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Aims: Metabolic disorders depend on genetic, hormonal and environmental factors, whose relations may differ between genders. Therefore, we compared the contribution of metabolic disorders to the metabolic syndrome in women and men. Methods: To this end, we used a hierarchical classification statistical method to classify subjects into similarity groups according to clinical and biological parameters. Data were collected from 3,508 men and women aged 35–64 years, from a cardiovascular disease survey. Results: In both women and men, hierarchical classification identified a cluster corresponding to the metabolic syndrome representing 14 and 15% of the women’s and men’s sample, respectively. In women, elevated body weight (women’s Z-score: 1.59 vs. men’s Z-score: 1.29; p < 0.005), waist girth (1.62 vs. 1.30; p < 0.001) and low HDL cholesterol (–0.95 vs. –0.75; p < 0.05) were significantly larger contributors to the metabolic syndrome than in men. In contrast, systolic (0.59 vs. 0.95; p < 0.0001) and diastolic (0.55 vs. 0.99; p < 0.0001) blood pressure and apolipoprotein B (0.51 vs. 0.71; p < 0.0001) contributed significantly less in women than in men. Finally, insulin (n.s.), glucose (n.s.), triglycerides (n.s.) and LDL-cholesterol (n.s.) contributions were not different between genders. Conclusion: These results are consistent with the concept that a clustering of metabolic disorders occurs frequently in both women and men. However, the contribution of several metabolic disorders to the metabolic syndrome is different in men and women. This finding supports the concept that different criteria are necessary to define the metabolic syndrome in women and men. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Aim: To evaluate the reliability of the ExSel® self-questionnaire to detect an excess salt intake (≥12g/24h) in patients consulting for hypertension and/or renal failure., Methods: Results of the ExSel® self-questionnaire were compared to 24h sodium excretion using the Cohen's kappa test and a Chi 2 test. Sensitivity, specificity, VPP and VPN were calculated. A ROC curve was realized to find an accurate cut-off., Results: Mean characteristics of the 101 patients with reliable results were: age of 67±12 years, Body Mass Index 28.4±5.6kg/m 2 , SBP/DBP 139±23/74±13mmHg (98% were hypertensives. Mean salt intake was 7.5±3.1g/24h and mean creatininuria was 13.9±20.1mmol/24h. An excess salt intake (≥12g/24h) was observed in 8% of the patients. The Kappa test at 0.17 and the Chi 2 at 0.66 signify that the agreement was very low. Sensitivity was 37%, specificity 90%, PPV 20% and NPV 94%. The AUC under the ROC curve was too low (0.665) to determine a threshold adapted to the renal patients., Conclusions: The ExSel® autoquestionnaire is not adapted to outpatients, mainly hypertensives (98%) followed in a nephrology consultation to detect an excess salt consumption., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

To improve the management of resistant hypertension, the French Society of Hypertension, an affiliate of the French Society of Cardiology, has published a set of eleven recommendations. The primary objective is to provide the most up-to-date information based on the strongest scientific rationale and that is easily applicable to daily clinical practice. Resistant hypertension is defined as uncontrolled blood pressure on office measurements and confirmed by out-of-office measurements despite a therapeutic strategy comprising appropriate lifestyle and dietary measures and the concurrent use of three antihypertensive agents including a thiazide diuretic, a renin-angiotensin system blocker (ARB or ACEI) and a calcium channel blocker, for at least 4 weeks, at optimal doses. Treatment compliance must be closely monitored, as must factors that are likely to affect treatment resistance (excessive dietary salt intake, alcohol, depression, drug interactions and vasopressor drugs). If the diagnosis of resistant hypertension is confirmed, the patient should be referred to a hypertension specialist to screen for potential target organ damage and secondary causes of hypertension. The recommended treatment regimen is a combination therapy comprising four treatment classes, including spironolactone (12.5-25 mg per day). In the event of a contraindication or a non-response to spironolactone, or if adverse effects occur, a β-blocker, an α-blocker, or a centrally acting antihypertensive drug should be prescribed. Because renal denervation is still undergoing assessment for the treatment of hypertension, this technique should only be prescribed by a specialist hypertension clinic.

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.

Aim: We report the first experience of Lyon's university hospital regarding renal denervation to treat patients with resistant essential hypertension., Patients and Methods: Over a one-year period, 17 patients were treated (12 men, 5 women) with renal denervation. Baseline characteristics were as follows: age 56.5±11.5 years, BMI 33±5kg/m(2) and ambulatory blood pressure 157±16/87±13mmHg with 4.2±1.5 anti-hypertensive treatment., Results: We did not observe intra-operative or early complications. After a median follow-up of 3 months and with the same anti-hypertensive treatment, office systolic blood pressure (SBP) and diastolic blood pressure (DBP) decrease respectively of 20±15 (P<0.001) and 10±13mmHg (P=0.014) (n=17). After six months of follow-up, ambulatory blood pressure (ABPM) decrease of 17.5±14.9mmHg (P=0.027) for SBP and of 10.5±9.6mmHg (P=0.029) for DBP (n=6). Among these patients, five of them were controlled (ABPM inferior to 130/80mmHg) and electrical left ventricular hypertrophy indexes decreased: R wave in aVL lead of 4±3mm (P=0.031), Sokolow index of 3±3mm (P=0.205), Cornell voltage criterion of 9±7mm (P=0.027) and Cornell product of 1310±1104 (P=0.027)., Conclusion: Our results are in accordance with data from other centers. On average blood pressure decreases significantly but important inter individual variations are observed. The procedure seems safe., (Copyright © 2014. Published by Elsevier SAS.)

