Mailing address: Dr. Priscilla Ornellas Neves. E-mail: moc. Received Dec 11; Accepted Jun This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
This article has been cited by other articles in PMC. Abstract The coronary artery calcium score plays an Important role In cardiovascular risk stratification, showing a significant association with the medium- or long-term occurrence of major cardiovascular events.
The following results were obtained: - CAC score of relative risk of 4. Table 1 Comparison of the CAC score and Framingham risk score, alone and in combination, as predictors of major cardiovascular events, based on the area under the curve.
Open in a separate window. Table 2 Recommendation for the use of the CAC score in asymptomatic patients. Interpretation of the CAC score result The values obtained from the CAC score can be interpreted and classified in two ways: using the absolute values with fixed cut-off points; and adjusting values for patient age, gender, and ethnicity, as well as calculating distribution percentiles in the general population through the use of several population databases, the Multi-Ethnic Study of Atherosclerosis MESA 26 being the most widely used.
Figure 1. Table 3 Degree of coronary artery calcification by absolute CAC scores and CAC scores adjusted for gender, age and ethnicity, with clinical interpretations. Figure 2. Figure 3. Table 4 CAC score. Prognosis and recommended treatment strategies.
Therefore, when the anticipated benefit exceeds the risk e. CAC score Agatston method. FRS, Framingham risk score. Prognostic value of a CAC score of zero in asymptomatic patients Various studies have shown that asymptomatic patients with a CAC score of zero have a low risk of cardiovascular events or all-cause mortality in the medium and long term 9.
When should the use of the CAC score be repeated? A CAC score of zero and the occurrence of cardiovascular events On the topic of the occurrence of cardiovascular events in patients with a CAC score of zero, we identified seven studies, collectively involving patients, with an average follow-up of 42 months. A CAC score of zero and acute coronary syndrome in the emergency room On the topic of acute coronary syndrome in the emergency room in patients with a CAC score of zero, we identified three studies, involving a collective total of patients with acute chest pain, testing negative for troponin, and with inconclusive electrocardiography results.
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The absolute score is the best predictor of the total risk of a CHD event for an individual in the near to midterm in the next 5 to 10 years. In contrast, the percentile score best represents relative risk of CHD event for the individual compared with other individuals of the same age, race, and sex In this way, the percentile score is the better predictor of lifetime risk of developing CHD.
While percentile scores are particularly useful in clinical practice for conveying relative and lifetime risk to patients, the absolute score is of more prognostic value and predicts risk better over the traditional year time horizon Table 1 4 , To better portray the difference in these two values, consider the following scenarios:. Scenario 1. Scenario 2. While there are no currently established reference range values for CAC in individuals younger than 45 years old, any evidence of CAC in this age range is considered very high, with high risk for CHD and CVD mortality 13 , Thus, patient Y would be considered for preventive therapy.
Scenario 3. His year risk of a CHD event is 5. Given his low percentile and competing risks, preventive therapy can most likely be deferred. The progression of CAC over time has been found in some studies to have incremental value in predicting subsequent CHD events and overall mortality 27 , Other studies, however, have found that the most recent CAC value in addition to risk factor assessment is sufficient for risk prediction 29 , The differing outcomes from studies could be attributed to differences in methods for assessing CAC progression 11 , Consistently, however, the presence of any CAC at baseline, diabetes, age, systolic blood pressure, low-density lipoprotein cholesterol, and smoking have been found to be strong predictors for CAC progression and conversion 31 — 33 , and the rate of conversion from CAC score of 0 to CAC of greater than 0 over time was found to be nonlinear and dependent on age, sex, and baseline risk profile While CAC scores of greater than or greater than have been traditionally recognized as the highest risk classification of CAC, there are however a unique group of individuals with CAC scores of greater than , many of whom are asymptomatic at the time of scanning 6 , Arguments have been made that high CAC values are heavily influenced by CAC density, which might be associated with more favorable prognosis, as denser CAC are more indicative of stable plaques, which are less prone to rupture 6 , These patients have been found to have as much risk as those in secondary prevention who have had prior myocardial infarction , suggesting that even more aggressive management of modifiable risk factors might be warranted in this subgroup of individuals 36 , In addition, in limited circumstances it is important to note the vessel affected, as CAC involving the left main has been associated with increased mortality risk 6 , 38 , While the Agatston score does not factor in the distribution of CAC, other proposed scores, like the calcium coverage score, take CAC distribution into consideration but are less reproducible and require much longer reading time than the Agatston score, limiting their incremental value Currently, a simple expression of the number of coronary arteries with CAC and whether there is CAC in the left main is sufficient to enhance risk discrimination.
Presence of left main CAC should also be noted in the study conclusions. It incorporates traditional risk factors age, sex, high-density lipoprotein cholesterol, systolic blood pressure, antihypertensive medication use, current smoking status, and diabetes and CAC, as well as family history of heart attack, body mass index, race and ethnicity, and lipid-lowering medication use Fig 1 Compared with a similar model without CAC, the addition of CAC improved the accuracy of the calculator significantly, increasing the area under the curve from 0.
