Five-year Results of Elastin and Collagen Markers as Predictive Tools in the Management of Small Abdominal Aortic Aneurysms

AbstractObjective small abdominal aortic aneurysms (AAAs) do rupture and only half of AAAs above 5 cm would have ruptured unoperated. Furthermore, conservative treatment of AAAs may cause psychological side effects and impaired quality of life. To optimise the indication and time for operation for AAAs, we analysed whether serum elastin peptides (EP), procollagen-IIIN-terminal propeptide (PIIINP), and the initial AAA size could predict operation for AAAs in initially conservatively treated AAA. Material and methods in 1994, 4404 65–73 year old males were invited to hospital-based screening for AAAs by ultrasonography. Seventy-six percent attended. One hundred and forty-one (4.2%) had AAAs (def: +30 mm). Nineteen were offered operation (AAA +50 mm), and 112 were followed with annual control scans for 1–5 years (mean 2.5 years). Of these, 99 had their EP (ng/ml) and PIIINP (ng/ml) determined using ELISA and RIA techniques. Two observers and one scanner were used. Results the mean expansion rate was 2.7 mm/year. The initial AAA size (r=0.46; 0.26–0.61), EP ( r =0.31; 0.11–0.49), and NPIIIP ( r =0.24; 0.02–0.44) was independently significant associated to expansion rate in a multiple linear regression analysis including the three mentioned variables. The multivariate formula could by ROC curve analysis predict cases reaching 5 cm in diameter within 5 years with a sensitivity and specificity of 91% and 87%, respectively, increasing to 91% and 94%, respectively, by accepting a 2 mm variation in those measurements. Twenty-three were lost to follow up, 21 of these due to death or severe illness. Of these, seven would have been predicted to reach an AAA size recommendable for surgery. If all 23 were included in the analysis, the sensitivity and specificity would have been 87% and 85%, respectively. Conclusion a predictive model using EP, PIIINP, and initial AAA size seems capable of predicting nine out of 10 AAAs that will be operated on within 5 years. However, a larger sample size is needed for clinical recommendations

The Plasma Level of Matrix Metalloproteinase 9 may Predict the Natural History of Small Abdominal Aortic Aneurysms. A Preliminary Study

AbstractObjectives: increased levels of various proteinases have been detected in abdominal aortic aneurysms (AAA) and are assumed to cause the degradation of the aortic wall. To determine whether systemic measurement of these proteinases and their inhibitors may predict the natural cause of AAA. Methods and material: serum (S) and plasma (P) samples were obtained from 121 men following the diagnosis of a small AAA (3–5 cm) at population screening. Annual control scans were performed to check for expansion. Circulating levels of elastase-alpha 1 antitrypsin-complexes, alpha 1antitrypsin, matrix metalloproteinase (MMP) 2 & 9, tissue-inhibitor-matrixproteinase 1 & 2, procollagen III-N-terminal-propeptide, and elastin-peptides were measured in a random group of 36 men. Results: alpha 1 antitrypsin was significantly and positively associated with expansion. Similarly, P-MMP9 levels were significantly associated with size and expansion. There was a difference between median serum and plasma values, probably because of secretion from platelets. Conclusion: P-MMP9 and P-alpha 1 antitrypsin may predict the natural history of AAA

Perturbation of hyaluronan metabolism predisposes patients with type 1 diabetes mellitus to atherosclerosis

AIMS/HYPOTHESIS: Cardiovascular disease contributes to mortality in type 1 diabetes mellitus, but the specific pathophysiological mechanisms remain to be established. We recently showed that the endothelial glycocalyx, a protective layer of proteoglycans covering the endothelium, is severely perturbed in type 1 diabetes, with concomitantly increased plasma levels of hyaluronan and hyaluronidase. In the present study, we evaluated the relationship between hyaluronan and hyaluronidase with carotid intima-media thickness (cIMT), an established surrogate marker for cardiovascular disease. SUBJECTS AND METHODS: Non-smoking type 1 diabetes patients without micro- or macrovascular complications and matched controls were recruited and cIMT of both carotid arteries was measured. To evaluate the relationship between cIMT and hyaluronan and hyaluronidase as well as other parameters, uni- or multivariate regression analyses were performed. RESULTS: We included 99 type 1 diabetes patients (age 10-72 years) and 99 age- and sex-matched controls. Mean cIMT, HbA(1c), high sensitivity C-reactive protein, hyaluronan and hyaluronidase were significantly increased in type 1 diabetes vs controls. Plasma hyaluronan and hyaluronidase were correlated in type 1 diabetes. In univariate regression analyses, mean IMT was associated with plasma hyaluronan, age and male sex, whereas after multivariate analysis only age and sex remained statistically significant. CONCLUSIONS/INTERPRETATION: We conclude that type 1 diabetes patients show structural changes of the arterial wall associated with increased hyaluronan metabolism. These data may lend further support to altered glycosaminoglycan metabolism in type 1 diabetes as a potential mechanism involved in accelerated atherogenesi

Vitamin D Status and Bone and Connective Tissue Turnover in Brown Bears (Ursus arctos) during Hibernation and the Active State

BACKGROUND: Extended physical inactivity causes disuse osteoporosis in humans. In contrast, brown bears (Ursus arctos) are highly immobilised for half of the year during hibernation without signs of bone loss and therefore may serve as a model for prevention of osteoporosis. AIM: To study 25-hydroxy-vitamin D (25OHD) levels and bone turnover markers in brown bears during the hibernating state in winter and during the active state in summer. We measured vitamin D subtypes (D₂ and D₃), calcitropic hormones (parathyroid hormone [PTH], 1,25-dihydroxy-vitamin D [1,25(OH)₂D]) and bone turnover parameters (osteocalcin, ICTP, CTX-I), PTH, serum calcium and PIIINP. MATERIAL AND METHODS: We drew blood from seven immobilised wild brown bears during hibernation in February and in the same bears while active in June. RESULTS: Serum 25-hydroxy-cholecalciferol (25OHD₃) was significantly higher in the summer than in the winter (22.8±4.6 vs. 8.8±2.1 nmol/l, two tailed p-2p = 0.02), whereas 25-hydroxy-ergocalciferol (25OHD₂) was higher in winter (54.2±8.3 vs. 18.7±1.7 nmol/l, 2p<0.01). Total serum calcium and PTH levels did not differ between winter and summer. Activated 1,25(OH)₂D demonstrated a statistically insignificant trend towards higher summer levels. Osteocalcin levels were higher in summer than winter, whereas other markers of bone turnover (ICTP and CTX-I) were unchanged. Serum PIIINP, which is a marker of connective tissue and to some degree muscle turnover, was significantly higher during summer than during winter. CONCLUSIONS: Dramatic changes were documented in the vitamin D₃/D₂ ratio and in markers of bone and connective tissue turnover in brown bears between hibernation and the active state. Because hibernating brown bears do not develop disuse osteoporosis, despite extensive physical inactivity we suggest that they may serve as a model for the prevention of this disease