Mediterranean diet, tobacco consumption and body composition during perimenopause. The FLAMENCO project.

OBJECTIVE: To study the association of the adherence to the Mediterranean diet (MD) and tobacco consumption with body composition during perimenopause. STUDY DESIGN AND METHODS: A cross-sectional study in 176 perimenopausal women from the FLAMENCO project. A food frequency questionnaire and the Mediterranean Diet Score were assessed. Body composition was measured using dual-energy X-ray absorptiometry. MAIN OUTCOMES MEASURES: Body mass index (BMI), fat mass (FM), ratio of gynecoid to total fat mass (G/T), ratio of android to gynecoid fat mass (A/G), visceral adipose tissue (VAT) and waist circumference (WC). RESULTS: Intake of whole-grain cereals was associated with lower WC, FM percentage, android FM, VAT and higher G/T (all p < 0.05). Intake of nuts was associated with lower BMI and FM percentage and intake of fruits with lower BMI, WC, total and android FM, FM percentage, A/G, VAT and higher G/T (all p < 0.05). Intake of pulses was associated with lower weight, BMI and android FM. Intake of whole dairy products was associated with lower weight, BMI, WC, total and android FM and VAT (all p < 0.05). Intake of olive oil was associated with lower WC and FM percentage (all p < 0.05). Intake of sweetened beverages was associated with higher weight, BMI, WC, FM percentage, android FM, VAT and total FM (all, p < 0.05). Smokers had a lower MD adherence (p < 0.05). Finally, a greater MD adherence was associated with higher G/T (p < 0.01) and lower A/G (p < 0.05). CONCLUSIONS: A higher MD adherence, avoiding tobacco, an increased consumption of whole-grain cereals, nuts, fruits, pulses, whole dairy products and olive oil, and a lower consumption of sweetened beverages might contribute to a healthier body composition during perimenopause.

Influence of the degree of adherence to the Mediterranean diet on the cardiometabolic risk in peri and menopausal women. The Flamenco project.

BACKGROUND AND AIMS: The Mediterranean diet (MD) has been associated with reduced morbidity from cardiovascular diseases in the general population. The aim of this study was to assess whether different degrees of adherence to the MD were associated with the cardiometabolic risk in peri and menopausal women. METHODS AND RESULTS: This cross-sectional study included 198 peri and menopausal women participating in the Flamenco project. Validated questionnaires were used to assess menopause health-related quality of life and degree of adherence to the MD (low, medium and high). The following cardiometabolic risk factors were assessed: fat mass percentage, waist circumference, blood pressure and resting heart rate, plasma markers (total cholesterol, high and low-density lipoprotein cholesterol [HDL-C and LDL-C, respectively], total cholesterol/HDL ratio, triglycerides, C-reactive protein and fasting glucose), Physical activity levels and smoking status. The degree of adherence to the MD among the study sample was 27%, 40% and 30% for low, medium and high adherence, respectively. After controlling for potential confounders, women with a high adherence to the MD showed lower plasma total cholesterol (p = 0.025), resting heart rate (p = 0.005), LDL-C (p = 0.019), triglycerides (p = 0.046) and C-reactive protein (p = 0.009) compared to those with a low adherence. Likewise women with high adherence to the MD showed lower total cholesterol/HDL-C ratio (p = 0.020) compared to those with a medium adherence. The high MD adherence group also showed lower clustered cardiometabolic risk (p = 0.004). Moreover, when analysing specific MD components, whole grain cereals, pulses (both p < 0.05) and red wine (p < 0.01) consumption were inversely associated with the clustered cardiometabolic risk. CONCLUSION: The present findings suggest that a high but not medium adherence to the MD is associated with a cardioprotective effect in peri and menopausal women. As a low percentage of the sample showed a high adherence to the MD, future research aimed at increasing the adherence to this dietary pattern for a better cardiometabolic status during peri and menopause is warranted.

Interval aerobic training combined with strength-endurance exercise improves metabolic markers beyond caloric restriction in Zucker rats.

