Aortic diameter at age 65 in men with newly diagnosed type 2 diabetes

Objectives. Type 2 diabetes mellitus has been linked to a decreased risk for abdominal aortic aneurysm (aortic diameter ≥30?mm, AAA) development in men. The aim of this study was to evaluate if such an effect is detectable already around the time of diabetes diagnosis. Design. We cross-sectionally compared aortic diameter at ultrasound screening for AAA in 691 men aged 65 years with incipient or newly diagnosed type 2 diabetes (group A) with 18,262 65-year old control men without diabetes (group B). Results. Aortic diameter did not differ between groups (18.8[17.4–20.8] vs. 19.0[17.5–28.7] mm; p?=?0.43). AAA prevalence was 2.5% in group A and 1.5% in group B (p?=?.010). In logistic regression taking group differences in body mass index (BMI), smoking, presence of atherosclerotic disease and hypertension into account, the difference in AAA prevalence was no longer significant (p?=?.15). Among men in group A, C-peptide (r?=?.093; p?=?.034), but not HbA1c (r?=?.060; p?=?.24) correlated with aortic diameter. Conclusion. Among 65 year old men aortic diameter and AAA prevalence do not differ between those with newly diagnosed type 2 diabetes and those without diabetes. Putative protective effects of type 2 diabetes mellitus against aortic dilatation and AAA development therefore probably occur later after diagnosis of diabetes.     

Aortic calcification in haemodialysis patients with diabetes mellitus.

BACKGROUND: Certain metabolic disorders, such as hyperphosphatemia induce vascular calcification in haemodialysis patients; it is unclear, however, whether these disorders contribute to aortic calcification in diabetic haemodialysis patients. This study examined the risk factors of aortic calcification in a large number of haemodialysis patients, and compared risk factors between diabetic and non-diabetic patients. METHODS: The subjects were 667 patients on maintenance haemodialysis: 184 with type 2 diabetes and 483 without. Aortic calcification was measured semi-quantitatively using a plain computed tomography image of the abdominal aorta, and an aortic calcification index (ACI) was calculated. RESULTS: The ACI of the diabetic subjects was significantly higher than that of those without diabetes (57.3+/-22.1 vs 44.8+/-28.3%, P < 0.0001), although the dialysis vintage of the former was significantly shorter (P < 0.001). Multiple regression analyses showed that diabetes was a significant independent risk factor for increased ACI. Multiple regression analyses, performed separately in diabetics and non-diabetics, revealed that advanced age, higher systolic blood pressure, smoking and longer haemodialysis vintage were common independent risk factors significantly associated with increased ACI in both patient groups (R2 = 0.296, P < 0.0001 for non-diabetics; R2 = 0.193, P < 0.0001 for diabetics). Higher serum phosphate concentration was not significantly associated with increased ACI in diabetic patients (P = 0.429), although it was a significant independent factor in non-diabetic patients (beta = 0.150, P < 0.0005). CONCLUSION: Aortic calcification in diabetic haemodialysis patients is more advanced, compared with non-diabetic patients, even with short haemodialysis vintage. Since disorders of mineral metabolism are not significantly associated with aortic calcification in diabetic haemodialysis patients, aortic calcification in these patients could be affected by metabolic abnormalities associated with the diabetic state per se, independent of other confounding factors; and aortic calcification may be advanced even before haemodialysis induction.     

Quantifying the risks of hypertension, age, sex and smoking in patients with abdominal aortic aneurysm

BACKGROUND: The prevalence of abdominal aortic aneurysm (AAA) in a community-based sample of men and women aged 65-79 years was correlated with known risk factors. In addition, the effect of high blood pressure and the use of antihypertensive medication on growth of AAAs were studied. METHODS: Aortic diameter was assessed by ultrasonography and data on risk factors were collected by self-administered questionnaire for 5356 men and women as part of a randomized controlled trial. RESULTS: Current hypertension increased the risk of having an aortic aneurysm by 30-40 per cent while use of antihypertensive medication increased the risk by 70-80 per cent, adjusting for current blood pressure. There was no clear relationship between hypertension and growth rates of existing aneurysms in this study, although these results were largely from data on small aneurysms. Men were nearly six times more likely to develop an AAA than women; the risk increased by 40 per cent every 5 years after the age of 65 years. Smoking was an independent risk factor for AAA, with level of exposure being more significant than duration. CONCLUSION: Male sex, smoking and hypertension are strong risk factors for the development of AAA. In this study hypertension did not significantly increase the growth rate of existing aneurysms. Smoking remains the most important avoidable risk factor for AAA. The analyses presented here suggest that selection for screening, other than by age and sex, is not worthwhile.     

Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes.

Abnormalities in vascular reactivity in the micro- and macrocirculation are well established in type 2 diabetes. However, little is known about changes in vascular reactivity in those at risk for developing type 2 diabetes. To address this situation, the vascular reactivity in both the micro- and macrocirculation was studied in four age and sex comparable groups: 30 healthy normoglycemic subjects with no history of type 2 diabetes in a first-degree relative (controls), 39 healthy normoglycemic subjects with a history of type 2 diabetes in one or both parents (relatives), 32 subjects with impaired glucose tolerance (IGT), and 42 patients with type 2 diabetes without vascular complications (diabetes). Laser Doppler perfusion imaging was used to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent) and 1% sodium nitroprusside (SNP) (endothelium-independent), whereas high-resolution ultrasound images were used to measure brachial artery diameter changes during reactive hyperemia. Plasma concentrations of endothelin-1 (ET-1), von Willebrand factor (vWF), soluble intercellular adhesion molecule (sICAM), and soluble vascular cell adhesion molecule (sVCAM) were also measured as indicators of endothelial cell activation. The vasodilatory responses to Ach, expressed as percent increase of blood flow over baseline, were reduced in relatives (98 +/- 48, mean +/- SD), IGT (94 +/- 52), and diabetes (74 +/- 45) compared with controls (126 +/- 67) (P < 0.001 controls versus relatives, IGT, and diabetes). The responses to SNP were similarly reduced: controls (123 +/- 46), relatives (85 +/- 46), IGT (83 +/- 48), and diabetes (65 +/- 31) (P < 0.001 controls versus relatives, IGT, and diabetes) as were the responses in the brachial artery diameter during reactive hyperemia: controls (13.7 +/- 6.1), relatives (10.5 +/- 6.7), IGT (9.8 +/- 4.5), and diabetes (8.4 +/- 5.0) (P < 0.01 controls versus relatives, IGT, and diabetes). Women had greater responses than men in both the micro- and macrovascular circulatory tests, but a similar progressive reduction was observed in both sexes with increasing degrees of glucose intolerance. A significant inverse correlation was found between microvascular reactivity and systolic blood pressure, fasting plasma glucose, HDL cholesterol, fasting plasma insulin, and homeostasis model assessment (HOMA) values, an index of insulin resistance. BMI and diastolic blood pressure had a significant inverse correlation only with endothelium-dependent vasodilation. In the macrocirculation, systolic blood pressure, HbA1c, HDL cholesterol, and HOMA had significant correlation with brachial artery diameter changes. Compared with control subjects, ET-1 was significantly higher in all groups, vWF was higher only in the diabetic group, sICAM levels were higher in the IGT and diabetic groups, while sVCAM concentrations were higher in the relatives and those with diabetes (P < 0.05). On stepwise multivariate analysis, age, sex, fasting plasma glucose, and BMI were the most important contributing factors to the variation of vascular reactivity. Addition of all clinical and biochemical measures explained only 32-37% of the variation in vascular reactivity. These results suggest that abnormalities in vascular reactivity and biochemical markers of endothelial cell activation are present early in individuals at risk of developing type 2 diabetes, even at a stage when normal glucose tolerance exists, and that factors in addition to insulin resistance may be operative.     

Abdominal aortic aneurysm in women.

OBJECTIVE: The purpose of this study was to compare abdominal aortic aneurysm (AAA) associations in men and women. METHODS: Veterans aged 50 to 79 years without a previous history of AAA underwent ultrasound screening for AAA after completing a questionnaire on demographic information and potential risk factors. RESULTS: A total of 122,272 men and 3450 women were successfully screened. An AAA of 3.0 cm or greater in diameter was found in 4.3% of men and 1.0% of women (P <.001). Contrary to a previous report, we did not find suprarenal aortic enlargement accompanying AAA to be more common in women. The principal associations that we have previously reported for AAA in this cohort (age, smoking, family history of AAA, and a negative association with diabetes) were all similar in women compared with men. In age- and smoking-adjusted models, the interaction terms indicated that black race and cancer were more strongly associated with AAA in women than men (P <.05). Height and cerebral vascular disease were also more strongly associated with AAA in women than in men, but these interaction terms did not reach statistical significance (P <.10). Although the other differences were unexpected and require confirmation, the trend toward a stronger association of cerebral vascular disease with AAA in women is consistent with two previous reports. CONCLUSIONS: Despite the much lower prevalence of AAA in women, the most important associations with AAA are similar to those seen in men. Our data provide some support for a previous finding that cerebrovascular disease may be more closely associated with AAA in women than in men.     

