Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-05T02:38:24.477Z Has data issue: false hasContentIssue false
  • English
  • Français

Plasma concentrations of ascorbic acid and C-reactive protein, and risk of future coronary artery disease, in apparently healthy men and women: the EPIC-Norfolk prospective population study

Published online by Cambridge University Press:  08 March 2007

S. Matthijs Boekholdt ,
Marijn C. Meuwese ,
Nicholas E. Day ,
Robert Luben ,
Ailsa Welch ,
Nicholas J. Wareham  and
Kay-Tee Khaw
S. Matthijs Boekholdt*
Affiliation:
Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands
Marijn C. Meuwese
Affiliation:
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Nicholas E. Day
Affiliation:
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK
Robert Luben
Affiliation:
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK
Ailsa Welch
Affiliation:
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK
Nicholas J. Wareham
Affiliation:
Medical Research Council Epidemiology Unit, Cambridge, UK
Kay-Tee Khaw
Affiliation:
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK
*
*Corresponding author: Dr S. M. Boekholdt, fax +31 20 5669343, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

High plasma concentrations of ascorbic acid, a marker of fruit and vegetable intake, are associated with low risk of coronary artery disease. Whether this relationship is explained by a reduction in systemic inflammation is unclear. We investigated the relationship between ascorbic acid plasma concentration and coronary artery disease risk, and in addition whether this relationship depended on classical risk factors and C-reactive protein (CRP) concentration. We used a prospective nested case–control design. The study consisted of 979 cases and 1794 controls (1767 men and 1006 women). Increasing ascorbic acid quartiles were associated with lower age, BMI, systolic and diastolic blood pressure, and CRP concentration, but with higher HDL-cholesterol concentration. No associations existed between ascorbic acid concentration and total cholesterol concentration or LDL-cholesterol concentration. When data from men and women were pooled, the risk estimates decreased with increasing ascorbic acid quartiles such that people in the highest ascorbic acid quartile had an odds ratio for future coronary artery disease of 0·67 (95% CI 0·52, 0·87) compared with those in the lowest quartile (P for linearity=0·001). This relationship was independent of sex, age, diabetes, smoking, BMI, LDL-cholesterol, HDL-cholesterol, systolic blood pressure and CRP level. These data suggest that the risk reduction associated with higher ascorbic acid plasma concentrations, a marker of fruit and vegetable intake, is independent of classical risk factors and also independent of CRP concentration.

Keywords

Ascordic acidVitamin COxidationC-reactive proteinInflammationCoronary artery disease
Type
Research Article
Information
British Journal of Nutrition , Volume 96 , Issue 3 , September 2006 , pp. 516 - 522
Copyright
Copyright © The Nutrition Society 2006