AIMS: To investigate the effects of interval aerobic training combined with strength-endurance exercise (IASE) and caloric restriction (CR) on body composition, glycaemic and lipid profile and inflammatory markers. METHODS AND RESULTS: Thirty-two Zucker diabetic fatty rats were randomised into 4 groups (sedentary + CR; sedentary + adlibitum; IASE + CR; and IASE + adlibitum). Training groups conducted an IASE programme in the same session, 5 days/week for 2 months. Body weight, fat and muscle mass and body water were measured using a body composition analyser. Plasma total, LDL and HDL cholesterol, phospholipids, triglycerides, insulin, adiponectin, tumour necrosis factor alpha, interleukin 1 and 10 were measured. Blood fasting and postprandial glucose were assessed. Body weight was lower in the CR compared to the adlibitum groups (p < 0.001). Fat mass was lower in the CR compared to the adlibitum (p < 0.05) and in the IASE compared to the sedentary groups (p < 0.001), but IASE increased lean mass (p < 0.001). Triglycerides were lower in the CR compared to the adlibitum groups (p < 0.001) whereas total and LDL-cholesterol and fasting glucose were reduced only in the IASE groups (all, p < 0.001). Phospholipids decreased in the CR compared to the adlibitum (p < 0.05) and the IASE compared to the sedentary groups (p < 0.001). The area under the curve after oral glucose tolerance test, insulin and homoeostatic model assessment were lower in the IASE and the CR compared to the sedentary and adlibitum groups, respectively (all, p < 0.001). Adiponectin was lower in the CR groups (p < 0.001). CONCLUSION: Overall, IASE as well as CR were both useful interventions, especially when combined. However, IASE showed greater improvements on body composition, inflammatory and glycaemic profile than CR did.

Interaction between orexin A and cannabinoid system in the lateral hypothalamus of rats and effects of subchronic intraperitoneal administration of cannabinoid receptor inverse agonist on food intake and the nutritive utilization of protein.

Crosstalk may occur between cannabinoids and other systems controlling appetite, since cannabinoid receptors are present in hypothalamic circuits involved in feeding regulation, and likely to interact with orexin. In this study, an immunohistochemical approach was used to examine the effect of the intracerebroventricular administration of cannabinoid receptor inverse agonist AM 251 on orexin neuropeptide in the hypothalamic system. AM-activated neurons were identified using c-Fos as a marker of neuronal activity. The results obtained show that AM 251 decreases orexin A immunoreactivity, and that it increases c-Fos-immunoreactive neurons within the hypothalamus when compared with the vehicle-injected control group. We also studied the effects of subchronic intraperitoneal administration of AM 251 on food intake, body weight, and protein utilization. The administration of AM 251 at 1, 2, or 5 mg/kg led to a significant reduction in food intake, along with a significant decrease in the digestive utilization of protein in the groups injected with 1 and 2 mg/kg. There was a dose-related slowdown in weight gain, especially at the doses of 2 and 5 mg/kg, during the initial days of the trial. The absence of this effect in the pair-fed group reveals that any impairment to digestibility was the result of administering AM 251. These data support our conclusion that hypothalamic orexigenic neuropeptides are involved in the reduction of appetite and mediated by the cannabinoid receptor inverse agonist. Furthermore, the subchronic administration of AM 251, in addition to its effect on food intake, has significant effects on the digestive utilization of protein.

Fitness testing as a discriminative tool for the diagnosis and monitoring of fibromyalgia.

We aimed to determine the ability of a set of physical fitness tests to discriminate between presence/absence of fibromyalgia (FM) and moderate/severe FM. The sample comprised 94 female FM patients (52 ± 8 years) and 66 healthy women (54 ± 6 years). We assessed physical fitness by means of the 30-s chair stand, handgrip strength, chair sit and reach, back scratch, blind flamingo, 8-feet up and go, and 6-min walking tests. Patients were classified as having moderate FM if the score in the Fibromyalgia Impact Questionnaire (FIQ) was <70 and as having severe FM if the FIQ was ≥70. FM patients and patients with severe FM performed worse in most of the fitness tests studied (P < 0.001). Except the back scratch test, all the tests were able to discriminate between presence and absence of FM [area under the curve (AUC) = 0.66 to 0.92; P ≤ 0.001], and four tests also discriminated FM severity (AUC = 0.62 to 0.66; P ≤ 0.05). The 30-s chair stand test showed the highest ability to discriminate FM presence and severity (AUC = 0.92, P < 0.001; and AUC = 0.66, P = 0.008, respectively), being the corresponding discriminating cutoffs 9 and 6 repetitions, respectively. Physical fitness in general, and particularly the 30-s chair stand test, is able to discriminate between women with FM from those without FM, as well as between those with moderate FM from their peers with severe FM.

