Cardiovascular risk factors in primary Sjögren's syndrome: a case-control study in 624 patients

Abstract

We evaluated the prevalence and clinical significance of cardiovascular risk factors in a large series of patients with primary Sjögren’s syndrome (SS), focusing on the possible association with clinical and immunological SS features, the therapies administered, and the impact on cardiovascular disease. The study cohort included 312 patients fulfilling the 2002 classification criteria for primary SS, consecutively evaluated and followed in our department between 1984 and 2009. The control group consisted of 312 age- and sex-matched patients without systemic autoimmune diseases followed during the study period in a primary care centre.

In comparison with the age- and sex-matched control group, patients with primary SS showed a higher frequency of diabetes mellitus (27% versus 13%, p < 0.001) and hypertriglyceridaemia (22% versus 15%, p = 0.023), and a lower frequency of hypertension (30% versus 46%, p < 0.001) and smoking (19% versus 31%, p < 0.001). The adjusted, multivariate analysis showed that SS patients with at least three cardiovascular risk factors had a higher mean age at SS diagnosis (p < 0.001), a higher frequency of liver involvement (p = 0.01) and central nervous system involvement (p = 0.001), higher mean levels of C-reactive protein (CRP, p = 0.001), a lower percentage of circulating gamma globulins (p = 0.001), and had received corticosteroids more frequently (p = 0.003) in comparison with patients without cardiovascular risk factors. Patients who had received corticosteroids showed a higher frequency of hypertension (37% versus 25%, p = 0.032), diabetes mellitus (37% versus 21%, p = 0.002), and hypertriglyceridaemia (33% versus 15%, p < 0.001).

Patients with primary SS showed a twofold higher prevalence of diabetes mellitus and a 1.5-fold higher prevalence of hypertriglyceridaemia in comparison with primary care patients. Corticosteroid use was closely associated with cardiovascular risk factors. These results suggest that cardiovascular risk factors should be taken into account in the management of patients with primary SS and show the importance of recognizing and controlling both traditional and SS-related modifiable risk factors.

Keywords

antimalarials cardiovascular disease corticosteroids diabetes Sjögren’s syndrome

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References

Fox RI Sjögren’s syndrome. Lancet 2005 ; 366: 321-331.

Kassan SS , Moutsopoulos HM Clinical manifestations and early diagnosis of Sjögren syndrome . Arch Intern Med 2004; 164: 1275-1284.

Ramos-Casals M. , Tzioufas AG , Font J. Primary Sjögren’s syndrome: new clinical and therapeutic concepts. Ann Rheum Dis 2005; 64: 347-354.

Sherer Y. , Zinger H. , Shoenfeld Y. Atherosclerosis in systemic lupus erythematosus. Autoimmunity 2010; 43: 98-102.

Font J. , Ramos-Casals M. , Cervera R. , et al. Cardiovascular risk factors and the long-term outcome of lupus nephritis. QJM 2001; 94: 19-26.

Nossent J. , Cikes N. , Kiss E. , et al. Current causes of death in systemic lupus erythematosus in Europe, 2000-2004: relation to disease activity and damage accrual. Lupus 2007; 16: 309-317.

Gonzalez-Gay MA , Gonzalez-Juanatey C. , Martin J. Rheumatoid arthritis: a disease associated with accelerated atherogenesis. Semin Arthritis Rheum 2005; 35: 8-17.

Gonzalez-Gay MA , Gonzalez-Juanatey C. , Piñeiro A. , GarciaPorrua C. , Testa A. , Llorca J. High-grade C-reactive protein elevation correlates with accelerated atherogenesis in patients with rheumatoid arthritis. J Rheumatol 2005; 32: 1219-1223.

Becker-Merok A. , Nossent J. Prevalence, predictors and outcome of vascular damage in systemic lupus erythematosus. Lupus 2009; 18: 508-515.

10.

Ahmad Y. , Shelmerdine J. , Bodill H. , et al. Subclinical atherosclerosis in systemic lupus erythematosus (SLE): the relative contribution of classic risk factors and the lupus phenotype . Rheumatology (Oxford) 2007; 46: 983-988.

11.

Font J. , Ramos-Casals M. , Brito-Zerón P. , et al. Association of mannose-binding lectin gene polymorphisms with antiphospholipid syndrome, cardiovascular disease and chronic damage in patients with systemic lupus erythematosus. Rheumatology ( Oxford) 2007; 46: 76-80.

12.

Rautaharju PM , Kooperberg C. , Larson JC , LaCroix A. Electrocardiographic abnormalities that predict coronary heart disease events and mortality in postmenopausal women: the Women’s Health Initiative. Circulation 2006; 113: 473-480.

13.

Corrado E. , Rizzo M. , Muratori I. , Coppola G. , Novo S. Older age and markers of inflammation are strong predictors of clinical events in women with asymptomatic carotid lesions. Menopause 2008; 15: 240-247.

14.

Lodde BM , Sankar V. , Kok MR , Leakan RA , Tak PP , Pillemer SR Serum lipid levels in Sjögren’s syndrome. Rheumatology (Oxford) 2006; 45: 481-484.

15.

Vaudo G. , Bocci EB , Shoenfeld Y. , et al. Precocious intima-media thickening in patients with primary Sjögren’s syndrome. Arthritis Rheum 2005; 52: 3890-3897.

16.

Ramos-Casals M. , Brito-Zerón P. , Sisó A. , et al. High prevalence of serum metabolic alterations in primary Sjögren’s syndrome: influence on clinical and immunological expression. J Rheumatol 2007; 34: 754-761.

17.

Vitali C. , Bombardieri S. , Jonsson R. , et al. Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002; 61: 554-558.

18.

