Daniel Fernández-Bergés

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.

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.

Tratamiento y control de los factores de riesgo según el riesgo coronario en la población española del estudio DARIOS

INTRODUCTION AND OBJECTIVES The treatment and control of cardiovascular risk factors both play key roles in primary prevention. The aim of the present study is to analyze the proportion of primary prevention patients aged 35-74 years being treated and controlled in relation to their level of coronary risk. METHODS Pooled analysis with individual data from 11 studies conducted in the first decade of the 21st century. We used standardized questionnaires and blood pressure measures, glycohemoglobin and lipid profiles. We defined optimal risk factor control as blood pressure < 140/90 mm Hg and glycohemoglobin <7%. In hypercholesterolemia, we applied both the European Societies and Health Prevention and Promotion Activities Programme criteria. RESULTS We enrolled 27 903 participants (54% women). Drug treatments were being administered to 68% of men and 73% of women with a history of hypertension (P<.001), 66% and 69% respectively, of patients with diabetes (P=.03), and 39% and 42% respectively, of those with hypercholesterolemia (P<.001). Control was good in 34% of men and 42% of women with hypertension (P<.001); 65% and 63% respectively, of those with diabetes (P=.626); 2% and 3% respectively, of patients with hypercholesterolemia according to European Societies criteria (P=.092) and 46% and 52% respectively, of those with hypercholesterolemia according to Health Prevention and Promotion Activities Programme criteria (P<.001). The proportion of uncontrolled participants increased with coronary risk (P<.001), except in men with diabetes. Lipid-lowering treatments were more often administered to women with ≥ 10% coronary risk than to men (59% vs. 50%, P = 0,024). [corrected] CONCLUSIONS The proportion of well-controlled participants was 65% at best. The European Societies criteria for hypercholesterolemia were vaguely reached. Lipid-lowering treatment is not prioritized in patients at high coronary risk.

Elevated serum neopterin levels and adverse cardiac events at 6 months follow-up in Mediterranean patients with non-ST-segment elevation acute coronary syndrome

BACKGROUND Little information exists regarding the prognostic role of biomarkers of inflammation in Mediterranean patients. High C-reactive protein and neopterin levels - a marker of macrophage activation - predict cardiovascular events in stable angina patients and patients with acute coronary syndromes (ACS). We sought to assess whether plasma neopterin levels predict adverse clinical outcomes in Mediterranean patients with non-ST elevation (NSTE) ACS, i.e. unstable angina (UA) and NSTE myocardial infarction (MI). METHODS We prospectively assessed 397 patients (74% men) admitted with NSTEACS, 147 (37%) had unstable angina and 250 (63%) NSTEMI. Blood samples for neopterin and CRP assessment were obtained at admission. The study endpoint was the composite of cardiac death, acute myocardial infarction and unstable angina at 180 days. RESULTS Baseline neopterin concentrations (nmol/L) were similar in unstable angina and NSTEMI patients (8.3 [6.6-10.7] vs. 7.9 [6.2-10.9]; p=0.4). Fifty-nine patients (14.9%) had events during follow-up. Twenty-nine (21.5%) patients with neopterin levels in the highest third experienced the combined endpoint, compared to 30 (11.5%) patients with neopterin levels in the second and the lowest thirds (log-rank 7.435, p=0.024). On multivariable hazard Cox regression, neopterin (highest vs. 1st and 2nd thirds, HR 1.762, 95% CI [1.023-3.036]) was independently associated with the combined endpoint. CONCLUSION Increased neopterin levels are an independent predictor of 180-day adverse cardiac events in Mediterranean patients with NSTEACS.

A comparative study of biomarkers for risk prediction in acute coronary syndrome—Results of the SIESTA (Systemic Inflammation Evaluation in non-ST-elevation Acute coronary syndrome) study

