Metabolic syndrome: A predictor of adverse outcomes after carotid revascularization
Article Outline
- Abstract
- Methods
- Results
- Discussion
- Conclusion
- Author contributions
- Table III online only.
- References
- Copyright
Background
Metabolic syndrome (MetS) is rapidly increasing in prevalence and is associated with carotid plaque development and is a risk factor for stroke. The aim of this study is to describe the outcomes for patients with MetS after carotid revascularization (carotid endarterectomy [CEA] and carotid stenting [CAS]).
Methods
A database of patients undergoing carotid revascularization for primary atherosclerotic lesions was queried from 1996 to 2006. MetS was defined as the presence of ≥3 of the following criteria: blood pressure ≥130 mm Hg/≥90 mm Hg; Triglycerides ≥150 mg/dL; high-density lipoproteins (HDL) ≤50 mg/dL for women and ≤40 mg/dL for men; fasting blood glucose ≥110 mg/dL; or Body Mass Index (BMI) ≥30 kg/m2. Multivariate and Kaplan-Meier analyses were performed to outcomes. The average follow-up period was 4.5 years. A major adverse event (MAE) was defined as the occurrence of stroke, myocardial infarction (MI), or death.
Results
A total of 921 patients (mean age: 71 ± 10 years; 64% male) underwent 750 CEAs and 171 CAS. Thirty-one percent were identified as having MetS, 48% were asymptomatic, 87% had hypertension, 27% had hyperlipidemia, 32% were considered diabetic, and 14% had chronic renal insufficiency. The morbidity and mortality rates for all patients were 16.9% and 1.1%, respectively. The 30-day combined stroke/death rate was 3.6%. The 30-day MAE rates were: 6.7% vs 3.3% for MetS vs No-MetS (P = .02). The 90-day MAE rates were 8.7% vs 4.9% for MetS vs No-MetS (P = .03). MetS patients were more likely to experience a complication than No-MetS patients (23% vs 14%, P = .001). By Kaplan-Meier analysis, there was no difference between MetS and No-MetS patients with respect to patency, restenosis, re-intervention, or survival, but a difference existed for freedom from stroke, MI, and MAE. The difference between stroke rates was maintained between MetS and No-MetS, when subgrouped by those with and without symptoms. For patients with diabetes mellitus (DM), those with MetS had a 68% and 410% higher risk of developing an MAE and MI, respectively. However, for patients without diabetes, MetS was not significantly associated with MAE, stroke, or MI. No factors were found to be significantly associated with risk of stroke in all cases (in all patients, patients with diabetes, and patients without diabetes).
Conclusion
MetS is prevalent among patients undergoing carotid revascularization. MetS patients are at a greater risk for perioperative morbidity as well as stroke, MI, and MAE during follow-up when compared to patients without MetS. Long-term stroke prevention is poor in the presence of MetS. MetS should be considered a significant risk factor for patients undergoing carotid revascularization.
Metabolic Syndrome (MetS) is a condition manifested by hypertension, obesity, and a prediabetic state (high fasting blood glucose, high triglycerides, and low high-density lipoproteins [HDL]) and is rapidly increasing in prevalence1 and is an emerging risk factor for cardiovascular morbidity and mortality.2 Prior studies have shown that the presence of MetS can be correlated with increased carotid intima-media thickness in both men3 and women.4 MetS has also been demonstrated to amplify vascular wall thickness and stiffness5 and create an overall prothrombotic state.6 Carotid atherosclerosis is increased in incidence and progression in patients with MetS.7 Patients with MetS exhibit impaired fibrinolysis through increased plasminogen activator-1 levels compared to those without MetS.8 The effects of MetS and stroke are not limited to preclinical pathophysiologic observations. The risk of stroke and transient ischemic attack (TIA) are increased for patients in the presence of MetS.9 McGirt et al10 have already demonstrated that an elevated operative day glucose levels increases the risk of perioperative stroke, myocardial infarction (MI), and death after carotid endarterectomy (CEA). The risk of developing atrial fibrillation (another potential cause of stroke) postoperatively from coronary artery bypass grafting is increased for patients with MetS.11
Despite these observations of MetS's influence on vascular remodeling and its poor prognostic factor during cardiovascular procedures, the outcomes after carotid revascularization have not been studied. The primary objective of this report is to analyze the impact of the presence of MetS on short-term (30-day) and long-term outcomes of patients undergoing carotid revascularization.
Methods
Study design
A database of patients undergoing carotid revascularization from 1996 to 2006 was queried. Patients undergoing CEA and carotid artery stenting (CAS) for significant primary atherosclerotic occlusive disease were analyzed. Vessels treated for intimal hyperplasia, in-stent restenosis, radiation-induced arteritis, and trauma were excluded. Data utilization fell under the category of secondary use of pre-existing data.
