Vitamin B 12 deficiency and hyperhomocysteinaemia in outpatients with stroke or transient ischaemic attack: a cohort study at an academic medical centre

Abstract

Objective: We sought to assess the current magnitude of the opportunity for secondary stroke prevention with B vitamins.

Design: A cohort study.

Setting: The Urgent TIA (Transient Ischaemic Attack) Clinic at an academic medical centre.

Main outcome measures: We assessed the prevalence of biochemical vitamin B12 deficiency (B12Def, serum B12 <156 pmol/L), hyperhomocysteinaemia (HHcy; plasma total homocysteine [tHcy] >14 µmol/L) and metabolic B12 deficiency (MetB12Def, serum B12 <258 pmol/L and HHcy) between 2002 and 2017, by age group and by stroke subtype.

Results: Data were available in 4055 patients. B12Def was present in 8.2% of patients overall; it declined from 10.9% of patients referred before 2009 to 5.4% thereafter (p=0.0001). MetB12Def was present in 10.6% of patients, and HHcy was present in 19.1% of patients. Among the patients aged ≥80 years, MetB12Def was present in 18.1% and HHcy in 35%. Among the 3410 patients whose stroke subtype was determined, HHcy was present in 18.4% of patients: 23.3% of large artery atherosclerosis, 18.1% of cardioembolic, 16.3% of small vessel disease, 10.8% of other unusual aetiologies and 13.6% of undetermined subtypes (p=0.0001).

Conclusions: Despite a decline in our referral area since 2009, B12Def, MetB12Def and HHcy remain common in patients with stroke/TIA. Because these conditions are easily treated and have serious consequences, all patients with stroke/TIA should have their serum B12 and tHcy measured.

Keywords: B12; homocysteine; stroke.

Conflict of interest statement

Competing interests: After this paper was written, JDS became a consultant to Orphan Technologies, a company that makes a truncated human cystathionine beta synthase for treatment of classical homocystinuria.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Distribution of serum B12 from 2002 to 2008 versus 2009–2017. (A) Distribution of serum B12 from 2002 to 2008. (B) Distribution of serum B12 from 2009 to 2017. Serum B12 is shown for all patients referred to the Urgent TIA (transient ischaemic attack) Clinic with serum B12 levels, including those without total homocysteine available. The distributions are significantly different by a Kruskal-Wallis test (p=0.0001).

Figure 2

Plasma total homocysteine (tHcy) and serum B12 by quartiles of estimated glomerular filtration rate (eGFR). (A) tHcy was clearly elevated with impaired renal function. (B) Serum B12 was not significantly affected by renal impairment.

Figure 3

Plasma tHcy by age group and frequency of hyperhomocysteinaemia by stroke subtype. (A) tHcy clearly increases with age (ANOVA p=0.0001). (B) Stroke subtypes are shown for patients referred between 2002 and 2012; hyperhomocysteinaemia differed significantly by stroke subtype (χ2 p=0.0001). ANOVA, analysis of variance; CE, cardioembolic; LAA, large artery atherosclerosis; Other, other unusual aetiologies; SVD, small vessel disease; tHcy, total homocysteine; UE, undetermined aetiology.

Figure 4

Serum B12 by year of referral and per cent of patients with serum B12 >700 pmol/L at the time of referral. (A) Serum B12 levels increased among patients referred to our clinic after the 2009 report of a high prevalence of hyperhomocysteinaemia in our patients. Before 2009 the mean serum B12 (SD) was 326.62 (214.68); thereafter it was 374.90 (234.29) (p=0.0001). (B) The per cent of patients with serum B12 >700 pmol/L increased markedly in recent years, indicating probable B12 supplementation.