**4. Role of various types of food intake for the risk of thrombosis**

There are many reports suggesting the increase/decrease in the risk of thrombosis by various food and beverage intake. Framingham study suggested that coffee

**63**

*Mechanism of Thrombus Formation in Regard to Diet DOI: http://dx.doi.org/10.5772/intechopen.92382*

thrombosis.

thrombosis) is complex.

consumption is related to lower risk of myocardial infarction [42]. However, the influence of coffee intake for the onset and recurrence of myocardial infarction is still under discussion because other reports suggested higher rate of sudden cardiac death in coffee intake in patients after myocardial infarction [43]. People have consensus that food intake should influence the risk of arterial and venous thrombosis. The problem is that it is still hard to state which food reduces/increases the risk of

Old epidemiological studies suggested that the risk of myocardial infarction increased in Japanese people who immigrated to Hawaii or California than that of the ones staying in Japan. They have the same genetic background. Environmental factors including food should contribute to the change in the risk of population when moved to the US than staying in Japan. Lower cardiovascular death rate in Japan is still noted in the international registry of patients with atherothrombosis or non-valvular atrial fibrillation. Despite epidemiological data, it is still hard to

There are many specific diets that potentially influence thrombotic risk. Among

them, sodium intake should be one of the most established factors to avoid cardiovascular diseases. Low sodium intake clearly decreases the risk of heart failure [44], but its direct effects for thrombosis is still to be elucidated. Mediterranean diet is also related to lower risk of cardiovascular diseases [45]. But it is still difficult to identify the specific content of Mediterranean diet related to the reduction in the risk of CV disease. A plant-based diet seems beneficial in reducing the risk of cardiovascular disease, but it has both good qualities and bad qualities [46]. The relationship between food and the risk of cardiovascular diseases (mostly arterial

A recent publication suggested the positive correlation between red and processed meat intake and risk of cardiovascular diseases. This study also suggested the negative relationship between the intake of yogurt, cheese, and eggs and CV disease risk [47]. The observation study is useful to find potential contributing factors but still includes many potential biases. Just like drug or medical intervention, randomized trials comparing a variety of food intake with hard endpoint of cardiovascular death, myocardial infarction, and ischemic stroke will give us more insight. However, in reality, it is hard to design such trials because people have the right to eat whatever they like. It is hard to make a restriction in food intake for a long period of time. The combination of observational study and the study to clarify the

**5. Metabolic syndrome and thrombosis: view from the mechanism**

exercise to prevent metabolic syndrome and future onset of thrombosis [52].

Metabolic syndrome is characterized as the presence of three apparent characteristics including visceral obesity manifested as increasing waist circumference, dyslipidemia, hypertension, and high blood glucose. Underlining pathophysiology is insulin resistance and lipid accumulation. It is noteworthy that various cytokines (adipocytokines) were identified from adipose tissue. Adiponectin is the one identified as factor reducing the risk of thrombosis by preventing endothelial dysfunction [48]. Indeed, decreased plasma concentration of adiponectin observed in obese patients may suggest the potential regulatory role of adiponectin for the onset of thrombotic diseases [49]. Despite difficulty in understanding the precise relationship among various cytokines and adiponectin [50], an apparent link between metabolic syndrome and decreased adiponectin is noteworthy. Various parameters for coagulation and fibrinolysis are also influenced in metabolic syndrome patients [51]. It is reasonable to recommend regular

identify what food specifically modulated the rate of thrombosis.

mechanism will give us the best available evidence now.

#### *Mechanism of Thrombus Formation in Regard to Diet DOI: http://dx.doi.org/10.5772/intechopen.92382*

*New Insights into Metabolic Syndrome*

platelet through thrombin receptor stimulations [35].

tors. Recently, a larger load of vitamin K on health is cautioned [37].

**4. Role of various types of food intake for the risk of thrombosis**

There are many reports suggesting the increase/decrease in the risk of thrombosis by various food and beverage intake. Framingham study suggested that coffee

adhesion and activation. Platelet adhesion is implemented to be medicated by its GPIbα binding with von Willebrand factor (VWF) (① in **Figure 4**). GPIbα binding with VWF is a chemical phenomenon, but the binding force is a physical one. We have implemented both in the same model. Platelets were implemented to be activated to change their biological roles (② in **Figure 4**). This process is a biological process. The detailed process model of platelet activation was published elsewhere [33]. Briefly, platelets were settled to be captured by VWF under blood flow condition. Collagen exposed at the site of endothelial injury also interacts with platelet and contributed to platelet activation through its receptor, namely, GPVI [34]. Then, activated platelet was settled to have stronger capacity to bind with injured vessel wall, cohesion each other, and possess the capacity to express coagulogenic phospholipids. Then, prothrombin conversion to thrombin was settled to occur only on the surface of activated platelets (③ in **Figure 4**). Thrombin function is neutralized promptly by its interaction with antithrombin III. Thrombin implemented to have function to convert fibrinogen to fibrin (④ in **Figure 4**) and further activated

