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The main objective of this study was to determine plasma levels of PS and to study SNVs rs41360247, rs4245791, rs4148217, and rs11887534 of ABCG8 and the r657152 SNV at the ABO blood group locus in a sample of a population treated at our hospital, and to determine whether these SNVs are related to plasma PS concentrations. The secondary objective was to establish the variables associated with plasma PS concentrations in adults. Participants completed a dietary habit questionnaire and a blood sample was collected to obtain the following variables: campesterol, sitosterol, sitostanol, lanosterol, stigmasterol, biochemical parameters, and the SNVs. In addition, biometric and demographic variables were also recorded. In the generalized linear model, cholesterol and age were positively associated with total PS levels, while BMI was negatively related. For rs4245791, homozygous T allele individuals showed a significantly lower campesterol concentration compared with C homozygotes, and the GG alleles of rs657152 had the lowest levels of campesterol compared with the other alleles of the SNV. Conclusions: The screening of certain SNVs could help prevent the increase in plasma PS and maybe PNALD in some patients. However, further studies on the determinants of plasma phytosterol concentrations are needed.

The burden of depression is increasing worldwide, specifically in older adults. Unhealthy dietary patterns may partly explain this phenomenon. In the Spanish PREDIMED-Plus study, we explored (1) the cross-sectional association between the adherence to the Prime Diet Quality Score (PDQS), an a priori-defined high-quality food pattern, and the prevalence of depressive symptoms at baseline (cross-sectional analysis) and (2) the prospective association of baseline PDQS with changes in depressive symptomatology after 2 years of follow-up. After exclusions, we assessed 6612 participants in the cross-sectional analysis and 5523 participants in the prospective analysis. An energy-adjusted high-quality dietary score (PDQS) was assessed using a validated FFQ. The cross-sectional association between PDQS and the prevalence of depression or presence of depressive symptoms and the prospective changes in depressive symptoms were evaluated through multivariable regression models (logistic and linear models and mixed linear-effects models). PDQS was inversely associated with depressive status in the cross-sectional analysis. Participants in the highest quintile of PDQS (Q5) showed a significantly reduced odds of depression prevalence as compared to participants in the lowest quartile of PDQS (Q1) (OR (95 %) CI = 0·82 (0·68, 0·98))). The baseline prevalence of depression decreased across PDQS quintiles ( P for trend = 0·015). A statistically significant association between PDQS and changes in depressive symptoms after 2-years follow-up was found ( β (95 %) CI = -0·67 z-score (-1·17, -0·18). A higher PDQS was cross-sectionally related to a lower depressive status. Nevertheless, the null finding in our prospective analysis raises the possibility of reverse causality. Further prospective investigation is required to ascertain the association between PDQS and changes in depressive symptoms along time.

Aim: Both apical periodontitis (AP) and metabolic syndrome (MetS) are associated with atherosclerotic cardiovascular disease (ACVD), the main cause of cardiovascular events. The aim of this study was to investigate the prevalence of AP and the oral inflammatory burden in control subjects and patients suffering cardiovascular events, analyzing the possible association between AP and the oral inflammatory burden with MetS., Materials and Methods: Using a cross-sectional design, 83 patients suffering a cardiovascular event were recruited in the study group (SG), and 48 patients without cardiovascular events were included in the control group (CG). Periapical index (PAI) was used to diagnose AP, and total dental index (TDI) was used to assess the total oral inflammatory burden. Diagnosis of MetS was made by meeting three or more American Heart Association Scientific Statement components., Results: In the multivariate logistic regression analysis, the number of teeth with AP (OR = 2.3; 95% C.I. = 1.3-4.3; p = 0.006) and TDI scores (OR = 1.5; 95% C.I. = 1.2-1.9; p = 0.001), significantly correlated with cardiovascular events. MetS was strongly associated (OR = 18.0; 95% C.I. = 6.5-49.7; p = 0000) with cardiovascular events. Higher TDI scores were significantly associated with MetS (OR = 1.3; 95% C.I. = 1.1-1.6; p = 0.003. Neither the number of root-filled teeth (RFT) (OR = 0.9; 95% C.I. = 0.6-1.3; p = 0.61) nor the number of teeth with apical periodontitis (OR = 1.1; 95% C.I. = 0.8-1.7; p = 0.49) were associated with MetS., Conclusions: Apical periodontitis is significantly associated with cardiovascular events. Total oral inflammatory burden assessed by TDI, but not AP alone, is associated with MetS.

