Copeptin and insulin resistance: effect modification by age and 11 ß-HSD2 activity in a population-based study.

PURPOSE: Arginine vasopressin (AVP) may be involved in metabolic syndrome (MetS) by altering liver glycogenolysis, insulin and glucagon secretion, and pituitary ACTH release. Moreover, AVP stimulates the expression of 11ß-hydroxysteroid-dehydrogenase-type 2 (11ß-HSD2) in mineralocorticosteroid cells. We explored whether apparent 11ß-HSD2 activity, estimated using urinary cortisol-to-cortisone ratio, modulates the association between plasma copeptin, as AVP surrogate, and insulin resistance/MetS in the general adult population. METHODS: This was a multicentric, family-based, cross-sectional sample of 1089 subjects, aged 18-90 years, 47% men, 13.4% MetS, in Switzerland. Mixed multivariable linear and logistic regression models were built to investigate the association of insulin resistance (HOMA-IR)/fasting glucose and MetS/Type 2 Diabetes with copeptin, while considering potential confounders or effect modifiers into account. Stratified results by age and 11ß-HSD2 activity were presented as appropriate. RESULTS: Plasma copeptin was higher in men [median 5.2, IQR (3.7-7.8) pmol/L] than in women [median 3.0, IQR (2.2-4.3) pmol/L], P < 0.0001. HOMA-IR was positively associated with copeptin after full adjustment if 11ß-HSD2 activity was high [ß (95% CI) = 0.32 (0.17-0.46), P < 0.001] or if age was high [ß (95% CI) = 0.34 (0.20-0.48), P < 0.001], but not if either 11ß-HSD2 activity or age was low. There was a positive association of type 2 diabetes with copeptin [OR (95% CI) = 2.07 (1.10-3.89), P = 0.024), but not for MetS (OR (95% CI) = 1.12 (0.74-1.69), P = 0.605), after full adjustment. CONCLUSIONS: Our data suggest that age and apparent 11ß-HSD2 activity modulate the association of copeptin with insulin resistance at the population level but not MeTS or diabetes. Further research is needed to corroborate these results and to understand the mechanisms underlying these findings.

Seasonality of sodium and potassium consumption in Switzerland. Data from three cross-sectional, population-based studies.

BACKGROUND AND AIM: Blood pressure displays a seasonal pattern. Whether this pattern is related to high sodium and/or low potassium intakes has not been investigated. We assessed if sodium and potassium consumption present a seasonal pattern. We also simulated the impact of seasonality of sodium consumption on systolic blood pressure levels. METHODS AND RESULTS: Data from three Swiss population-based studies (n = 2845). Sodium and potassium consumption were assessed by urinary excretion using 24 h urine collection. Seasonality was assessed using the cosinor model and was adjusted for study, gender, age, body mass index, antihypertensive drug treatment, urinary creatinine and atmospheric relative humidity. The effect of sodium variation on blood pressure levels was estimated using data from a recent meta-analysis. Both sodium and potassium excretions showed a seasonal pattern. For sodium, the nadir occurred between August and October, and the peak between February and April, with a multivariate-adjusted seasonal variation (difference between peak and nadir) of 9.2 mmol. For potassium, the nadir occurred in October and the peak in April, with a multivariate-adjusted seasonal variation of 4.0 mmol. Excluding participants on antihypertensive drug treatment or stratifying the analysis by gender cancelled the seasonality of sodium consumption. The maximum impact of the seasonal variation in sodium consumption on systolic blood pressure ranged from 0.4 to 1.1 mm Hg, depending on the model considered. CONCLUSION: Sodium and potassium consumptions present specific seasonal variations. These variations do not explain the seasonal variations in blood pressure levels.

[Screening and management of hypertension in elderly]. / Dépistage et prise en charge de l'hypertension artérielle chez la personne âgée.

The prevalence of hypertension in elderly is extremely high. Because of the burden of ageing of population, this condition considered as the most important risk factor for mortality is supposed to increase. There are some specific pitfalls in the diagnosis and management of hypertension in elderly. The definition of hypertension is the same in all age groups, however the phenotype is different in the elderly: white coat effect, non-dipping pattern, orthostatic hypotension, dysautonomia and pseudohypertension. The hallmark of hypertension in the elderly is pure systolic hypertension and an increased variability of blood pressure. The diagnosis is often difficult to establish. The elderly can be overtreated with undesirable effects of falls or hypoperfusion, particularly when there is frailty, or polymedication.