Abdominal Aortic Aneurysm Screening Using Non-imaging Hand-held Ultrasound Volume Scanner – A Pilot Study

BACKGROUND: Screening for abdominal aortic aneurysms (AAA) is cost-effective and timely repair improves outcome. Using standard ultrasound (US) an AAA can be accurately diagnosed or ruled-out. However, this requires training and bulk equipment. AIM: To evaluate the diagnostic potential of a new hand-held ultrasound bladder volume indicator (BVI) in the setting of AAA screening. METHODS: In total, 94 patients (66 +/- 14 years, 67 men) referred for atherosclerotic disease were screened for the presence of AAA (diameter > 30 mm using US). All patients underwent both examinations, with US and BVI. Using the BVI, aortic volume was measured at 6 pre-defined points. Maximal diameters (US) and volumes (BVI) were used for analyses. RESULTS: In 54 (57%) patients an AAA was diagnosed using US. The aortic diameter by US correlated closely with aortic volume by BVI (r = 0.87, p < 0.0001). Using a cut-off value of > or = 50 ml for the presence of AAA by BVI, sensitivity, specificity, positive and negative predictive value of BVI in detection of AAA were 94%, 82%, 88% and 92%, respectively. The agreement between the two methods was 89%, kappa 0.78. CONCLUSION: The bladder volume indicator is a promising tool in screening patients for AAA.     

Aminoterminal propeptide of type III procollagen and matrix metalloproteinases-2 and -9 failed to serve as serum markers for abdominal aortic aneurysm.

OBJECTIVES: Matrix-metalloproteinase (MMP)-2 and -9 and aminoterminal propeptide of type III collagen (NIIINP) have been reported to be elevated in patients with abdominal aortic aneurysm (AAA). The aim of our study was to test NIIINP, MMP-2 and -9 as potential serum markers for AAA in a large population group at risk for AAA. METHODS: Fifty-five to 70 year old men were screened for AAA by abdominal ultrasound. Simultaneously, blood samples were taken and the patients were interviewed for known risk factors for AAA. Patients with a dilatation of the infrarenal aorta of > or =25mm (Group 1, n=76) were compared to randomly assigned patients with normal aortic diameters (Group 2, n=83). A third group consisted of patients scheduled for operation of AAA (n=19). RESULTS: A total of 987 men were investigated with ultrasound. Seventy-six (7.7%) had an aortic dilatation > or =25mm. Aortic dilatation was correlated with age (P=0.0001). However, serum levels of NIIINP and MMP 2 were not different between the three groups of patients. For MMP-9 there was a weak inverse correlation with lower serum levels in patients with aortic dilatation (P=0.043). CONCLUSIONS: Both MMP-2 and -9 and NIIINP failed to show relevance as serum markers for aortic dilatation. Our results are, therefore, in contradiction to previous published results. AAAs cannot be diagnosed with a simple blood test.     

The influence of peripheral vascular disease on the carotid and femoral wall mechanics in subjects with abdominal aortic aneurysm

AIM: Aortic and carotid stiffness is elevated in patients with abdominal aortic aneurysm (AAA). Peripheral vascular disease (PVD) frequently coexists with AAA and may further impair the arterial wall mechanics and increase the cardiovascular load. We therefore studied the elastic carotid and muscular femoral biomechanical properties and intima-media thickness (IMT) in this group of patients. METHODS: The elastic indices and IMTs of the common carotid and common femoral arteries were determined in 30 patients with AAA (15 with PVD) with a duplex scanner coupled with a wall tracking system. Fasting plasma creatinine level, glucose and lipid concentrations, and their physiologic variables known to influence the arterial wall mechanics were also assessed. RESULTS: Patients with AAA and PVD have significantly stiffer carotid (Petersen's elastic modulus, 2207 +/- 905 mm Hg versus 1268 +/- 432 mm Hg; P =.001; stiffness index, 22.73 +/- 9.63 versus 12.60 +/- 4.24; P =.001] and femoral (Petersen's elastic modulus, 4906 +/- 4057 mm Hg versus 2599 +/- 1169 mm Hg; P =.043; stiffness index, 49.02 +/- 40.04 versus 26.07 +/- 13.22; P =.044) arteries than subjects with AAA alone. Although patients with PVD have thicker carotid and femoral IMTs, no statistical difference was seen between the two groups. The subjects were matched for age, body mass index, heart rate, systolic and diastolic blood pressures, total vascular risk score, plasma creatinine level, and fasting lipid and glucose concentrations. CONCLUSION: Subjects with PVD and AAA have significantly stiffer carotid and femoral arteries, which may indicate increased cardiovascular load and may account for the highest mortality rate seen in these patients in the UK Small Aneurysm Trial. Therefore, treatment of associated cardiovascular risk factors is important and may have to be tailored on an individual basis according to the findings of the arterial wall mechanics.     

