Just a small reduction in the current levels of cholesterol, smoking and blood pressure could save some 50,000 lives a year in England and Wales, the Government's Health Development Agency (HDA) has estimated.
This would halve the current burden of about 100,000 deaths from coronary heart disease each year, it added in a report.
Report co-author Professor Mike Kelly, HDA director of evidence and guidance, said: "Reducing cholesterol levels by even a small amount would prevent approximately 25,000 deaths each year. This is quite possible. These lower cholesterol levels were achieved in the US and Scandinavia 10 years ago.
"Reducing smoking prevalence to US levels would result in 17,000 fewer deaths annually," he added.
Figures published by the HDA in November estimated that smoking was the factor in 11,500 deaths from ischaemic heart disease each year among those over 65 in England.
The HDA is also urging local councils to work more closely with primary care trusts.