Procedures
Patients underwent carotid endarterectomy or carotid stenting where carotid stenosis was ≥80% for asymptomatic and ≥50% for symptomatic patients was detected on duplex scan imaging and was confirmed in most cases on computed tomography angiography or magnetic resonance angiography. Routine pre- and postprocedural neurology consultations were not requested, unless the patient was symptomatic. For carotid endarterectomy, patients were maintained on aspirin therapy and the majority underwent endarterectomy under regional block with the remainder undergoing general anesthesia with electroencephalography (EEG) monitoring. Both Dacron patch angioplasty and eversion endarterectomy were performed. For carotid stenting the patient was given clopidogrel (75 mg/dL) and aspirin (81 mg) beginning 3 days before the intervention. After the stenting procedure, clopidogrel was continued for 1 month, and aspirin was continued for life. All patients undergoing carotid stenting received an intravenous heparin bolus (100 U/kg) to achieve systemic anticoagulation during the carotid intervention (activated coagulation time [ACT] ≥250 seconds). All carotid stenting procedures were performed in fixed imaging procedure rooms under conscious sedation. The technique of stenting with an embolic protection device has been described previously.12 Self-expanding monorail carotid stent (Wallstent, Boston Scientific, Natick, Mass; Precise, Cordis, Warren, NJ; or Acculink, Guidant, Santa Clara, Calif) were deployed across the internal carotid stenosis. Post stenting balloon angioplasty was performed with either a 5- or 6-mm-diameter angioplasty balloon, depending on the appearance of the completion angiogram. Procedures were performed with local Institutional Review Board (IRB) approval and/or as part of an approved multi center clinical trial and followed Center for Medicare services (CMS) guidelines. Patients, after both CEA and CAS, were routinely kept in the hospital overnight and discharged home on the following day. In general, patients were followed by duplex ultrasound scan every 6 months for 2-3 years and then yearly thereafter if there was no contralateral disease. If there was >50% disease present, 6 monthly follow-ups was the norm. Lesions >80% were intervened on during follow-up. All duplex ultrasound scans were performed at approved vascular laboratories accredited by the Intersociety Commission on Accreditation of Vascular Laboratories using the University of Washington criteria.
Definitions
MetS was defined based on the presence of three or more of the following five criteria: hypertension (systolic blood pressure >140 mm Hg or diastolic pressure >90 mm Hg on three occasions during a 6-month period), reduced high-density lipoprotein cholesterol (<40 mg/dL for men, <50 mg/dL for women), elevated triglycerides (>150 mg/dL), impaired glucose control (>110 mg/dL fasting serum glucose), and a body mass index (BMI) ≥30.0 kg/m2.13, 14 Coronary artery disease was defined as a history of angina pectoris, MI, congestive heart disease, or prior coronary artery revascularizations. Cerebrovascular disease included a history of stroke, transient ischemic attack, or carotid artery revascularization. Hypercholesterolemia was defined as fasting cholesterol (>200 mg/dL). Diabetes was defined as a fasting plasma glucose (>110 mg/dL) or an HbA1c >7%. Diabetics were characterized as insulin dependent diabetes mellitus (IDDM) or non-insulin dependent diabetes mellitus (NIDDM). Hypertension was defined as a systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg on three occasions during a 6-month period. Restenosis was defined as the development of >50% stenosis. Technical failure was defined as an inability to perform the intended procedure or if a re-intervention occurred within 30 days of the initial procedure. A major adverse event (MAE) was defined as an ipsilateral stroke, MI, or death during follow-up. The time to MAE was determined as the first occurrence of any of the three MAE factors (stroke, MI, or death). Unlike Stenting with Angioplasty and Protection in Patients at High Risk for Endarterectomy (SAPPHIRE),15 patients did not have a troponin series performed or formal neurological consultations postprocedure. A death ≤30 days of the procedure was considered procedure-related. Perioperative was defined as a stroke occurring during the hospital admission and less than 30 days postprocedure. A major complication was defined as any event, regardless of how minimal, not routinely observed after therapy that required treatment with a therapeutic intervention or rehospitalization ≤30 days of the procedure.
Statistical analysis
Measured values are reported as percentages or means ± standard deviations (SDs). Rates for comorbidities, complications, and 30-day outcomes were compared between patients with MetS and No-MetS by χ2 test. Survival, patency, neurologic-free, and MAE rates were calculated using Kaplan-Meier analysis and are reported using current Society for Vascular Surgery (SVS) criteria.16 Standard errors are reported in Kaplan-Meier analyses. The log-rank test was used to determine survival differences between patients with MetS and No-MetS. The Cox proportional hazards models were used to examine the associations between MetS and MAE, stroke, and MI, adjusted for age, gender, history of MI, congestive heart failure (CHF), atrial fibrillation (AFIB), and chronic obstructive pulmonary disease (COPD). Interactions between MetS and all covariates were not statistically significant. The proportionality assumption of Cox models was assessed by including time-dependent interaction of each covariate with survival time in the model. There was no evidence of violation of this assumption for any covariate. Statistical significance is defined as two-tailed P value of less than .05 for all tests.