MF-tricyclic inhibits growth of experimental abdominal aortic aneurysms

BACKGROUND: Experimental abdominal aortic aneurysm (AAA) development can be pharmacologically suppressed by inhibiting matrix metalloproteinase-9 (MMP-9). Cyclooxygenase-2 (COX-2) inhibitors are potent anti-inflammatory agents that have been demonstrated to inhibit experimental aneurysm development. We hypothesized that treatment with MF-tricyclic, a selective COX-2 inhibitor, incorporated into rodent chow would inhibit aneurysm development in a rat AAA model. METHODS: Twelve male Sprague Dawley rats underwent induction of experimental AAA using intra-aortic porcine elastase infusion. Six rats received control feed, and six received MF-tricyclic rodent chow for a period of 14 days. Aortic diameters were measured pre- and postinfusion as well as at harvest. Aortic tissue samples were evaluated by real-time polymerase chain reaction (RT-PCR) for MMP-9, by immunohistochemistry for elastin. RESULTS: Elastase infusion produced AAA in all untreated rats. At 14 days MF-tricyclic-treated rats had significantly reduced aortic diameter (1.9 +/- 0.1 mm versus 2.4 +/- 0.0 mm, P = 0.00001). Percent increase in aortic diameter was also significantly less in animals receiving MF-tricyclic (65.7 +/- 8.5% versus 132.3 +/- 7.3%, P = 0.0001). RT-PCR demonstrated a decrease in the mean expression of MMP-9 in the treated animals (0.414 ng of RNA versus 1.114 ng of RNA) (P = 0.07). Sections stained for elastin demonstrated preserved elastin integrity in MF-tricyclic treated aortas. CONCLUSIONS: COX-2 inhibition helps to retard the growth of experimental AAAs possibly through inhibition of MMP-9. Experimentally treated animals demonstrated smaller aortic diameters and lower levels of tissue MMP-9 when compared to untreated animals. Selective COX-2 inhibition may offer an additional method to pharmacologically inhibit AAAs.     

No association between glucose at age 30 and aortic diameter at age 65 in men: a population-based study

Objectives Impaired glucose metabolism and diabetes mellitus has been linked to a decreased risk for abdominal aortic aneurysm development in men. We evaluated potential relationships between blood glucose levels in 1722 men with mean age 34 years and their aortic diameter measured by ultrasound at age 65 years. Design Prospective cohort study. Results Mean follow-up between baseline glucose investigation and aortic ultrasound was 32.8?±?1.8 years. There was no correlation between baseline blood glucose and later aortic diameter (r?=?0.035, p?=?0.146), whereas a weak correlation between body mass index (BMI) and aortic diameter was observed (r?=?0.097 p?<?0.001). In a partial correlation between aortic diameter and glucose levels adjusted for BMI, the correlation did not change (r?=?0.011, p?=?0.66). Neither were there any significant differences in mean aortic diameter between men belonging to different quartiles of baseline blood glucose levels (19.5, 19.1, 19.6 and 19.7?mm, p?=?0.18). Conclusion Fasting blood glucose in 33-year-old men was not associated with their aortic diameter at age 65 years. Potential pathophysiological processes linking disturbed glucose metabolism to a decreased risk for development of abdominal aortic aneurysm in men are therefore probably not relevant until later in life.     

Diabetes is associated independently of body composition with BMD and bone volume in older white and black men and women: The Health, Aging, and Body Composition Study.

