TY - JOUR

T1 - Repurposing Antihypertensive and Statin Medications for Spinal Pain: A Mendelian Randomization Study

AU - Suri, Pradeep

AU - Elgaeva, Elizaveta E

AU - Williams, Frances M K

AU - Freidin, Maxim B

AU - Verzun, Dmitrii A

AU - Tsepilov, Yakov A

N1 - CONFLICTS OF INTEREST AND SOURCES OF FUNDING: Dr. Suri is an employee of the VA Puget Sound Health Care System and the Director of the Resource Core of the University of Washington Clinical Learning, Evidence and Research (CLEAR) Center, which was funded by NIAMS/NIH P30AR072572. Ms. Elgaeva was supported by the Russian Science Foundation (RSF) grant № 22-15-20037 and Government of the Novosibirsk region. Dr. Tsepilov was supported by the budget project of the Institute of Cytology and Genetics № FWNR-2022-0020. The other authors declare that they have no competing interests. The contents of this work do not represent the views of the US Department of Veterans Affairs, the National Institutes of Health, or the US government. We are grateful to the UK Biobank participants for making such research possible. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2023/11/15

Y1 - 2023/11/15

N2 - STUDY DESIGN: Mendelian randomization (MR) study.OBJECTIVE: To examine whether antihypertensive medications (beta-blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors) and statins can be repurposed to prevent or treat spinal pain (back or neck pain).SUMMARY OF BACKGROUND DATA: Observational studies and a recent MR study have found associations between elevated blood pressure and a greater risk of back pain. Observational studies have found associations between hyperlipidemia and statin use and greater risk of back pain. No prior MR studies have examined the effects of antihypertensives or statins on spinal pain.MATERIALS AND METHODS: This was a two-sample MR study using publicly available summary statistics from large-scale genome-wide association studies (GWAS). Sample sizes in exposure GWASs were n=757,601 (systolic blood pressure) and n=173,082 (low-density lipoprotein cholesterol), and n=1,028,947 for the outcome GWAS of spinal pain defined as health care seeking for any spinal pain-related diagnosis. Genes and cis-acting variants were identified as proxies for the drug targets of interest. MR analyses used inverse-variance weighted meta-analysis. The threshold for statistical significance after correction for multiple testing was P <0.0125.RESULTS: No statistically significant associations of these medications with spinal pain were found. However, findings were suggestive of a protective effect of beta-blockers on spinal pain risk (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.72-0.98; P =0.03), and calcium channel blockers on greater spinal pain risk (OR 1.12, 95% CI 1.02-1.24; P =0.02).CONCLUSIONS: A protective effect of beta-blockers on spinal pain was suggested in the current study, consistent with findings from observational studies of various other pain phenotypes. The detrimental effect of calcium channel blockers on spinal pain suggested in the current study must be interpreted in the context of conflicting directions of effect on nonspinal pain phenotypes in other observational studies.This Mendelian randomization study examined whether antihypertensive medications (beta-blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors) and statins can be repurposed to prevent or treat spinal.This was a two-sample MR study using publicly available summary statistics from large-scale genome-wide association studies ranging size from 173,082 to 1,028,947 adults.While no statistically significant associations were found, a protective effect of beta-blockers on spinal pain was suggested (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.72 to 0.98; p= 0.03), as was a detrimental effect of calcium channel blockers on spinal pain (OR 1.12, 95% CI 1.02 to 1.24; p= 0.02).

AB - STUDY DESIGN: Mendelian randomization (MR) study.OBJECTIVE: To examine whether antihypertensive medications (beta-blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors) and statins can be repurposed to prevent or treat spinal pain (back or neck pain).SUMMARY OF BACKGROUND DATA: Observational studies and a recent MR study have found associations between elevated blood pressure and a greater risk of back pain. Observational studies have found associations between hyperlipidemia and statin use and greater risk of back pain. No prior MR studies have examined the effects of antihypertensives or statins on spinal pain.MATERIALS AND METHODS: This was a two-sample MR study using publicly available summary statistics from large-scale genome-wide association studies (GWAS). Sample sizes in exposure GWASs were n=757,601 (systolic blood pressure) and n=173,082 (low-density lipoprotein cholesterol), and n=1,028,947 for the outcome GWAS of spinal pain defined as health care seeking for any spinal pain-related diagnosis. Genes and cis-acting variants were identified as proxies for the drug targets of interest. MR analyses used inverse-variance weighted meta-analysis. The threshold for statistical significance after correction for multiple testing was P <0.0125.RESULTS: No statistically significant associations of these medications with spinal pain were found. However, findings were suggestive of a protective effect of beta-blockers on spinal pain risk (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.72-0.98; P =0.03), and calcium channel blockers on greater spinal pain risk (OR 1.12, 95% CI 1.02-1.24; P =0.02).CONCLUSIONS: A protective effect of beta-blockers on spinal pain was suggested in the current study, consistent with findings from observational studies of various other pain phenotypes. The detrimental effect of calcium channel blockers on spinal pain suggested in the current study must be interpreted in the context of conflicting directions of effect on nonspinal pain phenotypes in other observational studies.This Mendelian randomization study examined whether antihypertensive medications (beta-blockers, calcium channel blockers, and angiotensin-converting enzyme inhibitors) and statins can be repurposed to prevent or treat spinal.This was a two-sample MR study using publicly available summary statistics from large-scale genome-wide association studies ranging size from 173,082 to 1,028,947 adults.While no statistically significant associations were found, a protective effect of beta-blockers on spinal pain was suggested (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.72 to 0.98; p= 0.03), as was a detrimental effect of calcium channel blockers on spinal pain (OR 1.12, 95% CI 1.02 to 1.24; p= 0.02).

KW - Adult

KW - Angiotensin-Converting Enzyme Inhibitors/therapeutic use

KW - Antihypertensive Agents/therapeutic use

KW - Back Pain/drug therapy

KW - Calcium Channel Blockers/therapeutic use

KW - Drug Repositioning

KW - Genome-Wide Association Study

KW - Humans

KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use

KW - Mendelian Randomization Analysis

KW - Neck Pain/drug therapy

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85175356016&origin=inward&txGid=64ad6484b5f0f416ba2561b48f7897d6

UR - https://www.mendeley.com/catalogue/e2ebcb73-2285-392f-affd-57a0e32d19d9/

U2 - 10.1097/BRS.0000000000004790

DO - 10.1097/BRS.0000000000004790

M3 - Article

C2 - 37539717

VL - 48

SP - 1568

EP - 1574

JO - Spine

JF - Spine

SN - 0362-2436

IS - 22

ER -