References

Afridi, N & Keaney, JF (1996) Animal studies on antioxidants. J Cardiovasc Risk 3, 358–362.CrossRefGoogle ScholarPubMed
Bates, CJ, Thurnham, SI, Bingham, SA, Margetts, BM & Nelson, M (1991) Biochemical markers of nutrition intake. In Design Concepts in Nutritional Epidemiology, pp. 192–265 [Margetts, BM and Nelson, M, editors]. Oxford: Oxford Medical Publications.Google Scholar
Binder, CJ, Chang, MK, Shaw, PX, Miller, YI, Hartvigsen, K, Dewan, A & Witztum, JL (2002) Innate and acquired immunity in atherogenesis. Nat Med 8, 1218–1226.CrossRefGoogle ScholarPubMed
Bruins, P, te Velthuis, H, Yazdanbakhsh, AP, Jansen, PG, van Hardevelt, FW, de Beaumont, EM, Wildevuur, CR, Eijsman, L, Trouwborst, A & Hack, CE (1997) Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia. Circulation 96, 3542–3548.CrossRefGoogle ScholarPubMed
Bruunsgaard, H, Poulsen, HE, Pedersen, BK, Nyyssonen, K, Kaikkonen, J & Salonen, JT (2003) Long-term combined supplementations with alpha-tocopherol and vitamin C have no detectable anti-inflammatory effects in healthy men. J Nutr 133, 1170–1173.CrossRefGoogle ScholarPubMed
Carr, AC, Tijerina, T & Frei, B (2000) Vitamin C protects against and reverses specific hypochlorous acid-and chloramine-dependent modifications of low-density lipoprotein. Biochem J 346, 491–499.CrossRefGoogle ScholarPubMed
Day, N, Oakes, S, Luben, R, Khaw, KT, Bingham, S, Welch, A & Wareham, N (1999) EPIC-Norfolk: study design and characteristics of the cohort. European Prospective Investigation of Cancer. Br J Cancer 80, 95–103.Google Scholar
Dietrich, M, Block, G, Norkus, EP, Hudes, M, Traber, MG, Cross, CE & Packer, L (2003) Smoking and exposure to environmental tobacco smoke decrease some plasma antioxidants and increase gamma-tocopherol in vivo after adjustment for dietary antioxidant intakes. Am J Clin Nutr 77, 160–166.CrossRefGoogle ScholarPubMed
Duthie, GG & Bellizzi, MC (1999) Effects of antioxidants on vascular health. Br Med Bull 55, 568–577.CrossRefGoogle ScholarPubMed
Ford, ES, Liu, S, Mannino, DM, Giles, WH & Smith, SJ (2003) C-reactive protein concentration and concentrations of blood vitamins, carotenoids, and selenium among United States adults. Eur J Clin Nutr 57, 1157–1163.CrossRefGoogle ScholarPubMed
Frei, B, England, L & Ames, BN (1989) Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci USA 86, 6377–6381.CrossRefGoogle ScholarPubMed
Friedewald, WT, Levy, RI & Fredrickson, DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18, 499–502.CrossRefGoogle ScholarPubMed
Gaziano, JM (1996) Randomized trials of dietary antioxidants in cardiovascular disease prevention and treatment. J Cardiovasc Risk 3, 368–371.CrossRefGoogle ScholarPubMed
Heart Protection Study Collaborative Group (2002) MR/HF Heart protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360, 23–33.CrossRefGoogle Scholar
Jialal, I & Grundy, SM (1991) Preservation of the endogenous antioxidants in low density lipoprotein by ascorbate but not probucol during oxidative modification. J Clin Invest 87, 597–601.CrossRefGoogle Scholar
Khaw, KT, Bingham, S, Welch, A, Luben, R, Wareham, N, Oakes, S & Day, N (2001) Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. Lancet 357, 657–663.CrossRefGoogle ScholarPubMed
Langlois, M, Duprez, D, Delanghe, J, De Buyzere, M & Clement, DL (2001) Serum vitamin C concentration is low in peripheral arterial disease and is associated with inflammation and severity of atherosclerosis. Circulation 103, 1863–1868.CrossRefGoogle ScholarPubMed
Lehr, HA, Frei, B, Olofsson, AM, Carew, TE & Arfors, KE (1995) Protection from oxidized LDL-induced leukocyte adhesion to microvascular and macrovascular endothelium in vivo by vitamin C but not by vitamin E. Circulation 91, 1525–1532.CrossRefGoogle Scholar
Loria, CM, Klag, MJ, Caulfield, LE & Whelton, PK (2000) Vitamin C status and mortality in US adults. Am J Clin Nutr 72, 139–145.CrossRefGoogle ScholarPubMed
Ness, AR, Khaw, KT, Bingham, S & Day, NE (1996a) Vitamin C status and serum lipids. Eur J Clin Nutr 50, 724–729.Google ScholarPubMed
Ness, AR, Khaw, KT, Bingham, S & Day, NE (1996b) Vitamin C status and blood pressure. J Hypertension 14, 503–508.CrossRefGoogle ScholarPubMed
Nyyssonen, K, Parviainen, MT, Salonen, R, Tuomilehto, J & Salonen, JT (1997) Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland. BMJ 314, 634–638.CrossRefGoogle ScholarPubMed
Rexrode, KM & Manson, JE (1996) Antioxidants and coronary heart disease: observational studies. J Cardiovasc Risk 3, 363–367.CrossRefGoogle ScholarPubMed
Ross, R (1999) Atherosclerosis: an inflammatory disease. N Engl J Med 340, 115–126.CrossRefGoogle ScholarPubMed
Sahyoun, NR, Jacques, PF & Russell, RM (1996) Carotenoids, vitamins C and E, and mortality in an elderly population. Am J Epidemiol 144, 501–511.CrossRefGoogle Scholar
Sargeant, LA, Wareham, NJ, Bingham, S, Day, NE, Luben, RN, Oakes, S, Welch, A & Khaw, KT (2000) Vitamin C and hyperglycemia in the European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk) study: a population-based study. Diabetes Care 23, 726–732.CrossRefGoogle Scholar
Siow, RC, Richards, JP, Pedley, KC, Leake, DS & Mann, GE (1999) Vitamin C protects human vascular smooth muscle cells against apoptosis induced by moderately oxidized LDL containing high levels of lipid hydroperoxides. Arterioscler Thromb Vasc Biol 19, 2387–2394.CrossRefGoogle ScholarPubMed
Siow, RC, Sato, H, Leake, DS, Pearson, JD, Bannai, S & Mann, GE (1998) Vitamin C protects human arterial smooth muscle cells against atherogenic lipoproteins: effects of antioxidant vitamins C and E on oxidized LDL-induced adaptive increases in cystine transport and glutathione. Arterioscler Thromb Vasc Biol 18, 1662–1670.CrossRefGoogle Scholar
Vuilleumier, J & Keck, E (1989) Fluorometric assay of vitamin C in biological materials using a centrifugal analyser with fluorescence attachment. J Micronutrient Anal 5, 25–34.Google Scholar
World Health Organization (1977) International Classification of Diseases, 9th rev. Geneva: World Health Organization.Google Scholar
Yusuf, S, Dagenais, G, Pogue, J, Bosch, J & Sleight, P (2000) Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342, 154–160.Google Scholar
Zhu, XY, Rodriguez-Porcel, M, Bentley, MD, Chade, AR, Sica, V, Napoli, C, Caplice, N, Ritman, EL, Lerman, A & Lerman, LO (2004) Antioxidant intervention attenuates myocardial neovascularization in hypercholesterolemia. Circulation 109, 2109–2115.CrossRefGoogle ScholarPubMed