Unlabelled: Adrenal venous sampling (AVS) is a challenging technical procedure and few patients had AVS procedure twice., Aim: To evaluate the reproducibility of the AVS, why AVS were repeated and the conclusions drawn from them., Patients and Methods: From 1997-2012, 12 patients underwent two AVS. A cortisol level in the adrenal vein greater than or equal to 1.1 to inferior vena cava defined a successful catheterization and a lateralization of secretion corresponded to an aldosterone-to-cortisol vein ratio greater than or equal to 2 between the one side to another., Results: The same side of lateralization of secretion was found in 75% of them. The second AVS were due to technical failure (n=4), unproven lateralization (n=2), a lateralization opposite to the main nodule and ipsilateral to hyperplasia (n=4) on first AVS. For two patients, as the CT was normal, AVS was required again. The second AVS was successful in all patients, including those with an initial technical failure but only patient with technical failure underwent surgery, as BP and kaliemia were controlled. Lateralization on the side of hyperplasia or opposite to the biggest nodule was confirmed in two of four cases., Conclusion: When AVS is unsuccessful for technical reasons, it is worth doing it again but after being sure that surgery is still possibly indicated., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: The bridge between food intake and weight is not fully understood. Recently, the role of gut microbiota and bacterial lipopolysacharides (LPS) in weight has been noted., Objective: The objective was to evaluate the relation between plasma LPS concentration and food intake., Design: A dietary survey was conducted in 1015 subjects randomly recruited in France. The participants were given oral and written instructions on how to keep a consecutive 3-d food record. Plasma LPS was measured in a subsample of 201 men. To assess, under controlled conditions, the differential impact of various high-energy diets, plasma LPS concentrations were measured in mice fed a high-fat or a high-carbohydrate diet over a 4-wk period., Results: In humans, no significant relation was observed between cardiovascular disease risk factors, carbohydrate and protein intakes, and plasma LPS concentration. Conversely, positive correlations were observed with fat and energy intakes. In a multivariate analysis, endotoxemia was independently associated with energy intake. Compared with the control mice, mice fed a high-energy diet showed an increase in plasma LPS. However, in mice fed a high-carbohydrate diet, the increase in plasma LPS was blunted compared with mice fed a high-fat diet., Conclusions: In this large sample of healthy men from a population-based sample, we found a link between food intake and plasma LPS. Experimental data suggest that fat was more efficient in transporting bacterial LPS from the gut lumen into the bloodstream. The results of this study add to the knowledge of mechanisms responsible for relations between food intake and metabolic diseases.

Unlabelled: Measurement of urinary albumin excretion (UAE) may be done on a morning urinary sample or on a 24 hour-urine sample. Values defining microalbuminuria are: - 24-hour urine sample: 30-300 mg/24 hours - Morning urine sample: 20-200 mg/mL or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mol (women). - Timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been shown in humans. In diabetic subjects, microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is also a marker of CV and renal risk in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. In non-diabetic subjects, microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of the renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence or elevation of UAE overtime is associated with deleterious outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic, non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome as it is in diabetic or hypertensive subjects. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is annually recommended in all subjects with microalbuminuria., Management: in patients with microalbuminuria, weight reduction, sodium restriction (< 6 g/day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of ACEI or ARB are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.

The incidence and the magnitude of lipodystrophy and dyslipidemia in HIV-treated people reported in previous studies are very variable. Several predisposing factors have been identified, but there are few data on genetic factors. To search for a correlation between APOC3 polymorphisms and lipid disorders and lipodystrophy in HIV patients under d4T and protease inhibitors (PI)-containing HAART, we designed a monocenter, cross-sectional study in a University Hospital in Southern France during the period 2001-2004. Forty patients under HAART were included, with d4T for > or = 2 years and PI for > or = 1 year. We determined body mass composition by DXA, lipoprotein markers, and the -455/-482 apo C3 genotypes. Carriers of APOC3 variant alleles (-455 1/-482 1) displayed higher levels of triglycerides (3.72 vs. 2.57 mmol/liter), apo C3 (45.3 vs. 34.5 mg/liter), and apo E (130.2 vs. 66.5 mg/liter) and a lower fat mass (13.9 vs. 19.7%) than patients with nonvariant alleles (-455 0/-482 0). APOC3 polymorphisms might be associated with both dyslipidemia and lipoatrophy in HAART-treated patients.

Objective: The polymorphic deletion of exon 3 of the GH receptor (d3-GHR) has recently been linked to the magnitude of growth response to recombinant human GH (rhGH) therapy in short children with or without GH deficiency. We investigated this association in a large multinational cohort from the Network of European Studies of Genes in Growth (NESTEGG), comprising short children born small for gestational age (SGA)., Design: The study included short prepubertal SGA children treated with rhGH for 1 or 2 years., Population: Two hundred and forty white Caucasian SGA children (138 male, 102 female) aged 6.6 +/- 2.3 years with a height at -3.0 +/- 0.7 SDS at start of rhGH treatment; 193 ethnically matched controls., Methods: The GHR polymorphism (fl/fl, fl/d3 or d3/d3) was genotyped by polymerase chain reaction (PCR) multiplex assay. Growth velocity (G/V) in cm/year and changes in GV during the first and second year of rhGH treatment were evaluated., Results: The change in GV was significantly greater in SGA children carrying one or two copies of the d3-GHR allele (P = 0.038 for the first year and P = 0.041 for the second year of GH treatment), but the change in height was not significantly different. Birthweight was significantly lower in SGA children with the d3/d3 genotype than in SGA children with the fl/fl genotype (P = 0.034) and in those with the fl/d3 genotype (P = 0.016)., Conclusion: Our data, based on a large cohort, showed that the exon 3 GHR polymorphism is associated with responsiveness to rhGH treatment in SGA children with short stature.

