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Published on: September 15, 2018
Parabolic relationship between plasma triacylglycerols and LDL-cholesterol in familial combined hyperlipidaemia: the
Martijn C G J Brouwers1, Jacqueline de Graaf, Marleen M J van Greevenbroek
1Department of Medicine, University Hospital Maastricht, Maastricht, The Netherlands. martijn.brouwers@intmed.unimaas.nl
Insights
Familial combined hyperlipidaemia (FCHL) shows varied lipid levels due to a parabolic link between triglycerides and LDL-cholesterol. This relationship explains FCHL
Area of Science:
- Cardiovascular Medicine
- Genetics
- Biochemistry
Background:
- Familial combined hyperlipidaemia (FCHL) is a common genetic disorder.
- FCHL contributes significantly to premature cardiovascular events.
- FCHL presents complex lipid phenotypes within families and over time.
Purpose of the Study:
- To investigate the hypothesis of a parabolic relationship between plasma triacylglycerols and LDL-cholesterol in FCHL.
- To explain the 'multiple-type hyperlipidaemia' observed in FCHL patients.
- To assess the diagnostic and predictive utility of apoB versus LDL-cholesterol in FCHL.
Main Methods:
- Analysis of two FCHL cohorts (Maastricht, n=145; Nijmegen, n=299) over 5 years.
- Categorization into three groups based on plasma triacylglycerol levels (below 1.5 mmol/l, mixed, above 1.5 mmol/l).
- Examination of relationships between triacylglycerols, LDL-cholesterol, apoB, and cardiovascular disease prevalence.
Main Results:
- A significant positive relationship between triacylglycerols and LDL-cholesterol in group A (males).
- A significant negative relationship between triacylglycerols and LDL-cholesterol in group C (males).
- A linear relationship observed between triacylglycerols, apoB levels, and cardiovascular disease prevalence.
Conclusions:
- A parabolic relationship between plasma triacylglycerols and LDL-cholesterol explains the variable lipid phenotypes in FCHL.
- The linear association of triacylglycerols with apoB and cardiovascular disease supports apoB's utility.
- Apolipoprotein B is recommended over LDL-cholesterol for FCHL diagnosis and cardiovascular risk prediction.
Abstract:
FCHL (familial combined hyperlipidaemia) is a highly prevalent genetic lipid disorder that accounts for a substantial number of premature cardiovascular events. To date, FCHL has been complicated by the different lipid phenotypes that are present within one family and one individual patient over time. In the present study, we hypothesized that a parabolic relationship between plasma triacylglycerols (triglycerides) and LDL (low-density lipoprotein)-cholesterol can explain this so-called 'multiple-type hyperlipidaemia' in FCHL. Our hypothesis was tested in two well-documented FCHL cohorts [Maastricht (n=145) and Nijmegen (n=299)] that were followed over a 5-year interval. Three groups were constructed depending on plasma triacylglycerols: group A (individuals with both measurements below 1.5 mmol/l), group B (one measurement below and one measurement above 1.5 mmol/l) and group C (both measurement above 1.5 mmol/l). In both male, but not female, cohorts, a significant positive relationship between plasma triacylglycerols and LDL-cholesterol was observed in group A (P=0.02 for Maastricht cohort and P=0.001 for the Nijmegen cohort), a significant negative relationship in group C (P=0.01 for Maastricht cohort and P=0.02 for the Nijmegen cohort), and a relationship intermediate to group A and C in group B. In contrast, both apoB (apolipoprotein B) levels and the prevalence of cardiovascular disease were related with plasma triacylglycerols in a more linear fashion. In conclusion, a parabolic relationship between plasma triacylglycerols and LDL-cholesterol explains the 'multiple-type hyperlipidaemia' in FCHL. In addition, the linear relationship between triacylglycerols and both apoB levels and the prevalence of cardiovascular disease substantiate the use of apoB instead of LDL-cholesterol in the diagnosis of FCHL and the prediction of cardiovascular disease.
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