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Homocysteine and stroke


There is growing evidence that high levels of homocysteine are associated with heart disease. This study examines whether there is an association between homocysteine levels and stroke.


Non-fasting total homocysteine is an independent risk factor for stroke in men and women aged 60 years or older. Levels above 14 µmol/L are associated with an 80% increased risk of total stroke.


AG Bostom et al. Nonfasting plasma total homocysteine levels and stroke incidence in elderly persons: The Framingham Study. Annals of Internal Medicine 1999 131: 352-355.


Participants were 1,158 women and 789 men from the Framingham Study (who had not had stroke) who were examined between 1979 and 1982 and re-examined in 1992. Non-fasting total homocysteine levels were measured and demographic information and medical histories taken. Participants' average age was 70 years (range 59 to 91 years); systolic blood pressure 141 mm Hg (range 86 to 225 mm Hg); and total homocysteine level 12.65 µmol/L (range 4.13 to 219.84 µmol/L).

Total homocysteine levels were divided into quartiles: quartile one, 4.13 to 9.25 µmol/L; quartile two, 9.26 to 11.43 µmol/L; quartile three, 11.44 to 14.23 µmol/L; and quartile four, 14.24 to 219.84 µmol/L. Levels below 14 µmol/L are considered 'normal'.

Participants were followed for a median of 9.9 years during which time 165 total strokes occurred, 153 of which were non-hemorrhagic strokes and 100 were atherothrombotic brain infarctions.


Total homocysteine levels were higher in men than in women (12.35 compared with 11.32 µmol/L), in patients with a history of atrial fibrillation than in those without (13.17 compared with 11.66 µmol/L) and in patients with a history of coronary heart disease than in those without (12.49 compared with 11.57 µmol/L). Levels did not differ between patients with or without diabetes or between cigarette smokers and non-smokers.

Age, systolic blood pressure, smoking, diabetes, history of atrial fibrillation and coronary heart disease were risk factors for total stroke (see Table 1).

Table 1. Risk factors for total stroke.


Relative risk (95% confidence interval)

Age, per one-year increase

1.06 (1.04 - 1.09)

Systolic blood pressure, per 20 mmHg increase

1.16 (1.01 - 1.34)


1.52 (1.03 - 2.24)


1.90 (1.25 - 2.89)

Atrial fibrillation

2.29 (1.29 - 4.04)

Coronary heart disease

1.49 (1.04 - 2.16)

Total homocysteine level (quartile 4 compared with quartile 1)

1.82 (1.14 - 2.91)


Compared with total homocysteine levels in quartile one, levels in quartile four were associated with an 82% increased risk of total stroke (relative risk 1.82, 95% confidence interval 1.14 to 2.91); a 79% increased risk of non-hemorrhagic stroke (relative risk 1.79, 95% confidence interval 1.11 to 2.89) and a 90% increased risk of atherothrombotic brain infarction (relative risk 1.90, 95% confidence interval 1.02 to 3.51). These results were adjusted for age, gender, smoking, diabetes, systolic blood pressure and history of coronary heart disease or atrial fibrillation.


This study is interesting because it shows an association between homocysteine levels and stroke and also because it allows a comparison between this association and other risk factors for stroke.