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Familial hypercholesterolemia (FH) is an autosomal dominant disease that has a prevalence of approximately 1/250 inhabitants and is the most frequent cause of early coronary heart disease (CHD). We included 1.343.973 women and 1.210.671 men with at least one LDL-c measurement from the Catalan primary care database. We identified 14.699 subjects with Familial hypercholesterolemia-Phenotype (FH-P) based on LDL-c cut-off points by age (7.033 and 919 women, and 5.088 and 1659 men in primary and secondary prevention, respectively). Lipid lower therapy (LLT), medication possession ratio (MPR) as an indicator of adherence, and number of patients that reached their goal on lipid levels were compared by sex. In primary and secondary prevention, 69% and 54% of women (P = 0.001) and 64% and 51% of men (P = 0.001) were on low-to-moderate-potency LLT. Adherence to LLT was reduced in women older than 55 years, especially in secondary prevention (P = 0.03), where the percentage of women and men with LDL-c > 1.81 mmol/L were 99.9% and 98.9%, respectively (P = 0.001). Women with FH-P are less often treated with high-intensity LLT, less adherent to LLT, and have a lower probability of meeting their LDL-c goals than men, especially in secondary prevention.

To explore the role of chronic inflammation inherent to autoimmune diseases in the development of subclinical atherosclerosis and arterial stiffness, this study recruited two population-based samples of individuals with and without autoimmune disease (ratio 1:5) matched by age, sex, and education level and with a longstanding (≥6 years) diagnosis of autoimmune disease. Common carotid intima-media thickness (IMT) and arterial distensibility and compliance were assessed with carotid ultrasound. Multivariable linear and logistic regression models were adjusted for 10-year cardiovascular risk. In total, 546 individuals with and without autoimmune diseases (91 and 455, respectively) were included. The mean age was 66 years (standard deviation 12), and 240 (43.9%) were women. Arterial stiffness did not differ according to the presence of autoimmune diseases. In men, the diagnosis of autoimmune diseases significantly increased common carotid IMT [beta-coefficient (95% confidence interval): 0.058 (0.009; 0.108); p value = 0.022] and the percentage with IMT ≥ 75th percentile [1.012 (0.145; 1.880); p value = 0.022]. Women without autoimmune disease were more likely to have IMT ≥ the 75th percentile [-2.181 (-4.214; -0.149); p value = 0.035], but the analysis of IMT as a continuous variable did not yield significant results. In conclusion, subclinical carotid atherosclerosis, but not arterial stiffness, was more common in men with autoimmune diseases. Women did not show significant differences in any of these carotid features. Sex was an effect modifier in the association between common carotid IMT values and the diagnosis of autoimmune diseases.

Background DNA methylation is associated with atherosclerosis and cardiovascular risk factors. However, little evidence regarding its association with cardiovascular diseases in large studies is currently available. We aimed to assess the association between DNA methylation and cardiovascular events, and to determine both the predictive capacity of the identified loci and the causality of those associations. Methods We defined two strategies: epigenome-wide (EWAS) and candidate-gene association studies. In both strategies, we designed one approach with prevalent cases of coronary heart disease (CHD) and another with incident cases of CHD and cardiovascular disease. We used data from three independent cohorts: the REgistre GIroní del COR (REGICOR) study, the Framingham Offspring Study and the Women’s Health Initiative. We also assessed the association between the identified CpGs and cardiovascular risk factors in the three populations. Then, we developed methylation risk scores to evaluate whether their inclusion in the Framingham risk function improved its predictive capacity. Finally, we performed a Mendelian randomization study to determine the causality of the identified associations. Results We found 17 CpGs related to prevalent CHD and/or incident cardiovascular events, two of them observed using both approaches ( p

