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Comorbidity: A novel insight to aortic dissection
International Journal of Cardiology 207 (2016) 53–54
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Comorbidity: A novel insight to aortic dissection Gui-fangYang 1, Li-juan Sheng 1, Wen Peng, Zhen-yu Peng, Xiang-ping Chai ⁎ Department of Emergency, the Second Xiangya Hospital, Central South University, Changsha, China
a r t i c l e
i n f o
Article history: Received 27 November 2015 Accepted 1 January 2016 Available online 6 January 2016 Keywords: Comorbidity Aortic dissection Renal cyst Pregnancy
Dear Editors, We have recently read with great interest the letter by Fujita D et al. [1] concerning “A novel mutation of TGFBR2 causing Loeys-Dietz syndrome complicated with pregnancy-related fatal cervical arterial dissections”, they proposed that a novel missense mutation of the TGFBR2 gene in a Japanese woman with LDS. This woman was associated with acute type A aortic dissection in the first postpartium period and acute extensive type B aortic dissection involving the bilateral vertebral arteries and the right internal carotid artery with fatal subarachnoid hemorrhage in the second postpartum period. Acute aortic dissection (AD) is a catastrophic aortic disease with high mortality and morbidity, and it requires quick diagnosis and treatment [2]. However, the pathogenesis of AD is still not clear. Disease of the aortic media, with degeneration of the medial collagen and elastin, is the most common predisposing factor for AD. Evidence is increasing that patients with AD are always concomitant with other disorders sharing common pathogenesis. For instance, both Loeys-Dietz syndrome and aortic dissection have the common mutation of TGFB2 gene. Therefore, we propose a novel concept which is supposed to describe this phenomenon: comorbidity. According to Feinstein [3], who first introduced the concept ‘comorbidity’ in literature, described its definition as “in a patient with a particular index disease, the term co-morbidity refers to any additional co-
existing ailment”, which to date highlights the concomitance of one or more disorders (or diseases) with primary one [4]. In fact, both in clinical practice or previous literature, the comorbidity is very common. Recent studies demonstrated a close association between AD and renal cyst. EK et al. [5] found that the prevalence of renal cysts was higher in AD group compared with control group (33.8% vs 25.7%, p = 0.023). Furthermore, AD was forming in the PKD gene knocked out mouse model with autosomal dominant polycystic kidney disease. Chen et al. [6] found that the variation of matrix metalloproteinase 9 gene, which is known to be associated with renal cyst, plays an important role in the formation of AD. Meanwhile, Peng et al. [7] showed that both AD and renal cyst may be associated with low expression of polycystin1(PC1), which could be a potential biomarker for early diagnosis of acute AD. In addition, our previous study revealed an association between pregnancy and AD [8]. Pregnancy-related hormonal changes, such as the overexpression of estrogen and progestogen in late period of pregnancy, may add additional risk due to the upregulation of the estrogen and progestogen receptors in aorta. Therefore, high level of estrogen and progestogen has been suggested to be related with aorta degeneration, which includes hyperplasia of aortic smooth muscle, decrease of acid mucopolysaccharides and disintegrity of elastic fibers. Genetic diseases, such as Marfan syndrome and Turner syndrome, have very close relationship with AD. In the past few decades, an increase number of hereditary traits linked to AD have been discovered. It is reported that nearly 20% of AD patients are associated with a genetic disorder resulting in altered connective tissues [9]. Large clinical research revealed that both AD and other genetic diseases share similar gene mutation. For instance, mutations of FBN1 gene have been characterized in the patients with Marfan's syndrome, and the suppressed expression of FBN1 could induce aortic elastic fiber fracture and damage, which are also common in the progression of AD pathology [10]. As mentioned above, numerous researches have shown that AD patients share pathologic similarities with other diseases. Therefore, we propose a new concept of “comorbidity” in AD to describe this phenomenon. Moreover, comorbidity will be beneficial for a better understanding of the progress and prognosis of other diseases. Funding This manuscript was supported by the National Natural Science Foundation of China (81471896).
⁎ Corresponding author at: Department of Emergency, the Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, Hunan 410011, China. E-mail address: [email protected] (X. Chai). 1 These authors contributed equally to this study.
http://dx.doi.org/10.1016/j.ijcard.2016.01.054 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
Conflict of interest The authors have no real or perceived conflicts of interest to disclose.
