Common variation in cholesteryl ester transfer protein: relationship of first major adverse cardiovascular events with the apolipoprotein B/apolipoprotein A-I ratio and the total cholesterol/high-density lipoprotein cholesterol ratio.

Background: The preference of the apolipoprotein (apo) B/apoA-I ratio over the total cholesterol/HDL cholesterol (TC/HDL-C) ratio in cardiovascular risk prediction is disputed. Cholesteryl ester transfer protein (CETP) is instrumental in lipoprotein remodelling and affects the cholesterol content in pro- and antiatherogenic lipoproteins relative to their major apolipoproteins. We tested the influence of common CETP variations on the strength of associations of a first major adverse cardiovascular event (MACE) with the apoB/apoA-I ratio compared with the TC/HDL-C ratio.

Lower carotid intima media thickness is predicted by higher serum bilirubin in both non-diabetic and Type 2 diabetic subjects.

Background: Higher serum bilirubin levels may be implicated cardiovascular protection. It is unknown whether the impact of serum bilirubin on carotid artery intima media thickness (IMT), a marker of subclinical atherosclerosis, is different in diabetic subjects compared to non-diabetic subjects. We assessed relationships of IMT with serum total bilirubin in non-diabetic and Type 2 diabetic subjects without clinically manifest cardiovascular disease.

The plasma leptin/adiponectin ratio predicts first cardiovascular event in men: a prospective nested case-control study.

Objective: The plasma leptin/adiponectin (L/A) ratio has been proposed as a preferential marker of atherosclerosis susceptibility compared to leptin and adiponectin alone. We determined the extent to which the L/A ratio predicts incident cardiovascular disease (CVD) taking account of clinical risk factors, microalbuminuria, the total cholesterol/HDL cholesterol (TC/HDL-C ratio), triglycerides, high sensitive C-reactive protein (hs-CRP) and insulin sensitivity (homeostasis model assessment (HOMA(ir))).

Methods: A community-based prospective nested case-control study was carried out in 103 non-diabetic men who developed a first cardiovascular event (cases) and 106 male control subjects (no clinically manifest CVD and no lipid lowering drug use at baseline; median follow-up of 3.

Plasma lipoprotein-associated phospholipase A2 is inversely correlated with proprotein convertase subtilisin-kexin type 9.

Background And Aims: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a pro-atherogenic phospholipase A(2), which is predominantly complexed to low-density lipoprotein (LDL) particles. Proprotein convertase subtilisin-kexin type 9 (PCSK9) provides a key step in LDL metabolism by stimulating LDL receptor degradation. We determined relationships between plasma PCSK9 and Lp-PLA(2) mass.

Increased LCAT activity and hyperglycaemia decrease the antioxidative functionality of HDL.

Background: Type 2 diabetes mellitus increases the risk of atherosclerotic cardiovascular disease. Antioxidative properties of high density lipoprotein (HDL) are important for atheroprotection. This study investigated whether the antioxidative functionality of HDL is altered in type 2 diabetes mellitus and aimed to identify potential determinants of this parameter.

Lower serum paraoxonase-1 activity is related to higher serum amyloid a levels in metabolic syndrome.

Background And Aims: High-density lipoproteins (HDL) contain the anti-oxidative enzyme, paraoxonase-1 (PON-1), which is important for atheroprotection. The acute phase reactant, serum amyloid A (SAA), an HDL-associated apolipoprotein, may impair PON-1 activity, whereas SAA and PON-1 are reciprocally regulated in response to acute inflammatory stimuli. The relationship of serum PON-1 activity with SAA during low-grade chronic inflammation is unclear.

High plasma cholesteryl ester transfer but not CETP mass predicts incident cardiovascular disease: a nested case-control study.

Objective: The relationship of cardiovascular disease (CVD) with plasma cholesteryl ester transfer protein (CETP) levels is controversial. We determined whether plasma cholesteryl ester transfer (CET), reflecting CETP-mediated transfer of cholesteryl esters from endogenous HDL towards apolipoprotein B-lipoproteins, predicts incident CVD.

Methods: A prospective nested case-control study was carried out in 114 men who developed CVD and 105 controls.

Plasma phospholipid transfer protein activity is independently determined by obesity and insulin resistance in non-diabetic subjects.

Background: Phospholipid transfer protein (PLTP) is an emerging cardio-metabolic risk factor which is intricately involved in lipoprotein metabolism. Elevated plasma PLTP activity levels are reported in obesity and diabetes mellitus, but the relative contributions of obesity and insulin resistance to plasma PLTP activity remain unclear. We tested whether plasma PLTP activity is independently related to (central) obesity and insulin resistance in non-diabetic subjects.

Plasma proprotein convertase subtilisin-kexin type 9 does not change during 24h insulin infusion in healthy subjects and type 2 diabetic patients.

Purpose: Proprotein convertase subtilisin-kexin type 9 (PCSK9) promotes low density lipoprotein (LDL) receptor degradation, thereby providing a key pathway for LDL metabolism. PCSK9 mRNA expression may be upregulated by insulin in murine models. Here we examined effects of exogenous hyperinsulinemia on plasma PCSK9 levels in humans without and with type 2 diabetes mellitus.

Relationship of plasma apolipoprotein M with proprotein convertase subtilisin-kexin type 9 levels in non-diabetic subjects.

Purpose: Apolipoprotein M (apoM) retards atherosclerosis development in murine models, and may be regulated by pathways involved in LDL metabolism. Proprotein convertase subtilisin-kexin type 9 (PCSK9) plays a key role in LDL receptor processing. We determined the extent to which plasma apoM is related to PCSK9 levels in subjects with varying degrees of obesity.

Plasma apolipoprotein M responses to statin and fibrate administration in type 2 diabetes mellitus.

Purpose: Plasma apolipoprotein M (apoM) is potentially anti-atherogenic, and has been found to be associated positively with plasma total, LDL and HDL cholesterol in humans. ApoM may, therefore, be intricately related to cholesterol metabolism. Here, we determined whether plasma apoM is affected by statin or fibrate administration in patients with diabetes mellitus.

Cholesteryl ester transfer protein inhibition in cardiovascular risk management: ongoing trials will end the confusion.

As delineated in this review, cholesteryl ester transfer protein (CETP) contributes to an atherogenic lipoprotein profile by redistributing cholesteryl esters from high density lipoprotein (HDL) toward apolipoprotein B-containing lipoproteins, especially when the concentration of acceptor triglyceride-rich lipoproteins is elevated. However, this lipid transfer protein may have antiatherogenic proprerties as well. Experimental evidence is accumulating which suggests that the atheroprotective reverse cholesterol transport pathway, whereby cholesterol is removed from peripheral macrophages to the liver for metabolism and biliary excretion, is stimulated by CETP in vivo.

Carotid intima media thickness is associated with plasma adiponectin but not with the leptin:adiponectin ratio independently of metabolic syndrome.

Purpose: A recent report showed no benefit of the leptin:adiponectin ratio (L:A ratio) over individual adipokine levels in CHD prediction [8]. We determined associations of carotid intima media thickness (IMT) with the L:A ratio taking account of cardiovascular risk factors in a high risk population.

Methods: IMT, plasma leptin, adiponectin and the L:A ratio were determined in 161 middle-aged men and women (45% metabolic syndrome).

Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus: Relevance for non-HDL cholesterol and apolipoprotein B guideline targets.

The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein (apo) B. Changes in LDL size and RLP-C were determined in fasting plasma from type 2 diabetic patients after 30 weeks administration of atorvastatin (10 mg daily, n=65; 80 mg daily, n=62) or placebo (n=58).