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Am J Prev Cardiol
Am J Prev Cardiol
American Journal of Preventive Cardiology
2666-6677
Elsevier

S2666-6677(24)00087-4
10.1016/j.ajpc.2024.100719
100719
Original Research Contribution
Integrating cardiovascular risk assessment into mobile low-dose CT lung screenings in rural Appalachia: A comprehensive analysis of the relationship between lung cancer risk, coronary artery calcium burden, and cardiovascular risk reduction strategies
Berzingi Seher scberzingi@hsc.wvu.edu
ac⁎
Piechowski Kara bc
Hendricks Emily ac
Colantonio Mark ac
Anandarm Asuwin cd
Perkowski Gregory cd
Miller Tyler cd
Conte Justin ac
Nassar Sameh cd
Kaseer Belal cd
Liriano Marcelino Mederos ac
Avalon Juan Carlo cd
Chapman Kyle ce
Patel Brijesh cd
a Department of Medicine, West Virginia University (WVU) School of Medicine, Morgantown, WV, USA
b Marshall University, Joan C. Edwards School of Medicine, Huntington, WV, USA
c West Virginia University (WVU) Medicine, Morgantown, WV, USA
d Department of Cardiology, West Virginia University (WVU) School of Medicine, Morgantown, WV, USA
e Department of Pulmonology and Critical Care, West Virginia University (WVU) School of Medicine, Morgantown, WV, USA
⁎ Corresponding author at: 3703 Sun Place, Morgantown, WV 26505. 304-276-4014. scberzingi@hsc.wvu.edu
11 8 2024
9 2024
11 8 2024
19 10071920 3 2024
21 7 2024
10 8 2024
© 2024 The Authors. Published by Elsevier B.V.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Objective

Mobile low-dose computed tomography (LDCT) lung screenings are part of an outreach program in rural Appalachia to detect early lung cancer. Coronary artery calcium (CAC) scoring on LDCT can identify calcium deposits in coronary arteries and can prompt consideration of risk modification for prevention of cardiovascular disease (CVD) events. It is not known if Lung CT Screening Reporting & Data System (Lung-RADS) scoring correlates with CAC scores. There is no clear guidance for patients undergoing LDCT screenings to receive follow-up regarding CAC or prevention of associated CVD risk.

Methods

This was a retrospective review of mobile LDCT LCS in adults with no known history of CVD. CT images were obtained at 100 kVp with a slice thickness of 3 mm. Agatston CAC scoring was performed retroactively. Lung-RADS scores were categorized as: Negative (1), Benign (2), Probably Benign (3), and Suspicious (4). CAC scoring was grouped as 0, 1–100, 101–399, and ≥400. Descriptive statistics and chi-square analyses were utilized.

Results

A total of 526 LDCT screenings were included. Over 54 % of patients had coronary calcification on LDCT LCS. 161 patients (30.6 %) had a CAC score of ≥100 and 75 patients (14.3 %) had a CAC score ≥400. Of patients with a CAC score ≥100, 7.5 % received referrals for follow-up after the LDCT screen and 9.3 % had additional cardiac testing. Of those with a CAC score ≥100 not already on a statin (45.3 %) and not already on aspirin (63.3 %), few were started within 3 months of LDCT for prevention (8.2 % and 5.9 % respectively). Among patients with a Lung-RADS score of 4, 17 % had a CAC score >400, whereas only 12 % with a Lung-RADS score of 1 fell into the same CAC category. Higher Lung-RADS scores correlated with fewer patients with CAC of 0. A significant correlation was observed between higher Lung-RADS scores and elevated CAC scores (p = 0.02).

Conclusion

In patients with no CVD history, coronary artery calcification was frequently identified on mobile LDCT lung screenings in rural communities. Patients with higher probabilities of malignant lung nodules may also be at increased risk for significant coronary artery disease. Calcium scoring from LDCT screenings allowed for simultaneous assessment of lung cancer and CVD risk. Unfortunately, few referrals or CVD prevention medications were initiated. Awareness of CAC score utility, follow-up for identified coronary calcifications, and consideration of primary prevention medications when indicated, would be beneficial in patients undergoing LDCT lung screenings, especially in rural areas with limited healthcare access.

