Utilidad clínica de la hormona antimülleriana en la predicción de la edad ovárica en España / Clinical use of antimüllerian hormone to predict ovarian age in Spain

Objetivo: la hormona antimülleriana es un marcador clínico de la reserva ovárica pero no disponemos de sus valores de referencia en la población española. Se han determinado sus valores de normalidad en relación a la edad en una amplia muestra de población española. Sujetos y métodos: se estudiaron 10.443 mujeres (edad 20-45 años). Todas las determinaciones séricas de hormona antimülleriana se realizaron mediante un test de ELISA (hormona antimülleriana Gen II ELISA assay; Beckman Coulter, Brea, CA, USA). Resultados: la edad media fue 36,6 ± 4,3 años. Los niveles de la hormona antimülleriana se correlacionaron inversamente con la edad (r = −0,35; p < 0,001). La edad ovárica aumentaba 1 año por cada descenso medio de 0,2 ng/ml de hormona antimülleriana. Se obtuvieron diferencias significativas en los valores de hormona antimülleriana entre Cataluña, Baleares y Andalucía. Conclusiones: este estudio ofrece estimaciones de los valores de referencia de hormona antimülleriana en función de la edad y contribuye a determinar con mayor precisión la reserva ovárica de las mujeres españolas (AU)

Objetives: Antimüllerian hormone is considered clinically useful in the evaluation of ovarian reserve, and few data exists regarding its distribution in the Spanish population. We determine normality values of antimüllerian hormone related to age in a large Spanish community cohort. Subjects and methods: We study 10,443 women (aged 20-45). Antimüllerian hormone values were analysed using an ELISA assay (antimüllerian hormone Gen II ELISA assay; Beckman Coulter, Brea, CA, USA). Results: The mean age of women was 36.6 ± 4.3 years. Antimüllerian hormone values were inversely correlated with age (r = −0.35; p < 0.001). From the regression equation, the estimated yearly decrease in antimüllerian hormone was 0.2 ng/ml. Significant differences were obtained in mean values of antimüllerian hormone among Cataluña, Baleares, and Andalucía. Conclusions: This study reports the distribution of antimüllerian hormone values in different age groups in Spain, and contribute to determine the ovarian reserve in Spanish women (AU)

Dietary factors and incident atrial fibrillation: the Framingham Heart Study.

BACKGROUND: There have been conflicting reported associations between dietary factors and incident atrial fibrillation (AF). OBJECTIVE: We evaluated associations between consumption of alcohol, caffeine, fiber, and polyunsaturated fatty acids (PUFAs) and incident AF in the Framingham Heart Study. DESIGN: Participants without AF (n = 4526; 9640 examinations; mean age: 62 y; 56% women) from the original and offspring cohorts completed food-frequency questionnaires and were followed prospectively for 4 y. We examined the associations between dietary exposures and AF with Cox proportional hazards regression. RESULTS: A total of 296 individuals developed AF (177 men, 119 women). In multivariable analyses, there were no significant associations between examined dietary exposures and AF risk. Hazard ratios (HRs) for increasing quartiles of dietary factors were as follows: for alcohol, 0.73 (95% CI: 0.5, 1.05), 0.85 (95% CI: 0.61, 1.18), and 1.12 (95% CI: 0.83, 1.51) (P for trend = 0.48); for caffeine, 0.84 (95% CI: 0.62, 1.15), 0.87 (95% CI: 0.64, 1.2), and 0.98 (95% CI: 0.7, 1.39) (P for trend = 0.84); for total fiber, 0.86 (95% CI: 0.61, 1.2), 0.64 (95% CI: 0.44, 0.92), and 0.81 (95% CI: 0.54, 1.2) (P for trend = 0.16); and for n-3 (omega-3) PUFAs, 1.11 (95% CI: 0.81, 1.54), 0.92 (95% CI: 0.65, 1.29), and 1.18 (95% CI: 0.85, 1.64) (P for trend = 0.57; quartile 1 was the reference group). In exploratory analyses, consumption of >4 servings of dark fish/wk (5 cases and 21 individuals at risk) was significantly associated with AF risk compared with the consumption of <1 serving of dark fish/wk (HR: 6.53; 95% CI: 2.65, 16.06; P < 0.0001). CONCLUSIONS: Consumption of alcohol, caffeine, fiber, and fish-derived PUFAs was not significantly associated with AF risk. The observed adverse association between the consumption of dark fish and AF merits further investigation. Our findings suggest that the dietary exposures examined convey limited attributable risk of AF in the general population.

