Sex and age differences of major cardiovascular events in patients after percutaneous coronary intervention.

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.

Association between visit-to-visit blood pressure variability and adverse events in coronary artery disease patients after coronary intervention.

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.

Utilization of Amplitude-Integrated Electroencephalography to Predict Neurologic Function after Resuscitation in Adults with Cardiogenic Cardiac Arrest.

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.

Association between phosphate and long-term outcome in CAD patients underwent coronary intervention.

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.

Association between Preoperative Nutritional Status and Clinical Outcomes of Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

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).

Systemic immune-inflammation index (SII) predicted clinical outcome in patients with coronary artery disease.

BACKGROUND: This study examines the predictive value of a novel systemic immune-inflammation index (SII, platelet × 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 × 109 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.

Association of variability in uric acid and future clinical outcomes of patient with coronary artery disease undergoing percutaneous coronary intervention.

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).

Plasma haptoglobin level can augment NT-proBNP to predict poor outcome in patients with severe acute decompensated heart failure.

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.

The impact of successful revascularization of coronary chronic total occlusions on long-term clinical outcomes in patients with non-ST-segment elevation myocardial infarction.

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.

Higher post-acute myocardial infarction plasma haptoglobin level is associated with poor long-term overall survival.

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 (288.4ng/ml), patients were classified as higher Hp group (>288.4ng/ml) and lower Hp group (≤288.4ng/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.

Plasma haptoglobin concentrations are elevated in patients with coronary artery disease.

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.

Efficacy and tolerability between an olmesartan/amlodipine fixed-dose combination and an amlodipine double dose in mild to moderate hypertension.

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.

Effect of invasive strategy on different genders of Chinese patients with non-ST-elevation myocardial infarction.

OBJECTIVES: The aim of this study was to determine the impact of in-hospital revascularization on different genders and to compare the gender difference in short- and long-term prognosis of Chinese patients with non-ST-elevation myocardial infarction (NSTEMI). BACKGROUND: The benefit of invasive strategy between the genders of Asian ethnic populations with NSTEMI remains unclear. METHODS: A total of 343 consecutive NSTEMI patients were enrolled, 104 (30%) of them were women. All patients were followed up for at least 3 years or until the occurrence of a major event. The primary end point was all-cause death. The secondary end point was the combined occurrence of death or myocardial (re-)infarction (MI). RESULTS: The adjusted in-hospital and long-term clinical outcomes were similar between men and women. However, in-hospital revascularization significantly reduced long-term mortality and composite endpoint in men (P < 0.001), but not in women. After risk stratification by GRACE score, there was favorable effect of invasive strategy in high-risk women. In a multivariate Cox regression analysis, GRACE score (hazard ratio; HR, 1.017; P < 0.001) and in-hospital revascularization (HR, 0.516; P = 0.008) were the independent predictors of death or MI in men. However, only GRACE score was the independent predictor of composite endpoint in women (HR, 1.012; P = 0.004). CONCLUSIONS: In Asian ethnic patients with NSTEMI, the in-hospital and long-term prognosis were similar between men and women. In-hospital revascularization has a benefit in men and high-risk women for reducing the all-cause death at 1 and 3 years. Our data provide evidence supporting the guideline recommendation for an invasive strategy in high-risk women.

Human haptoglobin phenotypes and concentration determination by nanogold-enhanced electrochemical impedance spectroscopy.

Haptoglobin (Hp) is an acute phase protein that binds free hemoglobin (Hb), preventing Hb-induced oxidative damage in the vascular system. There are three phenotypes in human Hp, whose heterogeneous polymorphic structures and varying concentrations in plasma have been attributed to the cause of diseases and outcome of clinical treatments. Different phenotypes of Hp may be composed of the same subunits but different copy numbers, rendering their determination difficult by a single procedure. In this study, we have developed a simple, fast, reliable and sensitive method, using label-free nanogold-modified bioprobes coupled with self-development electrochemical impedance spectroscopy (EIS). By this method, probe surface charge transfer resistance is detected. The relative charge transfer resistance ratios for Hp 1-1, Hp 2-1 and Hp 2-2 were characterized. We were able to determine protein size difference within 3 nm, and the linear region of the calibration curve for Hp levels in the range of 90 pg ml(-1) and 90 µg ml(-1) (∼1 fM to 1 pM). We surmise that similar approaches can be used to investigate protein polymorphism and altered protein-protein interaction associated with diseases.

