Mitochondrial Genetic Background May Impact Statins Side Effects and Atherosclerosis Development in Familial Hypercholesterolemia.

Heredity of familial hypercholesterolemia (FH) can present as a dominant monogenic disorder of polygenic origin or with no known genetic cause. In addition, the variability of the symptoms among individuals or within the same families evidence the potential contribution of additional factors than monogenic mutations that could modulate the development and severity of the disease. In addition, statins, the lipid-lowering drugs which constitute the first-line therapy for the disease, cause associated muscular symptoms in a certain number of individuals. Here, we analyze the evidence of the mitochondrial genetic variation with a special emphasis on the role of CoQ10 to explain this variability found in both disease symptoms and statins side effects. We propose to use mtDNA variants and copy numbers as markers for the cardiovascular disease development of FH patients and to predict potential statin secondary effects and explore new mechanisms to identify new markers of disease or implement personalized medicine strategies for FH therapy.

Prevalence of FLG loss-of-function mutations R501X, 2282del4, and R2447X in Spanish children with atopic dermatitis.

BACKGROUND/OBJECTIVES: Atopic dermatitis (AD) is the most prevalent inflammatory skin disorder, and is often associated with a personal or family history of atopic disease. The presence of loss-of-function mutations in the filaggrin gene (FLG) is the main predisposing factor for AD FLG mutations show ethnic and geographical variations, even between European populations. We sought to determine the frequency of the 3 most common FLG null mutations in a population of Spanish children consisting of healthy controls and AD patients. We also investigated the association between these 3 FLG mutations and AD. METHODS: A total of 214 participants (111 AD patients and 103 healthy controls) were enrolled in this study. Genotyping for 3 FLG null mutations (R501X, 2282del4, and R2447X) was performed by conventional Sanger sequencing. RESULTS: The combined mutation frequency was 1.9% in the control group and 12.6% in the AD group. The most common FLG mutation in AD patients was R501X (9.9%), followed by R2447X (2.7%) and 2282del4 (1.8%). CONCLUSION: These findings further our understanding of the prevalence of FLG null mutations in the Spanish population, and suggest that the frequency of FLG mutations in AD patients in Spain is slightly higher than that of other Mediterranean countries.

The association between atopic dermatitis and serum 25-hydroxyvitamin D in children: Influence of sun exposure, diet, and atopy features-A cross-sectional study.

BACKGROUND: Previous studies have linked low serum vitamin D (VD) or 25-hydroxyvitamin D (25(OH)D) levels with increased severity of atopic dermatitis (AD) in children. OBJECTIVE: To investigate the association between serum VD (25(OH)D) levels and AD and AD severity, considering the influence of diet and sun exposure. METHODS: We performed a prospective cross-sectional study of healthy controls and children diagnosed with AD. Participants were recruited between January 2011 and December 2012, and the following parameters were assessed: age, sex, body mass index (BMI), AD severity, Fitzpatrick skin type, asthma and rhinitis history, dietary VD intake, daily potential sun-induced VD production, sunscreen use, 25(OH)D and IgE serum levels, and results of the ImmunoCAP Phadiatop Infant test. RESULTS: The study population consisted of 105 healthy controls and 134 AD patients. Serum 25(OH)D levels were significantly lower in moderate and severe AD than in mild AD, although this association was only significant for patients with light Fitzpatrick skin type (mean(SD) 36.7 (11.9) ng/mL; moderate 28.8 [11.5] ng/mL; and severe 27.6 [12.1] ng/mL, P = .045). Logistic regression analysis revealed a positive association between severe AD and both positive ImmunoCAP Phadiatop test and BMI. CONCLUSION: Our data support an association between VD deficiency and AD severity only in patients with light complexion.

Body mass index and serum lipid profile: Association with atopic dermatitis in a paediatric population.