Carotid and femoral plaque burden is inversely associated with the α-linolenic acid proportion of serum phospholipids in Spanish subjects with primary dyslipidemia.

OBJECTIVE: α-Linolenic acid (ALA), the vegetable n-3 fatty acid, appears to have antiatherosclerotic properties akin to those of marine n-3 fatty acids. A prior study in a US population with low fish intake showed an inverse association between ALA intake and carotid plaque. We examined the association between the ALA status and advanced carotid and femoral atherosclerosis in subjects at high cardiovascular disease risk from Spain, a country with low coronary heart disease (CHD) rates and high fish consumption. METHODS: Cross-sectional study of 211 patients with primary dyslipidemia, with determination of fatty acid composition of serum phosphatidylcholine by gas chromatography and plaque outcomes (frequency, number, maximum height and sum of plaque heights) in carotid and femoral arteries by sonography. RESULTS: In multivariate regression analyses after adjusting for age, gender, lipid genotype, BMI, smoking, hypertension, diabetes mellitus, APOE4 genotype, prior statin treatment, and serum proportions of other unsaturated fatty acids known to relate to atherosclerosis, the proportion of ALA showed an inverse association with the risk of carotid plaque (OR [95% CI] 0.66 [0.44-0.91]) and concomitant carotid and femoral artery plaque (0.57 [0.38-0.86]). CONCLUSION: The inverse relationship between ALA in serum phosphatidylcholine and plaque burden in carotid and femoral arteries supports its antiatherosclerotic effect independently of fish-derived n-3 fatty acids. However, whether ALA enrichment in phospholipids is beneficial per se or is a surrogate of the consumption of bioactive compounds in parent foods deserves further research.

Predicting cardiovascular disease morbidity and mortality in chronic kidney disease in Spain. The rationale and design of NEFRONA: a prospective, multicenter, observational cohort study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Cardiovascular risk assessment in this population is hampered by the failure of traditional risk factors to fully account for the elevated CVD risk (reverse epidemiology effect) and the presence of emerging risk factors specifically related to kidney failure. Therefore, diagnostic tools capable of improving cardiovascular risk assessment beyond traditional risk factors are currently warranted. We present the protocol of a 4-year prospective study aimed to assess the predictive value of non-invasive imaging techniques and biomarkers for CVD events and mortality in patients with CKD. METHODS: From November 2009 to October 2010, 4137 asymptomatic adult patients with stages 2 to 5 CKD will be recruited from nephrology services and dialysis units throughout Spain. During the same period, 843 participants without CKD (control group) will be recruited from lists of primary care physicians, only at baseline. During the follow-up, CVD events and mortality will be recorded from all CKD patients. Clinical and laboratory characteristics will be collected in a medical documentation sheet. Three trained itinerant teams will carry out a carotid ultrasound to assess intima-media thickness and presence of plaques. A composite atherosclerosis score will be constructed based on carotid ultrasound data and measurement of ankle-brachial index. In CKD patients, presence and type of calcifications will be assessed in the wall of carotid, femoral and brachial arteries, and in cardiac valves, by ultrasound. From all participants, blood samples will be collected and stored in a biobank to study novel biomarkers. CONCLUSIONS: The NEFRONA study is the first large, prospective study to examine the predictive value of several non-invasive imaging techniques and novel biomarkers in CKD patients throughout Spain. Hereby, we present the protocol of this study aimed to explore the most effective way in which these tests can be integrated with traditional risk factors to maximize CVD detection in this population.

Fatty acids in serum phospholipids and carotid intima-media thickness in Spanish subjects with primary dyslipidemia.

