Thursday, August 12, 2010

Ruth Ann Marrie Vascular Comorbiity and Progession of MS

 Ruth Ann Marrie Discusses Vascular Comorbidity and Rapid Disability Progression in MS

March 22, 2010

 Ruth Ann Marrie, MD, PhD, Director of the Multiple Sclerosis Clinic, and Assistant Professor of Medicine and Community Health Sciences at the University of Manitoba, talks about vascular comorbidities and risk factors and their effect on the progression of multiple sclerosis. Her paper, "Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis," was published recently in Neurology®' (2009;72:117-124). She spoke with José G. Merino, MD, MPhil, Science Editor of Please describe the methodology of your study.

Marrie: We were interested in the effect of vascular comorbidities on the progression of disability in patients with multiple sclerosis (MS). In October 2006, we asked participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry to report their comorbidities, including the year of diagnosis. We linked this information to demographic and clinical information reported by participants upon enrollment in the Registry and in their semi-annual updates. We grouped diabetes, hypertension, heart disease, hyperlipidemia, and peripheral vascular disease together as vascular comorbidities.

We considered two scenarios. In the first, we examined whether vascular comorbidity at diagnosis affects subsequent progression of ambulatory disability. For this analysis, we compared participants who reported one or more vascular comorbidities at the time of their MS diagnosis to those who never developed one. This scenario was meant to reflect the situation faced by a clinician treating a patient with newly diagnosed MS. In the second scenario, we examined whether the development of vascular comorbidity at any point in the disease course affected the time between symptom onset and the same disability outcomes, using Cox proportional hazards models with time dependent covariates. We found that vascular comorbidities adversely affected the course of the disease. In your study, what vascular comorbidities or risk factors were the most closely associated with the progression of disability in patients with MS?

Marrie: The effects of all of the vascular comorbidities studied were quite similar, except for heart disease, for which there was no significant effect. How did the timing of the appearance of the vascular comorbidities (at onset versus later in the course of the disease) alter the association between these conditions and disease progression?

Marrie: The association between the vascular comorbidities and disability progression was similar regardless of whether the comorbidity was present at MS onset, diagnosis, or later in the disease course. Study participants with vascular comorbidities had more rapid disability progression than those without vascular comorbidities. Do vascular comorbidities affect disease progression among patients with MS by promoting and potentiating cerebrovascular disease?

Marrie: We did not examine cerebrovascular disease in this study, though this is an important issue—and a potential explanation for our findings. The question requires further study. What are possible explanations for the observed association between vascular risk factors and disease progression in MS patients?

Marrie: Our study did not examine the mechanisms by which vascular comorbidities affected disease progression, but altered blood vessel structure and function, increased susceptibility to oxidative stress, or increased peripheral inflammation are all considerations. The presence of vascular comorbidities and risk factors has been associated with the development of cognitive impairment, including Alzheimer's disease, on elderly patients. Did you find any effect of the presence of vascular risk factors on cognition in patients with MS?

Marrie: In this study we focused on the impact of vascular risk factors on gait disability, and did not examine other aspects of disability such as vision, cognition, or hand function. To my knowledge, other studies examining the impact of comorbidities on MS also have focused on gait disability, not cognitive disability. For your outcome assessment you used the Patient Determined Disease Steps scale. What are the features of this scale? How does it differ from the Expanded Disability Status Scale (EDSS)?

Marrie: Patient Determined Disease Steps is a validated self-report measure that assesses gait disability. It is scored from 0 (no disability) to 8 (bedbound). A score of 3 represents early gait disability without needing an assistive device and approximates an EDSS score of 4.0 to 4.5; and scores of 4, 5, and 6 represent EDSS scores of 6 (uses unilateral assistive device to walk) to 6.5 (uses bilateral assistance to walk). It correlates well with a physician scored EDSS (r = 0.94) and can be completed easily by patients. What is the NARCOMS Registry?

Marrie: The NARCOMS Registry is a project of the Consortium of MS Centers; it is a large self-report registry for persons with MS. Participants voluntarily provide sociodemographic information and clinical information about their MS at enrollment and semi-annually thereafter. Clinical information provided includes disability and treatment status. The registry includes more than 30,000 unique participants, more than 15,000 of whom are in active status. What is the main message from your findings for general neurologists?

Marrie: Our findings suggest that vascular comorbidity at any point in the course of MS is associated with an increased risk of disability progression. This raises the question of whether treating these comorbidities more aggressively could improve outcomes in MS.

Author Disclosure

Dr. Merino performed a one-time consultation with staff from Bell, Falla and Associates.

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