Cerebrovascular complications of fibromuscular dysplasia

Opinion statement  Patients with cerebral ischemia or hemorrhage due to fibromuscular dysplasia (FMD) should be admitted to a monitored hospital bed and receive supportive stroke care. Based on our personal clinical experience, we recommend antiplatelet agents for future stroke prevention in patients with symptomatic FMD. In patients with watershed stroke due to hemodynamically significant FMD, our opinion is that hypertensive, hypervolemic therapy should be initiated immediately. Additionally, we suggest that potential revascularization therapies, such as intraoperative or primary percutaneous angioplasty, should be discussed.     

Fibromuscular dysplasia

Optional statement The most common clinical manifestations of fibromuscular dysplasia (FMD) are hypertension due to renal artery involvement and transient ischemic attack or stroke due to carotid or vertebral artery involvement. Patients with renal artery FMD and hypertension should undergo primary angioplasty with the goal of curing the hypertension. If the blood pressure fails to normalize following angioplasty, the physician should institute antihypertensive medications according to the recommendations of the Joint National Committee on the Prevention, Detection, and Treatment of High Blood Pressure VII. In patients with cerebrovascular FMD, antiplatelet agents represent the cornerstone of therapy. Percutaneous angioplasty has emerged as the preferred treatment for symptomatic cerebrovascular FMD.     

Fibromuscular Dysplasia of Renal and Carotid Arteries

We report here two cases of fibromuscular dysplasia (FMD). The first case describes an asymptomatic 75-year-old man with FMD of the right internal carotid artery. The second case reports a 17-year-old man who presented with arterial hypertension caused by FMD of the left renal artery and was subsequently successfully treated by angioplasty. FMD is a rare nonatherosclerotic, noninflammatory angiopathy, which can involve almost every arterial vascular bed. It is a less common cause of stenosis of renal and carotid arteries. FMD can present with arterial hypertension when it involves renal arteries or with ischemic stroke or transient ischemic attack when the disease affects the carotid or vertebral arteries. Many cases are asymptomatic and may be discovered incidentally. Percutaneous transluminal angioplasty should be used in patients with a stenosis of the renal artery causing arterial hypertension. On the contrary, conservative therapy should be chosen in patients with asymptomatic and extensive lesions of the carotid arteries.     

The association between endothelial dysfunction and cardiovascular outcomes in a population-based multi-ethnic cohort

BACKGROUND: Brachial artery flow-mediated dilation (FMD) may predict cardiovascular events in selected high-risk patients. Whether FMD testing predicts cardiovascular events in asymptomatic, lower risk individuals from the general population is unknown. METHODS AND RESULTS: As a part of a multi-ethnic, prospective cohort study, the Northern Manhattan Study, we examined FMD by high-resolution ultrasonography in 842 community participants who were free of stroke or myocardial infarction. Lower FMD levels predicted cardiovascular events (myocardial infarction, stroke and vascular death) at 36 months of follow-up (hazard ratio (HR)=1.12 for every 1% decrease in FMD, 95% CI 1.01-1.25, p=0.03). The risk of events in patients with FMD in the lower two tertiles (FMD<7.5%) was significantly higher than those in the highest tertile (HR=3.28, 95% CI 1.07-10.06, p=0.04 for lowest versus highest tertile, and HR=3.05, 95% CI 1.03-9.66, p=0.04 for middle versus highest tertile). In a multivariate analysis including cardiovascular risk factors, the increase in risk associated with FMD was no longer statistically significant. CONCLUSIONS: Non-invasive FMD testing predicts incident cardiovascular events in this multi-ethnic, population-based sample, but its predictive value is not independent of cardiovascular risk factors.     

Endothelial dysfunction is an independent risk factor for stroke patients irrespective of the presence of patent foramen ovale

Background

Paradoxical embolization through the patent foramen ovale (PFO) is the major cause of most cryptogenic stroke cases. However, the presence of PFO may simply be an incidental finding in these patients, and endothelial dysfunction may be the underlying reason of ischemic stroke. The aim of this study was to compare the endothelial function of cryptogenic stroke patients according to the presence of PFO.