Urinary albumin excretion (UAE) may be assayed on a morning urinary sample or a 24 h-urine sample. Values defining microalbuminuria are: 1) 24-h urine sample: 30-300 mg/24 h; 2) morning urine sample: 20-200 mg/ml or 30-300 mg/g creatinine or 2.5-25 mg/mmol creatinine (men) or 3.5-35 mg/mmol (women); 3) timed urine sample: 20-200 mug/min. The optimal use of semi-quantitative urine test-strip is not clearly defined. It is generally believed that microalbuminuria reflects a generalized impairment of the endothelium; however, no definite proof has been obtained in humans., In Diabetic Subjects: Microalbuminuria is a marker of increased risk of cardiovascular (CV) and renal morbidity and mortality in type 1 and type 2 diabetic subjects. The increase in UAE during follow-up is associated with greater CV and renal risks in type 1 and type 2 diabetic subjects; its decrease during follow-up is associated with lower risks. IN NON-DIABETIC SUBJECTS: Microalbuminuria is a marker of increased risk for diabetes mellitus, deterioration of renal function, CV morbidity and all-cause mortality. It is a marker of increased risk for the development of hypertension in normotensive subjects, and is associated with unfavorable outcome in patients with cancer and lymphoma. Persistence of elevated UAE during follow-up is associated with poor outcome in some hypertensive subjects. Measurement of UAE may be recommended in hypertensive medium-risk subjects with 1 or 2 CV risk factors in whom CV risk remains difficult to assess, and in those with refractory hypertension: microalbuminuria indicates a high CV risk and must lead to strict control of arterial pressure. Studies focused on microalbuminuria in non-diabetic non-hypertensive subjects are limited; most of them suggest that microalbuminuria predicts CV complications and deleterious outcome. Subjects with a history of CV or cerebrovascular disease have an even greater CV risk if microalbuminuria is present than if it is not; however, in all cases, therapeutic intervention must be aggressive regardless of whether microalbuminuria is present or not. It is not recommended to measure UAE in non-diabetic non-hypertensive subjects in the absence of history of renal disease. Monitoring of renal function (UAE, serum creatinine and estimation of GFR) is recommended annually in all subjects with microalbuminuria., Management: In patients with microalbuminuria, weight reduction, sodium restriction (<6 g per day), smoking cessation, strict glucose control in diabetic subjects, strict arterial pressure control are necessary; in diabetic subjects: use of maximal doses of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are recommended; ACEI/ARB and thiazides have synergistic actions on arterial pressure and reduction of UAE; in non-diabetic subjects, any of the five classes of anti-hypertensive medications (ACEI, ARB, thiazides, calcium channel blockers or beta-blockers) can be used.

Objective: We evaluated the respective value of insulin, C-peptide and proinsulin levels in 33 patients with endogenous hyperinsulinism and in 67 controls to determine the best parameters and thresholds to make or to rule out the diagnosis of endogenous hyperinsulinism., Results: When blood glucose levels were below 2.5 mmol/l, insulin was <21 pmol/l in 8-35% of the patients and in all controls; C-peptide was >0.2 nmol/l in all insulinomas but not in the nesidioblastosis or in the controls; proinsulin was >5 pmol/l in all patients but not in the controls. When fasting blood glucose levels reached 2.5-3.3 mmol/l, proinsulin was <22 pmol/l in all the controls and >22 pmol/l in 74% of the patients. Proinsulin after an overnight fast was below 22 pmol/l in all non-obese controls and above 22 pmol/l in 73% of non-obese patients., Conclusion: Proinsulin levels above 5 pmol/l with blood glucose levels below 2.5 mmol/l during a 72 h fast test represent the best criterion for the diagnosis of endogenous hyperinsulinism, reaching 100% diagnostic specificity and sensitivity. Concomitant C-peptide levels above 0.2 nmol/l also make the diagnosis of all our insulinoma patients, not the diagnosis of nesidioblastosis, while insulin levels have much less diagnostic accuracy. Whether proinsulin levels above 22 pmol/l could also make the diagnosis of endogenous hyperinsulinism in part of the patients at the time of fasting blood glucose levels between 2.5 and 3.3 mmol/l or after an overnight fast in non-obese subjects needs further study.

Active anti-HIV therapy can induce hypertriglyceridemia, low high-density lipoprotein (HDL) and insulin resistance, eventually accompanied by clinical lipodystrophy, associated loss of subcutaneous adipose tissue and an increase in abdominal adiposity. The frequency of these metabolic disorders is approximately 50% and host genetic factors might confer particular susceptibility. Variants of apolipoproteins (apo) A5 and C3, interacting with APOE genotypes, have been associated with the severity of antiretroviral therapy-induced dyslipidemia and with occurrence of lipodystrophy, and for APOC3, with objective criteria of fat redistribution. Genetic polymorphisms of the nuclear transcription-factor sterol response element-binding proteins (SREBP1c) and of tumor necrosis factor-alpha (TNFalpha) have yielded contrasting results. Other candidate genes will be explored to define a pharmacogenomic strategy to identify patients at high risk of metabolic disorders upon antiretroviral therapy.

