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. 2007 May 1;6(4):583–592. doi: 10.1111/j.1582-4934.2002.tb00456.x

Blood histamine is associated with coronary artery disease, cardiac events and severity of inflammation and atherosclerosis

Sanda Clejan 1,3,✉, Shenkar Japa 1,3, C Clemetson 2, Sanjeev S Hasabnis 2, Odile David 1, J V Talano 2
PMCID: PMC6741342  PMID: 12611642

Abstract

Background: Mast cells are prevalent in the shoulder of unstable atheromas; cardiac mast cells secrete proteases capable of activating matrix metalloproteinases. Histamine is essential in the inflammatory cascade of the unstable plaque. Ascorbate depletion has been correlated with histaminemia which has been shown to impair endothelial‐dependent vasodilation. This study evaluates whether oxidative stress as measured by isoprostanes (PGF2α) coupled with an inflammatory state characterized by histaminemia predisposes patients to acute coronary syndrome (ACS).

Methods: Whole blood histamine, serum vitamin C, and serum PGF2α levels were drawn on 50 patients with ACS as determined by standard diagnostic criteria, 50 patients with stable coronary artery disease (SCAD), and 50 age and sex matched normal controls (C).

Results: Data were analyzed by stepwise discriminant and Spearman's rank correlation coefficient. A significant relationship exists between histamine and PGF2α. As PGF2α rises above 60 pg/mL, an increase in histamine occurs in both the ACS and SCAD groups. A significant inverse relationship exists between ascorbate and histamine in the ACS versus C groups (P < 0.01) and the SCAD versus C groups (P < 0.01).

Conclusion: Histamine and isoprostane levels increase in SCAD and ACS patients. Mast cell activation and lipid oxidation generated during atherosclerosis manifest this inflammatory response. Accelerated isoprostane formation and depleted ascorbate paired with histaminemia is active in CAD and predispose patients to acute coronary syndrome. Blood histamine alone may be a better risk factor for coronary events, and a better prognostic indicator than CRP even when combined with lipid indexes.

Keywords: histaminemia, coronary artery disease syndrome, risk factors, oxidative stress, biochemical markers of inflammation, atherosclerosis

