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Published on: October 12, 2017
Homocysteine hypothesis for atherothrombotic cardiovascular disease: not validated
Sanjay Kaul1, Andrew A Zadeh, Prediman K Shah
1Division of Cardiology, Cedars-Sinai Medical Center, University of California, Los Angeles, California 90048, USA. kaul@cshs.org
Insights
Elevated homocysteine levels show a small risk for vascular disease. Current evidence is insufficient to recommend routine screening or vitamin treatment for preventing atherothrombotic vascular disease.
Area of Science:
- Cardiovascular Medicine
- Metabolic Research
- Vascular Biology
Background:
- Homocysteine is linked to atherosclerotic and thrombotic vascular disease.
- Observational studies have evaluated its predictive utility for atherothrombotic vascular disease risk.
- The overall risk associated with homocysteine is generally small.
Purpose of the Study:
- To review homocysteine metabolism and pathophysiology.
- To summarize findings from observational and interventional trials.
- To identify uncertainties and future research directions.
Main Methods:
- Review of observational studies (case-control, cross-sectional, longitudinal).
- Analysis of randomized controlled trials (RCTs) of homocysteine-lowering therapy.
- Synthesis of existing literature on homocysteine and vascular disease.
Main Results:
- Prospective studies show a weaker association between homocysteine and atherothrombotic vascular disease than retrospective studies.
- RCTs of homocysteine-lowering therapy have not established a causal relationship.
- Insufficient evidence exists to support routine screening and treatment.
Conclusions:
- Current evidence does not support routine screening for elevated homocysteine.
- Vitamin treatment to lower homocysteine is not recommended for preventing atherothrombotic vascular disease.
- Further research is needed to clarify the role of homocysteine.
Abstract:
Homocysteine has been implicated in promoting atherosclerotic and thrombotic vascular disease. During the last decade, the utility of homocysteine in predicting risk for atherothrombotic vascular disease has been evaluated in several observational studies in a large number of patients. These studies show that the overall risk for vascular disease is small, with prospective, longitudinal studies reporting a weaker association between homocysteine and atherothrombotic vascular disease compared to retrospective case-control and cross-sectional studies. Furthermore, randomized controlled trials of homocysteine-lowering therapy have failed to prove a causal relationship. On the basis of these results, there is currently insufficient evidence to recommend routine screening and treatment of elevated homocysteine concentrations with folic acid and other vitamins to prevent atherothrombotic vascular disease. This review outlines the metabolism and pathophysiology of homocysteine, highlights the results of homocysteine observational and interventional trials, and presents areas of uncertainty and potential future work.
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