Vitamin D may protect against young-onset ischaemic stroke

Vitamin D may protect against young-onset ischaemic stroke through preventing atrial fibrillation (AF), a University of Hong Kong (HKU) study on Southern Chinese has found.

The first part of the study was performed based on the existing platform of the HKU Theme-Based Research Scheme Cohort (HKU-TRS), which recruited a total of 6,048 Southern Chinese subjects from the Hong Kong Chinese Coronary Artery Disease (CAD) Cohort, the Hong Kong West Diabetes Registry (HKWDR), as well as the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS/CRISPS2). The second part of the study involved verification and generalizability analyses where findings from the HKU-TRS were studied in parallel with those from the UK Biobank (n=392,010; male, 46 percent; AF cases, n=14,878; ischaemic stroke cases, n=4,050; controls, n=374,102). [J Clin Biochem Nutr 2024;75:228-236; Nat Commun 2015;6:10206; Arterioscler Thromb Vasc Biol 2018;38:2519-2527; Atherosclerosis 2014;237:504-513; Europace 2017;I9(Suppl 4):iv25-iv31; J Clin Endocrinol Metab 2014;99:E2169-E2177; BMJ 2019;364:l476; Diabetes Care 2018;41:1991-1997]

Mendelian randomization (MR) analyses were performed by applying the Genetic Risk Score (GRS) for vitamin D derived from 3,922 of 6,048 subjects (derivation cohort) to an independent sample of 1,297 subjects (translational cohort; from the Hong Kong CAD Cohort; vitamin D deficiency [ie, serum 25-hydroxyvitamin D <20 ng/mL] prevalence, 36 percent). Results showed that vitamin D was causally protective against the primary endpoint of a composite of AF and/or ischaemic stroke (odds ratio [OR], 0.81; 95 percent confidence interval [CI], 0.65–0.98). Serological vitamin D deficiency was independently associated with AF and/or ischaemic stroke (OR, 1.77; 95 percent CI 1.24–2.52; p=0.002), while higher genetically predicted vitamin D, denoted by GRS, independently predicted reduced risk of AF and/or ischaemic stroke (OR, 0.83; 95 percent CI, 0.72–0.95), p=0.008).

Independent analyses of UK Biobank data revealed that vitamin D was protective against young-onset ischaemic stroke at age <50 years and AF combined (OR, 0.36; 95 percent CI, 0.14–0.94), with predominant effect amongst men (OR, 0.28; 95 percent CI, 0.09–0.91) compared with women (OR, 0.60; 95 percent CI, 0.11–3.22).

According to the authors, this is the first MR study or series that investigated the effect of genetically predicted vitamin D on AF and its composite endpoint with ischaemic stroke. They also noted that the analyses included Asian and European populations from different continents, substantiating the study’s generalizability. Furthermore, the data provided a unique and complimentary perspective unexplored by prior studies by including younger subjects (<50 years old) and a wider spectrum of vitamin D serological status (vitamin D deficiency status in the HKU-TRS, 45 percent), as well as incorporating the robust and pathophysiologically-linked endpoint of ischaemic stroke in the primary analyses.

“Backed by extensive studies of vitamin D in recent years, nondiscriminate supplementation of vitamin D for primary prevention of atherosclerotic cardiovascular diseases in healthy subjects with normal vitamin D levels is unlikely to result in any benefit,” they noted. “Rather, targeting the ‘right’ group of subjects, such as those with confirmed serological vitamin D deficiency or important cardiovascular risk factors or high risk, might be a crucial factor in assessing benefit, as suggested by other studies as well. Our study has unveiled a group of vulnerable subjects with young-onset ischaemic stroke and AF whose risk is altered with genetic vitamin D exposure.”