- Email: [email protected]
Seasonal variation of P-wave dispersion in healthy subjects
Journal of Electrocardiology Vol. 35 No. 4 2002
Seasonal Variation of P-wave Dispersion in Healthy Subjects
Sedat Kose, MD, Kudret Aytemir, MD,* Ilknur Can, MD,* Atilla Iyisoy, MD, Ayhan Kilic, MD, Basri Amasyali, MD, Hurkan Kursaklioglu, MD, Ersoy Isik, MD, Ali Oto, MD,* and Ertan Demirtas, MD
Abstract: We studied the seasonal variability of P dispersion in 523 healthy male patients, aged 22 ⫾ 4 years (range, 20-26). Four seasonal 12-lead resting electrocardiograms were recorded at 2 mV/cm standardization and at 50 mm/s paper speed at intervals of three months. Electrocardiograms were recorded between the hours 10 to 12 AM. The difference between the maximum P-wave duration and minimum P-wave duration was calculated and defined as “P dispersion.” There was a significant seasonal variation in the maximum P-wave duration (P ⫽ .001) and P dispersion (P ⫽ .001), with the longest maximum P-wave duration (121 ⫾ 16 ms) and P dispersion (41 ⫾ 7 ms) observed in winter and the shortest maximum P-wave duration (106 ⫾ 15 ms) and P dispersion (24 ⫾ 8 ms) observed in summer. The minimum P-wave duration did not show any significant seasonal variation. In conclusion, there exists a significant seasonal variation in the maximum P-wave duration and P dispersion in healthy patients. Seasonal variation of P dispersion resulted from the significant variation of maximum P-wave duration. Key words: ECG, P-wave duration, P dispersion, and seasonal variation.
times and the inhomogenous propagation of sinus impulses which are well known electrophysiologic characteristics of the atrium prone to fibrillation (4,5). Pd was defined as the difference between maximum P wave duration and minimum P wave duration (Pmin) (4). Prolonged P-wave duration and Pd have been reported to represent an increased risk for atrial fibrillation in patients with no underlying heart disease (4,5), and those undergoing coronary artery bypass surgery (6). In an epidemiologic study, Frost et al. (7) examined the relation between seasons, outdoor temperature and atrial fibrillation, and showed that the risk of atrial fibrillation was modestly higher during winter as compared to summer. The winter season is known to stimulate the sympathetic nervous
P-wave abnormalities, detected from the electrocardiogram (ECG), have been thought to reflect left atrial enlargement (1), left atrial hypertension (2), and altered conduction (3). Two simple electrocardiographic markers, maximum P wave duration (Pmax) and P dispersion (Pd), have been used to evaluate the intraatrial and interatrial conduction
Department of Cardiology, Gu¨lhane Military Medical Academy; and Department of Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey. Reprint requests: Sedat Kose, MD, GATA Department of Cardiology, Etlik, Ankara-Turkey 06018; e-mail: aiyisoy@ hotmail.com. Copyright 2002, Elsevier Science (USA). All rights reserved. 0022-0736/02/3504-0007$35.00/0 doi:10.1054/jelc.2002.35848
*
307
308 Journal of Electrocardiology Vol. 35 No. 4 October 2002 system (8,9). Pd in normal subjects has been reported to be influenced by the autonomic tone, which induces changes in atrial size and the velocity of impulse propagation (10). However, the association between Pd and seasonal changes has not been studied in normal subjects. This study investigates the effect of seasons on P-wave duration and Pd in healthy subjects.
Materials and Methods Patient Population Five hundred twenty three healthy volunteers from a military service, all men, aged 22 ⫾ 4 years (range, 20-26) were included in this study. History, physical examination, 12-lead ECG, and chest Xray did not reveal any acute or chronic disorder. They were all in sinus rhythm during the follow-up period of 1 year. The study was conducted in the central region of Turkey, which has relatively cold winter and hot summer seasons. Subjects using drugs known to affect P-wave duration, taking alcohol, and smokers were not included. P Dispersion Measurements in 12-Lead ECGs During the period between January 2000 and October 2001, all subjects underwent four seasonal 12-lead rest ECG recordings, roughly 3 months apart. All standard 12-lead ECGs were obtained simultaneously using a recorder (Hewlett Packard, Pagewriter XLi) set at a 50 mm/s paper speed and 2 m V/cm standardization in the supine position. The winter ECG was recorded in January (average temperature 4°C), the spring ECG in April (average temperature 21°C), the summer ECG in July (average temperature 28°C) and the fall ECG in October (average temperature 15°C). Because all subjects in the study were soldiers (military persons), they had to wake up at 6.30 a.m., breakfast at 7:00 a.m., and have the same food. All subjects were asked to refrain from military training during the day of ECG recording and rested in sitting position for 20 minutes before ECG. For standardization, ECGs were taken between 10 and 11 a.m. within an interval of 3.5 and 4.5 hours between waking up and ECG recording. The ECGs were numbered and presented to the analyzing investigators without name and date information. All measurements of P-wave duration
were made blindly by 2 medically qualified observers. The P-wave duration was measured manually in all simultaneously recorded 12 leads of the surface ECG. The mean P-wave duration for at least 3 complexes were calculated in each lead. The average values of P-wave duration and P dispersion obtained by two investigators were used for comparisons between seasons. For greater accuracy, measurements were performed with calipers and magnifying lens, as described by previous investigators (4,6). The onset of the P wave was defined as the point of first visible upward departure from baseline for positive waveforms, and as the point of first downward departure from baseline for negative waveforms. The return to the baseline was considered to be the end of the P wave. The Pmax measured in any of the 12 leads of the surface ECG was used as the longest atrial conduction time. The difference between the Pmax and the Pmin was calculated and defined as Pd (4). Blinded inter-and intraobserver reproducibility of the P wave duration and Pd measurement were evaluated, and comparison revealed a Spearman correlation coefficient of 0.92 and 0.93 for the P wave duration and 0.90 and 0.91 for Pd, respectively (P ⬍ .001). Statistical Anaysis All data were expressed as mean ⫾ SD. The SPSS for Windows was used for statistical analysis. The seasonal differences of the ECG recording time were analyzed by one-sample t-test with the test value being set at zero. Comparisons of the Pd between seasons were made by repeated measures one-way ANOVA. The paired-samples t-test was applied to test the significance of the differences between paired measurements. A value of P ⬍ .05 was considered statistically significant.
