Sex-Related Differences in Patient Characteristics, Risk Factors, and Symptomatology in Older Adults with Pulmonary Embolism: Findings from the SERIOUS-PE Study

Abstract

Sex-specific factors are implicated in pulmonary embolism (PE) presentation in young patients, as indicated by increased risk in pregnancy. Whether sex differences exist in PE presentation, comorbidities, and symptomatology in older adults, the age group in which most PEs occur, remains unknown. We identified older adults (aged ≥65 years) with PE in a large international PE registry replete with information about relevant clinical characteristics (RIETE registry, 2001–2021). To provide national data from the United States, we assessed sex differences in clinical characteristics and risk factors of Medicare beneficiaries with PE (2001–2019). The majority of older adults with PE in RIETE (19,294/33,462, 57.7%) and in the Medicare database (551,492/948,823, 58.7%) were women. Compared with men, women with PE less frequently had atherosclerotic diseases, lung disease, cancer, or unprovoked PE, but more frequently had varicose veins, depression, prolonged immobility, or history of hormonal therapy (p < 0.001 for all). Women less often presented with chest pain (37.3 vs. 40.6%) or hemoptysis (2.4 vs. 5.6%) but more often with dyspnea (84.6 vs. 80.9%) (p < 0.001 for all). Measures of clot burden, PE risk stratification, and use of imaging modalities were comparable between women and men. PE is more common in elderly women than in men. Cancer and cardiovascular disease are more common in men, whereas transient provoking factors including trauma, immobility, or hormone therapy are more common in elderly women with PE. Whether such differences correlate with disparities in treatment or differences in short- or long-term clinical outcomes warrants further investigation.