Methods

Sixty consecutive patients with cryptogenic stroke referred for transesophageal echocardiography (TEE) and 39 consecutive nonstroke patients referred for TEE examination because of suspected PFO were included in the study. Endothelial functions were assessed by brachial artery ultrasonography. PFO was diagnosed by the presence of right-to-left passage of contrast bubbles during TEE. Stroke and nonstroke patients were further subdivided into two groups according to the presence of PFO.

Results

Stroke patients had significantly lower flow-mediated dilation (FMD) values than nonstroke patients (8.36?±?4.38?% vs. 12.57?±?4.90?%, p?<?0.001). The stroke patients with PFO had significantly lower FMD measures than nonstroke patients with PFO (6.60?±?3.98?% vs. 10.84?±?4.40?%, p?=?0.001). Similarly, cryptogenic stroke patients without PFO had significantly lower FMD measures than nonstroke patients without PFO (9.90?±?4.18?% vs. 14.22?±?4.88, p?=?0.002). Logistic regression analysis showed FMD as an independent predictor of cryptogenic stroke when adjusted by age, sex, and presence of PFO (odds ratio: 0.809, 95?% confidence interval: 0.719–0.911, p?<?0.001). An FMD value of ?11.30?% or lower predicted cryptogenic stroke with a sensitivity of 78.3?%, a specificity of 66.7?%, and positive and negative predictive values of 78.3 and 66.7?%, respectively.

Conclusion

Endothelial dysfunction seems to play a more important role than PFO in the underlying mechanism of cryptogenic stroke.     

Interrelationship between non-invasive measurements of atherosclerosis: flow-mediated dilation of brachial artery, carotid intima-media thickness and pulse wave velocity

Flow-mediated dilation (FMD) of the brachial artery, carotid intima-media thickness (IMT) and pulse wave velocity (PWV) have been shown to be good surrogate markers of clinical atherosclerosis. We determined the interrelation between these measurements, and examined whether their combination would be of clinical significance. One hundred and thirty-five consecutive subjects (79 women/56 men) were enrolled, including 110 patients with risk factors for atherosclerosis, and 33 patients with atherosclerotic disease such as coronary heart disease, stroke or arteriosclerosis obliterans. IMT and plaque formation of the carotid artery and FMD of the brachial artery were assessed using ultrasonography. Brachial-ankle PWV (baPWV) was measured using an automated device (form ABI/PWV, Colin). Age, FMD, IMT and PWV were significantly correlated with each other. Multivariate analysis revealed an independent correlation between the parameters except for FMD, and all four parameters were independently correlated with each other in subjects <70 years. Next, we classified the subjects by tertile according to the values of FMD, IMT and PWV. Each of the worst tertiles was associated with a higher prevalence of atherosclerotic disease and carotid plaques compared to the other tertiles. Moreover, subjects with the worst tertiles of all three measurements had a markedly higher prevalence of atherosclerotic disease and carotid plaques. These results suggest that FMD, IMT and PWV are related to each other, but the combination of these measurements will be of stronger clinical relevance.     

Intima Media Thickness and Endothelial Function in Chronic Hemodialysis Patients

The purpose of our study was to evaluate the intima‐media thickness (IMT) of the carotid and brachial arteries, flow‐mediated dilatation (FMD), and nitroglycerin‐mediated dilatation (NMD) in diabetic and non‐diabetic hemodialysis patients. We also examined the effects of traditional and other risk factors on carotid and brachial IMT, FMD and NMD in all hemodialysis patients. Fifty‐eight adult hemodialysis patients, 14 of whom had diabetes, were studied. They had been on hemodialysis for 1–340 months. Using B‐mode ultrasonography, we measured the carotid and brachial IMT, FMD and NMD, and correlated the values with cardiovascular risk factors. FMD and NMD were significantly lower in diabetic patients (FMD 4.01 ± 0.99 vs. 6.69 ± 2.37 mm; NMD 9.1 ± 1.95 vs. 11.23 ± 2.86 mm), while no such differences were found between the two groups with respect to carotid or brachial IMT. In all patients with respect to age a positive correlation was found with carotid and brachial IMT, and a negative one with FMD and NMD. With respect to hypertension as well as diabetes, a negative correlation was found with FMD and NMD. Age is the most important factor that significantly affected all studied markers of atherosclerosis in hemodialysis patients. The endothelial and smooth vascular functions are significantly impaired in diabetic and hypertensive hemodialysis patients, and hypertension is shown to be an independent risk factor for smooth vascular dysfunction in hemodialysis patients. According to our results, intensive antihypertensive treatment is recommended in hypertensive chronic hemodialysis patients.     

