One-Year Outcome of Patients with Chest Pain in the Rule-Out Group According to the 0-Hour/1-Hour Algorithm.

The European Society of Cardiology recommends the 0/1-hour algorithm for risk stratification of patients with suspected non-ST-elevation myocardial infarction as class I, level B; however, there are few reports on the long-term prognosis, resulting in a rule-out group. We aimed to determine whether implementation of the 0-hour/1-hour algorithm is safe and effective in emergency department (ED) patients with possible acute coronary syndrome (ACS) through a 1-year follow-up period. Our study analyzed the 1-year follow-up data from a prospective pre-post study of 1106 ED patients with possible ACS from 4 hospitals in Japan and Taiwan. Patients were 18 years or older. Accrual occurred for 1 year after implementing the 0-1-hour algorithm from November 2014 to December 2018. Overall, 520 patients were stratified into the rule-out group. Major advanced cardiovascular events (all-cause death, acute myocardial infarction [AMI], stroke, unstable angina, and revascularization) at 1-year were determined using data from health records and phone calls. The 0-1-hour algorithm stratified 47.0% of patients in the rule-out group. Over the 1-year follow-up period (follow-up rate = 86.9%), cardiovascular death and subsequent AMI did not occur in the rule-out group. Among the 27 patients who underwent the procedure within 30 days post-index visit, 3 patients (0.7%) had a stroke, 6 patients (1.3%) died of non-cardiovascular cause, and 30 patients (6.7%) underwent coronary revascularization within 1 year. At the 1-year follow-up, implementation of the 0-hour/1-hour algorithm was associated with very low rates of adverse event among patients in the rule-out group.

Clinical Evaluation of a New High-Sensitivity Cardiac Troponin I Assay for Diagnosis and Risk Assessment of Patients with Suspected Acute Myocardial Infarction.

INTRODUCTION: Current assays based on the 0-hour/1-hour (0-/1-h) algorithm using high-sensitivity cardiac troponin (hs-cTn) are limited to only Abbott Architect hs-cTnI, Siemens Vista hs-cTnI, and Roche Elecsys hs-cTnT. OBJECTIVE: This study aimed to evaluate this new hs-cTnI assay, LumipulsePresto hs Troponin I, for diagnosis of acute myocardial infarction (AMI) on admission and on 0-/1-h algorithm to stratify AMI patients precisely. METHODS: This prospective cohort study included 442 patients with suspected non-ST-elevation myocardial infarction in three hospitals in Japan and Taiwan from June 2016 to January 2019. We enrolled patients presenting to the emergency department with symptoms suggestive of AMI and collected blood samples on admission and 1 hour later. Two independent cardiologists centrally adjudicated final diagnoses; all clinical information was reviewed twice: first, using serial hs-cTnT (Roche-Elecsys, primary analysis) and Lumipulse Presto Lumipulse Presto, second, using the Lumipulse Presto hs-cTnI measurements. At first, we compared diagnostic accuracy quantified using receiver operating characteristic (ROC) curves for AMI. Then, we evaluated major adverse cardiovascular events (cardiac death, AMI) in the rule-out group according to a 0-hour/1-hour algorithm at the 30-day follow-up. RESULTS: Diagnostic accuracy at presentation by the ROC curve for AMI was very high and similar for the LumipulsePresto hs-cTnI and hs-cTnT,(area under the curve [AUC]: LumipulsePresto hs-cTnI, 0.89, 95% confidence interval [CI] 0.86-0.93; hs-cTnT, 0.89, 95% CI 0.85-0.93; p = 0.82). In early presenters, the LumipulsePresto hs-cTnI appeared to maintain the diagnostic performance of hs-cTn for patients with <3 h (AUC: LumipulsePresto hs-cTnI, 0.87, 95% CI 0.81-0.92; hs-cTnT, 0.86, 95% CI 0.80-0.92; p = 0.81). The algorithm using the LumipulsePresto hs-cTnI ruled out AMI in 200 patients with negative predictive value and sensitivity of 100% (95% CI 97.3%-100%) and 100% (95% CI 92.7%-100%), respectively, in the rule-out group. CONCLUSION: Diagnostic accuracy and clinical utility of the novel LumipulsePresto hs-cTnI assay are high and comparable with the established hs-cTn assays.