Results All ECG measurements are shown in Table 1. There was no interseasonal differences in the ECG recording time (P ⫽ .82 to .98). There was not any significant interseasonal difference in the heart rates (P ⫽ .72). Pmin values did not show any interseasonal difference (P ⬎ .05). However, there was a seasonal variability in the Pmax values (P ⬍ .05); it was 121 ⫾ 16 ms, 112 ⫾ 18 ms, 106 ⫾ 15 ms and 117 ⫾ 14 ms in winter, spring, summer and fall, respectively. The seasonal differences in the Pmax were significant between winter and spring
P-wave Dispersion in Healthy Subjects •
Kose et al. 309
Table 1. P-wave Duration and P Dispersion Values at Different Seasons
Heart rate (bpm) Maximum P-wave duration (ms)* Minimum P-wave duration (ms) P dispersion (ms)†
Winter
Spring
Summer
Fall
77 ⫾ 12 121 ⫾ 16 83 ⫾ 14 41 ⫾ 7
74 ⫾ 11 112 ⫾ 18 81 ⫾ 10 30 ⫾ 9
75 ⫾ 10 106 ⫾ 15 82 ⫾ 13 24 ⫾ 8
74 ⫾ 13 117 ⫾ 14 81 ⫾ 12 36 ⫾ 7
* Winter vs. Spring, P ⬍ .01; winter vs. summer, P ⬍ .001; winter vs. fall, P ⬍ .05; spring vs. summer, P ⬍ .05; spring vs. fall, P ⬍ .05, summer vs. fall, P ⬍ .05. † Winter vs. spring, P ⬍ .05; winter vs. summer, P ⬍ .001, winter vs. fall, P ⬍ .01, spring vs. summer, P ⬍ .05; spring vs. fall, P ⬍ .05; summer vs. fall, P ⬍ .001.
(P ⬍ .01), between winter and summer (P ⬍ .001), between winter and fall (P ⬍ .05), between spring and summer (P ⬍ .05), between spring and fall (P ⬍ .05), and between summer and fall (P ⬍ .05). There was a significant seasonal variability in the Pd values (P ⫽ .001)(Fig. 1). It was 41 ⫾ 7 ms, 30 ⫾ 9 ms, 24 ⫾ 8 ms, 36 ⫾ 7 ms in winter, spring, summer, and fall, respectively. The highest Pd occurred in winter and the smallest one in summer. The seasonal differences in the Pd were significant between winter and spring (P ⬍ .05), between winter and summer (P ⬍ .001), between winter and fall (P ⬍ .01), between spring and summer (P ⬍ .05), between spring and fall (P ⬍ 0.05), and between summer and fall (P ⬍ .001).
Discussion Our results in healthy young subjects showed a significant seasonal variability of Pmax and P dispersion. To the best of our knowledge, this is the first study to show the seasonal dynamic behaviour of Pmax and Pd.
Pmax and Pd as Electrocardiographic Predictors of Atrial Fibrillation The electrophysiological properties of atrial myocardium prone to fibrilllate due to atrial conduction abnormalities could possibly result in prolonged and highly variable P waves that can be reflected in differently oriented ECG leads. Pd is derived from a standard, simultaneously recorded 12-lead ECG and is used as a marker of the interlead variation in P wave duration (4,5). In accordance with this hypothesis, Pmax and Pd have been shown to distinguish patients with paroxysmal or postoperative atrial fibrillation (4-6). Aytemir et al. (11) found Pmax to be significantly higher in patients with paroxysmal atrial fibrillation (PAF) compared to healthy controls (116 ⫾ 17 ms versus 101 ⫾ 11 ms, P ⬍ .001). In the same study, Pd was also significantly higher in the patient group than controls (44 ⫾ 15 ms vs 27 ⫾ 10 ms, P ⬍ .001). Dilaveris et al. (12) found Pmax to be a significant independent predictor of the recurrent paroxysms of atrial fibrillation. Ozer et al. (13) studied Pd in hypertensive patients with and without a history of PAF and concluded that Pd ⬎ 44 significantly discriminated patients with a history of PAF than those without. In their study, Pmax was not significantly different between hypertensive patients with and without a history of PAF, but Pmin was significantly lower in hypertensive patients with PAF. Effect of Winter Season and Age on the Prevalence of Atrial Fibrillation
Fig. 1. P dispersion values. Winter vs. spring, P ⬍ .05; winter vs. summer, P ⬍ .001, winter vs. fall, P ⬍ .01, spring vs. summer, P ⬍ .05; spring vs. fall, P ⬍ .05; summer vs. fall, P ⬍ .001.
