Premature Coronary Artery Disease in Women - Risk Factors and Prognosis
Condition: Coronary Atherosclerosis
MeSH terms: Premature Birth; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Atherosclerosis
Study type: Observational

Summary: 
      Cardiovascular risk in women is systematically underestimated by both - society and
      physicians. Women younger than 50 years of age with acute coronary syndrome have 2x higher
      mortality compared with age-matched men. A number of common vascular-disease-related
      conditions are more frequent in women than in men. Women develop a more severe or different
      form of vascular disease then men. Variability of onset, relative risk, and the synergy of
      traditional and novel risk factors creates a challenge to physicians possibly resulting in
      suboptimal management and disregard in women presenting with angina symptoms.

      During last 10 years the rise in coronary artery disease (CAD) prevalence in younger women is
      observed. Emerging data suggest a unique risk profile in women (hypoestrogenemia with adverse
      effects of a protracted dysmetabolic state). The risk factors assessment and the risk factors
      profiles in women that are associated with CAD may be different than in men and thus merit
      reassessment.

      Purpose The primary objective of this study is to determine characteristics and prognosis of
      women with premature coronary artery disease and to evaluate the extent of atherosclerosis
    

Detailed description: 
      • Study Design Single-center, standardized, case-control study designed to assess the
      prevalence and significance of novel and traditional risk factors of premature coronary
      artery disease in women. Phase I (April 30th 2005- January 1st 2008) enrolled women with
      onset of symptomatic coronary artery disease before 55 years of age. The control group of 347
      clinically healthy, age matched women was selected from the National Health Survey WOBASZ
      study (Polish Multicenter Population Study designed by Epidemiology and Cardiovascular
      Disease Prevention and Health Promotion Department of Institute of Cardiology) according to
      specifically designed questionnaire for WOBASZ study, and only subjects with negative history
      of CVD or negative exertional chest pain were included (Rywik S, Kupść W, Piotrowski W, et
      al. Wieloośrodkowe ogólnopolskie badanie stanu zdrowia ludności - projekt WOBASZ Założenia
      metodyczne oraz logistyka. Kardiol Pol 2005;63(supl.IV) 605:613).

      Definition of premature CAD in women contained onset of coronary artery disease (myocardial
      infarction or coronary revascularization) before 55 years of age. Study participants are
      enrolled after coronary angiography and after identification and screening the age of
      admitted patients for acute coronary syndrome, stable angina or revascularization procedure.
      At the time of enrollment, participants give written informed consent for the study.

      Information on demographic factors, social characterization, life style, education,
      anthropometric measurements, symptom characteristics and anamnesis, gynecologic history,
      family history on CVD and cancer, physical examination data, personal or family history of
      CVD, socioeconomic status, cardiovascular assessments and medication used was obtained
      through the use of a structured case report form questionnaire (CRF).

      Additional fasting blood samples (15ml) are drawn from every individual (patients and
      controls) and frozen immediately at -70 for genetic study and in patients only half blood
      samples are centrifuged, separated, and frozen immediately at -70o after processing.

      Baseline evaluation consisted of CRF data, and collection of coronary angiography, carotid
      ultrasonography and laboratory data.

      The study protocol is approved by the Institutional Review Boards and Local Bioethics
      Committee.

        -  Follow-up All patients are contacted at 6 months after discharge from the hospital, and
           then every 6 months, for at least 4 years, to assess symptom status, menstrual status
           and occurrence of cardiovascular events (MACE) including death, nonfatal myocardial
           infarction, coronary revascularization, cardiac surgery and hospitalization for unstable
           angina.

        -  Study Endpoints

      Primary Outcome Measures:

        1. To evaluate the prevalence of atherosclerosis risk factors in women with premature CAD,
           including family history, social, environmental, clinical, traditional and novel risk
           factors, menopausal status and its association with early onset of the disease as
           compared to matched controls.

        2. To evaluate the association of clinical factors to extent and advance of atherosclerosis

        3. To evaluate predictive role of clinical factors and in particular: impaired fasting
           glucose, abdominal obesity, hypertension, metabolic syndrome, inflammatory markers,
           coexisting inflammatory and immunologic diseases on prognosis at 1 year and long-term
           follow-up in terms of MACE (cardiovascular death, nonfatal MI, revascularization,
           hospitalization due to heart failure III/IV or acute coronary syndrome)

      Secondary Outcome Measures:

        1. To evaluate predictive role of clinical factors and in particular: impaired fasting
           glucose, abdominal obesity, hypertension, metabolic syndrome, inflammatory markers,
           coexisting inflammatory and immunologic diseases on prognosis in terms of Vascular
           Events (MACE, hospitalization due to CAD progression, major arrhythmia, with ICD
           implantation, and stroke)

        2. To evaluate predictive role of clinical factors and in particular: impaired fasting
           glucose, abdominal obesity, hypertension, metabolic syndrome, inflammatory markers,
           coexisting inflammatory and immunologic diseases on prognosis in terms of components of
           Vascular Events and total mortality

      Endpoints assessment:

      Independent endpoint classification committee comprising of 2 not involved into study
      procedures cardiologists will review documentation of the event and classify it.

      The study may have significant implications for improvement, identification and management of
      female patients at risk of premature atherosclerosis providing more gender-specific data for
      efficacy and safety of cardiovascular medication. Better scientific recognition will result
      in better awareness of risk and effective prevention of coronary artery disease in young
      females, in optimizing the delivery of heart care to population of young women and rationale
      for guidelines specific for women.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Cases: Consecutive women with onset of evident CAD before 55 years of age (admitted to
        coronary angiography because of acute coronary syndrome, stable angina or revascularization
        procedure Controls: age-matched healthy women selected from participants examined between
        2004-2006 in the National Health Survey - WOBASZ study with negative history of exertional
        chest pain, angina, hospitalization of revascularization procedures or coronary treatment
      
Biospecimen description: 
      whole blood, serum
    
Keywords: Coronary Artery Disease; Premature; Female