[Vitamin B complex and homocysteine in chronic renal failure]. / Vitaminas B y homocisteína en la insuficiencia renal crónica.

Metabolic, biochemical, and hormonal changes occur in chronic renal failure usually associated with hyponutrition states. In predialysis patients, knowing the nutritional state about water-soluble vitamins such as thiamine, riboflavin, pyridoxine, cianocobalamine, and folic acid is becoming more and more important since some of the manifestations of chronic renal failure may be due to the deficiency of some of these water-soluble vitamins. The metabolic pathways in which most of these vitamins participate are interrelated and it is difficult to understand how the individual deficits of each vitamin affect renal pathology. This work aims at reviewing not only this issue but also the status of these water-soluble vitamins that different authors have found in groups of predialysis patients. On the other hand, the issue on the high prevalence of hyperhomocysteinemia in chronic renal failure as the main mortality risk factor due to cardiovascular pathologies as well as the implication of these vitamins in the metabolism of homocysteine, and consequently in plasma levels of this metabolite in predialysis patients is reviewed.

High frequency of mutation G377S in Brazilian type 3 Gaucher disease patients

Gaucher disease (GD), the most prevalent lysosome storage disorder, presents an autosomal recessive mode of inheritance. It is a paradigm for therapeutic intervention in medical genetics due to the existence of effective enzyme replacement therapy. We report here the analysis of GD in 262 unrelated Brazilian patients, carried out in order to establish the frequency of the most common mutations and to provide prognostic information based on genotype-phenotype correlations. Among 247 type 1 GD patients, mutation N370S was detected in 47 percent of all the alleles, but N370S/N370S homozygosity was found in only 10 percent of the patients, a much lower frequency than expected, suggesting that most individuals presenting this genotype may not receive medical attention. Recombinant alleles were detected at a high frequency: 44 percent of the chromosomes bearing mutation L444P had other mutations derived from the pseudogene sequence, present in 25 percent of patients. Three neuronopathic type 2 patients were homozygous for L444P, all presenting additional mutations (E326K or recombinant alleles) that probably lead to the more severe phenotypes. Six children, classified as type 1 GD patients, had a L444P/L444P genotype, showing that neuronopathic symptoms may only manifest later in life. This would indicate the need for a higher treatment dose during enzyme replacement therapy. Finally, mutation G377S was present in 4 homozygous type 1 patients and also in compound heterozygosity in 5 (42 percent) type 3 patients. These findings indicate that G377S cannot be unambiguously classified as mild and suggest an allele-dose effect for this mutation.

[Mycophenolate mofetil in high risk IgA glomerulonephritis]. / Micofenolato mofetil en la glomerulonefritis IgA de alto riesgo.

Mesangial IgA glomerulonephritis (MIgAGn) is the most common biopsied primary glomerulonephritis worldwide, with a poor long-term prognosis for renal function in over a third of all patients. No proven therapy currently exists for MIgAGn. Recent studies have suggested some benefit with mycophenolate mofetil (MMF), especially in hypertensive patients with kidney failure and proteinuria, though other studies have failed to corroborate these findings. We report eight adult patients with biopsy proven MIgAGn followed in a single hospital. They all received angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Compassionate use of MMF was based on the presence of clinical and analytical data suggesting a high risk of short- to medium-term progression to chronic renal failure. MMF treatment was stopped after two and three months in two patients who had advanced renal failure at the start of therapy because of disease progression and greater fluid retention. Several months later they both required dialysis and kidney transplantation. The mean duration of MMF therapy in the other six patients was 15 (range: 10-18) months. The mean serum creatinine concentration fell from 1.82 +/- 0.47 to 1.55 +/- 0.41 mg/dl (p = 0.04). Protein loss in 24-hour urine collection fell from 1.95 +/- 1.35 to 0.77 +/- 0.58 g/day (p = 0.02). These results in this low number of patients showed that treatment with MMF in high-riks patients with MIgAGn and early stage kidney failure generally stabilized the disease and reduced proteinuria. MMF was well tolerated and may be of some benefit in a subgroup of patients with MIgAGn and a poor prognosis.

