Multivariate brain-behaviour associations in psychiatric disorders.

Mapping brain-behaviour associations is paramount to understand and treat psychiatric disorders. Standard approaches involve investigating the association between one brain and one behavioural variable (univariate) or multiple variables against one brain/behaviour feature ('single' multivariate). Recently, large multimodal datasets have propelled a new wave of studies that leverage on 'doubly' multivariate approaches capable of parsing the multifaceted nature of both brain and behaviour simultaneously. Within this movement, canonical correlation analysis (CCA) and partial least squares (PLS) emerge as the most popular techniques. Both seek to capture shared information between brain and behaviour in the form of latent variables. We provide an overview of these methods, review the literature in psychiatric disorders, and discuss the main challenges from a predictive modelling perspective. We identified 39 studies across four diagnostic groups: attention deficit and hyperactive disorder (ADHD, k = 4, N = 569), autism spectrum disorders (ASD, k = 6, N = 1731), major depressive disorder (MDD, k = 5, N = 938), psychosis spectrum disorders (PSD, k = 13, N = 1150) and one transdiagnostic group (TD, k = 11, N = 5731). Most studies (67%) used CCA and focused on the association between either brain morphology, resting-state functional connectivity or fractional anisotropy against symptoms and/or cognition. There were three main findings. First, most diagnoses shared a link between clinical/cognitive symptoms and two brain measures, namely frontal morphology/brain activity and white matter association fibres (tracts between cortical areas in the same hemisphere). Second, typically less investigated behavioural variables in multivariate models such as physical health (e.g., BMI, drug use) and clinical history (e.g., childhood trauma) were identified as important features. Finally, most studies were at risk of bias due to low sample size/feature ratio and/or in-sample testing only. We highlight the importance of carefully mitigating these sources of bias with an exemplar application of CCA.

A neuroimaging measure to capture heterogeneous patterns of atrophy in Parkinson's disease and dementia with Lewy bodies.

INTRODUCTION: Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) show heterogeneous brain atrophy patterns which group-average analyses fail to capture. Neuroanatomical normative modelling overcomes this by comparing individuals to a large reference cohort. Patient-specific atrophy patterns are measured objectively and summarised to index overall neurodegeneration (the 'total outlier count'). We aimed to quantify patterns of neurodegenerative dissimilarity in participants with PD and DLB and evaluate the potential clinical relevance of total outlier count by testing its association with key clinical measures in PD and DLB. MATERIALS AND METHODS: We included 108 participants with PD and 61 with DLB. PD participants were subclassified into high and low visual performers as this has previously been shown to stratify those at increased dementia risk. We generated z-scores from T1w-MRI scans for each participant relative to normative regional cortical thickness and subcortical volumes, modelled in a reference cohort (n = 58,836). Outliers (z < -1.96) were aggregated across 169 brain regions per participant. To measure dissimilarity, individuals' Hamming distance scores were calculated. We also examined total outlier counts between high versus low visual performance in PD; and PD versus DLB; and tested associations between these and cognition. RESULTS: There was significantly greater inter-individual dissimilarity in brain-outlier patterns in PD poor compared to high visual performers (W = 522.5; p < 0.01) and in DLB compared to PD (W = 5649; p < 0.01). PD poor visual performers had significantly greater total outlier counts compared to high (ß = -4.73 (SE = 1.30); t = -3.64; p < 0.01) whereas a conventional group-level GLM failed to identify differences. Higher total outlier counts were associated with poorer MoCA (ß = -0.55 (SE = 0.27), t = -2.04, p = 0.05) and composite cognitive scores (ß = -2.01 (SE = 0.79); t = -2.54; p = 0.02) in DLB, and visuoperception (ß = -0.67 (SE = 0.19); t = -3.59; p < 0.01), in PD. CONCLUSIONS: Neuroanatomical normative modelling shows promise as a clinically informative technique in PD and DLB, where patterns of atrophy are variable.

Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning.

Cognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual's long-term clinical response therefore remains an important challenge. This study aimed at assessing neural predictors of long-term treatment outcome in participants with SAD 1 year after completion of Internet-delivered CBT (iCBT). Twenty-six participants diagnosed with SAD underwent iCBT including attention bias modification for a total of 13 weeks. Support vector machines (SVMs), a supervised pattern recognition method allowing predictions at the individual level, were trained to separate long-term treatment responders from nonresponders based on blood oxygen level-dependent (BOLD) responses to self-referential criticism. The Clinical Global Impression-Improvement scale was the main instrument to determine treatment response at the 1-year follow-up. Results showed that the proportion of long-term responders was 52% (12/23). From multivariate BOLD responses in the dorsal anterior cingulate cortex (dACC) together with the amygdala, we were able to predict long-term response rate of iCBT with an accuracy of 92% (confidence interval 95% 73.2-97.6). This activation pattern was, however, not predictive of improvement in the continuous Liebowitz Social Anxiety Scale-Self-report version. Follow-up psychophysiological interaction analyses revealed that lower dACC-amygdala coupling was associated with better long-term treatment response. Thus, BOLD response patterns in the fear-expressing dACC-amygdala regions were highly predictive of long-term treatment outcome of iCBT, and the initial coupling between these regions differentiated long-term responders from nonresponders. The SVM-neuroimaging approach could be of particular clinical value as it allows for accurate prediction of treatment outcome at the level of the individual.

Using structural neuroanatomy to identify trauma survivors with and without post-traumatic stress disorder at the individual level.

BACKGROUND: At present there are no objective, biological markers that can be used to reliably identify individuals with post-traumatic stress disorder (PTSD). This study assessed the diagnostic potential of structural magnetic resonance imaging (sMRI) for identifying trauma-exposed individuals with and without PTSD. METHOD: sMRI scans were acquired from 50 survivors of the Sichuan earthquake of 2008 who had developed PTSD, 50 survivors who had not developed PTSD and 40 healthy controls who had not been exposed to the earthquake. Support vector machine (SVM), a multivariate pattern recognition technique, was used to develop an algorithm that distinguished between the three groups at an individual level. The accuracy of the algorithm and its statistical significance were estimated using leave-one-out cross-validation and permutation testing. RESULTS: When survivors with PTSD were compared against healthy controls, both grey and white matter allowed discrimination with an accuracy of 91% (p < 0.001). When survivors without PTSD were compared against healthy controls, the two groups could be discriminated with accuracies of 76% (p < 0.001) and 85% (p < 0.001) based on grey and white matter, respectively. Finally, when survivors with and without PTSD were compared directly, grey matter allowed discrimination with an accuracy of 67% (p < 0.001); in contrast the two groups could not be distinguished based on white matter. CONCLUSIONS: These results reveal patterns of neuroanatomical alterations that could be used to inform the identification of trauma survivors with and without PTSD at the individual level, and provide preliminary support to the development of SVM as a clinically useful diagnostic aid.

Examination of the predictive value of structural magnetic resonance scans in bipolar disorder: a pattern classification approach.

BACKGROUND: Bipolar disorder (BD) is one of the leading causes of disability worldwide. Patients are further disadvantaged by delays in accurate diagnosis ranging between 5 and 10 years. We applied Gaussian process classifiers (GPCs) to structural magnetic resonance imaging (sMRI) data to evaluate the feasibility of using pattern recognition techniques for the diagnostic classification of patients with BD. METHOD: GPCs were applied to gray (GM) and white matter (WM) sMRI data derived from two independent samples of patients with BD (cohort 1: n = 26; cohort 2: n = 14). Within each cohort patients were matched on age, sex and IQ to an equal number of healthy controls. RESULTS: The diagnostic accuracy of the GPC for GM was 73% in cohort 1 and 72% in cohort 2; the sensitivity and specificity of the GM classification were respectively 69% and 77% in cohort 1 and 64% and 99% in cohort 2. The diagnostic accuracy of the GPC for WM was 69% in cohort 1 and 78% in cohort 2; the sensitivity and specificity of the WM classification were both 69% in cohort 1 and 71% and 86% respectively in cohort 2. In both samples, GM and WM clusters discriminating between patients and controls were localized within cortical and subcortical structures implicated in BD. CONCLUSIONS: Our results demonstrate the predictive value of neuroanatomical data in discriminating patients with BD from healthy individuals. The overlap between discriminative networks and regions implicated in the pathophysiology of BD supports the biological plausibility of the classifiers.

Pattern recognition analysis of anterior cingulate cortex blood flow to classify depression polarity.

Differentiating bipolar from recurrent unipolar depression is a major clinical challenge. In 18 healthy females and 36 females in a depressive episode--18 with bipolar disorder type I, 18 with recurrent unipolar depression--we applied pattern recognition analysis using subdivisions of anterior cingulate cortex (ACC) blood flow at rest, measured with arterial spin labelling. Subgenual ACC blood flow classified unipolar v. bipolar depression with 81% accuracy (83% sensitivity, 78% specificity).