Graphical abstract

Image, graphical abstract

Keywords

Cardiovascular disease prevention
Coronary artery calcium score
Lung-RADS
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pmc1 Introduction

While the primary goal of low-dose CT (LDCT) lung cancer screenings (LCS) is to detect early-stage lung cancer, the identification of coronary artery calcium (CAC) can provide insight to a patient's cardiovascular risk and prompt consideration of aggressive risk factor modification for primary prevention of atherosclerotic cardiovascular disease (CVD) [1]. The Agatston method for CAC scoring on LDCT scans offers an efficient and cost-effective means to identify individuals at risk for CVD events. While multiple patient characteristics and factors should be considered, a CAC score of 1–100 indicates mild CVD risk, 101–400 indicates moderate risk, and >400 indicates high risk [2]. CAC scores ≥100 Agatston units are clinically significant and indicate increased risk of cardiac mortality, suggesting consideration of aspirin and statin therapy [1].

Access to healthcare is limited in many areas of Appalachia, where smoking and heart disease rates are highest in the nation [3]. The convergence of risk factors for both CVD and lung cancer in this region provides a unique opportunity for comprehensive health assessments. The integration of CAC scoring within LCS may be particularly pertinent in underserved areas, where a single screening can yield vital insights into two prevalent health concerns. The West Virginia University Cancer Institute introduced a mobile lung cancer screening unit, denoted “LUCAS,” which travels to rural communities to bring early detection lung scans to a population that would not otherwise have access [4,5]. Coronary artery calcification is not always included in these LDCT LCS.

Despite the potential advantages of incorporating cardiovascular risk assessment into LCS, a gap exists in the literature concerning the practical implementation of preventive measures based on these assessments [6]. No data exists for mobile screening units. Additionally, it is unknown if CAC burden on LCS may correlate with severity of Lung CT Screening Reporting and Data System (Lung-RADS) scores.

The aim of this study was to determine if previously completed mobile LUCAS LCS could identify clinically significant CAC in patients with no known history of CVD, evaluate the correlation between Lung-RADS score and CAC burden, and determine if appropriate CVD preventative measures were initiated when indicated.

2 Methods

A retrospective review of baseline mobile LDCT LCS in the LUCAS program from official launch in September 2021 to December 2022 was conducted in one large, rural tertiary health system. Adult patients with no previous CVD history were included. Patients obtained a LDCT LCS after physician referral to the mobile unit. The primary objective was to determine how many patients with no known CVD had the presence of coronary artery calcium on baseline LDCT LCS. Secondary objectives were to determine if LUNG-RADS scores correlated with CAC score, and if patients at moderate to high risk of CVD (CAC scores ≥100) received appropriate follow-up and additional testing.

LDCT images were obtained at 100 kVp with a slice thickness of 3 mm. Baseline characteristics, pertinent comorbidities, cardiac medications, smoking history were obtained from electronic medical record, and Lung-RADS scores were recorded from the radiology report at the original time of LDCT LCS. Lung-RADS scores are divided into the following categories: negative (1), benign (2), probably benign (3), and suspicious (4) nodules. Chest radiologists are instructed to report moderate or severe CAC when interpreting a LDCT LCS but no calcium score is provided. Radiologist reported coronary calcium on original LDCT report was documented, and then Agatston CAC scoring was manually performed retrospectively by the Cardiology team.

Additional data collected included if patients that were not previously on aspirin or statin therapy were started on these preventive medications within 3 months, if patients received additional cardiovascular testing within 6 months (cardiac catheterization, stress testing, echocardiogram, or angiography), and whether or not patients received CVD risk follow-up after the LCS. CVD risk follow-up was defined as a referral to a primary care provider or cardiologist regarding CAC. Data points and patient referrals were collected via electronic medical record chart review. WVU Medicine health-system has a shared medical record with affiliated hospitals and clinics, including rural clinics. Descriptive statistics and chi-square analyses were utilized and the study was approved by the local Institutional Review Board.

3 Results

A total of 526 LDCT screenings were included. 98 % of patients were white, 62 % female, and median age was 61 years (Table 1). Included patients had a median 36 pack-year smoking history, 56.7 % had hypertension, 15.8 % had diabetes, and 42.8 % had hyperlipidemia. Over 54 % of patients had coronary calcification on LDCT LCS. 161 patients (30.6 %) had a CAC score of ≥100 and 75 patients (14.3 %) had a CAC score ≥400.Table 1 Baseline characteristics of LDCT LCSb retrospectively reviewed in patients with no history of cardiovascular disease.

