|Home | About | Journals | Submit | Contact Us | Français|
The Centers for Medicare & Medicaid Services (CMS) recently approved lung cancer screening with computed tomography (CT); smoking is a risk factor for lung cancer and atherosclerotic cardiovascular disease (ASCVD).1 Data are needed regarding the cardiovascular risk of patients eligible for lung cancer screening, including implications of coronary artery calcification (CAC) visible on lung cancer screening CT.
In a longitudinal primary prevention cohort study, we determined lung cancer screening eligibility in the community and its association with statin eligibility, CAC, and incident ASCVD events. A total of 3000 asymptomatic Framingham Heart Study (FHS) Offspring Cohort participants aged 55-77 and free of prevalent cardiovascular disease or lung cancer were divided based on eligibility for lung cancer screening CT by CMS criteria: (1) aged 55-77 (all by definition), 2) current or recent (≤15 years) former smoker, and 3) ≥30 pack-year cigarette smoking history.1 Participants were enrolled at exam 3 (1984-1987) and/or exam 7 (1998-2001) and followed for the primary outcome of incident ASCVD (myocardial infarction, death due to coronary heart disease, or ischemic stroke) and the secondary outcome of lung cancer. Participants were contacted annually, with suspected ASCVD or lung cancer events adjudicated by a panel of 3 physicians based on review of medical records, histopathology reports, and death certificates. A subgroup of 980 from exam 7 had ECG-gated calcium score multidetector CT. The institutional review boards of Boston University Medical Center and Massachusetts General Hospital approved the study. All participants provided written informed consent.
Hazard ratios for incident ASCVD and lung cancer were compared between lung cancer screening eligible and ineligible groups using multivariable Cox proportional hazards regression. Interaction of enrollment exam on these associations was assessed with separate Cox models. Secondary analyses assessed statin eligibility by 2013 ACC/AHA guidelines, predicted vs. observed 10-year ASCVD risk, and the extent of CAC and association with ASCVD.2 Multivariable models were adjusted for age, sex, BMI, SBP, HDL, LDL, total cholesterol, lipid lowering therapy, antihypertensive treatment, and diabetes. Statistical analysis was performed with SAS version 9.4.
Of 3000 participant visits (mean age 62.8±5.9 years; 54.6% female), 20% (596; 62.1±5.4 years; 49.0% female) were eligible for lung cancer screening. Eligible participants were more likely male (51% vs. 44%, p=0.002) or current smokers (56% vs. 4%, p<0.001), but otherwise had similar age (62 vs. 63 years) and risk profile to ineligible participants. The screening eligible had median 50.1 (quartiles: 39.4–65.7) pack-years of cigarette smoking.
Over median follow-up of 11.4 (9.7–12.0) years, screening eligible individuals had more incident ASCVD than ineligible persons (12.6% vs. 8.0%, multivariable-adjusted HR 1.8 (95%CI 1.4–2.3), p<0.001, Figure). ASCVD was more frequent than lung cancer in both groups (eligible: 12.6% vs. 7.2%, p=0.002; ineligible: 8.0% vs. 1.0%, p<0.001). There was no interaction between when the participant was enrolled and the association with incident ASCVD or lung cancer (p>0.3).
In the lung cancer screening eligible, predicted and observed 10-year ASCVD risk were similar (predicted 11.4% vs. observed 11.7%, p=0.31). In contrast the screening ineligible had higher predicted than observed risk (9.6% vs. 6.9%, p=0.001). By 2013 ACC/AHA guidelines, 78.9% (470/596) of screening eligible participants qualified for statin.
Among 980 with calcium score CT, the 13.6% who were screening eligible were more likely to have any or high CAC (Agatston Score (AS) >0: 90.2% vs. 78.0%, p=0.010 and AS >300: 39.1% vs. 27%, p=0.045). Overall 94.7% of the screening eligible persons either qualified for statin or had CAC. In the screening eligible, ordinal calcium score categories were associated with ASCVD, with 0% (0/13) for AS=0, 4.7% (2/43) for AS 1-100, 12.0% (3/25) for AS 101-300, and 19.2% (10/52) for AS >300 (adjusted p=0.003).
Prior research in lung cancer screening trials demonstrates that standard low-dose non-ECG gated lung cancer screening CT accurately assigns CAC to semi-quantitative ordinal categories that predict future ASCVD.3, 4 We extend these findings, demonstrating that in a community cohort aged 55-77 and eligible for primary cardiovascular prevention, 20% met CMS eligibility criteria for lung cancer screening CT with nearly 60% greater incident ASCVD than the ineligible over 11.4 years of follow-up. Nearly all (95%) of the screening eligible participants had CAC or were statin eligible; 39% had AS >300. CMS requires a consultation for shared decision-making and smoking cessation before lung cancer screening CT.1 Given the substantial risk of ASCVD, we propose that cardiovascular prevention counseling should be considered as part of this consultation.
Reporting CAC on lung cancer screening CT personalizes risk and may improve compliance with cardiovascular prevention as a supportive measure.4 While non ECG-gated lung cancer screening CT does not discriminate between 0 and very low AS in 10% compared to gated CT4, most events in our study occurred with AS >100. Finally, our results suggest that considering long-term heavy smoking may improve risk prediction. The ASCVD risk calculator performed well in the screening eligible (predicted 11.4% vs. observed 11.7% at 10 years, p=0.31). In contrast, ASCVD risk was substantially overestimated in the screening ineligible (predicted 9.6% vs. observed 6.9%, p=0.001) concordant with other population-based studies.2 Thus knowledge of lung cancer screening eligibility may give physicians greater confidence in the projected ASCVD risk.
Our study limitations include enrollment periods ending 29 and 15 years ago during a period of lower statin awareness. Nevertheless, an interaction analysis found no difference in results based on when participants enrolled. Furthermore the screening eligible had cumulative pack years (50 vs. 48 in the National Lung Screening Trial) representative of the contemporary US screening population.5
In conclusion, in a community-based primary prevention cohort, 20% aged 55-77 are eligible for lung cancer screening CT. The lung cancer screening eligible are at high risk for ASCVD events, even greater than the risk of lung cancer, and have a high prevalence of subclinical atherosclerosis. Cardiovascular prevention should be considered as part of the consultation for lung cancer screening.
Sources of Funding: This work was supported by the National Heart, Lung, and Blood Institute’s Framingham Heart Study (contracts N01-HC-25195, HL076784, AG028321, HL070100, HL060040, HL080124, HL071039, HL077447, and HL107385). Dr Lu was supported by National Institutes of Health grant T32 HL076136 and the American Roentgen Ray Society Scholarship. The National Institutes of Health and American Roentgen Ray Society had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Dr Hoffmann reports receipt of grants from HeartFlow Inc, Siemens Healthcare, Genentech, and the American College of Radiology Imaging Network and personal fees from the American Heart Association (all significant).
Disclosures: No other disclosures were reported.