Multivariate decoding of brain images using ordinal regression.

Neuroimaging data are increasingly being used to predict potential outcomes or groupings, such as clinical severity, drug dose response, and transitional illness states. In these examples, the variable (target) we want to predict is ordinal in nature. Conventional classification schemes assume that the targets are nominal and hence ignore their ranked nature, whereas parametric and/or non-parametric regression models enforce a metric notion of distance between classes. Here, we propose a novel, alternative multivariate approach that overcomes these limitations - whole brain probabilistic ordinal regression using a Gaussian process framework. We applied this technique to two data sets of pharmacological neuroimaging data from healthy volunteers. The first study was designed to investigate the effect of ketamine on brain activity and its subsequent modulation with two compounds - lamotrigine and risperidone. The second study investigates the effect of scopolamine on cerebral blood flow and its modulation using donepezil. We compared ordinal regression to multi-class classification schemes and metric regression. Considering the modulation of ketamine with lamotrigine, we found that ordinal regression significantly outperformed multi-class classification and metric regression in terms of accuracy and mean absolute error. However, for risperidone ordinal regression significantly outperformed metric regression but performed similarly to multi-class classification both in terms of accuracy and mean absolute error. For the scopolamine data set, ordinal regression was found to outperform both multi-class and metric regression techniques considering the regional cerebral blood flow in the anterior cingulate cortex. Ordinal regression was thus the only method that performed well in all cases. Our results indicate the potential of an ordinal regression approach for neuroimaging data while providing a fully probabilistic framework with elegant approaches for model selection.

Using genetic, cognitive and multi-modal neuroimaging data to identify ultra-high-risk and first-episode psychosis at the individual level.

BACKGROUND: Group-level results suggest that relative to healthy controls (HCs), ultra-high-risk (UHR) and first-episode psychosis (FEP) subjects show alterations in neuroanatomy, neurofunction and cognition that may be mediated genetically. It is unclear, however, whether these groups can be differentiated at single-subject level, for instance using the machine learning analysis support vector machine (SVM). Here, we used a multimodal approach to examine the ability of structural magnetic resonance imaging (sMRI), functional MRI (fMRI), diffusion tensor neuroimaging (DTI), genetic and cognitive data to differentiate between UHR, FEP and HC subjects at the single-subject level using SVM. METHOD: Three age- and gender-matched SVM paired comparison groups were created comprising 19, 19 and 15 subject pairs for FEP versus HC, UHR versus HC and FEP versus UHR, respectively. Genetic, sMRI, DTI, fMRI and cognitive data were obtained for each participant and the ability of each to discriminate subjects at the individual level in conjunction with SVM was tested. RESULTS: Successful classification accuracies (p < 0.05) comprised FEP versus HC (genotype, 67.86%; DTI, 65.79%; fMRI, 65.79% and 68.42%; cognitive data, 73.69%), UHR versus HC (sMRI, 68.42%; DTI, 65.79%), and FEP versus UHR (sMRI, 76.67%; fMRI, 73.33%; cognitive data, 66.67%). CONCLUSIONS: The results suggest that FEP subjects are identifiable at the individual level using a range of biological and cognitive measures. Comparatively, only sMRI and DTI allowed discrimination of UHR from HC subjects. For the first time FEP and UHR subjects have been shown to be directly differentiable at the single-subject level using cognitive, sMRI and fMRI data. Preliminarily, the results support clinical development of SVM to help inform identification of FEP and UHR subjects, though future work is needed to provide enhanced levels of accuracy.

PRoNTo: pattern recognition for neuroimaging toolbox.

In the past years, mass univariate statistical analyses of neuroimaging data have been complemented by the use of multivariate pattern analyses, especially based on machine learning models. While these allow an increased sensitivity for the detection of spatially distributed effects compared to univariate techniques, they lack an established and accessible software framework. The goal of this work was to build a toolbox comprising all the necessary functionalities for multivariate analyses of neuroimaging data, based on machine learning models. The "Pattern Recognition for Neuroimaging Toolbox" (PRoNTo) is open-source, cross-platform, MATLAB-based and SPM compatible, therefore being suitable for both cognitive and clinical neuroscience research. In addition, it is designed to facilitate novel contributions from developers, aiming to improve the interaction between the neuroimaging and machine learning communities. Here, we introduce PRoNTo by presenting examples of possible research questions that can be addressed with the machine learning framework implemented in PRoNTo, and cannot be easily investigated with mass univariate statistical analysis.

Test-retest reliability of the BOLD pharmacological MRI response to ketamine in healthy volunteers.