Table 1Characteristic	Total N = 526	
Age in Years, median (range)	61 (47–100)	
Sex, N (%)		
 Female
 Male	328 (62.4 %)
198 (37.6 %)	
Race, N (%)		
 White
 Black	517 (98.3 %)
9 (1.7 %)	
Comorbidities, N (%)		
 Hypertension
 Hyperlipidemia
  Type 2 Diabetes
 History of Cancer
 History of Arrhythmia
 Chronic Kidney Disease
 Congestive Heart Failure	298 (56.7 %)
225 (42.8 %)
83 (15.8 %)
51 (9.7 %)
24 (4.6 %)
21 (4 %)
8 (1.5 %)	
Active Daily Tobacco Smoking, N (%)	357 (67.9 %)	
Tobacco Smoking Pack-Years, median (range)	36 (5–160)	
Other Social History, N (%)		
 Alcohol Use
 Illicit Drug Use	152 (28.9 %)
7 (1.3 %)	
Medications taking at time of LDCTaLCSb, N (%)		
 Statin
 Aspirin	231 (43.9 %)
143 (27.2 %)	
CACcScore, N (%)		
 0 Agatston Units
 1–100 Agatston Units
 101–399 Agatston Units
 400+ Agatston Units	238 (45.2 %)
127 (24.1 %)
86 (16.3 %)
75 (14.3 %)	
Lung-RADSdScore, N (%)		
 Category 1
 Category 2
 Category 3
 Category 4	239 (45.4 %)
213 (40.5 %)
45 (8.6 %)
29 (5.5 %)	
a Low-dose Computed Tomography.

b Lung cancer screening.

c Coronary artery calcium.

d Lung CT Screening Reporting and Data System.

Among patients with a Lung-RADS score of 4, 17 % had a CAC score >400, whereas only 12 % with a Lung-RADS score of 1 fell into the same CAC category (Fig. 1). Conversely, 31 % of patients with Lung-RADS 4 had a CAC score of 0, compared to 52 % with Lung-RADS 1. A significant correlation was observed between higher Lung-RADS scores and elevated CAC scores (p = 0.02). There was a positive correlation between CAC scores and smoking pack-years (p < 0.05). There was not a significant correlation between the severity of Lung-RADS and smoking pack-years (p = 0.16).Fig. 1 Correlation between CAC burden and Lung-RAD score. Percentage of patients with coronary artery calcium scores of 0, 1–100, 101–400, and >400 in comparison to identified Lung-RADS score.

Fig 1

Of patients with a CAC score ≥100, 7.5 % received referrals for follow-up after the LDCT screen and 9.3 % received additional cardiac testing within 6 months (Table 2). Of those with a CAC score ≥1 and not already on a statin (n = 128), 6.2 % were initiated on statin therapy after LDCT. Of those with a CAC score ≥1 and not already on aspirin therapy (n = 181), 3.3 % were initiated on aspirin therapy after LDCT. Patients with higher CAC scores were more likely to be initiated on statin therapy (P < 0.01) (Fig. 2). Patients with higher CAC scores were also more likely to be initiated on aspirin therapy (P < 0.01) (Fig. 3). Patients were more likely to have already been taking an aspirin and statin if their CAC score was higher.Table 2 Preventive measures taken after lung cancer screening.

Table 2Characteristic		
Referrals made for CVDa follow-up in patients with CACb score ≥100, N (%)	12 (7.5 %)	
Additional cardiac testing completed within 6 months of LDCTb LCSc in patients with CACb score ≥100, N (%)	15 (9.3 %)	
Not on statin at time of LDCTcLCSdand CACbscore 1–100, N	64	
 Started on statin within 3 months, N (%)	2 (3.1 %)	
Not on statin at time of LDCTcLCSdand CACbscore 101–400, N	33	
 Started on statin within 3 months, N (%)	2 (6.1 %)	
Not on statin at time of LDCTcLCSdand CACbscore >400, N	31	
 Started on statin within 3 months, N (%)	4 (12.9 %)	
Not on aspirin at time of LDCTcLCSdand CACbscore 1–100, N	89	
 Started on aspirin within 3 months, N (%)	1 (1.1 %)	
Not on aspirin at time of LDCTcLCSdand CACbscore 101–400, N	49	
 Started on aspirin within 3 months, N (%)	1 (2 %)	
Not on aspirin at time of LDCTcLCSdand CACbscore >400, N	43	
 Started on aspirin within 3 months, N (%)	4 (9.3 %)	
a Cardiovascular disease.

b Coronary artery calcium.

c Low-dose Computed Tomography.

d Lung cancer screening.

Fig. 2 Relationship between Statin Initiation and Coronary Artery Calcium Scoring. Percentage of patients with coronary artery calcium score of 0, 1–100, 101–400, and >400 who were either already on a statin, newly started on a statin, or not started on statin therapy.

Fig 2

Fig. 3 Relationship between Aspirin Initiation and Coronary Artery Calcium Scoring. Percentage of patients with coronary artery calcium score of 0, 1–100, 101–400, and >400 who either already on aspirin therapy, newly started on aspirin, or not started on aspirin therapy.

