Causal association between cervical vertebra related disorders and essential hypertension: a bidirectional two-sample Mendelian randomization study_Chinese Journal of Evidence-Based Medicine

Authors：

ZHONG Wenqing , ZHOU Shibo ,  YU Xing

The Third Orthopedics Department, Dongzhimen Hospital of Beijing University of Chinese Medicine, Beijing 100010, P. R. China;

Corresponding author：

YU Xing, Email: 20210941245@bucm.edu.cn

Keywords：

Mendelian randomization; Cervical; Essential hypertension; Causal relationship

DOI：

10.7507/1672-2531.202311185

Video：

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Objective To assess the causal relationship between cervical vertebra related disorders and essential hypertension using a bidirectional two-sample Mendelian randomization study approach. Method The research data comes from the genome-wide association study dataset. Four types of cervical vertebra related disorders: cervicalgia, cervical disc disorders, cervical root disorders, injury of nerves and spinal cord at neck level, as well as data on essential hypertension, were selected for the study. Relevant single nucleotide polymorphisms were selected as instrumental variables to assess the causal relationship between cervical vertebra related disorders and essential hypertension mainly by inverse variance weighted model ratio. Cochran's Q test was used to detect heterogeneity, MR-Egger intercept term and MR-PRESSO was used to detect multiplicity, and leave-one-out method was used for sensitivity analysis. Results Cervicalgia had a positive causal relationship with the essential hypertension (OR=1.01, 95%CI 1.00 to1.02, P=0.019). Essential hypertension had a positive causal relationship with the cervical disc disorders (OR=4.08, 95%CI 1.57 to10.61, P=0.004). There was no significant causal relationship between cervical root disorders, injury of nerves and spinal cord at neck level and essential hypertension. Reliability assessment indicates that the study results were reliable. Conclusion Cervicalgia is a risk factor for essential hypertension; Essential hypertension is a risk factor for cervical disc lesions; There is no correlation between cervical root disorders, injury of nerves and spinal cord at neck level and essential hypertension.

