Left ventricles of aging athletes: better untwisters but not more relaxed during exercise.

OBJECTIVE: With an aging population and the increasing prevalence of heart failure with preserved ejection fraction, developing strategies to prevent diastolic dysfunction is crucial. Regular endurance training has been suggested to be one such strategy. However, the underlying mechanisms of training, including the effect on left ventricular (LV) untwist, which promotes LV filling, are unclear and studies exploring the heart during exercise in the aging heart are lacking. METHODS: Cardiopulmonary exercise testing with speckle tracking echocardiography was realized in male subjects: 16 young athletes (YA), 19 young controls (YC), 22 middle-aged athletes (MA) with a lifelong history of endurance training, and 20 middle-aged controls (MC). RESULTS: During exercise, the early filling was lower in MC compared to YC, whereas it was preserved between YA and MA. At exercise, peak untwisting rate/peak twist ratio and the percentage of untwist during isovolumic relaxation time were decreased in senior groups but higher in YA and MA compared to age-matched controls. Early diastolic filling reserve correlated with untwisting rate/peak twist reserve in YA and MA (R 2 = 0.22, p < 0.05) but not in controls. LV relaxation indices in athletes at rest and during exercise were not improved compared to age-matched controls. CONCLUSION: LV intrinsic relaxation was similarly lower with age, independently of training, while the age-related decrease of untwist during exercise was lower with lifelong exercise training. The preservation of untwist mechanics in MA could thus sustain the early filling during exercise. Further studies are needed to confirm the role of exercise training as a preventive strategy for diastolic dysfunction and heart failure.

From Korotkoff and Marey to automatic non-invasive oscillometric blood pressure measurement: does easiness come with reliability?

The auscultatory technique remains the point of reference for the validation of non-invasive blood pressure measurement devices, although the exact origin of the Korotkoff sounds is still debated and comparison with intra-arterial measurement shows limits and pitfalls. Automatic oscillometric devices are now widely used by nurses, physicians, and patients. However, many available devices have not been duly validated. Moreover, they calculate systolic and diastolic blood pressures using undisclosed algorithms. Therefore, these devices are not interchangeable, and their reliability may be questionable in some clinical situations. Nevertheless, oscillometry is increasingly used, beside NIBP, for the assessment of central blood pressure and systemic arterial wall stiffness. Awareness of its limits and causes of error is all the more necessary.

[B-mode sonography visualizing microemboli flow in the main cerebral arteries]. / Visualisation du passage de micro-emboles cérébraux par ultrasonographie en mode B-Flow.

In a patient with a mechanical prosthetic aortic valve admitted for transient amnesia, transcranial duplex Doppler and B-mode sonography visualized the transit of microemboli along the main cerebral arteries. Gaseous microemboli resulting from a cavitation phenomenon at valve closure were seen as high-intensity transient signals (HITS). To our knowledge, this is the first report of microemboli flow visualized in B-mode.

[Deep venous thrombosis complications during infections in pediatric patients: analysis of a series of 24 cases]. / Infections et thromboses veineuses en pédiatrie : analyse d'une série de 24 cas.

Venous thromboembolism disease (VTE) is rare in children (5.3 of 10,000 hospitalized children). However, morbidity and mortality are high, especially when the child is already suffering from severe sepsis. We report an analytical study of 24 cases of deep venous thrombosis occurring in children during infection, recorded at the Montpellier University Hospital between 1999 and 2009. Many parameters were studied in each population (age, sex, familial and personal history of thrombosis, history of thrombophilia, the presence of a venous catheter, a causative organism, time to onset of thrombus, topography of lesions, acquired abnormalities of hemostasis, and thrombosis prophylaxis). The children were aged from 1 day of life to 16 years. Thromboses occurred in two clinical contexts: "contact" thrombosis (which appeared near the infection) and disseminated thrombosis. This is an early complication because in most of the cases, it appeared in the first 10 days of sepsis. Infection and coagulation appear to be closely related and the states of latent or decompensated disseminated intravascular coagulation are common. Nevertheless, it is not possible to predict the occurence of a thrombotic event. The presence of risk factors (venous catheters, acquired thrombophilia, or constitutional thrombophilia) may increase the thrombogenic potential of the infection. VTE should always be suspected and sought in case of an unfavorable clinical course, and routine prophylaxis of thrombosis during sepsis should be discussed.

