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Height is associated with incident atrial fibrillation in a large Asian cohort
IJCA-28272; No of Pages 3 International Journal of Cardiology xxx (xxxx) xxx
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Short communication
Height is associated with incident atrial fibrillation in a large Asian cohort Young Min Park a, Jeonggeun Moon b, In Cheol Hwang c,⁎, Hyunsun Lim d, Bokeum Cho e a
Department of Family Medicine, National Health Insurance Service Ilsan Hospital, Goyang, South Korea Cardiology Division, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea c Department of Family Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea d Department of Policy Research Affairs, National Health Insurance Service Ilsan Hospital, Goyang, South Korea e Division of Humanities Arts and Social Sciences, Underwood International College of Yonsei University, Seoul, South Korea b
a r t i c l e
i n f o
Article history: Received 10 December 2019 Received in revised form 1 January 2020 Accepted 9 January 2020 Available online xxxx Keywords: Asian Atrial fibrillation Height Risk factors
a b s t r a c t Background: Although increased height is associated with a risk of atrial fibrillation (AF), the mechanism is not well understood. We aimed to explore whether this association varies with metabolic conditions. Methods and results: We used the database from the 14-year Korea National Health Insurance Service–National Sample Cohort. The data of 368,206 adults older than 20 years who received a health check-up were analyzed to explore the association of height and AF risk. Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of height with the risk of AF. During the median follow up duration of 8.46 years, 2641 (0.72%) patients were diagnosed with AF at 3,070,724 person-years. Overall, greater height was significantly associated with AF risk (HR per 5 cm, 1.22; 95% CI, 1.03–1.05). The association did not vary with age, sex, obesity, hypertension, and diabetes. Conclusion: Metabolic conditions do not affect the higher risk of AF in tall people. © 2020 Elsevier B.V. All rights reserved.
1. Introduction Atrial fibrillation (AF) amplifies the risk of major adverse cardiovascular events including stroke, heart failure, ischemic heart disease, sudden cardiac death, and all-cause mortality [1]. The prevalence of AF is projected to increase, primarily due to the aging population [2]. However, many cases of AF still occur among younger adults, leading researchers to explore other risk factors. The increase in AF may, at least in part, be attributable to the increasing body size of the population. Prior studies have established that diverse adiposity measures are associated with the risk of AF [3]. In addition, the association between increased height and AF has been observed in a wide range of Western cohorts [4–7]. Because a critical mass of atrial tissue necessary for AF to occur, the most plausible hypothesis is that increased heart size is associated with a higher risk of AF [7]. The pathophysiology of AF is heterogeneous and influenced by structural (e.g., left atrial size per se), hemodynamic (e.g., left atrial stretch), electrical, and neural factors [8]. Frequent AF in obese patients has been explained by several conditions causing atrial stretch, such as left ventricular hypertrophy, increased total blood volume, and metabolic clusters [9]. By contrast, it is unclear whether the elevated AF risk in tall people is simply due to the large left atrium or whether it is ⁎ Corresponding author at: Namdong-daero 774 beon-gil, Namdong-gu, Incheon 21565, South Korea. E-mail address: [email protected] (I.C. Hwang).
influenced by other metabolic disorders such as obesity, hypertension, and diabetes. The present study aimed to determine the interactive effects of these risk factors on AF in a large, population-based cohort. 2. Materials and methods 2.1. Database and study population The Korean National Health Insurance Service–National Sample Cohort (NHIS–NSC) 2002–2015 database was used for this populationbased cohort study [10]. The NHIS–NSC is compiled by the NHIS with a systematic sampling method and comprises approximately 1 million nationally representative randomly selected subjects. It is mandatory that all Koreans join the NHIS, and the NHIS database includes the national records of health care utilization and prescriptions for the entire Korean population. In addition, all insured individuals and their dependents are required to undergo a periodic (generally biennial) general health examination. The NHIS database (NHIS-2019-2-023) is open to researchers whose study protocols are approved by the Institutional Review Board of the NHIS Ilsan Hospital (2018-01-019). Because the NHIS data are encrypted to protect private information, the need for informed consent was waived. To yield height data, we identified 376,402 adults older than 20 years who underwent a national medical check-up between 2006 and 2009. Of these, we excluded patients who were diagnosed before January 2006 (2002–2005) AF (n = 2129), valvular heart disease
https://doi.org/10.1016/j.ijcard.2020.01.017 0167-5273/© 2020 Elsevier B.V. All rights reserved.