[Innovative instruction for assisting patients with arterial hypertension]. / Une formation innovante sur l'accompagnement du patient atteint d'hypertension artérielle.

The MOOC In The Heart of Hypertension is an innovative online training for students and health providers. Its aim is to strengthen skills for professionals caring people suffering from hypertension. A MOOC is a free online training aiming unlimited participation. It widely promotes a high quality education. Medical and paramedical training recently seized upon this powerful tool, for initial and continuing training. Indeed, MOOC responds to several pedagogic challenges, particularly through educational strategies focused on the learner's skills: mastery of pedagogy, retrieval practice and peer grading. This MOOC about hypertension aims at responding to the needs of caregivers to enhance their therapeutic support skills.

[Atypical presentation of preeclampsia]. / Les présentations cliniques atypiques de la prééclampsie.

Preeclampsia is a pregnancy-related syndrome, which still represents one of the major causes of maternal-fetal mortality and morbidity. Diagnosis can be made difficult due to the complexity of the disorder and its wide spectrum of clinical manifestations. In order to provide an efficient diagnostic tool to the clinician, medical societies regularly rethink the definition criteria. However, there are still clinical presentations of preeclampsia that escape the frame of the definition. The present review will address atypical forms of preeclampsia, such as preeclampsia without proteinuria, normotensive preeclampsia, preeclampsia before 20 weeks of gestation and post-partum preeclampsia.

Blood pressure changes after renal denervation at 10 European expert centers.

We did a subject-level meta-analysis of the changes (Δ) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P0.08). Normalization was a systolic BP of <140 mm Hg on office measurement or <130 mm Hg on 24-h monitoring and improvement was a fall of 10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20-µmol l(-1) increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment.

[Sexuality, heart and chocolate]. / Sexualité, coeur et chocolat.

All along the history, many kinds of magic and aphrodisiac properties were attributed to the chocolate. Because of the presence of certain active substances, cacao and chocolate are supposed to have some potentially beneficial effects on human health, particularly on cardiovascular system. Containing flavoniods, cacao and its products have antioxidant, anti-inflammatory, anti-atherogenic, anti-thrombotic, antihypertensive and neuroprotective effects, as well as influence on insulin sensitivity, vascular endothelial function, and activation of nitric oxide. Other molecules, like methyxantin, biogenic amines and cannabinoid-like fatty acids, may have a psychoactive action. Synergic effect of all these substances could have a positive direct and indirect influence on sexual health and function. Nevertheless, randomized studies are needed to confirm these hypotheses and to elaborate recommendations about cacao consumption.

[Arterial blood pressure circadian rhythm: significance and clinical implications]. / Implications cliniques du cycle circadien de la pression artérielle.

Arterial blood pressure circadian rhythm: significance and clinical implications Arterial blood pressure exhibits a circadian rhythm characterized by a decrease during the sleep period and a steep increase in the early morning hours that can be characterized by 24 h ambulatory blood pressure monitoring (ABPM). The absence of a nocturnal dipping or an excessive morning surge, commonly observed in hypertensive patients, is associated with an increased cardiovascular and renal risk. Numerous studies show that a better control of nocturnal blood pressure can be obtained by the administration of anti-hypertensive medication at the evening time, improving microalbuminuria, left heart hypertrophy, or arterial intima-media thickness, but only one study has so far demonstrated a decrease of major cardiovascular events. In this context, the decision on restoring or not the nocturnal dipping should be left to the judgement of the clinician, and applied in an individual manner to each patient.

[Is ABPM an extension of a well done physical examination?]. / La MAPA: prolongation de l'examen physique bien fait?

Hypertension is a key risk factor for developing cardiovascular and renal diseases and one of the most important causes of morbidity and mortality worldwide. Iterative measurement of the clinical blood pressure is the method proposed by international and national organizations to establish the diagnosis of hypertension. However, current data suggest that neither in-hospital nor self home blood pressure measurement is sensitive and specific enough for one to recommend them as the sole diagnostic test. More accurate diagnosis of hypertension would allow a significant cost saving by reducing both cardiovascular and renal complication burden, and costs induced by erroneously diagnosing normal subjects as hypertensives. Therefore, 24h ABPM is increasingly becoming the gold standard for diagnosing hypertension.

