Aging of the venous valves as a new risk factor for venous thrombosis in the elderly: the BATAVIA study.

Essentials Risk of venous thrombosis (VT) related to valve thickness and valvular reflux in unknown. Venous valves and reflux were measured by ultrasonography in cases and controls aged 70+. Risk of VT was associated with increased valve thickness and valvular reflux >1second. Thickening of valves is a generic process: there was no difference between right and left legs. SUMMARY: Background Increasing age is the strongest risk factor for venous thrombosis (VT). Increasing age has been related to a thickening of the venous valves and a decreased valvular function. The association between valve thickness and the risk of VT is not known. Objectives To assess the association between increased valve thickness and valve closure time (VCT) and the risk of VT. Methods Analyses were performed in the BATAVIA study, including 70 cases aged 70 + with a first VT and 96 controls. We performed an ultrasound examination of the valves in the popliteal veins. The valves were imaged with a 9 MHz linear probe using B-mode ultrasonography. VCT was measured as an indicator for valve function using an automatic inflatable cuff. To estimate the risk of VT, valve thickness was dichotomized at the 90th percentile as measured in controls and VCT was dichotomized at 1 s. Results Mean valve thickness of controls was similar in the left (0.36 mm, 95% CI 0.34-0.37) and right (0.36 mm, 95% CI 0.35-0.38) leg. In 45 cases a valve was observed in the contralateral leg with a mean valve thickness of 0.39 mm (95% CI 0.36-0.42). Cases had an increased valve thickness compared with controls: mean difference 0.028 mm (95%CI 0.001-0.055). Valve thickness > 90th percentile increased the risk of VT 2.9-fold. Mean VCT in controls was 0.38 s, in contralateral leg of cases 0.58 s. VCT > 1 s increased the risk of VT 2.8-fold (95% CI 0.8-10.4). Conclusions Risk of VT was associated with increased valve thickness and valvular reflux of > 1 s.

Barrel index of bulky cervical tumours and intrauterine fluid determined by MRI as additional prognostic factors for survival.

OBJECTIVE: to investigate whether morphologic characteristics determined by magnetic resonance imaging (MRI) can discriminate between bulky cervical tumours with a favourable or worse prognosis. MATERIALS AND METHODS: MRI examinations were performed in 24 patients with cervical cancer Stage >or= 1B2. The ratio between tumour width and length (barrel index: BI) and the presence of intrauterine fluid retention were related to survival in a multivariate regression analysis. RESULTS: BI and intracavital fluid were predictors of survival, independent from tumour diameter and other known important factors for survival. A cut-off value of 1.40 for the BI proved to be the best prognostic factor with respect to recurrence and death: the hazard ratios of BI > 1.40 as compared to BI

Management and outcome in 32 neonates with thrombotic events.

Objective. To determine the incidence, management, complications, and outcome in neonates with thrombotic events. Study Design. We performed a retrospective study of all neonates with thrombotic events admitted to our neonatal intensive care unit from January 2004 to July 2010. Results. Thrombotic events were identified in 32 of 4734 neonates (0.7%). Seven neonates were managed expectantly and 25 neonates received anticoagulant treatment. Complete resolution of the clot within 3 months of age was found in 68% (17/25) of the treated and in 86% (6/7) of the nontreated neonates. Major complications due to anticoagulant therapy occurred in 3/25 cases (12%) and included severe hemorrhage (n = 2) and abscess at the injection site (n = 1). Conclusion. Complete or partial clot resolution in neonatal thrombosis occurred in both the treated group and nontreated group. Randomized controlled trials are warranted to determine the optimal management in neonatal thrombosis.

Is screening for renal anomalies warranted in neonates with isolated single umbilical artery?

AIM: To determine the prevalence of renal anomalies in patients with an isolated single umbilical artery (SUA). METHODS: We performed a retrospective study of all renal ultrasound examinations assessed at our centre between January 1998 and December 2008 in neonates with SUA with or without associated anomalies. RESULTS: Renal ultrasound examination was performed in 65 neonates with SUA (57 neonates with isolated SUA and 8 neonates with nonisolated SUA). The prevalence of renal anomalies in the group with and without isolated SUA was 2% (1/57) and 38% (3/8), respectively. Only one patient with isolated SUA had a mild renal abnormality without clinical consequences. CONCLUSIONS: The prevalence of renal anomalies in neonates with isolated SUA is low. We suggest that routine ultrasound screening for renal anomalies is not warranted in neonates with isolated SUA.

