Psoriasis Increases Risk for Myocardial Infarction

PHILADELPHIA, Oct. 10 -- Psoriasis appears to be an independent risk factor for myocardial infarction, especially for younger patients with severe disease, researchers reported.

Younger patients, 30 to 40 years old, with severe psoriasis had almost twice the risk of an MI compared with similar patients without psoriasis. By contrast, 60-year-old patients with severe disease had only a 36% increased MI risk, reported Joel Gelfand, M.D., of the University of Pennsylvania here, and colleagues in the Oct. 11 issue of the Journal of the American Medical Association.

These findings came from a prospective, population-based cohort study in the United Kingdom comparing 556,995 controls and 127,139 patients with mild psoriasis and 3,837 with severe disease, in which the researchers controlled for major cardiovascular risk factors. The data have been used widely in epidemiological studies.

Psoriasis has been associated with cardiovascular diseases in the past, but has been studied only in hospital-based studies that did not control for major cardiovascular risk factors. Thus it has not been clear whether psoriasis itself or comorbidities and behavior associated with the disease explain the association, said Dr. Gelfand and colleagues.

The data were collected from 1988 to 2002 by more than 500 British general practitioners as part of the patient's medical record and stored in a general practice database. Each patient was matched with up to five controls who were randomly selected during similar time periods from the same practices. Patients were 20 to 90 years old, and the mean follow-up was 5.4 years.

Patients with psoriasis were more likely to be men and to be older. They were classified as severe if they ever received systemic therapy (usually methotrexate). Adjustments were made for hypertension, diabetes, history of myocardial infarction, hyperlipidemia, age, sex, smoking, and body mass index, all more common in psoriasis patients.

Patients with severe psoriasis had a higher rate of MI compared with controls The MI rate was 2% in the control population, 1.8% among the mild psoriasis patients and 2.9% among those with severe psoriasis.

The incidence per 1,000 person-years for severe psoriasis was 5.13 (CI, 4.22-6.17), and for mild psoriasis, it was 4.04 (CI, 3.88-4.21). By contrast, for controls, the heart attack incidence was 3.58 (CI 3.52-3.65).

Patients with psoriasis had an increased adjusted relative risk for MI that varied by age. For example, the researchers said, for a 30-year-old patient with mild or severe psoriasis, the adjusted relative risk of having an MI was 1.29 (CI 1.14-1.46), and 3.10 (CI, 1.98-4.86) respectively. However, for a 60-year-old with mild or severe psoriasis, the adjusted relative risk of an MI was only 1.08 (CI, 1.03-1.13) and 1.36 (CI, 1.13-1.64), respectively.

A series of sensitivity analyses found no evidence of confounding by traditional cardiovascular risk factors. In addition, results were similar when analysis excluded MIs occurring in the first six months of follow-up to ensure capture of incident, not prevalent, MI. Other analyses found the relative MI risk for psoriasis patients persisted in a model that included a composite endpoint of MI or death due to any cause, the researchers reported.

The reason for the higher risk of MI among younger patients may relate to the fact that psoriasis is a heterogeneous disease. For example, the researchers wrote, it has been hypothesized that persons with disease onset before age 40 have more severe disease and a stronger association with human leukocyte antigen than patients with later-onset disease. Higher immune activity in psoriasis may be related to a higher risk of MI.

It is also possible, the researchers said, that there may be a survivorship effect, in that after decades of psoriasis, patients predisposed to MI would be less likely to available since they may have died.

In discussing the study's limitations, the researchers mentioned the fact that there may have been unknown or unmeasured confounding variables, such as obesity, stress, and smoking. However, in this study, they said, they did not find any association with body mass index for those patients (61%) for whom the information was recorded.

Additionally, because the researchers defined severe psoriasis on the basis of a history of systemic therapies, it was not possible to differentiate between the impact of psoriasis severity and systemic therapy on the risk of MI. However, they said, the findings in the severe group were robust to sensitivity analysis that excluded patients treated with drugs such as methotrexate and cyclosporine.

The results, the researchers said, add to growing evidence linking T-helper cell type 1 diseases to atherosclerosis and coronary artery disease. In fact, they said, psoriasis is the most prevalent T_H1 autoimmune disease.

Other T_H1 diseases, such as rheumatoid arthritis, have also been shown to be an independent risk factor for acute MI and multi-vessel coronary artery disease. The exact mechanism by which these diseases predispose a patient to cardiovascular disease is unclear, but may be due to common immunological pathways that function abnormally, the researchers said.

Furthermore, they noted, the link between MI and psoriasis may be mediated by other factors beyond inflammation, such as psychological stress, sedentary lifestyle, or possibly poor compliance with management of cardiovascular risk factors.

"Our findings are novel," Dr. Gelfand's team wrote, and therefore it is important that additional studies be performed to confirm these results and determine their therapeutic implications. The authors stressed studying the impact of clinical markers, such as body surface area for psoriasis, as well as biomarkers of systemic inflammation, such as C-reactive protein.

"In the meantime," Dr. Gelfand said, "as part of good medical care, patients with psoriasis should be encouraged to aggressively address their modifiable cardiovascular risk factors."

Dr Gelfand reported receiving grant support (unrestricted grants to the Trustees of the University of Pennsylvania) from Biogen Idec, Amgen, Astellis, and Centocor. He reports consulting agreements with Genentech, Novartis, Warner-Chilcott, AMGEN, Wyeth, Biogen Idec, and Centocor.

Coauthor David Margolis, M.D., Ph.D., has received grant support (unrestricted grant to the Trustees of the University of Pennsylvania) from Biogen Idec; he is also on the data and safety monitoring boards for Abbott, Biogen Idec (which is now Astellis), and Centocor, companies with studies investigating potential treatments for psoriasis.