[Diabetic nephropathy: an update]. / Néphropathie diabétique.

Diabetes has a constantly growing prevalence and leads to a number of complications such as diabetic nephropathy. A systematic screening and an adapted management are needed to limit the renal and also the cardiovascular complications linked to diabetic nephropathy. An adequate glycemic and tensional control and control of proteinuria are the priority in the care of diabetic nephropathy. Other aspects such as phospho-calcium balance, lipid panel or lifestyle changes are also important and therefore a multidisciplinary approach is essential. A better understanding of the physiopathology may lead to even more effective treatments in the future. We resume in this article the actual management of a patient suffering from diabetic nephropathy and the future treatment perspectives.

OS108. Preeclamptic women display salt sensitivity and cardiovascular damage before their menopause.

INTRODUCTION: Salt sensitivity is an important cardiovascular risk factor. It has been shown that preeclamptic (PEC) women may not be totally cured after the delivery and keep a higher cardiovascular risk than nonPEC women. OBJECTIVES: We aimed to study the salt sensitivity of the blood pressure in women with a history of severe preeclamspia and women with no history of hypertensive complications.The design was a case control study with intervention, including 42 women recruited 5 to 17 years following delivery. METHODS: 21 women having suffered from a severe preeclampsia before 34 weeks of pregnancy and 19 age, race matched controls women,were randomized to follow for one week a low salt (LS) diet and a high salt (HS) diet (adding 6g NACL/d to usual diet). On day seven of each dietary period, 24h ambulatory blood pressure was recorded, and 24h urine collected in order to measure sodium excretion.Salt sensitivity was assigned if the mean 24h blood pressure increased by ⩾ 3mmHg on a high- compared with a low-salt diet. RESULTS: Preeclamptic women were aged 39.1(24-49) and controls 40.1(29-49), p=NS.Two of the PEC women already suffered from a cardiovascular event (2coronary events). The PEC women showed a significant increase of the BP and standard deviation (SD) of the BP compared to the controls.10 (47.6%) preeclamptic women showed salt sensitivity (odd ratio 5.4, 95% CI 0.972-30.601;P=0.042).Recurrent preeclampsia was associated with a significantly high risk to salt sensitivity status (OR 5; 95% confidence interval 1.1-31.6). CONCLUSION: Severe PEC women display already salt sensitivity of the blood pressure before their menopause and increased variability of the BP. Recurrent preeclampsia is a high risk factor for salt sensitivity and could allow to target this high-risk group at an early stage for preventive measures for cardiovascular disease.

PP108. Post-partum evaluation of the blood pressure and the kidney function in pre-eclamptic women.

INTRODUCTION: Recent data have shown that preeclampsia is not just a disease of pregnancy that resolves with delivery. Preeclampsia may be considered a 'risk marker' for later-life diseases, including cardiovascular and renal diseases and the metabolic syndrome. OBJECTIVES: We aimed a longitudinal prospective study to analyze the renal abnormalities in the post-partum. METHODS: We studied 127 post-preeclamptic women at 6 weeks post-partum. Twenty-four hour urine collection, ambulatory blood pressure and renal function were evaluated. RESULTS: The mean age (±SD) was 32±6years, BMI was 29.4±5.7, the race distribution was Caucasian 69%, Hispanic 14%, Black 12% and Orient 5%. Ten % were active smokers, 10% have been suffering from gestational diabetes. The mean duration of the pregnancy was 36 weeks 3/7±4. Our results show that the prevalence of hypertension defined by office blood pressure ⩾140/90 mmHg or ongoing antihypertensive treatment was 35%. The daytime ambulatory blood pressure (ABPM) was 122±16/85±11 mmHg, heart rate 84±8, and 111±20/75±11 mmHg at nighttime.Sixteen % had a daytime ABPM ⩾135/85mmHg corresponding to the definition of ambulatory hypertension. Ultrasensitive CRP was 4.9±5.1mg/ml, of them 31% had a frank elevation of the CRP >4. The glomerular filtration rate evaluated by the Gault-Cockroft equation showed a hyperfiltration with a mean value of 150±42ml/min. Eleven% had a decreased GFR < 90 ml/min. Microalbumine/creatinine ratio measured in the urine spot was 7 ±4. Mean microalbuminuria was 225±529mg/d measured on the 24h urine collection.Urine 24h Na excretion rate was 204±48 mmol/d. CONCLUSION: In conclusion, after the post-partum period, women having suffered from a pre-eclampsia display many cardiovascular risk factors with a high prevalence of hypertension, microalbuminuria, renal hyperfiltration and elevated CRP. These women should be carefully screened, and sub-groups with the higher risk have to be targeted for prevention and treatment, and close follow-up.