Results
Patient population
A total of 921 carotid revascularizations were performed in 843 patients. The mean age was 71 ± 10 years. One hundred seventy-four (19%) patients were greater than 80 years of age. Of them, 64% were male. Forty-eight percent of the patients were asymptomatic. The most common presenting symptom was ipsilateral TIA in 30% of the patients, 19% presented with ipsilateral stroke, and 2% presented with vertebrobasilar symptoms that were believed to be a watershed phenomenon. All of the patients with vertebrobasilar symptoms had ≥80% stenosis at presentation.
Metabolic syndrome status
Two hundred eighty-eight patients (31%) were identified as having MetS. MetS and No-MetS patients had equivalent rates of patients presenting symptomatically. Of the five criteria used to define MetS, hypertension was most prevalent among the patients with an overall rate of 87%. Forty-one percent had elevated fasting blood sugar. Thirty percent had elevated triglycerides (≥150 mg/dL), 27% had reduced HDL (≤50 mg/dL for females and ≤40 mg/dL for men), and 26% had an elevated BMI (≥30 kg/m2). The distribution of MetS scores were: 5 (1%), 4 (9%), 3 (21%), 2 (31%), 1 (31%), and 0 (7%).
Comorbidities
Twenty-seven percent of the patients had a previous MI, and 12% had a history of congestive heart failure (Table I). Eighty-seven percent had hypertension. Two hundred ninety-three patients were diabetic: 33 (4%) with IDDM and 260 (28%) with NIDDM. One hundred four (11%) were hypothyroid. MetS patients were more likely to have a prior MI (40% vs 21%, P < .001), hypertension (98% vs 82%, P < .001), NIDDM (50% vs 19%, P = .001), IDDM (7% vs 2%, P < .001), and a serum creatinine greater than 1.5 mg/dL (19%, vs 12%, P = .004). MetS patients were more likely to have current or prior tobacco use (84.5% vs 61.9%, P < .001) (Table I). The two procedural groups had several significantly different rates of comorbidities. The CAS group had a greater proportion of patients with a history of MI, CHF, serum creatinine >1.5 mg/dL, MetS, and were older (Table I).
Table I. Patient comorbidities
| Total | MetS | No Met-S | CEA | CAS | |||
|---|---|---|---|---|---|---|---|
| n = 921 | n = 288 | n = 633 | n = 750 | n = 171 | |||
| n (%) | n (%) | n (%) | P value | n (%) | n (%) | P value | |
| Myocardial infarction | 27% | 40% | 21% | < .001⁎ | 23% | 46% | <.001⁎ |
| Congestive heart failure | 12% | 14% | 10% | .102 | 7% | 30% | <.001⁎ |
| Hypertension | 87% | 98% | 82% | <.001⁎ | 87% | 88% | .661 |
| Non-insulin-dependent DM | 28% | 50% | 19% | .001⁎ | 3% | 5% | .19 |
| Insulin-dependent DM | 4% | 7% | 2% | <.001⁎ | 29% | 27% | .668 |
| Hypothyroid | 11% | 12% | 11% | .603 | 11% | 14% | .209 |
| Cr >1.5 mg/dL | 14% | 19% | 12% | .004⁎ | 12% | 23% | <.001⁎ |
⁎Significant. |
Procedures
Of the 921 carotid revascularizations, 750 (81%) were by CEA and 171 (19%) were by CAS. Of the 921 CEAs performed, 49% were performed under cervical block while 51% under general endotracheal anesthesia. Of the CEAs performed, the arteriotomy closure was performed by eversion in 64% of cases and patch (prosthetic or vein) in 36%. During CAS, 137 patients (80%) involved successful deployment of an embolic protection device (EPD), 10 (6%) failed attempts of EPD deployment occurred, and 24 (14%) did not attempt EPD usage. Technical success was achieved in 98.9% of procedures initiated. For all patients, the 30-day and 90-day mortality rates were 1.1% and 2.1%, respectively. Perioperative was defined as a stroke occurring during the hospital admission and less than 30 days (22 events, 2.4%). The 30-day stroke rate was 28 events, 3.0%. Thus, 6 patients were discharged post-procedure and returned within 30 days with a cardiovascular accident (CVA).
The overall morbidity rate was 16.9%. MetS patients experienced a 22.9% rate and No-MetS patients experienced a 14.3% rate (P = .001). Complications were divided into systemic, regional, and local groups. The systemic complications were 16 (1.7%) cardiac, 9 (1.0%) pulmonary, and 2 (0.2%) renal. Among regional complications, bradycardia (2.9%) and hypotension (2.5%) were most common (see Table II for a complete list). The most common local complications were hematoma (7.1%) and vasospasm (1.1%), (see Table II for a complete list). Among individual complications, MetS patients suffered greater rates of ipsilateral stroke (4.6% vs 1.4%, P = .004), bradycardia (4.6% vs 2.2%, P = .048), hypotension (4.2% vs 1.7%, P = .025), and vasospasm (2.5% vs 0.5%, P = .007) when compared to No-MetS patients. There was no complication category that was higher in No-MetS patients when compared to MetS patients. BMI was not uniquely associated with 30-day mortality or morbidity.
