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Dietary and circulating antioxidant vitamins in relation to carotid plaques in middle-aged women
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American Journal of Clinical Nutrition
Arcangelo Iannuzzi, Egidio Celentano, Salvatore Panico, Rocco Galasso, Giuseppe Covetti, Lucia Sacchetti, Federica Zarrilli, Mario De Michele and Paolo Rubba
1 From the Dietology Unit, A Cardarelli Hospital, Naples (AI); the Epidemiology Unit, National Cancer Institute, Naples (EC); and the Departments of Clinical and Experimental Medicine (SP, RG, GC, MDM, and PR) and Biochemistry and Biotechnologies in Medicine (LS and FZ), Federico II University, Naples.
2 Supported by funds from the Consiglio Nazionale delle Ricerche "Progetto finalizzato Biotecnologie," Rome; PRIN 1997, Ministero dell’Università e della Ricerca scientifica etecnologica; and Regione Campania "Fondi ricerca sanitaria finalizzata." The Progetto Atena was supported by funds from the Consiglio Nazionale delle Ricerche "Progetto finalizzatoFATMA."
ABSTRACTBackground: The results of the few studies conducted on the relation between antioxidant vitamins and carotid atherosclerosis have been inconclusive.
Objective: We evaluated the association between preclinical carotid atherosclerosis, as determined by high-resolution B-mode ultrasound, and boththe intake amounts and plasma concentrations of antioxidant vitamins.
Design: Among 5062 participants in Progetto Atena, a population-based study on the etiology of cardiovascular disease and cancer in women, 310 women were examined by B-mode ultrasound to detect early signs of carotid atherosclerosis. The participants answered a food-frequency questionnaire, and their plasma concentrations of vitamin E, vitamin A, and carotenoids were measured. None of the women took vitamin supplements.
Results: The occurrence of atherosclerotic plaques at the carotid bifurcation was inversely associated with tertiles of vitamin E intake; the test for a linear trend across tertiles was significant (P < 0.05). Similarly, the ratio of plasma vitamin E to plasma cholesterol was inversely related to the presence of plaques at the carotid bifurcation; the test for a linear trend across tertiles was significant (P < 0.02). No association was found between the intake of other antioxidant vitamins (vitamins A and C and carotenoids) or their plasma concentrations and the presence of carotid plaques.
Conclusions: An inverse association was found between both the intake amount and plasma concentration of vitamin E and preclinical carotid atherosclerosis in middle-aged women. This association was independent of other cardiovascular risk factors, was not related to vitamin supplements, and supports the hypothesis that low vitamin E intake is a risk factor for early atherosclerosis.
INTRODUCTION
In the oxidation hypothesis of atherosclerosis, antioxidant protection may play a role in preventing the formation of early lesions. However, the wealth of data regarding the preventive role of dietary or serum antioxidants has yielded conflicting results. A possible explanation for this inconsistency is that most authors considered overt ischemia (myocardial infarction, angina, stroke, transient ischemic attack) rather than preclinical atherosclerosis as an endpoint.
Carotid intima-media thickness (IMT) is a well-recognized marker of early, generalized atherosclerosis and is widely used in epidemiologic studies. Increased IMT is correlated with coronary atherosclerosis. The relation between dietary antioxidants and the thickness of carotid artery walls has been evaluated in a few studies, some focusing on intakes and others on serum concentrations.
However, the relation between antioxidant vitamin intake, plasma vitamin concentrations, and carotid atherosclerosis has not yet been evaluated. The aim of this study was to investigate whether the dietary intake of antioxidant vitamins and the plasma concentrations of vitamin A, carotenoids, and vitamin E are associated with the presence of plaques in the common carotid arteries and carotid bifurcation in a sample of middle-aged women.
DISCUSSION
To our knowledge, this is the first study that combines information on the dietary intakes of antioxidant vitamins and determination of their plasma concentrations with high-resolution ultrasound imaging of carotid atherosclerosis. It shows an inverse association between both the intake and the plasma concentration of vitamin E and the presence of carotid plaques, independently of other conventional risk factors.