The association between type 2 diabetes, BMD, and bone volume was examined to determine the effect of lean and fat mass and fasting insulin in the Health, Aging, and Body Composition Study, which included white and black well-functioning men and women 70-79 years of age (N = 2979). Diabetes predicted higher hip, whole body, and volumetric spine BMD, and lower spine bone volume, independent of body composition and fasting insulin. INTRODUCTION: The purpose of this study was to determine if the association between type 2 diabetes and higher BMD observed in older white women is seen in elderly white men and blacks and to evaluate if higher BMD in diabetic individuals is accounted for by lean mass, fat mass, or fasting insulin differences. MATERIALS AND METHODS: In the Health, Aging, and Body Composition Study, which included white and black well-functioning men and women 70-79 years of age (N = 2979), 19% of participants had diabetes at baseline. Of those with diabetes, 57% were men, and 62% were black. Multivariate linear regression models examined independent effects of diabetes, lean mass, fat mass, visceral fat, and fasting insulin on BMD and bone volume while adjusting for relevant covariates. RESULTS AND CONCLUSIONS: Fasting insulin, visceral fat, and volumetric spine BMD, assessed by CT, and lean mass, fat mass, and total hip and whole body BMD, assessed by DXA, were higher (p < or = 0.05 for all) for those with diabetes. Hip BMD was higher in white men (0.99 +/- 0.14 versus 0.93 +/- 0.14 g/cm2, p < 0.001), black men (1.06 +/- 0.17 versus 1.00 +/- 0.15 g/cm2, p < 0.001), white women (0.83 +/- 0.13 versus 0.76 +/- 0.13 g/cm2, p < 0.001), and black women (0.90 +/- 0.15 versus 0.85 +/- 0.15 g/cm2, p < 0.001) with diabetes compared with those without diabetes, although the relationship was attenuated by body composition. In multiple regression models, diabetes was an independent predictor of higher hip, whole body, and volumetric spine BMD in all participants (p < or = 0.001), but lower spine volume (p = 0.01) and higher hip BMD for each race-gender group (p < or = 0.01). Type 2 diabetes was associated with a 4-5% higher total hip BMD in all race-gender groups of elderly adults, independent of body composition and fasting insulin levels.     

Aortoiliac hemodynamic and morphologic adaptation to chronic spinal cord injury

BACKGROUND: Reduced lower limb blood flow and resistive hemodynamic conditions potentially promote aortic inflammation and aneurysmal degeneration. We used abdominal ultrasonography, magnetic resonance imaging, and computational flow modeling to determine the relationship between reduced infrarenal aortic blood flow in chronic spinal cord injury (SCI) subjects and risk for abdominal aortic aneurysm (AAA) disease. METHODS: Aortic diameter in consecutive SCI subjects (n = 123) was determined via transabdominal ultrasonography. Aortic anatomic and physiologic data were acquired via magnetic resonance angiography (MRA; n = 5) and cine phase-contrast magnetic resonance flow imaging (n = 4) from SCI subjects whose aortic diameter was less than 3.0 cm by ultrasonography. Computational flow models were constructed from magnetic resonance data sets. Results were compared with those obtained from ambulatory control subjects (ultrasonography, n = 129; MRA/phase-contrast magnetic resonance flow imaging, n = 6) who were recruited at random from a larger pool of risk factor-matched individuals without known AAA disease. RESULTS: Age, sex distribution, and smoking histories were comparable between the SCI and control groups. In the SCI group, time since injury averaged 26 +/- 13 years (mean +/- SD). Aortic diameter was larger (P < .01), and the prevalence of large (> or = 2.5 cm; P < .01) or aneurysmal (> or = 3.0 cm; P < .05) aortas was greater in SCI subjects. Paradoxically, common iliac artery diameters were reduced in SCI subjects (< 1.0 cm; 48% SCI vs 26% control; P < .0001). Focal preaneurysmal enlargement was noted in four of five SCI subjects by MRA. Flow modeling revealed normal flow volume, biphasic and reduced oscillatory flow, slower pressure decay, and reduced wall shear stress in the SCI infrarenal aorta. CONCLUSIONS: Characteristic aortoiliac hemodynamic and morphologic adaptations occur in response to chronic SCI. Slower aortic pressure decay and reduced wall shear stress after SCI may contribute to mural degeneration, enlargement, and an increased prevalence of AAA disease.     

Carotid intima-media thickness in patients with abdominal aortic aneurysms.

