Adherence to Antihypertensive Treatment and the Blood Pressure-Lowering Effects of Renal Denervation in the Renal Denervation for Hypertension (DENERHTN) Trial.

BACKGROUND: The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure-lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report the influence of adherence to antihypertensive treatment on blood pressure control. METHODS: One hundred six patients with hypertension resistant to 4 weeks of treatment with indapamide 1.5 mg/d, ramipril 10 mg/d (or irbesartan 300 mg/d), and amlodipine 10 mg/d were randomly assigned to renal denervation plus standardized stepped-care antihypertensive treatment, or the same antihypertensive treatment alone. For standardized stepped-care antihypertensive treatment, spironolactone 25 mg/d, bisoprolol 10 mg/d, prazosin 5 mg/d, and rilmenidine 1 mg/d were sequentially added at monthly visits if home blood pressure was ≥135/85 mm Hg after randomization. We assessed adherence to antihypertensive treatment at 6 months by drug screening in urine/plasma samples from 85 patients. RESULTS: The numbers of fully adherent (20/40 versus 21/45), partially nonadherent (13/40 versus 20/45), or completely nonadherent patients (7/40 versus 4/45) to antihypertensive treatment were not different in the renal denervation and the control groups, respectively (P=0.3605). The difference in the change in daytime ambulatory systolic blood pressure from baseline to 6 months between the 2 groups was -6.7 mm Hg (P=0.0461) in fully adherent and -7.8 mm Hg (P=0.0996) in nonadherent (partially nonadherent plus completely nonadherent) patients. The between-patient variability of daytime ambulatory systolic blood pressure was greater for nonadherent than for fully adherent patients. CONCLUSIONS: In the DENERHTN trial, the prevalence of nonadherence to antihypertensive drugs at 6 months was high (≈50%) but not different in the renal denervation and control groups. Regardless of adherence to treatment, renal denervation plus standardized stepped-care antihypertensive treatment resulted in a greater decrease in blood pressure than standardized stepped-care antihypertensive treatment alone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Metabolic syndrome, insulin resistance, and periodontitis: a cross-sectional study in a middle-aged French population.

AIM: Metabolic syndrome consists of a cluster of clinical and biological abnormalities, influenced by insulin resistance and promoting cardiovascular diseases. We examined the relationships between metabolic syndrome, its various components, insulin resistance, and periodontitis. MATERIALS AND METHODS: The study included 276 subjects (35-74 years) recruited within a cross-sectional survey on cardiovascular risk factors. Twenty-one were excluded because of infectious risk or total tooth loss. Clinical attachment loss (CAL), probing pocket depth (PD), gingival and plaque indexes were recorded. Periodontitis was classified into moderate and severe forms. RESULTS: The mean age was 58, 41% of the subjects had moderate and 39% had severe periodontitis. In univariate comparisons, periodontitis was associated with metabolic syndrome (p=0.050), most of its components, and HOMA index (homoeostasis model assessment of insulin resistance). After adjustment for confounders, only HOMA index remained associated with severe periodontitis (odds ratio [OR]=3.97 [95% confidence interval: 1.22-12.9], OR=3.78 [1.14-12.5] for third and fourth versus the first quartile of the HOMA index, respectively). The HOMA index was also associated with the number of periodontal sites with CAL>or=4 mm, CAL>or=5 mm, or PD>or=4 mm (greater number for higher HOMA-index values). This relationship disappeared in never-smokers. CONCLUSIONS: Our data support the relationships between metabolic disturbances and periodontitis, with a central role of insulin resistance.

Additional prognostic value of physical examination, exercise testing, and arterial ultrasonography for coronary risk assessment in primary prevention.

