Influence of Sex on Stroke Prognosis: A Demographic, Clinical, and Molecular Analysis.

Emilio Rodríguez-Castro,Iria López-Dequidt,Pablo Hervella,Susana Arias,Ramón Iglesias-Rey,María Santamaría,Tomás Sobrino,Ignacio López-Loureiro,José Castillo,Manuel Rodríguez-Pérez,Francisco Campos,Manuel Rodríguez-Yáñez

doi:10.3389/fneur.2019.00388

Abstract

Identifying the complexities of the effect of sex on stroke risk, etiology, and lesion progression may lead to advances in the treatment and care of ischemic stroke (IS) and non-traumatic intracerebral hemorrhage patients (ICH). We studied the sex-related discrepancies on the clinical course of patients with IS and ICH, and we also evaluated possible molecular mechanisms involved. The study's main variable was the patient's functional outcome at 3-months. Logistic regression models were used in order to study the influence of sex on different inflammatory, endothelial and atrial dysfunction markers. We recruited 5,021 patients; 4,060 IS (54.8% male, 45.2% female) and 961 ICH (57.1% male, 42.9% female). Women were on average 5.7 years older than men (6.4 years in IS, 5.1 years in ICH), and more likely to have previous poor functional status, to suffer atrial fibrillation and to be on anticoagulants. IS patients showed sex-related differences at 3-months regarding poorer outcome (55.6% women, 43.6% men, p < 0.0001), but this relationship was not found in ICH (56.8% vs. 61.9%, p = 0.127). In IS, women had higher levels of NT-proBNP and 3-months worse outcome in both cardioembolic and non-cardioembolic stroke patients. Stroke patients showed sex-related differences in pre-hospital data, clinical variables and molecular markers, but only IS patients presented independent sex-related differences in 3-months poor outcome and mortality. There was a relationship between the molecular marker of atrial dysfunction NT-proBNP and worse functional outcome in women, resulting in a possible indicator of increased dysfunction.

Highlights

Stroke among adults is a common cause of death, disability and poor functional outcome in Europe and other developed countries
We conducted a retrospective study enrolling patients with ischemic stroke and nontraumatic intracerebral hemorrhage admitted to the Stroke Unit (Neurology Department of the Hospital Clínico Universitario de Santiago de Compostela) and who were included in a prospective stroke registry (BICHUS)
The inflammatory response is slightly higher in women; there are no sex differences in their functional behavior

Summary

Introduction

Stroke among adults is a common cause of death, disability and poor functional outcome in Europe and other developed countries. Due to the aging of the population, the incidence of cerebrovascular disease is increasing and it seems that it will continue to do so in the decades [1, 2]. In this situation, the demographic conditions (lifestyle habits and socio-economic status), therapeutics strategies, healthcare structures, as well as clinical and molecular variables are known to play an important role in stroke incidence, treatment, clinical course and patient mortality [3,4,5]. Ischemic stroke (IS) and nontraumatic intracerebral hemorrhage (ICH) patients present sexrelated differences in functional outcomes and mortality [6, 7]. Conventional stroke risk factors as hypertension, atrial fibrillation, diabetes mellitus and inflammation processes have recently received more sex differences attention [12, 13]

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