Características socioeconômicas e demográficas associadas à perda de excesso de peso em pacientes submetidos à cirurga bariátrica

Pós-graduação em Saúde Coletiva - FMB

Evaluation of quality of life in severely obese patients after bariatric surgery carried out in the public healthcare system

Objectives: To assess QoL of obese patients in the Brazilian public healthcare system, before and after bariatric surgery, and to determine the appropriateness of the Moorehead-Ardelt Questionnaire II (M-A-QoLQII) compared with the Short-Form Health Survey (SF-36). Subjects and methods: Forty-one severe obese patients in a waiting-list, and 84 patients who underwent bariatric surgery were included. Correlations were tested and reliability determined by the Cronbach's coefficient. Results: BMI differed between the pre- and post-surgery groups (52.3 +/- 8.3 kg/m(2) vs. 32.5 +/- 6.4 kg/m(2), p < 0.001). The latter showed better scores in the SF-36 domains than in the pre-surgery. SF-36 and M-A-QoLQII categories were correlated (r = 0.53, 0.49 and 0.47, for vitality, mental health, and general health domains, p < 0.001). In the logistic regression, age, previous BMI, and loss of excess weight were associated with functional capacity. Conclusions:The outcomes of bariatric surgery obtained in a Brazilian public healthcare center were successful. M-A-QoLII represents a useful tool to assess surgery outcomes, including QoL. Arq Bras Endocrinol Metab. 2012;56(1):33-8

Characterization of circulating steroids and endocannabinoids levels in obese subjects by liquid chromatography tandem mass spectrometry

Nowadays obesity can be defined as a global epidemic. The precise identification of circulating biomarkers involved in this pathology could be essential to early diagnose potential co-morbidities and to better address the development of future therapeutic strategies. Published evidences show that circulating steroid hormones and endocannabinoids might have a role in the physiopathology of obesity; however, a precise and reliable quantification of these molecules is still lacking. In the first part of the present thesis, we developed a sensitive, specific and accurate quantification method for nine steroid hormones using a liquid chromatography tandem mass spectrometry (LC-MS/MS) system. This method has been used first for a comparative study with immunoassays, currently used in the clinical practice to quantify these molecules and then to redefine circulating reference intervals in healthy subjects. Furthermore, we measured circulating steroid hormones in three groups of subjects: normo-weight, over-weight and obese, defining different steroid hormones profiles depending on the obesity state. The role of circulating endocannabinoids in humans is still unclear, however there are several evidences concerning their involvement in obesity. In the second part of the thesis, we determined changes of circulating endocannabinoids in obese patients after a weight loss induced by bariatric surgery, currently the most effective long-term treatment for obesity, using LC/MS-MS. We measured basal and dynamic endocannabinoids plasma levels in 12 patients with severe obesity before, one month after and six months after the Roux-en-Y gastric bypass intervention, currently one of the most performed types of bariatric surgery. All together the findings illustrated in this thesis project will help better define the role of steroid hormones and endocannabinoids in the framework of obesity in humans and the role that each type of molecule might have in its pathophysiology.

Respiratory function during anesthesia: effects on gas exchange

Anaesthesia causes a respiratory impairment, whether the patient is breathing spontaneously or is ventilated mechanically. This impairment impedes the matching of alveolar ventilation and perfusion and thus the oxygenation of arterial blood. A triggering factor is loss of muscle tone that causes a fall in the resting lung volume, functional residual capacity. This fall promotes airway closure and gas adsorption, leading eventually to alveolar collapse, that is, atelectasis. The higher the oxygen concentration, the faster will the gas be adsorbed and the aleveoli collapse. Preoxygenation is a major cause of atelectasis and continuing use of high oxygen concentration maintains or increases the lung collapse, that typically is 10% or more of the lung tissue. It can exceed 25% to 40%. Perfusion of the atelectasis causes shunt and cyclic airway closure causes regions with low ventilation/perfusion ratios, that add to impaired oxygenation. Ventilation with positive end-expiratory pressure reduces the atelectasis but oxygenation need not improve, because of shift of blood flow down the lung to any remaining atelectatic tissue. Inflation of the lung to an airway pressure of 40 cmH2O recruits almost all collapsed lung and the lung remains open if ventilation is with moderate oxygen concentration (< 40%) but recollapses within a few minutes if ventilation is with 100% oxygen. Severe obesity increases the lung collapse and obstructive lung disease and one-lung anesthesia increase the mismatch of ventilation and perfusion. CO2 pneumoperitoneum increases atelectasis formation but not shunt, likely explained by enhanced hypoxic pulmonary vasoconstriction by CO2. Atelectasis may persist in the postoperative period and contribute to pneumonia.

