Abstract
Background:
Metabolic syndrome (MS) plays a crucial role in the long‐term prognosis and primary or secondary prevention of coronary artery disease, regardless of the presence or absence of diabetes mellitus (DM). We previously reported that after percutaneous coronary intervention (PCI), patients with MS had worse long‐term outcome. However, there is no evidence indicating the importance of MS with and without DM on re‐revascularization procedures in Japanese patients undergoing PCI.
Hypothesis:
We hypothesized that MS patients without DM have an increased risk of re‐revascularization following PCI.
Methods:
We classified 748 consecutive Japanese patients who had undergone PCI into 4 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 subsequent revascularization (repeat PCI and bypass surgery), adjusting for baseline covariates.
Results:
The progress of 321 (42.9%) patients without DM or 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 duration of 12.0 ± 3.6 years. Patients with MS alone (hazard ratio: 1.38, 95% confidence interval: 1.01–1.89, P = 0.04) and those with both DM and MS (hazard ratio: 1.36, 95% confidence interval: 1.02–1.81, P = 0.04) had a significantly increased risk for revascularization.
Conclusions:
The presence of MS significantly increased the risk for subsequent revascularization among Japanese patients who underwent PCI, regardless of the presence or absence of DM. © 2011 Wiley Periodicals, Inc.
The authors have no funding, financial relationships, or conflicts of interest to disclose.
Introduction
The prevalence of metabolic syndrome (MS) is increasing, and MS has been associated with increased cardiovascular disease morbidity and mortality even in the Japanese population.1, 2, 3, 4 We previously reported that MS patients after coronary revascularization had worse outcomes than non‐MS patients.5, 6, 7 Diabetes mellitus (DM) is included in the definitions of MS, and DM has been well known to be strongly associated with a high restenosis rate and progression of coronary atherosclerosis.8, 9 There have been several studies indicating that MS itself is associated with a risk of coronary artery disease (CAD) progression or mortality, both in patients with and without preexisting CAD, regardless of the presence of DM.6, 10, 11, 12, 13 However, it remains unclear whether there is a relationship between MS and increased restenosis or subsequent revascularization rate following coronary revascularization.14, 15, 16, 17, 18, 19, 20 Furthermore, it was reported that MS without DM does not have an impact on increased restenosis and/or subsequent revascularization rate in patients following percutaneous coronary intervention (PCI).15, 16, 17, 18 However, most of those studies were conducted in a Western population, and the impact of MS regardless of the presence or absence of DM on the revascularization rate among Asians has not been investigated. Therefore, we examined whether MS affects the subsequent revascularization rate of Japanese patients with and without DM who had undergone PCI.
Methods
Subjects
This study is an additional analysis of data from a previous study using the same population investigating the impact of MS on long‐term mortality and incidence of acute coronary syndrome (ACS) regardless of the presence or absence of DM.13 In brief, we analyzed data from 748 consecutive Japanese patients who had undergone PCI at Juntendo University Hospital in Japan between January 1984 and December 1992. The indications for PCI included objective evidence of myocardial ischemia (positive stress test) or ischemic symptoms associated with significant angiographic stenosis. This study was performed according to the ethics policies of our institution.
Data Collection
Demographic data including age, gender, body mass index (BMI), and coronary risk factors including blood sampling data, medication use, and interventional procedures were prospectively collected in the database at our institution, as previously described.13 Because intravascular ultrasound was not performed in all cases, the reference vessel diameter was estimated by the size of the balloon used for PCI and was also collected in the database. The degree of luminal narrowing was determined by the consensus opinion of 2 experienced interventional cardiologists.
Outcome Data
Subsequent revascularization data, including repeat PCI and coronary artery bypass grafting (CABG), were assessed from the medical records of patients who were followed up at our hospital until September 2002. In patients who were followed up elsewhere, whether they underwent subsequent revascularization or not and details of the subsequent revascularization were supplied by the institutions where they had been followed up, or where the subsequent revascularization was performed. The repeat PCI was further classified into 2 outcomes: (1) target vessel revascularization (TVR), if subsequent revascularization was performed in the same vessel as the target vessel of the baseline PCI; and (2) revascularization of a new lesion (NL), if subsequent revascularization was performed in vessels different from those targeted in the baseline PCI.
