A ‘third prevention paradigm’ for reducing lifetime cardiovascular risk would see more intensive lowering of lipid levels at an earlier age.

Blood concentrations of non-HDL cholesterol and LDL cholesterol are strongly associated with increased long-term risk of atherosclerotic cardiovascular disease, especially when increased before the age of 45 years, according to a large study in The Lancet.

The analysis of data from almost 400,000 individuals participating in the Multinational Cardiovascular Risk Consortium from 19 countries, including Australia, showed a stepwise increase of cardiovascular disease events across increasing concentrations of non-HDL cholesterol.

Thirty-year cardiovascular disease event rates were approximately three-to-four times higher in women and men in the highest non-HDL cholesterol category (≥5·7 mmol/L) than those in the lowest category (<2·6 mmol/L; 3253 [33·7%] vs 262 [7·7%] in women and 7689 [43·6%] vs 375 [12·8%] in men).

The steepest increase of the relative hazard associated with non-HDL cholesterol was found in individuals younger than 45 years at baseline.

For example, non-HDL cholesterol concentrations of 2·6 mmol/L (100 mg/dL) to below 3·7 mmol/L (145 mg/L) before 45 years of age increased the relative risk of atherosclerotic cardiovascular disease 10–20% more than when concentration increases occurred later in life.

Furthermore, when concentrations of non-HDL cholesterol were higher than 3·7 mmol/L (145 mg/dL) before the age 45 years, the relative risk of atherosclerotic cardiovascular disease was at least doubled, reported the research team led by Professor Stefan Blankenberg of University Heart and  Vascular Center Hamburg in Germany.

According to the authors,  until now considerable uncertainty existed about the extent to which cholesterol concentrations affected lifetime cardiovascular risk and about which thresholds should be used to merit a treatment recommendation, particularly in young people.

“Our study extends current knowledge because it suggests that increasing concentrations of non-HDL cholesterol predict long-term cardiovascular risk, particularly in cases of modest increase at a young age,” they wrote.

The researchers – including Australians Professor Leon Simons and Professor Jonathan Shaw – used the data to create an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol how much risk could be reduced if cholesterol was lowered.

Writing in an accompanying comment, Dr Jennifer Robinson of the Division of Cardiology, University of Iowa, said the novelty of the findings were in the fact that they projected the effects of starting cholesterol lowering therapy early in life, in people who currently rate as low risk according established cardiovascular risk tools.

“Such therapy could reduce the lifetime risk of atherosclerotic cardiovascular disease in patients with increased concentrations of non-HDL and LDL cholesterol, especially when risk is further amplified by the presence of comorbid factors,” she wrote.

“Lowering cholesterol with more intensive therapy is also supported by findings that generic statins are cost-saving or highly cost-effective even for primary prevention in patients at low risk of cardiovascular disease,” she added.

Also commenting on the study, Paul Leeson, a Professor of Cardiovascular Medicine at the University of Oxford, UK, said the findings demonstrated for the first time that having a high cholesterol before the age of 45 disproportionately increases the lifetime risk of heart disease.

“ [This] suggests it is not just the cholesterol level but how long you have high cholesterol that puts you at risk … the findings support the idea that getting cholesterol controlled early in life may have more benefit than waiting till you are older,” he said.

“Exactly how to reduce cholesterol effectively in young people and, in particular, whether you would need to take drugs for decades to do this is not explored but will be important to consider before these findings can be included into medical guidance,” he added.

The study was funded by the EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research.