Apolipoprotein B attenuates albuminuria-associated cardiovascular disease in prevention of renal and vascular endstage disease (PREVEND) participants.
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.
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York; and James_Corsetti@urmc.rochester.edu.
James P
JP
Corsetti
Departments of Nephrology.
Ron T
RT
Gansevoort
Departments of Nephrology.
Stephan J L
SJ
Bakker
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York; and.
Charles E
CE
Sparks
Health Sciences, Community and Occupational Medicine, and.
Priya
P
Vart
Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Robin P F
RP
Dullaart
D000328:Adult; D000368:Aged; D000418:Albumins / Q000737:chemistry; D000419:Albuminuria / Q000150:complications*; D001055:Apolipoproteins B / Q000097:blood* / Q000652:urine; D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications*; D008078:Cholesterol, LDL / Q000097:blood; D002986:Clinical Trials as Topic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014280:Triglycerides
D000418:Albumins; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D014280:Triglycerides
albuminuria; cardiovascular disease; lipids; microalbuminuria