Please cite this article as: Y.M. Park, J. Moon, I.C. Hwang, et al., Height is associated with incident atrial fibrillation in a large Asian cohort, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.017
2
Y.M. Park et al. / International Journal of Cardiology xxx (xxxx) xxx
(n = 5460), or other vascular diseases (n = 427) such as stroke, transient ischemic accident, heart failure, thromboembolism, myocardial infarction, and peripheral arterial obstructive disease. All diseases were identified using the International Classification of Disease 10th Revision (ICD-10) codes. Finally, 368,206 adults were eligible for follow up to collect incident AF data. 2.2. Ascertainment of atrial fibrillation AF diagnosis was defined using ICD-10 codes I480–I484 and I489. To ensure diagnostic accuracy, patients were considered to have AF only when AF was a discharge diagnosis or confirmed at least twice in the outpatient department. The positive predictive value of AF diagnosis in the NHIS database is 94.1%.
Table 1 Factors associated with incident atrial fibrillation in the cohort.
Height, per 5 cm increment Age, per 1 year Female sex Low incomeb Current smoking Moderate or heavy drinking Body mass index, kg/m2 b18.5 18.5–22.9 23.0–24.9 ≥25 Hypertension Type 2 diabetes
Hazard ratioa
95% confidence interval
P value
1.223 1.068 0.958 1.029 0.917 1.137
1.034–1.049 1.064–1.072 0.835–1.098 0.949–1.117 0.823–1.022 0.848–1.524
b0.001 b0.001 0.537 0.488 0.118 0.392
0.806 1 1.126 1.263 2.473 0.821
0.606–1.071
0.136
1.011–1.254 1.145–1.394 2.254–2.713 0.727–0.927
0.031 b0.001 b0.001 0.002
a
2.3. Exposures and covariates During an examination, height and weight are measured using standard protocols. Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters. We primarily considered height as a continuous variable and classified the individuals into four groups by BMI (underweight, normal, overweight, and obese). Menopause was assumed at the age of 50 years based on nationwide Korean data. Smoking status (never or ex-smoking/current) and alcohol consumption (rarely or light/moderate or heavy) were assessed by a questionnaire. Because the total annual health insurance premium paid by insured individuals is proportional to income, it was used to categorize individuals into ten ranking groups by economic status. We obtained information on comorbidities (i.e., hypertension and type 2 diabetes) from the hospital diagnoses in the medical records. These comorbidities were defined according to the ICD-10 codes and prescription medication use at the time of AF diagnosis. 2.4. Statistical analysis We calculated the incidence per 1000 person-years by dividing the number of AF events by the total number of person-years at risk and multiplying this result by 1000. We assessed the accumulated personyears of risk, beginning with the date of examination and ending with the date of AF diagnosis, death, or December 31, 2015, whichever came first. To investigate the independent effect of height on AF risk, we conducted multivariable survival analyses using the Breslow method after adjusting for all potential confounders. We also conducted subgroup analyses stratified by age, sex, obesity, and medical comorbidities. In these stratified multivariable analyses, the association between height and the risk of AF was reexamined in the different subgroups. All time-varying factors were modeled as time-dependent covariates. All tests were two-tailed, and a P value b 0.05 was considered to be significant. We conducted all analyses using SAS version 9.3 (SAS Institute, Cary, NC, USA). 3. Results Mean age was 43.2 ± 13.6 years for men and 45.2 ± 14.1 years for women. Mean height was 170.1 ± 6.4 for men and 156.8 ± 6.1 years for women. Among the 368,206 individuals in this cohort, 2641 were diagnosed with AF at 3,070,724 person-years of follow up (mean, 8.46 years). Factors associated with AF in the current cohort were presented in Table 1. Table 2 shows the risk of AF in the overall study population and by subgroup in 5-cm increments of height. Overall, the AF risk increased 1.22 times per 5-cm increment. The significant relationship between height and AF risk was found to remain uninfluenced by any clinical factors such as age, sex, obesity, hypertension, and type 2 diabetes (all Pheterogeneity N 0.05).
