Repurposing Antihypertensive and Statin Medications for Spinal Pain: A Mendelian Randomization Study.
Adult
Humans
Antihypertensive Agents
/ therapeutic use
Calcium Channel Blockers
/ therapeutic use
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ therapeutic use
Genome-Wide Association Study
Mendelian Randomization Analysis
Drug Repositioning
Angiotensin-Converting Enzyme Inhibitors
/ therapeutic use
Neck Pain
/ drug therapy
Back Pain
/ drug therapy
Journal
Spine
ISSN: 1528-1159
Titre abrégé: Spine (Phila Pa 1976)
Pays: United States
ID NLM: 7610646
Informations de publication
Date de publication:
15 Nov 2023
15 Nov 2023
Historique:
received:
20
05
2023
accepted:
24
07
2023
medline:
30
10
2023
pubmed:
4
8
2023
entrez:
4
8
2023
Statut:
ppublish
Résumé
Mendelian randomization (MR) study. 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). 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. 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. 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). 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).
Sections du résumé
STUDY DESIGN
METHODS
Mendelian randomization (MR) study.
OBJECTIVE
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
BACKGROUND
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
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
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
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).
Identifiants
pubmed: 37539717
doi: 10.1097/BRS.0000000000004790
pii: 00007632-202311150-00003
doi:
Substances chimiques
Antihypertensive Agents
0
Calcium Channel Blockers
0
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Angiotensin-Converting Enzyme Inhibitors
0
Types de publication
Meta-Analysis
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1568-1574Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
P.S. 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. E.E.E. was supported by the Russian Science Foundation (RSF) grant № 22-15-20037 and the Government of the Novosibirsk region. Y.A.T. was supported by the budget project of the Institute of Cytology and Genetics № FWNR-2022-0020. The remaining authors report no conflicts of interest.
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