Atsushi Ohira

Behavior of C-reactive protein levels in medically treated aortic dissection and intramural hematoma.

C management of aortic dissection and intramural hematoma not involving the ascending aorta yields acceptable survival outcomes.1–3 However, a variety of aortic events can often arise during the follow-up phase.4–6 Although C-reactive protein (CRP) levels are inevitably elevated in patients with acute aortic dissection and intramural hematoma, variability exists among patients. However, few previous studies have investigated the behavior of CRP levels in these aortic disorders.7 The purpose of this prospective study was to assess the consequences of CRP levels on the course of aortic dissection and intramural hematoma, by means of comparison with findings from serial computed tomography (CT). • • • One hundred eight patients were diagnosed as having acute aortic dissection or intramural hematoma and admitted to our hospital from June 1997 to May 1999. Of these, 47 consecutive cases who presented within 24 hours (median 6 hours) of onset and were treated medically were initially enrolled in this prospective study. Four patients were excluded from this aggregate because of infectious diseases during the study in 3 cases and contraindication to the use of contrast material in 1 case. Data pertaining to the remaining 43 patients were analyzed: involvement of ascending aorta in 11 patients (type A) and no involvement in 32 patients (type B); there were 36 men and 7 women, average age 65.5 years old (range 42 to 84). Indication for medical treatment was based on the following criteria: (1) type B with descending aorta of ,55 mm in diameter, (2) type A with both ascending aorta of ,50 mm in diameter and no blood flow in false lumen of ascending aorta, and (3) patients without compromised organ perfusion, cardiac tamponade, aortic valve involvement, or aortic rupture. Diagnosis and disease classification was made on the basis of 2 imaging modalities: contrast-enhanced electron beam CT with contiguous slices of 6 mm thickness, and gadolinium-enhanced magnetic resonance imaging with a 1.5-T superconducting magnetic unit. Patients with typical aortic intimal flap were diagnosed as classic dissection (n 5 13, including 4 patients with type A). Aortic dissection with thrombosed false lumen (n 5 10, including 2 patients with type A) was defined by a large amount of intramural thrombus with intimal disruption (entry), as distinct from penetrating atherosclerotic ulcer.8 On the day of onset, the findings of hyperdense precontrast crescent in the aortic wall, no intimal flap, no intimal disruption, and no compressed aortic lumen, were considered diagnostic of intramural hematoma (n 5 20, including 5 patients with type A). All participants were initially treated according to a single protocol as follows. During a 4to 7-day stay in an intensive care unit, systolic blood pressure was maintained at ,130 mm Hg. Nicardipine hydrochloride was intravenously infused for the first 48 hours from onset, if appropriate. Thereafter, oral antihypertensive medications were administered in a fixed order. All patients underwent a uniform rehabilitation program that facilitated a stepwise restoration to normal daily life over a 3-week period. Contrast-enhanced electron beam CT was performed on the day of onset, after a few days, and thereafter at 1-week intervals for 4 to 5 weeks during hospitalization. Subsequent follow-up by electron beam CT was carried out at 3-month intervals after discharge (average 16 months). All tests consisted of early and delayed images, and changes in aortic condition were carefully evaluated by a specially trained radiologist and 2 physicians. In intramural hematoma and aortic dissection with thrombosed false lumen, 3 types of serious evolution of hematoma or thrombus were anticipated: (1) perceptible enlargement of localized contrast filling, suggesting secondary formed microdisruption of the intima9 or initial entry site, (2) abrupt expansion of the hematoma or thrombus, and (3) transition to classic dissection. These findings were designated as intramural events. Circulating CRP levels were measured daily until the initial peak had passed, and thereafter once or twice a week until discharge. The measurements were properly added when an abnormal change was found. Re-elevation of CRP levels was defined as an elevation of .1.0 mg/dl after the initial peak level. CRP was measured by latex agglutination nephelometry with an assay sensitivity of 0.3 mg/dl and a normal range of ,0.6 mg/dl. The study protocol was approved by our hospital ethics committee, and informed consent was obtained from all subjects. Intergroup differences in the proportion of patients with CRP re-elevation were compared by chi-square test. The unpaired Student’s t test was used for comparison of CRP levels between the groups. Significance was set at p ,0.05. All values are expressed as mean 6 SD. In 9 of 20 patients with intramural hematoma, From the Departments of Internal Medicine II and Radiology, Iwate Medical University, Morioka, Japan. Dr. Makita’s address is: Department of Internal Medicine II, Iwate Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan. E-mail: makitas@seagreen.ocn.ne.jp. Manuscript received November 22, 1999; revised manuscript received and accepted January 27, 2000.

