The risk of cardiovascular events with increased apolipoprotein CIII: A systematic review and meta-analysis

Ballmoos, Moritz C. Wyler von; Haring, Bernhard; Sacks, Frank M.

doi:10.1016/j.jacl.2015.05.002

Cited by 113 publications

(92 citation statements)

References 48 publications

(161 reference statements)

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“…These triglyceriderich lipoproteins carry various atherogenic proteins such as apolipoprotein C-III, itself associated with atherosclerosis and CVD. 93 Replacing 1% of daily energy intake from saturated fat with polyunsaturated or monounsaturated fat lowers triglyceride by 0.9 or 0.4 mg/dL, respectively (Figure 5, left), 4 perhaps more in those with hypertriglyceridemia. 91 Replacing the 1% saturated fat with 1% carbohydrates raises serum triglycerides by ≈1 mg/dL.…”

Section: Triglyceridesmentioning

confidence: 99%

Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association

Sacks¹,

Lichtenstein²,

Wu³

et al. 2017

Circulation

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1,026

684

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Cardiovascular disease (CVD) is the leading global cause of death, accounting for 17.3 million deaths per year. Preventive treatment that reduces CVD by even a small percentage can substantially reduce, nationally and globally, the number of people who develop CVD and the costs of caring for them. This American Heart Association presidential advisory on dietary fats and CVD reviews and discusses the scientific evidence, including the most recent studies, on the effects of dietary saturated fat intake and its replacement by other types of fats and carbohydrates on CVD. In summary, randomized controlled trials that lowered intake of dietary saturated fat and replaced it with polyunsaturated vegetable oil reduced CVD by ≈30%, similar to the reduction achieved by statin treatment. Prospective observational studies in many populations showed that lower intake of saturated fat coupled with higher intake of polyunsaturated and monounsaturated fat is associated with lower rates of CVD and of other major causes of death and all-cause mortality. In contrast, replacement of saturated fat with mostly refined carbohydrates and sugars is not associated with lower rates of CVD and did not reduce CVD in clinical trials. Replacement of saturated with unsaturated fats lowers low-density lipoprotein cholesterol, a cause of atherosclerosis, linking biological evidence with incidence of CVD in populations and in clinical trials. Taking into consideration the totality of the scientific evidence, satisfying rigorous criteria for causality, we conclude strongly that lowering intake of saturated fat and replacing it with unsaturated fats, especially polyunsaturated fats, will lower the incidence of CVD. States died of heart disease, stroke, and other CVDs in 2014, translating to about 1 of every 3 deaths. The annual direct and indirect costs of these deaths total more than $316.1 billion, including health expenditures and lost productivity.1 Preventive treatment that reduces CVD by even a small percentage can substantially reduce, nationally and globally, the number of people who develop CVD and the costs of caring for them.Since 1961, the American Heart Association (AHA) has recommended reduction in dietary saturated fat to reduce the risk of CVD.2,3 The purpose of this AHA presidential advisory on dietary fats and CVD is to review and discuss the scientific evidence, including the most recent studies, on the effects on CVD of dietary saturated fat and its replacement by other types of fats and carbohydrates. A presidential advisory is initiated by the AHA president to address a topic of special current importance. This report discusses the major classes of dietary fatty acids, except for the verylong-chain n-3 fatty acids in fish, which are covered by other AHA reports.The scientific rationale for decreasing saturated fat in the diet has been and remains based on wellestablished effects of saturated fat to raise low-density lipoprotein (LDL) cholesterol, a leading cause of atherosclerosis 4 ; to cause atherosclerosis in seve...

