Ruth Ann Marrie, MD, PhD––University of Manitoba, GF 543, Health Sciences Centre, Winnipeg, MB

Introduction
Comorbidity, or co-existing health conditions, is common. In 1987, 88.5 million Americans had one or more chronic health conditions which needed medical care or affected activity levels (Hoffman, Rice, & Sung, 1996). Forty-four percent of persons with chronic conditions had more than one. The presence of chronic conditions increased with age (Hoffman et al., 1996).

Multiple sclerosis (MS) is a chronic disease affecting more than 300,000 Americans (Anderson et al., 1992). Patients with MS may also have other health problems, such as diabetes or high blood pressure. We do not know much about how often other health problems occur in MS or whether MS behaves differently when another chronic condition is present.

How Could Co-Existing Health Conditions Affect MS?
Co-existing health problems could affect MS in a few ways. Having a pre-existing condition could change how long it takes to be diagnosed with MS after symptoms first start. A person with a pre-existing problem could get diagnosed earlier because they see doctors more often (Fleming et al., 2005). A person with a pre-existing problem could get diagnosed later because that problem masks symptoms of a new condition. Co-existing health problems could affect decisions about treatment. For example, liver disease is a contraindication to using interferon-beta (Betaseron®, Avonex®, Rebif®) (Francis, 2004). We do not know enough about how co-existing health problems affect MS. This article discusses what is known about other health problems among persons with MS participating in the NARCOMS Registry.

The Questions
In the Fall 2006 update questionnaire we asked NARCOMS participants whether they had other health problems in addition to MS. For each condition we asked what year the condition was diagnosed, and whether participants were receiving any treatment for the condition. The list of physical conditions we asked about is shown below (Table 1). We asked about a history of depression, anxiety, bipolar disorder (manic depression), and schizophrenia. We also asked participants whether they were smokers, and their current height and weight. We used height and weight to calculate the body mass index (BMI).

Study Participants
A total of 8,983 NARCOMS participants were included in the study.(Marrie et al., 2008). Of these 24% were men and 76% were women. Ninety-four percent were whites, 2.4% were African American, while 3.3% reported another race. Their average age was 52.7 years.

Co-existing Conditions and Health Behaviors
Most participants (77%) had another chronic condition along with MS (Marrie et al., 2008). The most common conditions were high cholesterol (37%), high blood pressure (30%), arthritis (16%), irritable bowel syndrome (13%), and lung disease (13%). The least common conditions were cancers of the lung, colon and rectum, and HIV (all 0.5% or less). Women and African Americans were more likely to report another chronic condition than men and Whites. Older participants reported more health conditions than younger participants.

Forty-eight percent of participants reported a co-existing mental condition. Nearly half reported having a history of depression, while 16.5% reported a history of anxiety (Marrie et al., 2009a). Women, whites and single persons were more likely to report a history of depression (Marrie et al., 2009a).

We compared how often NARCOMS participants reported these conditions to how often Americans in the general population reported these conditions. To do this we had to make the ages of NARCOMS participants comparable to the ages of the general population (Rothman & Greenland, 1998). We focused on the five most common physical conditions reported by participants (Table 2). NARCOMS participants reported high cholesterol, high blood pressure, arthritis, and lung disease as often as the general population. They reported irritable bowel syndrome more often than the general population.

Fifty-four percent of participants reported that they had ever smoked. Only 1,542 (17.3%) currently smoked (Marrie et al., 2009b). One quarter of participants were obese and one-third were overweight.

Delays in Diagnosis
The average age when symptoms of MS first started was 31.2 years, and the average age of diagnosis was 38.2 years. The average delay between first symptoms and the diagnosis of MS was 7.0 years (Marrie et al., 2009b). The delay between first symptoms and diagnosis was shorter in men than women, and shorter in persons who were older when their symptoms first started. The average delay in diagnosis has decreased over time. For participants whose symptoms first started in 1980 or earlier, the average delay in diagnosis was more than 10 years. For participants whose symptoms first started in 2000 or later, the average delay in diagnosis was a year.

