Worse Cardiovascular Disease Seen in Chronic Hypoparathyroidism

People with chronic hypoparathyroidism have a higher risk of disorders affecting the heart and blood vessels — known as cardiovascular disease — compared with those without the rare endocrine system disorder, according to a large-scale analysis of a medical claims database.

“Further studies are warranted to investigate reasons for these risks and to develop strategies for reducing cardiovascular conditions in patients with chronic hyperparathyroidism,” the researchers wrote.

The analysis, “Risk of Cardiovascular Conditions in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study,” was published in the journal Advances in Therapy.

Chronic hypoparathyroidism is characterized by low levels of calcium, called hypocalcemia, and high levels of phosphate, or hyperphosphatemia, due to a deficiency in the parathyroid hormone — known as PTH — which plays an essential role in balancing these two minerals in the body.

Disordered calcium regulation, either hypocalcemia or episodes of high calcium — known as hypercalcemia — has been associated with diseases of the heart and blood vessels or cardiovascular (CV) disease. This includes cardiomyopathy or heart muscle disease, congestive heart failure, and arrhythmia, which refers to irregular heartbeats.

To date, studies investigating an association between cardiovascular disease risk and hypoparathyroidism have been small in scope and yielded mixed results.

As such, “there is a need for large-scale studies to better our understanding of hypoparathyroidism and CV risk,” the researchers wrote.

Now, an international team of investigators examined 10 years of data to compare CV outcomes in 8,097 adults with hypoparathyroidism and 40,485 adults without the chronic disorder. The data were extracted from medical records held in a large healthcare claims database in the U.S.

Eligible chronic hypoparathyroidism patients had a confirmed diagnosis and were not treated with recombinant human PTH replacement therapies. Participants without the condition were randomly selected from the claims database. The patients were followed for up to five years or until the end of continuous claims eligibility, whichever occurred first.

At the start of the claims analysis (baseline), the mean age of those with chronic hypoparathyroidism was 58.6, and 76.2% were female. In the comparison group, the mean age was 47.3, with women comprising 54.4% of the participants.

The eight CV conditions assessed included atrial fibrillation or arrhythmia, coronary artery disease, heart attack (myocardial infarction), heart failure, and tachyarrhythmia, or fast heartbeat. Cerebrovascular or brain disease, stroke, and peripheral vascular disease — outside the heart — also were evaluated.

A combined CV outcome included one or more diagnoses of cerebrovascular disease, coronary artery disease, heart failure, and peripheral vascular disease.

Compared with participants without chronic hypoparathyroidism, a significantly higher proportion of people with the condition had a cardiovascular disease that met the combined CV outcome (19.4 vs. 9.5%).

Patients with hypoparathyroidism also had a significantly higher rate of atrial fibrillation (6.0% vs. 2.7%), coronary artery disease (9.6% vs. 5.3%), and cerebrovascular disease (6.0% vs. 3.0%) than those without the disorder. The rates of peripheral vascular disease (7.4% vs. 2.8%), heart failure (5.9% vs. 2.4%), and tachyarrhythmia (0.7% vs 0.4%) also were higher in hypoparathyroidism patients than those not diagnosed with the disease.

More than half (53%) of chronic hypoparathyroidism patients received medications that could influence cardiovascular disease compared with 30.3% of those without hypoparathyroidism.

Co-existing conditions such as chronic kidney disease, high blood pressure, and diabetes type 1 and 2 also were found to be more prevalent in people with chronic hypoparathyroidism.

Risk analysis showed a significantly increased likelihood of a new cardiovascular event that met the combined CV outcome and all other individual cardiovascular disease conditions in the hypoparathyroidism group.

The researchers then adjusted for factors that might influence the results, including demographics — age, sex, race, U.S. region, and diagnosis year — and clinical characteristics at the study’s start. Those characteristics included co-existing cardiovascular disease and medications, chronic kidney disease, high blood pressure, and diabetes.

However, there remained a significantly increased CV disease risk across all eight cardiovascular disease outcomes, as well as the combined CV outcome, in people with hypoparathyroidism.

“This study contributes to emerging evidence concerning the link between hypoparathyroidism and CV outcomes and suggests a need for increased monitoring and awareness of CV risk in patients with chronic hypoparathyroidism,” the scientists concluded.

“The mechanisms that mediate the relationship between chronic hypoparathyroidism and CV conditions warrant further research,” they added.

Among the study’s limitations was the unavailability of full medical histories, which limited the possibility of testing the effect of potential confounders, such as smoking history or family history of cardiovascular disease.