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Whether urinary albumin excretion relates to higher levels of atherogenic apolipoprotein B fractions in the nondiabetic population is uncertain. Such a relationship could explain, in part, the association of elevated urinary albumin excretion with cardiovascular disease risk. We assessed the relationship of urinary albumin excretion with apolipoprotein B fractions and determined whether the association of elevated urinary albumin excretion with incident cardiovascular events is modified by high apolipoprotein B fraction levels. We performed a prospective study on 8286 nondiabetic participants (580 participants with cardiovascular disease; 4.9 years median follow-up time) with fasting lipids, apolipoprotein B, and urinary albumin excretion determined at baseline. With adjustment for sex and age, micro- and macroalbuminuria were associated with increased apolipoprotein B fractions (non-HDL cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B). All four apolipoprotein B fractions modified associations of urinary albumin excretion with incident cardiovascular disease (hazard ratios for interaction terms ranged from 0.89 to 0.94 with 95% confidence intervals ranging from 0.84 to 0.99 and P values ranging from 0.001 to 0.02 by Cox proportional hazards modeling). These interactions remained present after additional adjustment for conventional risk factors, eGFR, cardiovascular history, and lipid-lowering and antihypertensive drug treatments. Such modification was also observed when urinary albumin excretion was stratified into normo-, micro-, and macroalbuminuria. We conclude that there is an association between elevated urinary albumin excretion and apolipoprotein B fraction levels and a negative interaction between these variables in their associations with incident cardiovascular events. Elevated urinary albumin excretion may share common causal pathways with high apolipoprotein B fractions in the pathogenesis of cardiovascular disease.

Apolipoprotein B Attenuates Albuminuria-Associated Cardiovascular Disease in Prevention of Renal and Vascular Endstage Disease (PREVEND) Participants