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Diabetic Patients with Small Abdominal Aortic Aneurysms Have Slower Aneurysm Growth Without Differences in Inflammatory Markers
Matthew Nordness1, Bernard T. Baxter2, Jon Matsumura3, Michael Terrin4, Nancy Webb5, John Curci1
1Vanderbilt University School of Medicine, Nashville, TN, 2University of Nebraska Medical Center, Omaha, NE, 3University of Wisconsin Madison, Madison, WI, 4University of Maryland School of Medicine, Baltimore, MD, 5University of Kentucky, Lexington, KY

INTRODUCTION Abdominal Aortic Aneurysm (AAA) is a common progressive disease and a significant cause of morbidity and mortality. Despite being a leading risk factor in most cardiovascular diseases, diabetes mellitus (DM) is protective of AAA. DM has been repeatedly shown to be negatively associated with AAA incidence, diameter, growth, and rupture. The relationship of these growth changes to the pro-inflammatory effects of diabetes has not been studied. METHODS This is a subgroup investigation within the Non-invasive Treatment of Aortic Aneurysm Clinical Trial, a double-blind placebo-controlled multicenter trial of 261 patients with AAAs between 3.5cm and 5cm investigating the effects of doxycycline on aneurysm growth. Following baseline CT scan and biomarker collection (matrix metallopeptidase-9 [MMP-9], C-reactive protein [CRP] and serum amyloid A [SAA]), patients were longitudinally followed for 24 months with CT scans and lab work every 6 months. CT scans were analyzed by a central laboratory. Descriptive statistics were performed with t-tests for continuous and chi-square tests for categorical variables to compare across groups. Unadjusted analysis was performed with Wilcoxon rank-sum test to compare AAA MTD growth rates across groups given the non-normal distribution of growth rates. Multivariable linear regression was performed to model the association between diabetes and aneurysm maximal transverse diameter (MTD) growth rate. Covariates included age, sex, baseline MTD, smoking. Biomarker data was analyzed after log-transformation. RESULTS Of 261 patients, 250 subjects had sufficient imaging for growth rate measurements and were included in this study. There were 56 (22.4%) diabetics and 194 (77.6%) non-diabetics with baseline demographics in Table 1. Diabetes was associated with higher BMI and increased rates of hypercholesterolemia, and coronary artery disease (CAD) (p< 0.05). It was also associated with increased frequency of treatment for atherosclerosis and hypertension including treatment with statin, angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker (ARB), aspirin, any anti-platelet, and diuretic therapy (p< 0.05). There was no significant difference in baseline MMP-9, CRP or SAA (p=0.85, p=0.67, p=0.19). Baseline aneurysm MTD was not significantly different between groups (p=0.67). Median AAA MTD growth rate for diabetics was 0.12 cm/yr (IQR 0.07-0.22) and for non-diabetics was 0.19 cm/yr (IQR 0.12-0.27). In an unadjusted analysis, AAA MTD growth rate in diabetics was significantly lower than non-diabetics (p=0.001). In multivariable linear regression controlling age, sex, baseline MTD, and smoking, diabetes remained significantly associated with AAA MTD growth rate (coef -0.053; p=0.007; 95% CI -0.091, -0.015). CONCLUSIONS The diabetic group was associated with an overall reduction in aneurysm growth rate despite more severe concomitant vascular co-morbidities and similar initial sizes of aneurysms. The distribution of growth rates was generally similar to non-diabetics but lacked patients with relatively fast growth. Diabetes was not associated with increased circulating inflammatory biomarkers at baseline.

Baseline Characteristics: Non-diabetic and Diabetic
CharacteristicNo history of Diabetes Mean (SD);Median (IQR);N(%)History of Diabetes Mean (SD);Median (IQR);N(%)Total Mean (SD); Median (IQR);N(%)
BMI*28.4 (5.2)31.2 (4.4)29.0 (5.2)
CAD* 74 (38.1%)30 (53.6%)104 (41.6%)
CHF* 11 (5.7%)8 (14.3%)19 (7.6%)
Rx Statin*151 (77.8%)54 (96.4%)205 (82.0%)
Rx ACE inhibitor* 61 (31.4%)26 (46.4%)87 (34.8%)
Rx ARB*29 (15%)16 (28.6%)45 (18%)
CRP (mg/L)2.5 (1.2-4.7)2.1 (1.3-3.8)2.3 (1.2-4.6)
MMP-9 (g/L)38.9 (26.5-59.8)34.4 (27.9-45.2)37.9 (27.1-56.8)
SAA (mg/L)19.1 (10.8-40.4)23.0 (14.0-40.7)20.7 (12.0-40.4)

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