[Role of duplex ultrasound for lower limb artery, abdominal aorta, and carotid artery surgery follow-up]. / Le rôle de l'échographie-Doppler dans la surveillance après chirurgie artérielle des artères des membres inférieurs, de l'aorte et des artères carotides.

Long-term post-surgery follow-up is an essential part of the surgical and medical care for vascular surgery patients with peripheral arterial disease. Close collaboration with the patient's primary care physician is essential. In addition to close surveillance of the outcome after vascular surgery, follow-up includes an assessment and appropriate treatment of cardiovascular risk factors. Duplex ultrasound is a safe and noninvasive surveillance method, which should be performed by an experimented physician. We summarize the specific features of duplex ultrasound examinations after arterial surgery of the carotid arteries, the abdominal aorta and the lower limbs, and propose a surveillance schedule.

Vascular reactivity at rest and during exercise in middle-aged obese men: effects of short-term, low-intensity, exercise training.

OBJECTIVE: Although increased blood flow (BF) in exercising muscles is thought to be impaired in obese subjects and may contribute to physical inactivity, data are scarce in this regard and the involvement of endothelium dysfunction remains partly hypothetical. METHODS: A total of 16 middle-aged obese men (body mass index, BMI ≥ 30 kg m(-2)) and 16 normal-weight men (BMI<25 kg m(-2)), matched for age, were recruited. We used ultrasonography to compare intima-media thickness (IMT) and distensibility of the carotid artery, flow-mediated dilation (FMD), nitrate-dependent dilation (NDD) and peak BF during post-ischemic hyperemia in the brachial artery (a conduit artery), and leg BF during knee-extensor exercise (indicative of resistance vessel function) in obese and in normal-weight men. In addition, 10 obese men participated in an 8 week individualized low-intensity training program. RESULTS: Compared with normal-weight men, obese men had higher carotid IMT (0.50 ± 0.01 vs 0.62 ± 0.04 mm, P < 0.05) but lower carotid distensibility (0.26 ± 0.03 vs 0.11 ± 0.03 mm Hg(-1) 10(-2), P < 0.05), FMD (5.7 ± 0.4 vs 3.3 ± 0.5%, P < 0.05) and peak BF during post-ischemic hyperemia (398 ± 52 vs 229 ± 24%, P < 0.05), despite similar maximal shear rate, without NDD differences. Lower limb BF (ml min(-1) 100 g(-1)) increased significantly from rest to maximal exercise in both groups with lower values in obese men (at peak power, 36.9 ± 1.6 vs 31.5+2.2 ml min(-1) 100 g(-1), P < 0.05). Exercise training normalized carotid distensibility (0.14 ± 0.04 before vs 0.23 ± 0.03 mm Hg(-1) 10(-2) after training, P = 0.09) and FMD (2.7 ± 0.4 before vs 4.8 ± 0.5% after training, P < 0.05), but did not improve brachial post-ischemic peak BF or exercising leg BF. CONCLUSIONS: In obese men, conduit and resistance vessel reactivity is depressed, but a short-term low-intensity exercise training improves distensibility and endothelium dependent vasodilation in the large conduit artery, but not post ischemic or exercise muscle BF.

Validation of a fully automatic photoplethysmographic device for toe blood pressure measurement.