Size-adjusted aortic valve area: refining the definition of severe aortic stenosis.

AIMS: Severe aortic valve stenosis (AS) is defined by an aortic valve area (AVA) <1 cm2 or an AVA indexed to body surface area (BSA) <0.6 cm/m2, despite little evidence supporting the latter approach and important intrinsic limitations of BSA indexation. We hypothesized that AVA indexed to height (H) might be more applicable to a wide range of populations and body morphologies and might provide a better predictive accuracy. METHODS AND RESULTS: In 1298 patients with degenerative AS and preserved ejection fraction from three different countries and continents (derivation cohort), we aimed to establish an AVA/H threshold that would be equivalent to 1.0 cm2 for defining severe AS. In a distinct prospective validation cohort of 395 patients, we compared the predictive accuracy of AVA/BSA and AVA/H. Correlations between AVA and AVA/BSA or AVA/H were excellent (all R2 > 0.79) but greater with AVA/H. Regressions lines were markedly different in obese and non-obese patients with AVA/BSA (P < 0.0001) but almost identical with AVA/H (P = 0.16). AVA/BSA values that corresponded to an AVA of 1.0 cm2 were markedly different in obese and non-obese patients (0.48 and 0.59 cm2/m2) but not with AVA/H (0.61 cm2/m for both). Agreement for the diagnosis of severe AS (AVA < 1 cm2) was significantly higher with AVA/H than with AVA/BSA (P < 0.05). Similar results were observed across the three countries. An AVA/H cut-off value of 0.6 cm2/m [HR = 8.2(5.6-12.1)] provided the best predictive value for the occurrence of AS-related events [absolute AVA of 1 cm2: HR = 7.3(5.0-10.7); AVA/BSA of 0.6 cm2/m2 HR = 6.7(4.4-10.0)]. CONCLUSION: In a large multinational/multiracial cohort, AVA/H was better correlated with AVA than AVA/BSA and a cut-off value of 0.6 cm2/m provided a better diagnostic and prognostic value than 0.6 cm2/m2. Our results suggest that severe AS should be defined as an AVA < 1 cm2 or an AVA/H < 0.6 cm2/m rather than a BSA-indexed value of 0.6 cm2/m2.

Implementing the European Society of Cardiology 0-h/1-h algorithm in patients presenting very early after chest pain.

BACKGROUND: The European Society of Cardiology (ESC) recommends a 0-h/1-h (0/1-h) algorithm to classify patients with suspected non-ST-segment elevation myocardial infarction (NSTEMI). However, reliable evidence about patients who present early after the onset of symptoms is limited, likely because high-sensitivity cardiac troponin (hs-cTn) values cannot increase sufficiently within that time. This study aimed to evaluate the outcomes in real-world situations that utilized the 0/1-h algorithm. METHODS: In a prospective, international, multicenter cohort study that enrolled 1638 patients presenting with acute chest pain to the emergency department, we assessed the performance of the 0/1-h algorithm using hs-cTnT and the associated 30-day rates of major adverse cardiac events: death and acute myocardial infarction (AMI). RESULTS: Among 1074 patients, the prevalence of AMI was 16.0%. An approximately 60.1% (n = 645) of patients visited the hospital within 3 h after onset of chest pain (less than 1 h; 18.2% [n = 196], less than 2 h; 27.5% [n = 295], and less than 3 h; 14.3% [n = 154]). Moreover, the prevalence rates of AMI were similar at all times (1 h, 16.8%; 1-2 h, 20.7%; 2-3 h, 18.2%; p = .5). According to the ESC 0/1-h algorithm, the distribution patterns of rule-out, observe, and rule-in groups were similar; however, none of the patients was diagnosed with AMI or cardiac death in the rule-out group. CONCLUSION: This study revealed the applicability of the 0/1-h algorithm for the management of early presenters.

Primary Cardiac Diffuse Large B-cell Lymphoma Promptly and Safely Diagnosed with Pericardial Effusion Cytology.

