Question:
I have a brother with Down syndrome who recently turned 49. I am his legal guardian. He sees a cardiologist for a number of reasons, but primarily for low blood pressure and occasional fainting or near-fainting spells. Over the past couple of years, the cardiologist has begun to check his cholesterol and found it to be high. (Total cholesterol was 216 and LDL cholesterol was 147 on the most recent test. All the other lipids were normal.) The cardiologist wants to put my brother on a statin, but I have resisted so far because I’m not sure it’s necessary or that the benefits would outweigh the risks of side effects. In November, my brother had a coronary artery calcium test which showed that all his coronary arteries were clean – except for one. The LAD had some calcium deposits and the result was a score of 22.65. Now the cardiologist wants to put my brother on a statin and bring the LDL level down to 70. I’m still not sure what to do. My brother is on a lot of medication already – he takes almost 20 pills a day – and I’m concerned about adding another medication to his regimen as well as the possibility of drug interactions and side effects. I believe my brother has been harmed – inadvertently – by prescription medications in the past and I don’t want him harmed again by statins. Of course, I don’t want him to have a heart attack or stroke, either, but I thought he was at low risk for those kinds of events due to DS. (I am more concerned about Alzheimer’s because it is so prevalent among people with DS.) How do I decide what to do about my brother? He has many doctors, including a primary care physician he has seen for over 25 years, but his doctors don’t have any patients like him. I want to get a second opinion from a doctor who has more experience treating adults with DS. Does that seem like a reasonable approach? And do you think this is one of those cases where the person with DS should be treated the same as someone without DS, or should he be treated differently?
Answer:
Thank you for your question.
It is well known that people with Down syndrome (DS) have high rates of congenital heart disease (CHD). Various studies have found that 40-60% of children born with DS have CHD, with atrioventricular septal defect being the most common. As people with DS age, they also may acquire additional structural heart problems including mitral valve prolapse and other valvular disease.
However, interestingly, people with DS have less atherosclerotic disease. That is the disease that one is trying to prevent by lowering cholesterol. In a published study on the individuals served at our clinic, we found a markedly decreased rate of coronary artery disease (blockages of the arteries that supply blood to the heart muscle by atherosclerotic plaques). That included much lower rates of myocardial infarctions (heart attacks) and angina (pain related to decrease blood flow to the heart muscle).
In another study with those seen in our health care system, when matching people with and without DS by age and sex, we found a significantly lower rate of coronary artery disease but only a slightly reduced incidence of heart attacks. With a lower incidence of coronary artery disease, other factors must be playing a role in the heart attacks. Sleep apnea and congenital heart disease (which are more common in people with DS) both probably play a role, but it is not clear that lowering cholesterol would reduce the heart attacks since atherosclerosis seems to be less of a factor.
When the GLOBAL Medical Care Guidelines for Adults with Down Syndrome (published in 2020) were being developed, the information from those two studies above was not available. Even without those studies, the lower incidence of atherosclerotic disease in people with DS was recognized. However, the difference was not so great as to preclude some evaluation and consideration of possible treatment. Therefore, the Global guidelines followed the United States Preventive Services Task Force guidelines for those without DS. For adults with Down syndrome without a history of atherosclerotic cardiovascular disease, the GLOBAL guidelines recommend assessing the appropriateness of statin therapy every 5 years starting at age 40 years by using a 10-year risk calculator. The 10-year risk calculators use cardiac risk factors to determine risk. These factors include smoking, hypertension (high blood pressure), diabetes mellitus, age, and gender. One example of one of the calculators can be found here.
In my experience, calculating risk based on these factors (using one of the calculators) for people with DS very infrequently results in a risk high enough to be in the range in which statins are recommended. In addition, since the risk of atherosclerotic disease appears to be less in people with DS (as noted in the above studies), the calculators likely predict a risk that is greater than it really is for a person with DS.
As far as the calcium score, there is debate as to how well that data adds to the calculations for cardiac risk based on the factors noted above (used in the 10-year cardiac risk calculators). Even with that limitation in mind, the findings you reported show a low score in only one artery (and the others are apparently normal).
Another consideration for the use of statins in people with DS is the potential for side effects. Statins have been found to cause muscle aches or muscle inflammation. We have had patients develop this side effect, but it is not known how often this occurs in people with DS. Some individuals with DS have limited ability to report symptoms so it may be they are having the side effect but not reporting it. Another side effect is impaired cognition. Again, we have seen this side effect in people with DS but how frequently it occurs is not known. If a person with DS does have cognitive decline on a statin, it might be difficult to delineate if it is caused by the statin, by Alzheimer’s disease, or some other condition.
There are data in people without DS that support the phrase, “what is good for the heart is good for the brain.” That phrase suggests that what is done to prevent atherosclerotic disease may help prevent Alzheimer’s disease. Based on that, there has been some interest in whether statins may prevent Alzheimer’s disease in people with DS. Studies have not clearly demonstrated that. In addition, one disconnect in that phrase in people with DS is that atherosclerotic disease is less common and Alzheimer’s disease is much more common. Therefore, the connection between atherosclerotic disease and Alzheimer’s disease is not clear (and seems less likely) in people with DS.
Our approach at our Center is to follow the GLOBAL guidelines. We screen cholesterol starting at age 40 years and calculate risk based on a 10-year cardiac risk calculator.
Some additional thoughts regarding risk. People with DS may be more at risk for strokes. Admittedly, this is based on limited data. In our study, there was a mild increase, but it was not a statistically significant difference. In a study done on hospitalized patients in Australia, individuals with DS were more at risk for embolic strokes. These were not strokes caused by buildup of plaques due to high cholesterol (and, therefore, less likely to be reduced by statin use), but strokes caused by clots that typically started in the heart and “broke off” and went to the brain to cause a stroke. Those are largely related to a history of having congenital heart disease and associated structural abnormalities of the heart and abnormal rhythms. Again, it is less likely these are prevented by lowering cholesterol.
Another common cause of strokes in people with DS is the changes that occur in small blood vessels related to the buildup of amyloid associated with Alzheimer’s disease. This is not due to cholesterol plaques but rather amyloid damage to blood vessels.
Another cause of stroke that is more common in people with DS is Moyamoya. This is a condition that causes abnormalities in the structure of blood vessels in the brain and is not related to cholesterol plaques.
I recommend that you discuss this information with your brother’s cardiologist to determine what is the right approach for him.