Siblings of LMD Patients at High Heart Risk

According to a study by German researchers, healthy siblings of people with heart disease of the left main coronary artery (LMD) are at increased risk of developing some form of heart disease. The researchers also found that heart disease of the left main coronary artery runs in families through generations.

Led by Professor Heribert Schunkert and Dr. Marcus Fischer, the research team from the University of Regensburg, Germany examined coronary angiograms from 1,801 patients. Each patient hailed from a family that had two or more siblings affected by coronary artery disease (CAD). The examination revealed that 12% of the patients had LMD, which is characterised by 50% or greater narrowing of the left main coronary artery.

“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 researchers also found that if one sibling was affected by LMD, another sibling was 3.6 times likely to be affected by it.

The research team then conducted a parallel study lasting five years in which 1,369 healthy siblings of CAD patients were followed. During this period, 79 of the healthy siblings had to undergo heart surgery or had a heart attack or both. Analysis revealed that LMD was more prevalent in families where initially healthy siblings subsequently developed heart disease than in those that did not – 13.9% versus 6.4%.

Similarly healthy siblings in families with at least one LMD sibling had 2.5 times higher risk of developing heart disease as compared to healthy siblings of patients who had some other form of heart disease. In families that had two or more siblings with heart disease, if LMD was present in one sibling, the other siblings with heart disease had more than 3 times the risk of developing an LMD-related incident.

According to the researchers, these are important findings as they would allow doctors to set up more intensive screening and prevention strategies for people who have a family history of LMD.

Prof. Schunkert, head of cardiology at the University of Luebeck, Germany 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,” he 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,” Prof. Schunkert added.

Continuing about their study published in the European Heart Journal, he said, “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,” he said.

“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,” Prof. Schunkert added.

“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,” he concluded.

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