OBJECTIVES: This study was designed to assess the accuracy and reliability of a new, portable, fully automated photoplethysmography (PPG) device for toe blood pressure (TBP) measurement. DESIGN: Within-subject comparison with conventional laser Doppler (LD) measurement. MATERIALS AND METHODS: Four TBP measurements were performed on both lower limbs, alternatively with LD and PPG in 200 patients recruited at the Nîmes University Hospital. Reproducibility was assessed by the intraclass correlation coefficient (ICC). The concordance between the two methods was evaluated by Lin's concordance correlation coefficient (CCC), in the whole population as well as in comorbidity subgroups. A potential bias was investigated with the Bland and Altman method. RESULTS: The ICC was 0.887 (95% confidence interval (CI) 0.852-0.913) and 0.893 (0.860-0.918) on the right side (n = 193), 0.905 (0.875-0.928) and 0.898 (0.866-0.922) on the left side (n = 188) for PPG and LD measurements, respectively. The CCC was 0.913 (0.885-0.934) on the right side and 0.915 (0.888-0.937) on the left side, and remained >0.8 regardless of co-morbidities. CONCLUSIONS: This new, fully automatic, photoplethysmographic device yielded reliable TBP measurements and showed good agreement with the reference LD system over a wide range of values.

Paternal endothelial protein C receptor 219Gly variant as a mild and limited risk factor for deep vein thrombosis during pregnancy.

BACKGROUND: Half of all venous thromboembolism (VTE) cases during pregnancy are associated with a maternal thrombophilia. The influence of paternal genotype on the placenta and in the genesis of VTE has not been described. OBJECTIVES: To determine if the maternal and paternal Ser219Gly dimorphism of the endothelial protein C receptor (EPCR), evaluated through detection of the PROCR 6936G allele, is a risk factor for VTE during pregnancy. METHODS: Using a case-control study nested in the NOHA first cohort of primigravidae, 66 patient couples with a first episode of gestational VTE and randomly selected non-thrombotic control couples were investigated. For each couple, factor V gene (F5) G1691A, factor II gene (F2) G20210A, factor XII gene (F12) C46T and PROCR A6936G polymorphisms were determined. RESULTS: Only maternal F5 1691A, F2 20210A and F12 46T alleles were independently associated with iliac and infra-iliac deep vein thromboses (DVT). The maternal PROCR 6936G allele was a mild risk factor for iliac DVT (OR = 5.5 [2.3-13.0]). The paternal PROCR 6936G allele was also a mild independent risk factor for iliac DVT (OR = 2.6 [1.1-6.2]) and only during pregnancy (rather than postpartum) among maternal carriers of the F5 1691A allele (OR = 77.6 [4.2 to > 999.9]). CONCLUSIONS: The paternal PROCR 6936G allele could be a risk factor for maternal iliac DVT. Its impact was milder than the F5 1691A and F2 20210A polymorphisms in mothers. We hypothesize that the prothrombotic effect of the paternal PROCR 6936G allele is localized. Therefore, DVT during pregnancy may be influenced by trophoblastic cell-surface proteins inherited from both maternal and paternal alleles.

Alteration of endothelium-mediated vasodilator response in the rat hindlimb vasculature consecutive to chronic hypoxic stress: NO and EDHF involvement.

The previously documented impairment of hindlimb blood flow consecutive to chronic hypoxia might be related to endothelial vasomotor dysfunction. The aim of this study was to assess in-vivo the effect of chronic hypoxic stress on endothelium-mediated vasodilator response of hindlimb vascular bed, especially as regards to endothelium-derived hyperpolarizing factor (EDHF) and nitric oxide (NO) pathway contribution. Dark Agouti rats were randomly assigned to live at barometric pressure approximately 760 mmHg (N rats) or approximately 550 mmHg (CH rats). Under anesthesia, catheters were placed in the carotid artery for arterial pressure measurement, and in the saphenous vein and iliac artery for drug delivery. Hindlimb blood flow (HBF) was measured by transit-time ultrasound flowmetry, at baseline and during endothelium-dependent vasodilator response induced by intra-arterial injection of acetylcholine (0.75 ng and 7.5 ng) with and without specific blockers of NOS (L-NAME) and EDHF (Charybdotoxin+Apamin). HBF and hindlimb vascular conductance changes in response to ACh infusion were significantly lower in CH than in N rats. The mechanisms responsible for this blunted response involved impairment in both NO pathway and EDHF. The chronic hypoxia-induced alteration of NO pathway was mainly related to the bioavailability of its substrate l-Arginine, since the infusion of l-Arginine restored the endothelial response to ACh in CH rats to the level of N rats. These results demonstrate that the impairment in endothelium-mediated vasodilator response of the hindlimb vascular tree induced by chronic hypoxic stress involves both NO and EDHF.