The prolongation of P-wave duration is thought to be an accepted indicator of an interatrial conduction disturbance that can occur independent of an increase in atrial size (3). In an epidemiologic study, the risk of atrial fibrillation was found to be modestly higher among 32,992 subjects aged 50-89 years during the winter season and was inversely associated with the outdoor temperature (relative
310 Journal of Electrocardiology Vol. 35 No. 4 October 2002 risk ⫽ 1.2, 95% confidence interval 1.12-1.29) (7). It is known that prevalence of atrial fibrillation increases with age; it is 0.5% in the age range of 50-59 years and 8.8% in the age range of 80-89 years (14,15). In healthy elderly subjects using P-wave signal-averaged electrocardiogram (SAECG), which also has good correlation with atrial activation time (16), Babaev et al. (17) have shown a positive correlation between P-wave duration on SAECG and age (r ⫽ .39, P ⬍ .0001). They concluded that age-related atrial conduction delay in healthy subjects is present, which could be detected by P-wave SAECG, a potential measure of agerelated risk for development of AF. Winter season has been associated with elevations in systolic and diastolic blood pressure both in normotensives and hypertensives (18). In healthy individuals, plasma levels of endothelin-1, which is a powerful vasoconstrictor, and vasorelaxant nitric oxide also show seasonal variation with the highest values of endothelin-1 and lowest levels of nitric oxide occurring during winter (19). Review of the studies about the effect of cold weather on human nervous system has shown that plasma levels and urinary excretion of norepinephrine and epinephrine increases in winter season (8,9). Cheema et al. (10) studied the effect of epinephrine on signal-averaged P-wave duration in healthy young subjects and found that epinephrine resulted in significant prolongation of P-wave duration. Although the subjects in our study were healthy young volunteers without any history of arrhythmia, the stimulation of sympathetic nervous system during the winter season may be the underlying mechanism of prolonged of Pmax and Pd. On the other hand, Tukek et al. (20) showed that Pmax increased and Pmin decreased during the release phase of Valsalva maneuver with sympathetic withdrawal and parasympathetic activation, increasing the Pd in healthy controls. Seasonal Variation of Stroke Incidence Stroke is another important clinical condition showing seasonal variation with a peak in winter season (21). Cerebrovascular accidents associated with atrial fibrillation occur in a higher percentage in the elderly. They were found to represent 6.7% of the total number of cerebrovascular accidents between 50-59 years of age and 36.2% between 80-89 years of age (22). In our study, we found winter seasonal prolongation of Pmax (121 ⫾ 16 ms) and Pd (41 ⫾ 7 ms) to be very close to the values of Aytemir et al. (11) that
were discriminative for PAF, which may suggest the significant effect of winter season on Pmax and Pd. Although we did not see any case of PAF among our healthy young population during the study period, such prolongation of Pmax and Pd during winter season might predispose hypertensive individuals for the development of PAF attacks during winter. Further studies about the effects of seasons on Pd and Pmax in hypertensive patients may prove to be more informative in this field. Winter season might cause an increased susceptibility to atrial fibrillation especially in older ages who already have age-related atrial conduction delay. Winter season may act as a trigger, inducing further prolongation of interatrial and intraatrial conduction time, leading to an increased incidence of atrial fibrillation in the old age group. Although we did not evaluate the seasonal variation of blood pressure or vasoactive substances in our study, it is possible that longer Pd during winter might have been affected by the seasonal variation of blood pressure. Since blood pressure elevation is not sustained as in the case of hypertensive patients, this may not have predisposed these healthy subjects to the development of PAF. In our study, we found significant seasonal variation in Pmax and Pd with the longest durations seen in winter. Winter season, by inducing atrial conduction delays, which is reflected on the ECG as prolonged Pmax and Pd, might predispose the elderly to an increased likelihood of atrial fibrillation and stroke.
Study Limitations Although Pd and Pmax have been found to be increased in healthy young subjects in winter season, there is no prospective study that evaluates via serial ECG measurements whether the increased Pmax and Pd during winter precede atrial fibrillation. Our study population included only healthy young subjects, and seasonal variability might have not induced arrhythmia in this age group. Further prospective clinical studies are needed to evaluate the role of seasonal changes in Pmax and Pd on the occurrence of atrial fibrillation in other age groups and disease states. Unfortunately, time and financial constraints have prevented inclusion of echocardiographic variables related to the atria (dimensions, ratios) in the study. Also, we did not anticipate any significant echocardiographic changes in this healthy, young and athletic cohort.
