Jan. 20, 2012

Optimizing Assessment of Heart Disease Risk in People with Lupus

Importance of cumulative exposure to elevated cholesterol and blood pressure in development of atherosclerotic coronary artery disease in systemic lupus erythematosus: a prospective proof-of-concept cohort study.
Nikpour M, Urowitz MB, Ibanez D, Harvey PJ, and Gladman DD. Arthritis Research & Therapy. 2011 Sept 29: R156. [epub ahead of print].

What is the topic?

People with lupus are at substantially increased risk for the development of heart disease. Previous studies indicate that traditional risk factors for heart disease, such as high blood pressure or cholesterol, account for only a small portion of this increased risk among people with lupus. 

The risk of heart disease is typically assessed based on measurement of blood pressure and cholesterol levels at a certain point in time for a person of a given sex and age. However, blood pressure and cholesterol levels can vary considerably over time in individual lupus patients. For this reason, the researchers argue that it is important to consider blood pressure and cholesterol levels over multiple time points in order to obtain an optimal assessment of heart disease risk. 

What did the researchers hope to learn?

The researchers hoped to learn about the potential effectiveness of assessing heart disease risk in people with lupus by measuring blood pressure and cholesterol levels over multiple time points (as opposed to single time points).

Who was studied?

The study included 991 people with lupus who were evaluated for blood pressure (“blood pressure patients”) and 956 people with lupus who were evaluated for cholesterol levels (“cholesterol patients”). 

How was the study conducted?

The study participants visited the University of Toronto Lupus Clinic at two- to six-month intervals. Blood pressure and cholesterol levels were measured at each study visit. Events indicative of heart disease (including myocardial infarction, angina, and sudden cardiac death) were documented upon occurrence. For patients that experienced more than one event indicative of heart disease, only the first event was included in the data analysis. Patients having a history of heart disease prior to the study were excluded. 

Several variables were documented for each patient at each visit, including disease duration and activity, anti-phospholipid antibodies, classic heart disease risk factors (such as diabetes and smoking), and medication use (including anti-malarial drugs, immune-suppressing drugs, anti-hypertensive drugs, and lipid-lowering drugs).

Advanced statistics were used to assess heart disease risk based on multiple measurements of cholesterol and blood pressure (as well as other patient-related variables) over time. 

What did the researchers find?

In both the blood pressure and cholesterol datasets, most of the patients were Caucasian women, with an average age of 37 years, who had lupus for an average of six years. For each dataset, upon entry to the study, about 60% of patients were taking steroids, 40% were taking anti-malarial drugs, 25% were taking immune-suppressing drugs, 25% were taking anti-hypertensive drugs, and 5% were taking drugs to lower cholesterol. For each dataset, upon entry to the study, about 40% of patients had high cholesterol, 22% had high blood pressure, 19% were smokers, and 3% had diabetes. 

Among the blood pressure patients, there were a total 94 cardiac events (75 angina, 25 myocardial infarction, and 2 sudden cardiac deaths; 8 had both angina and myocardial infarction). Among the cholesterol patients, there were a total of 86 cardiac events (71 angina, 20 myocardial infarction, and 2 sudden cardiac deaths; 7 had both angina and myocardial infarction). The following were independently associated with increased risk of heart disease (when present upon entry to the study) in both sets of patients (cholesterol and blood pressure patients): being Caucasian, older, menopausal, or hypertensive, or being treated with steroids. In addition, the following were associated with increased risk of heart disease when present during the follow-up period: being older when diagnosed with lupus, having anti-phospholipid antibodies, high cholesterol or blood pressure, or diabetes (mellitus), being treated with anti-hypertensive drugs, cholesterol-lowering drugs, or higher cumulative doses of steroids. Importantly, for both sets of patients, taking anti-malarial drugs during the follow-up period rendered heart disease risk significantly reduced. 

When advanced statistics were used to evaluate heart disease risk imposed when taking into account changing values for blood pressure and cholesterol levels between study visits, the following variables were associated with significant risks for the development of heart disease in both sets of patients (cholesterol and blood pressure patients): male sex, age, lupus disease activity upon study entry, and having been treated with steroids (ever). In this analysis, taking anti-malarial drugs also significantly decreased the risk of heart disease in both sets of patients. 

What were the limitations of the study?

This study suggests that optimal assessment of heart disease risk in people with lupus may best be accomplished by use of multiple measures of blood pressure over time. However, at present, the ideal number of measurements has not been established. Further study will be required to help clarify this. Also, this study was not ideally suited to assess heart disease risk in people with lupus depending on blood cholesterol levels. Lastly, this study does not constitute an exhaustive evaluation of traditional risk factors for heart disease and, therefore, the role of other variables (such as family history of heart disease, body mass index, and waist-to-hip ratio) merit further study. 

What do the results means for you?

This study highlights the important role of traditional risk factors (such as elevated blood pressure and/or cholesterol) in the development of heart disease among people with lupus. In particular, this study suggests that traditional methods of blood pressure assessment (such as single-point-in-time measures) tend to underestimate its potential role in the development of heart disease and do not predict heart disease-related outcomes in people with lupus. Instead, the researchers suggest, measures that indicate cumulative exposure to elevated blood pressure (which take into account multiple measures of blood pressure over time) are better predictors of heart disease risk in people with lupus. The researchers suggest that a minimum of three measures of blood pressure over time may be most useful. This may be because, unlike that seen in the general population, blood pressure takes a dynamic course over time, due to factors related to treatment and varying disease activity, in people with lupus. Future studies may help establish whether this is also true for cholesterol levels, but the current study was not ideally suited to make this determination.


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