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. 2025 Jun 1;166(6):1425-1435.
doi: 10.1097/j.pain.0000000000003486. Epub 2024 Dec 3.

Chronic widespread musculoskeletal pain shares a highly heritable latent pathway with atherosclerosis and arterial stiffness

Maryam Kazemi Naeini  1 , Marina Cecelja  1 , Maxim B Freidin  1   2 , Isabelle Granville Smith  1 , Pirro Hysi  1 , Christopher Sivert Nielsen  3   4 , Frances M K Williams  1
Affiliations

Chronic widespread musculoskeletal pain shares a highly heritable latent pathway with atherosclerosis and arterial stiffness

Maryam Kazemi Naeini et al. Pain. .

Abstract

Chronic widespread pain (CWP) is prevalent and associated with reduced life expectancy. Cardiovascular disease is one possible mechanism for this. The purpose of this study was to examine the association of CWP with arterial stiffness and carotid plaque measured using ultrasound to determine if shared environmental or genetic factors might account for any observed association. Around 3000 participants from the TwinsUK with CWP information and measures of carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and plaque were considered. The relationship between CWP and cfPWV, cIMT, and plaque was determined. UK Biobank data were used to replicate the association. Cholesky decomposition and multivariate pathway twin models were examined. Using a 2-sample Mendelian randomisation approach, the causal association between CWP and coronary artery disease was assessed. TwinsUK participants demonstrated a significant association between CWP and increased cfPWV consistent with arterial stiffening (OR = 1.35, P -value = 0.012), as well as the presence of carotid plaque (OR = 1.45, P -value = 0.8e-5). The twin modelling showed a common latent component and pathway underlying CWP, cfPWV, and carotid plaque, with genetic factors accounting for 68% and 90% of the latent factor variation, respectively. The 2-sample MR revealed a potential causal association between CWP and coronary artery disease. This study found that those with CWP have increased the risk of arterial stiffness and atherosclerosis and suggests that CWP leads to an increased risk of cardiovascular disease through genetic factors.

Keywords: Arterial stiffness; Atherosclerosis; Carotid intima–media thickness; Carotid plaque; Carotid–femoral pulse wave velocity; Chronic widespread pain.

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Conflict of interest statement

The authors have no relevant financial or nonfinancial interests to disclose. The authors have no conflicts of interest to declare that are relevant to the content of this article. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or nonfinancial interest in the subject matter or materials discussed in this manuscript. The authors have no financial or proprietary interests in any material discussed in this article.

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Figures

Figure 1.
Figure 1.
Association analysis of CWP with cIMT and cfPWV flowchart in TwinsUK and UKB. cfPWV, carotid–femoral pulse wave velocity; cIMT, carotid intima–media thickness; CWP, chronic widespread pain; UKB, UK Biobank.
Figure 2.
Figure 2.
The standardised path coefficients in the AC common pathway between CWP and cfPWV are derived from latent genetic and environmental factors. Ac, Cc, and Ec denote common additive genetic, shared environmental, and unique environmental effects. (A, C, and E) denoted trait-specific additive genetic, shared environmental, and unique environmental effects, respectively. Squares of the path coefficients give corresponding variance proportions. cfPWV, carotid–femoral pulse wave velocity; CWP, chronic widespread pain.
Figure 3.
Figure 3.
The standardised path coefficients in the AE common pathway between CWP and carotid plaque derived from latent genetic and environmental factors. Ac, Cc, and Ec denote common additive genetic, shared environmental, and unique environmental effects. (A, C, and E) denoted trait-specific additive genetic, shared environmental, and unique environmental effects, respectively. Squares of the path coefficients give corresponding variance proportions. CWP, chronic widespread pain.
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