Remnant Cholesterol and Its Visit-to-Visit Variability Predict Cardiovascular Outcomes in Patients With Type 2 Diabetes: Findings From the ACCORD Cohort

Liyao Fu, Shi Tai, Jiaxing Sun, Ningjie Zhang, Ying Zhou, Zhenhua Xing, Yongjun Wang, Shenghua Zhou, Liyao Fu, Shi Tai, Jiaxing Sun, Ningjie Zhang, Ying Zhou, Zhenhua Xing, Yongjun Wang, Shenghua Zhou

Abstract

Objective: Remnant cholesterol (remnant-C) predicts atherosclerotic cardiovascular disease, regardless of LDL-cholesterol (LDL-C) levels. This study assessed the associations between remnant-C and cardiovascular outcomes in type 2 diabetes.

Research design and methods: This post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial used patient (type 2 diabetes >3 months) remnant-C and major adverse cardiovascular event (MACE) data from the study database. The associations between remnant-C and MACEs were evaluated using Cox proportional hazards regression analyses. We examined the relative MACE risk in remnant-C versus LDL-C discordant/concordant groups using clinically relevant LDL-C targets by discordance analyses.

Results: The baseline analysis included 10,196 participants, with further visit-to-visit variability analysis including 9,650 participants. During follow-up (median, 8.8 years), 1,815 patients (17.8%) developed MACEs. After adjusting for traditional cardiovascular risk factors, each 1-SD increase in remnant-C was associated with a 7% higher MACE risk (hazard ratio [HR] 1.07, 95% CI 1.02-1.12, P = 0.004). In the fully adjusted model, the visit-to-visit remnant-C variability calculated using logSD (HR 1.41, 95% CI 1.18-1.69, P < 0.001) and logARV (HR 1.45, 95% CI 1.22-1.73, P < 0.001) was associated with MACEs. Residual lipid risk (remnant-C ≥31 mg/dL) recognized individuals at a higher MACE risk, regardless of LDL-C concentrations. Within each LDL-C subgroup (>100 or ≤100 mg/dL), high baseline remnant-C was associated with a higher MACE risk (HR 1.37, 95% CI 1.09-1.73, P = 0.007; HR 1.22, 95% CI 1.04-1.41, P = 0.015, respectively).

Conclusions: Remnant-C levels were associated with MACEs in patients with type 2 diabetes independent of LDL-C, and visit-to-visit remnant-C variability helped identify those with higher cardiovascular risk.

Trial registration: ClinicalTrials.gov NCT00000620.

© 2022 by the American Diabetes Association.

Figures

Figure 1
Figure 1
Discordance analyses of remnant-C and LDL-C levels. In order to assess the risk of MACEs by categories of low and high LDL-C and remnant-C levels, HRs were estimated relative to the lowest risk category (LDL-C ≤100 mg/dL and remnant-C 1c level, LDL-C level, biguanide treatment, statin treatment, and insulin treatment. A high remnant-C level was associated with MACEs, regardless of LDL-C values.

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