Abnormal vascular reactivity at rest and exercise in obese boys.

BACKGROUND: Obese children exhibit vascular disorders at rest depending on their pubertal status, degree of obesity, and level of insulin resistance. However, data regarding their vascular function during exercise remain scarce. The aims of the present study were to evaluate vascular morphology and function at rest, and lower limb blood flow during exercise, in prepubertal boys with mild-to-moderate obesity and in lean controls. MATERIALS AND METHODS: Twelve moderately obese prepubertal boys [Body Mass Index (BMI: 23.9+/-2.6 kg m(-2))] and thirteen controls (BMI:17.4+/-1.8 kg m(-2)), matched for age (mean age: 11.6+/-0.6 years) were recruited. We measured carotid intima-media thickness (IMT) and wall compliance and incremental elastic modulus, resting brachial flow-mediated dilation (FMD) and nitrate-dependent dilation (NDD), lower limb blood flow during local knee-extensor incremental and maximal exercise, body fat content (DEXA), blood pressure, blood lipids, insulin and glucose. RESULTS: Compared to lean controls, obese boys had greater IMT (0.47+/-0.06 vs. 0.42+/-0.03 mm, P<0.05) but lower FMD (4.6+/-2.8 vs. 8.8+/-3.2%, P<0.01) in spite of similar maximal shear rate, without NDD differences. Lower limb blood flow (mL min(-1).100 g(-1)) increased significantly from rest to maximal exercise in both groups, although obese children reached lower values than lean counterparts whatever the exercise intensity. CONCLUSIONS: Mild-to-moderate obesity in prepubertal boys without insulin resistance is associated with impaired endothelial function and blunted muscle perfusion response to local dynamic exercise without alteration of vascular smooth muscle reactivity.

Anatomical basis of transgluteal pudendal nerve block.

BACKGROUND: The pudendal nerve may become entrapped either within the pudendal canal or near the sacrotuberous ligament resulting in a partial conduction block. The goal of the present anatomical study was to assess a new transgluteal injection technique in terms of the precise injection site and the resulting distribution of the injected agent. MATERIALS AND METHODS: This study was carried out using eight fresh human cadavers. An epidural needle with a removable wing was inserted and the catheter position visualized using MRI. Through the catheter 10 ml of gadolinium contrast medium was injected into three of the cadavers. A further four cadavers were injected with latex and blue pigment and the pelvi-perineal area of each then separated from the trunk for freezing before being cut into 4-8 mm thick sections with an electric bandsaw. One final cadaver was injected with a mix of gadolinium (5 ml) and latex (5 ml) and both the MRI and anatomical procedures outlined above were performed. RESULTS: Using MRI, we clearly imaged both the site of injection, near the trunk of the pudendal nerve, and the gadolinium contrast medium in different pelvic and perineal areas and around the fascia of the obturator internus and levator ani muscle. Concerning the anatomical study, latex was observed mainly around the sacrotuberous ligament, along the obturator internus muscle and in the perineal area in contact with the dividing branches of the pudendal nerve. The mixed injection of latex and gadolinium in the pudendal canal was found with the same localization between MRI and anatomical studies. CONCLUSION: This easily performed technique should provide a new approach for treating perineal neuralgia via pudendal nerve block in the consultation room without the need for computed tomography.

