The combination of abdominal obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance or type 2 diabetes mellitus defines metabolic syndrome (MetS). MetS is associated with cardiovascular diseases such as coronary heart disease and peripheral vascular disease.1–5 Only a few studies have examined the association of this syndrome with electrocardiographic (ECG) subclinical risk factors such as long corrected QT (QTc) interval or long corrected QT dispersion (QTcd) interval.6–8
P wave dispersion (Pwd) is an easy, basic, and noninvasive ECG indicator of atrial arrhythmias.9–11 An increase in Pwd has been accepted as an independent predictor of postoperative atrial fibrillation after coronary artery bypass graft surgery.12,13 Previous studies have shown that Pwd and QTcd intervals may be extended in conditions such as diabetes mellitus,14,15 prehypertension16,17 and obesity.18,19 MetS is associated with a frequent prevalence of paroxysmal atrial fibrillation, atrial flutter, or both,20 but published data about the prevalence of Pwd in MetS are rare.21
We hypothesized that Pwd and QTcd durations are extended in MetS patients. To test this hypothesis, we investigated the Pwd and QTcd intervals of patients with MetS in the preanesthesia assessment and compared these values with those obtained from normal subjects.
After obtaining the approval of the hospital ethics committee and written consent from the patients, adult patients (older than 18 years) evaluated in the anesthesia preoperative assessment center April–July 2009 were included in this prospective study. The patients with MetS diagnoses were evaluated as part of group M, whereas the control subjects were included in group C.
The height, weight, and waist circumferences (WaC) of all patients were measured and recorded at the anesthesia preoperative assessment center. Patients' heights were measured, without shoes, to the nearest 0.1 cm using inextensible tape. After voiding, patient weights were measured while wearing light clothing and no shoes. Weights were measured to the nearest 0.1 kg by using a portable scale. To measure the WaC, we placed a measuring tape in a horizontal plane around the abdomen at the level of the iliac crest. Before reading the tape measure, the tape was pulled tight, but it did not compress the skin and was parallel to the floor. Each measurement was made at the end of a normal expiration.22 Each patient's body mass index (BMI) was calculated with the following formula: weight (kg)/height2 (m2).
The venous blood samples were drawn between 8 AM and 10 AM and the sodium, potassium, magnesium, chloride, calcium, triglyceride, high-density lipoprotein (HDL) cholesterol, and fasting glucose levels were determined and recorded.
Definition of the Metabolic Syndrome (MetS)
MetS was defined according to the revised Adult Treatment Panel (ATP) III guidelines23 that require the presence of the following criteria: (a) systolic blood pressure ≥130 and diastolic blood pressure ≥85 mm Hg, (b) HDL <40 mg · dL−1 for men and <50 mg · dL−1 for women, (c) triglycerides ≥150 mg · dL−1, (d) fasting blood glucose ≥100 and ≤126 mg · dL−1, and (e) WaC >102 cm for men and >88 cm for women. Patients with at least 3 criteria listed by the ATP III guidelines were included in the MetS group (group M). Using a computer program, we chose a control group (group C) from those patients who did not meet MetS criteria but who were matched with group M regarding age and gender. This selection was completed before ECG analysis.