Fig 3

4 Discussion

This is the first study to date to review mobile LDCT LCS and associated CAC in an underserved population. In patients with no CVD history, coronary artery calcification was frequently identified on mobile LDCT LCS in rural communities. There was a statistically significant correlation between Lung-RADS scores and CAC burden, indicating the higher the Lung-RADS score on LDCT LCS, the more likely patients were to have higher CAC scores as well. Despite this, few follow-up referrals, additional testing, or CVD prevention medications were initiated.

In our evaluation of previously completed LDCT LCS, coronary calcification was inconsistently reported, and Agatston unit technique was not used on the initial CT read. In one study, CAC scores from gated CT scans were compared to non-gated chest CT scans completed for the same patient [7]. They found that ordinal scores on non-gated CTs correlated with Agatston CAC scores on gated CTs. They also found that the majority of non-gated chest CTs did not include CAC in the final report. Multiple imaging societies released a consensus statement stating the heart should be reviewed on all non-gated chest CTs and CAC reported in the final read [8]. A retrospective analysis completed at a healthcare network in Boston, Massachusetts evaluated the accuracy of radiologist reported findings of atherosclerosis on LDCT in comparison to CAC grading using Agatston scoring and noted a significant underestimation of calcium burden [6]. Since in our study a number of patients had a high CAC Agatston score on retrospective manual review, standardization of CAC Agatston scoring on LDCT LCS may be considered.

In over 54 % of mobile LDCT LCS reviewed in this study, CAC scores of 1 or greater were identified in patients with no previously known CVD. Over 14 % had CAC scores greater than 400. This indicates that mobile LDCT LCS may help identify patients with mild, moderate, or high CVD risk who would not otherwise receive heart disease screening. In addition to having high rates of heart disease, people in the Appalachian region experience significant social, attitudinal, and geographical barriers to CVD screenings [9,10]. Additionally, CAC testing is not commonly covered by patient insurance [11]. The incorporation of CAC scoring on mobile LDCT LCS may be beneficial to detect undiagnosed CVD and more cost-effective, especially in rural, underserved areas.

The observed statistically significant correlation between Lung-RADS and CAC scores may be attributed to several factors. A plausible explanation is the shared association of both CAC scoring and Lung-RADS with the cumulative burden of tobacco use, as smoking is a well-established risk factor for both conditions. Our study revealed a robust positive correlation between CAC scores and pack-years (p < 0.05). While smoking clearly increases risk of CVD, there is limited data on the correlation of CAC burden and pack-year history, specifically [[12], [13], [14]]. There is also limited data on correlation between Lung-RADS score and pack-year history [15,16]. We did not find a significant correlation between the severity of Lung-RADS and pack-years (p = 0.16). This discrepancy in correlation strength could indicate nuanced relationships between smoking history and the two imaging-based scoring systems.

Regarding CVD preventative measures, the 2018 cholesterol guidelines recommend statin therapy for any patient with a CAC score of ≥100, unless otherwise deferred by a clinician-patient risk discussion [17]. In our review, few patients (only 9.4 %) meeting this criteria were started on a statin within 3 months of the LDCT LCS. Additionally, even fewer patients (only 5.4 %) with a CAC score of ≥100 not already on aspirin were initiated on the medication. The higher the CAC score, the more likely patients were to be started on statin or aspirin therapy (p < 0.01). However, overall new starts after identified CAC were low. Patients with even mild CAC benefit from early initiation of preventative therapy [17]. Patients with a CAC score of 1 or greater may have benefited from statin therapy after consideration of tolerability and contraindications. Regarding aspirin for primary prevention, a study published in JAMA Cardiology in 2020 found that aspirin therapy may be beneficial for people with a CAC score of ≥100, but only if they have a low risk of bleeding and an intermediate or borderline cardiovascular risk [18]. The study also found that aspirin's benefits only outweighed its risks for people with a CAC score above 100. For people with a high risk of bleeding, aspirin may actually be harmful, regardless of their CAC score or 10-year ASCVD risk. In Fig. 3, we displayed patients with CAC scores >100 where opportunities for new-start aspirin therapy for primary prevention may exist. We also displayed patients with CAC scores <100 who were already on aspirin at the time of the LCS. Since these patients had no known history of CAD, an opportunity for de-escalation of aspirin therapy may exist. While we could not evaluate if risk-benefit discussions occurred with patients in our review, these discussions are crucial and may be an area of needed attention. While many patient-specific factors are important to consider when initiating preventative medications, the age and comorbidities of the population included likely show missed opportunities for prevention.

