Accurate Location of Catheter Tip With the Free-to-Total Metanephrine Ratio During Adrenal Vein Sampling.

Background: The selectivity index (SI) of cortisol is used to document correct catheter placement during adrenal vein sampling (AVS) in patients with primary aldosteronism (PA). We aimed to determine the cutoff values of the SIs based on cortisol, free metanephrine, and the free-to-total metanephrine ratio (FTMR) using an adapted AVS protocol in combination with CT. Methods: Adults with PA and referred for AVS were recruited in two hypertension centers. The cortisol and free metanephrine-derived SIs were calculated as the concentration of the analyte in adrenal veins divided by the concentration of the analyte in the distal vena cava. The FTMR-derived SI was calculated as the concentration of free metanephrine in the adrenal vein divided by that of total metanephrine in the ipsilateral adrenal vein. The AVS was classified as an unequivocal radiological success (uAVS) if the tip of the catheter was seen in the adrenal vein. The SI cutoffs of each index marker were established using receiver operating characteristic curve analysis. Results: Out of 125 enrolled patients, 65 patients had an uAVS. The SI cutoffs were 2.6 for cortisol, 10.0 for free metanephrine, 0.31 for the FTMR on the left side, and 2.5, 9.9, and 0.25 on the right side. Compared to free metanephrine and the FTMR, cortisol misclassified AVS as unsuccessful in 36.6% and 39.0% of the cases, respectively. Conclusion: This study is the first to calculate the SIs of cortisol, free metanephrine, and the FTMR indices for the AVS procedure. It confirms that free metanephrine-based SIs are better than those based on cortisol.

Renal Resistive Index Is Associated With Inactive Matrix Gla (γ-Carboxyglutamate) Protein in an Adult Population-Based Study.

Background Increased renal resistive index (RRI) has been associated with target organ damage as well as renal and cardiovascular outcomes. Matrix Gla (γ-carboxyglutamate) protein (MGP) is a strong inhibitor of soft tissue calcification. Its inactive form (dephospho-uncarboxylated MGP [dp-ucMGP]) has been associated with vascular stiffness, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP were associated with increased RRI. Methods and Results We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Levels of dp-ucMGP were measured in plasma by sandwich ELISA. RRI was measured by Doppler ultrasound in 3 segmental arteries in both kidneys. We used mixed regression models to assess the relationship between dp-ucMGP and RRI. We adjusted for common determinants of RRI as well as renal function and cardiovascular risk factors. We included 1006 participants in our analyses: 526 women and 480 men. Mean values were 0.44±0.20 nmol/L for dp-ucMGP and 64±5% for RRI. After multivariable adjustment, dp-ucMGP was positively associated with RRI (P=0.001). In subgroup analysis by age tertiles, this association was not significant in the youngest age group (<38 years; P=0.62), whereas it was significant in older age groups (38-55 and >55 years; P=0.016 and P<0.001, respectively). Conclusions Levels of dp-ucMGP are positively and independently associated with RRI after adjustment for common determinants of RRI, cardiovascular risk factors, and renal function. The stronger association among older adults is probably due, in part, to age-related arterial stiffness. RRI thus seems to reflect the global atherosclerotic burden in a general adult population.

[The vascular access of hemodialysis patients - What should the primary care physician know about ?] / Accès vasculaire du patient hémodialysé - Que doit savoir le spécialiste en médecine interne générale ?

The most frequent dialysis modality in Switzerland is hemodialysis. Patients need a proper vascular access for this modality. There are three types of vascular access for hemodialysis : arteriovenous fistula, arteriovenous graft and central venous catheters. In this article, we will discuss the most important parameters that need to be taken into account when choosing the most appropriate access. We present the advantages and disadvantages of each vascular access, as well as their main local (thrombosis, infection, steal syndrome) and systemic (heart failure, pulmonary hypertension) complications, which may also be encountered by primary care physicians.

La majorité des patients dialysés en Suisse utilisent comme modalité l'hémodialyse. Cette technique nécessite un accès vasculaire permanent, dont il existe trois types : la fistule artérioveineuse native, la fistule artérioveineuse prothétique et le cathéter veineux central. Dans cet article, nous passerons en revue les paramètres à prendre en compte avant la création et l'utilisation d'une fistule. Nous discuterons les avantages et les inconvénients des différents accès ainsi que des complications locales (thrombose, infection, syndrome de vol) et systémiques (insuffisance cardiaque, hypertension pulmonaire) les plus fréquentes qu'ils peuvent engendrer et auxquelles les médecins en première ligne peuvent aussi être confrontés.