OBJECTIVE We compared the 1-year predictive value of several inflammatory and non-inflammatory biomarkers in ACS patients. METHODS In 610 patients (73.0% male)--36.0% unstable angina (UA) and 64.0% NSTEMI--we assessed high-sensitivity C-reactive protein (hs-CRP), interleukins 6, 10 and 18, soluble CD40 ligand, P- and E-selectin, NT-proBNP, fibrinogen and cystatin C at hospital admission. Two outcomes at 1-year follow up were selected for analysis: (1) all-cause death, MI, UA, or coronary revascularization, and (2) all-cause death, and non-fatal MI. The effect of biomarker levels on endpoints was examined by the Cox proportional hazards model, and their discrimination ability with the C statistic (AUC). RESULTS Of 549 patients (90.0%) who completed the 1-year follow up, 206 (37.5%) and 54 (8.9%) reached the first and second composite endpoints, respectively. None of the biomarkers studied improved prediction of the first endpoint. However, considered as continuous variables, and in combination, NT-proBNP and fibrinogen, increased the AUC from 0.64 (95% CI 0.55-0.72) to 0.73 (95% CI 0.64-0.81; p=0.02) for prediction of the second endpoint. Cut-off values for NT-proBNP and fibrinogen, regarding best sensitivity and specificity for prediction of the secondary endpoint were 1043.9 ng/L and 4.47 mg/dL, respectively. For these cut-off points, sensitivity, specificity, positive predictive value and negative predictive value were 40.5% vs 59.5%, 83.3% vs 67.1%, 18.8% vs 14.9% and 93.5% vs 94.4% for NT-proBNP and fibrinogen, respectively. CONCLUSION In ACS patients, inflammatory biomarkers offer modest incremental information to that provided by clinical risk markers. Fibrinogen and NT-proBNP measurements, however, improve cardiovascular risk prediction.

Marcadores de inflamación y estratificación de riesgo en pacientes con síndrome coronario agudo: diseño del estudio SIESTA (Systemic Inflammation Evaluation in patients with non-ST segment elevation Acute coronary syndromes)

Introduccion y objetivos A pesar de que se conoce el valor pronostico de varios marcadores de inflamacion en el sindrome coronario agudo sin elevacion del segmento ST (SCASEST), aun se ignora que subconjunto de estos proporciona mejor informacion y que grado de asociacion existe entre ellos. El objetivo del estudio SIESTA es establecer el valor pronostico de la proteina C reactiva, fibrinogeno, neopterina, interleucinas 6, 8, 10 y 18, factor de necrosis tumoral, e-selectina, endotelina 1, factor tisular, molecula de adhesion celular vascular-1 (VCAM-1) e intercelular-1 (ICAM-1), proteina plasmatica-A asociada al embarazo (PAPP-A), peptido natriuretico ventricular (tipo B), troponina I o T, leucocitos e isoforma MB de la creatinfosfocinasa (CK-MB), en pacientes con SCASEST. Pacientes y metodo SIESTA es un estudio prospectivo, multicentrico, que incluira a pacientes que hayan presentado dolor toracico sugestivo de sindrome coronario agudo en las ultimas 48 h y alguna de las siguientes condiciones: signos electrocardiograficos de isquemia miocardica, enfermedad vascular documentada o elevacion de la concentracion de troponinas. Se realizara un seguimiento clinico durante un ano, con determinaciones hematologicas y bioquimicas en el momento del ingreso, del alta, y a los 30, 180 y 365 dias. Se validaran las escalas TIMI (Thrombolysis In Myocardial Infarction) y PEPA (Proyecto de Estudio del Pronostico de la Angina). La variable principal estara compuesta de muerte por cualquier causa, muerte de origen cardiaco, infarto de miocardio no letal y angina inestable que requiera hospitalizacion o revascularizacion urgente. La evaluacion individual de cada una de las variables se considerara como objetivo secundario. Este estudio ofrecera valiosa informacion prospectiva acerca del valor pronostico de un importante numero de marcadores inflamatorios en pacientes de origen mediterraneo asistidos en la practica medica habitual.

Severity of obesity and cardiometabolic risk factors in adults: Sex differences and role of physical activity. The HERMEX study

