Breast Calcifications May Reflect Cardiovascular Risk in Kidney Disease

Norra MacReady

January 20, 2011

January 20, 2011 — Routine mammography may reveal an important, but difficult to detect, marker of possible cardiovascular risk in women with end-stage renal disease (ESRD), according to investigators at Emory University in Atlanta, Georgia.

The researchers found that women with end-stage renal disease (ESRD) were significantly more likely to have breast arterial calcification (BAC) than a control group of women without ESRD. Unlike the atherosclerotic plaques commonly associated with cardiovascular disease, which occur in the arterial intima, BAC develops in the medial layer of the arterial walls. As described in a press release, arterial calcium may contribute to the high rate of death from heart disease in those with ESRD. Arterial calcium in the medial layers contributes to arterial stiffness, but it is difficult to detect.

This study is the first to examine BAC and its relationship to chronic kidney disease (CKD) in detail, lead author Valerie Duhn, MD, and colleagues write.

"Calcification in the medial layer is independent of atherosclerosis or inflammation, occurs in small arteries in addition to large arteries, and is thought to be detrimental by decreasing arterial compliance," the authors explain. "It is observed specifically in renal failure, diabetes, and aging, but its pathophysiology and natural history are otherwise poorly understood." These calcifications are thought to contribute to the increased risk for cardiovascular disease associated with renal failure.

Mammography detects arterial calcifications that should be located in the media, based on their histology and vessel size, but this has never been conclusively demonstrated. The prevalence of BAC in ESRD also has been unclear, the authors note. They hypothesized that BAC could serve as a marker of generalized medial calcification, and that mammography could help determine the prevalence and risk factors for medial calcification in women with kidney disease.

The authors retrospectively identified 71 women with ESRD who had undergone screening mammography within the Emory healthcare system within the last 10 years. Each patient was randomly paired with a control patient with normal renal function who had undergone screening mammography between 2007 and 2009. The controls were matched for age (to within 1 year), race, and diabetes status. One individual reviewed all of the mammograms without knowing the characteristics of the participants.

Of the women with ESRD, 45 (63%) had BACs compared with 12 of the control patients (17%; P <. 001). Patients with ESRD with and without BAC were also compared. Patients with ESRD with BAC were significantly older (P = .013) and had been on dialysis longer (P = .024) than the patients with ESRD without BAC. There was also a trend toward a higher prevalence of diabetes in the BAC group (62% vs 39%; P = .053). In a logistic multivariate model, only age and ESRD were significant predictors of calcification.

To determine whether BAC could act as a marker of generalized medial calcification, one of the authors, who was unaware of the mammography findings, reviewed radiographs from 62 participants with ESRD for medial calcification in the arteries of their hands, wrists, lower legs, ankles, or feet. Of 21 patients with findings indicative of medial calcification, 19 had BAC (90%). Peripheral arterial calcification was present in only 2 (6%) of 31 patients without BAC.

Also of note, BAC was present in 36% of mammograms 5.5 ± 0.7 years before the onset of ESRD (P < .05 compared with healthy control patients), but only 14% of those with stage 3 CKD had BAC on mammogram before onset of the disease.

Three important findings emerged from this study, the authors point out. First, no intimal calcification or other signs of atherosclerosis were seen in the breast arteries; second, calcification was limited to the media or the internal elastic lamina; and third, "early stages of calcification were detected [on mammography] that were not apparent on the specimen radiographs, indicating that the prevalence of medial calcification is greater than that indicated by radiography."

Because most women with CKD are at an age where yearly mammograms are recommended, mammograms may also help in studying the development and progression of medial calcifications. The authors suggest that future studies determine the prevalence of BAC at different stages of CKD and identify more risk factors, as well as optimal treatment. Computed tomography of the breast should allow for even more precise characterization of these lesions.

Limitations to this study included the small sample size, the use of retrospective analysis, and the subjective nature of detecting BAC on the mammograms. Nevertheless, the authors write, "the results demonstrate the utility of mammography as a specific tool for examining medial vascular calcification in chronic kidney disease."

The authors have disclosed no relevant financial relationships.

Clin J Am Soc Nephrol. Published online January 20, 2011.

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