Homocysteine levels are independently associated with damage accrual in systemic lupus erythematosus patients from a Latin-American cohort
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To determine the impact of homocysteine levels on damage accrual in systemic lupus erythematosus (SLE) patients.
This longitudinal study was conducted in consecutive patients seen every 6 months at our Rheumatology Department since 2012. Patients with available homocysteine levels and who had at least one subsequent visit were included. Univariable and multivariable Cox regression models were done to determine if homocysteine levels were predictive of damage accrual as per the SLICC Damage Index (SDI). The multivariable model was adjusted for pertinent variables (age at diagnosis, gender, socioeconomic status, disease duration, disease activity (SLEDAI), Framingham score, antimalarial and immunosuppressive drug use, average daily dose, and exposure time to prednisone (PDN)).
One hundred forty-five patients were included; their mean (SD) age at diagnosis was 43.70 (12.09) years, 136 (93.8%) were female, and nearly all were Mestizo. At baseline, disease duration was 7.55 (6.73) years; patients were followed for 3.54 (1.27) years. The SLEDAI was 5.60 (4.34), and the SDI 0.97 (1.35). The average daily PDN dose was 7.30 (5.78) mg/day and the time of PDN exposure was 7.36 (6.73) years. Mean homocysteine levels were 10.07 (3.71) μmol/L. The highest tertile of homocysteine levels predicted new damage accrual in the univariable and multivariable models [HR 1.78 (95% CI, 1.042–3.039); p = 0.035 and HR 2.045 (95% CI, 1.077–3.883); p = 0.029, respectively]. Increased levels (> 15 μmol/L) were found in 12 (8.3%) patients; 75 (51.7%) patients increased ≥ 1 SDI point.
In SLE patients, homocysteine levels predicted damage accrual independently of other well-known risk factors for such occurrence.
KeywordsDamage accrual Homocysteine Systemic lupus erythematosus
All authors were involved in drafting or critically revising this manuscript for important intellectual content, and all authors approved the final version to be published. Drs. Paola A. Zeña Huancas and Manuel F. Ugarte-Gil have full access to all the study’s data and take responsibility for their integrity and the accuracy of the analyses performed.
The Almenara Lupus Cohort is partially supported by three institutional grants from EsSalud (1483-GCGP-ESSALUD-2013, 1733-GCGP-ESSALUD-2014 and the 2015 Kaelin Prize 2015) and one from the Panamerican League of Associations for Rheumatology (PANLAR) (2015 PANLAR Prize).
Compliance with ethical standards
- 1.Manzi S, Meilahn EN, Rairie JE, Conte CG, Medsger TA Jr, Jansen-McWilliams L, D'Agostino RB, Kuller LH (1997) Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol 145:408–415CrossRefGoogle Scholar
- 7.Petri M, Fu W (2016) Hyperhomocysteinemia in SLE [abstract 2792]. Arthritis Rheumatol 68(suppl 10):3744–3347Google Scholar
- 12.Faraci FM, Lentz SR (2004) Hyperhomocysteinemia, oxidative stress, and cerebral vascular dysfunction. Stroke 35:345–347. https://doi.org/10.1161/01.STR.0000115161.10646.67 CrossRefPubMedGoogle Scholar
- 18.Mak A, Cheung MW, Chiew HJ, Liu Y, Ho RC (2012) Global trend of survival and damage of systemic lupus erythematosus: meta-analysis and meta-regression of observational studies from the 1950s to 2000s. Semin Arthritis Rheum 41:830–839. https://doi.org/10.1016/j.semarthrit.2011.11.002 CrossRefPubMedGoogle Scholar
- 19.Ugarte-Gil MF, Gamboa-Cárdenas RV, Zevallos F, Medina M, Cucho-Venegas JM, Perich-Campos RA, Alfaro-Lozano JL, Rodriguez-Bellido Z, Alarcón GS, Pastor-Asurza CA (2014) High prolactin levels are independently associated with damage accrual in systemic lupus erythematosus patients. Lupus 23:969–974. https://doi.org/10.1177/0961203314531083 CrossRefPubMedGoogle Scholar
- 20.Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):1725. https://doi.org/10.1002/1529-0131(199709)40:9<1725::AID-ART29>3.0.CO;2-Y CrossRefGoogle Scholar
- 21.Méndez-Csstellano HM, Méndez MC (1994) Sociedad y Estratificación. Método Graffar-Méndez Castellano FUNDACREDESA, Caracas, pp 7–35Google Scholar
- 23.Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M et al (1996) The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum 39:363–369. https://doi.org/10.1002/art.1780390303 CrossRefPubMedGoogle Scholar
- 24.Sabio JM, Vargas-Hitos JA, Martinez-Bordonado J, Navarrete-Navarrete N, Díaz-Chamorro A, Olvera-Porcel C, Zamora-Pasadas M, Jiménez-Alonso J (2014) Relationship between homocysteine levels and hypertension in systemic lupus erythematosus. Arthritis Care Res (Hoboken) 66(10):1528–1535. https://doi.org/10.1002/acr.22340 CrossRefGoogle Scholar
- 30.McMahon M, Skaggs BJ, Grossman JM, Sahakian L, FitzGerald J, Wong WK, Lourenco EV, Ragavendra N, Charles-Schoeman C, Gorn A, Karpouzas GA, Taylor MB, Watson KE, Weisman MH, Wallace DJ, Hahn BH (2014) A panel of biomarkers is associated with increased risk of the presence and progression of atherosclerosis in women with systemic lupus erythematosus. Arthritis Rheumatol 66(1):130–139. https://doi.org/10.1002/art.38204 CrossRefPubMedPubMedCentralGoogle Scholar
- 31.Castejon R, Jimenez-Ortiz C, Rosado S, Tutor-Ureta P, Mellor-Pita S, Yebra-Bango M et al (2016) Metabolic syndrome is associated with decreased circulating endothelial progenitor cells and increased arterial stiffness in systemic lupus erythematosus. Lupus 25(2):129–136. https://doi.org/10.1177/0961203315603138 CrossRefPubMedGoogle Scholar
- 36.Padjas A, Undas A, Swadźba J, Musial J (2007) Antibodies to N-homocysteinylated albumin in patients with systemic lupus erythematosus. Pol Arch Med Wewn 117(3):80–85Google Scholar
- 39.Bruce IN, O'Keeffe AG, Farewell V, Hanly JG, Manzi S, Su L, Gladman DD, Bae SC, Sanchez-Guerrero J, Romero-Diaz J, Gordon C, Wallace DJ, Clarke AE, Bernatsky S, Ginzler EM, Isenberg DA, Rahman A, Merrill JT, Alarcón GS, Fessler BJ, Fortin PR, Petri M, Steinsson K, Dooley MA, Khamashta MA, Ramsey-Goldman R, Zoma AA, Sturfelt GK, Nived O, Aranow C, Mackay M, Ramos-Casals M, van Vollenhoven RF, Kalunian KC, Ruiz-Irastorza G, Lim S, Kamen DL, Peschken CA, Inanc M, Urowitz MB (2015) Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort. Ann Rheum Dis 74(9):1706–1713. https://doi.org/10.1136/annrheumdis-2013-205171 CrossRefPubMedGoogle Scholar
- 40.Fu W, Petri M (2016) Treatment of homocysteine improves urine protein/Cr ratio in SLE [abstract 963]. Arthritis Rheumatol 68(suppl 10):1276–1277Google Scholar