BACKGROUND: The choice of noninvasive tests used in primary prevention of cardiovascular diseases must be based on medical evidence. The aim of this study was to assess the additional prognostic value, over conventional risk factors, of physical examination, exercise testing, and arterial ultrasonography, in predicting a first coronary event. METHODS: A prospective cohort study was conducted between 1996 and 2004 (n = 2,709), with follow-up in 2006 (response rate 96.6%). Participants had no history or symptoms of cardiovascular disease and had a standardized physical examination, a cardiac exercise testing, and carotid and femoral ultrasonography at baseline. Incident cases of definite coronary events were recorded during follow-up. RESULTS: Over the Framingham risk score, femoral bruit, positive exercise test, intima-media thickness >0.63 mm, and a femoral plaque provided significant additional information to the prediction model. The addition of the exercise test to the traditional risk factors, then the intima-media thickness and lastly the presence of femoral plaques, produces incremental increases in the area under the receiver operating characteristic curve (0.73-0.78, P = .02) and about a 50% increase in the positive predictive value (15.8%-31.4%), with no effect on the negative predictive value (96.4%-96.9%). CONCLUSION: Physical examination, exercise testing, and arterial ultrasonography provide incremental information on the risk of coronary event in asymptomatic adults. Exercise testing and femoral ultrasonography also improve the accuracy of the risk stratification.

Blood pressure and cognitive performances in middle-aged adults: the Aging, Health and Work longitudinal study.

BACKGROUND: Our objective was to investigate the impact of both prevalent and incident hypertension on cognition in middle-aged individuals followed up for 10 years and to explore the extent to which blood pressure control by antihypertensive drugs could modify this relationship. METHOD: Three thousand, two hundred and one participants from the Vieillissement Santé Travail (Aging, Health and Work) (VISAT) cohort study, aged 32, 42, 52 and 62 years at baseline were followed up 5 and 10 years later. Blood pressure, antihypertensive medication use as well as memory and speed cognitive performances were assessed at baseline and follow-up. Linear mixed models were used for analyses. RESULTS: At 10-year follow-up, compared with nonhypertensive participants, prevalent hypertensive individuals showed poorer global cognitive performances (ß = -2.99 ±â€Š0.96, P = 0.002 for participants aged 32 or 42 years at baseline and ß = -5.94 ±â€Š1.00, P < 0.001 for those aged 52 or 62). Patients with incident hypertension had poorer global cognitive performances over time compared with patients without hypertension. When considering prevalent hypertension and blood pressure control status by antihypertensive therapy, untreated and uncontrolled hypertension were associated with poorer cognitive performances than controlled and no hypertension (untreated hypertension compared with no hypertension: ß = -5.51 ±â€Š0.75, P < 0.001; uncontrolled hypertension compared with no hypertension: ß = -6.13 ±â€Š1.40, P < 0.001). CONCLUSION: Our findings showed that both prevalent and incident hypertension are associated with poorer global cognitive function in middle-aged individuals and suggested a potential preventive effect of antihypertensive therapy on cognition. Thus, for brain functioning, heightened efforts to detect hypertension and adequately treat it are of critical importance.

Appropriate antibiotic prescribing among final-year medical students in Europe.

Little is known about undergraduate education on antibiotic prescribing in Europe and even less about the antibiotic prescribing skills of nearly-graduated medical students. This study aimed to evaluate the antibiotic prescribing skills of final-year medical students across Europe and the education they received during medical training. In a cross-sectional study, final-year medical students from 17 medical schools in 15 European countries were asked to prescribe for two written case reports of infectious diseases (acute bronchitis and community-acquired pneumonia). The appropriateness of antimicrobial therapy was determined using a scoring form based on local guidelines. Teachers from each medical school were asked to complete a standardised questionnaire about the teaching and assessment of undergraduate education on antibiotic use. In total, 856 final-year medical students (95.6%) completed the assessment and 16 teachers (94.1%) completed the questionnaire. Overall, 52.7% (range 26-83%) of the 1.683 therapies prescribed were considered appropriate. The mean number of contact hours for undergraduate education on antimicrobials was 25.6 (range 2-90). Differences in education styles were found to have a significant impact on students' performance, with a problem-based learning style being associated with more appropriate antimicrobial prescribing than a traditional learning style (46.0% vs. 22.9%; P < 0.01). Although there are differences between medical schools, final-year medical students in Europe lack prescribing skills for two common infectious diseases, possibly because of inadequate undergraduate education on antibiotic use and general prescribing. To improve students' skills, interactive teaching methods such as prescribing for simulated and real patients should be used.

