Abstract
Background context
Cardiovascular risk factors (hypertension, dyslipidemia, and type II diabetes) have
been proposed as risk factors for back pain. However, few longitudinal studies have
found significant associations between cardiovascular risk factors and back pain,
and these may be explained by confounding or reverse causation.
Purpose
To examine potential causal effects of cardiovascular risk factors on back pain, and
vice versa.
STUDY DESIGN
Bidirectional Mendelian randomization (MR) study.
Patient samples
Genome-wide association studies (GWAS) with sample sizes between 173,082 and 1,028,947
participants.
Outcome measures
Outcomes included (1) back pain associated with health care use (BP-HC) in the forward
MR; and (2) seven cardiovascular phenotypes in the reverse MR, including 2 measurements
used for the evaluation of hypertension (diastolic blood pressure and systolic blood
pressure), 4 phenotypes related to dyslipidemia (LDL cholesterol, HDL cholesterol,
total cholesterol, and triglycerides), and type II diabetes.
Methods
We used summary statistics from large, publicly available GWAS for BP-HC and the 7
cardiovascular phenotypes to obtain genetic instrumental variables. We examined MR
evidence for causal associations using inverse-variance weighted (IVW) analysis, Causal
Analysis Using Summary Effect (CAUSE), and sensitivity analyses.
Results
In forward MR analyses of seven cardiovascular phenotypes, diastolic blood pressure
was associated with BP-HC across all analyses (IVW estimate: OR = 1.10 per 10.5 mm
Hg increase [1.04–1.17], p-value = .001), and significant associations of systolic
blood pressure with BP-HC were also found (IVW estimate: OR = 1.09 per 19.3 mm Hg
increase [1.04–1.15], p-value = .0006). In reverse MR analyses, only type II diabetes
was associated with BP-HC across all analyses (IVW estimate: OR = 1.40 [1.13–1.73],
p-value = .002).
Conclusions
These findings from analyses of large, population-based samples indicate that higher
blood pressure increases the risk of BP-HC, and BP-HC itself increases the risk of
type II diabetes.
Keywords
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Article info
Publication history
Published online: April 13, 2023
Accepted:
April 7,
2023
Received in revised form:
March 1,
2023
Received:
November 14,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
FDA device/drug status: Not applicable.
PS: Grants: NIAMS/NIH P30AR072572 (Level G ($500,001--$1M) (Paid directly to institution). EE: Nothing to disclose. FW: Nothing to disclose. MF: Nothing to disclose. OZ: Nothing to disclose. YA: Nothing to disclose. YT: Nothing to disclose.
Identification
Copyright
Published by Elsevier Inc.
