Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort.

Phytosterol intake with natural foods, a measure of healthy dietary choices, increases plasma levels, but increased plasma phytosterols are believed to be a coronary heart disease (CHD) risk factor. To address this paradox, we evaluated baseline risk factors, phytosterol intake, and plasma noncholesterol sterol levels in participants of a case control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort who developed CHD (n = 299) and matched controls (n = 584) who remained free of CHD after a 10 year follow-up. Sitosterol-to-cholesterol ratios increased across tertiles of phytosterol intake (P = 0.026). HDL-cholesterol level increased, and adiposity measures, cholesterol/HDL ratios, and levels of glucose, triglycerides, and lathosterol, a cholesterol synthesis marker, decreased across plasma sitosterol tertiles (P < 0.02; all). Compared with controls, cases had nonsignificantly lower median levels of phytosterol intake and plasma sitosterol. The multivariable-adjusted odds ratio for CHD across the lowest to highest plasma sitosterol tertile was 0.59 (95% confidence interval, 0.36-0.97). Associations were weaker for plasma campesterol. The apolipoprotein E genotype was unrelated to CHD risk or plasma phytosterols. The data suggest that plasma sitosterol levels are associated with a lower CHD risk while being markers of a lower cardiometabolic risk in the EPIC-Spain cohort, a population with a high phytosterol intake.

Qualitative assessment of previous evidence and an updated meta-analysis confirms lack of association between the ESR1 rs2234693 (PvuII) variant and coronary heart disease in men and women.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of mortality worldwide. CHD clusters in families but this familial aggregation remains largely unexplained. ESR1 is a candidate gene for CHD although recent meta-analyses of the rs2234693 variant reported inconsistent evidence for association with myocardial infarction (MI) in men. The objectives of this study were to perform a qualitative and a quantitative assessment of all evidence to date regarding this association. METHODS: We performed structured literature searches for studies addressing the association between the ESR1 rs2234693 and CHD. We assessed the quality of these studies collectively and individually according to recently published guidelines on the reporting and interpretation of genetic association studies. We also performed a meta-analysis of all studies to date, including a sample of MI cases and controls from our region. RESULTS: The qualitative assessment indicated that many studies met a low proportion of the criteria proposed by the current guidelines. No significant association between ESR1 rs2234693 and MI was observed in our sample or in the meta-analysis (16 studies; N approximately 32,000; OR approximately 1). Strong between-study heterogeneity was largely explained by a quality score based on the quality criteria. Studies that reported significant associations were generally of poorer quality. CONCLUSION: We confirm the lack of association between the ESR1 rs223469 and CHD, and show that inconsistencies between previous studies is explained by differences in their quality.

Fitoesteroles plasmáticos: marcadores de una dieta saludable y un riesgo cardiometabólico menor en la población española del estudio EPIC / Plasma phytosterols: markers of a healthy diet and a lower cardiometabolic risk in the Spanish EPIC population study

Introducción. Las concentraciones elevadas de fitoesteroles plasmáticos, que reflejan una mayor absorción intestinal de colesterol se han relacionado con un aumento del riesgo cardiovascular. Sin embargo, una situación de riesgo alto, el síndrome metabólico (SM), se asocia a un aumento de la síntesis y una disminución de la absorción de colesterol y, por tanto, a una menor fitoesterolemia. En este estudio hemos investigado la relación entre los fitoesteroles del plasma y la dieta y la presencia de factores de riesgo cardiovascular, incluidos los componentes del SM. Métodos y resultados. En un estudio transversal, se evaluaron la ingesta de fitoesteroles y concentraciones plasmáticas de esteroles nocolesterol ajustadas por colesterol en 592 individuos sanos de la cohorte española del estudio EPIC (European Prospective Investigation into Cancer and Nutrition) fenotipados para factores de riesgo cardiovascular, incluidas las variables del SM. La ingesta de fitoesteroles, que se asoció a alimentos saludables, y el colesterol unido a lipoproteínas de alta densidad (HDL) aumentaron, y las medidas de adiposidad, cociente colesterol/ HDL y concentraciones de glucosa, triglicéridos y latosterol, un precursor del colesterol, disminuyeron con los terciles de sitosterol plasmático ajustado por colesterol (p < 0,05; todos). Los resultados para latosterol fueron opuestos a los de sitosterol. El genotipo de la apolipoproteína E no se relacionó con los terciles de esteroles no-colesterol del plasma. Las odds ratio (OR) ajustadas de ser portador de un SM o sus componentes para el tercil superior de sitosterol plasmático comparado con el inferior oscilaron entre 0,23 y 0,42 (p < 0,05; todas). Las OR de las mismas variables para los terciles respectivos de latosterol variaron entre 1,99 y 3,00 (p < 0,05; todas) (..) (AU)