Table II. Complications
| CEA | CAS | MetS N = 288 [n(%)] | No Met-S N = 633 [n(%)] | P value | |||||
|---|---|---|---|---|---|---|---|---|---|
| No MetS | MetS | P | No MetS | MetS | P | ||||
| (n%) | (n%) | value | (n%) | (n%) | value | ||||
| Systemic | |||||||||
| Cardiac | 1% | 1% | .975 | 2% | 4% | .530 | 2% | 2% | .971 |
| Pulmonary | 1% | 0% | .417 | 0% | 3% | .125 | 1% | 1% | .574 |
| Renal | 0% | 0% | .109 | 1% | 0% | .530 | 1% | 1% | .557 |
| Regional | |||||||||
| Stroke | 1% | 4% | .027⁎ | 2% | 6% | .172 | 5% | 1% | .004⁎ |
| Transient ischemic attack | 1% | 2% | .269 | 4% | 4% | .856 | 4% | 2% | .560 |
| Bradycardia | 1% | 0% | .279 | 10% | 19% | .084 | 2% | 2% | .048⁎ |
| Hypotension | 1% | 0% | .162 | 9% | 14% | .180 | 1% | 2% | .025⁎ |
| Local | |||||||||
| Vasospasm | 0% | 0% | — | 4% | 8% | .367 | 2% | 1% | .007⁎ |
| Dissection | 1% | 0% | .109 | 2% | 0% | .187 | 1% | 1% | .178 |
| Hematoma | 7% | 9% | .417 | 8% | 4% | .290 | 8% | 7% | .586 |
| Cranial nerve injury | 1% | 1% | .720 | 0% | 0% | — | 1% | 1% | .870 |
| Arterio-venous fistula | 0% | 0% | — | 0% | 0% | — | 0% | 0% | — |
| Hemorrhage | 1% | 0% | .377 | 0% | 0% | — | 0% | 1% | .344 |
| Pseudoaneurysm formation | 0% | 0% | — | 1% | 1% | .914 | 0% | 1% | .344 |
| Total | 12% | 17% | .109 | 26% | 39% | .066 | 23% | 14% | .001⁎ |
⁎Significant. |
Outcomes
The 30-day all-cause mortality rate was 1.1% (10 deaths). The combined stroke and death rate for all patients was 3.6% (33 events). During the first 30 days, 28 (3.0%) experienced an ipsilateral stroke, 12 (1.3%) had an MI, and 10 (1.1%) required re-intervention. The overall 30-day and 90-day ALL stroke rate was 3.8% and 4.1%, for all patients. The overall 30-day and 90-day MAE rates were 4.3% and 5.9%, respectively, for all patients. MetS patients had higher 30-day and 90-day MAE rates (6.7% vs 3.3%, P = .020 and 8.8% vs 4.6%, P = .011, respectively).
Long-term follow-up revealed 15 (2%) vessel occlusions and 132 (14%) restenosed vessels. No statistical difference existed between groups for both patency and freedom from restenosis. The median time to vessel restenosis was 18.2 months. By Kaplan-Meier analysis the 5-year patency and freedom from restenosis was 98.0 ± 0.6% and 78.0 ± 1.9%, respectively. Between the two groups there was no difference in patency and restenosis rates (Table III, online only).
The mean duration of follow-up was 4.5 years (range of 0.0 to 11.8 years). During follow-up, 33 (4%) required re-intervention, 50 (5%) experienced an ipsilateral stroke, 89 (10%) had an MI, and 259 (28%) expired. The cumulative MAE rate was 35% (321 patients) during follow-up (Fig 1).
Fig 1.
Freedom from major adverse events (MAE). Two hundred five (32%) No-MetS and 116 (41%) MetS patients experienced a MAE (stroke, MI, or death) during follow-up, (P < .05). The 3-year freedom from MAE rates were 42% and 32% for MetS and No-MetS, respectively. Error bars are omitted for clarity. Standard error did not exceed 10% at all time intervals that were analyzed. The number of patients at risk at each time interval is shown below the Fig.
MetS patients experienced greater stroke, MI, and MAE rates when compared to No-MetS by Kaplan-Meier analysis. Survival did not differ between groups. MetS patients had a 1-, 2-, and 3-year freedom from ipsilateral stroke rates of 95 ± 1%, 95 ± 1%, and 93 ± 1%, while No-MetS patients had rates of 97 ± 1%, 97 ± 1%, and 96 ± 1% (P = .027) (Fig 2). This difference was maintained if the patients were subgrouped as symptomatic or asymptomatic. The 1-, 2-, and 3-year freedom from MI rates between MetS and No-MetS were 95 ± 1%, 92 ± 2%, 88 ± 2%, and 98 ± 1%, 96 ± 1%, and 96 ± 1%, respectively, (P < .001) (Fig 3). Total survival rates were 94 ± 1%, 90 ± 1%, 86 ± 1% (Fig 4). MetS patients had an MAE rate for 1-, 2-, and 3-years of 87 ± 2%, 80.0 ± 2%, 72 ± 3%, and No-MetS had 91 ± 1%, 86 ± 1%, 83 ± 2%, P < .001 (Fig 1).
