Coronary Artery Disease Risk Factors In SLE

With excellent survival rates in Systemic Lupus Erythematosis (over 90% survival 10 years after diagnosis), attention is now focused reducing complications of lupus and its treatment that cause disability and a decrease in the quality of patients’ lives. Cardiovascular disease has been recognized for some time as a problem in some patients with lupus. Dr. Urowitz and his colleagues in Toronto reported that deaths early in the source of lupus tended to be from active disease of infection, whereas deaths later in the course of lupus were usually from heart disease and stroke. Because most patients with lupus can count o excellent control of their lupus and quick eradication of any infections with antibiotics, it makes sense to pay more attention to some of the other causes of health problems in lupus, namely heart disease.

In the Hopkins Lupus Cohort, 8% of the patients with lupus have coronary artery disease. Why do some people with lupus develop heart disease? Heart disease is a major problem in the American population, but what is unusual about heart disease in lupus is that it develops 20 or 30 years earlier than we expect in the general population. Lupus itself can affect blood vessels, including the coronary (heart) arteries. We know that the immune complexes of lupus can injure blood vessels in animal models of lupus. In a very few people with lupus, lupus has caused severe inflammation of the coronary arteries called “vasculitis”. Is it just lupus itself, then, that is the cause of angina (heart pain) and myocardial infarction (heart attack) in the fraction of people with lupus who have heart disease?

Finding out what causes heart disease in lupus is complicated, because there are a lot of potential ways that coronary arteries could be injured. A very important clue was the finding by pathologists that atherosclerosis (hardening of the arteries) was the major problem found in the coronary arteries of people with lupus who had heart disease. Artherosclerosis in people with lupus became a problem after corticosteroids (usually prednisone)became available as a treatment for lupus and was not common before corticosteroids were invented. It may not have been common in the presteroid era as patients may not have lived long enough to develop it. However, this is circumstantial evidence -- that prednisone use and coronary atherosclerosis go together -- and does not prove that prednisone use causes coronary atherosclerosis. We have to remember that prednisone is prescribed to treat lupus -- the more severe the lupus, the more prednisone is given -- and that we already have evidence in animal models that lupus itself can damage blood vessels.

One way to help figure out how prednisone and coronary atherosclerosis might be connected is to apply techniques of clinical research. Clinical research allows us to find characteristics of people with lupus who develop heart disease that are different from people with lupus who do not have heart disease. The important benefit of clinical research is to identify risk factors for heart disease in lupus that can be reduced or modified to make it less likely that heart disease will develop later -- what we commonly call “preventive medicine”. Six years ago, to help us find the causes of heart disease and other complications of lupus, we began the Hopkins Hospital and the rheumatologists who care for them. our patients help the research effort by filling out our questionnaires on heart disease every year and by allowing us to record information about them -- such as weight, cholesterol, and blood pressure -- that may affect the development of heart disease. The Lupus Foundation of America, the Maryland Lupus Foundation and the National Institutes of Health have supported this effort by research grants. The Hopkins Lupus Cohort is definitely an example of “your lupus research dollars at work”. What have we learned so far from this research effort?

First of all, we compared out patients who developed heart disease with those patients who had no heart disease to see how they differed. We did not find any simple answer that tied the amount of prednisone or the highest dose of prednisone to heart disease; instead, we found that the number of years the person had taken prednisone was a risk factor for heart disease. It is not easy to figure out what this means, because the longer the person has lupus, the longer she will have taken prednisone. This means that the duration of prednisone use might simply be a marker for the number of years lupus has been injuring the coronary arteries. In other words, prednisone may not be the cause of heart disease.

We also identified several risk factors for heart disease in our patients who had angina or myocardial infaction that we call “typical risk factors”, because they also predict heart disease in the general population. The major risk factors were high blood pressure, high cholesterol, and being overweight. We looked at how common these risk factors for heart disease were in our lupus patients -- not just the above three but all risk factors, including smoking, diabetes, not exercising, and a family history of heart disease. Considering that our average patient with lupus is only in her 30’s, it is astonishing to learn that the average patient has 3 or more risk factors for heart disease. Physicians commonly find that young people often downplay the importance of bad health habits, such as smoking, poor dietary habits, because they believe they will escape later problems. For lupus patients, though, “the future is now” -- because heart disease in lupus patients can occur in the 30’s and 40’s.

