Obesity alone - without other risk factors like high cholesterol, inactivity and diabetes - raises a person's risks of heart disease by nearly a third, previous research has shown.
At last, the Karolinska Institute researchers used a method called Mendelian randomization prove that high BMI is a direct cause of heart disease.
And that meas that a third of the world's population - the proportion of humans that are now overweight or obese - could be on a path toward the number one cause of death without lifestyle changes and medical interventions.
The first study of its kind was based on hundreds of thousands of Britons and a revolutionary statistical technique called Mendelian randomization.
This enabled the Swedish team to use genetic variants as a tool to show the causal relationship between cardiovascular disease and BMI (body mass index).
In particular, they discovered as BMI and fat mass increased so did the risk of many more than half a dozen conditions - especially aortic stenosis.
This where the valve controlling the flow of blood from the heart to the body's largest blood vessel, the aorta, narrows and fails to open fully.
If left untreated it can lead to serious problems - and even death.Professor Susanna Larsson, of the Karolinska Institute, Stockholm, said: 'The causal association between BMI and fat mass and several heart and blood vessel diseases, in particular aortic valve stenosis, was unknown.
'Using Mendelian randomization we found that higher BMI and fat mass are associated with an increased risk of aortic valve stenosis and most other cardiovascular diseases, suggesting that excess body fat is a cause of cardiovascular disease.'
The 'fat but fit' theory suggests a bulging waistline is not harmful as long as other metabolic factors like blood pressure and glucose are within recommended levels.
But evidence is growing that this is wrong - an may be sending out the wrong message to millions of people.
Using data from 367,703 men and women aged 40 to 69 they identified 96 gene mutations linked to BMI and body fat mass to estimate their effect on 14 cardiovascular diseases.
The participants were from the UK Biobank, which holds biomedical information on half a million people. They were all of white British descent and aged 40 to 69.
Those with variants predicting higher BMI were at increased risk of aortic valve stenosis - as well as a host of other life threatening conditions.
These included heart failure, deep vein thrombosis, high blood pressure, peripheral artery disease, coronary artery disease, atrial fibrillation and pulmonary embolism.
For every genetically-predicted one unit rise in BMI, the increased risk ranged from six percent for pulmonary embolism to 13 percent for aortic valve stenosis.Above a BMI that is considered 'healthy' (20-25), this corresponded to a weight gain of around six and a half pounds (nearly three kilos) for someone who is 5ft 7in tall.
The study, published in the European Heart Journal, also found cardiovascular disease risk rose in tandem with mutations predicting increases in fat mass.
Again, the connection with aortic stenosis was most pronounced - with a risk increase of 46 percent.
The damaged valve means less blood leaves the heart and it has to work harder to pump enough blood out to circulate round the body.
Blood can back up in other parts of the heart and sometimes the lungs. This can lead to shortness of breath, tiredness, fainting, chest pain and an irregular heart beat.
This was followed by stroke, atrial fibrillation, heart failure, peripheral artery disease, deep vein thrombosis, high blood pressure and coronary artery disease.
These gene variants can all predispose people to be more likely to put on weight, said the researchers.
But they stressed the most important factors implicated in the development of cardiovascular disease are diet and physical activity.
Prof Larsson said: 'Our genes can make us somewhat more predisposed to gain body weight but lifestyle factors, such as overeating and lack of physical activity, are the major determinants of overweight.
'A healthy diet is the cornerstone of cardiovascular disease prevention, and how much we eat should be limited to the amount of energy required to maintain a healthy body weight,' of 18.5 to 24.9.
'People who are predisposed to a higher BMI may need to work a bit harder to maintain a healthy weight.' Mendelian randomisation uses mutations known to be associated with potential risk factors, such as BMI and body fat, as indirect indicators or 'proxies'.
This enables researchers to discover whether the risk factor is the cause of the disease - rather than the other way around.
It also reduces bias in results because variants are determined at conception and cannot be affected by subsequent external or environmental factors, or by the development of disease.
Two years ago scientists who conducted a 20-year study of 3.5 million Britons by the University of Birmingham found those who were obese but who had no initial signs of heart disease, diabetes or high cholesterol were not protected in later life.
Last year a study of 300,000 middle aged Britons by the University of Glasgow found the risk of illnesses such as heart attack and stroke increased in every measurement the fatter a person was.
The findings go against previous studies that suggest carrying too much weight is not necessarily a sign of ill health.
Having a BMI of 25 to 29.9 is considered overweight, and 30 or above obese
Above a BMI that is considered 'healthy' (20-25), this corresponded to a weight gain of around six and a half pounds (nearly three kilos) for someone who is 5ft 7in tall.
The study, published in the European Heart Journal, also found cardiovascular disease risk rose in tandem with mutations predicting increases in fat mass.
Again, the connection with aortic stenosis was most pronounced - with a risk increase of 46 percent.
The damaged valve means less blood leaves the heart and it has to work harder to pump enough blood out to circulate round the body.
Blood can back up in other parts of the heart and sometimes the lungs. This can lead to shortness of breath, tiredness, fainting, chest pain and an irregular heart beat.
This was followed by stroke, atrial fibrillation, heart failure, peripheral artery disease, deep vein thrombosis, high blood pressure and coronary artery disease.
These gene variants can all predispose people to be more likely to put on weight, said the researchers.
But they stressed the most important factors implicated in the development of cardiovascular disease are diet and physical activity.
Prof Larsson said: 'Our genes can make us somewhat more predisposed to gain body weight but lifestyle factors, such as overeating and lack of physical activity, are the major determinants of overweight.
'A healthy diet is the cornerstone of cardiovascular disease prevention, and how much we eat should be limited to the amount of energy required to maintain a healthy body weight,' of 18.5 to 24.9.
'People who are predisposed to a higher BMI may need to work a bit harder to maintain a healthy weight.' Mendelian randomisation uses mutations known to be associated with potential risk factors, such as BMI and body fat, as indirect indicators or 'proxies'.
This enables researchers to discover whether the risk factor is the cause of the disease - rather than the other way around.
It also reduces bias in results because variants are determined at conception and cannot be affected by subsequent external or environmental factors, or by the development of disease.
Two years ago scientists who conducted a 20-year study of 3.5 million Britons by the University of Birmingham found those who were obese but who had no initial signs of heart disease, diabetes or high cholesterol were not protected in later life.
Last year a study of 300,000 middle aged Britons by the University of Glasgow found the risk of illnesses such as heart attack and stroke increased in every measurement the fatter a person was.
The findings go against previous studies that suggest carrying too much weight is not necessarily a sign of ill health.
Having a BMI of 25 to 29.9 is considered overweight, and 30 or above obese.