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Association of Genetic Variants Related to Serum Calcium Levels With Coronary Artery Disease and Myocardial Infarction.

Abstract Serum calcium has been associated with cardiovascular disease in observational studies and evidence from randomized clinical trials indicates that calcium supplementation, which raises serum calcium levels, may increase the risk of cardiovascular events, particularly myocardial infarction.
PMID
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A Mendelian randomization study of the effect of calcium on coronary artery disease, myocardial infarction and their risk factors.

Authors

Mayor MeshTerms
Keywords
Journal Title jama
Publication Year Start




PMID- 28742912
OWN - NLM
STAT- In-Process
DA  - 20170725
LR  - 20170725
IS  - 1538-3598 (Electronic)
IS  - 0098-7484 (Linking)
VI  - 318
IP  - 4
DP  - 2017 Jul 25
TI  - Association of Genetic Variants Related to Serum Calcium Levels With Coronary
      Artery Disease and Myocardial Infarction.
PG  - 371-380
LID - 10.1001/jama.2017.8981 [doi]
AB  - Importance: Serum calcium has been associated with cardiovascular disease in
      observational studies and evidence from randomized clinical trials indicates that
      calcium supplementation, which raises serum calcium levels, may increase the risk
      of cardiovascular events, particularly myocardial infarction. Objective: To
      evaluate the potential causal association between genetic variants related to
      elevated serum calcium levels and risk of coronary artery disease (CAD) and
      myocardial infarction using mendelian randomization. Design, Setting, and
      Participants: The analyses were performed using summary statistics obtained for
      single-nucleotide polymorphisms (SNPs) identified from a genome-wide association 
      meta-analysis of serum calcium levels (N = up to 61079 individuals) and from the 
      Coronary Artery Disease Genome-wide Replication and Meta-analysis Plus the
      Coronary Artery Disease Genetics (CardiogramplusC4D) consortium's 1000
      genomes-based genome-wide association meta-analysis (N = up to 184305
      individuals) that included cases (individuals with CAD and myocardial infarction)
      and noncases, with baseline data collected from 1948 and populations derived from
      across the globe. The association of each SNP with CAD and myocardial infarction 
      was weighted by its association with serum calcium, and estimates were combined
      using an inverse-variance weighted meta-analysis. Exposures: Genetic risk score
      based on genetic variants related to elevated serum calcium levels. Main Outcomes
      and Measures: Co-primary outcomes were the odds of CAD and myocardial infarction.
      Results: Among the mendelian randomized analytic sample of 184305 individuals
      (60801 CAD cases [approximately 70% with myocardial infarction] and 123504
      noncases), the 6 SNPs related to serum calcium levels and without pleiotropic
      associations with potential confounders were estimated to explain about 0.8% of
      the variation in serum calcium levels. In the inverse-variance weighted
      meta-analysis (combining the estimates of the 6 SNPs), the odds ratios per
      0.5-mg/dL increase (about 1 SD) in genetically predicted serum calcium levels
      were 1.25 (95% CI, 1.08-1.45; P = .003) for CAD and 1.24 (95% CI, 1.05-1.46; P = 
      .009) for myocardial infarction. Conclusions and Relevance: A genetic
      predisposition to higher serum calcium levels was associated with increased risk 
      of CAD and myocardial infarction. Whether the risk of CAD associated with
      lifelong genetic exposure to increased serum calcium levels can be translated to 
      a risk associated with short-term to medium-term calcium supplementation is
      unknown.
FAU - Larsson, Susanna C
AU  - Larsson SC
AD  - Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska
      Institutet, Stockholm, Sweden.
FAU - Burgess, Stephen
AU  - Burgess S
AD  - MRC Biostatistics Unit, University of Cambridge, United Kingdom3Department of
      Public Health and Primary Care, University of Cambridge, Cambridge, United
      Kingdom.
FAU - Michaelsson, Karl
AU  - Michaelsson K
AD  - Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - JAMA
JT  - JAMA
JID - 7501160
EDAT- 2017/07/26 06:00
MHDA- 2017/07/26 06:00
CRDT- 2017/07/26 06:00
AID - 2645106 [pii]
AID - 10.1001/jama.2017.8981 [doi]
PST - ppublish
SO  - JAMA. 2017 Jul 25;318(4):371-380. doi: 10.1001/jama.2017.8981.