Nur77 regulates lipolysis in skeletal muscle cells - Evidence for cross-talk between the beta-adrenergic and an orphan nuclear hormone receptor pathway

Skeletal muscle is a major mass peripheral tissue that accounts for similar to 40% of total body weight and 50% of energy expenditure and is a primary site of glucose disposal and fatty acid oxidation. Consequently, muscle has a significant role in insulin sensitivity, obesity, and the blood-lipid profile. Excessive caloric intake is sensed by the brain and induces beta-adrenergic receptor (beta-AR)- mediated adaptive thermogenesis. beta-AR null mice develop severe obesity on a high fat diet. However, the target gene(s), target tissues(s), and molecular mechanism involved remain obscure. We observed that 30 - 60 min of beta-AR agonist ( isoprenaline) treatment of C2C12 skeletal muscle cells strikingly activated (> 100-fold) the expression of the mRNA encoding the nuclear hormone receptor, Nur77. In contrast, the expression of other nuclear receptors that regulate lipid and carbohydrate metabolism was not induced. Stable transfection of Nur77-specific small interfering RNAs (siNur77) into skeletal muscle cells repressed endogenous Nur77 mRNA expression. Moreover, we observed attenuation of gene and protein expression associated with the regulation of energy expenditure and lipid homeostasis, for example AMP-activated protein kinase gamma 3, UCP3, CD36,adiponectin receptor 2, GLUT4, and caveolin-3. Attenuation of Nur77 expression resulted in decreased lipolysis. Finally, in concordance with the cell culture model, injection and electrotransfer of siNur77 into mouse tibialis cranialis muscle resulted in the repression of UCP3 mRNA expression. This study demonstrates regulatory cross-talk between the nuclear hormone receptor and beta-AR signaling pathways. Moreover, it suggests Nur77 modulates the expression of genes that are key regulators of skeletal muscle lipid and energy homeostasis. In conclusion, we speculate that Nur77 agonists would stimulate lipolysis and increase energy expenditure in skeletal muscle and suggest selective activators of Nur77 may have therapeutic utility in the treatment of obesity.

Características psicológicas do paciente obeso grave e suas implicações pós-operatórias na cirurgia bariátrica

Obesity is a chronic disease that has multi-factorial aetiology, characterized by high degree of body fat; the degree of obesity will vary according to the Body Mass Index (BMI=m2 /kg). The severe degree of obesity is characterized by BMI>40 and it is regularly associated to endocrine-metabolic or mechanic clinical alterations, and to psychological disorders. Binge Eating (BE) results were overly high for this population. The Bariatric Surgery has been the treatment chosen by those diagnosed with severe obesity as this intervention provides prompt outcomes for loss of weight and clinical improvement conditions. However, recent research has acquiesced that after two years between 20% and 30% of people subject to this intervention gained weight. The main objective of this research is to assess the psychological and behavioral characteristics of those diagnosed with severe obesity that have been subject to Gastric Bypass Surgery in the past 24 months. Specific aspects were investigated: (1) characteristics of different personalities and diagnose of clinic and personality disorders; (2) BE and its relation with loss of weight; (2) the difference between the groups regarding post-surgery care, e.g. physical activity, psychological and dietician input. Method: 40 adults (women and men) aged 23 and 60 year-old who went through a bariatric surgery in the past 24 months, in the city of Natal-RN (Brazil); they were assembled in two groups n=20, Gain group displaying loss of < 50% of their initial surplus of weight, and the Loss group displaying loss of >50%. The research protocol is made of a socio-demographic questionnaire and 3 psychometric instruments: Rorschach – Comprehensive System; Millon Personality Inventory (MCMI-III); and the Binge Eating Scale (Escala de Compulsão Alimentar Periódica (ECAP). Through Rorschach significant differences between these groups were verified according to the kind of personality (EB) - more EB Extratensivo in Gain group and Intratensivo in Loss group – and the lack of control to express affect, increasing the answer for Color Pure at Group I. Concerning the people standardization, the sample as a whole tends to show psychic pain, denigrated selfperception, high levels of self-criticism, distorted perceptions, vulnerability to develop mood disorders and high scores regarding Suicide. MCMI-III results showed more clinic and personality disorders in Group I: Depressive Disorder and Schizotypal, Anxiety, Dysthymia, Major Depressive Disorder; Thought Disorder, Bipolar- Manic and Posttraumatic Stress Disorder. In relation to ECAP, the results indicated significant differences, showing increased BE results in Gain group. There were found significant differences between BE severity and the presence of clinic and personality disorders. Concerning the post-surgery care, the observed differences are statistically significant regarding physical activities with median-increased differences in Loss group. There is a difference between the initial weight and the time post-surgery, indicating that the higher the initial weight and the time after the surgery the higher the re-gain of weight post-surgery. Finally, the results show that the participants with more than 3 years of surgery will have Clinic and Major Depressive Disorders; Somatoform Disorder; Dysthymia. These results confirm prior studies related to BE post-surgery and re-gain of weight as well as the proneness of clinic disorders in severe obesity people. That means the results reinforce that the surgery process is a facet of the severe obesity treatment. The post-surgery process needs to be the main focus of attention and have a long-term input to sustain the care of the surgery results and the quality of life of the patients.

