[Homocysteine and cardiovascular risk]

Area of Science:

• Biochemistry
• Cardiovascular Science
• Genetics

Context:

• Raised serum/plasma total homocysteine (tHcy) levels are associated with increased risk of coronary, cerebral, and peripheral artery disease.
• Hyperhomocysteinemia risk appears concentration-dependent and independent of traditional risk factors.
• Factors influencing tHcy include age, gender, renal function, vitamin B/folate intake, and genetic defects.

Purpose:

• To evaluate the evidence for a causal relationship between total homocysteine (tHcy) and atherothrombotic diseases.
• To address conflicting results from genetic, observational, and experimental studies on tHcy and cardiovascular disease.
• To determine if interventions lowering tHcy levels can reduce cardiovascular events.

Summary:

• Conflicting evidence exists regarding the causal role of tHcy in atherosclerosis, particularly in individuals with genetically elevated levels.
• While many studies show an association between tHcy and cardiovascular disease, causality is not definitively established.
• Irrefutable proof of tHcy's direct role in atherothrombosis pathogenesis requires demonstrating that interventions reducing tHcy also decrease cardiovascular events.

Impact:

• Clarifies the current understanding of hyperhomocysteinemia as a risk factor for arterial thrombosis.
• Highlights the need for clinical trials investigating the efficacy of tHcy-lowering interventions for cardiovascular event reduction.
• Provides a foundation for future research into the precise mechanisms linking tHcy to atherothrombosis.