From stepwise multivariable regression analysis. By the total annual national health insurance premium (rank 1–8 groups vs. rank 9–10 groups). b
4. Discussion Currently, height is well-recognized as a definite risk factor for AF. In this large national cohort study, we found that tall people are at high risk for AF and that this association is not affected by metabolic risk factors, such as obesity or diabetes. Our results would explain, at least in part, the variation in AF epidemiology, suggesting that high AF incidence in tall people is attributable to height itself. The high prevalence of AF is noted among men and in Western countries [2], and parallels the increasing mean height over time worldwide [11]. In addition to the large sample size, which allowed for stratified analysis, our study has several strengths. First, this is a nationwide representative study focused on the association between height and AF, not skewed in the distribution of age. Although a study including older adults inherently contains survival bias [7], inclusion of younger subjects yields too few comorbidities to analyze [5,6]. To date, no adequately powered studies have shown that these conditions can affect the association between height and AF. Second, only one Asian study on this topic has been reported; it was a single-hospital study that found a nearly crude association when considering BMI separately [12]. Both height and AF vary with many factors including sex, race, and socioeconomic status of a given society [13]. Currently, larger left atrial size—needed to enhance and/or propagate the ectopic activity—is recognized as an important risk factor for AF [14,15]. Given that height correlates positively with left atrial size [16], taller people are at higher risk for AF. However, there has been some reports that left atrial size has little effect on the increased AF risk of tall people [7,12]. Therefore, further exploration of the mechanisms by which increased height mediates risk of AF is necessary.
5. Study limitations One potential flaw with this study is the residual confounding factors inherent in any observational study. We were not able to obtain the clinical data such as echocardiographic findings, which might be helpful to interpret our results. Lifestyles, particularly for physical activity [17], were also not considered but are highly variable over time. Another limitation of our study is healthy user bias. We may have overestimated the risk of AF associated with increasing height because tall people have higher incomes [18] and receive health check-ups more often than short people. Finally, we just relied on the ICD-codes for identification of AF events leading to the underestimation of AF prevalence, because it neglects asymptomatic AF. Well-designed prospective cohort studies are required before these defects can be dismissed.
Please cite this article as: Y.M. Park, J. Moon, I.C. Hwang, et al., Height is associated with incident atrial fibrillation in a large Asian cohort, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.017
Y.M. Park et al. / International Journal of Cardiology xxx (xxxx) xxx
3
Table 2 Risk of atrial fibrillation in 5-cm height increments by group.
Overall Age, years 20–39 40–59 ≥60 Sex Men Premenopausal women Postmenopausal women Body mass index, kg/m2 b18.5 18.5–22.9 23.0–24.9 ≥25 With hypertension Yes No With type 2 diabetes Yes No
No.
Cases
Person-years
Incidence rate (per 103 person-years)
Hazard ratioa (95% CI)
368,206
2641
3,070,724
0.86
1.22 (1.03–1.05)
146,768 165,863 55,575
233 1105 1303
1,209,881 1,391,530 469,313
0.19 0.79 2.78
1.19 (1.01–1.06) 1.14 (1.02–1.04) 1.16 (1.02–1.04)
0.961
193,506 110,616 64,084
1641 195 805
1,629,825 902,293 538,606
1.01 0.22 1.49
1.24 (1.04–1.05) 1.21 (1.01–1.07) 1.19 (1.02–1.05)
0.463
15,084 149,637 89,108 114,377
58 800 698 1085
124,962 1,246,715 746,354 952,694
0.46 0.64 0.94 1.14
1.22 (0.99–1.09) 1.18 (1.02–1.05) 1.25 (1.03–1.06) 1.24 (1.03–1.06)
0.871
67,739 300,467
1455 1186
570,655 2,500,069
2.55 0.47
1.22 (1.03–1.05) 1.24 (1.03–1.06)
0.251
23,167 345,039
355 2286
194,426 2,876,299
1.83 0.79
1.26 (1.03–1.07) 1.22 (1.03–1.05)
0.678
PHeterogeneity
CI, confidence interval. a Adjusted for age, sex, insurance premium level, body mass index, smoking history, drinking history, hypertension and diabetes.