BACKGROUND: Low rates of incident ischemic heart disease (IHD) and cardiac death occur in Spain despite a high prevalence of cardiovascular risk factors. High consumption of unsaturated fatty acid-rich foods, such as olive oil, nuts, and seafood, might underlie this paradox. OBJECTIVE: We investigated whether serum phosphatidylcholine enrichment in oleic, linoleic, alpha-linolenic, and n-3 (omega-3) long-chain polyunsaturated fatty acids (as biomarkers of olive oil, seed oil, walnut, and fish intake, respectively) relate to carotid atherosclerosis in Spanish subjects at risk of IHD. DESIGN: In a cross-sectional study, we measured fatty acid concentrations in serum phosphatidylcholine and measured carotid intima-media thickness (IMT) by using ultrasound in 451 asymptomatic subjects (261 men, 190 women; mean age: 45 y) with primary dyslipidemia. Main and secondary outcomes were mean and maximum IMT in the common carotid artery (CCA) and other carotid segments, respectively. RESULTS: Phosphatidylcholine fatty acid composition was similar to that reported for other Spanish populations. Multiple regression analyses showed that proportions of oleic and docosahexaenoic acids were inversely related to mean CCA IMT (P < 0.02, all) after adjustment for several confounders. In similar models, alpha-linolenic acid related inversely to mean and maximum internal carotid artery IMT (P < 0.05 for all). Linoleic and eicosapentaenoic acids were unrelated to IMT. CONCLUSIONS: Higher phospholipid proportions of oleic, alpha-linolenic, and docosahexaenoic acids showed inverse associations with IMT at specific carotid segments in subjects with primary dyslipidemia. High intakes of healthy fats might explain, in part, the Spanish paradox of low IHD rates in the face of a high burden of cardiovascular risk factors.

Cardiovascular risk factors underestimate atherosclerotic burden in chronic kidney disease: usefulness of non-invasive tests in cardiovascular assessment.

BACKGROUND: Cardiovascular risk scoring (Score) does not specifically address chronic kidney disease (CKD) patients. The aim of our study is to quantify atherosclerosis using carotid ultrasound and ankle-brachial index (ABI) and to assess its additional value in risk scoring. METHODS: In this cross-sectional, observational study, patients were studied according to a standardized protocol including carotid ultrasound and ABI to determine the atherosclerosis score (AS), ranging from absence of to severe atherosclerosis (AS 0 to AS 3). RESULTS: We included 409 CKD-affected patients (231 on dialysis, 99 in CKD Stages IV-V and 79 in CKD Stages I-III) and 851 subjects with normal renal function. The presence and severity of atherosclerosis was significantly higher in the CKD group than in the controls at every decade of age studied. Among the CKD-affected subjects, the prevalence of carotid plaques was significantly higher in the dialysis group (78.3%) than in the group in CKD Stages I-III (55.6%, P < 0.001). We identified 174 patients at low-intermediate risk. Among them, 110 (63.2%) presented either moderate (AS 2) or severe (AS 3) atherosclerosis. Variables significantly (P < 0.05) and positively related to atherosclerosis were being on dialysis [OR = 3.40, 95% CI (1.73, 6.78) vs CKD Stages I-III], age [OR = 1.08, 95% CI (1.06-1.11)] and C-reactive protein [OR = 1.04, 95% CI (1.01-1.08)]. Conversely, female sex was negatively related to atherosclerosis [OR = 0.40, 95% CI (0.23-0.71), P = 0.002]. CONCLUSION: The use of carotid ultrasound and ABI identifies atherosclerosis in a population of CKD patients in which risk scoring underestimates atherosclerosis burden.

Impact of low-density lipoprotein receptor mutational class on carotid atherosclerosis in patients with familial hypercholesterolemia.