Reduced cortical oxygenation predicts a progressive decline of renal function in patients with chronic kidney disease.

Renal tissue hypoxia is a final pathway in the development and progression of chronic kidney disease (CKD), but whether renal oxygenation predicts renal function decline in humans has not been proven. Therefore, we performed a prospective study and measured renal tissue oxygenation by blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) in 112 patients with CKD, 47 with hypertension without CKD, and 24 healthy control individuals. Images were analyzed with the twelve-layer concentric objects method that divided the renal parenchyma in 12 layers of equal thickness and reports the mean R2* value of each layer (a high R2* corresponds to low oxygenation), along with the change in R2* between layers called the R2* slope. Serum creatinine values were collected to calculate the yearly change in estimated glomerular function rate (MDRD eGFR). Follow up was three years. The change in eGFR in CKD, hypertensive and control individuals was -2.0, 0.5 and -0.2 ml/min/1.73m2/year, respectively. In multivariable regression analysis adjusted for age, sex, diabetes, RAS-blockers, eGFR, and proteinuria the yearly eGFR change correlated negatively with baseline 24 hour proteinuria and the mean R2* value of the cortical layers, and positively with the R2* slope, but not with the other covariates. Patients with CKD and high outer R2* or a flat R2* slope were three times more likely to develop an adverse renal outcome (renal replacement therapy or over a 30% increase in serum creatinine). Thus, low cortical oxygenation is an independent predictor of renal function decline. This finding should stimulate studies exploring the therapeutic impact of improving renal oxygenation on renal disease progression.

Glycaemic, blood pressure and lipid goal attainment and chronic kidney disease stage of type 2 diabetic patients treated in primary care practices.

INTRODUCTION: The prevalence of chronic kidney disease and diabetes is rising in Europe. These patients are at high cardiovascular and renal risk and need a challenging multifactorial therapeutic approach. METHOD: The goal of this cross-sectional study was to examine the treatment and attainments of goals related to cardiovascular risk factors within chronic kidney disease stages in type 2 diabetic patients followed up by primary care physicians in Switzerland. Each participating physician entered into a web database the anonymised data of up to 15 consecutive diabetic patients attending her/his office between December 2013 and June 2014. Diabetes, hypertension and lipid lowering therapies were analysed, as well as glycated haemoglobin (HbA1c), blood pressure and low-density lipoprotein-cholesterol (LDL-c) levels and goal attainments by KDIGO chronic kidney disease stage 1 to 4. RESULTS: A total of 1359 patients (mean age 66.5±12.4 years) were included by 109 primary care physicians. Chronic kidney disease stages 0-2, 3a, 3 b and 4 were present in 77.6%, 13.9%, 6.1%, and 2.4%, respectively. Average HbA1c was independent of chronic kidney disease stage and close to 7%; more than half of the patients reached the HbA1c goal. Eighty-four percent of patients were hypertensive and only 18.2% reached the then current Swiss or American Diabetes Association 2013 blood pressure goals. Despite loosening of blood pressure goals in 2015, only half of the patients reached them and most needed multiple therapies. Increased body mass index and advanced chronic kidney disease stage decreased the chance of reaching blood pressure goals. Lipid lowering therapy was prescribed in 62.1% of cases, with average LDL-c levels similar across chronic kidney disease stages. Only 42% of patients reached the LDL-c goal of <2.5 mmol/l in primary prevention and 32% reached <1.8 mmol/l in secondary prevention. Younger patients were treated significantly less aggressively than older patients (≥68 years, median age) for HbA1c, LDL-c and diastolic blood pressure control. CONCLUSION: This cross-sectional study demonstrates that blood pressure and lipid goals are less often achieved than blood glucose control in type 2 diabetic patients followed up by primary care physicians in Switzerland. Goal attainments for HbA1c and LDL-c were not influenced by chronic kidney disease stages, in contrast to blood pressure. Reaching all three goals was rare (2.2%). There is a need for improvement in blood pressure control in advanced chronic kidney disease, whereas HbA1c goals may be loosened in the elderly and in advanced chronic kidney disease.