To illustrate this, consider the case of patient A, a year-old Hispanic female smoker currently taking antihypertensives and lipid-lowering medication, with a CAC score of Interestingly, if her CAC score was 0, the risk would be 2.
The more accurate risk prediction for patient A would be The MESA risk score calculator is currently available and easily accessible for use on the MESA website with an aim to enhance CHD risk assessment and communication between physicians and their patients More than 7 million CT scans are performed in the United States annually, with projected doubling of that number if thoracic screening with annual low-dose chest CT is performed in all patients at risk for lung cancer per the United States Preventive Services Task Force recommendation 4.
CAC can be assessed visually on almost any chest CT scan but has been mostly ignored until recently 4. CAC scores on nongated thoracic scans can be estimated qualitatively on visual assessment as present or not present or as mild, moderate, or severe 4 , One previously proposed score is calculated as the sum of the score for each of the coronary arteries and can be categorized into three categories of severity: 0, 1—3, and 4—12 4. Although not as accurate, CAC scores assessed from nongated thoracic scans have been found to correlate well with scores obtained from electrocardiographically gated non—contrast-enhanced CT scans 4 , Despite the many established benefits of the CAC score, more work needs to be done to optimize and standardize its application in clinical medicine.
One approach is to merge traditional and qualitative CAC scoring to yield a score that classifies individuals accurately regardless of the method of CAC assessment used. This is easily achievable, as evidence suggests that experienced readers of nongated studies can visually estimate CAC on these scans, classifying patients into general CAC score groups that correlate accurately with traditional Agatston score groups The CAC-DRS categories of 0—3 were defined to correspond with the traditional Agatston score categories of 0 very low risk , 1—99 mild CAC, mildly increased risk , — moderate CAC, moderately increased risk , and higher than moderately to severely increased risk Visual assessment of CAC on nongated scans is done with these same categories in mind, with scores of 0—3 corresponding to similar risk categories B , Axial image of CAC in the left anterior descending artery.
C , Axial image of CAC in the left circumflex vessels. D , Axial image of CAC in the right coronary artery. Adapted from reference Work has also been done on automating CAC scoring on thoracic scans, and although the CAC scores were underestimated, initial testing showed good reliability and agreement with traditional scores If further developed, this holds significant potential for further reducing the time required to assess CAC on thoracic scans, increasing the efficiency and maximizing the value from routine lung cancer screening thoracic scans.
Elevated CAC scores have been associated with increased risk of other noncardiovascular diseases including cancer, chronic kidney disease, and chronic obstructive pulmonary disease 49 , These comorbidities raise the issue of competing risks of mortality in those with elevated CAC and should be considered when analyzing CAC as a predictor of mortality. Tools are currently being developed to further translate the CAC score into a likelihood estimator for mortality from CVD compared with cancer, which will inform and potentially impact clinical management decisions.
Framingham risk estimated using this CAC-derived vascular age was also more predictive of short-term incident coronary events than when chronologic age was used Furthermore, vascular age has also been found to be a better representation of cardiovascular risk that is more easily understood by patients and more likely to result in compliance with treatment recommendations Widely varying definitions and methods for calculating vascular age, however, currently limit its widespread use in clinical practice 53 ; however, a MESA coronary age calculator has recently been developed to better harmonize vascular age estimation and will be available for use on the MESA website in late or early Despite its shortcomings, the Agatston score remains the standard of reporting, as many previous proposed upgrades in CAC scoring methods have had limited applicability clinically 6.
Further considerations to improve the CAC score include addition of parameters for CAC distribution pattern diffuse vs concentrated , total number of CAC lesions, consideration of mean CAC density, radiomic assessment for individual lesions, and quantification of extracoronary calcification for example aortic calcification or aortic valve calcification; Fig 5 6 , Using CAC to predict new outcomes is also on the horizon, for example, using aortic valve calcification to predict future stenosis To ensure applicability in clinical practice, any new CAC score needs to be reproducible, relatively easy and quick to interpret, and adaptable to automated algorithms 6.
Approaches to improving the CAC score. Another consideration for improving CAC assessment is to further reduce the amount of radiation associated with CAC scans. While it is important to use the least amount of radiation possible, it is imperative that the image quality is maintained with minimal background noise However, these techniques have been associated with some drawbacks, including increased background noise and underestimation of CAC scores 6 , Polygenic risk scores are also being tested as a way to determine when a patient should get a first CAC score Additionally, recent developments in the application of artificial intelligence show promising prospects, with the development of CAC CT postprocessing algorithms and software to automate the estimation and reporting of CAC Fig 5 58 , These methods show significant agreement with the conventional assessment of the Agatston CAC score 58 , CAC has been extensively shown to be invaluable in CVD risk prediction and has shown value in predicting other non-CVD conditions, as well as all-cause mortality.
CAC also serves as the basis for new concepts, such as coronary and cardiovascular age, to improve risk communication between health care providers and patients.
