Growth Rate Of Small Aneurysms Research Articles

Systematic review and meta-analysis of growth rates of small abdominal aortic aneurysms

Small abdominal aortic aneurysms are usually asymptomatic and managed safely in ultrasound surveillance programmes until they grow to a diameter threshold where intervention is considered. The aim of this study was to synthesize systematically the published data on growth rates for small aneurysms to investigate the evidence basis for surveillance intervals. This was a systematic review of the literature published before January 2010, which identified 61 potentially eligible reports. Detailed review yielded 15 studies providing growth rates for aneurysms 3·0-5·5 cm in diameter (14 in millimetres per year, 1 as percentage change per year). These studies included 7630 people (predominantly men) enrolled during 1976-2005. The pooled mean growth rate was 2·32 (95 per cent confidence interval 1·95 to 2·70) mm/year but there was very high heterogeneity between studies; the growth rate ranged from - 0·33 to + 3·95 mm/year. Six studies reported growth rates by 5-mm diameter bands, which showed the trend for growth rate to increase with aneurysm diameter. Simple methods to determine growth rate were associated with higher estimates. Meta-regression analysis showed that a 10-mm increase in aneurysm diameter was associated with a mean(s.e.m.) 1·62(0·20) mm/year increase in growth rate. Neither mean age nor percentage of women in each study had a significant effect. On average, a 3·5-cm aneurysm would take 6·2 years to reach 5·5 cm, whereas a 4·5-cm aneurysm would take only 2·3 years. There was considerable variation in the reported growth rates of small aneurysms beyond that explained by aneurysm diameter. Fuller evidence on which to base surveillance intervals for patients in screening programmes requires a meta-analysis based on individual patient data.

A comparison of two commercial inhibitors of aneurysm MMP-2 activity in vitro

Introduction. Abdominal aortic aneurysms (AAA) are characterized by degradation of the extracellular matrix. These changes are mediated by endogenous metalloproteinases (MMPs) in the wall of the aorta, which provide a potential target for agents aimed at reducing the growth rate of small aneurysms. Periostat™ is the only MMP-inhibitor approved FDA, targeting MMPs in periodontal disease. A clinical trial of this agent for AAA disease has been disappointing in early reports. In the present study, a comparison was made between Periostat™ and Aneumastat™ in inhibition of the most abundant MMP of early aneurysmal development, MMP-2. Aneumastat™ is a green tea extract with potent MMP inhibitory activity. Methods. Inhibitory properties of Aneumastat™ and Periostat™ against MMP-2 activity of aneurysmal fibroblast origin were examined on 10% polyacrylamide gels containing 1.0 mg/ml of gelatin. Fibroblasts cultured from AAA specimens were lysed using the CellLytic-M lysis/extraction reagent (Sigma). The protein concentration of each supernatant was determined by the Bradford method. Routine methods of substrate gel enzymography were used. Quantity One (Bio-Rad Version 4.3.1) was used as the densitometric method to quantitate test compound inhibitory ability. Results. Aneumastat has a major inhibitory activity against MMP-2 in vitro, whereas Periostat™ showed no inhibition in the same mM concentrations. Aneumastat™ reduced the activity of MMP-2 by 50% at a dose of 1.25 μg/μl. The most abundant tea polyphenol of Aneumastat™ has a molecular weight of 458. This gives Aneumastat™ a 2.7 mM inhibitory capacity at 50%. Using Periostat™, no inhibition was detected at this concentration. Even at the highest dose tested, 25.0 μg/μl to 48.8mM, there is no sign of inhibition. Please see Figure following conclusion. Conclusion. Aneumastat™ is a potent inhibitor of MMP-2 in vitro. Periostat™ has little or no activity under the same conditions in vitro. Further testing with an in vivo model will be needed to determine this possible therapeutic benefit of Aneumastat™ by comparison with Periostat™.

Are antihypertensive drugs associated with abdominal aortic aneurysms?

The aim of this study was to investigate the association between anti-hypertensive drugs, the risk of developing an abdominal aortic aneurysm (AAA), aortic wall stiffness, collagen turnover, and change in aortic diameter. STUDY DESIGN, SETTINGS AND METHODS: Data on present medication, smoking status, and medical history of participants in two population-based aneurysm screening programs in the United Kingdom were collected by use of questionnaire. Aortic elasticity was measured by M-mode ultrasound scanning. A serum radioimmunoassay of the amino-terminal propeptide of type III procollagen was used to assess collagen turnover in one of the patient series. Data from 438 cases with an AAA >29 mm and 5373 controls were analyzed. Calcium-channel blockers were independently associated with AAA. The odds ratio of having an AAA was 2.6 (95% confidence interval [CI], 1.5-4.2) after adjusting for all relevant confounders. Other antihypertensive drugs showed no increased risk. No significant differences in growth rates were found in cases exposed to any of the main antihypertensive drugs. An increased collagen turnover was found in subjects receiving angiotensin-converting enzyme (ACE) inhibitors: 4.26 mg/L (95% CI, 3.73-4.79) compared with 3.62 mg/L (95% CI, 3.49-3.76) for subjects not receiving ACE inhibitors. No differences in type III collagen turnover was found with use of any other antihypertensive drug. The mean aortic wall stiffness was greater for all subjects exposed to calcium-channel blockers, whether with AAA or not: 25.1 arbitrary units (95% CI, 20.0-30.2) vs 19.3 (95% CI, 18.1-20.4)(P =.002). By contrast, the mean stiffness for cases receiving ACE inhibitors was smaller than for those not receiving ACE inhibitors: 19.0 (95% CI, 13.9-24.0) vs 25.2 (95% CI, 23.0-27.4). Calcium-channel blockers were an independent risk factor for the presence of an AAA and were associated with an increased arterial aortic wall stiffness. ACE inhibitors were associated with decreased stiffness and greater collagen turnover. No significant effects on the growth rate of small aneurysms were detected.

