Impact of Serum Uric Acid on Left Ventricular Diastolic Function in Patients with Autoimmune Diseases
Left ventricular diastolic dysfunction (LVDD) is a subclinical manifestation of autoimmune diseases (AD) that often goes unrecognized but carries a significant prognostic burden. Elevated serum uric acid (SUA), a proinflammatory factor, has been associated with changes in cardiac function in the general population and in patients with cardiac diseases. However, its role in patients with AD has not been thoroughly investigated. This study aimed to explore the prevalence of LVDD and its relationship with SUA levels in a large cohort of patients with a wide spectrum of AD.
The study was conducted as a retrospective analysis of patients admitted to the Rheumatology Department of West China Hospital from January 2011 to December 2017. Inclusion criteria were: (1) a definite diagnosis of AD at discharge, (2) age 18 years or older, (3) a standard transthoracic echocardiography (TTE) examination, and (4) at least one SUA measurement during the index hospitalization. Exclusion criteria included confirmed gout, atrial fibrillation or flutter, and structural heart diseases. The study was approved by the Ethics Committee of West China Hospital, Sichuan University.
Data were extracted from the hospital information system using unique patient identifiers. Clinical data included demographics, blood pressure (BP) at admission, last laboratory tests before discharge, AD diagnosis, comorbidities, and medications recorded in the discharge summary. Hyperuricemia was defined as SUA >420 mmol/L. Echocardiographic data included left ventricular dimension (LVD), thickness (interventricular septal [IVS] and left ventricular posterior wall [LVPW]), mass (LVM), ejection fraction (LVEF), left atrial dimension (LAD), Doppler-derived transmitral E wave divided by mitral annular e’ (E/e’), and any positive comments in the TTE report such as left atrial enlargement (LAE), left ventricular hypertrophy (LVH), pericardial effusion, pulmonary hypertension, and valvular lesions. LVDD was defined as E/e’ ≥ 13 or coexisting LVH and LAE if E/e’ < 13 in patients with LVEF ≥ 50%.
Data analysis was performed using SPSS version 22. Continuous variables were presented as means ± standard deviations or medians (interquartile ranges), and categorical variables as frequencies (percentages). Differences among SUA quartiles were assessed using the chi-square test for categorical variables, one-way analysis of variance for normally distributed variables, and the Kruskal-Wallis H test for non-normally distributed variables. Comparisons between patients with and without LVDD were performed using Student’s t-test and the chi-square test. Variables associated with LVDD with a P value of ≤0.20 were included in a multivariate logistic regression model to identify factors related to LVDD. A P value of <0.05 was considered statistically significant.
A total of 5873 patients (mean age 45 ± 16 years, 78.9% female) were included. Systemic lupus erythematosus (SLE) (29.4%) and rheumatoid arthritis (RA) (20.2%) were the most common AD types. An LVEF < 50% was observed in 1.6% of patients. LVDD was identified in 26.7% of patients, while 71.7% had isolated LVH, isolated LAE, or none of the features of LVDD. Valvular lesions were observed in 21.8% of patients, predominantly mild regurgitation. Pericardial effusion was found in 15.2% of patients, and pulmonary hypertension in 4.2% of patients.
The mean SUA level was 300 ± 115 mmol/L. Patients were divided into quartiles based on SUA levels: Q1 (49–222 mmol/L, n = 1461), Q2 (223–283 mmol/L, n = 1468), Q3 (284–362 mmol/L, n = 1469), and Q4 (363–996 mmol/L, n = 1472). Hyperuricemia was present in 54.5% of patients in Q4. The percentages of males, hypertension, use of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), SUA-lowering drugs, and BP increased from Q1 to Q4. Renal insufficiency was highest in Q4, while the use of disease-modifying antirheumatic drugs (DMARDs), cytotoxic drugs, or nonsteroidal anti-inflammatory drugs (NSAIDs) was lowest in Q4. Higher C-reactive protein (CRP) levels were observed in Q1 and Q4, while the erythrocyte sedimentation rate (ESR) was highest in Q1 and decreased from Q1 to Q4. TTE parameters showed that LAD, LVD, and LVM progressively increased from Q1 to Q4. IVS and LVPW were thicker in Q3 and Q4, while a lower LVEF and higher E/e’ were observed only in Q4. The prevalence of LVDD increased from 21.7% in Q1 to 36.2% in Q4 (P < 0.05).
Comparing the LVDD+ and LVDD- groups, the LVDD+ group had older patients with higher BP, CRP, and SUA, more females, and more patients with hypertension, diabetes, renal dysfunction, and hyperuricemia. These patients were also more likely to be treated with glucocorticoids, DMARDs, ACEI/ARBs, and CCBs (all P < 0.001). No differences were observed in ESR or the use of cytotoxic drugs, NSAIDs, or SUA-lowering drugs. Multivariate regression analysis (Model I) showed that the adjusted odds ratio (OR) of LVDD increased with higher SUA levels. Hypertension was a major comorbidity leading to LV diastolic dysfunction. Another regression model (Model II) excluded patients with known hypertension and hypertension as covariates, showing the same trend. When hyperuricemia was used instead of SUA quartiles in the regression models, the ORs were 1.408 in Model I and 1.447 in Model II (both P < 0.001).
This study revealed that LVDD was the most common abnormality observed by TTE, affecting one-third of AD patients. Emerging evidence suggests that AD itself can increase LV stiffness through atherosclerosis, endothelial dysfunction, and myocardial fibrosis. Traditional cardiovascular risk factors such as age, sex, hypertension, diabetes, and renal insufficiency were also significant in this study. AD patients with hypertension had the highest risk of LVDD, more than twice that of those without hypertension, with an OR similar to that in the general population. Therefore, BP control remains a cornerstone of heart failure prevention and management in AD patients.
SUA has been related to the development of osteoarthritis and renal dysfunction in SLE and RA. This study proposed a link between SUA and the presence of LVDD in patients with a wide spectrum of AD. As a mediator of inflammation and atherosclerosis, further confirmation is needed to determine whether elevated SUA strengthens the association between AD and target organ damage. SUA-lowering drugs have been shown to decrease cardiovascular events, but it remains unknown whether these drugs could prevent or improve LVDD.
The study has some limitations, including potential data selection bias and the lack of follow-up data, which means the observed relationship between SUA and LVDD cannot be regarded as causal, and its prognostic value in cardiovascular events cannot be determined.
In conclusion, LVDD was a predominant echocardiographic abnormality in AD patients. In addition to traditional cardiovascular risk factors, elevated SUA was independently associated with the presence of LVDD. Further investigation is warranted to determine whether the control of SUA could prevent or reverse LVDD.
doi.org/10.1097/CM9.0000000000001902
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