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.
To examine potential causal effects of cardiovascular risk factors on back pain, and vice versa.
Bidirectional Mendelian randomization (MR) study.
Genome-wide association studies (GWAS) with sample sizes between 173,082 and 1,028,947 participants.
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.
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.
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).
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.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to The Spine Journal
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Global low back pain prevalence and years lived with disability from 1990 to 2017: estimates from the Global Burden of Disease Study 2017.Ann Transl Med. 2020; 8: 299
- 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet. 2018; 392: 1789-1858
- US Health Care Spending by Payer and Health Condition, 1996-2016.JAMA. 2020; 323: 863-884
- Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.Lancet. 2020; 396: 1223-1249
- Causal role of high body mass index in multiple chronic diseases: a systematic review and meta-analysis of Mendelian randomization studies.BMC Med. 2021; 19: 320
- Association between obesity and cardiovascular outcomes: a systematic review and meta-analysis of Mendelian randomization studies.JAMA Netw Open. 2018; 1e183788
- Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians.BMJ. 2018; 362: k601
- ISSLS Prize in Clinical Science 2020. Examining causal effects of body mass index on back pain: a Mendelian randomization study.Eur. Spine J. 2020; 29: 686-691
- The association between obesity and low back pain: a meta-analysis.Am. J. Epidemiol. 2010; 171: 135-154
- Associations between serum lipid levels and chronic low back pain.Epidemiology. 2010; 21: 837-841
- Does high blood pressure reduce the risk of chronic low back pain? The Nord-Trondelag Health Study.Eur. J. Pain. 2014; 18: 590-598
- Association between hypertension and the prevalence of low back pain and osteoarthritis in koreans: a cross-sectional study.PLoS One. 2015; 10e0138790
- Does diabetes influence the probability of experiencing chronic low back pain? A population-based cohort study: the Nord-Trondelag Health Study.BMJ Open. 2019; 9e031692
- Is there an association between diabetes and neck pain and lower back pain? Results of a population-based study.J Pain Res. 2018; 11: 1005-1015
- Disc degeneration/back pain and calcification of the abdominal aorta. A 25-year follow-up study in Framingham.Spine. 1997; 22 (discussion 8-9): 1642-1647
- Atherosclerosis and disc degeneration/low-back pain–a systematic review.Eur. J. Vasc. Endovasc. Surg. 2009; 37: 661-670
- Atherosclerotic disease and its relationship to lumbar degenerative disk disease, facet arthritis, and stenosis with computed tomography angiography.PM R. 2018; 10: 331-337
- The pathophysiology of disc degeneration: a critical review.J. Bone Joint Surg. Br. 2008; 90: 1261-1270
- Nutrition of the intervertebral disc.Spine (Phila Pa 1976). 2004; 29: 2700-2709
- Do medical conditions predispose to the development of chronic back pain? A longitudinal co-twin control study of middle-aged males with 11-year follow-up.BMC Musculoskelet Disord. 2018; 19: 362
- Do abnormal serum lipid levels increase the risk of chronic low back pain? The Nord-Trondelag Health Study.PLoS One. 2014; 9e108227
- Mapping the association between back pain and type 2 diabetes: a cross-sectional and longitudinal study of adult Spanish twins.PLoS One. 2017; 12e0174757
- Quantitative assessment of abdominal aortic calcification and associations with lumbar intervertebral disc height loss: the Framingham Study.Spine J. 2012; 12: 315-323
- Assessment of bidirectional relationships between physical activity and depression among adults: a 2-sample mendelian randomization study.JAMA Psychiatry. 2019; 76: 399-408
- Apparent latent structure within the UK Biobank sample has implications for epidemiological analysis.Nat Commun. 2019; 10: 333
- Mendelian randomization accounting for correlated and uncorrelated pleiotropic effects using genome-wide summary statistics.Nat. Genet. 2020; 52: 740-747
- The variant call format provides efficient and robust storage of GWAS summary statistics.Genome Biol. 2021; 22: 32
- Discovery and refinement of loci associated with lipid levels.Nat. Genet. 2013; 45: 1274-1283
- Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps.Nat. Genet. 2018; 50: 1505-1513
- Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology.Nat Commun. 2022; 13: 634
- Use of the International Classification of Diseases (ICD-9-CM) to identify hospitalizations for mechanical low back problems in administrative databases.Spine (Phila Pa 1976). 1992; 17: 817-825