References

  • 1. Clemetson C.A.B., The key role of histamine in the development of atherosclerosis and coronary heart disease, Medical Hypotheses, 52: 1–8, 1999. [DOI] [PubMed] [Google Scholar]
  • 2. Chatterjee I.B., Majumder A.K., Nandi B.K., Subramanian N., Synthesis and some major functions of vitamin C in animals, Ann. NY Acad. Sci., 258: 24–47, 1975. [DOI] [PubMed] [Google Scholar]
  • 3. Clemetson C.A.B., Histamine and ascorbic acid in human blood, 110: 662–668, 1980. [DOI] [PubMed] [Google Scholar]
  • 4. Gore I., Tanaka Y., Fujinami T., Shirahama T., Endothelial changes produced by ascorbic acid deficiency in guinea pigs, Arch. Pathol., 80: 371–376, 1965. [PubMed] [Google Scholar]
  • 5. Majno G., Palade C.E., Studies on inflammation: The effect of histamine and serotonin on vascular permeability, J. Biophys. Biochem. Cytol., 11: 571–605, 1961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Cutforth R.H., Adult scurvy, Lancet, 1: 454–456, 1958. [DOI] [PubMed] [Google Scholar]
  • 7. Paterson J.C., Some factors in the causation of internal hemorrhages and in the precipitation of coronary thrombi, Can. Med. Assoc. J., 44: 114–120, 1941. [PMC free article] [PubMed] [Google Scholar]
  • 8. Johnston C.S., Solomon R.E., Corte C., Vitamin C depletion is associated with alterations in blood histamine in adults, J. Am. Col. Nutr., 15: 586–591, 1996. [DOI] [PubMed] [Google Scholar]
  • 9. Manson J.E., Stampler M.J., Willett W.C., et al. A prospective study of vitamin C and incidence of coronary artery disease in women, Circulation 85: 865 (14a), 1992. [Google Scholar]
  • 10. Stenvinkel P., Heimburger F.P., Dicfalusy U., et al., Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure, Kidney International, 55: 1899–1911, 1999. [DOI] [PubMed] [Google Scholar]
  • 11. Black D., Reilly C.F., Inflammatory mechanisms in atherosclerosis, Inflammation Research, 46: 237–241, 1997. [DOI] [PubMed] [Google Scholar]
  • 12. Dhariwal K.R., Whashko P.W., Levine M., Determination of dehydroascorbic acid using high performance chromatography with coulometric detection, Anal. Biochem., 189: 18–23, 1990. [DOI] [PubMed] [Google Scholar]
  • 13. Vuilleumier J.P., Keck E., Fluorometric assay of vitamin C in biological materials using a centrifugal analyser with fluorescence attachment, J. Micronutrient Anal., 5: 25–34, 1989. [Google Scholar]
  • 14. Zhao Z., Hjelm M.N., Lam C.W.K., Ho C.S., Onestep solid‐phase extraction procedure of F2‐isoprostanes, Clin. Chem., 47: 1306–1308, 2001. [PubMed] [Google Scholar]
  • 15. Nourooz‐Zadeh J., Gas chromatography‐mass spectrometry assay for measurement of plasma isoprostanes, Methods Enzymol., 300: 13–7, 1999. [DOI] [PubMed] [Google Scholar]
  • 16. Bataile R., Klein B., C‐reactive protein levels as a direct indicator of Interleukin 6 levels in human in vivo , Arthritis Rheum. 35: 982–984, 1992. [DOI] [PubMed] [Google Scholar]
  • 17. Frei B., Stocker R, England L., Ames B.N., Ascorbate: the most effective antioxidant in human blood plasma, Adv. Exp. Med. Biol., 264: 155–163, 1990. [DOI] [PubMed] [Google Scholar]
  • 18. Frei B., England L., Ames B.N., Ascorbate is an outstanding antioxidant in human blood plasma, Proc. Natl. Acad. Sci., U.S.A., 86: 6377–6381, 1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Jialal I., Grundy S.M., Preservation of endogenous antioxidants in LDL by ascorbate but not probucol during oxidative modification, J. Clin. Invest., 87: 597–601, 1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Frei B., Acerbic acid protects lipids in human plasma and low‐density lipoprotein against oxidative damage, Am. J. Clin. Nutr., 54: 1113–1185, 1991. [DOI] [PubMed] [Google Scholar]
  • 21. Riemersma R.A., Wood D.A., Maclntyre C.C.A., Elton R.A., Gey K.F., Oliver M.F., Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene, Lancet, 337: 1–5, 1991. [DOI] [PubMed] [Google Scholar]
  • 22. Morrow J.D., Harris T.M., Roberts L.J., A series of prostaglandin F2‐like compounds are produced in vivo in humans by non‐cyclooxygenase, free radical‐catalyzed mechanism, Proc. Natl. Acad. Sci. U.S.A., 87: 9383–9387, 1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Comiancini L., Fratta Pasini A., Garbin U., Camapagnola M., Davoli A., Rigoni A., Zenti M.G., Pastorino A.M., LoCascio V., E‐selectin plasma concentration is influenced by glycemic control in NIDDM patients: possible role of oxidative stress, Diabetologia, 40: 584–589, 1997. [DOI] [PubMed] [Google Scholar]
  • 24. Santini S.A., Marra G., Giardina B., Cotroneo P., Mordente A., Martorana G.E., Manto A., Ghirlanda G., Defective plasma antioxidant defenses and enhanced susceptibility to lipid peroxidation in uncomplicated IDDM, Diabetes, 46: 1853–1858, 1997. [DOI] [PubMed] [Google Scholar]
  • 25. Yoshida H., Ishikawa T., Nakamura H., Vitamin E/lipid peroxide ratio and susceptibility of LDL to oxidative modification in non‐insulin dependent diabetes mellitus, Arterioscler. Thromb. Vase. Biol., 17: 1438–1446, 1997. [DOI] [PubMed] [Google Scholar]
  • 26. Jenkins A.J., Klein R.L., Chassereau C.N., Hermayer K.L., Lopes‐Virella M.F., LDL from patients with well‐controlled IDDM is not more susceptible to in vitro oxidation, Diabetes, 45: 762–767, 1996. [DOI] [PubMed] [Google Scholar]
  • 27. Listen T.E., Roberts L.J.I.I., Metabolic fate of radiolabeled prostaglandin D2 in a normal human male volunteer, J. Biol. Chem. 260 (24): 13172–13180, 1985. [PubMed] [Google Scholar]

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