- Elevated blood level of homocysteine is a risk factor for thrombogenesis (blood clots), atherogenesis (plaque buildup), and CAD (coronary artery disease).1 Since several homocysteine lowering trials have consistently failed to produce any beneficial outcome, measuring and or treating homocysteine cannot be recommended at this time.2, 3 However, the value of homocysteine lowering in people without heart disease (primary prevention) has not been ascertained.
- High homocysteine level may be a risk marker, rather than causal risk factor, allowing many intermediate risk individuals to be reclassified as high-risk qualifying for more aggressive medical management.1-4
- Several classes of drugs, such as biguanides, fibrates and hydrochlorothiazide have been reported to raise circulating homocysteine levels. On the other hand beta-blockers, calcium channel blockers, statins, sulphonylureas, TZDs, biguanide, and meglitinide reduce homocysteine level.5
- Homocysteine augments the deposition of Lp(a)on fibrin surfaces and its pathological effects are exponentially increased with the concomitant presence of elevated Lp(a) (30-fold) and Factor V Leiden (20-fold).6, 7 Homocysteine, even at low concentration markedly increases the affinity of Lp(a) for fibrin.8
- Raised homocysteine and serum Lp(a) levels were found to be independently associated with ischemic stroke with a significant positive correlation between the two parameters in Indians.9 Elevated homocysteine levels may modulate the toxicity of Lp(a) in ischemic stroke.
- Homocysteine levels are higher among Asian Indians than Europids in several countries.10-16 Homocysteine levels > 15 mmol/L are found in 75-84% of subjects in India.12, 17 High homocysteine levels in Asian Indians in India and the Diasporas appear to be related more to subnormal levels of vitamin B12 rather than folic acid deficiency.12, 16, 17 Overall, 47%- 67% of Indian men had low vitamin B12 concentration (<150 pmol/L)12, 17 Low vitamin B12 concentration contributed 28% to the risk of hyperhomocysteinemia (population attributable risk) while low red cell folate contributed 2%.17
- Many experts believe that intrauterine growth retardation (IUGR) is a risk factor for insulin resistance and premature cardiometabolic risk. High maternal levels of homocysteine associated with low maternal and cord folate levels) have been implicated in IUGR warranting further studies.18
- High homocysteine level is now considered the single best measure of poor dietary habits such as not eating fresh fruits and vegetables as well as overcooking and deep-frying which destroy most of the nutrients, especially folate. It appears that widespread B12 deficiency is another perhaps more important risk factor for Indians.
- In India, most people adhere to a vegetarian diet, which may lead to cobalamin deficiency. Vegetarians have 3.0 times higher risk of hyperhomocysteinemia compared to those who ate non-vegetarian foods frequently.17 Vegetarians also had 4 times higher risk of low vitamin B12 concentrations17Thus, impaired cobalamin status appears more important than folate deficiency among Asian Indians.
- Some reports have suggested that higher homocysteine levels in South Asians are due to high levels amongst Hindus many of whom are vegtarians.19 Only 2.5% of the Asian Indians are homozygous for the MTHFR 677C–>T polymorphism and thus genetic abnormalities plays no significant role in elevated homocysteine levels in Asian Indians.
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