Should All Patients With A High Coronary Calcium Score Undergo Stress Testing?

Coronary artery calcium (CAC) scans are an excellent tool for better defining coronary heart disease risk in many individuals. In light of the recent ACC/AHA guidelines endorsement of CAC, the skeptical cardiologist anticipates that primary care physicians will be ordering more and will often be faced with the question of what to do with abnormally high results.

There are two, diametrically opposed viewpoints which have been taken on this issue.

The Argument For Stress Testing

The majority of cardiologists are likely to fall into the camp of “more testing is good” which was summarized in a  State of The Art article that Dr. Harvey Hecht wrote in JACC recently.

The argument appears logical and is as follows:

1. There is a high yield of abnormal results from stress testing when done on patients with high CAC.

The appropriateness of stress testing after CAC scanning in asymptomatic patients is directly related to the CAC score. The incidence of abnormal nuclear stress testing is 1.3%, 11.3%, and 35.2% for CAC scores 400, respectively .

2. The higher yield for ischemia/abnormal tests in patients with >400 CAC implies the ability to further risk stratify patients thus leading to guideline recommendations:

It is only in the >400 group that the pretest likelihood is sufficiently high to warrant further evaluation with myocardial perfusion imaging, for which there is a IIb recommendation

Hecht references a 2010 guideline issued by ACC/AHA (2010 ACCF/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults) which states

1. Stress myocardial perfusion imaging (MPI) may be considered for advanced cardiovascular risk assessment in asymptomatic adults with diabetes or asymptomatic adults with a strong family history of CHD or when previous risk assessment testing suggests a high risk of CHD, such as a coronary artery calcium (CAC) score of 400 or greater. (Level of Evidence: C)

Stress MPI testing is more sensitive than stress ECG testing alone but in clinical practice I see a very high rate of false positive stress MPI results. Stress MPI is also much more expensive than stress ECG testing and delivers significant radiation exposure to patients.

Thus if stress MPI is performed on all individuals with CAC>400 we are likely to generate lots of abnormal tests followed by lots of unnecessary down-stream testing.

Further support for the stress test approach comes from a 2013 report on appropriate use issued by an alphabet soup of cardiovascular professional organizations

Below is the incredibly complicated chart summarizing what tests can follow another abnormal test. Interestingly, in this chart the report consider it appropriate (A) to perform stress tests on individuals with calcium scores >100

Stress Testing-Costs and Downsides

The cynic in me has to point out that the average CAC score  for white males of 67 years is 98 and that of 68 years is 115. Thus, this algorithm has the potential to recommend stress testing be performed on half of all white males with no symptoms over the age of 67.

The costs of this approach would be astronomical.

This guideline supports stress ECG, stress MPI and stress echo as appropriate.  Stress MPI is considerably more expensive than stress ECG and carries substantial radiation burden. Stress echo in my experience,  if performed and read properly has the lowest incidence of false positives and is more appropriate therefore for screening asymptomatic individuals.

All this stress testing stands to benefit the various members of the alphabet soup above, especially those who read nuclear stress tests or stress echo or who do catheterizations with stents. (Full disclosure I am board certified in nuclear cardiology and echocardiography and read both stress MPI and stress echos. I don’t do catheterizations.)

It’s also important to point out that these appropriate usage criteria, with rare exceptions are based primarily on the expert opinion of the stakeholders who stand to benefit from the additional testing.

The unspoken third leg of the argument for stress testing is that once an abnormal stress test is found and the patient is noted to be in a higher risk category for events, therapy will be changed and this therapeutic intervention will improve outcomes.

This therapeutic intervention could be more intense management of risk factors for CAD but in most cardiologist’s and patient’s minds the next step is coronary angiography with the potential to stent blocked coronaries or to perform coronary bypass surgery.

Diabetic Patients With High CAC

Asymptomatic individuals with diabetes are recognized as intrinsically higher risk for cardiac events and commonly do not experience symptoms even with advanced CAD.

Thus, they are often the focus of more intense screening recommendations.

In 2017, The Imaging Council of the American College of Cardiology published their review of evidence regarding the use of noninvasive testing to stratify asymptomatic patients with diabetes with regard to to coronary heart disease, ultimately coming up with the algorithm below.

