Silent Myocardial Ischaemia and Long-Term Coronary Artery Disease Outcomes in Apparently Healthy People From Families With Early-Onset Ischaemic Heart Disease

Study Questions:

Is inducible myocardial ischemia associated with long-term incident coronary artery disease (CAD) in apparently healthy siblings of early-onset CAD patients?


Asymptomatic siblings (n = 1,287, ages 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 ischemia 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 ischemia and a 10-year risk of incident CAD that were near or ≥20%. In female siblings ≥40 years of age, the presence of inducible ischemia was also independently associated with incident CAD, but the prevalence of inducible ischemia was markedly lower, as was the risk of incident CAD.


Inducible ischemia is highly prevalent in male siblings of persons with premature CAD, suggesting a previously unknown long quiescent period before the occurrence of a clinical event. Male siblings with negative tests still bear a high risk of incident disease, such that in male siblings over 40 years of age, aggressive primary prevention interventions should be instituted without nuclear testing. For women, the prevalence of ischemia was so low as to not warrant screening, but the incidence of CAD was high enough to at least warrant lifestyle interventions.


This report from the Johns Hopkins Sibling and Family Heart Study supports the import of family history of premature CAD, which from a nongender and nonage risk factor perspective is often a low high-density lipoprotein cholesterol with mild increase in triglycerides. A safer and lower cost option than nuclear stress testing to assess for premature CAD in siblings would be a coronary calcium score.

Clinical Topics: Acute Coronary Syndromes, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Acute Heart Failure, Nuclear Imaging

Keywords: Coronary Artery Disease, Myocardial Ischemia, Acute Coronary Syndrome, Risk Factors, Primary Prevention, Perfusion Imaging, Cholesterol, Incidence, Dyslipidemias, Heart Failure, Risk Assessment, Triglycerides, Siblings, Exercise Test

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