BACKGROUND AND OBJECTIVES: Defects in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a highly atherogenic condition. The effect of different LDLR mutations on coronary heart disease (CHD) risk is insufficiently defined. We assessed carotid intima-media thickness (IMT), a surrogate marker of CHD, in relation to LDLR mutational class in FH. METHODS: In 436 Spanish FH patients (223 men and 213 women, age 44+/-14 years) with known LDLR mutations, alleles were classified by standard criteria as null (n=269), defective (n=162), or undetermined (n=5). LDLR defects were detected using a microarray (Lipochip) designed to uncover prevalent mutations in Spain and gene sequencing when no mutations were detected. Carotid IMT and plaque were assessed in FH patients and 268 healthy subjects. RESULTS: All carotid measurements were increased in FH patients versus controls (p<0.05), irrespective of genotype. After adjustment for gender and age, patients with null alleles compared with defective alleles had similar mean and maximum common carotid artery (CCA) IMT, but higher maximum IMT at any carotid segment, with median values (95% confidence interval) of 1.25 mm (1.19-1.31) and 1.11 mm (1.05-1.18), respectively. Multivariate analysis showed that null alleles were independently associated with maximum CCA-IMT (beta=0.09, p=0.033) with an impact similar to that of gender (beta=0.10, p=0.035). CONCLUSIONS: FH patients show advanced carotid atherosclerosis in relation to LDLR mutational class. The findings support the utility of genetic testing in FH beyond providing a secure diagnosis.

Novel variants at KCTD10, MVK, and MMAB genes interact with dietary carbohydrates to modulate HDL-cholesterol concentrations in the Genetics of Lipid Lowering Drugs and Diet Network Study.

BACKGROUND: Several genome-wide association studies have identified novel loci (KCTD10, MVK, and MMAB) that are associated with HDL-cholesterol concentrations. Of the environmental factors that determine HDL cholesterol, high-carbohydrate diets have been shown to be associated with low concentrations. OBJECTIVE: The objective was to evaluate the associations of 8 single nucleotide polymorphisms (SNPs) located within the KCTD10, MVK, and MMAB loci with lipids and their potential interactions with dietary carbohydrates. DESIGN: KCTD10, MVK, and MMAB SNPs were genotyped in 920 subjects (441 men and 479 women) who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study. Biochemical measurements were made by using standard procedures. Dietary intakes were estimated by using a validated questionnaire. RESULTS: For the SNPs KCTD10_i5642G-->C and MVK_S52NG-->A, homozygotes for the major alleles (G) had lower HDL-cholesterol concentrations than did carriers of the minor alleles (P = 0.005 and P = 0.019, respectively). For the SNP 12inter_108466061A-->G, homozygotes for the minor allele (G) had higher total cholesterol and LDL-cholesterol concentrations than did AG subjects (P = 0.030 and P = 0.034, respectively). Conversely, homozygotes for the major allele (G) at MMAB_3U3527G-->C had higher LDL-cholesterol concentrations than did carriers of the minor allele (P = 0.034). Significant gene-diet interactions for HDL cholesterol were found (P < 0.001-0.038), in which GG subjects at SNPs KCTD10_i5642G-->C and MMAB_3U3527G-->C and C allele carriers at SNP KCTD10_V206VT-->C had lower concentrations only if they consumed diets with a high carbohydrate content (P < 0.001-0.011). CONCLUSION: These findings suggest that the KCTD10 (V206VT-->C and i5642G-->C) and MMAB_3U3527G-->C variants may contribute to the variation in HDL-cholesterol concentrations, particularly in subjects with high carbohydrate intakes.

Utilidad de la ecografía carotídea en la evaluación de la eficacia terapéutica del tratamiento hipolipemiante / no disponible

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Apolipoprotein C3 polymorphisms, cognitive function and diabetes in Caribbean origin Hispanics.

