The number of studies on remnant lipoproteins is still quite low. One reason for this is that remnant particles are extremely heterogeneous and hence difficult to measure. However, determining the remnant cholesterol content similar to LDL cholesterol permits drawing conclusions about the number of remnant particles and their atherogenicity. A team of researchers led by Renato Quispe from John Hopkins University in the United States took advantage of the findings. They suspected that the concentration of remnant cholesterol in the blood is an independent risk factor for cardiovascular diseases.
Lipoproteins containing apoprotein B (ApoB) play an important role in the development of atherosclerosis. The most well-known representative of this group is the low-density lipoprotein (LDL). Relatively speaking, it carries the most cholesterol through the body and can penetrate vessel walls and there promote the formation of plaques. There is now increasing evidence that other lipoproteins are also linked to atherosclerosis. Attention is focused on so-called "remnant" lipoproteins. They are derivatives of very-low-density lipoprotein (VLDL) or chylomicrons and are essentially similar in structure to an LDL particle, but have more triglycerides in their core.
The researchers analysed data from over 17,500 individuals who participated in three large US studies on the prevention of cardiovascular disease (ARIC, MESA and CARDIA). They only included those study participants who did not have a history of cardiovascular disease at baseline. The mean age was 52 years and 57% of the participants were female. The mean LDL cholesterol was 118 mg/dl. In this study, the remnant cholesterol was not measured directly, but calculated using the following formula: non-HDL cholesterol minus the calculated LDL cholesterol.
The mean level of remnant cholesterol at the start of the study was 20 mg/dl. The team then investigated whether people with elevated remnant cholesterol at study entry were more likely to develop cardiovascular disease. They adjusted their results for age, sex, pre-existing conditions, lifestyle, obesity and also LDL and ApoB levels. The average follow-up time of the participants was 19 years.
Within the study population, 2,143 cardiovascular events (12.2%) occurred during the observation period. The risk of a cardiovascular event rose with increasing levels of remnant cholesterol (hazard ratio 1.65; 95% confidence interval: 1.45-1.89), independent of LDL cholesterol and ApoB. For the purpose of better illustrating their findings, the research team divided the study population into four groups according to their concentration of remnant cholesterol and LDL cholesterol in the blood.
Compared to the cohort with normal levels of remnant and LDL cholesterol, the group with high remnant and normal LDL cholesterol, which still made up about one third of the study population, had a 21% increased cardiovascular risk compared to the first group. However, this was not the case in the group with normal remnant and elevated LDL cholesterol. These results support the hypothesis that remnant cholesterol is an independent cardiovascular risk factor.
This retrospective study shows that it is not only the familiar LDL cholesterol, but also the cholesterol of the triglyceride-rich remnant lipoproteins that have an effect on cardiovascular risk that should not be underestimated. This is of clinical relevance, as it can explain why people with optimal LDL cholesterol control sometimes still show a progression of their atherosclerosis.
One weakness of the study is that the concentration of remnant cholesterol was not measured but only calculated. It is a known fact that the calculated remnant cholesterol levels can be distorted, especially at high concentrations.
In the future, the role of remnant cholesterol in atherosclerosis should be studied more closely. This could lead to further therapeutic options that can help reduce the cardiovascular risk independently of LDL cholesterol.
Source:
Quispe et al. Remnant cholesterol predicts cardiovascular disease beyond LDL and ApoB: a primary prevention study. European Heart Journal, Volume 42, Issue 42, 7 November 2021, Pages 4324–4332