The pharmacological MRI (phMRI) technique is being increasingly used in both pre-clinical and clinical models to investigate pharmacological effects on task-free brain function. Ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist, induces a strong phMRI response and represents a promising pharmacological model to investigate the role of glutamatergic abnormalities in psychiatric symptomatology. The aim of this study was to assess whether the brain response to ketamine is reliable in order to validate ketamine phMRI as a mechanistic marker of glutamatergic dysfunction and to determine its utility in repeated measures designs to detect the modulatory effect of other drugs. Thus we assessed the test-retest reliability of the brain response to ketamine in healthy volunteers and identified an optimal modelling approach with reliability as our selection criterion. PhMRI data were collected from 10 healthy male participants, at rest, on two separate occasions. Subanaesthetic doses of I.V. ketamine infusion (target plasma levels 50 ng/mL and 75 ng/mL) were administered in both sessions. Test-retest reliability of the ketamine phMRI response was assessed voxel-wise and on pre-defined ROIs for a range of temporal design matrices including different combinations of nuisance regressors designed to model shape variance, linear drift and head motion. Effect sizes are also reported. All models showed a significant and widespread response to low-dose ketamine in predicted cerebral networks and as expected, increasing the number of model parameters improved model fit. Reliability of the predefined ROIs differed between the different models assessed. Using reliability as the selection criterion, a model capturing subject motion and linear drift performed the best across two sessions. The anatomical distribution of effects for all models was consistent with results of previous imaging studies in humans with BOLD signal increases in regions including midline cingulate and supracingulate cortex, thalamus, insula, anterior temporal lobe and ventrolateral prefrontal structures, and BOLD signal decreases in the subgenual cingulate cortex. This study represents the first investigation of the test-retest reliability of the BOLD phMRI response to acute ketamine challenge. All models tested were effective at describing the ketamine response although the design matrix associated with the highest reliability may represent a robust and well-characterised ketamine phMRI assay more suitable for repeated-measures designs. This ketamine assay is applicable as a model of neurotransmitter dysfunction suitable as a pharmacodynamic imaging tool to test and validate modulatory interventions, as a model of NMDA hypofunction in psychiatric disorders, and may be adapted to understand potential antidepressant and analgesic effects of NMDAR antagonists.

PROBABILISTIC PREDICTION OF NEUROLOGICAL DISORDERS WITH A STATISTICAL ASSESSMENT OF NEUROIMAGING DATA MODALITIES.

For many neurological disorders, prediction of disease state is an important clinical aim. Neuroimaging provides detailed information about brain structure and function from which such predictions may be statistically derived. A multinomial logit model with Gaussian process priors is proposed to: (i) predict disease state based on whole-brain neuroimaging data and (ii) analyze the relative informativeness of different image modalities and brain regions. Advanced Markov chain Monte Carlo methods are employed to perform posterior inference over the model. This paper reports a statistical assessment of multiple neuroimaging modalities applied to the discrimination of three Parkinsonian neurological disorders from one another and healthy controls, showing promising predictive performance of disease states when compared to nonprobabilistic classifiers based on multiple modalities. The statistical analysis also quantifies the relative importance of different neuroimaging measures and brain regions in discriminating between these diseases and suggests that for prediction there is little benefit in acquiring multiple neuroimaging sequences. Finally, the predictive capability of different brain regions is found to be in accordance with the regional pathology of the diseases as reported in the clinical literature.

[Home blood pressure monitoring in addition to office blood pressure determination is useful in patients with systolic hypertension before their inclusion into a drug trial]. / L'automesure tensionnelle en complément de la mesure de consultation est utile pour l'inclusion dans un essai clinique de sujets avec une HTA systolique.

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.

[Systolic blood pressures are not comparable when home blood pressure is measured with a wrist or an arm validated monitor]. / Comparaison des valeurs de PAS/PAD obtenues lors d'une utilisation séquentielle d'un auto-tensiomètre de bras ou de poignet.