The object of this study was to compare the management of uncontrolled hypertensives (BP > 140/90 mmHg) by general practitioners with respect to the presence or absence of overweight (BMI > or =25 Kg/m2). A 2/1 stratification allowed comparison of 4080 patients who were overweight and 1951 patients with a normal body weight (normal BMI < 25 Kg/m2). The BP of patients who were overweight (> or =25 Kg/m2) was slightly higher than those with a normal BMI (161 +/- 12 mmHg vs. 159 +/- 12 mmHg, p < 0.001). The presence of a metabolic syndrome (43% vs. 7%, ATPIII criteria) was, logically, commoner in the patients overweight. However, the practitioners only recognised the presence of a metabolic syndrome in 65% of the overweight patients (28% true positives and 37% true negatives). The practitioners fixed their target value of systolic BP at 136.5 +/- 5.6 mmHg, in accordance with the recent recommendations of the Health Authorities. The targets were judged to be difficult to obtain in 18% of the overweight group and in 5% of patients with normal body weights. This optimism contrasted with the prescriptions, especially in the overweight patients, 46% of whom were treated by monotherapy and who remained for 44% on monotherapy at the end of the consultation. This descriptive study confirms the lack of awareness of the metabolic syndrome in overweight patients and identifies barriers to effective management of the hypertension of these high risk patients.

Multiple atrial septal defects can be closed by interventional catheterisation. The procedure requires an accurate morphological evaluation: number of defects, distance from their edges to the main cardiac structures, resistance of the septum. The authors report the case of a 63 year old woman presenting with cardiac failure in whom 3 atrial septal defects were diagnosed. All 3 defects were successfully closed by the implantation of two Amplatz devices. Control echocardiography at 6 months showed the occluders in a normal position with no residual shunt and the patient was asymptomatic.

Objective: In patients with uncontrolled systolic hypertension, to estimate the value of home blood pressure monitoring in addition to office blood pressure for inclusion in a trial., Methods: 80 patients with systolic hypertension, defined as SBP > or =140 mmHg and pulse pressure > or =60 mmHg, were treated for 4 weeks with a thiazide diuretic at usual dose (25 mg HCTZ or 1.5 mg indapamide or methyclothiazide 5 mg). Blood pressure was measured using an automatic monitor (Omron M6) at office and at home in the 3 days prior the visit. Subjects with an uncontrolled hypertension were included in the second part of the trial only if there fulfilled inclusion criteria: office SBP > or =140 mmHg and home SBP > or =135 mmHg (mean of 18 measurements obtained on 3 consecutive days) and office pulse pressure > or =60 mmHg., Results: After 4 weeks with diuretic treatment, 62% of patients fulfilled 3 criteria and were included in the second part of the trial. It was observed 76% of patients with office SBP > or =140 mmHg, 72% with office pulse pressure > or =60 mmHg and 70% with both office SBP and PP criteria. However, only 67% of patients had home SBP > or =135 mmHg. Discrepancy between office and home SBP was observed and subjects with a white coat hypertension was noticed in 14% and masked hypertension in 5%., Conclusion: If patients with systolic hypertension have to be included into a drug trial because there are uncontrolled, home blood pressure monitoring in addition to office blood pressure is a very useful criteria for inclusion because misclassifications due to white coat or masked hypertension is frequent in these patients.

The authors report a case of paroxysmal, complete atrioventricular block during an anterior acute myocardial infarction, leading to asystolia. The different possible physiopathological mechanisms are discussed, suggesting a paroxysmal nodal conduction defect, secondary to transient parasympathetic stimulation, triggered by a Bezold-Jarish type of cardiac reflex. This reflex is frequently involved in various pathologic situations or diagnostic procedures, usual in cardiology. Although it is frequently observed in inferior myocardial infarction, it can occur during an anterior acute myocardial infarction.

Objective: To evaluate the role of PTH-related peptide (PTH-rP) and 1,25-dihyhydroxyvitamin D3 in a case of hypercalcemia related to an ovarian adenocarcinoma., Design: We report a case of humoral hypercalcemia in a patient aged 74 yr with a clear cell adenocarcinoma of the right ovary at an early stage of its development (stage T1aN0M0) revealed by moderate and persistent hypercalcemia (variable level between 2.7 and 3.2 mmol/l without any treatment) over six months., Methods: PTH-rP and 1,25-dihydroxyvitamin D3 were measured in blood samples taken before and after hysterectomy and bilateral salpingooophorectomy and in blood samples taken intraoperatively from the right ovarian vein and a peripheral vein., Results: High levels of plasma PTH-rP and 1,25-dihydroxyvitamin D3 concomitant with high serum calcium and low PTH levels were found before surgery, which was followed by normalisation of all parameters studied. A concentration gradient was found regarding plasma PTHrP (right ovarian vein 60.4 pmol/l, peripheral vein 4.5 pmol/l), not 1,25-dihydroxyvitamin D3., Conclusion: 1) moderate and persistent hypercalcemia can be observed at an early stage of an ovarian carcinoma; 2) the gradient of PTH-rP concentration between the samples taken from the right ovarian vein and a peripheral vein provides evidence for a direct secretion of PTH-rP by the ovarian tumor; 3) the increased 1,25-dihydroxyvitamin D3 level is not related to a direct ovarian production, but is a consequence of PTH-rP secretion.

A 33 year old woman suffered a lateral myocardial infarction for the first time, and was treated by pre-hospital thrombolysis and secondary angioplasty on the diagonal artery. Fifteen days before the cardiac event she had undergone a left ovarian cyst excision and left salpingectomy for an ectopic pregnancy. She was a moderate smoker and had been taking a second-generation biphasic minidose oral contraceptive (ethinyl-estradiol 30-40mg and levonorgestrel 150-200 mg) for about ten years. Fifteen days before the myocardial infarction and due to the ectopic pregnancy she had changed to a combined monophasic minidose oral contraceptive pill containing ethinylestradiol (30 mg) and drospirenone (3 mg). The eventual outcome was favourable, with no complications. In this article we discuss the possible implications of the various factors (oral contraceptive, tobacco use, and surgical intervention) in this young woman with a myocardial infarction.