Marimastat inhibits elastin degradation and matrix metalloproteinase 2 activity in a model of aneurysm disease.

Abdominal aortic aneurysms are characterized by degradation of the extracellular matrix, with a reduction in the elastin concentration of the arterial media. These changes have been linked to increased levels of endogenous metalloproteinases (MMPs) within the aorta, particularly MMP-2 and MMP-9. This provides a potential therapeutic target for pharmacological agents aimed at reducing the growth rate of small aneurysms. In this study, the ability of marimastat (an MMP inhibitor) to reduce matrix degradation was assessed in a previously described model of aneurysm disease. Porcine aortic segments (n = 12) were preincubated in exogenous pancreatic elastase for 24 h before culture in standard conditions for 13 days with marimastat 10(-5), 10(-6) and 10(-7) mol/l. Control segments were cultured both without marimastat and without elastase. At the termination of culture, MMPs were extracted from the tissue and quantified by substrate gel enzymography. The volume fractions of elastin and collagen were determined by stereological analysis of sections stained with Miller's elastin and van Gieson's stain. Stereological analysis demonstrated preservation of elastin in aorta treated with marimastat at 10(-6) and 10(-5) mol/l; this was significant at the latter concentration (P = 0.007). This was accompanied by a significant reduction in active MMP-2 activity in the samples treated with marimastat 10(-5) mol/l (P < 0.01). Marimastat significantly inhibited elastin degradation and active MMP-2 production within aortic organ cultures.

Doxycycline inhibits elastin degradation and reduces metalloproteinase activity in a model of aneurysmal disease

Purpose: Abdominal aortic aneurysms are characterized by degradation of the extracellular matrix, with a reduction in the elastin concentration of the arterial media. These changes are mediated by increased levels of endogenous metalloproteinases (MMPs) within the aorta, which provide a potential therapeutic target for pharmacologic agents aimed at reducing the growth rate of small aneurysms. In this study, the ability of doxycycline—an MMP inhibitor—to reduce matrix degradation was assessed in a previously described model of aneurysmal disease that used a brief pulse of elastase to induce MMP production and elastin degradation in arterial organ cultures. Methods: Porcine aortic segments (n = 8) were preincubated in exogenous pancreatic elastase for 24 hours before culture in standard conditions for 13 days with both 1 and 10 mg/L doxycycline. Control segments were cultured both without doxycycline and without elastase. At the termination of culture, MMPs were extracted from the tissue and quantified by a combination of substrate gel enzymography and immunoblotting. The volume fractions of elastin and collagen were determined by stereologic analysis of sections stained with Miller's elastin and van Gieson's stain. Results: Stereologic analysis demonstrated a significant preservation of elastin in aorta treated with doxycycline 10 mg/L ( p < 0.001) and demonstrated that this preservation was accompanied by a significant reduction in MMP-9 activity ( p < 0.02). Immunoblotting for tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) showed no decreased production in the doxycycline-treated groups. Conclusions: Therapeutic ranges of doxycycline significantly inhibited elastin degradation and MMP-9 production within aortic organ cultures. These data suggest that doxycycline may have a potential application in reducing the growth rates of small abdominal aortic aneurysms. (J Vasc Surg 1998;27:354-61.)

Smoking and growth rate of small abdominal aortic aneurysms

Smoking is an important risk factor for abdominal aortic aneurysm. Limiting the growth rate of small aneurysms has the potential to prevent them reaching a size at which surgical repair is considered. In 43 patients, with small aneurysms, growth rates were studied by serial ultrasound over 3 years. The median expansion rate of these small aneurysms was 0·13 cm per year. Growth rates were higher in those who continued to smoke (0·16 vs 0·09 cm per year in those who no longer smoked, p=0·038). Higher growth rates were significantly correlated with the concentration of serum cotinine. Stopping smoking could reduce the growth rate of small abdominal aortic aneurysms.

The spontaneous course of small abdominal aortic aneurysms. Aneurysmal growth rates and life expectancy

Since abdominal ultrasonography has become a routine diagnostic procedure, increasing numbers of small asymptomatic abdominal aortic aneurysms are detected incidentally. Of 128 patients (108 male, 20 female) with abdominal aortic aneurysms, 96 patients were observed clinically and by repeated ultrasound studies for an average of 3.47 years, adding up to a total observation period of 333 patient-years. Among these 96 patients, 72 had small aneurysms (averaged diameters less than 5 cm). Three of them were lost to follow up. None of the remaining 69 patients died from rupture, 20 died from other causes and 8 patients were successfully operated. Of the patients with a large aneurysm one was lost to follow up. Five patients of the remaining 23 died as a result of rupture, 7 were successfully operated. The average growth rate of small aneurysms was 0.18 cm/year, whereas the larger aneurysms showed a growth rate of 0.28 cm/year (diameter). The survival rate of patients with small aneurysms was 94% after one year, 80% after 3 years, and 73% after 5 years, indicating that life expectancy is reduced in patients with an aneurysm of the abdominal aorta, but not because of complications of the aneurysm.