内皮功能对阵发性房颤患者心血管事件的影响

目的 旨在探讨阵发性房颤患者内皮功能受损与心血管事件的关系。方法 选择291例阵发性房颤患者为观察组,选择无房颤病史窦性心律者40例作为对照组。对观察组进行肱动脉血流介导的血管舒张功能（flowmediated vasodilation,FMD）测定,并根据FMD水平将房颤患者分为低FMD房颤组（n=97,FMD<5.9%）和高FMD房颤组（n=194,FMD≥5.9%）。进行30个月的临床随访,首要终点事件定义为复合心血管事件（心血管死亡、非致死性心肌梗死、卒中和需住院的心力衰竭）。结果 低FMD房颤组平均年龄较对照组增高（P<0.05）,也较高FMD房颤组增高（P<0.05）。低FMD房颤组CHA2DS2-VASc积分较高FMD房颤组显著增加（P<0.05）。同时心脏超声数据显示低FMD房颤组左房末径值较对照组增高（P<0.01）、也较高FMD房颤组增高（P<0.05）;高FMD组左房末径值较对照组也明显升高（P<0.01）。与对照组比较,低FMD房颤组心血管事件发生率增加（P<0.01）,高FMD房颤组亦增加（P<0.05）;...     

Coronary Angiographic Manifestations and Outcomes in Spontaneous Coronary Artery Dissection Patients With and Without Fibromuscular Dysplasia

BackgroundFibromuscular dysplasia (FMD) is widely recognized as an important predisposing condition for spontaneous coronary artery dissection (SCAD). However, it remains unclear in SCAD patients with coexistent extracoronary FMD whether SCAD can be attributed to coronary FMD.MethodsWe retrospectively analyzed consecutive patients enrolled in our Vancouver SCAD registries between September 2009 and October 2019 who were screened for extracoronary FMD. We reviewed coronary angiograms for manifestations of coronary FMD that were previously described (ie, irregular stenosis, smooth stenosis, dilatation/ectasia, and severe tortuosity). Outcome of interest was major adverse cardiovascular event (MACE).ResultsWe included 346 SCAD patients, of these, 250 (72.3%) had extracoronary FMD. Patients with FMD were older (54.6 ± 9.5 vs 51.7 ± 9.8 years) and more likely to have prior history of myocardial infarction (7.2% vs 1.0%, P = 0.047) and stroke (4.4% vs 0%, P = 0.081) compared with non-FMD patients. On coronary angiography, severe tortuosity was more prevalent in patients with extracoronary FMD (58.4% vs 36.5%, P < 0.001). Rates of irregular stenosis, smooth stenosis, and dilatation/ectasia were numerically higher in patients with extracoronary FMD, but differences were not significantly different. The rate of MACE at median follow-up of 807 (interquartile range, 392-1096) days was not different between groups (19.6% vs 15.6%; non-FMD as a reference: hazard ratio 1.44; 95% confidence interval, 0.76-2.71, P = 0.261).ConclusionSCAD patients with extracoronary FMD were more likely to have coronary FMD manifestations on angiogram, especially severely tortuous vessels, compared with those without extracoronary FMD, with similar clinical outcomes. This may suggest that SCAD can occur at sites of pre-existent subclinical coronary FMD.     