OBJECTIVE: The contribution of atherosclerosis to the development of Abdominal Aortic Aneurysms (AAA) is still controversial. Ultrasound scans can detect intima-media thickening of the carotid arteries as an early sign of atherosclerosis. The aim of this study was to investigate whether patients with Abdominal Aortic Aneurysms (AAAs) have thickened carotid IMT as patients with atherosclerotic peripheral arterial disease (PAD). METHODS: With high-resolution B-mode ultrasonography, the intima-media thickness (IMT) in the carotid arteries (right and left common carotid artery) was measured in AAA patients and compared with that of age and sex-matched patients with atherosclerotic peripheral arterial disease (PAD). A third group of healthy age and sex- matched control subjects were included for comparison. The corresponding carotid artery lumen was also determined in all groups. Comparison of the three groups was made by ANOVA. RESULTS: Fifty-eight AAA patients and 69% were men (mean age of 72.3 years) were studied. Aged and sex-matched groups comprised of 111 PAD patients and 71 healthy. The mean carotid IMT was highest in PAD patients (1.036+/-0.18mm). The values of controls and AAA patients were similar and significantly lower than that of atherosclerotic patients (0.875+/-0.11mm and 0.812+/-0.53mm respectively, both p<0.005 vs. PAD). Narrowing of the corresponding lumen was found in PAD patients compared with that of AAA patients, but no difference can be seen between healthy subjects and AAA patients. The mean carotid IMT was greater in men (P<0.05) in all studied groups, but no similar gender specificity was found in the lumen diameter. CONCLUSIONS: This study shows that the carotid artery IMT of AAA patients is similar to healthy subjects, but not as thick as patients with atherosclerotic disease. As carotid (IMT) is a surrogate marker of atherosclerosis, the findings support the notion that the formation of AAA may not be fully atherosclerosis-dependent. Gender may be a confounding factor for carotid intima-media thickening.     

A single normal ultrasonographic scan at age 65 years rules out significant aneurysm disease for life in men.

BACKGROUND: Screening for abdominal aortic aneurysm (AAA) has been carried out in Gloucestershire since 1990. All men in the county are offered aortic ultrasonography in their 65th year. Men with an aortic diameter of less than 26 mm are considered 'normal' and no follow-up is arranged. The aim of this study was to ascertain if men with 'normal' aortic diameters at age 65 years ever develop a clinically significant aneurysm. METHODS: A cohort study was performed on 223 65-year-old men who had an aorta of less than 26 mm in diameter in 1988. These men had repeat ultrasonography in 1993 and 2000. The causes of death in men who died during this interval were investigated. RESULTS: Eight men were lost to follow-up. As far as it was possible to ascertain, none of the 86 men who died over the 12-year interval did so from ruptured AAA. There was no clinically significant increase in mean aortic diameter in the remaining 129 men who had three serial ultrasonographic scans over the 12-year interval. CONCLUSION: A single, 'normal' ultrasound scan at age 65 years effectively rules out the risk of clinically significant aneurysm disease for life in men.     

Growth rate and associated factors in small abdominal aortic aneurysms.

OBJECTIVE: To study the growth rate and factors influencing progression of small infrarenal abdominal aortic aneurysms (AAA). DESIGN: Observational, longitudinal, prospective study. PATIENTS AND METHODS: We followed patients with AAA <5 cm in diameter in two groups. Group I (AAA 3-3.9 cm, n = 246) underwent annual ultrasound scans. Group II (AAA 4-4.9 cm, n = 106) underwent 6-monthly CT scans. RESULTS: We included 352 patients (333 men and 19 women) followed for a mean of 55.2+/-37.4 months (6.3-199.8). The mean growth rate was significantly greater in group II (4.72+/-5.93 vs. 2.07+/-3.23 mm/year; p<0.0001). Group II had a greater percentage of patients with rapid aneurysm expansion (>4 mm/year) (36.8 vs. 13.8%; p<0.0001). The classical cardiovascular risk factors did not influence the AAA growth rate in group I. Chronic limb ischemia was associated with slower expansion (< or = 4 mm/year) (OR 0.47; CI 95% 0.22-0.99; p = 0.045). Diabetic patients in group II had a significantly smaller mean AAA growth rate than non-diabetics (1.69+/-3.51 vs. 5.22+/-6.11 mm/year; p = 0.032). CONCLUSIONS: The expansion rate of small AAA increases with the AAA size. AAA with a diameter of 3-3.9 cm expand slowly, and they are very unlikely to require surgical repair in 5 years. Many 4-4.9 cm AAA can be expected to reach a surgical size in the first 2 years of follow-up. Chronic limb ischemia and diabetes are associated with reduced aneurysm growth rates.     