Primary cardiac lymphoma is a rare condition with a poor prognosis, and patients are at risk for sudden cardiac death. A prompt diagnosis and early treatment are therefore essential. A 68-year-old woman was admitted for shortness of breath and peripheral edema. Echocardiograms showed massive pericardial effusion and a mass on the free wall of the right atrium and ventricle. Subsequent pericardial effusion cytology revealed diffuse large B-cell lymphoma. We started chemotherapy with rituximab and achieved a good clinical course. This case is made unique by the use of pericardial effusion cytology, which allowed us to diagnose primary cardiac lymphoma promptly and safely.

Impact of Fetuin-A on progression of calcific aortic valve stenosis - The COFRASA - GENERAC study.

BACKGROUND: Aortic stenosis (AS) is an active disease, but the determinants of AS progression remain largely unknown. Low levels of Fetuin-A, a powerful inhibitor of ectopic calcification, have been linked to ectopic calcium tissue deposition but its role in AS progression has not been clearly evaluated. METHODS: In our ongoing prospective cohort (COFRASA/GENERAC), serum Fetuin-A level was measured at baseline and AS severity was evaluated at baseline and yearly thereafter using echocardiography (mean pressure gradient (MPG)) and computed tomography (degree of aortic valve calcification (AVC)). Annual progression was calculated as [(final measurement-baseline measurement)/follow-up duration] for both MPG and AVC measurements. RESULTS: We enrolled 296 patients (74 ±â€¯10 years,73% men); mean follow-up duration was 3.0 ±â€¯1.7 years. No correlation was found between baseline serum Fetuin-A (0.55 ±â€¯0.15 g/L) and baseline AS severity (r = 0.25, p = 0.87 for MPG; r = 0.06, p = 0.36 for AVC). More importantly, there was no correlation between baseline serum Fetuin-A level and AS progression either assessed using MPG or AVC (both r = 0.01, p = 0.82). In bivariate analysis, after adjustment for age, gender, baseline AS severity, or valve anatomy, Fetuin-A was not associated with AS progression (all p > 0.20). The absence of link with AS progression was further confirmed by the absence of link betwen serum Fetuin-A and the occurrence of AS-related events (p = 0.17). CONCLUSIONS: In a large prospective cohort of AS patients, serum Fetuin-A was not associated to hemodynamic or anatomic AS progression. Despite its capacity to inhibit ectopic calcium deposition, Fetuin-A serum level seemed to have minor influence on AS progression.

Prognostic Value of Exercise-Stress Echocardiography in Asymptomatic Patients With Aortic Valve Stenosis.

OBJECTIVES: This study sought to evaluate the prognostic value of mean pressure gradient (MPG) increase and peak systolic pulmonary artery pressure (SPAP) measured during exercise stress echocardiography in asymptomatic patients with aortic stenosis (AS). BACKGROUND: Exercise testing is recommended in asymptomatic AS patients, but the additional value of exercise-stress echocardiography, especially the prognostic value of MPG increase and peak SPAP, is still debated. METHODS: We enrolled all consecutive patients with pure, isolated, asymptomatic AS and preserved ejection fraction ≥50% and normal SPAP (<50 mm Hg) who underwent symptom-limited exercise echocardiography at our institution. Occurrence of AS-related events (symptoms or congestive heart failure) or occurrence of aortic valve replacement was recorded. RESULTS: We enrolled 148 patients (66 ± 15 years of age; 74% males; MPG: 47 ± 13 mm Hg; SPAP: 34 ± 6 mm Hg). No complications were observed. Thirty-six patients (24%) had an abnormal exercise test result (occurrence of symptoms, fall in blood pressure, and/or ST-segment depression) and were referred for surgery. Among the 112 patients with a normal exercise test result, 38 patients (34%) had abnormal exercise echocardiography scores (MPG increase >20 mm Hg and/or SPAP at peak exercise >60 mm Hg). These 112 patients were managed conservatively. During a mean follow-up of 14 ± 8 months, an AS-related event occurred in 30 patients, and 25 patients underwent surgery. Neither MPG increase >20 mm Hg nor peak SPAP >60 mm Hg was predictive of occurrence of AS-related events or aortic valve replacement (all p > 0.20). In contrast, baseline AS severity was an important prognostic factor (all p < 0.01). CONCLUSIONS: In this observational study including 148 patients with asymptomatic AS, we confirmed and extended the importance of exercise testing for unveiling functional limitation. More importantly, neither the increase in MPG nor in SPAP at peak exercise was predictive of outcome. Our results do not support the use of these parameters in risk-stratification and clinical management of asymptomatic AS patients.

