Mean platelet volume modifies the contribution of homocysteine to cardiovascular disease: A real-world study.

BACKGROUND AND AIMS: The effect of reductions in homocysteine (Hcy) on cardiovascular disease (CVD) was suggested to be modified by platelet activation, but the interaction between Hcy and platelet activation on CVD events is not well studied. Here, we aimed to examine the interaction between Hcy and platelet activation on CVD in a large, real-world population. METHODS AND RESULTS: A total of 27,234 patients with hypertension (mean 63 years, 48% male) who were registered in Taicang city and free of CVD were prospectively followed up for new CVD events from 2017 to 2020. Hcy and platelet indices including mean platelet volume (MPV) were assayed at baseline. A total of 1063 CVD events were recorded during follow-up. Hcy at baseline was significantly associated with a higher risk of CVD (HR = 1.85, P < 0.001 for log-transformed Hcy). MPV showed a significant interaction effect with Hcy on CVD (HR = 1.20, P = 0.030 for the interaction term). The association between Hcy and CVD was significantly stronger in participants with a large (vs. small) MPV (HR = 2.71 vs. 1.32, P = 0.029 for log-transformed Hcy). For participants with both elevated Hcy and a large MPV, the attributable proportion of CVD events due to their interaction was 0.26 (95% CI: 0.06-0.45). CONCLUSIONS: The association between Hcy and CVD was significantly stronger in patients with hypertension with a larger MPV. MPV may modify the contribution of Hcy to CVD events through synergistic interactions with Hcy. These findings suggest that MPV could be monitored and controlled in the prevention of CVD.

Modification of Platelet Count on the Association between Homocysteine and Blood Pressure: A Moderation Analysis in Chinese Hypertensive Patients.

BACKGROUND: Platelet consumption followed by homocysteine-induced endothelial injury suggests a crosstalk between platelet activation and homocysteine on hypertension. Platelet count has been found to modify the effect of folic acid on vascular health. However, whether platelet count could modify the contribution of homocysteine to blood pressure (BP) remains unclear. METHODS: Leveraging a community-based cross-sectional survey in 30,369 Chinese hypertensive patients (mean age 62 years, 52% female), we examined the moderation of platelet count on the association between serum homocysteine and BP by constructing hierarchical multiple regression models, adjusting for conventional risk factors. If adding the interaction term of homocysteine and platelet count could explain more variance in BP and the interaction is significant, then we believe that moderation is occurring. RESULTS: The association between serum homocysteine and diastolic BP was significantly stronger (ß = 0.092 vs. 0.035, P = 0.004) in participants with low platelet count (<210 × 109/L) than in those with high platelet count (≥210 × 109/L). Adding the interaction term of homocysteine and platelet count additionally explained 0.05% of the variance in diastolic BP (P = 0.004) in participants with low platelet count (<210 × 109/L) than in those with high platelet count (≥210 × 109/L). Adding the interaction term of homocysteine and platelet count additionally explained 0.05% of the variance in diastolic BP (ß = 0.092 vs. 0.035, P = 0.004) in participants with low platelet count (<210 × 109/L) than in those with high platelet count (≥210 × 109/L). Adding the interaction term of homocysteine and platelet count additionally explained 0.05% of the variance in diastolic BP (. CONCLUSIONS: The association between homocysteine and BP was significantly stronger in participants with low vs. high platelet count and was partially moderated by platelet count. These results indicate that platelet count may be useful in the identification of individuals who are most beneficial to reducing-homocysteine treatments but this usefullness still needs further investigation.