Arterial stiffness evaluated by pulse wave velocity is not predictive of the improvement in hypertension after adrenal surgery for primary aldosteronism: A multicentre study from the French European Society of Hypertension Excellence Centres.

BACKGROUND: Predictive factors associated with normal blood pressure (BP) after unilateral adrenalectomy for primary aldosteronism (PA) are not clearly identified. AIMS: To evaluate the predictive value of arterial stiffness before surgery on BP after surgery. METHODS: During 2009-2013, 96 patients with PA due to unilateral adrenal adenoma who underwent surgery were enrolled in a multicentre open-label, prospective study. Aortic pulse wave velocity (PWV) was assessed before surgery. Patients underwent ambulatory blood pressure monitoring (ABPM) before surgery and 6 and 12months after surgery. Twenty-four h SBP/DBP values were compared in subjects with PWV

Cardiovascular risk factors, atherosclerosis and pulse pressure.

Blood pressure is a complex phenomenon that can be divided into two components: a steady and a pulsatile component. The pulsatile component is estimated by the pulse pressure which is mainly influenced by the large artery stiffness. The purpose of this review was to describe the relation between pulse pressure, cardiovascular risk factors and atherosclerosis. Epidemiological studies have shown positive correlations between pulse pressure and smoking or glucose metabolism impairment. More controversial data have been reported on the relation between blood lipids and large artery stiffness or pulse pressure. In cross-sectional studies, carotid, aortic and coronary plaques were associated with aortic stiffness, particularly echogenic or ulcerative plaques, and in a longitudinal study, the progression of atherosclerosis is accompanied by an increase in pulse pressure. From a pathophysiological point of view, the deleterious influence of most risk factors on endothelial function and the development of atheroma are likely to contribute to these relations. Furthermore, with respect to the connections observed between C-reactive protein, most cardiovascular risk factors, atherosclerotic diseases and pulse pressure, subclinical inflammation might also underlie these relations.

[Retroperitoneal laparoscopic surgery for phaeochromocytoma: analysis of morbidity and haemodynamic instability]. / Chirurgie du phéochromocytome par laparoscopie rétropéritonéale: analyse de la morbidité et de l'instabilité hémodynamique.

OBJECTIVE: To study the morbidity and haemodynamic parameters on a consecutive series of adrenalectomies performed Jbr phaeochromocytoma by retroperitoneal laparoscopy. MATERIAL AND METHODS: The study population comprised 23 phaeochromocytomas in 20 patients treated by controlled retroperitoneal laparoscopic surgery. The following parameters were studied: intraoperatively: operating time, blood loss, blood pressure, heart rate, and postoperatively: infectious, haemorrhagic and thromboembolic complications. RESULTS: The mean operating time was 156 minutes (range: 105-224). Mean blood loss was 58 ml (range: 0-300). Intraoperatively, 1500 of patients presented a peak SBP >220 mmHg and 70% presented a peak SBP >200 mmHg. In contrast, 200 of patients presented a nadir SBP <60 mmHg, but no patient presented a nadir SBP less than 40 mmHg. One case of intraoperative haemorrhage was observed (4.3%). Three postoperative complications (1 case of respiratory distress, 1 case of haemorrhagic shock, and 1 abscess) were observed (13%). CONCLUSION: Laparoscopic surgery for phaeochromocytoma is associated with a risk of haemodynamic instability. Phaeochromocytoma surgery should therejbre continue to be performed in specialized centres (surgical, anaesthetic and endocrinological).

Twenty-Four-Hour Blood Pressure Monitoring to Predict and Assess Impact of Renal Denervation: The DENERHTN Study (Renal Denervation for Hypertension).

