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Table 1 Studies investigating a link between hyperhomocysteinemia and cardiovascular diseases in rheumatoid arthritis patients

From: Therapeutic potential of folic acid supplementation for cardiovascular disease prevention through homocysteine lowering and blockade in rheumatoid arthritis patients

Author, year of publication, location Population Study design Cardiovascular outcome Key findings Comments
Berglund et al., 2009, Sweden [10] 235 RA patients; 68 males (52 ± 16 years)a and 166 females (46 ± 16 years)a Prospective cohort study Atherothrombotic events HHcy levels adjusted for age and sex were a significant predictor of atherothrombotic events (OR = 1.96, 95 % CI 0.99–3.50, p = 0.05). When adjusted for hypertension alongside age and sex, The predictive value of HHcy was reduced (OR = 1.84, 95 % CI 0.92–3.69, p = 0.084] for hypertension and OR = 1.80, 95 % CI 0.90–3.59, p = 0.096 for diabetes mellitus).
Anan et al., 2009, Japan [40] 25 RA women with WML (61 ± 6 years)a and and 40 RA women without WML (60 ± 7 years)a Case–control study WML HHcy independently predicted WML (OR 1.35, 95 % CI: 1.12-1.63, p < 0.0001). Adjusted for the duration of RA, triglyceride, HDL, FPG
Dala et al., 2012, Egypt [41] 180 RA patients with no history of IHD Cross-sectional study SIHD Serum Hcy was significantly higher in patients with SIHD as compared to those without (p < 0.001)  
Chung et al., 2005, USA [42] 141 patients with RA (median age 54, IQR 46–64), 68 % of females; and 86 controls without RA (median age 52, IQR 44–59), 65.1 % of females Case–control study Coronary-artery atherosclerosis (calcification) In unadjusted comparisons, HHcy was more common in RA patients with coronary-artery calcification than in those without. After adjusting for age and sex, the association was no more significant
Cisternas et al., 2002, Chili [43] 54 RA patients (51 ± 13 years)a; and 32 age and sex matched healthy controls Case–control study History of CVD There were higher Hcy plasma levels in RA patients with a history of CVD than in those without.  
Seriolo et al., 2001, Italy [21] 168 female RA women with WML (cases), 50 ± 10 yearsa; and 72 age and sex matched healthy controls (52 ± 9 years)a. Case–control study. History of thrombotic events Plasma levels of hcy in aPL antibody-positive patients with thrombosis were found to be significantly higher than in aPL antibody-negative RA patients without thrombosis (p < 0.001) Adjusted for the duration of RA, triglyceride, HDL-Cholesterol, fasting plasma glucose
  1. RA rheumatoid arthritis, SD standard deviation, OR odds ratio, 95 % CI 95 % confidence interval, FPG fasting plasma glucose, HHcy hyperhomocysteinemia, White matter lesions (WML) are considered as ischemic complications of cerebral microvascular disease, and important prognostic factor for the development of stroke, HDL high density lipoprotein cholesterol, ECG electrocardiogram, Hcy homocysteine, CVD cardiovascular disease, aPL-positive antiphospholipid antibody positive, aPL-negative antiphospholipid antibody negative, silent ischemic heart disease (SIHD) was diagnosed as ischemia on stress test in the absence of angina and/or ECG changes of either a bundle branch block or ST segment abnormality consistent with, IHD ischaemic heart disease, IQR interquartile range
  2. aAge is expressed as mean ± standard deviation