Routinely measured hematological parameters and prediction of recurrent vascular events in patients with clinically manifest vascular disease

Abstract

Background and aimsThe predictive value of traditional risk factors for vascular events in patients with manifest vascular disease is limited, underscoring the need for novel biomarkers to improve risk stratification. Since hematological parameters are routinely assessed in clinical practice, they are readily available candidates.MethodsWe used data from 3,922 vascular patients, who participated in the Second Manifestations of ARTerial Disease (SMART) study. We first investigated associations between recurrent vascular events and 22 hematological parameters, obtained from the Utrecht Patient Oriented Database (UPOD), and then assessed whether parameters associated with outcome improved risk prediction.ResultsAfter adjustment for all SMART risk score (SRS) variables, lymphocyte %, neutrophil count, neutrophil % and red cell distribution width (RDW) were significantly associated with vascular events. When individually added to the SRS, lymphocyte % improved prediction of recurrent vascular events with a continuous net reclassification improvement (cNRI) of 17.4% [95% CI: 2.1, 32.1%] and an increase in c-statistic of 0.011 [0.000, 0.022]. The combination of lymphocyte % and neutrophil count resulted in a cNRI of 22.2% [3.2, 33.4%] and improved c-statistic by 0.011 [95% CI: 0.000, 0.022]. Lymphocyte % and RDW yielded a cNRI of 18.7% [3.3, 31.9%] and improved c-statistic by 0.016 [0.004, 0.028]. However, the addition of hematological parameters only modestly increased risk estimates for patients with an event during follow-up.ConclusionsSeveral hematological parameters were independently associated with recurrent vascular events. Lymphocyte % alone and in combination with other parameters enhanced discrimination and reclassification. However, the incremental value for patients with a recurrent event was limited.

Survival analysis under the Cox proportional hazards model with pooled covariates

“…Additional description of the rationale of the SMART study, study design, and exclusion/inclusion criteria has been published earlier 41 . It has been used extensively to address important clinical questions 42‐45 …”

Red Blood Cell Distribution Width Predicts Myocardial Infarction and Mortality After Vascular Surgery–A Prospective Cohort Study

“…All these factors predispose the patient to a greater susceptibility for the emergence of adverse cardiovascular outcomes, resulting in a worse clinical prognosis. The NLR has been broadly studied as a marker of systemic inflammation and hence, of cardiovascular risk 2,21 . It has been proven that neutrophils contribute to endothelial dysfunction along with the recruitment of monocytes to atherosclerotic lesions, leading to the disruption of atherosclerotic plaques 2 .…”

“…Cardiovascular diseases are a leading cause of morbidity and mortality worldwide 1 . The identification and strict control of cardiovascular risk factors, such as hypertension, diabetes, obesity, smoking, or dyslipidemia, play an important role in the prevention of future cardiovascular events 2 , however, there are other useful markers that may provide valuable information for the risk stratification and early management of these events. The red blood cell distribution width (RDW) is a measure of the variability in size of circulating erythrocytes [3][4][5] .…”

Scalable cardiovascular risk assessment using artificial intelligence-enabled event adjudication and widely available hematologic predictors

“…Others have shown association of hematologic indices with all-cause mortality and cardiovascular events, including a focus on red-cell distribution width 23,[30][31][32][33][34] and specific leukocyte subpopulations such as the neutrophil-to-lymphocyte ratio 35 . The utility of RDW for predicting outcomes may be related to its association with anemias of chronic disease or with clonal hematopoiesis of indeterminate potential 6 , which appear to predict similar patterns of events.…”