OBJECTIVES: To compare home blood pressure values obtained with two validated OMRON (wrist or arm) monitors used sequentially in the same subject. METHODS: In 265 hypertensive subjects referred to hypertension specialists, a self measurement of blood pressure was performed sequentially with an OMRON M4-I (arm cuff, A/A, BHS validation) or OMRON RX-I (wrist cuff, B/B, BHS validation). Each patient recorded home blood pressure during two periods of 4 days with 3 measures in the morning and 3 in the evening. Order for use of each monitor was randomised. With wrist devices, subjects were advised to keep the arm at heart level during measurements. BP values were reported on a standardized document. Patients were asked by a questionnaire about the tolerance and feasibility of the 2 methods. RESULTS: In this population, aged 59 +/- 14 years, with 60% of men and a mean blood pressure of 152 +/- 21 / 86 +/- 14 mmHg, the home blood pressure values were 143 +/- 20/81 +/- 11 mmHg with the arm monitor and 135 +/- 10 / 80 +/- 11 mmHg with the wrist monitor. Mean SBP adjusted on age, initial blood pressure level and period order was significantly lower when home blood pressure monitoring has been recorded with a wrist monitor as compared to an arm monitor (p < 0.001). Self measurement of blood pressure was felt as easy in 92% with the arm monitor and in 96% with the wrist monitor (p < 0.05). Self measurement of blood pressure was felt as constraining in 14% with the arm monitor and in 7% with the wrist monitor (p < 0.01). The feasibility between the two devices was good with none of the value missing in 86% with the arm monitor and in 85% with the wrist monitor. The missing values were in 56% the fourth day. CONCLUSION: Despite the use of two validated monitors, mean SBP is significantly lower when home blood pressure monitoring is recorded with a wrist monitor as compared to an arm monitor. Uncertainty in the arm position with the use of wrist device could explain these results. When advising home blood pressure monitoring, care should be taken to recommend only the use of validated devices and to prefer the use of arm devices in order to avoid the uncertainty of an inadequate utilisation.

[Association between blood pressure level and the follow up of the guidelines concerning the use of self blood pressure measurement]. / Association entre le niveau tensionnel en consultation et le suivi d'un protocole d'automesure.

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.

[Medical management of libido disturbances in treated hypertensive patients: differences between men and women]. / Prise en charge médicale des troubles de la libido chez les hypertendus traités: différence entre homme et femme.

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.

[Sexual dysfunction in treated hypertensive patients. Results of a national survey]. / Troubles de la sexualité chez les hypertendus traités. Résultats d'une enquête nationale.

OBJECTIVES: To evaluate, using an self-administered questionnaire, the characteristics of sexual function in treated hypertensives. METHODS: In 459 hypertensive subjects, aged of 59 +/- 12 years, living in France and referred to hypertension specialists, a self-administered questionnaire evaluating quality of life and antihypertensive treatment was given before the consultation. Several questions focused on the quality of sexual function since the last 12 months (interest for sexuality, sexual pleasure, quality of erection). Details on antihypertensive treatments and cardiovascular characteristics were obtained from medical records. Antihypertensive treatments were prescribed since more than 10 years for 39% of subjects, since 5-10 years for 25%, since 1-5 years for 26%, and since less than 1 year for 10%. RESULTS: In this population of treated hypertensives, blood pressure level was higher in men than in women (145 +/- 22/86 +/- 13 vs 135 +/- 25/76 +/- 15; p < 0.01). In the questionnaire, the section with sexual function questions was filled out extensively in 92% of men (248/268), but only in 74% of women (142/191). Sexual disturbance was declared by 38% of cases (148/390), but rate was significantly higher in men as compared to women (49% vs 18%; p < 0.01). In men, these modifications were characterised by an interest for sexuality decreased for 58%, unchanged for 41% and increased for 1%. Sexual pleasure was decreased for 49%, unchanged for 50%, and increased for 1%. Quality of erection was modified in 45%. The erections were less frequent for 31%, less durable for 19% and impossible for 11%. In women, interest for sexuality was decreased for 41% and unchanged for 59%, sexual pleasure was decreased for 34% and unchanged for 66%. Logistic regression analysis indicates that gender (p < 0.001), greater number of antihypertensive tablets (p < 0.01), prescription of diuretics (p = 0.03) and presence of coronaropathy (p = 0.01) were independent determinants for sexual disturbance in treated hypertensives. CONCLUSION: This study indicates that sexual disturbance is declared by 38% of patients treated for hypertension. Because complaints are more frequent in men, treated with multiple medications including a diuretic, a specific interrogation should be proposed more regularly in these patients in order to detect and to deal with, if possible, sexual disability.

[Blood pressure self-monitoring contributes to improved patient education among hypertensive subjects]. / La possession d'un appareil d'automesure tensionnelle contribue à améliorer l'éducation des patients hypertendus.

