Triglycerides and heart disease: still a hypothesis?

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Atherosclerosis Research

Background:

• Plasma triglyceride metabolism, transport, and uptake are well-understood.
• The precise relationship between plasma triglyceride levels and cardiovascular disease (CVD) is not definitively established.
• Existing research presents conflicting evidence regarding the direct role of triglycerides in vascular disease.

Purpose of the Study:

• To review the basic and clinical science linking plasma triglycerides to cardiovascular disease.
• To critically evaluate the evidence implicating triglyceride-rich lipoproteins and metabolic defects in CVD.
• To highlight the limitations of current research and advocate for novel approaches.

Main Methods:

• Literature review of basic physiology, animal models, in vitro studies, correlative studies, genetic associations, and human intervention trials.
• Analysis of the influence of triglyceride-rich lipoproteins on other lipoproteins (HDL, LDL).
• Examination of genetic factors regulating triglyceride levels and their association with vascular disease.

Main Results:

• Animal models have primarily shown early fatty lesions, not advanced atherosclerosis, from triglyceride-rich lipoproteins.
• In vitro studies suggest metabolic products of triglyceride metabolism can be toxic to arterial cells.
• Correlative and genetic studies implicate remnant lipoproteins in atherosclerosis, but confounding factors obscure direct triglyceride links.

Conclusions:

• The direct causal role of plasma triglycerides in cardiovascular disease remains uncertain.
• Confounding factors in existing studies, including alterations in other lipoproteins and risk factors, limit definitive conclusions.
• New and innovative research strategies are essential to clarify the relationship between triglycerides and heart disease.