Importance of so called “novel cardiovascular risk factors” in severity of coronary artery calcification; how serious they should be taken: a systematic review and metaanalysis

Cardiovascular diseases are among important causes of death. Atherosclerosis is an important etiology for coronary artery diseases in which coronary artery calcification plays a principal role. Recently novel cardiovascular risk factors in coronary calcification are under attention. In this study, we investigated possible association between novel cardiovascular risk factors and coronary calcification. This is a prospectively registered systematic review and meta-analysis in PROSPERO and was performed in accordance with PRISMA guidelines. Medical databases were searched. Primary papers were screened and studies reporting our outcomes of interest were selected for data extraction. Quantitative data syntheses were performed using Comprehensive Meta-analysis Ver.3. In this study, 5252 papers were screened and finally 28 papers including 31241 patients underwent data extraction. Based on our findings, neutrophil/lymphocyte ratio (8 out of 10), red cell distribution width (r = 0.250, p < 0.0001), and interleukin 6 (odds ratio [OR]: 1.101 [95% confidence interval (CI): 1.001-1.210], p = 0.047) were associated with severity of coronary calcification while C-reactive protein (one out of eight) was not associated with coronary calcification. Results of lymphocyte/monocyte ratio (r = –0.120, p < 0.001), platelet/lymphocyte ratio (OR: 1.47 [95% CI: 0.89-2.41, p = 0.124]), and MPV (r = 0.017, p = 0.814 vs. OR: 1.91 [95% CI: 1.28-2.85, p = 0.002]) remained controversial due to few number of included studies or contrary results. We can conclude that neutrophil/lymphocyte ratio, red cell distribution width, and interleukin-6 are significantly associated with coronary calcification and C-reactive protein is not significantly associated with severity of coronary calcification. Our results about mean platelet volume, platelet/lymphocyte ratio, and lymphocyte/monocyte ratio are not reliable and require further investigations.