Relation of thrombogenesis in systemic hypertension to angiogenesis and endothelial damage/dysfunction (a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial [ASCOT])

Increasing evidence points toward a prothrombotic state in hypertension and atherosclerosis, conditions associated with thrombosis-related complications, such as myocardial infarction and stroke. We hypothesized that this increased risk of thrombogenesis may be related to endothelial damage/dysfunction and abnormal angiogenesis, and thus, an increased risk of future cardiovascular disease. Thrombogenesis, endothelial damage/dysfunction, and angiogenesis can be assessed by measurement of tissue factor (TF), von Willebrand Factor (vWF), flow-mediated dilatation (FMD), and vascular endothelial growth factor (VEGF), respectively. To test this hypothesis, we measured TF, vWF, FMD, and VEGF in 76 patients with systemic hypertension (71 men; mean age 64; mean blood pressure 167/72 mm Hg), considered additional risk factors such as diabetes, and related them to the patient's 10-year cardiovascular and cerebrovascular risk score using the Framingham equation. Patients were compared with 48 healthy normotensive controls. In these patients, the effects of 6 months of intensified blood pressure and (where appropriate) lipid-lowering treatment were investigated. In our patients, TF, VEGF, and vWF levels were higher, but FMD was lower (all p <0.001) compared with the controls. All markers correlated with each other and with both cardiovascular and cerebrovascular risk scores (all p <0.001). After intensified blood pressure and hypercholesterolemia treatment, total cholesterol, blood pressure, TF, VEGF, and vWF levels all decreased, whereas FMD increased (all p <0.001). Thus, in subjects with hypertension and other risk factors, endothelial damage/dysfunction (and thus, atherogenesis), thrombogenesis, and angiogenesis are abnormal, correlate with overall cardiovascular risk, and importantly, can be related to each other in a "Birmingham Vascular Triangle." Furthermore, these processes are beneficially affected by intensive blood pressure and lipid treatment.     

Measurement of flow-mediated dilatation of the brachial artery is affected by local elastic vessel wall properties in high-risk patients

OBJECTIVES: To assess whether the validity of endothelial function measurement by flow-mediated dilatation (FMD) is affected by local brachial artery stiffness (distensibility coefficient; DC) and arterial wall thickness (intima-media thickness, IMT). BACKGROUND: FMD measurement relies on assessment of arterial diameter change. Increased IMT and decreased DC might physically limit dilatation of the brachial artery in spite of healthy endothelium. METHODS: DC, IMT and FMD of the brachial artery were simultaneously measured in 349 patients with advanced atherosclerosis or cardiovascular risk factors. The relations between FMD and age, and FMD and current smoking were regarded as a proxy for the relation between FMD and true endothelial function. RESULTS: The relations between FMD and age, and FMD and smoking, were significantly modified by brachial artery DC. No modification was found for IMT. The interaction terms were statistically significant (p=0.03 and 0.04, respectively). The relation between FMD and age, and FMD and smoking was progressively more pronounced in patients with more elastic arteries. CONCLUSION: The results of our study indicate that increased arterial stiffness may interfere with valid measurement of FMD and that patients with stiff arteries may be considered for exclusion from analyses involving FMD to ensure its validity.     

Improvement in Brachial Endothelial Vasomotor Function and Brachial-Ankle Pulse Wave Velocity Reduces the Residual Risk for Cardiovascular Events after Optimal Medical Treatment in Patients with Coronary Artery Disease

Aim: To examine whether improvement in flow-mediated endothelium-dependent dilatation (FMD) of the brachial artery and brachial-ankle pulse wave velocity (baPWV) has an additive effect on achieving optimal goals of traditional risk factors to reduce cardiovascular risk in patients with coronary artery disease (CAD). Methods: We assessed 323 patients with CAD and impaired vascular function, defined as an impaired FMD of the brachial artery (＜5.5%) and increased baPWV (＞1,440 cm/sec). After FMD and baPWV measurements at 24 weeks of optimal medical treatment (OMT), the study patients were followed up for ＜60 months or until a composite of cardiac death, nonfatal myocardial infarction (MI), unstable angina, or ischemic stroke occurs. Results: During the median follow-up period of 35 months, cardiovascular events occurred in 72 patients. Multivariate Cox hazards analysis showed that patients with an improvement in FMD and baPWV had the lowest probability of future cardiovascular events. In addition, the improvement in FMD and baPWV had a significant incremental effect on the predictive value of the achievement of optimal goals for blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and hemoglobin A1c (HbA1c) using net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Conclusions: The improvement in FMD and baPWV had additive effects on risk reduction of the achievement of the optimal goals of traditional risk factors in patients with CAD. Thus, serial measurements of FMD and baPWV may be useful for identifying CAD patients at residual risk for adverse cardiovascular events following OMT.     

