New research details a link between non-high density cholesterol levels (non-HDL cholesterol) and long-term risk for cardiovascular disease in people as young as age 30.

Non-HDL cholesterol levels are often calculated and reported as part of lipid panels. Non-HDL cholesterol reflects all of the lipoproteins (lipid-carrying proteins) that are associated with a higher risk of heart disease, including low density lipoprotein cholesterol (LDL) or “bad” cholesterol. Other lipoproteins included in non-HDL cholesterol are very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL). Over time, excess lipids in the blood can build up in artery walls (atherosclerosis) and form plaques that narrow blood vessels. Plaques on the surfaces of arteries can fracture, leading to arterial thrombosis (e.g., a blood clot that obstructs the artery), resulting in heart attacks and strokes.

Atherosclerosis can begin as early as childhood, leading to increased risk of heart disease later in life. However, current models for heart disease risk are typically only applied to people ages 40 to 75 and can only estimate risk over the following 10 years. This may underestimate lifetime risk, particularly in young people, say the report’s authors.

To date, the report published on December 6, 2019 in the online version of The Lancet is among the most comprehensive analyses of the long-term risk of cardiovascular disease related to non-HDL cholesterol. Findings by the international team of researchers could help people in their 20s and 30s know the long-term risks of elevated non-HDL cholesterol levels and consider steps to lower them.

The researchers looked at 43 years of data from almost 400,000 people ages 30 to 85 from 38 long-term studies in Europe, the U.S., and Australia. Individuals were included in the analyses if they had no obvious evidence of heart disease initially (at baseline) and there was sufficient data on whether they subsequently developed cardiovascular disease. About one-third were younger than age 45 when they joined the studies. These younger participants made it possible for researchers to create a risk modelling tool to predict very long-term risks of heart attack and stroke. The tool also estimated how reducing non-HDL cholesterol could lower people’s risk by age 75.

Using the new tool, researchers were able to compare lifetime risk of different age groups and determine that those most at risk for developing future heart problems related to non-HDL cholesterol were younger than age 45. A higher lifetime risk may have been observed in this age group because young people have more time throughout their lives to accumulate unhealthy lipid levels and develop heart disease compared to older people who are closer to the end of life.

For example, women younger than age 45 with non-HDL cholesterol levels between 143-186 mg/dL (3.7-4.8 mmol/L) and at least two additional cardiovascular risk factors (e.g., overweight, high blood pressure, smokes) had a 16% chance of suffering a cardiovascular disease event by age 75. In contrast, women age 60 or over with the same characteristics had an estimated risk of 12%. For men with the same characteristics, the estimated risk for those under age 45 was 29%, and 21% for those over age 60.

The researchers say their risk tool improves on current ones because it estimates lifetime risk based on non-HDL cholesterol in a way that patients can understand. The researchers hope the tool will help healthcare practitioners and patients talk about ways to prevent or reverse early signs of heart disease.

Making lifestyle changes—such as healthier eating and exercise—to lower cholesterol at a younger age could substantially reduce lifetime risk of cardiovascular disease, the research suggests.

Younger people with very high non-HDL cholesterol levels (216 mg/dL [5.6mmol/L] or above) and other risk factors may dramatically reduce the chance of heart problems if they lower cholesterol levels by 50%, estimate the researchers. Men under age 45 could reduce their risk of heart problems from about 29% to 6%, while women in this age group could reduce their risk from approximately 16% to 4%.

However, the researchers note that no studies have specifically examined whether drug treatment (e.g., statins) to lower non-HDL cholesterol before age 45 results in less cholesterol build-up in arteries over the long term. Other areas of uncertainty include how moderately increased cholesterol levels affect lifetime cardiovascular risk and what non-HDL levels warrant treatment, particularly in young people. The authors call for more research to answer these questions.

In an editorial that accompanied the report, Jennifer G. Robinson, MD, a University of Iowa epidemiologist, also called for more research. She notes that no studies have examined the effects of taking lipid-lowering drugs for decades, so risks of very long-term treatment are unclear.

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