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18-05-2017 | Ankylosing spondylitis | Article

Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events? A prospective nationwide population-based cohort study

Journal: Arthritis Research & Therapy

Authors: Karin Bengtsson, Helena Forsblad-d’Elia, Elisabeth Lie, Eva Klingberg, Mats Dehlin, Sofia Exarchou, Ulf Lindström, Johan Askling, Lennart T. H. Jacobsson

Publisher: BioMed Central

Abstract

Background

To investigate the risk of first-time acute coronary syndrome (ACS), stroke and venous thromboembolism (VTE) in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA) and undifferentiated spondyloarthritis (uSpA), compared to each other and to the general population (GP).

Methods

This is a prospective nationwide cohort study. Cohorts with AS (n = 6448), PsA (n = 16,063) and uSpA (n = 5190) patients and a GP (n = 266,435) cohort, were identified 2001–2009 in the Swedish National Patient and Population registers. The follow-up began 1 January 2006, or 6 months after the first registered spondyloarthritis (SpA) diagnosis thereafter, and ended at ACS/stroke/VTE event, death, emigration or 31 December 2012. Crude and age- and sex-standardized incidence rates (SIRs) and hazard ratios (HRs) were calculated for incident ACS, stroke or VTE, respectively.

Results

Standardized to the GP cohort, SIRs for ACS were 4.3, 5.4 and 4.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort, respectively, compared to 3.2 in the GP cohort. SIRs for stroke were 5.4, 5.9 and 5.7 events per 1000 person-years at risk in the AS, PsA and uSpA cohort compared to 4.7 in the GP cohort. Corresponding SIRs for VTE were 3.6, 3.2 and 3.5 events per 1000 person-years at risk compared to 2.2 in the GP cohort. Age-and sex-adjusted HRs (95% CI) for ACS events were significantly increased in AS (1.54 (1.31–1.82)), PsA (1.76 (1.59–1.95)) and uSpA (1.36 (1.05–1.76)) compared to GP. Age-adjusted HRs for ACS was significantly decreased in female AS patients (0.59 (0.37–0.97)) compared to female PsA patients. Age-and sex-adjusted HRs for stroke events were significantly increased in AS (1.25 (1.06–1.48)) and PsA (1.34 (1.22–1.48)), and nonsignificantly increased in uSpA (1.16 (0.91–1.47)) compared to GP. For VTE the age-and sex-adjusted HRs for AS, PsA and uSpA were equally and significantly increased with about 50% compared to GP.