The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure (BP) lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report here the effect of denervation on 24-hour BP and its variability and look for parameters that predicted the BP response. Patients with resistant hypertension were randomly assigned to denervation plus stepped-care treatment or treatment alone (control). Average and standard deviation of 24-hour, daytime, and nighttime BP and the smoothness index were calculated on recordings performed at randomization and 6 months. Responders were defined as a 6-month 24-hour systolic BP reduction ≥20 mm Hg. Analyses were performed on the per-protocol population. The significantly greater BP reduction in the denervation group was associated with a higher smoothness index (P=0.02). Variability of 24-hour, daytime, and nighttime BP did not change significantly from baseline to 6 months in both groups. The number of responders was greater in the denervation (20/44, 44.5%) than in the control group (11/53, 20.8%; P=0.01). In the discriminant analysis, baseline average nighttime systolic BP and standard deviation were significant predictors of the systolic BP response in the denervation group only, allowing adequate responder classification of 70% of the patients. Our results show that denervation lowers ambulatory BP homogeneously over 24 hours in patients with resistant hypertension and suggest that nighttime systolic BP and variability are predictors of the BP response to denervation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01570777.

Genetic testing in pheochromocytoma or functional paraganglioma.

PURPOSE: To assess the yield and the clinical value of systematic screening of susceptibility genes for patients with pheochromocytoma (pheo) or functional paraganglioma (pgl). PATIENTS AND METHODS: We studied 314 patients with a pheo or a functional pgl, including 56 patients having a family history and/or a syndromic presentation and 258 patients having an apparently sporadic presentation. Clinical data and blood samples were collected, and all five major pheo-pgl susceptibility genes (RET, VHL, SDHB, SDHD, and SDHC) were screened. Neurofibromatosis type 1 was diagnosed from phenotypic criteria. RESULTS: We have identified 86 patients (27.4%) with a hereditary tumor. Among the 56 patients with a family/syndromic presentation, 13 have had neurofibromatosis type 1, and germline mutations on the VHL, RET, SDHD, and SDHB genes were present in 16, 15, nine, and three patients, respectively. Among the 258 patients with an apparently sporadic presentation, 30 (11.6%) had a germline mutation (18 patients on SDHB, nine patients on VHL, two patients on SDHD, and one patient on RET). Mutation carriers were younger and more frequently had bilateral or extra-adrenal tumors. In patients with an SDHB mutation, the tumors were larger, more frequently extra-adrenal, and malignant. CONCLUSION: Genetic testing oriented by family/sporadic presentation should be proposed to all patients with pheo or functional pgl. We suggest an algorithm that would allow the confirmation of suspected inherited disease as well as the diagnosis of unexpected inherited disease.

Interleukin 6 is associated with subclinical atherosclerosis: a link with soluble intercellular adhesion molecule 1.

BACKGROUND: Among the markers of inflammation, a cytokine, interleukin (IL)-6, promotes the expression of intercellular adhesion molecule 1 (ICAM-1), C-reactive protein (CRP) synthesis, and leads to a series of procoagulant actions with potential major implications on the progression of atherosclerosis. AIM OF THE STUDY: To analyse in a population-based study, the relationship between IL-6 and atherosclerotic lesions and the role of serum ICAM-1 and CRP on this relationship. POPULATION: Among 1015 individuals randomly recruited between 1995 and 1997 in Haute-Garonne, a French region with a low cardiovascular risk, 953 subjects with complete data for all measurements were analysed. Common carotid intima-media thickness (IMT) and the presence of plaques in the carotid and femoral arteries were assessed by ultrasonography. RESULTS: Quartiles of IL-6, serum ICAM-1 and CRP were positively associated with plaques and IMT. After adjustment for traditional risk factors, IL-6 (P < 0.001) and serum ICAM-1 (P < 0.002) remained positively associated with plaques but not CRP (P = 0.20). Neither IL-6, nor serum ICAM-1, nor CRP were independently associated with IMT. When serum ICAM-1 was entered into the model in addition to traditional risk factors and IL-6, the percentage of variance in the number of plaques explained by the model did not increase significantly. CONCLUSION: IL-6 levels are associated with subclinical atherosclerotic lesions independently of traditional risk factors; the influence of IL-6 on ICAM-1 secretion may play a role in this association. These results argue the interest of IL-6 in the stratification of cardiovascular risk.