1.	Saxena T, Ali AO, Saxena M. Pathophysiology of essential hypertension: an update. Expert Rev Cardiovasc Ther, 2018, 16(12): 879-887.
2.	Singh M, Mensah GA, Bakris G. Pathogenesis and clinical physiology of hypertension. Cardiol Clin, 2010, 28(4): 545-559.
3.	Muller DN, Kvakan H, Luft FC. Immune-related effects in hypertension and target-organ damage. Curr Opin Nephrol Hypertens, 2011, 20(2): 113-117.
4.	Ceravolo GS, Montezano AC, Jordão MT, et al. An interaction of renin-angiotensin and kallikrein-kinin systems contributes to vascular hypertrophy in angiotensin II-induced hypertension: in vivo and in vitro studies. PLoS One, 2014, 9(11): e111117.
5.	2017 ACC/AHA Hypertension Guideline Writing Committee. Prevention, detection, evaluation, and management of high blood pressure in adults: synopsis of the 2017 American College of Cardiology/American Heart Association hypertension guideline. Ann Intern Med, 2018, 168(5): 351-358.
6.	2017 ACC/AHA Hypertension Guideline Writing Committee. Essential hypertension. Lancet, 2007, 370(9587): 591-603.
7.	Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol, 2020, 16(4): 223-237.
8.	Lawes CM, Vander Hoorn S, Rodgers A, et al. Global burden of blood-pressure-related disease, 2001. Lancet, 2008, 371(9623): 1513-1518.
9.	Vallée A, Safar ME, Blacher J. Essential hypertension: definitions, hemodynamic, clinical and therapeutic review. Presse Med, 2019, 48(1): 19-28.
10.	Makka N, Adam N, Rose D. A study on the prevalence of pathologies of the cervical spine in patients with essential hypertension. J Hyper, 2016, 34(Suppl 1): e130.
11.	Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report JAMA, 2003, 289(19): 2560-2572.
12.	Wang X, Bots ML, Yang F, et al. Prevalence of hypertension in China: a systematic review and meta-regression analysis of trends and regional differences. J Hypertens, 2014, 32(10): 1919-1927.
13.	Kalb S, Zaidi HA, Ribas-Nijkerk JC, et al. Persistent outpatient hypertension is independently associated with spinal cord dysfunction and imaging characteristics of spinal cord damage among patients with cervical spondylosis. World Neurosurg, 2015, 84(2): 351-357.
14.	Perdomo-Pantoja A, Chara A, Kalb S, et al. The effect of renin-angiotensin system blockers on spinal cord dysfunction and imaging features of spinal cord compression in patients with symptomatic cervical spondylosis. Spine J, 2020, 20(4): 519-529.
15.	Saccò M, Meschi M, Regolisti G, et al. The relationship between blood pressure and pain. J Clin Hypertens (Greenwich), 2013, 15(8): 600-605.
16.	Saxena T, Ali AO, Saxena M. Pathophysiology of essential hypertension: an update. Expert Rev Cardiovasc Ther, 2018, 16(12): 879-887.
17.	Seravalle G, Grassi G. Sympathetic nervous system and hypertension: new evidences. Auton Neurosci, 2022, 238: 102954.
18.	Perdomo-Pantoja A, Chara A, Liu A, et al. Surgical decompression for cervical spondylotic myelopathy in patients with associated hypertension: a single-center retrospective cohort and systematic review of the literature. World Neurosurg, 2021, 155: e119-e130.
19.	Peng B, Pang X, Li D, et al. Cervical spondylosis and hypertension: a clinical study of 2 cases. Medicine (Baltimore), 2015, 94(10): e618.
20.	Perdomo-Pantoja A, Chara A, Liu A, et al. Surgical decompression for cervical spondylotic myelopathy in patients with associated hypertension: a single-center retrospective cohort and systematic review of the literature. World Neurosurg, 2021, 155: e119-e130.
21.	Yang L, Yang C, Pang X, et al. Cervical decompression surgery for cervical spondylotic myelopathy and concomitant hypertension: a multicenter prospective cohort study. Spine (Phila Pa 1976), 2017, 42(12): 903-908.
22.	Katikar MD, Katikar DB, Sharma R. Effect of decompressive cervical spine surgery on hypertension in patients with cervical spondylotic myelopathy - a retrospective observational study. Indian J Anaesth, 2022, 66(Suppl 3): S169-S172.
23.	Sharma R, Garg K, Agrawal S, et al. Atypical symptoms of cervical spondylosis: is anterior cervical discectomy and fusion useful. - an institutional experience. Neurol India, 2021, 69(3): 595-601.
