The potential impact of computed tomography coronary calcium score screening on patients with dyslipidemia

Abstract

Background

Coronary artery calcium (CAC) scoring helps determine whether patients with known coronary artery disease (CAD) should initiate medical management by predicting future cardiac event risk. CAC scoring is underutilized because many insurance companies consider it experimental. This study aimed to determine whether CAC screening of patients at risk for CAD is associated with decreased risk of myocardial infarction and improved survival.

Methods

The TriNetX research network was used for this study. Two cohorts of 86,574 patients aged 40 to 70 years were created. All patients were diagnosed with dyslipidemia and without CAD, and the cohorts were matched for demographics, comorbidities, and statin use. One cohort had been screened with CAC scoring while the other had not. The primary outcomes of this study were myocardial infarction and overall survival at 5 years.

Results

Screened patients had 44% fewer myocardial infarction events at 5 years with a 76% lower risk of death.

Conclusion

CAC scoring is associated with reduced risk of myocardial infarction and death in asymptomatic dyslipidemia patients and should be considered as a screening tool in these patients. The presumed mechanism for improved outcomes is that early identification of CAD results in earlier or more intensive treatment, reducing future cardiac event risk.

CME

Target audience: Internists, radiologists.

Learning objectives: After completing the article, the learner should be able to

1. Understand the significance of coronary artery calcium (CAC) scoring as a predictive tool for future cardiac events.

2. Recognize the potential benefits of CAC screening in reducing the risk of myocardial infarction and improving survival in asymptomatic patients with dyslipidemia.

3. Reflect on the importance of increasing insurance coverage and patient access to CAC scoring for improved cardiovascular risk assessment and preventive strategies.

Faculty credentials/disclosure: Dr. Miles is now a resident in radiology at Baylor University Medical Center, and Dr. Zeinoddini is now a resident in radiology at the University of Texas Medical Branch. Bunnarin Theng and Bright Etumuse are medical students at the University of Texas Medical Branch. Dr. Saleem is an interventional radiologist on the faculty of the University of Texas Medical Branch.

Accreditation: The A. Webb Roberts Center for Continuing Medical Education is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

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Expiration date: September 1, 2025.

Cardiovascular disease (CVD) first became the most common cause of death in the mid-20th century and continues to be the leading cause of death globally despite numerous advances in screening tools and treatments.¹ Coronary artery disease (CAD) accounts for approximately 610,000 deaths annually (estimated 1 in 4 deaths) and is the leading cause of mortality in the United States.² According to the World Health Organization, an estimated 17.9 million people died from CVD in 2019, representing 32% of all global deaths.³ Of these, 85% were caused by strokes and heart attacks—the most serious CVD outcomes encountered in humans.³ Many studies have shown a strong association between CVD and an increased risk of developing a heart attack or acute myocardial infarction (AMI). According to the Centers for Disease Control and Prevention, about 805,000 people in the United States have a heart attack annually, and about one in five heart attacks are silent. This raises the importance of understanding the underlying risk factors and stresses the need for screening, particularly in asymptomatic patients at higher risk.⁴ Although many risk factors can contribute to the development of AMI, one of the major and most common risk factors is dyslipidemia, defined as raised plasma concentrations of total cholesterol, low-density lipoprotein, or triglycerides; a low plasma concentration of high-density lipoproteins; or a combination of these features.⁵

Due to the high prevalence and mortality rates of CVD, early detection and diagnosis are major healthcare priorities.⁶ The association between vascular calcification and CVD is well established, and a screening modality such as a noncontrast computed tomographic (CT) detection of coronary artery calcium (CAC) improves the ability to predict risk for at-risk groups accurately, as shown by the recent Multi-Ethnic Study of Atherosclerosis.⁷ In asymptomatic patients without established atherosclerotic CVD, coronary artery calcification on CT scan is a well-validated measure of subclinical atherosclerosis.⁸ However, despite clinical evidence proving that CAC scoring is one of the most important predictors of subsequent CAD, its application in asymptomatic patients remains vastly underutilized, particularly as many insurance companies in the United States still regard the test as experimental or unproven.⁹ Therefore, this may leave millions of asymptomatic patients with dyslipidemia unaware of their high risk for a heart attack and cause their CAD to remain undetected and untreated.¹⁰

In this study, the TriNetX research database was used to compare a cohort of patients who received CT coronary calcium score testing to a control cohort of unscreened patients. The purpose was to determine if CAC testing is associated with impact on the eventual development of AMI and, if so, has potential utility as a broad screening tool for at-risk populations.

