Incidence and Risk Factors of Pulmonary Hypertension After Venous Thromboembolism: An Analysis of a Large Health Care Database

Abstract

Background Pulmonary hypertension (PH) is a devastating potential complication of pulmonary embolism, a manifestation of venous thromboembolism (VTE). The incidence of and risk factors for PH in those with prior VTE are poorly characterized. Methods and Results International Classification of Diseases (ICD) codes from inpatient and outpatient medical claims from MarketScan administrative databases for years 2011 to 2018 were used to identify cases of VTE, comorbidities before the VTE event, and PH occurring subsequent to the VTE event. Cumulative incidence and hazard ratios (HR), and their 95% CI, were calculated. The 170 021 VTE cases included in the analysis were on average (±SD) 57.5±15.8 years old and 50.5% were female. A total of 5943 PH cases accrued over an average follow-up of 1.94 years. Two years after incident VTE, the cumulative incidence (95% CI) of PH was 3.5% (3.4%-3.7%) overall. It was higher among older individuals, among women (3.9% [3.8%-4.1%]) than men (3.2% [3.0%-3.3%]), and among patients presenting with pulmonary embolism (6.2% [6.0%-6.5%]) than those presenting with deep vein thrombosis only (1.1% [1.0%-1.2%]). Adjusting for age and sex, risk of PH was higher among patients with VTE with underlying comorbidities. Using the Charlson comorbidity index, there was a dose-response relationship, whereby greater scores were associated with increased PH risk (score ≥5 versus 0: HR, (2.50 [2.30-2.71])). When evaluating individual comorbidities, the strongest associations were observed with concomitant heart failure (HR, 2.17 [2.04-2.31]), chronic pulmonary disease (2.01 [1.90-2.14]), and alcohol abuse (1.66 [1.29-2.13]). Conclusions In this large, real-world population of insured people with VTE, 3.5% developed PH in the 2 years following their initial VTE event. Risk was higher among women, with increasing age, and in those with additional comorbidities at the time of the VTE event. These data provide insights into the burden of PH and risk factors for PH among patients with VTE.

Keywords: epidemiology; pulmonary hypertension; venous thromboembolism.

Figure 1. Flowchart for selection of retrospective cohort design study population.

ICD indicates International Classification of Diseases; OAC, oral anticoagulant; PH, pulmonary hypertension; and VTE, venous thromboembolism.

Figure 2. Graphical representation of retrospective cohort study design.

^AExcluded if: Not aged 18 to 99 years, did not have <3 months of steady enrollment, or had a pulmonary hypertension diagnosis before VTE index date. ^BCovariates include age at time of incident VTE, sex, and a full list of covariates and code algorithms provided in Table S2. ^CCensored at earliest outcome of pulmonary hypertension, disenrollment, or end of the study period. PH indicates pulmonary hypertension; and VTE, venous thromboembolism.