Elastin-Specific Autoimmunity in Smokers With Thoracic Aortic Aneurysm and Dissection is Independent of Chronic Obstructive Pulmonary Disease.

Background Thoracic aortic aneurysm ( TAA ) and dissection ( TAD ) are characterized by progressive disorganization of the aortic wall matrix, including elastin, a highly immunogenic molecule. Whether acquired autoimmune responses can be detected in TAA / TAD patients who are smokers is unknown. The objectives of this study were to determine whether TAA / TAD smokers have increased T-cell responses to human elastin fragments, and to determine whether autoimmune responses in TAA / TAD smokers are dependent on chronic obstructive pulmonary disease. Methods and Results In a cross-sectional study (N=86), we examined peripheral blood CD 4+ T cell responses to elastin fragments in never-, former-, or current-smokers with or without TAA / TAD . CD 4+ T cells were co-cultured with irradiated autologous peripheral blood CD 1a+/ CD 14+ antigen presenting cells pulsed with or without elastin fragments to measure cytokine production. Baseline plasma concentration of anti-elastin antibodies and elastin-degrading enzymes (eg, matrix metalloproteinase-9, and -12, and neutrophil elastase) were measured in the same cohort. elastin fragment-specific CD 4+ T cell expression of interferon-γ, and anti-elastin antibodies were dependent on history of smoking in TAA / TAD patients but were independent of chronic obstructive pulmonary disease. Matrix metalloproteinase-9, and -12, and neutrophil elastase plasma concentrations were also significantly elevated in ever-smokers with TAA / TAD . Conclusions Cigarette smoke is associated with loss of self-tolerance and induction of elastin-specific autoreactive T- and B-cell responses in patients with TAA / TAD . Development of peripheral blood biomarkers to track immunity to self-antigens could be used to identify and potentially prognosticate susceptibility to TAA / TAD in smokers.

Matrix metalloproteinase levels in chronic thoracic aortic dissection.

BACKGROUND: Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) can lead to aortic wall failure. We hypothesized that patients with aneurysms resulting from chronic descending thoracic aortic dissection have elevated tissue and plasma levels of specific MMPs and decreased tissue levels of TIMPs. MATERIALS AND METHODS: Aortic tissue was obtained from 25 patients who required surgical repair of descending thoracic aortic aneurysm due to chronic aortic dissection and from 17 organ-donor controls without aortic disease. Tissue levels of MMP-1, -2, -3, -9, -12, and -13 and TIMP-1 and -2 were measured by colorimetric activity assay or enzyme-linked immunosorbent assay and confirmed by Western blot and immunohistochemistry. Blood obtained from the 25 patients and 15 controls without aortic diseases was used to compare plasma levels of MMP-3, -9, and -12. RESULTS: Total MMP-1, total MMP-9, and active MMP-9 levels were higher and total MMP-2 levels were lower in dissection tissue than in control tissue. Additionally, the MMP-9 to TIMP-1 and active to total MMP-2 ratios were higher and the MMP-2 to TIMP-2 ratio was lower in dissection tissue. Furthermore, patients had higher plasma active to total MMP-9 ratios than the controls. Age and hypertension were associated with increased MMP levels. CONCLUSIONS: Increased levels of several MMPs and increased MMP to TIMP ratios in aortic tissue from patients suggest an environment that favors proteolysis, which may promote progressive extracellular matrix destruction and medial degeneration after aortic dissection. An elevated active to total MMP-9 ratio in plasma may be a biomarker for end-stage aneurysm development in patients with chronic thoracic aortic disease.

Inflammatory Cell Infiltrates in Acute and Chronic Thoracic Aortic Dissection.

