This trait may also be a major risk factor for fatal heart attack and coronary thrombosis (a blood clot in the heart) in early middle age, say the researchers.
About one in five Finnish Caucasian men studied carried the trait which is one several genes that affects blood clotting, says lead author, Jussi Mikkelsson, M.D., Ph.D. a senior research fellow and resident in Internal Medicine at the University of Tampere Medical School in Tampere, Finland. It seems to be less common among African-Americans and Asians.
The gene is known as HPA-2 Met, which is a variation of the platelet glycoprotein (GP) Ib- IX-V gene. Platelets are disk-shaped factors in the blood and platelet glycoproteins are essential to blood clotting.
The researchers conducted autopsies on 700 white Finnish men who suffered violent or sudden out-of-hospital deaths. They found that, in men younger than 55 years of age, the HPA-2 Met trait was found 2.2 times more often among those who died of SCD.
“This study identifies a major new risk factor for sudden cardiac death in early middle age,” says Mikkelsson. Learning about the mechanism behind this potential risk factor will reveal even more information. This could lead to a way to level off the increased risk for people with this trait through use of targeted anti-clotting therapy, he says.
Sudden cardiac death occurs when the heart beats in an irregular pattern that makes it unable to pump blood to the rest of the body (cardiac arrest). The condition results in a complete loss of blood pressure, quickly followed by death unless the person is resuscitated. SCD can be caused by disturbances within the heart’s electrical system or by a large blood clot, called a thrombus, that cuts off oxygen to the heart so quickly and completely that it disrupts the heart’s electrical signaling system. Sudden cardiac death is often the first sign of coronary heart disease in early middle-aged individuals.
Having a close relative who died of sudden cardiac death and cigarette smoking are risk factors for sudden cardiac death, but much is unknown about the condition, Mikkelsson says.
“Sudden cardiac death has a strong familial risk component, so we anticipated that variants like the one in the present study could be associated with fatal heart attack in young individuals,” Mikkelsson explains. “However, the frequency of this particular genetic variation among young men with fatal heart attack was surprisingly high.”
In addition, researchers found that men who died of heart attack were twice as likely to have the HPA-2 Met trait and men who died of coronary thrombosis were 2.6 times more likely to have the trait, than men who died of non heart-related causes.
The increased risk was especially evident in men younger than 55. The HPA-2 Met variation was found in nearly 59 percent of men younger than 55 who died of heart attack and in nearly 70 percent of the men who died of coronary thrombosis before age 55.
The researchers stressed that more than 80 percent of the men in the study had smoked and many had other coronary heart disease risk factors such as high cholesterol levels, high blood pressure and diabetes, all well-known factors that increase the risk of heart disease.
Approximately 50 percent of all deaths caused by coronary heart disease are sudden and take place outside a hospital, but for younger people the figure is much higher, notes Mikkelsson. Up to 90 percent of coronary heart disease mortality in people under age 55 occurs outside the hospital, he says.
According to American Heart Association statistics, 220,000 people a year die of coronary heart disease without being hospitalized and most of these are sudden deaths caused by cardiac arrest.
“These findings suggest that the HPA-2 Met variation may be a predictor of fatal complications of atherosclerosis in early middle age,” Mikkelsson says. “This may be due to an effect of gene variants on platelet function or may serve as a marker for an as yet unknown factor associated with platelet function.”
There is currently no general screening for the HPA-2 Met trait. Mikkelsson advises that individuals with a family history of premature heart death consult their physician and be screened for the known risk factors of heart disease.
Co-authors include: Markus Perola, M.D., Ph.D.; Antti Penttilä, M.D., Ph.D.; and Pekka J. Karhunen, M.D., Ph.D.
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