MMP-12 has a role in abdominal aortic aneurysms in mice

BACKGROUND: Matrix metalloproteinase (MMP)-12 levels are increased in the abdominal aortic aneurysm (AAA), implicating this protease in AAA pathogenesis. The purpose of this study was to assess the role of MMP-12 in aneurysm formation. METHODS: A murine aneurysm model was generated by periaortic application of 0.25 mol/L calcium chloride (CaCl 2 ) for 15 minutes. Aortic diameters were measured and compared before and 10 weeks after aneurysm induction. Aortic diameter changes for wild type (WT) and MMP-12 knockout (MMP-12 -/- ) mice were determined. MMP-12 production in mouse aorta was analyzed by casein zymography. MMP-2 and MMP-9 expressions were examined by gelatin zymography. Immunohistochemical study was used to measure macrophage infiltration into the aorta. RESULTS: There is an increase of 63 +/- 5% (mean +/- SEM) in aortic diameters of WT mice after CaCl 2 inductions, while MMP-12 -/- mice increased only 26 +/- 14%. Connective tissue staining of aortic sections from WT mice showed disruption and fragmentation of medial elastic fibers, while MMP-12 -/- mice showed only focal elastic lamellae breakdown. MMP-12 levels in WT mice were significantly increased after CaCl 2 treatment, whereas no MMP-12 was detected in MMP-12 -/- mice. There was no difference in the MMP-2 and MMP-9 productions between WT and MMP-12 -/- mice. Immunohistochemical analysis demonstrated that infiltrating macrophages in the aorta of MMP-12 -/- mice were significantly less than WT controls. CONCLUSIONS: MMP-12 deficiency attenuates aneurysm growth, possibly by decreasing macrophage recruitment.     

Independent impact of glycemia and blood pressure in albuminuria on high-risk subjects for metabolic syndrome

BACKGROUND: Microalbuminuria may reflect diffuse endothelial damage. Considering that diabetes and hypertension cause vasculopathy, we investigated associations of albumin-to-creatinine ratio (ACR) with plasma glucose and blood pressure levels in high-risk subjects for metabolic syndrome. METHODS: A sample of 519 (246 men) Japanese-Brazilians (aged 60 +/- 11 years), who participated in a population-based study, had their ACR determined in a morning urine specimen. Backward models of multiple linear regression were created for each gender including log-transformed values of ACR as dependent variable; an interaction term between diabetes and hypertension was included. RESULTS: Macroalbuminuria was found in 18 subjects. ACR mean values for subjects with normal glucose tolerance, impaired fasting glycemia, impaired glucose tolerance and diabetes were 9.9 +/- 6.0, 19.0 +/- 35.4, 20.7 +/- 35.4, and 33.9 +/- 55.0 mg/g, respectively. Diabetic subjects showed higher ACR than the others (p < 0.05). An increase in the proportion of albuminuric subjects was observed as glucose metabolism deteriorated (4.9, 17.0, 23.0 and 36.0%). Stratifying into 4 groups according to postchallenge glycemia (< 7.8 mmol/l, n = 91; > or = 7.8 mmol/l, n = 410) and hypertension, hypertensive and glucose-intolerant subgroups showed higher ACR values. ACR was associated with gender, waist circumference, blood pressure, plasma glucose and triglyceride (p < 0.05); albuminuric subjects had significantly higher levels of such variables than the normoalbuminuric ones. In the final models of linear regression, systolic blood pressure and 2-hour glycemia were shown to be independent predictors of ACR for both genders (p < 0.05). In men, also waist was independently associated with ACR. No interaction was detected between "diabetes and hypertension". CONCLUSIONS: These findings suggest that both glucose intolerance and hypertension could have independent but not synergistic effects on endothelial function--reflected by albumin loss in urine. Such hypothesis needs to be confirmed in prospective studies.     

Abdominal aortic aneurysm and aortic occlusive disease: a comparison of risk factors and inflammatory response.

OBJECTIVE: to compare patients with abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) with regard to risk factors for atherosclerosis, co-morbid conditions and inflammatory activity. PATIENTS AND METHODS: a total of 155 patients undergoing abdominal aortic surgery between January 1993 and October 1997: 82 (53%) had aneurysmal disease and 73 (47%) had occlusive disease. Principal risk factors were compared: age; gender; smoking; hypertension; hyperlipidaemia; diabetes mellitus; severe peripheral vascular disease (PVD) and ischaemic heart disease. Aortic wall tissue samples were obtained during surgery. A prospective blind analysis was performed for the presence of inflammatory cytokines TNF-alpha, IL-1 beta, IL-6 and TGF-beta. RESULTS: the average age of AAA patients was 74 years (50-88), while that of AOD patients was 61 years (43-82) (p<0.0001). Diabetes mellitus was found to be much more prevalent in the AOD group (p<0.001), while hypertension and severe PVD were more prevalent in the AAA group (p<0.001). No differences were found concerning any of the risk factors. Inflammatory cytokine activity: AAA tissue samples contained significantly higher mean TNF-alpha and IL-6 levels compared to the AOD samples (5.6+/-2.7 x 10 E-4 vs. 4.4+/-2.7 x 10 E-5 atmoles/microl (p=0. 01), and 0.6+/-0.4 vs. 0.01+/-0.006 atmoles/microl (p=0.02) respectively). No differences were found related to IL-1 beta and TGF-beta. CONCLUSIONS: (1) Patients with AAA have fewer atherosclerotic risk factors than do patients with AOD. (2) Patients with AAA and AOD have significantly different inflammatory activity. (3) The data supports the hypothesis that AAA and AOD are probably two different pathological entities.     