Influence of metabolic syndrome and diabetes on progression of calcific aortic valve stenosis.

BACKGROUND: Determinants of the progression of aortic stenosis (AS) remained unclear. Metabolic syndrome (MetS) and diabetes are suspected to play an active role but literature is scarce and results conflicting. We sought to assess their impact in an ongoing prospective cohort of asymptomatic patients with at least mild AS. METHODS: We enrolled 203 patients (73±9years, 75% men) with at least 2years of follow-up. Risk-factors assessment was performed at baseline. Annual progression was calculated as [(final-baseline measurements)/follow-up duration] for both mean pressure gradient (MPG) and degree of aortic valve calcification (AVC) measurements. RESULTS: Ninety-nine patients (49%) had MetS and 50 (25%) had diabetes (including 39 with MetS). After a mean follow-up of 3.2±1.2years, AS progression was not different between patients with and without MetS either using MPG (+3±3 vs. +4±4mmHg/year, p=0.25) or AVC (+211±231 vs. +225±222AU/year, p=0.75). Same results were obtained for patients with diabetes (3±3 vs. 4±4mmHg/year p=0.53, 187±140 vs. 229±248AU/year p=0.99). MetS had no impact on AS progression in all tested subgroups based on age, statin prescription, valve anatomy and AS severity (all p≥0.10). CONCLUSION: In our prospective cohort of AS patients, we found no impact of MetS or diabetes on AS progression. Although MetS and diabetes should be actively treated, no impact on AS progression should be expected. Our results support the theory that if cardiovascular risk-factors may play a role at the early phase of AS disease they have no or limited influence on AS progression.

Mortality risk of triglyceride levels in patients with coronary artery disease.

OBJECTIVE: The association between triglyceride level and the risk of coronary artery disease (CAD) remains controversial. In particular, the prognostic significance of triglyceride levels in established CAD is unclear. We aimed to assess the relationship between triglyceride levels and long-term (>10 years) prognosis in a cohort of patients after complete coronary revascularisation. DESIGN: Observational cohort study. SETTING: Departments of cardiology and cardiovascular surgery in a university hospital. PATIENTS: Consecutive patients who had undergone complete revascularisation between 1984 and 1992. All patients were categorised according to the quintiles of fasting triglyceride levels at baseline. MAIN OUTCOME MEASURES: The risk of fasting triglyceride levels for all-cause and cardiac mortality was assessed by multivariable Cox proportional hazards regression analyses. RESULTS: Data from 1836 eligible patients were assessed. There were 412 (22.4%) all-cause deaths and 131 (7.2%) cardiac deaths during a median follow-up of 10.5 years. Multivariable analyses including total and high-density lipoprotein cholesterol and other covariates revealed no significant differences in linear trends for all-cause mortality according to the quintiles of triglyceride (p for trend=0.711). However, the HR increased with the triglyceride levels in a significant and dose-dependent manner for cardiac mortality (p for trend=0.031). Multivariable analysis therefore showed a significant relationship between triglyceride levels, when treated as a natural logarithm-transformed continuous variable, and increased cardiac mortality (HR 1.51, p=0.044). CONCLUSIONS: Elevated fasting triglyceride level is associated with increased risk of cardiac death after complete coronary revascularisation.

Prognostic impact of chronic kidney disease on 10-year clinical outcomes among patients with acute coronary syndrome.