There is limited prospective evidence at population scale of the impacts of lifestyle and surrogate measures of general and abdominal adiposity on the transition of a metabolically healthy (absence of a metabolic disorder) overweight/obese (MHOO) phenotype to a metabolically abnormal overweight/obese (MAOO) phenotype. Therefore, we determined the relationship between 10-year body mass index (BMI), waist circumferences (WC), waist to height ratio (WHtR), and lifestyle changes and the transition of the MHOO phenotype.We conducted a prospective population-based study of 3,052 male and female Spaniards aged 25-74 years who were followed from 2000 through 2009. Diet and leisure-time physical activity were recorded on validated questionnaires. Weight, height, WC, blood lipids, glycemia, and blood pressure were measured. All variables were obtained at baseline (BL) and follow-up (FL). Participants with a BMI ≥ 25 kg/m(2) and free from hypercholesterolemia, hypertriglyceridemia, diabetes, hypertension, and low HDL and high LDL cholesterol levels were characterized as the MHOO phenotype. A composite healthy lifestyle index (HLI) was constructed by including temporary changes in 3 lifestyle variables (diet, leisure-time physical activity, and smoking).Initially, 20.8% of subjects had the MHOO phenotype; 49.2% of these shifted to MAOO phenotype. In multivariate analysis, changes in BMI, WC, WHtR were positively associated (p = 0.004, p = 0.018, and p = 0.016, respectively) with this transition. One unit increase in the HLI was associated with a 33% lower risk (p = 0.025) to the MAOO phenotype transition after adjusting for age, sex, educational level, and baseline energy intake, BMI, WC, and WHtR.The presence of metabolic disorders in the MHOO phenotype is predicted by an increase in anthropometric surrogate measures of general and abdominal adiposity. In contrast, a healthy lifestyle protects against a transition to the MAOO phenotype.

The estimation of the cardiovascular risk is important for guiding individual preventive strategies. Various functions are available and have been shown to provide an accurate estimation of risk. However, while the majority of individuals in the general population fall within categories of low and moderate risk, a high proportion of cardiovascular events also occur in individuals within these categories. Therefore, renewed efforts have been made recently to improve the predictive capacity of classical risk functions through the inclusion of new risk biomarkers, including genetic variants associated with coronary or cardiovascular diseases. In this narrative review, we will focus on the utility and limitations of cardiovascular risk functions, assessment of the predictive capacity of new biomarkers, current knowledge of genetic variants associated with clinical cardiovascular phenotypes, and their potential predictive value. We will also identify some priorities for future research in this area.

Dyslipidemia is a well-established risk factor for cardiovascular disease, the main cause of death worldwide. Blood lipid profiles are patterned by both genetic and environmental factors. In recent years, epigenetics has emerged as a paradigm that unifies these influences. In this review, we have summarized the latest evidence implicating epigenetic mechanisms—DNA methylation, histone modification, and regulation by RNAs—in lipid homeostasis. Key findings have emerged in a number of novel epigenetic loci located in biologically plausible genes (e.g. CPT1A, ABCG1, SREBF1, and others), as well as microRNA-33a/b. Evidence from animal and cell culture models suggests a complex interplay between different classes of epigenetic processes in the lipid-related genomic regions. While epigenetic findings hold the potential to explain the interindividual variability in lipid profiles as well as the underlying mechanisms, they have yet to be translated into effective therapies for dyslipidemia.

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2,3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways ( P=0.016) and that underlie skeletal growth defects ( P

This study was designed to assess the incidence of peripheral arterial occlusive disease (PAOD) in a population-based cohort of men aged 55–74 years and to establish a predictive function based on risk factors for the disease. This was a prospective study of 699 men representative of an urban population. Cardiovascular risk factors, history of cardiovascular events, and ankle-brachial index (ABI) at baseline and at 5 years were measured. PAOD was defined as a confirmed ABI

Objective: Dietary intake is strongly influenced by the energy density of the diet. The purpose of this study was to determine the association of energy density with diet quality, dietary reference intake (DRI) for energy and lifestyle characteristics in free-living people. Subjects: The subjects were Spanish men (n ¼ 1491) and women (n ¼ 1563) selected in between 1999 and 2000 among the general population according to the 1996 census. Results: A low-energy density diet was significantly associated (Po0.001) with a higher consumption of vegetables, fruits, legumes, fish and white meat as compared to high-energy density diets. More subjects (Po0.001) with a high adherence to low-energy density diets meet DRI for energy intake and tended to be closer (Po0.05) to the recommendations of dietary intakes, established by the Spanish Society of Community Nutrition than those following a high-energy density diet. Alcohol consumption, the prevalence of a sedentary lifestyle and smoking significantly increased (Po0.01) across quartile distribution of energy density. Conclusion: Low-energy density diets of the present population were associated with a healthier lifestyle. Furthermore, our data suggest that adherence to low-energy density diets, with similar characteristics to those found in the present population, promote adequate energy intakes and increase overall diet quality. European Journal of Clinical Nutrition (2008) 62, 1194–1200; doi:10.1038/sj.ejcn.1602843; published online 11 July 2007