Genome-wide association study of caffeine metabolites provides new insights to caffeine metabolism and dietary caffeine-consumption behavior.

Caffeine is the most widely consumed psychoactive substance in the world and presents with wide interindividual variation in metabolism. This variation may modify potential adverse or beneficial effects of caffeine on health. We conducted a genome-wide association study (GWAS) of plasma caffeine, paraxanthine, theophylline, theobromine and paraxanthine/caffeine ratio among up to 9,876 individuals of European ancestry from six population-based studies. A single SNP at 6p23 (near CD83) and several SNPs at 7p21 (near AHR), 15q24 (near CYP1A2) and 19q13.2 (near CYP2A6) met GW-significance (P < 5 × 10-8) and were associated with one or more metabolites. Variants at 7p21 and 15q24 associated with higher plasma caffeine and lower plasma paraxanthine/caffeine (slow caffeine metabolism) were previously associated with lower coffee and caffeine consumption behavior in GWAS. Variants at 19q13.2 associated with higher plasma paraxanthine/caffeine (slow paraxanthine metabolism) were also associated with lower coffee consumption in the UK Biobank (n = 94 343, P < 1.0 × 10-6). Variants at 2p24 (in GCKR), 4q22 (in ABCG2) and 7q11.23 (near POR) that were previously associated with coffee consumption in GWAS were nominally associated with plasma caffeine or its metabolites. Taken together, we have identified genetic factors contributing to variation in caffeine metabolism and confirm an important modulating role of systemic caffeine levels in dietary caffeine consumption behavior. Moreover, candidate genes identified encode proteins with important clinical functions that extend beyond caffeine metabolism.

[News in blood pressure in 2015]. / Hypertension artérielle.

In this short review, we present 4 studies published in 2014-2015 which appear to important for clinicians. The results of the SPRINT trial are challenging the target systolic blood pressure (BP) to be achieved in non-diabetic hypertensive. It shows that a target BP <120 mmHg provides clear mortality and morbidity advantages over a <140 mmHg target. The PATHWAY2 and 3 studies reemphasize the important role of potassium sparing diuretics in patients with resistant hypertension and in patients with metabolic syndrome. At last the DENERHTN study conducted in France suggests that renal denervation is not dead and that additional studies are needed to position this technique in management of resistant hypertension.

Sociodemographic, behavioral and genetic determinants of allostatic load in a Swiss population-based study.

Allostatic load (AL) is a marker of physiological dysregulation which reflects exposure to chronic stress. High AL has been related to poorer health outcomes including mortality. We examine here the association of socioeconomic and lifestyle factors with AL. Additionally, we investigate the extent to which AL is genetically determined. We included 803 participants (52% women, mean age 48±16years) from a population and family-based Swiss study. We computed an AL index aggregating 14 markers from cardiovascular, metabolic, lipidic, oxidative, hypothalamus-pituitary-adrenal and inflammatory homeostatic axes. Education and occupational position were used as indicators of socioeconomic status. Marital status, stress, alcohol intake, smoking, dietary patterns and physical activity were considered as lifestyle factors. Heritability of AL was estimated by maximum likelihood. Women with a low occupational position had higher AL (low vs. high OR=3.99, 95%CI [1.22;13.05]), while the opposite was observed for men (middle vs. high OR=0.48, 95%CI [0.23;0.99]). Education tended to be inversely associated with AL in both sexes(low vs. high OR=3.54, 95%CI [1.69;7.4]/OR=1.59, 95%CI [0.88;2.90] in women/men). Heavy drinking men as well as women abstaining from alcohol had higher AL than moderate drinkers. Physical activity was protective against AL while high salt intake was related to increased AL risk. The heritability of AL was estimated to be 29.5% ±7.9%. Our results suggest that generalized physiological dysregulation, as measured by AL, is determined by both environmental and genetic factors. The genetic contribution to AL remains modest when compared to the environmental component, which explains approximately 70% of the phenotypic variance.

[Does pollution have an impact on blood pressure ?] / La pollution a-t-elle un impact sur la pression artérielle ?

Several important public health issues such as cardiovascular events are resulting from the actual levels of pollution. There are many sources of pollution ; the most common are loud noise, ambient temperature changes and air pollution. In this article, we try to bring out the impact of these factors on blood pressure, which is probably one of the mechanisms implicated in the upsurge of cardiovascular diseases and mortality.