Each year in France, 150,000 to 180,000 new patients are the subject of prescriptions following acute coronary syndrome with or without ST segment elevation. There are two targets of the treatment, atherosclerosis, a diffuse, evolving trouble which, in this situation, is coming out of an unstable phase, and the myocardium, which has often been revascularised and has suffered deterioration of its contractile and electrophysiological characteristics to a greater or lesser extent. Prescriptions, based on proven factors and always centred on hygiene and dietary advice and the use of a combination of statins and aspirin, are adapted to suit the atherosclerotic and myocardial risk assessed for the individual patient. The prescription starts off the secondary preventive phase. It marks the first stage of the follow up, which is inevitable though of variable duration, for a disease which may evolve. It is the first step in the accompaniment of an attentive, informed patient whose confidence has been restored and who must now avoid falling into the double trap of not taking the treatment sufficiently seriously or of obsessively over-reacting.

Lysophosphatidic acid (LPA) is present in abundance in serum resulting from platelet activation and is also found in other biological fluids. LPA controls numerous cellular responses and plays a role in specific functions such as wound healing, especially in the skin. Nevertheless, its presence in the skin has never been investigated. Since re-epithelialization occurs after blister rupture, we tested the presence of endogenous LPA in blister fluid and investigated a possible mechanism for its biosynthesis and biological functions. Using a radioenzymatic assay, LPA was detected in 33 blister fluids originating from 24 bullous dermatoses, and at higher concentrations than in plasma. In parallel, blister fluids contained a lysophospholipase D (LPLD) activity but no detectable phospholipase A2 activity. The expressions of the LPLD autotaxin (ATX) and of LPA1-receptor (LPA1-R) were greatly increased in blister skin when compared with normal skin. Finally, LPA was found to have a positive effect on the migration of cultured keratinocytes. These results show that LPA is present in blister fluid synthesized by the LPLD ATX. Due to its ability to enhance keratinocyte migration, LPA in blister fluid could, via the LPA1-R, play an important role in re-epithelialization occurring after blister rupture.

Despite the improvement in revascularisation techniques, coronary artery disease remains the principal aetiology of cardiac failure in developed countries. The therapeutic management of cardiac failure has been improved over recent years, yet cardiac failure is still associated with significant morbidity and mortality. As cardiac transplantation lacks donors, techniques that allow myocardial regeneration represent an attractive alternative. To date, several types of cells are under study and are suitable for implantation into infarcted myocardium (myoblasts, medullary stem cells...). Following good preclinical study results, the first human cell therapy trials, using the intramyocardial route, have begun, in the course of aorto-coronary bypass surgery in patients with chronic ischaemic cardiopathy and little altered left ventricular function, and then in those with ventricular dysfunction. Different modes of administration of these cell therapy products are under study and could be envisaged in clinical situations such as just after infarction in order to improve ventricular remodelling with an intracoronary injection technique. As for every new treatment, there are numerous problems to resolve, from understanding the relevant mechanisms of cellular transplantation, to the secondary effects that it could entail. Nevertheless, cardiac cellular transplantation is expanding rapidly and with the evolution of techniques it allows a glimpse of a new field of treatment for cardiac failure.

Background: Primary stenting leads to a better short-term outcome than balloon angioplasty for acute myocardial infarction in randomised trials. However few data are available about the long-term outcome of primary stenting in acute myocardial infarction (AMI)., Objectives: The aim of this study was to compare the three-year outcome after primary stenting versus balloon angioplasty in patients with acute myocardial infarction., Methods: We conducted a retrospective study including 157 patients with AMI in a single center. Patients underwent balloon angioplasty (N = 48) or primary stenting (N = 109) within six hours after the onset of chest pain. We looked at the outcome during three years focusing on global mortality, major adverse cardiac events (MACE), reinterventions and target vessel revascularization (TVR)., Results: The two groups are similar for their baseline characteristics. No difference was noted for in-patient mortality in the balloon angioplasty group and the primary stenting group (2.1 vs 2.8%; P = ns). The three-year mortality was not significantly different in the two groups. Regarding MACE (27.8 vs 31.7; P = 0.95), reinterventions (20.4 vs 24.7%; P = 0.98) and TVR (18.6 vs 17.8%; P = 0.69), both groups were statistically not different., Conclusion: In the long-term patients treated with stent placement have similar rates of MACE, reinterventions or TVR than patients undergoing balloon angioplasty. If few studies noted a benefit in short-term outcomes, primary stenting doesn't improve the prognosis of acute myocardial infarction on long-term follow-up, which is dependent on atherosclerosis.

High job strain has been reported to be associated with higher blood pressure. Job strain could lead to hypertension if individual perception of stress or cardiovascular reactivity to stress are high. We report the results of the first five-year follow up study, which aimed to assess the respective influences of perception of professional strain and cardiovascular reactivity to a mental stress test on BP. A cohort of 292 healthy subjects (mean +/- SEM, 38 +/- 1 years) was followed for progression to hypertension outcome which was defined as an increase in SBP or DBP higher than 7 mmHg or a DBP higher than 95 mmHg during the follow-up. The high strain (HS) group representing 20.9% of the subjects was compared with the remaining subjects (NHS). Similarly the 20.9% subjects with the highest BP stress reactivity (HR) were compared with the remaining subjects (NHR). The Kaplan-Meier survival estimates revealed that neither high job strain, nor high stress reactivity, increased incidence of progression to hypertension. Age, alcohol, salt diet, BMI, and occupation did not interfere with our results. In conclusion, high stress cardiovascular reactivity and high job strain do not appear to be major risk markers for future high BP in healthy young adults. Stress could be associated with high BP at a short term and could explain high blood pressure in a long run only in stress-sensible subjects.