There are several coagulation factors, the function of which is regulated strongly by food intake. Gla-domain of coagulation factors plays crucial roles in the accumulation of coagulation factors around exposed negatively charged phospholipids on activated platelets [36]. Gla-domain also plays crucial roles for enzymatic function of coagulation factors. Carboxylation of Gla-domain is mediated by vitamin K. Thus, coagulation cascade does not work well in the absence of vitamin K or in patients taking vitamin K inhibitor. It is noteworthy that there are many foods including fermented food that are known to contain abundant vitamin K. Strict food restriction is necessary to keep the anticoagulant effects of vitamin K inhibi-

The amount of fibrin formed at the site of endothelial injury was reduced by the effect of intrinsic fibrinolysis. Fibrinolysis is a complex pathway, but the details of which is simplified to be incorporated as shown in **Figure 4**. Vascular endothelial cells have balanced roles for fibrinolysis by releasing both fibrinolytic tissue-type plasminogen activator (t-PA: ⑥) and the one has antifibrinolytic effects of plasminogen activator inhibitor (PAI)-1 (⑦). Both of them are constitutively released from endothelial cells. But the rates of their releases were individually controlled in individual endothelial cells. When the rate of t-PA release increases, the amount of fibrin formed around the endothelial cells becomes smaller. It becomes larger in the case when the rate of PAI-1 release increases. Free t-PA has a potential to convert plasminogen to plasmin. (⑧) Plasmin is a strong protease, which can dissolve many functional proteins including fibrinogen. To avoid too much protein degradation, activity of plasmin is promptly neutralized by the function of α2-plasmin inhibitor (α2-PI: ⑨). Previous publication suggested increased PAI-1 release after acute myocardial infarction and its role for the increased recurrence of myocardial infarction [38]. Animal experiments revealed that the food coloring agent of crocin reduces activity of PAI-1 and prevents thrombosis [39]. In human, increased PAI-1 activity is reported at the time of too much intake of fat [40]. Total fibrinolytic activity in humans is also reported to be low in obese patients [41]. Decreased fibrinolytic activity in patients taking too much lipid is one potential reason of increased risk of

**62**

thrombosis in these patients.

consumption is related to lower risk of myocardial infarction [42]. However, the influence of coffee intake for the onset and recurrence of myocardial infarction is still under discussion because other reports suggested higher rate of sudden cardiac death in coffee intake in patients after myocardial infarction [43]. People have consensus that food intake should influence the risk of arterial and venous thrombosis. The problem is that it is still hard to state which food reduces/increases the risk of thrombosis.

Old epidemiological studies suggested that the risk of myocardial infarction increased in Japanese people who immigrated to Hawaii or California than that of the ones staying in Japan. They have the same genetic background. Environmental factors including food should contribute to the change in the risk of population when moved to the US than staying in Japan. Lower cardiovascular death rate in Japan is still noted in the international registry of patients with atherothrombosis or non-valvular atrial fibrillation. Despite epidemiological data, it is still hard to identify what food specifically modulated the rate of thrombosis.

There are many specific diets that potentially influence thrombotic risk. Among them, sodium intake should be one of the most established factors to avoid cardiovascular diseases. Low sodium intake clearly decreases the risk of heart failure [44], but its direct effects for thrombosis is still to be elucidated. Mediterranean diet is also related to lower risk of cardiovascular diseases [45]. But it is still difficult to identify the specific content of Mediterranean diet related to the reduction in the risk of CV disease. A plant-based diet seems beneficial in reducing the risk of cardiovascular disease, but it has both good qualities and bad qualities [46]. The relationship between food and the risk of cardiovascular diseases (mostly arterial thrombosis) is complex.

A recent publication suggested the positive correlation between red and processed meat intake and risk of cardiovascular diseases. This study also suggested the negative relationship between the intake of yogurt, cheese, and eggs and CV disease risk [47]. The observation study is useful to find potential contributing factors but still includes many potential biases. Just like drug or medical intervention, randomized trials comparing a variety of food intake with hard endpoint of cardiovascular death, myocardial infarction, and ischemic stroke will give us more insight. However, in reality, it is hard to design such trials because people have the right to eat whatever they like. It is hard to make a restriction in food intake for a long period of time. The combination of observational study and the study to clarify the mechanism will give us the best available evidence now.
