© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Blood Pressure, LDL Cholesterol, and Intima-Media Thickness
A Test of the "Response to Injury" Hypothesis of Atherosclerosis
From the Department of Preventive Medicine, Institute for Prevention Research, Keck School of Medicine of the University of Southern California, Los Angeles, and the Division of Cardiology (C.N.B.M.), Department of Medicine, Cedars-Sinai Research Institute, Cedars-Sinai Medical Center and Department of Medicine, University of California at Los Angeles School of Medicine.
Abstract—The "response to injury" hypothesis is a plausible model of the development of atherosclerosis supported by observations from animal models. The present study uses epidemiological data to investigate the hypothesis that wall damage due to hypertension is a precursor of low density lipoprotein cholesterol (LDL-C)–mediated atherosclerosis. The Los Angeles Atherosclerosis Study is following a cohort of 576 participants who were aged 40 to 60 years and were free of symptomatic cardiovascular disease at recruitment. Common carotid artery intima-media thickness (IMT) was assessed by B-mode ultrasonography. After exclusion for nonfasting blood draw and other missing data, 511 subjects were available for analysis. IMT was regressed on LDL-C within tertiles of systolic blood pressure (SBP): low (93 to 122 mm Hg), middle (123 to 132 mm Hg), and high (133 to 175 mm Hg). Covariates were age, sex, body height, body mass index, ethnicity, smoking status, diabetes, and pharmacological treatment for hypertension or hypercholesterolemia. IMT was significantly related to LDL-C in the high SBP group (ß=0.025±0.008, where ß values are IMT [mm]/LDL-C [mmol/L]; P=0.002) but not in the middle (ß=-0.006±0.008, P=0.39) or low (ß=-0.004±0.009, P=0.64) SBP group. The slope in the high SBP group was significantly greater than in the middle (P=0.004) or low (P=0.014) SBP group. Results were similar for women and men, and after the exclusion of diabetics and persons using antihypertensive or lipid-lowering medications. Elevated LDL-C was associated with increased IMT in the upper tertile of SBP but not in the lower tertiles. These findings are consistent with the hypothesis that wall injury due to elevated SBP increases the susceptibility of the artery wall to LDL-C–mediated atherogenesis.
Key Words: atherosclerosis • response-to-injury model • intima-media thickness • LDL cholesterol • blood pressure
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