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Background: Cytochrome p450 is the main drug metabolic pathway. CYP2D6 is a highly polymorphic gene that encodes a cytochrome p450 enzyme with three activity levels: null, reduced and normal. Apart from another type of mutations CYP2D6 can suffer duplications and deletions of the entire gene. This is the pathway to metabolize one of the Gaucher disease treatments, whose dose administration is regulated according to the metabolizer phenotype, this being one of the administration limitations., Objectives: The aim of this paper is to evaluate the allelic frequencies and the metabolizer status of Gaucher type 1 patients in the Spanish population and compare it with the general Spanish population and other Gaucher disease groups., Methods: In this study, 109 type 1 Gaucher disease patients were analyzed with the xTAG®CYP2D6 kit to identify the CYP2D6 gene alleles., Results: We observed that eighty-seven patients could be classified as extensive, 14 as intermediate, 6 as poor and 2 as ultra-rapid metabolizers. The allelic duplication frequency is 5.5% and deletion is 4.5%. The most common allele is wild-type and the second is the null *4 allele. Intermediate phenotype frequency is higher than expected (p<0.05)., Conclusions: Our Spanish GD series shows an unexpected distribution of some alleles and phenotypic metabolizer status, in contrast to that previously reported in the Spanish population., (Copyright © 2020 Elsevier España, S.L.U. All rights reserved.)

Background and Objectives: Statins are safe but have a significant potential for pharmacological interactions. The objective of the study was to evaluate the prevalence of potential interactions throughout the cytochrome P450 isoenzyme 3A4 (CYP3A4) system in a large sample of statin-treated subjects and to determine which factors, from the patient and the physician, were associated with a higher risk of interactions., Patients and Methods: This is an observational, cross-over, population study that included 7,880 subjects treated with statins. Both data from patients and from the1,681 participating physicians were recorded and analyzed., Results: Fifty-nine percent of the participants were receiving a statin metabolized by the CYP3A4, and 21.5% of all participants received a drug, different from a statin, metabolized by the CYP3A4. There were no differences in the frequency of utilization of statins metabolized or not by the CYP3A4 in relation to the simultaneous prescription of drugs metabolized by the same pathway (22 vs. 21%, respectively). Globally, 12.9% of all participants were at risk of an interaction. These patients were older, received a higher number of drugs and had more comorbidity. Sixty percent of the physicians mentioned that the possibility of an interaction greatly conditioned their selection of a particular statin. Likewise, 56% of them had software that alerted of possible interactions. These aspects, however, did not influence the number of patients at risk of interactions., Conclusion: The proportion of statin-treated patients at risk of interaction is elevated. Physicians do not usually pay attention to this possibility despite having available alert software and therapeutic alternatives., (Copyright © 2013 Elsevier España, S.L.U. All rights reserved.)

Reduction in the risk of cardiovascular complications through modification of lipids is currently focused on lowering low density lipoproteins-cholesterol, with statins being the preferred drugs. New agents, under research, such as antibodies neutralizing PCSK9, will have a special place for the management of patients with intolerance to statins of severe dyslipemias. Drugs used to modify the concentration of high density lipoproteins-cholesterol and triglycerides have not been accompanied by the expected reductions in the rate of cardiovascular complications., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

Gluten-related disorders are a spectrum of systemic immune mediated conditions that occur at any age in genetically susceptible individuals upon ingesting gluten. Celiac disease and gluten sensitivity are the most important conditions of the spectrum. They may be associated with other autoimmune diseases, such as multiple sclerosis and neuromyelitis optica. Treatment with a gluten-free diet can provide considerable benefits to the patients having both a gluten-related disorder and one of these 2 demyelinating diseases of the central nervous system., (Copyright © 2012 Elsevier España, S.L. All rights reserved.)

