There may be several explanations for these differences. First, age is an important confounding factor; there is evidence showing that tHcy increases with age.
30 The present study showed the tHcy levels of the CRVO patients over 60 years old were significantly higher than in patients less than 60 years old at all time points. However, in several studies that demonstrated an association between increased tHcy and CRVO, the patients were significantly older than the control subjects.
6,11,31,32 Second, sex (male or female) is an important confounding factor because homocysteine concentrations are greater in males than in females.
33 Our study showed that the tHcy levels of the female CRVO patients were significantly lower than those in male CRVO patients at all time points. However, in several studies that demonstrated tHcy is an independent risk factor for CRVO, the constituent ratio of male patients was more than that of control subjects.
8,9,12 Third, patient condition (fasting or nonfasting state) is an important confounding factor because homocysteine concentrations are greater in the nonfasting than in the fasting state.
30 Two previous studies demonstrated an association between increased homocysteine and CRVO, but nonfasting blood samples were obtained from patients and control subjects in one study, and nonfasting blood samples were obtained from patients and fasting samples from control subjects in another study.
7,31 Finally, in studies with a retrospective design, patients typically were recruited at variable intervals after onset of CRVO, and the mean time between CRVO occurrence and the determination of tHcy levels ranged from 1 to 69 months, which may have introduced variability in the measured tHcy concentrations. The previous studies demonstrated that the plasma homocysteine concentration gradually increased over time from the acute to the convalescent phase after a stroke,
34 and after acute coronary syndrome.
35 Consistent with the previous studies, the tHcy levels gradually increased from acute to convalescent phases of CRVO in CRVO patients. In addition, the present studies showed no significant differences in tHcy levels between controls and CRVO patients at entry and 1 month after CRVO. However, the tHcy levels of the CRVO patients at 3 and 6 months after CRVO were significantly higher than in controls. Thus, the measurement of tHcy during the convalescent phase after CRVO may have led to the higher tHcy levels in the patients than in the control subjects.