Study suggests link between cholesterol and risk of heart disease, stroke

There is a strong link between non-high-density lipoproteins (HDL) cholesterol levels and long-term risk for cardiovascular disease in people under 45 years old, not just older ages, according to a new study published in The Lancet.

The amount of non-HDL cholesterol and low-density lipoproteins (LDL) in the blood are accepted as causal risk factors for cardiovascular disease and play a significant part in predicting a person's risk of developing 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.

In the study, the authors used individual-level data from almost 400,000 people from 38 studies from Europe, Australia and North America. The participants had no cardiovascular disease at the start of the study and were followed for up to 43.5 years, with a median 13.5 years follow-up, for the occurrence of a fatal or non-fatal coronary heart disease event or ischemic stroke.

Using their data, the authors assessed and confirmed the long-term association between cholesterol levels and cardiovascular event 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. The model also estimated how much risk could be reduced if non-HDL cholesterol levels were halved. During follow-up, there were 54,542 fatal or non-fatal cases of heart disease and stroke, the researchers said.

The study extends existing research because it suggests that increasing levels of non-HDL cholesterol may predict long-term cardiovascular risk by the age of 75 years. Past risk estimates of this kind are based on 10-year follow-up data.

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/L in the study.

The authors note some limitations within their study, including that their study results may not be generalizable to other regions or racial and ethnic groups as the study was based on data from people of European ancestry from high-income countries.

The authors used data about the participants' non-HDL cholesterol levels when they entered the study only, and so could not account for changes in cholesterol levels. However, they note that non-HDL cholesterol levels in young people are generally stable over the 30-year life course. They also could not account for participants beginning to take lipid-lowering therapy during the study, but adjusted cholesterol levels for people who were already taking lipid-lowering therapy at the start of the study.

Lastly, the researchers said their modelled 50 percent reduction posits that the effects of treatment apply over a longer period of 30 years than has been studied in clinical trials of around seven years, and note that real-world benefits of lipid-lowering therapies like statins are probably lower than the cholesterol reductions seen in trials because of sub-optimal adherence and side effects.