BACKGROUND: Apolipoprotein C3 (APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired glucose metabolism are linked to cognitive decline, and all three conditions may decrease lifespan. Associations between apolipoprotein C3 (APOC3) gene polymorphisms and impaired lipid and glucose metabolism are well-established, but potential connections between APOC3 polymorphisms, cognitive decline and diabetes deserve further attention. METHODS: We examined whether APOC3 single nucleotide polymorphisms (SNPs) m482 (rs2854117) and 3u386 (rs5128) were related to cognitive measures, whether the associations between cognitive differences and genotype were related to metabolic differences, and how diabetes status affected these associations. Study subjects were Hispanics of Caribbean origin (n = 991, aged 45-74) living in the Boston metropolitan area. RESULTS: Cognitive and metabolic measures differed substantially by type II diabetes status. In multivariate regression models, APOC3 m482 AA subjects with diabetes exhibited lower executive function (P = 0.009), Stroop color naming score (P = 0.014) and Stroop color-word score (P = 0.022) compared to AG/GG subjects. APOC3 m482 AA subjects with diabetes exhibited significantly higher glucose (P = 0.032) and total cholesterol (P = 0.028) compared to AG/GG subjects. APOC3 3u386 GC/GG subjects with diabetes exhibited significantly higher triglyceride (P = 0.004), total cholesterol (P = 0.003) and glucose (P = 0.016) compared to CC subjects. CONCLUSIONS: In summary, we identified significant associations between APOC3 polymorphisms, impaired cognition and metabolic dysregulation in Caribbean Hispanics with diabetes. Further research investigating these relationships in other populations is warranted.

Physical inactivity interacts with an endothelial lipase polymorphism to modulate high density lipoprotein cholesterol in the GOLDN study.

BACKGROUND: Plasma high density lipoprotein (HDL) cholesterol (HDL-C) concentration is highly heritable but is also modifiable by environmental factors including physical activity. HDL-C response to exercise varies among individuals, and this variability may be associated with genetic polymorphisms in the key regulators of HDL metabolism including endothelial lipase (LIPG). METHODS: We examined associations between variants LIPG T111I (rs2000813) and LIPG i24582 (rs6507931), HDL and television viewing/computer use ("screen time") as a marker for physical inactivity in a population with high prevalence of metabolic syndrome. Subjects consisted of 539 White men and 584 women (mean+/-S.D., 49+/-16 years) participating in the GOLDN study. RESULTS: We did not observe an association with either LIPG SNP or HDL independently of screen time. In multi-adjusted linear regression models, HDL interacted significantly with screen time as a continuous variable in LIPG i24582 subjects with TT genotype (P<0.05). By dichotomizing screen time into high and low levels, we found significant genotype-associated differences in HDL in women but not men. When screen time was >or=2.6h/day, the concentrations of total HDL-C, large HDL, large low density lipoprotein (LDL) were lower, the concentration of small LDL was higher and HDL and LDL particle sizes were smaller in subjects with LIPG i24582 TT compared to CT and CC subjects (P<0.05). CONCLUSIONS: We found a significant gene-physical inactivity interaction for HDL and some LDL measures for the LIPG i24582 polymorphism. Higher levels of physical activity may be protective for HDL-C concentrations and low activity detrimental in LIPG i24582 TT individuals, especially in women.

Genetic variants at the PDZ-interacting domain of the scavenger receptor class B type I interact with diet to influence the risk of metabolic syndrome in obese men and women.

The scaffolding protein PDZ domain containing 1 (PDZK1) regulates the HDL receptor scavenger receptor class B type I. However, the effect of PDZK1 genetic variants on lipids and metabolic syndrome (MetS) traits remains unknown. This study evaluated the association of 3 PDZK1 single nucleotide polymorphisms (SNP) (i33968C > T, i15371G > A, and i19738C > T) with lipids and risk of MetS and their potential interactions with diet. PDZK1 SNP were genotyped in 1000 participants (481 men, 519 women) included in the Genetics of Lipid Lowering Drugs and Diet Network study. Lipoprotein subfractions were measured by proton NMR spectroscopy and dietary intake was estimated using a validated questionnaire. The PDZK1_i33968C > T polymorphism was associated with MetS (P = 0.034), mainly driven by the association of the minor T allele with higher plasma triglycerides (P = 0.004) and VLDL (P = 0.021), and lower adiponectin concentrations (P = 0.022) than in participants homozygous for the major allele (C). We found a significant gene x BMI x diet interaction, in which the deleterious association of the i33968T allele with MetS was observed in obese participants with high PUFA and carbohydrate (P-values ranging from 0.004 to 0.020) intakes. Conversely, a there was a protective effect in nonobese participants with high PUFA intake (P < 0.05). These findings suggest that PDZK1_i33968C > T genetic variants may be associated with a higher risk of exhibiting MetS. This gene x BMI x diet interaction offers the potential to identify dietary and other lifestyle changes that may obviate the onset of MetS in individuals with a specific genetic background.

