Remnant-Like Particle Cholesterol, Low-Density Lipoprotein Triglycerides, and Incident Cardiovascular Disease

Saeed, Anum; Feofanova, Elena V.; Yu, Bing; Sun, Wei; Virani, Salim S.; Nambi, Vijay; Coresh, Josef; Guild, Cameron; Boerwinkle, Eric; Ballantyne, Christie M.; Hoogeveen, Ron C.

doi:10.1016/j.jacc.2018.04.050

Cited by 141 publications

(113 citation statements)

References 51 publications

(52 reference statements)

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“…Diabetic dyslipidaemia is characterized by hypertriglyceridaemia and accumulation of remnant particles, and apoC‐III may aggravate the hypertriglyceridaemia by impairing the lipolysis of triglyceride‐rich lipoproteins. In addition, our results indicate that apoC‐III also affects the removal of remnant particles, resulting in an accumulation of atherogenic remnant particles . This may explain the improved postprandial lipemia and robust reduction of surrogate markers of remnant particles during liraglutide therapy.…”

Section: Discussionmentioning

confidence: 64%

Role of apolipoprotein C‐III overproduction in diabetic dyslipidaemia

Adiels

Taskinen

Andersson

et al. 2019

Diabetes Obesity Metabolism

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Aims: To investigate how apolipoprotein C-III (apoC-III) metabolism is altered in subjects with type 2 diabetes, whether the perturbed plasma triglyceride concentrations in this condition are determined primarily by the secretion rate or the removal rate of apoC-III, and whether improvement of glycaemic control using the glucagon-like peptide-1 analogue liraglutide for 16 weeks modifies apoC-III dynamics.Materials and Methods: Postprandial apoC-III kinetics were assessed after a bolus injection of [5,5,5-2 H 3 ]leucine using ultrasensitive mass spectrometry techniques.We compared apoC-III kinetics in two situations: in subjects with type 2 diabetes before and after liraglutide therapy, and in type 2 diabetic subjects with matched body mass index (BMI) non-diabetic subjects. Liver fat content, subcutaneous abdominal and intra-abdominal fat were determined using proton magnetic resonance spectroscopy.Results: Improved glycaemic control by liraglutide therapy for 16 weeks significantly reduced apoC-III secretion rate (561 ± 198 vs. 652 ± 196 mg/d, P = 0.03) and apoC-III levels (10.0 ± 3.8 vs. 11.7 ± 4.3 mg/dL, P = 0.035) in subjects with type 2 diabetes.Change in apoC-III secretion rate was significantly associated with the improvement in indices of glucose control (r = 0.67; P = 0.009) and change in triglyceride area under the curve (r = 0.59; P = 0.025). In line with this, the apoC-III secretion rate was higher in subjects with type 2 diabetes compared with BMI-matched non-diabetic subjects (676 ± 208 vs. 505 ± 174 mg/d, P = 0.042). Conclusions:The results reveal that the secretion rate of apoC-III is associated with elevation of triglyceride-rich lipoproteins in subjects with type 2 diabetes, potentially through the influence of glucose homeostasis on the production of apoC-III.

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Section: Discussionmentioning

confidence: 64%

Role of apolipoprotein C‐III overproduction in diabetic dyslipidaemia

Adiels

Taskinen

Andersson

et al. 2019

Diabetes Obesity Metabolism

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“…These authors have concluded that LDL-TG may represent a marker of dysfunctional remnant lipoprotein metabolism associated with increased CVD risk. 62) …”

Section: Why Are Elevated Triglyceride-rich Lipoproteins a Risk Factomentioning

confidence: 99%

Triglyceride-Rich Lipoproteins and Novel Targets for Anti-atherosclerotic Therapy