Standard 12-lead ECG recordings for all patients were obtained using 25 mm/s paper speed and 10 mm/mV standards (Pagewriter 300 π, Hewlett Packard, Palo Alto, California) in the supine position with patients breathing freely and refraining from speech. Because of the circadian variation of QTc duration and its sensitivity to food intake, the ECG records of all patients were taken before breakfast and just before blood samples were drawn.10,11
Heart rate was calculated using mean RR time. The beginning of P waves was defined as positive deflection from the isoelectric line, and the end was defined as the point at which the positive deflection returned to the isoelectric line.9–11 If the beginning and end of P waves were not obvious on ECG records, these derivations were excluded from analysis. Pwd was the difference between the longest and shortest P wave durations. Extended Pwd was defined as a Pwd duration longer than 40 ms.9–11
The QT interval was defined as extending from the beginning of the QRS complex to where T waves descend onto the isoelectric baseline.10,11 When a U wave interrupted the T wave before returning to baseline, the QT interval was measured to the nadir of the curve between the T and U waves. The QTc interval was calculated using the Bazett formula: QTc (ms) = QT measured/√RR (where RR is the RR interval measured in seconds). Extended QTc interval was defined as a duration of >440 ms. The QT dispersion (QTd) value was determined as the difference between the longest and shortest QT intervals observed for the 12 ECG leads. Extended QTd was defined as longer than 60 ms. The QTcd duration, corrected to heart rate, was identified with the Bazett formula: QTcd (ms) = QTd measured/√RR.
Subjects having <9 leads in ECG records were excluded from the study. All ECG measurements were evaluated 3 times by 2 experts (Serhat Bilir and Mustafa Aydın) who were blinded to group assignment. The mean values provided by both experts were subjected to statistical analysis.
The intraobserver and interobserver variations for Pwd were 2.5% and 2.8%; for QT these values were 2.7% and 2.9%, respectively.
Analysis of Peroperative Arrhythmia Incidence
Perioperative patient anesthesia records were examined retrospectively for any evidence of atrial or ventricular arrhythmias.
We excluded pregnant or comatose patients and patients with conditions known to prolong QT interval duration, such as renal, liver, thyroid, or cerebrovascular disease; peripheral arterial or cardiovascular disease (i.e., Chagas's disease, ischemic heart disease, previous arrhythmic episodes, mitral valve prolapse, cardiomyopathy, cardiomegaly, cardiac insufficiency, diastolic blood pressure >90 mm Hg, QRS duration >120 ms and left or right bundle branch block, significant Q waves on surface ECG, and atrial fibrillation); and vascular interventional therapy, alcohol addiction, antidiabetic treatment, electrolyte abnormalities, or use of medication affecting QT interval duration.10,11
The size of the sample was based on previous investigations that have studied the QT, QTc, QTd, and QTcd durations in patients with and without MetS.6–8 Using reference values from a previous study7 reporting QTd duration of 55.3 ± 17.7 ms in patients with MetS and of 34.4 ± 12.7 ms in patients with no MetS (α error of 0.01 and a power of >90%), we calculated that 35 patients were required for each group.
The Statistical Package for the Social Sciences (SPSS) 11.5 was used for data analysis. An analysis of distribution was performed by Kolmogorov–Smirnov test. A one-way analysis of variance (ANOVA) was used to compare parametric variables, and χ2 was used for nonparametric variables. P < 0.05 was considered statistically significant.
During the study period, 278 adult patients who were admitted to the preoperative assessment center were evaluated for MetS criteria. Using the ATP III criteria, there were 104 patients with a MetS diagnosis. Sixty-eight of these 104 patients were excluded because of the following conditions: antihypertensive and β-blocking drug therapy affecting QT interval, history of coronary artery disease or ECG evidence of ischemia/infarct, fasting blood glucose level >126 mg · dL−1, atrial fibrillation, bundle branch block on ECG recording, creatinine level >4 mg · dL−1, alcohol abuse, and arterial blood pressure of 200/110 mm Hg at preoperative assessment.
Group M consisted of 36 patients who fulfilled the MetS criteria. Group C consisted of 40 of the original 278 patients who did not meet the MetS criteria but who matched age and gender characteristics of group M.
There were no significant differences between groups with regard to age or sex (Table 1). The BMI, body weight, and WaC values in group M were significantly higher than were those in group C (P < 0.05) (Table 1).
The serum sodium, potassium, calcium, and chloride levels were similar (Table 2). The serum triglyceride and glucose levels in group M were significantly higher than those in group C (P < 0.05). The serum HDL cholesterol levels in group M were significantly lower than those in group C (P < 0.05) (Table 2).
