Research Article: Kidney function, proteinuria and breast arterial calcification in women without clinical cardiovascular disease: The MINERVA study

Date Published: January 17, 2019

Publisher: Public Library of Science

Author(s): Rishi V. Parikh, Carlos Iribarren, Catherine Lee, Tory Levine-Hall, Thida C. Tan, Gabriela Sanchez, Huanjun Ding, Fatemeh Azamian Bidgoli, Sabee Molloi, Alan S. Go, Tatsuo Shimosawa.


Breast arterial calcification (BAC) may be a predictor of cardiovascular events and is highly prevalent in persons with end-stage kidney disease. However, few studies to date have examined the association between mild-to-moderate kidney function and proteinuria with BAC.

We prospectively enrolled women with no prior cardiovascular disease aged 60 to 79 years undergoing mammography screening at Kaiser Permanente Northern California between 10/24/2012 and 2/13/2015. Urine albumin-to-creatinine ratio (uACR), along with specific laboratory, demographic, and medical data, were measured at the baseline visit. Baseline estimated glomerular filtration rate (eGFR), medication history, and other comorbidities were identified from self-report and/or electronic medical records. BAC presence and gradation (mass) was measured by digital quantification of full-field mammograms.

Among 3,507 participants, 24.5% were aged ≥70 years, 63.5% were white, 7.5% had eGFR <60 ml/min/1.73m2, with 85.7% having uACR ≥30 mg/g and 3.3% having uACR ≥300 mg/g. The prevalence of any measured BAC (>0 mg) was 27.9%. Neither uACR ≥30 mg/g nor uACR ≥300 were significantly associated with BAC in crude or multivariable analyses. Reduced eGFR was associated with BAC in univariate analyses (odds ratio 1.53, 95% CI: 1.18–2.00), but the association was no longer significant after adjustment for potential confounders. Results were similar in various sensitivity analyses that used different BAC thresholds or analytic approaches.

Among women without cardiovascular disease undergoing mammography screening, reduced eGFR and albuminuria were not significantly associated with BAC.

Partial Text

Arterial calcification is a prominent predictor of cardiovascular morbidity and mortality, and is common among patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD).[1–5] Several studies have estimated the prevalence of arterial calcification in selected vascular beds to be approximately 60–70% in the CKD population, which independently increases the risk of cardiovascular disease (CVD) events by approximately 40%.[6, 7] Calcification of the intima of coronary arteries and aorta, specifically, has been the focus of previous work and has been consistently associated with an increase in atherosclerotic CVD events.[8, 9] However, both intimal (atherosclerotic) and medial (arteriosclerotic or Möneckberg’s sclerosis) calcification are present in the CKD population. It remains unclear whether intimal vs. medial calcification have similar strength of association with CVD risk, especially given differences in pathology between these forms of arterial calcification.[10–12]

Within a contemporary, ethnically diverse cohort of 3,507 women with no prior clinical CVD who were undergoing regular screening mammography, we found that quantifiable BAC (>0 mg) was present in 28% of participants which was higher than reported in previous studies, and approximately 1 in 12 participants had BAC >10 mg.[14] In addition to differences in our population compared with previously studied samples, an important feature in our study was the use of digital quantification of mammograms which has a higher sensitivity of BAC detection compared with visual inspection.[26] We observed no significant association between albuminuria with two different BAC thresholds in univariate or multivariable analyses. While there was a higher crude association of CKD with BAC >0 mg or BAC >10 mg, the relationship was attenuated and no longer statistically significant after adjustment for sociodemographic factors. Among blacks, the unadjusted association between CKD and BAC was stronger than in the overall population, but the association was no longer significant after accounting for differences in other sociodemographic characteristics. Furthermore, findings remained consistent in a variety of sensitivity analyses evaluating exposures of kidney function and albuminuria as well as BAC as continuous log-transformed measures.




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