Definitions
Patients were classified based on the presence or absence of MS at baseline using a modified American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) definition.21 In this definition, obesity was defined as BMI of ≥25 kg/m2 based on the Japanese criteria for obesity22 rather than waist circumference as in the AHA/NHLBI definition. The other MS criteria were the same as those in the AHA/NHLBI definition: triglycerides ≥150 mg/dL; high‐density lipoprotein cholesterol (HDL‐C) <40 mg/dL in males or <50 mg/dL for females; blood pressure (BP) ≥130/85 mm Hg or treatment with antihypertensive medications; and fasting blood glucose (FBG) ≥100 mg/dL or treatment with oral hypoglycemic drugs or insulin injection. Patients who had 3 of 5 criteria were regarded as having MS. Furthermore, patients in each group with and without MS were divided into 2 subgroups according to the presence or absence of DM, which was defined as a FBG level ≥126 mg/dL23 or treatment with oral hypoglycemic drugs or insulin injection. The patients were separated into 4 groups: neither DM nor MS, DM alone, MS alone, and both DM and MS. Definitions for other variables were described previously.13
Statistical Analysis
Continuous variables are expressed as mean ± SD and were compared using one‐way analysis of variance with Dunnett's test. Categorical data are tabulated as frequencies and ratios (%), and were compared using the χ 2 test. Cumulative revascularization‐free rate was analyzed by Kaplan‐Meier estimation with the log‐rank test. Multivariate Cox proportional hazards regression analysis adjusted for age, gender, low‐density lipoprotein cholesterol (LDL‐C) level, hypertension, current smoker, history of CABG, ACS, left ventricular ejection fraction (LVEF), number of diseased vessels, reference vessel diameter, percentage of stenosis before PCI, and procedural success (defined as residual stenosis <50% after PCI) was used to determine the risk of subsequent revascularization in MS patients with or without DM. In addition, in patients without DM, risks of each MS component, as well as of the cumulative effect of having multiple MS components, for subsequent revascularization were also assessed using multivariate analyses including age, gender, LDL‐C level, current smoker, history of CABG, ACS, LVEF, number of diseased vessels, reference vessel diameter, percentage of stenosis before PCI and procedural success. A P value of <0.05 was considered statistically significant. All data were analyzed using SPSS for Windows (SPSS Inc., Chicago, IL).
Results
Baseline and clinical event data were fully documented for all 748 enrolled patients during the follow‐up period (mean follow‐up, 12.0 ± 3.6 y). Most patients were middle‐aged, nonobese males who were treated with nitrates and aspirin and had normal LVEF. Simple balloon angioplasty was applied because stents were not yet available at the time of the PCI procedures. Of the 748 patients, 298 (39.8%) had DM at the time of PCI. None of the patients who underwent PCI during the study period had type 1 DM.
Baseline Characteristics of 4 Groups
Overall, of the 748 patients, 321 (42.9%) had neither DM nor MS, 109 (14.6%) had DM alone, 129 (17.2%) had MS alone, and 189 (25.3%) had both MS and DM. The baseline characteristics, medication use, and angiographic and procedural data in these 4 groups are shown in Table 1, which have been previously published.13 As compared with patients with neither DM nor MS, patients with DM alone were older, had a higher FBG level by definition, and were more frequently taking statins. Patients with MS alone had worse MS‐related baseline profiles, except for FBG level, than those with neither DM nor MS. A greater percentage of patients with MS alone were on β‐blockers and calcium channel blockers (CCBs) than those with neither DM nor MS. Patients with both DM and MS also had worse MS‐related baseline profiles, including FBG level, than those with neither DM nor MS. A greater percentage of patients with both DM and MS were on CCBs than those with neither DM nor MS. Interestingly, there was no significant difference in the LDL‐C levels across the groups. As compared with patients with neither DM nor MS, those with DM alone, MS alone, and both DM and MS more frequently had multivessel disease. However, there were no significant differences in other angiographic and procedural data.
Table 1.