Patients with type 3 severe von Willebrand disease are not protected against atherosclerosis: results from a multicenter study in 47 patients.

BACKGROUND: The results of a number of studies in pigs and mice suggest that absence of von Willebrand factor (vWF) protects against the development of atherosclerosis. We studied whether patients with a complete deficiency of vWF (type 3 von Willebrand disease [vWD]) develop fewer atherosclerotic vessel wall changes than healthy controls. METHODS AND RESULTS: This study included 47 individuals with type 3 vWD and 84 healthy controls. Early atherosclerotic changes were assessed by measuring the thickness of the intima-media in the carotid and femoral arteries by B-mode ultrasonography. Advanced atherosclerotic changes were quantified by summing the maximal thickness of atherosclerotic plaques in the carotid and femoral arteries and were expressed as a plaque score. Established risk factors were determined to adjust for possible differences between the groups. We found no substantial difference in intima-media thickness between vWD patients and controls (adjusted difference for carotid artery 0.007 mm, 95% CI -0.022 to 0.036 mm; femoral artery 0.069 mm, 95% CI -0.056 to 0.19 mm). Similar proportions of patients and controls had atherosclerotic plaques (19% and 17%, respectively). No difference was found in the plaque score between groups (adjusted difference -0.22 mm, 95% CI -0.69 to 0.26). Among vWD patients, we found no effect of treatment with vWF concentrates on intima-media thickness or plaque score. CONCLUSIONS: The results of this study indicate that vWF does not play a substantial role in human atherogenesis.

Decreased mortality of ischaemic heart disease among carriers of haemophilia.

BACKGROUND: Coagulation plays an important part in ischaemic cardiovascular disease. Results of studies have shown that extremes in hypocoagulability protect against ischaemic cardiovascular disease. We have investigated overall mortality and death from cardiovascular causes in carriers of haemophilia, who in most cases have mildly decreased coagulability without clinical signs. METHODS: We followed-up a cohort of 1012 mothers of all known people with haemophilia in the Netherlands from birth to death, or the end-of-study date (41984 person years of follow-up). We obtained vital status and causes of death, if deceased, and compared overall and cause-specific mortality in our cohort with that in the general Dutch female population adjusted for age and calendar period by calculating the standardised mortality ratio (SMR). FINDINGS: Overall mortality was reduced by 22% (261 observed deaths, 333.74 expected; SMR 0.78 [95% CI 0.69-0.88]). Deaths from ischaemic heart disease were reduced by 36% (39 observed deaths, 60.53 expected; SMR 0.64 [0.47-0.88]). We did not note decreased mortality for cerebral stroke (ischaemic and haemorrhagic combined) (28 observed deaths, 36.82 expected; SMR 0.76 [0.53-1.10]). A separate analysis of these two types of stroke was not possible. Women in our cohort had an increased risk of death from extracranial haemorrhage (5 observed deaths, 0.18 expected; SMR 27.78 [8.49-58.18]); however, the number of deaths from this cause was much lower than that for ischaemic heart disease. CONCLUSION: The results show that a mild decrease in coagulability has a protective effect against fatal ischaemic heart disease.

Lipoprotein(a) and ultrasonographically determined early atherosclerotic changes in the carotid and femoral artery.

Recent studies suggest that high lipoprotein(a) [Lp(a)] plasma levels are associated with symptomatic ischemic cardiovascular disease. We examined whether Lp(a) plasma levels are associated with early atherosclerotic vessel wall changes in a group of asymptomatic subjects. In a group of 142 asymptomatic men, the intima-media thickness (IMT) in the common carotid artery, the carotid bifurcation and the common femoral artery was determined by B-mode ultrasonography. In addition to Lp(a) levels, established risk factors, such as blood pressure and cholesterol levels were determined. Lipoprotein(a) values ranged from 2 mg L(-1) to 900 mg L(-1) (median 145 mg L(-1)). Linear regression analysis showed a clear association of IMT with the established risk factors but not with Lp(a) [regression coefficient carotid artery -0.0003, 95% confidence interval (CI) -0.002-0.001; regression coefficient femoral artery -0.0003, 95% CI -0.004-0.003]. We found no increased intima-media thickness in the carotid or femoral artery at high levels of Lp(a). Lipoprotein(a) levels are not associated with early atherosclerotic vessel wall changes in the carotid or femoral artery.