Conclusions

Patients with AS, PsA and uSpA are at increased risk for ACS and stroke events, which emphasizes the importance of identification of and intervention against cardiovascular risk factors in SpA patients. Increased alertness for VTE is warranted in patients with SpA.
Literature
1.
Sieper J, Rudwaleit M, Khan MA, Braun J. Concepts and epidemiology of spondyloarthritis. Best Pract Res Clin Rheumatol. 2006;20:401–17.CrossRefPubMed
2.
Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes IB, Peters MJ, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017;76(1):17–28. doi:10.​1136/​annrheumdis-2016-209775. 6.CrossRefPubMed
3.
Szabo SM, Levy AR, Rao SR, Kirbach SE, Lacaille D, Cifaldi M, et al. Increased risk of cardiovascular and cerebrovascular diseases in individuals with ankylosing spondylitis: a population-based study. Arthritis Rheum. 2011;63:3294–304.CrossRefPubMed
4.
Keller JJ, Hsu JL, Lin SM, Chou CC, Wang LH, Wang J, et al. Increased risk of stroke among patients with ankylosing spondylitis: a population-based matched-cohort study. Rheumatol Int. 2014;34:255–63.CrossRefPubMed
5.
Chou CH, Lin MC, Peng CL, Wu YC, Sung FC, Kao CH, et al. A nationwide population-based retrospective cohort study: increased risk of acute coronary syndrome in patients with ankylosing spondylitis. Scand J Rheumatol. 2014;43:132–6.CrossRefPubMed
6.
Brophy S, Cooksey R, Atkinson M, Zhou SM, Husain MJ, Macey S, et al. No increased rate of acute myocardial infarction or stroke among patients with ankylosing spondylitis-a retrospective cohort study using routine data. Semin Arthritis Rheum. 2012;42:140–5.CrossRefPubMed
7.
Essers I, Stolwijk C, Boonen A, De Bruin ML, Bazelier MT, de Vries F, et al. Ankylosing spondylitis and risk of ischaemic heart disease: a population-based cohort study. Ann Rheum Dis. 2016;75:203–9.CrossRefPubMed
8.
Haroon NN, Paterson JM, Li P, Inman RD, Haroon N. Patients with ankylosing spondylitis have increased cardiovascular and cerebrovascular mortality: a population-based study. Ann Intern Med. 2015;163:409–16.CrossRefPubMed
9.
Eriksson JK, Jacobsson L, Bengtsson K, Askling J. Is ankylosing spondylitis a risk factor for cardiovascular disease, and how do these risks compare with those in rheumatoid arthritis? Ann Rheum Dis. 2017;76(2):364–70. doi:10.​1136/​annrheumdis-2016-209315.CrossRefPubMed
10.
Han C, Robinson Jr DW, Hackett MV, Paramore LC, Fraeman KH, Bala MV. Cardiovascular disease and risk factors in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol. 2006;33:2167–72.PubMed
11.
Armstrong EJ, Harskamp CT, Armstrong AW. Psoriasis and major adverse cardiovascular events: a systematic review and meta-analysis of observational studies. J Am Heart Assoc. 2013;2, e000062.CrossRefPubMedPubMedCentral
12.
Ahlehoff O, Gislason GH, Lindhardsen J, Charlot MG, Jorgensen CH, Olesen JB, et al. Psoriasis carries an increased risk of venous thromboembolism: a Danish nationwide cohort study. PLoS One. 2011;6, e18125.CrossRefPubMedPubMedCentral
13.
Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB, Gelfand JM. Prevalence of cardiovascular risk factors in patients with psoriasis. J Am Acad Dermatol. 2006;55:829–35.CrossRefPubMed
14.
Ahlehoff O, Gislason GH, Charlot M, Jorgensen CH, Lindhardsen J, Olesen JB, et al. Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study. J Intern Med. 2011;270:147–57.CrossRefPubMed
15.
Gelfand JM, Dommasch ED, Shin DB, Azfar RS, Kurd SK, Wang X, et al. The risk of stroke in patients with psoriasis. J Invest Dermatol. 2009;129:2411–8.CrossRefPubMedPubMedCentral
16.
Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006;296:1735–41.CrossRefPubMed
17.
Ogdie A, Yu Y, Haynes K, Love TJ, Maliha S, Jiang Y, et al. Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study. Ann Rheum Dis. 2015;74:326–32.CrossRefPubMed
18.