Aims: Patients suffering from coronary heart disease with ventricular systolic dysfunction present a bad prognosis and should be potentially revascularized. Up to now, surgery appeared to be the most feasible revascularization technique for such patients. Aims of this study were to assess the influence of different treatments (surgery, angioplasty or exclusively medical treatment) on clinical outcome and to establish a prognostic score practitioners to select the most appropriate therapy adapted to their patient profiles., Method: From 1995 to 2000, 492 patients were included in this cohort: 365 in the angioplasty group, 96 in the surgical group and 31 in the medical group. Kaplan Meier curves were made with a multivariate analysis to determine the significant predictive factors of mortality and major adverse cardiac events., Results: After a mean follow-up of 32 +/- 19 months, there was no statistical difference in mortality rate between the groups. However, the survival rate without MACE is higher in the surgical group, intermediate in the angioplasty group and lower in the medical group. Using the significant predictive factors of MACE in multivariate analysis, a prognostic score has been established in order to discriminate three categories of severity. For each category, angioplasty was compared with surgery in terms of the event-free-survival rate. For the two extreme categories (severe and non-severe), both treatments were equal. For the intermediate category, surgery obtained greater results., Conclusion: This prognostic score could help physicians in choosing the appropriate revascularization technique to treat patients with severe ischemic heart failure.

The Aims of Our Study Were: (i). to estimate the yearly incidence rates based on one vs two visits in a working population and (ii). to identify incident hypertension modifiable risk factors. A total of 21566 normotensive subjects were included in a 1-year cohort study. Blood pressure (BP) levels at inclusion and at the second year screening were measured on the basis of two visits, that is, if BP was over 140/90 mmHg in untreated subjects, they were invited to a control visit 1 month later. Height and weight were measured and behavioural risk factors were collected. Among the 17465 subjects who completed the entire protocol (9691 men and 7774 women), 17026 remained normotensive at a 1-year interval and 439 (325 men and 114 women) became hypertensive. Crude yearly incidence rates based on one visit were 6.21% in men and 3.06% in women, compared with 3.04% in men and 1.34% in women when incidence rates were based on two visits, a more than twofold difference. Age and body mass index at baseline were the two major independent determinants of incident hypertension in both genders. Smoking and alcohol consumption were significant risk factors in men but not in women, and a low educational level only in women. BP measurement on separate occasions is necessary to avoid overestimation of incidence. Weight in both genders and alcohol consumption in men were the main modifiable predictors of hypertension.

Is the white coat effect an alert reaction? In this cross-sectional study we compared the white coat effect on systolic blood pressure with the systolic blood pressure reactivity obtained during a stress test. The influence of the sympathetic system (LF band of systolic BP) and the parasympathetic system (HF band of pulse rate) on white coat systolic blood pressure and stress test systolic blood pressure were analysed. We stratified 174 subjects into two groups, according to their blood pressure: hypertensives (HT, n=44, BP>140/90 mmHg) and normotensives (NT, n=130). The BP was recorded during an occupational health consultation, over 24 hours, and beat to beat during a stress test (Finapress). White coat systolic BP was calculated as the difference between the consultation BP and the average systolic BP over 24 hours. The white coat systolic BP was not related with an increase in pulse rate. In contrast, during the stress test the increases in systolic BP and pulse rate were correlated (r=0.44; p<0.001). The white coat systolic BP was lower than the stress test systolic BP in the NT (6.6 +/- 7.2 vs 23 +/- 12 mmHg; p<0.001) and in the HT (16 +/- 11 vs 29 +/- 17 mmHg; p<0.001). The HT had a lower parasympathetic index than the NT (0.45 +/- 0.43 vs 0.92 +/- 0.83 bpm2; p<0.001). In the HT the white coat systolic BP was positively correlated with the stress test systolic BP (r=0.47: p<0.01) and negatively with the parasympathetic activity index. In conclusion, for recently diagnosed and untreated HT an early alteration of the parasympathetic system reveals that the white coat effect is a low amplitude alert reaction.

Objectives: To evaluate the characteristics of hypertensive subjects who practise self measurement of blood pressure (SMBP) and their conditions of use, and to identify the properties of subjects using SMBP according the usual guidelines., Methods: In 531 consecutive hypertensive subjects, referred to hypertension specialists, possessing a SMBP a questionnaire evaluating the condition of use of SMBP was given. Subjects following the guidelines about the use of SMBP have been compared to those using SMBP without specific design of supervision., Results: In this population, aged 62 +/- 14 years, with 57% of men and a mean blood pressure of 147 +/- 23/82 +/- 12 mmHg, the SMBP devices have been bought without medical advice in 50% of cases (265/531). In 45% of cases (239/531), SMBP were made at the wrist. SMBP device was used every days in 26% of cases, every weeks in 27% of cases, every month or more in 22% of cases and only in case of uneasiness in 25% of cases. Blood pressure was measured only in the morning in 25% of cases, in the morning and evening in 31%, only the evening in 8% and at any time of the day in 36% of cases. More frequently 2 BP measurements were realized (47%) and in 19% of cases 3 measurements have been performed. In 15% of cases, the measurements were performed on 3 or 4 days consecutively, more frequently (85%) the measurements were realized without specific design ("once in awhile"). The data of SMBP were noted and showed to the doctor in 34% of cases. Only 12% (64/531) of subjects followed the usual guidelines concerning the use of SMBP (2 or 3 measurements, in the morning and the evening, during 3 or 4 consecutive days). Subjects following the guidelines for SMBP use have a higher SBP at the office than those using SMBP without specific design of supervision (155 +/- 25 mmHg vs 146 +/- 22 mmHg; p<0.01)., Conclusion: Among hypertensives referred to hypertension specialists most of subjects use SMBP device without a specific design of supervision. Subjects with the most severe hypertension are those who have the best formation for SMBP.

