Raynaud’s phenomenon is associated with an increased risk of cardiovascular disease and venous thromboembolism

Michael Hughes; Barbara Ruaro; Zsuzsanna  McMahan; Uazman Alam; Edward Jude; Sizheng Steven Zhao

doi:10.1016/j.semarthrit.2025.152799

Raynaud’s phenomenon is associated with an increased risk of cardiovascular disease and venous thromboembolism

Michael Hughes
, Barbara Ruaro
, Zsuzsanna McMahan
, Uazman Alam
, Edward Jude
, Sizheng Steven Zhao

Research output: Contribution to journal › Article › peer-review

Abstract

Objectives: Raynaud’s phenomenon (RP) is common affecting 3-5% of the population; however, there are little data concerning vascular outcomes. We aimed to estimate risk of cardiovascular disease (CVD) and venous thromboembolism (VTE) in individuals with RP without underlying relevant systemic autoimmune rheumatic diseases (SARDs).

Methods: A cohort study using data from North American electronic healthcare organization records. RP was defined using ≥2 ICD codes (I73.0), excluding those with SARDs. Comparators had ≥2 irritable bowel syndrome (IBS) ICD codes (K58); selected as a condition with similar demographics but not typically associated with adverse CVD outcomes. Cohorts were stratified by age (<45 and ≥45 years). Co-primary outcomes were 1) major adverse cardiovascular events (MACE), and 2) VTE. Secondary outcomes included: myocardial infarction, stroke, any CVD. Risk of each outcome was compared using 1:1 propensity score matched Cox proportional hazard models.

Results: Among 30,088 matched pairs aged <45, hazard ratios (HR [95% CI]) of MACE (HR 1.23 [1.07, 1.42]) and VTE (HR 1.32 [1.20, 1.46]) were higher in RP (excluding SARD) than IBS. Similarly, in 60,145 matched pairs ages ≥45, MACE (HR 1.17 [1.13, 1.22]) and VTE (HR 1.20 [1.14, 1.26]) were higher in RP. Risk of secondary outcomes was higher in RP, although estimates for DVT in both analyses and myocardial infarction in patients under 45 lacked precision.

Conclusions: RP was associated with an increased risk of CVD and VTE, independent of age and traditional cardiovascular risk factors. Future research is warranted to confirm, explore pathobiological mechanisms, and develop therapeutic strategies.

Original language	English
Article number	152799
Journal	Seminars in arthritis and rheumatism
Volume	74
Early online date	5 Aug 2025
DOIs	https://doi.org/10.1016/j.semarthrit.2025.152799
Publication status	Published - 31 Oct 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Raynaud’s phenomenon
Cardiovascular disease
DVT
Myocardial infraction
Stroke
Venous thromboembolism

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10.1016/j.semarthrit.2025.152799Licence: CC BY