METHODS

The federated global TriNetX research network was used for this study. It provides access to anonymized medical record information for >41 million patients in 75 large healthcare organizations. Because this study used only deidentified patient information and did not involve the collection, use, or transmittal of individually identifiable data, this study was exempted from institutional review board approval.

Two patient cohorts were created for comparison using the TriNetX platform. Both groups consisted of men and women between the ages of 40 and 70 years with a diagnosis of dyslipidemia identified by International Classification of Disease-10 (ICD-10) code E78 and no prior history of chronic ischemic heart disease (ICD-10 I25). One cohort consisted of patients who received CT coronary calcium score testing (procedure code 75571), while the other consisted of unscreened patients. The two cohorts were matched for age, race, gender, ethnicity, CVD-associated comorbidities, and use of tobacco products and statins (Table 1).

Table 1.

Propensity score matching of the two cohorts with regard to demographics, comorbidities, and statin utilization

Variable	Screened	Unscreened
Demographics
Current age	58.9 ± 7.6	58.9 ± 7.6
Age at inclusion	56.1 ± 7.7	56.1 ± 7.7
White	77.7%	77.5%
Male	52.3%	52.2%
Not Hispanic or Latino	52.0%	52.4%
Female	47.6%	47.8%
Unknown ethnicity	43.0%	42.4%
Unknown race	11.0%	10.7%
Black or African American	6.1%	6.4%
Hispanic or Latino	5.0%	5.2%
Asian	5.0%	4.7%
Comorbidities (ICD-10 code)
Essential hypertension (I10)	36.7%	36.6%
Obesity (E66)	15.4%	14.8%
Type II diabetes mellitus (E11)	9.5%	9.3%
Chronic kidney disease (N18)	2.5%	2.3%
Tobacco use (Z72.0)	1.8%	1.8%
Statin use
Atorvastatin	13.4%	12.6%
Rosuvastatin	8.5%	7.8%
Simvastatin	5.2%	4.5%
Pravastatin	3.2%	2.8%
Lovastatin	0.6%	0.5%

TriNetX performs propensity score matching by utilizing logistic regression analysis and the greedy nearest neighbor algorithm. This resulted in 86,574 patients in each arm.

The primary endpoint of this study was the subsequent diagnosis of an AMI within 5 years, identified by ICD-10 code I21. The secondary endpoint was all-cause mortality. The mean age for patients in both cohorts was 58.9 years ± 7.6 years.

To compare the risk of myocardial infarction within 5 years between the two patient cohorts, we calculated the risk ratio with a 95% confidence interval. The statistical significance of the results was determined using hypothesis testing with a two-sided P value. We used a predetermined threshold of statistical significance of 0.05. Additionally, we performed a Kaplan-Meier analysis to assess the survival rate at the 5-year mark for both patient cohorts. The hazard ratio with a 95% confidence interval was calculated to quantify the difference in survival rates between the CT CAC scoring and the unscreened cohort. The statistical significance of the hazard ratio was determined using a two-sided hypothesis test with a P value threshold of 0.05.

Results

Patients who underwent coronary calcium scoring were found to have a 44% lower risk of AMI in 5 years. The results were statistically significant, with a risk ratio of 0.56 (95% confidence interval 0.50, 0.63) and a P value of <0.0001 (Table 2). Kaplan-Meier analysis showed 5-year survival of 98.3% for the cohort screened with CT CAC versus 94.9% for the unscreened cohort. The hazard ratio for mortality was 0.24 (95% confidence interval 0.22, 0.27), and the results were significant with a P value of <0.0001 (Table 3).

Table 2.

Risk percentages for myocardial infarction events at 5 years for the computed tomography coronary calcium score–screened vs. unscreened cohorts^a

Cohort	Cohort size	Number of events	Risk (%)
CT calcium score	86,574	467	0.54
No CT calcium score	86,574	830	0.96

^aRisk ratio 0.56, 95% confidence interval (0.50, 0.63), P < 0.0001.

Table 3.