Gestação após gastroplastia para tratamento de obesidade mórbida: série de casos e revisão da literatura

Objetivo: relatar a evolução de uma série de casos de gestação em mulheres previamente submetidas à cirurgia de bypass gástrico para tratamento de obesidade grave. Métodos: cinco casos consecutivos de gravidez após gastroplastia ocorridos entre 2001 e 2004 foram avaliados. As pacientes tinham idade entre 30 e 34 anos e todas haviam sido submetidas à cirurgia de Capella. Aspectos clínicos, laboratoriais e do acompanhamento materno e fetal foram considerados, durante o período gestacional e após o parto. Foi realizada revisão da literatura internacional, por meio das bases de dados MEDLINE e Web of Science, utilizando os seguintes unitermos: gastroplasty, gastric bypass surgery, bariatric surgery e pregnancy. Resultados: todas as gestações observadas foram únicas e não ocorreram complicações obstétricas, durante o seguimento pré-natal e parto. Também não houve registro de recém-nascidos prematuros ou de baixo peso ao nascimento. Conclusão: nossos dados sugerem que a gravidez após gastroplastia é segura para a mãe e feto. Entretanto, em virtude do limitado volume de informação disponível sobre o tema, investigações adicionais são necessárias para estabelecer recomendações apropriadas com relação ao seguimento dessas gestações _________________________________________________ABSTRACT Purpose: we report a small series of pregnant women who underwent gastric bypass surgery for severe obesity, with a review of the literature on this topic. Methods: five consecutive cases of pregnancy after gastroplasty between 2001 and 2004 were evaluated, and clinical, laboratory and therapeutic features were considered. Patients were 30 to 34 years old and all had been submitted to gastroplasty by the Capella technique. The outcomes for both the pregnant woman and the fetus were evaluated. A search of the English language literature was done through MEDLINE and Web of Science databases with the following terms: gastroplasty, gastric bypass surgery, bariatric surgery, and pregnancy. Results: all 5 pregnancies were singleton. No major obstetric complications were observed and there were no premature or lowbirth weight infants. Conclusion: our data suggest that pregnancy following gastroplasty is safe for mother and fetus. However, since information about this topic is limited, further investigations are required to establish appropriate recommendations concerning the follow-up of these pregnancies

Mobilisation des dépôts ectopiques de tissu adipeux : ses implications dans la résolution des comorbidités associées à l'obésité sévère suivant une chirurgie bariatrique

