Abstract

Abstract Background Lymphopenia has been shown to be associated with adverse prognosis in chronic disease states that are related to immune dysregulation. Purpose We aimed to determine the association between lymphopenia and all-cause mortality in patients presenting to coronary angiography with or without acute coronary syndromes (ACS). We also investigated whether elevated red blood cell distribution width (RDW), an established cardiovascular prognostic marker, further refines risk stratification and improves predictive accuracy beyond lymphocytes count. Methods Retrospective cohort analysis of patients undergoing coronary angiography for evaluation or treatment of coronary artery disease between 2003 and 2018. Long-term mortality risk associated with relative (1000–1500 /μL) or severe (<1000 /μL) lymphopenia was analyzed using Cox proportional hazards regression models, adjusting for comorbidities, ACS and RDW. Results Overall, 15179 patients underwent coronary angiography, at a mean age of 65±12 years. On cross-sectional analysis, lymphopenia was associated with kidney disease, cancer, heart failure and presentation with ACS, but lower rates of smoking and obesity. During a median follow-up of 7 (IQR 3.5–11.5) years, 4253 patients died. Compared to normal lymphocytes count (1500–5000 /μL), the multivariable adjusted hazard ratio (HR) (95% confidence interval) for mortality was 1.31 (1.21–1.41) and 1.97 (1.75–2.22) for relative and severe lymphopenia, respectively. The increase in mortality associated with severe lymphopenia was significant in patients presenting with non-ACS [HR 2.18 (1.74–2.73)], ST-segment elevation myocardial infarction (STEMI) [HR 1.59 (1.15–2.21)], or unstable angina/non-STEMI [HR 2.00 (1.70–2.34)]; p-for-interaction 0.626. The association of lymphopenia with mortality remained significant after additional adjustment to RDW. High RDW (>14.5%) was associated with increased mortality risk in each of the lymphocytes count groups, and improved the predictive accuracy with AUC increase from 0.609 (0.601–0.616) to 0.646 (0.639–0.654) (p<0.001). Conclusions Lymphopenia is associated with increased risk for long-term mortality in patients undergoing coronary angiography, regardless of coronary presentation. High RDW may enhance the predictive ability of lymphopenia. Lymphocyte count and mortality risk Funding Acknowledgement Type of funding source: None

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