The effects of ABCG5/G8 polymorphisms on plasma HDL cholesterol concentrations depend on smoking habit in the Boston Puerto Rican Health Study.

Low HDL-cholesterol (HDL-C) is associated with an increased risk for atherosclerosis, and concentrations are modulated by genetic factors and environmental factors such as smoking. Our objective was to assess whether the association of common single-nucleotide polymorphisms (SNPs) at ABCG5/G8 (i18429G>A, i7892T>C, Gln604GluC>G, 5U145A>C, Tyr54CysA>G, Asp19HisG>C, i14222A>G, and Thr400LysC>A) genes with HDL-C differs according to smoking habit. ABCG5/G8 SNPs were genotyped in 845 participants (243 men and 602 women). ABCG5/G8 (i7892T>C, 5U145A>C, Tyr54CysA>G, Thr400LysC>A) SNPs were significantly associated with HDL-C concentrations (P < 0.001-0.013) by which carriers of the minor alleles at the aforementioned polymorphisms and homozygotes for the Thr400 allele displayed lower HDL-C. A significant gene-smoking interaction was found, in which carriers of the minor alleles at ABCG5/G8 (Gln604GluC>G, Asp19HisG>C, i14222A>G) SNPs displayed lower concentrations of HDL-C only if they were smokers (P = 0.001-0.025). Also, for ABCG8_Thr400LysC>A SNP, smokers, but not nonsmokers, homozygous for the Thr400 allele displayed lower HDL-C (P = 0.004). Further analyses supported a significant haplotype global effect on lowering HDL-C (P = 0.002) among smokers. In conclusion, ABCG5/G8 genetic variants modulate HDL-C concentrations, leading to an HDL-C-lowering effect and thereby a potential increased risk for atherosclerosis only in smokers.

[Femoral ultrasound in the assessment of preclinical atherosclerosis. Distribution of intima-media thickness and frequency of atheroma plaques in a Spanish community cohort]. / Ecografía femoral en la evaluación de la aterosclerosis preclínica. Distribución de valores del grosor íntima-media y frecuencia de placas de ateroma en una cohorte comunitaria española.

BACKGROUND AND OBJECTIVE: High-resolution B-mode ultrasound measurements of intima-media thickness (IMT) and plaque presence are useful to assess preclinical atherosclerosis. Normal carotid IMT values, but not normal femoral IMT values, have been reported in Spanish subjects. Our aim was to define the normality data of femoral ultrasound by sex and age. SUBJECTS AND METHOD: We studied 192 healthy subjects from a community cohort, 85 men and 107 women (mean age: 49 years; range: 20-81 years). We sonographically determined mean and maximum IMT in the far wall of the common femoral artery, plaque occurrence, and maximum plaque height. RESULTS: Reference values for femoral IMT, expressed as 25th, 50th, and 75th percentiles by sex and 5 age groups, were obtained. The 50th percentiles of mean IMT ranged from 0.50 to 1.04 mm in men in the age groups < or = 35 years and > or = 65 years, respectively. For women, corresponding IMT values ranged from 0.40 to 0.53 mm. IMT was positively related to age in both men (r = 0.44; p < 0.001) and women (r = 0.23; p = 0.019). From the regression equations of IMT versus age, the estimated yearly increase in IMT was 0.016 mm in men and 0.008 mm in women. More than 50% of men aged > or = 55 years and women aged > or = 65 years had plaques. CONCLUSIONS: Both IMT and plaque frequency are associated with age in men and women. Femoral IMT values in a Spanish community cohort are lower than those reported for geographical areas with higher cardiovascular risk, such as the Northern European countries and the US.

