Elevated cumulative remnant cholesterol exposure is associated with an increased risk of cardiometabolic multimorbidity, and discordantly high RC, not discordantly high LDL-C, is significantly associated with CMM onset among Chinese adults.
Key Findings
Results
Higher cumulative remnant cholesterol (CumRC) levels were associated with an increased risk of cardiometabolic multimorbidity (CMM) over a 7-year follow-up period.
5,867 participants without CMM were recruited from the China Health and Retirement Longitudinal Study (CHARLS) 2011 and followed up in 2018.
Over the 7-year follow-up period, 435 participants (approximately 7.4%) developed CMM.
Comparing the extreme quartiles of CumRC, the hazard ratio (HR) for CMM was 1.77 (95% CI: 1.31–2.40).
After adjusting for traditional risk factors, each 10 mg/dL increase in CumRC was associated with a 3% higher risk of CMM (HR: 1.03, 95% CI = 1.01–1.04).
CumRC was calculated as the average of RC values measured during waves 1 and 3, divided by the total exposure duration.
Results
Discordantly high RC (relative to LDL-C) was associated with a significantly higher risk of CMM compared to the discordantly high LDL-C group.
Discordance between RC and LDL-C was defined as a difference of more than 15 percentile units.
The discordantly high RC group showed a higher risk of CMM (HR: 1.31, 95% CI = 1.04–1.64) compared to those with higher LDL-C.
This association held even among individuals with well-controlled LDL-C levels.
Discordantly high LDL-C was not significantly associated with CMM onset.
Results
The association between CumRC and CMM risk remained robust across various sensitivity and subgroup analyses.
Cox proportional hazards models were used as the primary analytical approach.
Subgroup analyses and sensitivity analyses were conducted to evaluate the robustness of associations.
Results were consistent across different subgroups and analytical approaches.
The study population consisted of Chinese adults from the China Health and Retirement Longitudinal Study.
Methods
The study investigated cumulative RC exposure rather than a single time-point measurement to assess long-term lipid burden.
CumRC was calculated using RC values from wave 1 (2011) and wave 3, divided by total exposure duration.
This cumulative approach was intended to capture long-term remnant cholesterol exposure rather than a snapshot measurement.
RC and LDL-C are noted to have distinct roles in cardiovascular disease risk.
The study population included 5,867 participants free of CMM at baseline.
Background
RC and LDL-C were recognized as having distinct roles in cardiovascular disease risk, with their combined influence on cardiometabolic outcomes previously insufficiently studied.
The study was motivated by a gap in understanding the combined influence of RC and LDL-C on cardiometabolic outcomes.
The discordance analysis was designed to disentangle the independent contributions of RC versus LDL-C to CMM risk.
The study context was a Chinese middle-aged and older adult population from CHARLS.
CMM was defined as the co-occurrence of multiple cardiometabolic conditions.
What This Means
This research suggests that having persistently high levels of 'remnant cholesterol' (RC) — a type of cholesterol carried in triglyceride-rich lipoproteins — is linked to a significantly greater chance of developing multiple heart and metabolic diseases simultaneously (called cardiometabolic multimorbidity, or CMM) over a 7-year period in Chinese adults. Specifically, people in the highest quarter of cumulative RC exposure were 77% more likely to develop CMM than those in the lowest quarter, and every 10 mg/dL increase in cumulative RC was associated with a 3% higher risk even after accounting for other known risk factors.
A particularly notable finding is what happened when RC and LDL-C (the traditional 'bad cholesterol') levels did not move together — a situation called 'discordance.' When someone had relatively high RC but lower LDL-C, their CMM risk was 31% higher than those with the opposite pattern (high LDL-C, lower RC). Importantly, this elevated risk from high RC was present even in people whose LDL-C levels were considered well-controlled, suggesting that RC carries cardiovascular risk independently of LDL-C.
This research suggests that relying solely on LDL-C as a marker of cardiovascular and metabolic risk may miss important information provided by RC levels. Monitoring and managing remnant cholesterol — not just LDL-C — could be important for identifying people at higher risk of developing multiple cardiometabolic diseases, particularly in older Chinese populations. These findings highlight the potential value of measuring RC in clinical assessments of cardiometabolic risk.
Rong L, Fan H, Fang Q, Li X, Tan J, Huang J. (2026). Discordance between remnant cholesterol and LDL-C associated with the risk of new-onset cardiometabolic multimorbidity: A prospective cohort study.. Medicine. https://doi.org/10.1097/MD.0000000000049157