Stroke Prevention

We are making important strides in the understanding and management of cerebrovascular disease, yet there is much work still to be done. As I mentioned in the Preface to the first issue on stroke (Volume 25, Number 4, 2005), I challenged the authors in these issues of Seminars in Neurology to provide an update on various topics focusing on the translation of basic science, epidemiology, health services, and clinical research into clinical practice. I chose this strategy, rather than recapitulate the current state of our knowledge found in typical reviews of the management of stroke, for several reasons. The Table of Contents again includes many rising stars who undoubtedly will continue to contribute to cerebrovascular neurology over the next several decades. I wanted to provide a glimpse of the near future and specifically chose authors who are active participants in ongoing research. This issue focuses on risk factor conditions, vascular biology, and genetics.

I must acknowledge that despite our double issue, we are not able to cover all topics and in most cases these articles are an introduction to a much broader literature. Specifically, we have not directly addressed issues related to health disparities in cerebrovascular disease.[1] [2] [3] This topic deserves attention and could undoubtedly fill an entire issue of Seminars in Neurology. The National Institute on Neurological Disorders and Stroke (NINDS) has convened an advisory panel to set clinical and research priorities to address health disparities.[4] I encourage interested readers to review the report. Much work needs to be done to identify the underlying causes of these disparities and develop strategies to ameliorate the increased risk borne by specific populations.

This issue of Seminars in Neurology begins with an article on dietary habits for the prevention of stroke. Dariush Mozaffarian has written extensively on the complex relationship between diet and vascular disease.[5] [6] He and Eric Ding provide an excellent and detailed analysis of the current evidence linking specific nutrients and risk of stroke. In a complementary article, Peter Kelly and Karen Furie review the relationship diet, inflammation, and genetic factors play in defining risk associated with homocysteine, an emerging stroke risk factor. These researchers have both made important contributions to our current understanding of the relationship of homocysteine and B vitamins with stroke.[7] [8]

In the first of three articles focusing on genetic factors in stroke, Elaine Skalabrin and Jennifer Majersik review single-gene disorders that have stroke as a major component of the disease phenotype. In single-gene or genetically deterministic disorders, the genetic mutation is disease causing. Although rare, recognition of these disorders is clinically important and understanding the pathophysiology frequently gives a window into understanding general cerebrovascular disease. Dr. Skalabrin is currently developing a stroke genetics research program in Utah and Dr. Majersik is a stroke fellow at the University of Michigan with a strong interest in genetic mechanisms in stroke. In the second article, Dr. James Meschia reviews stroke as a complex genetic disorder. The genetic factors that he discusses are probabilistic risk factors for stroke; in other words, these are genetic factors that increase or decrease risk of stroke along with several other competing genetic and environmental factors. Dr. Meschia is the principal investigator on two important multicenter studies looking at genetic risk in ischemic stroke[9] [10] and continues to contribute to our understanding of genetic risk for cerebrovascular disease.[11] In the final article in this group, Salina Waddy, who is forging a career focused on genetic risk for stroke with a focus on mechanisms of thrombosis and hemostasis, writes a thorough and critical review of the data relating specific disorders of the coagulation cascade and arterial stroke risk. Her analysis raises important questions about what we should consider a “hypercoagulable workup” for stroke.

The next three articles focus on advances in our understanding of vascular biology and the roles that inflammation and infection play in atherosclerosis and stroke. Alison Baird and Violet Wright work together at the NINDS Stroke Neuroscience Unit in conjunction with the Women's Health Initiative focusing on vascular inflammation, brain injury, and recovery in stroke.[12] [13] They provide an excellent discussion of the potential translation of research using gene expression and other types of cellular and molecular profiling to the management of stroke patients and those at highest risk for stroke. Tom DeGraba then discusses inflammatory elements associated with atherosclerosis and stroke, and which of these may serve as markers of increased risk of stroke. He also reviews currently available medications and future strategies for reducing inflammation that may have a beneficial impact on atherosclerosis and stroke. Dr. DeGraba is an indisputable authority on the role of inflammation on cerebrovascular atherosclerosis and stroke risk; he has led the field for more than 10 years. [14] [15] [16] The third article in this block by Mitch Elkind and John Cole reviews the current evidence that infection plays a role in stroke risk. Drs. Elkind and Cole have both conducted important research looking at the role of specific infections and host response to infection as risk factors for ischemic stroke.[17] [18] [19]

The next three articles are directly or indirectly related to the obesity epidemic. Brett Kissela and Ellen Air discuss the increasing role that diabetes plays at all stages of cerebrovascular disease, from increasing stroke risk to influencing recovery following stroke. Dr. Kissela has devoted much of his recent research to the impact that diabetes and glucose dysregulation have on stroke.[22] Next, Bernadette Boden-Albala discusses the much-vaunted metabolic syndrome, revealing both the strengths and weaknesses of reducing numerous potent vascular risk factors to the inconsistently defined metabolic syndrome. Dr. Boden-Albala continues to challenge our understanding of social and lifestyle factors in determining stroke risk.[20] [21] I asked her to write this article in part because of a heated discussion we had about the metabolic syndrome during which the epidemiologist and biostatistician George Howard said, “Why should we take a group of established vascular risk factors, dichotomize them, assign arbitrary weights of 1.0 for each factor (regardless of the real potency of the risk factor), combine them, and then ‘redichotomize' the summary score?” Dr. Boden-Albala provides a balanced discussion from her work and that of others looking at the complex interaction of vascular risk factors regardless of what label is applied. Devin Brown discusses the relationship of sleep disorders and stroke.[23] Dr. Brown is actively researching the connections between sleep apnea and stroke. Her analysis should be a wake-up call to clinicians to attend to disorders of sleep in their cerebrovascular patients.

The next article in this issue focuses on women, specifically the impact hormone replacement therapy has on stroke risk. In light of the publication of the Women's Health Initiative studies, enthusiasm for estrogen replacement has waned. Dr. Bushnell points out the gaps in our current knowledge and the need for further research. She continues to investigate the relationship of hormones, hormone replacement, and stroke risk.[24] [25]

Clinical research is essential to address management challenges in stroke and related diseases. There are many initiatives that are bringing the clinical research enterprise into the traditional practice setting as opposed to academe. The NINDS has initiated a Clinical Research Collaboration network that will allow clinicians to contribute to the advancement of scientific knowledge through participating in clinical research.[26] [27] The last two articles in this issue discuss practical and ethical considerations related to the introduction of research into clinical practices. These articles offer useful frameworks that physicians can use to decide about whether to add clinical research in general or specific protocols to their practice. Donna Chen has written on ethical issues related to research on brain disorders.[28] [29] She has also written on the need for education about research and research ethics for all physicians, given the increasing presence of clinical research.[30] [31]

In compiling these two issues focused on the translation of research to clinical practice, I sought to demonstrate the breadth and depth of research in ischemic stroke. The application of the data emerging from ongoing and future research will continue to shape all stages of clinical care from prevention to treatment to recovery. In this inaugural year for vascular neurology as a subspecialty, I hope that these articles convey excitement and optimism for the future of cerebrovascular medicine.

REFERENCES

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