Relative Predictive Value of Circulating Immune Markers in US Adults Without Cardiovascular Disease: Implications for Risk Reclassification

Kartik Gupta, Rajat Kalra, Mike Pate, Shivaraj Nagalli, Sameer Ather, Indranee Rajapreyar, Pankaj Arora, Ankur Gupta, Wunan Zhou, Raul San Jose Estepar, Marcelo Di Carli, Sumanth D. Prabhu, Navkaranbir S. Bajaj

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To investigate the relative predictive value of circulating immune cell markers for cardiovascular mortality in ambulatory adults without cardiovascular disease. Methods: We analyzed data of participants enrolled in the National Health and Nutrition Examination Survey from January 1, 1999, to December 31, 2010, with the total leukocyte count within a normal range (4000-11,000 cells/μL [to convert to cells ×109/L, multiply by 0.001]) and without cardiovascular disease. The relative predictive value of circulating immune cell markers measured at enrollment—including total leukocyte count, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count, monocyte-lymphocyte ratio (MLR), neutrophil-lymphocyte ratio, and C-reactive protein—for cardiovascular mortality was evaluated. The marker with the best predictive value was added to the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to estimate net risk reclassification indices for 10-year cardiovascular mortality. Results: Among 21,599 participants eligible for this analysis, the median age was 47 years (interquartile range, 34-63 years); 10,651 (49.2%) participants were women, and 10,713 (49.5%) were self-reported non-Hispanic white. During a median follow-up of 9.6 years (interquartile range, 6.8-13.1 years), there were 627 cardiovascular deaths. MLR had the best predictive value for cardiovascular mortality. The addition of elevated MLR (≥0.3) to the 10-year ASCVD risk score improved the classification by 2.7%±1.4% (P=.04). Elevated MLR had better predictive value than C-reactive protein and several components of the 10-year ASCVD risk score. Conclusion: Among ambulatory US adults without preexisting cardiovascular disease, we found that MLR had the best predictive value for cardiovascular mortality among circulating immune markers. The addition of MLR to the 10-year risk score significantly improved the risk classification of participants.

Original languageEnglish (US)
Pages (from-to)1812-1821
Number of pages10
JournalMayo Clinic Proceedings
Volume96
Issue number7
Early online dateApr 8 2021
DOIs
StatePublished - Jul 1 2021

Bibliographical note

Funding Information:
Grant Support: Dr Bajaj is supported by the Walter B. Frommeyer Jr Fellowship in Investigative Medicine awarded by the University of Alabama at Birmingham , the American College of Cardiology Presidential Career Development Award , and the National Center for Advancing Translational Research of the National Institutes of Health under award number UL1TR001417. Dr Prabhu is or was supported by NIH R01 grants HL125735 and HL147549 and a VA Merit Award (I01 BX002706).

Publisher Copyright:
© 2020

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