Article Text

Hyperhomocysteinaemia, Helicobacter pylori , and coronary heart disease
  1. V SAXENA
  1. Division of Gastroenterology,Endocrinology and Metabolism,
  2. St George’s Hospital Medical School,
  3. London, UK
  4. Department of Clinical Neurosciences,
  5. King’s College School of Medicine and Dentistry,
  6. London, UK
  7. Department of Clinical Chemistry,
  8. St Thomas Hospital,
  9. London, UK
  10. Division of Gastroenterology,Endocrinology and Metabolism,
  11. St George’s Hospital Medical School,
  12. London, UK
    1. H MARKUS
    1. Division of Gastroenterology,Endocrinology and Metabolism,
    2. St George’s Hospital Medical School,
    3. London, UK
    4. Department of Clinical Neurosciences,
    5. King’s College School of Medicine and Dentistry,
    6. London, UK
    7. Department of Clinical Chemistry,
    8. St Thomas Hospital,
    9. London, UK
    10. Division of Gastroenterology,Endocrinology and Metabolism,
    11. St George’s Hospital Medical School,
    12. London, UK
      1. S SWAMINATHAN
      1. Division of Gastroenterology,Endocrinology and Metabolism,
      2. St George’s Hospital Medical School,
      3. London, UK
      4. Department of Clinical Neurosciences,
      5. King’s College School of Medicine and Dentistry,
      6. London, UK
      7. Department of Clinical Chemistry,
      8. St Thomas Hospital,
      9. London, UK
      10. Division of Gastroenterology,Endocrinology and Metabolism,
      11. St George’s Hospital Medical School,
      12. London, UK
        1. M E MENDALL
        1. Division of Gastroenterology,Endocrinology and Metabolism,
        2. St George’s Hospital Medical School,
        3. London, UK
        4. Department of Clinical Neurosciences,
        5. King’s College School of Medicine and Dentistry,
        6. London, UK
        7. Department of Clinical Chemistry,
        8. St Thomas Hospital,
        9. London, UK
        10. Division of Gastroenterology,Endocrinology and Metabolism,
        11. St George’s Hospital Medical School,
        12. London, UK

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          Sir,—Hyperhomocysteinaemia and Helicobacter pylori infection have recently been implicated in the pathogenesis of coronary heart disease and a possible link between these factors has been suggested in this journal.1 Our work has shown that chronic infection with H pyloriconfers a twofold risk of coronary heart disease2 and this association, like hyperhomocysteinaemia, is independent of hypertension, smoking, and hyperlipidaemia. Our studies have shown that fibrinogen concentrations and total leucocyte counts were higher inH pylori seropositive patients with cardiovascular disease.3 We therefore suggested that the mechanism is chronic infection accompanied by persistent inflammation.

          Sir,—Hyperhomocysteinaemia andHelicobacter pylori infection have recently been implicated in the pathogenesis of coronary heart disease and a possible link between these factors has been suggested in this journal.1Our work has shown that chronic infection with H pyloriconfers a twofold risk of coronary heart disease2 and this association, like hyperhomocysteinaemia, is independent of hypertension, smoking, and hyperlipidaemia. Our studies have shown that fibrinogen concentrations and total leucocyte counts were higher inH pylori seropositive patients with cardiovascular disease.3 We therefore suggested that the mechanism is chronic infection accompanied by persistent inflammation.

          It has recently been postulated that chronic gastritis caused byH pylori infection may cause clinical or subclinical cobalamin deficiency. This damage to the gastric parietal cell may be initiated by autoimmune cross reactivity between identical lipopolysaccharides on the bacterium and the gastric parietal cell itself.4 As a result, either through reduced acid output leading to malabsorption of food bound cobalamin or intrinsic factor production, subclinical cobalamin deficiency may develop. As a consequence of reduced cobalamin, hyperhomocysteinaemia develops.5 Homocysteine is directly toxic to endothelial cells and can inhibit the secretion of nitric oxide from endothelial cells, therefore facilitating platelet aggregation and vasoconstriction.6 Thus, the possible link between H pylori and serum homocysteine levels lent itself to investigation.

          We assessed both the H pylori status measured by enzyme linked immunosorbent assay (ELISA), and total homocysteine concentrations measured by reverse phase high performance liquid chromatography with precolumn derivatisation and fluorometric detection based on the method of Fiskerstrand et al,7on serum from a population of 220 individuals (143 men, 77 women; mean (SD) age 66 (9.4), range 35–86). The mean (SD) serum homocysteine concentration was 22.7 (11) nmol/l. As the data were positively skewed, they was log transformed before statistical analysis (unpairedt test).

          We found no significant difference (p = 0.30) between the homocysteine concentrations in the H pylori seropositive (n = 122, mean 21.8 (8.6) nmol/l) and seronegative groups (n = 98, 24.0 (13.4) nmol/l). There was, however, a non-significant trend (p = 0.20) in patients over the age of 50 towards lower homocysteine in the seropositive (21.7 (8.6) nmol/l) compared to the seronegative group (24.3 (13.8) nmol/l).

          It has been suggested that serum homocysteine may exhibit a sex difference, with men having higher concentrations. This was not borne out by our data: seronegative women 23.6 (15.2) nmol/l, seropositive women 21.4 (6.8) nmol/l (p = 0.82); seronegative men 24.2 (12.2) nmol/l, seropositive men 21.9 (9.3) nmol/l) (p = 0.26).

          Our data, therefore, do not show that H pyloriseropositivity is associated with hyperhomocysteinaemia; if anything, there was a trend towards lower homocysteine being associated withH pylori seropositivity. This may reflect the age of the study population and we may need to focus measurements on an older group in whom gastric atrophy resulting from H pylorigastritis is more advanced.

          This shows that serum homocysteine levels are not altered by H pylori infection, and that if the association of H pylori with coronary heart disease is a true one then other mechanisms must be sought. Chronic inflammation remains the leading candidate.

          References

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