Lowering triglycerides
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Lowering Triglycerides: Insights from Recent Research
Introduction to Triglyceride Lowering
High triglyceride levels are a known risk factor for cardiovascular diseases (CVD). Various therapeutic strategies have been explored to lower triglycerides and potentially reduce cardiovascular risk. This article synthesizes findings from recent studies on the effectiveness of different triglyceride-lowering interventions.
Pemafibrate and Cardiovascular Risk Reduction
Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, has shown significant triglyceride-lowering effects. In a large-scale study involving patients with type 2 diabetes and hypertriglyceridemia, pemafibrate reduced triglyceride levels by 26.2% compared to placebo. However, this reduction did not translate into a significant decrease in cardiovascular events, suggesting that lowering triglycerides alone may not be sufficient to reduce cardiovascular risk in this population1.
Systematic Review of Lipid-Lowering Therapies
A comprehensive meta-regression analysis examined the impact of various lipid-lowering therapies, including fibrates, niacin, and omega-3 fatty acids, on cardiovascular events. The study found that while triglyceride reduction was associated with a lower risk of major vascular events, the effect was modest and less pronounced when the influential REDUCE-IT trial was excluded. This indicates that the benefits of triglyceride-lowering therapies may vary depending on the specific agent and patient population2.
Probiotics and Triglyceride Reduction
Probiotic supplementation with Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 has been shown to significantly lower triglyceride levels. In a 12-week study, participants who consumed these probiotics experienced a 20% reduction in serum triglycerides. The mechanism appears to involve increased levels of apolipoprotein A-V and changes in plasma metabolites, suggesting a potential role for probiotics in managing hypertriglyceridemia3 8.
Omega-3 Fatty Acids and Long-Term Effects
Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA), have demonstrated triglyceride-lowering effects. In a study involving patients with coronary heart disease and hypertriglyceridemia, a high-dose omega-3 concentrate (Omacor) reduced triglycerides by 20-30% over one year. This reduction was accompanied by a decrease in very low-density lipoprotein (VLDL) cholesterol, without adverse effects on other lipid parameters or glycemic control5.
Mechanistic Insights from Animal Models
Research using the Zucker obese rat model has provided insights into the mechanisms of triglyceride reduction by HMG-CoA reductase inhibitors like lovastatin. The study found that lovastatin significantly lowered plasma triglycerides by reducing hepatic secretion of VLDL. This effect was partially reversible with mevalonolactone supplementation, highlighting the role of hepatic pathways in triglyceride metabolism4.
ANGPTL3 Inhibition and Lipid Profile Improvement
Vupanorsen, an antisense oligonucleotide targeting ANGPTL3, has shown promise in reducing triglycerides and other atherogenic lipoproteins. In a phase 2 study, vupanorsen significantly lowered triglycerides by up to 53% and improved the overall lipid profile in patients with diabetes and hypertriglyceridemia. These findings suggest that targeting ANGPTL3 could be a viable strategy for managing residual cardiovascular risk7.
Conclusion
While various therapies effectively lower triglyceride levels, their impact on reducing cardiovascular events remains inconsistent. The evidence suggests that triglyceride reduction alone may not be sufficient to significantly lower cardiovascular risk. Future research should focus on understanding the complex interactions between different lipid parameters and cardiovascular outcomes to develop more effective treatment strategies.
Sources and full results
Most relevant research papers on this topic
Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.
Pemafibrate effectively lowers triglyceride levels in patients with type 2 diabetes and low HDL and LDL cholesterol levels, but its impact on cardiovascular events remains unclear.
RCT
Large Human Trial
Rigorous Journal
Highly CitedAssociation Between Triglyceride Lowering and Reduction of Cardiovascular Risk Across Multiple Lipid-Lowering Therapeutic Classes: A Systematic Review and Meta-Regression Analysis of Randomized Controlled Trials.
In randomized controlled trials, triglyceride lowering is associated with lower risk of major vascular events, even after adjusting for LDL-C lowering.
Meta-Analysis
Very Rigorous JournalHighly CitedThe triglyceride-lowering effect of supplementation with dual probiotic strains, Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032: Reduction of fasting plasma lysophosphatidylcholines in nondiabetic and hypertriglyceridemic subjects.
Probiotic supplementation with Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032 reduces triglyceride levels and increases apolipoprotein A-V in borderline to moderate hypertriglyceridemic individuals.
RCTMechanisms of triglyceride-lowering effect of an HMG-CoA reductase inhibitor in a hypertriglyceridemic animal model, the Zucker obese rat.
Lovastatin reduces triglyceride levels in the hypertriglyceridemic Zucker rat model by decreasing the rate of secretion of very low density lipoproteins, which can be partially reversed by mevalonolactone.
RCT
Animal StudyHighly CitedAn omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia
Omacor is a safe and effective method to lower triglycerides in patients with coronary heart disease and combined hyperlipidaemia, despite simvastatin treatment.
RCTHighly CitedMechanistic Insights from REDUCE-IT STRENGTHen the Case Against Triglyceride Lowering as a Strategy for Cardiovascular Disease Risk Reduction.
Triglyceride lowering alone is ineffective in reducing cardiovascular risk, but icosapent ethyl may help by reducing cardiovascular events in high-risk patients.
Vupanorsen, an N-acetyl galactosamine-conjugated antisense drug to ANGPTL3 mRNA, lowers triglycerides and atherogenic lipoproteins in patients with diabetes, hepatic steatosis, and hypertriglyceridaemia
Vupanorsen effectively lowers triglycerides and atherogenic lipoproteins in patients with diabetes, hepatic steatosis, and hypertriglyceridaemia, potentially reducing residual cardiovascular risk.
RCTRigorous JournalHighly CitedTriglyceride-Lowering Effects of Two Probiotics, Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601, in a Rat Model of High-Fat Diet-Induced Hypertriglyceridemia.
Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 effectively lower triglycerides in hypertriglyceridemic rats by upregulating ApoA-V, PPAR, and FXR.
RCTAnimal StudyRationale and design of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) study
Pemafibrate may reduce cardiovascular events in individuals with type 2 diabetes mellitus by lowering triglycerides.
RCTLarge Human TrialRigorous JournalHighly CitedDo triglyceride-lowering drugs decrease risk of cardiovascular disease?
Lowering triglycerides and TG-rich lipoprotein cholesterol levels may reduce atherosclerotic cardiovascular disease risk.
Literature Review