Blood pressure, LDL cholesterol, and intima-media thickness - A test of the "response to injury" hypothesis of atherosclerosis

The "response to injury" hypothesis is a plausible model of the development of atherosclerosis supported by observations from animal models. The prese nt study uses epidemiological data to investigate the hypothesis that wall damage due to hypertension is a precursor of low density lipoprotein choles terol (LDL-C)-mediated atherosclerosis. The Los Angeles Atherosclerosis Stu dy is following a cohort of 576 participants who were aged 40 to 60 years a nd were free of symptomatic cardiovascular disease at recruitment. Common c arotid artery intima-media thickness (LMT) was assessed by B-mode ultrasono graphy. After exclusion for nonfasting blood draw and other missing data, 5 11 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 (1 23 to 132 mm Hg), and high (133 to 175 mm Hg). Covariates were age, sex, bo dy height, body mass index, ethnicity, smoking status, diabetes, and pharma cological treatment for hypertension or hypercholesterolemia. IMT was signi ficantly related to LDL-C in the high SEP group (beta=0.025+/-0.008, where beta values are IMT [mm]/LDL-C [mmol/L]; P=0.002) but not in the middle (be ta=-0.006+/-0.008, P=0.39) or low (beta=-0.004+/-0.009, P=0.64) SEP group. The slope in the high SEP group was significantly greater than in the middl e (P=0.004) or low (P=0.014) SEP group. Results were similar for women and men, and after the exclusion of diabetics and persons using antihypertensiv e or lipid-lowering medications. Elevated LDL-C was associated with increas ed IMT in the upper tertile of SEP but not in the lower tertiles. These fin dings are consistent with the hypothesis that wall injury due to elevated S EP increases the susceptibility of the artery wall to LDL-C-mediated athero genesis.