The protective role of HDL-cholesterol against atherosclerosis has been established in epidemiological and experimental studies. In spite of this, there are a few of clinical trials that have unequivocally demonstrated that raising HDL-cholesterol reduces the cardiovascular risk. In the present article we review the putative protective mechanisms associated with HDL particles, the evidence linking HDL-cholesterol increase with a reduction in cardiovascular risk as well as the pharmacological and non-pharmacological therapies for increasing HDL-cholesterol. Finally, we comment on experimental drugs currently under development, that elevate HDL-cholesterol.

Background and Objective: To evaluate the factors associated with intima-media thickness (IMT) and carotid plaques in patients with familial hypercholesterolemia (FH) and to assess the evolution following 1 year of treatment., Patients and Method: Subjects (n=201) diagnosed as having probable or definite FH according to the MED-PED criteria had a clinical history, physical examination, blood chemistry and lipid profile determined. Ultrasound was used to measure the IMT in both common carotid arteries and to assess the presence of plaques. The measurements were repeated in 123 of the patients after 1 year of treatment., Results: Mean age (standard deviation) was 47.8 (13.2) years; 46.3% were males; 11.4% had a clinical history of cardiovascular disease (CVD); 15.9% were hypertensive; 26.4% were smokers; mean plasma total cholesterol concentration was 362 (49)mg/dL; 66.2% had received previous treatment with statins. In the multivariate analysis, baseline IMT was directly associated with age and history of CVD and inversely related to the years of treatment with statins. The presence of carotid plaques was associated directly with the cholesterol-years index and inversely with years of treatment with statins. The mean LDL-cholesterol reduction at 1 year of treatment was 50%. Neither the IMT nor the percentage of patients with plaques changed significantly following 1 year of treatment., Conclusions: Intensive hypocholesterolemic treatment in our patients with probable or definite FH did not increase significantly either the carotid IMT or the prevalence of plaques.

Background and Objective: Chronic kidney disease (CKD) increases cardiovascular risk mainly in subjects with coronary heart disease. The aim of this study was to evaluate the prevalence of occult CKD (OCKD) in stable coronary heart disease patients and to study the factors associated in order to improve its detection., Patients and Method: Cross sectional study of 7,884 patients who had had a coronary event requiring hospitalization in the previous 6 months to 10 years. Glomerular filtration rate was estimated by means of the Modification of Diet in Renal Disease (MDRD) study equation. CKD was defined as a glomerular filtration rate lower than 60 ml/min/1.73 m(2), and OCKD when, in addition, serum creatinine was < 133 mmol/l in men and < 124 mmol/l in women., Results: The mean age was 65.3 years, 73.7% male and 22.4% had CKD, 68.3% of them with normal serum creatinine. In subjects with OCKD the prevalence of risk factors and cardiovascular diseases associated was intermediate between subjects without CKD and subjects with CKD and high serum creatinine. Age, female sex, hypertension, diabetes, heart failure, cerebrovascular disease and peripheral artery disease were significantly and independently associated with OCKD in the multivariate analysis., Conclusions: Almost one in 4 subjects with stable coronary heart disease had CKD, most of them with normal serum creatinine, mainly women and older patients.

Background and Objective: The aim of this study was to determine the percentage of subjects receiving statin treatment that was inappropriate and to evaluate the associated clinical factors., Patients and Method: A cross-sectional multi-centred study conducted across the Autonomous Regions of Spain. The appropriateness of prescription was based on the guidelines of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) and the European Guidelines on Cardiovascular Disease Prevention., Results: Of the 1,817 patients studied, 52.9% were male, the overall mean age was 59.4 years, 36% had cardiovascular disease and 32.7% had diabetes. In 90.8% of the population the prescription was correct according to at least one of the two guides being used, with a low concordance between them (kappa = 0.279). Almost 100% of subjects with cardiovascular disease or diabetes had an appropriate prescription. In primary prevention, 82.7% had an appropriate prescription according to at least one of the two guides used, but this percentage decreased to 20.7% when based on the European Guidelines. In multivariate analysis, there was agreement with both guides. The inappropriate prescription was directly, and significantly, associated with primary prevention and female gender, while being inversely related to age, smoking habit and LDL-cholesterol concentration., Conclusions: Most of the patients receiving statin treatment have an appropriate prescription, but the percentage of inappropriate prescription increases significantly in patients in primary prevention following European Guidelines.