P-wave Dispersion in Healthy Subjects •
We obtained only one ECG recording per season, so we did not study the same-season reproducibility of these variables. Nevertheless, we obtained the ECGs in the month best representing the season.
8.
9.
Conclusion Seasonal variation of Pmax and Pd shown in this study in healthy subjects with greater values during winter compared to other seasons might help us to understand the seasonal predilection of atrial fibrillation and stroke. Studies in groups of people more prone to atrial fibrillation such as the elderly and hypertensive population will help us to understand further the effects of seasons on event outcomes.
10.
11.
12.
13.
Acknowledgment 14.
The authors thank Nazire Zengi and Faik Tosun for their great help in data collection. 15.
References 16. 1. Surawicz B: Electrocardiographic diagnosis of chamber enlargement. J Am Coll Cardiol 8:711, 1986 2. Chandraratna PAN, Hodges M: Electrocardiographic evidence of left atrial hypertension in acute myocardial infarction. Circulation 47:493, 1973 3. Josephson ME, Kastor JA, Morganroth J: Electrocardiographic left atrial enlargement. Electrophysiologic, echocardiographic and hemodynamic correlates. Am J Cardiol 39:967, 1977 4. Dilaveris P, Gialafos EJ, Sideris S, et al: Simple electrocardiographic markers for the prediction of paroxysmal idiopathic atrial fibrillation. Am Heart J 135:733, 1998 5. Gialafos JE, Dilaveris PE, Gialafos EJ, et al: P dispersion: A valuable electrocardiographic marker for the prediction of paroxysmal lone atrial fibrillation. Ann Noninvasive Electrocardiol 4:39, 1999 6. Kloter-Weber U, Osswald S, Huber M, et al: Selective versus non-selective antiarrhythmic approach for prevention of atrial fibrillation after coronary surgery: Is there a need for pre-operative risk stratification? A prospective placebo-controlled study using low dose sotalol. Eur Heart J 19:794, 1998 7. Frost L, Johnsen SP, Pedersen L, et al: Seasonal
17.
18.
19.
20.
21.
22.
Kose et al. 311
variation in hospital discharge diagnosis of atrial fibrillation: A population based study. Epidemiology 13:211, 2002 Hata T, Ogihara T, Maruyama A, et al: The seasonal variation of blood pressure in patients with essential hypertension. Clin Exp Hypertens 4:341, 1982 Sharma BK, Sagar S, Sood GK, et al: Seasonal variation of arterial blood pressure in normotensive and essential hypertensives. Indian Heart J 42:66, 1990 Cheema AN, Ahmed MW, Kadish AH, et al: Effects of autonomic stimulation and blockade on signal-averaged P wave duration. J Am Coll Cardiol 26:497, 1995 Aytemir K, Ozer N, Atalar E, et al: Dispersion on 12-lead electrocardiography in patients with paroxysmal atrial fibrillation. PACE 23:1109, 2000 Dilaveris PE, Gialafos EJ, Andrikopoulos GK, et al: Clinical and electrocardiographic predictors of recurrent atrial fibrillation. PACE 23:352, 2000 Ozer N, Aytemir K, Atalar E, et al: P dispersion in hypertensive patients with paroxysmal atrial fibrillation. PACE 23(Pt. II):1859, 2000 Kannel WB, Abbot RD, Savage DD, et al: Epidemiologic features of chronic atrial fibrillation: The Framingham Study. N Engl J Med 306:1018, 1982 Brand FN, Abott RD, Kannel WB, et al: Characteristics and prognosis of lone atrial fibrillation: 30-years follow up in the Framingham Study. JAMA 254: 3449, 1985 Michelucci A, Toso A, Mezzani A: Noninvasive recording of sinus node activity by P wave triggered SAECG. Validation using direct intra-atrial recording of sinus node electrocardiogram. Am J Noninvasive Cardiol 7:132, 1993 Babaev AA, Vloka ME, Sadurski F, et al: Influence of age on atrial activation time as measured by P-wave SAECG. Am J Cardiol 86:692, 2000 Sega R, Cesana G, Bombelli M, et al: Seasonal variations in home and ambulatory blood pressure in the PAMELA population. J Hypertens 16:1585, 1999 Mc Laren M, Kirk G, Bolton-Smith C, et al: Seasonal variation in plasma levels of endothelin-1 and nitric oxide. Int Angiol 19:351, 2000 Tukek T, Akkaya V, Demirel S, et al: Effect of Valsalva maneuver on surface electrocardiographic P-wave dispersion in paroxysmal atrial fibrillation. Am J Cardiol 85:896, 2000 Sheth T, Nair C, Mu¨ ller J, et al: Increased winter mortality from acute myocardial infarction and stroke: the effect of age. J Am Coll Cardiol 33:1916, 1999 Wolf PA, Abbott RD, Kannel WB: A major contributor to stroke in the elderly. Arch Int Med 147:1561, 1987
Seasonal Variation of P-wave Dispersion in Healthy Subjects
Sedat Kose, MD, Kudret Aytemir, MD,* Ilknur Can, MD,* Atilla Iyisoy, MD, Ayhan Kilic, MD, Basri Amasyali, MD, Hurkan Kursaklioglu, MD, Ersoy Isik, MD, Ali Oto, MD,* and Ertan Demirtas, MD
Abstract: We studied the seasonal variability of P dispersion in 523 healthy male patients, aged 22 ⫾ 4 years (range, 20-26). Four seasonal 12-lead resting electrocardiograms were recorded at 2 mV/cm standardization and at 50 mm/s paper speed at intervals of three months. Electrocardiograms were recorded between the hours 10 to 12 AM. The difference between the maximum P-wave duration and minimum P-wave duration was calculated and defined as “P dispersion.” There was a significant seasonal variation in the maximum P-wave duration (P ⫽ .001) and P dispersion (P ⫽ .001), with the longest maximum P-wave duration (121 ⫾ 16 ms) and P dispersion (41 ⫾ 7 ms) observed in winter and the shortest maximum P-wave duration (106 ⫾ 15 ms) and P dispersion (24 ⫾ 8 ms) observed in summer. The minimum P-wave duration did not show any significant seasonal variation. In conclusion, there exists a significant seasonal variation in the maximum P-wave duration and P dispersion in healthy patients. Seasonal variation of P dispersion resulted from the significant variation of maximum P-wave duration. Key words: ECG, P-wave duration, P dispersion, and seasonal variation.
