Does homocysteine (elevated homocysteine level) influence hypertension (high blood pressure)?

From the Guidelines

Elevated homocysteine levels are not a direct cause of hypertension, and lowering homocysteine levels through B-vitamin supplementation does not reduce the risk of cardiovascular disease, including hypertension. The relationship between homocysteine and hypertension is complex, and while some studies suggest a link between hyperhomocysteinemia and increased blood pressure, the evidence is not strong enough to support a causal relationship [ 1 ].

Key Findings

• A meta-analysis of eight RCTs found that homocysteine-lowering interventions did not reduce the risk of fatal/non-fatal myocardial infarction, stroke, or death by any cause [ 1 ].
• Three large secondary prevention trials (SEARCH, VITATOPS, and SU.FOL.OM3) concluded that supplementation with folic acid and vitamin B6 and/or B12 offers no protection against the development of cardiovascular disease [ 1 ].
• A meta-analysis of 30 studies found a 25% difference in plasma homocysteine concentration to be associated with a 19% difference in stroke risk, but this does not necessarily imply a causal relationship with hypertension [ 1 ].

Clinical Implications

• The current evidence does not support the use of B-vitamin supplementation to lower homocysteine levels for the prevention or treatment of hypertension.
• A diet rich in leafy greens, legumes, and fortified grains provides essential nutrients, but its impact on homocysteine levels and hypertension is unclear.
• Further research is needed to fully understand the relationship between homocysteine and hypertension, but current evidence prioritizes other risk factors and interventions for the prevention and management of cardiovascular disease.

From the Research

Relationship Between Homocysteine and Hypertension

• Several studies have investigated the link between plasma homocysteine levels and blood pressure, with some finding a weak association, especially with systolic pressure 2, 3.
• The mechanisms that could explain the relationship between homocysteine and blood pressure include increased arterial stiffness, endothelial dysfunction, and insulin resistance 2.
• However, the evidence is not conclusive, and some studies suggest that the association between homocysteine and blood pressure may be confounded by renal function or other factors 2, 3.
• Homocysteine-lowering therapies with folic acid-based treatments have been followed by decreases in blood pressure in some studies, raising the possibility that the link between homocysteine and blood pressure is causal 2, 3.

Epidemiological Studies

• A large epidemiological study found that each 5 micromol/l increase in plasma homocysteine was associated with an increase in systolic and diastolic blood pressure of 0.7/0.5 mmHg in men and 1.2/0.7 mmHg in women, independent of renal function and B vitamin status 3.
• Another study found that elevated plasma homocysteine concentrations were associated with an increased risk of cardiovascular disease, with a linear dose-response relationship starting at a plasma homocysteine concentration of approximately 10 micromol/l 4.

Intervention Studies

• A randomized controlled trial found that lowering homocysteine with B vitamins had no effect on blood pressure in older adults with elevated homocysteine concentrations 5.
• The results of this study suggest that the relationship between homocysteine and blood pressure may be more complex than previously thought, and that lowering homocysteine levels may not necessarily lead to a decrease in blood pressure 5.

Clinical Implications

• The assessment and treatment of homocysteine should be approached in the context of other modifiable risk factors for cardiovascular disease 6.
• While some studies suggest that reducing homocysteine levels may have some benefit in reducing cardiovascular risk, the evidence is not yet conclusive, and more research is needed to fully understand the relationship between homocysteine and hypertension 4, 6.