Serum Apolipoproteins and Apolipopprotein-Defined Lipoprotein Subclasses: A Hypothesis-Generation Prospective Study of Cardiovascular Events in Type 1 Diabetes
Apolipoproteins and apolipoprotein-defined lipoprotein subclasses have been associated with dyslipidemia and cardiovascular disease (CVD). Our main objective was to define associations of serum apolipoproteins and ADLS with any CVD and major atherosclerotic cardiovascular events (MACE) in a prospective study of T1D. Serum apolipoproteins and ADLS (14 biomarkers in total) were measured in sera (obtained 1997-2000) from a subset (n=465) of the Epidemiology of Diabetes Interventions and Complications (EDIC) cohort. Prospective associations of any CVD (myocardial infarction, stroke, confirmed angina, silent MI, revascularization, or congestive heart failure) and MACE (fatal or nonfatal myocardial infarction or stroke), over 5942 and 6180 patient-years follow-up respectively, were investigated using Cox proportional hazards models, unadjusted and adjusted for risk factors. During 15 years follow-up, 50 any CVD and 24 MACE events occurred. Nominally significant positive univariate associations with any CVD were APOB, APOC3 and its sub-fractions [heparin precipitate (HP), heparin soluble (HS)], and ADLS-defined Lp-B. Nominally significant positive univariate associations with MACE were APOC3 and sub-fractions, and Lp-B:C; those with total APOC3 and APOC3-HS persisted in adjusted analyses. However, these associations did not reach significance after adjustment for multiple testing. There were no significant associations of APOA1, APOA2, APOE, or other ADLS with either any CVD or MACE. These hypothesis-generating data suggest that total serum APOC3 and APOC3 in HDL are potentially important predictive biomarkers for any CVD and MACE in T1D adults.