The average heart rate in group M (84 ± 17 beats per minute [bpm]) was significantly higher than that in group C (74 ± 11 bpm) (P = 0.004) (Table 3). Eight patients in group M, but none in group C, had sinus tachycardia (P = 0.002). All other patients in the study had sinus rhythms. No patient had atrial or ventricular ectopic beats, or atrioventricular or bundle branch block.
The minimum P wave duration in group M was significantly shorter than that in group C (P < 0.05). The maximum P wave duration and Pwd interval were significantly longer in group M (P < 0.001) (Table 3).
Twenty-two (61.1%) patients in group M but only 7 (17.5%) patients in group C had Pwd intervals longer than 40 ms (P < 0.001).
The QT interval durations were similar between groups (P = 0.358) (Table 3). In group M, QTc, QTd, and QTcd intervals were significantly longer (P < 0.001) (Table 3).
The QTc interval was longer than 440 ms in 8 patients (22.2%) from group M, but this interval was extended in only 1 patient (2.5%) in group C (P = 0.011). Twenty-one patients in group M (58.3%) and 5 patients in group C (12.5%) had QTcd intervals longer than 60 ms (P < 0.001).
None of the patients in group C had perioperative arrhythmias, whereas 4 patients (11.1%) in group M had atrial arrhythmias such as supraventricular tachycardia, atrial extrasystole, atrial flutter, or fibrillation. In addition, 1 patient (2.8%) in group M experienced ventricular arrhythmias. Perioperative arrhythmia incidences differed significantly between the study groups (P < 0.05, Fisher's exact test). Patients with ventricular arrhythmia were treated with IV lidocaine; 1 patient with atrial arrhythmia was treated with a beta-blocker, whereas the other cases were self-limiting and did not require treatment.
Preoperative ECG records of 4 patients who had atrial arrhythmias were analyzed; P disp and P max values were longer in these 4 patients with atrial arrhythmias (median; 65 ms, 120 ms) in comparison with all the other patients (median: 40 ms, 100 ms) (P = 0.008; 0.013, respectively, Mann–Whitney U test).
The frequent prevalence of MetS is one of the major public health problems worldwide.22 In our study, we found that the Pwd, QTc, QTd, and QTcd intervals were extended in patients with MetS.
Umetani et al.20 demonstrated that MetS is strongly associated with paroxysmal atrial fibrillation and atrial flutter. Yasar et al.21 showed that patients with MetS have higher Pwd, indicating increased risk for atrial fibrillation. We also demonstrated that MetS patients have extended Pwd values, associated with an increased rate of perioperative arrhythmias. Because serum electrolyte levels were similar in both groups, in our opinion, extended Pwd is not related to serum electrolyte levels. According to our findings, WaC, BMI, systolic arterial blood pressure, serum glucose, triglyceride, and HDL levels are related independently of Pwd extension.
A limitation of our study was the manual calculation of Pwd with printed ECGs. However, several studies have demonstrated a low error in the measurement of Pwd using printed ECGs.9,24 Therefore, future studies should include the entire perioperative process and a Holter monitorization, which could better document the increased rates of atrial and ventricular arrhythmias as well as the clinical impact on patients. Thus evaluation of the pre- to post-operative changes in a future study might be helpful.
In conclusion, we showed that patients with MetS had extended Pwd, QTc, QTd, and QTcd intervals. Our patients with MetS had a higher incidence of arrhythmia during anesthesia and postoperative care, and this finding is consistent with data showing an association between these ECG abnormalities and postoperative arrhythmias. These ECG measurements are easily obtained and might help guide the selection of anesthetic drugs and techniques, avoiding choices known to prolong Pwd, QTc, QTd, and QTcd intervals in MetS patients.25 In addition, the use of these markers preoperatively might also allow better prediction of postoperative care needs.
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