Apolipoprotein C‐III predicts cardiovascular events and mortality in individuals with type 1 diabetes and albuminuria

OBJECTIVES: We studied apolipoprotein C‐III (apoC‐III) in relation to diabetic kidney disease (DKD), cardiovascular outcomes, and mortality in type 1 diabetes. METHODS: The cohort comprised 3966 participants from the prospective observational Finnish Diabetic Nephropathy Study. Progression of DKD was determined from medical records. A major adverse cardiac event (MACE) was defined as acute myocardial infarction, coronary revascularization, stroke, or cardiovascular mortality through 2017. Cardiovascular and mortality data were retrieved from national registries. RESULTS: ApoC‐III predicted DKD progression independent of sex, diabetes duration, blood pressure, HbA(1c), smoking, LDL‐cholesterol, lipid‐lowering medication, DKD category, and remnant cholesterol (hazard ratio [HR] 1.43 [95% confidence interval 1.05–1.94], p = 0.02). ApoC‐III also predicted the MACE in a multivariable regression analysis; however, it was not independent of remnant cholesterol (HR 1.05 [0.81–1.36, p = 0.71] with remnant cholesterol; 1.30 [1.03–1.64, p = 0.03] without). DKD‐specific analyses revealed that the association was driven by individuals with albuminuria, as no link between apoC‐III and the outcome was observed in the normal albumin excretion or kidney failure categories. The same was observed for mortality: Individuals with albuminuria had an adjusted HR of 1.49 (1.03–2.16, p = 0.03) for premature death, while no association was found in the other groups. The highest apoC‐III quartile displayed a markedly higher risk of MACE and death than the lower quartiles; however, this nonlinear relationship flattened after adjustment. CONCLUSIONS: The impact of apoC‐III on MACE risk and mortality is restricted to those with albuminuria among individuals with type 1 diabetes. This study also revealed that apoC‐III predicts DKD progression, independent of the initial DKD category.