Objective: We report the case of a 36-yr-old woman with nesidioblastosis treated throughout pregnancy with high doses of octreotide. We studied the course of blood glucose, foetal growth and development., Methods: Blood samples were obtained every month throughout pregnancy and taken at birth from the umbilical cord. Sonography was performed repeatedly to monitor foetal growth., Results: The daily dose of octreotide was adapted to blood glucose levels: a dose of 1000 microg was infused during the first part of pregnancy, then it was decreased step by step during the last trimester of gestation. An elective cesarean section was performed at 32 weeks of gestation. High octreotide concentrations were obtained during the first part of gestation (range 2888-5021 pg/ml). During the third trimester of pregnancy blood glucose increased despite high insulin levels attesting physiological insulin-resistance. Plasma levels of placental GH and IGF-1 levels were similar to those observed in a normal pregnancy. Despite the presence of octreotide in the umbilical cord, TSH, free T4, PRL and pituitary GH concentrations were normal at birth. The female newborn (weight 3520 g, length 52 cm) had no malformation, and presented with normal postnatal development., Conclusion: Our study demonstrates that: 1) octreotide treatment can be effective in controlling endogenous hyperinsulinism during pregnancy; 2) octreotide does not affect physiological changes during pregnancy such as insulin-resistance or placental GH level; 3) exposure of the foetus to octreotide throughout pregnancy does not induce any malformation and does not affect foetal development.

Aims: To design a simple method to produce active recombinant Pseudomonas aeruginosa haemolytic phospholipase C (PLC)., Method and Results: Pseudomonas aeruginosa PLC is a virulence factor mainly involved in inflammatory and cytotoxic responses. While ammonium sulphate purification requires large amounts of bacterial suspensions and leads to low yields, production of recombinant protein in Escherichia coli is no more successful because of frequent inclusion bodies and accumulation of inactive PLC in the periplasmic space. Using an inducible system based on the glucose-repressed inv1 promoter in the yeast Schizosaccharomyces pombe, we were able to produce up to 10 IU ml(-1) of pure toxin within 24 h., Conclusions: This work describes the first method to easily get recombinant haemolytic PLC., Significance and Impact of the Study: This method provides a powerful tool to study the mechanisms leading to its cellular toxicity.

It has been shown that human group IIa secreted phospholipase A(2) (sPLA(2)), found at high levels in inflammatory fluids, displays direct bactericidal properties against Gram-positive bacteria, while activity against Gram-negative bacteria requires the complement system or additional co-factors produced by neutrophils. Pseudomonas aeruginosa, an increasingly prevalent opportunistic human pathogen, is the most common Gram-negative rod found in cystic fibrosis lung infections, where it is associated with an inflammatory environment. Because murine intestinal group II sPLA(2) produced by Paneth cells has been shown to be directly bactericidal against Gram-negative bacteria, IIa sPLA(2) activity against P. aeruginosa clinical isolates was evaluated and provides the first evidence that the enzyme can be fully bactericidal in a concentration- and time-dependent manner against Gram-negative rods. Furthermore, it was demonstrated that these bactericidal properties were unaffected by high protein and salt concentrations, as observed in cystic fibrosis secretions, and that bacterial killing paralleled phospholipid hydrolysis. Finally, no cytotoxicity was observed when IIa sPLA(2) was incubated with human pulmonary cells, highlighting its potential use to synergize bactericidal antibiotics by promoting sublethal alterations of the bacterial cell wall.

The effects of the apolipoprotein E epsilon and angiotensin-converting enzyme insertion/deletion alleles on lipid levels and hypolipidemic drug treatment was assessed in 400 men with stable angina pectoris or healed myocardial infarction and 338 healthy controls. The data indicate that epsilon4 carriers have increased total and low-density lipoprotein cholesterol levels, that the epsilon4 allele unfavorably decreases the efficiency of statin treatment, and that the angiotensin-converting enzyme insertion/deletion polymorphism exerts no significant effect, with the exception of an increase in apolipoprotein E levels.

Objective: To assess the interaction between apolipoprotein (apo) E polymorphism, alcohol consumption, and BMI on insulin, lipid, and lipoprotein levels in men., Research Methods and Procedures: Cross-sectional study of 266 healthy men without hypolipidemic or antidiabetic drug treatment. BMI, apo E polymorphisms, insulin, and lipid and lipoprotein levels were assessed. Alcohol consumption was assessed by questionnaire. epsilon2/epsilon4 carriers were excluded from the analysis., Results: On bivariate analysis, epsilon2 carriers had lower levels of total and low-density lipoprotein cholesterol and higher levels of apo E and lipoparticle B:E than epsilon3 carriers, the opposite being found for epsilon4 carriers compared with epsilon3 carriers; epsilon4 carriers also had significantly higher insulin levels. On multivariate analysis, significant interactions (p < 0.04) between apo E alleles and increased BMI were found for total and low-density lipoprotein cholesterol and insulin levels, the increase in those parameters with BMI being stronger among epsilon4 carriers than among epsilon3 or epsilon2 carriers. Significant interactions (p < 0.02) between apo E alleles and alcohol consumption were also found for apo B levels, which increased in epsilon2 carriers but remained relatively stable in epsilon3 and tended to decrease in epsilon4 carriers., Discussion: These data suggest that effects of apo E alleles on lipids and insulin levels are partly dependent on environmental variables such as BMI and alcohol intake. These findings highlight the importance of gene x environment interactions on the deleterious effect of obesity on cardiovascular risk factors.

