Circulating biomarkers associated with aortic diameter in male and female patients with thoracic aortic disease: a cross-sectional study

Abstract

Objective: As thoracic aortic disease (TAD) is generally asymptomatic, biomarkers are needed to provide insight into early progression. We aimed to examine the association between circulating blood biomarkers and the maximal thoracic aortic diameter (TADmax).

Methods: In this cross-sectional study, consecutive adult patients with a thoracic aortic diameter ≥40 mm and/or genetically proven hereditary TAD (HTAD) visiting our specialised outpatient clinic between 2017 and 2020 were prospectively included. Venous blood sampling and CT angiography and/or transthoracic echocardiography of the aorta were performed. Linear regression analyses were performed and estimates were presented as mean difference in TADmax in mm per doubling of standardised biomarker level.

Results: In total, 158 patients were included (median age 61 (50.3-68.8) years, 37.3% female). HTAD diagnosis was confirmed in 36 of 158 (22.7%) patients. TADmax was 43.9±5.2 mm in men vs 41.9±5.1 in women (p=0.030). In unadjusted analysis, significant associations with TADmax were found for interleukin-6 (1.15 (95% CI 0.33 to 1.96), p=0.006), growth differentiation factor-15 (1.01 (95% CI 0.18 to 1.84), p=0.018), microfibrillar-associated protein 4 (MFAP4) (-0.88 (95% CI -1.71 to 0.05), p=0.039) and triiodothyronine (T3) (-2.00 (95%CI -3.01 to 0.99), p<0.001). The association of MFAP4 with TADmax was stronger in women (p for interaction=0.020) and for homocysteine, an inverse association with TADmax was observed when compared with men (p for interaction=0.008). When adjusted for age, sex, hyperlipidaemia and HTAD, total cholesterol (1.10 (95% CI 0.27 to 1.93), p=0.010) and T3 (-1.20 (95% CI -2.14 to 0.25), p=0.014) were significantly associated with TADmax.

Conclusions: Circulating biomarkers indicative of inflammation, lipid metabolism and thyroid function might be associated with TAD severity. Possible distinct biomarker patterns for men and women warrant further investigation.

Keywords: Aortic Aneurysm; Aortic Diseases; Biomarkers.

Figure 1

Flow chart of patient selection. *Reasons for exclusion were not showing up for venous blood sampling or other logistical difficulties to the clinical chemistry laboratory.

Figure 2

Univariable linear regression analyses with the TADmax as dependent variable and clinical variables (A) and biomarkers (B) as independent variables. Estimates and corresponding 95% CI are derived from linear regression analysis with log2-transformed and standardised biomarkers as independent variables, that is, doubling of the standardised MFAP4 value results in a decrease of 0.876 mm in TADmax. P values of <0.05 are depicted in bold. ACEi, ACE inhibitor; ARB, angiotensin receptor blocker; BAV, bicuspid aortic valve; BSA, body surface area; COPD, chronic obstructive pulmonary disease; CVA, cerebrovascular accident; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FBN1, human fibrillin-1; fT4, free thyroxine; GDF-15, growth differentiation factor-15; Hb, haemoglobin; HDL, high-density lipoprotein; hsCRP, high-sensitivity C reactive protein; hsTnT, high-sensitivity troponin T; IL-6, interleukin-6; LDL, low-density lipoprotein; LVEF, left ventricular ejection fraction; MFAP4, microfibrillar-associated protein 4; NT-proBNP, N-terminal pro B-type natriuretic peptide; PIIINP, procollagen III N-terminal propeptide; RDW, red cell distribution width; SBP, systolic blood pressure; T3, triiodothyronine; T4, thyroxine; TAD, thoracic aortic disease; TADmax, maximal thoracic aortic diameter; TSH, thyroid-stimulating hormone.