Lack of C4d deposition may reveal susceptibility for ascending aortic dissection

Figures & data

Figure 1. Representative photograph (× 40) of aortic adventitial wall immunohistochemistry of C4d during ascending aortic dilatation (A) and during ascending aortic dissection (B). Note positive C4d staining (arrows) in A suggesting stabile aortic wall during aortic dilatation.

Table I. Patient demographics.

	All patients	C4d +	C4d−
Number of patients	91 (100%)	53	38
Age (years)	62±13	61±13	64±13
Male, n (%)	61 (67%)	37	24
Hypertension, n (%)	28 (31%)	15	13
Diabetes, n (%)	4 (5%)	2	2
Hypercholesterolemia, n (%)	11 (12%)	7	4
Marfan, n (%)	7 (8%)	5	2
Obese, n (%)	3 (4%)	2	1
Myasthenia, n (%)	1 (1%)	1	0
Myositis, n (%)	3 (4%)	1	2
Arthrosis, arthritis, n (%)	10 (11%)	4	6
Dry eye sydrome, n (%)	1 (1%)	1	0
Diverticulitis, n (%)	4 (5%)	3	1
Vasculitis, n (%)	1 (1%)	1	0
Gastritis, n (%)	1 (1%)	1	0
Gingivitis, n (%)	2 (2%)	1	1
Abdominal aneurysm, n (%)	3 (4%)	2	1
Myocardial coronary artery disease, infarction, n (%)	16 (18%)	9	7
Previous cardiothoracic operation
Coronary artery bypass surgery, n (%)	6 (7%)	4	2
Aortic valve replacement, n (%)	3 (4%)	2	1
Correction of aortic coarctation, n (%)	3 (4%)	3	0
St post AAA operata	2 (2%)	1	1
Mid-ascending aorta diameter, mm	57±9	55±8	60±17
3-cusp aortic valve, n (%)	65 (72%)	33	32
Aortic valve insufficiency
Moderate to severe, n (%)	44 (49%)	28	16
Aortic valve stenosis
Moderate to severe, n (%)	28 (31%)	21	7

Table II. Operative details according to surgical evaluation of extension of diseased aorta.

	All patients	C4d+	C4d−
	91 (100%)	53	38
Graft replacement of root and ascending aorta
Mechanical conduit	33 (37%)	19	14
Biological conduit	15 (17%)	7*	8*
David operation	4 (5%)	4	0
Graft replacement of ascending aorta
Mechanical valve + prosthesis	11 (12%)	9	2
Biological valve + prosthesis	8 (9%)	6	2
Prosthesis	20 (22%)	8*	12*
Additional procedures
Thymectomy	1 (1%)	1	0
Ablation	2 (2%)	2	0
Mitral valve plasty	1 (1%)	0	1
Coronary artery bypass surgery	12 (13%)	7	5

*Includes 1 patient with prosthesis extending up to the aortic arch.

Table III. Histology and quantitative immunohistochemistry.

Mean grade of staining	All patients	C4d+	C4d−	p-value
Adventitia
T cells	1.6±0.8	1.5±0.7	1.7±0.8	Ns
B cells	0.9±0.9	0.8±0.8	1.0±1.1	Ns
Macrophages	1.8±0.8	1.7±0.8	1.8±0.7	Ns
Plasma cells	1.1±0.9	1.1±0.8	1.2±1.1	Ns
Inflammation	1.9±0.7	1.8±0.5	2.0±0.8	Ns
Thickness	5.5±4.8	5.0±2.5	6.2±6.9	Ns
Proliferation	1.1±0.8	1.0±0.8	1.2±1.0	Ns
vWF density	20.3±12.3	25.0±11.7	14.3±10.9	<0.0001
D240 density	4.1±3.8	5.1±4.0	2.5±2.8	<0.003
Podo density	4.2±4.5	5.4±5.2	2.5±2.6	<0.004
Media
T cells	0.6±0.9	0.5±0.8	0.7±1.0	Ns
B cells	0.2±0.5	0.1±0.4	0.2±0.6	Ns
Macrophages	1.3±0.9	1.1±0.8	1.5±1.0	Ns
Plasma cells	0.2±0.7	0.3±0.7	0.2±0.6	Ns
Inflammation	1.2±0.9	1.0±0.8	1.3±1.0	Ns
Proliferation	1.1±0.9	0.9±0.8	1.2±1.0	Ns
Degeneration	1.7±1.0	1.6±1.0	1.8±1.0	Ns
Elastase	1.5±1.0	1.4±1.0	1.6±1.1	Ns
vWF density	0.6±1.1	0.5±0.8	0.7±1.3	Ns
D240 density	0.1±0.2	0.1±0.1	0.1±0.3	Ns
Podo density	0.1±0.2	0	0.1±0.3	Ns
Intima
T cells	1.3±0.9	1.2±0.9	1.4±0.9	Ns
B cells	0.2±0.5	0.2±0.5	0.2±0.4	Ns
Macrophages	1.6±0.9	1.5±0.9	1.8±0.9	Ns
Plasma cells	0.4±0.7	0.3±0.6	0.6±0.9	<0.05
Inflammation	1.5±0.9	1.3±0.9	1.8±0.9	<0.05
Proliferation	0.9±0.8	0.8±0.7	1.0±0.8	Ns
Thickness	1.9±0.9	1.7±0.9	2.1±0.9	<0.05
Cellularity	1.7±0.7	1.5±0.7	1.9±0.7	<0.05
vWF density	0.2±1.2	0.1±0.6	0.3±1.6	Ns
D240 density	0.1±0.6	0.1±0.5	0.1±0.7	Ns
Podo density	0.1±0.4	0.1±0.4	0.1±0.4	Ns

Table IV. Immediate postoperative outcome.

	All patients	C4d+	C4d−
	91 (100%)	53	38
Acute dissection	15 (17%)	1	14
Chronic dissection	6 (7%)	3	3
Aortitis	19 (21%)	13*	6
Pulmonary embolism	1 (1%)	1	0
Mediastinitis	1 (1%)	1	0
Mortality	4 (5%)	1	3

*Includes 1 patient with giant cell aortitis and 1 patient with temporal arteritis

Figure 2. Receiver operating characteristic curve (ROC) analysis of C4d associated with stabile nondissecting ascending aortic dilatation (A) and histologically defined aortitis (B). C4d is significantly associated with the prevalence of nondissecting ascending aortic dilatation (AUC 0.792; SE 0.053; p = 0.000; 95% CI 0.688–0.895, A), but not with aortitis (AUC 0.523; SE 0.069; p = 0.752; 95 % CI 0.388–0.658, B).