Lipid profile in cardiac transplantation: a closer look at bad cholesterol

Abstract Background When it comes to lipid-lowering therapy, the primary goal is still to reduce the low-density lipoprotein levels. Although remnant cholesterol (RC), including predominantly intermediate- and very-low-density lipoproteins, is a known cardiovascular risk factor, reliable reference values, as well as therapy strategies, are yet to be validated. Additionally, the role of RC after heart transplantation is still unclear. Aim To assess the clinical and prognostic relevance of lipid profile and, in particular, of remnant cholesterol in very long-term follow-up after HTx. Methods We performed a retrospective analysis of the clinical and laboratory parameters collected at last follow-up in an outpatient setting. Additionally, remnant cholesterol levels were estimated using the formula (in mg/dL): remnant cholesterol = total cholesterol – (HLD-C + LDL-C). Results Out of 174 patients with a mean age of 45.2±15.0 years at the time of HTx and a mean follow-up of 13.1±6.5 years, 142 (81.6%) were on statin treatment. Mean cholesterol level was borderline high (184.1±48.4 mg/dL), whereas mean LDL and triglyceride values were markedly elevated (103.6±39.2 and 161.8±83.8 mg/dL, respectively). HDL results were found to be 57.1±17.5 mg/dL. Statin treatment was associated with significantly lower LDL levels (124.6±53.5 vs. 98.8±33.6 mg/dL on statins, p=0.013), but failed to show prognostic relevance in a univariate cox-regression analysis (HR 0.79, 95% CI 0.37 – 1.72, p=0.57). RC was elevated in comparison to the background population with a mean level of 23.5±17.3 mg/dL (24.2±18.1 in male and 21.3±14.8 mg/dL in female) and a tendency for lower values when on treatment with statins but without statistical significance (28.5±19.2 vs. 22.3±16.8 mg/dL on statins, p=0.07). Treatment with higher doses of statins showed no relevant influence on the RC levels (p=0.62). Additionally, elevated RC was associated with higher C-reactive protein values as a sign of systemic inflammation (CRP >0.5 mg/dL, OR 1.1, 95% CI 1.007 – 1.046, p=0.007). In a multivariate cox-regression analysis (adjusted for total cholesterol, LDL and triglycerides) RC was identified as a significant factor influencing mortality (HR 1.11, 95% CI 1.05 – 1.17, p<0.001). Conclusions When addressing dyslipidaemia in heart transplantation, statin therapy can help reduce LDL levels, but this approach seems to be insufficient in achieving clinical benefit. Remnant cholesterol is a factor, which has proinflammatory properties and can potentially influence the prognosis in HTx. The possible therapeutic alternatives for this overseen component of the lipid profile are yet to be elucidated. Funding Acknowledgement Type of funding sources: None.