Background/Purpose: Women with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease (CVD).  We have shown that clinically CVD-free women with SLE have an increased volume of descending aortic perivascular adipose tissue (aPVAT).  This small adipose depot was also associated with aortic calcification (AC) independent of overall adiposity.  Thus, we hypothesized that clinically CVD-free women with SLE increased aPVAT volume and premature vascular calcification measured by AC and coronary artery calcification (CAC) will predict cardiovascular events.(CVE)

Methods: Women participating in the “Heart Effects on Atherosclerosis and Risk of Thrombosis in SLE” (HEARTS) study were clinically CVD-free and diagnosed with SLE for at least 2 years.  CAC/AC were measured using electron beam computed tomography (EBCT) and quantified by Agaston scoring.  The aPVAT was quantified using commercially available software and standard attenuations values for adipose tissue (–190 to –30 HU).  Participants were followed for incident CVE confirmed by a physician. (SLE without CVE, n=128; SLE with CVE n=28).  CVE included myocardial infarction, congestive heart failure, stroke, transient ischemic attack, angina, blood clot, percutaneous coronary intervention, and catherization.

Results: Twenty eight participants (17%) experienced a first CVE within 4.6 +/- 12 months (Mean +/- SD) with three participants having multiple CVE. There were no differences in surrogate adiposity measures such as waist-to-hip ratio (p=0.58) or BMI (p=0.23) by CVE status suggesting similar adipose distribution. Traditional CVD risk factors such as age (p=0.008), systolic blood pressure (p=0.0053), pulse pressure (p=0.0047), hypertensive status (p=0.0039), CRP (p=0.0081) and homocysteine levels (p=0.017) were all significantly greater in SLE women with CVE.  The SLE women with CVE were more likely to have AC (p=0.0052).  There were no differences in CAC (p=0.21) or aPVAT (p=0.17) between SLE groups with and without CVE.  Aortic PVAT was associated with adiposity measures such as BMI (r_s=0.515,p<0.0001), waist-to-hip ratio (r_s=0.332,p=0.0001), and circulating inflammatory markers such as CRP (r_s=0.393,p<0.0001).    In univariate models using Cox proportional-hazards regression, CAC (Hazard ratio/HR [95%CI]: 2.43 [1.1-5.5], p=0.03) was a predictor of first CVE, but AC (p=0.74) and aPVAT (p=0.20) were not predictors.  In the multivariable Cox regression models, age per 5 years (HR 1.61 [1.3-2.1], p=0.0001) and CRP (HR 1.10 [1.0-1.2], p=0.0055) remained predictors of first CVE. 

Conclusion:   Traditional CVD risk factors were independent predictors of first CVE in women with SLE in this study.  The clinically CVD free SLE women experiencing a CVE were more likely to have hypertension along with AC indicating premature vascular dysfunction.  CAC was an independent predictor of first CVE emphasizing the significant influence of calcification in this vascular bed.  Aortic PVAT was found to be significantly associated with traditional CVD risk factors, but not found to be predictive of first CVE.  Considering our previous findings, aPVAT and AC may be considered precursors to measurable subclinical CAC.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/association-of-vascular-calcification-and-perivascular-adipose-tissue-of-the-descending-aorta-with-cardiovascular-events-in-sle/