Arterial intima-media thickness and its relationship with cardiovascular disease and atherosclerosis: a possible contribution of medium-sized arteries.

The intima-media thickness (IMT) of the arterial wall, measured by B-mode ultrasonography, has been related to cardiovascular disease and atherosclerosis in many studies, most of which have considered carotid and common femoral arteries. No study has related the IMT of medium-sized arteries (e.g. brachial) to the atherosclerotic process. The aim of this study was to evaluate whether more peripheral arteries (e.g. brachial, superficial femoral and popliteal) represent a good model in studies of arterial wall IMT, as well as carotid artery. Twenty-six male patients with demonstrated coronary artery disease (median age 63 yrs; range 41-70) and twenty-four male controls (median age 62 yrs; range 53-74) were studied. The far-wall IMT of the common carotid, brachial, superficial femoral and popliteal arteries was measured by high-resolution B-mode ultrasonography. Its relationship with ischemic cardiovascular disease and the presence of atherosclerotic plaques in all the arteries was also evaluated. Mean IMT values were higher in patients than controls, more so in superficial femoral artery (IMT difference 0.08 mm [95% confidence interval 0.02 - 0.14]) and popliteal artery (0.08 [0.01-0.15]) than in common carotid artery (0.02 [-0.07-0.11]) or brachial artery (0.01[-0.01-0.03]). The difference did not change after adjustment for age. The prevalence of plaques was consistently higher in patients than controls, except for brachial artery, in which no plaque was found either in patients and controls. In all the arteries except brachial we found an association between increase in IMT and number of plaques. Age was strongly related to the presence of plaques in the carotid artery, and less markedly in superficial femoral and popliteal arteries. The brachial artery does not seem a good model to study atherosclerosis by ultrasound measurements of arterial IMT, whereas superficial femoral and popliteal arteries might be chosen for these studies besides carotid artery.

Decreased coagulability has no clinically relevant effect on atherogenesis: observations in individuals with a hereditary bleeding tendency.

BACKGROUND: Hemostasis affects ischemic cardiovascular disease through its role in formation of occluding arterial thrombi. Several studies suggest that hemostasis also might play a role in atherogenesis. We investigated whether individuals with an inherited bleeding tendency are protected against development of atherosclerosis. METHODS AND RESULTS: A total of 76 individuals with an inherited bleeding tendency (hemophilia and von Willebrand disease) and 142 healthy controls were included in the present study. Early atherosclerotic vessel-wall changes were quantified by measurement of intima-media thickness in the carotid and femoral arteries by B-mode ultrasonography. To validate intima-media thickness measurements, measurements also were performed in 77 individuals with clinically proven atherosclerosis and in 34 healthy, age-matched controls. A large difference in intima-media thickness was found between individuals with proven atherosclerosis and healthy controls, in particular for the femoral artery (difference for carotid artery, 0.16 mm; femoral artery, 0.53 mm). Comparison between patients with a bleeding tendency and healthy controls showed only minimally reduced intima-media in femoral artery in individuals with a bleeding tendency (adjusted difference, -0.078 mm; 95% CI, -0.17 to 0.018 mm). Subgroup analysis revealed that in subjects with moderate to severe hemophilia, vessel walls were thinnest (adjusted difference, -0.10 mm; 95% CI, -0.27 to 0.061 mm). CONCLUSIONS: Hypocoagulability caused by hemophilia or von Willebrand disease has at most a limited effect on atherogenesis.

Ultrasound assessment of atherosclerotic vessel wall changes: reproducibility of intima-media thickness measurements in carotid and femoral arteries.