times and the inhomogenous propagation of sinus impulses which are well known electrophysiologic characteristics of the atrium prone to fibrillation (4,5). Pd was defined as the difference between maximum P wave duration and minimum P wave duration (Pmin) (4). Prolonged P-wave duration and Pd have been reported to represent an increased risk for atrial fibrillation in patients with no underlying heart disease (4,5), and those undergoing coronary artery bypass surgery (6). In an epidemiologic study, Frost et al. (7) examined the relation between seasons, outdoor temperature and atrial fibrillation, and showed that the risk of atrial fibrillation was modestly higher during winter as compared to summer. The winter season is known to stimulate the sympathetic nervous
P-wave abnormalities, detected from the electrocardiogram (ECG), have been thought to reflect left atrial enlargement (1), left atrial hypertension (2), and altered conduction (3). Two simple electrocardiographic markers, maximum P wave duration (Pmax) and P dispersion (Pd), have been used to evaluate the intraatrial and interatrial conduction
Department of Cardiology, Gu¨lhane Military Medical Academy; and Department of Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey. Reprint requests: Sedat Kose, MD, GATA Department of Cardiology, Etlik, Ankara-Turkey 06018; e-mail: aiyisoy@ hotmail.com. Copyright 2002, Elsevier Science (USA). All rights reserved. 0022-0736/02/3504-0007$35.00/0 doi:10.1054/jelc.2002.35848
*
307
308 Journal of Electrocardiology Vol. 35 No. 4 October 2002 system (8,9). Pd in normal subjects has been reported to be influenced by the autonomic tone, which induces changes in atrial size and the velocity of impulse propagation (10). However, the association between Pd and seasonal changes has not been studied in normal subjects. This study investigates the effect of seasons on P-wave duration and Pd in healthy subjects.
Materials and Methods Patient Population Five hundred twenty three healthy volunteers from a military service, all men, aged 22 ⫾ 4 years (range, 20-26) were included in this study. History, physical examination, 12-lead ECG, and chest Xray did not reveal any acute or chronic disorder. They were all in sinus rhythm during the follow-up period of 1 year. The study was conducted in the central region of Turkey, which has relatively cold winter and hot summer seasons. Subjects using drugs known to affect P-wave duration, taking alcohol, and smokers were not included. P Dispersion Measurements in 12-Lead ECGs During the period between January 2000 and October 2001, all subjects underwent four seasonal 12-lead rest ECG recordings, roughly 3 months apart. All standard 12-lead ECGs were obtained simultaneously using a recorder (Hewlett Packard, Pagewriter XLi) set at a 50 mm/s paper speed and 2 m V/cm standardization in the supine position. The winter ECG was recorded in January (average temperature 4°C), the spring ECG in April (average temperature 21°C), the summer ECG in July (average temperature 28°C) and the fall ECG in October (average temperature 15°C). Because all subjects in the study were soldiers (military persons), they had to wake up at 6.30 a.m., breakfast at 7:00 a.m., and have the same food. All subjects were asked to refrain from military training during the day of ECG recording and rested in sitting position for 20 minutes before ECG. For standardization, ECGs were taken between 10 and 11 a.m. within an interval of 3.5 and 4.5 hours between waking up and ECG recording. The ECGs were numbered and presented to the analyzing investigators without name and date information. All measurements of P-wave duration
were made blindly by 2 medically qualified observers. The P-wave duration was measured manually in all simultaneously recorded 12 leads of the surface ECG. The mean P-wave duration for at least 3 complexes were calculated in each lead. The average values of P-wave duration and P dispersion obtained by two investigators were used for comparisons between seasons. For greater accuracy, measurements were performed with calipers and magnifying lens, as described by previous investigators (4,6). The onset of the P wave was defined as the point of first visible upward departure from baseline for positive waveforms, and as the point of first downward departure from baseline for negative waveforms. The return to the baseline was considered to be the end of the P wave. The Pmax measured in any of the 12 leads of the surface ECG was used as the longest atrial conduction time. The difference between the Pmax and the Pmin was calculated and defined as Pd (4). Blinded inter-and intraobserver reproducibility of the P wave duration and Pd measurement were evaluated, and comparison revealed a Spearman correlation coefficient of 0.92 and 0.93 for the P wave duration and 0.90 and 0.91 for Pd, respectively (P ⬍ .001). Statistical Anaysis All data were expressed as mean ⫾ SD. The SPSS for Windows was used for statistical analysis. The seasonal differences of the ECG recording time were analyzed by one-sample t-test with the test value being set at zero. Comparisons of the Pd between seasons were made by repeated measures one-way ANOVA. The paired-samples t-test was applied to test the significance of the differences between paired measurements. A value of P ⬍ .05 was considered statistically significant.