Introduction. Increased plasma phytosterols, which reflect increased cholesterol absorption, have been related to an increased cardiovascular risk. However, the metabolic syndrome (MetS), a cluster of risk factors that carries a high risk for cardiovascular diseases, has been associated with increased cholesterol synthesis and reduced cholesterol absorption, which translate into lower plasma phytosterol levels. In this study we investigated the relationships between plasma and dietary phytosterols and cardiovascular risk factors, including the components of MetS. Methods and results. In a cross-sectional study, we measured phytosterol intake and cholesterol-adjusted plasma non-cholesterol sterol levels in 592 healthy subjects of the Spanish EPIC (European Prospective Investigation into Cancer and Nutrition) cohort who were phenotyped for cardiovascular risk factors, including MetS constituents. Phytosterol intake, which reflects healthy food choices, and the HDL-cholesterol level increased and adiposity measures, cholesterol/HDL ratios, and glucose levels, triglycerides and lathosterol, a cholesterol synthesis marker, decreased across tertiles of plasma sitosterol-to-cholesterol ratios (P<0.05; all). Results were inverse for plasma lathosterol. The ApoE genotype was unrelated to plasma non-cholesterol sterol tertiles. The multivariable-adjusted odds ratios (OR) for the MetS and its components across the lowest to the highest plasma sitosterol tertile ranged between 0.23 and 0.42 (P<0.05; all). The OR for the same variables across respective lathosterol tertiles ranged between 1.99 and 3.00 (P<0.05; all). Conclusions. The MetS is associated with increased plasma lathosterol, a cholesterol synthesis marker, and decreased plasma sitosterol, a joint marker of cholesterol absorption and a healthy diet. Thus, elevated plasma phytosterol concentrations are related to a lower cardiometabolic risk (AU)

Serum sterol responses to increasing plant sterol intake from natural foods in the Mediterranean diet.

BACKGROUND: Phytosterols in natural foods are thought to inhibit cholesterol absorption. The Mediterranean diet is rich in phytosterol-containing plant foods. AIM OF THE STUDY: To assess whether increasing phytosterol intake from natural foods was associated with a cholesterol-lowering effect in a substudy of a randomized trial of nutritional intervention with Mediterranean diets for primary cardiovascular prevention (PREDIMED study). METHODS: One hundred and six high cardiovascular risk subjects assigned to two Mediterranean diets supplemented with virgin olive oil (VOO) or nuts, which are phytosterol-rich foods, or advice on a low-fat diet. Outcomes were 1-year changes in nutrient intake and serum levels of lipids and non-cholesterol sterols. RESULTS: Average phytosterol intake increased by 76, 158 and 15 mg/day in participants assigned VOO, nuts and low-fat diets, respectively. Compared to participants in the low-fat diet group, changes in outcome variables were observed only in those in the Mediterranean diet with nuts group, with increases in intake of fibre, polyunsaturated fatty acids and phytosterols (P < 0.020, all) and significant (P < 0.05) reductions of LDL-cholesterol (0.27 mmol/l or 8.3%) and the LDL/HDL-cholesterol ratio (0.29 mmol/l or 11.5%). Variations in saturated fat, cholesterol or fibre intake were unrelated to LDL-cholesterol changes. In the whole group, changes in serum sitosterol-to-cholesterol, which reflect those of dietary phytosterol intake and absorption, correlated inversely to LDL-cholesterol changes (r = -0.256; P = 0.008). In multivariate analyses, baseline LDL-cholesterol, increases in serum sitosterol ratios and statin use were independently associated with LDL-cholesterol reductions. CONCLUSIONS: Small amounts of phytosterols in natural foods appear to be bioactive in cholesterol lowering.

Plant sterol intake and education level in the Spanish EPIC cohort.