- Outcome measures for studying patients with low back pain.Spine. 1994; 19: 2032S-2036S
- Indications for spine surgery: validation of an administrative coding algorithm to classify degenerative diagnoses.Spine (Phila Pa 1976). 2014; 39: 769-779
- Trajectories of symptoms and function in older adults with low back disorders.Spine (Phila Pa 1976). 2015; 40: 1352-1362
- Genome-wide association studies of low back pain and lumbar spinal disorders using electronic health record data identify a locus associated with lumbar spinal stenosis.Pain. 2021; 162: 2263-2272
- To seek or not to seek? Care-seeking behaviour among people with low-back pain.Scand. J. Public Health. 2003; 31: 194-203
- Low back pain–a community-based study of care-seeking and therapeutic effectiveness.Disabil. Rehabil. 2003; 25: 67-76
- Care-seeking among individuals with chronic low back pain.Spine (Phila Pa 1976). 1995; 20: 312-317
- Causal effects of psychosocial factors on chronic back pain: a bidirectional Mendelian randomisation study.Eur Spine J. 2022; 31: 1906-1915
- Big five personality traits and disabling chronic low back pain: association with fear-avoidance, anxious and depressive moods.J Pain Res. 2020; 13: 745-754
- The GWAS-MAP platform for aggregation of results of genome-wide association studies and the GWAS-MAP|homo database of 70 billion genetic associations of human traits.Vavilov J Genet Breed. 2020; 24: 876-884
- A global reference for human genetic variation.Nature. 2015; 526: 68-74
- Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases.Nat. Genet. 2018; 50: 693-698
- The MR-Base platform supports systematic causal inference across the human phenome.Elife. 2018; 7e34408
- Second-generation PLINK: rising to the challenge of larger and richer datasets.Gigascience. 2015; 4: 7
- PLINK: a tool set for whole-genome association and population-based linkage analyses.Am. J. Hum. Genet. 2007; 81: 559-575
- Computationally efficient whole-genome regression for quantitative and binary traits.Nat. Genet. 2021; 53: 1097-1103
- Bias due to participant overlap in two-sample Mendelian randomization.Genet Epidemiol. 2016; 40: 597-608
- Nature or nurture in low back pain? Results of a systematic review of studies based on twin samples.Eur. J. Pain. 2013;
- Bidirectional relationships between cigarette use and spinal pain in adolescents accounting for psychosocial functioning.Br J Health Psychol. 2014; 19: 113-131
- Are lifestyle-factors in adolescence predictors for adult low back pain? A cross-sectional and prospective study of young twins.BMC Musculoskelet Disord. 2006; 7: 27
- Is chronic low back pain a risk factor for diabetes? The Nord-Trondelag Health Study.BMJ Open Diabetes Res Care. 2018; 6e000569
- The association between smoking and low back pain: a meta-analysis.Am. J. Med. 2010; 123: 87 e7-35
- Low-back pain ratings for lifetime, 1-month period, and point prevalences in a large occupational population.Hum. Factors. 2014; 56: 86-97
- Sedentary lifestyle and nonspecific low back pain in medical personnel in North-East Poland.Biomed Res Int. 2018; 20181965807
- Cardiovascular risk factors and low-back pain in a long-term follow-up of industrial employees.Scand. J. Work Environ. Health. 2006; 32: 12-19
- Age- and sex-specific effects of obesity, metabolic syndrome and its components on back pain: The English Longitudinal Study of Ageing.Joint Bone Spine. 2022; 89105366
- Back pain and co-occurring conditions: findings from a nationally representative sample.Spine (Phila Pa 1976). 2018; 43: E935-EE41
- A prediction model of low back pain risk: a population based cohort study in Korea.Korean J Pain. 2020; 33: 153-165
- Baroreflex sensitivity associated hypoalgesia in healthy states is altered by chronic pain.Pain. 2008; 138: 87-97
- Relationship between pain sensitivity and resting arterial blood pressure in patients with painful temporomandibular disorders.Psychosom. Med. 1997; 59: 503-511
- The impact of blood pressure and baroreflex sensitivity on wind-up.Anesth. Analg. 2008; 107: 1018-1025
- Somatotosensory evoked potentials during baroreceptor stimulation in chronic low back pain patients and normal controls.Int. J. Psychophysiol. 1997; 25: 201-210
- Is there an association between diabetes and neck and back pain? A systematic review with meta-analyses.PLoS One. 2019; 14e0212030
- Does type 2 diabetes increase the risk of musculoskeletal pain? Cross-sectional and longitudinal analyses of UK biobank data.Semin. Arthritis Rheum. 2020; 50: 728-734
Published online: April 13, 2023
Accepted: April 7, 2023
Received in revised form: March 1, 2023
Received: November 14, 2022
Publication stageIn Press Journal Pre-Proof
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.
Published by Elsevier Inc.