Carlos Lahoz

Association of Cholesteryl Ester Transfer Protein–TaqIB Polymorphism With Variations in Lipoprotein Subclasses and Coronary Heart Disease Risk : The Framingham Study

Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides and cholesteryl esters between lipoprotein particles, a key step in reverse cholesterol transport in humans. Variations at the CETP locus have been shown to be determinants of the levels and activity of CETP and high density lipoprotein (HDL) plasma concentration. The associations of the common CETP polymorphism, TaqIB in intron 1, with lipoprotein levels and particle size distribution, CETP activity, and coronary heart disease (CHD) risk were examined in a population-based sample of 1411 men and 1505 women from the Framingham Offspring Study. The B2 allele frequency was 0.444 in men and 0.433 in women, and its presence was significantly (P<0.05) associated with decreased CETP activity. B1B1 men had lower HDL cholesterol (HDL-C) levels (1.07 mmol/L) compared with B1B2 (1.14 mmol/L) and B2B2 (1.18 mmol/L) men (P<0.001). Likewise, B1B1 women had lower HDL-C levels (1.40 mmol/L) compared with B1B2 (1.46 mmol/L) and B2B2 (1.53 mmol/L) women (P<0.001). In men, the B2 allele was associated with increased particle size for HDL and low density lipoprotein. In women, a similar effect was demonstrated only for HDL particle size. The odds ratio for prevalent CHD associated with the B2 allele was 0.696 (P=0.035) in men. After adjusting for age, body mass index, systolic blood pressure, diabetes, smoking, alcohol consumption, beta-blocker use, total cholesterol, and HDL-C, this odds ratio was 0.735 (P=0.187), suggesting that the protective effect of the B2 allele was due in part to its association with HDL-C levels. No significant protective effects were observed in women. These data demonstrate that variation at the CETP gene locus is a significant determinant of HDL-C levels, CETP activity, and lipoprotein size in this population. Moreover, these effects appear to translate into a lower CHD risk among those men with the B2 allele.

A Short Screener Is Valid for Assessing Mediterranean Diet Adherence among Older Spanish Men and Women

Ensuring the accuracy of dietary assessment instruments is paramount for interpreting diet-disease relationships. The present study assessed the relative and construct validity of the 14-point Mediterranean Diet Adherence Screener (MEDAS) used in the Prevención con Dieta Mediterránea (PREDIMED) study, a primary prevention nutrition-intervention trial. A validated FFQ and the MEDAS were administered to 7146 participants of the PREDIMED study. The MEDAS-derived PREDIMED score correlated significantly with the corresponding FFQ PREDIMED score (r = 0.52; intraclass correlation coefficient = 0.51) and in the anticipated directions with the dietary intakes reported on the FFQ. Using Bland Altmans analysis, the average MEDAS Mediterranean diet score estimate was 105% of the FFQ PREDIMED score estimate. Limits of agreement ranged between 57 and 153%. Multiple linear regression analyses revealed that a higher PREDIMED score related directly (P < 0.001) to HDL-cholesterol (HDL-C) and inversely (P < 0.038) to BMI, waist circumference, TG, the TG:HDL-C ratio, fasting glucose, and the cholesterol:HDL-C ratio. The 10-y estimated coronary artery disease risk decreased as the PREDIMED score increased (P < 0.001). The MEDAS is a valid instrument for rapid estimation of adherence to the Mediterranean diet and may be useful in clinical practice.

Apolipoprotein E genotype and cardiovascular disease in the Framingham Heart Study

BACKGROUND Apolipoprotein (apo) E is a constituent of lipoproteins with considerable variation due to cysteine-arginine exchanges. The apo E4 (Arg112-Cys) polymorphism has been associated with dementia and hypercholesterolemia. We investigated the relation of APOE genotype to cardiovascular disease (CVD) in the Framingham Offspring Study. METHODS AND RESULTS DNA was isolated from 3413 study participants and APOE genotypes were determined utilizing the polymerase chain reaction and restriction isotyping. In the entire group of subjects, 20.7% had apo E4/4 or E3/4 (Group E4); 14.1% had apo E2/2 or E2/3 (Group E2) and 63.9% had the apo E3/3 genotype (Group E3). Subjects with E2/4 (1.3%) were excluded. Period prevalence of CVD between examinations 1 and 5 (1971-1994) (366 events) was related to APOE genotype. Age adjusted period prevalence of CVD in men was 18.6% for Group E4, 18.2% for Group E2 and 12.7% for Group E3 (P=0.004); while in women these rates were 9.9, 4.9, and 6.6%, respectively (P=0.037). After adjustment for non-lipid risk factors the relative odds for CVD in Group E2 men was 1.79 (P=0.0098) and in Group E4 it was 1.63 (P=0.0086) compared with the Group E3; while in Group E4 women it was 1.56 (P=0.054). After adjustment for all CVD risk factors, the relative odds in Group E2 men was 1.94 (P=0.004) and in Group E4 men it was 1.51 (P=0.0262). CONCLUSIONS The presence of the apo E2 or apo E4 alleles in men is associated with significantly greater CVD risk. This genotypic information may help to identify individuals at increased risk for CVD events.

