Abstract
Lipoprotein characteristics were analyzed in familial combined hyperlipidemia (FCH) patients before and after statin treatment. Twenty-six FCH patients were classified according to the presence (HTG group, n = 13) or absence (normotriglyceridemic (NTG) group, n = 13) of hypertriglyceridemia. Fifteen healthy subjects comprised the control group. Lipid profile, inflammation markers, and qualitative characteristics of lipoproteins were assessed. Both groups of FCH subjects showed high levels of plasma C-reactive protein (CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and apolipoprotein J. Statins reverted the increased levels of Lp-PLA2 and CRP. Lipoprotein composition alterations detected in FCH subjects were much more frequent in the HTG group, leading to dysfunctional low-density lipoproteins (LDL) and high-density lipoproteins (HDL). In the HTG group, LDL was smaller, more susceptible to oxidation, and contained more electronegative LDL (LDL(-)) compared to the NTG and control groups. Regarding HDL, the HTG group had less Lp-PLA2 activity than the NTG and control groups. HDL from both FCH groups was less anti-inflammatory than HDL from the control group. Statins increased LDL size, decreased LDL(-), and lowered Lp-PLA2 in HDL from HTG. In summary, pro-atherogenic alterations were more frequent and severe in the HTG group. Statins improved some alterations, but many remained unchanged in HTG.
Highlights
In addition to the quantitative alterations of the lipid profile, it is well-known that the qualitative properties of lipoproteins are a strong determinant of the cardiovascular risk
It has been widely reported that high-density lipoprotein (HDL) exerts atheroprotective functions by counteracting the oxidation of low-density lipoprotein (LDL), the inflammatory and apoptotic effects of modified LDL, inhibiting platelet coagulation mediated by an anti-platelet activating factor (PAF) effect, as well as by promoting cholesterol efflux [4,5,6,7]
Several characteristics or components of HDL, such as particle size, lipoprotein-associated phospholipase A2 (Lp-PLA2 ) and paraoxonase activity, apolipoprotein A-I/apoA-II ratio, and apoC-III and apoJ content [5,8,9,10], are related to these antiatherogenic properties, which are compromised in disorders with high risk for coronary artery disease [10,11]
Summary
In addition to the quantitative alterations of the lipid profile, it is well-known that the qualitative properties of lipoproteins are a strong determinant of the cardiovascular risk. Several characteristics or components of HDL, such as particle size, lipoprotein-associated phospholipase A2 (Lp-PLA2 ) and paraoxonase activity, apolipoprotein (apo) A-I/apoA-II ratio, and apoC-III and apoJ ( known as clusterin) content [5,8,9,10], are related to these antiatherogenic properties, which are compromised in disorders with high risk for coronary artery disease [10,11]. FCH is associated with high risk for coronary artery disease, which has been related to alterations in lipid profile as well as to the presence of low-grade inflammation [14,15] This disorder is characterized by a high interindividual and intraindividual variation throughout the patient’s life, and in addition to elevated levels of plasma cholesterol, it can display with or without increased triglycerides [12,14,16,17]. Despite its relevance in cardiovascular diseases, FCH is frequently undiagnosed and very often undertreated [17]
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