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. 2024 Apr 24;10(2):e003559.
doi: 10.1136/rmdopen-2023-003559.

Primary Sjögren's syndrome independently promotes premature subclinical atherosclerosis

Nadine Zehrfeld  1 , Malin Abelmann  2 , Sabrina Benz  3 , Clara Luisa Zippel  1 , Sonja Beider  1 , Emelie Kramer  1 , Tabea Seeliger  4 , Georgios Sogkas  1 , Vega Gödecke  1 , Gerrit Ahrenstorf  1 , Franz Paul Armbruster  5 , Thomas Skripuletz  4 , Torsten Witte  1 , Anselm Arthur Derda  2 , Kristina Sonnenschein #  2 , Diana Ernst #  6
Affiliations

Primary Sjögren's syndrome independently promotes premature subclinical atherosclerosis

Nadine Zehrfeld et al. RMD Open. .

Abstract

Objectives: Cardiovascular comorbidities are common in patients with autoimmune diseases. This study investigates the extent of subclinical atherosclerosis in patients with primary Sjögren's syndrome (pSS). Correlations with clinical factors such as organ involvement (OI) or disease activity were analysed and oxLDL antibodies (oxLDL ab) were measured as potential biomarkers of vascular damage.

Methods: Patients with pSS were consecutively included from the rheumatology outpatient clinic. Age- and sex-matched controls were recruited (2:1 ratio). Data collection was performed by a standardised questionnaire and Doppler ultrasound to evaluate the plaque extent and carotid intima-media thickness (cIMT). Propensity score matching included all cardiovascular risk (CVR) factors and corresponding laboratory markers.

Results: Data were available for 299 participants (199 pSS/100 controls), aged 59.4 years (50.6-65.0), 19.1% male. After matching, the pSS cohort had greater cIMT (p<0.001) and plaque extent (OR=1.82; 95% CI 1.14 to 2.95). Subgroup analyses of patients with pSS revealed that OI was associated with increased cIMT (p=0.025) and increased plaque occurrence compared with patients without OI (OR=1.74; 95% CI 1.02 to 3.01). OxLDL ab tended to be lower in patients with plaque (p=0.052). Correlations of higher Oxidized Low Density Lipoprotein (oxLDL) ab with EULAR Sjögren's Syndrome Disease Activity Index (p<0.001) and anti-Sjögren's-syndrome-related antigen A autoantibodies (SSA/Ro antibodies) (p=0.026) were observed.

Conclusions: Subclinical atherosclerosis occurs earlier and more severely in patients with pSS. The difference in cIMT between pSS and controls seems mainly driven by patients with OI, suggesting that this subgroup is particularly at risk. OxLDL ab might protect against atherosclerotic progression in patients with pSS. CVR stratification and preventive medications such as Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors should be discussed and further longitudinal studies are needed.

Keywords: Atherosclerosis; Autoantibodies; Cardiovascular Disease; Sjogren's Syndrome.

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Conflict of interest statement

Competing interests: Novartis did not contribute to the study design, analyses or data interpretation. The oxLDL antibody analyses were performed as a commissioned service by Immundiagnostik AG, Bensheim, Germany, under the direction of Dr Franz Paul Armbruster, without further information on the samples. Immundiagnostik AG therefore had no influence on the analyses or the interpretation of the data.

Figures

Figure 1
Figure 1
Study design. *Diagnosis of cancer recurrence and multiple sclerosis shortly after study inclusion. MI, myocardial infarction.
Figure 2
Figure 2
Ultrasound image of a left common carotid artery with thickened cIMT. Yellow lines show the measurement of cIMT according to the Mannheim Consensus. cIMT, carotid intima-media thickness.
Figure 3
Figure 3
cIMT-density plot of matched sample (n=100 participants in each cohort) showing the cIMT distribution by group. X indicates cohort-specific cIMT means, that is, 0.65 mm for control cohort and 0.71 mm for pSS cohort. Significance level indicates main effect for cohort in hierarchical regression predicting cIMT. cIMT, carotid intima-media thickness; pSS, primary Sjögren’s syndrome.
Figure 4
Figure 4
Scatter plot showing the correlation between cIMT and age, subdivided by cohorts. Each person is represented by two dots (left and right cIMT) and a linear regression line was calculated to illustrate the differences in increasing cIMT. cIMT, carotid intima-media thickness; pSS, primary Sjögren’s syndrome.
See this image and copyright information in PMC

References

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