6. Conclusion In summary, a robust association between tall stature and AF was found in this large Asian cohort, with no interaction of age, sex, obesity, and metabolic comorbidities. These findings suggest the important role of absolute heart size on the development of AF. Regardless of clinical factors, tall people may be a high-risk subgroup for incident AF. Further basic or genetic studies are needed to fully understand the role of height in the development of AF. CRediT authorship contribution statement Young Min Park:Conceptualization, Writing - original draft. Jeonggeun Moon:Conceptualization, Supervision, Writing - review & editing.In Cheol Hwang:Conceptualization, Methodology, Supervision, Writing - review & editing.Hyunsun Lim:Methodology, Data curation, Formal analysis.Bokeum Cho:Methodology, Data curation, Formal analysis. Declaration of competing interest There are no potential conflicts of interest. Acknowledgements Drs. Park and Moon contributed equally to this work. We received no financial support for the research, authorship and/or publication of this article. References [1] A. Odutayo, C.X. Wong, A.J. Hsiao, S. Hopewell, D.G. Altman, C.A. Emdin, Atrial fibrillation and risks of cardiovascular disease, renal disease, and death: systematic review and meta-analysis, BMJ. 354 (2016) i4482. [2] S.S. Chugh, R. Havmoeller, K. Narayanan, D. Singh, M. Rienstra, E.J. Benjamin, et al., Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study, Circulation. 129 (2014) 837–847.
[3] D. Aune, A. Sen, S. Schlesinger, T. Norat, I. Janszky, P. Romundstad, et al., Body mass index, abdominal fatness, fat mass and the risk of atrial fibrillation: a systematic review and dose-response meta-analysis of prospective studies, Eur. J. Epidemiol. 32 (2017) 181–192. [4] J.L. Marott, A.K. Skielboe, U. Dixen, J.B. Friberg, P. Schnohr, G.B. Jensen, Increasing population height and risk of incident atrial fibrillation: the Copenhagen City Heart Study, Eur. Heart J. 39 (2018) 4012–4019. [5] K. Andersen, F. Rasmussen, M. Neovius, P. Tynelius, J. Sundstrom, Body size and risk of atrial fibrillation: a cohort study of 1.1 million young men, J. Intern. Med. 283 (2018) 346–355. [6] M. Schmidt, H.E. Botker, L. Pedersen, H.T. Sorensen, Adult height and risk of ischemic heart disease, atrial fibrillation, stroke, venous thromboembolism, and premature death: a population based 36-year follow-up study, Eur. J. Epidemiol. 29 (2014) 111–118. [7] M.A. Rosenberg, K.K. Patton, N. Sotoodehnia, M.G. Karas, J.R. Kizer, P.J. Zimetbaum, et al., The impact of height on the risk of atrial fibrillation: the Cardiovascular Health Study, Eur. Heart J. 33 (2012) 2709–2717. [8] Y.K. Iwasaki, K. Nishida, T. Kato, S. Nattel, Atrial fibrillation pathophysiology: implications for management, Circulation. 124 (2011) 2264–2274. [9] C.J. Nalliah, P. Sanders, H. Kottkamp, J.M. Kalman, The role of obesity in atrial fibrillation, Eur. Heart J. 37 (2016) 1565–1572. [10] J. Lee, J.S. Lee, S.H. Park, S.A. Shin, K. Kim, Cohort profile: the National Health Insurance Service-National Sample Cohort (NHIS-NSC), South Korea, Int. J. Epidemiol. 46 (2017) e15. [11] Collaboration NCDRF, A century of trends in adult human height, Elife. 5 (2016). [12] S. Suzuki, T. Yamashita, T. Ohtsuka, K. Sagara, T. Uejima, Y. Oikawa, et al., Body size and atrial fibrillation in Japanese outpatients, Circ. J. 74 (2010) 66–70. [13] Y.G. Li, D. Pastori, A. Farcomeni, P.S. Yang, E. Jang, B. Joung, et al., A simple clinical risk score (C2HEST) for predicting incident atrial fibrillation in Asian subjects: derivation in 471,446 Chinese subjects, with internal validation and external application in 451,199 Korean subjects, Chest. 