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Other Factors Renal Failure Hypothyroidism Drugs Dilantin Methotrexate Niacin Plasma Homocysteine and Mortality in CHD Patients Prospective Evaluation of 587 CHD Patients, Followed for 4.6 Years Fasting Plasma Homocysteine Measured at Baseline Strong, Graded Relationship between Homocysteine Levels and All-Cause Mortality Nygard et al. N Eng J Med. 1997;337:230-236. Homocysteine Level (?mol/L) Mortality Ratio 9 - 14.9 15 - 19.9 ?20 1.9 2.8 4.5 Relation between Plasma Homocysteine Level and Mortality Nygard et al. N Eng J Med. 1997;337:230-236. Prospective Case-Cohort Study of CHD Incidence and Homocysteine: ARIC Results 3.3 year follow-up in ARIC population (15,792 subjects), with 232 incident CHD cases compared to 537 reference subjects tHcy was not associated with CHD incidence after controlling for all CHD risk factors. Folate, B12 and B6 levels also not predictive No genetic determinants (MTHFR, CBS) were associated with CHD Conclusion: tHcy is not an independent risk factor for CHD Circulation 1998;98:204 Homocysteine, Vitamins and Cardiovascular Disease Authors suggest that tHcy and CVD relationship can be explained through several possibilities tHcy is elevated because of the presence of vascular disease Low levels of folate, B6 and B12 could be the primary cause of CHD, and tHcy is a marker. tHcy is directly causal to atherosclerosis development tHcy may increase CHD risk other than atherosclerosis— thrombosis, inflammation Circulation 1998;98:196 Homocysteine, Diet and Cardiovascular Disease: AHA Science Advisory Report Most, but not all, prospective studies suggest an increased risk of CAD, stroke and peripheral vascular disease with homocysteine levels 15 ?mol/L. May be a graded relationship between homocysteine levels 10 ?mol/L and subsequent total and CHD death. No clinical trials have been done to evaluate effect of lowering homocysteine. Do not recommend routine homocysteine screening except in high-risk individuals or cases of premat