A common genetic flaw in the DNA of some men may increase the risk of coronary artery disease by 50%, researchers found.
The discovery could lead to more sensitive versions of profiling tools, such as the Framingham risk score.
The British Heart Foundation, which funded the study, said the findings could lead to new treatments for heart disease.
Scientists suggested the faulty DNA may affect the immune and inflammatory systems.
Study lead Dr Maciej Tomaszewski of the University of Leicester said the team was 'very excited' by the results.
'The major novelty of these findings is that the human Y chromosome appears to play a role in the cardiovascular system beyond its traditionally perceived determination of male sex.’
Men are more likely to develop CHD than women. The disease led to 88,236 deaths in the UK in 2008, with 49,665 deaths among men and 38,571 among women.
Although it was suspected that inherited traits on the Y chromosome may contribute to this risk, the nature of this relationship was unclear.
Researchers analysed DNA from 3,233 British men. Participants were then grouped depending on genetic traits within the main part of the Y chromosome, male-specific region, which is passed intact from father to son.
Of nine groups identified, 90% of men belonged to two groups, called haplogroup I or haplogroup R1b1b2.
The risk of coronary artery disease was 50% higher among those in haplogroup I compared with men in other genetic groups. This risk was independent of traditional risk factors such as high BP, high cholesterol and smoking.
Study authors suggested that men with haplogroup I DNA may suffer flaws in both their immune system and inflammation response. These pathways are linked to cardiovascular disease.
In an accompanying editorial, Dr Virginia Miller of the Mayo Clinic in Rochester, Minnesota said existing risk assessment tools could be improved by adding questions about whether patients’ parents had a history of MI.
‘Both sex and family do matter in inheritance of coronary artery disease,’ she concluded.
Dr Hélène Wilson, research adviser at the British Heart Foundation, said: 'Lifestyle choices such as poor diet and smoking are major causes, but inherited factors carried in DNA are also part of the picture.
'This discovery could help lead to new treatments for heart disease in men, or tests that could tell men if they are at particularly high risk of a heart attack.'
She added: 'The next step is to identify specifically which genes are responsible and how they might increase heart attack risk.'