Ecografía femoral en la evaluación de la aterosclerosis preclínica. Distribución de valores del grosor íntima-media y frecuencia de placas de ateroma en una cohorte comunitaria española / Femoral ultrasound in the assessment of preclinical atherosclerosis. Distribution of intima-media thickness and frequency of atheroma plaques in a Spanish community cohort

FUNDAMENTO Y OBJETIVO: La ecografía permite valorar la aterosclerosis preclínica mediante la determinacióndel grosor íntima-media (GIM) y el hallazgo de placas de ateroma. En poblaciónespañola se han definido los valores normales del GIM carotídeo, pero no del GIM femoral, yéste ha sido nuestro objetivo.SUJETOS Y MÉTODO: Se ha estudiado a 192 personas sanas (85 varones y 107 mujeres) de unacohorte comunitaria (edad media: 49 años; extremos: 20-81 años). Mediante ecografía se midióel GIM medio y máximo en la pared posterior de la arteria femoral común y se cuantificaronlas placas de ateroma.RESULTADOS: Se han obtenido los valores de referencia del GIM femoral, que se expresan como percentiles25; 50, y 75 por sexo y grupo de edad. En los varones, los percentiles 50 del GIM mediovariaron entre 0,50 y 1,04 mm en los grupos de edad igual o menor de 35 años y mayor de 65años, respectivamente. En las mujeres, las cifras correspondientes oscilaron entre 0,40 y 0,53mm. El GIM se correlacionó con la edad, tanto en varones (r = 0,44; p < 0,001) como en mujeres(r = 0,23; p = 0,019). El incremento anual del GIM derivado de las ecuaciones de regresión fuede 0,016 y 0,008 mm por año en varones y mujeres, respectivamente. Más de la mitad de los varonescon edad igual o superior a 55 años y mujeres de 65 años o más tenían placas.CONCLUSIONES: El GIM y la presencia de placas se asocian con la edad en ambos sexos. Los valoresnormales de la ecografía femoral en España son inferiores a los descritos en poblaciones demayor riesgo cardiovascular

BACKGROUND AND OBJECTIVE: High-resolution B-mode ultrasound measurements of intima-mediathickness (IMT) and plaque presence are useful to assess preclinical atherosclerosis. Normalcarotid IMT values, but not normal femoral IMT values, have been reported in Spanish subjects.Our aim was to define the normality data of femoral ultrasound by sex and age.SUBJECTS AND METHOD: We studied 192 healthy subjects from a community cohort, 85 men and107 women (mean age: 49 years; range: 20-81 years). We sonographically determined meanand maximum IMT in the far wall of the common femoral artery, plaque occurrence, and maximumplaque height.RESULTS: Reference values for femoral IMT, expressed as 25th, 50th, and 75th percentiles bysex and 5 age groups, were obtained. The 50th percentiles of mean IMT ranged from 0.50 to1.04 mm in men in the age groups 35 years and 65 years, respectively. For women, correspondingIMT values ranged from 0.40 to 0.53 mm. IMT was positively related to age inboth men (r = 0.44; p < 0.001) and women (r = 0.23; p = 0.019). From the regression equationsof IMT versus age, the estimated yearly increase in IMT was 0.016 mm in men and0.008 mm in women. More than 50% of men aged 55 years and women aged 65 yearshad plaques.CONCLUSIONS: Both IMT and plaque frequency are associated with age in men and women. FemoralIMT values in a Spanish community cohort are lower than those reported for geographicalareas with higher cardiovascular risk, such as the Northern European countries and the US

Femoral atherosclerosis in heterozygous familial hypercholesterolemia: influence of the genetic defect.

