High ApoB in Young Adults Predicts Midlife Atherosclerosis

Marlene Busko

January 14, 2016

CHICAGO, IL — Young adults aged 18 to 30 who had higher-than-average apolipoprotein B (apoB) levels showed an increased risk of developing coronary artery calcification (CAC) by middle age, in an analysis from the Coronary Artery Risk Development in Young Adults (CARDIA) study[1].

Moreover, apoB was better than LDL cholesterol or non–HDL cholesterol for predicting this risk of midlife subclinical atherosclerosis, especially in individuals with discordant values for apoB and these two other biomarkers, Dr John T Wilkins (Northwestern University Feinberg School of Medicine, Chicago, IL) and colleagues report in the article published in the January 19, 2016 issue of the Journal of the College of Cardiology.

However, although some clinicians favor measuring apoB as well as traditional lipid biomarkers to help predict CVD risk, and apoB is included in some guidelines, it is not part of current ACC/AHA guidelines, and others are not convinced that studies have demonstrated that apoB adds predictive value. .

"There is certainly debate" about whether apoB should be used in clinical practice to assess CVD risk or as a therapeutic target, Wilkins conceded to heartwire from Medscape. Although the most recent AHA/ACC guidelines say there is not enough evidence to promote the measurement of apoB in clinical practice, "a lot of lipidologists, myself included . . . feel it may add some important information to the assessment of cardiovascular risk," he said.

Dr Robert S Rosenson (Icahn School of Medicine at Mount Sinai) and coauthors of an accompanying editorial[2] agree that apoB can add information. "We take the viewpoint that apoB is a more robust biomarker of CVD risk [than LDL cholesterol and non–HDL cholesterol] based on observational studies and clinical trials such as AFCAPS/TexCaps," he told heartwire . "For all patients with metabolic syndrome and type 2 diabetes, I routinely measure either apoB or LDL particle concentration," he said, adding that "it has been shown that apoB or LDL-particle concentration is more strongly associated with CV risk than LDL cholesterol and non–HDL cholesterol in most studies."

However, Dr Scott Grundy (University of Texas Southwestern Medical Center) and first author of the International Atherosclerosis Society position paper on the management of dyslipidemia[3] told heartwire that although there's no question that apoB is a better predictor of atherosclerosis and heart attack than LDL cholesterol, "it's much more difficult to show that apoB is a better predictor than non–HDL cholesterol." Moreover, some of the limitations described by the authors—such as measuring apoB only once and that CAC is only a surrogate for hard events—are major, according to Grundy.

Interesting Science

Apart from the debatable clinical implications, "the science behind apoB is interesting," Grundy admitted.

Measuring apolipoprotein B entails measuring the total number of very low-density lipoprotein (VLDL), LDL, intermediate-density lipoprotein (IDL), and lipoprotein (a) (Lp[a]) particles, because each lipoprotein particle contains one molecule of apoB, Wilkins explained. On the other hand, measuring non–HDL cholesterol gives the total concentration of cholesterol within VLDL, LDL, IDL, and Lp(a) particles.

When apoB particles contain an average amount of cholesterol, which is the case in about 80% to 90% of individuals, values of apoB are concordant with values of LDL cholesterol or non–HDL cholesterol, and the three biomarkers predict CVD risk equally well, he added.

However, about 10% to 20% of individuals have apoB particles that have more-than-average or less-than-average amounts of cholesterol, so their apoB values are discordant with values of LDL cholesterol or non–HDL cholesterol, and the three biomarkers would predict different levels of CVD risk.

Studies in adults have shown that high levels of apoB predicted risk of atherosclerotic CVD, even in the context of low levels of LDL cholesterol or non–HDL cholesterol, Wilkins and colleagues write. However, this relationship had not been studied in a younger population.

They aimed to quantify how discordance between apoB and LDL cholesterol or non–HDL cholesterol in young adults predicts CAC in midlife.

They analyzed data from 2794 participants in CARDIA, who were 18 to 30 in 1985–1986 when they were recruited in four American cities and had complete baseline data as well as CAC determination by computed tomography (CT) 25 years later (at midlife, when they were 43 to 55 years old). The presence of CAC was defined as a total Agatston score >0, based on a sum of the Agatston scores for each coronary artery and across all coronary arteries.

Close to half of the participants were male (44.4%) and African American (47.6%). At baseline they had a mean age of 25 and a mean BMI of 24.5, and 27% were current smokers. Their mean lipid values were total cholesterol 177 mg/dL, HDL cholesterol 53 mg/dL, LDL cholesterol 109.9 mg/dL, non–HDL cholesterol 124 mg/dL, and apoB 90.7 mg/dL, and their median triglycerides were 61 mg/dL.

Compared with participants in the lowest tertile of apoB at baseline, those in the middle or highest tertiles of apoB were increasingly more likely to have CAC detected at midlife (odds ratios 1.53 and 2.28, respectively), after adjustment for traditional CV risk factors.

Similarly, when participants were classed as having high (above-median) or low (below-median) values of apoB, LDL cholesterol, or HDL cholesterol at baseline, those with high apoB and low LDL cholesterol or with high apoB and low non–HDL cholesterol were also more likely to have CAC at midlife (adjusted odds ratio 1.55 and 1.45, respectively).

Debatable Implications

Wilkins and colleagues acknowledge that they only measured apoB once and they used CAC as a surrogate marker of CHD risk, even though multiple studies have shown that CAC is strongly linked to hard clinical end points. Also, given the young age of the participants, there were not enough hard events to generate a robust estimate for CV events.

Many studies show that apoB and non–HDL cholesterol similarly predict cardiovascular risk, Grundy added. And only 8.6% of the participants had the discordant high-risk combination of high apoB with low LDL cholesterol or low non–HDL cholesterol.

Furthermore, non–HDL is easily measured in a clinical lab, whereas apoB requires an extra test (an immunoassay) with added cost. "Should we all start going out and measuring apoB? I think the answer is 'No,' " according to Grundy.

It is also not clear if an apoB target treatment goal would be better than a non–HDL goal, he continued. This may be moot, though, since "the latest [ACC/AHA] guidelines [have eliminated treatment targets and] say that you come up with a certain level of risk and treat [the patient] with a statin and don't ever measure cholesterol again."

For now, "these data suggest a dose-response association between apoB in young adults and the presence of midlife CAC independent of baseline traditional CVD risk factors," the researchers conclude, adding that "further follow-up is warranted to determine if apoB measurement in young adulthood is a marker of later CHD risk as well."

This authors report they have no relevant financial relationships related to this study. Rosenson reports receiving research grants to his institution from Amgen, AstraZeneca, Catabasis, and Sanofi. He has also served on the advisory board for Akcea, Amgen, AstraZeneca, Eli Lilly, GlaxoSmithKline, Regeneron, and Sanofi; has received honoraria from Kowa; and has received royalties from UpToDate. Grundy has no relevant financial relationships.

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