Response by Lattanzi and Silvestrini to Letter Regarding Article, “Neutrophil-to-Lymphocyte Ratio Predicts the Outcome of Acute Intracerebral Hemorrhage”
We agree that medical conditions such as premorbid atherosclerotic disease, underlying inflammation, and intercurrent infections could have influenced the NLR and partly accounted for its association with outcome. The prevalence of all the major cardiovascular risk factors such as smoking, dyslipidemia, diabetes mellitus, or hypertension, however, did not significantly differ among the outcome groups, and correlations did not emerge between age and NLR. Additionally, the leukocyte counts resulted within the normal ranges in most of the patients either with good and poor outcome.
The plasma inflammatory biomarkers and leukocyte counts are time-sensitive variables, and the NLR is a dynamic index whose variations and significance accompany the disease course. Accordingly, only patients who underwent admission routinely blood sampling within 24 hours from symptom onset were included in the analysis as per study protocol. Furthermore, the time from onset of symptoms to blood collection, labeled as time onset-to-sample, did not statistically differ between the prognosis groups (17.3 [interquartile range, 15.8–19.5] versus 17.7 [15.8–18.5] hours for patients with good and poor outcome, respectively; P=0.953). Obviously, prospective studies providing data on the time trends in cell counts are warranted to find the optimal period at which the NLR show the best predictive value and set benchmark cutoff points.
The in-hospital treatment may influence the intracerebral hemorrhage (ICH) course and affect the clinical outcome. In this respect, patients received the best practice standard of care according to the current stroke guidelines.3 Additionally, the variability in blood pressure levels was considered as a reliable synthesis of the effects of the blood pressure–lowering strategies during the acute ICH stage and a potential confounding predictor,4 and the discharge National Institutes of Health Stroke Scale (NIHSS) score was provided as surrogate marker of the treatment and neurological status during admission. The Kaplan–Meier and Cox regression analyses for the time to in-hospital mortality or complications may be one way to expound on the link between inflammatory response and ICH prognosis.
Platelets are involved in thrombosis and hemostasis, vessel constriction and clot retraction, and tissue inflammation and repair. Herein, platelet reactivity and thrombotic potential play role in the pathophysiology of ICH, and biomarkers of thrombocyte function may be predictive. The sensitivities, specificities, and informative values of the different inflammatory and thrombotic indices, either alone or combined into prognostic scores, should be, however, addressed by means of direct comparisons in ICH patient cohorts. We think that the NLR and any other reliable and simple-to-obtain outcome predictor could be easily integrated into the daily practice in the frame of the multidimensional prognostic assessment of the patient.
Ultimately, sufficient preclinical and clinical data exist implicating the immune pathways and inflammatory cells as mediators of the secondary brain damage and outcome predictors. We agree that there is a need for further investigations to provide mechanistic insights into the underlying molecular and cellular links, characterize the specific role of leukocytes subsets, and identify potential targets for the ICH treatment.
Simona Lattanzi, MD
Mauro Silvestrini, MD
Department of Experimental and Clinical Medicine
Marche Polytechnic University
- © 2016 American Heart Association, Inc.
- Du R,
- Li D,
- Zhang Q
- Lattanzi S,
- Cagnetti C,
- Provinciali L,
- Silvestrini M
- 3.↵Catel Hyperphar Group Spa. Stroke Prevention and Educational Awareness Diffusion (SPREAD). The Italian Stroke Guidelines. Milan, Italy: Catel Hyperphar Group Spa; 2007.