Remnant Cholesterol is Prospectively Associated With Cardiovascular Disease Events and All-Cause Mortality in Kidney Transplant Recipients

The FAVORIT Study

Reuben William Horace; Mary Roberts; Theresa I. Shireman; Basma Merhi; Paul Jacques; Andrew G. Bostom; Simin Liu; Charles B. Eaton

Disclosures

Nephrol Dial Transplant. 2022;37(2):382-389. 

In This Article

Results

Our analytic cohort consisted of 3812 kidney transplant participants, the mean age was 51.9 ± 9.4 years and they were predominantly male (62.9%) and predominantly non-Hispanic white (76.3%). A large percentage had a history of diabetes mellitus (59.6%), largely normotensive and with modestly decreased eGFR (46.5 ± 17.6 mL/min/1.73 m2) (Table 1). The mean serum remnant cholesterol was 34.8 ± 5.2 mg/dL. Individuals with higher remnant cholesterol levels were more overweight or obese, had higher triglycerides, had lower HDL levels, were predominantly male and had slightly lower eGFRs, more albumuria and were more likely to be on lipid-lowering medications.

Among the 3812 participants with complete outcome data, there were 584 new CVD events with 777 participants at risk of an event. When remnant cholesterol was examined as a categorical variable, risk increased progressively through the quartiles (Figure 2A) (P for linear trend <0.001). Within our univariate hazard ratio (HR), we found that smoking status, statins and SBP were all significant covariates within our model across all three outcomes (Table 2). Comparing the highest quartile (Q4: 41.2 ± 2.4 mg/dL) to the reference group (Q1: 28.9 ± 2.4 mg/dL) revealed a statistically significant result of a 32% increase in CVD risk {HR 1.32 [95% confidence interval (CI) 1.04–1.67]} (Table 3). Remnant cholesterol was also associated with increased all-cause mortality compared with Q4 (Figure 2B). There were 466 participants at risk of an event, with 452 events over a mean follow-up time of 4.0 (standard deviation 1.5) years. We observed a higher proportion of events occurring at higher remnant cholesterol levels. Comparison of Q1 with Q4 showed a statistically significant increased risk of 31% [HR 1.31 (95% CI 1.01–1.69); P < 0.04, P for trend = 0.01] (Table 3). A test for trend among quartiles was significant as well (P < 0.02). We found no statistically significant association between remnant cholesterol and graft failure, with 343 graft failure events (Figure 2C).

Figure 2.

Survival estimates for (A) primary CVD outcomes, (B) all-cause mortality outcomes and (C) renal graft failure stratified by baseline remnant cholesterol levels. Analyses exclude participants with missing covariate data.

Sensitivity analyses for the outcome of CVD and all-cause mortality risk was examined to assess and compare remnant cholesterol with categorical LDL, HDL and triglycerides (Supplementary Table S1). Our results show decreased risk of CVD events among HDL cholesterol groups (>50 mg/dL) in Q1–Q4 [HR 1.02 (95% CI 0.83–1.26)] compared with lower levels of HDL [<40 mg/dL; HR 1.18 (95% CI 0.98–1.42)]. Increased levels of LDL also carried a 26% increased risk of CVD events with higher levels of LDL >160 mg/dL [HR 1.2 (95% CI 1.01–1.53)] compared with medium (100–159 mg/dL) and lower levels (<99 mg/dL) of LDL. Similar results were seen among the all-cause mortality group, with increased LDL conferring a 16% increased mortality rate in those with LDL >160 mg/dL [HR 1.16 (95% CI 1.04–1.51)]. The total risk for triglycerides showed a nonsignificant and minimal overall effect for CVD risk in all categories. Additionally, our mediation analysis found nonsignificant and marginal effects of graft loss on transplant failure outcome. We found that each 5 mg/dL increase in remnant cholesterol was associated with a 14% increased risk of CVD events and a 13% increased risk of all-cause mortality.

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