Genetic studies of osteoporosis have focused on analysing single polymorphisms in individual genes - with inconclusive results. An alternative approach may involve haplotypes and gene-gene interactions. The aim of the study was to test the association between the COL1A1, ESR1, VDR and TGFB1 polymorphisms or haplotypes and bone mineral density (BMD) in Spanish postmenopausal women.Sixteen polymorphisms were analysed in 719 postmenopausal women. ANOVA, ANCOVA and Xi2 tests were used to perform the statistical analysis.COL1A1 -1997GT (p=0.04) and TGFB1 Leu10Pro (p=0.02) were found to be associated with adjusted lumbar spine (LS) BMD. Interactions were observed between: the COL1A1 -1997 G/T and Sp1 polymorphisms (p0.01 for LS BMD) and the COL1A1 -1663 indelT and VDR ApaI polymorphisms (p0.01 for femoral neck (FN) BMD). The COL1A1 GDs and ESR1 LPX haplotypes were associated with FN BMD (p=0.03 and p=0.03).Polymorphisms at COL1A1 and TGFB1 and haplotypes at COL1A1 and ESR1 were found to be associated with BMD in a cohort of postmenopausal Spanish women. Moreover, COL1A1 polymorphisms showed significant interactions among them and with the VDR 3' polymorphisms.

Objective: The aim of the present study was to analyse the relation between age and both dietary habits and leisure-time physical activity, and to determine nutrient inadequacy of aged groups in our population. Design: Cross-sectional study. Setting: A random sample of the 25–74-y-old population of Gerona, Spain. Subjects: A total of 838 men and 910 women were selected from among the general population according to the 1991 census. Outcome measures: Analysis of dietary habits, including amount and type of alcohol consumption, and detailed evaluation of leisure-time physical activity. Results: Nutrient densities of carbohydrates, vitamin B1, vitamin B12, vitamin C, vitamin E, folate, potassium, iron, magnesium, copper, and dietary fiber increased significantly (P

The objectives were to analyse whether cardiovascular risk factors appear simultaneously in the population and to determine whether it depends on age. The participants belong to a random sample of individuals 25-74 years of age, representative of the non-diabetic population free of coronary heart disease of the province of Gerona, Spain, studied during 1994-1996. Exploratory factor analysis was used to assess clustering of cardiovascular risk factors and confirmatory factor analysis to compare clus- tering among age groups (25-54 and 55-74). Results: In the 25-54 age group, we observed in both sexes the Central Metabolic Syndrome factor, which included glucose, lipids, and waist-to-hip ratio, and Metabolic Hypertension factor, which included systolic and di- astolic blood pressures, waist-to-hip ratio, low-den- sity lipoproteins, glycaemia, and triglycerides. In the 55-74 age group we observed in both sexes the Cen- tral Metabolic Syndrome factor, with the same com- position as in younger subjects, and Isolated Hypertension factor, composed only of systolic and diastolic blood pressures. In both sexes, the v 2 value for the model of the combined age groups was higher than the sum of v 2 values of the best models for each age group separately (p < 0.01), which indicates that both sexes presented factor structures that differed by age group. Conclusions: The Central Metabolic Syn- drome factor was common to all four sex and age groups studied. In younger subjects blood pressure was related to lipids, obesity, and glycaemia, sug- gesting the existence of a Metabolic Hypertension factor, while systolic and diastolic blood pressures were found to be the only significant variables in the hypertension factor after 54 years.

Background and objectives: The myocardial infarction (MI) incidence rate, prognosis and hospi- talisation rate in the population 65 and over are rarely studied. We sought to determine MI hospital- isation and incidence rates, and 28-day case-fatality, in the 65 year and older population, and to analyse whether their management and prognosis differed from that of younger patients. Methods: All residents in Gerona (Spain) older than 24 years with suspected fatal or non-fatal MI were investigated and included in a population registry. Results: MI mortality, inci- dence, and case-fatality dramatically increased with age after 64. Smoking, thrombolysis, antiplatelet and betablocker drug use, coronary angiograms, and coronary revascularisation decreased with age. The risk of death of patients between 75 and 84 years (OR: 4.15, 95% confidence interval, CI: 1.70-10.15) and between 85 and 94 years (OR: 4.68, 95% CI: 1.62-13.52) was higher than in the 34-64 years age group, independently of any patient characteristic. Conclusions: The magnitude of the impact of MI in the elderly at population and hospital levels is sub- stantially higher than in those younger than 65 years of age. After this age patients receive less treatments and procedures than their younger counterparts.

