Premature atherosclerosis and cardiovascular morbidity are known in adults with Systemic Lupus Erythematosus (SLE); however, there is paucity of data in Indian children with lupus nephritis (LN), who may be at higher cardiovascular risk due to ethnic differences.
Methods
This cross-sectional study was conducted at the pediatric nephrology clinic of a referral hospital in south India. Forty children with LN >1 year disease duration and 40 healthy-controls were enrolled. Brachial artery flow-mediated dilatation (FMD), carotid intima medial thickness (cIMT), and echocardiography for left ventricular (LV) mass, LV systolic and diastolic function, and global-longitudinal-strain (GLS) were done.
Results
Mean age at SLE and LN diagnosis were 10.07 years and 10.68 years respectively, with median LN disease duration of 3.2 years. Class 3 and Class 4 LN accounted for 67.5% of the cases. Overall, 6 (15%) LN cases had concentric LVH, while 4 (10%) had biplane ejection fraction≤ 55%. Mean resting brachial artery diameter was lower in cases (n = 40) than age and sex-matched healthy-controls (n = 40) (2.7 mm vs 2.9 mm, p 0.010), although median proportionate change in FMD was comparable [13.84% (8.17%, 20.31%) versus 14.49% (12.21%, 17.24%); p 0.413]. However, proportionate change in FMD <10% was more prevalent in cases vs controls (35% vs 10%, p 0.007). Cardiac assessments showed higher A-wave velocity (69.03 ± 18.0 cm/s vs 58.64 ± 11.93 cm/s, p 0.003) and lower E/A ratio (1.56 ± 0.49 vs 1.80 ± 0.44, p 0.030) in cases vs controls; with elevated medial a′ velocity (8.98 ± 2.01 vs 7.94 ± 2.12 cm/s, p 0.030). Pulmonary venous Doppler revealed shorter atrial reversal duration (85.82 ± 18.7 vs 102.25 ± 17.8 ms, p 0.001) and reduced A-wave duration (118.08 ± 19.73 vs 128.67 ± 20.27 ms, p 0.023) among cases. GLS was lower in cases (−21.59 ± 3.06% vs −22.95 ± 2.38%, p 0.030), and median LV mass was higher in cases vs controls (92.7 g vs 72.1 g, p < .001).
Conclusion
South Indian children with LN of >1 year disease duration demonstrate significant cardiovascular comorbidities, including evidence of endothelial dysfunction, as well as LV systolic and diastolic dysfunction.
ManziSMeilahnENRairieJE, et al.Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol1997; 145: 408–415. https://doi.org/10.1093/oxfordjournals.aje.a009122
SharmaSKRathiMSahooS, et al.Assessment of premature atherosclerosis in systemic lupus erythematosus patients with and without nephritis. Lupus2016; 25: 525–531. https://doi.org/10.1177/0961203315622822
4.
LivingstonBBonnerAPopeJ. Differences in clinical manifestations between childhood-onset lupus and adult-onset lupus: a meta-analysis. Lupus2011; 20: 1345–1355. https://doi.org/10.1177/0961203311416694
5.
Mendoza-PintoCRojas-VillarragaAMolano-GonzálezN, et al.Endothelial dysfunction and arterial stiffness in patients with systemic lupus erythematosus: a systematic review and meta-analysis. Atherosclerosis2020; 297: 55–63. https://doi.org/10.1016/j.atherosclerosis.2020.01.028
6.
GazarianMFeldmanBMBensonLN, et al.Assessment of myocardial perfusion and function in childhood systemic lupus erythematosus. J Pediatr1998; 132: 109–116. https://doi.org/10.1016/s0022-3476(98)70494-9
7.
SoepJBMietus-SnyderMMalloyMJ, et al.Assessment of atherosclerotic risk factors and endothelial function in children and young adults with pediatric-onset systemic lupus erythematosus. Arthritis Rheum2004; 51: 451–457. https://doi.org/10.1002/art.20392
PatraPKBandayAZAsgharA, et al.Early atherosclerosis in pediatric systemic lupus erythematosus: a systematic review and meta-analysis. Int J Rheum Dis2025; 28: e70217. https://doi.org/10.1111/1756-185X.70217
10.
TuzcuEMKapadiaSRTutarE, et al.High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults: evidence from intravascular ultrasound. Circulation2001; 103: 2705–2710. https://doi.org/10.1161/01.cir.103.22.2705
ChangJCSearsCTorresV, et al.Racial disparities in renal outcomes over time among hospitalized children with systemic lupus erythematosus. Arthritis Rheumatol2022; 74: 1430–1439. https://doi.org/10.1002/art.42127
13.
ParsaALovettDHPedenEA, et al.Renin–angiotensin system gene polymorphisms predict the progression to renal insufficiency among Asians with lupus nephritis. Gene Immun2005; 6: 217–224. https://doi.org/10.1038/sj.gene.6364179
14.
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 Clinical practice guideline for the management of glomerular diseases. Kidney Int2021; 100: S1–S276. https://doi.org/10.1016/j.kint.2021.05.021
15.
PetriMOrbaiA-MAlarcónGS, et al.Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum2012; 64: 2677–2686. https://doi.org/10.1002/art.34473
16.
AringerMCostenbaderKDaikhD, et al.European League against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol2019; 71: 1400–1412. https://doi.org/10.1002/art.40930
17.
BajemaIMWilhelmusSAlpersCE, et al.Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int2018; 93: 789–796. https://doi.org/10.1016/j.kint.2017.11.023
18.