Endothelial functional and structural impairment in patients with different degrees of coronary artery disease development

Flow-mediated dilatation (FMD) and intima-media thickness (IMT) are noninvasive methods for patient evaluation. In this study we aimed to estimate the correlation between FMD and IMT in patients with different degree of coronary artery disease (CAD) development, and to explore their prognostic significance for the presence of angiographically significant coronary artery stenosis. We included 198 patients divided into five groups according to the degree of CAD development. All patients had FMD and IMT measured, 105 (53.03%) performed a Treadmill test in our clinic, and 146 (73.7%) underwent coronary arteriography (CAG). Patients with significant (> or = 50%) coronary artery stenosis had lower FMD and higher IMT values compared to patients without significant CAD: FMD: 2.78% +/- 2.71% vs 8.24% +/- 5.16%, respectively, P < 0.001; IMT: 0.882 +/- 0.17 mm vs 0.763 +/- 0.16 mm, respectively, P < 0.001. There existed a weak negative correlation between FMD and IMT (correlation coefficient: 0.242, P < 0.001), which was lost in subgroups and after controlling for the presence of significant CAD, number of diseased coronary arteries, and percent coronary artery stenosis. Analyzing the receiver operating characteristic curves we found that FMD values < or = 4.5% had 74% sensitivity, 77% specificity, positive predictive value (PPV) 81.8%, and negative predictive value (NPV) 68%, and IMT values > or = 0.81 mm had sensitivity 71%, specificity 67%, PPV 76.1%, and NPV 63.1% for the presence of significant CAD. Patients with advanced CAD had lower FMD and higher IMT values compared to patients with minor changes. The correlation between FMD and IMT was weak and inconsistent. Both methods demonstrated an acceptable prognostic significance for the presence of significant CAD.     

Renal artery stenosis and ambulatory blood pressure monitoring: A case report and review of the literature

Renal artery stenosis (RAS) is a prevalent cause of secondary hypertension. Elderly patients with atherosclerosis and young women with fibromuscular dysplasia (FMD) are particularly at risk. Blood pressure screening is often key to this diagnosis, although the reliability of clinical screening has been questioned, and ambulatory blood pressure monitoring (ABPM) likely offers superior ability to diagnose poorly controlled hypertension. In patients with RAS, medical management should be the primary means of therapy; however, in a select group of these patients, renal revascularization may be considered, and has been shown to reduce blood pressure and stabilize chronic kidney disease. In this report, we present a patient diagnosed with RAS due to FMD, found to have significant hypertension via ABPM, and treated successfully with percutaneous renal artery angioplasty; importantly, continuous 24‐hr ambulatory monitoring after pressure gradient guided renal angioplasty confirmed reduction in blood pressure.     

Combined use of endothelial function assessed by brachial ultrasound and high-sensitive C-reactive protein in predicting cardiovascular events