Background and Objective: The measurement of the ankle-brachial index (ABI) is a straightforward method for the detection of atherosclerosis in the lower limbs. An abnormal ABI (< 0.9 or > 1.4) is associated with the development of cardiovascular disease and cardiovascular and all-cause mortality. Despite this, its measurement in clinical practice is underused. The objective of the present study was to evaluate the relation of the ABI with the cardiovascular risk determined by traditional risk functions in a population in primary prevention., Patients and Method: 1001 subjects without known cardiovascular disease attended in primary care were invited to participate in the study. Cardiovascular risk and ABI measurements were calculated in all participants., Results: A low (< 0.9) ABI was found in a 3.8% of the participants, 3.9% females and 3.6% males. An abnormal ABI (< 0.9 or > 1.4) was found in 6.4% of all subjects, 5.2% females and 8.8% males. In a multivariable analysis age (OR = 1.09 for each year; 95% CI 1.03-1.15), smoking habit (OR = 2.96; 95% CI 1.51-5.80), HDL-cholesterol levels (OR = 0.98 for each mg/dl; 95% CI, 0.95-0.99) and hypertension (OR = 1.80; 95% CI, 1.05-3.06) were related with an abnormal ABI. Subjects were divided according to their risk stratification. The percentage of low, moderate and high risk individuals with an abnormal ABI was 2.6%, 8.7% and 14.9% respectively., Conclusions: In primary prevention, one in ten individuals with moderate risk and one in six individuals with high risk have an abnormal ABI. In these subjects there is an indication for intensive preventive strategies and antiagregation.

Background and Objective: The Framingham function, recommended by the National Cholesterol Education Program in its document Adult Treatment Panel III (ATP III), and the risk charts of the Systematic Coronary Risk Evaluation (SCORE) program are the most used functions for risk stratification. In both, intensive hygienic and therapeutic measures are recommended for high risk individuals. The objective of the present study was to compare the risk stratification obtained with both functions in a population of subjects older than 60 years., Subjects and Method: 1001 non-diabetic subjects between 60 and 79 years old (mean: 69 years, 67% female) with no evidence of cardiovascular disease were included in the study. Participants were classified as low, moderate or high risk by ATP-III (< 10%, 10-20% y > 20% of risk at 10 years, respectively) and by SCORE (< 3%, 3-4% y > or = 5% of risk at 10 years respectively)., Results: 11.7% of the population was classified as high risk by Framingham and 17.6% by SCORE. Only 5% of the females were classified as high risk with either function. In males, 16.7% and a 44.4% were classified as high risk by Framingham and SCORE respectively. The results did not differ by age group. A 39% of males and a 20% of females were candidates to hypolipidemic treatment as recommended by SCORE guidelines., Conclusions: Compared to Framingham function, the application of SCORE charts to spanish males over 60 years triplicate the number of high risk individuals and candidates to intensive risk factor treatment.

Background: Apolipoprotein E (Apo E) plays an important role in atherogenesis. Apo E is polymorphic with three codominant alleles: *2, *3 and *4. Inthis study we evaluated the association between *4 allele and coronary heart disease in hypercholesterolemic subjects from Spain., Subjects and Method: We selected 389 subjects (56% women, mean age 57 years) with hypercholesterolemia who had been on a 6-weeks low fat, low cholesterol diet. Measurement of lipid and lipoprotein concentrations and determination of apoE genotype were carried out in a centralized laboratory., Results: ApoE distribution was as follows: *2/*33%, *3/*3 75%, *3/*4 20%, *4/*4 1% and *2/*41%. Subjects were grouped into *4 (n = 83) or no *4 (n = 303) according to the presence or absence of the *4 allele. Three *2/*4 cases were excluded. Prevalence of coronary artery disease was 15.7% in *4 and 6.9% in no *4 (OR 2.49, 95% CI 1.19-5.22). The relationship persisted significant after correction for age, sex, cardiovascular risk factors and serum concentrations of total cholesterol, HDL-cholesterol and triglycerides by multiple logistic regression analysis (OR2.56, 95% CI 1.03-6.39).Conclusión:In Spain, *4 carriers have a higher prevalence of coronary artery disease than no analysis *4 carriers.

