European Primary Care Cardiovascular Society

Little attention for remnants in recent decades, unrightful so

News - June 7, 2019

A risky lipoprotein – remnants

A presentation by Børge Nordestgaard at EAS Congress 2019, in Maastricht, The Netherlands.

According to professor Nordestgaard, the clinical focus has shifted away from remnant cholesterol and triglycerides (TG) since the 1990’s, and unrightfully so. He thinks the reason might be the demonstration that HDL was a better predictor of risk than TG. Interest is now diverting away from HDL, as a consequence of insights from genetic studies and “failed” HDL-lowering trials.

Nordestgaard stated that remnants heve been largely ignored so far. He thinks that is a mistake, because clear links have been described between elevated levels of remnants and the risk of heart attack, ischemic stroke, and death. On the other hand, when critically looking at the literature on LDL, he said that it has only been shown really well that elevated LDL causes heart attack, and not stroke for instance.

Using data of the Copenhagen Heart study (CHS), when comparing the top quartile of remnant cholesterol levels with the top quartile of LDL-c, they showed a similarly elevated risk of myocardial infarction. The risk of all-cause mortality, on the other hand, is only strongly elevated in the top quartile of remnant cholesterol. LDL-c on the other hand, is not a good predictor of all-cause mortality.

In data of the Copenhagen General Population Study (CGPS), they showed that the amount of fat one has in the body, largely determines the remnant level: the remnant cholesterol levels shows a clear positive relationship with deciles of BMI. A study published very recently (Balling et al., Atherosclerosis 2019) showed that a third of nonfasting plasma cholesterol is in fact in the remnant lipoproteins. This is problematic, because in contrast to LDL-c, remnants do not need to be modified before they can exert negative effects. For instance, they directly lead to inflammation: if plasma TG go up, so do CRP levels. LDL does not show this relationship (TG and LDL and CRP levels tested in the same individuals of the CHS and CGPS).

Concerning TG lowering therapy, Nordestgaard pointed out some interesting new and ongoing trials. He said that ‘Even he was surprised that the results were so clear’, about the MACE risk reduction achieved in the REDUCE-IT trial, in which patients with high TG levels were randomised to n-3 fatty acids (icosapent ethyl [EPA]) or placebo. 25% Event reduction was seen, which coincided with 20% lower TG and 40% lower CRP levels. Results are awaited from the STRENGTH trial, which studies a mix of omega-3 fatty acids (eicosapentaenoic acid, or EPA, and docosahexaenoic acid, or DHA) and the PROMINENT study, which evaluates a selective peroxisome proliferator alpha modulator (SSPARM-alpha) pemafibrate.

Nordestgaard concluded by stating what he advises his patients with high remnant and TG levels: eat less, exercise more, treat diabetes, reduce alcohol intake, take high intensity statins, take icosapent ethyl and some have good results with fibrates. The evidence for over-the-counter fish oils is less convincing, likely because their dose is too low. He stressed that lowering TG with omega-3 fatty acids works well, in those with high TG levels, parallel to LDL lowering being effective in those with elevated LDL.

Unpublished data by Langsted et al. now also suggests that in individuals from the CGPS cohort who previously had an ischemic stroke or myocardial infarction, the MACE event rate is higher with increasing remnant cholesterol level.

Our reporting is based on the information provided at the EAS 2019 congress

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