Refining the Atherogenic Lipoprotein Model of Cardiovascular Disease  

ApoB Particles Take Center Stage

There is now overwhelming evidence that atherosclerotic cardiovascular disease is driven primarily by atherogenic lipoproteins containing apolipoprotein B (ApoB). ApoB is the main structural protein enveloping lipid molecules to form lipoproteins that traffic cholesterol and other hydrophobic substances through circulation.

As contemporary cardiovascular guidelines have embraced, it is the penetration of ApoB particles into arterial walls that allows for retention and chemical modification of sterols contained within them, inciting an inflammatory response. Higher ApoB concentrations equate to greater lipoprotein particle numbers, which proportionally increase the probability of instigating atherogenesis.

Advantages of ApoB Measurement by Immunoassay

While LDL particle number (LDL-P) is another indicator of atherogenicity, ApoB offers consistency across laboratories and assays, availability at low cost, and alignment with major society guidelines. Clinicians should order ApoB on every lipid panel and track serially over time.

Looking Beyond LDL: Emerging Importance of Triglycerides and Lp(a)

Though LDL particles comprise the majority of ApoB lipoproteins by virtue of their days-long circulation time, research now suggests other ApoB-containing particles influence atherosclerotic potential as well. In particular, triglyceride content and lipoprotein(a) (Lp(a)) are gaining increasing attention.

Higher triglycerides appear to impart greater atherogenicity to all ApoB particles. Additionally, genetically determined elevations in Lp(a) contribute significantly to cardiovascular risk through mechanisms that are not fully LDL-mediated. quantify non-HDL cholesterol.

Limitations of LDL Cholesterol and HDL Cholesterol Metrics

While LDL cholesterol and non-HDL cholesterol are still commonly used in guidelines, they do not reliably reflect true ApoB particle number. Similarly, HDL cholesterol is progressively being recognized as less informative for risk stratification and decision-making.

Intensifying Lipid Therapies

Beyond statins, additional therapies for ApoB particle reduction continue to emerge, including PCSK9 inhibitors, omega-3 fatty acids, and new agents like bempedoic acid. The importance of treatment intensity has also become clearer, given atherosclerosis is a lifelong process requiring continually suppressed lipoprotein particle traffic.

Key Takeaways

• Atherogenic lipoproteins are undisputedly the primary pathway driving atherosclerotic cardiovascular disease.
• ApoB particle number measured by immunoassay surpasses LDL cholesterol and LDL-P for CVD risk assessment.
• Other lipoprotein attributes like triglycerides and Lp(a) also modulate atherosclerotic potential.
• Maximally reducing ApoB particle number should be the goal of therapy.