Physical activity has been identified as a protective factor against the occurrence and progression of coronary heart disease. The lipoprotein lipase (LPL) HindIII polymorphism has been associated with changes in triglyceride and high density lipoprotein (HDL)-cholesterol levels. We have investigated whether the association between the LPL HindIII genetic polymorphism and lipid levels is modified by physical activity. We have also tested the hypothesis that physical activity may interact with smoking and the LPL HindIII polymorphism to determine an individual's plasma lipid concentrations. A total of 520 men were selected from a representative sample used in a population study conducted in Gerona, Spain. The median value (291 kcal/day) of energy expenditure in leisure-time physical activity of the studied sample was selected as a cut-off to define sedentary or active subjects. Serum HDL-cholesterol was positively and significantly associated with the amount of daily energy expenditure in physical activity, whereas inverse associations were seen between physical activity and triglyceride concentration and with the triglyceride to HDL-cholesterol ratio. These effects were consistent across LPL HindIII genotypes. There was a statistically significant interaction between LPL genotype and smoking on lipid concentrations. No statistically significant differences were observed in lipid levels of active or sedentary non-smokers between H- carriers and H+H+ homozygotes for the LPL HindIII polymorphism. In smokers, sedentary H+H+ homozygotes showed significantly higher triglyceride and lower HDL-cholesterol concentrations than sedentary H- carriers. These differences were smaller and not statistically significant when lipid values of active H+H+ homozygotes were compared with active H- carriers. Among all subgroups, sedentary smokers with the H+H+ genotype had the most adverse lipid profile, which was considerably less adverse in H+H+ smokers who were physically active. These findings suggest that the presence of the H+H+ genotype has a deleterious effect on lipid profile in an adverse environment such as smoking, and that the expenditure of more than 291 kcal/day in physical activity attenuates this effect.

The aim of the study was to assess the association between fibrinogen and other cardiovascular risk factors. A cross-sectional population-based study in Gerona (Spain) was designed, 1544 subjects (747 men, 797 women) participated. Anthropometric measurements, blood pressure and blood samples were obtained. Fibrinogen was measured by a coagulometric method. Smoking habits, alcohol consumption and physical activity practice were recorded by questionnaires. Fibrinogen was directly related to age, body mass index (BMI) and female gender and inversely to alcohol and moderate-heavy physical activity practice. Fibrinogen was also higher in men and young women who smoked. In the multivariate analysis, age (regression coefficient (RC): 1.33; standard error (SE): 0.13; unit = 1 year), female gender (RC: 12.24; SE: 3.56) and BMI (RC: 1.83; SE: 0.39; unit = 1 kg/m2) were directly associated with fibrinogen, whereas alcohol (RC: -0.04; SE: 0.01; unit = 1 g/d) was inversely associated. A statistically significant interaction between smoking and age was observed. Age was the strongest variable associated with fibrinogen and modifies the association between smoking and fibrinogen; the magnitude of this association increases with age.

The frequency of coronary heart disease in a community is usually measured by myocardial infarction incidence and mortality rates. The measurement of the prevalence of angina pectoris may, however, become a convenient way of assessing coronary heart disease morbidity in the future. The aim of this study was to determine the prevalence of angina and validity of the Rose questionnaire in the Spanish population aged from 45 to 74 years. A cross-sectional study was conducted in 10,248 subjects (45-74 years), representative of the Spanish population. The WHO Rose questionnaire was used and a construct validation against regional mortality rates and cardiovascular risk factor prevalence was devised. The overall angina prevalence increased with age both in men and women, but was higher in the latter (7.3% and 7.7%, respectively). Angina prevalence also increased with the number of cardiovascular risk factors present and correlated with regional CHD mortality rates (r = 0.66). Sensitivity and specificity results of the Rose questionnaire were low when tested against exercise test (52.9% and 52.1%, respectively). As conclusions, Rose questionnaire is a reliable tool for assessing angina prevalence in the Spanish population which is similar to that of other industrialized countries with higher myocardial infarction morbidity and mortality.