BACKGROUND/OBJECTIVES: The association between atopic dermatitis, body weight and serum lipid levels is not well known, and very few studies have examined this relationship in children. METHODS: Children (n = 239) under 14 years old participated in this prospective cross-sectional study. The following variables were recorded: age, gender, weight, height, atopic dermatitis severity, serum levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides. RESULTS: Mean body mass index was slightly higher in atopic dermatitis patients than healthy controls and significantly higher in atopic dermatitis patients aged 0-2 years (atopic dermatitis, 16.7 ± 4.6; controls, 15.7 ± 1.3; P = 0.04) and 12-14 years (atopic dermatitis, 24.9 ± 5.3; controls, 20.6 ± 3.4; P = 0.03). Among atopic dermatitis patients, body mass index was significantly higher in those with severe atopic dermatitis in the 9-12 (P = 0.03) and 12-14 (P = 0.01) years groups. Mean serum lipid levels were higher in patients with severe atopic dermatitis than in the atopic dermatitis group as a whole. These differences reached statistical significance for total cholesterol (P = 0.04) and triglycerides (P = 0.02). CONCLUSION: The prevalence of overweight, obesity and dyslipidemia is greater in children with atopic dermatitis than in age-matched healthy counterparts.

Serum lipid responses to weight loss differ between overweight adults with familial hypercholesterolemia and those with familial combined hyperlipidemia.

The effect of weight loss on lipids differs among individuals, although whether it can modify the management of hereditary hyperlipidemias has not yet been explored. The objective of this study was to examine the effect of weight loss on cholesterol metabolism, assessed by circulating noncholesterol sterols, in overweight adults with familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCHL). We conducted a 6-mo weight loss intervention in untreated individuals (FH: n = 28; FCHL: n = 50) with a body mass index of >25 kg/m(2) and mean age of 46.9 ± 11.3 y, of whom 53.8% were men. A hypocaloric diet was implemented and serum lipid analyses, including noncholesterol sterols, were assessed. Global significant mean weight losses of 5.7 kg (-6.6%) and 6.6 kg (-7.6%) were achieved after 3 and 6 mo, respectively. Mean non-HDL cholesterol and triglyceride (TG) changes at 3 and 6 mo compared with baseline were -5.8% (P = 0.004) and -7.1% (P = 0.014), and -30.1% (P < 0.001) and -31.4% (P < 0.001), respectively. Among participants who lost ≥5% body weight, only significant changes in TGs and non-HDL cholesterol were observed in FCHL participants. Sterol precursors of cholesterol synthesis decreased significantly by 10.4% at 6 mo in FCHL participants, mostly because of a 23.9% lathosterol reduction. Baseline synthesis precursors were associated with TG reduction in FCHL participants (P = 0.039; R(2) = 0.20), and intestinally derived sterols were inversely associated with non-HDL cholesterol changes in FH participants (P = 0.036; R(2) = 0.21). Thus, FCHL participants had a better lipid-lowering response to weight loss than did FH participants. This response was positively associated with baseline cholesterol synthesis, which was reduced by weight loss. Our results confirm the cholesterol overproduction mechanism of FCHL and its interaction with fat mass, while also supporting the differential management of familial hyperlipidemias if obesity coexists. This trial was registered at clinicaltrials.gov as NCT01995149.

Influence of triglyceride concentration in lipoprotein (a) as a function of dyslipidemia. / Influencia de la concentración de triglicéridos en la lipoproteína(a) en función de la dislipidemia.

BACKGROUND: Recently, an inverse relationship between the blood concentration of lipoprotein(a) (Lp(a)) and triglycerides (TG) has been demonstrated. The larger the VLDL particle size, the greater the presence of VLDL rich in apoliprotein E and in subjects with the apoE2/E2 genotype, the lower Lp(a) concentration. The mechanism of this inverse association is unknown. The objective of this analysis was to evaluate the Lp(a)-TG association in patients treated at the lipid units included in the registry of the Spanish Society of Atherosclerosis (SEA) by comparing the different dyslipidemias. PATIENTS AND METHODS: Five thousand two hundred and seventy-five subjects ≥18 years of age registered in the registry before March 31, 2023, with Lp(a) concentration data and complete lipid profile information without treatment were included. RESULTS: The mean age was 53.0 ± 14.0 years, with 48% women. The 9.5% of subjects (n = 502) had diabetes and the 22.4% (n = 1184) were obese. The median TG level was 130 mg/dL (IQR 88.0-210) and Lp(a) 55.0 nmol/L (IQR 17.9-156). Lp(a) concentration showed a negative association with TG concentration when TG values exceeded 300 mg/dL. Subjects with TG > 1000 mg/dL showed the lowest level of Lp(a), 17.9 nmol/L, and subjects with TG < 300 mg/dL had a mean Lp(a) concentration of 60.1 nmol/L. In subjects without diabetes or obesity, the inverse association of Lp(a)-TG was especially important (p < 0.001). The median Lp(a) was 58.3 nmol/L in those with TG < 300 mg/dL and 22.0 nmol/L if TG > 1000 mg/dL. No association was found between TG and Lp(a) in subjects with diabetes and obesity, nor in subjects with familial hypercholesterolemia. In subjects with multifactorial combined hyperlipemia with TG < 300 mg/dL, Lp(a) was 64.6 nmol/L; in the range of 300-399 mg/dL of TG, Lp(a) decreased to 38. 8 nmol/L, and up to 22.3 nmol/L when TG > 1000 mg/dL. CONCLUSIONS: Our results show an inverse Lp(a)-TG relationship in TG concentrations > 300 mg/dL in subjects without diabetes, obesity and without familial hypercholesterolemia. Our results suggest that, in those hypertriglyceridemias due to hepatic overproduction of VLDL, the formation of Lp(a) is reduced, unlike those in which the peripheral catabolism of TG-rich lipoproteins is reduced.

