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Coronary heart disease mortality, plasma homocysteine, and B-vitamins: a prospective study
Angelika de Bree1, W Monique M Verschuren, Henk J Blom
1Department of Chronic Disease Epidemiology (pb 101), National Institute of Public Health and the Environment (RIVM), PO Box 1, NL-3720 BA Bilthoven, The Netherlands.
Insights
Elevated total homocysteine (tHcy) levels do not appear to increase coronary heart disease (CHD) mortality risk in young, healthy Dutch adults. High folate levels may offer protection against fatal CHD, warranting further investigation.
Area of Science:
- Cardiovascular Epidemiology
- Nutritional Science
- Biochemistry
Background:
- Prospective studies on total homocysteine (tHcy) and B-vitamins in relation to coronary heart disease (CHD) mortality have yielded inconclusive results, particularly concerning B-vitamins.
- Existing research is scarce regarding the specific association between B-vitamins and CHD mortality.
Purpose of the Study:
- To prospectively investigate the relationship between plasma concentrations of total homocysteine (tHcy), folate, vitamin B12, and pyridoxal-5'-phosphate (PLP, vitamin B6).
- To examine the association of these biomarkers with coronary heart disease (CHD) mortality in a Dutch adult population.
Main Methods:
- A case-cohort study design was employed, utilizing a random sample (n=630) from a full cohort of approximately 36,000 Dutch adults (aged 20-59 at baseline).
- All subjects who died of CHD (n=102) during a mean follow-up of 10.3 years were included.
- Plasma tHcy, folate, PLP, and vitamin B12 levels were measured at baseline in participants free of cardiovascular diseases (CVDs).
Main Results:
- Elevated tHcy concentrations were not significantly associated with increased CHD mortality risk in men or women, nor in combined analyses.
- High plasma folate levels showed a statistically significant protective association against fatal CHD in women (RR: 0.22, 95% CI: 0.06, 0.87).
- Plasma concentrations of vitamin B12 and PLP (vitamin B6) were not associated with CHD risk.
Conclusions:
- Elevated tHcy concentrations do not appear to be a risk factor for CHD mortality in this cohort of relatively young, healthy Dutch individuals without baseline CVD.
- Higher folate concentrations may offer a protective effect against fatal CHD, although this finding requires further confirmation.
- Vitamin B12 and vitamin B6 status were not linked to CHD mortality in this study population.
Abstract:
The results of prospective studies on the relations between the plasma concentration of total homocysteine (tHcy) and B-vitamins, on the one hand, and coronary heart disease (CHD) mortality, on the other hand, are inconclusive and scarce considering the relation with B-vitamins. We prospectively determined these relations in a case-cohort study. The full-cohort existed in approximately 36,000 Dutch adults aged 20-59 years at baseline. The statistical analyses were done with a random sample from the cohort (n=630) complemented with all subjects who died of CHD (n=102) during a mean follow-up of 10.3 years. All subjects reported the absence of cardiovascular diseases (CVDs) at baseline. The plasma concentrations of tHcy, folate, PLP, and vitamin B12 were determined in samples obtained at baseline. Men with a tHcy concentration in the highest tertile (T3) compared with men in the lowest tertile (T1) had a relative risk (RR) of 1.14 for CHD (95% confidence interval (CI): 0.50, 2.61) after adjusting for age, study center, hypertension, HDL and total cholesterol, smoking, and creatinine. For women, this RR was 2.04 (95% CI: 0.48, 8.62). For each 5 micromol/l increase in tHcy, the RR of CHD was 1.03 (95% CI: 0.83-1.29) for men and women combined. In women only, high folate levels were associated with a statistically significant protection of fatal CHD (T3 versus T1; RR: 0.22, 95% CI: 0.06, 0.87). Plasma PLP (B6) and vitamin B12 concentrations were not associated with CHD risk. We conclude that elevated tHcy concentrations do not seem to be a risk factor for CHD mortality in these relatively young healthy Dutch subjects free of baseline CVD. Higher folate concentrations may be protective of CHD, but this needs confirmation.