Low-density lipoprotein cholesterol (LDL-C) is an independent risk factor for coronary heart disease.1,2 A confluence of epidemiological, genetic, and clinical intervention research underscores that elevated LDL-C concentrations precipitate atherosclerotic cardiovascular incidents (ASCVD).3 Prior research posits that a reduction of 1 mmol/L in LDL-C corresponds to a 25 % diminution in major cardiovascular occurrences.4 Yet, certain investigations highlight that even with diminished LDL-C concentrations, there persists a tangible cardiovascular disease risk, potentially attributable to remnant cholesterol (RC).5, 6, 7 A Mendelian randomization study discerned a staggering 2.8-fold surge in ischemic heart disease (IHD) risk with every 1 mmol/l augmentation in RC, suggesting that escalated RC concentrations are instrumental in IHD onset.8 Furthermore, a plethora of research consistently indicates that heightened RC levels correlate with an amplified risk of cardiovascular diseases.6,9, 10, 11, 12 A 2021 cohort analysis revealed that within the broader populace, RC concentrations were intrinsically linked to ASCVD, independent of the conventional cardiovascular risk markers like LDL-C, non-HDL-C, or apoB concentrations.13

While prior research has delved into the correlation between RC levels and IHD, the emphasis has predominantly been on singular RC measurements. Such isolated measurements can be skewed by a myriad of variables, including age, lifestyle, and medicinal interventions, rendering them inadequate in capturing the enduring influence of RC levels on IHD. Several studies have adopted a more comprehensive approach, gauging the nexus between diseases and risk factors via recurrent long-term risk factor assessments. For instance, cumulative hyperlipidemia exposure during adolescence has been shown to proportionally escalate the likelihood of subsequent cardiovascular incidents.14 The 2020 CARDIA study discerned that cardiovascular event risks are contingent upon cumulative LDL-C exposure.15 Following this, a 2021 prospective cohort study ascertained that elevated cumulative LDL-C exposure during one's youth and midlife phases correlates with a heightened propensity for coronary heart disease onset.16 Yet, both national and international research spheres exhibit a conspicuous void in studies employing repeated RC level measurements to elucidate the long-term RC exposure's relationship with IHD. The Kailuan study stands out, having meticulously tracked and amassed extended multi-lipid data from participants through recurrent long-term follow-ups, thereby securing multiple RC level readings over time. Consequently, this research leveraged a prospective cohort methodology to probe the ramifications of cumulative remnant cholesterol (cumRC) exposure on IHD within the Kailuan Study cohort.