Arteries, inflammation and insulin resistance.

Inflammation plays a role in all stages of atherosclerosis from the formation to the rupture of the plaque. Guided by inflammatory mediators, monocytes bind to an endothelium damaged by cardiovascular risk factors, and then migrate towards the intima where, after incorporating oxidized low-density lipoprotein particles, they are transformed into foam cells. The lipid streak forms and develops as an atherosclerotic plaque, which is susceptible to erosion and rupture. Inflammation fed by excess adipose tissue decreases insulin sensitivity, which is the central feature of the metabolic syndrome. Inflammation therefore appears to be a common factor of atherosclerosis and the metabolic syndrome. The factors triggering this inflammation have yet to be determined. One line of thought would appear to point to diet.

[Hypertension etiological work up: Hormonological assessment always before imaging?] / Bilan étiologique de l'HTA : dosages hormonaux toujours avant imagerie ?

The purpose is to consider the practical management of etiological work up in hypertension, beyond national or international recommendations, leading to consider the prior practice of hormonal assays or renal, renovascular or adrenal imaging. The ease of access to imaging, difficulties to meet the requirements to obtain reliable hormonal assays explain the use of first-line imaging in clinical practice. The renal and adrenal CT angiography provides diagnostic orientation without allowing a formal conclusion. Incidentaloma prevalence in the general population, increasing with age, underlines the limitations of a decision based only on imaging. The discovery of adrenal morphological abnormalities justifies the realization of hormonal assays to determine their causal relationship with hypertension. The aldosterone/PRA ratio, in standardized conditions, has the best diagnostic performance to screen for primary aldosteronism and is the pivotal test of the etiological diagnosis of hypertension. The identification of a subclinical Cushing should be considered in patients with adrenal morphological abnormalities, particularly in case of metabolic syndrome. The abdominal CTscan is initially recommended in the diagnosis of pheochromocytoma, but the recommende boichemical testing is urine metanephrines whose result will lead to search a pheochromocytoma or an extra-abdominal paraganglioma. Many drug interactions must be considered in order to interpret hormonal measurements and avoid erroneous diagnosis. Finally, a genetic context and the possibility of endocrine causes with normal abdominal CT scan should be considered: extra-abdominal paraganglioma, parathyroid adenoma and Cushing's disease with pituitary adenoma, requiring a multidisciplinary decision. The efficiency of imaging as first-line in the screening of secondary hypertension is relative and confrontation with hormone assays will be critical to the diagnostic and therapeutic management. In young women, hormonal measurements precede imaging in the etiological investigation of hypertension.

[Management of arterial hypertension before 20weeks gestation in pregnant women]. / Traitements antihypertenseurs et objectifs thérapeutiques de l'hypertension de la femme enceinte (HTA chronique préexistante, HTA gestationnelle) avant le sixième mois de grossesse.

In the first 6 months of pregnancy, the primary goal of antihypertensive treatment is to prevent the complications of severe hypertension. Initiation of antihypertensive drug treatment is recommended in pregnant women with severe hypertension (blood pressure>160/110mmHg). Initiation of antihypertensive drug treatment should also be considered in pregnant women at high cardiovascular risk (diabetes, chronic kidney disease, personal history of cardiovascular disease) with moderate hypertension (blood pressure between 140-159/90-109mmHg). A systolic blood pressure goal<160 and a diastolic blood pressure goal between 85 and 100mmHg is recommended in pregnancy. Labetalol, nifedipine, nicardipine and alphamethyldopa should be considered preferential antihypertensive drugs in pregnancy. Salt restriction, physical exercise and weight loss have not demonstrated any effect in the prevention of preeclampsia and serious maternal complications of hypertension.

Prognostic value of systolic short-term blood pressure variability in systolic heart failure.

