Predicting coronary heart disease

“Measuring calcium deposits in the arteries of the heart is a good predictor of future heart disease, regardless of racial origin”, The Times reports today. The newspaper gives details on a new study that supports claims that a Computed Tomography (CT) scanning test can give an earlier indication of cardiovascular risk than the traditional risk factors of a person’s age, weight, whether or not they smoke, and having high blood pressure or cholesterol.

This cohort study of a selected group of recruits from multiple ethnicities has shown that those with higher scores for calcium were at more risk of heart disease. However, age, diabetes, high blood pressure and cholesterol, and smoking are all linked (independently of each other) with the risk of heart attack. This study is unable to say how much the new test would improve the predictive abilities of these factors in an unselected, healthy population. There are also additional risks in that the amount of radiation from a CT scan has been estimated to be four times as much as a standard chest X-ray. It is generally accepted that humans should not be exposed to large doses of radiation without good cause.

Where did the story come from?

Dr Robert Detrano from the University of California at Irvine and 14 colleagues from around the US carried out the research. The study was supported by grants from US organisation the National Heart, Lung, and Blood Institute. The study was published in the (peer-reviewed) medical journal: The New England Journal of Medicine

What kind of scientific study was this?

Atherosclerosis is a disease where plaque (made up of fatty substances, dead cells, cholesterol and calcium) is deposited by the blood on the inner walls of the arteries, narrowing them and impairing the flow of blood. When this build-up happens in the arteries that supply the heart muscles, the condition is known as coronary artery disease, and when these plaques rupture, blood clots can form and cause a heart attack.

The authors say that CT scanning can detect the build-up of calcium and therefore predict future heart disease, before other traditional symptoms of the condition are evident. However, so far this has only been confirmed in white populations. The authors say that due to there being “substantial differences in the extent and prevalence of coronary calcification among various ethnic groups”, they wanted to test the effectiveness of this method at predicting heart disease in black, Hispanic and Chinese populations.

In this cohort study, 6722 people between 45 and 84 years old were recruited from six areas of the US over a two-year period. The researchers used housing and telephone lists to select the participants. In order to include enough participants from different ethnicities the researchers decided to “over sample” people from black, Hispanic and Chinese ethnic groups. This resulted in a balance of about 38% white, 28% black, 22% Hispanic and 12% Chinese. The researchers excluded anyone who already had known heart disease. The participants were, on average, followed for 3.9 years.

Each of the six areas has a CT scanning facility and the participants were given a CT scan that assessed their amounts of coronary calcium. The amount of calcium on the scan was scored using standard scoring systems on two different types of CT scanner. Recruits were told whether they had none, below average, average or above average coronary calcium, and that they should discuss the results with their doctors.

The participants also gave information on cardiovascular risk factors such as family history of coronary heart disease, smoking, cholesterol levels, hypertension, and diabetes. The researchers also recorded their blood pressure, cholesterol levels, and BMI.

At 9 to 12 month intervals, the researchers contacted the participants or their families by phone and asked about hospital admissions, deaths and heart disease.  Their answers were verified by contacting the hospitals concerned or checking death certificates.

What were the results of the study?

There were 162 coronary events in all, which included diagnoses of angina. Out of these events, 89 were major events (heart attack or death from coronary heart disease). When the researchers compared participants with no coronary calcium to those who had scores above 300, the risk of a coronary event increased by a factor of 10. This difference was statistically significant (P<0.001) and was adjusted to take into account standard risk factors.

Among the four ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The researchers looked at how well the test discriminates between those who later go on to have either a major coronary event or any coronary event. They found that the test was a better predictor of these outcomes when the calcium score was added to the standard risk factors compared to when the risk factors were used on their own.

What interpretations did the researchers draw from these results?

The researchers conclude that “coronary calcium score is a strong predictor of the [first signs of] coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the US. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected”.

What does the NHS Knowledge Service make of this study?

This relatively large sample of recruits from differing ethnic backgrounds provides further data to refine the accuracy and clinical usefulness of the coronary calcium scoring as a test in people without known heart disease, i.e. for screening purposes. However, there are major implications for proposing that a test be used in this way, which the researchers do not address and which require further analysis.

• The claim that the calcium scoring test improves the ability of the usual cardiovascular risk assessments methods (relying on measures of traditional risk factors) to predict future events needs careful scrutiny. The researchers quote a measure called the area under the curve (AUC), which assesses the discriminatory power, or accuracy of the test. However, they do not show this curve or provide any of the sensitivity and specificity results on which these curves are usually based.
• The small significant difference between the area (AUC) in their model using conventional risk factors (0.77), compared to the AUC when calcium scoring is added (0.82), suggests that their conventional risk factor model which uses risk factors such as smoking, diabetes, high blood pressure or cholesterol was not particularly accurate as the AUCs for these can sometimes exceed 0.77. These conventional risk factors are also easier to measure.
• Harms of the test, such as exposure to radiation were not discussed, other sources suggest that the usual dose from a heart CT scan equates to about four standard chest X-rays.
• It is not clear if there was any bias introduced by the unusual selection methods. A selected population such as this may not be representative of the general population and selection bias may mean the trends are misleading. The number of people from which the sample was drawn is not quoted.

Despite the researchers’ belief in CT scanning as a method to screen for future heart disease, we do not yet know if knowledge of a calcium score would lead to improved outcomes that matter, such as reduced heart attack. Such outcomes are determined by the treatment that follows testing.

One concern is that patients with elevated calcium scores may be referred for an invasive coronary angiography without further clinical assessment or functional testing for heart disease on a treadmill. This has implications for potential costs both to society and to the patient.