Only a few studies have addressed the relation between antioxidant vitamins and carotid atherosclerosis. However, the methods used in those studies were quite different from ours: some studies focused on antioxidant vitamin intake as assessed by food-frequency questionnaires, some analyzed serum concentrations, and some verified the effect of vitamin E supplements on carotid atherosclerosis. In a cross-sectional study of the Atherosclerosis Risk in Communities (ARIC) population, dietary consumption of vitamins C and E was inversely associated with the thickness of the carotid artery wall in older women, although the use of dietary supplements partly accounted for this association. In a case-control study of subjects selected from the ARIC study cohort, serum -tocopherol concentrations were unrelated to carotid IMT. The effect of supplementary antioxidant vitamin intake on carotid atherosclerosis was analyzed in primates with experimentally induced atherosclerosis and in humans and yielded conflicting results: reduced progression of carotid IMT, no effect on carotid IMT changes in women but a beneficial effect of vitamin E + vitamin C in men, and a neutral effect on the progression of atherosclerosis. Vitamin E supplementation had various effects with regard to the modification of cardiovascular risk in patients with clinically overt heart diseases.
In the present study, a low dietary intake of vitamin E was associated with an increased risk of plaques at the carotid bifurcation, particularly in postmenopausal women, whereas no relation was found for plaques at the common carotid artery. From the analysis of the Progetto Atena food-frequency questionnaires and on the basis of dietary survey data, women in southern Italy obtain their vitamin E mainly from fresh vegetables, legumes, and olive oils. In addition, there is a high intake of monounsaturated fatty acids from olive oil, whereas the consumption of polyunsaturated fatty acids is relatively low.
A possible explanation for the association between vitamin E and plaques at the carotid bifurcation and for the lack of association for plaques at the common carotid artery is that early atherosclerosis usually begins at the bifurcations. The common carotid artery and the carotid bifurcation have different geometries, shear stresses, extracellular matrices, and cell compositions, and the mechanisms that regulate lesion development are also different. In addition, atherosclerotic plaques are known to develop mostly at the carotid bifurcation, where there is, on average, a greater wall thickness and therefore a higher likelihood of atherosclerotic lesion development.
Interesting data also come from the analysis of plasma antioxidant vitamin concentrations. It should be kept in mind that in epidemiologic studies it is important to adjust the plasma concentrations of vitamins A and E in relation to the plasma concentrations of lipoproteins. In particular, plasma concentrations of vitamin E are markedly influenced by both LDL and VLDL concentrations not only in hyperlipidemic patients but also in the general population. A simple way of dealing with this problem is to use the ratio of vitamin E to total cholesterol.
In the present study, lower plasma concentrations of vitamin E (adjusted for cholesterol) were found to be associated with an increased risk of plaques at the carotid bifurcation. Other plasma antioxidant vitamin concentrations (and the plasma ratio of vitamin A to cholesterol) showed no association with carotid plaques.
We could not rule out the possibility that the intake and the plasma concentration of vitamin E could reflect a healthier diet and that something other than vitamin E may be responsible for the apparent benefit on the development of carotid plaques. However, the lack of association between higher intakes of vitamin E or plasma concentrations of other antioxidant vitamins (ie, vitamins A and C, which are also considered markers of a healthier diet) and carotid plaques argue against this hypothesis. It should be remembered that none of the women in our study population took vitamin supplements.
Although recent studies on the association between vitamin E and atherosclerosis have been inconclusive, we have provided consistent evidence that both low intakes and low plasma concentrations of vitamin E are associated with early atherosclerotic carotid lesions. Therefore, a possible explanation for the benefit of vitamin E intake found in epidemiologic studies on healthy people without established atherosclerotic lesions and for the lack of benefit in clinical trials studying the effect of vitamin E supplementation in patients with clinically overtcardiovascular disease may be that the vascular protection occurs at early stages of atherosclerosis. The evidence of detectable arterial damage in the subjects in the lowest tertile of vitamin E intake and plasma concentration indicates that only individuals with an inadequate intake or a low plasma concentration of vitamin E are expected to benefit from an increase of vitamin E intake, either through dietary changes or supplementation. Thus, before advising subjects to change their diet or take antioxidant vitamin supplements, it would be helpful toevaluate their intakes and plasma concentrations, because knowing which individuals have the lowest intakes or plasma concentrations of vitamin E would help us identify those who could benefit the most from this type of intervention.
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