SEA 2024 Standards for Global Control of Vascular Risk. / Estándares de la Sociedad Española de Arteriosclerosis 2024 para el control global del riesgo vascular.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to the knowledge, prevention and treatment of vascular diseases, which are the leading cause of death in Spain and entail a high degree of disability and health expenditure. Atherosclerosis is a multifactorial disease and its prevention requires a global approach that takes into account the associated risk factors. This document summarises the current evidence and includes recommendations for patients with established vascular disease or at high vascular risk: it reviews the symptoms and signs to evaluate, the laboratory and imaging procedures to request routinely or in special situations, and includes the estimation of vascular risk, diagnostic criteria for entities that are vascular risk factors, and general and specific recommendations for their treatment. Finally, it presents aspects that are not usually referenced in the literature, such as the organisation of a vascular risk consultation.

State of affairs and future challenges in laboratory medicine in Spain: an analysis of the Spanish Society of Laboratory Medicine (SEQCML).

Objectives: Laboratory Medicine is a crucial discipline that contributes to the diagnosis, management and monitoring of patients. This branch of medicine faces two major challenges: New technologies and increased demand. There is limited information available of the state of affairs in Laboratory Medicine in Spain. This study provides a picture of clinical laboratories and clinical laboratory professionals. Methods: The Spanish Society of Laboratory Medicine distributed a questionnaire among the 250 most representative centers (the ones with the largest volume of determinations and training programs), of which 174 (69.6%) returned the questionnaire providing data for 2019. Results: Laboratories were classified according to the number of determinations. In total, 37% identified themselves as small (<1 million determinations per year); 40% considered themselves medium-sized (1-5 million determinations per year) and 23% considered they were large laboratories (>5 million determinations). The level of specialization of laboratory physicians and laboratory performance were higher in large laboratories. Most requests (87%) and determinations (93%) corresponded to biochemistry and hematology. As many as 63% of physicians had an indefinite contract, and 23% were older than 60 years. Conclusions: Laboratory medicine is a consolidated discipline that is gaining relevance in Spain. It adds value to the diagnosis, prognosis and follow-up of diseases, and to treatment response monitoring. The results of this study will help us address challenges such as the need for specialized training for laboratory professionals; the emergence of technological innovations; exploitation of Big Data; optimization of quality management systems and patient safety.

Triglyceride Metabolism Modifies Lipoprotein(a) Plasma Concentration.

