Inflammation reduces HDL protection against primary cardiac risk

被引:61
作者
Corsetti, James P. [1 ]
Gansevoort, Ron T. [2 ]
Sparks, Charles E.
Dullaart, Robin P. F. [3 ]
机构
[1] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Sch Med & Dent, Rochester, NY 14642 USA
[2] Univ Groningen, Dept Nephrol, NL-9700 RB Groningen, Netherlands
[3] Univ Groningen, Dept Endocrinol, NL-9700 RB Groningen, Netherlands
关键词
Atherosclerosis; cardiovascular risk; CRP; HDL cholesterol; inflammation; HIGH-DENSITY-LIPOPROTEIN; URINARY ALBUMIN EXCRETION; ESTER TRANSFER PROTEIN; THERAPEUTIC TARGET; CHOLESTEROL;
D O I
10.1111/j.1365-2362.2010.02287.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
P>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. Material and 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.
引用
收藏
页码:483 / 489
页数:7
相关论文
共 24 条
  • [1] The paradox of dysfunctional high-density lipoprotein
    Ansell, Benjamin J.
    Fonarow, Gregg C.
    Fogelman, Alan M.
    [J]. CURRENT OPINION IN LIPIDOLOGY, 2007, 18 (04) : 427 - 434
  • [2] An increased coronary risk is paradoxically associated with common cholesteryl ester transfer protein gene variations that relate to higher high-density lipoprotein cholesterol: A population-based study
    Borggreve, Susanna E.
    Hillege, Hans L.
    Wolffenbuttel, Bruce H. R.
    de Jong, Paul E.
    Zuurman, Mike W.
    van der Steege, Gerrit
    van Tol, Arie
    Dullaart, Robin P. F.
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2006, 91 (09) : 3382 - 3388
  • [3] Intensive versus moderate lipid lowering with statins after acute coronary syndromes
    Cannon, CP
    Braunwald, E
    McCabe, CH
    Rader, DJ
    Rouleau, JL
    Belder, R
    Joyal, SV
    Hill, KA
    Pfeffer, MA
    Skene, AM
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (15) : 1495 - 1504
  • [4] Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)
    Cleeman, JI
    Grundy, SM
    Becker, D
    Clark, LT
    Cooper, RS
    Denke, MA
    Howard, WJ
    Hunninghake, DB
    Illingworth, DR
    Luepker, RV
    McBride, P
    McKenney, JM
    Pasternak, RC
    Stone, NJ
    Van Horn, L
    Brewer, HB
    Ernst, ND
    Gordon, D
    Levy, D
    Rifkind, B
    Rossouw, JE
    Savage, P
    Haffner, SM
    Orloff, DG
    Proschan, MA
    Schwartz, JS
    Sempos, CT
    Shero, ST
    Murray, EZ
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2001, 285 (19): : 2486 - 2497
  • [5] Plasminogen activator inhibitor-1 polymorphism (4G/5G) predicts recurrence in nonhyperlipidemic postinfarction patients
    Corsetti, James P.
    Ryan, Dan
    Moss, Arthur J.
    Rainwater, David L.
    Zareba, Wojciech
    Sparks, Charles E.
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2008, 28 (03) : 548 - 554
  • [6] NAD(P)H oxidase polyrnorphism (C242T) and high HDL cholesterol associate with recurrent coronary events in postinfarction patients
    Corsetti, James P.
    Ryan, Dan
    Moss, Arthur J.
    Zareba, Wojciech
    Sparks, Charles E.
    [J]. ATHEROSCLEROSIS, 2008, 196 (01) : 461 - 468
  • [7] Elevated HDL is a risk factor for recurrent coronary events in a subgroup of non-diabetic postinfarction patients with hypercholesterolemia and inflammation
    Corsetti, James P.
    Zareba, Wojclech
    Moss, Arthur J.
    Rainwater, David L.
    Sparks, Charles E.
    [J]. ATHEROSCLEROSIS, 2006, 187 (01) : 191 - 197
  • [8] Serum glucose and triglyceride determine high-risk subgroups in non-diabetic postinfarction patients
    Corsetti, JP
    Zareba, W
    Moss, AJ
    Sparks, CE
    [J]. ATHEROSCLEROSIS, 2005, 183 (02) : 293 - 300
  • [9] Clinical significance of high-density lipoprotein cholesterol in patients with low low-density lipoprotein cholesterol
    deGoma, Emil M.
    Leeper, Nicholas J.
    Heidenreich, Paul A.
    [J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2008, 51 (01) : 49 - 55
  • [10] Plasma lecithin:cholesterol acyltransferase activity modifies the inverse relationship of C-reactive protein with HDL cholesterol in nondiabetic men
    Dullaart, R. P. F.
    Perton, F.
    Kappelle, P. J. W. H.
    de Vries, R.
    Sluiter, W. J.
    van Tol, A.
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2010, 1801 (01): : 84 - 88