In patients with CAC scores ≥100, we reviewed if CVD risk reduction strategies were implemented after LDCT LCS. Few patients received additional cardiac testing or a referral for follow-up with a primary care provider or cardiologist for CVD prevention after their baseline screen (Table 2). This may have been due to a lack of standardized CAC reporting, insufficient provider attention to noted coronary calcification as this was not the primary focus of the scan, or limited follow-up resources in rural areas.

Opportunistic CAC screening using a deep learning algorithm on non-gated chest CT scans, followed by clinician and patient notification, significantly increased statin prescriptions, per the NOTIFY-1 Project [19]. Among 194 patients with confirmed incidental CAC, those notified had a statin prescription rate of 51.2 % compared to 6.9 % in the usual care group. This approach demonstrates the potential for incidental CAC findings to enhance cardiovascular care in patients without known atherosclerotic disease. Given the degree of CAC in patients with no known CVD seen in our review, follow-up notification and referrals could greatly benefit this population. In addition to statin and aspirin therapy, many other preventative measures could be addressed in rural areas. 68 % of patients in this review were actively smoking tobacco. Since tobacco use is the single greatest preventable cause of mortality and cessation significantly reduces lung cancer and CVD, this may be an essential area of future focus [20].

Additionally, original LDCT reads may not have reported, or likely underestimated, severity of CAC [6]. Since the main goal of these mobile LDCTs is to identify early lung cancer, CAC and CVD risk may not receive enough emphasis. Per the American College of Radiology, radiologists are expected to report coronary artery calcium when it is denoted as moderate or severe during LDCT LCS, but providing a specific calcium score is not required [21]. Initial documentation of CAC is recommended, though repeating this documentation on annual scans is not obligatory. In practice, not all radiologists report this. This is where the concern lies for lack of standardized CAC reporting, potentially leading to poor follow-up. Standardized protocols for reporting of CAC in Agatston units on mobile LDCT LCS may be warranted. This could lead to better follow-up and initiation of preventative medications in rural populations. This may be beneficial beyond mobile screenings and could be valuable for all LDCT LCS.

Limitations to this study include the retrospective design and collection of information from the electronic medical record. This study also retroactively completed CAC Agatston scoring from previously completed LDCT. Preventive measures and follow-up may have differed if this scoring was initially reported. Additionally, CT images were obtained at 100 kVp with a slice thickness of 3 mm while standard images for CAC calculation are at 130 kVp. This may have led to an increase in image noise which can alter the final score [22]. Under reporting of coronary calcification may have occurred which may have contributed to low referrals and preventative medications started. Finally, the study was small and conducted within one rural health system.

LDCT LCS may be an effective and cost-efficient way to provide concurrent information on lung cancer and CVD risk. The correlation between Lung-RADS and CAC scores may inform clinical practice and policy decisions regarding preventive cardiology in underserved areas. Limited implementation of preventive strategies in our study raises concerns, and emphasizes the need for targeted interventions and improved integration of cardiovascular risk assessment into routine LDCT screenings.

5 Conclusion

Integrating cardiovascular risk assessment into mobile LDCT lung screenings offers a unique opportunity to identify patients at risk for both lung cancer and cardiovascular disease. The observed correlation between Lung-RADS and CAC emphasizes the importance of a comprehensive approach to patient care. Enhanced cardiovascular evaluations and implementing risk modification strategies in patients with suspicious lung nodules can contribute to a more nuanced and holistic approach to patient care in rural areas. Our study advocates for the integration of standardized CAC scoring on LDCT LCS, as well as incorporation of follow-up referrals and initiation of preventive medications based on these scores, especially in regions with limited healthcare access.

CRediT authorship contribution statement

Seher Berzingi: Writing – review & editing, Writing – original draft, Visualization, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Kara Piechowski: Writing – review & editing, Writing – original draft, Visualization, Data curation. Emily Hendricks: Writing – review & editing, Data curation. Mark Colantonio: Writing – review & editing, Data curation. Asuwin Anandarm: Writing – review & editing. Gregory Perkowski: Writing – review & editing. Tyler Miller: Writing – review & editing. Justin Conte: Writing – review & editing. Sameh Nassar: Writing – review & editing. Belal Kaseer: Writing – review & editing. Marcelino Mederos Liriano: Writing – review & editing, Data curation. Juan Carlo Avalon: Writing – review & editing, Writing – original draft, Validation, Supervision, Project administration, Investigation, Data curation. Kyle Chapman: Writing – review & editing, Supervision, Project administration, Investigation, Formal analysis. Brijesh Patel: Writing – review & editing, Validation, Supervision, Project administration, Methodology, Data curation, Conceptualization.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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