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- Publisher Website: 10.1161/STROKEAHA.120.032634
- Scopus: eid_2-s2.0-85121051223
- PMID: 34565175
- WOS: WOS:000720456100040
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Article: Mendelian randomization focused analysis of vitamin D on the secondary prevention of ischemic stroke
Title | Mendelian randomization focused analysis of vitamin D on the secondary prevention of ischemic stroke |
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Authors | |
Keywords | Ischemic stroke Myocardial infarction Recurrence Secondary prevention Vitamin D |
Issue Date | 2021 |
Publisher | American Heart Association. The Journal's web site is located at http://stroke.ahajournals.org |
Citation | Stroke, 2021, v. 52 n. 12, p. 3926-3937 How to Cite? |
Abstract | Background and Purpose:
Experimental studies showed vitamin D (Vit-D) could promote vascular regeneration and repair. Prior randomized studies had focused mainly on primary prevention. Whether Vit-D protects against ischemic stroke and myocardial infarction recurrence among subjects with prior ischemic insults was unknown. Here, we dissected through Mendelian randomization any effect of Vit-D on the secondary prevention of recurrent ischemic stroke and myocardial infarction.
Methods:
Based on a genetic risk score for Vit-D constructed from a derivation cohort sample (n=5331, 45% Vit-D deficient, 89% genotyped) via high-throughput exome-chip screening of 12 prior genome-wide association study–identified genetic variants of Vit-D mechanistic pathways (rs2060793, rs4588, and rs7041; F statistic, 73; P<0.001), we performed a focused analysis on prospective recurrence of myocardial infarction (MI) and ischemic stroke in an independent subsample with established ischemic disease (n=441, all with prior first ischemic event; follow-up duration, 41.6±14.3 years) under a 2-sample, individual-data, prospective Mendelian randomization approach.
Results:
In the ischemic disease subsample, 11.1% (n=49/441) had developed recurrent ischemic stroke or MI and 13.3% (n=58/441) had developed recurrent or de novo ischemic stroke/MI. Kaplan-Meier analyses showed that genetic risk score predicted improved event-free survival from recurrent ischemic stroke or MI (log-rank, 13.0; P=0.001). Cox regression revealed that genetic risk score independently predicted reduced risk of recurrent ischemic stroke or MI combined (hazards ratio, 0.62 [95% CI, 0.48–0.81]; P<0.001), after adjusted for potential confounders. Mendelian randomization supported that Vit-D is causally protective against the primary end points of recurrent ischemic stroke or MI (Wald estimate: odds ratio, 0.55 [95% CI, 0.35–0.81]) and any recurrent or de novo ischemic stroke/MI (odds ratio, 0.64 [95% CI, 0.42–0.91]) and recurrent MI alone (odds ratio, 0.52 [95% CI, 0.30–0.81]).
Conclusions:
Genetically predicted lowering in Vit-D level is causal for the recurrence of ischemic vascular events in persons with prior ischemic stroke or MI. |
Persistent Identifier | http://hdl.handle.net/10722/306409 |
ISSN | 2023 Impact Factor: 7.8 2023 SCImago Journal Rankings: 2.450 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Chan, YH | - |
dc.contributor.author | Schooling, CM | - |
dc.contributor.author | Zhao, J | - |
dc.contributor.author | Au Yeung, SL | - |
dc.contributor.author | Hai, JJ | - |
dc.contributor.author | Thomas, GN | - |
dc.contributor.author | Cheng, KK | - |
dc.contributor.author | Jiang, CQ | - |
dc.contributor.author | Wong, YK | - |
dc.contributor.author | Au, KW | - |
dc.contributor.author | Tang, CS | - |
dc.contributor.author | Cheung, CYY | - |
dc.contributor.author | Xu, A | - |
dc.contributor.author | Sham, PC | - |
dc.contributor.author | Lam, TH | - |
dc.contributor.author | Lam, KSL | - |
dc.contributor.author | Tse, HF | - |
dc.date.accessioned | 2021-10-20T10:23:10Z | - |
dc.date.available | 2021-10-20T10:23:10Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Stroke, 2021, v. 52 n. 12, p. 3926-3937 | - |
dc.identifier.issn | 0039-2499 | - |
dc.identifier.uri | http://hdl.handle.net/10722/306409 | - |
