The Role of Age in Intracerebral Hemorrhage: An Intricate Relationship

Review Article

Austin J Cerebrovasc Dis & Stroke. 2014;1(5): 1022.

The Role of Age in Intracerebral Hemorrhage: An Intricate Relationship

Camacho EJ#, LoPresti MA#, Bruce S, Lin D, Abraham ME, Appelboom G#*, McDowell M, Du Bois BG, Sathe M and Connolly ES

Cerebrovascular laboratory, Columbia University College of Physicians and Surgeons, USA

*Corresponding author: Appelboom G, Cerebrovascular laboratory, Columbia University Medical Center, Columbia University College of Physicians and Surgeons, 630 West 168th Street, P&S 5-454,10032, New York, USA

Received: August 20, 2014; Accepted: September 17, 2014; Published: September 19, 2014

Abstract

Strokes are one of the leading causes of death in the United States, and intracerebral hemorrhage is the deadliest type of stroke. Age is a strong risk factor for intracerebral hemorrhages and it also affects the body in numerous ways—including changes to the cardiovascular and central nervous systems— that interplay with multiple risk factors. Understanding the role of age in risk and outcomes can guide treatment and future clinical trials. We reviewed the literature for intracerebral hemorrhage risk factors. This review aimed to identify the role of age, as well as characterize the most commonly used age cut-off points in the literature. Current review of the literature suggests the age cut-off for mortality and morbidity vary between 60-80 years of age, with the most common values of 65 or 70 years. In addition to age as a determinant of outcomes, it increases the risk of multiple chronic health conditions and comorbidities including hypertension, diabetes, and treatment with anticoagulants which contribute to the pathology of intracerebral hemorrhages. The interaction of these chronic conditions, age, and intracerebral hemorrhage is evident; however, the exact mechanism and extent of impact remain unclear. The ambiguity of these connections may be further obscured by the current recommendations, individual patient preferences, and literature supported trials of treatment options for aging patients.

Keywords: Intracerebral hemorrhage; Age; Outcome; Predictor and comorbidities

Introduction

In the United States, stroke is the fourth leading cause of death and is one of the leading causes of long-term disability [1,2]. Intracerebral Hemorrhages (ICH) account for approximately 10-15% of all strokes and are considered to have the highest mortality rate [3]. Unlike other types of strokes, ICH does not have an effective treatment, making understanding risks factors and predictors of ICH imperative to proper risk stratification and management. One common risk associated with stroke is advancing age. Hemphill et al. created one of the first widely accepted ICH scores, and in their univariate analysis, individuals aged 80 or older were a significant independent predictor of 30-day mortality, with an odds ratio of 9.55 [4]. Natural and pathological changes that occur with aging carry numerous implications for the body, including changes to the cardiovascular and central nervous systems that interact with many other risk factors for ICH. Although there has been a recent decrease in ICH rates among patients younger than 75, rates have increased in those 75 years or older [5]. Moreover, with the trend of an aging population, there is an increase in incidence rates for many comorbidities that occur with aging, and with the associated increase in incidence rates of stokes, the potential risk of ICH among the elderly is vast. Therefore, it is the aim of this review to characterize and examine age as a predictor of ICH risk and outcomes, and identify significant markers for intervention and treatment.

Effects of Aging

Advanced age is associated with worse clinical outcomes in many conditions. In the case of ICH, this association may be independent or directly related to the pathology of multiple risk factors of stroke, such as hypertension. There are numerous effects of aging on the body, and most significant in the case of ICH, are age related changes of the cerebrovascular system and the aging brain.

The effect of aging on the brain’s microvasculature is well-recognized, and includes decreased vascular density, micro embolic brain injury, vessel basement membrane thickening, endothelial dysfunction, and increased blood brain barrier permeability. In addition, cerebral white matter lesions known as leukoaraiosis— characterized by spongiosis, gliosis, demyelination, and capillary degeneration [6]—are seen in the elderly population with vascular risk factors and/or vascular dementia, and are thought to be related to cerebrovascular disease in this population. Systemic conditions such as hypertension and diabetes mellitus may also contribute to these changes of the cerebrovasculature. These structural changes to the brain’s vasculature make the parenchyma that it supplies more susceptible to injury, which increases the risk of stroke. Pathology involving further endothelial damage, changes in vessel elasticity, or fluctuations in blood flow and pressure, implicate chronic diseases such as hypertension, atherosclerosis, diabetes, and atrial fibrillation in worsening risks of neurologic injury.