24.	Liu H, Ploumis A. Cervicogenic hypertension-a possible etiology and pathogenesis of essential hypertension. Hypothesis. 2012, 10: 1.
25.	Garg K, Aggarwal A. Effect of cervical decompression on atypical symptoms cervical spondylosis-a narrative review and meta-analysis. World Neurosurg, 2022, 157: 207-217.
26.	Lawlor DA, Harbord RM, Sterne JA, et al. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med, 2008, 27(8): 1133-1163.
27.	Hartwig FP, Borges MC, Horta BL, et al. Inflammatory biomarkers and risk of schizophrenia: a 2-sample Mendelian randomization study. JAMA Psychiatry, 2017, 74(12): 1226-1233.
28.	Sang N, Li BH, Zhang MY, et al. Bidirectional causal relationship between depression and frailty: a univariate and multivariate Mendelian randomisation study. Age Ageing, 2023, 52(7): afad113.
29.	Soremekun O, Musanabaganwa C, Uwineza A, et al. A Mendelian randomization study of genetic liability to post-traumatic stress disorder and risk of ischemic stroke. Transl Psychiatry, 2023, 13(1): 237.
30.	Smith GD, Lawlor DA, Harbord R, et al. Clustered environments and randomized genes: a fundamental distinction between conventional and genetic epidemiology. PLoS Med, 2007, 4(12): e352.
31.	Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA, 2017, 318(19): 1925-1926.
32.	Burgess S, Thompson SG,. Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol, 2011, 40(3): 755-764.
33.	周学龙, 何心愉, 马斗文, 等. 颈椎病与高血压的相关性研究概况. 广西中医药, 2022, 45(5): 71-74.
34.	于娟, 赵晓平, 范小璇, 等. 颈源性高血压病因病理研究进展. 实用心脑肺血管病杂志, 2021, 29(1): 128-133.
35.	Li ZQ, Zhao YP, Jia WY, et al. Surgical treatment of cervical spondylotic myelopathy associated hypertension--a retrospective study of 309 patients. PLoS One, 2015, 10(7): e0133828.
36.	Li P, Wei Z, Zhang H, et al. Effects of decompressive operation on cardiac autonomic regulation in patients with cervical spondylotic myelopathy: analysis of blood pressure, heart rate, and heart rate variability. Eur Spine J, 2019, 28(8): 1864-1871.
37.	Garg K, Aggarwal A. Effect of cervical decompression on atypical symptoms cervical spondylosis-a narrative review and meta-analysis. World Neurosurg, 2022, 157: 207-217.
38.	Liu H, Wang HB, Yue L, et al. Effects of decompressive cervical surgery on blood pressure in cervical spondylosis patients with hypertension: a time series cohort study. Int J Spine Surg, 2021, 15(4): 683-691.
39.	Li CY, Lin WC, Lu CY, et al. Prevalence of pain in community-dwelling older adults with hypertension in the United States. Sci Rep, 2022, 12(1): 8387.
40.	Hamam MS, Kunjummen E, Hussain MS, et al. Anxiety, depression, and pain: considerations in the treatment of patients with uncontrolled hypertension. Curr Hypertens Rep, 2020, 22(12): 106.
41.	Wang X, Ju J, Xu H. Nondrug therapies for hypertensive patients complicated with cervical spondylosis: a systematic review and meta-analysis. Medicine (Baltimore), 2020, 99(5): e19006.
42.	许建美, 杨佳曼, 梁满光, 等. 低头摇正法联合颈三针治疗颈源性高血压的临床观察. 广州中医药大学学报, 2023, 40(6): 1414-1419.
43.	Guan H, Zhu H, Gao J, et al. A systematic review of Tuina for cervical hypertension: a protocol for systematic review and meta-analysis. Medicine (Baltimore), 2022, 101(40): e30699.
44.	Lotan R, Oron A, Anekstein Y, et al. Lumbar stenosis and systemic diseases: is there any relevance. J Spinal Disord Tech, 2008, 21(4): 247-251.
45.	Teraguchi M, Yoshimura N, Hashizume H, et al. Metabolic syndrome components are associated with intervertebral disc degeneration: the wakayama spine study. PLoS One, 2016, 11(2): e0147565.
46.	Jhawar BS, Fuchs CS, Colditz GA, et al. Cardiovascular risk factors for physician-diagnosed lumbar disc herniation. Spine J, 2006, 6(6): 684-691.
47.	Libby P, Buring JE, Badimon L, et al. Atherosclerosis. Nat Rev Dis Primers, 2019, 5(1): 56.
48.	Kauppila LI. Atherosclerosis and disc degeneration/low-back pain--a systematic review. Eur J Vasc Endovasc Surg, 2009, 37(6): 661-670.
49.	Hangai M, Kaneoka K, Kuno S, et al. Factors associated with lumbar intervertebral disc degeneration in the elderly. Spine J, 2008, 8(5): 732-740.
50.	Dowdell J, Erwin M, Choma T, et al. Intervertebral disk degeneration and repair. Neurosurgery, 2017, 80(3S): S46-S54.

