‘Negative’ Atherosclerotic Imaging Results Shift 10-Year CVD Risk Downward: MESA Analysis

Among a host of “negative” cardiovascular risk factors, the complete absence of calcification in the coronary arteries is associated with the largest downward shift in the estimation of patient risk assessed by conventional risk calculators, according to the results of a new analysis.

Its authors suggest there is an opportunity to turn risk management on its head by identifying lower-risk patients with negative findings on imaging tests, raising the possibility of saving healthcare resources by better identifying patients who will not benefit from additional tests and treatment.

According to the investigators, who used data from the large, prospective Multi-Ethnic Study of Atherosclerosis (MESA), a coronary artery calcium (CAC) score of zero yielded the most negative diagnostic likelihood ratio. This novel statistic calculates the change in a patient’s predicted risk given new information from the test. Overall, the absence of calcification and a low amount of subclinical atherosclerosis assessed with carotid intima-media thickness (IMT) resulted in the greatest revision in the patient’s risk score following the negative results from the imaging studies.

Lead investigator Michael Blaha, MD, of Johns Hopkins Hospital (Baltimore, MD), told TCTMD that a “negative” result from a CT coronary calcium test and carotid IMT are “the most reassuring risk factors an individual could have in reducing the predicted probability of having a heart attack and stroke.” Other negative risk factors, such as healthy diet or the absence of the metabolic syndrome, are less “reassuring” when it comes to predicting the future risk of cardiovascular events, he said.

The results of the study are published January 22, 2016, in Circulation.

Lowering Patient Risk Assessment Could Lead to Less Treatment

In the analysis, the researchers examined 6,814 participants from the MESA cohort and compared 13 negative risk markers using the diagnostic likelihood ratio to model the change in the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) based on new information from the negative results. In addition to the atherosclerosis imaging tests, they assessed such risk markers as brachial flow-mediated dilation, ankle brachial index, C-reactive protein, family history, metabolic syndrome, and lifestyle factors, among others, to determine if these markers could shift the patient’s predicted risk scores. 

The concept of negative risk factors, said Blaha, complement conventional thinking about risk factors but the goal is to identify individuals at lower risk rather than those at higher risk for cardiovascular disease.

“The implications here are that we spend a lot of time trying to find those people who have unheralded high risk in order to treat them aggressively,” he said. The present study, focusing on negative risk factors, is a novel way of thinking about patients, “to potentially treat less or do less tests so that we can rationally spend our healthcare resources on the appropriate patients.”

For patients with a CAC score of zero, the calculated mean diagnostic likelihood ratio is 0.35 for all coronary heart disease events. This means that if such a patient has a 10-year ASCVD risk of 10% based on the American College of Cardiology/American Heart Association (ACC/AHA) pooled cohort equations, they’re actual risk of coronary heart disease is closer to 3.5%. In this way, information gleaned from the negative CAC result shifts their predicted risk downward.

Comparatively, the mean diagnostic likelihood ratio for patients with a carotid IMT score in the lowest quartile (a negative finding) was 0.53 for all coronary heart disease events. Again, this means that if a patient’s 10-year ASCVD risk is 10%, the negative IMT score would translate into a downward shift in coronary heart disease risk to approximately 5.3%. Negative results on other cardiovascular markers, including low C-reactive protein and low homocysteine levels, as well as the absence of the metabolic syndrome, had much higher diagnostic likelihood ratios. As a result, additional information gained from negative results with these tests did little to shift the 10-year ASCVD risk score.

Blaha explained that the mean diagnostic likelihood ratio changes with the patient’s age and 10-year risk of ASCVD. For example, the mean ratios are even lower for patients considered high-risk for cardiovascular disease based on the pooled cohort equations. For patients with a 10-year ASCVD risk between 5% and 7.5%, the likelihood ratio is 0.37 for all coronary heart disease events. In contrast, the ratio is 0.31 for those with a 10-year risk ≥ 7.5%, meaning those at higher risk have a larger downward shift in predicted risk with a CAC score of zero.

“The diagnostic likelihood ratio gets stronger the older you are or the higher risk you are,” said Blaha. “This makes sense because the higher risk we thought you were, or the older you were, the more likely it is that we thought you would have calcium. If you have no calcification, this results in a larger downward shift in the patient’s risk. If you’re very low risk, or very young, it’s much more likely that you’re going to have no calcium so this moves the needle less. This is the whole concept. It’s not just 1 fixed number. It varies on the individual’s characteristics.”

Providing Reassurance Rather Than Escalation

In the 2013 ACC/AHA guidelines for cholesterol treatment, the threshold for considering statin therapy was lowered. Based on the recommendations, individuals with an LDL cholesterol level between 70 mg/dL and 189 mg/dL who have a 10-year risk of ASCVD ≥ 7.5% are eligible for statins. In clinical situations where a physician might be uncertain about a patient’s risk after conventional risk assessment, CAC screening is an option (class IIb recommendation).

To TCTMD, Blaha said the ACC/AHA recommendations on the use of CAC screening are based on identifying at-risk patients using positive risk factors, such as high LDL cholesterol or an elevated CAC score. Instead of using the imaging test to shift patients upward, CAC screening could be used to reassure patients about not necessarily needing to take a lifelong statin. He would like to see the future guidelines include a statement that if the decision to treat with statins is uncertain, and you find a calcium score of zero, that might be a patient in whom lifestyle therapy, rather than drugs, would be the best treatment approach.

James K. Min, MD, of Weill Cornell Medical College (New York, NY), who commented on the study for TCTMD, said that while a patient might have a CAC score of zero at 1 time point, a finding that would downgrade their risk and lead potentially to a physician’s decision to take them off therapy, calcification could still occur over time. “Unless we’re planning on doing repeat screening over and over again, which I do not believe we should be doing at this time, I don’t think this is necessarily safe,” he said.

For Min, he believes that the current CAC screening recommendations from the ACC/AHA are reasonable, although he suspects that many patients with any calcium would benefit from statin therapy. In this way, a positive CAC test can be used to identify patients who might not otherwise qualify for statins based on their 10-year ASCVD risk score. It can also be used to convince a patient to seriously consider lifestyle modification to improve their heart health.

“It individualizes care so rather than a population-based approach, it’s a patient-based approach,” said Min. “For example, If a patient has hypertension or diabetes or dyslipidemia, we often consider them in a binary fashion: ‘Do you or don’t you have diabetes?’ But the duration or severity of the condition is also of high import. One salutary feature of coronary calcium is that it allows us to integrate the lifetime exposure of the totality of risk factors and quantify the effects of those risk factors on the coronary artery in 1 quantifiable metric.”