BACKGROUND: Lipoprotein(a) (Lp(a)) is a significant cardiovascular risk factor. Knowing the mechanisms that regulate its concentration can facilitate the development of Lp(a)-lowering drugs. This study analyzes the relationship between triglycerides (TGs) and Lp(a) concentrations, cross-sectionally and longitudinally, and the influence of the number and composition of TG-rich lipoproteins, and the APOE genotype. METHODS: Data from Aragon Workers Health Study (AWHS) (n = 5467), National Health and Nutrition Examination Survey III phase 2 (n = 3860), and Hospital Universitario Miguel Servet (HUMS) (n = 2079) were used for cross-sectional TG and Lp(a) relationship. Lp(a) intrasubject variation was studied in AWHS participants and HUMS patients with repeated measurements. TG-rich lipoproteins were quantified by nuclear magnetic resonance in a subsample from AWHS. Apolipoproteins B and E were quantified by Luminex in very low-density lipoprotein (VLDL) isolated by ultracentrifugation, from HUMS samples. APOE genotyping was carried in AWHS and HUMS participants. Regression models adjusted for age and sex were used to study the association. RESULTS: The 3 studies showed an inverse relationship between TG and Lp(a). Increased VLDL number, size, and TG content were associated with significantly lower Lp(a). There was an inverse association between the apoE concentration in VLDL and Lp(a). No significant association was observed for apolipoprotein (apo)B. Subjects carrying the apoE2/E2 genotype had significantly lower levels of Lp(a). CONCLUSION: Our results show an inverse relationship Lp(a)-TG. Subjects with larger VLDL size have lower Lp(a), and lower values of Lp(a) were present in patients with apoE-rich VLDL and apoE2/E2 subjects. Our results suggest that bigger VLDLs and VLDLs enriched in apoE are inversely involved in Lp(a) plasma concentration.

Effects of an Optimized Aged Garlic Extract on Cardiovascular Disease Risk Factors in Moderate Hypercholesterolemic Subjects: A Randomized, Crossover, Double-Blind, Sustainedand Controlled Study.

The consumption of aged black garlic (ABG) has been related to improvements in several cardiovascular disease (CVD) risk factors. However, the extent of the beneficial effects depends on the garlic aging process and the amount and type of chemical compounds accumulated. The main objective of this study was to assess the effect of daily intake of a well-characterized ABG extract with a standardized S-allyl-L-cysteine (SAC) yield in combination with dietary recommendations regarding CVD risk factors in individuals with moderate hypercholesterolemia. Sixty-seven hypercholesterolemic individuals with low-density lipoprotein cholesterol levels ≥115 mg/dL were randomized in a crossover, double-blind, sustained, and controlled intervention study. The participants consumed 250 mg (1.25 mg SAC)/tablet/day ABG or a placebo for 6 weeks, with 3 weeks of washout. Blood and pulse pressure and other CVD risk biomarkers were determined at the beginning and end of each intervention. At 6 weeks, ABG extract reduced diastolic blood pressure (DBP) (mean (95% CI) −5.85 (−10.5; −1.3) mm Hg) compared to the placebo, particularly in men with a DBP > 75 mm Hg. The consumption of an improved ABG extract with 1.25 mg of SAC decreased DBP, particularly in men with moderate hypercholesterolemia. The potential beneficial effects of ABG may contribute to obtaining an optimal DBP.

Functional analysis of LDLR promoter and 5' UTR mutations in subjects with clinical diagnosis of familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is a dominant disorder due to mutations in the LDLR gene. Several mutations in the LDLR promoter are associated with FH. Screening of 3,705 Spanish FH patients identified 10 variants in the promoter and 5' UTR. Here, we analyse the functionality of six newly identified LDLR variants. Mutations located in the LDLR promoter regulatory elements R2 and R3 (c.-155_-150delACCCCinsTTCTGCAAACTCCTCCC, c.-136C>G, c.-140C>G, and c.-140C>T) resulted in 6 to 15% residual activity in reporter expression experiments and changes in nuclear protein binding affinity compared to wild type. No reduction was observed when cells were transfected with c.-208T, c.-88A, and c.-36G mutant fragments. Our results indicate that mutations localized in R2 and R3 are associated with hypercholesterolemia, whereas mutations outside the LDLR response elements are not a cause of FH. This data emphasizes the importance of functional analysis of variants in the LDLR promoter to determine their association with the FH phenotype.

Cataract Surgery in Elderly Subjects with Heterozygous Familial Hypercholesterolemia in Prolonged Treatment with Statins.