OBJECTIVE: A cross-sectional study was conducted in the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to investigate the association among education level, as a measurement of socioeconomic position, gender, and dietary nutrient intake, focusing on plant sterols, in a Mediterranean population. METHODS: A sample of 25 615 women and 15 552 men (29-69 y old) from the Spanish EPIC cohort was recruited in 1992-1996. Nutrient and plant sterol intakes were estimated using a validated dietary history questionnaire and Spanish food composition tables. RESULTS AND CONCLUSION: Few differences in nutrient or plant sterol consumption existed between men and women with different education levels. Age and energy-adjusted linear regression models of plant sterol intake showed a small increase in subjects with lower education and higher consumption in men than in women. Homogeneity of healthy dietary habits across different socioeconomic groups in this population reflects a wide availability of characteristic Mediterranean foods at the time of recruitment. However, current changes in food supply and the increasing cost of healthy foods may lead to socioeconomic inequalities in Spain parallel to those taking place in other European populations.

Relationship of classical and non-classical risk factors with genetic variants relevant to coronary heart disease.

BACKGROUND: In addition to the well established cardiovascular risk factors, evidence suggests a possible role of genetic and non-classical risk factors in the development and progression of atherothrombosis. We aimed to determine the relationship of classical and non-classical cardiovascular risk factors with candidate gene polymorphisms potentially involved in cardiovascular risk in the general Mediterranean population. DESIGN: Cross-sectional study. METHODS: We have determined the prevalence of classical (lipid profile, blood pressure, glycaemia, diabetes, smoking, body mass index, menopause and family history of coronary heart disease) and non-classical cardiovascular risk factors (infectious processes, homocysteinaemia, oxidative status, C-reactive protein, lipoprotein (a) and fibrinogen) in a population-based study. We analysed the relationship of these risk factors with the following five gene polymorphisms potentially involved in cardiovascular risk: ATP-binding cassette transporter A1-R219K, Peroxisome proliferator-activated receptor (PPAR)-alpha-L162V, Lipoprotein lipase (LPL)-HindIII, Paraoxonase (PON)1-Q192R, and Tumour necrosis factor (TNF)-alpha-G-308A. RESULTS: We found PPAR-alpha-V and LPL-H alleles to be associated with decreased high-density lipoprotein-cholesterol (HDL-c) concentration and with increased total cholesterol : HDL-c and triglyceride : HDL-c ratios. Regarding the non-classical risk factors, C-reactive protein concentration was higher for the PPAR-alpha-V allele. A higher oxidative status was shown in homozygotes for LPL-H and TNF-alpha-G alleles, although the latter also had lower homocysteinaemia. CONCLUSIONS: Three of the genetic variants analysed, PPAR-alpha-L162V, LPL-HindIII, and TNF-alpha-G-308A, were associated with non-classical risk factors, specifically lipid profile, inflammation, and oxidative status.

Circulating oxidized LDL is associated with increased waist circumference independent of body mass index in men and women.

BACKGROUND: Obesity is associated with oxidative stress, and the oxidation of LDL is thought to play a crucial role in the generation of atherosclerotic lesions. OBJECTIVE: The objective was to describe the association of waist circumference (WC) and body mass index (BMI; in kg/m2) with plasma circulating oxidized LDL (ox-LDL) and C-reactive protein (CRP). DESIGN: This cross-sectional study included data for circulating ox-LDL and CRP from a subpopulation of 586 men and women enrolled in a population-based survey conducted in 2000 in Girona, Spain. Multivariate analysis was performed to describe the independent association of WC and BMI with ox-LDL and CRP. RESULTS: Multivariate logistic regression analysis adjusted for lifestyle, educational level, and dietary confounders showed a direct association of WC (quartile distribution) and BMI categories with ox-LDL (P for linear trend = 0.002) and CRP (P for linear trend = 0.004). Subjects in the top quartile of WC and with a BMI > 29.9 were at high risk of elevated circulating concentrations of ox-LDL and CRP. Further adjustment for cardiovascular disease risk factors did not substantially modify these associations. The risk of high ox-LDL concentrations in overweight (BMI = 25.0-29.9) or obese (BMI > or = 30) subjects with a WC < 102 cm (men) or < 88 cm (women) was not significantly different from that in normal-weight subjects with these WCs. In contrast, overweight or obese subjects with higher WCs (WC > or = 102 cm for men and > or = 88 cm for women) were at significantly higher risk of increased ox-LDL. CONCLUSION: High WC was associated with high concentrations of ox-LDL independently of BMI in the study population.