Alteration in left ventricular normal and shear strains evaluated by 2D-strain echocardiography in the athlete's heart.

The contraction of cardiomyocytes induces a systolic increase in left ventricular (LV) normal (radial, circumferential and longitudinal) and shear strains, whose functional consequences have not been evaluated, so far, in athletes. We used 2D ultrasound speckle tracking imaging (STI) to evaluate LV regional strain in high-level cyclists compared to sedentary controls. Sixteen male elite cyclists and 23 sedentary controls underwent conventional, tissue Doppler, and STI echocardiography at rest. We assessed LV long and short axis normal strains and shear strains. We evaluated circumferential-longitudinal shear strain from LV torsion, and circumferential-radial shear strain from the difference between subendocardial and subepicardial torsion. Apical radial strain (42.7 +/- 10.5% versus 52.2 +/- 14.3%, P < 0.05) and LV torsion (6.0 +/- 1.8 deg versus 9.2 +/- 3.2 deg, P < 0.01) were lower in cyclists than in controls, respectively. Rotations and torsion were higher in the subendocardial than in the subepicardial region in sedentary controls, but not in cyclists. Haemodynamic and tissue Doppler based indexes of global LV diastolic and systolic functions were not different between cyclists and controls. Athlete's heart is associated with specific LV adaptation including lower apical strain and lower myocardial shear strains, with no change in global LV diastolic and systolic function. These mechanical alterations could improve the cardiovascular adjustments to exercise by increasing the radial strain and torsional (and thus untwisting) response to exercise, a key element of diastolic filling and thus of cardiac performance in athletes.

High plasmatic angiotensin-converting enzyme (ACE) activity is not correlated with training-induced left ventricular growth in ACE congenic rats.

AIM: The aim of this study was to determine the influence of angiotensin-converting enzyme (ACE) genotype on left ventricular growth after endurance training, in ACE congenic rats with plasma ACE activity twice as high as the donor strain (LOU), thus mimicking the ACE I/D polymorphism observed in humans. METHODS: LOU and congenic rats (n = 12) were submitted to an endurance training on a treadmill for 7 weeks, while similar LOU and congenic rats (n = 10) constituted the control groups. Blood pressure, skeletal muscle citrate synthase activity, plasma and left ventricular ACE activity were assessed, and echocardiography was performed before and after the training. RESULTS: Angiotensin-converting enzyme plasmatic activity of congenic rats (188.2 +/- 26.6 in controls and 187.1 +/- 22.6 IU in trained rats respectively) was twofold that of the LOU strain (91.9 +/- 23.3 in controls, and 88.3 +/- 18.1 IU in trained rats respectively). After training, congenic and LOU rats showed a similar significant increase in citrate synthase activity (P < 0.05), and in the left ventricular mass/body mass ratio x 10(3): 3.7 +/- 0.3 and 3.6 +/- 0.6 in the trained congenic and LOU groups, respectively, vs. 3.0 +/- 0.1 and 2.9 +/- 0.2 in the control congenic and LOU groups respectively (P < 0.05). There was no significant correlation between ACE plasma activity and left ventricular mass in trained or untrained congenic rats. CONCLUSION: We conclude that training-induced left ventricular growth is not associated with plasma ACE activity in congenic rats.

Flow-mediated dilation and exercise-induced hyperaemia in highly trained athletes: comparison of the upper and lower limb vasculature.