FlynnJTKaelberDCBaker-SmithCM, et al.Subcommittee on screening and management of high blood pressure in children. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics2017; 140: e20171904. https://doi.org/10.1542/peds.2017-1904
GhiadoniLTaniCBrunoRM, et al.Prognostic value of flow-mediated dilation in patients with systemic lupus erythematosus: a pilot prospective cohort study. Atherosclerosis2014; 236: 381–384. https://doi.org/10.1016/j.atherosclerosis.2014.07.023
21.
SitzerMMarkusHSMendallMA, et al.C-reactive protein and carotid intimal medial thickness in a community population. J Cardiovasc Risk2002; 9: 97–103. https://doi.org/10.1177/174182670200900205
22.
GokhrooRKAnantharajABishtD, et al.A pediatric echocardiographic Z-score nomogram for a developing country: Indian pediatric echocardiography study - the Z-score. Ann Pediatr Cardiol2018; 11: 109–111. https://doi.org/10.4103/apc.APC_123_17
23.
LevyPTMachefskyASanchezAA, et al.Reference ranges of left ventricular strain measures by two-dimensional speckle-tracking echocardiography in children: a systematic review and meta-analysis. J Am Soc Echocardiogr2016; 29: 209–225.e6. https://doi.org/10.1016/j.echo.2015.11.016
24.
EidemBWMcMahonCJCohenRR, et al.Impact of cardiac growth on Doppler tissue imaging velocities: a study in healthy children. J Am Soc Echocardiogr2004; 17: 212–221. https://doi.org/10.1016/j.echo.2003.12.005
25.
DallaireFSlorachCHuiW, et al.Reference values for pulse wave Doppler and tissue Doppler imaging in pediatric echocardiography. Circ, Cardiovasc Imaging2015; 8: e002167. https://doi.org/10.1161/CIRCIMAGING.114.002167
RahulIKrishnamurthySSatheeshS, et al.Brachial artery flow-mediated dilatation and carotid intima medial thickness in pediatric nephrotic syndrome: a cross-sectional case-control study. Clin Exp Nephrol2015; 19: 125–132. https://doi.org/10.1007/s10157-014-0958-1
28.
SozeriBDeveciMDincelN, et al.The early cardiovascular changes in pediatric patients with systemic lupus erythematosus. Pediatr Nephrol2013; 28: 471–476. https://doi.org/10.1007/s00467-012-2342-2
29.
FontJRamos-CasalsMCerveraR, et al.Cardiovascular risk factors and the long-term outcome of lupus nephritis. QJM Mon J Assoc Physicians2001; 94: 19–26. https://doi.org/10.1093/qjmed/94.1.19
30.
HermansenM-LLindhardsenJTorp-PedersenC, et al.The risk of cardiovascular morbidity and cardiovascular mortality in systemic lupus erythematosus and lupus nephritis: a Danish nationwide population-based cohort study. Rheumatol Oxf Engl2017; 56: 709–715. https://doi.org/10.1093/rheumatology/kew475
31.
KissESolteszPDerH, et al.Reduced flow-mediated vasodilation as a marker for cardiovascular complications in lupus patients. J Autoimmun2006; 27: 211–217. https://doi.org/10.1016/j.jaut.2006.09.008
32.
WangD-GTangX-WFanY, et al.Decreased flow-mediated dilatation in patients with systemic lupus erythematosus: a meta-analysis. Inflammation2014; 37: 2067–2075. https://doi.org/10.1007/s10753-014-9940-z
33.
HenrotPForetJBarnetcheT, et al.Assessment of subclinical atherosclerosis in systemic lupus erythematosus: a systematic review and meta-analysis. Jt Bone Spine2018; 85: 155–163. https://doi.org/10.1016/j.jbspin.2017.12.009
34.
RobinsonGAWaddingtonKECoelewijL, et al.Increased apolipoprotein-B: A1 ratio predicts cardiometabolic risk in patients with juvenile onset SLE. EBioMedicine2021; 65: 103243. https://doi.org/10.1016/j.ebiom.2021.103243
35.
SchanbergLESandborgCBarnhartHX, et al.Understanding premature atherosclerosis in pediatric SLE: risk factors of increased Carotid Intima Medial Thickness (CIMT) in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) cohort. Arthritis Rheum2009; 60: 1496–1507. https://doi.org/10.1002/art.24469
36.
QuinlanCKariJPilkingtonC, et al.The vascular phenotype of children with systemic lupus erythematosus. Pediatr Nephrol2015; 30: 1307–1316. https://doi.org/10.1007/s00467-015-3059-9
37.
BarsalouJBradleyTJTyrrellPN, et al.Impact of disease duration on vascular surrogates of early atherosclerosis in childhood-onset systemic lupus erythematosus. Arthritis Rheumatol2016; 68: 237–246. https://doi.org/10.1002/art.39423
38.
ChangJCWhiteBREliasMD, et al.Echocardiographic assessment of diastolic function in children with incident systemic lupus erythematosus. Pediatr Cardiol2019; 40: 1017–1025. https://doi.org/10.1007/s00246-019-02107-1
39.
GünalNKaraNAkkökN, et al.Cardiac abnormalities in children with systemic lupus erythematosus. Turk J Pediatr2003; 45: 301–305.
40.
ChowP-CHoMH-KLeeT-L, et al.Relation of arterial stiffness to left ventricular structure and function in adolescents and young adults with pediatric-onset systemic lupus erythematosus. J Rheumatol2007; 34: 1345–1352.
41.
LealGNSilvaKFLianzaAC, et al.Subclinical left ventricular dysfunction in childhood-onset systemic lupus erythematosus: a two-dimensional speckle-tracking echocardiographic study. Scand J Rheumatol2016; 45: 202–209. https://doi.org/10.3109/03009742.2015.1063686
