The association of innate and adaptive immunity, subclinical atherosclerosis, and cardiovascular disease in the Rotterdam Study: A prospective cohort study

Autoři: Lana Fani aff001;  Kimberly D. van der Willik aff001;  Daniel Bos aff001;  Maarten J. G. Leening aff001;  Peter J. Koudstaal aff005;  Dimitris Rizopoulos aff006;  Rikje Ruiter aff001;  Bruno H. C. Stricker aff001;  Maryam Kavousi aff001;  M. Arfan Ikram aff001;  M. Kamran Ikram aff001
Působiště autorů: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands aff001;  Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, the Netherlands aff002;  Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands aff003;  Department of Cardiology, Erasmus MC, Rotterdam, the Netherlands aff004;  Department of Neurology, Erasmus MC, Rotterdam, the Netherlands aff005;  Department of Biostatistics, Erasmus MC, Rotterdam, the Netherlands aff006
Vyšlo v časopise: The association of innate and adaptive immunity, subclinical atherosclerosis, and cardiovascular disease in the Rotterdam Study: A prospective cohort study. PLoS Med 17(5): e1003115. doi:10.1371/journal.pmed.1003115
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003115



Atherosclerotic cardiovascular disease (ASCVD) is driven by multifaceted contributions of the immune system. However, the dysregulation of immune cells that leads to ASCVD is poorly understood. We determined the association of components of innate and adaptive immunity longitudinally with ASCVD, and assessed whether arterial calcifications play a role in this association.

Methods and findings

Granulocyte (innate immunity) and lymphocyte (adaptive immunity) counts were determined 3 times (2002–2008, mean age 65.2 years; 2009–2013, mean age 69.0 years; and 2014–2015, mean age 78.5 years) in participants of the population-based Rotterdam Study without ASCVD at baseline. Participants were followed-up for ASCVD or death until 1 January 2015. A random sample of 2,366 underwent computed tomography at baseline to quantify arterial calcification volume in 4 vessel beds. We studied the association between immunity components with risk of ASCVD and assessed whether immunity components were related to arterial calcifications at baseline. Of 7,730 participants (59.4% women), 801 developed ASCVD during a median follow-up of 8.1 years. Having an increased granulocyte count increased ASCVD risk (adjusted hazard ratio for doubled granulocyte count [95% CI] = 1.78 [1.34–2.37], P < 0.001). Higher granulocyte counts were related to larger calcification volumes in all vessels, most prominently in the coronary arteries (mean difference in calcium volume [mm3] per SD increase in granulocyte count [95% CI] = 32.3 [9.9–54.7], P < 0.001). Respectively, the association between granulocyte count and incident coronary heart disease and stroke was partly mediated by coronary artery calcification (overall proportion mediated [95% CI] = 19.0% [−10% to 32.3%], P = 0.08) and intracranial artery calcification (14.9% [−10.9% to 19.1%], P = 0.05). A limitation of our study is that studying the etiology of ASCVD remains difficult within an epidemiological setting due to the limited availability of surrogates for innate and especially adaptive immunity.


In this study, we found that an increased granulocyte count was associated with a higher risk of ASCVD in the general population. Moreover, higher levels of granulocytes were associated with larger volumes of arterial calcification. Arterial calcifications may explain a proportion of the link between granulocytes and ASCVD.

Klíčová slova:

Blood cells – Blood counts – Calcification – Coronary heart disease – Granulocytes – Innate immune system – Lymphocytes – Acquired immune system


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