La pollution est responsable de nombreux problèmes de santé publique de grande importance, dont la survenue d'événements cardiovasculaires. Différentes sources de pollution existent ; le bruit, les changements de température, la pollution de l'air sont les plus connus. Dans cet article, nous essayons de souligner l'effet de ces différents polluants sur la pression artérielle comme l'un des mécanismes potentiels pouvant expliquer l'augmentation de la morbi/mortalité cardiovasculaire associée à la pollution.

[Usefulness of night-time blood pressure measurement]. / La recherche d'une hypertension nocturne est-elle utile ?

Since the use of ambulatory blood pressure monitoring (ABPM) in the beginning of the 70's, our perception of blood pressure based only on office blood pressure has been challenged. Indeed, more specific phenotypes such as white coat hypertension, masked hypertension or different circadian patterns of blood pressure have been described and studied. This has resulted in increased use of ambulatory blood pressure measurements for diagnostic and therapeutic purposes. The main focus of this paper is night-time blood pressure. We review, in a non-systematic way, the diagnostic, the prognostic and therapeutic utility of night-time blood pressure. Finally, studies in which antihypertensive drugs are given at night will be presented.

Depuis les années 1970, la mesure ambulatoire de la pression artérielle sur 24 heures a permis d'apporter un regard différent de celui habituellement fixé sur la mesure au cabinet du médecin. Grâce à son emploi, des phénotypes plus spécifiques tels que l'hypertension de la blouse blanche, l'hypertension masquée ou encore les variations circadiennes de la pression artérielle ont été décrits et étudiés, si bien que la prise en charge des patients repose de plus en plus sur cette mesure ambulatoire de la pression artérielle. Dans cet article, nous nous intéresserons à la pression artérielle nocturne. Nous passerons en revue son utilité diagnostique, son pronostic et la thérapeutique. Finalement nous présentons les études avec un traitement antihypertenseur pris spécifiquement le soir.

Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population-Based Study.

Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7.87±2.10 m/s for PWV and 0.43±0.20 nmol/L for dp-ucMGP. PWV was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, height, systolic and diastolic blood pressure (BP), heart rate, renal function, low- and high-density lipoprotein, glucose, smoking status, diabetes mellitus, BP and cholesterol lowering drugs, and history of cardiovascular disease (P≤0.01). In conclusion, high levels of dp-ucMGP are independently and positively associated with arterial stiffness after adjustment for common cardiovascular risk factors, renal function, and age. Experimental studies are needed to determine whether vitamin K supplementation slows arterial stiffening by increasing MGP carboxylation.

Characteristics and treatment response of self-identified problematic Internet users in a behavioral addiction outpatient clinic.

AIMS: Controversies remain about the validity of the diagnosis of problematic Internet use. This might be due in part to the lack of longitudinal naturalistic studies that have followed a cohort of patients who self-identify as having Internet-related problems. METHODS: This retrospective study included 57 patients who consulted the Geneva Addiction Outpatient Clinic from January 1, 2007, to January 1, 2010. Patients underwent an initial clinical psychiatric evaluation that included collection of data on socio-demographics, method of referral, specific Internet usage, psychiatric diagnosis, and Internet Addiction Test (IAT) and Clinical Global Impression Scale (CGI) scores. Treatment consisted of individual psychotherapeutic sessions. RESULTS: Of these patients, 98% were male and 37% were 18 years or younger. Most patients were online gamers (46% playing massively multiplayer online role-playing games). The mean IAT score was 52.9 (range 20-90). Sixty-eight percent of patients had a co-morbid psychiatric diagnosis, with social phobia being the most prevalent (17.8%). Patients who remained in treatment (dropout rate 24%) showed an overall improvement of symptoms: 38.6% showed significant or average improvement on their CGI score, 26.3% showed minimal improvement, and 14% showed no change. CONCLUSIONS: Our results support the hypothesis that there are specific types of Internet use, with online gaming mainly affecting young male patients. As Internet addiction is not yet an official diagnosis, better instruments are needed to screen patients and to avoid false-negative and false-positive diagnoses. Successful care should integrate the treatment of co-morbid symptoms and involve families and relatives in the therapeutic process.