NIHR Manchester Biomedical Research Centre
Bruce, I. (PI), Lord, G. (CoI), Lennon, R. (CoI), Black, G. (CoI), Wedge, D. (CoI), Morris, A. (CoI), Hussell, T. (CoI), Sharrocks, A. (CoI), Stivaros, S. (CoI), Buch, M. (CoI), Gough, J. (CoI), Kostarelos, K. (CoI), Thistlethwaite, F. (CoI), Kadler, K. (CoI), Barton, A. (CoI), Hyrich, K. (CoI), Mcbeth, J. (CoI), O'Neill, T. (CoI), Vestbo, J. (CoI), Simpson, A. (CoI), Singh, S. (CoI), Smith, J. (CoI), Felton, T. (CoI), Murray, C. (CoI), Griffiths, C. (CoI), Cullum, N. (CoI), Rhodes, L. (CoI), Warren, R. (CoI), Paus, R. (CoI), Dumville, J. (CoI), Viros Usandizaga, A. (CoI), Keavney, B. (CoI), Tomaszewski, M. (CoI), Allan, S. (CoI), Body, R. (CoI), Cartwright, E. (CoI), Heagerty, A. (CoI), Kalra, P. (CoI), Miller, C. (CoI), Rutter, M. (CoI), Smith, C. (CoI), Trafford, A. (CoI), Evans, D. (CoI), Davidson, E. (CoI), Crosbie, P. (CoI), Harvie, M. (CoI), Howell, S. (CoI), Renehan, A. (CoI), Dive, C. (CoI), Blackhall, F. (CoI), Landers, D. (CoI), Krebs, M. (CoI), Cook, N. (CoI), Clarke, R. (CoI), Taylor, S. (CoI), Jorgensen, C. (CoI), Lorigan, P. (CoI), Jayson, G. (CoI), Valle, J. (CoI), Mccabe, M. (CoI), Armstrong, A. (CoI), Freitas, A. (CoI), Illidge, T. (CoI), Choudhury, A. (CoI), Hoskin, P. (CoI), West, C. (CoI), Van Herk, M. (CoI), Faivre-Finn, C. (CoI), Bristow, R. (CoI), Kirkby, K. (CoI), Birtle, A. (CoI), Mackay, R. (CoI), Radford, J. (CoI), Linton, K. (CoI), Higham, C. (CoI), Munro, K. (CoI), Plack, C. (CoI), Arden Armitage, C. (CoI), Bruce, I. (CoI), Moore, D. (CoI), Saunders, G. (CoI), Stone, M. (CoI), Haddock, G. (CoI), Lewis, S. (CoI), Elliott, R. (CoI), Green, J. (CoI), Lovell, K. (CoI), Morrison, A. (CoI), Shaw, J. (CoI), Bucci, S. (CoI), Ainsworth, J. (CoI), Webb, R. (CoI), Newman, W. (CoI), Banka, S. (CoI), Clayton-Smith, J. (CoI), Payne, K. (CoI), Moldovan, R. (CoI), Wynn, R. (CoI) & Jones, S. (CoI)
1/12/22 → 30/11/27
Project: Research

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@article{ccab1493e5e747a3bf2ca6d86265ff4c,

title = "Raynaud{\textquoteright}s phenomenon is associated with an increased risk of cardiovascular disease and venous thromboembolism",

abstract = "Objectives: Raynaud{\textquoteright}s phenomenon (RP) is common affecting 3-5\% of the population; however, there are little data concerning vascular outcomes. We aimed to estimate risk of cardiovascular disease (CVD) and venous thromboembolism (VTE) in individuals with RP without underlying relevant systemic autoimmune rheumatic diseases (SARDs). Methods: A cohort study using data from North American electronic healthcare organization records. RP was defined using ≥2 ICD codes (I73.0), excluding those with SARDs. Comparators had ≥2 irritable bowel syndrome (IBS) ICD codes (K58); selected as a condition with similar demographics but not typically associated with adverse CVD outcomes. Cohorts were stratified by age (<45 and ≥45 years). Co-primary outcomes were 1) major adverse cardiovascular events (MACE), and 2) VTE. Secondary outcomes included: myocardial infarction, stroke, any CVD. Risk of each outcome was compared using 1:1 propensity score matched Cox proportional hazard models. Results: Among 30,088 matched pairs aged <45, hazard ratios (HR [95\% CI]) of MACE (HR 1.23 [1.07, 1.42]) and VTE (HR 1.32 [1.20, 1.46]) were higher in RP (excluding SARD) than IBS. Similarly, in 60,145 matched pairs ages ≥45, MACE (HR 1.17 [1.13, 1.22]) and VTE (HR 1.20 [1.14, 1.26]) were higher in RP. Risk of secondary outcomes was higher in RP, although estimates for DVT in both analyses and myocardial infarction in patients under 45 lacked precision. Conclusions: RP was associated with an increased risk of CVD and VTE, independent of age and traditional cardiovascular risk factors. Future research is warranted to confirm, explore pathobiological mechanisms, and develop therapeutic strategies. ",

keywords = "Raynaud{\textquoteright}s phenomenon, Cardiovascular disease, DVT, Myocardial infraction, Stroke, Venous thromboembolism",

author = "Michael Hughes and Barbara Ruaro and Zsuzsanna McMahan and Uazman Alam and Edward Jude and Zhao, \{Sizheng Steven\}",

year = "2025",

month = oct,

day = "31",

doi = "10.1016/j.semarthrit.2025.152799",

language = "English",

volume = "74",

journal = "Seminars in arthritis and rheumatism",

issn = "0049-0172",

publisher = "W.B. Saunders Company",

}

TY - JOUR

T1 - Raynaud’s phenomenon is associated with an increased risk of cardiovascular disease and venous thromboembolism