54
Correspondence
References [1] D. Fujita, N. Takeda, H. Morita, et al., A novel mutation of TGFBR2 causing LoeysDietz syndrome complicated with pregnancy-related fatal cervical arterial dissections, Int. J. Cardiol. 201 (2015) 288–290. [2] R. Erbel, V. Aboyans, C. Boileau, et al., 2014 ESC guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The task force for the diagnosis and treatment of aortic diseases of the European Society of Cardiology (ESC), Eur. Heart J. 35 (2014) 2873–2926. [3] A.R. Feinstein, The pre-therapeutic classification of co-morbidity in chronic disease, J. Chronic Dis. 23 (1970) 455–468. [4] M. Jakovljević, L. Ostojić, Comorbidity and multimorbidity in medicine today: challenges and opportunities for bringing separated branches of medicine closer to each other, Psychiatr. Danub. 25 (Suppl. 1) (2013) 18–28.
[5] E.K. Kim, E.R. Choi, B.G. Song, et al., Presence of simple renal cysts is associated with increased risk of aortic dissection: a common manifestation of connective tissue degeneration? Heart 97 (2011) 55–59. [6] L. Chen, X. Wang, S.A. Carter, et al., A single nucleotide polymorphism in the matrix metalloproteinase 9 gene (-8202 A/G) is associated with thoracic aortic aneurysms and thoracic aortic dissection, J. Thorac. Cardiovasc. Surg. 131 (2006) 1045–1052. [7] W. Peng, Z. Peng, X. Chai, et al., Potential biomarkers for early diagnosis of acute aortic dissection, Heart Lung 44 (2015) 205–208. [8] G. Yang, W. Peng, Q. Zhao, J. Peng, X. Xiang, X. Chai, Aortic dissection in women during the course of pregnancy or puerperium: a report of 11 cases in central south China, Int. J. Clin. Exp. Med. 8 (2015) 11607–11612. [9] C.A. Nienaber, R.E. Clough, Management of acute aortic dissection, Lancet 385 (2015) 800–811. [10] C. Li, J. Shi, Y. Shi, Y. Guo, Unusual association of type A aortic dissection and aberrant right subclavian artery in Marfan syndrome, Int. J. Cardiol. 175 (2014) e14–e15.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Comorbidity: A novel insight to aortic dissection Gui-fangYang 1, Li-juan Sheng 1, Wen Peng, Zhen-yu Peng, Xiang-ping Chai ⁎ Department of Emergency, the Second Xiangya Hospital, Central South University, Changsha, China
a r t i c l e
i n f o
Article history: Received 27 November 2015 Accepted 1 January 2016 Available online 6 January 2016 Keywords: Comorbidity Aortic dissection Renal cyst Pregnancy
Dear Editors, We have recently read with great interest the letter by Fujita D et al. [1] concerning “A novel mutation of TGFBR2 causing Loeys-Dietz syndrome complicated with pregnancy-related fatal cervical arterial dissections”, they proposed that a novel missense mutation of the TGFBR2 gene in a Japanese woman with LDS. This woman was associated with acute type A aortic dissection in the first postpartium period and acute extensive type B aortic dissection involving the bilateral vertebral arteries and the right internal carotid artery with fatal subarachnoid hemorrhage in the second postpartum period. Acute aortic dissection (AD) is a catastrophic aortic disease with high mortality and morbidity, and it requires quick diagnosis and treatment [2]. However, the pathogenesis of AD is still not clear. Disease of the aortic media, with degeneration of the medial collagen and elastin, is the most common predisposing factor for AD. Evidence is increasing that patients with AD are always concomitant with other disorders sharing common pathogenesis. For instance, both Loeys-Dietz syndrome and aortic dissection have the common mutation of TGFB2 gene. Therefore, we propose a novel concept which is supposed to describe this phenomenon: comorbidity. According to Feinstein [3], who first introduced the concept ‘comorbidity’ in literature, described its definition as “in a patient with a particular index disease, the term co-morbidity refers to any additional co-