BACKGROUND: Endothelial function plays a key role in determining the clinical manifestations of atherosclerotic lesions. Elevated high-sensitive C-reactive protein (hsCRP) relates to long-term prognosis of cardiovascular disease. HYPOTHESIS: We test the hypothesis that combined use of endothelial function and hsCRP could increase predictive value of future cardiovascular events. METHODS AND RESULTS: 205 patients were followed up for a median period of 24 months. Endothelial function was assessed using brachial ultrasound to measure endothelium-dependent flow-mediated vasodilation (FMD). Cox regression analyses were conducted for the 205 subjects, with cardiovascular events being defined as myocardial infarction, hospitalization due to congestive heart failure, percutaneous coronary intervention, coronary artery bypass grafting, and ischemic stroke. Twenty nine (14%) developed cardiovascular events. Both FMD and hsCRP were significantly predictive of cardiovascular events (relative risk for patients with FMD<3% as compared to those with FMD>6%, 4.65, 95% confidence interval (CI): 1.30-16.66, p=0.018; relative risk for the highest as compared with the lowest tertile of hsCRP level, 3.59, 95% CI: 1.32-9.74, p=0.012, respectively). Further risk analysis was performed among four groups classified by FMD (FMD >or= 6% or<6%) and half percentile of hsCRP (hsCRP >or= 1 or<1 mg/dL). Relative risks for the FMD<6%/hsCRP >or= 1 mg/dL group compared to FMD >or= 6%/hsCRP<1 mg/dL group increased markedly to 12.598 (95% CI: 1.69 to 94.14, p=0.014) for cardiovascular events. CONCLUSIONS: Patients with suspected coronary artery disease may benefit from risk stratification based on both endothelium-dependent FMD and hsCRP, since combined these two factors contribute significantly toward the incidence of cardiovascular events.     

Mechanism of stroke complicating cardiopulmonary bypass surgery

Background: Stroke is a devastating complication of cardiopulmonary bypass (CPB) surgery which occurs in 1 to 5% of cases. Strategies to reduce its incidence require a knowledge of the underlying pathology and aetiology.
Aims: To determine the incidence, pathology and aetiology of stroke complicating CPB.
Methods: Prospective review of clinical, operative and cranial CT scan findings in all cases of stroke complicating CPB procedures in our institution over an 18 month period.
Results:. Twenty-one (1.6%, 95% CI 0.9–2.3%) cases of stroke were identified from 1336 CPB procedures. Cranial CT scan, performed in all but one patient, was normal in three patients or consistent with ischaemic stroke in 17 patients. There were no cases of haemorrhagic infarction or intracerebral haemorrhage. It was difficult to differentiate embolic and borderzone infarcts in two cases. After considering the clinical, operative and CT scan features together, 12 (57%, 95% CI 36–78%) of the cases were felt to be embolic in origin and nine (43%, 95% CI 22–64%) due to hypoperfusion in a borderzone.
Conclusions: This study demonstrates that stroke remains an important complication of CPB procedures with an incidence in our series of 1.6%. The pathologic type of stroke is predominantly ischaemic in nature due to either cerebral embolism or borderzone infarction. Strategies for stroke prevention in patients undergoing CPB should be targeted primarily at these two mechanisms.     

The relationship between endothelial function in the brachial artery and intima plus media thickening of the coronary arteries in patients with chest pain syndrome

Endothelial dysfunction precedes the development of clinical atherosclerosis. A decrease in endothelium-derived nitric oxide activity shows impaired vasodilator function and causes arterial intimal hyperplasia or thickening. Others and we have reported the close relation of endothelial function in brachial artery and coronary artery. To compare the flow-mediated endothelium-dependent vasodilation (FMD) in brachial artery and the intima+media area in coronary artery, we measured brachial artery vasodilator response following transient occlusion with high resolution ultrasound transducer and intima+media area in coronary arteries with intravascular ultrasound in 25 patients with normal coronary angiograms (age 61.6+/-8.7 years old, men 14 and women 11). FMD was measured at least 7 days after the cessation of all vasodilators. The mean FMD of 25 patients was 3.83+/-2.38%, the mean intima+media area in coronary arteries of 25 patients was 39.9+/-15.5% of total vessel wall. FMD has a close negative relation with the largest percent intima+media area (r=-0.77, p<0.01). Especially, the patients whose FMD was less than 3.83% had larger percent intima+media area than those whose FMD was 3.83% or more (48.7+/-10.7% versus 30.3+/-14.2%, p<0.01). There is an intima+media thickening even in the patients who had normal coronary angiograms, and that the percent intima+media area correlated with FMD. The measurement of FMD is useful for screening the coronary artery intima+media thickening noninvasively. The pathogenesis of acute coronary syndrome has been reported to be the plaque rupture even in the patients with normal coronary angiograms. Thus, we must pay much attention in the patients with impaired FMD even in the normal coronary angiograms.     