BACKGROUND: Cataracts are the main cause of blindness and represent one fifth of visual problems worldwide. It is still unknown whether prolonged statin treatment favors the development of cataracts. We aimed to ascertain the prevalence of cataract surgery in elderly subjects with genetically diagnosed heterozygous familial hypercholesterolemia (HeFH) receiving statin treatment for ≥5 years, and compare this with controls. METHODS: This is an observational, multicenter, case-control study from five lipid clinics in Spain. We collected data with the following inclusion criteria: age ≥65 years, LDL cholesterol levels ≥220 mg/dL without lipid-lowering drugs, a pathogenic mutation in a candidate gene for HeFH (LDLR, APOB, or PCSK9) and statin treatment for ≥5 years. Controls were selected from relatives of HeFH patients without hypercholesterolemia. Linear and logistic regressions based on generalized linear models and generalized estimating equations (GEE) were used. Cataract surgery was used as a proxy for cataract development. RESULTS: We analyzed 205 subjects, 112 HeFH, and 93 controls, with a mean age of 71.8 (6.5) and 70.0 (7.3) years, respectively. HeFH subjects presented no difference in clinical characteristics, including smoking, hypertension, and type 2 diabetes mellitus, compared with controls. The mean duration of lipid-lowering treatment in HeFH was 22.5 (8.7) years. Cataract surgery prevalence was not significantly different between cases and controls. The presence of cataracts was associated neither with LDLc nor with the length of the statin therapy. CONCLUSION: In the present study, HeFH was not a risk factor for cataract surgery and prolonged statin treatment did not favor it either. These findings suggest that statin treatment is not related with cataracts.

Consensus document of an expert group from the Spanish Society of Arteriosclerosis (SEA) on the clinical use of nuclear magnetic resonance to assess lipoprotein metabolism (Liposcale®). / Documento de consenso de un grupo de expertos de la Sociedad Española de Arteriosclerosis (SEA) sobre el uso clínico de la resonancia magnética nuclear en el estudio del metabolismo lipoproteico (Liposcale).

The assessment and prevention of cardiovascular risk (CVR) that persists in patients with dyslipidaemia despite treatment and achievement of goals specific to the plasma concentration of cholesterol linked to low density (c-LDL) is a clinical challenge today, and suggests that conventional lipid biomarkers are insufficient for an accurate assessment of CVR. Apart from their lipid content, there are other lipid particle characteristics. The results of this study show that there are a number of lipoprotein compounds that determine atherogenic potential and its influence on the CVR. However, such additional characteristics cannot be analysed by the techniques commonly used in clinical laboratories. Nuclear Magnetic Resonance (NMR) is a technique that allows a detailed analysis to be made of the amount, composition, and size of lipoproteins, as well as providing more information about the detailed status of lipid metabolism and CVR in dyslipidaemia patients. In this article a group of lipidologists from the Spanish Society of Arteriosclerosis review the existing evidence on the atherogenic mechanisms of particles and describe the technical basis and interpretation of the profiles lipoproteins obtained by MRI, with special reference to the test available in Spain (Liposcale®). Likewise, the main patient profiles are defined as such that an analysis would provide information of greater clinical interest. These include: a) Suspected mismatch between lipid concentrations and particles, a common situation in diabetes, obesity, metabolic syndrome; b) Early atherothrombotic cardiovascular disease (ECVA) or recurrent without CVR factors to justify it; c) Lipid disorders, rare or complex, such as extreme concentrations of c-HDL, and d) Clinical situations where classical analytical techniques cannot be applied, such as very low c-LDL values.

Aortic Valvular Disease in Elderly Subjects with Heterozygous Familial Hypercholesterolemia: Impact of Lipid-Lowering Therapy.

Hypercholesterolemia and statins are risk factors for aortic stenosis (AS) and vascular calcification, respectively. Whether heterozygous subjects with familial hypercholesterolemia (HeFH) treated with statins are at risk of AS is unknown. We study the prevalence of AS, aortic valve calcification (AoVC), and aortic sclerosis (ASc) in elderly subjects with HeFH in a prolonged statin treatment. Case-control study, cases were adults ≥65 years of age with a genetic diagnosis of HeFH, LDLc >220 mg/dl, and statin treatment ≥5 years. Controls were relatives of HeFH patients, with LDLc <190 mg/dl. Participants underwent a cardiac ultrasound for aortic valve analysis. We studied 205 subjects, 112 HeFH and 93 controls, with mean age 71.8(6.5) years and 70.0(7.3) years, respectively. HeHF, with respect to controls, presented greater gradients of aortic transvalvular pressure, 7.4(7.3) mmHg versus 5.0(2.8) mmHg, and maximum aortic velocity, 1.7(0.7) m/s versus 1.5(0.4) m/s, and lower aortic valve opening area, 2.0(0.7) cm2 versus 2.4(0.6) cm2 (all p < 0.05). AoVC and ASc were also more prevalent in HeFH (p < 0.05 between groups). Moderate/severe AS prevalence was higher among HeFH: 7.1% versus 1.1% (age- and sex-adjusted odds ratio (OR) 8.33, p = 0.03). Independent risk factors for aortic valve disease in HeFH were age and LDLc before treatment. The number of years under statin treatment was not associated with any aortic valve measurement. Subjects ≥65 years with HeFH in prolonged statin treatment show more aortic valvular disease and higher frequency of AS than controls. Life-long elevated LDLc exposure, rather than time of exposure to statins, explains this higher risk.