155 (2019) 510–518. [14] D. Conen, M. Adam, F. Roche, J.C. Barthelemy, D. Felber Dietrich, M. Imboden, et al., Premature atrial contractions in the general population: frequency and risk factors, Circulation. 126 (2012) 2302–2308. [15] L. Mont, D. Tamborero, R. Elosua, I. Molina, B. Coll-Vinent, M. Sitges, et al., Physical activity, height, and left atrial size are independent risk factors for lone atrial fibrillation in middle-aged healthy individuals, Europace. 10 (2008) 15–20. [16] R.S. Vasan, M.G. Larson, D. Levy, J.C. Evans, E.J. Benjamin, Distribution and categorization of echocardiographic measurements in relation to reference limits: the Framingham Heart Study: formulation of a height- and sex-specific classification and its prospective validation, Circulation. 96 (1997) 1863–1873. [17] B. Morseth, M.L. Lochen, I. Ariansen, M. Myrstad, D.S. Thelle, The ambiguity of physical activity, exercise and atrial fibrillation, Eur. J. Prev. Cardiol. 25 (2018) 624–636. [18] J. Tyrrell, S.E. Jones, R. Beaumont, C.M. Astley, R. Lovell, H. Yaghootkar, et al., Height, body mass index, and socioeconomic status: mendelian randomisation study in UK Biobank, BMJ. i582 (2016) 352.
Please cite this article as: Y.M. Park, J. Moon, I.C. Hwang, et al., Height is associated with incident atrial fibrillation in a large Asian cohort, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.017
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Short communication
Height is associated with incident atrial fibrillation in a large Asian cohort Young Min Park a, Jeonggeun Moon b, In Cheol Hwang c,⁎, Hyunsun Lim d, Bokeum Cho e a
Department of Family Medicine, National Health Insurance Service Ilsan Hospital, Goyang, South Korea Cardiology Division, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea c Department of Family Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, South Korea d Department of Policy Research Affairs, National Health Insurance Service Ilsan Hospital, Goyang, South Korea e Division of Humanities Arts and Social Sciences, Underwood International College of Yonsei University, Seoul, South Korea b
a r t i c l e
i n f o
Article history: Received 10 December 2019 Received in revised form 1 January 2020 Accepted 9 January 2020 Available online xxxx Keywords: Asian Atrial fibrillation Height Risk factors
a b s t r a c t Background: Although increased height is associated with a risk of atrial fibrillation (AF), the mechanism is not well understood. We aimed to explore whether this association varies with metabolic conditions. Methods and results: We used the database from the 14-year Korea National Health Insurance Service–National Sample Cohort. The data of 368,206 adults older than 20 years who received a health check-up were analyzed to explore the association of height and AF risk. Cox proportional hazards regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of height with the risk of AF. During the median follow up duration of 8.46 years, 2641 (0.72%) patients were diagnosed with AF at 3,070,724 person-years. Overall, greater height was significantly associated with AF risk (HR per 5 cm, 1.22; 95% CI, 1.03–1.05). The association did not vary with age, sex, obesity, hypertension, and diabetes. Conclusion: Metabolic conditions do not affect the higher risk of AF in tall people. © 2020 Elsevier B.V. All rights reserved.
