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Serum apolipoproteins and apolipoprotein-defined lipoprotein subclasses: a hypothesis-generating prospective study of
Arpita Basu1, Ionut Bebu2, Alicia J Jenkins3
1Department of Kinesiology and Nutrition Sciences, University of Nevada, Las Vegas, Las Vegas, NV.
Insights
Serum apolipoprotein C3 (APOC3) and its subfractions may predict cardiovascular disease (CVD) and major adverse cardiovascular events (MACEs) in adults with type 1 diabetes (T1D). Further research is needed to confirm these findings.
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Lipid Metabolism
Background:
- Apolipoproteins (APOB, APOC3, APOE) and apolipoprotein-defined lipoprotein subclasses (ADLSs) are linked to dyslipidemia and cardiovascular disease (CVD).
- Type 1 diabetes (T1D) is associated with an increased risk of CVD.
Purpose of the Study:
- To investigate the associations of serum apolipoproteins and ADLSs with "any CVD" and "major atherosclerotic cardiovascular events" (MACEs) in a prospective cohort of T1D patients.
- To identify potential predictive biomarkers for CVD risk in adults with T1D.
Main Methods:
- Serum samples from 465 T1D patients (Epidemiology of Diabetes Interventions and Complications cohort) were analyzed for 14 biomarkers, including apolipoproteins and ADLSs.
- Prospective associations with "any CVD" and MACEs were assessed over 15 years using Cox proportional hazards models.
- Analyses included unadjusted and adjusted models accounting for traditional risk factors.
Main Results:
- APOC3 and its subfractions (heparin-soluble APOC3) showed nominally significant positive associations with "any CVD" and MACEs in univariate and adjusted analyses.
- ADLS-defined Lp-B and Lp-B:C were also nominally associated with CVD outcomes.
- Associations did not reach statistical significance after adjusting for multiple testing; APOA1, APOA2, APOE, and other ADLSs showed no significant associations.
Conclusions:
- Total serum APOC3 and APOC3 within high-density lipoprotein (HDL) particles are potentially important predictive biomarkers for "any CVD" and MACEs in adults with T1D.
- These findings are hypothesis-generating and warrant further investigation to confirm the predictive value of APOC3 in T1D.
Abstract:
APOB, APOC3, and APOE and apolipoprotein-defined lipoprotein subclasses (ADLSs; based on qualitative apolipoprotein complement) have been associated with dyslipidemia and CVD. Our main objective was to define associations of serum apolipoproteins and ADLSs with "any CVD" and "major atherosclerotic cardiovascular events" (MACEs) in a prospective study of T1D. Serum apolipoproteins and ADLSs (14 biomarkers in total) were measured in sera (obtained between 1997 and 2000) from a subset (n = 465) of the Epidemiology of Diabetes Interventions and Complications cohort. Prospective associations of "any CVD" (myocardial infarction, stroke, confirmed angina, silent myocardial infarction, revascularization, or congestive heart failure) and MACEs (fatal or nonfatal myocardial infarction or stroke), over 5,943 and 6,180 patient-years follow-up, respectively, were investigated using Cox proportional hazards models that were unadjusted and adjusted for risk factors. During 15 years of follow-up, 50 "any CVD" events and 24 MACEs occurred. Nominally significant positive univariate associations with "any CVD" were APOB, APOC3 and its subfractions [heparin precipitate, heparin-soluble (HS)], and ADLS-defined Lp-B. In adjusted analyses, APOC3-HS remained nominally significant. Nominally significant positive univariate associations with MACEs were APOC3 and its subfractions and Lp-B:C; those with total APOC3 and APOC3-HS persisted in adjusted analyses. However, these associations did not reach significance after adjusting for multiple testing. There were no significant associations of APOA1, APOA2, APOE, or other ADLSs with either "any CVD" or MACEs. These hypothesis-generating data suggest that total serum APOC3 and APOC3 in HDL are potentially important predictive biomarkers for any CVD and MACEs in adults with T1D.
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