Diana Gavrila

Factores de riesgo cardiovascular en España en la primera década del siglo xxi: análisis agrupado con datos individuales de 11 estudios de base poblacional, estudio DARIOS ☆

INTRODUCTION AND OBJECTIVES To estimate the prevalence of cardiovascular risk factors in individuals aged 35-74 years in 10 of Spains autonomous communities and determine the geographic variation of cardiovascular risk factors distribution. METHODS Pooled analysis with individual data from 11 studies conducted in the first decade of the 21st century. The average response rate was 73%. Lipid profile (with laboratory cross-validation), glucose level, blood pressure, waist circumference, height, and weight were measured and standard questionnaires administered. Age-standardized prevalence of smoking, diabetes, hypertension, dyslipidemia, and obesity in the European population were calculated. Furthermore, the coefficient of variation between component studies was determined for the prevalence of each risk factor. RESULTS In total, 28,887 participants were included. The most prevalent cardiovascular risk factors were high blood pressure (47% in men, 39% in women), total cholesterol ≥ 250 mg/dL (43% and 40%, respectively), obesity (29% and 29%, respectively), tobacco use (33% and 21%, respectively), and diabetes (16% and 11%, respectively). Total cholesterol ≥ 190 and ≥ 250 mg/dL were the respective minimum and maximum coefficients of variation (7%-24% in men, 7%-26% in women). Average concordance in lipid measurements between laboratories was excellent. CONCLUSIONS Prevalence of high blood pressure, dyslipidemia, obesity, tobacco use and diabetes is high. Little variation was observed between autonomous communities in the population aged 35-74 years. However, presence of the most prevalent cardiovascular risk factors in the Canary Islands, Extremadura and Andalusia was greater than the mean of the 11 studies.

Inflammatory and metabolic biomarkers and risk of liver and biliary tract cancer.

Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however, there are little data on the role of obesity‐related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intrahepatic bile duct (IBD), and gallbladder and biliary tract cancers outside of the liver (GBTC) in a nested case‐control study within the European Prospective Investigation into Cancer and Nutrition. Over an average of 7.7 years, 296 participants developed HCC (n = 125), GBTC (n = 137), or IBD (n = 34). Using risk‐set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, and time of blood collection. Baseline serum concentrations of C‐reactive protein (CRP), interleukin‐6 (IL‐6), C‐peptide, total high‐molecular‐weight (HMW) adiponectin, leptin, fetuin‐a, and glutamatdehydrogenase (GLDH) were measured, and incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection, and adiposity measures, higher concentrations of CRP, IL‐6, C‐peptide, and non‐HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95% CI = 1.02‐1.46; P = 0.03; 1.90; 95% CI = 1.30‐2.77; P = 0.001; 2.25; 95% CI = 1.43‐3.54; P = 0.0005; and 2.09; 95% CI = 1.19‐3.67; P = 0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95% CI = 1.05‐1.42; P = 0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95% CI = 1.25‐2.11; P = 0.0003) and IBD (IRR = 10.5; 95% CI = 2.20‐50.90; P = 0.003). The continuous net reclassification index was 0.63 for CRP, IL‐6, C‐peptide, and non‐HMW adiponectin and 0.46 for GLDH, indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors. (Hepatology 2014;60:858–871)

Common Genetic Variants Highlight the Role of Insulin Resistance and Body Fat Distribution in Type 2 Diabetes, Independent of Obesity

We aimed to validate genetic variants as instruments for insulin resistance and secretion, to characterize their association with intermediate phenotypes, and to investigate their role in type 2 diabetes (T2D) risk among normal-weight, overweight, and obese individuals. We investigated the association of genetic scores with euglycemic-hyperinsulinemic clamp– and oral glucose tolerance test–based measures of insulin resistance and secretion and a range of metabolic measures in up to 18,565 individuals. We also studied their association with T2D risk among normal-weight, overweight, and obese individuals in up to 8,124 incident T2D cases. The insulin resistance score was associated with lower insulin sensitivity measured by M/I value (β in SDs per allele [95% CI], −0.03 [−0.04, −0.01]; P = 0.004). This score was associated with lower BMI (−0.01 [−0.01, −0.0]; P = 0.02) and gluteofemoral fat mass (−0.03 [−0.05, −0.02; P = 1.4 × 10−6) and with higher alanine transaminase (0.02 [0.01, 0.03]; P = 0.002) and γ-glutamyl transferase (0.02 [0.01, 0.03]; P = 0.001). While the secretion score had a stronger association with T2D in leaner individuals (Pinteraction = 0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI or waist strata (Pinteraction > 0.31). While insulin resistance is often considered secondary to obesity, the association of the insulin resistance score with lower BMI and adiposity and with incident T2D even among individuals of normal weight highlights the role of insulin resistance and ectopic fat distribution in T2D, independently of body size.

Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis: The EPIC cohort

Objectives: The aim of this study was to investigate for the first time the association between body fat and risk of amyotrophic lateral sclerosis (ALS) with an appropriate prospective study design. Methods: The EPIC (European Prospective Investigation into Cancer and Nutrition) study included 518,108 individuals recruited from the general population across 10 Western European countries. At recruitment, information on lifestyle was collected and anthropometric characteristics were measured. Cox hazard models were fitted to investigate the associations between anthropometric measures and ALS mortality. Results: Two hundred twenty-two ALS deaths (79 men and 143 women) occurred during the follow-up period (mean follow-up = 13 years). There was a statistically significant interaction between categories of body mass index and sex regarding ALS risk (p = 0.009): in men, a significant linear decrease of risk per unit of body mass index was observed (hazard ratio = 0.93, 95% confidence interval 0.86–0.99 per kg/m2); among women, the risk was more than 3-fold increased for underweight compared with normal-weight women. Among women, a significant risk reduction increasing the waist/hip ratio was also evident: women in the top quartile had less than half the risk of ALS compared with those in the bottom quartile (hazard ratio = 0.48, 95% confidence interval 0.25–0.93) with a borderline significant p value for trend across quartiles (p = 0.056). Conclusion: Increased prediagnostic body fat is associated with a decreased risk of ALS mortality.

Síndrome metabólico en España: prevalencia y riesgo coronario asociado a la definición armonizada y a la propuesta por la OMS. Estudio DARIOS

INTRODUCTION AND OBJECTIVES To update the prevalence of metabolic syndrome and associated coronary risk in Spain, using the harmonized definition and the new World Health Organization proposal (metabolic premorbid syndrome), which excludes diabetes mellitus and cardiovascular disease. METHODS Individual data pooled analysis study of 24,670 individuals from 10 autonomous communities aged 35 to 74 years. Coronary risk was estimated using the REGICOR function. RESULTS Prevalence of metabolic syndrome was 31% (women 29% [95% confidence interval, 25%-33%], men 32% [95% confidence interval, 29%-35%]). High blood glucose (P=.019) and triglycerides (P<.001) were more frequent in men with metabolic syndrome, but abdominal obesity (P<.001) and low high-density lipoprotein cholesterol (P=.001) predominated in women. Individuals with metabolic syndrome showed moderate coronary risk (8% men, 5% women), although values were higher (P<.001) than in the population without the syndrome (4% men, 2% women). Women and men with metabolic syndrome had 2.5 and 2 times higher levels of coronary risk, respectively (P<.001). Prevalence of metabolic premorbid syndrome was 24% and the increase in coronary risk was also proportionately larger in women than in men (2 vs 1.5, respectively; P<.001). CONCLUSIONS Prevalence of metabolic syndrome is 31%; metabolic premorbid syndrome lowers this prevalence to 24% and delimits the population for primary prevention. The increase in coronary risk is proportionally larger in women, in both metabolic syndrome and metabolic premorbid syndrome.

Dietary Glycemic Index, Glycemic Load, and Digestible Carbohydrate Intake Are Not Associated with Risk of Type 2 Diabetes in Eight European Countries

The association of glycemic index (GI) and glycemic load (GL) with the risk of type 2 diabetes remains unclear. We investigated associations of dietary GI, GL, and digestible carbohydrate with incident type 2 diabetes. We performed a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition Study, including a random subcohort (n = 16,835) and incident type 2 diabetes cases (n = 12,403). The median follow-up time was 12 y. Baseline dietary intakes were assessed using country-specific dietary questionnaires. Country-specific HR were calculated and pooled using random effects meta-analysis. Dietary GI, GL, and digestible carbohydrate in the subcohort were (mean ± SD) 56 ± 4, 127 ± 23, and 226 ± 36 g/d, respectively. After adjustment for confounders, GI and GL were not associated with incident diabetes [HR highest vs. lowest quartile (HR(Q4)) for GI: 1.05 (95% CI = 0.96, 1.16); HR(Q4) for GL: 1.07 (95% CI = 0.95, 1.20)]. Digestible carbohydrate intake was not associated with incident diabetes [HR(Q4): 0.98 (95% CI = 0.86, 1.10)]. In additional analyses, we found that discrepancies in the GI value assignment to foods possibly explain differences in GI associations with diabetes within the same study population. In conclusion, an expansion of the GI tables and systematic GI value assignment to foods may be needed to improve the validity of GI values derived in such studies, after which GI associations may need reevaluation. Our study shows that digestible carbohydrate intake is not associated with diabetes risk and suggests that diabetes risk with high-GI and -GL diets may be more modest than initial studies suggested.

