Nov. 08, 2012

Steroid-Related Risk of Heart Disease in Lupus

Incidence of and risk factors for adverse cardiovascular events among patients with systemic lupus erythematosus
Magder LS and Petri M. American Journal of Epidemiology. 2012. Sept 27. doi: 10.1093/aje/kws130. [Epub ahead of print]

What is the topic?

Individuals with lupus are at increased risk of heart disease. However, it is unclear whether this increased risk is mediated by traditional risk factors (smoking, gender, and age, for example), or factors related to the disease itself or its current or past treatments.

What did the researchers hope to learn?

The researchers hoped to learn which of the above risk factors for heart disease in lupus is most influential.

Who was studied?

Over 1,800 individuals who were enrolled in the Hopkins Lupus Cohort from April 1987 to June 2010 were eligible for inclusion in the study. Patients who had a heart disease-related event prior to entry into the Hopkins Lupus Cohort were excluded from the analysis.

How was the study conducted?

Upon enrollment in the study, the participants underwent a comprehensive evaluation of medical history, including date of lupus diagnosis, and information about drug treatments and prior heart disease-related events. During quarterly clinic visits, participants underwent a battery of physical and laboratory tests, including measurement of the following: complement, anti-double-stranded DNA (anti-dsDNA) antibodies, lupus disease activity, and at least one additional immunological marker related to lupus (including anti-Smith antibodies, anti-ribonucleoprotein antibodies, anti-Ro, anti-La, and anti-phospholipid antibodies).

Heart disease-related events were defined to include the following: myocardial infarction (heart attack), thrombotic stroke (blood clot in a brain artery), angina (chest pain), percutaneous coronary intervention (angioplasty), a coronary bypass procedure (surgical correction of coronary artery disease), or claudication (pain during exercise).

Lupus disease activity was assessed with use of the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), a modified version of the SLEDAI.

What did the researchers find?

Of the 1,874 patients eligible for the study, 95% fulfilled four or more of the American College of Rheumatology Classification Criteria for systemic lupus erythematosus. Most of them (93%) were women, and most were either Caucasian (56%) or African-American (37%). The patients were, on average, 37 years old and many joined the Hopkins Lupus Cohort within one (39%) to five years (27%) of lupus diagnosis. The follow-up period was 1-10+ years, and most (85%) of the clinic visits were within 115 days of the previous visit. Therefore, 80% of the measurements included in the analysis were made within the previous three months or less.

There were 134 incidents of heart disease-related events in these patients; these included 65 strokes, 27 myocardial infarctions, 29 cases of angina or coronary artery procedures, and 13 cases of claudication. Among the patients for whom heart disease-related risk factor information was available (62%), 109 incidences of heart disease-related events were observed. This was substantially higher than what would be expected in the general population.

The number of heart disease-related events increased significantly with age, and was especially more common among those aged 50 years and older. Heart disease-related events were significantly more common among men, and those with increased average systolic blood pressure, elevated average cholesterol levels, and those having diabetes mellitus. Even after accounting for the increased risk due to increased lupus disease activity, and increased blood pressure and cholesterol, patients currently taking steroids at a dose of 20 mg/day or more had significantly more heart disease-related events. Also at increased risk were those with significantly increased average past levels of lupus disease activity and elevated recent levels of anti-ds DNA antibodies.

Overall, body mass index made no significant difference in the risk of heart disease-related events. After adjustment for age, there was no significant association between the incidence of heart disease-related events and any of the following: duration of lupus disease, age at lupus diagnosis, average lupus disease activity, history of skin or musculoskeletal involvement, or history of immunological involvement (anti-dsDNA antibodies, anti-Smith, anti-Ro, anti-La, or anti-ribonucleoprotein antibodies, or low complement).

What were the limitations of the study?

First, clinical variables (such as blood pressure and lupus disease activity) were only assessed quarterly, so some variables included in the analysis may not reflect current values. Second, some patients missed quarterly visits, so some data included in the analysis did not reflect the most recent measurement of clinical variables. Third, some autoantibodies were only measured once during cohort participation, so information about them is limited.

What do the results mean for you?

The results suggest that the current dose of steroids taken, rather than the cumulative dose, is perhaps the most critical factor in determining the risk of heart disease-related events in individuals with lupus. This suggests that the short-term impact of steroid use on heart disease risk is relatively more important than the history of steroids taken in the past.

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