BACKGROUND: Thoracic aortic dissection (TAD) is a highly lethal cardiovascular disease. Injury to the intima and media allows pulsatile blood to enter the media, leading to dissection formation. Inflammatory cells then infiltrate the site of aortic injury to clear dead cells and damaged tissue. This excessive inflammation may play a role in aneurysm formation after dissection. METHODS: Using immunohistochemistry, we compared aortic tissues from patients with acute TAD (n = 11), patients with chronic TAD (n = 35), and donor controls (n = 20) for the presence of CD68+ macrophages, neutrophils, mast cells, and CD3+ T lymphocytes. RESULTS: Tissue samples from patients with acute or chronic TAD generally had significantly more inflammatory cells in both the medial and adventitial layers than did the control samples. In tissues from patients with acute TAD, the adventitia had more of the inflammatory cells studied than did the media. The pattern of increase in inflammatory cells was similar in chronic and acute TAD tissues, except for macrophages, which were seen more frequently in the adventitial layer of acute TAD tissue than in the adventitia of chronic TAD tissue. CONCLUSIONS: The inflammatory cell content of both acute and chronic TAD tissue was significantly different from that of control tissue. However, the inflammatory cell profile of aneurysmal chronic TAD was similar to that of acute TAD. This may reflect a sustained injury response that contributes to medial degeneration and aneurysm formation.

Morbid obesity is associated with increased resource utilization in coronary artery bypass grafting.

BACKGROUND: Studies have shown good outcomes for morbidly obese patients who undergo cardiac surgery. However, little is known about how much additional resource utilization treating these challenging patients requires. We hypothesized that morbidly obese patients (body mass index ≥40 kg/m(2)) undergoing coronary artery bypass grafting needed longer operating room times and had longer hospital and intensive care unit stays than non-morbidly obese patients. METHODS: We reviewed data from all morbidly obese patients (n = 56, body mass index = 42.7 ± 2.6 kg/m(2)) who underwent coronary artery bypass grafting at our institution between 1999 and 2009. These patients' outcomes were compared with those of non-morbidly obese patients (n = 168, body mass index = 30.0 ± 2.8 kg/m(2)) who were propensity-matched 3:1 with the morbidly obese patients. RESULTS: Of the 14 preoperative characteristics examined, only 1, creatinine level, differed significantly between the two groups (p = 0.02). Intraoperative and postoperative complication rates and the mortality rate were similar between groups (p > 0.09). However, morbidly obese patients had longer operating times (449 ± 70 versus 420 ± 59 minutes; p = 0.002), intensive care unit stays (5.2 versus 3.3 days; p < 0.005), and postoperative hospital stays (14.2 versus 9.5 days; p < 0.005) than the non-morbidly obese patients. CONCLUSIONS: Although good outcomes can be achieved for morbidly obese patients who undergo coronary artery bypass grafting, these patients require considerably more resource utilization in the operating room and intensive care unit, and they spend more time in the hospital after surgery. At a cardiac surgical operating room cost of approximately $50 per minute and $4,500 per intensive care unit day, the financial implications for morbidly obese patients who need coronary artery bypass grafting are not insignificant.

Outcomes of coronary surgery at a Veterans Affairs hospital versus other hospitals.

BACKGROUND: The aim of this study was to compare outcomes of coronary artery bypass grafting (CABG) operations at a VA hospital and non-VA hospitals. MATERIALS AND METHODS: Using the 2004 Nationwide Inpatient Sample database, we identified 48,669 discharge records of patients who underwent CABG in non-VA hospitals and compared these patients' outcomes with those of 688 patients who underwent CABG at our VA hospital from 2002 to 2006. Student t- tests and chi(2) tests were used to identify significant intergroup differences. RESULTS: The VA patients were slightly younger than the non-VA patients (62 +/- 8 versus 66 +/- 11 y, P < 0.0001). The VA patients also had a higher prevalence of prior myocardial infarction (60.6% versus 34.6%), congestive heart failure (38.2% versus 22.1%), peripheral vascular disease (25.9% versus 7.2%), cerebral vascular disease (23.4% versus 5.9%), chronic obstructive pulmonary disease (32.3% versus 16.6%), and diabetes (41.7% versus 29.7%) (P < 0.0001 for all). Nonetheless, the in-hospital mortality rate was significantly lower in VA patients than in non-VA patients (1.6% versus 3.0%, P = 0.03). CONCLUSIONS: Despite the higher prevalence of comorbidities, patients who underwent CABG at a VA hospital had a significantly lower mortality rate than CABG patients in non-VA hospitals.