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抗高血压和他汀类药物在治疗脊柱疼痛中的再利用:一项孟德尔随机化研究。

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

机构信息

Division of Rehabilitation Care Services, VA Puget Sound Health Care System, Seattle, WA.

Seattle Epidemiologic Research and Information Center, VA Puget Sound Health Care System, Seattle, WA.

出版信息

Spine (Phila Pa 1976). 2023 Nov 15;48(22):1568-1574. doi: 10.1097/BRS.0000000000004790. Epub 2023 Aug 4.

Abstract

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).

摘要

研究设计

孟德尔随机化(MR)研究。

目的

检验降压药物(β受体阻滞剂、钙通道阻滞剂和血管紧张素转换酶抑制剂)和他汀类药物是否可被重新用于预防或治疗脊柱疼痛(背部或颈部疼痛)。

背景资料概要

观察性研究和最近的一项 MR 研究发现,血压升高与更大的背痛风险之间存在关联。观察性研究发现,血脂异常与他汀类药物使用和更大的背痛风险之间存在关联。以前没有 MR 研究检验过降压药或他汀类药物对脊柱疼痛的影响。

材料和方法

这是一项两样本 MR 研究,使用了来自大型全基因组关联研究(GWAS)的公开汇总统计数据。暴露 GWAS 的样本量分别为 n=757601(收缩压)和 n=173082(低密度脂蛋白胆固醇),而脊柱疼痛结局 GWAS 的样本量为 n=1028947,定义为寻求任何脊柱疼痛相关诊断的医疗保健。基因和顺式作用变异被确定为药物靶点的替代物。MR 分析使用逆方差加权荟萃分析。经多重检验校正后,统计学意义的阈值为 P<0.0125。

结果

这些药物与脊柱疼痛之间没有发现具有统计学意义的关联。然而,结果提示β受体阻滞剂可能对脊柱疼痛风险具有保护作用(比值比[OR]0.84,95%置信区间[CI]0.72-0.98;P=0.03),钙通道阻滞剂可能增加脊柱疼痛风险(OR 1.12,95%CI 1.02-1.24;P=0.02)。

结论

当前研究提示β受体阻滞剂对脊柱疼痛具有保护作用,与各种其他疼痛表型的观察性研究结果一致。当前研究提示钙通道阻滞剂对脊柱疼痛的有害影响必须在其他观察性研究中对非脊柱疼痛表型的作用方向相互矛盾的情况下进行解释。

这项孟德尔随机化研究检验了降压药物(β受体阻滞剂、钙通道阻滞剂和血管紧张素转换酶抑制剂)和他汀类药物是否可被重新用于预防或治疗脊柱疼痛。

这是一项两样本 MR 研究,使用了来自大规模全基因组关联研究的公开汇总统计数据,研究对象为 173082 至 1028947 名成年人。

虽然没有发现具有统计学意义的关联,但提示β受体阻滞剂对脊柱疼痛具有保护作用(比值比[OR]0.84,95%置信区间[CI]0.72-0.98;p=0.03),钙通道阻滞剂对脊柱疼痛具有有害影响(OR 1.12,95%置信区间[CI]1.02-1.24;p=0.02)。

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