PMID- 35093020
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220319
IS  - 1555-8932 (Print)
IS  - 1865-3499 (Electronic)
IS  - 1555-8932 (Linking)
VI  - 17
IP  - 1
DP  - 2022 Jan 29
TI  - Mendelian randomization analysis of vitamin D in the secondary prevention of 
      hypertensive-diabetic subjects: role of facilitating blood pressure control.
PG  - 1
LID - 10.1186/s12263-022-00704-z [doi]
LID - 1
AB  - BACKGROUND: Vitamin D (Vit-D) promotes vascular repair and its deficiency is 
      closely linked to the development of type 2 diabetes mellitus (T2DM) and 
      hypertension. Whether genetially predicted vitamin D status (serological 
      25-hydroxyvitamin D [25(OH)D]) confers secondary protection against 
      cardiovascular diseases (CVD) among high-risk hypertensive-diabetic subjects was 
      unknown. METHODS: This is a prospective, individual-data, two-sample Mendelian 
      randomization study. We interrogated 12 prior GWAS-detected SNPs of comprehensive 
      Vit-D mechanistic pathways using high-throughput exome chip analyses in a 
      derivation subcohort (n = 1460) and constructed a genetic risk score (GRS) 
      (rs2060793, rs4588, rs7041; F-statistic = 32, P < 0.001) for causal inference of 
      comprehensive CVD hard clinical endpoints in an independent sample of 
      hypertensive subjects (n = 3746) with prevailing co-morbid T2DM (79%) and 
      serological 25(OH)D deficiency [< 20 ng/mL] 45%. RESULTS: After 
      55.6 +/- 28.9 months, 561 (15%) combined CVD events including myocardial 
      infarction, unstable angina, ischemic stroke, congestive heart failure, 
      peripheral vascular disease, and cardiovascular death had occurred. Kaplan-Meier 
      analysis showed that genetically predicted reduced vitamin D status was 
      associated with reduced event-free survival from combined CVD events 
      (log-rank = 13.5, P = 0.001). Multivariate-adjusted per-allele increase in GRS 
      predicted reduced combined CVD events (HR = 0.90 [0.84 to 0.96], P = 0.002). 
      Mendelian randomization indicates that increased Vit-D exposure, leveraged 
      through each 1 ng/mL genetically instrumented rise of serum Vit-D, protects 
      against combined CVD events (Wald's estimate: OR = 0.86 [95%CI 0.75 to 0.95]), 
      and myocardial infarction (OR = 0.76 [95%CI 0.60 to 0.90]). Furthermore, 
      genetically predicted increase in Vit-D status ameliorates risk of deviation from 
      achieving guideline-directed hypertension control (JNC-8: systolic target 
      < 150 mmHg) (OR = 0.89 [95%CI 0.80 to 0.96]). CONCLUSIONS: Genetically predicted 
      increase in Vit-D status [25(OH)D] may confer secondary protection against 
      incident combined CVD events and myocardial infarction in a hypertensive-diabetic 
      population where serological 25(OH)D deficiency is common, through facilitating 
      blood pressure control.
CI  - (c) 2022. The Author(s).
FAU - Chan, Yap-Hang
AU  - Chan YH
AUID- ORCID: 0000-0001-5384-8468
AD  - Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, Hong 
      Kong, China.
FAU - Schooling, C Mary
AU  - Schooling CM
AD  - School of Public Health, The University of Hong Kong, Hong Kong, SAR, China.
FAU - Zhao, Jie V
AU  - Zhao JV
AD  - School of Public Health, The University of Hong Kong, Hong Kong, SAR, China.
FAU - Yeung, Shiu-Lun Au
AU  - Yeung SA
AD  - School of Public Health, The University of Hong Kong, Hong Kong, SAR, China.
FAU - Hai, Jo Jo
AU  - Hai JJ
AD  - Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, Hong 
      Kong, China.
AD  - Department of Medicine, Shenzhen Hong Kong University Hospital, Shenzhen, China.