Results All ECG measurements are shown in Table 1. There was no interseasonal differences in the ECG recording time (P ⫽ .82 to .98). There was not any significant interseasonal difference in the heart rates (P ⫽ .72). Pmin values did not show any interseasonal difference (P ⬎ .05). However, there was a seasonal variability in the Pmax values (P ⬍ .05); it was 121 ⫾ 16 ms, 112 ⫾ 18 ms, 106 ⫾ 15 ms and 117 ⫾ 14 ms in winter, spring, summer and fall, respectively. The seasonal differences in the Pmax were significant between winter and spring
P-wave Dispersion in Healthy Subjects •
Kose et al. 309
Table 1. P-wave Duration and P Dispersion Values at Different Seasons
Heart rate (bpm) Maximum P-wave duration (ms)* Minimum P-wave duration (ms) P dispersion (ms)†
Winter
Spring
Summer
Fall
77 ⫾ 12 121 ⫾ 16 83 ⫾ 14 41 ⫾ 7
74 ⫾ 11 112 ⫾ 18 81 ⫾ 10 30 ⫾ 9
75 ⫾ 10 106 ⫾ 15 82 ⫾ 13 24 ⫾ 8
74 ⫾ 13 117 ⫾ 14 81 ⫾ 12 36 ⫾ 7
* Winter vs. Spring, P ⬍ .01; winter vs. summer, P ⬍ .001; winter vs. fall, P ⬍ .05; spring vs. summer, P ⬍ .05; spring vs. fall, P ⬍ .05, summer vs. fall, P ⬍ .05. † Winter vs. spring, P ⬍ .05; winter vs. summer, P ⬍ .001, winter vs. fall, P ⬍ .01, spring vs. summer, P ⬍ .05; spring vs. fall, P ⬍ .05; summer vs. fall, P ⬍ .001.
(P ⬍ .01), between winter and summer (P ⬍ .001), between winter and fall (P ⬍ .05), between spring and summer (P ⬍ .05), between spring and fall (P ⬍ .05), and between summer and fall (P ⬍ .05). There was a significant seasonal variability in the Pd values (P ⫽ .001)(Fig. 1). It was 41 ⫾ 7 ms, 30 ⫾ 9 ms, 24 ⫾ 8 ms, 36 ⫾ 7 ms in winter, spring, summer, and fall, respectively. The highest Pd occurred in winter and the smallest one in summer. The seasonal differences in the Pd were significant between winter and spring (P ⬍ .05), between winter and summer (P ⬍ .001), between winter and fall (P ⬍ .01), between spring and summer (P ⬍ .05), between spring and fall (P ⬍ 0.05), and between summer and fall (P ⬍ .001).
Discussion Our results in healthy young subjects showed a significant seasonal variability of Pmax and P dispersion. To the best of our knowledge, this is the first study to show the seasonal dynamic behaviour of Pmax and Pd.
Pmax and Pd as Electrocardiographic Predictors of Atrial Fibrillation The electrophysiological properties of atrial myocardium prone to fibrilllate due to atrial conduction abnormalities could possibly result in prolonged and highly variable P waves that can be reflected in differently oriented ECG leads. Pd is derived from a standard, simultaneously recorded 12-lead ECG and is used as a marker of the interlead variation in P wave duration (4,5). In accordance with this hypothesis, Pmax and Pd have been shown to distinguish patients with paroxysmal or postoperative atrial fibrillation (4-6). Aytemir et al. (11) found Pmax to be significantly higher in patients with paroxysmal atrial fibrillation (PAF) compared to healthy controls (116 ⫾ 17 ms versus 101 ⫾ 11 ms, P ⬍ .001). In the same study, Pd was also significantly higher in the patient group than controls (44 ⫾ 15 ms vs 27 ⫾ 10 ms, P ⬍ .001). Dilaveris et al. (12) found Pmax to be a significant independent predictor of the recurrent paroxysms of atrial fibrillation. Ozer et al. (13) studied Pd in hypertensive patients with and without a history of PAF and concluded that Pd ⬎ 44 significantly discriminated patients with a history of PAF than those without. In their study, Pmax was not significantly different between hypertensive patients with and without a history of PAF, but Pmin was significantly lower in hypertensive patients with PAF. Effect of Winter Season and Age on the Prevalence of Atrial Fibrillation
Fig. 1. P dispersion values. Winter vs. spring, P ⬍ .05; winter vs. summer, P ⬍ .001, winter vs. fall, P ⬍ .01, spring vs. summer, P ⬍ .05; spring vs. fall, P ⬍ .05; summer vs. fall, P ⬍ .001.
