Haematologica 1999; 84:E02

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HYPERHOMOCYSTEINEMIA IN SPANISH PATIENTS: MORE INFORMATION
Manuel Vargas, Inmaculada Soto, Carmen R. Pinto, Manuel F. Urgelles
Servicio de Hematologia, Hospital Central de Asturias, Oviedo, Spain

Correspondence: Manuel Vargas, Servicio de Hematologia, Hospital Central de Asturias, Oviedo, Spain
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Recently, González and coworkers have published a report on hyperhomocysteinemia in Spanish patients.1 We would like to do several considerations. In that article, the authors comment that it is the first report on the prevalence of hyperhomocysteinemia in a Spanish population with venous thromboembolism (VTE), but we want to remind them that our group have published previously data on hyperhomocysteinemia in Spanish patients with VTE.2
Our results differ from those of González et al. We did not find association between mild hyperhomocysteinemia and VTE. The differences may be explained by several facts. González et al. performed a methionine-loading test; this method might have detected more patients with hyperhomocysteinemia, but we think that there are also some methodological aspects which may have influenced the results. The patients are older than controls (52 years vs. 46), and there are more females in the control group. Advanced age and male sex have been associated with higher levels of homocysteine in many reports.2,3 Probably, this is the answer for the relatively low 95th percentile reported for the control group 11.43 µmol/L. When they analyse the clinical aspects, the most relevant result is the difference in age at first thrombotic event between hyperhomocysteinemic and non-hyperhomocysteinemic patients. It's really surprising that patients with hyperhomocysteinemia, apparently considered as a risk factor for VTE, develop their thrombotic episodes later than patients without this condition. Undoubtly, this result is related to the strong association between age and plasmatic levels of homocysteine, because the group of hyperhomocysteinemic patients have a relatively advanced age (63 years). Actually, we have included 107 patients with VTE in our study (70 males, 37 females; mean age 44 years). Comparing with 49 controls (32 males, 17 females; mean age 42.1 years) we did not find differences in homocysteine levels and percentages of hyperhomocysteinemic persons (table 1). Moreover, as we published previously, we have evaluated the possible causes of hyperhomocysteinemia. We have found that homocysteinemia is determined by genetic (MTHFR C677T polymorphism), but specially, adquired conditions (liver and kidney function, dietary habits).3

Table 1
Plasmatic homocysteine levels and percentage of hyperhomocysteinemic individuals in patients and controls.

 

 Patients

 Controls

p

 n

 107

 49

 

 Hcy (mmol/l)

 10.6

11.1

ns*

 HHcy (%)

12.1%

8.1%

ns**
Hcy: homocysteinemia. HHcy: Hyperhomocysteinemic persons.
n.s.: non-significant
* t-Student test. ** Pearson's chi-square test.

 

Recently, Brattström et al. have performed a meta-analysis of MTHFR C677T mutation in arterial and venous thrombosiS.4 This mutation is not associated with thrombotic disease, but it is a common cause of mild hyperhomocysteinemia. The authors suggest that the hyperhomocysteinemia found in the vast majority of the studies, specially in arterial disease, may be an epiphenomenon, without causal relation with the thrombotic event.
We think that there are many confounding factors in hyperhomocysteinemia and thrombotic disease, which must be studied in proof before we can do some recommendations.

References

  1. González Y, Souto JC, Mateo J, Córdoba A, Blanco-Vaca F, Fontcuberta J. Moderate hyperhomocysteinemia is a highly prevalent defect in Spanish patients with venous thromboembolic disease. Haematologica 1998;83:1126-7.
  2. Vargas M, Soto I, R.Pinto C; F.Urgellés M, Coto E. Mild hyperhomocysteinemia and MTHFR C677T do not increase the risk for venous thrombosis in a Spanish population. Blood Coagul Fibrinolysis 1998;9:555-6.
  3. Lindgren A, Brattström L, Norrving B, Hultberg B, Andersson A, Johansson BB. Plasma homocysteine in the acute and convalescent phases after stroke. Stroke 1995;26:795-800.
  4. Brattström L, Wilcken DE, Ohrvk J, Brudin L. Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis. Circulation 1998;98:2520-6.