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Plasma homocysteine in subjects with familial combined hyperlipidemia
M J Veerkamp1, J de Graaf, M den Heijer
1Department of Medicine, Division of General Internal Medicine, 541, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. m.veerkamp@aig.umcn.nl
Insights
Familial combined hyperlipidemia (FCH) does not involve higher homocysteine levels or increased cardiovascular disease risk from hyperhomocysteinemia. This study found no link between homocysteine and lipid levels or insulin resistance in FCH patients.
Area of Science:
- Cardiovascular Medicine
- Metabolic Disorders
- Genetics
Background:
- Familial combined hyperlipidemia (FCH) presents with elevated cholesterol and triglycerides, increasing cardiovascular disease (CVD) risk.
- The moderate lipid elevations in FCH do not fully account for the heightened CVD risk.
- Hyperhomocysteinemia, a methionine metabolism disorder, is an independent CVD risk factor.
Purpose of the Study:
- To determine if FCH patients have higher plasma homocysteine concentrations than controls.
- To investigate if homocysteine contributes to the increased CVD risk in FCH.
- To assess associations between homocysteine levels and lipid metabolism or insulin resistance in FCH.
Main Methods:
- Studied 667 subjects: 161 with FCH, 109 controls (spouses), and 397 normolipidemic relatives.
- Defined FCH by plasma lipid levels above the 90th percentile (age/gender-adjusted).
- Measured plasma homocysteine, lipid profiles, and assessed insulin resistance.
Main Results:
- Mean homocysteine concentrations did not significantly differ between the FCH and control groups.
- Hyperhomocysteinemia did not confer a higher CVD risk in FCH subjects compared to non-FCH subjects.
- No significant associations were found between plasma homocysteine and lipid levels (including small dense LDL) or insulin resistance.
Conclusions:
- Elevated plasma homocysteine is not a characteristic feature of familial combined hyperlipidemia.
- Homocysteine does not appear to exacerbate cardiovascular risk in individuals with FCH.
- Homocysteine levels are independent of lipid metabolism and insulin resistance parameters in this FCH cohort.
Abstract:
Familial combined hyperlipidemia (FCH) is characterised by hypercholesterolemia and/or hypertriglyceridemia and associated with an increased risk of cardiovascular disease (CVD). The plasma lipid and lipoprotein levels in subjects with FCH are relatively moderately elevated and do not fully explain the increased risk of CVD. Hyperhomocysteinemia is a disorder of methionine metabolism and also a well-known independent risk factor for CVD. We investigated whether subjects with FCH have higher plasma homocysteine concentrations than controls, and whether homocysteine contributes to the increased risk of CVD in FCH. Furthermore we evaluated whether parameters of lipid and lipoprotein metabolism and/or insulin resistance are associated with the homocysteine level. In total 667 subjects, including 161 subjects with FCH, 109 spouses who referenced as control group and 397 normolipidemic relatives were studied. FCH was defined by the presence of plasma total cholesterol and/or triglyceride levels above the 90th percentile adjusted for age and gender. The mean homocysteine concentration of the FCH group did not significantly differ from the control group. The risk for CVD due to hyperhomocysteinemia in subjects with FCH was not higher than in subjects without FCH. No associations were observed between plasma homocysteine concentration and plasma lipid and lipoprotein levels, including small dense low density lipoprotein, nor between homocysteine concentration and insulin resistance.