FAU - Thomas, G Neil
AU  - Thomas GN
AD  - Department of Public Health and Epidemiology, University of Birmingham, 
      Birmingham, UK.
FAU - Cheng, Kar-Keung
AU  - Cheng KK
AD  - Department of Public Health and Epidemiology, University of Birmingham, 
      Birmingham, UK.
FAU - Jiang, Chao-Qiang
AU  - Jiang CQ
AD  - Guangzhou No. 12 Hospital, Guangzhou, People's Republic of China.
FAU - Wong, Yuen-Kwun
AU  - Wong YK
AD  - Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, Hong 
      Kong, China.
FAU - Au, Ka-Wing
AU  - Au KW
AD  - Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, Hong 
      Kong, China.
FAU - Tang, Clara S
AU  - Tang CS
AD  - Department of Psychiatry and Centre for Genomic Sciences, University of Hong 
      Kong, Hong Kong, China.
FAU - Cheung, Chloe Y Y
AU  - Cheung CYY
AD  - Division of Endocrinology, Queen Mary Hospital, The University of Hong Kong, Hong 
      Kong, China.
FAU - Xu, Aimin
AU  - Xu A
AD  - Division of Endocrinology, Queen Mary Hospital, The University of Hong Kong, Hong 
      Kong, China.
FAU - Sham, Pak-Chung
AU  - Sham PC
AD  - Department of Psychiatry and Centre for Genomic Sciences, University of Hong 
      Kong, Hong Kong, China.
FAU - Lam, Tai-Hing
AU  - Lam TH
AD  - School of Public Health, The University of Hong Kong, Hong Kong, SAR, China. 
      hrmrlth@hku.hk.
FAU - Lam, Karen Siu-Ling
AU  - Lam KS
AD  - Division of Endocrinology, Queen Mary Hospital, The University of Hong Kong, Hong 
      Kong, China. ksllam@hku.hk.
FAU - Tse, Hung-Fat
AU  - Tse HF
AD  - Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, Hong 
      Kong, China. hftse@hkucc.hku.hk.
AD  - Department of Medicine, Shenzhen Hong Kong University Hospital, Shenzhen, China. 
      hftse@hkucc.hku.hk.
AD  - Hong Kong-Guangdong Joint Laboratory on Stem Cell and Regenerative Medicine, The 
      University of Hong Kong, Hong Kong, China. hftse@hkucc.hku.hk.
AD  - Shenzhen Institutes of Research and Innovation, The University of Hong Kong, Hong 
      Kong, SAR, China. hftse@hkucc.hku.hk.
LA  - eng
GR  - Project no. 10111531/health and medical research fund, hksar/
GR  - T12-705/11/hong kong research grants council theme-based research scheme/
GR  - 777511M, 776412M, 776513M and 17128515/general research fund/
GR  - ITS/303/12/innovation and technology support programme (tier 3)/
PT  - Journal Article
DEP - 20220129
PL  - Germany
TA  - Genes Nutr
JT  - Genes & nutrition
JID - 101280108
PMC - PMC8903706
OTO - NOTNLM
OT  - Chinese
OT  - Exome Chip
OT  - Hypertension
OT  - Mendelian randomization
OT  - Secondary prevention
OT  - Type 2 diabetes
OT  - Vitamin D
COIS- The authors declare no competing interests.
EDAT- 2022/01/31 06:00
MHDA- 2022/01/31 06:01
PMCR- 2022/01/29
CRDT- 2022/01/30 20:26
PHST- 2021/07/17 00:00 [received]
PHST- 2022/01/18 00:00 [accepted]
PHST- 2022/01/30 20:26 [entrez]
PHST- 2022/01/31 06:00 [pubmed]
PHST- 2022/01/31 06:01 [medline]
PHST- 2022/01/29 00:00 [pmc-release]
AID - 10.1186/s12263-022-00704-z [pii]
AID - 704 [pii]
AID - 10.1186/s12263-022-00704-z [doi]
PST - epublish
SO  - Genes Nutr. 2022 Jan 29;17(1):1. doi: 10.1186/s12263-022-00704-z.