Potentially inappropriate prescribing according to STOPP-2 criteria among patients discharged from Internal Medicine: prevalence, involved drugs and economic cost.

AIM: This study aims to determine the prevalence of potentially inappropriate prescribing (PIP) among patients discharged from Internal Medicine, the drugs and factors associated and economic cost of PIP. METHODS: This retrospective cross-sectional, single-center study included participants aged ≥65 years consecutively discharged from the Internal Medicine Unit in a tertiary hospital of Southern Spain. PIP was defined by the Screening Tool for Older Persons Prescriptions (STOPP-2) criteria version 2 (2015 update). The association of PIP with chronic conditions was analyzed using multilevel logistic regression model. Data on economic cost associated to PIP were determined according to the computerized prescribing database of Andalusia ("Receta XXI"). RESULTS: Out of the 275 patients studied, a total of 249 PIPs were detected in 114 (41.5%) patients of whom 79 (28.7%) had one or two STOPP-2 criteria and 35 (12.7%) 3 or more criteria. The most involved drugs were benzodiazepines (45.5%); antithrombotics (14.5%), including anticoagulants or antiplatelets, and opioids (11.4%). The multivariate logistic regression analysis identified polypharmacy (OR=11.00; 95% CI 1.41-85.52) and extreme polypharmacy (OR=26.25; 95% CI 3.34-206.07) as independent risk factors for PIP. The mean cost of PIP was €18.75±4.24 per patient and month. Opioids accounted for the highest percentage expenditure of PIP (39.02%), followed by inhaled bronchodilator drugs (30.30%), antithrombotics (12.20%) and benzodiazepines (7.92%). CONCLUSIONS: PIP is frequent among patients discharged from Internal Medicine. The number of prescribed drugs was independently associated to PIP and benzodiazepines were the most involved drugs. PIP was associated to a significant economic cost.

[Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases]. / Acción inmunomoduladora de las células madre mesenquimales en las enfermedades autoinmunitarias.

Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use.

Erythema nodosum as azathioprine hypersensitivity reaction in a patient with bullous pemphigoid.

A 65-year-old woman with bullous pemphigoid presented with fever and several red-purple nodular subcutaneous lesions on both lower legs 1 week after starting treatment with azathioprine (AZA). Biopsy of a skin nodule was compatible with erythema nodosum (EN) and hypersensitivity reaction to AZA was suspected. AZA was subsequently discontinued, observing complete remission of fever and EN within 2 weeks. This case highlights the importance of recognizing EN as a possible manifestation of hypersensitivity reaction to AZA.

Novel association of acid phosphatase locus 1*C allele with systemic lupus erythematosus.

The red cell acid phosphatase (ACP1) gene, which encodes a low-molecular-weight phosphotyrosine phosphatase, has been suggested as a common genetic factor of autoimmunity. In the present study, we aim to investigate the possible association of ACP1 with the susceptibility of systemic lupus erythematosus (SLE). A total of 1,546 SLE patients and 1,947 healthy individuals from 4 Caucasians populations were included in the present study. Four single-nucleotide polymorphisms (SNPs) were genotyped in this study: rs10167992, rs11553742, rs7576247, and rs3828329. ACP1*A, ACP1*B, and ACP1*C codominant ACP1 alleles were determined using 2 of the SNPs and analyzed. After the meta-analysis test was performed, a significant association of rs11553742*T was observed (p(pooled) = 0.005, odds ratios = 1.37 [1.10-1.70]), retaining significance after multiple testing was applied (p(FDR) = 0.019). Our data indicate for first time the association of rs11553742*T with increased susceptibility in SLE patients.

Metabolic syndrome is associated with increased arterial stiffness and biomarkers of subclinical atherosclerosis in patients with systemic lupus erythematosus.

