Prevalence, molecular mechanisms and diagnostic approaches to pulmonary arterial hypertension in connective tissue diseases.

Abstract

Pulmonary arterial hypertension (PAH) is a severe and life-threatening complication in patients with systemic connective tissue diseases (CTD). This review aims to explore the prevalence, clinical implications, diagnostic strategies, and management of PAH in CTD, emphasizing the need for early detection and effective treatment. A detailed analysis of original research and review articles published between 2004 and 2024, available in English, was conducted, including both primary studies and reviews. These sources were retrieved from databases such as PUBMED, Medline, Web of Science, Scopus, and DOAJ. PAH is frequently associated with systemic sclerosis (SSc), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), undifferentiated connective tissue disease (UCTD), rheumatoid arthritis (RA), Sjögren syndrome, vasculitis, and other CTDs. The general prevalence of PAH in CTD varies between populations, races, and methods used for evaluation. For example, the highest prevalence of SLE is observed in Asian and African Americans compared to European populations. In Caucasians, the leading cause of PAH-CTD is SSc. The PAH prevalence in SSc ranges from 6.4 (Spanish) to 13.6% (Polish National PAH Registry), in SLE from 4.2% (British population) to 2.8-23.3% in Chinese regions. In MCTD, PAH has been detected in 3.4% of the French population and 43% in Japan, while RA-PAH develops in 1.3% (Canadian data) and 31% according to British data. pSS-PAH ranges from 0.49% in French patients to 23.4% in Turkish analysis. In vasculitis, the incidence of PAH develops is several or a dozen percent, depending on the background disease. Regardless of the disease, population, or disease, the development of PAH is always associated with an increased mortality rate, which increases with each year of survival with CTD. The complexity and multifactorial PAH reflect the complicated mechanism underlying the development of this life-threatening complication. They include endothelial dysfunction caused by elevated endothelin-1 level (strong vasoconstrictor and modulator of pro-inflammatory pathways), altered nitric oxide (NO) signaling, reduced prostacyclin synthase signaling, activation of myofibroblasts, pathological angiogenesis, and excessive platelet activation, elevated levels of chemokines and inflammatory cytokines. The diagnosis of PAH in CTD patients is complex, requiring careful evaluation of cardiological symptoms, echocardiography, electrocardiogram (ECG), and serum biomarkers. Right heart catheterization remains the gold standard for diagnosing PAH. Awareness of the high incidence of PAH in CTD and the need for systematic screening for early detection of pulmonary pathology nay contribute to earlier initiation of appropriate treatment, thereby prolonging patient survival.