Is Calcium Scoring of the Coronary Arteries Necessary for Proper Management of Asymptomatic Subjects With Classic Risk Factors?

Significance of Calcium in the Coronary Arteries

Most agree that the presence of calcium in the coronary arteries indicates coronary atherosclerosis and heightens the level of awareness about potential problems. It should also stimulate the physician and the patient to control known risk factors. However, in patients who are free from symptoms or any evidence of myocardial ischemia, it is highly unlikely that these atherosclerotic lesions are flow‐limiting and thus symptom‐producing. I have always been concerned about the presence of calcification in the coronaries, since it may mean that there are other non‐calcified plaques that in the future can cause trouble, ie, plaque rupture and myocardial infarction. Unfortunately, non‐calcified plaques are not detected by current calcium scoring scanning techniques using ionizing radiation without contrast.

Ionizing Radiation to Detect Coronary Calcification

There is no question that the amount of ionizing radiation delivered to the patient using Electron Beam Computed Tomography (EBCT) to detect coronary calcium is quite low. In the study by Min et al, the estimated effective biologic radiation dose of coronary artery calcium scans using EBCT was considered to be 0.5 millisieverts (mSv). This is lower than most other imaging modalities used to evaluate patients with possible coronary artery disease and ischemic heart disease. However, it is not quite as low as a chest x‐ray. For example, a chest x‐ray exposes the patient to approximately 0.02 mSv; thus, if calcium scoring requires 0.5 mSv, this is equivalent to 25 chest x‐rays on the same day. Recent cardiovascular literature indicates that coronary calcification can be detected using 64‐slice computed tomography requiring 1‐2 mSv of ionizing radiation.3

If 1 mSv is required, then the radiation exposure is equivalent to 50 chest x‐rays, and if 2 mSv are required, the amount of ionizing radiation is equivalent to 100 chest x‐rays. Annual studies for 5 years would result in the ionizing radiation exposure of 125 chest x‐rays if 0.5 mSv was the ionizing radiation dose, 250 chest x‐rays if 1mSv is required and 500 chest x‐rays if 2 mSv is required.

Is Conversion to Coronary Artery Calcification a Prognostic Indicator?

Min and colleagues have reported that there is a “warranty period” during which there is no progression in subjects with a zero calcium score. Progression to coronary artery calcification does not occur until about 5 years after the initial zero calcium score. At 5 years, 25.1% of subjects with a zero calcium score converted to more than zero calcium score (106 of 422 patients at five years). Among those who converted, coronary artery calcium score on conversion was 19 plus or minus 19.

Thus, repetitive yearly coronary artery calcium scanning is not necessary to determine progression of coronary artery calcification. As with all patients being evaluated for possible atherosclerosis, it will be valuable to collect calcium scoring data as well as outcome data beyond five years.

A point that needs emphasis is that prognosis from zero coronary calcium score to more than zero calcium score in the coronary arteries is not a clinical endpoint. The clinical endpoint is development of ischemic heart disease, eg, chronic or acute angina, myocardial infarction, sudden cardiac death, etc.

Framingham Risk Score and Coronary Artery Calcification Score

In my opinion any risk score identifies populations at risk, not individuals. Those interested in this subject and working in this field believe that there is evidence suggesting that asymptomatic individuals with an “intermediate” Framingham risk score may be “reasonable candidates for using coronary artery calcification scanning as a potential means of modifying risk predictions and altering therapy.”

I am not quite clear what is meant by this statement since, in my view, the Framingham risk score can and should be modified by aggressive medical management, ie, hypertension control, lipid management, diabetes control, smoking cessation, etc. regardless of the presence or absence of coronary artery calcium. Many of these subjects are asymptomatic but are treated, and their Framingham risk score is “altered” with therapy, which may lower their risk from intermediate to low risk. Unfortunately, no risk score is useful clinically if there is no intervention that might alter the clinical outcome.

I believe that most cardiologists would aggressively treat an asymptomatic patient with risk factors such as hypertension, diabetes mellitus, dyslipidemia, or smoking independent of coronary calcification. However, any risk scoring system to prevent excessive use of therapies in low‐risk patients needs further study since it is not a static snapshot of risk as patients age.4 It might be worth considering here the Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial, which investigated whether aggressive LDL lowering in apparently healthy subjects with LDL less than 130mg/dl who had hsCRP greater than or equal to 2mg/l would improve clinical outcome. Results showed a significant reduction in major adverse cardiac events compared to placebo.5

Coronary Calcification Results in More Calcification Progression

The data indicate, and most agree, that presence and absolute amount of coronary artery calcification may trump other risk factors for the endpoint of coronary artery calcium progression. An important question to address is, “Do the data indicate that presence and absolute amount of coronary artery calcification also trump other risk factors for the development of major adverse cardiac events related to coronary artery calcification progression?” Those who are experts in this area indicate that a positive test is associated with a 6‐ to 35‐fold increased risk of developing a cardiac event. It would be interesting to know the number of patients who had calcium on initial scan who had regression of calcium at 5 years. It must be remembered that although 25% of asymptomatic subjects with zero calcium score had progression of calcification of the coronary arteries at 5 years, 75% did not. Were these the patients who were aggressively treated for risk factors?

A Brief Case Presentation to Make a Point

What would you recommend for a 55‐year‐old asymptomatic man who has mildly elevated blood pressure, moderately elevated cholesterol, moderately elevated LDL, and a low HDL? I guess this patient could be considered an intermediate risk by Framingham criteria (9% estimated risk at 10 years) and that a finding of calcium in the coronaries would elevate this risk (20% risk at 10 years) and thus justify aggressive medical management. I cannot argue that point, but I think most cardiologists (including me) would be fairly aggressive with blood pressure management and lipid management in this particular patient whether or not coronary artery calcium is present.

Summary

Coronary artery calcification equals zero may be a good thing, but remember 25.1% of zero calcium patients developed calcified (atherosclerotic) coronary arteries in 5 years. Whatever treatment was prescribed for these patients to delay calcification of the coronary arteries did not work very well. A question that needs answering is, “Does aggressive modern medical management delay the conversion from zero calcium score to something greater than zero in 5 years and beyond in asymptomatic subjects.”

Finally, as far as I can tell there were no major adverse cardiac events reported in patients who did or did not develop calcification of the coronary arteries at 5 years. I believe that coronary artery calcification should not be considered a major adverse cardiac event, at least at 5 years. Longer follow‐up, ie, 10 years, is necessary to understand the clinical relevance of the progression to coronary artery calcification and to obtain outcome data.

Conclusion

To answer the question posed in the title of this editorial, I do not believe it is necessary to identify patients who have calcified coronary arteries in order to make clinical management decisions about treatment of known classic risk factors regardless of the estimated 10 year predicted risk of a cardiac event.