1. Introduction Atrial fibrillation (AF) amplifies the risk of major adverse cardiovascular events including stroke, heart failure, ischemic heart disease, sudden cardiac death, and all-cause mortality [1]. The prevalence of AF is projected to increase, primarily due to the aging population [2]. However, many cases of AF still occur among younger adults, leading researchers to explore other risk factors. The increase in AF may, at least in part, be attributable to the increasing body size of the population. Prior studies have established that diverse adiposity measures are associated with the risk of AF [3]. In addition, the association between increased height and AF has been observed in a wide range of Western cohorts [4–7]. Because a critical mass of atrial tissue necessary for AF to occur, the most plausible hypothesis is that increased heart size is associated with a higher risk of AF [7]. The pathophysiology of AF is heterogeneous and influenced by structural (e.g., left atrial size per se), hemodynamic (e.g., left atrial stretch), electrical, and neural factors [8]. Frequent AF in obese patients has been explained by several conditions causing atrial stretch, such as left ventricular hypertrophy, increased total blood volume, and metabolic clusters [9]. By contrast, it is unclear whether the elevated AF risk in tall people is simply due to the large left atrium or whether it is ⁎ Corresponding author at: Namdong-daero 774 beon-gil, Namdong-gu, Incheon 21565, South Korea. E-mail address: [email protected] (I.C. Hwang).
influenced by other metabolic disorders such as obesity, hypertension, and diabetes. The present study aimed to determine the interactive effects of these risk factors on AF in a large, population-based cohort. 2. Materials and methods 2.1. Database and study population The Korean National Health Insurance Service–National Sample Cohort (NHIS–NSC) 2002–2015 database was used for this populationbased cohort study [10]. The NHIS–NSC is compiled by the NHIS with a systematic sampling method and comprises approximately 1 million nationally representative randomly selected subjects. It is mandatory that all Koreans join the NHIS, and the NHIS database includes the national records of health care utilization and prescriptions for the entire Korean population. In addition, all insured individuals and their dependents are required to undergo a periodic (generally biennial) general health examination. The NHIS database (NHIS-2019-2-023) is open to researchers whose study protocols are approved by the Institutional Review Board of the NHIS Ilsan Hospital (2018-01-019). Because the NHIS data are encrypted to protect private information, the need for informed consent was waived. To yield height data, we identified 376,402 adults older than 20 years who underwent a national medical check-up between 2006 and 2009. Of these, we excluded patients who were diagnosed before January 2006 (2002–2005) AF (n = 2129), valvular heart disease
https://doi.org/10.1016/j.ijcard.2020.01.017 0167-5273/© 2020 Elsevier B.V. All rights reserved.
Please cite this article as: Y.M. Park, J. Moon, I.C. Hwang, et al., Height is associated with incident atrial fibrillation in a large Asian cohort, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.017
2
Y.M. Park et al. / International Journal of Cardiology xxx (xxxx) xxx
(n = 5460), or other vascular diseases (n = 427) such as stroke, transient ischemic accident, heart failure, thromboembolism, myocardial infarction, and peripheral arterial obstructive disease. All diseases were identified using the International Classification of Disease 10th Revision (ICD-10) codes. Finally, 368,206 adults were eligible for follow up to collect incident AF data. 2.2. Ascertainment of atrial fibrillation AF diagnosis was defined using ICD-10 codes I480–I484 and I489. To ensure diagnostic accuracy, patients were considered to have AF only when AF was a discharge diagnosis or confirmed at least twice in the outpatient department. The positive predictive value of AF diagnosis in the NHIS database is 94.1%.
Table 1 Factors associated with incident atrial fibrillation in the cohort.
