M.A. Sánchez-Chaparro

Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

BackgroundHypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information.MethodsA subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG ≥ 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption.ResultsWe found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-ε4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p < 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; p < 0.001) were associated with HTG.ConclusionOur results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the ε4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia.

Postprandial apolipoprotein B48 is associated with asymptomatic peripheral arterial disease: a study in patients with type 2 diabetes and controls.

BACKGROUND Postprandial hyperlipidemia is a common feature in type 2 diabetes; our aim was to investigate whether there is an association between subclinical peripheral arterial disease (PAD) and the levels of apolipoprotein B48, as a specific marker for postprandial lipidemia. METHODS We enrolled 101 patients with type 2 diabetes and 73 controls free from clinical cardiovascular disease. Main outcome measures were the presence of subclinical PAD, assessed by the ankle-brachial index, and the intestinal particles measured as the concentration of apolipoprotein B48 at fasting and 4h after a mixed breakfast. RESULTS No control had subclinical PAD. Of the 101 diabetic patients, 21 had subclinical PAD. The levels of apo B48, both fasting and postprandial, were only significantly raised in the diabetic patients who had PAD. The diabetic patients without vascular disease had similar concentrations of triglycerides and apo B48 to the controls. In binary logistic regression analyses, only smoking and postprandial B48 levels, in addition to diabetes, were independently associated with PAD. On the other hand, PAD but not diabetes was associated with the fasting and postprandial levels of apo B48. CONCLUSION Our study suggests that apolipoprotein B48 levels might be a marker of occult PAD in patients suffering from type 2 diabetes mellitus. Accordingly, subclinical PAD should be taken into account in studies on postprandial lipidemia involving patients with diabetes.

The relationship between job stress and dyslipidemia

Aims: To investigate whether there is an association between job stress, lipid profile and dyslipidemia diagnosis. Methods: This study used a questionnaire to evaluate job stress and lifestyle variables in 91,593 workers undergoing periodic checkups. Serum lipid levels were measured in all cases. Results: The prevalence of job stress was 8.7% (95% CI, 8.5–8.8%). In bivariate analyses, job stress was significantly associated with previous dyslipidemia diagnosis (p < 0.001), lipid-lowering therapy (p < 0.001), and altered total-cholesterol (p = 0.001), HDL-cholesterol (p < 0.001) and LDL-cholesterol levels (p = 0.025). After adjusting for potential confounding variables, job stress was still associated with current dyslipidemia diagnosis (OR = 1.10; 95% CI, 1.04–1.17), high LDL-cholesterol (OR = 1.14; 95% CI, 1.05–1.23), low HDL-cholesterol (OR 1.08; 95% CI, 1.01–1.15), high total cholesterol/HDL-cholesterol ratio (OR 1.13; 95% CI, 1.05–1.23) and high LDL-cholesterol/HDL-cholesterol ratio (OR 1.11; 95% CI, 1.04–1.19). Conclusion: These results support the hypothesis of an association between job stress and lipid disturbances.

Alta prevalencia de obesidad en una población laboral en España

BACKGROUND AND OBJECTIVES To report the prevalence of obesity in a Spanish working population and its changes in recent years. MATERIAL AND METHODS Data were collected from routine medical examinations performed on workers by a national mutual insurance society for occupational accidents and diseases (Ibermutuamur). A structured questionnaire was completed and physical examinations were performed. Overweight was defined as BMI ranging from 25 and 29.9, obesity as BMI of 30-39.9, and morbid obesity as BMI ≥ 40 kg/m(2). RESULTS Data from 1,336,055 medical examinations performed from May 2004 to November 2007 were collected. Prevalence rates in the population examined in 2004 (n=230,684; 73% males; average age, 36.4 years) were: morbid obesity, 0.5% (0.6% males, 0.5% females); obesity, 14.5% (17.0% males, 7.7% females); overweight, 38.4% (44.8% males, 21.3% females). Prevalence rates of obesity and overweight were higher in blue-collar workers (16.4% and 40.5% respectively) as compared to white-collar workers (10.9% and 34.4% respectively). There was a progressive increase in prevalence of obesity during the 4-year study (2004-2007) in both males (17.0%, 17.6%, 17.9%, 18.2%) and females (7.6%, 8.0%, 8.4%, 8.7%). CONCLUSIONS Prevalence of obesity and overweight in the Spanish working population is high, especially in male blue-collar workers, and is increasing. There is a need to promote early prevention programs and specific treatments for obesity.

