World Health 10 Part Healthy Heart Series: Part VI

Determining Arterial Age

The concept of “arterial age” to predict longevity goes back to at least the 1600’s when a leading English physician, Thomas Sydenham, MD, wrote that “a man is as old as his arteries”. Fast forward nearly 400 years and we are at the verge of many breakthroughs that may extend human healthspan and lifespan. Silent heart disease, however, may result in sudden cardiac death or massive myocardial infarction and still remains the leading medical risk that can disrupt plans for a long and healthy life. The best measure of arterial age is a matter of debate but the coronary artery calcium scoring (CACS) has had the leading role for over a decade.  The CACS is a quantification of calcium in the epicardial coronary arteries by CT imaging without contrast. The results can range from a score measured in Agatston units of zero (the most desirable) to 1000’s. The CACS differs from traditional risk factors in that it is a direct measurement of atherosclerosis.

Recently, The U.S. Preventive Services Task Force concluded that current evidence is insufficient to recommend adding CACS to traditional CV risk assessment in asymptomatic adults for the prevention of atherosclerotic CVD. This position from the USPSTF is disappointing and it is at odds with recommendations from the American College of Cardiology, American Heart Association, European Society of Cardiology and Society of Cardiovascular Computed Tomography. Did the USPSTF get it all right?

CACS: Intermediate Risk Patients Are the Sweet Spot

Some points about the USPSTF article are worth noting. The USPSTF authors referenced the research on CACS testing (2,3). In an analysis of nearly 7,000 patients, adding CACS to the risk model improved the area under the receiver operator curve by 0.02 to 0.04, which was considered only a modest improvement by the USPSTF. The Pooled Cohort Equation that was used has been questioned as the test may perform best in a group of persons judged to be at intermediate risk for coronary atherosclerosis Indeed, in the same population limited to 1,330 individuals with a baseline intermediate Framingham Risk Score of 5% to 20%, adding CACS improved the area under the ROC curve by 0.16 (from 0.62 to 0.78) and was much more useful. CACS may be particularly useful in guiding choices of pharmacologic, lifestyle, and regenerative prevention strategies when applied to patients assessed to be at intermediate risk.  

Reclassification: Zero Remains King

The USPSTF authors reported that CACS tended to reclassify more persons without a future clinical event into a higher-risk category. The other side of the scale of CACS, the predictive value of a zero score, is more clear-cut. A study by Nasir and colleagues outlined the reclassification potential of CAC testing in the intermediate-risk population. In the Framingham Risk Score cohort, those with a CAC score of zero had a 10-year incidence of atherosclerotic CVD events of 1.6%. In the Jackson Heart Study, 40% of statin-eligible patients according to ACC/AHA Guidelines had a CAC score of zero, and the atherosclerotic CVD event rate in this population was 3%.

Safety of CACS: Agreement

The USPSTF authors acknowledge that radiation exposure from CAC is low (approximately 1 mSv) and that the potential harms from false-positive results, incidental findings (pulmonary nodule or enlarged aorta), and further testing (eg, cardiac catheterization) are overall low. The 1-mSv radiation dose is approximately one-third of average annual exposure from natural sources. Also, there are no well-established reasons for repeating CAC testing, so the majority of individuals who undergo testing will only have it done once in their life span.

Impact of CACS Testing: Hopeful Data

The USPSTF authors opined that CACS ultimately did not improve cardiac outcome. Clearly, the absence of randomized, high-quality data showing a reduction in CVD outcomes such as mortality and nonfatal strokes or MI by CACS testing is a liability. However, in one of the studies cited in the USPSTF report, investigators randomly assigned 1,005 asymptomatic patients with CAC greater than 80th percentile to atorvastatin 20 mg daily, vitamin C and vitamin E vs. placebo. After follow-up of approximately 4 years, patients receiving atorvastatin had a 40% reduction in LDL (baseline 146 mg/dL). The incidence of pooled CVD endpoints was 6.9% in the atorvastatin group vs. 9.9% in the placebo group. Although this did not quite reach statistical significance (P = .08), reduction with statin therapy is fully consistent with the expected benefit of statins.

Conclusion

The summary by the USPSTF may have some impact on general acceptance of the CACS for the public at risk, but the CT scan remains the best path to determine arterial age. A high score requires a massive effort to halt and reverse disease to “remain in the game” for new anti-aging therapies coming soon. Since the publication of the USPSTF summary on CACS, a new cardiac risk calculator called AstroCHARM has been published by a collaboration between NASA and the University of Texas Southwestern University School of Medicine. This program incorporates the CACS result and clinical and laboratory data to predict 10-year risk of cardiac events including death.