BACKGROUND: Chronic kidney disease (CKD) is closely associated with a higher risk of cardiovascular disease. However, whether patients with acute coronary syndrome (ACS) and CKD are at increased risk for long-term mortality after coronary revascularization remains unknown. METHODS AND RESULTS: Data from consecutive patients with ACS who had undergone coronary revascularization, including percutaneous coronary intervention (PCI) and coronary artery bypass surgery (CABG) were analyzed. The estimated glomerular filtration rate (eGFR) was calculated using the current Japanese equation and CKD was defined as eGFR < 60 mL/min/1.73 m(2). Among 375 enrolled patients with ACS, 75 (20.0%) had CKD. During a follow-up period of 10.0 ± 3.4 years, the total number of deaths was 80 (21.3%), of which 36 (9.6%) were due to cardiovascular causes. Kaplan-Meier analysis showed that the presence of CKD was associated with a significant increase in mortality from all causes (log-rank test, p<0.001) and cardiovascular mortality (p<0.001). Cox proportional-hazard analysis revealed that CKD increased the risk of mortality with a hazard ratio of 2.31 (95% confidence interval (CI): 1.25-4.29, p=0.008) and of cardiovascular death with a hazard ratio of 3.76 (95% CI: 1.60-8.80, p=0.002) in patients with ACS. CONCLUSIONS: CKD is a powerful determinant of long-term all-cause and cardiovascular mortality after ACS.

Probucol therapy improves long-term (>10-year) survival after complete revascularization: a propensity analysis.

OBJECTIVE: Probucol has anti-atherosclerotic properties and has been shown to reduce post-angioplasty coronary restenosis. However, the effect of probucol therapy on long-term (>10 years) outcome following coronary revascularization is less well established. Accordingly, we sought to determine if probucol therapy at the time of complete coronary revascularization reduces mortality in patients with coronary artery disease (CAD). METHODS: We collected data from 1694 consecutive patients who underwent complete revascularization (PCI and/or bypass surgery). Mortality data were compared between patients administered probucol and those not administered probucol at the time of revascularization. A propensity score (PS) was calculated to evaluate the effects of variables related to decisions regarding probucol administration. The association of probucol use and mortality was assessed using 3 Cox regression models, namely, conventional adjustment, covariate adjustment using PS, and matching patients in the probucol and no-probucol groups using PS. RESULTS: In the pre-match patients, 231 patients were administered probucol (13.6%). During follow-up [10.2 (SD, 3.2) years], 352 patients died (including 113 patients who died of cardiac-related issues). Probucol use was associated with significant decrease in all-cause death (hazard ratio [HR], 0.65; P=0.036 [conventional adjustment model] and HR, 0.57; P=0.008 [PS adjusted model]). In post-match patients (N=450, 225 matched pair), the risk of all-cause mortality was significantly lower in the probucol group than in the no-probucol group (HR, 0.45; P=0.002). CONCLUSION: In CAD patients who had undergone complete revascularization, probucol therapy was associated with a significantly reduced risk of all-cause mortality.

Long-term outcomes of women with coronary artery disease following complete coronary revascularization.

BACKGROUND: Although coronary artery disease (CAD) is less prevalent in women than in men, early mortality rate is higher in women with CAD than in men with CAD following coronary revascularization. In terms of the long-term outcomes after coronary revascularization, limited data are available. Especially, in the Japanese CAD population, no data about sex-related differences in long-term outcomes after coronary revascularization exist. The aim of this study was to compare long-term outcomes between men and women following complete revascularization in Japanese patients with CAD. METHODS: We collected data from 1836 consecutive patients who underwent complete revascularization by percutaneous coronary interventions and/or bypass surgeries. All-cause and cardiac mortality and the incidence of stroke were compared between men and women. In addition to the univariate analysis, a multivariate Cox regression was carried out in order to adjust for differences in baseline characteristics. RESULTS: There were 274 female patients (14.9%). They were older, had greater total cholesterol levels, and were more likely to have multivessel disease than men. During follow-up [mean (SD), 11.4 (2.9) years], 412 patients died (including 131 patients who died of cardiac causes), and 130 had a stroke. In the multivariate analysis, female patients did not have a significant risk for all-cause mortality (hazard ratio [HR], 1.01; p=0.993), cardiac mortality (HR, 1.41; p=0.256), or stroke (HR, 0.71; p=0.309). CONCLUSIONS: In the present study involving CAD patients who underwent complete revascularization, we showed that, although women were older and had more unfavorable risk profiles, they did not have a greater risk of long-term all-cause mortality, cardiac mortality, or stroke incidence, compared to men.

