Background and Aims: Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of mortality worldwide, with lipid abnormalities playing a central role in disease development. While the causal role of low-density lipoprotein cholesterol (LDL-C) in ASCVD is well-established, the long-term population impact of combined lipid profiles, particularly the HDL-C/LDL-C ratio, remains less clearly quantified. This study aimed to estimate the lifetime burden of cardiovascular outcomes associated with different lipid risk profiles using a patient-level simulation framework. Methods: The authors analyzed projected lifetime ASCVD events across four HDL-C/LDL-C risk strata, ranging from low (≥0.45) to very high ( 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: MI events rose from 5000 to 73,090 per 100,000 births, with onset in the highest risk group occurring as early as age 20. Ischaemic heart disease followed a similar pattern, showing up to 92% of events attributable to elevated lipid risk. While ischaemic stroke risk displayed a more complex pattern due to earlier MI mortality in high-risk groups, overall cardiovascular mortality and lifetime event burden were dominated by LDL-driven disease. These findings demonstrate that sustained LDL-C reduction and balanced HDL-C/LDL-C ratios confer substantial survival benefits across both sexes and all age groups. Conclusions: This study shows that lipid balance has a decisive influence on cardiovascular survival. Sustained LDL-C reduction and favourable HDL-C/LDL-C ratios markedly extend life expectancy and delay the onset of MI and IHD. The magnitude of this survival benefit highlights the need for early and continuous lipid control as a cornerstone of ASCVD prevention. The NHM quantifies these lifetime effects, offering valuable insights for targeted strategies that improve both longevity and quality of life.
Parker et al. (Sun,) studied this question.