Thrombotic, Inflammatory & Gene Markers of CVD in Women
Condition: Cardiovascular Diseases; Heart Diseases; Myocardial Infarction; Postmenopause
MeSH terms: Cardiovascular Diseases; Heart Diseases; Myocardial Infarction; Infarction
Study type: Observational

Summary: 
      To evaluate a series of thrombotic, inflammatory, and genetic markers for myocardial
      infarction among participants in the Women's Health Initiative Observational Study (WHI-OS).
    

Detailed description: 
      BACKGROUND:

      Over the past 50 years, considerable progress has been made in understanding factors that
      stimulate the development of atherosclerosis and other manifestations of "preclinical
      cardiovascular disease," and in documenting the 2- to 4-fold higher risk of subsequent
      myocardial infarction or other morbid events in asymptomatic individuals with such
      pathological transformations in arteries or the heart. However, much less information is
      available about the factors ("triggers") that precipitate morbid and mortal events in
      high-risk individuals. Recent work by Paul Ridker and colleagues and other groups has
      identified associations between the presence of markers of prothrombotic tendencies,
      inflammation and immune activation and myocardial infarction and other cardiovascular disease
      (CVD) events. However, most available data have been obtained in men and less is known about
      the relevance of these newer risk factors and potential "triggers" to stimulation of
      atherosclerosis and precipitation of CVD events in women. In this context, research to
      examine the relation of both relatively new and potentially novel "triggers" to subsequent
      myocardial infarction in women is of considerable potential clinical and biological
      significance.

      DESIGN NARRATIVE:

      Drs. Ridker and colleagues comprehensively evaluated a series of thrombotic, inflammatory,
      and genetic markers for myocardial infarction (MI) among participants in the Women's Health
      Initiative Observational Study (WHI-OS), a prospective cohort study of over 90,000 ethnically
      representative post-menopausal American women aged 50-79 years. Employing a prospective
      nested case-control design, they assayed baseline plasma and buffy coat samples for nine
      markers of increased thrombotic potential (tissue-type plasminogen activator (tPA),
      plasminogen activator inhibitor type 1 (PAI-1), total plasma homocysteine, prothrombin
      fragment F1+2, D-dimer, APC-R, C-reactive protein, interleukin-6, and sICAM-1) to determine
      whether elevations of these parameters led to future MI or coronary death. They also explored
      common genetic polymorphisms in the tPA, PAI-1, MTHFR, thrombomodulin, prothrombin, and
      factor V genes so that both inherited and environmental determinants of coronary thrombosis
      in women could simultaneously be evaluated. Case subjects were WHI-OS participants who were
      free of cardiovascular disease at study entry and subsequently developed a documented MI or
      coronary death during follow-up (N = 650). Control subjects were selected from study
      participants who remained free of disease during follow-up; controls were 1:1 matched to
      cases by age, smoking status, ethnicity, and follow-up time. Data on usual risk factors,
      hormone replacement therapy, and standard lipid profiles were used to evaluate for potential
      confounding and effect modification. The analyses took advantage of a unique and
      unprecedented blood bank from a well-characterized, ethnically diverse, large-scale cohort of
      post-menopausal women with ongoing follow-up and high quality endpoint verification, thereby
      providing an efficient way to critically evaluate the hypothesized roles of hemostasis,
      thrombosis and inflammation as risk factors for future MI and coronary death among American
      women.

      The study completion date listed in this record was obtained from the "End Date" entered in
      the Protocol Registration and Results System (PRS) record.