Apolipoprotein A-II influences apolipoprotein E-linked cardiovascular disease risk in women with high levels of HDL cholesterol and C-reactive protein.
BACKGROUND
In a previous report by our group, high levels of apolipoprotein E (apoE) were demonstrated to be associated with risk of incident cardiovascular disease in women with high levels of C-reactive protein (CRP) in the setting of both low (designated as HR1 subjects) and high (designated as HR2 subjects) levels of high-density lipoprotein cholesterol (HDL-C). To assess whether apolipoprotein A-II (apoA-II) plays a role in apoE-associated risk in the two female groups.


RESULTS
Outcome event mapping, a graphical data exploratory tool; Cox proportional hazards multivariable regression; and curve-fitting modeling were used to examine apoA-II influence on apoE-associated risk focusing on HDL particles with apolipoprotein A-I (apoA-I) without apoA-II (LpA-I) and HDL particles with both apoA-I and apoA-II (LpA-I:A-II). Results of outcome mappings as a function of apoE levels and the ratio of apoA-II to apoA-I revealed within each of the two populations, a high-risk subgroup characterized in each situation by high levels of apoE and additionally: in HR1, by a low value of the apoA-II/apoA-I ratio; and in HR2, by a moderate value of the apoA-II/apoA-I ratio. Furthermore, derived estimates of LpA-I and LpA-I:A-II levels revealed for high-risk versus remaining subjects: in HR1, higher levels of LpA-I and lower levels of LpA-I:A-II; and in HR2 the reverse, lower levels of LpA-I and higher levels of LpA-I:A-II. Results of multivariable risk modeling as a function of LpA-I and LpA-I:A-II (dichotomized as highest quartile versus combined three lower quartiles) revealed association of risk only for high levels of LpA-I:A-II in the HR2 subgroup (hazard ratio 5.31, 95% CI 1.12-25.17, p = 0.036). Furthermore, high LpA-I:A-II levels interacted with high apoE levels in establishing subgroup risk.


CONCLUSIONS
We conclude that apoA-II plays a significant role in apoE-associated risk of incident CVD in women with high levels of HDL-C and CRP.
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA. James_Corsetti@urmc.rochester.edu
James P
JP
Corsetti
Stephan J L
SJ
Bakker
Charles E
CE
Sparks
Robin P F
RP
Dullaart
D000328:Adult; D000368:Aged; D016633:Apolipoprotein A-II / Q000097:blood / Q000378:metabolism*; D001057:Apolipoproteins E / Q000097:blood / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism* / Q000401:mortality; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012306:Risk
D016633:Apolipoprotein A-II; D001057:Apolipoproteins E; D015415:Biomarkers; D008076:Cholesterol, HDL; D002097:C-Reactive Protein