The study published today in The Lancet is the most comprehensive analysis of long-term risk for cardiovascular disease related to non-high-density lipoprotein (non-HDL) cholesterol.

Professor Frank Kee from the Centre for Public Health at Queen’s University Belfast explains: “Non-HDL cholesterol is known as the ‘bad kind’ of cholesterol.  Previous studies have shown a link between non-HDL cholesterol and cardiovascular disease, particularly in people of older ages.

“Our research is the one of first studies to analyse data from hundreds of thousands of otherwise healthy participants over the span of decades to assess the long-term risk of high levels of non-HDL cholesterol in the blood.

“We are also among the first to provide robust estimates of the risks to young people aged under 45 years with high non-HDL cholesterol levels in their blood.”

The study involved looking at data from almost 400,000 people from 19 countries and 38 studies.  The participants had no cardiovascular disease at the start of the study and were followed for up to 43.5 years (median 13.5 years follow-up) for the occurrence of a fatal or non-fatal coronary heart disease event or ischaemic stroke between the years 1970 to 2013.

During the follow-up, there were 54,542 fatal or non-fatal cases of heart disease and stroke.

Using their data, the authors assessed and confirmed the long-term association between cholesterol levels and cardiovascular risk. They then used this data in a model to estimate the probability of a cardiovascular event by the age of 75 years for people aged 35-70 years, according to a person’s gender, non-HDL cholesterol levels, age, and cardiovascular disease risk factors (such as smoking status, diabetes, BMI, systolic blood pressure, and antihypertensive medication).

Looking at data for all age groups and both sexes, the authors found that the risk for a cardiovascular event decreased continuously with decreasing non-HDL levels and the risk was lowest for those individuals with the lowest non-HDL levels (classified as below 2.6 mmol non-HDL cholesterol per litre in the study).

Using the model to estimate the risk of a cardiovascular event by the age of 75 years for different age groups, the authors found that the highest long-term risks of cardiovascular disease were seen in individuals younger than 45 years of age.

Professor Barbara Thorand, German Research Center for Environmental Health said: “This increased risk in younger people could be due to the longer exposure to harmful lipids in the blood. The risk may also appear larger compared to older ages because people aged 60 years and older in our study had not developed cardiovascular disease up to this age, so they may be healthier than others of their age who were excluded from the study because they had had cardiovascular disease.”

The authors say that intervening early and intensively to reduce non-HDL cholesterol levels during the lifespan could potentially reverse early signs of atherosclerosis. However, considerable uncertainty exists about the extent to which slightly increased or apparently normal cholesterol levels affect lifetime cardiovascular risk, and about which levels should be used to make treatment recommendations, particularly in young people.

Professor Stefan Blankenberg, German Center for Cardiovascular Research, said: “Our estimates suggest that halving non-HDL cholesterol levels may be associated with reduced risk of cardiovascular events by the age of 75 years, and that this reduction in risk is larger the sooner cholesterol levels are reduced. The risk scores currently used in the clinic to decide whether a person should have lipid-lowering treatment only assess the risk of cardiovascular disease over 10 years, and so may underestimate lifetime risk, particularly in young people.

“In lieu of needed clinical trial results investigating the benefits of long-term lipid-lowering therapy in people younger than 45, this study may provide helpful insights on the benefits of lipid-lowering therapy as primary prevention from an earlier age. However, future research is needed to understand whether intervention in young people with a high lifetime risk, but low 10-year risk, would have more benefits than later intervention.”

Professor Kee concludes: “This longer-term evidence may be particularly important in people aged under 45 years.

“Further research is also needed on how useful lifetime absolute risk estimates are for motivating behaviour change among otherwise healthy young people, and whether titrating any intervention dose according to a non-HDL target would be more effective than to a target of overall life-time risk of cardiovascular diseases.”

This study was funded by European Union Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research.

 

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