Naozumi Kubota

Impact of Metabolic Syndrome among Patients with and without Diabetes Mellitus on Long-Term Outcomes after Percutaneous Coronary Intervention

Metabolic syndrome (MS) is highly prevalent and an established key risk factor for coronary artery disease, regardless of the presence or absence of diabetes mellitus (DM). Long-term follow-up studies have addressed the influence of MS with and without DM on the prognosis of patients undergoing percutaneous coronary intervention (PCI). We classified 748 consecutive patients who had undergone PCI into four groups as follows: neither DM nor MS, DM alone, MS alone, and both DM and MS. Post hoc analyses were conducted using prospectively collected clinical data. Multivariate Cox regression was used to evaluate the risk within each group for all-cause mortality and composite cardiac events (cardiac death, non-fatal acute coronary syndrome), adjusting for age, gender, body mass index, low-density lipoprotein (LDL) cholesterol level, hypertension, smoking, prior coronary artery bypass graft, presentation of acute coronary syndrome, left ventricular ejection fraction, multivessel disease, and procedural success. The progress of 321 (42.9%) patients with neither DM nor MS, 109 (14.6%) patients with DM alone, 129 (17.2%) patients with MS alone, and 189 (25.3%) patients with both DM and MS was followed up for a mean of 12.0±3.6 years. Patients with both DM and MS had significant risk for increased all-cause mortality (2.10 [1.19–3.70]). Patients with MS alone (2.14 [1.31–3.50]) and with both DM and MS (1.87 [1.18–2.96]) were at significant risk for increased cardiac events. In conclusion, the risk of cardiac events is significantly increased in patients with metabolic syndrome following PCI, irrespective of DM.

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.

Influence of diabetes on >10-year outcomes after percutaneous coronary intervention

There are few reports showing the relationship between diabetes and the long-term outcome following percutaneous coronary intervention (PCI) in Asians. As well, the association between glycosylated hemoglobin (HbA1c) level and outcome remains controversial. In this analysis, 748 Japanese patients including 298 with diabetes (DM) and 450 without diabetes (non-DM) who underwent PCI from 1984 to 1992 were evaluated over the long term. The mean follow-up was 12.0 ± 3.6 years. There were 47 (15.8%) total deaths in DM and 41 (9.1%) in non-DM [hazard ratio (HR) 1.71, 95% confidence interval (CI) 1.11–2.65, P = 0.013] and 28 (9.4%) cardiovascular deaths in DM and 19 (4.2%) in non-DM (HR 2.09, 95% CI 1.14–3.81, P = 0.016). Among DM, increased HbA1c was associated with both total (HR 1.25, 95% CI 1.03–1.53, P = 0.024) and cardiovascular (HR 1.30, 95% CI 1.00–1.69, P = 0.048) mortality. Even in Asians, DM showed an increased mortality following PCI. Among DM, increased HbA1c level was also associated with mortality.

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.

Therapy with statins and aspirin enhances long-term outcome of percutaneous coronary intervention

Aspirin is the standard therapy applied after coronary intervention, and statins are also prescribed to prevent secondary coronary heart disease. We assessed the ability of a combination of statins and aspirin to improve the longterm prognosis of patients after percutaneous coronary intervention (PCI). We collected data from 575 consecutive patients who underwent PCI. The patients were divided into groups depending on the presence or absence of statin or aspirin therapy as follows: both statin and aspirin (Group B: n = 190; 33%); aspirin only (Group A: n = 236; 41.1%); statin only (Group S: n = 53; 9.2%S); neither drug (Group N: n = 96; 16.7%). Data were statistically assessed using the Cox proportional hazard model for multivariate analysis with adjustment of baseline convariates. Sixty-eight patients died during follow-up (11 ± 3 years). Multivariate analysis showed that compared with group N, both groups S and A were independent predictors for survival from all causes [group S: hazards ratio (HR) 0.29, 95% confidence interval (CI) 0.10–0.81, P = 0.019; group A: HR 0.31, 95% CI 0.17–0.56, P < 0.0001] and cardiovascular (CV) death (group S: HR 0.16, 95% CI 0.04–0.73, P = 0.018; group A: HR 0.12, 95% CI 0.05–0.30, P < 0.001). risk for all causes and CV death was significantly lower in Group B (HR 0.25, 95% CI 0.12–0.53, P < 0.0001 and HR 0.10, 95% CI 0.03–0.31, P < 0.0001, respectively). Therapy with statins plus aspirin improves long-term clinical outcome in patients after PCI.

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.

The adverse prognostic significance of the metabolic syndrome with and without hypertension in patients who underwent complete coronary revascularization.

Objectives The metabolic syndrome is associated with high risk for long-term coronary artery disease mortality. However, few studies have examined the prognostic importance of the metabolic syndrome with and without hypertension. Methods The data of 1133 nondiabetic patients who underwent complete revascularization were analyzed. The patients were categorized by the presence of the metabolic syndrome using the modified American Heart Association/National Heart, Lung, and Blood Institute statement and by the presence of hypertension. All patients were divided into four groups: neither the metabolic syndrome nor hypertension (group 1); the metabolic syndrome without hypertension (group 2); hypertension without the metabolic syndrome (group 3); and both the metabolic syndrome and hypertension (group 4). Cox proportional hazards were used in adjusted analyses for all-cause and cardiac mortality, as well as for the composite incidence of fatal and nonfatal stroke. Results The progress of 276 (24.4%) patients in group 1, 413 (36.5%) in group 2, 105 (9.3%) in group 3, and 339 (29.9%) in group 4 was analyzed. The mean follow-up was 10.4 ± 3.4 years. Patients in group 4 had a higher risk of all-cause mortality (hazard ratio 1.78, P = 0.004). In addition, patients in groups 2 and 4 had a higher risk of cardiac mortality (group 2: hazard ratio 2.84, P = 0.04, group 4: hazard ratio 3.91, P = 0.001) and stroke (group 2: hazard ratio 2.46, P = 0.03, group 4: hazard ratio 2.09, P = 0.03). Conclusion The metabolic syndrome both with and without hypertension is associated with increased risk of cardiac mortality and stroke incidence in patients who underwent complete coronary revascularization.

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.

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.

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 ml min−1 per 1.73 m2, 917 (50.7%) had an eGFR of 60–89 ml min−1 per 1.73 m2, 298 (16.5%) had an eGFR of 30–59 ml min−1 per 1.73 m2 and 23 (1.3%) had an eGFR of <30 ml min−1 per 1.73 m2. 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 ml min−1 per 1.73 m2, and <30 ml min−1 per 1.73 m2 revealed significantly greater risk of all-cause mortality than those with eGFR of ⩾90 ml min−1 per 1.73 m2 (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 ml min−1 per 1.73 m2 than those with an eGFR of ⩾90 ml min−1 per 1.73 m2 (HR 2.89, P<0.001). GFR as estimated using the new Japanese equation had a prognostic significance among patients with complete coronary revascularization.