Survival rates at 5 years for the computed tomography coronary calcium score–screened vs unscreened cohorts^a

Cohort	Cohort size	Survival at 5 years (%)
CT calcium score	86,574	98.3
No CT calcium score	86,574	94.9

^aHazard ratio 0.24, 95% confidence interval (0.22, 0.27), P < 0.0001.

DISCUSSION

Many studies have shown a strong relationship between dyslipidemia and the risk of developing CVD, especially myocardial infarction. AMI may be “silent” and go undetected, or it could be catastrophic, leading to hemodynamic deterioration and sudden death.¹¹ AMI is one of the leading causes of death in the developed world, with a prevalence approaching 3 million people worldwide and more than 1 million deaths in the US annually.¹² The high mortality in AMI patients with dyslipidemia warrants risk assessment via the atherosclerotic CVD risk calculator along with CT CAC screening.

The CAC score assessment by CT scan is useful in determining an individual patient’s risk of major cardiovascular events, even in asymptomatic patients. Since 1990, it has been a reliable, noninvasive technique for estimating overall coronary plaque burden and identifying risk for future cardiac events.¹³ Studies have shown that coronary artery calcification is emerging as the most predictive cardiovascular risk marker in asymptomatic individuals with CAD, capable of adding predictive information beyond traditional cardiovascular risk factors.¹⁴ Large long-term population-based observational studies were launched in the US and Europe in the late 1990s and early 2000s that have produced consistent, reproducible, and convincing evidence of a strong association between CAC and major cardiovascular outcomes in asymptomatic CAD patients.¹⁴ Clinical practice guidelines in the US and Europe consider CAC scoring a potentially useful way of improving cardiovascular risk assessment in asymptomatic individuals and serving as a guide for initiating or deferring preventive therapies.¹⁴

Unfortunately, the application of CAC scoring in asymptomatic patients remains greatly underutilized because many US insurance companies still consider the test to be experimental or unproven.⁹ The American College of Cardiology and the American Heart Association do not generally recommend CAC testing of asymptomatic patients who are classified as “low risk” or “high risk,” as the score was thought to be unlikely to provide any new information that would aid in determining a patient’s risk or directing a personalized treatment plan.¹⁵ CAC testing is also considered a nontraditional risk marker by the US Preventive Services Task Force and would require legislative mandates for healthcare coverage on cardiovascular screening or wellness.¹⁵ As a result, CAC is predominantly covered by local rather than national coverage policies, with some policy coverage in 35 states. However, most patients pay an out-of-pocket expenditure of $75 to $150 for CAC imaging.¹⁵ Many patients with limited financial means will therefore not have adequate access to this important tool. One potential limitation of the present study is that patients with better access to healthcare could be present in a higher percentage in the screened cohort.

This study compared the relative risk of AMI events in asymptomatic patients with dyslipidemia who underwent CT CAC screening and those who did not. The results show CT CAC screening is associated with a significant reduction in the risk of future AMI and improved survival. One systematic review of CT CAC scoring published in 2017 reached a similar conclusion. This is particularly important because at least 25% of patients experiencing nonfatal AMI or sudden death had no previous symptoms.¹⁶ Therefore, identifying asymptomatic individuals at greater risk of experiencing future cardiovascular events is fundamental for implementing preventive strategies.¹⁷

The results presented here add to prior studies showing that CAC score screening helps clinicians make decisions about the initiation of statins and aspirin.¹⁸ In addition, early CAC score screening could lower out-of-pocket expenses when considering the cost of treatment of possible adverse events due to CVDs or alternative approaches when factoring in patient preferences about taking preventive medications.¹⁴ Because the cohorts in this study were matched for statin utilization, it is possible that CT CAC testing may stimulate earlier referral to cardiology, more intensive lipid management, earlier cardiac catheterization, and improved patient education and concern. These interventions may decrease the future risk of AMI and improve survival. Further studies will be needed to evaluate the mechanism of screening benefits, but it is important that CT CAC testing be performed with greater frequency for these benefits to be realized.

Based on these results, CAC scoring warrants serious consideration for use as a screening tool in all patients with dyslipidemia. To our knowledge, this is the first study to aggregate data on patient populations of this size. Hopefully, the compelling nature of these results will help facilitate improved insurance coverage and increase patient access to this important screening tool.

Funding Statement

The authors report no funding or conflicts of interest.

Disclosure statement/Funding

The authors report no funding or conflicts of interest.