Coronary Artery Disease and Serum Calcium Levels: Is There a Genetic Connection?

Individuals with a genetic predisposition to higher serum calcium levels may have an increased risk for coronary artery disease (CAD) and myocardial infarction (MI), according to an analysis of large-scale genome-wide association studies published in JAMA.

Researchers from the United Kingdom and Sweden used Mendelian randomization to determine whether a causal association existed between genetic variants related to serum calcium levels and risk for CAD and MI. Data were collected from thousands of individuals worldwide from a genome-wide association meta-analysis of serum calcium levels (n=61,079) and from the CAD Genome-wide Replication and Meta-analysis Plus the CAD Genetics (CardiogramplusC4D) consortium’s 1000 genomes-based genome-wide association meta-analysis (N=184,305).

The association of a single-nucleotide polymorphism (SNP) with CAD and MI was weighted by its association with calcium. The researchers used an inverse-variance weighted meta-analysis to calculate estimates.

Among the 184,305 individuals included in the Mendelian randomization, there were 60,801 cases of CAD, 70% of which included MI. According to the estimates, the 6 SNPs related to serum calcium explained about 0.8% of the variation in serum calcium levels. When they combined the estimates of the 6 SNPs, the researchers found that the odds ratios per 0.5 mg/dL increase (about 1 standard deviation) 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 MI.

“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,” the researchers wrote.

Study Limitations

• One specific genetic variant (CASR gene) provided more weight compared with the other variants to the overall estimate of the genetic association between serum calcium levels and CAD.
• Some overlap between the 2 studies may have occurred, meaning some of the same individuals may have been included in both the genome-wide association meta-analysis and the CardiogramplusC4D’s consortium
• Sex and age data were lacking, as well as a replication data set with a similar large number of CAD cases.