Height, per 5 cm increment Age, per 1 year Female sex Low incomeb Current smoking Moderate or heavy drinking Body mass index, kg/m2 b18.5 18.5–22.9 23.0–24.9 ≥25 Hypertension Type 2 diabetes
Hazard ratioa
95% confidence interval
P value
1.223 1.068 0.958 1.029 0.917 1.137
1.034–1.049 1.064–1.072 0.835–1.098 0.949–1.117 0.823–1.022 0.848–1.524
b0.001 b0.001 0.537 0.488 0.118 0.392
0.806 1 1.126 1.263 2.473 0.821
0.606–1.071
0.136
1.011–1.254 1.145–1.394 2.254–2.713 0.727–0.927
0.031 b0.001 b0.001 0.002
a
2.3. Exposures and covariates During an examination, height and weight are measured using standard protocols. Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters. We primarily considered height as a continuous variable and classified the individuals into four groups by BMI (underweight, normal, overweight, and obese). Menopause was assumed at the age of 50 years based on nationwide Korean data. Smoking status (never or ex-smoking/current) and alcohol consumption (rarely or light/moderate or heavy) were assessed by a questionnaire. Because the total annual health insurance premium paid by insured individuals is proportional to income, it was used to categorize individuals into ten ranking groups by economic status. We obtained information on comorbidities (i.e., hypertension and type 2 diabetes) from the hospital diagnoses in the medical records. These comorbidities were defined according to the ICD-10 codes and prescription medication use at the time of AF diagnosis. 2.4. Statistical analysis We calculated the incidence per 1000 person-years by dividing the number of AF events by the total number of person-years at risk and multiplying this result by 1000. We assessed the accumulated personyears of risk, beginning with the date of examination and ending with the date of AF diagnosis, death, or December 31, 2015, whichever came first. To investigate the independent effect of height on AF risk, we conducted multivariable survival analyses using the Breslow method after adjusting for all potential confounders. We also conducted subgroup analyses stratified by age, sex, obesity, and medical comorbidities. In these stratified multivariable analyses, the association between height and the risk of AF was reexamined in the different subgroups. All time-varying factors were modeled as time-dependent covariates. All tests were two-tailed, and a P value b 0.05 was considered to be significant. We conducted all analyses using SAS version 9.3 (SAS Institute, Cary, NC, USA). 3. Results Mean age was 43.2 ± 13.6 years for men and 45.2 ± 14.1 years for women. Mean height was 170.1 ± 6.4 for men and 156.8 ± 6.1 years for women. Among the 368,206 individuals in this cohort, 2641 were diagnosed with AF at 3,070,724 person-years of follow up (mean, 8.46 years). Factors associated with AF in the current cohort were presented in Table 1. Table 2 shows the risk of AF in the overall study population and by subgroup in 5-cm increments of height. Overall, the AF risk increased 1.22 times per 5-cm increment. The significant relationship between height and AF risk was found to remain uninfluenced by any clinical factors such as age, sex, obesity, hypertension, and type 2 diabetes (all Pheterogeneity N 0.05).
From stepwise multivariable regression analysis. By the total annual national health insurance premium (rank 1–8 groups vs. rank 9–10 groups). b
4. Discussion Currently, height is well-recognized as a definite risk factor for AF. In this large national cohort study, we found that tall people are at high risk for AF and that this association is not affected by metabolic risk factors, such as obesity or diabetes. Our results would explain, at least in part, the variation in AF epidemiology, suggesting that high AF incidence in tall people is attributable to height itself. The high prevalence of AF is noted among men and in Western countries [2], and parallels the increasing mean height over time worldwide [11]. In addition to the large sample size, which allowed for stratified analysis, our study has several strengths. First, this is a nationwide representative study focused on the association between height and AF, not skewed in the distribution of age. Although a study including older adults inherently contains survival bias [7], inclusion of younger subjects yields too few comorbidities to analyze [5,6]. To date, no adequately powered studies have shown that these conditions can affect the association between height and AF. Second, only one Asian study on this topic has been reported; it was a single-hospital study that found a nearly crude association when considering BMI separately [12]. Both height and AF vary with many factors including sex, race, and socioeconomic status of a given society [13]. Currently, larger left atrial size—needed to enhance and/or propagate the ectopic activity—is recognized as an important risk factor for AF [14,15]. Given that height correlates positively with left atrial size [16], taller people are at higher risk for AF. However, there has been some reports that left atrial size has little effect on the increased AF risk of tall people [7,12]. Therefore, further exploration of the mechanisms by which increased height mediates risk of AF is necessary.