The prolongation of P-wave duration is thought to be an accepted indicator of an interatrial conduction disturbance that can occur independent of an increase in atrial size (3). In an epidemiologic study, the risk of atrial fibrillation was found to be modestly higher among 32,992 subjects aged 50-89 years during the winter season and was inversely associated with the outdoor temperature (relative
310 Journal of Electrocardiology Vol. 35 No. 4 October 2002 risk ⫽ 1.2, 95% confidence interval 1.12-1.29) (7). It is known that prevalence of atrial fibrillation increases with age; it is 0.5% in the age range of 50-59 years and 8.8% in the age range of 80-89 years (14,15). In healthy elderly subjects using P-wave signal-averaged electrocardiogram (SAECG), which also has good correlation with atrial activation time (16), Babaev et al. (17) have shown a positive correlation between P-wave duration on SAECG and age (r ⫽ .39, P ⬍ .0001). They concluded that age-related atrial conduction delay in healthy subjects is present, which could be detected by P-wave SAECG, a potential measure of agerelated risk for development of AF. Winter season has been associated with elevations in systolic and diastolic blood pressure both in normotensives and hypertensives (18). In healthy individuals, plasma levels of endothelin-1, which is a powerful vasoconstrictor, and vasorelaxant nitric oxide also show seasonal variation with the highest values of endothelin-1 and lowest levels of nitric oxide occurring during winter (19). Review of the studies about the effect of cold weather on human nervous system has shown that plasma levels and urinary excretion of norepinephrine and epinephrine increases in winter season (8,9). Cheema et al. (10) studied the effect of epinephrine on signal-averaged P-wave duration in healthy young subjects and found that epinephrine resulted in significant prolongation of P-wave duration. Although the subjects in our study were healthy young volunteers without any history of arrhythmia, the stimulation of sympathetic nervous system during the winter season may be the underlying mechanism of prolonged of Pmax and Pd. On the other hand, Tukek et al. (20) showed that Pmax increased and Pmin decreased during the release phase of Valsalva maneuver with sympathetic withdrawal and parasympathetic activation, increasing the Pd in healthy controls. Seasonal Variation of Stroke Incidence Stroke is another important clinical condition showing seasonal variation with a peak in winter season (21). Cerebrovascular accidents associated with atrial fibrillation occur in a higher percentage in the elderly. They were found to represent 6.7% of the total number of cerebrovascular accidents between 50-59 years of age and 36.2% between 80-89 years of age (22). In our study, we found winter seasonal prolongation of Pmax (121 ⫾ 16 ms) and Pd (41 ⫾ 7 ms) to be very close to the values of Aytemir et al. (11) that
were discriminative for PAF, which may suggest the significant effect of winter season on Pmax and Pd. Although we did not see any case of PAF among our healthy young population during the study period, such prolongation of Pmax and Pd during winter season might predispose hypertensive individuals for the development of PAF attacks during winter. Further studies about the effects of seasons on Pd and Pmax in hypertensive patients may prove to be more informative in this field. Winter season might cause an increased susceptibility to atrial fibrillation especially in older ages who already have age-related atrial conduction delay. Winter season may act as a trigger, inducing further prolongation of interatrial and intraatrial conduction time, leading to an increased incidence of atrial fibrillation in the old age group. Although we did not evaluate the seasonal variation of blood pressure or vasoactive substances in our study, it is possible that longer Pd during winter might have been affected by the seasonal variation of blood pressure. Since blood pressure elevation is not sustained as in the case of hypertensive patients, this may not have predisposed these healthy subjects to the development of PAF. In our study, we found significant seasonal variation in Pmax and Pd with the longest durations seen in winter. Winter season, by inducing atrial conduction delays, which is reflected on the ECG as prolonged Pmax and Pd, might predispose the elderly to an increased likelihood of atrial fibrillation and stroke.
Study Limitations Although Pd and Pmax have been found to be increased in healthy young subjects in winter season, there is no prospective study that evaluates via serial ECG measurements whether the increased Pmax and Pd during winter precede atrial fibrillation. Our study population included only healthy young subjects, and seasonal variability might have not induced arrhythmia in this age group. Further prospective clinical studies are needed to evaluate the role of seasonal changes in Pmax and Pd on the occurrence of atrial fibrillation in other age groups and disease states. Unfortunately, time and financial constraints have prevented inclusion of echocardiographic variables related to the atria (dimensions, ratios) in the study. Also, we did not anticipate any significant echocardiographic changes in this healthy, young and athletic cohort.