Li L, Hagberg KW, Peng M, Shah K, Paris M, Jick S. Rates of cardiovascular disease and major adverse cardiovascular events in patients with psoriatic arthritis compared to patients without psoriatic arthritis. J Clin Rheumatol. 2015;21:405–10.CrossRefPubMedPubMedCentral
19.
Li WQ, Han JL, Manson JE, Rimm EB, Rexrode KM, Curhan GC, et al. Psoriasis and risk of nonfatal cardiovascular disease in U.S. women: a cohort study. Br J Dermatol. 2012;166:811–8.CrossRefPubMed
20.
Jamnitski A, Symmons D, Peters MJ, Sattar N, McInnes I, Nurmohamed MT. Cardiovascular comorbidities in patients with psoriatic arthritis: a systematic review. Ann Rheum Dis. 2013;72:211–6.CrossRefPubMed
21.
Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Miranda-Filloy JA, Dierssen T, Vaqueiro I, Blanco R, et al. The high prevalence of subclinical atherosclerosis in patients with ankylosing spondylitis without clinically evident cardiovascular disease. Medicine (Baltimore). 2009;88:358–65.CrossRef
22.
Tam LS, Shang Q, Li EK, Tomlinson B, Chu TT, Li M, et al. Subclinical carotid atherosclerosis in patients with psoriatic arthritis. Arthritis Rheum. 2008;59:1322–31.CrossRefPubMed
23.
Kimhi O, Caspi D, Bornstein NM, Maharshak N, Gur A, Arbel Y, et al. Prevalence and risk factors of atherosclerosis in patients with psoriatic arthritis. Semin Arthritis Rheum. 2007;36:203–9.CrossRefPubMed
24.
Gonzalez-Juanatey C, Llorca J, Amigo-Diaz E, Dierssen T, Martin J, Gonzalez-Gay MA. High prevalence of subclinical atherosclerosis in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors. Arthritis Rheum. 2007;57:1074–80.CrossRefPubMed
25.
Bremander A, Petersson IF, Bergman S, Englund M. Population-based estimates of common comorbidities and cardiovascular disease in ankylosing spondylitis. Arthritis Care Res (Hoboken). 2011;63:550–6.CrossRef
26.
Kang JH, Chen YH, Lin HC. Comorbidity profiles among patients with ankylosing spondylitis: a nationwide population-based study. Ann Rheum Dis. 2010;69:1165–8.CrossRefPubMed
27.
Gulati AM, Semb AG, Rollefstad S, Romundstad PR, Kavanaugh A, Gulati S, et al. On the HUNT for cardiovascular risk factors and disease in patients with psoriatic arthritis: population-based data from the Nord-Trondelag Health Study. Ann Rheum Dis. 2016;75:819–24.CrossRefPubMed
28.
Eder L, Zisman D, Barzilai M, Laor A, Rahat M, Rozenbaum M, et al. Subclinical atherosclerosis in psoriatic arthritis: a case-control study. J Rheumatol. 2008;35:877–82.PubMed
29.
Lindstrom U, Exarchou S, Sigurdardottir V, Sundstrom B, Askling J, Eriksson JK, et al. Validity of ankylosing spondylitis and undifferentiated spondyloarthritis diagnoses in the Swedish National Patient Register. Scand J Rheumatol. 2015;44:369–76.CrossRefPubMed
30.
Lofvendahl S, Theander E, Svensson A, Carlsson KS, Englund M, Petersson IF. Validity of diagnostic codes and prevalence of physician-diagnosed psoriasis and psoriatic arthritis in southern Sweden--a population-based register study. PLoS One. 2014;9, e98024.CrossRefPubMedPubMedCentral
31.
Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450.CrossRefPubMedPubMedCentral
32.
Holmqvist ME, Neovius M, Eriksson J, Mantel A, Wallberg-Jonsson S, Jacobsson LT, et al. Risk of venous thromboembolism in patients with rheumatoid arthritis and association with disease duration and hospitalization. JAMA. 2012;308:1350–6.CrossRefPubMed
33.
Kim SC, Schneeweiss S, Liu J, Solomon DH. Risk of venous thromboembolism in patients with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2013;65:1600–7.
34.
Choi HK, Rho YH, Zhu Y, Cea-Soriano L, Avina-Zubieta JA, Zhang Y. The risk of pulmonary embolism and deep vein thrombosis in rheumatoid arthritis: a UK population-based outpatient cohort study. Ann Rheum Dis. 2013;72:1182–7.CrossRefPubMed
35.
Grainge MJ, West J, Card TR. Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet. 2010;375:657–63.CrossRefPubMed
36.
Lee JJ, Pope JE. A meta-analysis of the risk of venous thromboembolism in inflammatory rheumatic diseases. Arthritis Res Ther. 2014;16:435.CrossRefPubMedPubMedCentral