Assessment of thiamin (vitamin B1) and riboflavin (vitamin B2) status in an adult Mediterranean population.

The aim of the present study was to assess the nutritional status for thiamin (vitamin B1) and riboflavin (vitamin B2) in an adult Mediterranean population, in order to identify patterns of intake, groups at risk for deficiency and factors that might influence this risk. A cross-sectional survey was carried out in Andalusia, a western Mediterranean region in southern Spain. Nutrient intakes were studied in a random sample of 3390 subjects (1746 men, 1644 women) who were between 25 and 60 years of age. Blood samples were obtained for biochemical assays in a random subsample of 372 subjects (181 men, 191 women). Food consumption was assessed by 48 h recall. Vitamin B1 and B2 were measured as erythrocyte transketolase and as erythrocyte glutathione reductase activation coefficients, respectively. Energy and vitamin intakes were significantly higher in men than in women. Intakes were below two-thirds of the recommended dietary allowance for vitamin B1 in 7.80 % of the men and 4.50 % of the woman, and were below this level for vitamin B2 in 18.00 % of the men and 11.70 % of the women. Age, educational level, alcohol use and smoking were also associated with differences in the intake of these nutrients. Biochemical analyses showed that vitamin B1 and B2 status was deficient in 6.40 and 5.30 % of the population, respectively. Although factors such as gender, age, level of education, drinking and smoking can have an effect on the risk of inadequate intake of these nutrients, these factors did not affect biochemical indices of nutritional status in the present study.

Influence of magnesium deficiency on the bioavailability and tissue distribution of iron in the rat.

We investigated the effect of dietary magnesium (Mg) deficiency on the nutritive utilization and tissue distribution of iron (Fe). Wistar rats were fed an Mg-deficient diet (56 mg/kg) for 70 days. Absorbed Fe, Fe balance, number of the erythrocytes [red blood cells (RBC)] and leukocytes white blood cells (WBC)], hemoglobin (Hb), and Fe content were determined in samples of plasma, whole blood, skeletal muscle, heart, kidney, liver, spleen, femoral bone, and sternum obtained on experimental days 21, 35, and 70. The Mg-deficient diet significantly increased Fe absorption and Fe balance from week 5 until the end of the experimental period. This effect was accompanied by a significant decrease in the concentration of RBC and Hb from day 35, which caused the decrease in whole blood Fe seen on day 70. However, WBC were significantly increased from day 21 until the end of the experimental period. Mg deficiency significantly increased plasma and liver Fe at all three time points investigated. Spleen, heart, and kidney Fe were significantly increased only at the end of the study. However, on day 70, Fe concentration in the sternum had decreased significantly. No changes were found in skeletal muscle or femur Fe content. Mg deficiency led to increased intestinal absorption of Fe and decreased RBC counts, possibly as a result of increased fragility of the erythrocytes. Intestinal interactions between Fe and Mg, together with activation of erythropoiesis as a result of hemolysis, favored intestinal absorption of Fe. This situation gave rise to an increase in plasma Fe levels, which in turn favored Fe uptake and storage by different organs, especially the liver and spleen. However, despite the increased Fe content seen in the tissues of rats fed the Mg-deficient diet, these animals were unable to compensate for the hemolysis caused by this nutritional deficiency.

The role of phytic acid in legumes: antinutrient or beneficial function?

This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect.

Cholesterol levels in untreated Spanish hypertensive patients. The Compas Study Group, Spanish Hypertension Society.

