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Abstract
Objective
The present study determined if vitamin D deficiency is a potential risk factor for increased carotid in-tima-media thickness (CIMT) in patients with rheumatoid arthritis (RA).
Methods
This cross-sectional study analyzed 50 consecutive female RA patients without cardiovascular disease history at the Pusan National University Hospital between September and December of 2013. CIMT was measured using a high-resolution ultrasonography. Serum 25-hydroxy vitamin D (25-OHD) levels were assessed by radioimmuno-assay, and vitamin D deficiency was defined as serum 25-OHD levels ＜20 ng/mL. Stepwise multivariable linear regression analyses were performed to evaluate the association between vitamin D deficiency and increased CIMT. Results. The median 25-OHD level (interquartile range) was 14.0 (11.0∼20.7) ng/mL, and 74% of patients had vitamin D deficiency. The mean± standard deviation of CIMT was 0.58±0.08 mm. RA patients with vitamin D deficiency had significantly higher CIMT than those without this feature (0.59±0.07 vs 0.54±0.05, p=0.028). In univariable linear regression models, vitamin D deficiency (β(SE)=0.047 (0.021), p=0.028), older age (β(SE)=0.003 (7.2-4), p＜0.001) and higher disease activity score 28-erythrocyte sedimentation rate (β(SE)=0.021 (0.010), p=0.034) and Korean version of health assessment questionnaire score (β(SE)=0.051 (0.015), p=0.002) were significantly associated with increased CIMT. Vitamin D deficiency remained statistically significant in multivariable regression models after adjusting for confounders.
REFERENCES
1. Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007; 92:2017–29.
2. McGreevy C, Williams D. New insights about vitamin D and cardiovascular disease: a narrative review. Ann Intern Med. 2011; 155:820–6.
3. Kim DH, Sabour S, Sagar UN, Adams S, Whellan DJ. Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004). Am J Cardiol. 2008; 102:1540–4.
4. Mao PJ, Zhang C, Tang L, Xian YQ, Li YS, Wang WD, et al. Effect of calcium or vitamin D supplementation on vascular outcomes: A meta-analysis of randomized controlled trials. Int J Cardiol. 2013; 169:106–11.
5. Wang L, Manson JE, Song Y, Sesso HD. Systematic review: Vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med. 2010; 152:315–23.
6. Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Wetterslev J, Simonetti RG, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2011; (7):CD007470.
7. Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002; 110:229–38.
8. Carthy EP, Yamashita W, Hsu A, Ooi BS. 1,25-Dihydro-xyvitamin D3 and rat vascular smooth muscle cell growth. Hypertension. 1989; 13:954–9.
9. Borges AC, Feres T, Vianna LM, Paiva TB. Effect of cholecalciferol treatment on the relaxant responses of spontaneously hypertensive rat arteries to acetylcholine. Hypertension. 1999; 34:897–901.
10. Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, et al. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994; 37:481–94.
11. Avina-Zubieta JA, Thomas J, Sadatsafavi M, Lehman AJ, Lacaille D. Risk of incident cardiovascular events in patients with rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis. 2012; 71:1524–9.
12. Meune C, Touzé E, Trinquart L, Allanore Y. Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford). 2009; 48:1309–13.
13. Gatenby P, Lucas R, Swaminathan A. Vitamin D deficiency and risk for rheumatic diseases: an update. Curr Opin Rheumatol. 2013; 25:184–91.
14. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988; 31:315–24.
15. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28:412–9.
16. Bae SC, Cook EF, Kim SY. Psychometric evaluation of a Korean Health Assessment Questionnaire for clinical research. J Rheumatol. 1998; 25:1975–9.
17. Prevoo ML, van't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995; 38:44–8.
18. Kang Y, Park HJ, Kang MI, Lee HS, Lee SW, Lee SK, et al. Adipokines, inflammation, insulin resistance, and carotid atherosclerosis in patients with rheumatoid arthritis. Arthritis Res Ther. 2013; 15:R194.
19. Veller MG, Fisher CM, Nicolaides AN, Renton S, Geroulakos G, Stafford NJ, et al. Measurement of the ultrasonic intima-media complex thickness in normal subjects. J Vasc Surg. 1993; 17:719–25.
20. Targońska-Stepniak B, Drelich-Zbroja A, Majdan M. The relationship between carotid intima-media thickness and the activity of rheumatoid arthritis. J Clin Rheumatol. 2011; 17:249–55.
21. Haque UJ, Bathon JM, Giles JT. Association of vitamin D with cardiometabolic risk factors in rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012; 64:1497–504.
22. Goshayeshi L, Saber H, Sahebari M, Rezaieyazdi Z, Rafatpanah H, Esmaily H, et al. Association between metabolic syndrome, BMI, and serum vitamin D concentrations in rheumatoid arthritis. Clin Rheumatol. 2012; 31:1197–203.
23. Kerekes G, Soltész P, Nurmohamed MT, Gonzalez-Gay MA, Turiel M, Végh E, et al. Validated methods for assessment of subclinical atherosclerosis in rheumatology. Nat Rev Rheumatol. 2012; 8:224–34.
24. Simpson RU, Hershey SH, Nibbelink KA. Characterization of heart size and blood pressure in the vitamin D receptor knockout mouse. J Steroid Biochem Mol Biol. 2007; 103:521–4.
25. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008; 168:1174–80.
26. Pilz S, Dobnig H, Fischer JE, Wellnitz B, Seelhorst U, Boehm BO, et al. Low vitamin d levels predict stroke in patients referred to coronary angiography. Stroke. 2008; 39:2611–3.
27. Melamed ML, Muntner P, Michos ED, Uribarri J, Weber C, Sharma J, et al. Serum 25-hydroxyvitamin D levels and the prevalence of peripheral arterial disease: results from NHANES 2001 to 2004. Arterioscler Thromb Vasc Biol. 2008; 28:1179–85.
28. Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, et al. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008; 168:1340–9.
29. Pittas AG, Chung M, Trikalinos T, Mitri J, Brendel M, Patel K, et al. Systematic review: Vitamin D and cardiometabolic outcomes. Ann Intern Med. 2010; 152:307–14.
30. Reis JP, von Mühlen D, Michos ED, Miller ER 3rd, Appel LJ, Araneta MR, et al. Serum vitamin D, parathyroid hormone levels, and carotid atherosclerosis. Atherosclerosis. 2009; 207:585–90.
31. de Boer IH, Kestenbaum B, Shoben AB, Michos ED, Sarnak MJ, Siscovick DS. 25-hydroxyvitamin D levels inversely associate with risk for developing coronary artery calcification. J Am Soc Nephrol. 2009; 20:1805–12.
32. Symmons DP, Gabriel SE. Epidemiology of CVD in rheumatic disease, with a focus on RA and SLE. Nat Rev Rheumatol. 2011; 7:399–408.
33. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007; 25:1105–87.
34. González-Gay MA, González-Juanatey C, Llorca J. Carotid ultrasound in the cardiovascular risk stratification of patients with rheumatoid arthritis: when and for whom? Ann Rheum Dis. 2012; 71:796–8.
35. Tyrrell PN, Beyene J, Feldman BM, McCrindle BW, Silverman ED, Bradley TJ. Rheumatic disease and carotid intima-media thickness: a systematic review and meta-analysis. Arterioscler Thromb Vasc Biol. 2010; 30:1014–26.
36. Welsh P, Peters MJ, Sattar N. Is vitamin D in rheumatoid arthritis a magic bullet or a mirage? The need to improve the evidence base prior to calls for supplementation. Arthritis Rheum. 2011; 63:1763–9.
37. Can M, Gunes M, Haliloglu OA, Haklar G, Inanç N, Yavuz DG, et al. Effect of vitamin D deficiency and replacement on endothelial functions in Behç et's disease. Clin Exp Rheumatol. 2012; 30(3 Suppl 72):S57–61.
38. Kiani AN, Fang H, Magder LS, Petri M. Vitamin D deficiency does not predict progression of coronary artery calcium, carotid intima-media thickness or high-sensitivity C-reactive protein in systemic lupus erythematosus. Rheumatology (Oxford). 2013; 52:2071–6.
Table 1.
Baseline demographics of 50 female patients with rheumatoid arthritis
IQR: interquartile range, RF: rheumatoid factor, Anti-CCP antibody: Anticitrullinated protein antibody, ESR: erythrocyte sedimentation rate, CRP: C-reactive protein, DAS28: disease activity score 28, GCs: glucocorticoids, K-HAQ: Korean Version of health assessment questionnaire, TNF-α: tumor necrosis factor-alpha, 25-OHD: 25-hydroxy vitamin D.
Table 2.
Cardiovascular risk factors in study subjects
BMI: body mass index, WHR: waist-to-hip ratio, HTN: hypertension, SBP: systolic blood pressure, DBP: diastolic blood pressure, LDL-C: low density lipoprotein cholesterol, TG: triglycerides, HDL-C: high density lipoprotein cholesterol, DM: diabetes mellitus, IQR: interquartile range HOMA-IR: homeostatic model assessment-insulin resistance, CIMT: carotid intima-media thickness.
Table 3.
Linear regression models for carotid intima media thickness in study subjects
|
Univariable analysis |
Model 1* |
Model 2† |
||||
|---|---|---|---|---|---|---|
| β (SE) | p-value | β (SE) | p-value | β (SE) | p-value | |
| Age, years | 0.003 (7.2-4) | ＜0.001 | 0.003 (6.9-4) | ＜0.001 | 0.003 (6.6-4) | ＜0.001 |
| Vitamin D deficiency | 0.047 (0.021) | 0.028 | 0.044 (0.017) | 0.014 | 0.041 (0.016) | 0.017 |
| BMI, kg/m2 | 0.005 (0.003) | 0.106 | 0.005 (0.002) | 0.032 | 0.006 (0.002) | 0.016 |
| Disease duration, months | 1.6-4 (1.6-4) | 0.318 | ||||
| HDL-C, mg/dL | −0.001 (5.2-4) | 0.054 | ||||
| DAS28-ESR | 0.021 (0.010) | 0.034 | ||||
| K-HAQ | 0.051 (0.015) | 0.002 | 0.044 (0.015) | 0.005 | ||
| Adjusted R2*=0.421 | Adjusted R2†=0.550 | |||||
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