Abstract 445: Pulmonary Surfactant Protein B Carried By HDL Is Associated With Incident Cardiovascular Disease In Patients With Type 1 Diabetes

Abstract

Atherosclerotic cardiovascular disease (CVD) is the major cause of death in people with type 1 diabetes mellitus (T1DM). Alterations in the HDL proteome associate with prevalent CVD in T1DM. We therefore determined which proteins carried by HDL are associated with incident CVD in T1DM patients. We conducted a case-cohort study of incident CVD in the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. We randomly sampled 145 CACTI participants without prevalent CVD, 11 of whom subsequently developed a CVD event as a cohort, plus all additional T1DM participants in CACTI (N=36) who developed an incident CVD event (a total of 47 CVD cases). Using targeted MS/MS, we quantified 51 proteins in HDL isolated from baseline plasma samples. We used Cox proportional regression analysis and a case-cohort design to test associations of HDL proteins with incident CVD (myocardial infarction, coronary artery bypass grafting, angioplasty, or death from coronary heart disease). Only one HDL protein—SFTPB (pulmonary surfactant protein B)—was associated with incident CVD in T1DM in all of the models tested. In a fully adjusted model that controlled for smoking status, lipids and other risk factors, the hazard ratio was 2.17 per SD increase of SFTPB (95% confidence interval, 1.12-4.21, P=0.022). Plasma fractionation and targeted MS/MS quantification demonstrated that nearly 95% of plasma SFTPB is quantitatively bound to HDL. Our results show that elevated levels of SFTPB in HDL are strongly associated with incident CVD in CACTI subjects with T1DM independently of smoking status and a wide range of other confounding factors. Because HDL is the major carrier of SFTPB in plasma, our observations support the proposal that SFTPB carried by HDL is a novel marker of CVD risk in patients with T1DM.