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Section: Triglyceridesmentioning

confidence: 99%

Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association

Sacks¹,

Lichtenstein²,

Wu³

et al. 2017

Circulation

Self Cite

1,026

684

View full text Add to dashboard Cite

show abstract

“…Elevated plasma TG levels represent a risk factor for CVD in humans, and an adjusted analysis of patients in the Framingham Heart Study suggests that each decrease of 1 mg/dl in plasma ApoC-III levels is associated with a 4% decrease in CVD risk (11), further supporting the potential therapeutic benefit of suppressing plasma ApoC-III levels in humans to reduce CVD. A number of correlative studies showed a greater incidence of CVD in persons with ApoC-III-rich LDL (38). These correlations using ApoC-III associated with LDL are more complex, as it was also reported that increased ApoE content in LDL fractions with ApoC-III is associated with a lower risk of CVD (39).…”

Section: Discussionmentioning

confidence: 99%

ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors

Gordts¹,

Nock²,

Son³

et al. 2016

Journal of Clinical Investigation

214

210

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“…FCS patients, in particular, have the highest triglyceride levels among patients with hypertriglyceridemia and have frequent episodes of acute pancreatitis, which can be fatal, as well as long-term complications such as pancreatic insuffi ciency and diabetes mellitus ( 25 ). Elevated apoC-III levels and triglycerides are independent risk factors for CVD ( 5,11 ). Recent genetic data has strongly suggested that apoC-III is a causal mediator of CVD ( 12,13 ).…”

Section: Downloaded Frommentioning

confidence: 99%

Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results

Yang

Lee

Choi

et al. 2016

Journal of Lipid Research

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ApoC-III is a 79 amino acid glycoprotein synthesized principally in the liver and associated with apoB-containing lipoproteins and HDL ( 1 ). apoC-III plays a key role in determining serum triglyceride levels and is a potent inhibitor of both the LPL-dependent and -independent pathways of triglyceride-rich lipoprotein (TRL) clearance. Thus, apoC-III inhibits the apoC-II-mediated activation of LPL and also inhibits hepatic lipase that plays an important role in the conversion of dense VLDL to IDL. Furthermore, apoC-III also inhibits TRL clearance by inhibiting receptor-mediated uptake of TRL by the liver ( 2 ).Recent work has shown that the CVD risk of circulating plasma apoC-III is not uniform, but rather dependent on its association with specifi c lipoproteins ( 3-5 ). This suggests that the effect of both LDL and HDL on CVD risk is context-dependent on the presence or absence of apoC-III. However, current methods to detect apoC-III on LDL or HDL utilize labor-intensive immunoprecipitation of apoC-III and/or ultracentrifugation methods that can only be Abstract Elevated apoC-III levels predict increased cardiovascular risk when present on LDL and HDL particles. We developed novel high-throughput chemiluminescent ELISAs that capture apoB, lipoprotein (a) [Lp(a)], and apoA-I in plasma and then detect apoC-III on these individual lipoproteins as apoCIII-apoB, apoCIII-Lp(a), and apoCIIIapoAI complexes, respectively. We assessed the effects on these complexes of placebo or 100-300 mg volanesorsen, a generation 2.0+ antisense drug that targets apoC3 mRNA in patients with hypertriglyceridemia, including familial chylomicronemia syndrome (n = 3), volanesorsen monotherapy (n = 51), and as add-on to fi brate (n = 26), treated for 85 days and followed for 176 days. Compared with placebo, volanesorsen was associated with an 82.3 ± 11.7%, 81.3 ± 15.7%, and 80.8 ± 13.6% reduction in apoCIII-apoB, apo-CIII-Lp(a), and apoCIII-apoA-I, respectively (300 mg dose; P < 0.001 for all), at day 92. Strong correlations in all assay measures were noted with total plasma apoC-III, chylomicron-apoC-III, and VLDL-apoC-III. In conclusion, novel high-throughput ELISAs were developed to detect lipoprotein-associated apoC-III, including for the fi rst time on Lp(a). Volanesorsen uniformly lowers apoC-III on apoB-100, Lp(a), and apoA-I lipoproteins, and may be a potent agent to reduce triglycerides and cardiovascular risk mediated by apoC-III.

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The risk of cardiovascular events with increased apolipoprotein CIII: A systematic review and meta-analysis

Cited by 113 publications

References 48 publications

Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association

Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association

ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors

Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results

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