OBJECTIVE: Aortic pulse wave velocity (PWV) is an independent predictor of risk for atherosclerotic cardiovascular disease. Metabolic syndrome (MetS) is more prevalent in patients with systemic lupus erythematosus (SLE) compared with matched healthy subjects. Aortic PWV is increased in MetS. The purpose of this cross-sectional study was to determine the association between MetS and aortic PWV and other surrogate biomarkers of subclinical atherosclerosis in SLE. METHODS: One hundred twenty-eight patients with SLE were studied. We established the presence of MetS according to the National Cholesterol Education Program Adult Treatment Panel III definition and we measured PWV, glucose, insulin, glycosylated hemoglobin (HbA(1c)), insulin sensitivity (HOMA index), lipid levels, uric acid, homocysteine, fibrinogen, D-dimer, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin 6 (IL-6), IL-8, IL-10, C3, C4, autoantibodies, SLE Disease Activity Index (SLEDAI), and Systemic Lupus International Collaborating Clinics/ACR Damage Index. Duration of SLE and treatment was also recorded. Multivariate logistic regression analysis was used to identify independent determinants of increased PWV. RESULTS: SLE patients with MetS had higher aortic PWV (9.8 +/- 2.4 vs 8.5 +/- 1.7 m/s; p = 0.002) and increased biomarkers of subclinical atherosclerosis such as CRP, IL-6, C3, uric acid, homocysteine, fibrinogen and D-dimer, compared to those without MetS. HOMA index and insulin and HbA(1c) levels were also higher in this group. No differences were found in variables related to lupus activity (ESR, C4, SLEDAI, IL-8, IL-10, and treatment for SLE). In the multivariate model, increased PWV was associated with age, male sex, MetS, duration of SLE, and CRP. CONCLUSION: MetS may contribute to the development of accelerated atherosclerosis in SLE.

Aplicación de la terapia de afrontamiento del estrés en dos poblaciones con alto estrés: pacientes crónicos y personas sanas / Effectiveness of stress management therapy in two populations with high stress: chronic patients and healty people

Introduction Stress is currently considered a health risk factor. Numerous studies have shown that people with high levels of perceived stress present a greater number of complaints at both the physical and psychological levels. In this context, programs have been developed directed toward adequately coping with stress, and the effectiveness of these programs on the symptomatology of a psychological nature in healthy persons with a high level of perceived stress has been shown. However, there have been fewer studies that have shown whether this type of therapy affects the somatic symptomatology of healthy people in any way. On the other hand, programs for chronically ill patients directed toward achieving a better adaptation to their life conditions are equally effective. A population that presents considerably high levels of stress is the one consisting of people suffering from a chronic illness. Thus, through the immunological modulation it produces, the stress may be exacerbating the course of the disease. One prototype of this is systemic lupus erythematosus (SLE). SLE is a syndrome whose clinical expression depends on the degree to which there is a convergence of an immune regulation disorder and a strong genetic base, hormonal influence, and various exogenous agents. SLE can be manifested by general malaise, fever, fatigue, weight loss, skin rashes, joint inflammation, anemia, inflammation of the lymphatic glands, lowering of the defenses against infection, and cardiac, kidney, neurological, and pulmonary alterations. This autoimmune disease is usually associated with high levels of pain and impairment in different systems, producing high levels of stress in the patients who suffer from it. Nevertheless, although stress has already been shown to be one environmental factor that can produce a worsening in lupus symptoms, there have been no studies carried out with the objective of testing the effectiveness of stress management therapy and its physical and emotional consequences in these patients. For this reason, this study has a double objective: on the one hand, to corroborate, once again, the efficacy of cognitive-behavioural stress management therapy in the control of certain psychological processes and, on the other hand, to take one more step by testing whether there is a reduction in the perception of self-reported somatic symptoms both in healthy people and in those with a chronic disease. Material and method Fifty-two people participated in this study. Twenty-two were patients with lupus from the University Hospital in Granada. The other 30 were people without chronic diseases who attended the Psychological Attention Service at the University of Granada to receive therapy for coping with stress, as they claimed to have high levels of it. To evaluate the level of stress, we used the Stress Vulnerability Inventory by Beech, Burns and Scheefield, and the Scale of Recent Life Experiences (SRLE) by Kohn and Macdonald. To evaluate depression, we used the Beck Depression Inventory (BDI), and for anxiety, the Trait Anxiety Inventory (STAI-R) by Spielberger, Gorsuch and Lushene. For the self-reported somatic symptoms, we used the Revised Somatic Symptoms Scale (SSS-R) by Sandín, Valiente and Chorot. In addition, in the patients with SLE, the SLEDAI index, or Index of Activity of the Disease, was obtained. The therapy received was cognitive-behavioural in nature, and it was carried out during 13 sessions which were grouped in the following blocks: Conceptualization of the stress, cognitive restructuring; Deactivation techniques; Approaching the self-management of the pain; Social skills; Time control and organization; Personality pattern and its relationship with health; Anger management; Humour and optimism as coping strategies. Results Results showed that both groups presented a statistically significant reduction in stressful life experiences [F(1 .50) = 28.6; p<.000], vulnerability to stress [F(1 .50) = 1 05.25; p<0.000], depression [F(1 .50) = 68.33; p<0.000], and anxiety [F(1 .49) = 54.53; p<0.000] after the treatment. Moreover, the effect size of these variables was high in the group of patients with lupus and in the group of healthy patients, although it was higher in the latter group. Likewise, both groups presented a statistically significant improvement in the physical function, producing a reduction in the perceived somatic symptoms [F(1 .48) = 37.7; p<0.000] after the treatment. Furthermore, the effect of the treatment was high in both groups. Discussion This paper addresses a critically important issue: the effectiveness of cognitive-behavioral intervention in ameliorating psychosocial stress and enhancing the well-being of individuals with lupus and the group of people with high stress. In this improvement, there was not only a significant reduction in the score on vulnerability to stress and stressful life experiences, but a reduction in the levels of anxiety and depression and somatic symptoms. The findings of improvements in somatic symptoms suggest that this intervention might facilitate coping and change the cognitive appraisals of symptoms. Likewise, the impact of the intervention on psychosocial outcomes (depression, anxiety and perceived vulnerability to stress) may have implications for longer-term health behaviors and health outcomes. Although this reduction is significant in both groups, the effect size is greater in the group of people with high stress than in the group of lupus patients. Specifically, the somatic symptoms where a lower effect of the therapy was observed were the immunological, respiratory, musculoskeletal, and dermatological symptoms, which coincide with the most characteristic symptoms of lupus. This study supports, therefore, the importance of stress management programs not only to reduce the amount of stress, but also to improve the emotional variables and physical condition, both in people with chronic diseases and in healthy people with a high level of stress. The cognitive-behavior therapy is a new effective line of action in dealing with lupus, being necessary an overall integrated view of the patients with lupus, treating the clinical and psychological aspects.

