Cumulative Atherogenic Index of Plasma Burden and Risk of Non-Fatal Myocardial Infarction and Ischemic Stroke Beyond Cumulative Low-Density Lipoprotein Cholesterol Burden.

BACKGROUND: A higher atherogenic index of plasma (AIP; calculated as log10[triglycerides/high-density lipoprotein cholesterol]) is an indicator of atherogenic dyslipidemia. Whether the cumulative AIP (cAIP) burden provides prognostic information beyond the cumulative low-density lipoprotein cholesterol (cLDL-C) burden remains unclear. METHODS AND RESULTS: This retrospective study analyzed data for 11,402 adults with at least 3 health checkups. cAIP and cLDL-C burdens were calculated from the first 3 lipid-complete visits, with the third visit defined as the index date. The primary outcome was first non-fatal myocardial infarction (MI) or ischemic stroke. Cox models were adjusted for conventional cardiovascular risk factors and cLDL-C burden. Over a mean follow-up of 4.96 years, 435 primary events occurred. Per 1-SD increase, cAIP burden was independently associated with the primary outcome after full adjustment including cLDL-C burden (hazard ratio 1.14; 95% confidence interval 1.02-1.27). Restricted cubic splines showed a progressive increase in risk with higher AIP burden. In discordance analysis, low cLDL-C/high cAIP burden, but not high cLDL-C/low cAIP burden, was associated with a higher risk than low cLDL-C/low cAIP burden (hazard ratio 1.40; 95% confidence interval 1.04-1.89). The addition of AIP burden did not improve global discrimination or reclassification. CONCLUSIONS: cAIP burden was associated with incident non-fatal MI or ischemic stroke and identified excess risk despite low cLDL-C burden, supporting its complementary value for characterizing residual lipid-related risk.