Association of low glomerular filtration rate with the incidence of stroke in patients following complete coronary revascularization.

BACKGROUND: Low glomerular filtration rate (GFR) is associated with a worse outcome after coronary revascularization. Recently, a new specific equation to calculate the estimated GFR (eGFR) in Japanese populations has been reported, and it might be more accurate than the previously used equations. However, the relationship between a low GFR defined using the new equation for the Japanese population and the incidence of stroke following complete coronary revascularization is not yet known. METHODS AND RESULTS: Consecutive patients who underwent complete coronary revascularization (percutaneous coronary intervention and bypass surgery) between 1984 and 1992 were enrolled. Patients on dialysis were excluded. Enrolled patients were divided into 2 groups: the preserved GFR group and the low GFR group. Low GFR was defined as eGFR<60 ml·min⁻¹·1.73 m⁻². The incidence of fatal and non-fatal stroke was compared between the groups. Among the 1,809 patients that were enrolled, 321 were placed in the low GFR group. During follow up (mean, 11.4 [2.9] years), there were 127 (7.0%) stroke events. Multivariable analysis using a Cox proportional hazards regression model revealed that the incidence of stroke was significantly higher in the low GFR group than in the preserved GFR group (hazard ratio, 1.66; 95% confidence interval, 1.10-2.48; P = 0.008). CONCLUSIONS: Low GFR, defined as eGFR <60 ml·min⁻¹·1.73 m⁻², using a new specific equation for the Japanese population was associated with an increased risk of fatal and non-fatal stroke over a 10-year period after complete coronary revascularization.

Candesartan with pioglitazone protects against endothelial dysfunction and inflammatory responses in porcine coronary arteries implanted with sirolimus-eluting stents.

BACKGROUND: Sirolimus-eluting stents (SES) are widely used in coronary artery disease as revascularization therapy. Although endothelial dysfunction induced by implanted SES can become a major clinical concern, therapeutic strategies to overcome this disorder remain unclear. The aim of the present study was therefore to identify effective therapies in a clinically relevant animal model. METHODS AND RESULTS: Twenty-one pigs were randomized to control, candesartan (CAN) and candesartan plus pioglitazone (CAN+PIO) groups. Drugs were administered orally for 7 days before SES implantation until the time of death. Forty-two SES were used in porcine coronary arteries. Early inflammatory cell adhesion in SES evaluated on scanning electron microscopy at 3 days was significantly suppressed in the CAN and CAN+PIO groups compared with controls. Bradykinin-induced endothelium-dependent relaxation at an adjacent segment distal to the SES evaluated using organ chambers was reduced compared with intact segments in control coronaries at 28 days. Endothelial dysfunction was reversed by CAN and even more obviously improved in the CAN+PIO group. CONCLUSIONS: Candesartan protected against vascular inflammation and restored endothelial function after SES implantation. The combination of candesartan and pioglitazone was more effective than candesartan monotherapy and might confer vascular protection when administered before SES implantation.

Prognostic significance of glomerular filtration rate estimated by the Japanese equation among patients who underwent complete coronary revascularization.