OBJECTIVE: The purpose of this study was to assess femoral atherosclerosis by ultrasound in patients with molecularly defined heterozygous familial hypercholesterolemia (FH) in comparison with matched control subjects and in relation to mutational class in the LDL receptor and apolipoprotein B (APOB) genes. METHODS AND RESULTS: Femoral intima-media thickness (IMT) and plaque were evaluated in 146 FH patients carrying null alleles (n=48), defective-receptor alleles (n=62), undetermined-function alleles (n=25), or APOB defects (n=11) and in 193 healthy subjects. Twenty-three patients had coronary heart disease (CHD). The frequency of both tendon xanthomas and CHD was approximately 2-fold higher and average LDL cholesterol was 30 mg/dL higher in null-allele genotype compared with receptor-defective mutations. All femoral measurements were increased in FH patients versus controls (P<0.001), and null-allele mutations showed higher age-, sex-, and LDL cholesterol-adjusted maximum IMT than receptor-defective or APOB defects (P for trend, 0.001). By multivariate analysis, independent associations of mean IMT, a measure of early atherosclerosis, were age, LDL cholesterol, sex, and systolic blood pressure. Age, null-allele genotype, sex, and smoking explained 42% of the variability of maximum IMT, a measure of advanced atherosclerosis. CONCLUSIONS: FH patients have increased femoral IMT in relation to mutational class. The findings support the usefulness of genetic testing in FH beyond securing the diagnosis.

Carotid atherosclerosis in familial combined hyperlipidemia associated with the APOB/APOA-I ratio.

OBJECTIVES: The effects of risk factors on carotid atherosclerosis in familial combined hyperlipidemia (FCHL) remain unclear. We assessed carotid intima-media thickness (IMT) and plaque in relation to classical risk factors and apolipoprotein A-I (apoA-I) and B (apoB) levels in patients with FCHL. METHODS AND RESULTS: We included 131 unrelated FCHL patients (27 with prior cardiovascular disease (CVD)) diagnosed by standard criteria and 190 age- and sex-matched control subjects. Cardiovascular risk factors were assessed and IMT in the far wall of all carotid segments and plaque burden were determined in FCHL patients and controls. All carotid measurements were increased in FCHL patients compared to controls (P<0.001), irrespective of CVD status. For asymptomatic FCHL, the adjusted difference in mean common carotid IMT was 0.08 mm, corresponding to approximately 16 years of physiological IMT increase. By multivariate analysis in a model with all risk factors, inclusive of the metabolic syndrome, independent associations of IMT were age, the apoB/apoA-I ratio, systolic blood pressure, fasting glucose, family history of CVD and total/HDL cholesterol ratio (r(2)=0.475, P<0.001). The strongest determinant of IMT was the apoB/apoA-I ratio (beta=0.422, P<0.001). CONCLUSIONS: Patients with FCHL have increased carotid IMT that is strongly related to the apoB/apoA-I ratio, a measure of overall lipid abnormalities. The findings support the atherogenicity of the lipid phenotype in FCHL beyond associated risk factors. They also have implications for diagnosis and management of CVD risk in this condition.

Carotid atherosclerosis and vascular age in the assessment of coronary heart disease risk beyond the Framingham Risk Score.

OBJECTIVES: To assess how ultrasound measurements of carotid intima-media thickness (CIMT) and plaque burden compare with the Framingham Risk Score (FRS) in a clinical setting. METHODS AND RESULTS: In a cross-sectional study, we determined CIMT and plaque in 409 asymptomatic, non-diabetic hyperlipidemic subjects (242 men, age 49+/-11 years) who were assessed for risk factors and classified into FRS categories: 10-year risk < or =5% (n=191), 6-20% (n=176), and >20% (n=42). Percentiles of CIMT and plaque height and regression equations of CIMT against age obtained in 250 controls subjects were used to define atherosclerosis and estimate vascular age, respectively. There was a wide dispersion of CIMT for each FRS category. CIMT values were discordant in 242 (59%) subjects, 80% of them showing more atherosclerosis than predicted. Smoking and the metabolic syndrome explained part of the discrepancies in the intermediate-risk group. Triglycerides, homocysteine, and lipoprotein(a) did not predict atherosclerotic burden. Mean vascular age was 14.5 years older than chronological age. CONCLUSIONS: Carotid atherosclerosis findings readjust FRS categories in many asymptomatic subjects. Both carotid atherosclerotic burden and vascular age may be used to refine CHD risk and tailor preventive treatment beyond the FRS.