title: Silent myocardial ischaemia and long-term coronary artery disease outcomes in apparently healthy people from families with early-onset ischaemic heart disease.
abstract: OBJECTIVE
  A family history of premature coronary artery disease (CAD) in an apparently healthy individual conveys an increased risk of future CAD. The extent to which inducible myocardial ischaemia exists and is associated with long-term incident CAD in apparently healthy siblings of early-onset CAD patients is unknown.
  
  
  RESULTS
  Asymptomatic siblings (n = 1287, aged 30-59 years) of patients with onset of CAD <60 years of age underwent risk factor screening and maximal graded treadmill testing with nuclear perfusion imaging, and were followed for incident CAD events for up to 25 years. Incident CAD occurred in 15.2% of siblings (68% acute coronary syndromes); mean time to first CAD event was 8.2 ± 5.2 years. Inducible ischaemia was highly prevalent in male siblings (26.9%), and was independently associated with incident CAD. Male siblings ≥ 40 years of age who were low or intermediate risk by traditional risk assessment, had a prevalence of inducible ischaemia and a 10-year risk of incident CAD that were near or ≥ 20%. In female siblings ≥ 40 years of age, the presence of inducible ischaemia was also independently associated with incident CAD, but the prevalence of inducible ischaemia was markedly lower, as was the risk of incident CAD.
  
  
  CONCLUSIONS
  Inducible ischaemia is highly prevalent in male siblings, suggesting a previously unknown long quiescent period before the occurrence of a clinical event. While inducible ischaemia is associated with a worse prognosis, male siblings with negative tests still bear a high risk of incident disease, such that we propose that in male siblings over 40 years of age, aggressive primary prevention interventions be instituted without nuclear testing. For women, the prevalence of ischaemia was so low as to not warrant screening, but the incidence of CAD was high enough to at least warrant lifestyle interventions.
authors.affiliation: The Johns Hopkins GeneSTAR Research Program, Division of Cardiology, Department of Medicine, The Johns Hopkins Medical Institutions, 1830 East Monument Street, Room 8023, Baltimore, MD 21287, USA. bkral@jhmi.edu
authors.forename: Brian G
authors.initials: BG
authors.lastname: Kral
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Becker
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Vaidya
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Yanek
authors.forename: Diane M
authors.initials: DM
authors.lastname: Becker
mesh_terms: D000328:Adult; D017668:Age of Onset; D000787:Angina Pectoris / Q000209:etiology; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D005080:Exercise Test; D005260:Female; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000235:genetics* / Q000517:prevention & control; D010375:Pedigree; D011379:Prognosis; D012307:Risk Factors