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A meta-analysis of cerebrovascular disease and hyperhomocysteinaemia
J Møller1, G M Nielsen, K C Tvedegaard
1Department of Clinical Biochemistry, Aarhus University Hospital at Skejby, Denmark. jan@kba.sks.au.dk
Insights
Elevated homocysteine levels (hyperhomocysteinaemia) are a significant risk factor for stroke and cerebrovascular disease. This meta-analysis confirms a strong association between high homocysteine and increased odds of developing these conditions.
Area of Science:
- Neurology
- Cardiovascular Science
- Biochemistry
Background:
- Hyperhomocysteinaemia is increasingly recognized as a potential risk factor for cerebrovascular diseases, including stroke.
- Previous studies have suggested a link, but a comprehensive evaluation of the evidence was needed.
Purpose of the Study:
- To conduct a meta-analysis evaluating the association between hyperhomocysteinaemia and the risk of stroke and cerebrovascular disease.
Main Methods:
- A systematic literature search was performed across multiple databases (Medline, Embase, Science Citation Index, Biological Abstract) from 1966 to July 1999.
- Included studies provided data on plasma or serum total homocysteine levels in cases and controls.
- Meta-analysis calculated odds-ratios for disease associated with homocysteine concentrations above the 95th percentile of controls, assuming a log-normal distribution.
Main Results:
- Twelve studies (8 cross-sectional, 4 longitudinal) met the inclusion criteria for meta-analysis.
- The overall weighted odds-ratio for cerebrovascular disease with homocysteine levels above the 95th percentile was 3.97 (95% CI: 3.07-5.12).
- Both cross-sectional (OR: 4.12) and longitudinal (OR: 3.74) studies showed a significant positive relationship.
Conclusions:
- The findings strongly support a significant association between hyperhomocysteinaemia and cerebrovascular disease.
- Elevated homocysteine levels represent a considerable risk factor for stroke and related conditions.
- Further research may elucidate the mechanisms and clinical implications of this association.
Abstract:
Hyperhomocysteinaemia has been identified as a risk factor for stroke and cerebrovascular disease in several studies. To evaluate the evidence we performed a meta-analysis. We found 21 studies searching Medline from 1966-July 1999 using the key words homocysteine, homocystine and cerebrovascular disease or stroke combined with a search of Embase, Science Citation Index and Biological Abstract. In 17 of these studies the populations were comparable. The studies were divided into two groups, cross-sectional studies and longitudinal studies where a pre-insult plasma or serum total homocysteine was used. The reports on 8 cross-sectional and 4 longitudinal studies gave data on the mean and standard deviations of plasma or serum homocysteine for both cases and controls, and these studies were included in the meta-analysis. The results of the 5 excluded studies all pointed to a positive relationship between hyperhomocysteinaemia and cerebrovascular disease. For each study, the expected fractions of the cases with total homocysteine higher than the 95-percentile for the controls were calculated, using the means and standard deviations, assuming a log-normal distribution, and the odds-ratios for disease with total homocysteine above the 95-percentile were computed. The overall weighted odds-ratio for disease with a concentration of homocysteine in plasma or serum above the 95-percentile (95% confidence interval) for the cross-sectional studies was 4.12 (2.94-5.77), for the longitudinal studies 3.74 (2.53-5.54), and for all 12 studies 3.97 (3.07-5.12). In conclusion, the results support the case for a strong relation between hyperhomocysteinaemia and cerebrovascular disease.