Fig 2.
Freedom from stroke. Twenty-seven (4%) No-MetS and 23 (8%) No-MetS patients experienced a stroke during follow-up, (P < .05). The 3-year freedom from stroke rates were 93% and 96% for MetS and No-MetS, respectively. Error bars are omitted for clarity. Standard error did not exceed 10% at all time intervals that were analyzed. The number of patients at risk at each time interval is shown below the Fig.
Fig 3.
Freedom from myocardial infarction (MI). Thirty-four (5%) No-MetS and 55 (19%) MetS patients experienced an MI during follow-up, (P < .05). The 3-year freedom from MI rates were 88% and 96% for MetS and No-MetS, respectively. Error bars are omitted for clarity. Standard error did not exceed 10% at all time intervals that were analyzed. The number of patients at risk at each time interval is shown below the fig.
Fig 4.
Survival. Four hundred sixty-one (72%) No-MetS and 201 (71%) MetS patients survived during follow-up, (P = NS). the 3-year survival rates were 84% and 87% for MetS and No-MetS, respectively. Error bars are omitted for clarity. Standard error did not exceed 10% at all time intervals that were analyzed. The number of patients at risk at each time interval is shown below the Fig.
Procedural differences
The majority of carotid revascularization procedures were done by CEA (81%) and the remainder was by CAS (19%). Outcomes were similar for CEA and CAS for patency, freedom from stroke, survival, and MAE. Patients undergoing CEA had a lower all cause morbidity (15.6% vs 32.2%, P < .001) and lower 30-day mortality (0.7% vs 2.9%, P = .010) than those undergoing CAS. The combined 30-day stroke and death rate was lower for CEA patients compared to CAS patients but statistically insignificant (3.1% vs 5.8%, respectively, P = .077) (Table IV). Additionally, those undergoing CEA had a greater freedom from MI than those undergoing CAS. The 1-, 2-, and 3-year freedom from MI were 98 ± 1%, 96 ± 1%, and 94 ± 1% for CEA patients and 93 ± 2%, 92 ± 2%, and 87 ± 3% for CAS patients (P = .028). Patients undergoing CAS tended to have a higher MAE rate. The 3-year freedom from MAE was 73 ± 4% for CAS and 81 ± 2% for CEA, P = .070. For freedom from MI, CAS patients experienced lower rates (93 ± 2%, 92 ± 2%, 87 ± 3% vs 98 ± 1%, 96.0 ± 0.8%, 94 ± 1% [P = .028] for 1-, 2-, and 3-year rates between CAS and CEA, respectively). CEA patients exhibited higher freedom from restenosis rates (91 ± 1%, 87 ± 1%, 84 ± 2% vs 77 ± 5%, 74 ± 5%, 70 ± 5% [P < .001] for 1-, 2-, and 3-year rates between CEA and CAS, respectively), but equivalent patency rates (Fig 5).
Table IV. 30-Day outcomes
| CEA | CAS | |||||
|---|---|---|---|---|---|---|
| MetS n (%) | No MetS n (%) | P value | MetS n (%) | No MetS n (%) | P value | |
| Mortality | 0.5% | 0.7% | 0.689 | 4.1% | 2.1% | 0.318 |
| Stroke | 4.8% | 1.7% | 0.025* | 5.4% | 2.2% | 0.436 |
| Myocardial infarction | 1.4% | 0.6% | 0.228 | 6.8% | 1.0% | 0.043* |
| Combined stroke & death | 5.2% | 2.2% | 0.031* | 6.8% | 5.2% | 0.417 |
| Major adverse event | 5.7% | 2.8% | 0.053 | 9.5% | 6.2% | 0.335 |
| Morbidity | 16.7% | 12.2% | 0.109 | 40.5% | 25.8% | 0.089 |
Fig 5.
Freedom from restenosis. The 3-year freedom from restenosis rates were 84% and 70% for patients undergoing CEA and CAS, respectively. Error bars are omitted for clarity. Standard error did not exceed 10% at all time intervals that were analyzed. The number of patients at risk at each time interval is shown below the Fig.
