Decreased low‑density lipoprotein and the presence of pulmonary arterial hypertension among newly diagnosed drug‑naïve patients with systemic lupus erythematosus: D‑dimer as a mediator

Abstract

Pulmonary arterial hypertension (PAH) is commonly associated with systemic lupus erythematosus (SLE). The present study investigated the relationship between coagulation and changes in lipid parameters in newly-diagnosed patients with SLE in the presence of PAH and whether the coagulation parameters were mediators between lipids and PAH presence. A total of 301 subjects scheduled for new-onset drug-naïve SLE were consecutively enrolled. Baseline data for patients without PAH and with PAH were gathered and compared. Coagulation and lipid parameters were compared across patients without lipid regulating and anticoagulation medications. Multivariable logistic regression model was applied to examine potential predictors of PAH in SLE. The relationships between them were examined using Spearman's correlation analysis. The relationship between coagulation index and lipids with SLE-PAH was evaluated using mediation analysis. Female patients accounted for 88.0% of the 301 subjects, and the average age was 32 years (range, 25-45 years). A total of 40 patients (13.3%) had PAH, and the average pulmonary artery systolic pressure (sPAP) was 55.825±26.67 mmHg. Patients with PAH were older and had higher levels of fibrin/fibrinogen degradation products (FDP), D-dimer, C-reactive protein, lower levels of complement 3, complement 4 and 25-hydroxy vitamin D3 compared with the non-PAH group. Multivariable logistic regression analysis showed that age and D-dimer were independent predictor factors for PAH. Among patients without lipid regulating and anticoagulation medications, patients in the PAH group had higher levels of D-dimer and FDP, and lower low-density lipoprotein (LDL) levels compared with patients without PAH. There was also a positive relationship between sPAP and D-dimer and FDP, and a negative relationship between sPAP and total cholesterol and LDL. Mediation analysis indicated that 25.61% of the effect of low LDL on PAH presence in systemic lupus erythematosus was mediated by D-dimer. Overall, the effect of low LDL on SLE-PAH appeared to be mediated by D-dimer, which mediated 25.61% of this effect.

Prognostic effect of pulmonary hypertension in patients with chronic kidney disease: Univariate and multivariate analyses of factors associated with survival

“…Low LDL may serve as an indicator of disease severity and prognosis in patients with PH, and LDL's anti-inflammatory properties may be relevant ( 27 ). We also found low LDL in CTD-PAH patients ( 28 ). Until recently, the exact mechanisms accounting for the association between low LDL and PH have been obscure, possible explanations include a chronic inflammatory state ( 29 ), malnutrition ( 30 ), and altered liver metabolism ( 31 ).…”

The Roles of Fibrinolytic Factors in Bone Destruction Caused by Inflammation

“…These factors play a regulatory role in the functions of both osteoclasts and osteoblasts ( Figure 2 ). On the other hand, the levels of fibrinolysis markers such as D-dimer and fibrin degradation products (FDP), as well as fibrinolytic factors in samples from patients with chronic inflammatory diseases like rheumatoid arthritis [ 38 , 39 , 40 , 41 ], systemic lupus erythematosus [ 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ], Crohn’s disease [ 50 , 51 , 52 , 53 ], and periodontitis [ 54 , 55 , 56 ], are higher than those in healthy controls ( Figure 3 ). These factors are associated with the pathology of chronic inflammatory diseases and may play a critical role in the context of inflammatory bone destruction.…”

An update on cardiovascular disorders in systemic lupus erythematosus

“…78 D-dimer levels are a known predictive factor for PAH and may act as a mediator of reduced low-density lipoprotein (LDL), although optimal cutoff points and estimations of individual pressure ranges are unknown. 92 Patients with SLE may benefit from PH screening using transthoracic ECG, lung function tests (forced vital capacity and diffusion lung capacity for carbon monoxide) and an N-terminal pro-B-type natriuretic peptide (NT-proBNP) test, particularly in combination. 93 Moreover, genetic phenotyping may be a standard beneficial option in the future.…”