Evidence against the association between alcohol use and ischemic stroke risk

To examine the relationship between alcohol consumption and ischemic stroke risk, we used data from our case-control study of stroke risk. Eighty-nine patients admitted to the hospital with ischemic stroke documented by computed tomography of the head were matched to 178 controls. Alcohol use was defined by an estimate of customary use (heavy, moderate, light, or none). We found no consistent or significant association between any level of alcohol use and ischemic stroke risk (odds ratios: any, 1.3; heavy, 0.5; moderate, 1.5; and light, 1.5). We repeated the analysis of our study using a control group assembled according to the study criteria of another case-control study that reported a significant association in men with heavy alcohol use (odds ratio, 4.2). We demonstrated that the association in the prior study may be spurious due to methodological problems.     

Long-term prognostic role of flow-mediated dilatation of the brachial artery after acute coronary syndromes without ST elevation

Coronary endothelial vasodilator dysfunction is associated with increased cardiac events; the close relation between coronary vasomotor dysfunction and brachial artery vasoreactivity has been previously described. This study assessed the prognostic value of noninvasively assessed brachial artery vasoreactivity in survivors of acute coronary syndromes without ST-segment elevation. We examined 98 men (63.1 +/- 10.8 years) who were referred to our hospital for acute coronary syndromes without ST-segment elevation. Brachial artery endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent nitrate-mediated dilation were examined in all patients using high-resolution echocardiographic Doppler ultrasound within 24 hours of admission. Plasma malondialdehyde, a marker of oxidative stress, and left ventricular ejection fraction were also assessed. Twenty-seven patients underwent coronary revascularization. Patients were followed for 24.8 +/- 5.9 months. Cardiovascular death, myocardial infarction, stroke, and unstable angina were designated as cardiovascular events (CEs). Twenty CEs were recorded. Kaplan-Meyer analysis showed that patients with FMD <1.9% (tertile 1 of FMD values) were more likely to have CEs than those with FMD >1.9% (log rank 5.29, p = 0.021). Multivariate Cox regression analysis showed that FMD <1.9% predicted CEs with an adjusted hazard ratio of 3.035 (95% confidence interval 1.148 to 8.023, p = 0.025) after adjustment for age, risk factors, troponin T, ejection fraction, revascularization procedures, number of diseased vessels, and medication. In conclusion, endothelium-dependent dilation of the brachial artery is a strong independent predictor of adverse outcome in survivors of acute coronary syndromes without ST-segment elevation.     

Alpha1-antitrypsin gene polymorphisms are not associated with renal arterial fibromuscular dysplasia

OBJECTIVE: We previously showed that fibromuscular dysplasia (FMD) of the renal artery may be familial. Case reports have associated alpha1-antitrypsin deficiency and FMD. The aim of this study was to test the implication of the alpha1-antitrypsin (AAT) gene in a large cohort of patients with renal FMD. MATERIALS AND METHODS: A case-control study comparing the genotype frequencies in 161 consecutive patients with angiographically proven renal FMD with those observed in three sets of controls (353 hypertensive patients, 288 normotensive patients, 444 normotensive women) was conducted. High-resolution echotracking of the carotid and radial arteries was performed in a subset of 77 FMD patients. Three functional polymorphisms of the AAT gene (PiM1, PiZ, PiS) were investigated. RESULTS: Clinical (age 44.3 +/- 13.8 years, 85.1% women) and radiological (77.1% of multifocal lesions) characteristics of the FMD population were consistent with those previously published. No differences were found in AAT genotype frequencies in the FMD subjects compared with the 1085 controls. We found no correlation between the AAT genotypes and the clinical and angiographical characteristics of the FMD patients. Echotracking results confirmed our previously published results in FMD patients with a specific pattern and a mean arterial phenotypic score greater than 3. However, no difference in the arterial score was observed across the genotypes. CONCLUSION: Polymorphisms PiM1, PiZ and PiS of the AAT gene are not associated with renal FMD or infraclinical carotid lesions detected by echotracking methods. As the true prevalence of renal FMD is not precisely known and alpha1-antitrypsin deficiency is not infrequent in the general population, the association of the two may occur by chance.