Increase in Hcy concentrations with age has been reported in Spanish children age 2 months to 18 yr21
but was not seen in a group of healthy Canadian adults having mean age of 36 yr with range of 23-59 yr22
. In our study, Hcy levels varied as per age with maximum being in 40 to 45 yr age group, amongst cases of CAD, however, no significant difference was seen amongst controls.
Our study showed an association of high Hcy level with CAD as supported by a few cross-sectional studies4
. A large number of case-control studies have examined the association between HCA and CAD and two23,24
reported significantly higher Hcy levels, either fasting or after methionine load, in persons with CAD as compared with persons without CAD.
Hcy levels depend upon the presence of homozygosity of the C677T mutation that is present in 5 to 20 per cent subjects of Caucasian descent. In these cases, with (TT) mutation higher Hcy has been observed1
. However, studies from India found the prevalence of the gene mutation to be low in Indians15,25
. We also found very few homozygous individuals in the present study. Thus association with homozygocity (TT) could not be analysed. In our heterozygote (CT) cases and controls as well as wild homozygous (CC), no significant association was found between Hcy levels and the gene polymorphism. Thus our findings are at variance from some Indian studies9–12
which did not find association between Hcy levels and CAD but similar to other studies which found HCA correlated with CAD in Indians13–15
. Our study is also at variance with a study from Mumbai which found MTHFR
polymorphism to be an important risk factor for HCA and CAD16
Smoking has been found to compound the modest effect of hypertension on plasma Hcy26
. The strong relationship between blood pressure and Hcy that exists only in smokers suggests that smoking induced Hcy elevations may raise systolic blood pressure. In our study, we found significant association between smoking and Hcy levels in controls but not in cases of CAD implying that other factors may also affect Hcy levels in CAD.
Hsu et al27
found no association between the C677T MTHFR
gene polymorphism and risk of CAD in Taiwan. A study on 24968 initially healthy American women found higher Hcy levels had significant association with incidents of CAD but no association with MTHFR
genotype as found in our study28
. A recent case-control study conducted on 121 patients having at least 50 per cent stenosis of one coronary artery compared with 155 healthy control found that MTHFR
genotype had no association with the risk of CAD29
. However, plasma Hcy (>12.5 μmol/l, OR-3.49; 95% CI, 1.23-9.88) had a significant association with increased risk of CAD similar to our study. A meta-analysis of MTHFR
C677T polymorphism and CAD found no strong evidence to support the association of C677T gene polymorphism and CAD in Europe, North America or Australia6
. This geographical variability may be attributed to higher folate intake in these countries.
A study showed that serum LDL cholesterol and triglyceride concentration were elevated and serum HDL levels were significantly lower in CAD patients than in controls and Hcy levels were significantly higher in CAD patients30
. In our study, individuals with cholesterol >200 mg/dl, LDL >130 mg/dl and HDL <40 mg/dl had higher odds ratio for association with CAD, similar to other studies31,32
. Also, in Indians, triglyceride level >199 mg/dl may be a risk factor for CAD. Multivariate analysis by logistic regression of various risk factors of CAD found high levels of Hcy, cholesterol, high LDL and low levels of HDL and smoking as independent predictors of CAD when all other factors were controlled.
Dietary supplementation with folic acid and vitamin B12
can reduce elevated Hcy levels in most patients. Regardless of the causes of elevation, supplementation with one or more of these vitamins can lower plasma levels of Hcy4
. Mean Hcy levels in our controls were much higher than the normal in the West and in comparison to other studies33,34
. Probably the dietary deficiency of vitamin B6,
and folic acid as seen in Indian population17,18
plays a significant role. A significant post-treatment decrease in Hcy levels, in our study subjects, supports that supplementation of multivitamin has a definitive role in bringing down the level of Hcy in CAD cases as was evident in a meta-analysis4
. Another meta-analysis6
found a strong evidence to support an association of the MTHFR
C677T polymorphism and Hcy levels with CAD in Asia but not in Europe, North America and Australia. Thus, vitamin supplementation has a major role in reducing Hcy levels in patients of CAD irrespective of the cause. Further studies to assess the folate and cobalamine levels in Indian patients with CAD and its association with Hcy need to be carried out.