Prevalence of dementia and cognitive impairment in Southeastern Spain: the Ariadna study.

Objectives  –  To estimate the prevalence of amnestic mild cognitive impairment (aMCI), cognitive impairment, no dementia (CIND) and dementia in a general elderly population and to examine the associated socio‐demographic factors.

A Mendelian Randomization Study of Circulating Uric Acid and Type 2 Diabetes

We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid–associated loci. We used data of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries. During a mean (SD) follow-up of 10 (4) years, 10,576 verified incident case subjects with type 2 diabetes were ascertained. Higher uric acid was associated with a higher diabetes risk after adjustment for confounders, with a hazard ratio (HR) of 1.20 (95% CI 1.11, 1.30) per 59.48 µmol/L (1 mg/dL) uric acid. The genetic score raised uric acid by 17 µmol/L (95% CI 15, 18) per SD increase and explained 4% of uric acid variation. By using the genetic score to estimate the unconfounded effect, we found that a 59.48 µmol/L higher uric acid concentration did not have a causal effect on diabetes (HR 1.01 [95% CI 0.87, 1.16]). Including data from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, increasing our dataset to 41,508 case subjects with diabetes, the summary odds ratio estimate was 0.99 (95% CI 0.92, 1.06). In conclusion, our study does not support a causal effect of circulating uric acid on diabetes risk. Uric acid–lowering therapies may therefore not be beneficial in reducing diabetes risk.

Validity of self-reported prevalent cases of stroke and acute myocardial infarction in the Spanish cohort of the EPIC study

Background Information on the validity of self-reported cases of stroke and acute myocardial infarction (AMI) is varied. The aim of this study was to assess the validity and agreement of self-reported prevalent cases of stroke and AMI in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods At recruitment, 1992–1996, and in the follow-up (3 years after recruitment), each participant in the Spanish EPIC cohort (15 630 men and 25 808 women) was asked if a doctor had ever said that they had had a stroke or AMI, and the results were compared with information available in medical records. Validity of self-reported prevalent cases of stroke and AMI was examined by calculating sensitivity, specificity, positive predictive values and κ statistics. Results The sensitivity of self-reported prevalent cases of stroke was 81.3% and that for AMI was 97.7%. The positive predictive value was 22.2% and 60.7% for stroke and AMI, respectively, whereas specificity was very high (>99%) for both diseases. The agreement between self-report questionnaire results and medical records was substantial (κ=0.75) for AMI but not for stroke (κ=0.35). Conclusion Self-reported information on stroke and AMI included in the EPIC questionnaire is a valid instrument for the assessment of AMI disease but should be used with caution in stroke.

Magnetic Resonance Spectroscopy Performance for Detection of Dementia, Alzheimer’s Disease and Mild Cognitive Impairment in a Community-Based Survey

Background/Aims: To evaluate 1H-labelled magnetic resonance spectroscopy (MRS) in patients with a low Mini Mental State Examination (MMSE) score identified during a dementia community-based survey. Methods: A population sample of 1,500 individuals (>64 years old) was randomly selected. Two hundred and fifteen individuals (MMSE ≤24) were sorted into clinical groups: dementia, Alzheimer’s disease, mild cognitive impairment (MCI), normal. Up to 56 of these individuals attended the MRS appointment. Two single-voxel sequences (TR 1,500, TE 35/144 ms) were carried out in the posterior cingulate gyrus of each individual, and the ratios N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, myo-inositol (mI)/Cr, NAA/mI and NAA/Cho were compared statistically. The ability of MRS to distinguish clinical groups was assessed by receiver-operating characteristics analysis. Cognition effects on metabolite ratios were estimated, with gender and cognition as categorical variables and age as a continuous covariate. Results: NAA/Cr and NAA/Cho ratios were lower in dementia or Alzheimer’s disease than in MCI and normal groups. The NAA/Cr ratio at TE 35 ms performed best when distinguishing dementia or Alzheimer’s disease from non-demented subjects (cut-off point 1.40). MRS could not distinguish between MCI patients and normal subjects. Dementia was an independent predictor of metabolite values. Conclusion: In a population sample, conventional MRS still proved to be a useful tool for dementia discrimination, but it is potentially far less useful as a surrogate marker for MCI.