Hazards analysis
Results of Cox proportional hazards models are listed in Table V. After adjustment for age, gender, history of MI, congestive heart failure, atrial fibrillation, and COPD, patients with MetS had 54% and 361% greater risk of developing MAE and MI compared with those without MetS, respectively. In addition, age, history of AFIB, and history of COPD were significant associated with risk of developing MAE; age, male, and history of CHF were significant associated with risk of developing MI. Among patients with diabetes, patients with MetS had 68% and 410% higher respective risk of developing MAE and MI compared with those without MetS after adjustment for the same variables listed above, respectively. In addition, age and history of CHF were significantly associated with risk of MAE and age, male, and history of CHF were significantly associated with risk of MI. For patients without diabetes, MetS was not significantly associated with MAE, stroke, or MI. No factors were found be significantly associated with risk of stroke in all cases (in all patients, patients with diabetes, and patients without diabetes).
Table V. Hazards ratios (HR) of major adverse event (MAE) and myocardial infarction (MI)
| Variable | MAE | MI | ||
|---|---|---|---|---|
| HR (95% CI) | P value | HR (95% CI) | P value | |
| All patients | ||||
| MetS | 1.54(1.15–2.05) | <.01 | 4.61(2.72–7.81) | <.001 |
| Age (year) | 1.05(1.04–1.07) | <.001 | 1.07(1.03–1.10) | <.001 |
| Male vs female | 1.28(0.96–1.70) | .09 | 2.33(1.27–4.29) | <.01 |
| History of | ||||
| MI | 1.02(0.75–1.39) | .88 | 0.82(0.47–1.45) | .50 |
| CHF | 1.42(0.92–2.18) | .11 | 2.53(1.25–5.12) | .01 |
| AFIB | 1.61(1.13–2.30) | <.01 | 1.06(0.52–2.14) | .87 |
| COPD | 1.44(1.02–2.04) | .04 | 1.69(0.92–3.09) | .09 |
| Patients with DM | ||||
| MetS | 1.68(1.07–2.63) | .02 | 5.10(2.21–11.76) | <.001 |
| Age (year) | 1.05(1.02–1.08) | <.01 | 1.11(1.06–1.67) | <.001 |
| Male vs female | 1.46(0.89–2.40) | .13 | 4.71(1.76–12.63) | <.01 |
| History of | ||||
| MI | 0.80(0.49–1.32) | .38 | 0.91(0.45–1.82) | .79 |
| CHF | 1.97(1.04–3.72) | .04 | 4.71(1.97–11.22) | <.001 |
| AFIB | 1.18(0.64–2.18) | .59 | 0.44(0.17–1.13) | .09 |
| COPD | 1.61(0.91–2.85) | .10 | 2.12(0.99–4.55) | .05 |
| Patients without DM | ||||
| MetS | 1.02(0.64–1.62) | .94 | 1.91(0.73–5.03) | .19 |
| Age (year) | 1.06(1.04–1.08) | <.001 | 1.06(1.01–1.12) | .02 |
| Male vs female | 1.15(0.80–1.65) | .44 | 1.19(0.50–2.80) | .69 |
| History of | ||||
| MI | 1.23(0.82–1.83) | .31 | 0.69(0.23–2.10) | .52 |
| CHF | 1.10(0.58–2.09) | .77 | 0.67(0.09–5.13) | .70 |
| AFIB | 1.79(1.13–2.83) | .01 | 1.24(0.35–4.36) | |
| COPD | 1.47(0.93–2.32) | .09 | 1.50(0.50–4.50) | .47 |
When considering each component of MetS in the Cox proportional models, age (hazard ratio [HR] = 1.06, 1.04-1.07, P < .001), diabetes (HR = 1.35, 1.04-1.77, P = .03), elevated blood pressure (systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg) (HR = 9.6, 1.62-56.92, P = .01), hypertension treatment (HR = 0.12, 0.02-0.71, P = .02), history of AFIB (HR = 1.62, 1.13-2.31, P < .01), and history of COPD (HR = 1.46, 1.03-2.06, P = .03) were significant predictors of risk of MAE. Age (HR = 1.07, 1.03-1.11, P < .001), male (HR = 2.23, 1.20-4.13, P = .01), diabetes (HR = 2.79, 1.63-4.78, P < .001), elevated triglycerides (>150 mg/dL) (2.17, 1.22-3.87, P < .01), reduced HDL (<40 mg/dL for men, <50 mg/dL for women) (1.77, 1.02-3.07, P = .04), and history of CHF (HR = 2.96, 1.41-6.22, P < .01) were significantly associated with risk of MI. No factors were found be significantly associated with risk of stroke.
Discussion
General
In this study, we analyzed the presence of MetS and its relation to short- and long-term outcomes in 921 patients undergoing carotid revascularization for both symptomatic and asymptomatic disease. We found MetS to be highly prevalent among patients undergoing carotid revascularization. Our prevalence of MetS in patients undergoing carotid revascularization of 31% was similar to Gorter et al,17 who found MetS present in 39-44% of patients with cerebral vascular disease. MetS patients had a twofold increase in their 30-day MAE rate. The MAE rate difference continued past 30-days and remained statistically higher at 90 days and during the remainder of clinical follow-up. The presence of MetS did not predispose patients to have poorer patency and freedom from restenosis outcomes. However, those with MetS had statistically significant higher stroke, MI, and complication rates. A strong covariant in this analysis was the diagnosis of diabetes. For patients without diabetes, MetS was not significantly associated with MAE, stroke, or MI.