existing ailment”, which to date highlights the concomitance of one or more disorders (or diseases) with primary one [4]. In fact, both in clinical practice or previous literature, the comorbidity is very common. Recent studies demonstrated a close association between AD and renal cyst. EK et al. [5] found that the prevalence of renal cysts was higher in AD group compared with control group (33.8% vs 25.7%, p = 0.023). Furthermore, AD was forming in the PKD gene knocked out mouse model with autosomal dominant polycystic kidney disease. Chen et al. [6] found that the variation of matrix metalloproteinase 9 gene, which is known to be associated with renal cyst, plays an important role in the formation of AD. Meanwhile, Peng et al. [7] showed that both AD and renal cyst may be associated with low expression of polycystin1(PC1), which could be a potential biomarker for early diagnosis of acute AD. In addition, our previous study revealed an association between pregnancy and AD [8]. Pregnancy-related hormonal changes, such as the overexpression of estrogen and progestogen in late period of pregnancy, may add additional risk due to the upregulation of the estrogen and progestogen receptors in aorta. Therefore, high level of estrogen and progestogen has been suggested to be related with aorta degeneration, which includes hyperplasia of aortic smooth muscle, decrease of acid mucopolysaccharides and disintegrity of elastic fibers. Genetic diseases, such as Marfan syndrome and Turner syndrome, have very close relationship with AD. In the past few decades, an increase number of hereditary traits linked to AD have been discovered. It is reported that nearly 20% of AD patients are associated with a genetic disorder resulting in altered connective tissues [9]. Large clinical research revealed that both AD and other genetic diseases share similar gene mutation. For instance, mutations of FBN1 gene have been characterized in the patients with Marfan's syndrome, and the suppressed expression of FBN1 could induce aortic elastic fiber fracture and damage, which are also common in the progression of AD pathology [10]. As mentioned above, numerous researches have shown that AD patients share pathologic similarities with other diseases. Therefore, we propose a new concept of “comorbidity” in AD to describe this phenomenon. Moreover, comorbidity will be beneficial for a better understanding of the progress and prognosis of other diseases. Funding This manuscript was supported by the National Natural Science Foundation of China (81471896).
⁎ Corresponding author at: Department of Emergency, the Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, Hunan 410011, China. E-mail address: [email protected] (X. Chai). 1 These authors contributed equally to this study.
http://dx.doi.org/10.1016/j.ijcard.2016.01.054 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
Conflict of interest The authors have no real or perceived conflicts of interest to disclose.
54
Correspondence
References [1] D. Fujita, N. Takeda, H. Morita, et al., A novel mutation of TGFBR2 causing LoeysDietz syndrome complicated with pregnancy-related fatal cervical arterial dissections, Int. J. Cardiol. 201 (2015) 288–290. [2] R. Erbel, V. Aboyans, C. Boileau, et al., 2014 ESC guidelines on the diagnosis and treatment of aortic diseases: document covering acute and chronic aortic diseases of the thoracic and abdominal aorta of the adult. The task force for the diagnosis and treatment of aortic diseases of the European Society of Cardiology (ESC), Eur. Heart J. 35 (2014) 2873–2926. [3] A.R. Feinstein, The pre-therapeutic classification of co-morbidity in chronic disease, J. Chronic Dis. 23 (1970) 455–468. [4] M. Jakovljević, L. Ostojić, Comorbidity and multimorbidity in medicine today: challenges and opportunities for bringing separated branches of medicine closer to each other, Psychiatr. Danub. 25 (Suppl. 1) (2013) 18–28.
[5] E.K. Kim, E.R. Choi, B.G. Song, et al., Presence of simple renal cysts is associated with increased risk of aortic dissection: a common manifestation of connective tissue degeneration? Heart 97 (2011) 55–59. [6] L. Chen, X. Wang, S.A. Carter, et al., A single nucleotide polymorphism in the matrix metalloproteinase 9 gene (-8202 A/G) is associated with thoracic aortic aneurysms and thoracic aortic dissection, J. Thorac. Cardiovasc. Surg. 131 (2006) 1045–1052. [7] W. Peng, Z. Peng, X. Chai, et al., Potential biomarkers for early diagnosis of acute aortic dissection, Heart Lung 44 (2015) 205–208. [8] G. Yang, W. Peng, Q. Zhao, J. Peng, X. Xiang, X. Chai, Aortic dissection in women during the course of pregnancy or puerperium: a report of 11 cases in central south China, Int. J. Clin. Exp. Med. 8 (2015) 11607–11612. [9] C.A. Nienaber, R.E. Clough, Management of acute aortic dissection, Lancet 385 (2015) 800–811. [10] C. Li, J. Shi, Y. Shi, Y. Guo, Unusual association of type A aortic dissection and aberrant right subclavian artery in Marfan syndrome, Int. J. Cardiol. 175 (2014) e14–e15.