Serum chitotriosidase activity, a marker of activated macrophages, predicts new cardiovascular events independently of C-reactive protein.

BACKGROUND: C-reactive protein (CRP) is a well-established inflammation marker associated with cardiovascular risk. However, its relationship with chitotriosidase activity, a novel marker of activated macrophages highly expressed in human atherosclerotic plaques, is unknown. Therefore, we sought to determine if serum chitotriosidase activity predicts the risk of new coronary events, and to analyze its relationship with CRP. METHODS: Chitotriosidase activity and genotype, and high-sensitivity CRP were measured at baseline in 133 middle-aged men with stable coronary heart disease, who were followed for the occurrence of cardiovascular morbidity and mortality for a mean of 4 years. We studied the value of these proteins in predicting the risk of new cardiovascular events. RESULTS: Serum chitotriosidase activity was higher in the group of subjects with a prespecified major event (nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization procedures and death from cardiovascular causes) than in the group of subjects without event, 116 +/- 30.9 nmol/ml x h versus 74.2 +/- 5.69 nmol/ml x h, respectively (p = 0.042). The baseline values of chitotriosidase activity and CRP did not correlate (R = 0.104, p = 0.266), but both parameters were related to a reduction of event-free survival in the Cox regression analysis, with relative risks of 2.61 (p = 0.060) and 2.56 (p = 0.019), respectively. Chitotriosidase activity seems to be a better marker for new events occurring after 2 years of follow-up than in the first 2 years. Both markers had similar predictive values, and their sensitivity (64%) and negative predictive value (84%) were improved when combined. CONCLUSIONS: Our results suggest that serum chitotriosidase activity predicts the risk of new cardiovascular events in the following 4 years. This new cardiovascular risk marker is independent of CRP and, when combined, the prediction of the risk of new cardiovascular events and the identification of a lower risk group seem to improve.

Effect of LDL cholesterol, statins and presence of mutations on the prevalence of type 2 diabetes in heterozygous familial hypercholesterolemia.

Patients with heterozygous familial hypercholesterolemia (HeFH) have been reported to be less vulnerable to type 2 diabetes mellitus (T2DM), although the mechanism is unknown. The aims of the present study were to assess the effects of low density lipoprotein (LDL) cholesterol concentration and the presence of FH-causing mutations on T2DM prevalence in HeFH. Data were collected from the Dyslipidemia Registry of the Spanish Arteriosclerosis Society. Inclusion criteria were definite or probable HeFH in patients aged ≥18 years. T2DM prevalence in HeFH patients was compared with data of the general population. 1732 patients were included. The prevalence of T2DM was lower in patients with HeFH compared with the general population (5.94% vs 9.44%; OR: 0.606, 95% CI 0.486-0.755, p < 0.001). Risk factors for developing T2DM were male sex, age, body mass index, hypertension, baseline triglyceride levels and years on statin therapy. The prevalence of T2DM in HeFH patients was 40% lower than that observed in the general population. Gene mutations and LDL cholesterol concentrations were not risk factors associated with the prevalence of T2DM in patients with HeFH. The prevalence of T2DM in patients with HeFH was 40% lower than in the general population matched for age and sex.

[Sociodemographic factors associated with adherence to the Mediterranean dietary pattern in elderly people]. / Factores sociodemográficos asociados con el grado de adherencia al patrón de dieta mediterránea en personas mayores.

