Hormone and Bone Tests May Predict Progression of Coronary Artery Calcification in Patients on Dialysis

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Many patients with chronic kidney disease (CKD) and end stage renal disease exhibit coronary artery calcification as well as low bone mass. A new study published in the Journal of the American Society of Nephrology now shows that monitoring bone loss in dialysis patients may provide early warning signs of cardiovascular problems.

“Coronary artery calcification progresses inexorably in patients on dialysis, and these patients have mortality rates related to cardiovascular events worse than many cancers,” said lead author Hartmut Malluche, MD, FACP, of the University of Kentucky. “The link between bone and vascular calcifications is a potentially very important avenue, and studies need to be done to find out whether prevention of bone loss will reduce progression of vascular calcifications.”

Malluche and his team noted that no information is available on the use of noninvasive bone mass assessments—such as dual energy x-ray absorptiometry or quantitative computed tomography—for predicting progression of coronary artery calcification. There’s also little information on how traditional and novel serum biochemical parameters relate to progression.

To fill these gaps, the researchers conducted tests to analyze abnormalities in blood, bone, and heart vessels in 213 patients on dialysis over a 1-year period. About 80% of the patients had measurable coronary artery calcification at baseline, and almost 50% had levels that confer a high risk for cardiovascular events.

Independent positive predictors of baseline coronary artery calcification included coronary artery disease, diabetes, dialysis vintage, fibroblast growth factor-23 concentration, and age.

Bone mineral density of the spine measured by quantitative computed tomography was an inverse predictor. Contrary to other studies, the investigators did not find a sex difference in baseline coronary artery calcification. Baseline coronary artery calcification was lower in patients who reported exercising compared with those who did not, which is a novel finding in dialysis patients but in agreement with studies done in adults without CKD.

While these baseline findings are important for gaining a better understanding of the factors that contribute to the prevalence of coronary artery calcification in patients on dialysis, they don’t necessarily help clinicians predict which patients will experience progression.

Dr. Malluche and his colleagues found that at 1 year, independent risk factors for progression of coronary artery calcification were age, baseline total or whole parathyroid hormone level greater than 9 times the normal value, and osteoporosis. Bone mineral density of the total hip, femoral neck, and spine was shown for the first time in dialysis patients to correlate with baseline coronary artery calcification as well as a diagnosis of osteoporosis by t scores.

“We discovered that high parathyroid hormone and the consequential bone loss are major risk factors for progression of vascular calcifications,” Malluche said. “These two factors were heretofore not appreciated and were independent from traditional known risk factors.” The researchers noted that patients who started and stayed within recommended parathyroid hormone ranges over the course of the study had the least progression of calcification.

The findings indicate that important information can be gained from monitoring parathyroid hormone levels and bone mass in patients on dialysis, to not only assess bone health but cardiovascular health as well. Additional controlled prospective studies are needed to evaluate the effects on coronary artery calcification of different therapies that are marketed to target osteoporosis or parathyroid hormone levels.

“This study adds a different perspective on mechanisms associated with vascular calcification in CKD that is different from the previously described associations of low bone turnover and low parathyroid hormone levels and increased risk of vascular disease in CKD,” said Paul Miller, MD, who was not involved with the research and is a Distinguished Clinical Professor of Medicine at the University of Colorado Health Sciences Center and the Medical Director of the Colorado Center for Bone Research, in Lakewood.

Study co-authors include Gustav Blomquist, MD, Marie-Claude Monier-Faugere, MD, Thomas Cantor, and Daniel Davenport, PhD.

Disclosures: The authors reported no financial disclosures.

The article, entitled “High Parathyroid Hormone Level and Osteoporosis Predict Progression of Coronary Artery Calcification in Patients on Dialysis,” is available at http://jasn.asnjournals.org/content/early/2015/04/01/ASN.2014070686.abstract.