BACKGROUND: Traditional cardiovascular risk factors in the general population are usually correlated to a better prognosis in patients with chronic heart failure (HF). Most of the studies show that blood pressure variability (BPV) has noxious effect on general population but data are missing for patients with systolic HF. The aim of this study was to assess the prognostic impact of short-term blood pressure variability (BPV) in systolic HF. METHODS AND RESULTS: We retrospectively studied 288 patients (60 ± 12 years-old; 79 % male) referred to our tertiary center of HF for the management of their systolic HF (left ventricular ejection fraction was 28 ± 9 %). All patients underwent ambulatory blood pressure monitoring (systolic BP: 110 ± 15; diastolic BP: 68 ± 10 and pulse pressure: 42 ± 11 mmHg) and the prognostic impact of BPV was collected with a mean follow-up of 4.4 ± 3.1 years. Twenty-five (9 %) patients were missing for follow-up. Among the others patients, 70 (27 %) cardiovascular events (cardiac deaths: 24 %; heart transplantation: 2 %) were recorded. By multivariate analysis BPV daytime (OR = 0.963, p = 0.033) and severe NYHA class (OR = 5.2, p < 0.0001) were found as independent predictors of cardiac event. Patients with a systolic daytime BPV under a cut-off value of 19 mmHg had the poorest prognosis with an OR for cumulative events of 1.65 (IC95 % 1.1-2.7; p < 0.04). CONCLUSION: BPV is simple tool and a predictor of cardiac events in patients with systolic HF.

SFE/SFHTA/AFCE consensus on primary aldosteronism, part 4: Subtype diagnosis.

To establish the cause of primary aldosteronism (PA), it is essential to distinguish unilateral from bilateral adrenal aldosterone secretion, as adrenalectomy improves aldosterone secretion and controls hypertension and hypokalemia only in the former. Except in the rare cases of type 1 or 3 familial hyperaldosteronism, which can be diagnosed genetically and are not candidates for surgery, lateralized aldosterone secretion is diagnosed on adrenal CT or MRI and adrenal venous sampling. Postural stimulation tests and (131)I-norcholesterol scintigraphy have poor diagnostic value and (11)C-metomidate PET is not yet available. We recommend that adrenal CT or MRI be performed in all cases of PA. Imaging may exceptionally identify adrenocortical carcinoma, for which the surgical objectives are carcinologic, and otherwise shows either normal or hyperplastic adrenals or unilateral adenoma. Imaging alone carries a risk of false positives in patients over 35 years of age (non-aldosterone-secreting adenoma) and false negatives in all patients (unilateral hyperplasia). We suggest that all candidates for surgery over 35 years of age undergo adrenal venous sampling, simultaneously in both adrenal veins, without ACTH stimulation, to confirm the unilateral form of the hypersecretion. Sampling results should be confirmed on adrenal vein cortisol assay showing a concentration at least double that found in peripheral veins. Aldosterone secretion should be considered lateralized when aldosterone/cortisol ratio on the dominant side is at least 4-fold higher than contralaterally.

Increased mean aliphatic lipid chain length in left ventricular hypertrophy secondary to arterial hypertension: A cross-sectional study.

About 77.9 million (1 in 4) American adults have high blood pressure. High blood pressure is the primary cause of left ventricular hypertrophy (LVH), which represents a strong predictor of future heart failure and cardiovascular mortality. Previous studies have shown an altered metabolic profile in hypertensive patients with LVH. The goal of this study was to identify blood metabolomic LVH biomarkers by H NMR to provide novel diagnostic tools for rapid LVH detection in populations of hypertensive individuals. This cross-sectional study included 48 hypertensive patients with LVH matched with 48 hypertensive patients with normal LV size, and 24 healthy controls. Two-dimensional targeted M-mode echocardiography was performed to measure left ventricular mass index. Partial least squares discriminant analysis was used for the multivariate analysis of the H NMR spectral data. From the H NMR-based metabolomic profiling, signals coming from methylene (-CH2-) and methyl (-CH3) moieties of aliphatic chains from plasma lipids were identified as discriminant variables. The -CH2-/-CH3 ratio, an indicator of the mean length of the aliphatic lipid chains, was significantly higher (P < 0.001) in the LVH group than in the hypertensive group without LVH and controls. Receiver operating characteristic curve showed that a cutoff of 2.34 provided a 52.08% sensitivity and 85.42% specificity for discriminating LVH (AUC = 0.703, P-value < 0.001). We propose the -CH2-/-CH3 ratio from plasma aliphatic lipid chains as a biomarker for the diagnosis of left ventricular remodeling in hypertension.