5. Study limitations One potential flaw with this study is the residual confounding factors inherent in any observational study. We were not able to obtain the clinical data such as echocardiographic findings, which might be helpful to interpret our results. Lifestyles, particularly for physical activity [17], were also not considered but are highly variable over time. Another limitation of our study is healthy user bias. We may have overestimated the risk of AF associated with increasing height because tall people have higher incomes [18] and receive health check-ups more often than short people. Finally, we just relied on the ICD-codes for identification of AF events leading to the underestimation of AF prevalence, because it neglects asymptomatic AF. Well-designed prospective cohort studies are required before these defects can be dismissed.
Please cite this article as: Y.M. Park, J. Moon, I.C. Hwang, et al., Height is associated with incident atrial fibrillation in a large Asian cohort, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.017
Y.M. Park et al. / International Journal of Cardiology xxx (xxxx) xxx
3
Table 2 Risk of atrial fibrillation in 5-cm height increments by group.
Overall Age, years 20–39 40–59 ≥60 Sex Men Premenopausal women Postmenopausal women Body mass index, kg/m2 b18.5 18.5–22.9 23.0–24.9 ≥25 With hypertension Yes No With type 2 diabetes Yes No
No.
Cases
Person-years
Incidence rate (per 103 person-years)
Hazard ratioa (95% CI)
368,206
2641
3,070,724
0.86
1.22 (1.03–1.05)
146,768 165,863 55,575
233 1105 1303
1,209,881 1,391,530 469,313
0.19 0.79 2.78
1.19 (1.01–1.06) 1.14 (1.02–1.04) 1.16 (1.02–1.04)
0.961
193,506 110,616 64,084
1641 195 805
1,629,825 902,293 538,606
1.01 0.22 1.49
1.24 (1.04–1.05) 1.21 (1.01–1.07) 1.19 (1.02–1.05)
0.463
15,084 149,637 89,108 114,377
58 800 698 1085
124,962 1,246,715 746,354 952,694
0.46 0.64 0.94 1.14
1.22 (0.99–1.09) 1.18 (1.02–1.05) 1.25 (1.03–1.06) 1.24 (1.03–1.06)
0.871
67,739 300,467
1455 1186
570,655 2,500,069
2.55 0.47
1.22 (1.03–1.05) 1.24 (1.03–1.06)
0.251
23,167 345,039
355 2286
194,426 2,876,299
1.83 0.79
1.26 (1.03–1.07) 1.22 (1.03–1.05)
0.678
PHeterogeneity
CI, confidence interval. a Adjusted for age, sex, insurance premium level, body mass index, smoking history, drinking history, hypertension and diabetes.
6. Conclusion In summary, a robust association between tall stature and AF was found in this large Asian cohort, with no interaction of age, sex, obesity, and metabolic comorbidities. These findings suggest the important role of absolute heart size on the development of AF. Regardless of clinical factors, tall people may be a high-risk subgroup for incident AF. Further basic or genetic studies are needed to fully understand the role of height in the development of AF. CRediT authorship contribution statement Young Min Park:Conceptualization, Writing - original draft. Jeonggeun Moon:Conceptualization, Supervision, Writing - review & editing.In Cheol Hwang:Conceptualization, Methodology, Supervision, Writing - review & editing.Hyunsun Lim:Methodology, Data curation, Formal analysis.Bokeum Cho:Methodology, Data curation, Formal analysis. Declaration of competing interest There are no potential conflicts of interest. Acknowledgements Drs. Park and Moon contributed equally to this work. We received no financial support for the research, authorship and/or publication of this article. References [1] A. Odutayo, C.X. Wong, A.J. Hsiao, S. Hopewell, D.G. Altman, C.A. Emdin, Atrial fibrillation and risks of cardiovascular disease, renal disease, and death: systematic review and meta-analysis, BMJ. 354 (2016) i4482. [2] S.S. Chugh, R. Havmoeller, K. Narayanan, D. Singh, M. Rienstra, E.J. Benjamin, et al., Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study, Circulation. 129 (2014) 837–847.
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Please cite this article as: Y.M. Park, J. Moon, I.C. Hwang, et al., Height is associated with incident atrial fibrillation in a large Asian cohort, International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.017