Baseline Characteristics
| Neither DM Nor MS | DM Alone | MS Alone | Both DM and MS | |
|---|---|---|---|---|
| No. | 321 | 109 | 129 | 189 |
| Age (y)a | 58.2 ± 10.3 | 62.4 ± 8.8b | 58.2 ± 10.5 | 60.0 ± 9.3 |
| Male, n (%) | 287 (89.4) | 93 (85.3) | 109 (84.5) | 162 (85.7) |
| BMI (kg/m2)a | 22.5 ± 2.5 | 22.3 ± 1.9 | 25.1 ± 2.4b | 24.9 ± 2.7b |
| Hypertension, n (%)a | 183 (57.0) | 53 (48.6) | 100 (77.5)b | 149 (78.8)b |
| Systolic BP (mm Hg)a | 128.0 ± 17.8 | 125.7 ± 16.0 | 133.4 ± 18.0c | 137.8 ± 19.4b |
| Diastolic BP (mm Hg)a | 74.3 ± 13.4 | 73.1 ± 12.0 | 77.6 ± 13.8c | 78.7 ± 12.3b |
| Cholesterol | ||||
| LDL (mg/dL) | 135.7 ± 38.7 | 128.8 ± 41.4 | 143.5 ± 42.2 | 137.3 ± 48.7 |
| HDL (mg/dL)a | 46.0 ± 13.2 | 48.0 ± 10.4 | 36.4 ± 9.7b | 38.3 ± 11.6b |
| Triglycerides (mg/dL)a | 123.5 ± 51.2 | 115.6 ± 52.9 | 203.8 ± 117.8b | 189.7 ± 98.8b |
| FBG (mg/dL)a | 88.3 ± 9.2 | 113.7 ± 37.5b | 94.4 ± 11.7 | 120.2 ± 45.2b |
| Current smoker, n (%) | 248 (77.3) | 82 (75.2) | 100 (77.5) | 149 (78.8) |
| Family history of CAD, n (%) | 103 (32.1) | 43 (39.5) | 46 (35.7) | 67 (35.5) |
| Medications, n (%) | ||||
| Nitrates | 286 (89.1) | 104 (95.4) | 116 (89.9) | 166 (87.8) |
| Nicorandil | 66 (20.6) | 15 (13.8) | 23 (17.8) | 36 (19.1) |
| ACEI | 19 (5.9) | 6 (5.5) | 13 (10.1) | 20 (10.6) |
| β‐Blockers | 75 (23.4) | 22 (20.2) | 42 (32.6)c | 47 (24.0) |
| CCBa | 78 (24.3) | 22 (20.2) | 54 (41.9)b | 67 (35.5)b |
| Aspirin | 227 (70.7) | 82 (75.2) | 88 (68.2) | 131 (73.2) |
| Warfarin | 127 (38.8) | 42 (38.5) | 41 (31.8) | 80 (42.3) |
| Statins | 99 (30.8) | 46 (42.2)c | 36 (27.9) | 62 (32.8) |
| Angiographic/procedural data | ||||
| Presentation of ACS, n (%) | 94 (29.2) | 36 (33.0) | 36 (27.9) | 50 (26.5) |
| Previous CABG, n (%) | 54 (16.8) | 26 (23.9) | 27 (20.9) | 28 (14.8) |
| No. of diseased vesselsa | 1.57 ± 0.74 | 1.76 ± 0.74 | 1.76 ± 0.74c | 1.57 ± 0.75 |
| Multivessel disease n (%)a | 135 (42.1) | 63 (57.8)b | 71 (55.0)c | 112 (59.3)b |
| Ref. vessel diameter (mm) | 2.92 ± 0.43 | 2.87 ± 0.43 | 2.98 ± 0.44 | 2.99 ± 0.49 |
| % of ≥2.50 mm (%) | 305 (95.0) | 12 (89.0) | 7 (94.6) | 13 (93.1) |
| % Stenosis before PCI (%) | 92.0 ± 8.3 | 92.4 ± 7.0 | 91.5 ± 8.3 | 93.3 ± 7.7 |
| % Stenosis after PCI (%) | 37.9 ± 2.4 | 36.9 ± 2.3 | 40.3 ± 2.5 | 36.1 ± 2.2 |
| Procedural success, n (%) | 283 (88.2) | 95 (87.2) | 109 (84.5) | 166 (87.8) |
| LVEF (%) | 67.5 ± 10.1 | 65.7 ± 12.6 | 68.2 ± 11.3 | 65.5 ± 13.1 |
Abbreviations: ACE, angiotensin‐converting enzyme inhibitors; ACS, acute coronary syndrome; BMI, body mass index; BP, blood pressure; CABG, coronary artery bypass graft; CCB, calcium channel blockers; DM, diabetes mellitus; FBG, fasting blood glucose; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; LVEF, left ventricular ejection fraction; MS, metabolic syndrome; Ref., reference; PCI, percutaneous coronary intervention.
