Individuals with high systemic thromboxane generation and low Life's Essential 8 scores had a 5-fold higher risk of heart failure (HR 5.07; 95% CI 3.26-7.89) and 2.5-fold higher risk of CVD.
Cohort (n=2,655)
Are modifiable lifestyle factors and omega-3 fatty acids associated with systemic thromboxane A2 generation, and does this generation modulate their association with cardiovascular outcomes?
Modifiable lifestyle factors are associated with lower systemic thromboxane A2 generation, which in turn modulates the risk of incident cardiovascular disease and heart failure.
Estimación del efecto: HR 5.07 for heart failure, HR 2.74 for CVD (95% CI 3.26-7.89 for heart failure, 2.04-3.68 for CVD)
BACKGROUND: Systemic thromboxane A2 generation, assessed via measurement of its urinary metabolites, is associated with cardiovascular disease (CVD) risk. Modifiable correlates with thromboxane A2 generation, including potentially nonplatelet sources not readily affected by aspirin, are poorly understood. METHODS: We investigated 2655 FHS (Framingham Heart Study) participants with measurements of urinary thromboxane B2 metabolites normalized for renal function (TXB2-MGFR). Life's Essential 8 (LE8) score was constructed from 8 modifiable factors. We additionally examined erythrocyte omega-3 fatty acids and omega-6 fatty acid levels, namely, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid. In a subset of participants, objective measurements of vascular stiffness and adiposity were obtained. We related these factors to TXB2-MGFR using linear models, adjusting for age, sex, and aspirin use. We also explored the association of LE8 or omega-3 fatty acids with total CVD or heart failure stratified by TXB2-MGFR. RESULTS: Both total LE8 score (P<0.001) and individual LE8 components (P<0.05 for each), including favorable diet, physical activity, blood glucose, blood pressure, and nonsmoking, were associated with lower TXB2-MGFR. Higher omega-3 fatty acids (eicosapentaenoic acid+docosahexaenoic acid) and lower arachidonic acid were associated with lower TXB2-MGFR (P<0.005 for each). Higher TXB2-MGFR was related to greater waist circumference, computed tomography-measured visceral adipose tissue, and hepatic steatosis (P<0.01 for each), and higher large artery vascular stiffness (P<0.001). Findings were generally consistent across aspirin use status. After median follow-up of 12.9 years (371 CVD and 214 heart failure events), individuals with both high TXB2-MGFR and low LE8 displayed an over 5-fold higher risk of heart failure (hazard ratio, 5.07 95% CI, 3.26-7.89) and 2.5-fold higher risk of CVD (hazard ratio, 2.74 95% CI, 2.04-3.68) compared with participants with low TXB2-MGFR and high LE8. CONCLUSIONS: Our findings suggest several modifiable factors that may impact systemic thromboxane A2 generation. Higher systemic thromboxane A2 generation also appears to modulate the association of lifestyle measures (as assessed by LE8 score) with CVD and heart failure.
Qian et al. (Thu,) conducted a cohort in Cardiovascular disease (n=2,655). High TXB2-MGFR and low Life's Essential 8 (LE8) score vs. Low TXB2-MGFR and high LE8 score was evaluated on Total cardiovascular disease or heart failure (HR 5.07 for heart failure, HR 2.74 for CVD, 95% CI 3.26-7.89 for heart failure, 2.04-3.68 for CVD). Individuals with high systemic thromboxane generation and low Life's Essential 8 scores had a 5-fold higher risk of heart failure (HR 5.07; 95% CI 3.26-7.89) and 2.5-fold higher risk of CVD.