In daily practice, arterial hypertension (AHT) and hypercholesterolaemia are frequently associated with the existence of multiple common etiopathogenic interrelationships. This situation leads to an exponential increase in cardiovascular risk for these patients, so it is essential to know the prevalence and therapeutic management of hypercholesterolaemia in the hypertensive patient. This national study analyses the distribution of total cholesterol levels and low-density lipoprotein cholesterol as well as hypercholesterolaemia prevalence and its therapeutic management in the uncontrolled hypertensive Spanish population. We observed mean total cholesterol levels of 227+/-41 mg/dl with a high prevalence of hypercholesterolaemia (34.2%) among hypertensive patients, and the percentage of those patients with "desirable" total cholesterol levels (<200 mg/dl) was <25%. The treated hypertensive patients presented both significantly higher mean cholesterol levels and greater hypercholesterolaemia prevalence than the untreated hypertensive patients. It appears that total cholesterol levels are scarcely related to the presence or non-presence of obesity, diabetes or smoking. Regarding treatment, only 14.6% of the hypercholesterolaemic hypertensive patients received hypolipaemic treatment with statins. These results support the need to introduce measures for better diagnostic and therapeutic management of hypercholesterolaemic hypertensive patients that will lead to a much higher reduction in cardiovascular risk for these patients.

Arterial hypertension in Spain: the experience of the Spanish League.

Cardiovascular diseases are the main cause of mortality in Spain. After smoking High Blood Pressure (HBP) is the most prevalent (25% in adult population) cardiovascular risk factor. HBP is considered as a public health problem due to its medical and socio-economic implications. The Spanish League Against HBP was formed in 1978. It focused its attention towards the health professionals involved in this field, the hypertensive patients (risk strategy) and the general population (mass strategy) by trying to improve the HBP control and to reduce the cardiovascular morbidity and mortality of our hypertensives. We have reviewed the results obtained during the last 15 years. Since then the levels of awareness (55.5%-80.8%), treatment (25.5%-61.5%) and control (7%-33.7%) of HBP have significantly increased. At the same time we have improved the diagnostic and therapeutic management of hypertensives as well as the number of national and international Spanish papers and communications on HBP which rose from 111 to 444 in 1993. In the future we aim to continue to coordinate all the efforts to improve the control of HBP in Spain.

Mortalidad infantil por bronconeumonia: evolución de las tasas chilenas 1977-1992 / Infant mortality by bronchopneumonia: evolution of chilean rates 1977-1992

Se describe la tasa de mortalidad infantil (por 1.000 nacidos vivos), específica para bronconeumonía (códigos 480 al 486 de la Clasificación Internacional de Enfermedades), para el período comprendido entre los años 1977 a 1982 en Chile. Las tasas son descendentes: 8.7 para el año 1977, y 2.0 para 1992. Se produce una interrupción entre los años 1982 y 1988, período en el cuál las tasas modifican su tendencia, aumentando de 2.41 a 3.22, respectivamente. Se analiza la estructura etárea de los fallecidos y se determinan las tasas para los niños menores de 28 días (tasa neonatal) y para el grupo de 28 días a 11 meses (tasa de mortalidad infantil tardía específica). Un 16.4 porciento de los niños fallecidos en un total del período, corresponde a niños menores de 28 días. El coeficiente de variación de la tasa neonatal es el doble de la tardía: 0.8 y 0.4 respectivamente. Se concluye que el diagnóstico neonatal con bronconeumonía, puede contener errores aleatorios, que alteran las cifras de las tasas descritas. Se sugiere que se utilice de preferencia a tasa de mortalidad tardía, que en 1992 fue de 1.62 constituyendo una de las más bajas observadas en las estadísticas chilenas

Broncodilatadores en aerosol en la prevención del asma inducida por ejercicio / Prevention of exercise induced asthma by bronchodilator drug aerosol

Se comparó el efecto de cuatro medicamentos broncodilatadores en aerosol a presión, en cuanto a su capacidad para inhibir el asma inducida por ejercicio (AIE) en 16 niños asmáticos de 4 a 12 años de edad, mediante cálculo del índice de caída del flujo espiratorio máximo después de prueba de ejercicio con carrera libre. Las cuatro drogas y sus respectivos promedios de índice de caída fueron fenoterol 1,96; bromuro de ipratropio 15,31; salbutamol 5,21 y la combinación de fenoterol más bromuro de ipratropio -0,47. Todas ellas fueron capaces de inhibir el asma inducida por ejercicio con respecto del placebo (beclometasona) cuyo índice promedio de caída de flujo fue 24,72. La eficacia del bromuro de ipratropio fue significativamente menor que la de las otras drogas estudiadas

