Evidence of causal effects of blood pressure on back pain and back pain on type II diabetes provided by a bidirectional Mendelian randomization study

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.