Homocysteine as a risk factor for coronary heart diseases and its association with inflammatory biomarkers, lipids and dietary factors
Section snippets
Background
tHcy, a highly reactive sulfur-containing amino acid, is an intermediary product of methionine metabolism which can be either remethylated to methionine or metabolized to cysteine. tHcy is a modest independent predictor of CHD [1], [2], but the pathophysiologic mechanism is unclear. tHcy might induce atherosclerosis by impairing coronary microvascular dilator function [3], by smooth muscle proliferation [4], platelet activation, thrombogenesis [5], endothelial dysfunction, and collagen
The Nurses’ Health Study (NHS) cohort population and blood collection
The NHS was initiated in 1976, with the enrollment of 121,700 female nurses aged 30–55. Since then, follow-up questionnaires have been mailed to the cohort every 2 years to update information on exposures and the occurrence of major illnesses. Between 1989 and 1990, blood samples were collected from 32,826 women. Within 24 h of collection 97% of the samples were returned. They were immediately centrifuged, aliquoted into plasma, red blood cell, and buffy-coat fractions, and stored in liquid
Population characteristics and MTHFRC677T polymorphism
After excluding 24 subjects who were taking cholesterol-lowering drugs at time of blood collection and 9 whose tHcy data were missing, we documented 237 incident MI cases (202 nonfatal MI and 35 fatal CHD) during 8 years of follow-up. Compared with 458 controls, case subjects had higher plasma tHcy levels (P = 0.02) were more likely to have diabetes, hypertension, higher BMI and a parental history of MI. In our population, the prevalence of heterozygosity and homozygosity of the thermolabile
Discussion
In a nested prospective case-control assessment including 202 nonfatal MI and 35 fatal CHD events during 8 years of follow-up, we found a positive association between tHcy levels and CHD risk. We observed a linear trend, but the elevated risk was significant only in the top quartile. This association persisted after controlling for other established CHD factors. tHcy levels were independently inversely correlated with elevated blood levels and dietary intake of folate, and modestly associated
Acknowledgments
This study was supported by NIH research grants CA42182, CA18293 and from Merck Research Laboratories. We thank Dr. Frank Speizer, the founding principal investigator and Dr. Graham Colditz, the current principal investigator of the Nurses’ Health Study, for their invaluable contributions and the participants of the Nurses’ Health Study for their continued cooperation and participation. We are indebted to the S. Daniel Abraham International Center for Health and Nutrition, Ben-Gurion University
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