Data are presented as mean ± SD, unless otherwise indicated.
P<0.01 across groups.
P<0.01 compared with neither DM nor MS.
P<0.05 compared with neither DM nor MS.
Subsequent Revascularization
Overall, subsequent revascularization was performed in 312 patients (41.7%); PCI was repeated in 255 patients (34.1%) and 57 patients (7.6%) underwent CABG during follow‐up. Furthermore, of the patients who underwent repeated PCI, 192 (25.7%) underwent TVR and 63 (8.5%) underwent PCI for a NL. Revascularization‐free rates of patients with MS alone and those with both MS and DM were significantly higher than those of patients with neither MS nor DM (Figure 1).
Figure 1.
Cumulative revascularization‐free rates. Revascularization‐free rates between patients with MS alone and those without DM and MS differed significantly (log‐rank test, P = 0.03). Patients with DM and MS and neither DM nor MS also differed significantly (log‐rank test, P = 0.04). However, there was no significant difference between patients with DM alone and those with neither DM nor MS (log‐rank test, P = 0.37). Abbreviations: DM, diabetes mellitus; MS, metabolic syndrome; PCI, percutaneous coronary intervention.
Multivariate analysis showed that patients with MS, regardless of the presence or absence of DM, have a significantly greater risk for subsequent revascularization compared with patients with neither MS nor DM (Table 2). In particular, patients with MS and DM have a significantly greater risk for repeat PCI than those with neither MS nor DM (Table 2). In terms of the target lesion in repeated PCI, only patients with both MS and DM had a significantly greater risk for TVR compared with patients with neither MS nor DM (Table 3).
Table 2.
Risk for Subsequent Revascularization in Patients With DM Alone, Those With MS Alone, and Those With Both DM and MS
| Incidence (%) | HR | 95% CI | P Value | |
|---|---|---|---|---|
| Revascularization | ||||
| Neither DM nor MS | 121 (30.5) | 1.00 | ||
| DM alone | 45 (41.2) | 1.12 | 0.79–1.59 | 0.51 |
| MS alone | 62 (48.0) | 1.38 | 1.01–1.89 | 0.04 |
| Both DM and MS | 82 (43.4) | 1.36 | 1.02–1.81 | 0.04 |
| Repeat PCI | ||||
| Neither DM nor MS | 98 (30.5) | 1.00 | ||
| DM alone | 36 (33.0) | 1.09 | 0.74–1.60 | 0.68 |
| MS alone | 49 (38.0) | 1.35 | 0.95–1.91 | 0.10 |
| Both DM and MS | 72 (38.1) | 1.42 | 1.04–1.95 | 0.03 |
| CABG | ||||
| Neither DM nor MS | 24 (7.5) | 1.00 | ||
| DM alone | 11 (8.5) | 1.21 | 0.56–2.66 | 0.94 |
| MS alone | 9 (8.3) | 1.14 | 0.54–2.40 | 0.73 |
| Both DM and MS | 13 (6.9) | 1.03 | 0.52–2.05 | 0.94 |
Abbreviations: ACS, acute coronary syndrome; CABG, coronary artery bypass graft; CI, confidence interval; DM, diabetes mellitus; HR, hazard ratio; LDL‐C, low‐density lipoprotein cholesterol; LVEF, left ventricular ejection fraction; MS, metabolic syndrome; PCI, percutaneous coronary intervention.
Hazard ratios and 95% CIs were adjusted for age, gender, LDL‐C, current smoker, hypertension, history of CABG, ACS, LVEF, number of diseased vessels, reference vessel diameter, percentage of stenosis before PCI, and procedural success.
