Stroke Risk Reduced With Declining Total Homocysteine Levels

brain scans
brain scans
Patients at risk of stroke may benefit from the total homocysteine-lowering effects of folic acid supplementation.

Serum total homocysteine (tHcy) may serve as a helpful biomarker to identify the risk for stroke in patients with hypertension, according to findings from a post hoc analysis published in Neurology.

Researchers performed an analysis of Chinese adults with hypertension who were included in the China Stroke Primary Prevention Trial (n=16,867) to determine the association between tHcy lowering and first stroke risk. Patients were randomized in a 1:1 ratio to either 1 tablet of 10-mg enalapril and 0.8 mg folic acid daily or 1 tablet of 10-mg enalapril only.

The secondary end point was a composite of cardiovascular death, stroke, and myocardial infarction.

Compared with patients who did not experience a stroke during the 4.5-year treatment period, those who did have a stroke had lower declining tHcy levels (β =-5.7; 95% CI, -8.8 to -2.6; P <.001). Investigators observed a 7% reduction in stroke risk among patients experiencing a 20% decline in tHcy (hazard ratio [HR] 0.93; 95% CI, 0.90-0.97; P <.001).

In addition, the researchers noticed a reduced stroke risk associated with greater reductions in tHcy across strata for gender, serum folate, and tHcy levels at baseline, age, blood pressure control, and treatment groups.

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This study analyzed patient data from Chinese adults only, and therefore, it fails to describe the effect of percent lowering of tHcy across all demographics. Additionally, because of the post hoc design, the investigators believe there was potential for residual imbalance in unadjusted baseline prognostic factors. The investigators also did not include supplementation with B vitamins, which limits the ability to determine whether the inclusion of these nutritive components may contribute to an additional risk-reduction effect.

According to the investigators, the monitoring of tHcy as a prognostic biomarker may “indicate the beneficial effect of folic acid therapy in the primary prevention of stroke” in people with hypertension.


Huang X, Li Y, Li P, et al. Association between percent decline in serum total homocysteine and risk of first stroke [published online October 13, 2017]. Neurology. doi: 10.1212/WNL.0000000000004648