Reiner

2018

Korean Circ J

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Although elevated serum low-density lipoprotein-cholesterol (LDL-C) is without any doubts accepted as an important risk factor for cardiovascular disease (CVD), the role of elevated triglycerides (TGs)-rich lipoproteins as an independent risk factor has until recently been quite controversial. Recent data strongly suggest that elevated TG-rich lipoproteins are an independent risk factor for CVD and that therapeutic targeting of them could possibly provide further benefit in reducing CVD morbidity, events and mortality, apart from LDL-C lowering. Today elevated TGs are treated with lifestyle interventions, and with fibrates which could be combined with omega-3 fatty acids. There are also some new drugs. Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha modulator which also decreases TGs, and improves other lipid parameters. It seems that it also has some other possible antiatherogenic effects. Alipogene tiparvovec is a nonreplicating adeno-associated viral vector that delivers copies of the LPL gene to muscle tissue which accelerates the clearance of TG-rich lipoproteins thus decreasing extremely high TGs levels. Pradigastat is a novel diacylglycerol acyltransferase 1 inhibitor which substantially reduces extremely high TGs levels and appears to be promising in treatment of the rare familial chylomicronemia syndrome.

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“…sdLDL-C is a distinct LDL-C subclass, which is associated with raised TG and decreased HDL-C levels in adiposity and diabetes, playing a distinct metabolic role in atherosclerosis [15][16][17][18]. In this study including patients with T2DM, we found that there was an independent association between sdLDL-C and CHD.…”

Section: Discussionmentioning

confidence: 49%

The Value of Small Dense Low-Density Lipoprotein Cholesterol in Predicting the Risk and Severity of Coronary Heart Disease in Patients with Type 2 Diabetes Mellitus

Huang

Bao

et al. 2020

Preprint

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Background: Elevated small density low – density lipoprotein cholesterol (sdLDL-C) particles are hallmarks of atherogenic dyslipidemia in patients with type 2 diabetes mellitus (T2DM), which is hypothesized to drive atherosclerotic risk. The present study aims to investigate the association between serum sdLDL-C level and the presence and severity of coronary heart disease (CHD). Method: A total of 3684 consecutive patients with T2DM who received selective coronary angiography (CAG) were enrolled. The patients were subsequently divided into CHD and non-CHD groups according to results of CAG. The severity of CHD was evaluated by the number of stenotic, and the Gensini Score (GS).The patients were subsequently divided into four groups by the quartiles of sdLDL-C and evaluate the risk and severity of sdLDL-C and CHD.Results: The sdLDL-C levels in CHD group were significantly higher than non-CHD group [0.80 (0.49) mmol/L vs 0.70 (0.30) mmol/L, P < 0.001]. The results from CHD subgroup analysis indicated that the patients with multiple-vessel disease and high GS had higher sdLDL-C levels compared with those in their matched subgroups (P < 0.05). By adjusting the confounding factors and analyzing by the multiple logistic regression, sdLDL-C had independent correlation with the presence and severity of CHD [CHD: OR = 2.757, 95%, CI = 1.662 - 5.364, P = 0.023; multiple-vessel disease: OR = 3.788, 95%, CI = 1.866 - 7.685, P = 0.026; High GS: OR = 3.054, 95%, CI = 1.944 - 5.699, P = 0.022].Conclusion: In T2DM patients, the increase of sdLDL-C is related to the increase the prevalence and the severity of CHD. After adjustment for other risk factors, sdLDL-C was found to be an independent risk factor for CHD. Therefore, measuring sdLDL-C may allow for T2DM patients to predict the presence and severity of CHD.

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Remnant-Like Particle Cholesterol, Low-Density Lipoprotein Triglycerides, and Incident Cardiovascular Disease

Cited by 141 publications

References 51 publications

Role of apolipoprotein C‐III overproduction in diabetic dyslipidaemia

Role of apolipoprotein C‐III overproduction in diabetic dyslipidaemia

Triglyceride-Rich Lipoproteins and Novel Targets for Anti-atherosclerotic Therapy

The Value of Small Dense Low-Density Lipoprotein Cholesterol in Predicting the Risk and Severity of Coronary Heart Disease in Patients with Type 2 Diabetes Mellitus

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