Table 3.
Risk of Repeat PCI in Patients With Neither DM nor DS, DM Alone, MS Alone, and Both DM and MS
| Incidence (%) | HR | 95% CI | P Value | |
|---|---|---|---|---|
| TVR | ||||
| Neither DM nor MS | 72 (22.4) | 1.00 | ||
| DM alone | 35 (32.1) | 1.01 | 0.63–1.60 | 0.98 |
| MS alone | 25 (19.4) | 1.30 | 0.86–2.00 | 0.22 |
| Both DM and MS | 12 (6.3) | 1.50 | 1.05–2.13 | 0.02 |
| NL | ||||
| Neither DM nor MS | 26 (8.1) | 1.00 | ||
| DM alone | 14 (12.8) | 1.45 | 0.70–3.01 | 0.46 |
| MS alone | 11 (8.5) | 1.45 | 0.82–2.53 | 0.22 |
| Both DM and MS | 12 (6.4) | 1.20 | 0.56–2.26 | 0.75 |
Abbreviations: ACS, acute coronary syndrome; CABG, coronary artery bypass graft; CI, confidence interval; DM, diabetes mellitus; HR, hazard ratio; LDL‐C, low‐density lipoprotein cholesterol; LVEF, left ventricular ejection fraction; MS, metabolic syndrome; NL, new lesion; PCI, percutaneous coronary intervention; TVR, target vessel revascularization.
Hazard ratios and 95% CIs were adjusted for age, gender, LDL‐C, current smoker, hypertension, history of CABG, ACS, LVEF, number of diseased vessels, reference vessel diameter, percentage of stenosis before PCI, and procedural success.
In patients without DM (n = 450), a low HDL‐C level was a significant risk factor for subsequent revascularization, in addition to the number of accumulated MS components (Table 4).
Table 4.
Risk of Subsequent Revascularization According to Each MS Component in Patients Without DM
| Incidence (%) | HR | 95% CI | P Value | |
|---|---|---|---|---|
| High BMI | 50/111 (45.0) | 1.25 | 0.88–1.78 | 0.21 |
| High BP | 121/285 (42.5) | 0.94 | 0.61–1.44 | 0.76 |
| High triglycerides | 71/167 (42.5) | 1.18 | 0.87–1.60 | 0.29 |
| Low HDL‐C | 95/202 (47.0) | 1.50 | 1.12–2.02 | 0.01 |
| High FBG | 35/83 (42.2) | 1.12 | 0.77–1.64 | 0.54 |
| No. of accumulated MS component (for each 1‐component increase) | 1.18 | 1.03–1.36 | 0.02 |
Abbreviations: ACS, acute coronary syndrome; CABG, coronary artery bypass graft; BMI, body mass index; BP, blood pressure; CI, confidence interval; HDL‐C, high‐density lipoprotein cholesterol; DM, diabetes mellitus; FBG, fasting blood glucose; HR, hazard ratio; LDL‐C, low‐density lipoprotein cholesterol; LVEF, left ventricular ejection fraction; MS, metabolic syndrome; PCI, percutaneous coronary intervention.
Hazard ratios and 95% CIs were adjusted for age, gender, LDL‐C, current smoker, hypertension, history of CABG, ACS, LVEF, number of diseased vessels, reference vessel diameter, percentage of stenosis before PCI, and procedural success.
Discussion
This additional analysis of long‐term follow‐up (≥10 y) data in patients who had undergone PCI revealed an association between MS and subsequent coronary revascularization, even in groups without DM at the baseline examination. To the best of our knowledge, this is the first study to evaluate the risk of MS regardless of the presence or absence of DM on coronary revascularization in an Asian population, with a long‐term follow‐up period.