An equation that accurately estimates the glomerular filtration rate (GFR) in the Japanese population has been proposed; however, the prognostic significance of estimated GFR (eGFR) defined according to this equation has not been reported. In addition, the prognostic significance of eGFR during long-term follow-up after complete coronary revascularization remains unclear. We assessed the prognostic significance of eGFR values, estimated by the new Japanese equation, in a cohort of patients following complete coronary revascularization. We studied consecutive patients with complete revascularization from 1984 to 1992. Patients on dialysis were excluded. A novel Japanese equation was used to estimate the GFR: eGFR=194×(serum creatinine)(-1.094)×(age)(-0.287)(×0.739 if female). Multivariate Cox proportional hazards regression analyses were performed to determine all-cause and cardiac mortality. We analyzed data of 1809 patients, of whom 571 (31.6%) had an eGFR of ≥90 mlmin(-1) per 1.73 m(2), 917 (50.7%) had an eGFR of 60-89 mlmin(-1) per 1.73 m(2), 298 (16.5%) had an eGFR of 30-59 mlmin(-1) per 1.73 m(2) and 23 (1.3%) had an eGFR of <30 mlmin(-1) per 1.73 m(2). During follow-up (11.4±2.9 years), there were 397 (22.0%) all-cause and 123 (6.8%) cardiac deaths overall. Patients with an eGFR of 30-59 mlmin(-1) per 1.73 m(2), and <30 mlmin(-1) per 1.73 m(2) revealed significantly greater risk of all-cause mortality than those with eGFR of ≥90 mlmin(-1) per 1.73 m(2) (hazard ratio (HR) 1.91, P<0.001, HR 3.35, P<0.001, respectively). Furthermore, incidence of cardiac death was higher in patients with an eGFR of 30-59 mlmin(-1) per 1.73 m(2) than those with an eGFR of ≥90 mlmin(-1) per 1.73 m(2) (HR 2.89, P<0.001). GFR as estimated using the new Japanese equation had a prognostic significance among patients with complete coronary revascularization.

Synergistic effects of calcium-channel and angiotensin-receptor blockers on endothelial function and inflammatory responses in a porcine drug-eluting stent model.

BACKGROUND: The rate of stent thrombosis is increased in association with drug-eluting stents (DES) due to delayed endothelialization and prolonged inflammation. Clinical studies have shown that either an angiotensin-receptor blocker (ARB) or a calcium-channel blocker (CCB) can improve endothelial dysfunction and inhibit inflammatory reactions in patients with hypertension. The effects of co-administered CCB and ARB on vascular protection after DES implantation, however, remain unknown. METHODS AND RESULTS: Pigs (n=24) were implanted with coronary stents and randomly assigned to control, CCB, ARB or CCB + ARB groups. Endothelium-mediated vasodilation at the distal edge was significantly impaired compared to the intact site in the control group (P<0.05), but the difference between two sites in the CCB + ARB group was not significant. The combination produced a synergistic effect at the distal edge compared to the ARB, CCB and control groups (P<0.05). The expression of tumor necrosis factor-alpha and inflammatory cell adhesion were significantly inhibited in the CCB or ARB monotherapy groups compared with the control (P<0.05). The combination of CCB + ARB also improved inflammation. CONCLUSIONS: Implanted DES exert adverse effects such as endothelial dysfunction and inflammatory reactions. The administration of either a CCB or an ARB reversed this adverse effect. Furthermore, recovery was synergistically enhanced by a CCB combined with an ARB.

Long-term efficacy of pravastatin therapy in diabetic patients undergoing complete coronary revascularization.

AIM: The long-term effect of statin therapy in diabetic patients after coronary revascularization is not well established. Accordingly, we sought to determine if whether statin therapy initiated at the time of complete revascularization including percutaneous coronary intervention (PCI) and/or bypass surgery reduces total and cardiac mortality among diabetic patients. METHODS: We collected data from 1,138 consecutive patients who underwent complete revascularization (PCI and/or bypass surgery). We then compared all-cause and cardiac mortality rates in 499 patients with diabetes mellitus of whom 149 (29.9%) were treated with statin at the time of revascularization. To adjust the variables that would have been related to the decision regarding statin administration, a propensity score was computed and multivariate Cox regression was carried out. RESULTS: During follow-up (8.8+/-2.6 years), 103 patients died (including 43 who died of cardiac causes). The Multivariate analysis showed statin therapy to be significantly associated with reduced cardiac mortality (HR 0.39, 0.16-0.95; p=0.039), but not with all-cause mortality. CONCLUSION: Statin therapy was associated with a significantly reduced risk of cardiac mortality in patients with diabetes mellitus and coronary artery disease after complete revascularization.

The impact of pravastatin therapy on long-term outcome in patients with metabolic syndrome undergoing complete coronary revascularization.

