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Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Role of Fibroblast Growth Factor 23- Phosphate Axis
Yaser Ammar1, Amira Mohamed1, Gihane Khalil2
1Internal Medicine Department, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Insights
Fibroblast growth factor-23 (FGF23) and phosphorus are key in accelerated cardiovascular disease for systemic lupus erythematosus (SLE) patients. Assessing serum phosphorus and FGF23 aids in cardiovascular risk evaluation for SLE and lupus nephritis patients.
Area of Science:
- Cardiovascular Research
- Nephrology
- Rheumatology
Background:
- Accelerated atherosclerotic cardiovascular disease (ACVD) is a major cause of mortality in systemic lupus erythematosus (SLE) patients, often unexplained by traditional risk factors.
- Fibroblast growth factor-23 (FGF23), a bone-derived hormone, promotes atherosclerosis and vascular calcification, especially in chronic kidney disease.
- Elevated FGF23 levels are observed in SLE patients, particularly those with lupus nephritis (LN), but its atherogenic role remains under-explored.
Purpose of the Study:
- To investigate the role of FGF23 in accelerated ACVD in SLE patients, with and without lupus nephritis (LN).
- To explore the association between FGF23, traditional cardiovascular risk factors, and markers of atherosclerosis in SLE and LN.
- To identify predictors of elevated FGF23 and its relationship with cardiovascular disease markers in SLE and LN.
Main Methods:
- The study included three groups: SLE (without LN), LN, and controls, matched for traditional cardiovascular disease (CVD) risk factors.
- Data collected included SLE activity, damage, steroid use, renal function, lipid profile, and serum levels of phosphorus, vitamin D3, parathyroid hormone, and intact FGF23 (iFGF23).
- Carotid ultrasonography assessed common carotid artery intima-media thickness (CC-IMT), plaque score (PS), and internal carotid resistive index (ICRI).
Main Results:
- CC-IMT, ICRI, and serum iFGF23 levels were significantly higher in LN patients compared to SLE and controls.
- Serum iFGF23 positively correlated with serum phosphorus, CC-IMT, and PS in both SLE and LN patients.
- Cumulative steroid dose was the strongest predictor of increased CC-IMT in SLE, while serum iFGF23 was the strongest predictor in LN. Hyperphosphatemia and proteinuria predicted higher iFGF23 in SLE and LN, respectively.
Conclusions:
- The FGF23-phosphate axis plays a critical role in accelerated ACVD in SLE patients.
- Serum phosphorus and iFGF23 levels should be incorporated into ACVD risk assessments for SLE patients.
- Future studies should examine the impact of managing hyperphosphatemia and proteinuria on circulating iFGF23 and ACVD risk in these patients.
Purpose:
Despite management advances, accelerated atherosclerotic cardiovascular disease (ACVD) remains a major cause of morbimortality in systemic lupus erythematosus (SLE) patients; that is not fully explained by traditional risk factors. Fibroblast growth factor-23 (FGF23) is a bone-derived phosphaturic hormone with multiple klotho-dependent and independent effects, including promotion of atherosclerosis and vascular calcification, particularly in the context of chronic kidney disease. Increased circulating FGF23 was reported in SLE patients, particularly with lupus nephritis (LN); but its atherogenic role in these disorders was not explored.
Subjects And Methods:
Three study groups of predominantly middle-aged females were categorized by the 2012 SLE International Collaborating Clinics (SLICC) criteria as SLE (without LN), LN, or controls matching for traditional CVD risk profile. Measures of SLE activity, damage, steroid therapy, and glomerular filtration rate were calculated. Fasting blood samples were checked for serum lipid profile, anti-DNA, urea, creatinine, uric acid, proteins, albumin, calcium, phosphorus, C3, C4, CRP, vitamin-D3, intact parathyroid hormone and FGF23 (iFGF23). By carotid ultrasonography, mean common carotid artery intima-media thickness (CC-IMT), plaque score (PS) and internal carotid resistive index (ICRI) were recorded.
Results:
CC-IMT, ICRI and serum iFGF23 differed along the study groups (LN>SLE>controls). In both SLE and LN patients, serum iFGF23 had a significant positive correlation with serum phosphorus, CC-IMT and PS. On multivariate analysis, the strongest predictor of increased CC-IMT was cumulative steroid dose in SLE and serum iFGF23 in LN patients. Most significant independent predictors of increased serum iFGF23 were hyperphosphatemia in SLE and proteinuria in LN patients.
Conclusion:
FGF23-phosphate axis has a key role in accelerated ACVD in SLE patients. Serum phosphorus and iFGF23 should be included in ACVD risk profile assessment of these patients. Prospective studies shall define the role of dietary and/or pharmacologic control of hyperphosphatemia and proteinuria in reducing circulating iFGF23 and ACVD in them.
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