Introducción Actualmente, el estrés se considera un factor de riesgo para la salud. Diversos estudios ponen de manifiesto que altos niveles de estrés presentan mayor número de quejas, tanto en el nivel físico como psicológico. En este contexto, se han desarrollado programas dirigidos a un adecuado afrontamiento del estrés, que han resultado eficaces en la modificación de variables emocionales. Sin embargo, no se ha estudiado la eficacia de la terapia en la mejoría de síntomas somáticos. Por otra parte, existen enfermedades en que, por la modulación inmunológica que produce, el estrés puede actuar exacerbando el curso de ésta. Un prototipo de lo anterior es el lupus eritematoso sistémico (LES), enfermedad de carácter autoinmune que suele conllevar importantes niveles de dolor y deterioro de diferentes sistemas, con lo que a su vez produce altos niveles de estrés en los pacientes que lo padecen. También está ampliamente demostrado que el estrés puede actuar como exacerbador de la enfermedad. Pese a ello, no se ha llevado a cabo ningún estudio que tenga como objetivo comprobar la eficacia de la terapia de afrontamiento al estrés por sus consecuencias físicas y emocionales. Por ello, el objetivo de este estudio ha sido valorar la eficacia de la terapia cognitivo-conductual en el manejo del estrés para comprobar si disminuye la percepción de los síntomas somáticos autoinformados, tanto en personas sanas como en personas con lupus. Material y método En este estudio han participado 52 personas, de las cuales 22 eran pacientes con lupus y 30 eran personas con alto estrés. Para evaluar el nivel de estrés hemos utilizado el Inventario de Vulnerabilidad al Estrés y la Escala de Experiencias Vitales Recientes (SRLE); para evaluar la depresión, el Inventario de Depresión de Beck (BDI); para la ansiedad, el Inventario de Ansiedad Rasgo (STAI-R); y para los síntomas somáticos autoinformados, la Escala de Síntomas Somáticos-Revisada (ESS-R). Además, en los pacientes con LES, se obtuvo el índice SLEDAI o índice de actividad de la enfermedad. Ambos grupos se evaluaron en las diferentes variables psicológicas descritas previamente antes y después del tratamiento. La terapia recibida fue de tipo cognitivo-conductual y se desarrolló a lo largo de 13 sesiones de hora y media. Resultados Los resultados mostraron que ambos grupos presentaban una reducción estadísticamente significativa en experiencias vitales estresantes [F(1 .50) = 28.6; p<0.000], vulnerabilidad al estrés [F(1.50) = 105.25; p<0.000], depresión [F(1.50) = 68.33; p<0.000] y ansiedad [F(1 .49)=54.53; p<0.000] después del tratamiento. El tamaño del efecto en estas variables fue alto tanto en el grupo de pacientes con lupus como en el grupo de personas sanas, siendo mayor en este último. Asimismo, ambos grupos presentaron una mejora estadísticamente significativa de la función física y se produjo una disminución de los síntomas somáticos percibidos [F(1 .48) = 37.7; p<0.000] después del tratamiento. Además, aunque es alto en ambos grupos, el efecto del tratamiento es mayor en el grupo de personas con alto estrés percibido. Discusión Nuestros datos indican que la terapia de afrontamiento del estrés influye positivamente tanto en el grupo de personas con alto estrés como en el grupo de pacientes de lupus. En dicha mejoría disminuyen de forma significativa las puntuaciones de vulnerabilidad al estrés, experiencias vitales estresantes, ansiedad y depresión. Por otro lado, con respecto a los síntomas somáticos experimentados por ambos grupos, los resultados muestran un descenso de la percepción de los mismos. Aunque esta disminución es significativa, el tamaño del efecto es mayor en el grupo de personas con alto estrés. Este estudio apoya, por tanto, la importancia de un programa de afrontamiento del estrés no sólo para disminuir la cantidad de estrés, sino para mejorar las variables emocionales y el estatus físico tanto en personas con enfermedades crónicas como en personas sanas, pero con alto estrés.

