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

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.

Health-related quality of life and lived experiences in males and females with thoracic aortic disease and their partners.

OBJECTIVE: Thoracic aortic disease (TAD) may have substantial impact on health-related quality of life (HRQOL). We described HRQOL in patients with TAD, cardiovascular screening participants and their partners; identified factors associated with HRQOL; and explored lived experiences and feelings of anxiety or depression using a mixed methods design. METHODS: For this cross-sectional study, all consecutive patients visiting the TAD outpatient clinic (2017-2019) at our centre were asked to complete three questionnaires: the Short Form 36 (SF-36), the Hospital Anxiety and Depression Scale (HADS) and the Rotterdam Disease Specific Questionnaire (RDSQ). A subsample was invited for in-depth interviews. RESULTS: In total, 261 participants were included: 147 patients with TAD (thoracic aortic diameter ≥40 mm; 54 females, 36.7%), 114 screening participants (cardiovascular family screening; 71 females, 62.3%) and 66 partners. Compared with the general population, patients with TAD showed markedly lower HRQOL, whereas screening participants' HRQOL was less impaired. Female and younger participants scored significantly lower on the SF-36 and HADS compared with male and older participants. Smaller aortic diameter was associated with better RDSQ score, and previous aortic surgery was associated with higher HADS depression scores. Furthermore, partners scored significantly lower on 2/8 SF-36 subdomains when compared with the general population. From 11 interviewees, determinants of psychological distress included coping strategies, impact on social and professional life, disease-related knowledge, state of aortic diameters and physical symptoms. CONCLUSIONS: Healthcare professionals must be aware of HRQOL impairments in patients with TAD, particularly in younger females. Moreover, attention for partners is needed. Coping strategies and communication within the family were found to be important factors influencing psychological distress, and might be valuable leads for counselling and HRQOL improvement in this population.

Aortic dilatation and outcome in women with Turner syndrome.

BACKGROUND: Women with Turner syndrome (TS) are at increased risk of aortic dissection, which is related to ascending aortic diameter. However, the relation between aortic diameter and outcome is not well determined. This study evaluates the prevalence of aortic dilatation, the growth rate of the aorta and the risk of aortic complications in adults with TS. METHODS: Single centre, retrospective study of all women with TS followed with a strict protocol in an outpatient TS clinic. Aortic diameters were analysed using advanced imaging. The primary outcome was a combined endpoint of aortic-related mortality, aortic dissection and preventive aortic surgery. The secondary endpoint was aortic growth and prevalence of aortic dilatation, defined as an aortic size index >20 mm/m2 at baseline. RESULTS: At least one cardiac MR/CT was available in 268 women with TS, having median age of 28.7 (IQR: 21.3-39.7) years. Aortic dilatation was present in 22%. Linear regression identified independent factors associated with larger aortic diameters: age (coefficient=0.23; p<0.001), hypertension (coefficient=2.7; p<0.001), bicuspid aortic valve (coefficient=3.3; p<0.001), 45XO karyotype (coefficient=1.7; p=0.002), weight (coefficient=0.075; p<0.001) and growth hormone treatment (coefficient=1.4; p=0.044). During follow-up (6.8±3.2 years), five women (2%) reached the primary endpoint (two dissections, three aortic surgery). Women withmore than one scan (n=171; 1015 patient-years follow-up), the median aortic growth was 0.20 (IQR: 0.00-0.44) mm/year. In multivariate analysis, aortic growth was not associated with baseline aortic diameter or other variables. CONCLUSIONS: Aortic dilatation is common and known associations were confirmed in large adult TS cohort However, aortic dissection, related mortality and preventive aortic surgery are rare. Growth hormone treatment in childhood was associated with aortic dimensions.