Link Between Abnormal Serum Calcium and Cardiovascular Events in Patients With Chronic Hypoparathyroidism

Adult patients with chronic hypoparathyroidism were more likely to experience a cardiovascular event if they had a higher proportion of albumin-corrected serum calcium measurements (outside of the 2.00 to 2.25 mmol/L [8.0 to 9.0 mg/100 ml] range) or any serum phosphate and any calcium-phosphate product measurements above the normal population range, according to a study published in The American Journal of Cardiology.¹

Sanjiv Kaul, MD

Credit: OHSU.edu

An insufficient production of the parathyroid hormone, an important regulator of serum calcium and phosphate, is the cause of chronic hypoparathyroidism. Oral calcium supplements and active vitamin D are the traditional therapy strategies for this patient population, although it does not affect other physiologic functions of the parathyroid hormone.²

“Although the body of evidence suggests the increased risk for cardiovascular events in patients with chronic hypoparathyroidism is related to abnormalities in serum calcium and phosphate, additional evidence is required,” wrote Sanjiv Kaul, MD, professor of medicine and founding director of the Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, and colleagues.

A retrospective, nested, risk-set sampled, case-control study of patients with chronic hypoparathyroidism with ≥1 calcitriol prescription who developed a cardiovascular event, as well as 1:1 matched controls, was conducted to assess any associations between cardiovascular events and albumin-corrected serum calcium, calcium phosphate product, and serum phosphate. A cardiovascular event was defined as ≥1 diagnosis of coronary artery disease, heart failure, cerebrovascular disease, or peripheral vascular disease. The primary outcome was the incidence of cardiovascular events or a matched date for the control group without a cardiovascular event.

The risk-set sampling design allowed for patients at risk of developing a cardiovascular event to be eligible for selection as a potential control during the period prior to diagnosis of a cardiovascular event as well as permitting patients to be matched more precisely for exposure window duration. The nationally representative database had collected data from approximately 360 hospitals and 330,000 different healthcare providers.

A total of 528 patients were included in the albumin-corrected serum calcium analysis and 200 patients were placed in the serum phosphate and calcium-phosphate product analyses using an electronic medical record database. Patients with a cardiovascular event and the controls had similar baseline clinical and demographic characteristics.

In the albumin-corrected serum calcium group, 28%, (n =75) had peripheral vascular disease, 27% (n = 72) reported a first cardiovascular event of cerebrovascular disease, 27% (n = 70) had coronary artery disease, and 22% (n = 57) had hard failure. In adjusted analyses, those with ≥67% of albumin-corrected serum calcium measurements outside of the study-defined limits had 1.9-fold higher odds of experiencing a cardiovascular event compared with patients with <33% of calcium measurements outside the range (adjusted odds ratio [aOR], 95% confidence interval [CI] 1.89, 1.10 to 3.25; P = .02).

Similarly, patients with serum phosphate measurements above .81 to 1.45 mmol/L (2.5 to 4.5 mg/100 ml) had 3.3-fold higher odds of developing a cardiovascular event compared with the control group (3.26; 1.24 to 8.58). Those with calcium phosphate product measurements above 4.40 mmol2/L2 (55 mg2/dL2) had 4.8-fold higher odds of experiencing a cardiovascular event (95% CI 1.36 to 16.81) when compared with patients within normal range. In this cohort, 32% (n = 32) had peripheral vascular disease, 28% (n = 28) had cerebrovascular disease, 22% (n = 22) had heart failure, 20% (n = 20) had coronary artery disease.

“The findings of this study provide further evidence for an association between abnormal mineral homeostasis and the odds of developing cardiovascular outcomes in patients with chronic hypoparathyroidism,” investigators concluded. “Controlling mineral homeostasis and optimizing treatment to achieve clinical goals of managing calcium and phosphate levels within ranges outlined in current guidelines may improve long-term cardiovascular outcomes for patients with chronic hypoparathyroidism.”

References

1. ^{Kaul S, Ayodele O, Chen K, et al. Association of Serum Calcium and Phosphate With Incident Cardiovascular Disease in Patients With Hypoparathyroidism. Am J Cardiol. 2023;194:60-70. doi:10.1016/j.amjcard.2023.01.029}
2. ^{Brandi ML, Bilezikian JP, Shoback D, et al. Management of Hypoparathyroidism: Summary Statement and Guidelines. J Clin Endocrinol Metab. 2016;101(6):2273-2283. doi:10.1210/jc.2015-3907}