Replication of the TNFSF4 (OX40L) promoter region association with systemic lupus erythematosus.

The tumor necrosis factor ligand superfamily member 4 gene (TNFSF4) encodes the OX40 ligand (OX40L), a costimulatory molecule involved in T-cell activation. A recent study demonstrated the association of TNFSF4 haplotypes located in the upstream region with risk for or protection from systemic lupus erythematosus (SLE). To replicate this association, five single nucleotide polymorphisms (SNPs) tagging the previously associated haplotypes and passing the proper quality-control filters were tested in 1312 cases and 1801 controls from Germany, Italy, Spain and Argentina. The association of TNFSF4 with SLE was replicated in all the sets except Spain. There was a unique risk haplotype tagged by the minor alleles of the SNPs rs1234317 (pooled odds ratio (OR)=1.39, P=0.0009) and rs12039904 (pooled OR=1.38, P=0.0012). We did not observe association to a single protective marker (rs844644) or haplotype as the first study reported; instead, we observed different protective haplotypes, all carrying the major alleles of both SNPs rs1234317 and rs12039904. Association analysis conditioning on the haplotypic background confirmed that these two SNPs explain the entire haplotype effect. This first replication study confirms the association of genetic variation in the upstream region of TNFSF4 with susceptibility to SLE.

Primary Sjögren syndrome in Spain: clinical and immunologic expression in 1010 patients.

We conducted the current study to characterize the clinical presentation of primary Sjögren syndrome (SS) in a large cohort of Spanish patients and to determine whether epidemiologic, clinical, and analytical features modulate disease expression. Patients were from the GEMESS Study group, which was formed in 2005 and included 12 Spanish reference centers. By March 2007, the database included 1010 consecutive patients, recruited since 1994, both incident and prevalent cases. The cohort included 937 women and 73 men (ratio, 13:1), with a mean age of 53 years at diagnosis and 59 years at inclusion in the registry. Multivariate analysis showed that male patients had a lower frequency of thyroiditis, Raynaud phenomenon, and antinuclear antibodies. Young-onset patients had a low degree of sicca involvement (xerostomia and parotid enlargement) and a high frequency of immunologic markers (anti-Ro/SS-A and low C4 levels). Patients with disease duration of more than 10 years had a higher prevalence of xerophthalmia, parotid enlargement, lung involvement, and peripheral neuropathy in comparison with incident cases. The subset of patients with anti-Ro/La antibodies had the highest prevalence of most systemic, hematologic, and immunologic alterations (higher frequency of Raynaud phenomenon, altered parotid scintigraphy, positive salivary gland biopsy, peripheral neuropathy, thrombocytopenia, and rheumatoid factor). Hypocomplementemia was associated with a higher frequency of vasculitis and lymphoma, and cryoglobulins with a higher frequency of parotid enlargement, vasculitis, and leukopenia.Epidemiologic, clinical, and analytical features have a significant impact on the clinical presentation of primary SS, influencing the results of the main diagnostic tests, the prevalence and diversity of extraglandular involvement, and the frequency of the main immunologic markers. Primary SS should be considered as a systemic autoimmune disease that can express in many guises beyond sicca involvement.