RATIONALE AND OBJECTIVES: Ultrasonography is widely used in cardiovascular research to quantify early atherosclerotic vessel wall changes. In this article, we examined the short- and long-term reproducibility of this technique in the common carotid artery, carotid bifurcation, common femoral artery, and superficial femoral artery. Furthermore, we assessed the effect of progressed atherosclerosis on reproducibility. METHODS: Repeated ultrasound examinations were performed by one observer on 15 healthy individuals and 18 patients suffering from coronary heart disease. Intima-media thickness was determined by B-mode ultrasonography. The examinations were repeated by the same observer after a short time interval (short-term) and after a few weeks (long-term) and expressed as the mean difference between the measurements and the coefficient of variation (CV). RESULTS: The reproducibility of the intima-media thickness determination turned out to be best in the common carotid artery and the superficial femoral artery when performed in healthy controls (CV 5.6% and 5.5%, respectively). Reproducibility was less in patients with clinical atherosclerosis; this especially affected the reliability of the superficial femoral artery measurement (CV in healthy controls was 5.5%; in coronary heart disease patients, 17.5 %). The reliability of the intima-media thickness measurements in the common carotid artery (CV in healthy controls was 5.6%; in coronary heart disease patients, 9.5%) proved to be least affected by progressed atherosclerosis. A longer time interval between measurements did not affect the reproducibility of intima-media thickness measurements in healthy controls, whereas in the patients it led to some decrease of reproducibility and to a major decrease in reproducibility of the superficial femoral artery measurements (CV changed from 12.7% to 17.5%). CONCLUSIONS: Ultrasonography is a reliable and accurate technique to determine intima-media thickness in superficial arteries. In studies in which the intima-media thickness determination is used as a marker for generalized and coronary atherosclerosis, the common carotid artery should always be included, whereas the benefit of inclusion of other arteries depends on age and the expected extent of atherosclerosis in the individuals studied.

Usefulness of patient interview in bleeding disorders.

BACKGROUND: It is not known which questions in a medical interview are most informative for diagnosing mild bleeding disorders, and what the value is of the entire interview in screening for hemostatic disorders. METHODS: A questionnaire was sent to 222 patients with a proven bleeding disorder, to 134 patients suspected of a bleeding disorder but whose hemostasis proved normal, and to 341 healthy volunteers. A first comparison, between patients with a bleeding disorder and patients with bleeding complaints whose hemostasis proved normal, mimics the situation in a department of hematology where patients are referred because of complaints. The second comparison, between patients with a proven bleeding disorder and healthy volunteers, may serve as a model for the situation where the interview is used as a screening tool to detect patients with a bleeding disorder in a population where there is no prior suspicion, eg, before surgical intervention. For each question we calculated a univariate odds ratio, multivariate odds ratios, and a positive and negative likelihood ratio. With a receiver operating characteristic curve analysis we evaluated the value of a simple vs an elaborate interview. RESULTS: Ninety-two percent of the questionnaires were returned. For both comparisons the most informative questions were questions about bleeding disorders in the family and traumatic events, with the exception of delivery. Noninformative questions were frequent gumbleeds and blood in the urine. A receiver operating characteristic curve analysis revealed that a simple interview has a high discriminating power in a screening situation, whereas in a referred situation even an elaborate interview has a low performance. CONCLUSIONS: A simple interview is useful as a screening tool for the dentist or surgeon. In a specialized hematology center with referred patients, however, the interview is of little value in identifying patients with a bleeding disorder.

A randomized and blinded comparison of three bleeding time techniques: the Ivy method, and the Simplate II method in two directions.

We compared the Ivy bleeding time method and two alternatives of the Simplate II method (incisions in horizontal and vertical direction) with each other, with regard to the sensitivity, the specificity, the costs and the burden for the patient. In the aspirin study an aspirin-induced bleeding defect was used. Seventy-two healthy volunteers were randomized to receive either 500 mg acetylsalicylic acid (ASA) or a placebo. Double blinding was maintained throughout the study. In the anticoagulation study 62 patients participated, who received oral anticoagulants (OAC) for various reasons. All participants received two bleeding time methods. The burden for the participants of each method was screened by a small standard questionnaire. The differences in sensitivity and specificity between the three methods proved minimal. The Ivy method was more often preferred by the participants than the Simplate methods. Since a choice on the basis of sensitivity and specificity appears not possible, we prefer the Ivy method because of lower costs and less burden.