La prévalence de l’obésité sévère ne cesse d’augmenter. La problématique associée à l’obésité sévère est la présence possible de nombreuses comorbidités qui peuvent coexister et altérer le système cardiovasculaire, pulmonaire, endocrinien, articulaire et même favoriser le développement de certains cancers. L’excès de poids, plus particulièrement l’excès de tissu adipeux, sont tous deux liés au développement de ces comorbidités. Aucune donnée n’est disponible quant au rôle de la déposition ectopique du tissu adipeux. Considérant le caractère morbide de l’obésité sévère, la mortalité de toute cause augmentée et l’espérance de vie réduite, à ce jour le seul traitement dit efficace à long terme pour le traitement de l’obésité sévère est la chirurgie bariatrique. L’efficacité est définie par la perte de poids, le maintien à long terme de cette perte de poids ainsi que par l’amélioration ou la résolution des comorbidités. L’intérêt clinique et scientifique pour la chirurgie bariatrique est grandissant. Un nombre important d’études s’intéresse aux mécanismes sous-jacents de la résolution des comorbidités. Le diabète de type 2 est la comorbidité la plus étudiée et peu d’études se sont intéressées aux déterm meil.inants de la résolution de l’hypertension artérielle et de l’apnée obstructive du som Comme premier objectif, cette thèse visait à caractériser les différences de la composition corporelle et de la distribution du tissu adipeux de patients obèses sévères avec ou sans diagnostic de diabète de type 2, d’hypertension artérielle et d’apnée obstructive du sommeil. Le deuxième objectif de cette thèse visait à comparer l’évolution postopératoire suite à une chirurgie bariatrique sur les changements de la composition corporelle et de la distribution du tissu adipeux selon le statut de résolution du diabète de type 2, de l’hypertension artérielle et de l’apnée obstructive du sommeil. De plus, considérant le peu d’évidences dans la littérature au sujet des déterminants de la résolution de l’hypertension artérielle et de l’apnée obstructive du sommeil, l’évaluation du profil inflammatoire, des adipokines et de l’activité du système nerveux autonome ont aussi été caractérisés. Premièrement, nous avons documenté qu’en présence d’obésité sévère, la déposition ectopique du tissu adipeux était plus importante chez les patients avec un diabète de type 2, une hypertension artérielle et une apnée obstructive du sommeil comparativement à ceux n’ayant pas ces comorbidités. Nous avons par la suite montré que la résolution du diabète de type 2 et de l’hypertension artérielle était caractérisée par une réduction plus importante du tissu adipeux viscéral. Au contraire, la résolution de l’apnée obstructive du sommeil était plutôt caractérisée par une réduction plus importante du tissu adipeux sous-cutané à la mi-cuisse et par une tendance à une perte de poids plus élevée. De plus, nous avons observé que chez les patients qui n’avaient pas résolu leur diabète de type 2, leur hypertension artérielle et leur apnée obstructive du sommeil, la quantité de tissu adipeux viscéral, à 12 mois suivant la chirurgie bariatrique, était plus importante comparativement à celle mesurée chez les patients n’ayant pas résolu ces comorbidités. Spécifiquement à l’évaluation du profil inflammatoire et des adipokines, nous avons observé que chez les patients obèses sévères, la présence de l’hypertension artérielle et de l’apnée obstructive du sommeil n’était pas caractérisée par un profil altéré au niveau des marqueurs inflammatoires et des adipokines. Également, nous n’avons pas observé de changements majeurs qui pouvaient expliquer, en partie, la résolution de l’hypertension artérielle et de l’apnée obstructive du sommeil. Quant à l’activité du système nerveux autonome, nous avons observé une faible activité du système nerveux parasympathique chez les patients obèses sévères avec hypertension artérielle et apnée obstructive du sommeil. Nous avons également documenté que la résolution de l’hypertension artérielle et de l’apnée obstructive du sommeil était associée à une tendance à une augmentation plus importante de l’activité parasympathique du système nerveux autonome. Les résultats obtenus au cours de ce doctorat supportent l’importance de la déposition ectopique du tissu adipeux en situation d’obésité sévère, particulièrement le rôle du tissu adipeux viscéral, dans le développement du diabète de type 2, de l’hypertension artérielle et de l’apnée obstructive du sommeil ainsi que dans la résolution de ces comorbidités suivant une chirurgie bariatrique. D’autres recherches devront davantage s’intéresser à la mobilisation des dépôts ectopiques de tissu adipeux comme un déterminant important dans la résolution à plus long terme de ces comorbidités.

Gestação após gastroplastia para tratamento de obesidade mórbida: série de casos e revisão da literatura

