15.49 vs. 10.46 ± 13.36 and 24.89 ± 14.09 vs. 17.03 ± 13.27 mmHg, p = 0.002 and 0.001, respectively). Among those using ABPM, the patients with 8-week OA had a greater SBP-lowering effect in comparison with those on DA (14.08 ± 10.74 vs. 6.32 ± 10.21, p = 0.018). Both treatment strategies were well tolerated. This study showed that an OA FDC is more effective than DA in reducing SBP for mild to moderate hypertension after the failure of amlodipine monotherapy.

Inflammation underlies the development and progression of coronary artery plaques. Haptoglobin (Hp) is an acute phase protein, the synthesis of which is increased during inflammation. The aim of this study was to investigate plasma Hp concentrations and phenotype in patients with coronary artery disease (CAD). We recruited 359 patients with fixed luminal stenosis ≥50% in at least one coronary artery (CAD group) and 83 patients with luminal stenosis ≤40%, normal ejection fraction, and normal regional wall motion (control group). Plasma Hp concentrations were measured using a phenotype-specific enzyme-linked immunosorbent assay. Hp phenotype was determined by native polyacrylamide gel electrophoresis. Plasma lipid concentrations were measured. Plasma Hp concentrations were significantly higher in the CAD compared with the control group (262.4±144.2 vs 176.0±86.7 ng/mL, P<0.001); however, there was no between group difference in the distribution of Hp phenotype (1-1 = 7.5% vs 7.2%; 2-1 = 40.4% vs 42.2%; 2-2 = 52.1% vs 50.6%). Stepwise multivariate logistic regression revealed that high Hp concentrations (odds ratio [OR] = 5.865), male sex (OR = 3.689), hypertension (OR = 2.632), diabetes mellitus (OR = 3.300), and low-density lipoprotein concentrations (OR = 1.480) were independently associated with CAD (all P<0.05). Hp phenotype was not associated with CAD. Plasma Hp concentrations were significantly correlated with the severity of luminal stenosis (r = 0.236, P<0.001). Our findings suggest that plasma Hp concentrations may be elevated in patients with CAD. There does not appear to be any relationship between Hp phenotype and CAD.

Patients with increased haemolytic haemoglobin (Hb) have 10-20-times greater incidence of cardiovascular mortality. The objective of this study was to evaluate the role of Hb peroxidase activity in LDL oxidation. The role of Hb in lipid peroxidation, H(2)O(2) generation and intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was assessed using NaN(3), a peroxidase inhibitor, catalase, a H(2)O(2) decomposing enzyme and human umbilical vein endothelial cells (HUVECs), respectively. Hb induced H(2)O(2) production by reacting with LDL, linoleate and cell membrane lipid extracts. Hb-induced LDL oxidation was inhibited by NaN(3) and catalase. Furthermore, Hb stimulated ICAM-1 and VCAM-1 expression, which was inhibited by the antioxidant, probucol. Thus, the present study suggests that the peroxidase activity of Hb produces atherogenic, oxidized LDL and oxidized polyunsaturated fatty acids (PUFAs) in the cell membrane and reactive oxygen species (ROS) formation mediated Hb-induced ICAM-1 and VCAM-1 expression.

Background Poor blood pressure (BP) control is a global problem. Fix-dose combination (FDC) is suggested to improve the BP goal attainment. We evaluated the efficacy and safety between olmesartan/ amlodipine FDC (OA) and double-dose amlodipine (DA) for the mild to moderate hypertensives not achieving target BP after amlodipine monotherapy. Methods This study was an open-label, randomized, multi-centers design. After failure of amlodipinemonotherapy, patients were randomized to receive either OA or DA for 8 weeks. This study was intended to compare the systolic BP (SBP)-lowering efficacy of OA and DA by using office BP and ambulatory BP monitoring (ABPM). Results 141 subjects were finally enrolled. The intent-to-treat analysis found early (2th week) and final visit (8th week) SBP reduction were significantly higher in those receiving OA (n = 70) than DA (n = 71) (17.57 ± 15.49 vs. 10.46 ± 13.36 and 24.89 ± 14.09 vs. 17.03 ± 13.27 mmHg, p = 0.002 and 0.001 respectively). Among those with ABPM, patients with 8-week OA (n = 35) also had higher SBP-lowering effect compared with those with DA (n = 25) (14.08 ± 10.74 vs. 6.53 ± 10.64, p = 0.036). Both treatment strategies were tolerated well. Conclusion This study showed that use of olmesartan/amlodipine FDC is more effective than double-dose amlodipine in the SBP reduction for the mild to moderate hypertensives with failure of amlodipine monotherapy.