Estimating the glomerular filtration rate in the Spanish working population: chronic kidney disease prevalence and its association with risk factors.

Objective: This study aims to investigate the influence of estimated glomerular filtration rate (eGFR) with two equations (and by one or two separate measurements), on the prevalence of chronic kidney disease (CKD) and its association with blood pressure, and cardiovascular and metabolic risk factors. Methods: Between January 2010 and October 2011, the Ibermutuamur CArdiovascular RIsk Assessment project included 128 588 workers (77.2% men, mean age 39.3 years, range 16–75), who underwent two consecutive yearly medical check-ups and had information for eGFR according to the MDRD-IDMS and CKD-EPI equations (serum creatinine was measured by a isotope-dilution mass spectrometry traceable method in a single central laboratory). CKD was defined by an eGFR less than 60 ml/min per 1.73 m2. Subclinical (occult) renal disease was defined as an eGFR less than 60 ml/min per 1.73 m2 in patients with serum creatinine below 1.3 mg/dl and below 1.2 mg/dl in men and women, respectively. Results: In this working population, prevalence of CKD was very low, but two to six times lower when two separate eGFRs below 60 ml/min per 1.73 m2 were used. The prevalence of CKD was significantly lower with the CKD-EPI compared to the MDRD-IDMS equation. The same applies to occult CKD. In male workers, occult CKD was practically nonexistent. Multivariate analyses show that blood pressure, total serum cholesterol, and serum glucose (positively), and high-density lipoprotein and low-density lipoprotein (negatively) were associated with CKD, with both equations. Another metabolic factor (waist circumference) was only associated (positively) with CKD defined by the CKD-EPI equation, which appears to be associated with most components of the metabolic syndrome. Conclusions: The CKD-EPI formula, calculated on the basis of two reported blood samples, may provide the most specific definition of CKD.

APPLICATION OF AN EXPERT SYSTEM TO IMPROVE CARDIOVASCULAR RISK IN THE WORKPLACE

Objective: The aim of this study was to design, develop and test an expert system to help professionals in clinical decision-making as providing an assessment of the health of workers at very high CVR. Design and method: lt was designed and developed an operational web-expert system in ASP Ianguage, which gathers information on risk factors and returns an output with recommendations for management of risk factors based on the 2012 European Guidelines on Cardiovascular Disease Prevention criteria. In the case of needing an intervention or modification of drug treatment, the expert system helps to plan them. The CVR was stratified by the European SCORE system for low-risk countries. A test was conducted with a pilot program providing workers with very high CVR (SCORE >  = 10). The adherence to the Mediterranean diet was assessed by a 14-item questionnaire and physical activity by the International Physical Activity Questionnaire (IPAQ). Results: This pilot study included 148 patients (mean age: 64.5 ± 8.3 years). All the participants were men, 73.6% and 55.2% had hypertension and dyslipidaemia, but only 50.7% and 34.3% of them were receiving anti-hypertensive treatment and lipid-lowering therapy at baseline, respectively. The participants were mostly manual workers (63.5%). 91.8% of them knew they had cardiovascular risk factors. 73.0% were smokers, of which 34.3% expressed their intention to give up smoking in the coming months. The mean BMI was 28.5 kg/m2 and the mean waist circumference was 100.5 cm. After 1-year follow-up, the percentage of patients who met the therapeutic objective for total cholesterol levels (<175 mg/dl) significantly increased (p = 0.03). The percentage of subjects with moderate-to-high adherence to the Mediterranean diet increased form 77.0% to 88.7% (p < 0.001). The percentage of subjects with sufficient-to-high physical activity also increased but not significantly (p = 0.547). Conclusions: Our preliminary results suggest that there is a high potential for improvement in Iifestyle and CVR control among patients at very high cardiovascular risk. The availability of an expert system could facilitate decision-making when providing medical advice. An expert system could be a value-added service in order to standardize health care and to promote the best clinical practice