37.
Feigin VL, Lawes CM, Bennett DA, Anderson CS. Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century. Lancet Neurol. 2003;2:43–53.CrossRefPubMed
38.
Ferro JM. Update on intracerebral haemorrhage. J Neurol. 2006;253:985–99.CrossRefPubMed
39.
Andersen KK, Olsen TS, Dehlendorff C, Kammersgaard LP. Hemorrhagic and ischemic strokes compared: stroke severity, mortality, and risk factors. Stroke. 2009;40:2068–72.CrossRefPubMed
40.
Rothwell PM, Howard SC, Power DA, Gutnikov SA, Algra A, van Gijn J, et al. Fibrinogen concentration and risk of ischemic stroke and acute coronary events in 5113 patients with transient ischemic attack and minor ischemic stroke. Stroke. 2004;35:2300–5.CrossRefPubMed
41.
Welsh P, Lowe GDO, Chalmers J, Campbell DJ, Rumley A, Neal BC, et al. Associations of proinflammatory cytokines with the risk of recurrent stroke. Stroke. 2008;39:2226–30.CrossRefPubMed
42.
Rost NS, Wolf PA, Kase CS, Kelly-Hayes M, Silbershatz H, Massaro JM, et al. Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study. Stroke. 2001;32:2575–9.CrossRefPubMed
43.
Anderson Jr FA, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107:I9–16.CrossRefPubMed
44.
Riva N, Donadini MP, Ageno W. Epidemiology and pathophysiology of venous thromboembolism: similarities with atherothrombosis and the role of inflammation. Thromb Haemost. 2015;113:1176–83.CrossRefPubMed
45.
Holst AG, Jensen G, Prescott E. Risk factors for venous thromboembolism: results from the Copenhagen City Heart Study. Circulation. 2010;121:1896–903.CrossRefPubMed
46.
Hansson PO, Eriksson H, Welin L, Svardsudd K, Wilhelmsen L. Smoking and abdominal obesity: risk factors for venous thromboembolism among middle-aged men: “the study of men born in 1913”. Arch Intern Med. 1999;159:1886–90.CrossRefPubMed
47.
Ageno W, Becattini C, Brighton T, Selby R, Kamphuisen PW. Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation. 2008;117:93–102.CrossRefPubMed
48.
Tsai AW, Cushman M, Rosamond WD, Heckbert SR, Polak JF, Folsom AR. Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology. Arch Intern Med. 2002;162:1182–9.CrossRefPubMed
49.
Glynn RJ, Rosner B. Comparison of risk factors for the competing risks of coronary heart disease, stroke, and venous thromboembolism. Am J Epidemiol. 2005;162:975–82.CrossRefPubMed
50.
Mahmoodi BK, Cushman M, Anne Naess I, Allison MA, Jan Bos W, Braekkan SK, et al. Association of traditional cardiovascular risk factors with venous thromboembolism: an individual participant data meta-analysis of prospective studies. Circulation. 2017;135:7–16.CrossRefPubMed
51.
Willerson JT, Ridker PM. Inflammation as a cardiovascular risk factor. Circulation. 2004;109:II2–10.CrossRefPubMed
52.
Holmqvist M, Gransmark E, Mantel A, Alfredsson L, Jacobsson LT, Wallberg-Jonsson S, et al. Occurrence and relative risk of stroke in incident and prevalent contemporary rheumatoid arthritis. Ann Rheum Dis. 2013;72:541–6.CrossRefPubMed
53.
Ljung L, Askling J, Rantapaa-Dahlqvist S, Jacobsson L. The risk of acute coronary syndrome in rheumatoid arthritis in relation to tumour necrosis factor inhibitors and the risk in the general population: a national cohort study. Arthritis Res Ther. 2014;16:R127.CrossRefPubMedPubMedCentral
54.
Ljung L, Simard JF, Jacobsson L, Rantapaa-Dahlqvist S, Askling J. Treatment with tumor necrosis factor inhibitors and the risk of acute coronary syndromes in early rheumatoid arthritis. Arthritis Rheum. 2012;64:42–52.CrossRefPubMed
55.
Koster M, Asplund K, Johansson A, Stegmayr B. Refinement of Swedish administrative registers to monitor stroke events on the national level. Neuroepidemiology. 2013;40:240–6.CrossRefPubMed
56.
Vaccarino V, Badimon L, Corti R, De Wit C, Dorobantu M, Manfrini O, et al. Presentation, management, and outcomes of ischaemic heart disease in women. Nat Rev Cardiol. 2013;10:508–18.CrossRefPubMed