As more thoracic CT scans are routinely performed in the United States, recent guidelines have recommended CAC interpretation on all thoracic scans regardless of the original indication. In Because risk scores are strongly influ- multivariable model controlling for age, sex, enced by age,29 they are least reliable in young ethnicity, and cardiac risk factors model chi- adults.
However, most of Akosah et al31 reviewed the records of the patients were already known to have car- young adults women age 55 or younger, men diac risk factors, making the study findings less age 65 or younger who presented with their generalizable to the general population.
Interestingly, those results in low specificity in elderly adults. Us- with no risk factors but a calcium score great- ing risk scores, elderly adults are systematically er than had a higher mortality rate than stratified in higher risk categories, expanding those with no coronary calcium but more than the indication for statin therapy to almost all 3 risk factors Moreover, our atherosclerosis symptoms but with elevated coronary calcium scores had higher all-cause mortality rates at knowledge about genetic and epigenetic fac- 15 years than those with a score of 0.
The dif- tors associated with the development of ath- ference remained significant after Cox regres- erosclerosis is still in its infancy, with current sion was performed, adjusting for traditional guidelines not supporting genetic testing as risk factors. Therefore, death in the subsequent 10 years. The score was vali- implications regarding whether to start thera- dated externally with 2 separate longitudinal pies such as statins and aspirin.
Thus, this may serve as another tool For considering statin therapy to help providers further risk-stratify patients. The number needed to treat to prevent an Cost-effectiveness depends not only on pa- atherosclerotic cardiovascular event in the tient selection but also on the cost of therapy. In the be beneficial. This is especially be at a lower risk. Those in the United States are believed to be un- with a calcium score higher than had a necessary and may lead to additional testing number needed to treat of in the group to investigate incidental findings.
The estimated number needed to tion exposure, healthcare costs, and increased harm for a major bleeding event was Therefore, the presence Some of these concerns have been ad- or absence of symptoms should guide the cli- dressed.
Modern scanners can acquire images nician on whether to pursue stress testing for in only a few seconds, entailing lower radia- invasive coronary angiography based on the tion doses than in the past. As discussed above, a score higher than preventive interventions guided by calcium could be a rationale for starting aspirin scores on hard event outcomes.
It can be ar- therapy, and a score higher than 0 for statin gued that there have been plenty of observa- therapy. The current guidelines also mention tional studies that have shown the benefit of that the coronary calcium score is comparable coronary calcium scoring when judiciously to other predictors such as the C-reactive pro- done in the appropriate population.
The feasibility and cost of a large The sensitivity consensus recently have added more specifics randomized controlled trial to assess outcomes of coronary in terms of using this test for asymptomatic pa- after coronary artery calcium measurement tients at intermediate risk year risk of ath- calcium scoring must also be considered.
This could have Given the negative predictive value of the been determined without an invasive test in coronary calcium score, our approach has been an otherwise asymptomatic patient. This is preceded by a lengthy patient- physician discussion about the risks and ben- Example 3 efits of the test.
A dis- is unremarkable, and cardiac enzyme tests are cussion can then take place on potentially negative. Would coronary calcium scoring be starting pharmacologic therapy, intensive life- reasonable? Therefore, she has a be shown to the patient in the office to point low pretest probability of obstructive coronary out coronary calcifications.
Seeing the lesions artery disease. Moreover, calcium scoring may may serve an as additional motivating factor not be helpful because at her young age there as patients embark on primary preventive ef- has not been enough time for calcification forts. Thus, she would be exposed to radiation consider appropriate and inappropriate use of unnecessarily at a young age.
What to do with an elevated calcium score? Despite an Force guidelines. Patients may also get the test cardiovascular extensive conversation about lifestyle modifica- done on their own and then present to a pro- disease events tions and pharmacologic therapy, he is reluctant vider with an elevated score.
He is otherwise asymp- It is important to consider the entire clini- and death tomatic. Would calcium scoring be reasonable? If a patient presents with an elevated onary artery calcium scoring in an otherwise calcium score but has no symptoms and falls in calcium score asymptomatic man to help reclassify his risk the intermediate-risk group, there is evidence for a coronary vascular event.
The objective to suggest that he or she should be started on data provided by the test could motivate the statin or aspirin therapy or both. However, if A year-old man who has a family history of the patient is symptomatic, then further car- coronary artery disease, is an active smoker, and has diabetes mellitus presents to the clinic with 2 diac evaluation would be recommended. Measuring coronary artery calcium has been This patient is symptomatic and is at high found to be valuable in detecting coronary ar- risk of coronary artery disease.
The test is relatively easy lines, since he has diabetes. It serves as a more documents are more specific in recommend- personalized measure of disease and can help ing the test in asymptomatic patients in the facilitate patient-physician discussions about intermediate-risk group.
J Cardiovasc Comput Tomogr ; 3 6 — Hansson GK. Low- vs. N Engl J Med ; 16 — Eur Heart J Cardiovasc Imaging doi Ross R. N Engl J Med J Am Coll Cardiol ; 15 4 — Role of coronary calcium for risk strati- the Council on Arteriosclerosis, American Heart Association. Coro- 4. Nat with an electron-beam CT volumetric method.
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