The aim of this study was to evaluate the influence of 10 factors suspected to be involved in hypertension genesis (age, body mass index, alcohol consumption, sodium to potassium urinary excretion ratio, systolic BP and heart rate response to mental stress, baroreflex sensitivity (BRS), job demand, job latitude (Karasec's questionnaire), and personality (Bortner's score). A cohort of 213 normotensive healthy subjects was followed during five years. Using K-means clustering technique we have defined 7 homogeneous groups of subjects. Four groups with different combinations of these factors had a significantly higher 5-year systolic BP increase. The common characteristic of these groups was a low BRS. In conclusion, cluster analysis is well suited to analyse combined effect of factors on hypertension genesis. Only low BRS seems to be the common factor involved in hypertension development.

Unlabelled: Decrease in sexual desire is a disturbance affecting treated hypertensive subjects of both sexes. In contrast with erection problems, this abnormality has rarely been studied in hypertensives treated with antihypertensive drugs., Objectives: To evaluate, using a self-administered questionnaire, the prevalence of sexual disturbance (decrease in sexual desire) in treated hypertensive subjects and to determine the management of these troubles., Methods: In 428 hypertensive subjects, living in France and referred to hypertension specialists, a self-administered questionnaire evaluating the quality of sexual activity was given before the consultation. Nine specific questions focused on the quality of sexual function for the last 6 months in men or women (interest for sexuality, sexual desire, sexual pleasure). Secondly, the doctors were questioned about their management of these sexual disturbances., Results: In this population of treated hypertensives, including 270 men and 158 women, with a blood pressure level of 139 +/- 20/84 +/- 13 mmHg, a decrease in sexual desire was reported by 47% of men (127/270) and 48% of women (76/158). Sexual disturbance was related to antihypertensive drugs in 46% of cases (93/203), more often in men (59% [75/127]) than in women (24%, [18/76]), p < 0.001). In subjects with sexual disturbance, a specific medical management has been proposed in 35% of cases (71/203), especially in men (in 46% of cases [58/127], and consisted in a specialized consultation for 34% (43/127) and/or the prescription of Sildenafil for 20% (26/127). In women, the lack of management of these troubles was more often observed than in men (82% vs 54%; p < 0.01). Modifications of antihypertensive treatments were rarely observed in 15% of cases (30/203) comparatively in men and women., Conclusions: Men and women with treated hypertension are at "high risk" of sexual disturbance. Management of sexual dysfunction in these subjects concerns only 35% of cases, especially men, including specific treatments and/or consultations, but changing in antihypertensive drugs still remains rare.

The parallel investigation of the renal and cardiac complications of recent and never treated systemic hypertension has only rarely been undertaken. The aim of this study was to define the renal function of never treated hypertensive subjects, separated into white coat hypertensives (HTbb: n = 19, BP at consultation 153/97 mmHg) or permanent hypertensives (HT: n = 49, BP at consultation 169/104 mmHg) as a function of their 24 hour BP. Their renal functions were then compared with those of normotensive subjects (NT: n = 10). The 68 hypertensive subjects seen consecutively underwent renal function investigation (DFG: glomerular filtration rate, DPR: renal plasmatic debit, and muAlb: microalbuminuria over 24 hours), and myocardial echography (measurement of the left ventricular mass index, IMVG). The white coat hypertensives had a normal renal function, while the permanent hypertensives had a significant decrease in DPR and a significantly higher muAlb compared to the normotensives. Compared to the white coat hypertensives, the permanent hypertensives had a significantly lower DFG and DPR, as well as a higher muAlb and IMVG. In all the hypertensives (white coat and permanent) the 24 hour systolic BP was significantly correlated with muAlb (r = 0.51, p < 0.001), filtration fraction (r = 0.30, p < 0.05), and IMVG (r = 0.52, p < 0.001). The renal and myocardial parameters were not significantly correlated. In conclusion, there seems to be a continuum between the level of ambulatory BP and the effect on target organs without a parallel progression of the renal and myocardial effects. From a practical point of view, only ambulatory BP measurement allows differentiation of permanent hypertensives who have a very early renal and/or myocardial effect, while white coat hypertensives are spared.

Background: Randomized trials comparing primary angioplasty and in-hospital fibrinolysis in acute myocardial infarction (AMI) have shown an advantage for primary angioplasty. The long-term follow-up of pre-hospital fibrinolysis followed by elective or rescue coronary angioplasty versus primary angioplasty is not well established after acute myocardial infarction. This study sought to assess the long-term clinical outcome of patients with AMI having either received pre-hospital fibrinolysis optimized by coronary angioplasty or primary angioplasty., Methods: We conducted a retrospective analysis involving 318 patients who either underwent primary angioplasty ( n = 157) or received pre-hospital fibrinolysis followed by an angioplasty (rescue or elective) ( n = 161) within 6 hours of the onset of chest pain., Results: The groups were similar regarding their baseline characteristics except for the ages. No difference was noted for in-hospital mortality (primary PTCA group: 2.48%, combined group: 2.54%; p = ns) with no increased risk of hemorrhage. The 3-year mortality was not significantly different in the two groups (9.7% vs. 4.9%; p = 0.15). Regarding major adverse cardiac events (29.5% vs. 37.5%; p = 0.23), reintervention (22.5% vs. 23.2%; p = 0.99) or target lesion revascularization (16.1% vs. 14.7%; p = 0.68), the groups were statistically similar., Conclusion: These data from real-life practice emphasize the safety and similar benefits on the long-term clinical outcome of AMI patients having undergone either pre-hospital fibrinolysis followed by angioplasty or primary angioplasty.