1. Saxena T, Ali AO, Saxena M. Pathophysiology of essential hypertension: an update. Expert Rev Cardiovasc Ther, 2018, 16(12): 879-887.
2. Singh M, Mensah GA, Bakris G. Pathogenesis and clinical physiology of hypertension. Cardiol Clin, 2010, 28(4): 545-559.
3. Muller DN, Kvakan H, Luft FC. Immune-related effects in hypertension and target-organ damage. Curr Opin Nephrol Hypertens, 2011, 20(2): 113-117.
4. Ceravolo GS, Montezano AC, Jordão MT, et al. An interaction of renin-angiotensin and kallikrein-kinin systems contributes to vascular hypertrophy in angiotensin II-induced hypertension: in vivo and in vitro studies. PLoS One, 2014, 9(11): e111117.
5. 2017 ACC/AHA Hypertension Guideline Writing Committee. Prevention, detection, evaluation, and management of high blood pressure in adults: synopsis of the 2017 American College of Cardiology/American Heart Association hypertension guideline. Ann Intern Med, 2018, 168(5): 351-358.
6. 2017 ACC/AHA Hypertension Guideline Writing Committee. Essential hypertension. Lancet, 2007, 370(9587): 591-603.
7. Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol, 2020, 16(4): 223-237.
8. Lawes CM, Vander Hoorn S, Rodgers A, et al. Global burden of blood-pressure-related disease, 2001. Lancet, 2008, 371(9623): 1513-1518.
9. Vallée A, Safar ME, Blacher J. Essential hypertension: definitions, hemodynamic, clinical and therapeutic review. Presse Med, 2019, 48(1): 19-28.
10. Makka N, Adam N, Rose D. A study on the prevalence of pathologies of the cervical spine in patients with essential hypertension. J Hyper, 2016, 34(Suppl 1): e130.
11. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report JAMA, 2003, 289(19): 2560-2572.
12. Wang X, Bots ML, Yang F, et al. Prevalence of hypertension in China: a systematic review and meta-regression analysis of trends and regional differences. J Hypertens, 2014, 32(10): 1919-1927.
13. Kalb S, Zaidi HA, Ribas-Nijkerk JC, et al. Persistent outpatient hypertension is independently associated with spinal cord dysfunction and imaging characteristics of spinal cord damage among patients with cervical spondylosis. World Neurosurg, 2015, 84(2): 351-357.
14. Perdomo-Pantoja A, Chara A, Kalb S, et al. The effect of renin-angiotensin system blockers on spinal cord dysfunction and imaging features of spinal cord compression in patients with symptomatic cervical spondylosis. Spine J, 2020, 20(4): 519-529.
15. Saccò M, Meschi M, Regolisti G, et al. The relationship between blood pressure and pain. J Clin Hypertens (Greenwich), 2013, 15(8): 600-605.
16. Saxena T, Ali AO, Saxena M. Pathophysiology of essential hypertension: an update. Expert Rev Cardiovasc Ther, 2018, 16(12): 879-887.
17. Seravalle G, Grassi G. Sympathetic nervous system and hypertension: new evidences. Auton Neurosci, 2022, 238: 102954.
18. Perdomo-Pantoja A, Chara A, Liu A, et al. Surgical decompression for cervical spondylotic myelopathy in patients with associated hypertension: a single-center retrospective cohort and systematic review of the literature. World Neurosurg, 2021, 155: e119-e130.
19. Peng B, Pang X, Li D, et al. Cervical spondylosis and hypertension: a clinical study of 2 cases. Medicine (Baltimore), 2015, 94(10): e618.
20. Perdomo-Pantoja A, Chara A, Liu A, et al. Surgical decompression for cervical spondylotic myelopathy in patients with associated hypertension: a single-center retrospective cohort and systematic review of the literature. World Neurosurg, 2021, 155: e119-e130.
21. Yang L, Yang C, Pang X, et al. Cervical decompression surgery for cervical spondylotic myelopathy and concomitant hypertension: a multicenter prospective cohort study. Spine (Phila Pa 1976), 2017, 42(12): 903-908.
22. Katikar MD, Katikar DB, Sharma R. Effect of decompressive cervical spine surgery on hypertension in patients with cervical spondylotic myelopathy - a retrospective observational study. Indian J Anaesth, 2022, 66(Suppl 3): S169-S172.
23. Sharma R, Garg K, Agrawal S, et al. Atypical symptoms of cervical spondylosis: is anterior cervical discectomy and fusion useful. - an institutional experience. Neurol India, 2021, 69(3): 595-601.
24. Liu H, Ploumis A. Cervicogenic hypertension-a possible etiology and pathogenesis of essential hypertension. Hypothesis. 2012, 10: 1.