Background: Patients with late-onset Alzheimer's disease show a higher frequency of the APOE-4 than controls. The usefulness of the APOE genotyping in the diagnosis of the disease is controversial. Recently, an age dependent prevalence of APOE-4 in Alzheimer's disease has been described, with a maximum frequency for patients with an age at onset between 65 and 80 years. Additionally, the APOE-4 frequency in healthy controls is similar among the different age-groups, including healthy octogenarians. These data suggest that APOE-4 determines when and not who will develop the disease., Patients and Methods: The APOE genotype was defined following a previously described PCR-protocol. We analysed 120 patients with clinically defined probable Alzheimer's disease and 250 controls from the same Caucasian population (Austrias, Northern Spain)., Results: We found a significantly higher frequency of the APOE-4 in patients, compared to controls (p = 0.00001). The prevalence of this allele was 65% among patients with an age at onset 66-70, falling to 36% and 18% in patients younger than 65 and older than 80 years, respectively. The average age (SD) at onset did not differ between the E-44 (69 years), E-34 (73 years) and E-33 (73 years). APOE-4 frequency was similar between the different age-groups of controls, including healthy octogenarians., Conclusions: In Asturias, APOE genotyping can not be used for the presimptomatic diagnosis of Alzheimer's disease. However, individuals carrying this allele would have a higher probability of developing the disease at an age between 65 and 80 years if they are predisposed (genetically and/or environmentally) to the disease.

Background: Plasma glucose, insulin and blood pressure are wellknown cardiovascular risk factors, which may be influence by dietary factors. The aim of the study was to investigate whether changes in dietary fatty acids could modify plasma concentration of glucose, insulin and mean blood pressure (MBP)., Subjects and Methods: Forty two subjects (18 women and 24 men) were placed in four consecutive five week diet periods. Energy intake from proteins, carbohydrates and fats was constant during the study and there was only changes on fatty acids composition. First period was enriched on saturated fatty acids (SFA), second period on monounsaturated fatty acids (MUFA) and third and fourth periods were enriched on polyunsaturated fatty acids (PUFA). Fourth period was also enriched on PUFA n-3., Results: No significant changes were found on glucose and insulin plasma concentration. However, a significant effect was detected on MBP on total population (p < 0.0001) and by gender. MUFA and PUFA n-3 enriched diet decreased significantly MBP compared to SFA enriched diet AGS (85.7, SD 9.1, 87.3, SD 8.7 y 90.3, SD 8.8 mmHg, respectively). In addition, a weak (r = 0.28) but significant (p = 0.002) correlation was found between MBP and plasma insulin., Conclusions: Diets enriched on MUFA fatty acids and n-3 fatty acids decrease significantly MBP without modifying glucose and insulin plasma concentration.

Background: Lipoprotein (a) (Lp[a]) is a known risk factor for coronary heart disease. Lp(a) plasma concentration mainly depends on genetic polymorphism. The aim of this study was evaluate the effect of dietary fat saturation on Lp(a) plasma concentration., Subjects and Methods: Forty two subjects (eighteen women and twenty four men) were placed in four consecutive 5 weeks diet periods. Energy intake from proteins, carbohydrates and fats was constant during the study and there were only changes on fatty acids composition. First period was enriched in saturated fatty acids (SFA), second period in monounsaturated fatty acids (MUFA) and third and fourth periods were enriched in polyunsaturated fatty acids (PUFA). Fourth period was also enriched in PUFA n-3 (blue fish)., Results: Changes on dietary fat saturation had a significant effect on plasma lipids and lipoproteins. Lp(a) plasma concentration was minimum in SFA phase (6.8 [SD 7.3] mg/dl), increasing during MUFA phase (8.7 [8.5] mg/dl) and was maximum in PUFA n-6 and PUFA n-3 (11.5 [11.1] and 12.7 [11.9] mg/dl, respectively) (p < 0.0001)., Conclusions: Changes on dietary fat saturation significantly modify Lp(a) plasma concentration. These variations went in opposite direction to LDL-cholesterol modifications and were clinically irrelevant.

