Coronary Artery Imaging May Be “Tremendously Significant”
A major mystery in heart disease—why most people who develop serious heart disease have normal blood pressure and cholesterol—may have been solved in a series of “tremendously significant” coronary artery calcium (CAC) studies, says a principle investigator on one. Some are calling these studies “important” and “frame-shifting.”
One of the recent studies—conducted on patients enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA)—found that CAC computed tomography (CT) scans can often more accurately predict heart disease than cholesterol and blood pressure readings.
“Our study clearly shows that making heart disease predictions with traditional risk factors or risk scores is inefficient, as we miss a significant percentage of individuals at risk,” Johns Hopkins cardiologist Khurram Nasir tells Bioscience Technology. “(We also) over-treat a huge proportion of those considered at high risk by traditional risk factors.”
That recent study, led by Nasir and appearing in a December European Heart Journal, found that, among 7,000 people with no heart disease, 15 percent of those at very low risk via traditional risk factors (including blood pressure, cholesterol, current smoking, and diabetes) turned out to have high CAC scores, and were at relatively high risk of a cardiac event over the next seven years.
On the other hand, 35 percent of participants thought to be at very high risk using traditional risk factor determinations, and thought to need aggressive therapy with aspirin and statins, had zero CAC. They also had a very low rate of cardiovascular events over seven years.
“I believe there is tremendous significance in this finding, as it challenges the decision-making process based on traditional risk factors to determine the intensity of primary prevention,” says Nasir. “Such assessments might fall short if relied upon too strictly for individual patient management. This becomes even more important in the current environment with the release of new CVD risk and cholesterol management guidelines that may greatly overestimate risk, resulting in millions of people being candidates for statin drugs who may not need them.”
“It’s not that (cholesterol lowering) statins are not effective,” Nasir continues. “They are great medications. But they work in particular populations.”
His group did some math. They looked at those with the highest risk of having a heart attack (>20 percent in 10 years) calculated by traditional methods (like the Framingham risk score) who were therefore candidates for lifelong statins. When such individuals also have absence of CAC (a feature seen in 35 percent of those individuals) “we would need to treat 285 of them for five years to prevent one event,” says Nasir. “By comparison, among those with no risk factors (not considered for statins) but elevated CAC scores, we may just need to treat 66 individuals for five years to prevent one event.”
This, says Nasir, “is a sobering reminder that the current decision-making tools for determining whom to treat are limited.” The final answer for heart disease prediction “may lie in relying on available technology (CAC testing) which is widely available, inexpensive ($75-$100), and easy to perform (two to three minutes).”
CAC testing provides a personalized assessment of risk, “and guides clinicians and policy makers in appropriately allocating healthcare resources to groups likely to receive net benefit from proven medications such as statins. In addition, by accurately providing the true risk of future cardiovascular disease, it allows patients to make a more informed decision on a) whether to take medications and b) how flexible they wish their goals to be.”
Next up, suggests Nasir: talk. “We are hopeful these findings will stimulate discussion about departure from the current approach of initial risk factor assessment, followed by CAC testing in only selected individuals.”
Far preferable, he says, in an approach “where CAC testing could serve as the initial step in evaluating cardiovascular risk. Our aim is not to dictate to clinicians what to do with certain CAC score results, but we are confident the results provide a strong framework to guide decisions based on a CAC score.”
Nasir’s team included researchers from Brigham and Women’s Hospital, Yale University School of Medicine, and the National Insitutes of Health.
University of California, San Diego, Chief of Preventive Medicine Michael Criqui has also analyzed MESA patients' CAC. But Criqui's team reports this month in the Journal of the American Medical Association (JAMA) that the issue is more subtle: CAC in any volume is associated with coronary heart disease (CHD) and cardiovascular disease (CVD) risk. But Criqui's team found that increased density of CAC is protective against heart disease.
"It has been known for some time that CAC provides incremental CHD prediction beyond standard risk scores," Criqui tells Bioscience, commenting on the Nasir paper. "In addition, it is now well-recognized that, of the various measures of sub-clinical atherosclerosis, CAC is likely the best at providing additional discrimination. No prior reports had suggested that the additional discrimination might vary with risk factor burden, and Nasir's paper confirms the absence of a differential predictive power of CAC at different levels of risk based on high or low levels of risk factors."
Cautions Criqui, however: "Readers should be careful about over-interpreting the low-risk status of persons with high levels of risk factors but absent CAC. The follow-up for Nasir's study was only seven years, and recent data have suggested that a focus on lifetime CVD risk is more appropriate. The proportion of persons with CAC increases sharply with age, and among persons without CAC, persons with a high risk-factor burden are more likely to develop CAC and/or subsequent CHD events with longer follow-up than persons with low risk-factor levels."
Criqui is working on a calcium scoring system that will incorporate both volume and density in its risk calculations.