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Hypertriglyceridemia and Cardiovascular Diseases: Revisited.

ABSTRACT: Residual cardiovascular risk and failure of high density lipoprotein cholesterol raising treatment have refocused interest on targeting hypertriglyceridemia. Hypertriglyceridemia, triglyceride-rich lipoproteins, and remnant cholesterol have demonstrated to be important risk factors for cardiovascular disease; this has been demonstrated in experimental, genetic, and epidemiological studies. Fibrates can reduce cardiovascular event rates with or without statins. High dose omega-3 fatty acids continue to be evaluated and new specialized targeting treatment modulating triglyceride pathways, such as inhibition of apolipoprotein C-III and angiopoietin-like proteins, are being tested with regard to their effects on lipid profiles and cardiovascular outcomes. In this review, we will discuss the role of hypertriglyceridemia, triglyceride-rich lipoproteins and remnant cholesterol on cardiovascular disease, and the potential implications for treatment stargeting hypertriglyceridemia.

SUBMITTER: Han SH

PROVIDER: S-EPMC4805556 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Hypertriglyceridemia and Cardiovascular Diseases: Revisited.

Han Seung Hwan SH Nicholls Stephen J SJ Sakuma Ichiro I Zhao Dong D Koh Kwang Kon KK

Korean circulation journal 20160321 2

Residual cardiovascular risk and failure of high density lipoprotein cholesterol raising treatment have refocused interest on targeting hypertriglyceridemia. Hypertriglyceridemia, triglyceride-rich lipoproteins, and remnant cholesterol have demonstrated to be important risk factors for cardiovascular disease; this has been demonstrated in experimental, genetic, and epidemiological studies. Fibrates can reduce cardiovascular event rates with or without statins. High dose omega-3 fatty acids conti ...[more]

PMID: 27014342

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Project description:Genetic variants in the genomic region containing SORT1 (encoding the protein sortilin) are strongly associated with cholesterol levels and the risk of coronary artery disease (CAD). Circulating sortilin has therefore been proposed as a potential biomarker for cardiovascular disease. Multiple studies have reported association between plasma sortilin levels and cardiovascular outcomes. However, the findings are not consistent across studies, and most studies have small sample sizes. The aim of this study was to evaluate sortilin as a biomarker for CAD in a well-characterized cohort with symptoms suggestive of CAD. In total, we enrolled 1,173 patients with suspected stable CAD referred to coronary computed tomography angiography. Sortilin was measured in plasma using two different technologies for quantifying circulating sortilin: a custom-made enzyme-linked immunosorbent assay (ELISA) and OLINK Cardiovascular Panel II. We found a relative poor correlation between the two methods (correlation coefficient = 0.21). In addition, genotyping and whole-genome sequencing were performed on all patients. By whole-genome regression analysis of sortilin levels measured with ELISA and OLINK, two independent cis protein quantitative trait loci (pQTL) on chromosome 1p13.3 were identified, with one of them being a well-established risk locus for CAD. Incorporating rare genetic variants from whole-genome sequence data did not identify any additional pQTLs for plasma sortilin. None of the traditional CAD risk factors, such as sex, age, smoking, and statin use, were associated with plasma sortilin levels. Furthermore, there was no association between circulating sortilin levels and coronary artery calcium score (CACS) or disease severity. Sortilin did not improve discrimination of obstructive CAD, when added to a clinical pretest probability (PTP) model for CAD. Overall, our results indicate that studies using different methodologies for measuring circulating sortilin should be compared with caution. In conclusion, the well-known SORT1 risk locus for CAD is linked to lower sortilin levels in circulation, measured with ELISA; however, the effect sizes are too small for sortilin to be a useful biomarker for CAD in a clinical setting of low- to intermediate-risk chest-pain patients.

Dataset Information

Hypertriglyceridemia and Cardiovascular Diseases: Revisited.

Publications

Hypertriglyceridemia and Cardiovascular Diseases: Revisited.

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