Their arguments were similar to Hecht’s for the general population:

Asymptomatic patients with diabetes who have high CAC scores have a high prevalence of inducible ischemia on stress imaging. In a prospective study, 48% of patients with diabetes with a CAC score of 400 had silent ischemia on SPECT imaging, and in those with a score of 1000, 71.4% had inducible ischemia . The majority of the defects were moderate to severe. Patients with diabetes with inducible ischemia have a higher annual death

Despite higher rates of ischemic stress test results in diabetics they did not recommend stress testing for all:

the data in DM suggest that routine screening with MPI of all asymptomatic patients is likely to have a low yield and have a limited effect on patient outcome. The yield of MPI can be improved by selecting a higher-risk group of patients with symptoms, peripheral vascular disease, CKD, an abnormal ECG, or a high CAC score (e.g., >400) (83,84). In such patients, intense medical therapy appears to retard progression of asymptomatic and symptomatic CAD (72).

Importantly, they noted the absence of evidence for revascularization in this population:

Whether coronary revascularization offers additive prognostic benefit to medical therapy when the ischemic burden exceeds any particular threshold is still unclear for the asymptomatic diabetic population.

The Argument Against Stress Testing

The argument for stress testing for high CAC rests on the assumption that identifying those individuals with significant ischemia due to tightly blocked coronary arteries can improve outcomes. This hypothesis has never been tested, let alone proven.

It may seem logical that those asymptomatic individuals with high risk CAC scores >400 and ischemia would benefit from an invasive strategy with coronary angiography followed by either stenting or bypass surgery but it is entirely possible that such an invasive strategy could cause more harm than good.

Harm comes from subjecting those individuals with abnormal stress tests to a potentially lethal procedure-cardiac catheterization.

David Schade, an endocrinologist, has opined persuasively on the inadvisability of either stress testing or cardiology referral in those with high CACS.

He correctly points out the limitations of coronary angiography which some cardiologists are very eager to perform

In many locations, stress testing is performed after referring the asymptomatic patient to a cardiologist. After a positive stress test, the next step is usually coronary angiography to identify obstructive lesions. A recent review of coronary angiography recommends caution in the use of this test because (1) the resolution of coronary angiography is low; (2) the obtained images are two dimensional, making it difficult to define the shape of the vessel; and (3) the assessment of obstruction does not include the presence of previously developed collateral vessels, which may provide adequate blood flow past the obstruction 

He quotes the USPSTF on the possible harm of this approach:

And he correctly points out that since the 2007 publication of the COURAGE trial we have known that catheterization followed by stenting does not improve outcomes in patients with stable CAD

Accord to the US Preventive Services Task Force: “The primary tangible harm of screening exercise tolerance testing is the potential for medical complications related to cardiac catheterization done to further evaluate a positive result. Coronary angiography is generally considered a safe procedure. Of all persons undergoing outpatient coronary angiography, however, an estimated 0.08% will die as a result of the procedure and 1.8% will experience a complication. Complications of coronary angiography include myocardial infarction, stroke, arrhythmia, dissection of the aorta and coronary artery, retroperitoneal bleeding, femoral artery aneurysm, renal dysfunction, and systemic infection”

In many locations, stress testing is performed after referring the asymptomatic patient to a cardiologist. After a positive stress test, the next step is usually coronary angiography to identify obstructive lesions. A recent review of coronary angiography recommends caution in the use of this test because (1) the resolution of coronary angiography is low; (2) the obtained images are two dimensional, making it difficult to define the shape of the vessel; and (3) the assessment of obstruction does not include the presence of previously developed collateral vessels, which may provide adequate blood flow past the obstruction 

Schade’s algorithm for management of a high CAC specifically recommends against referral to a cardiologist or performance of a stress test.

It emphasizes very intense management of risk factors with lifestyle changes and medical therapy with LDL goal <70.

As a cardiologist with a strong interest in prevention of atherosclerosis I agree with many of Schade’s points. I do, however, believe that high risk patients can benefit from seeing a cardiologist who is very focused on prevention of atherosclotic complications rather than performing procedures.

I don’t routinely recommend stress testing for my patients with high CAC but I have a low threshold for recommending stress testing in them based on worrisome symptoms, especially in those who are more sedentary or are diabetic.

A randomized trial comparing the outcomes of stress testing versus aggressive optimal medical therapy for the asymptomatic individual with high CAC is sorely needed. Until then, I remain

Skeptically Yours,

-ACP