Patients With Coronary Endothelial Dysfunction Have Impaired Cholesterol Efflux Capacity and Reduced HDL Particle Concentration.
Coronary endothelial dysfunction (ED)-an early marker of atherosclerosis-increases the risk of cardiovascular events.



We tested the hypothesis that cholesterol efflux capacity and high-density lipoprotein (HDL) particle concentration predict coronary ED better than HDL-cholesterol (HDL-C).



We studied 80 subjects with nonobstructive (<30% stenosis) coronary artery disease. ED was defined as <50% change in coronary blood flow in response to intracoronary infusions of acetylcholine during diagnostic coronary angiography. Cholesterol efflux capacity and HDL particle concentration (HDL-PIMA) were assessed with validated assays. Cholesterol efflux capacity and HDL-PIMA were both strong, inverse predictors of ED (P<0.001 and 0.005, respectively). In contrast, HDL-C and other traditional lipid risk factors did not differ significantly between control and ED subjects. Large HDL particles were markedly decreased in ED subjects (33%; P=0.005). After correction for HDL-C, both efflux capacity and HDL-PIMA remained significant predictors of ED status. HDL-PIMA explained cholesterol efflux capacity more effectively than HDL-C (r=0.54 and 0.36, respectively). The efflux capacities of isolated HDL and serum HDL correlated strongly (r=0.49).



Cholesterol efflux capacity and HDL-PIMA are reduced in subjects with coronary ED, independently of HDL-C. Alterations in HDL-PIMA and HDL itself account for a much larger fraction of the variation in cholesterol efflux capacity than does HDL-C. A selective decrease in large HDL particles may contribute to impaired cholesterol efflux capacity in ED subjects. These observations support a role for HDL size, concentration, and function as markers-and perhaps mediators-of coronary atherosclerosis in humans.
From the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle (J.S.M., P.M.H., G.E.R., J.W., A.D.I., C.T., B.S., T.V., J.W.H.); and Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN (J.D.S., A.L.).
Jeffrey S
JS
Monette
From the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle (J.S.M., P.M.H., G.E.R., J.W., A.D.I., C.T., B.S., T.V., J.W.H.); and Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN (J.D.S., A.L.).
Patrick M
PM
Hutchins
From the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle (J.S.M., P.M.H., G.E.R., J.W., A.D.I., C.T., B.S., T.V., J.W.H.); and Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN (J.D.S., A.L.).
Graziella E
GE
Ronsein
From the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle (J.S.M., P.M.H., G.E.R., J.W., A.D.I., C.T., B.S., T.V., J.W.H.); and Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN (J.D.S., A.L.).
Jake
J
Wimberger
From the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle (J.S.M., P.M.H., G.E.R., J.W., A.D.I., C.T., B.S., T.V., J.W.H.); and Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN (J.D.S., A.L.).
Angela D
AD
Irwin
From the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle (J.S.M., P.M.H., G.E.R., J.W., A.D.I., C.T., B.S., T.V., J.W.H.); and Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN (J.D.S., A.L.).
Chongren
C
Tang
From the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle (J.S.M., P.M.H., G.E.R., J.W., A.D.I., C.T., B.S., T.V., J.W.H.); and Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN (J.D.S., A.L.).
Jaskanwal D
JD
Sara
From the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle (J.S.M., P.M.H., G.E.R., J.W., A.D.I., C.T., B.S., T.V., J.W.H.); and Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN (J.D.S., A.L.).
Baohai
B
Shao
From the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle (J.S.M., P.M.H., G.E.R., J.W., A.D.I., C.T., B.S., T.V., J.W.H.); and Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN (J.D.S., A.L.).
Tomas
T
Vaisar
From the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle (J.S.M., P.M.H., G.E.R., J.W., A.D.I., C.T., B.S., T.V., J.W.H.); and Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN (J.D.S., A.L.).
Amir
A
Lerman
From the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle (J.S.M., P.M.H., G.E.R., J.W., A.D.I., C.T., B.S., T.V., J.W.H.); and Division of Cardiovascular Disease, Mayo Clinic, Rochester, MN (J.D.S., A.L.). heinecke@uw.edu.
Jay W
JW
Heinecke
D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D008076:Cholesterol, HDL
apolipoproteins; atherosclerosis; cardiovascular diseases; cholesterol; lipoproteins