Objetivo: relatar a evolução de uma série de casos de gestação em mulheres previamente submetidas à cirurgia de bypass gástrico para tratamento de obesidade grave. Métodos: cinco casos consecutivos de gravidez após gastroplastia ocorridos entre 2001 e 2004 foram avaliados. As pacientes tinham idade entre 30 e 34 anos e todas haviam sido submetidas à cirurgia de Capella. Aspectos clínicos, laboratoriais e do acompanhamento materno e fetal foram considerados, durante o período gestacional e após o parto. Foi realizada revisão da literatura internacional, por meio das bases de dados MEDLINE e Web of Science, utilizando os seguintes unitermos: gastroplasty, gastric bypass surgery, bariatric surgery e pregnancy. Resultados: todas as gestações observadas foram únicas e não ocorreram complicações obstétricas, durante o seguimento pré-natal e parto. Também não houve registro de recém-nascidos prematuros ou de baixo peso ao nascimento. Conclusão: nossos dados sugerem que a gravidez após gastroplastia é segura para a mãe e feto. Entretanto, em virtude do limitado volume de informação disponível sobre o tema, investigações adicionais são necessárias para estabelecer recomendações apropriadas com relação ao seguimento dessas gestações _________________________________________________ABSTRACT Purpose: we report a small series of pregnant women who underwent gastric bypass surgery for severe obesity, with a review of the literature on this topic. Methods: five consecutive cases of pregnancy after gastroplasty between 2001 and 2004 were evaluated, and clinical, laboratory and therapeutic features were considered. Patients were 30 to 34 years old and all had been submitted to gastroplasty by the Capella technique. The outcomes for both the pregnant woman and the fetus were evaluated. A search of the English language literature was done through MEDLINE and Web of Science databases with the following terms: gastroplasty, gastric bypass surgery, bariatric surgery, and pregnancy. Results: all 5 pregnancies were singleton. No major obstetric complications were observed and there were no premature or lowbirth weight infants. Conclusion: our data suggest that pregnancy following gastroplasty is safe for mother and fetus. However, since information about this topic is limited, further investigations are required to establish appropriate recommendations concerning the follow-up of these pregnancies

Experiências adversas na infância e depressão em adultos com obesidade

Dissertação de Mestrado apresentada no Instituto Superior de Psicologia Aplicada para obtenção do grau de Mestre na especialidade de Psicologia Clínica

Obesity associated severe asthma represents a distinct clinical phenotype - Analysis of the British Thoracic Society Difficult Asthma Registry patient cohort according to body mass index

BACKGROUND: Obesity has emerged as a risk factor for the development of asthma and it may also influence asthma control and airways inflammation. However, the role of obesity in severe asthma remains unclear. OBJECTIVE: To explore the association between obesity (defined by BMI) and severe asthma. METHODS: Data from the National Registry for dedicated UK Difficult Asthma Services were used to compare patient demographics, disease characteristics and healthcare utilisation between three body mass index (BMI) categories (normal weight: 18.5 -24.99, overweight: 25 -29.99, obese: =30) in a well characterised group of severe asthmatic adults. RESULTS: The study population consisted of 666 severe asthmatics with a median BMI of 29.8 (interquartile range 22.5 -34.0). The obese group exhibited greater asthma medication requirements in terms of maintenance corticosteroid therapy (48.9% versus 40.4% and 34.5% in the overweight and normal weight groups, respectively), steroid burst therapy and short-acting ß2-agonist (SABA) use per day. Significant differences were seen with gastro-oesophageal reflux disease (GORD) (53.9% versus 48.1% and 39.7% in the overweight and normal weight groups, respectively) and proton pump inhibitor (PPI) use. Bone density scores were higher in the obese group, whilst pulmonary function testing revealed a reduced FVC and raised Kco. Serum IgE levels decreased with increasing BMI and the obese group were more likely to report eczema, but less likely to have a history of nasal polyps. CONCLUSIONS: Severe asthmatics display particular characteristics according to BMI that support the view that obesity associated severe asthma may represent a distinct clinical phenotype.1Royal Brompton Hospital, London, UK;2Department of Computing, Imperial College, UK3Airways Disease, National Heart & Lung Institute, Imperial College, UK;4Centre for infection and immunity, Queen's University of Belfast, UK;5University of Leicester, UK;6The University of Manchester and University Hospital of South Manchester, UK;7Birmingham Heartlands Hospital, University of Birmingham, UK;8Gartnavel General Hospital, University of Glasgow, UK;9Glasgow Royal Infirmary, Glasgow, UKCorrespondence: Dr Andrew N. Menzies-Gow, Royal Brompton Hospital, Fulham Road, London SW3 6HP.

[Calculating the basal metabolic rate and severe and morbid obesity]

The aim of this study was to evaluate the currently available predictive equations for basal metabolic rate (BMR) in subjects with obesity class II and III, and to assess the contribution by the components of a two-compartment model of body composition, namely the lean body mass (LBM) and the fat mass (FM) to the prediction. A second objective was to examine the reliability of the Harris Benedict equation in obese subjects, especially with a weight > or = 120 kg.

Does metabolic compensation explain the majority of less-than-expected weight loss in obese adults during a short-term severe diet and exercise intervention?