In terms of the relationship between MS and restenosis/revascularization following PCI, Rana and colleagues showed that the presence of MS at baseline is not associated with TVR or the composite endpoint 12 months after PCI.14 Their study differs from ours because it was conducted among a Western population and patients were followed up for only 12 months. Canibus et al also reported that MS was not associated with an increased restenosis rate 12 months after PCI using drug‐eluting stents (DES).19 More recently, Kim and colleagues reported that MS at baseline was not a significant independent predictor of increased restenosis or revascularization after PCI.20 The patients in their study were Asians and were followed up for a longer period (36 mo) than in the study by Rana and colleagues14; however, the follow‐up period was still shorter than that in our study and they did not separate DM from MS. According to the entire definition of MS, patients with DM simultaneously satisfied the high blood glucose criterion.21, 24, 25 In other words, the MS groups included many patients with DM, and most of the diabetic patients were classified as having MS among the population in which type 2 DM resulted from obesity. Therefore, there may be significant overlap between DM and MS in the risk for subsequent revascularization. In this regard, Stellbrink et al reported that MS without DM did not result in an increase of TVR 6 months after DES implantation.16 However, this negative finding might be associated with an insufficient number of TVR. Hoffmann and colleagues evaluated the risk of MS separate from DM, and they showed that MS without DM was not associated with increased restenosis and revascularization rates following PCI.15 More recently, another study showed similar negative results17; however, their follow‐up term was approximately 2 to 3.5 years, much shorter than in our study. Yatskar et al investigated the impact of MS on long‐term outcome in nondiabetic patients with multivessel CAD who were undergoing coronary revascularization in the Bypass Angioplasty Revascularization Investigation (BARI) trial and registry.18 They found that the 10‐year risk of subsequent revascularization was not greater in nondiabetic patients with MS compared with patients with neither MS nor DM. Patients in their study were followed up for a time period that was similar to ours, but their study was conducted in a Western population. Therefore, the impact of MS without DM on the long‐term restenosis and revascularization rates among Asian patients following PCI was still unclear.
Here, we examined the risk of restenosis and revascularization among Asian patients with MS alone, DM alone, and with both MS and DM following PCI. The results showed that patients with MS were at significantly increased risk for subsequent revascularization, regardless of the presence or absence of DM. In particular, patients with both MS and DM were at significantly increased risk for repeat PCI and TVR. Furthermore, we demonstrated that low HDL‐C level may be a risk factor for subsequent revascularization in patients without DM, and that there was a dose‐response relationship between the number of accumulated MS components and the subsequent rate of revascularization. These results indicate that MS is important to reduce subsequent revascularization rates and that aggressive and multifactorial intervention in MS is required for the secondary prevention of CAD.
The mechanism for an increased revascularization rate in MS patients without DM is likely related to impaired endothelial function, increased inflammation, and increased platelet function. However, we do not know why results of our study were different from those of other studies.15, 16, 17, 18 Clinical manifestations of MS in Asian patients may be different from MS in Western patients. For example, the BMI of MS patients in the previous Western studies are quite different from the BMI in the Asian studies. Therefore, obesity‐related clinical features in Asians, specifically in Japanese, might be considerably different from those in others,26, 27, 28 and these different clinical features may affect the outcome. The precise mechanism behind the adverse effect of MS without DM on subsequent revascularization remains uncertain and should be investigated further.
Study Limitations
We did not find a significant risk for revascularization among patients with DM alone. Although we cannot fully explain this, ethnic differences might influence the risk of MS and DM. Of course, the relatively small number of patients and differences in patient characteristics between our study and previous studies that indicated the relationship between DM and increased revascularization rate8, 9 also might have contributed to this disparity. Patients with DM alone had the lowest BMI, were the least hypertensive, and smoked the least among the 4 groups, which may have led to the biased results.
The present study had several other limitations. First, because waist circumference was not measured, we used BMI to classify individuals as obese. Recent clinical studies have shown that most individuals identified as having MS based on BMI would also have been identified as obese had waist circumference cutoff points been applied.29, 30 Clinical trials conducted in Western populations used BMI ≥30 kg/m2 as the cutoff point for obesity, which differs from the cutoff of BMI ≥25 kg/m2 used in the present study. We selected BMI ≥25 kg/m2 as the cutoff for obesity based on results from a study of the relationship between BMI, visceral fat area or waist circumference, and obesity in the Japanese population.22
Second, balloon angioplasty was the sole PCI used in all patients. The outcomes might have been quite different if stents and other supportive devices that are currently available had been applied. Indeed, most studies that did not find a significant relationship between MS without DM and increased restenosis and revascularization included patients who underwent PCI with bare‐metal stents and DES.15, 16, 17 In addition, because we analyzed patients who underwent PCI 20–25 years ago to assess long‐term outcomes following PCI, patterns of medication use for these patients differed from those of present day and were not based on the evidence from the current randomized study.
