A genetic predisposition to higher serum parathyroid hormone concentration is not an independent risk factor for developing coronary artery disease, according to findings from a Mendelian randomization analysis. “The results of this Mendelian randomization study showed that genetic predisposition to higher [serum parathyroid hormone] concentrations is not associated with CAD or other common cardiovascular diseases,” Hakan Melhus, MD, PhD, a professor in the department of medical sciences, clinical pharmacogenomics and osteoporosis at Uppsala University, Sweden, and colleagues wrote.
The parathyroid hormone
Parathyroid hormone is secreted from four parathyroid glands; which are small glands in the neck, locate behind the thyroid gland. Parathyroid hormone regulates calcium levels in the blood, largely by increasing the levels when they are too low. It does this through its actions on the kidneys, bones and intestine.
“These findings confirm those of a large, population-base prospective study; which did not support an association between circulating [parathyroid hormone] concentrations and cardiovascular disease. It also corroborates the results of a randomize control trial that show no benefit of parathyroidectomy on cardiovascular disease risk factors in mild primary hyperparathyroidism.”
Melhus and colleagues use five single nucleotide polymorphisms (SNPs) from five different genomic regions shown to be strongly associate with serum parathyroid hormone (PTH) concentrations at a genome-wide significance level as instrumental variables to estimate the association of genetically higher serum PTH concentrations with CAD. Summary statistics data for CAD were obtain from a genetic consortium with data from 184,305 individuals, including 60,801 CAD cases (77% European ancestry).
The myocardial infarction
Researchers use the inverse variance weight method to calculate Mendelian randomization; hence estimates for the associations between genetically predict serum PTH concentrations with CV outcomes. Researchers find that genetically higher serum PTH concentration; so across the five SNPs was not with CAD or myocardial infarction. The ORs per genetically predict one standard deviation; so increase in serum PTH concentration were 1.01 (95% CI, 0.93-1.09) for CAD and 1.02 (95% CI, 0.94-1.1) for MI in the inverse-variance weight analysis. Results persisted in sensitivity analyses.
The researchers noted that there was no indication of directional pleiotropy (P = .41); however, several of the serum PTH-related SNPs were with serum calcium and serum phosphorus concentrations, reflecting mediate pleiotropy. Genetically predict serum PTH concentration was similarly not with any secondary CV outcomes. “Many studies in primary [hyperparathyroidism] patients; which have explore the association between high PTH concentrations and cardiovascular disorders other than CAD,” the researchers wrote.
“However, They found no association between genetically higher [serum] PTH concentrations and any cardiovascular disorder. The exclusion of studies that include individuals with cardiac diseases only result in attenuate results; which may suggest that cardiac patients are more prone to PTH excess and thus have a higher risk of developing secondary cardiovascular disease events.