Objective: We investigated to what extent changes in metabolic rate and composition of weight loss explained the less-than-expected weight loss in obese men and women during a diet-plus-exercise intervention. Design: 16 obese men and women (41 ± 9 years; BMI 39 ± 6 kg/m2) were investigated in energy balance before, after and twice during a 12-week VLED (565–650 kcal/day) plus exercise (aerobic plus resistance training) intervention. The relative energy deficit (EDef) from baseline requirements was severe (74-87%). Body composition was measured by deuterium dilution and DXA and resting metabolic rate (RMR) by indirect calorimetry. Fat mass (FM) and fat-free mass (FFM) were converted into energy equivalents using constants: 9.45 kcal/gFM and 1.13 kcal/gFFM. Predicted weight loss was calculated from the energy deficit using the '7700 kcal/kg rule'. Results: Changes in weight (-18.6 ± 5.0 kg), FM (-15.5 ± 4.3 kg), and FFM (-3.1 ± 1.9 kg) did not differ between genders. Measured weight loss was on average 67% of the predicted value, but ranged from 39 to 94%. Relative EDef was correlated with the decrease in RMR (R=0.70, P<0.01) and the decrease in RMR correlated with the difference between actual and expected weight loss (R=0.51, P<0.01). Changes in metabolic rate explained on average 67% of the less-than-expected weight loss, and variability in the proportion of weight lost as FM accounted for a further 5%. On average, after adjustment for changes in metabolic rate and body composition of weight lost, actual weight loss reached 90% of predicted values. Conclusion: Although weight loss was 33% lower than predicted at baseline from standard energy equivalents, the majority of this differential was explained by physiological variables. While lower-than-expected weight loss is often attributed to incomplete adherence to prescribed interventions, the influence of baseline calculation errors and metabolic down-regulation should not be discounted.

Associations exist between food insecurity, poor diet, chronic illness and obesity among an Australian population

Food insecurity is the limited availability of, or access to, sufficient amounts of nutritious, culturally-appropriate and safe foods, or the inability to access such foods by socially-acceptable means. Evidence from the United States and Canada suggests that food insecurity may be associated with poor dietary intakes, obesity, and chronic disease including depression and diabetes, thus constituting a significant public health issue. Currently, no existing studies have investigated the dietary and health factors associated with food insecurity among the general Australian population. The current study investigated the potential associations between food insecurity, diet and health among Australian adults (18 years and over) participating in the cross-sectional National Health Survey (n = 19,500). Data were analysed by logistic regression adjusting for sociodemographic covariates. Those from food insecure households were 50% less likely to consume the recommended number of servings of fruit, 60% more likely to report poor health and experienced a 6-fold increase in the risk of severe depressive disorders, compared to their food secure counterparts. Furthermore, food insecurity was associated with a 50% increase in the risk of being diagnosed with ‘high sugar levels’. Finally, women from food insecure households were 30% more likely to be obese compared to their food secure counterparts. These findings suggest that food insecurity may play an important role in preventing adherence with national dietary recommendations, and may increase the risk of obesity and chronic illness. This has important implications for both clinical practice, and the development of interventions and policy to address food insecurity.

Association of HincII RFLP of low density lipoprotein receptor gene with obesity in essential hypertensives

Obese (BMI ≥ 26 kg/m 2; n = 51) and lean (BMI <26 kg/m 2; n = 61) Caucasian patients with severe, familial essential hypertension, were compared with respect to genotype and allele frequencies of a HincII RFLP of the low density lipoprotein receptor gene (LDLR). A similar analysis was performed in obese (n = 28) and lean (n = 68) normotensives. A significant association of the C allele of the T→C variant responsible for this RFLP was seen with obesity (χ 2 = 4.6, P = 0.029) in the hypertensive, but not in the normotensive, group (odds ratio = 3.0 for the CC genotype and 2.7 for CT). Furthermore, BMI tracked with genotypes of this allele in the hypertensives (P = 0.046). No significant genotypic relationship was apparent for plasma lipids. Significant linkage disequilibrium was, moreover, noted between the HincII RFLP and an ApaLI RFLP (χ 2 = 33, P<0.0005) that has previously shown even stronger association with obesity (odds ratio 19.6 for cases homozygous for the susceptibility allele and 15.2 for het-erozygotes). The present study therefore adds to our previous evidence implicating LDLR as a locus for obesity in patients with essential hypertension.