Circulating biochemical marker levels of collagen metabolism are abnormal in patients with abdominal aortic aneurysm.

Changes in extracellular matrix composition induced by abnormal collagen metabolism in the aortic wall may be an important factor in the progression of aortic structural changes. The authors have measured several types of biochemical marker for collagen metabolism in plasma: carboxyterminal propeptide of type I collagen (PICP) for a pure collagen synthesis marker, matrix metalloproteinase-1 (MMP-1) for a degradation marker of collagen matrix, and tissue inhibitors of metalloproteinase-1 (TIMP-1) as a native inhibitor of MMP-1. Subjects of this study were 17 patients with abdominal aortic aneurysm (AAA), 14 patients with atherosclerosis obliterans (ASO), and 22 age/sex matched healthy controls (HC). Blood samples were drawn from a forearm vein and measured by radioimmunoassay or enzyme-linked immunosorbent assay. Plasma concen trations of PICP in patients with AAA were significantly decreased compared to those in HC patients (82.0 ±16.4 vs 111.3 ±40.3 ng/mL; p<0.01), but those in patients with ASO (105.4 ±55.4 ng/mL) were comparable to control concentrations. Although no differences in plasma concentrations of MMP-1 were observed among the three subject groups (HC, 20.0 ± 5.6 ng/mL; ASO, 21.4 ± 13.8 ng/mL; AAA, 24.5 ±11.7 ng/mL; NS), MMP-1/PICP ratio as an index of collagen degradation to collagen neosynthesis in AAA was significantly elevated compared to HC (0.32 ±0.18 vs 0.20 ±0.08; p < 0.01). Plasma concentrations of TIMP-1 in patients with AAA (293.8 ±61.2 ng/mL) or ASO (327.6 ±54.9 ng/mL) were significantly higher than in HC (227.3 ±60.2 ng/mL; both p < 0.01). In conclusion, these data suggest that although a compensatory mechanism such as increased TIMP-1 may be activated, collagen neosynthesis may decrease with relatively increased collagen degradation in patients with AAA.

Peripheral resistance vessel dysfunction in Marfan syndrome

BACKGROUND Patients with Marfan syndrome show a hereditary abnormality of elastin metabolism that may cause aortic enlargement and dissection. We have hypothesized that abnormal elastin may alter peripheral vascular structure and function. METHODS Forearm blood flow (FBF) (in milliliters per minute per 100 mL) response to the endothelium-dependent dilator acetylcholine (0.75 to 4.5 microg/min per 100 mL), the endothelium-independent dilator sodium nitroprusside (0.05 to 0.3 microg/min per 100 mL), and structure-related maximum dilator response (10-minute occlusion-induced reactive hyperemia) were measured by plethysmograph in 10 patients with Marfan syndrome (mean age 44 years) and 10 healthy age- and sex-matched controls. Patients with the complications of hypercholesterolemia, diabetes mellitus, or heart failure were excluded from the study. RESULTS Basal FBF (mean +/- SE) did not differ between the 2 groups (2.7 +/- 0.3 vs 2.3 +/- 0.4). Maximum FBF response to acetylcholine in patients with Marfan syndrome was significantly lower than that of healthy controls (8.5 +/- 2.1 vs 15.4 +/- 1.7 mL/min per 100 mL; P <.05). Reactive hyperemia was also lower in patients with Marfan syndrome (at peak 23.0 +/- 2.5 vs 29.5 +/- 2.3 mL/min per 100 mL; P <.05), but sodium nitroprusside-induced FBF changes did not differ between the 2 groups (10.3 +/- 1.1 vs 10.2 +/- 1.5 mL/min per 100 mL; P = not significant). CONCLUSION These observations suggest that endothelium-dependent dilation and maximum dilator reserve capacity are both abnormal in peripheral resistance vessels of patients with Marfan syndrome. These peripheral vasomotion abnormalities may have a detrimental impact on the cardiovascular system in this disorder.