Keywords

sex - comorbidity - risk factory - pulmonary embolism - elderly - symptomatology

• References

• 1 Barrios D, Morillo R, Guerassimova I. et al. Sex differences in the characteristics and short-term prognosis of patients presenting with acute symptomatic pulmonary embolism. PLoS One 2017; 12 (11) e0187648
• 2 Blanco-Molina A, Enea I, Gadelha T. et al; RIETE Investigators. Sex differences in patients receiving anticoagulant therapy for venous thromboembolism. Medicine (Baltimore) 2014; 93 (17) 309-317
• 3 Jarman AF, Mumma BE, Singh KS, Nowadly CD, Maughan BC. Crucial considerations: sex differences in the epidemiology, diagnosis, treatment, and outcomes of acute pulmonary embolism in non-pregnant adult patients. J Am Coll Emerg Physicians Open 2021; 2 (01) e12378
• 4 Bikdeli B, Khairani CD, Barns BM. et al. Women's representation in venous thromboembolism randomized trials and registries: the illustrative example of direct oral anticoagulants for acute treatment. Contemp Clin Trials 2022; 115: 106714
• 5 Scheres LJJ, Brekelmans MPA, Beenen LFM, Büller HR, Cannegieter SC, Middeldorp S. Sex-specific differences in the presenting location of a first venous thromboembolism. J Thromb Haemost 2017; 15 (07) 1344-1350
• 6 Raisi-Estabragh Z, Kobo O, Elbadawi A. et al. Differential patterns and outcomes of 20.6 million cardiovascular emergency department encounters for men and women in the United States. J Am Heart Assoc 2022; 11 (19) e026432
• 7 Keller K, Rappold L, Gerhold-Ay A. et al. Sex-specific differences in pulmonary embolism. Thromb Res 2019; 178: 173-181
• 8 Tormene D, Ferri V, Carraro S, Simioni P. Gender and the risk of venous thromboembolism. Semin Thromb Hemost 2011; 37 (03) 193-198
• 9 Brush Jr JE, Krumholz HM, Greene EJ, Dreyer RP. Sex differences in symptom phenotypes among patients with acute myocardial infarction. Circ Cardiovasc Qual Outcomes 2020; 13 (02) e005948
• 10 Canto JG, Rogers WJ, Goldberg RJ. et al; NRMI Investigators. Association of age and sex with myocardial infarction symptom presentation and in-hospital mortality. JAMA 2012; 307 (08) 813-822
• 11 Bikdeli B, Jimenez D, Hawkins M. et al; RIETE Investigators. Rationale, design and methodology of the computerized Registry of Patients with Venous Thromboembolism (RIETE). Thromb Haemost 2018; 118 (01) 214-224
• 12 Bikdeli B, Wang Y, Jimenez D. et al. Pulmonary embolism hospitalization, readmission, and mortality rates in US older adults, 1999-2015. JAMA 2019; 322 (06) 574-576
• 13 Ageno W, Haas S, Weitz JI. et al; GARFIELD-VTE Investigators. Characteristics and management of patients with venous thromboembolism: the GARFIELD-VTE Registry. Thromb Haemost 2019; 119 (02) 319-327
• 14 Elgendy IY, Fogerty A, Blanco-Molina Á. et al. Clinical characteristics and outcomes of women presenting with venous thromboembolism during pregnancy and postpartum period: findings from the RIETE Registry. Thromb Haemost 2020; 120 (10) 1454-1462
• 15 Albertsen IE, Søgaard M, Goldhaber SZ. et al. Development of sex-stratified prediction models for recurrent venous thromboembolism: a Danish Nationwide Cohort Study. Thromb Haemost 2020; 120 (05) 805-814
• 16 Barco S, Valerio L, Ageno W. et al. Age-sex specific pulmonary embolism-related mortality in the USA and Canada, 2000-18: an analysis of the WHO Mortality Database and of the CDC Multiple Cause of Death database. Lancet Respir Med 2021; 9 (01) 33-42
• 17 Bates SM, Rajasekhar A, Middeldorp S. et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy. Blood Adv 2018; 2 (22) 3317-3359
• 18 Bikdeli B, Piazza G, Jimenez D. et al. Sex Differences in PrEsentation, Risk Factors, Drug and Interventional Therapies, and OUtcomes of Elderly PatientS with Pulmonary Embolism: Rationale and design of the SERIOUS-PE study. Thromb Res 2022; 214: 122-131
• 19 van der Pol LM, Tromeur C, Bistervels IM. et al; Artemis Study Investigators. Pregnancy-adapted YEARS algorithm for diagnosis of suspected pulmonary embolism. N Engl J Med 2019; 380 (12) 1139-1149
• 20 Verma AA, Masoom H, Pou-Prom C. et al. Developing and validating natural language processing algorithms for radiology reports compared to ICD-10 codes for identifying venous thromboembolism in hospitalized medical patients. Thromb Res 2022; 209: 51-58
• 21 White RH, Garcia M, Sadeghi B. et al. Evaluation of the predictive value of ICD-9-CM coded administrative data for venous thromboembolism in the United States. Thromb Res 2010; 126 (01) 61-67
• 22 Bikdeli B, Jiménez D, Del Toro J. et al; RIETE Investigators †. Association between preexisting versus newly identified atrial fibrillation and outcomes of patients with acute pulmonary embolism. J Am Heart Assoc 2021; 10 (17) e021467
• 23 Velasco D, Jiménez D, Bikdeli B. et al; RIETE investigators. Outcome of patients with acute symptomatic pulmonary embolism and psychiatric disorders. Thromb Res 2020; 193: 90-97
• 24 Konstantinides SV, Meyer G, Becattini C. et al; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020; 41 (04) 543-603
• 25 Jiménez D, Aujesky D, Moores L. et al; RIETE Investigators. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 2010; 170 (15) 1383-1389
• 26 Bikdeli B, Lobo JL, Jiménez D. et al; RIETE Investigators. Early use of echocardiography in patients with acute pulmonary embolism: findings from the RIETE Registry. J Am Heart Assoc 2018; 7 (17) e009042
• 27 Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med 2009; 28 (25) 3083-3107
• 28 Jin X, Chandramouli C, Allocco B, Gong E, Lam CSP, Yan LL. Women's participation in cardiovascular clinical trials from 2010 to 2017. Circulation 2020; 141 (07) 540-548
• 29 Wells PS, Anderson DR, Rodger M. et al. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and D-dimer. Ann Intern Med 2001; 135 (02) 98-107
• 30 Bromen K, Pannier-Fischer F, Stang A, Rabe E, Bock E, Jöckel KH. [Should sex specific differences in venous diseases be explained by pregnancies and hormone intake?]. Gesundheitswesen 2004; 66 (03) 170-174
• 31 Laporte S, Chapelle C, Caillet P. et al. Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: a meta-analysis of observational studies. Pharmacol Res 2017; 118: 19-32
• 32 Parkin L, Balkwill A, Sweetland S, Reeves GK, Green J, Beral V. Million Women Study Collaborators. Antidepressants, depression, and venous thromboembolism risk: large prospective study of UK women. J Am Heart Assoc 2017; 6 (05) 6
• 33 Dreyer RP, Dharmarajan K, Hsieh AF, Welsh J, Qin L, Krumholz HM. Sex differences in trajectories of risk after rehospitalization for heart failure, acute myocardial infarction, or pneumonia. Circ Cardiovasc Qual Outcomes 2017; 10 (05) 10
• 34 Mentias A, Vaughan-Sarrazin M, Saad M, Girotra S. Sex differences in management and outcomes of critical limb ischemia in the Medicare population. Circ Cardiovasc Interv 2020; 13 (10) e009459
• 35 Bikdeli B, Hogan H, Morrison RB. et al. Extended-duration low-intensity apixaban to prevent recurrence in patients with provoked venous thromboembolism and enduring risk factors: rationale and design of the HI-PRO trial. Thromb Haemost 2022; 122 (06) 1061-1070