Hypertension Meets Osteoarthritis - Revisiting the Vascular Aetiology Hypothesis

Overview

Journal Nat Rev Rheumatol

Specialty Rheumatology

Date 2021 Jul 28

PMID 34316066

Citations 31

Authors

Karen Ching

Xavier Houard

Francis Berenbaum

Chunyi Wen

Affiliations

Soon will be listed here.

Abstract

Osteoarthritis (OA) is a whole-joint disease characterized by subchondral bone perfusion abnormalities and neovascular invasion into the synovium and articular cartilage. In addition to local vascular disturbance, mounting evidence suggests a pivotal role for systemic vascular pathology in the aetiology of OA. This Review outlines the current understanding of the close relationship between high blood pressure (hypertension) and OA at the crossroads of epidemiology and molecular biology. As one of the most common comorbidities in patients with OA, hypertension can disrupt joint homeostasis both biophysically and biochemically. High blood pressure can increase intraosseous pressure and cause hypoxia, which in turn triggers subchondral bone and osteochondral junction remodelling. Furthermore, systemic activation of the renin-angiotensin and endothelin systems can affect the Wnt-β-catenin signalling pathway locally to govern joint disease. The intimate relationship between hypertension and OA indicates that endothelium-targeted strategies, including re-purposed FDA-approved antihypertensive drugs, could be useful in the treatment of OA.

Citing Articles

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References

Hunter D, March L, Chew M . Osteoarthritis in 2020 and beyond: a Lancet Commission. Lancet. 2020; 396(10264):1711-1712. DOI: 10.1016/S0140-6736(20)32230-3. View

Kendzerska T, Juni P, King L, Croxford R, Stanaitis I, Hawker G . The longitudinal relationship between hand, hip and knee osteoarthritis and cardiovascular events: a population-based cohort study. Osteoarthritis Cartilage. 2017; 25(11):1771-1780. DOI: 10.1016/j.joca.2017.07.024. View

Haugen I, Ramachandran V, Misra D, Neogi T, Niu J, Yang T . Hand osteoarthritis in relation to mortality and incidence of cardiovascular disease: data from the Framingham heart study. Ann Rheum Dis. 2013; 74(1):74-81. PMC: 3959628. DOI: 10.1136/annrheumdis-2013-203789. View

Nuesch E, Dieppe P, Reichenbach S, Williams S, Iff S, Juni P . All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study. BMJ. 2011; 342:d1165. PMC: 3050438. DOI: 10.1136/bmj.d1165. View

Wallace I, Worthington S, Felson D, Jurmain R, Wren K, Maijanen H . Knee osteoarthritis has doubled in prevalence since the mid-20th century. Proc Natl Acad Sci U S A. 2017; 114(35):9332-9336. PMC: 5584421. DOI: 10.1073/pnas.1703856114. View

Zhang Y, Wang J, Liu X . Association between hypertension and risk of knee osteoarthritis: A meta-analysis of observational studies. Medicine (Baltimore). 2017; 96(32):e7584. PMC: 5556207. DOI: 10.1097/MD.0000000000007584. View

Xie Y, Zhou W, Zhong Z, Zhao Z, Yu H, Huang Y . Metabolic syndrome, hypertension, and hyperglycemia were positively associated with knee osteoarthritis, while dyslipidemia showed no association with knee osteoarthritis. Clin Rheumatol. 2020; 40(2):711-724. DOI: 10.1007/s10067-020-05216-y. View

Wen C, Chen Y, Tang H, Yan C, Lu W, Chiu K . Bone loss at subchondral plate in knee osteoarthritis patients with hypertension and type 2 diabetes mellitus. Osteoarthritis Cartilage. 2013; 21(11):1716-23. DOI: 10.1016/j.joca.2013.06.027. View

Niu J, Clancy M, Aliabadi P, Vasan R, Felson D . Metabolic Syndrome, Its Components, and Knee Osteoarthritis: The Framingham Osteoarthritis Study. Arthritis Rheumatol. 2017; 69(6):1194-1203. PMC: 5449217. DOI: 10.1002/art.40087. View

10.

Findlay D . Vascular pathology and osteoarthritis. Rheumatology (Oxford). 2007; 46(12):1763-8. DOI: 10.1093/rheumatology/kem191. View

11.

Hussain S, Dawson C, Wang Y, Tonkin A, Chou L, Wluka A . Vascular Pathology and Osteoarthritis: A Systematic Review. J Rheumatol. 2019; 47(5):748-760. DOI: 10.3899/jrheum.181236. View

12.

Calvet J, Orellana C, Larrosa M, Navarro N, Chillaron J, Pedro-Botet J . High prevalence of cardiovascular co-morbidities in patients with symptomatic knee or hand osteoarthritis. Scand J Rheumatol. 2015; 45(1):41-44. DOI: 10.3109/03009742.2015.1054875. View

13.

Funck-Brentano T, Nethander M, Moverare-Skrtic S, Richette P, Ohlsson C . Causal Factors for Knee, Hip, and Hand Osteoarthritis: A Mendelian Randomization Study in the UK Biobank. Arthritis Rheumatol. 2019; 71(10):1634-1641. PMC: 6790695. DOI: 10.1002/art.40928. View

14.

Singh G, Miller J, Huse D, Pettitt D, DAgostino R, Russell M . Consequences of increased systolic blood pressure in patients with osteoarthritis and rheumatoid arthritis. J Rheumatol. 2003; 30(4):714-9. View

15.

Jamsen E, Peltola M, Eskelinen A, Lehto M . Comorbid diseases as predictors of survival of primary total hip and knee replacements: a nationwide register-based study of 96 754 operations on patients with primary osteoarthritis. Ann Rheum Dis. 2012; 72(12):1975-82. PMC: 3841739. DOI: 10.1136/annrheumdis-2012-202064. View

16.

Lo G, McAlindon T, Katz J, Driban J, Price L, Eaton C . Systolic and pulse pressure associate with incident knee osteoarthritis: data from the Osteoarthritis Initiative. Clin Rheumatol. 2017; 36(9):2121-2128. PMC: 5709188. DOI: 10.1007/s10067-017-3656-z. View

17.

Gandhi R, Razak F, Tso P, Davey J, Mahomed N . Asian ethnicity and the prevalence of metabolic syndrome in the osteoarthritic total knee arthroplasty population. J Arthroplasty. 2009; 25(3):416-9. DOI: 10.1016/j.arth.2009.02.005. View

18.

Poornima S, Subramanyam K, Ali Khan I, Hasan Q . The insertion and deletion (I28005D) polymorphism of the angiotensin I converting enzyme gene is a risk factor for osteoarthritis in an Asian Indian population. J Renin Angiotensin Aldosterone Syst. 2014; 16(4):1281-7. DOI: 10.1177/1470320314547403. View

19.

Hong S, Yang H, Yoo M, In C, Yim S, Jin S . Angiotensin converting enzyme gene polymorphism in Korean patients with primary knee osteoarthritis. Exp Mol Med. 2003; 35(3):189-95. DOI: 10.1038/emm.2003.26. View

20.

Lin C, Chen H, Fang W, Wang C, Peng Y, Lee H . Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Susceptibility to Osteoarthritis of the Knee: A Case-Control Study and Meta-Analysis. PLoS One. 2016; 11(9):e0161754. PMC: 5033346. DOI: 10.1371/journal.pone.0161754. View