AU - Hughes, Michael

AU - Ruaro, Barbara

AU - McMahan , Zsuzsanna

AU - Alam, Uazman

AU - Jude, Edward

AU - Zhao, Sizheng Steven

PY - 2025/10/31

Y1 - 2025/10/31

N2 - Objectives: Raynaud’s phenomenon (RP) is common affecting 3-5% of the population; however, there are little data concerning vascular outcomes. We aimed to estimate risk of cardiovascular disease (CVD) and venous thromboembolism (VTE) in individuals with RP without underlying relevant systemic autoimmune rheumatic diseases (SARDs). Methods: A cohort study using data from North American electronic healthcare organization records. RP was defined using ≥2 ICD codes (I73.0), excluding those with SARDs. Comparators had ≥2 irritable bowel syndrome (IBS) ICD codes (K58); selected as a condition with similar demographics but not typically associated with adverse CVD outcomes. Cohorts were stratified by age (<45 and ≥45 years). Co-primary outcomes were 1) major adverse cardiovascular events (MACE), and 2) VTE. Secondary outcomes included: myocardial infarction, stroke, any CVD. Risk of each outcome was compared using 1:1 propensity score matched Cox proportional hazard models. Results: Among 30,088 matched pairs aged <45, hazard ratios (HR [95% CI]) of MACE (HR 1.23 [1.07, 1.42]) and VTE (HR 1.32 [1.20, 1.46]) were higher in RP (excluding SARD) than IBS. Similarly, in 60,145 matched pairs ages ≥45, MACE (HR 1.17 [1.13, 1.22]) and VTE (HR 1.20 [1.14, 1.26]) were higher in RP. Risk of secondary outcomes was higher in RP, although estimates for DVT in both analyses and myocardial infarction in patients under 45 lacked precision. Conclusions: RP was associated with an increased risk of CVD and VTE, independent of age and traditional cardiovascular risk factors. Future research is warranted to confirm, explore pathobiological mechanisms, and develop therapeutic strategies.

AB - Objectives: Raynaud’s phenomenon (RP) is common affecting 3-5% of the population; however, there are little data concerning vascular outcomes. We aimed to estimate risk of cardiovascular disease (CVD) and venous thromboembolism (VTE) in individuals with RP without underlying relevant systemic autoimmune rheumatic diseases (SARDs). Methods: A cohort study using data from North American electronic healthcare organization records. RP was defined using ≥2 ICD codes (I73.0), excluding those with SARDs. Comparators had ≥2 irritable bowel syndrome (IBS) ICD codes (K58); selected as a condition with similar demographics but not typically associated with adverse CVD outcomes. Cohorts were stratified by age (<45 and ≥45 years). Co-primary outcomes were 1) major adverse cardiovascular events (MACE), and 2) VTE. Secondary outcomes included: myocardial infarction, stroke, any CVD. Risk of each outcome was compared using 1:1 propensity score matched Cox proportional hazard models. Results: Among 30,088 matched pairs aged <45, hazard ratios (HR [95% CI]) of MACE (HR 1.23 [1.07, 1.42]) and VTE (HR 1.32 [1.20, 1.46]) were higher in RP (excluding SARD) than IBS. Similarly, in 60,145 matched pairs ages ≥45, MACE (HR 1.17 [1.13, 1.22]) and VTE (HR 1.20 [1.14, 1.26]) were higher in RP. Risk of secondary outcomes was higher in RP, although estimates for DVT in both analyses and myocardial infarction in patients under 45 lacked precision. Conclusions: RP was associated with an increased risk of CVD and VTE, independent of age and traditional cardiovascular risk factors. Future research is warranted to confirm, explore pathobiological mechanisms, and develop therapeutic strategies.

KW - Raynaud’s phenomenon

KW - Cardiovascular disease

KW - DVT

KW - Myocardial infraction

KW - Stroke

KW - Venous thromboembolism

U2 - 10.1016/j.semarthrit.2025.152799

DO - 10.1016/j.semarthrit.2025.152799

M3 - Article

SN - 0049-0172

VL - 74

JO - Seminars in arthritis and rheumatism

JF - Seminars in arthritis and rheumatism

M1 - 152799

ER -

Raynaud’s phenomenon is associated with an increased risk of cardiovascular disease and venous thromboembolism

Abstract

UN SDGs

Keywords

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NIHR Manchester Biomedical Research Centre

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