Initial results of ultrasound screening for aneurysm of the abdominal aorta in Western Australia: relevance for endoluminal treatment of aneurysm disease

BACKGROUND: Increased life expectancy in men during the last thirty years is largely due to the decrease in mortality from cardiovascular disease in the age group 29--69 yr. This change has resulted in a change in the disease profile of the population with conditions such as aneurysm of the abdominal aorta (AAA) becoming more prevalent. The advent of endoluminal treatment for AAA has encouraged prophylactic intervention and fueled the argument to screen for the disease. The feasibility of inserting an endoluminal graft is dependent on the morphology and growth characteristics of the aneurysm. This study used data from a randomized controlled trial of ultrasound screening for AAA in men aged 65--83 yr in Western Australia for the purpose of determining the norms of the living anatomy in the pressurized infrarenal aorta. AIMS: To examine (1) the diameters of the infra-renal aorta in aneurysmal and non-aneurysmal cases, (2) the implications for treatment modalities, with particular reference to endoluminal grafting, which is most dependent on normal and aneurysmal morphology, and (3) any evidence to support the notion that northern Europeans are predisposed to aneurysmal disease. METHODS: Using ultrasound, a randomized control trial was established in Western Australia to assess the value of a screening program in males aged 65--83 yr. The infra-renal aorta was defined as aneurysmal if the maximum diameter was 30 mm or more. Aortic diameter was modelled both as a continuous (in mm) and as a binary outcome variable, for those men who had an infra-renal diameter of 30 mm or more. ANOVA and linear regression were used for modelling aortic diameter as a continuum, while chi-square analysis and logistic regression were used in comparing men with and without the diagnosis of AAA. FINDINGS: By December 1998, of 19,583 men had been invited to undergo ultrasound screening for AAA, 12,203 accepted the invitation (corrected response fraction 70.8%). The prevalence of AAA increased with age from 4.8% at 65 yr to 10.8% at 80 yr (chi(2)=77.9, df=3, P<0.001). The median (IQR) diameter for the non-aneurysmal group was 21.4 mm (3.3 mm) and there was an increase (chi(2)=76.0, df=1, P<0.001) in the diameter of the infra-renal aorta with age. Since 27 mm is the 95th centile for the non-aneurysmal infra-renal aorta, a diameter of 30 mm or more is justified as defining an aneurysm. The risk of AAA was higher in men of Australian (OR=1.0) and northern European origin (OR=1.0, 95%CL: 0.9, 1.2) compared with those of Mediterranean origin (OR=0.5, 95%CL: 0.4, 0.7). CONCLUSION: Although screening has not yet been shown to reduce mortality from AAA, these population-based data assist the understanding of aneurysmal disease and the further development and use of endoluminal grafts for this condition.     

Immunoglobulin A antibodies against Chlamydia pneumoniae are associated with expansion of abdominal aortic aneurysm.

BACKGROUND: The aim of this study was to examine the possible association between the progression of small abdominal aortic aneurysm (AAA) and chronic infection with Chlamydia pneumoniae. METHODS: Patients from a hospital-based mass screening programme for AAA with annual follow-up (mean 2.7 years) were included. After initial interview, 139 men aged 65-73 years with a small AAA underwent examination and blood sampling. Immunoglobulin (Ig) G and IgA titres against C. pneumoniae were measured by a microimmunofluorescence test. RESULTS: Some 83 (95 per cent confidence interval 74-93) per cent of the men had an IgA titre of 20 or more, or an IgG titre of 32 or more. Men with an IgA titre of 20 or more had a 48 per cent higher AAA expansion rate than those with a titre of less than 20 (3.1 versus 2.1 mm/year; P < 0.05). Multiple linear and logistic regression analyses showed that an IgA titre of 20 or more was a significant independent predictor of increased AAA expansion, adjusted for known risk factors of expansion. Initial AAA size and serum total cholesterol level were also predictors of expansion. CONCLUSION: A high proportion of men with a small AAA had signs of chronic infection with C. pneumoniae. Aneurysm progression correlated with evidence of chronic C. pneumoniae infection.