BACKGROUND: Few studies dealing with the efficacy of statin therapy among patients with metabolic syndrome (MS) and coronary artery disease (CAD) have been conducted. In particular, there have been no studies of the efficacy of statins among Asian MS patients with treated CAD. METHODS AND RESULTS: Data from 1,138 consecutive patients who underwent complete revascularization (coronary intervention or bypass surgery) were collected. Of these, 529 patients who satisfied the criteria for MS using the American Heart Association/National Heart, Lung and Blood Institute statement (body mass index >or=25 was used instead of waist circumference) were assessed. All-cause and cardiovascular mortality of patients given statins and those not given statins at least 2 weeks before the complete revascularization were compared. To adjust for the variables that would have been related to the decision to give statins, the propensity score was calculated, and multivariate Cox regression was carried out. Statins were given to 146 patients. During follow-up (9.1 +/-2.5 years), 104 patients died. On multivariate analysis, statin use was significantly associated with reduced all-cause (hazard ratio (HR) 0.56, 0.31-0.99; P=0.049) and cardiovascular (HR 0.53, 0.30-0.96; P=0.042) mortality. CONCLUSIONS: In patients with MS and CAD, statins given at least 2 weeks before the complete revascularization, was associated with a reduced risk of all-cause and cardiovascular mortality.

Relationship between the metabolic syndrome and the incidence of stroke after complete coronary revascularization over a 10-year follow-up period.

OBJECTIVES: The prevalence of the metabolic syndrome, regarded as an important risk factor for coronary artery disease and stroke, is growing. However, the association between the metabolic syndrome and stroke, particularly in patients following coronary revascularization, remains unknown. Therefore, the relationship between the metabolic syndrome and stroke was examined among patients who had achieved complete coronary revascularization. METHODS: 1836 consecutive patients who had achieved complete revascularization from 1984 to 1992 were studied. The patients were categorized according to the presence or absence of the metabolic syndrome using the modified AHA/NHLBI statement (obesity was defined as a body mass index >or=25 kg/m(2)). Multivariate Cox proportional hazards regression was used for adjusted analyses for all-cause and cardiac mortality, as well as for the incidence of fatal and non-fatal stroke. RESULTS: The progress of 826 (45.0%) patients with the metabolic syndrome and 1010 (55.0%) patients without the metabolic syndrome was analyzed. The mean follow-up was 11.4+/-2.9 years. Overall, there were 130 (7.1%) strokes, and the risk of stroke was significantly higher in patients with metabolic syndrome than in those without metabolic syndrome (HR 1.3; 95% CI 1.0-2.1; P=0.045). CONCLUSION: The presence of the metabolic syndrome is a significant predictor of stroke, as well as all-cause and cardiac mortality, among patients who achieve complete coronary revascularization.

Impact of metabolic syndrome on 10-year clinical outcomes among patients with acute coronary syndrome.

BACKGROUND: Metabolic syndrome (MetS) is a risk factor and prognosticator for ischemic heart disease, but its actual effect on long-term mortality after acute coronary syndrome (ACS) remains unknown. METHODS AND RESULTS: All-cause death and cardiovascular death were investigated among patients with ACS upon admission who underwent complete revascularization by either percutaneous coronary intervention or bypass surgery between 1984 and 1992. MetS was defined according to the NCEP/ATPIII criteria modified for waist circumference. From among 1,836 patients who underwent complete revascularization during the study period, 384 (21.0%) with ACS were enrolled, of whom 163 (42.5%) had MetS. During a mean follow-up of 10.4 +/-3.4 years, the total number of deaths was 83 (21.6%), of which 38 (9.9%) were from cardiovascular causes. Cox proportional hazard analysis revealed that MetS increased the risk of mortality by a ratio of 1.62 (95% confidence interval (CI) 1.01-2.59, P=0.046) and of cardiovascular death by 2.40 (95%CI 1.16-4.94, P=0.018) in patients with ACS. CONCLUSIONS: MetS is a powerful determinant of long-term all-cause and cardiovascular death after ACS. Furthermore, MetS and ACS might jointly exacerbate poor long-term outcomes.