Melchor Rodríguez-Gaspar

Factors involved in the paradox of reverse epidemiology.

BACKGROUND & AIMS The hypothesis of reverse epidemiology holds that some cardiovascular risk factors, such as obesity, hypercholesterolemia and hypertension, in the elderly or in some chronic diseases are not harmful but permit better survival. However, this phenomenon is controversial and the underlying reasons are poorly understood. OBJECTIVE To search for factors simultaneously linked to reverse epidemiology and to short or long term survival. METHODS We included 400 patients, older than 60 years, hospitalized in a general internal medicine unit; 61 died in hospital and 338 were followed up by telephone. RESULTS Obesity, higher blood pressure and serum cholesterol, besides being related to lower mortality both in hospital and after discharge, were associated with better nutrition and functional capacity, less intense acute phase reaction and organ dysfunction, and lower incidence of high-mortality diseases such as dementia, pneumonia, sepsis or cancer. These associations may explain why obesity and other reverse epidemiology data are inversely related to mortality. Weight loss was related to mortality independently of BMI. Patients with BMI under 30 kg/m(2) who died in hospital showed more weight loss than those who survived; the lower the BMI, the greater the weight loss. In contrast, patients with BMI over 30 kg/m(2) who died in hospital gained more weight than those who survived; the higher the BMI, the greater the weight gain. CONCLUSION In patients over 60 years of age admitted to an internal medicine ward, obesity did not show independent survival value, being displaced by other nutritional parameters, functional capacity, acute phase reaction, organ dysfunction and diseases with poor prognosis.

Interleukin-15 and Other Myokines in Chronic Alcoholics

AIMS Interleukin (IL)-15 is highly expressed in skeletal muscle, where it exerts anabolic effects, increasing protein content in muscle fibres and promoting muscle growth. Alcoholics frequently suffer myopathy. Therefore, we analyse the behaviour of IL-15 (and other myokines, such as IL-6, IL-8 and tumour necrosis factor α (TNF-α)) in alcoholics. METHODS These myokines and also malondialdehyde (MDA)--a lipid peroxidation product--were determined by radioimmunoanalytic techniques in blood samples of 35 chronic alcoholics and 13 age- and sex-matched controls, and compared with body composition, nutritional status, liver function, amount of ethanol and routine biochemical variables. RESULTS IL-15, IL-6, TNF-α, IL-8 and MDA were all higher in alcoholics than in controls; MDA and IL-6 were clearly related with liver function impairment and short-term prognosis, whereas IL-15 was higher among those who died and was related to serum bilirubin. No relation was found between IL-15 and lean mass. CONCLUSION IL-15 levels were higher in alcoholics than in controls, especially among those who died within 18 months after admission. They are not related with muscle mass, intensity of alcoholism or nutritional status, but only with serum bilirubin. IL-6 showed inverse correlations with liver function, intensity of alcoholism, nutritional status, left arm muscle mass and short-term mortality.

Changes in cytokine levels during admission and mortality in acute alcoholic hepatitis

Cytokine levels are raised in acute alcoholic hepatitis. However, there are disparate results regarding the duration of altered plasma levels, and there are also discrepancies about the relation of changes during the first 15 days after admission with short-term (in-hospital) or long-term mortality. In 56 patients with acute alcoholic hepatitis we found that IL-8, IL-4, Interferon-γ (IFN-γ), malondialdehyde and C-reactive protein remained higher in patients than in 18 age- and sex-matched controls at admission, at the 7th day and at the 15th day after admission. Moreover, IL-4 levels (and to a lesser extent, IL-10 and IFN-γ ones) increased along the three determinations. However, comparing patients who died during the admission with those who did not, there were no statistically significant differences, but there was a nearly significant trend for MDA (Z=1.89; p=0.059), with higher levels among those who died. When changes between the first and the second determinations were compared with long-term survival, only IL-8 and IFN-γ showed a relation with mortality. IFN-γ values increased among those who survived and decreased among those who died (p=0.048). IFN-γ values at the first determination also showed a relation with long-term mortality, especially when patients with IFN-γ values in the first quartile were compared with those of the 4th one (log rank=5.64; p=0.018; Breslow=4.64; p=0.031). Besides Interferon-γ, only C-reactive protein showed differences between the first and the 4th quartile regarding mortality (Log rank=4.50; p=0.034; Breslow 4.33; p=0.038). In contrast with other studies, no relation was found between TNF-α or IL-6 and mortality.

Alpha Klotho and Fibroblast Growth Factor-23 Among Alcoholics

Aims Alcoholism may be a cardiovascular risk factor. Osteocyte derived molecules such as fibroblast growth factor 23 (FGF-23) and soluble α Klotho have recently been associated with cardiovascular disease, but their role in alcoholics is unknown. We here analyze the behavior of FGF23 and α Klotho in alcoholics. Methods Ninety-seven alcoholic patients were assessed for liver function, presence of hypertension, diabetes, atrial fibrillation, left ventricular hypertrophy (LVH), vascular calcifications (assessed by chest X-ray) and nutritional status (lean and fat mass measured by densitometry). We measured plasma levels of FGF-23 and serum soluble α Klotho, using ELISA in 97 patients and 20 age- and sex-matched controls. Results FGF-23 levels were higher in patients than in controls (Z = 3.50; P < 0.001). FGF-23 (Z = 5.03; P < 0.001) and soluble α Klotho (Z = 5.61; P < 0.001) were higher in cirrhotics, and both were related to liver function, independently of serum creatinine FGF-23 levels were higher among alcoholics with diabetes (Z = 2.55; P = 0.011) or hypertension (Z = 2.56; P = 0.01), and increased body fat (ρ = 0.28; P = 0.022 for trunk fat), whereas α Klotho levels were higher in patients with LVH (Z = 2.17; P = 0.03) or atrial fibrillation (Z = 2.34; P = 0.019). Conclusions FGF-23 was higher in alcoholics than in controls, especially among cirrhotics, and soluble α Klotho levels were also higher among cirrhotics. Both were related to liver function impairment, independently of serum creatinine levels, and also showed significant associations with vascular risk factors, such as hypertension, diabetes or trunk fat amount in the case of FGF-23, or LVH or atrial fibrillation in the case of α Klotho. Short summary We report increased values of fibroblast growth factor 23 (FGF-23) and soluble α Klotho in cirrhotic alcoholics. Both molecules are associated with liver function impairment, and with some cardiovascular risk factors such as diabetes, hypertension, increased body fat, left ventricular hypertrophy and atrial fibrillation independently of serum creatinine.

Vitamin D, Vascular Calcification and Mortality among Alcoholics

AIMS To analyze the relationship between low vitamin D levels and mortality among alcoholics. METHODS One hundred twenty-eight alcoholic patients admitted to our hospital were followed up as outpatients. Nutritional status was evaluated measuring percentages of fat and lean mass in different body compartments. RESULTS Lower vitamin D levels were observed in patients with worse liver function. Vitamin D was lower in patients with lower total lean mass (Z = 2.8, P = 0.005), but it was not related to fat mass. There was a significant trend to higher long-term mortality among non-cirrhotics with vitamin D levels below 30 ng/ml, although Coxs regression model revealed that only Child score and age were independently related to mortality. CONCLUSION Vitamin D deficiency is common among alcoholic patients and is associated with low lean mass and liver dysfunction. Among non-cirrhotics, serum vitamin D levels below 30 ng/ml are associated with a greater long-term mortality.