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Homocysteine reflects year of birth rather than age

Editorial background Johan Hultdin, MD, defended his theses (Illustration) May 27, 2005 (Umeå University Medical Dissertations, New Series No 969, ISSN 0346-6612, ISBN 91-7305-887-4, Department of Medical Biosciences, Clinical Chemistry, Umeå University, Umeå, Sweden), "Homocysteine in cardiovascular disease with special reference to longitudinal changes". Opponent of the Faculty was professor Bertil Kågedal, Linköping. One surprising finding was that homocysteine levels did not appear to increase on an individual level during an observation time of nine years. The changes of homocysteine over life time need further exploration.

Main findings

Both total plasma homocysteine and the MTHFR 677T allele may be risk factors for haemorrhagic stroke; the finding has not been reported previously in the same prospective study. In contrast, no association with ischaemic stroke was found.

A first myocardial infarction does not appear to increase long-term elevations of total plasma homocysteine in patients followed longitudinally in a prospective setting (nested case-control study). There was an association between first myocardial infarction and elevated homocysteine after the event; no longer significant after adjustment for creatinine as a measure of renal function.

Age-related differences in homocysteine levels were seen in cross-sectional analysis at baseline and at follow-up. However, no net changes of individual homocysteine levels were seen over a nine-year period in men and women. Furthermore, no increase in the prevalence of hyperhomocysteinemia could be observed in individuals observed for nine years.

Baseline levels of albumin, creatinine, cystatin C and hs-CRP were predictors of homocysteine levels at follow-up. After adjustment for homocysteine level at baseline, cystatin C was still singled out as an independent predictor.

It was demonstrated that the use of acidic medium (StabilyteTM) provides a simplification of sampling for epidemiological studies and biobank purposes.

Discussion and conclusions

The observations in the Hultdin dissertation suggest that the relationship between age and homocysteine level is more complex than previously assumed. The findings are compatible with the hypothesis that mechanistic - e.g. life-style, metabolic disorders, and intercurrent disease - modify homocysteine levels over time. Thus, homocysteine value may reflect year of birth rather than chronological age in some settings.

Prospective biobank studies of the Hultdin type are thought to provide an additional valuable source of information on diseases associated with homocysteine, since treatment studies often are confounded by e.g. population-based fortification with B vitamins, self-medication with B vitamins, and cholesterol-lowering prescriptions from the health care system.

Bo Norberg

Published September 30, 2005