PREDICTIVE PERFORMANCE AND CLINICAL UTILITY OF A NEW PREDICTIVE MODEL OF CARDIOVASCULAR RISK FOR YOUNG AND MIDDLE-AGED WORKING POPULATION

Objective: Identifying people at high cardiovascular risk is challenging, especially at young age. The main objective of the IberScore study was to derive a mathematical model for risk prediction of fatal and non-fatal cardiovascular events from a relatively young and healthy working population. Design and method: A predictive function for fatal and non-fatal CV events was derived from a cohort of 774,404 workers (70.4% of the target population), free of CV disease at entry, who were followed during 10 years. Workers ages ranged 16–65 years (mean 35.7, SD 10.7). 71.7% were men, which represented the real proportion in the target population. Cardiovascular ageing was estimated (independently by genders) based on the effects of well-known cardiovascular risk factors as: smoking; cholesterol; blood glucose; HDL; systolic blood pressure (SBP); obesity; history of dyslipidemia, diabetes and hypertension. Results: Along the 10-year follow-up we found 3,762 first cardiovascular events (6‰) in derivation cohort. Most of them (80.3%) were non-fatal ischemic events. We derived a logistic flexible parametric model to predict 10-year cardiovascular risk. 82% of those who suffered a cardiovascular event during the follow-up span had been previously classified as “high risk” or “very high risk” using our model, whereas only 12% of them were classified in the same groups using SCORE. The latter also showed a weak discrimination power for risk stratification while IberScore clearly distinguished the four risk categories. IberScore was well calibrated and showed outstanding predictive performance and clinical utility even at young and middle-age workers. Cut-off points were fixed taking on account their discriminatory capacity and the balance between costs and benefits of the treatments that will be prescribed based on them. Conclusions: IberScore worked much better to estimate cardiovascular risk in a relatively young and healthy Spanish working population when compared to other models. Cardiovascular aging, as the result of the effects of risk factors, should be at the core of CV risk estimation. Cut-off points should be set considering the benefit we seek with the treatments we have in mind.

[PP.LB03.08] APPLICATION OF AN EXPERT SYSTEM TO IMPROVE CARDIOVASCULAR RISK IN THE WORKPLACE

Objective: The aim of this study was to design, develop and test an expert system to help professionals in clinical decision-making as providing an assessment of the health of workers at very high CVR. Design and method: It was designed and developed an operational web expert system in ASP language, which gathers information on risk factors and returns an output with recommendations for management of risk factors based on the 2012 criteria of the European Guidelines on Cardiovascular Disease Prevention. In the case of needing an intervention or modification of drug treatment, the expert system helps to plan them. The CVR was stratified by the European SCORE system for low-risk countries. A test was conducted with a pilot program providing workers with very high CVR (SCORE >=10). The adherence to the Mediterranean diet was assessed by a 14-item questionnaire and physical activity by the International Physical Activity Questionnaire (IPAQ). Results: This pilot study included 11 patients with a mean age of 63.2 years (± 4.2). All the participants were men, 71.7% and 45.5% had hypertension and dyslipidaemia, but only 36.4% and 18.2% of them were receiving anti-hypertensive treatment and lipid-lowering therapy at baseline, respectively. These patients, mostly manual workers (63.6%), showed a high level of adherence to the Mediterranean diet in 27.3% of the cases, and moderate over the remaining 72.7%. 81.8% knew they had cardiovascular risk factors. 45.5% were smokers, of which 66.6% expressed their intention to give up smoking in the coming months. The mean BMI was 28.1 kg/m2 and the mean waist circumference was 99.36 cm. A 36.4% of the workers reported being physically very active in the 7 days prior to the follow-up assessment (36.4% sufficiently active and 27.2% insufficiently active). Conclusions: Our preliminary results suggest that there is a high potential for improvement in lifestyle and CVR control among patients at very high cardiovascular risk. The availability of an expert system could facilitate decision-making when providing medical advice. An expert system could be a value-added service in order to standardize health care and to promote the best clinical practice.