Ramos-Casals M. , Solans R. , Rosas J. , et al. Primary Sjögren syndrome in Spain: clinical and immunologic expression in 1010 patients. Medicine (Baltimore) 2008; 87: 210-219.

19.

Ramos-Casals M. , Font J. , Garcia-Carrasco M. , et al. Primary Sjögren syndrome: hematologic patterns of disease expression. Medicine (Baltimore) 2002; 81: 281-292.

20.

Robinson CP , Yamachika S. , Alford CE , et al. Elevated levels of cysteine protease activity in saliva and salivary glands of the non-obese diabetic (NOD) mouse model for Sjögren syndrome. Proc Natl Acad Sci U S A 1997; 94: 5767-5771.

21.

Ramos-Remus C. , Suarez-Almazor M. , Russell AS Low tear production in patients with diabetes mellitus is not due to Sjögren’s syndrome . Clin Exp Rheumatol 1994; 12: 375-380.

22.

Binder A. , Maddison PJ , Skinner P. , Kurtz A. , Isenberg DA Sjögren’s syndrome: association with type-1 diabetes mellitus . Br J Rheumatol 1989; 28: 518-520.

23.

Sada KE , Yamasaki Y. , Maruyama M. , et al. Altered levels of adipocytokines in association with insulin resistance in patients with systemic lupus erythematosus. J Rheumatol 2006; 33: 1545-1552.

24.

El Magadmi , M. , Ahmad Y. , Turkie W. , et al. Hyperinsulinemia, insulin resistance, and circulating oxidized low density lipoprotein in women with systemic lupus erythematosus. J Rheumatol 2006; 33: 50-56.

25.

Gonzalez-Gay MA , De Matias JM , Gonzalez-Juanatey C. , et al. Anti-tumor necrosis factor-alpha blockade improves insulin resistance in patients with rheumatoid arthritis. Clin Exp Rheumatol 2006 ; 24: 83-86.

26.

Dessein PH , Joffe BI , Stanwix AE Inflammation, insulin resistance, and aberrant lipid metabolism as cardiovascular risk factors in rheumatoid arthritis. J Rheumatol 2003; 30: 1403-1405.

27.

Perlemuter G. , Bigorgne A. , Cassard-Doulcier AM , Naveau S. Nonalcoholic fatty liver disease: from pathogenesis to patient care. Nat Clin Pract Endocrinol Metab 2007; 3: 458-469.

28.

Rader DJ Effect of insulin resistance, dyslipidemia, and intra-abdominal adiposity on the development of cardiovascular disease and diabetes mellitus. Am J Med 2007; 120(Suppl 1): S12-S18.

29.

Said G. Diabetic neuropathy: a review. Nat Clin Pract Neurol 2007; 3: 331-340.

30.

Eshbaugh CG , Siatkowski RM , Smith JL , Kline LB Simultaneous, multiple cranial neuropathies in diabetes mellitus. J Neuroophthalmol 1995 ; 15: 219-224.

31.

Nikpour M. , Gladman DD , Ibañez D. , Urowitz MB Variability and correlates of high sensitivity C-reactive protein in systemic lupus erythematosus. Lupus 2009 ; 18: 966-973.

32.

Pons-Estel GJ , Gonzalez LA , Zhang J. , et al. Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multiethnic US cohort. Rheumatology ( Oxford) 2009; 48: 817-822.

33.

Lee SS , Singh S. , Magder LS , Petri M. Predictors of high sensitivity C-reactive protein levels in patients with systemic lupus erythematosus. Lupus 2008 ; 17: 114-123.

34.

Gonzalez-Gay MA , Gonzalez-Juanatey C. , Lopez-Diaz MJ , et al. HLA-DRB1 and persistent chronic inflammation contribute to cardiovascular events and cardiovascular mortality in patients with rheumatoid arthritis. Arthritis Rheum 2007; 57: 125-132.

35.

Danenberg HD , Szalai AJ , Swaminathan RV , et al. Increased thrombosis after arterial injury in human C-reactive protein-transgenic mice. Circulation 2003; 108: 512-515.

36.

Paul A. , Ko KWS , Li L. , et al. C-reactive protein accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice. Circulation 2004; 109: 647-655.

37.

Ruiz-Irastorza G. , Egurbide MV , Pijoan JI , et al. Effect of antimalarials on thrombosis and survival in patients with systemic lupus erythematosus. Lupus 2006; 15: 577-583.

38.

Ruiz-Irastorza G. , Ramos-Casals M. , Brito-Zeron P. , Khamashta MA Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review. Ann Rheum Dis 2010; 69: 20-28.

39.

Bessant R. , Duncan R. , Ambler G. , et al. Prevalence of conventional and lupus-specific risk factors for cardiovascular disease in patients with systemic lupus erythematosus: A case-control study. Arthritis Rheum 2006; 55: 892-899.

40.

Doria A. , Shoenfeld Y. , Wu R. , et al. Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus. Ann Rheum Dis 2003; 62: 1071-1077.

41.

Swanson CA , Levy JA , Morrow WJ Effect of low dietary lipid on the development of Sjögren’s syndrome and haematological abnormalities in (NZB x NZW) F1 mice. Ann Rheum Dis 1989; 48: 765-770.

42.

Davidson MH Management of dyslipidemia in patients with complicated metabolic syndrome. Am J Cardiol 2005; 96: 22E-25E.

43.

Theander E. , Manthorpe R. , Jacobsson LT Mortality and causes of death in primary Sjögren’s syndrome: a prospective cohort study . Arthritis Rheum 2004; 50: 1262-1269.

44.

Brito-Zerón P. , Ramos-Casals M. , Bove A. , Sentis J. , Font J. Predicting adverse outcomes in primary Sjögren’s syndrome: identification of prognostic factors. Rheumatology (Oxford) 2007; 46: 1359-1362.