Circulating Biomarkers Associated With Coronary Artery Calcification

The coronary artery calcification (CAC) score is a measure of how much calcification is in the coronary arteries, and accordingly, is an in vivo measure of atherosclerosis. Why is the CAC score important? Besides its role in atherosclerosis, risk of death for all causes goes up at any age as the CAC score increases. For ex., in people younger than 50 (left side below), as the CAC score increases from 0 to 1-399, 400-999, and > 1000, risk of death for all causes increases by ~10-fold, from 2.3 per 1000 person years (PY) to 6.1/1000, 9.7/1000, and 22.7/1000. Similarly, for people older than 70y (right side below), as the CAC score increases, baseline all-cause mortality risk increases ~15-fold, from 5.6/1000 to 21.6/1000, 44.3/1000, and 76/1000, respectively (Hartaigh et al. 2016):

Screen Shot 2019-10-20 at 8.40.05 AM.png

Are blood biomarkers associated with CAC? When the CAC score was elevated, a greater percentage of white blood cells (WBCs) that were neutrophils and the red blood cell distribution width (RDW%) were higher, whereas lower CAC scores were associated with higher levels for the fraction of lymphocytes divided by total WBCs and higher total red blood cells (den Harder et al. 2018):

n l rdw cac

In agreement with these data, CAC scores > 100 were associated with a higher RDW% (13.0%) and a higher neutrophil/lymphocyte ratio (NLR; 1.54), when compared with CAC < 100 (RDW = 12.8%; NLR = 1.39; Gürel et al. 2019).

The findings that a higher RDW% and higher levels of neutrophils, but lower levels of lymphocytes are associated with a higher CAC score is in agreement with the data for how these variables change with aging and their associations with all-cause mortality risk. First, note that I previously reported that RDW% increases during aging and is associated with an increased risk of death from all causes ( Similarly, neutrophils increase, whereas lymphocytes decrease, thereby leading to a higher neutrophil/lymphocyte ratio during aging, which is associated with an increased all-cause mortality risk (

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den Harder AM, de Jong PA, de Groot MCH, Wolterink JM, Budde RPJ, Iŝgum I, van Solinge WW, Ten Berg MJ, Lutgens E, Veldhuis WB, Haitjema S, Hoefer IE, Leiner T. Commonly available hematological biomarkers are associated with the extent of coronary calcifications. Atherosclerosis. 2018 Aug;275:166-173. doi: 10.1016/j.atherosclerosis.2018.06.017.

Gürel OM, Demircelik MB, Bilgic MA, Yilmaz H, Yilmaz OC, Cakmak M, Eryonucu B. Association between Red Blood Cell Distribution Width and Coronary Artery Calcification in Patients Undergoing 64-Multidetector Computed TomographyKorean Circ J. 2015 Sep;45(5):372-7. doi: 10.4070/kcj.2015.45.5.372.

Hartaigh BÓ, Valenti V, Cho I, Schulman-Marcus J, Gransar H, Knapper J, Kelkar AA, Xie JX, Chang HJ, Shaw LJ, Callister TQ, Min JK. 15-Year prognostic utility of coronary artery calcium scoring for all-cause mortality in the elderly. Atherosclerosis. 2016 Mar;246:361-6. doi: 10.1016/j.atherosclerosis.2016.01.039.

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