Association of apolipoprotein J polymorphism 1598delT with coronary artery disease and lipoprotein levels.

OBJECTIVES: To investigate a polymorphism of the apolipoprotein J (APOJ) gene in relation to coronary artery disease (CAD) and lipid variables in a Chinese male population of genetically unrelated individuals. METHODS: In this study, we recruited 126 control male subjects and 237 CAD male patients. CAD was defined as a fixed stenotic lesion with luminal narrowing ≥50% in at least one of the major or minor coronary arteries. In cases with documented myocardial infarction, only those rated as fully recovered for more than 3 months were enrolled. Patients with acute or chronic infectious diseases and those with malignancies were excluded. All subjects with a fasting serum triglyceride level higher than 300 mg/dl were likewise excluded. RESULTS: We identified a single nucleotide polymorphism, 1598delT, and showed its association with CAD. Subjects with the I/I genotype showed a significantly higher CAD risk compared to those with the D/D genotype (OR 2.34, 95% CI 1.11-4.94, p = 0.026). Patients with the I/I genotype also had abnormal levels of high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol associated with CAD. CONCLUSIONS: Our data indicated that the APOJ single nucleotide polymorphism (1598delT) is associated with risk factors for CAD in a Chinese population.

Haptoglobin phenotypes and plasma haptoglobin levels in patients with abdominal aortic aneurysm.

OBJECTIVE: Inflammation is associated with the disruption of the aortic media and appears to play a fundamental role in the progression and development of abdominal aortic aneurysm (AAA). Haptoglobin (Hp) is a genetically determined acute phase protein, the synthesis of which is increased during inflammation. This study was designed to investigate both phenotype and plasma levels of Hp in patients with AAA. METHODS: Patients with documented AAA who were admitted for elective open repair operation or endograft stent implantation, and non-AAA subjects admitted for coronary arteriography, but found to have normal or insignificant coronary artery disease, were included in the study. Plasma Hp levels were determined using a standard specific enzyme-linked immunosorbent assay, while Hp phenotype was determined by native polyacrylamide gel electrophoresis. Total cholesterol, high density lipoprotein, low density lipoprotein, and triglyceride levels were analyzed enzymatically, and C-reactive protein was analyzed by immunochemistry. RESULTS: Forty-five patients with AAA and 49 non-AAA subjects were included. The Hp 2-2 phenotype was more predominant in AAA patients compared with non-AAA subjects, but this difference was not significant (67% vs 47%; P = .141), while plasma Hp concentrations were significantly higher in AAA patients (237 ± 144 vs 163 ± 86 ng/mL; P = .024). Further analysis revealed that plasma Hp concentrations were significantly higher in AAA patients with the 2-2 phenotype compared with corresponding non-AAA subjects (238 ± 144 vs 163 ± 86 ng/mL;P = .024). CONCLUSIONS: Our findings suggest that plasma Hp concentrations are elevated in patients with AAA, particularly those with the Hp 2-2 phenotype.

Haemoglobin-induced oxidative stress is associated with both endogenous peroxidase activity and H2O2 generation from polyunsaturated fatty acids.

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.

Immunochemical property of human haptoglobin phenotypes: determination of plasma haptoglobin using type-matched standards.