BACKGROUND The aims of this study were 1) to examine potential sex-related differences in major cardiometabolic risk factors among severe/morbid obese (body mass index [BMI]≥35) individuals; 2) to assess whether severity of obesity is associated with more adverse cardiometabolic risk factors in women and men, and 3) to assess whether being physically active (≥500 metabolic equivalents [MET-minutes per week]) may play a role in the association between severity of obesity and the cardiometabolic risk profile. METHODS A total of 886 (438 men) obese individuals participated in a population-based cross-sectional study. We categorized participants as grade I (BMI 30-34.99) and grade II/III (BMI≥35) obese. We measured markers of lipid and glucose metabolism, inflammation (high sensitivity C-reactive protein [hs-CRP]) blood pressure and renal function, as well as self-reported physical activity. RESULTS Triglycerides, insulin, HOMA-IR, systolic blood pressure and creatinine levels were higher in severe/morbid obese men than women (all, P<0.05), while women presented higher HDL cholesterol and hs-CRP (P<0.05) than men. Severe/morbid obesity was associated with higher triglycerides, hs-CRP, insulin and insulin resistance, diastolic blood pressure and higher odds of hypertension than grade I obesity both in women and men (all, P<0.05). Severe/morbid obese individuals who were physically inactive presented the least favorable cardiometabolic profile (P<0.05). CONCLUSIONS Severe/morbid obesity is associated with more adverse cardiometabolic risk factors both in women and men. Severe/morbid obese men are more affected than women regarding their cardiometabolic profile, although women presented higher inflammation. Physically inactive individuals with severe/morbid obesity had the most adverse clustered cardiometabolic risk profile.

Metabolic and Inflammatory Profiles of Biomarkers in Obesity, Metabolic Syndrome, and Diabetes in a Mediterranean Population. DARIOS Inflammatory Study

INTRODUCTION AND OBJECTIVES There is a paucity of data regarding the differences in the biomarker profiles of patients with obesity, metabolic syndrome, and diabetes mellitus as compared to a healthy, normal weight population. We aimed to study the biomarker profile of the metabolic risk continuum defined by the transition from normal weight to obesity, metabolic syndrome, and diabetes mellitus. METHODS We performed a pooled analysis of data from 7 cross-sectional Spanish population-based surveys. An extensive panel comprising 20 biomarkers related to carbohydrate metabolism, lipids, inflammation, coagulation, oxidation, hemodynamics, and myocardial damage was analyzed. We employed age- and sex-adjusted multinomial logistic regression models for the identification of those biomarkers associated with the metabolic risk continuum phenotypes: obesity, metabolic syndrome, and diabetes mellitus. RESULTS A total of 2851 subjects were included for analyses. The mean age was 57.4 (8.8) years, 1269 were men (44.5%), and 464 participants were obese, 443 had metabolic syndrome, 473 had diabetes mellitus, and 1471 had a normal weight (healthy individuals). High-sensitivity C-reactive protein, apolipoprotein B100, leptin, and insulin were positively associated with at least one of the phenotypes of interest. Apolipoprotein A1 and adiponectin were negatively associated. CONCLUSIONS There are differences between the population with normal weight and that having metabolic syndrome or diabetes with respect to certain biomarkers related to the metabolic, inflammatory, and lipid profiles. The results of this study support the relevance of these mechanisms in the metabolic risk continuum. When metabolic syndrome and diabetes mellitus are compared, these differences are less marked.

Prevalence of abnormal urinary albumin excretion in a population‐based study in Spain: results from the HERMEX Study

Eur J Clin Invest 2012; 42 (12): 1272–1277

On the problem of type 2 diabetes-related mortality in the Canary Islands, Spain. The DARIOS Study

AIMS To compare diabetes-related mortality rates and factors associated with this disease in the Canary Islands compared with other 10 Spanish regions. METHODS In a cross-sectional study of 28,887 participants aged 35-74 years in Spain, data were obtained for diabetes, hypertension, dyslipidemia, obesity, insulin resistance (IR), and metabolic syndrome. Healthcare was measured as awareness, treatment and control of diabetes, dyslipidemia, and hypertension. Standardized mortality rate ratios (SRR) were calculated for the years 1981 to 2011 in the same regions. RESULTS Diabetes, obesity, and hypertension were more prevalent in people under the age of 64 in the Canary Islands than in Spain. For all ages, metabolic syndrome and insulin resistance (IR) were also more prevalent in those from the Canary Islands. Healthcare parameters were similar in those from the Canary Islands and the rest of Spain. Diabetes-related mortality in the Canary Islands was the highest in Spain since 1981; the maximum SRR was reached in 2011 in men (6.3 versus the region of Madrid; p<0.001) and women (9.5 versus Madrid; p<0.001). Excess mortality was prevalent from the age of 45 years and above. CONCLUSIONS Diabetes-related mortality is higher in the Canary Islands population than in any other Spanish region. The high mortality and prevalence of IR warrants investigation of the genetic background associated with a higher incidence and poor prognosis for diabetes in this population. The rise in SRR calls for a rapid public health policy response.