Third, crossover among the 4 groups during follow‐up was not considered. For example, data about new‐onset DM, particularly among patients with MS alone, were not available. This may have introduced bias to our results. In addition, we did not take into account changes in the status and control level of other risk factors (ie, control of weight, BP, lipid levels, FBG, and smoking status), which may alter our results.
Conclusion
The presence of MS without DM at the time of PCI was associated with an increased incidence of subsequent revascularization during a follow‐up period of >10 years. The association of MS with a greater risk for subsequent revascularization was significant regardless of the presence of DM in multivariate analysis. The present study showed the clinical importance of MS in the secondary prevention of CAD regardless of the presence of DM in an Asian population, and highlights the need for aggressive treatment for MS.
References
- 1. Takeuchi H, Saitoh S, Takagi S, et al. Metabolic syndrome and cardiac disease in Japanese men: applicability of the concept of metabolic syndrome defined by the National Cholesterol Education Program‐Adult Treatment Panel III to Japanese men—the Tanno and Sobetsu Study. Hypertens Res. 2005;28:203–208. [DOI] [PubMed] [Google Scholar]
- 2. Saito I, Iso H, Kokubo Y, et al. Metabolic syndrome and all‐cause and cardiovascular disease mortality: Japan Public Health Center‐based Prospective (JPHC) Study. Circ J. 2009;73:878–884. [DOI] [PubMed] [Google Scholar]
- 3. Noda H, Iso H, Saito I, et al. The impact of the metabolic syndrome and its components on the incidence of ischemic heart disease and stroke: the Japan Public Health Center‐based study. Hypertens Res. 2009;32:289–298. [DOI] [PubMed] [Google Scholar]
- 4. Irie F, Iso H, Noda H, et al. Associations between metabolic syndrome and mortality from cardiovascular disease in Japanese general population, findings on overweight and non‐overweight individuals. Ibaraki Prefectural Health Study. Circ J. 2009;73:1635–1642. [DOI] [PubMed] [Google Scholar]
- 5. Kasai T, Miyauchi K, Kurata T, et al. Prognostic value of the metabolic syndrome for long‐term outcomes in patients undergoing percutaneous coronary intervention. Circ J. 2006;70:1531–1537. [DOI] [PubMed] [Google Scholar]
- 6. Kajimoto K, Kasai T, Miyauchi K, et al. Metabolic syndrome predicts 10‐year mortality in non‐diabetic patients following coronary artery bypass surgery. Circ J. 2008;72:1481–1486. [DOI] [PubMed] [Google Scholar]
- 7. Kasai T, Miyauchi K, Kajimoto K, et al. Relationship between the metabolic syndrome and the incidence of stroke after complete coronary revascularization over a 10‐year follow‐up period. Atherosclerosis. 2009;207:195–199. [DOI] [PubMed] [Google Scholar]
- 8. Kip KE, Faxon DP, Detre KM, et al. Coronary angioplasty in diabetic patients: the National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry. Circulation. 1996;94:1818–1825. [DOI] [PubMed] [Google Scholar]
- 9. Rozenman Y, Sapoznikov D, Mosseri M, et al. Long‐term angiographic follow‐up of coronary balloon angioplasty in patients with diabetes mellitus: a clue to the explanation of the results of the BARI study. Balloon Angioplasty Revascularization Investigation. J Am Coll Cardiol. 1997;30:1420–1425. [DOI] [PubMed] [Google Scholar]
- 10. Malik S, Wong ND, Franklin SS, et al. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation. 2004;110:1245–1250. [DOI] [PubMed] [Google Scholar]
- 11. Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24:683–689. [DOI] [PubMed] [Google Scholar]
- 12. Alexander CM, Landsman PB, Teutsch SM, et al. NCEP‐defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes. 2003;52:1210–1214. [DOI] [PubMed] [Google Scholar]