Recently, we have begun to tackle the problem of how prednisone is tied in to the development of heart disease. We are faced with the fact that most patients with lupus will need to take prednisone -- in varying doses and for varying periods of time -- during their lifetimes. Nothing better has yet been invented to treat lupus. Of course, physicians who treat patients with lupus try to “limit” prednisone. By this we mean that we prescribe the lowest dose necessary to control the disease and try to use other medicines, such as anti-inflammatory medicines, hydroxychloroquine (Plaquenil), and immunosuppressive medicines (Imuran, Cytoxan), whenever possible and when indicated.

To understand how prednisone might be tied into heart disease, we have benefited from work done by other researchers, sometime working with other diseases. Dr. Ettinger and colleagues have studied how prednisone affects blood lipids (fats) in patients with lupus. They have found that prednisone use is associated with higher lipid levels. This suggests that prednisone affects blood lipids which we know are a risk factor for heart disease. Patients with organ transplant, have very high rates of heart disease that are associated with their blood lipids. And as every physician who treats lupus knows -- and as many patients have learned from their own experience -- taking prednisone may cause high blood pressure that is already present to worsen and may cause weight gain.

Clinical research involves putting numbers to these things that seem to connect prednisone with risk factors for heart disease. We believe that the best way to do this is to see how out patients change form visit to visit as their prednisone dose up, down, or stays the same. This is called “longitudinal data analysis”. It is possible for us to learn important things from our group of patients, because we have information from over 4,000 visits on over 300 patients.

We have been able to show that prednisone does have a predictable effect on risk factors for heart disease. For example, if the prednisone dose is increased by 10 mg., the cholesterol tends to increase by 7 points, and the mean blood pressure also increases significantly. An increase in prednisone also causes an average increase in weight of 5 pounds three months later. However, we have also found that many of out patients who so not take prednisone have heart disease risk factors.

It is also important not to throw up our hands and say “Oh well -- the patient needs prednisone, so there’s nothing to be done.” Patients should not be afraid to take the prednisone that they need to preserve their health. Instead, this should be viewed as an opportunity for the physician and the person with lupus to band together to reduce the risk factors for heart disease, regardless of whether they are connected with prednisone of not. There are many “non-drug” approaches that help reduce risk factors. Limiting sodium (salt) and increasing exercise can help blood pressure (and, or course, blood pressure medicines can be prescribed). Following the American Heart Association Step 1 -- and, even better -- Step 2 diet can help to reduce cholesterol. Reducing calorie intake and increasing exercise can help reduce weight.

We are sure whether drug treatment to lower cholesterol is indicated in lupus. The use of cholesterol lowering medications is a medical controversy in the general population -- not because they don’t work, because they do lower cholesterol -- but because there isn’t adequate follow-up to determine if they lower heart disease, especially in women. At least two cholesterol-lowering medicines, lovastatin and gemfibrozil, have been used in people with lupus (or, for that matter, in women). For now, patients with lupus who have very high cholesterol levels should make decisions about non-drug and/or drug treatments individually with their physicians.

The long term answer is that “knowledge is power”. Both the person with lupus -- and her physician -- need to monitor for the typical risk factors for heart disease and to start efforts to reduce them if they appear. the members of the Hopkins Lupus Cohort now spontaneously ask their physicians, “How’s my cholesterol?”, whereas 6 years ago, the physician would not have known the answer -- because no one would have measured it! We pay a lot of attention to controlling blood pressure. Our patients are much more likely to see a nutritionist of dietitian for professional help with good diet habits. Times change, and in the case of heart disease in lupus patients, for the better. People with lupus and their physicians, armed with the knowledge gained from clinical research studies, can help to prevent problems such as heart disease.