Objective: Hyperhomocysteinemia is a well-known marker that is associated with an increased risk of atherosclerosis due to its toxic effect on endothelial cells. This, in turn, leads to cardiovascular injury and increases morbidity. Different studies have shown alterations in the levels of homocysteine with respect to multiple disease states. Whether this non-traditional marker is associated with cardiovascular injury or not is subject to conflicting results. The purpose of this systematic review is to evaluate the role of homocysteine in the formation of atherosclerotic cardiovascular disease in young adults and children.

Materials and methods: This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). A search was done using specific keywords, including "homocysteine", "coronary artery disease", and "atherosclerosis", amongst several others, from the databases of PubMed, COCHRANE, and EBSCO. The data items included the diseased sample population along with the intervention used, or investigations carried out and the findings of the studies. Finally, 35 eligible studies were included.

Results: Young patients with atherosclerotic cardiovascular disease were more likely to have elevated levels of homocysteine compared to elderly patients. Elevated levels of homocysteine have been observed with several genetic, nutritional deficiencies, and autoimmune states such as rheumatoid arthritis. On the other hand, decreased levels of homocysteine have been observed after certain intervention treatments, such as oral contraceptive pills, L-thyroxine, and even the adoption of certain diets. In the majority of studies, whenever homocysteine levels were higher than normal, this was reflected by an increased carotid intima-media thickness.

Conclusions: Homocysteine has a high correlation with atherosclerotic cardiovascular disease in young and overweight patients. In addition, the relationship of homocysteine with smoking, genetic polymorphism, specific hormonal and renal disorders, nutritional deficiencies (vitamin B12 and folic acid), and the use of specific medicines are among the other recurring findings. Given that many of these studies focus only on women, the relationship between homocysteine and atherosclerotic cardiovascular diseases in males is still unclear. Whether males are more prone to hyperhomocysteinemia needs to be assessed. Still, precise processes underlying variations in homocysteine in relation to all influencing factors are unclear and need further studies.