Background: Juvenile myoclonic epilepsy (JME) constitutes 10% of all epilepsies. Despite this syndrome being well defined, its diagnosis is usually delayed. The aim of this study was to analyze the clinical and electroencephalographic characteristics to facilitate guidelines to contribute to its recognition., Methods: From January 1986 to July 1993 the clinical and EEG data of 85 patients with JME were prospectively studied. In 68 cases (80%) the polygraphic study of sleep was also analyzed during a nap period., Results: The series included 44 males and 41 females of a mean age of 28 years (range: 13-63). Fifty-six percent of the cases showed family history of epilepsy and/or febrile convulsions. All the patients had myoclonic crisis with the age of 15 being the mean age of initiation (range: 8-27). Eighty-seven percent also had generalized tonic-clonic crisis and 18% typical absences. Myoclonias were presented daily up the administration of adequate treatment in 60% of the cases with 21% having myoclonic status. The mean interval from the initiation of the myoclonic crisis to diagnosis of JME was of 10.6 years. On monotherapy with valproic acid and following a mean follow up period of 23.8 months, 86% of the patients remained free of crisis. Nonetheless, the rate of recurrence was 100% in the 19 patients who discontinued the treatment. Surveillance EEG was normal on some occasion in 88% of the cases. The most characteristic paroxysms were the following: wave-point at 4-5 Hz and generalized rapid wave-polypoint. Light stimulation provoked a paroxysmal response in one third of the cases. Sleep EEG was abnormal in all the patients. An activation of the paroxysms during non-REM sleep in 78% of the cases and on waking up in 25%., Conclusions: Juvenile myoclonic epilepsy is a well defined syndrome. Its diagnosis is based on directed anamnesis allowing myoclonic jerks to be collected which often remain unperceived, and EEG exploration with sleep tracing in which the characteristic outbreaks of wave-point or generalized rapid wave-polypoints may be discovered.

The cases of pulmonary thromboembolism (PTE) diagnosed in the clinical autopsies performed in our hospital during a 15-year period were reviewed. The incidence was 2.7% (63 cases). The most common disease associated with thromboembolism was cancer (41%). In 30 cases, thromboembolism involved more than 60% of the pulmonary circulation (group I), between 40% and 60% in 18 cases (group II), and less than 40% in 15 cases (group III). 30% of the embolisms were recurrent. A statistically significant correlation between the extension of the involved pulmonary circulation and the condition associated with thromboembolism was found. Whereas in patients with neoplasia the extension of pulmonary circulation involved by PTE was quite variable, the patients with cardiovascular disease or thrombophlebitis had PTE with invariably severe compromise of pulmonary vasculature (groups I and II).

A series of 63 cases of fatal acute pulmonary thromboembolism (PTE) with available necropsy study was evaluated The diagnosis was established ante mortem in 20 cases (predictive index 31%). The diagnosis was only suspected in 2 of the 16 patients in whom PTE was associated with pneumonia (predictive index 12.5%, p less than 0.01), in 3 of the 26 cases if PTE associated with neoplasia (predictive index 11.5% p less than 0.01) and in 8 of the 41 cases with terminal disease (predictive index 19.5%, p less than 0.01). On the contrary, thrombophlebitis and relapsing PTE had a significative facilitation effect on the diagnosis (predictive indexes 53.3% and 52.6%, respectively; p less than 0.01). It was concluded that the presence of neoplasia, pneumonia or terminal illness make the diagnosis of pulmonary thromboembolism difficult.