Age-related changes of gross brain volume are also well documented, with an annual loss of volume ranging from 0.2-0.5% [4], especially in regions such as the prefrontal cortex [3], and are thought to be the result of neuronal atrophy. In a study by Gottesman et al., the authors suggested that since the elderly tend to have anatomically smaller brains than their younger counterparts, a given stroke volume in the elderly would affect a greater proportion of brain parenchyma, which may be a factor in the poorer neurological outcome [7]. Older populations also have a higher probability of having a history of prior strokes, which could impair their ability to recover from and make them more susceptible to additional injuries [8]. Additionally, several animal studies have shown that white matter vulnerability increases with age and could explain why post-ictus cognitive decline is higher in older populations [9–11].

Prevalence of Comorbidities

Many common chronic conditions including essential hypertension, coronary artery disease, atrial fibrillation, cardiovascular disease, and diabetes mellitus have a higher prevalence with increasing age [12], and as a result, may confound the attributable risk of age with regards to the odds of having an ICH and the outcomes in patients who survive. Hypertension is a widely identified risk factor for ICH [13–16]——a meta-analysis by Jackson et. al. showed that essential hypertension increases the risk of ICH by approximately two-fold [17], and another study estimated that 83% of ICH patient carry the diagnosis of essential hypertension [18]. Additionally, although atrial fibrillation is primarily a risk factor for cardio embolic stroke [19], this patient population is routinely anti coagulated with agents such as warfarin, which may increase the risk of ICH by two to fivefold in a dose-dependent manner [20–22]. In patients who survive the initial ICH, certain studies have shown that those with other comorbidities, such as diabetes and peripheral vascular disease, have a higher 30-day and 1-year mortality, as well as worse functional outcome [23,24]. Moreover, Pooled data of case-control studies showed that diabetic individuals are 1.3 times more likely than non-diabetics to develop ICH [13]. While diabetes has been identified as a weak risk factor, perhaps the pathogenesis of disease, with both microvascular and macrovascular changes developing over time, increases susceptibility of ICH.

Additionally, a review of the literature indicates other risk factors including alcohol use and smoking historyas potential predictors of ICH [13]. The prevalence of multi morbidity, namely vascular diseases, greatly increases with age and has been found to be present in most people age 65 or older, contributing to higher mortality and reduced functional status, possibly worsening outcomes of ICH [25– 28]. In effect, comorbidities likely have varying degrees of influence on the risk of having an ICH and on the functional outcome. However, it is the potential, and likely, culmination of synergy when they act together in the elderly population that could greatly account for the higher incidence and mortality rates seen in this population.

Prognosis

Understanding the independent predictors associated with aging that lead to worse mortality rates and prognoses, such as comorbidities and treatment options, could allow for more effective interventions and reductions in unfavorable outcomes. Factors predicting mortality at 30 days and 1 year include age, cognitive function upon admission, hematoma volume, intra ventricular extension of hematoma, infratentorial location of hematoma, and heart disease [29]. Many of these known risk factors influence each other but after accounting for other variables, age is an independent predictor [30]. Table 1 explores the impact of age on prognosis of ICH morbidity and mortality and characterizes age and ICH outcomes in several well-known studies. Examination of these findings indicates that older age is associated with increased mortality, worse functional outcomes, and decreased long-term survival. As shown in Table 1, the ages most commonly used as a cut-off in the literature range from 60-80 years of age, with the majority being either 65 or 70 years of age.

Citation: Camacho EJ, LoPresti MA, Bruce S, Lin D, Abraham ME, et al. The Role of Age in Intracerebral Hemorrhage: An Intricate Relationship. Austin J Cerebrovasc Dis & Stroke. 2014;1(5): 1022. ISSN: 2381-9103.