Background: Several prospective studies reported that fibrates might increase blood total homocysteine (tHcy). In this study we aimed to establish whether the reported fibrate treatment was associated with an increased risk of mild hyperhomocysteinaemia in patients with clinical coronary heart disease, and to establish whether confounding variables may influence this effect.
Design: A retrospective, case-control analysis.
Methods: A total of 410 patients, 301 males and 109 females, mean age 59.2 were examined in a Czech sample from the EUROASPIRE II survey. In addition to examinations and measurements, defined by the protocol, we estimated serum total homocysteine (tHcy), folate, B12 vitamin and methylenetetrahydrofolate reductase (MTHFR) genotypes.
Results: We found significantly higher tHcy concentrations in patients with reported treatment with fibrate (16.6 +.- 0.66 micromol/l) compared with no lipid-lowering treatment (13.5 +/- 0.64 micromol/l, P<0.001) or to statin (12.4 +/- 0.39 micromol/l, P<0.001). Concentrations of tHcy > or =15 mmol/l (i.e. mild hyperhomocysteinaemia) as a dependent variable were positively associated with age (OR 1.18, P<0.0003), serum vitamin B12 (OR 0.87, P<0.003), serum creatinine (OR 1.35, P<0.0001 and treatment with fibrates (OR 1.30, P<0.0001), using multiple regression. Using unifactorial or multifactorial analyses, association between fibrate and tHcy is independent from conventional confounders such as age, gender, smoking, folate or B12 concentration, serum creatinine and MTHFR genotypes, however interference of low folate or B12 and fibrate treatment resulted in concentrations of tHcy more than 20 micromol/l.
Conclusions: Fibrate treatment was associated with a significant increase in prevalence of the risk of mild hyperhomocysteinaemia in coronary patients, independently from conventional confounders.