Riesgo relativo de mortalidad pediátrica por bronconeumonía en las distintas áreas de la región metropolitana, Chile 1985-1986 / Relative risk of pediatric mortality by bronchopneumonia in different areas of Santiago, Chile during 1985-1986

Se calculó el riesgo relativo de fallecer por bronconeumonia de los menores de 5 años, según lugar de residencia en la Región Metropoliitana. De un total de 534 fallecidos en los dos años, un 87 porciento, correspondieron a menores de 1 año. La relación hombre/mujer fue de 1.12. Las 50 comunas metropolitanas se agruparon en 7 áreas. Los resultados para las áreas fueron los siguientes: Oriente=0.52, Central=0.76. Norte=0.77, Rural=0.91, Sur=1.14, Occidente=1.24, Suroriente=1.70. El riesgo relativo de fallecer por bronconeumonia fue significcativamente mayor (X(2)) en las Areas Occidentes y Sur Oriente de Santiago y fue significativamente menor en el Area Oriente

Diagnóstico alimentario nutricional de cinco comunidades campesinas del distrito de Ocongate-Cusco / Diagnostic food nutrition of five communities at Ocongage village - Cusco

Se realizó un estudio alimentario y antropométrico en 5 comunidades campesinas del Distrito de Ocongate, pertenecientes a 3 pisos ecológicos: Quechua, Suni y Puna, durante 2 épocas del año agrícola (siembra y cosecha). Se encontró que hay variaciones en cuanto al aporte nutricional y estilo nutricional de acuerdo a las épocas del año agrícola. También se observaron diferencias de acuerdo al piso ecológico al que pertenecía la comunidad. Los resultados obtenidos muestran que el consumo calórico está en un 86.9 por ciento de adecuación para la época de siembra y 96.9 por ciento para la época de la cosecha. En relación al estado nutricional de los menores de 6 años durante la época de siembra, el porcentaje de desnutridos oscila entre 11.7 por ciento y 52.8 por ciento de acuerdo al piso ecológico. Este porcentaje disminuye en la época de cosecha a valores que oscilan entre el 11.1 por ciento y el 47.0 por ciento.

Comparación de 2 preparados de salbutamol en aerosol en la inhibición del asma inducido por ejercicio: un estudio doble ciego / Prevention of exercice-induced asthma with salbutamol in aerosol: a double blind comparisson of two comercial brands

Se comparan 2 preparados comerciales de Salbutamol en aerosol disponibles en nuestro medio (Aaerolin R y Fesema R) en cuanto a su capacidad para inducir el asma inducido por ejercicio (AIE) en 19 niños asmáticos, mediante la prueba de ejercicio con carrera libre y usando la caída del flujo expiratorio máximo como el parámetro de evaluación. Tanto el Aerolin como Fesema fueron capaces de inhibir significativamente el AIE respecto del placebo. En promedio, hubo una diferencia de 6,4% en los índices de caída de la flujometría entre ambos preparados de Salbutamol en favor de Aerolín R, sin embargo esta diferencia no tuvo significación estadística

Cámara aérea para medicamentos presurizados / Air chamber for pressurized drugs

Las dificultades para la inhalación de drogas envasadas a presión excluyen de esta importante arma terapéutica, a un numeroso grupo de pacientes. Buscando solucionar esto, desarrollamos un método alternativo consistente en una mascarilla confeccionada con parte de un matraz desechable para soluciones endovenosas. El asma inducida por ejercicio fue inhibida por la inhalación de Salbutamol en dosificador presurizado administrado mediante el método clásico directo y el método alternativo usando la aerocámara descrita en un grupo de 17 niños asmáticos (5 a 11 años), con índices iniciales de caída del FEM iguales o mayores que 12%, provocados con prueba de ejercicio estándar