Non-HDL Cholesterol Levels May Predict CAD Risk for All Ages

Matthew Armstrong, PhD

Elevated non–HDL-C at all stages of lives are associated with the presence of coronary artery calcification (CAC) in mid-adulthood, a new study found.

Even more, this association was found to be much stronger for non–HDL-C levels in adolescents.

These findings thus indicate that increased awareness of non–HDL-C as a risk factor for coronary atherosclerosis is needed for patients of all ages, especially for those in their adolescent years.

A team led by Matthew Armstrong, PhD, Menzies Institute for Medical Research, University of Tasmania, Australia, analyzed a 28-year cohort study that measured non–HDL-C in patients during adolescence (12-18 years), young adulthood (21-30 years), and mid-adulthood (33-45). 

“Among children and adults, previous studies have shown that non–HDL-C is at least as good as LDL-C and other lipid measures for predicting future atherosclerotic burden,” Armstrong and colleagues wrote.

“This has led to the National Heart, Lung, and Blood Institute (NHLBI) recommending non–HDL-C for primary screening of dyslipidemia in childhood,” they continued.

Predicting Atherosclerotic Burden from Non–HDL-C

The team’s analysis was based off data collected during the Cardiovascular Risk in Young Finns Study, which began in 1980 and included 3596 participants at baseline. Participants were aged 3, 6, 9, 12, 15, and 18 years and were drawn from 3 population centers in Finland.

Subsequent follow-up occurred in 1983, 1986, 1989, 1992, 2001, and 2007. At baseline and follow-up, non–HDL-C levels were consistently measured; in 2008, CAC was determined using computed tomography.

CAC was thus categorized as 0 (no CAC, Agatston score = 0) or 1 (presence of CAC, Agatston score ≥1) for purposes of analysis.

The investigators then used a Bayesian relevant life course exposure model to determine the relative association between non–HDL-C at each life stage and the presence of CAC in mid-adulthood.

Of the 589 participants in their final analysis, a majority (56%) were female. Further, 19.2% had CAC in adulthood, of which 12.4% were male.

“Briefly, among individuals who had evidence of CAC in mid-adulthood, non–HDL-C was higher at every observed age compared with those without CAC,” the investigators wrote.

The team then adjusted analysis for year of birth, sex, body mass index, systolic blood pressure, blood glucose level, smoking status, lipid-lowering and antihypertensive medication use, and family history of heart disease.

Accordingly, cumulative exposure to non–HDL-C across all life stages was associated with CAC (odds ratio [OR], 1.50; 95% CI, 1.14-1.92).

The investigators reported the ORs of CAC presence due to elevated non–HDL-C exposure during young adulthood and mid-adulthood were 1.14 (95%, 1.01-1.43) and 1.12 (95% CI, 1.01-1.34), respectively.

However, exposure to non–HDL-C during adolescence had the strongest association—with an OR of 1.16 (95%, 1.01-1.46).

Managing Cholesterol Levels

This data points to the increasing importance of early-life cardiovascular risks and early screening in young populations.

However, they acknowledged that much of cholesterol levels is controlled by genetics, with 61-83% heritability observed for LDL-C. Thus, lipid tracking from childhood to adulthood is partly controlled by preprogrammed factors.

“That said, it has been shown that lifestyle modification, including increasing physical activity, healthy diet, and cessation of smoking, elicits clinically important changes in serum lipid levels,” they wrote.

While genetic factors are virtually immutable, focusing on modifiable risk factors should be a focus for at-risk young individuals.

“Altogether, early screening, identification, and management of elevated non–HDL-C levels may represent an important goal toward reducing the burden of heart disease in adulthood,” Armstrong and colleagues emphasized.

The study, “Association of Non–High-Density Lipoprotein Cholesterol Measured in Adolescence, Young Adulthood, and Mid-Adulthood with Coronary Artery Calcification Measured in Mid-Adulthood,” was published online in JAMA Cardiology.