Pulmonary hypertension-associated mortality among patients with lung cancer: A CDC WONDER analysis (2003-2023).

Abstract

e20775 Background: Lung cancer remains a leading cause of cancer-related mortality globally. In advanced stages, tumor-driven vascular remodeling can predispose patients to secondary Pulmonary Hypertension (PH), contributing to significant cardiopulmonary morbidity. Despite recognition of cancer-associated PH, its epidemiology in lung cancer is poorly characterized. Methods: In this retrospective cohort study, we analyzed mortality records from the CDC WONDER database (2003–2023) for decedents aged ≥45 years with both lung cancer (ICD-10: C34) and secondary PH (ICD-10: I27.2) listed as contributing or underlying causes of death. Analyses adhered to STROBE guidelines for observational studies. Age-adjusted mortality rates (AAMRs) per 100,000 population, annual percent changes (APCs), and average annual percent changes (AAPCs) were estimated using Joinpoint regression, stratified by age, sex, US census region, urbanization, state, and place of death. Results: We identified 8,428 deaths over 21 years. Overall AAMR increased from 0.15 in 2003 to 0.52 per 100,000 in 2023 (AAPC 6.31%, 95% CI 5.54–7.09). Adults aged ≥65 years experienced the largest increases, with a rapid rise from 2003–2011 (APC 10.08%, 95% CI 7.82–12.37), plateau 2011–2014, and further increase 2014–2023 (APC 8.07%, 95% CI 6.89–9.24; AAPC 7.15%, 95% CI 4.81–9.52). Males exhibited consistently higher AAMRs than females (AAPC 6.66%, 95% CI 3.68–9.74). Regional variation was notable, with the West showing the highest AAPC (8.12%, 95% CI 7.32–8.92), followed by Midwest, South, and Northeast. Mortality increased significantly in metropolitan areas from 2003–2020 (APC 5.87%, 95% CI 4.84–6.91) and in non-metropolitan areas after 2005 (APC 6.41%, 95% CI 5.06–7.78). Most deaths occurred in inpatient facilities (3,431), followed by home (2,846). States with the greatest mortality burden included California, Florida, Texas, Ohio, Pennsylvania, and Colorado. Conclusions: A three-fold rise in AAMR over two decades highlights secondary PH as an under-recognized contributor to morbidity among lung cancer patients, particularly older males in Western metropolitan regions. These findings underscore the need for enhanced screening, early recognition, and further research into tumor-mediated mechanisms driving PH in lung cancer.