25. Garg K, Aggarwal A. Effect of cervical decompression on atypical symptoms cervical spondylosis-a narrative review and meta-analysis. World Neurosurg, 2022, 157: 207-217.
26. Lawlor DA, Harbord RM, Sterne JA, et al. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med, 2008, 27(8): 1133-1163.
27. Hartwig FP, Borges MC, Horta BL, et al. Inflammatory biomarkers and risk of schizophrenia: a 2-sample Mendelian randomization study. JAMA Psychiatry, 2017, 74(12): 1226-1233.
28. Sang N, Li BH, Zhang MY, et al. Bidirectional causal relationship between depression and frailty: a univariate and multivariate Mendelian randomisation study. Age Ageing, 2023, 52(7): afad113.
29. Soremekun O, Musanabaganwa C, Uwineza A, et al. A Mendelian randomization study of genetic liability to post-traumatic stress disorder and risk of ischemic stroke. Transl Psychiatry, 2023, 13(1): 237.
30. Smith GD, Lawlor DA, Harbord R, et al. Clustered environments and randomized genes: a fundamental distinction between conventional and genetic epidemiology. PLoS Med, 2007, 4(12): e352.
31. Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA, 2017, 318(19): 1925-1926.
32. Burgess S, Thompson SG,. Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol, 2011, 40(3): 755-764.
33. 周学龙, 何心愉, 马斗文, 等. 颈椎病与高血压的相关性研究概况. 广西中医药, 2022, 45(5): 71-74.
34. 于娟, 赵晓平, 范小璇, 等. 颈源性高血压病因病理研究进展. 实用心脑肺血管病杂志, 2021, 29(1): 128-133.
35. Li ZQ, Zhao YP, Jia WY, et al. Surgical treatment of cervical spondylotic myelopathy associated hypertension--a retrospective study of 309 patients. PLoS One, 2015, 10(7): e0133828.
36. Li P, Wei Z, Zhang H, et al. Effects of decompressive operation on cardiac autonomic regulation in patients with cervical spondylotic myelopathy: analysis of blood pressure, heart rate, and heart rate variability. Eur Spine J, 2019, 28(8): 1864-1871.
37. Garg K, Aggarwal A. Effect of cervical decompression on atypical symptoms cervical spondylosis-a narrative review and meta-analysis. World Neurosurg, 2022, 157: 207-217.
38. Liu H, Wang HB, Yue L, et al. Effects of decompressive cervical surgery on blood pressure in cervical spondylosis patients with hypertension: a time series cohort study. Int J Spine Surg, 2021, 15(4): 683-691.
39. Li CY, Lin WC, Lu CY, et al. Prevalence of pain in community-dwelling older adults with hypertension in the United States. Sci Rep, 2022, 12(1): 8387.
40. Hamam MS, Kunjummen E, Hussain MS, et al. Anxiety, depression, and pain: considerations in the treatment of patients with uncontrolled hypertension. Curr Hypertens Rep, 2020, 22(12): 106.
41. Wang X, Ju J, Xu H. Nondrug therapies for hypertensive patients complicated with cervical spondylosis: a systematic review and meta-analysis. Medicine (Baltimore), 2020, 99(5): e19006.
42. 许建美, 杨佳曼, 梁满光, 等. 低头摇正法联合颈三针治疗颈源性高血压的临床观察. 广州中医药大学学报, 2023, 40(6): 1414-1419.
43. Guan H, Zhu H, Gao J, et al. A systematic review of Tuina for cervical hypertension: a protocol for systematic review and meta-analysis. Medicine (Baltimore), 2022, 101(40): e30699.
44. Lotan R, Oron A, Anekstein Y, et al. Lumbar stenosis and systemic diseases: is there any relevance. J Spinal Disord Tech, 2008, 21(4): 247-251.
45. Teraguchi M, Yoshimura N, Hashizume H, et al. Metabolic syndrome components are associated with intervertebral disc degeneration: the wakayama spine study. PLoS One, 2016, 11(2): e0147565.
46. Jhawar BS, Fuchs CS, Colditz GA, et al. Cardiovascular risk factors for physician-diagnosed lumbar disc herniation. Spine J, 2006, 6(6): 684-691.
47. Libby P, Buring JE, Badimon L, et al. Atherosclerosis. Nat Rev Dis Primers, 2019, 5(1): 56.
48. Kauppila LI. Atherosclerosis and disc degeneration/low-back pain--a systematic review. Eur J Vasc Endovasc Surg, 2009, 37(6): 661-670.
49. Hangai M, Kaneoka K, Kuno S, et al. Factors associated with lumbar intervertebral disc degeneration in the elderly. Spine J, 2008, 8(5): 732-740.
50. Dowdell J, Erwin M, Choma T, et al. Intervertebral disk degeneration and repair. Neurosurgery, 2017, 80(3S): S46-S54.

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Latest ArticlesCausal association between cervical vertebra related disorders and essential hypertension: a bidirectional two-sample Mendelian randomization study

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