[Primary hyperaldosteronism]. / Hyperaldostéronisme primaire.

After the age of 45 years more than 50% of the population will suffer from hypertension. The most common etiology is primary hypertension; however, in cases of severe or refractory hypertension, one should always look for secondary causes. Primary hyperaldosteronism will be the most common etiology. We will review the causes of hyperaldosteronism and discuss its diagnosis, algorithms and treatment.

[Anticancer drugs under pressure]. / Anticancéreux sous haute tension.

Angiogenesis inhibitor drugs, targeting VEGF (vascular endothelial growth factor) are used increasingly in oncology for a wide range of advanced cancers (colorectal cancer, lung cancer, renal cell cancer,...). Generally, they are well tolerated but cardiovascular and renal side effects may appear. The most frequent complications are hypertension and proteinuria which, very often, remain asymptomatic. Therefore, they have to be searched for systematically before and during the treatment. Sometimes, anti-hypertensive medication is needed. We are just beginning to understand the pathophysiological mechanisms of antiangiogenic therapies. Only a multidisciplinary approach will improve our knowledge of those target agents and allow a better management of the cancer patient.

[Hypertension: is the actual definition adapted to women?]. / Hypertension: la définition actuelle est-elle adaptée la femme?

The control of blood pressure in men and women differs due to different physiological pathways. Moreover, conditions increasing the risk of hypertension, such as pre-eclampsia, exposure to oral contraceptives are specific to women. Men have a higher blood pressure than women from pubertal growth to advanced age. However, the definition of hypertension (blood pressure--140/90 mmHg) is the same for adult men and women. The management of hypertension should be based not only on the level of blood pressure, but also on the global cardiovascular risk. Sex is included in the global evaluation of the cardiovascular risk.

Effects of the peroxisome proliferator-activated receptor (PPAR)-gamma agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals.

AIMS/HYPOTHESIS: Glitazones are powerful insulin sensitisers prescribed for the treatment of type 2 diabetes. Their use is, however, associated with fluid retention and an increased risk of congestive heart failure. We previously demonstrated that pioglitazone increases proximal sodium reabsorption in healthy volunteers. This study examines the effects of pioglitazone on renal sodium handling in individuals prone to insulin resistance, i.e. those with diabetes and/or hypertension. METHODS: In this double-blind randomised placebo-controlled four-way crossover study, we examined the effects of pioglitazone (45 mg daily during 6 weeks) or placebo on renal, systemic and hormonal responses to changes in sodium intake in 16 individuals, eight with type 2 diabetes and eight with hypertension. RESULTS: Pioglitazone was associated with a rapid increase in body weight and an increase in diurnal proximal sodium reabsorption, without any change in renal haemodynamics or in the modulation of the renin-angiotensin aldosterone system to changes in salt intake. A compensatory increase in brain natriuretic peptide levels was observed. In spite of sodium retention, pioglitazone dissociated the blood-pressure response to salt and abolished salt sensitivity in salt-sensitive individuals. CONCLUSIONS/INTERPRETATION: Pioglitazone increases diurnal proximal sodium retention in diabetic and hypertensive individuals. These effects cause fluid retention and may contribute to the increased incidence of congestive heart failure with glitazones. TRIAL REGISTRATION: ClinicalTrial.gov NCT01090752 FUNDING: Hypertension Research Foundation Lausanne.

[Nutrition and hypertension: more than table salt]. / Alimentation et hypertension artérielle: au-delà du sel de table.

The role of dietary sodium intake in the development, and its impact on the treatment, of hypertension are well recognized. However, many other nutritional compounds have been shown, or are believed, to influence blood pressure. Some compounds, such as caffeine and fructose, may raise arterial blood pressure, whereas others might lower arterial blood pressure, for example garlic, dark chocolate, fibers and potassium. In this article, we review several alimentary compounds and their (hypothesized) mechanisms of action, as well as the available evidence supporting a role of these compounds in the "non pharmacological" treatment and prevention of hypertension.