Components of the mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease

Objective:To evaluate associations between components of the Mediterranean diet and circulating markers of inflammation in a large cohort of asymptomatic subjects at high risk for cardiovascular disease.Subjects/Methods:A total of 339 men and 433 women aged between 55 and 80 years at high cardiovascular risk because of presence of diabetes or at least three classical cardiovascular risk factors, food consumption was determined by a semi-quantitative food frequency questionnaire. Serum concentrations of high-sensitivity C-reactive protein (CRP) were measured by immunonephelometry and those of interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by enzyme-linked immunosorbent assay.Results:After adjusting for age, gender, body mass index, diabetes, smoking, use of statins, non-steroidal antiinflammatory drugs and aspirin, a higher consumption of fruits and cereals was associated with lower concentrations of IL-6 (P for trend 0.005;both). Subjects with the highest consumption of nuts and virgin olive oil showed the lowest concentrations of VCAM-1, ICAM-1, IL-6 and CRP; albeit only for ICAM-1 was this difference statistically significant in the case of nuts (for trend 0.003) and for VCAM-1 in the case of virgin olive oil (P for trend 0.02). Participants with higher adherence to the Mediterranean-type diet did not show significantly lower concentrations of inflammatory markers (P<0.1 for VCAM-1 and ICAM-1).Conclusions:The consumption of some typical Mediterranean foods (fruits, cereals, virgin olive oil and nuts) was associated with lower serum concentrations of inflammatory markers especially those related to endothelial function, in subjects with high cardiovascular risk living in a Mediterranean country.

Association of the C−514T Polymorphism in the Hepatic Lipase Gene With Variations in Lipoprotein Subclass Profiles The Framingham Offspring Study

Hepatic lipase is involved in the metabolism of several lipoproteins and has a key role in reverse cholesterol transport. A common C-to-T substitution at position -514 of the hepatic lipase promoter has been associated with variations in plasma high density lipoprotein cholesterol (HDL-C) levels and hepatic lipase activity. The aim of the current study was to investigate the association of this polymorphism to lipoprotein levels in a population-based sample of 1314 male and 1353 female Framingham Offspring Study participants. In men and women, carriers of the -514T allele had higher HDL-C and apolipoprotein A-I (apoAI) concentrations compared with noncarriers. The higher HDL-C levels associated with the -514T allele was due to an increase in the HDL(2)-C subfraction, and this association was stronger in women compared with men (P=0.0043 versus 0.0517). To gain further understanding about the metabolic basis of these effects, HDL and low density lipoprotein (LDL) subclass profiles were measured by using automated nuclear magnetic resonance spectroscopy and gradient gel electrophoresis, respectively. The association of the -514T allele with higher HDL-C levels seen in men and women was primarily due to significant increases in the large HDL subfractions (size range 8.8 to 13.0 nm). In contrast, there was no relationship between the hepatic lipase polymorphism at position -514 and the LDL particle size distribution after adjustment for familial relationships, age, body mass index, smoking, alcohol intake, use of beta-blockers, apoE genotype, and menopausal status and estrogen therapy in women. Moreover, multiple regression analyses suggested that the C-514T polymorphism contributed significantly to the variability of HDL particle size in men and women (P<0.04). Thus, our results show that the C-514T polymorphism in the hepatic lipase gene is associated with significant variations in the lipoprotein profile in men and women.

Effects of dietary fibre intake on risk factors for cardiovascular disease in subjects at high risk

Background: Epidemiological studies and feeding trials with supplements suggest that fibre intake is associated with a reduction in cardiovascular risk. However, the effects of changes in dietary fibre on risk factor levels have not been evaluated in free-living individuals. Thus, the effects of changes in dietary fibre intake on cardiovascular risk factors were assessed over 3 months in free-living high-risk subjects. Methods: 772 high-risk subjects (age 69±5 years) were assigned to a low-fat diet or two Mediterranean-style diets. All participants received behavioural and nutritional education, including recommendations for increasing the consumption of vegetables, fruits, and legumes. Changes in food and nutrient intake, body weight, blood pressure, lipid profiles, glucose control and inflammatory markers were evaluated. Results: Most participants increased consumption of vegetable products, but the increase in dietary fibre exhibited wide between-subject variability (6–65 g/day). Body weight, waist circumference, and mean systolic and diastolic blood pressure decreased across quintiles of fibre intake (p<0.005; all). Reductions in fasting glucose and total cholesterol levels, and increments in HDL cholesterol were highest among participants in the upper 20% of fibre intake (p = 0.04 and 0.02 respectively). Plasma concentrations of C-reactive protein, but not those of inflammatory cytokines, decreased in parallel with increasing dietary fibre (p = 0.04). Significant reductions in LDL cholesterol were observed only among participants with the greatest increases in soluble fibre intake (p = 0.04). Conclusions: Increasing dietary fibre intake with natural foods is associated with reductions in classical and novel cardiovascular risk factors in a high-risk cohort.