P-wave Dispersion in Healthy Subjects •
We obtained only one ECG recording per season, so we did not study the same-season reproducibility of these variables. Nevertheless, we obtained the ECGs in the month best representing the season.
8.
9.
Conclusion Seasonal variation of Pmax and Pd shown in this study in healthy subjects with greater values during winter compared to other seasons might help us to understand the seasonal predilection of atrial fibrillation and stroke. Studies in groups of people more prone to atrial fibrillation such as the elderly and hypertensive population will help us to understand further the effects of seasons on event outcomes.
10.
11.
12.
13.
Acknowledgment 14.
The authors thank Nazire Zengi and Faik Tosun for their great help in data collection. 15.
References 16. 1. Surawicz B: Electrocardiographic diagnosis of chamber enlargement. J Am Coll Cardiol 8:711, 1986 2. Chandraratna PAN, Hodges M: Electrocardiographic evidence of left atrial hypertension in acute myocardial infarction. Circulation 47:493, 1973 3. Josephson ME, Kastor JA, Morganroth J: Electrocardiographic left atrial enlargement. Electrophysiologic, echocardiographic and hemodynamic correlates. Am J Cardiol 39:967, 1977 4. Dilaveris P, Gialafos EJ, Sideris S, et al: Simple electrocardiographic markers for the prediction of paroxysmal idiopathic atrial fibrillation. Am Heart J 135:733, 1998 5. Gialafos JE, Dilaveris PE, Gialafos EJ, et al: P dispersion: A valuable electrocardiographic marker for the prediction of paroxysmal lone atrial fibrillation. Ann Noninvasive Electrocardiol 4:39, 1999 6. Kloter-Weber U, Osswald S, Huber M, et al: Selective versus non-selective antiarrhythmic approach for prevention of atrial fibrillation after coronary surgery: Is there a need for pre-operative risk stratification? A prospective placebo-controlled study using low dose sotalol. Eur Heart J 19:794, 1998 7. Frost L, Johnsen SP, Pedersen L, et al: Seasonal
17.
18.
19.
20.
21.
22.
Kose et al. 311
variation in hospital discharge diagnosis of atrial fibrillation: A population based study. Epidemiology 13:211, 2002 Hata T, Ogihara T, Maruyama A, et al: The seasonal variation of blood pressure in patients with essential hypertension. Clin Exp Hypertens 4:341, 1982 Sharma BK, Sagar S, Sood GK, et al: Seasonal variation of arterial blood pressure in normotensive and essential hypertensives. Indian Heart J 42:66, 1990 Cheema AN, Ahmed MW, Kadish AH, et al: Effects of autonomic stimulation and blockade on signal-averaged P wave duration. J Am Coll Cardiol 26:497, 1995 Aytemir K, Ozer N, Atalar E, et al: Dispersion on 12-lead electrocardiography in patients with paroxysmal atrial fibrillation. PACE 23:1109, 2000 Dilaveris PE, Gialafos EJ, Andrikopoulos GK, et al: Clinical and electrocardiographic predictors of recurrent atrial fibrillation. PACE 23:352, 2000 Ozer N, Aytemir K, Atalar E, et al: P dispersion in hypertensive patients with paroxysmal atrial fibrillation. PACE 23(Pt. II):1859, 2000 Kannel WB, Abbot RD, Savage DD, et al: Epidemiologic features of chronic atrial fibrillation: The Framingham Study. N Engl J Med 306:1018, 1982 Brand FN, Abott RD, Kannel WB, et al: Characteristics and prognosis of lone atrial fibrillation: 30-years follow up in the Framingham Study. JAMA 254: 3449, 1985 Michelucci A, Toso A, Mezzani A: Noninvasive recording of sinus node activity by P wave triggered SAECG. Validation using direct intra-atrial recording of sinus node electrocardiogram. Am J Noninvasive Cardiol 7:132, 1993 Babaev AA, Vloka ME, Sadurski F, et al: Influence of age on atrial activation time as measured by P-wave SAECG. Am J Cardiol 86:692, 2000 Sega R, Cesana G, Bombelli M, et al: Seasonal variations in home and ambulatory blood pressure in the PAMELA population. J Hypertens 16:1585, 1999 Mc Laren M, Kirk G, Bolton-Smith C, et al: Seasonal variation in plasma levels of endothelin-1 and nitric oxide. Int Angiol 19:351, 2000 Tukek T, Akkaya V, Demirel S, et al: Effect of Valsalva maneuver on surface electrocardiographic P-wave dispersion in paroxysmal atrial fibrillation. Am J Cardiol 85:896, 2000 Sheth T, Nair C, Mu¨ ller J, et al: Increased winter mortality from acute myocardial infarction and stroke: the effect of age. J Am Coll Cardiol 33:1916, 1999 Wolf PA, Abbott RD, Kannel WB: A major contributor to stroke in the elderly. Arch Int Med 147:1561, 1987