Metabolic syndrome definition
There are multiple definitions of MetS.18, 19, 20, 21, 22 Our definition is similar to the National Cholesterol Education Program (NCEP) definition14 in the scoring system for four of the five criteria. We substituted abdominal obesity with a BMI >30 kg/m2. Due to the retrospective design of our study, we could not determine the abdominal circumference of each individual patient, as it is not routinely determined. However, we also analyzed the short- and long-term outcomes using the World Health Organization (WHO) definition23 of MetS, which permits substituting an elevated BMI >30 kg/m2 for abdominal obesity. Using the WHO definition of MetS, our results remained consistent to the results using our modified NCEP definition. However, total body fatness, measured by BMI, is insufficiently sensitive as a risk factor, and fat distribution (upper-body vs low-body type, as reflected by waist circumference and waist:hip ratio) appears to have a more unique prognostic value.24 A recent paper on cerebrovascular events showed that markers of abdominal adiposity showed a graded and significant association with risk of stroke/TIA, independent of other vascular risk factors. Waist circumference and related ratios were better at predicting cerebrovascular events than BMI. BMI showed a positive association with cerebrovascular risk which became nonsignificant after adjustment for physical inactivity, smoking, hypertension, and diabetes (odds ratio 1.18; 95% CI, 0.77 to 1.79, top tertile vs bottom tertile).25
Diabetes mellitus as a risk factor
Others26, 27 have previously examined DM as a potential risk factor for morbidity surrounding carotid revascularization. Our findings were consistent, and found DM patients to have equal morbidity with non-DM patients (15.1% vs 17.8%, P = .303). For specifically 30-day ipsilateral stroke, no difference existed between diabetics and non-diabetics (3.1% vs 3.0%, P = .96). For 30-day MI, again no difference existed between diabetics and non-diabetics (1.7% vs 1.1%, P = .46). For all perioperative cardiac complications, the two groups were similar (2.1% vs 1.6%, P = .62). However, during long-term follow-up those patients with DM had statistically lower survival, freedom from MI, and freedom from MAE, but equivalent long-term freedom from ipsilateral stroke. While DM increases the perioperative risk of other vascular procedures, we did not find the presence of DM to influence perioperative outcomes for carotid revascularization. However, when we excluded patients with a pre-existing diagnosis of diabetes and looked at the truly prediabetic patients in the metabolic syndrome group, the influence of the diagnosis of metabolic syndrome was not significant. It, therefore, appears the patients with metabolic syndrome who have diabetes as a qualifying criterion are the higher risk category. This conclusion may be a type II error and further work on a large population set is likely necessary to completely answer this question.
Age greater than 80
As shown in the Results section, a patient's age greater than 80 years was found as a negative risk factor for survival, freedom from MI, and freedom from MAE. The lower long-term survival rates are not unexpected. While this group of patients fared worse in freedom from MI and MAE, it is important to point out that they did not have higher rates of MetS, which was also shown to lower these outcomes. Patients over the age of 80 years had a 23.6% rate of MetS compared to those under 80 years with a 32.5% rate, P = .02. In the short-term, age did not appear to influence outcomes. Those greater than 80 years of age had equivalent 30-day and 90-day MAE rates with those under the age of 80 years (respectively: 1.7% vs 2.1%, P = .727; 3.4% vs 2.5%, P = .508). The type of carotid revascularization did not differ between the two age groups, 77.6% of those >80 years undergoing CEA and 82.3% of those <80 years undergoing CEA (P = .147).
Examining the subgroup of patients greater than 80 years of age demonstrates multiple differences in outcomes based upon type of carotid revascularization. Those greater than 80 years had higher morbidity while undergoing CAS as opposed to CEA (35.9% vs 13.3%, P < .001, respectively). These CAS patients had greater 30-day stroke (7.7% vs 3.0%, P < .001), 30-day MI (5.1% vs 1.5%, P < .001), and death rates (5.1% vs 0.7%). The 30-day MAE and 90-day MAE rates were also higher for CAS patients greater than 80 years (10.3% vs 4.4%, P < .001; 17.9% vs 6.7%, P < .001) when compared to those patients greater than 80 years and undergoing CEA. While the differences are clear in outcomes between these two procedures for this age group, we cannot exclude the possibility of bias towards procedure selection for this age group in that the greater “optimized” patients were steered towards CEA and the remainder was offered CAS.
