They also found that in families where two or more siblings were already suffering from heart disease, if one had left main coronary artery disease (LMD), the other affected siblings were over three times more likely to suffer an LMD-related recurrence.
Professor Heribert Schunkert, head of cardiology at the University of Luebeck, Germany, who led the study, said: "Although other studies have shown that myocardial infarction (MI) and coronary artery disease (CAD) run in families, few have examined the role of specific morphologic disease characteristics. In our study we focused on the coronary disease pattern underlying CAD and found that, for LMD, nearly half (49%) of the phenotypic variation that is due to genetic effects was inherited. This substantial heritability is even higher than that for CAD or MI in general.
"This knowledge of coronary morphology may increase our ability to predict disease. In addition, it may help us to find susceptibility factors that underlie the complex causes of heart disease."
Prof Schunkert and Dr Marcus Fischer and his colleagues from the University of Regensburg, Germany, analysed coronary angiograms from 1,801 patients from families with two or more siblings affected by CAD. They found LMD (defined as 50% or greater narrowing of the left main coronary artery) in 12% of the patients. "This reflected the familial accumulation of this condition in high risk CAD families," explained Prof Schunkert. "These data suggest that, not only does LMD cluster in families, but also that the outbreak of the disease at the same location in the coronary tree relates to the genetic basis of this disease." The likelihood of a sibling presenting with LMD when another sibling was affected by the condition was 3.6.
In a parallel, prospective study, the researchers followed 1,369 healthy siblings of CAD patients for approximately five years. During this time, 79 of the healthy siblings either had a heart attack or required heart surgery or both. LMD was found more frequently in those families where the initially healthy sibling subsequently developed heart disease (13.9 versus 6.4%), and there was a 2.5 times higher risk for the healthy sibling to develop heart disease in families with an LMD sibling compared to families where the patient suffered from some other form of heart disease.
Prof Schunkert said: "Remarkably, the risk in these siblings was significantly higher than that in siblings with a strong positive family history of heart disease, including premature MI in addition to CAD manifestations other than LMD."
He continued: "The high heritability of LMD may have important clinical implications with respect to screening strategies. Despite a decline in CAD mortality over the last decade, only a small proportionate change has been seen in the characteristics of unexpected cardiac deaths or survived MIs. The majority of these events is sudden and occurs out of hospital. Although the presence of clinically symptomatic CAD markedly increases the risk of MI, over half of sudden cardiac death victims were asymptomatic before the event. Although the number of such cases in asymptomatic patients is low, the national burden of cardiovascular disease is substantial, as is the individual lifetime risk. A major challenge for heart disease screening is to define populations in which the chance to detect relevant coronary atherosclerosis is high enough to justify the costs and risks of in-depth testing.
"Sophisticated screening tests may include non-invasive coronary angiography, which could be used to identify lesions in or near the left main coronary artery. In this context, asymptomatic siblings from families with the occurrence of LMD might benefit from intensified screening and prevention strategies.
"Further studies might address the question whether LMD is also detectable with elevated frequencies in asymptomatic relatives of patients known to be affected by this condition in order to utilise this information for primary prevention in selected families."