Apolipoprotein CIII predicts cardiovascular events in patients with coronary artery disease: a prospective observational study

Julius L Katzmann, Christian M Werner, Tatjana Stojakovic, Winfried März, Hubert Scharnagl, Ulrich Laufs, Julius L Katzmann, Christian M Werner, Tatjana Stojakovic, Winfried März, Hubert Scharnagl, Ulrich Laufs

Abstract

Background: Apolipoprotein CIII (apoCIII) is associated with triglyceride-rich lipoprotein metabolism and has emerged as independent marker for risk of cardiovascular disease. The objective was to test whether apoCIII is regulated postprandially and whether apoCIII concentrations in native and chylomicron-free serum predict future cardiovascular events in patients with stable coronary artery disease (CAD).

Methods: ApoCIII concentrations were measured in native and chylomicron-free serum in the fasting state and after a standardized oral fat load test in 195 patients with stable CAD. Clinical follow-up was 48 months. Chylomicron-free serum was prepared by ultracentrifugation (18,000 rpm, 3 h). The log-rank test and Cox regression analyses were used to investigate the association of apoCIII with recurrent cardiovascular events.

Results: Of the 195 patients included, 92 had a cardiovascular event, and 103 did not. 97% were treated with a statin. No significant changes in apoCIII concentration were observed after the oral fat load test. The apoCIII concentration was associated with event-free survival independent of conventional risk factors. This association reached statistical significance only for apoCIII concentration measured in chylomicron-free serum (hazard ratio [95% confidence interval] for apoCIII above the mean: postprandial: 1.67 (1.06-2.29), P = 0.028, fasting: 2.09 (1.32-3.32), P = 0.002), but not for apoCIII concentration measured in native serum (postprandial: 1.47 [0.89-2.43], P = 0.133, fasting: 1.56 [0.95-2.58], P = 0.081). The effects were independent of other risk factors.

Conclusions: ApoCIII concentrations in chylomicron-free serum are independently associated with event-free survival in patients with CAD both in fasting and postprandial state. This findings support considering apoCIII for risk assessment and attempting to test the hypothesis that lowering apoCIII reduces residual cardiovascular risk.

Take home message: Apolipoprotein CIII concentration measured in chylomicron-free serum predicts recurrent cardiovascular events in patients with stable coronary artery disease.

Trial registration: The trial which included the participants of this study was registered at https://ichgcp.net/clinical-trials-registry/NCT00628524" title="See in ClinicalTrials.gov">NCT00628524) on March 5, 2008.

Keywords: Antisense oligonucleotide; Apolipoprotein CIII; Cardiovascular disease; Chylomicron; Coronary artery disease; Oral fat tolerance test; Risk factor; Triglyceride; Ultracentrifugation.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Kaplan-Meier curves of event-free survival for 48 months, stratified by tertiles of apoCIII concentrations in chylomicron-free serum fasting (a) and postprandial after standardized fat load test (b). HR: hazard ratio, CI: confidence interval
Fig. 2
Fig. 2
Multivariable Cox regression analyses of the association of fasting and postprandial apoCIII below and above the mean (chylomicron-free serum) and the primary end point (fully adjusted for age*time, gender, LDL cholesterol, HOMA index, fasting triglycerides for fasting samples and 5-h triglyceride area under the curve for postprandial samples, respectively, metabolic syndrome, and smoking status). CI: confidence interval

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