Some NARCOMS participants had chronic health conditions before their MS was diagnosed. We found that participants were obese, smoked, or had chronic health conditions when their MS symptoms first started took from one to 10 years longer to be diagnosed with MS as compared to participants without those conditions (Marrie, et al., 2009c). The length of the delay varied with the condition and the age when the MS symptoms started. For a person with a vascular condition such as high blood pressure or diabetes, whose MS symptoms started between the ages of 25 and 40 years, the average delay was 2 years. For a person with a muscle or joint condition such as fibromyalgia whose MS symptoms started between the ages of 25 and 40 years, the average delay was nearly 5 years.

Disability at Diagnosis
A total of 2,375 participants (26.4%) enrolled in NARCOMS within two years of their diagnoses of MS. We compared the amount of disability reported by participants at diagnosis according to whether or not they had pre-existing health conditions. Participants reported disability using Patient Determined Disease Steps, a questionnaire included in all NARCOMS update questionnaires. Participants with pre-existing conditions such as obesity, high blood pressure, diabetes and fibromyalgia tended to have more disability at the time they were diagnosed with MS than participants without those problems.(Marrie, et al., 2009c) Participants with any pre-existing condition were more than 50% more likely to have moderate disability (some difficulty walking) than participants without any pre-existing conditions.

Summary
Co-existing health conditions are common in multiple sclerosis. Pre-existing health conditions seem to delay the diagnosis of MS, and are associated with more severe disability at diagnosis. It is not known what other effects co-existing health conditions may have on multiple sclerosis. Further research is needed.

References
Anderson, D. W., Ellenberg, J. H., Leventhal, C. M., Reingold, S. C., Rodriguez, M. and Silberberg, D. H. (1992). Revised estimate of the prevalence of multiple sclerosis in the United States. Annals of Neurology 31: 333-336.

Centers for Disease Control and Prevention (2002). Prevalence of self-reported arthritis or chronic joint symptoms among adults — United States, 2001. MMWR 51: 948-950.
Centers for Disease Control and Prevention (2006). Summary Health Statistics for U.S. Adults: National Health Interview Survey, 2004. Vital and Health Statistics. Hyattsville, Maryland, National Center for Health Statistics. 10: 1-164.

Fleming, S. T., Pursley, H. G., Newman, B., Pavlov, D. and Chen, K. (2005). Comorbidity as a predictor of stage of illness for patients with breast cancer. Medical Care 43: 132-140.

Francis, G. (2004). Benefit-risk assessment of interferon-b therapy for relapsing multiple sclerosis. Expert Opinion on Drug Safety 3: 289-303.

Hoffman, C., Rice, D. and Sung, H. Y. (1996). Persons with chronic conditions. Their prevalence and costs. JAMA 276: 1473-1479.

Hungin, A. P. S., Chang, L., Locke, G. R., Dennis, E. H. and Barghout, V. (2005). Irritable bowel syndrome in the United States: Prevalence, symptom patterns and impact. Aliment Pharmacol Therapy 21: 1365-1375.

Marrie, R. A., Horwitz, R., Cutter, G., Tyry, T., Campagnolo, D. and Vollmer, T. (2008). Comorbidity, socioeconomic status, and multiple sclerosis. Multiple Sclerosis 14(8): 1091-1098.

Marrie, R. A., Horwitz, R., Cutter, G., Tyry, T., Campagnolo, D. and Vollmer, T. (2009a). High frequency of adverse health behaviors in multiple sclerosis. Multiple Sclerosis Oct 9. [Epub ahead of print].

Marrie, R. A., Horwitz, R. I., Cutter, G., Tyry, T., Campagnolo, D. and Vollmer, T. (2009b). The burden of mental comorbidity in multiple sclerosis: Frequent, underdiagnosed, and under-treated. Neurology 70(Suppl 1)(A208).

Marrie, R. A., Horwitz, R. I., Cutter, G., Tyry, T., Campagnolo, D. and Vollmer, T. (2009c). Comorbidity delays diagnosis and increases disability at diagnosis in MS. Neurology In Press.

Rothman, K. J. and Greenland, S., Eds. (1998). Modern Epidemiology. Philadelphia, PA, Lippincott Williams & Wilkins.

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