Effect of Aspirin on Hemostatic and Vascular Function After Live Fire Fighting

• Vascular function [ Time Frame: Less than 60 minutes before initiating firefighting activity ] [ Designated as safety issue: No ]
  Vascular function will be assessed via pulse wave analysis, pulse wave velocity, carotid artery compliance, beta stiffness index, forearm rsistance artery vasodilatory capacity, and brachial artery blood flow.
• Hemostatic balance [ Time Frame: Less than 60 minutes before initiating firefighting activity ] [ Designated as safety issue: No ]
  Blood samples will be collected by a trained phlebotomist from the antecubital vein directly into vacutainers with little or no stasis using a 21-gauge needle. Samples will be used to quantify platetlet number and function, fibrinogen, prothrombin and partial thromboplastin time, t-PA and PAI-1 activities and antigen
• Inflammatory and Oxidative Stress markers [ Time Frame: Less than 60 minutes before initiating firefighting activity ] [ Designated as safety issue: No ]
  CRP,Intercellular adhesion molecule (ICAM)-1, IL-6, MMP-9, TIMP-1, TIMP-2,8-iso-prostaglandin F2a, soluble P-selectin
• Vascular function [ Time Frame: Less than 60 minutes after completing 20 minutes of firefighting activity ] [ Designated as safety issue: No ]
  Vascular function will be assessed via pulse wave analysis, pulse wave velocity, carotid artery compliance, beta stiffness index, forearm rsistance artery vasodilatory capacity, and brachial artery blood flow.
• Hemostatic balance [ Time Frame: Less than 60 minutes after completing 20 minutes of firefighting activity ] [ Designated as safety issue: No ]
  Blood samples will be collected by a trained phlebotomist from the antecubital vein directly into vacutainers with little or no stasis using a 21-gauge needle. Samples will be used to quantify platetlet number and function, fibrinogen, prothrombin and partial thromboplastin time, t-PA and PAI-1 activities and antigen
• Inflammatory and Oxidative Stress markers [ Time Frame: Less than 60 minutes after completing 20 minutes of firefighting activity ] [ Designated as safety issue: No ]
  CRP,Intercellular adhesion molecule (ICAM)-1, IL-6, MMP-9, TIMP-1, TIMP-2,8-iso-prostaglandin F2a, soluble P-selectin

The investigators hypothesize that

1. an acute treatment of low-dose aspirin will lead to a) decreased resting platelet activation, platelet aggregation, and clotting potential, b) increased fibrinolytic potential following fire fighting, c) no significant effect on endothelial function or arterial stiffness versus the placebo condition.
2. chronic treatment with low-dose aspirin will lead to a) decreased resting and fire fighting induced platelet activation, platelet aggregation, clotting potential, b) increased fibrinolytic potential, and c) increased endothelial function and decreased arterial stiffness in response to live fire fighting versus the placebo condition.
3. short-term fire fighting activity will result in: a) a reduction in arterial function (reduced endothelial function, increased augmentation index and an attenuated arterial stiffness response); b) a disruption in hemostasis that is characterized by an increase in platelet number and function, an increased coagulatory potential and altered fibrinolytic potential; and c) an elevation in procoagulatory cytokines, systemic inflammation, monokine chemoattractant protein, and matrix metalloproteinases.

• Cardiovascular Disease Risk
• Vascular Function
• Hemostatic Function

• Active Comparator: Acute, Aspirin
  Acute single dosage of 81 mg asprin provided 30 minutes prior to firefighting
  Intervention: Drug: 81 mg enteric coated aspirin
• Placebo Comparator: Acute, Placebo
  Acute single dosage of placebo provided 30 minutes prior to firefighting
  Intervention: Drug: 81 mg enteric coated aspirin
• Active Comparator: Chronic, Aspirin
  14 day dosage of 81 mg asprin provided prior to firefighting
  Intervention: Drug: 81 mg enteric coated aspirin
• Placebo Comparator: Chronic, Placebo
  14 day dosage of placebo provided prior to firefighting
  Intervention: Drug: 81 mg enteric coated aspirin

Inclusion Criteria:

• Male firefighters (career and volunteer), medically cleared by home fire department.
• Ages 40 - 60
• Completion of a yearly period medical evaluation based on NFPA 1582 within the past 12 months or an evaluation by an occupational medical group through this study.

Exclusion Criteria:

• Over 60 or under 40 years of age.
• Not a firefighter.
• Individuals at risk for developing gastrointestinal (GI) complications while on aspirin therapy due to a combination of the following: smoking; concurrent NSAID, steroid, Clopidogrel, or Warfarin therapy; history of upper GI complications; history of renal impairment; history of elevated serum creatinine; hypertension; and cardiac failure.
• Individuals with cases of allergy or asthma, intolerance, and recurrent vascular events.
• Individuals taking statins.
• Individuals who are currently taking aspiring regularly.