UNLABELLED: Education of hypertensive subject must sensitize the patient to its pathway and to the prescribed treatment. Self-measurement of blood pressure, which directly implicates the patient, should ameliorate the education of hypertensive subject. OBJECTIVES: To evaluate if the possession of a self-measurement blood pressure device improves patients' knowledge of hypertension. METHODS: In 484 treated hypertensive subjects referred to hypertension specialists, a questionnaire evaluating patients knowledge of hypertension and its treatment was given before the consultation. During this consultation, the practitioner evaluated the concordance between antihypertensive treatments declared by the patient and those effectively prescribed. RESULTS: In this population, aged 61 +/- 12 years, with 55% of men, a self-measurement blood pressure device was possessed by 165 subjects (34%). These devices have been bought without medical advice by 83 patients. For a minority of subjects (n = 41), self-measurements of blood pressure were made at the wrist. Blood pressure level was similar in subjects with (141 +/- 19/80 +/- 10 mmHg) or without (140 +/- 19/80 +/- 10 mmHg) self-measurement devices. Subjects possessing a self measurement device had a better knowledge of their usual blood pressure level and of the normal blood pressure values (< 140/90 mmHg), than subjects without self measurement device (93% vs 77%, p < 0.01, and 56% vs 33%, p < 0.01, respectively). Moreover, subjects in possession of self-measurement devices had a better knowledge of their antihypertensive treatment than those without device (83% vs 70%, p < 0.05). Logistic regression analysis including age, sex, smoking, education level, blood pressure level and the number of antihypertensive tablets confirm the statistical differences observed. CONCLUSION: Hypertensive subjects who possess a self-measurement blood pressure device have a better knowledge of their hypertension. These results indicate that the possession of a self-measurement device contributes to the education of hypertensive patients.

[What tests should be conducted for secondary arterial hypertension in hypertensive patients resistant to treatment?]. / A quoi conduit la recherche d'une HTA secondaire chez des patients hypertendus résistant aux traitements?

UNLABELLED: The aim of this study was to determine the prevalence of secondary hypertension in a population of refractory hypertension without initial clinical or biological findings suggesting identifiable causes of hypertension. METHODS: A survey included 200 consecutive hypertensive patients referred to hypertension specialists for refractory hypertension (BP > 140/90 mmHg on at least two antihypertensive drugs). Prior inclusion, the permanent elevation of blood pressure was confirmed by ambulatory monitoring. In each subject an extensive work-up was performed to detect a secondary cause for hypertension. RESULTS: An essential hypertension was confirmed in 61% of this cohort. A secondary hypertension was detected in 20% of the patients; 8.5% with a primary hyperaldosteronism, 8% with a reno-vascular hypertension and 3% with a nephropathy. Moreover, 18.5% had a low renin hypertension. Thus, 27% of these patients had an abnormality of the renin-aldosterone axis. CONCLUSION: Patients with refractory hypertension should be explored to detect secondary hypertension even without findings suggesting such causes. This additional diagnostic procedure must include at least renovascular investigations and plasma renin/aldosterone level determinations in appropriate conditions.

[Validity of the clinical prediction rule for the diagnosis of renal arterial stenosis in hypertensive patients resistant to treatment]. / Validation d'une règle clinique de prédiction pour le diagnostic d'une sténose artérielle rénale chez des patients hypertendus résistants aux traitements.

PURPOSE: To perform an external validation of the clinical prediction rule established by Krijnen et al. (Ann Intern Med 1998; 129: 705-11) designed to identify renal artery stenoses (RAS) in hypertensive patients. METHODS: We included 102 patients with a refractory hypertension treated with at least two antihypertensive drugs. All subjects had the research of RAS by renal angiography, or angio-computed tomography, or doppler ultrasound. Probability to detect RAS was calculated with Krijnen's algorithm (Pre-test probability) from the following parameters: age, smoking status, diffuse atherosclerosis, recent hypertension (< 2 y), obesity (BMI > 25), abdominal bruit, hypercholesterolemia (> 6.5 mmol/L), creatinine. ROC curves were plotted for each pre-test probability value. A "post-test probability" was obtained from the likelihood ratio calculated at each pre-test probability level. RESULTS: RAS prevalence in this population was 49%. Area under the ROC curve was 0.79 and Youden index was maximal for a pre-test probability of 15%. Maximal likelihood ratio was obtained for a pre-test probability of 46%. Table shows post-test probability as a function of pre-test probability obtained with Krijnen's algorithm. [table: see text] CONCLUSION: Krijnen's algorithm is valid in a population of resistant hypertensives treated with a bi-therapy. This external validation obtained on a population with a high prevalence of RAS should also be tested on a population with a lower prevalence of SAR.