Effects of a Mediterranean-Style Diet on Cardiovascular Risk Factors

The authors assigned 772 participants to a low-fat diet or to 1 of 2 Mediterranean diets that emphasized consumption of either olive oil or nuts. They then measured changes in body weight, blood pr...

La aplicación de las tablas del SCORE a varones de edad avanzada triplica el número de sujetos clasificados de alto riesgo en comparación con la función de Framingham

Fundamento y objetivo La funcion de Framingham, recomendada por el National Cholesterol Education Program en su documento Adult Treatment Panel III (ATP-III) y las tablas de riesgo del Systematic Coronary Risk Evaluation (SCORE) son las funciones mas utilizadas para la estratificacion del riesgo cardiovascular, y ambas recomiendan intensificar las medidas higienicas y terapeuticas en las personas que presenten un riesgo alto. El objetivo del presente estudio fue comparar la estratificacion del riesgo obtenida con ambas clasificaciones en una poblacion de sujetos mayores de 60 anos. Sujetos y metodo Se incluyo en el estudio a 1.001 personas no diabeticas de entre de 60 y 79 anos (media de 69 anos, un 67%, mujeres) sin evidencia de enfermedad vascular. Se clasifico a los participantes segun su riesgo fuera bajo, medio o alto de acuerdo con el ATP-III ( 20% de riesgo a los 10 anos, respectivamente) y el SCORE ( Resultados Un 11,7% de la poblacion se considero de riesgo alto segun la ecuacion de Framingham, frente a un 17,6% segun el SCORE. Unicamente un 5% de las mujeres fueron clasificadas de riesgo alto con cualquiera de las funciones, frente a un 16,7 y un 44,4% de los varones segun las tablas de Framingham y de SCORE, respectivamente. Los resultados fueron similares al dividir por grupos de edad. De acuerdo con las guias del SCORE, un 39% de los varones y un 20% de las mujeres eran candidatos a recibir tratamiento hipolipemiante. Conclusiones En comparacion con la funcion de Framingham, la aplicacion del SCORE en varones mayores de 60 anos triplica el numero de sujetos de alto riesgo candidatos a medidas de prevencion energicas.

Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation

Previous studies have shown that the A to G transition occurring at position -75 bp upstream of the transcriptional start site in the human apolipoprotein A-I gene may affect plasma high density lipoprotein cholesterol (HDL-C) levels and low density lipoprotein cholesterol (LDL-C) response to changes in amount of dietary fat. We have examined the response to dietary fat saturation as a function of this mutation in 50 men and women. Subjects were first fed a saturated (SAT) fat diet (35% fat, 17% SAT) for 28 days, followed by a diet rich in monounsaturated fatty (MUFA) acids (35% fat, 22% MUFA) for 35 days and a diet rich in polyunsaturated (PUFA) fat (35% fat, 13% PUFA) for 35 days. All meals were prepared and consumed at the study sites. Lipoproteins were measured at the end of each diet period. The allele frequency for the A allele was 0.13. Subjects carrying the A allele had higher plasma cholesterol, LDL-C and triglyceride levels than those homozygotes for the G allele. As compared to the SAT diet, a PUFA diet induced significantly greater plasma total (P = 0.003) and LDL-C decreases (P = 0.001) in G/A women (-1.62 and -1.32 mmol/l, respectively) than in G/G subjects (-0.87 and -0.74 mmol/l for plasma and LDL-C, respectively). Multiple regression analysis demonstrated that in women, the variability in LDL-C response from a diet rich in SAT fat to a diet rich in PUFA was primarily due to LDL-C levels (during the SAT phase), accounting for 55.1% of the variance, waist to hip ratio (W/H; 11.4%) and the G/A polymorphism (10%). Whereas in men the major determinant of this response was smoking (21.4%). In conclusion, the G/A polymorphism appears to have a small but significant effect on plasma LDL-C responsiveness to changes in dietary fat saturation specially in women.

Effects of dietary fat saturation on eicosanoid production, platelet aggregation and blood pressure

The effects of dietary fat saturation on eicosanoid urinary excretion, platelet aggregation (PA) and blood pressure (BP) were studied in 42 healthy subjects. They consumed four consecutive diets differing in their fat saturation [saturated (SFA); monounsaturated (MUFA); polyunsaturated n‐6 (PUFA n‐6); and polyunsaturated n‐6/n‐3, (PUFA n‐3)]. Each diet period lasted 5 weeks. There were no differences in 24‐h 2,3‐dinor‐6‐keto‐prostaglandin F1α excretion among dietary periods. A significant effect was noted regarding the excretion of 11‐dehydro‐thromboxane B2 (P < 0.0001). During the PUFA n‐6 phase the excretion was significantly higher than during SFA and MUFA periods. Dietary fatty acid composition had a significant effect on ADP (1 μmol L−1) and collagen (2 mg L−1) induced PA. Dietary fat also had a significant effect on systolic and diastolic blood pressure (P < 0.0001). Both were significantly higher during the SFA period than during the other three periods. Our findings suggest that changes in dietary fatty acids may have mild, but significant, effects on eicosanoid production, platelet aggregation and blood pressure.