SFE/SFHTA/AFCE primary aldosteronism consensus: Introduction and handbook.

The French Endocrinology Society (SFE) French Hypertension Society (SFHTA) and Francophone Endocrine Surgery Association (AFCE) have drawn up recommendations for the management of primary aldosteronism (PA), based on an analysis of the literature by 27 experts in 7 work-groups. PA is suspected in case of hypertension associated with one of the following characteristics: severity, resistance, associated hypokalemia, disproportionate target organ lesions, or adrenal incidentaloma with hypertension or hypokalemia. Diagnosis is founded on aldosterone/renin ratio (ARR) measured under standardized conditions. Diagnostic thresholds are expressed according to the measurement units employed. Diagnosis is established for suprathreshold ARR associated with aldosterone concentrations >550pmol/L (200pg/mL) on 2 measurements, and rejected for aldosterone concentration<240pmol/L (90pg/mL) and/or subthreshold ARR. The diagnostic threshold applied is different if certain medication cannot be interrupted. In intermediate situations, dynamic testing is performed. Genetic forms of PA are screened for in young subjects and/or in case of familial history. The patient should be informed of the results expected from medical and surgical treatment of PA before exploration for lateralization is proposed. Lateralization is explored by adrenal vein sampling (AVS), except in patients under 35 years of age with unilateral adenoma on imaging. If PA proves to be lateralized, unilateral adrenalectomy may be performed, with adaptation of medical treatment pre- and postoperatively. If PA is non-lateralized or the patient refuses surgery, spironolactone is administered as first-line treatment, replaced by amiloride, eplerenone or calcium-channel blockers if insufficiently effective or poorly tolerated.

A polymorphism in the endothelin-A receptor gene is linked to baroreflex sensitivity.

BACKGROUND: The baroreflex plays an essential role in regulating the cardiovascular system. However, very few studies have focused on the links between genetic polymorphisms and baroreflex sensitivity (BRS). METHODS: A total of 146 hypertensive individuals who had never been treated, and 105 healthy individuals (controls) were included in the study. The genotypes of 17 polymorphisms of 11 genes involved in the regulation of the cardiovascular system were studied. BRS was measured using a sequence method: BRS was evaluated as the slope of spontaneous increases [systolic blood pressure (SBP)+/reflex response (RR)+] or decreases (SBP-/RR-) in SBP and pulse interval by recording blood pressure (BP) continuously for 20 min. RESULTS: Following univariate analysis, the genetic polymorphism of endothelin receptor A EDNRA/C+1222T was found to be significantly correlated with the BRS (SBP-/RR-) level in both populations. In normotensive subjects, mean BRS values (SBP-/RR-) were 11.93 +/- 3.69 ms/mmHg in EDNRA CC homozygotes, 9.94 +/- 2.97 ms/mmHg in CT heterozygotes and 9.51 +/- 3.16 ms/mmHg in TT homozygotes (P = 0.01). In hypertensive subjects, mean BRS values (SBP-/RR-) were 9.26 +/- 3.59 ms/mmHg in EDNRA CC homozygotes, 9.03 +/- 4.14 ms/mmHg in CT heterozygotes and 6.60 +/- 2.42 ms/mmHg in TT homozygotes (P = 0.01). After adjustment for age, sex, SBP and diastolic blood pressure and body mass index, the EDNRA/C+1222T polymorphism remained significantly correlated with BRS in both normotensive (P = 0.01) and hypertensive (P = 0.01) subjects. CONCLUSIONS: These results suggest that the endothelin system may be involved in the regulation of BRS in humans. In particular, the T allele of the EDNRA/C+1222T polymorphism is associated with a reduction in BRS in both healthy and hypertensive subjects.