Serum S-adenosylhomocysteine levels are associated with first stroke in Chinese adults with hypertension.

Background: The association between S-adenosylhomocysteine (SAH) and stroke has not been confirmed due to the specialized equipment and time requirements necessary for S-adenosylhomocysteine testing. We aimed to explore the association between SAH and stroke.

Methods: A nested, case-control study drawn from the China Stroke Primary Prevention Trial of rural adults with hypertension, including 557 first stroke cases and 557 matched controls was conducted. Serum SAH was measured by stable-isotope dilution liquid chromatography-tandem mass spectrometry using 4500MD. Multiple conditional logistic regression models were used to evaluate the association between SAH and first stroke.

Results: In females, SAH levels were significantly higher in the stroke population than in the control group (16.0 ng/mL vs. 14.6 ng/mL). When SAH was assessed as quartiles, the odds of stroke were 1.78 (95 % CI: 1.02-3.09) in Quartile 2, 1.31 (95 % CI: 0.73-2.33) in Quartile 3, and 1.93 (95 % CI: 1.03-3.62) in Quartile 4, compared to Quartile 1. When Quartiles 2-4 were combined, the adjusted odds ratio of first stroke was 1.64 (95 % CI: 1.03-2.62) compared with Quartile 1. In subgroup analysis, a significant SAH-stroke association was observed in the lower vitamin D3 group (OR = 3.35, 95 % CI:1.72-6.53; P interaction, 0.035). In males, higher levels of SAH were associated with an increased risk of stroke in those under age 60. Compared with the reference group, the adjusted odds ratio of total stroke was 2.40 (95 % CI: 1.02-5.91) in the combined group (Quartile 2-4). In contrast, no significant association between SAH and stroke was found in males aged 60 or older.

Conclusions: This study reveals that SAH is associated with a higher risk of stroke independently of homocysteine, especially in females. SAH may be a second predictor of stroke in the metabolic pathway of methionine, after homocysteine.