Elevated risk of first-time pulmonary hypertension among COVID-19 survivors: a 4.5-year longitudinal study.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection could result in pulmonary vascular injury, systemic inflammation, and endothelial dysfunction, which could increase future risk of pulmonary hypertension (PH) and related complications. Methods: We conducted a retrospective cohort study from the Montefiore Medical Center (Bronx, NY, USA) (1 March 2020 to 17 August 2024). Patients who had a COVID-19 PCR test were compared to those who did not have a positive COVID-19 PCR test on record. There were 15 721 hospitalised COVID-19 patients, 43 740 non-hospitalised COVID-19 patients, and 870 458 contemporary COVID-negative controls, and 634 892 historical (1 May 2016 to 31 December 2019) controls. The main analysis used propensity score matching for demographics, tobacco, substance use disorder, vaccination for SARS-CoV-2, and pre-existing comorbidities. New-onset PH and PH-related complications were assessed using Fine-Gray subdistribution hazard ratios (sHR). Sensitivity analyses included multivariable cause-specific Cox proportional hazard model, inverse probability weighting, and using matched historical cohort as controls. Long-term PH-related complications included heart failure, chronic kidney disease, and all-cause mortality compared to matched controls. Blood biomarkers during acute COVID-19 were analysed with respect to new-onset PH. Results: Compared to propensity-matched COVID-negative controls, COVID-19 hospitalised patients were (sHR) 1.41 (95% CI 1.27-1.57) times more likely to experience new-onset PH, and COVID-19 non-hospitalised patients were 1.42 (95% CI 1.25-1.61) times more likely to do so. Sensitivity analyses corroborated our main findings. Among those with new-onset PH, only hospitalised COVID-19 survivors had higher risks of subsequent heart failure (sHR 1.61, 95% CI 1.11-2.35), chronic kidney disease (2.18, 1.50-3.16), and all-cause mortality (1.81, 1.47-2.24) compared to matched controls. Abnormal troponin (sHR 1.61, 95% CI 1.05-2.48), brain natriuretic peptide (1.59, 1.20-2.11) and creatinine (1.24, 1.01-1.51) during acute COVID-19 were associated with outcomes, but not D-dimer, ferritin and haematological markers. Conclusions: SARS-CoV-2 infection is independently associated with elevated long-term risk of new-onset PH, whereas only hospitalised COVID-19 status is associated with higher risk of downstream PH-related complications. These findings underscore the importance of ongoing PH surveillance in COVID-19 survivors.