La hidroxicloroquina en el tratamiento del lupus eritematoso sistémico / Hydroxychloroquine in the treatment of systemic lupus erythematosus

The positive effects of hydroxychloroquine in treating systemic lupus erythematosus is well known. Hydroxychloroquine is a well tolerated and safe drug even during pregnancy and breast feeding, and it has a low cost. Retinopathy is the most serious side-effect associated with its use since irreversible blindness can occur; therefore, an appropriate monitoring of the eye by an ophthalmologist becomes essential. The remarkable effectiveness of hydroxychloroquine to control disease activity has been demonstrated; and there is also evidence suggesting that this drug contributes to prevent damage accrual and to improve survival in lupus patients. Besides the immunomodulating and immunosuppressant properties of hydroxychloroquine, it also has beneficial effects on lipid and glucose metabolism as well as antithrombotic effects that could contribute to prevent arteriosclerosis in these patients

La utilidad de la hidroxicloroquina en el tratamiento del lupus eritematoso sistémico está ampliamente demostrada. Es un fármaco seguro (incluso durante el embarazo y la lactancia), bien tolerado y económico. La retinopatía asociada a su uso es el único efecto adverso realmente peligroso por cuanto puede provocar ceguera irreversible, que puede evitarse mediante un adecuado control oftalmológico. Existen suficientes datos que respaldan el notable efecto que tiene la hidroxicloroquina sobre el control de la actividad de la enfermedad. También hay hallazgos que sugieren que disminuye el daño acumulado en los pacientes lúpicos y podría aumentar su supervivencia. Las propiedades de la hidroxicloroquina parecen ir más allá de su efecto inmumodulador e inmunosupresor. Así, tiene efectos beneficiosos sobre el metabolismo lipídico y glucémico y efectos antitrombóticos que podrían contribuir a prevenir la aterosclerosis

MYO9B gene polymorphisms are associated with autoimmune diseases in Spanish population.

The aim of the study was to test MYO9B gene polymorphisms for association with three autoimmune diseases, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and celiac disease (CD), in a Spanish population. We analyzed three SNPs (rs2305767, rs1457092, and rs2305764) in a case-control cohort composed of 349 SLE patients, 356 RA patients, 90 CD patients, and 345 healthy controls. All three SNPs showed a consistent increased frequency of the A allele in SLE, RA, and CD patients compared with healthy controls. An association was observed between CD and rs2305764 (p=0.01, OR=2.3), between SLE and rs1457092 (p=0.002, OR=1.4), and between RA and rs1457092 (p=0.02, OR=1.3). The three autoimmune diseases combined showed significant association with rs1457092 and rs2305764 and with the AAA haplotype (p haplotype=0.005, OR=1.3). Our data demonstrate consistent association with the A allele and AAA haplotype of three SNPs in the MYO9B gene, which were previously reported to be associated with CD in the Dutch population. This suggests that genetic variation in MYO9B is associated with CD, SLE, and RA and that MYO9B is a general risk factor for autoimmunity.

[Primary aldosteronism: analysis of a series of 54 patients]. / Hiperaldosteronismo primario: análisis de una serie de 54 pacientes.

BACKGROUND AND OBJECTIVE: The prevalence of primary aldosteronism (PA) has experienced an important increase, and many authors consider this condition as the main cause of secondary hypertension (HT). PATIENTS AND METHOD: Retrospective study of a series of 54 patients having PA who were studied in our Unit between 1999 and 2003. RESULTS: The prevalence of PA was 5.1%. Out of 54 PA cases, 13 corresponded to aldosterone-producing adenomas (APA), 30 to bilateral adrenal hyperplasia (BAH), one was one case of nodular bilateral hyperplasia and another case was a nodular unilateral hyperplasia. In 9 cases, an etiologic diagnosis could not be done. APA were more frequent in women and BAH in men; with regard to sex, no significant differences were found. The blood pressure (BP) was significantly higher in patients with APA compared with BAH patients. In patients with APA, kalemia was significantly lower than in BAH patients. Adrenal CT scan identified 90% of APA, while scintigraphy detected 100% of BAH. Spironolactone therapy significantly decreased the BP in APA and BAH patients, although this fall was higher in patients with APA. CONCLUSIONS: The prevalence of PA was 5.1%. Although the tests used for the screening and diagnosis of PA are controversial, a PA ought to be investigated in all patients with refractory HT, independently of the existence of hypokalemia. Spironolactone is an effective therapy for BAH and it is an adequate option for APA treatment when an adrenalectomy is not viable.

