Relationship of systolic blood pressure with plasma homocysteine: importance of smoking status

Background Elevated plasma homocysteine is a risk factor for cardiovascular disease. Elevations in plasma homocysteine occur in both smokers and hypertensives, but the combined effect of smoking and hypertension on homocysteine is unknown. Methods Resting plasma homocysteine levels and blood pressure were determined in 56 normotensives (112 smokers) and 20 essential hypertensives 0 0 smokers). Results Plasma homocysteine was significantly higher in all smokers versus all non-smokers (9.46 +/- 0.5 versus 7.9 +/- 0.5 mumol/l, P = 0.041) by two-way ANOVA, and was also significantly higher in all hypertensives versus all normotensives (9.8 +/- 0.6 versus 7.6 +/- 0.4 mumol/l, P = 0.004). There was no interaction between the effects of hypertension and smoking on plasma homocysteine. Hypertensive smokers had significantly higher plasma homocysteine than either normotensive non-smokers (10.65 +/- 0.84 versus 7.05 +/- 0.26 mumol/l), hypertensive non-smokers (7.88 +/- 0.64 mumol/l) or normotensive smokers (8.36 +/- 0.5 mumol/l). In subjects overall, homocysteine levels were correlated (r = 0.306, P = 0.015) with systolic blood pressure but not with diastolic (r = 0.186). This relationship was also significant in smokers, but not non-smokers. Furthermore, subjects in the highest quintile for plasma homocysteine had significantly higher systolic BP than those in the lowest quintile. This effect was not observed when smokers were removed from the analysis. Conclusion Smoking compounds the modest effect of hypertension on plasma homocysteine. The strong relationship between systolic blood pressure and homocysteine that exists only in smokers suggests that smoking-induced homocysteine elevations may raise systolic blood pressure. We speculate that smoking compounds the risk of cardiovascular disease in hypertensives, in part, by elevating homocysteine.