AIM: The main purpose of the present study was to assess whether similar vascular adaptive changes could be obtained by long-term intensive training involving predominantly either the lower or the upper limb musculature. METHODS: In 11 cyclists (C), 10 swimmers (S) and 10 sedentary controls (Sed), duplex Doppler ultrasonography was used to measure post-occlusion endothelium-dependent flow-mediated dilation (FMD), endothelium-independent, glycerine trinitrate-induced dilation (GTND) and exercise-induced blood flow changes in the arm (axillary artery) and leg (superficial femoral artery). Limb-specific exercise was achieved by one elbow-flexion or one leg-extension maximal exercise test, thereby allowing assessment of upper and lower limb muscle perfusion, vascular conductance and vasodilatory capacity of resistance vessels during effort. RESULTS: C and S exhibited vascular remodelling associated with improved FMD and GTND in the predominantly trained limbs compared to Sed. Both showed greater muscle perfusion and vascular conductance than Sed during isolated exercise involving the predominantly trained musculature. C showed also higher FMD in the brachial artery and greater peak muscle perfusion and conductance in the non-exercising muscles, whereas S presented only enhanced FMD in the superficial femoral artery. CONCLUSION: Therefore, in the upper as well as in the lower limb vasculature, repetitive exposure to increased shear stress over a long-term period results in improved FMD of large conduit arteries as well as greater vasodilatory capacity during isolated exercise in the predominantly trained muscles. Long-term training involving predominantly the lower limbs also results in enhanced vascular reactivity in upper limb conduit and resistance vessels.

Use of the PFA-100 closure time to predict cardiovascular events in aspirin-treated cardiovascular patients: a systematic review and meta-analysis.

BACKGROUND: PFA-100 is a point-of-care assay that evaluates platelet reactivity in high-shear-stress conditions by measuring the closure time (CT) of a membrane aperture. When determined with a collagen/epinephrine cartridge (CEPI), the CT is usually prolonged by aspirin. Studies of the predictive value of a short PFA-100CT(CEPI) for ischemic events in aspirin-treated patients have given variable results. OBJECTIVES: To conduct a systematic review and meta-analysis of studies on the clinical predictive value of a short PFA-100CT(CEPI) in aspirin-treated cardiovascular patients. PATIENTS AND METHODS: Relevant studies were identified by scanning electronic databases. Studies were selected if they included aspirin-treated patients with symptomatic atherosclerosis, measured the PFA-100CT(CEPI), used a CT cut-off value to define aspirin 'responders' and 'non-responders', and reported ischemic events. RESULTS: We selected seven non-prospective studies (1466 patients) and eight prospective studies (1227 patients). In non-prospective studies, the PFA-100CT(CEPI) was performed after the ischemic clinical endpoint, and a publication bias was identified. In prospective studies, the global odds ratio (OR) for the recurrence of an ischemic event in 'aspirin non-responders' relative to 'aspirin responders' was 2.1 [95% confidence interval (CI) 1.4-3.4, P < 0.001]. Pooled analysis with a random effect model revealed no heterogeneity (Q Cochran P = 0.36 and I(2) = 9.4%). CONCLUSIONS: A short PFA-100CT(CEPI) is associated with increased recurrence of ischemic events in aspirin-treated cardiovascular patients. This finding needs to be confirmed in stable ischemic patients, and the PFA-100CT(CEPI) cut-off needs to be refined in these patients.

Aortic vasoconstriction related to smooth muscle cells ET-A and ET-B receptors is not involved in hypoxia-induced sustained systemic arterial hypertension in rats.

