Abstract
Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 g/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit.
Highlights
Dyslipidemias, the recognized risk factors for atherosclerotic cardiovascular disease (ASCVD) [13], are defined as an abnormal lipid profile including elevated triglycerides (TG), low-density lipoprotein (LDL) cholesterol (LDL-C), and low high-density lipoprotein (HDL) cholesterol (HDL-C)
A total of 1605 patients enrolled in the analysis, of which, 359 (22.4%) patients were hypertriglyceridemia, 250 (15.6%) were hypercholesterolemia, 312 (19.4%) were combined hyperlipidemia, 323 (20.1%) hypo HDL cholesterolemia, www.impactjournals.com/oncotarget
In the cohort of patients who were not taking a lipid-lowering drug before the first coronary angiography (CAG), we showed that lipid disorders were associated with multiple parameters of lipid and lipoproteins, and the novel lipid measurements such as proprotein convertase subtilisin/kexin type 9 (PCSK9), apoC3, and small dense low density lipoprotein cholesterol (sdLDL-C) seemed to play important roles
Summary
Dyslipidemias, the recognized risk factors for atherosclerotic cardiovascular disease (ASCVD) [13], are defined as an abnormal lipid profile including elevated triglycerides (TG), low-density lipoprotein (LDL) cholesterol (LDL-C), and low high-density lipoprotein (HDL) cholesterol (HDL-C). Other lipoprotein classes or lipid regulators, whose plasma levels can not be improved significantly or even be increased by statin treatment, play important roles in determining cardiovascular risk [4,5,6]. A wealth of information from biological or genetic researches on lipid metabolism has led to the identification of several markers, that may be targeted to improve lipid profiles and possible cardiovascular risk in patients with dyslipidemias.
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