Background Alcohol consumption is linked to decreased platelet function. Whether this link is dependent on sex or type of beverage remains unclear. Methods Cross-sectional data were obtained from the Framingham Heart Study (N = 3427). Alcohol consumption was assessed by using standardized medical history and Harvard semi-quantitative food frequency questionnaires. Five bioassays measured 120 platelet reactivity traits across agonists in whole-blood and platelet-rich plasma samples. Linear mixed-effects models adjusted for age, sex and aspirin use, hypertension, body mass index, cholesterol, high-density lipoprotein, triglycerides, smoking and diabetes evaluated associations between platelet reactivity and alcohol consumption. Beta effects, the regression coefficients that estimate the amount of change in each unit of the predictor variable whereas all other predictor variables remain fixed, for heavy alcohol consumption were compared with effects of aspirin use. Results Alcohol consumption was associated with decreased platelet reactivity, with more associations among wine and liquor compared with beer. Many platelet–alcohol associations in the full sample (86%, P < 0.01) had larger effect sizes in females. Lower light transmission aggregometry adenosine diphosphate (1.82 µM) maximum aggregation (P = 2.6E-3, 95% CI = –0.07, –0.02, β = –0.042) and area under the curve (P = 7.7E-3, 95% CI = –0.07, –0.01, β = –0.039) were associated with white wine consumption; however, red wine had no associations with platelet reactivity. The effect of aspirin use was on average 11.3 (±4.0) times greater than that of heavy drinking in our full sample. Conclusions We confirm associations between alcohol consumption and decreased platelet reactivity. Effects appeared larger for liquor and wine intake and in our female cohort. Red wine consumption is not associated with lower platelet function, contrasting with prior population studies. Although we report an inhibitory relationship between alcohol intake and platelet function, these effects appear much smaller than that of aspirin use.

Introduction: Dietary modification that reflects healthy eating is a notable strategy for CVD prevention on a population level. The cardioprotective role diet plays in hemostasis and thrombosis, particularly in respect to platelet function remains unclear. Hypothesis: Healthier Alternative Healthy Eating Index (AHEI) scores associate with attenuated platelet reactivity in a large-scale population cohort. Methods: Cross-sectional data was obtained from Framingham Heart Study participants (N=3,429). AHEI scores were derived from self-reported Harvard semi-quantitative food frequency questionnaires. Ranging from 0 to 110, higher AHEI scores reflect healthier overall diet quality. Five bioassays measured platelet reactivity traits across several agonists in whole blood and platelet-rich plasma samples. Linear mixed effects models adjusted for age, sex, aspirin use, family relatedness, daily energy intake, and BMI evaluated associations between platelet reactivity and AHEI scores and components. Results: Higher AHEI scores associated with attenuated platelet reactivity among 16 different traits (P<0.01), with notable decreased platelet aggregation to collagen, TRAP6 (PAR1 agonist), ADP, and ristocetin. Of the 11 AHEI components, higher EPA & DHA intake was most strongly associated to decreased platelet function with the greatest number of significant associations to platelet traits (18 traits, P<0.01) and moderate negative effect sizes (Figure 1). Conclusions: We report that higher AHEI scores associate with decreased platelet reactivity. Effects appear strongest for EPA & DHA intake consistent with several small randomized controlled trials. However, we found that a holistic AHEI score reflects a better interpretation of diet as a modulator of platelet function compared to individual components. Our results conclude that the impact of a healthier diet in preventing thrombosis may be partially mediated through a decline in platelet reactivity through multiple independent activation pathways.

Introduction: The liver plays an essential role in thrombopoiesis and coagulation, and circulating liver enzymes are associated with altered platelet counts. However, the role of liver enzymes in the modulation of platelet reactivity remains unclear. Methods: A total of 3,429 Framingham Heart Study participants were included in this study. Platelet reactivity to 8 agonists, including adenosine diphosphate (ADP), thromboxane A 2 mimetic (U46619) and arachidonic acid (AA), was measured using light transmission aggregometry (LTA), Multiplate impedance aggregometry and Optimul aggregometry. Platelet counts and platelet-red blood cell aggregates were enumerated using flow cytometry. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also measured. Associations of platelet reactivity phenotypes with liver circulating liver enzyme levels analyzed using linear mixed-effects models and adjusted for sex, age, relatedness, smoking, aspirin-, and statin-use. To correct for multiple testing, a Bonferroni-correction threshold of P<0.0011 was used to account for multiple comparisons. Results: Higher ALT levels were associated with platelet disaggregation in LTA to ADP (β=0.056, SE=0.02, P=3.54E-04), and with decreased platelet reactivity in response to U46619 in Optimul (EC 50 : β=0.064, SE=0.019, P=7.65E-04). Interestingly, higher AST levels were associated with decreased platelet counts (β=-0.082, SE=0.019, P=1.04E-05), platelet reactivity to U46619 (β=-0.069, SE=0.018, P=1.04E-04) and AA (β=-0.047, SE=0.013, P=3.12E-04), and circulating platelet-red blood cell aggregates (β=-0.062, SE=0.018, P=9.54E-04). Conclusion: Our findings suggest that ALT levels could alter primary platelet aggregation. AST may indirectly modulate platelet counts. In addition, lower AST levels may contribute to platelet hyperresponsiveness. Lastly, ALT and AST levels may have antagonistic effects on the formation of platelet and red blood cell aggregates, which may indirectly influence platelet margination within vessels. Additional studies are underway to examine whether liver fat, a marker of fibrosis associated with cardiovascular disease, is also associated with altered platelet function.