OBJECTIVES: Haptoglobin (Hp) phenotypes 1-1, 2-1, and 2-2 are associated with inflammatory diseases. Since their biochemical structures are rather heterogeneous, it is necessary to accurately determine the plasma Hp levels. DESIGN AND METHODS: Immunodiffusion, immunoturbidimetric, and noncompetitive ELISA were conducted to determine the differences in immunoreactivity among Hp phenotypes and to verify that such difference may significantly affect the outcome of Hp determinations. A novel ELISA using phenotype-matched calibrators was performed to compared with a commercial GenWay ELISA kit using a single calibrator in normal healthy males. RESULTS: In immunodiffusion and immunoturbidimetric assays, the immunoreactivity of Hp 1-1 was markedly higher than 2-1 and 2-2, while an opposite result was observed using an ELISA. The latter was primarily due to the repeated antigenic epitopes in polymeric 2-1 and 2-2. Thus, Hp levels could be significantly over- or underestimated depending on the method. An accurate ELISA could be achieved when using each type-specific Hp calibrator matched to each type subject. We show the mean levels of Hp 1-1 subjects (n=16; 184+/-42 mg/dL) to be significantly and differentially greater than 2-1 (n=28; 153+/-55 mg/dL) (p<0.05) and 2-2 (n=24; 93+/-54 mg/dL) (p<0.01) subjects. CONCLUSIONS: Due to the diverse immunochemical structure among the Hp types, phenotyping should be performed in all the patients and a type-matched Hp calibrator should be used in clinical Hp determination.

Gel electrophoresis of polyphenol oxidase with instant identification by in situ blotting.

Polyphenol oxidase (PPO) or tyrosinase is an important and ubiquitous enzyme responsible for browning in plants and melanization in animals. The molecular size of the plant PPO is varied among the species and its activity can be enhanced by a variety of anionic detergents. In the present study, we developed a simple method for the first-step identification of PPO in fruit and vegetable extracts. First, 3mm chromatographic paper was immersed in 0.5% (w/v) catechol solution as an immobilized PPO substrate. After running the extract with 10% sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), one side of the glass plate was removed. The plate was immediately laid on top of the dried catechol-paper. A dark-brown band corresponding to PPO was visualized within 1 min and was further confirmed by a conventional Western blot using an antibody prepared against mushroom PPO. It also reveals that some vegetation (such as tomato, radish, and oriental melon) with low or no detectable activity in a conventional enzyme assay actually possessed marked levels of PPO activity when assessed by PAGE-blot. We propose that an inhibitor is associated with PPO in some plants; the inhibitor, however, is dissociated during the electrophoresis. Therefore, in addition to identify the molecular form of PPO, the present technique may explore the existence of PPO inhibitor(s) in plants. The detail of the method with respect to its relevance for searching a natural PPO inhibitor is described and discussed.

beta(2)-glycoprotein I protects J774A.1 macrophages and human coronary artery smooth muscle cells against apoptosis.

beta(2)-Glycoprotein I (beta(2)-GPI) is a plasma glycoprotein with multifactorial relevance to clinical consequences. It was previously indicated that beta(2)-GPI can selectively bind to apoptotic cells. This study was designed to determine the role of beta(2)-GPI in apoptosis. Using an immunohistochemical study, we observed that beta(2)-GPI was co-localized with the apoptotic macrophages and smooth muscle cells (SMCs) of human coronary arteries. The contribution of beta(2)-GPI to apoptotic death was then investigated in vascular cells. Two nitric oxide (NO) donors, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetyl penicillamine (SNAP) were used in this study to trigger apoptosis in J774A.1 macrophages and human coronary artery smooth muscle cells (HCASMC). Cell viability was significantly improved in beta(2)-GPI-treated cells. It was also possible to detect a remarkable inhibitory effect by beta(2)-GPI on the NO-induced apoptosis by preventing nuclear shrinkage. Furthermore, the NO-induced apoptosis was associated with increase in caspase-3 activity and in the protein levels of caspase-3, c-Fos, and c-Jun. However, all these apoptosis-related events were inhibited in vascular cells treated with 200 microg/ml beta(2)-GPI. This is the first study to show that beta(2)-GPI may be important in the prevention of apoptosis in vascular cells.