OBJECTIVE: To assess the level of adherence to the Mediterranean dietary pattern (DMedit) in people over 65 in rural and urban areas of the region of Hoya de Huesca (Spain) and investigate whether there are sociodemographic factors related to that adherence. MATERIAL AND METHODS: Exploratory cross-sectional study. Two questionnaires were used: one self-made for sociodemographic factors, and the PREDIMED validated questionnaire to assess the level of adherence to the DMedit. After prior informed consent, a total of 240 questionnaires were collected over a period of 2 consecutive weeks in March 2014. RESULTS: The mean age was 74±6.8 years, with an equal proportion of rural and urban areas and both sexes. Both populations showed a similar adherence pattern to Dmedit, with an average overall score of 9 on a scale of 0 to 14. Furthermore, the influence of sociodemographic factors was observed on the level of adherence to the Dmedit, such as purchasing power or presence of chronic diet-related diseases. CONCLUSIONS: The urban and rural population of the Hoya de Huesca seems to have a good adherence to the Dmedit, although some economic and health factors could modify it.

Genetic Variants of LDLR and PCSK9 Associated with Variations in Response to Antihypercholesterolemic Effects of Armolipid Plus with Berberine.

BACKGROUND: Armolipid Plus (AP) is a nutraceutical that contains policosanol, fermented rice with red yeast, berberine, coenzyme Q10, folic acid, and astaxanthin. It has been shown to be effective in reducing plasma LDL cholesterol (LDLc) levels. In the multicenter randomized trial NCT01562080, there was large interindividual variability in the plasma LDLc response to AP supplementation. We hypothesized that the variability in LDLc response to AP supplementation may be linked to LDLR and PCSK9 polymorphisms. MATERIAL AND METHODS: We sequenced the LDLR 3' and 5' untranslated regions (UTR) and the PCSK9 5' UTR of 102 participants with moderate hypercholesterolemia in trial NCT01562080. In this trial, 50 individuals were treated with AP supplementation and the rest with placebo. RESULTS: Multiple linear regression analysis, using the response of LDLc levels to AP as the dependent variable, revealed that polymorphisms rs2149041 (c.-3383C>G) in the PCSK9 5' UTR and rs14158 (c.*52G>A) in the LDLR 3' UTR explained 14.1% and 6.4%, respectively, of the variability after adjusting for gender, age, and BMI of individuals. Combining polymorphisms rs2149041 and rs14158 explained 20.5% of this variability (p < 0.004). CONCLUSIONS: Three polymorphisms in the 3' UTR region of LDLR, c.*52G>A, c.*504G>A, and c.*773A>G, and two at the 5' UTR region of PCSK9, c.-3383C>G and c.-2063A>G, were associated with response to AP. These results could explain the variability observed in the response to berberine among people with moderate hypercholesterolemia, and they may be useful in identifying patients who could potentially benefit from supplementation with AP.

Serum chitotriosidase activity is increased in subjects with atherosclerosis disease.

OBJECTIVE: This study was undertaken to analyze the relation between serum activity of chitotriosidase enzyme, a protein synthesized exclusively by activated macrophages, and atherosclerotic lesion extent in subjects with atherothrombotic stroke (ATS) and in subjects with ischemic heart disease (IHD). METHODS AND RESULTS: We assayed the serum chitotriosidase activity and a common chitotriosidase gene polymorphism that causes deficiency in chitotriosidase activity in 3 Spanish populations, ATS (n=153), IHD (n=124), and control (n=148) subjects. Statistical differences were found in serum chitotriosidase activity between ATS (88.1+/-4.6 nmol/mL. h, P<0.0001) and IHD subjects (79.0+/-6.3, P=0.002) versus control group (70.9+/-5.2). These observed differences were not attributable to a distinct allelic or genotype distribution. The extension of the atherosclerotic lesion in carotids of ATS subjects was measured by duplex sonography. Chitotriosidase activities were 66.9+/-9.6, 88.7+/-8.3, and 107.7+/-11.8 for subjects with carotid stenosis 60%, respectively. Statistical differences were observed between subjects with major and intermediate stenosis grade compared with subjects with minor stenosis, P=0.005 and P=0.016, respectively. CONCLUSIONS: Serum chitotriosidase activity is significantly increased in individuals suffering from atherosclerosis disease and is related to the severity of the atherosclerotic lesion, suggesting a possible role as atherosclerotic extent marker.