Increased Carotid Artery Stiffness Without Atherosclerotic Change in Patients With Aortic Dissection

The arterial properties and pathogenesis of aortic dissection remain obscure. To examine the arterial properties of patients with aortic dissection, the authors studied the ultrasonographic characteristics of the carotid artery in patients with an aortic dissection (AD, n=86), and compared these findings with data of patients suffering from arteriosclerosis obliterans (ASO, n=151), coronary artery disease (CAD, n=163), and with healthy controls (HC, n=77). Atherosclerotic intimal changes, such as intima-media thickness (IMT) and plaque formation, were milder in AD than in ASO or CAD (IMT: 0.83 ±0.16 vs 0.93 ±0.20/0.86 ±0.17 mm, p<0.05; plaque number: 0.6 ±1.1 vs 2.7 ±2.4/2.5 ±2.1, p<0.05). Luminal diameter in AD, ASO, and CAD was significantly higher than in HC. The luminal distensibility in AD was decreased compared with HC but was the same as in ASO and CAD. Intra-AD group analysis showed that in patients with an intramural hematoma (IMH) or a dissection with a thrombosed false lumen (TLF) the IMT was higher than in patients with a classic dissection. In addition, plaque formation was more severe in AD patients with a coexisting abdominal aortic aneurysm (AAA). Reduced distensibility without severe intimal disease was found in AD. These findings suggest that patients with AD may have several arterial alterations, including structural abnormalities. Patients with IMH, TFL, or coexisting AAA may differ from patients who have a classic type of dissection or who do not have AAA, in terms of arterial characteristics including intimal disease and wall elastic property, and the initiating cause of the dissection. Introduction Owing to the progress that has been made in various imaging modalities, the improvement in the accuracy of diagnosing an aortic dissection has resulted in an increase in the detection rate of the various subtypes of classic dissection, such as those associated with an intramural hematoma (IMH), hemorrhage, or a penetrating atherosclerotic ulcer.1,2 However, the etiology and pathogenesis of these catastrophic aortic disorders remain obscure. From the clinical perspective, it has Angiology 57:478–486, 2006 From the Department of Medicine II, Iwate Medical University, Morioka, Japan Correspondence: DOI: 10.1177/0003319706290625 Copyright

Noninvasive Detection of Iliac Artery Disease and Prediction of Its Severity from Doppler Spectral Analysis in Common Femoral Artery

The direct interrogation of iliac artery disease (IAD) with color-coded duplex scanning is limited by the presence of intestinal gas or obesity. The purposes of this study were to examine the diagnostic accuracy of duplex ultrasound (DUS) analysis of spectral waves in common femoral artery (CFA) for detection of IAD and to predict its severity. DUS and arteriography were performed in 107 lower extremities in this study. The following were calculated from the CFA spectral waves obtained by DUS: peak systolic velocity (PSV), acceleration (PSV/pulse rise time), and deceleration (PSV/pulse decay time). In patients with isolated IAD, the treadmill exercise test was also performed to evaluate the ischemic severity expressed as recovery rate of ankle pressure index five minutes after exercise (RR-API). Forty-six lower extremities with IAD and 61 without IAD were diagnosed by arteriography. PSV was significantly reduced in lower extremities with IAD (109.5 ±32.7 vs 59.8 ±32.9 cm/s, P<0.05). The deceleration detected IAD with a greater specificity and sensitivity vs acceleration (100.0 vs 82.0% and 97.8 vs 82.6%, respectively). Moreover, the acceleration and deceleration significantly corre lated with the RR-API (r=0.589, P<0.05 and r=0.779, P < 0.01, n=14, respectively). The present evaluation is a simple and accurate technique to augment other exami nations for detection of IAD and to assess its ischemic severity.

