High parathyroid hormone level fails to predict CV risk
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,” Håkan Melhus, MD, PhD, a professor in the department of medical sciences, clinical pharmacogenomics and osteoporosis at Uppsala University, Sweden, and colleagues wrote. “These findings confirm those of a large, population-based prospective study which did not support an association between circulating [parathyroid hormone] concentrations and cardiovascular disease. It also corroborates the results of a randomized controlled trial that showed no benefit of parathyroidectomy on cardiovascular disease risk factors in mild primary hyperparathyroidism.”
Melhus and colleagues used five single nucleotide polymorphisms (SNPs) from five different genomic regions shown to be strongly associated 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 obtained from a genetic consortium with data from 184,305 individuals, including 60,801 CAD cases (77% European ancestry). Researchers used the inverse-variance weighted method to calculate Mendelian randomization estimates for the associations between genetically predicted serum PTH concentrations with CV outcomes.
Researchers found that genetically higher serum PTH concentration across the five SNPs was not associated with CAD or myocardial infarction. The ORs per genetically predicted one standard deviation 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 weighted 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 associated with serum calcium and serum phosphorus concentrations, reflecting mediated pleiotropy. Genetically predicted serum PTH concentration was similarly not associated with any secondary CV outcomes.
“Many studies in primary [hyperparathyroidism] patients have explored the association between high PTH concentrations and cardiovascular disorders other than CAD,” the researchers wrote. “However, we found no association between genetically higher [serum] PTH concentrations and any cardiovascular disorder. The exclusion of studies that included individuals with cardiac diseases only resulted in attenuated 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.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.