Association of the CT60 marker of the CTLA4 gene with systemic lupus erythematosus.

OBJECTIVE: To investigate the possible association of the CT60A/G marker with systemic lupus erythematosus (SLE) in Spanish patients, and to identify the possible CTLA4 haplotype responsible for the association, taking into account other polymorphisms described at positions -1722T/C, -319C/T, +49A/G, and the microsatellite (AT)(n) in the 3'-untranslated region (3'-UTR) of the CTLA4 gene. METHODS: Genotyping of CT60 was performed in 395 patients with SLE and 293 healthy controls using polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis. Genotyping of the rest of the dimorphisms has been previously reported. Genotyping of microsatellite polymorphism (AT)(n) in the 3'-UTR was performed using PCR with a fluorescence-labeled primer. RESULTS: With regard to CT60A/G, the frequency of the AA genotype was significantly decreased among the SLE patients (18.7% versus 28.3% in the control group; P = 0.003, corrected P [P(corr)] = 0.009, odds ratio [OR] = 0.58, 95% confidence interval [95% CI] 0.40-0.85). In other words, the frequency of individuals bearing the G phenotype was increased in the patient group compared with the control group (81.2% versus 71.7%; P = 0.003, P(corr) = 0.006, OR = 1.71, 95% CI 1.18-2.49). The distribution of allele frequency was also significantly different between patients and controls (P = 0.01, P(corr) = 0.02, OR [for allele G] = 1.32, 95% CI 1.06-1.65). After combining the data on the different polymorphisms, 2 neutral haplotypes were found: +49A;(AT)(7);CT60A and +49G;(AT)(8-19);CT60G. In addition, a susceptibility haplotype was found: +49A;(AT)(>19);CT60G. CONCLUSION: The 3'-UTR of the CTLA4 gene is involved in susceptibility to SLE.

[Predictive factors of hypertension in patients with diagnostic doubts of persistent hypertension]. / Factores predictivos de hipertensión arterial en pacientes con dudas diagnósticas de hipertensión mantenida.

BACKGROUND: White coat hypertension (WCH) is a prevalent clinical situation which requires a therapeutic management different from persistent hypertension (PH). To distinguish between patients with WCH and uncertain hypertension from patients with PH, an ambulatory blood pressure monitoring (ABPM) is usually indicated, yet it is not available in primary care. Thereby, predictors of WCH on the basis of pre-test (pre-ABPM) clinical characteristics have been suggested. However, little is known about the predictors of PH. The aim of this study was to ascertain predictors of PH in patients referred from the primary care due to suspicion of WCH or uncertain hypertension. PATIENTS AND METHOD: A 24-hours ABPM was performed in 230 consecutive patients referred from primary care because of suspicion of WCH or uncertain hypertension. WCH was defined as an increased office BP with a mean daytime BP, as measured by ABPM, < 135/85 mmHg. Uncertain hypertension was diagnosed when patients had had episodic (2 or more) office BP >140 and/or 90 mmHg together with normal BP determinations. Patients with increased office BP with a mean daytime BP [by ABPM]3 135/85 mmHg were considered as having PH. RESULTS: In 178 patients, ABPM was successful. Eighty-six patients (48.3%) had PH and the remainder (92 patients; 51.7%) were considered as having WCH. In the PH group, there were more males (67.4% vs 43.5%; p < 0.001), patients were older (42.8 [11.8] years vs 35.7 [11.2] years), there were more smokers (39.5 vs 26.1%; p = 0.056), they consumed more alcohol (p = 0.001) and coffee (p < 0.001) and they had higher levels of hemoglobin (p = 0.001) and creatinine (p = 0.003) and lower levels of uric acid (p<0.001) than the WCH group. Also they had an office BP and an ambulatory BP higher than WCH patients. A multivariate logistic regression analysis revealed that PH was significantly associated with a male gender (odds ratio [OR] = 3.26; confidence interval [CI]: 1.54-6.88; p = 0.001), office systolic BP > 145 mmHg (OR = 6.53; CI, 2.67-16.11; p < 0.001), age (> 35 years) (OR = 5.03; CI, 2.35-10.78; p < 0.001) and smoking (OR = 3.07; CI, 1.38-6.84; p = 0.005). CONCLUSIONS: Our findings indicate that in patients referred from primary care due to suspicion of WCH or uncertain hypertension, the prevalence of PH was 48.3%. PH was more frequent among men older than 35 years, smokers and those with an ambulatory systolic BP > 145 mmHg.