The blood levels of non-high density lipoprotein (HDL) cholesterol were found to have a strong association with the long-term risk for a cardiovascular disease event, according to study results published in The Lancet.

With this this study, investigators sought to examine the link between the concentration of all non-HDL cholesterol and the long-term risk of developing cardiovascular disease, to create a tool to assess this risk, and to develop a model to evaluate the benefits associated with lipid-lowering strategies in individuals without prevalent cardiovascular disease.

In this risk-evaluation and risk-modeling study, researchers used data from the Multinational Cardiovascular Risk Consortium to evaluate long-term outcomes in patients without prevalent cardiovascular disease at baseline. The outcome measure was the first occurrence of a major cardiovascular event, and the primary composite end point included the first nonfatal or fatal coronary heart disease or ischemic stroke event. Threshold concentrations for cholesterol were based on those defined in the 2016 European guidelines on cardiovascular disease prevention, ie, non-HDL cholesterol threshold was determined by adding 30 mg/dL to the set threshold for LDL cholesterol. The researchers created a tool to estimate the probabilities of a cardiovascular disease event by age 75, based on data on age category, sex, non-HDL cholesterol category, and risk factors including smoking, diabetes, and obesity. This risk could be adjusted with lipid-lowering therapies leading to a 50% reduction of non-HDL cholesterol.

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Of the 524,444 individuals in the Multinational Cardiovascular Risk Consortium database, the data of 398,846 patients from 38 cohorts (48.7% women; median age, 51 years; interquartile range [IQR], 40.7-59.7 years) were assessed. Median follow-up time was 13.5 years (IQR, 7.0-20.1 years), with a maximum follow-up of 43.6 years. A total of 12,311 patients (4.9%) received lipid-lowering therapy. During the follow-up period, 54,542 cardiovascular disease end points occurred.

There were higher rates of 30-year cardiovascular disease events with increasing non-HDL cholesterol categories: from 7.7% to 33.7% in women, and from 12.8% to 43.6% in men for non-HDL cholesterol <2.6 mmol/L and ≥5.7 mmol/L, respectively (P <.0001), in cumulative incidence curve analyses.

The largest increase of the relative hazard associated with non-HDL cholesterol was observed in patients <45 years at baseline (for non-HDL cholesterol ≥5.7 mmol/L: maximum hazard ratio [HR], 4.3; 95% CI, 3.0-6.1 in women; HR, 4.6; 95% CI, 3.3-6.5 in men). These data allowed investigators to create a tool for the assessment of the risk for a cardiovascular disease event, based on non-HDL cholesterol levels in derivation and validation cohorts. This tool was accurate, as indicated by a root mean square error <1% for estimated probabilities of cardiovascular disease events.

According to this tool, a 50% reduction of non-HDL cholesterol levels was associated with a lower risk for a cardiovascular disease event by age 75. This effect was augmented with earlier non-HDL cholesterol reductions. The absolute risk reduction of a cardiovascular disease event was more evident in men than in women, and in patients with ≥2 vs ≤1 disease risk factors.

Study limitations include the fact that the end point information was based mainly on medical reports and local registers, the sole use of baseline data for blood lipids, a majority of participants living in high-income countries and of European ancestry, and the assumption of a stable reduction of non-HDL cholesterol associated with lipid-lowering strategies.

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“Our study…suggests that increasing concentrations of non-HDL cholesterol predict long-term cardiovascular risk, particularly in cases of modest increase at a young age,” concluded the study authors.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Brunner FJ, Waldeyer C, Ojeda F, et al. Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium. Lancet. 2019;394(10215):2173-2183.

This article originally appeared on Clinical Advisor