- 13. Kasai T, Miyauchi K, Kurata T, et al. Impact of metabolic syndrome among patients with and without diabetes mellitus on long‐term outcomes after percutaneous coronary intervention. Hypertens Res. 2008;31:235–241. [DOI] [PubMed] [Google Scholar]
- 14. Rana JS, Monraats PS, Zwinderman AH, et al. Metabolic syndrome and risk of restenosis in patients undergoing percutaneous coronary intervention. Diabetes Care. 2005;28:873–877. [DOI] [PubMed] [Google Scholar]
- 15. Hoffmann R, Stellbrink E, Schroder J, et al. Impact of the metabolic syndrome on angiographic and clinical events after coronary intervention using bare‐metal or sirolimus‐eluting stents. Am J Cardiol. 2007;100:1347–1352. [DOI] [PubMed] [Google Scholar]
- 16. Stellbrink E, Schröder J, Grawe A, et al. Impact of metabolic syndrome on clinical and angiographic outcome after sirolimus‐eluting stent implantation. Coron Artery Dis. 2007;18:601–606. [DOI] [PubMed] [Google Scholar]
- 17. Almalla M, Schröder J, Deserno V, et al. Long‐term clinical outcome of sirolimus‐eluting stent implantation in metabolic syndrome and diabetes. J Invasive Cardiol. 2010;22:317–321. [PubMed] [Google Scholar]
- 18. Yatskar L, Holper E, Bansilal S, et al. Long‐term outcomes in non‐diabetic patients with metabolic syndrome undergoing revascularization for multi‐vessel coronary artery disease. Atherosclerosis. 2008;198:389–395. [DOI] [PubMed] [Google Scholar]
- 19. Canibus P, Faloia E, Piva T, et al. Metabolic syndrome does not increase angiographic restenosis rates after drug‐eluting stent implantation. Metabolism. 2008;57:593–597. [DOI] [PubMed] [Google Scholar]
- 20. Kim JS, Lee HC, Choi BK, et al. Impact of metabolic syndrome on in‐stent restenosis and clinical outcomes after percutaneous coronary stent implantation. Diabetes Res Clin Pract. 2010;88:e38–e41. [DOI] [PubMed] [Google Scholar]
- 21. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:2735–2752. [DOI] [PubMed] [Google Scholar]
- 22. New criteria for ‘obesity disease’ in Japan. Circ J. 2002;66:987–992. [DOI] [PubMed] [Google Scholar]
- 23. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2007;30(suppl 1):S42–S47. [DOI] [PubMed] [Google Scholar]
- 24. Executive Summary of the Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486–2497. [DOI] [PubMed] [Google Scholar]
- 25. Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group . The metabolic syndrome—a new worldwide definition. Lancet. 2005;366:1059–1062. [DOI] [PubMed] [Google Scholar]
- 26. Seidell JC, Kahn HS, Williamson DF, et al. Report from a Centers for Disease Control and Prevention workshop on use of adult anthropometry for public health and primary health care. Am J Clin Nutr. 2001;73:123–126. [DOI] [PubMed] [Google Scholar]
- 27. Ko GT, Chan JC, Cockram CS, et al. Prediction of hypertension, diabetes, dyslipidaemia or albuminuria using simple anthropometric indexes in Hong Kong Chinese. Int J Obes Relat Metab Disord. 1999;23:1136–1142. [DOI] [PubMed] [Google Scholar]
- 28. Shiwaku K, Anuurad E, Enkhmaa B, et al. Overweight Japanese with body mass indexes of 23.0–24.9 have higher risks for obesity‐associated disorders: a comparison of Japanese and Mongolians. Int J Obes Relat Metab Disord. 2004;28:152–158. [DOI] [PubMed] [Google Scholar]
- 29. Wong ND, Sciammarella MG, Polk D, et al. The metabolic syndrome, diabetes, and subclinical atherosclerosis assessed by coronary calcium. J Am Coll Cardiol. 2003;41:1547–1553. [DOI] [PubMed] [Google Scholar]
- 30. Janssen I, Katzmarzyk PT, Ross R. Body mass index, waist circumference, and health risk: evidence in support of current National Institutes of Health guidelines. Arch Intern Med. 2002;162:2074–2079. [DOI] [PubMed] [Google Scholar]