Aims Abdominal aortic aneurysm is a life-threatening condition due to the risk of aneurysm growth and rupture. There are no approved diagnostic or prognostic biomarkers for abdominal aortic aneurysm. We aimed to identify diagnostic and prognostic biomarkers for abdominal aortic aneurysm and to investigate their relationship with abdominal aortic aneurysm diameter and growth. Methods In this case-control study, patients were included from an abdominal aortic aneurysm screening study on men aged ≥65 years. Of 24,589 examined men, 415 had abdominal aortic aneurysm, out of whom 134 consented to participate in the present study. One hundred and thirty-six screened men with aortic diameter <30 mm, matched for comorbidities and time of sampling were included as non-abdominal aortic aneurysm patients. Ninety-one cardiovascular specific proteins in plasma samples were measured by the Proseek Multiplex CVD III96x96 panel. Results After Bonferroni correction, plasma levels of 21 proteins associated with proteolysis, oxidative-stress, lipid metabolism, and inflammation were significantly increased, whereas levels of paraoxonase 3, associated with high-density lipoprotein metabolism, were decreased in abdominal aortic aneurysm patients. Combination of growth/differentiation factor 15 and cystatin B had the best ability to discriminate abdominal aortic aneurysm from non-abdominal aortic aneurysm (area under the curve, 0.76; sensitivity, 80% and specificity, 52%). Myeloperoxidase showed the best prognostic value (area under the curve, 0.71; sensitivity, 80% and specificity, 59%) and higher baseline levels of myeloperoxidase were significantly associated with faster abdominal aortic aneurysm growth compared with lower levels, independent of baseline diameter. Conclusions We have identified multiple proteins associated with abdominal aortic aneurysm diameter and growth with a potential to become novel diagnostic and prognostic biomarkers for abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a life-threatening condition with a mortality rate of over 80%. Persistent smoking, which is a risk factor for AAA, has lasting effects on DNA methylation. Moreover, a plasma-amino acid, homocysteine, previously implicated in vascular diseases, including aneurysms, has well-established biological association with methylation. In the present study, we aimed to determine the global DNA methylation, homocysteine levels and their association with AAA and its growth. Enzyme-linked immunosorbent assay (ELISA) was used to quantify global DNA methylation in whole blood-DNA samples and diagnostic enzymatic assay quantified plasma homocysteine, from 65-year old men with (n = 116) and without AAA (n = 230) diagnosed at ultrasound screening. We found significantly higher global DNA methylation (p b .001) and homocysteine levels (p b .001) in men with AAA compared to those without AAA, and direct linear associations with baseline aortic diameter. On multivariable regression analysis, global DNA methylation (odds ratio [OR]: 1.8; 95% confidence interval [CI]: 1.1-2.9) and homocysteine levels (OR: 1.1; 95% CI:1.0-1.1) were positively associated with AAA, independent of smoking, medication use, and major co-morbidities. However, we did not find any significant association between DNA methylation or homocysteine levels with AAA growth during follow-up. We found that global DNA methylation and homocysteine levels are higher in men with AAA but are not associated with AAA growth. This indicates that different pathways and mechanisms may be involved in initiation and progression of AAA. More studies are needed to understand the precise role of DNA methylation, homocysteine and their interplay in AAA pathophysiology.

Summary: Background: Peripheral arterial disease (PAD) is a common atherosclerotic disease with severity ranging from asymptomatic to chronic limb threatening ischemia. The aim of the present cross-sectional study was to identify novel biomarkers associated with PAD. Patients and methods: Levels of 91 cardiovascular specific proteins in plasma samples were measured by the Proseek Multiplex CVD III96x96 panel from a cohort consisting of 267 65-year-old men recruited from a screening program for abdominal aortic aneurysm (AAA) Levels of protein biomarkers were compared in men with and without PAD (defined as an ankle brachial index of <0.9) and their diagnostic potential was calculated by receiver-operating characteristic analysis. Results: The prevalence of PAD was 14.2% (38/267). After adjustment for multiple comparisons, levels of the following 11 biomarkers remained significantly higher ( p<0.0001) in patients with PAD: secretoglobin family 3A member 2, osteoprotegerin, urokinase-type plasminogen activator surface receptor, serum macrophage chemokine ligand 16, matrix metalloproteinase 9, p-selectin, growth differentiation factor 15, elafin, cystatin B, trefoil factor 3, and fatty acid-binding protein 4. Multivariable logistic regression analysis (adjusted for smoking, use of antihypertensive and lipid-lowering medication, and metformin) showed that 11 biomarkers were significantly associated with higher risk of PAD with odds ratios ranging from 1.6 to 2.4. Area under curve calculated by receiver operating characteristic curve analysis (diagnostic value) for each protein biomarker ranged from 0.63 to 0.74. Conclusions: We have identified multiple proteins with a potential to be diagnostic biomarkers for PAD, and further research is warranted to clarify their potential predictive and prognostic value.