Inflammation reduces HDL protection against primary cardiac risk.
BACKGROUND
We recently reported high high-density lipoprotein (HDL) cholesterol as a predictor of recurrent risk in a subgroup of postinfarction patients defined by hypercholesterolemia and high C-reactive protein (CRP) levels. We investigated whether a similar high-risk subgroup might exist for incident cardiovascular disease.


METHODS
A graphical exploratory data analysis tool was used to identify high-risk subgroups in a male population-based cohort (n = 3405) from the prevention of renal and vascular end-stage disease study by generating 3-dimensional mappings of risk over the HDL-cholesterol/CRP domain with subsequent use of Kaplan-Meier analysis to verify high-risk. Within-subgroup risk was assessed using Cox proportional hazards regression and Kaplan-Meier analysis.


RESULTS
Mappings revealed two high-risk subgroups: a low HDL-cholesterol/high CRP subgroup and a high HDL-cholesterol/high CRP subgroup. The low HDL-cholesterol subgroup demonstrated a pattern of metabolic syndrome dyslipidemia contrasted with a predominantly unremarkable biomarker pattern for the high HDL-cholesterol subgroup. However, in the high HDL-cholesterol subgroup, CRP levels were higher than the low HDL-cholesterol subgroup; and within the high HDL-cholesterol subgroup, CRP predicted risk. Moreover, in the high HDL-cholesterol subgroup, risk was associated with lower triglyceride levels in conjunction with presumptively larger HDL particles.


CONCLUSIONS
High HDL-cholesterol and high CRP levels define a subgroup of men at high-risk for incident cardiovascular disease. High HDL cholesterol-associated risk likely relates to impaired HDL particle remodelling in the setting of inflammation. This approach may facilitate identification of additional inflammation-related mechanisms underlying high HDL cholesterol-associated risk; and potentially influence management of such patients.
Corsetti
James P
JP
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. james_corsetti@urmc.rochester.edu
Gansevoort
Ron T
RT
Sparks
Charles E
CE
Dullaart
Robin P F
RP
D000328:Adult; D050197:Atherosclerosis / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D005843:Geography; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008075:Lipoproteins, HDL / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010316:Particle Size; D016016:Proportional Hazards Models; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D014280:Triglycerides; D002097:C-Reactive Protein