Abnormal Peripheral Vasodilatory Reserve Without Endothelial Dysfunction in Patients With Aortic Dissection

Structural changes in the aortic wall have been reported to be present in aortic dissection (AD), while there have been no investigations concerning peripheral vasomotion characteristics. Peripheral arterial stiffness is an important factor in the regulation of the central aortic pressure because it produces excessive wave reflection. The present study investigated in AD patients endothelium-dependent peripheral vasodilation and the reactive hyperemic response which is considered to be altered by the structural abnormality of the peripheral resistance artery. Forearm blood flow (FBF) changes induced by intra-arterial infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and by occlusion-induced reactive hyperemia (RH) were measured plethysmographically in 10 AD patients, 7 healthy volunteers, and 7 patients with uncomplicated hypertension (UHT). There were no significant differences in the peak FBF response to ACh and SNP infusion for the three groups (ACh, 14.2±1.8 vs 17.2±4.5 vs 15.7±2.3 ml/min/dl tissue, NS; SNP 9.5±1.3 vs 10.6±1.7 vs 11.9±0.8 vs ml/min/dl tissue, NS). In the case of RH, however, peak FBF and maximum conductance were significantly lower in AD patients than in healthy volunteers and UHT patients (21.1±2.6 vs 36.1±4.7 and 32.4±2.6 ml/min/dl tissue volume,p<0.01, and 0.25±0.03 vs 0.46±0.06 and 0.37±0.03 ml/min/dl per mmHg,p<0.05, respectively). Peripheral vasodilatory function depending on the endothelium and smooth muscle in AD patients was not significantly different from that in healthy volunteers and UHT patients. However, reactive hyperemic vasodilatory reserve, which is a well-established, noninvasive measure of arterial structure, was significantly impaired in AD. These findings indicate that arterial structural abnormalities rather than systemic atherosclerotic changes represented by endothelial dysfunction may be present. We speculated that this aspect of peripheral resistance artery might possibly have an unfavorable effect on the postonset aortic conditions in AD patients.

Impaired Peripheral Vasodilation in Ischemic and Nonischemic Limbs of Patients with Unilateral Arteriosclerosis Obliterans Effect of Revascularization on Leg Hemodynamics

Limb vessel vasodilation plays an important role in the regulation of skeletal muscle blood flow during exercise. However, little documentation is available that describes the vasodilatory response of peripheral vessels in patients with arteriosclerosis obliterans (ASO). This study investigates possible impairment of basal blood flow and response in ischemic and nonischemic legs of patients with ASO, and the effect of revascularization on leg hemodynamics. Basal calf blood flow and reactive hyperemic response to femoral occlusion were measured plethysmographically in 20 patients with unilateral ASO (20 stenotic legs and 20 nonstenotic legs) and eight healthy subjects (eight control legs). Eight stenotic legs underwent percutaneous transluminal angioplasty or surgical revascularization. Basal calf blood flow and peak hyperemic flow was significantly lower in stenotic and nonstenotic legs than in control legs. After revascularization, basal flow was unchanged in stenotic legs but elevated in nonstenotic legs (from 2.5 ±0.3 to 3.4 ±0. 4 mL/min/dL tissue, p<0.01). Peak flow in both legs was significantly elevated (stenotic legs, from 12.8 ± 1.9 to 17.6 ± 1.6 mL/min/dL tissue, p<0.01; nonstenotic legs, from 14.3 ± 1.0 to 20.0 ±1.6 mL/min/dL tissue, p<0.01), although still below control values. Basal blood flow and maximum vasodilatory response of resistance vessels are impaired irrespective of the side of conduit vessel involvement. The vascular response of the nonstenotic side is significantly enhanced after revascularization of the contralateral stenotic lesions. These suggest that neural or circulating vasoacting factor(s) originating from the stenotic limb may contribute to peripheral circulatory disturbance in claudicants.