Procedural differences
The presence of equivalence or difference among outcomes between CEA and CAS are continually debated. As reported in the Results discussion, the MetS patients suffered higher morbidity rates and poorer long-term outcomes, but also underwent CAS at a higher rate as compared to the No-MetS group, which was more likely to undergo CEA for revascularization. For the short-term outcomes the CEA group had lower 30-day mortality and morbidity. To assure these outcome differences involved the presence of MetS and not just the procedure performed, we isolated the procedure groups, and compared the MetS and No-MetS patients for each revascularization type. For the CEA patients alone, those identified with MetS had a higher 30-day stroke rate (4.8% vs 1.7%, P = .025) and a greater combined stroke and death rate (5.2% vs 2.2%, P = .031). For the CAS patients alone, those identified as MetS had a greater 30-day MI rate (6.8% vs 1.0%, P = .043) (Table IV).
Future directions
Glitazones have been shown to reduce ischemic damage after middle cerebral artery occlusion in animal models.28, 29, 30, 31, 32 If future studies support hyperglycemia and metabolic syndrome as a risk factor for perioperative events during carotid revascularization, then a study examining the potential benefit of glitazones during the perioperative period would be interesting.
Study limitations
This study is retrospective in nature and clinical decision-making was individual not to a standard protocol. The definitions of metabolic syndrome are continual changing and we have used a surrogate marker of body adiposity that is not currently in all definitions of metabolic syndrome. We did not have formal neurological assessments or biochemical assessments of myocardial ischemia which have been the norm in clinical trials and may have led us to under report stroke and MI.
Conclusion
MetS is prevalent among patients undergoing carotid revascularization. MetS patients are at a greater risk for perioperative morbidity as well as stroke, MI, and major adverse events during follow-up when compared to patients without MetS. Long-term stroke prevention is poor in the presence of MetS. MetS should be considered a significant risk factor for patients undergoing carotid revascularization. However, for patients without diabetes, MetS was not significantly associated with MAE, stroke, or MI. No factors were found to be significantly associated with risk of stroke in all cases (in all patients, patients with diabetes, and patients without diabetes).
Author contributions
Table III online only.
Long-term outcomes
| Total | MetS | No Met-S | ||
|---|---|---|---|---|
| n = 921 | n = 288 | n = 633 | ||
| n (%) | n (%) | n (%) | P value | |
| Patency | ||||
| 1-year | 99±0.3% | 99±0.7% | 99±0.5% | .074 |
| 2-year | 99±0.5% | 97±1.1% | 99±0.5% | |
| 3-year | 99±0.5% | 96±1.4% | 99±0.5% | |
| 4-year | 98±0.6% | 96±1.4% | 99±0.6% | |
| 5-year | 98±0.6% | 96±1.4% | 99±0.6% | |
| Freedom from restenosis | ||||
| 1-year | 89±1.2% | 88±2.2% | 89±1.4% | .390 |
| 2-year | 85±1.4% | 86±2.4% | 85±1.7% | |
| 3-year | 82±1.6% | 80±3.0% | 84±1.8% | |
| 4-year | 81±1.7% | 79±3.1% | 82±2.0% | |
| 5-year | 78±1.9% | 76±3.7% | 80±2.3% | |
| Freedom from stroke | ||||
| 1-year | 97±0.6% | 95±1.3% | 97±0.7% | .027* |
| 2-year | 96±0.6% | 95±1.3% | 97±0.7% | |
| 3-year | 95±0.7% | 93±1.3% | 96±0.7% | |
| 4-year | 95±0.7% | 92±1.7% | 96±0.8% | |
| 5-year | 94±0.9% | 92±1.8% | 95±0.9% | |
| Freedom from myocardial infarction | ||||
| 1-year | 97±0.6% | 95±1.2% | 98±0.6% | <.001* |
| 2-year | 95±0.7% | 92±1.6% | 96±0.8% | |
| 3-year | 93±0.9% | 88±2.0% | 96±0.9% | |
| 4-year | 92±1.0% | 86±2.2% | 95±1.0% | |
| 5-year | 90±1.2% | 80±3.0% | 94±1.1% | |
| Survival | ||||
| 1-year | 94±1.0% | 93±1.5% | 94±1.0% | .451 |
| 2-year | 90±1.0% | 88±1.9% | 90±1.2% | |
| 3-year | 86±1.1% | 84±2.2% | 87±1.4% | |
| 4-year | 80±1.4% | 81±2.5% | 80±1.8% | |
| 5-year | 75±1.7% | 74±3.1% | 75±2% | |
| Freedom from major adverse event | ||||
| 1-year | 90±1.0% | 87±2.0% | 91±1.2% | <.001* |
| 2-year | 84±1.2% | 80±2.4% | 86±1.4% | |
| 3-year | 79±1.4% | 72±2.7% | 83±1.5% | |
| 4-year | 73±1.6% | 67±2.9% | 76±1.9% | |
| 5-year | 68±1.8% | 61±3.0% | 70±2.1% | |
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Competition of interest: none.
Additional material for this article may be found online at www.jvascsurg.org.
PII: S0741-5214(08)02154-X
doi:10.1016/j.jvs.2008.12.011
© 2009 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
