Apolipoprotein B attenuates albuminuria-associated cardiovascular disease in prevention of renal and vascular endstage disease (PREVEND) participants

Abstract

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.

Keywords: albuminuria; cardiovascular disease; lipids; microalbuminuria.

Figure 1.

Plots illustrating negative interaction effects in terms of continuous variables (Table 2) of UAE with apoB fractions (non–HDL-C, LDL-C, triglycerides, and apoB). Plots give HRs for CV events adjusted for sex and age as a function of UAE and apoB fractions as follows: (A) non–HDL-C, (B) LDL-C, (C) triglycerides, and (D) apoB. HRs were derived analytically using Cox modeling results including UAE, apoB fraction, and the respective interaction term.

Figure 2.

Plots showing negative interaction effects in terms of stratified variables (Table 3) of UAE with apoB fractions (non–HDL-C, LDL-C, triglycerides, and apoB). Plots give HRs for CV events adjusted for sex and age as a function of UAE (<30, 30–300, and >300 mg/d) and tertiles of apoB fractions as follows: (A) non–HDL-C, (B) LDL-C, (C) triglyceride, and (D) apoB. The reference group in each case was taken as UAE<30 mg/d and the lowest tertile of respective apoB fraction.