OBJECTIVES: We report in the present study the role of endothelin (ET-1) and ET-1 receptors in the sustained hypoxia-induced systemic hypertension. METHODS: Wistar rats were randomly assigned to live continuously in hypobaric hypoxia (CH rats) or normoxia (N rats). At the end of hypoxic stress exposure (5 weeks at 450 mm Hg), measurements of mean systemic arterial pressure were done. The effects of ET-1 in the presence or not of the endothelium and/or of specific ET-A inhibitors (BQ-123) or ET-B inhibitors (BQ-788), have been investigated in an isolated model of rat thoracic aorta. Finally, plasmatic ET-1 concentrations have been determined by assay procedure. RESULTS: Following five weeks of chronic hypoxic stress, CH rats presented a significant increase of mean systemic arterial pressure (N: 129.1+/-6.8 mm Hg vs CH: 152.5+/-3.4 mm Hg; P<0.05). Despite of this hypoxia-induced hypertension, ET-1 plasmatic concentration was not different between N and CH rats. Finally, CH rats presented a reduce response to ET-1 when compared to N rats. This phenomenon seems to be associated to the ET-A vascular smooth muscle cell receptors, since difference between N and CH rats was still present in endothelium denuded aortic rings in the presence or not of the specific ET-B inhibitors (BQ-788). In addition, in the presence of the specific ET-A inhibitor (BQ-123) response to ET-1 was abolished in N and CH rats to the same extent (N:-98%; CH:-99%). CONCLUSION: This work clearly suggests that, following long term exposure to hypoxia, ET-1 and ET-1 receptors are not involved in the persistence of systemic hypertension in a rat model, and that chronic exposure to severe hypoxic stress was associated with a downregulation of the ET-A receptors response to ET-1.

[Visceral artery aneurysms. Multiple aneurysmal localization: a case report and literature review]. / Les anévrismes des artères digestives. A propos d'un cas clinique de localisation anévrismale multiple et revue de la littérature.

Visceral artery aneurysms constitute a rare vascular disease, with a risk of rupture associated to a high mortality. Often asymptomatic, they are discovered following a routine radiological examination. We present the case of a 71-year-old patient with multiple aneurysms involving the celiac trunk, the splenic artery, and the common hepatic artery. The surgical treatment consisted of an aortohepatic bypass using polytetrafluoroethylene prosthesis, after exclusion of all the aneurysms. The angiography and postoperative angioscan demonstrated the perfect patency of the prosthesis, totally excluding the aneurysms. Given the variety of presentations and the absence of precise predictive factors, there is no therapeutic consensus so far. Surgery is the first therapeutic choice. Endovascular treatment by angioembolization must be reserved for particular conditions. The purpose of this article is to propose the best therapeutic approach on the basis of evidence in the literature.

Homozygosity for the C46T polymorphism of the F12 gene is a risk factor for venous thrombosis during the first pregnancy.

BACKGROUND: A first thromboembolic event during pregnancy and puerperium is predisposed to by polymorphisms G1691A in the factor V gene (F5) (F5G1691A) and G20210A in the prothrombin gene (F2) (F2G20210A). OBJECTIVES: To study another potentially frequent thrombogenic polymorphism, C46T in the factor XII gene (F12) (F12C46T). PATIENTS AND METHODS: The 32 463 previously asymptomatic women included in the NOHA First cohort in their first pregnancy were investigated for these three polymorphisms. No other constitutional or acquired thrombophilic risk factor was studied. RESULTS: The overall incidence--absolute risk--of venous thromboembolic events (VTE) was 127 per 100,000 woman-years and was reduced to 22 per 100,000 women-years in women negative for the three polymorphisms (P < 0.0001). Homozygosity for F12C46T was associated with a significant relative risk (RR) of VTE [RR: 5.99, 95% confidence interval (95% CI): 2.1-17.3, P = 0.001], as was heterozygosity for F5G1691A (RR: 18.7, 95% CI: 8.3-42, P < 0.0001), heterozygosity for F2G20210A (RR: 14.3, 95% CI: 6.2-33.2, P < 0.0001), maternal age (RR: 1.18, 95% CI: 1.07-1.29, P = 0.0006), maternal body mass index (RR: 1.31, 95% CI: 1.11-1.55, P = 0.002), conceptus weight (percentiles adjusted for term of delivery; RR: 0.90, 95% CI: 0.88-0.93, P < 0.0001) and pre-eclampsia (RR: 3.03, 95% CI: 1.06-8.69, P = 0.039). CONCLUSIONS: Homozygosity for the C46T polymorphism of the F12 gene is associated with venous thrombosis during the first pregnancy/puerperium in previously asymptomatic women.