Inverse J-shaped relation between coronary arterial calcium density and mortality in advanced chronic kidney disease

Nephrol Dial Transplant. 2020 Jul 1;35(7):1202-1211. doi: 10.1093/ndt/gfy352.


Background: The coronary artery calcium (CAC) score from cardiac computed tomography (CT) is a composite of CAC volume and CAC density. In the general population, CAC volume is positively and CAC density inversely associated with cardiovascular disease (CVD) events, implying that decreased CAC density reflects atherosclerotic plaque instability. We analysed associations of CAC indices with mortality risk in patients with end-stage renal disease [chronic kidney disease Stage 5 (CKD5)].

Methods: In 296 CKD5 patients undergoing cardiac CT (median age 55 years, 67% male, 19% diabetes, 133 dialysed), the Framingham risk score (FRS), presence of CVD and protein-energy wasting (PEW; subjective global assessment) and high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were determined at baseline. During follow-up for a median of 35 months, 51 patients died and 75 patients underwent renal transplantation. All-cause mortality risk was analysed with competing-risk regression models. Vascular calcification was analysed in biopsies of the arteria epigastrica inferior in 111 patients.

Results: Patients in the middle tertile of CAC density had the highest CAC score, CAC volume, age, CVD, PEW, FRS, hsCRP and IL-6. In competing risk analysis, the middle {subhazard ratio [sHR] 10.7 [95% confidence interval (CI) 2.0-57.3]} and high [sHR 8.9 (95% CI 1.5-51.8)] tertiles of CAC density associated with increased mortality, independent of CAC volume. The high tertile of CAC volume, independent of CAC density, associated with increased mortality [sHR 8.9 (95% CI 1.5-51.8)]. Arterial media calcification was prominent and associated with CAC volume and CAC density.

Conclusions: In CKD5, mortality increased linearly with higher CAC score and CAC volume whereas for CAC density an inverse J-shaped pattern was observed, with the crude mortality rate being highest for the middle tertile of CAC density. CAC volume and CAC density were associated with the extent of arterial media calcification.

Keywords: chronic kidney disease; coronary artery calcium density; coronary artery calcium score; coronary artery calcium volume; mortality risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • C-Reactive Protein / metabolism
  • Calcium / metabolism*
  • Calcium, Dietary / metabolism
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / metabolism
  • Coronary Artery Disease / mortality*
  • Coronary Artery Disease / pathology
  • Coronary Vessels / metabolism
  • Coronary Vessels / pathology*
  • Female
  • Humans
  • Kidney Failure, Chronic / complications*
  • Male
  • Middle Aged
  • Prognosis
  • Risk Factors
  • Survival Rate
  • Vascular Calcification / etiology
  • Vascular Calcification / metabolism
  • Vascular Calcification / mortality*
  • Vascular Calcification / pathology
  • Young Adult


  • Calcium, Dietary
  • C-Reactive Protein
  • Calcium