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Background— Increased levels of acute-phase reactants predict the onset of poor health outcomes. A U-shaped association has been reported between alcohol intake and health outcomes, which suggests that alcohol intake may modify levels of acute-phase reactants. We investigated the relationship between weekly alcohol intake and interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and plasminogen activator inhibitor-1 (PAI-1). Methods and Results— Data are from year 1 of the Health, Aging, and Body Composition study, a biracial cohort of 3075 well-functioning men and women aged 70 to 79 years, living in Memphis, Tenn, and Pittsburgh, Pa. The analysis included 2574 persons (51.2% women; 40.1% black) with complete data. After adjustment for age, race, smoking status, history of diabetes, history of cardiovascular disease, physical activity, high-density lipoprotein cholesterol, antiinflammatory medications, statins, and total fat mass, alcohol intake showed a J-shaped relationship with mean IL-6 ( P for quadratic term P =0.014) levels. The association was consistent in both men and women. Compared with subjects who consumed 1 to 7 drinks per week, those who never drank had an increased likelihood of having high levels of both IL-6 and CRP, as did those who drank 8 or more drinks per week. We found no relationship between alcohol intake and levels of TNF-α and PAI-1 ( P =0.137 and 0.08, respectively). Conclusions— In well-functioning older persons, light alcohol consumption is associated with lower levels of IL-6 and CRP. These results might suggest an additional biological explanation to the epidemiological link between moderate alcohol consumption and cardiovascular events.

Background —Native and oxidized LDLs (n-LDL and ox-LDL) are involved in the atherogenic process and affect endothelium-dependent vascular tone through their interaction with nitric oxide (NO). Methods and Results —In this study we evaluated directly, by using a porphyrinic microsensor, the effect of increasing lipoprotein concentrations on endothelial NO and superoxide (O 2 − ) production. We investigated where lipoproteins may affect the l -arginine–NO pathway by pretreating cells with l -arginine, l - N -arginine methyl ester (L-NAME), and superoxide dismutase. Bovine aortic endothelial cells were exposed for 1 hour to increasing concentrations of n-LDL (from 0 to 240 mg cholesterol/dL) and ox-LDL (from 0 to 140 mg cholesterol/dL). A stimulated (calcium ionophore) NO concentration decreased to 29% of the control at n-LDL concentration of 80 mg cholesterol/dL and to 15% of the control at 20 mg cholesterol/dL of ox-LDL. l -Arginine partially neutralized the inhibitory effect of n-LDL and ox-LDL on the NO generation. Superoxide dismutase pretreatment did not modify NO production, whereas L-NAME blunted NO generation at all LDL concentrations. O 2 − production was increased at low n-LDL and very low ox-LDL concentrations; this was reversed by l -arginine. Conclusions —These findings confirm the inhibitory role of n-LDL and ox-LDL on NO generation and suggest that lipoproteins may induce a decreased uptake of l -arginine. The local depletion of the l -arginine substrate may derange the NO synthase, leading to overproduction of O 2 − from oxygen, the other substrate of NO synthase.

BACKGROUND Different patterns of risk factors might be related to the involvement of specific vascular districts by atherosclerosis. In this sense, many investigations have addressed coronary artery disease, whereas extracoronary atherosclerosis has received less extensive attention. METHODS AND RESULTS Vascular risk factors, with particular attention to lipid parameters (total cholesterol [TC]; triglycerides; high density lipoprotein cholesterol [HDL-C], HDL2 and HDL3 cholesterol [HDL2-C, HDL3-C]), were evaluated by means of univariate and multivariate (discriminant) analysis in a group of 169 patients (128 men and 41 women; mean ages, 58 +/- 7 and 62 +/- 7 years, respectively) with clinically and angiographically demonstrated atherosclerosis of the supra-aortic trunk and/or lower limbs. Patients with coronary artery disease were excluded from this study. The control group consisted of 140 age- and sex-matched individuals. By univariate analysis, smoking was more closely associated with peripheral atherosclerosis, whereas blood pressure was higher in patients with supra-aortic disease. Unrecognized diabetes mellitus was a frequent finding in patients with peripheral disease. The percentage of hyperlipidemias was fourfold higher in patients than in control subjects, with differences consisting of higher triglycerides and lower HDL-C, HDL2-C, and HDL3-C concentrations. By discriminant analysis, high correct classification (CC) rates were achieved in the various patient subgroups on the basis of variables selected from the statistical function. In male patients with peripheral disease, the variables HDL-C, smoking, diastolic blood pressure, uric acid, and glucose, in that order, yielded a CC in 90.4% of the cases; in female patients, smoking, TC/HDL-C, and body mass index gave a CC rate of 95.9%. In men with cerebral disease, the selected variables TC/HDL-C, diastolic blood pressure, and TC yielded a CC of 90.7%; in women, uric acid, TC/HDL-C, and fibrinogen levels produced a CC rate of 89.2%. CONCLUSIONS Risk profiles in atherosclerosis of the supra-aortic trunks and lower limbs seem to differ in relation to gender and circulatory district involved. The importance of lipid parameters, in particular HDL-C, HDL2-C, and TC/HDL-C, as extracoronary risk factors is further confirmed.