The Complex Relationship Between HDL/LDL Cholesterol, Stroke and Cardiovascular Disease

Area of Science:

• Cardiology
• Public Health
• Epidemiology

Background:

• Atherosclerotic cardiovascular disease (ASCVD) is a leading global cause of mortality, with lipid abnormalities being central to its development.
• The impact of combined lipid profiles, particularly the HDL-C/LDL-C ratio, on long-term population health outcomes requires further quantification.

Purpose of the Study:

• To estimate the lifetime burden of cardiovascular outcomes associated with various lipid risk profiles.
• To utilize a patient-level simulation framework for projecting individual health trajectories and quantifying ASCVD impact.

Main Methods:

• Analysis of projected lifetime ASCVD events across four HDL-C/LDL-C risk strata (low to very high).
• Utilized the National Health Model Database of Projected and Estimated Outcomes (NHM-DPEO), a digital twin of national healthcare systems.
• Employed a patient-level simulation model projecting individual health trajectories over a lifetime horizon.

Main Results:

• A strong, graded relationship was observed between lipid profiles and cardiovascular survival, with life expectancy declining by up to 17.2 years in the very-high-risk group (HDL-C/LDL-C < 0.25).
• Participants with LDL-C > 5.0 mmol/L had a life expectancy 13.4 years shorter than those with LDL-C < 3.1 mmol/L.
• The burden of ASCVD increased exponentially with worsening lipid ratios, with MI events rising significantly and onset occurring as early as age 20 in the highest-risk group.

Conclusions:

• Lipid balance decisively influences cardiovascular survival, with sustained LDL-C reduction and favorable HDL-C/LDL-C ratios markedly extending life expectancy.
• Early and continuous lipid control is crucial for ASCVD prevention, offering substantial survival benefits across all demographics.
• The NHM framework provides valuable insights for targeted strategies to improve longevity and quality of life by quantifying lifetime effects of lipid management.