dc.description.abstract | Background and Purpose: Experimental studies showed vitamin D (Vit-D) could promote vascular regeneration and repair. Prior randomized studies had focused mainly on primary prevention. Whether Vit-D protects against ischemic stroke and myocardial infarction recurrence among subjects with prior ischemic insults was unknown. Here, we dissected through Mendelian randomization any effect of Vit-D on the secondary prevention of recurrent ischemic stroke and myocardial infarction. Methods: Based on a genetic risk score for Vit-D constructed from a derivation cohort sample (n=5331, 45% Vit-D deficient, 89% genotyped) via high-throughput exome-chip screening of 12 prior genome-wide association study–identified genetic variants of Vit-D mechanistic pathways (rs2060793, rs4588, and rs7041; F statistic, 73; P<0.001), we performed a focused analysis on prospective recurrence of myocardial infarction (MI) and ischemic stroke in an independent subsample with established ischemic disease (n=441, all with prior first ischemic event; follow-up duration, 41.6±14.3 years) under a 2-sample, individual-data, prospective Mendelian randomization approach. Results: In the ischemic disease subsample, 11.1% (n=49/441) had developed recurrent ischemic stroke or MI and 13.3% (n=58/441) had developed recurrent or de novo ischemic stroke/MI. Kaplan-Meier analyses showed that genetic risk score predicted improved event-free survival from recurrent ischemic stroke or MI (log-rank, 13.0; P=0.001). Cox regression revealed that genetic risk score independently predicted reduced risk of recurrent ischemic stroke or MI combined (hazards ratio, 0.62 [95% CI, 0.48–0.81]; P<0.001), after adjusted for potential confounders. Mendelian randomization supported that Vit-D is causally protective against the primary end points of recurrent ischemic stroke or MI (Wald estimate: odds ratio, 0.55 [95% CI, 0.35–0.81]) and any recurrent or de novo ischemic stroke/MI (odds ratio, 0.64 [95% CI, 0.42–0.91]) and recurrent MI alone (odds ratio, 0.52 [95% CI, 0.30–0.81]). Conclusions: Genetically predicted lowering in Vit-D level is causal for the recurrence of ischemic vascular events in persons with prior ischemic stroke or MI. | - |
dc.language | eng | - |
dc.publisher | American Heart Association. The Journal's web site is located at http://stroke.ahajournals.org | - |
dc.relation.ispartof | Stroke | - |
dc.subject | Ischemic stroke | - |
dc.subject | Myocardial infarction | - |
dc.subject | Recurrence | - |
dc.subject | Secondary prevention | - |
dc.subject | Vitamin D | - |
dc.title | Mendelian randomization focused analysis of vitamin D on the secondary prevention of ischemic stroke | - |
dc.type | Article | - |
dc.identifier.email | Chan, YH: chanwill@hku.hk | - |
dc.identifier.email | Schooling, CM: cms1@hkucc.hku.hk | - |
dc.identifier.email | Zhao, J: janezhao@hku.hk | - |
dc.identifier.email | Au Yeung, SL: ayslryan@hku.hk | - |
dc.identifier.email | Hai, JJ: haishjj@hku.hk | - |
dc.identifier.email | Wong, YK: debbieyk@hku.hk | - |
dc.identifier.email | Au, KW: aukawing@hku.hk | - |
dc.identifier.email | Tang, CS: claratang@hku.hk | - |
dc.identifier.email | Cheung, CYY: cyy0219@hku.hk | - |
dc.identifier.email | Xu, A: amxu@hkucc.hku.hk | - |
dc.identifier.email | Sham, PC: pcsham@hku.hk | - |
dc.identifier.email | Lam, TH: hrmrlth@hkucc.hku.hk | - |
dc.identifier.email | Lam, KSL: ksllam@hku.hk | - |
dc.identifier.email | Tse, HF: hftse@hkucc.hku.hk | - |
dc.identifier.authority | Chan, YH=rp01313 | - |
dc.identifier.authority | Schooling, CM=rp00504 | - |
dc.identifier.authority | Zhao, J=rp02336 | - |
dc.identifier.authority | Au Yeung, SL=rp02224 | - |
dc.identifier.authority | Hai, JJ=rp02047 | - |
dc.identifier.authority | Tang, CS=rp02105 | - |
dc.identifier.authority | Cheung, CYY=rp02243 | - |
dc.identifier.authority | Xu, A=rp00485 | - |
dc.identifier.authority | Sham, PC=rp00459 | - |
dc.identifier.authority | Lam, TH=rp00326 | - |
dc.identifier.authority | Lam, KSL=rp00343 | - |
dc.identifier.authority | Tse, HF=rp00428 | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1161/STROKEAHA.120.032634 | - |
dc.identifier.pmid | 34565175 | - |
dc.identifier.scopus | eid_2-s2.0-85121051223 | - |
dc.identifier.hkuros | 326684 | - |
dc.identifier.volume | 52 | - |
dc.identifier.issue | 12 | - |
dc.identifier.spage | 3926 | - |
dc.identifier.epage | 3937 | - |
dc.identifier.isi | WOS:000720456100040 | - |
dc.publisher.place | United States | - |