Background: LDL-C lowering is the main measure in cardiovascular disease prevention but a residual risk of ischemic events still remains. Alterations of lipoproteins, specially, increase in small dense LDL (sdLDL) particles are related to this risk., Objective: To investigate the potential use of sdLDL cholesterol concentration (sdLDL-C) isolated by an easy precipitation method and to assess the impact of a set of clinical and biochemical variables determined by NMR on sdLDL concentration., Methods: sdLDL-C and NMR lipid profile were performed in 85 men samples. Association among them was evaluated using Pearson coefficients (r xy ). A multivariate regression was performed to identify the influence of NMR variables on sdLDL-C., Results: A strong association between sdLDL-C and LDLLDL-P (r xy  = 0.687) and with LDL-Z (r xy  = -0.603) was found. The multivariate regression explained a 56.8% in sdLDL-C variation (P = 8.77.10-12). BMI, ApoB, triglycerides, FFA, and LDL-Z showed a significant contribution. The most important ones were ApoB and LDL-Z; a 1nm increase (LDL-Z) leads to decrease 126 nmol/L in sdLDL-C., Conclusion: The association between sdLDL-C, LDL-Z, and LDL-P is clear. From a large number of variables, especially LDL-Z and apoB influence on sdLDL-C. Results show that the smaller the LDL size, the higher their cholesterol concentration. Therefore, sdLDL-C determination by using this easy method would be useful to risk stratification and to uncover cardiovascular residual risk., (© 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

Statin therapy response is highly variable. Variants of lipid metabolism genes and statin pharmacokinetic modulators could play a role, however, the impact of most of these variants remains unconfirmed. A prospective and multicenter study included 252 patients was carried out in order to assess, according to achievement of LDL-C or non-HDL-C therapeutic targets and quantitative changes in lipid profiles, the impact of CETP, ABCA1, CYP2D6, and CYP2C9 gene candidate variants on the simvastatin, atorvastatin, and rosuvastatin response. Patients carrier ABCA1 rs2230806 and CYP2D6*3 variants are less likely to achieve therapeutic lipid targets (p = 0.020, OR = 0.59 [0.37, 0.93]; p = 0.040, OR = 0.23 [0.05, 0.93], respectively). Among CETP variants, rs708272 was linked to a 10.56% smaller reduction in LDL-C with rosuvastatin (95% CI = [1.27, 19.86] %; p = 0.028). In contrast, carriers of rs5882 had a 13.33% greater reduction in LDL-C (95% CI = [25.38, 1.28]; p = 0.032). If these findings are confirmed, ABCA1, CYP2D6, and CETP genotyping could be used to help predict which statin and dosage is appropriate in order to improve personalized medicine.

Background and Aims: Periodontal disease (PD) is believed to be associated with cardiovascular disease (CVD) events. Nevertheless, the additive prognostic value of PD for the prediction of CVD events beyond traditional risk factors is unclear, particularly when self-reported using a short questionnaire., Methods: In the community-based, multicenter, prospective, Multi-Ethnic Study of Atherosclerosis (MESA), PD was assessed at baseline using a two-item questionnaire. We used Cox proportional hazards regression models to evaluate the independent associations between self-reported PD and coronary heart disease (CHD), CVD events, and all-cause death. In addition, the area under the receiver-operator characteristic curve (AUC) was calculated for each of the study endpoints, for models including traditional CVD risk factors alone and models including traditional CVD risk factors plus information on PD. Subgroup analyses were performed stratifying by age and tobacco use., Results: Among the 6640 MESA participants, high education level, high income, and access to healthcare were more frequent among individuals who self-reported PD. In multivariable analyses, null associations were observed between self-reported PD and incident CVD events, CHD events, and all-cause mortality; and self-reported PD did not improve risk prediction beyond traditional CVD risk factors in terms of AUC, for any of the three study endpoints. Subgroup analyses were consistent with the overall results., Conclusions: Our findings suggest that the prevalence of self-reported PD may be strongly influenced by educational status and other socioeconomic features. In this context, self-reported PD does not improve CVD risk assessment when evaluated using a brief questionnaire. Future studies should prioritize objective, dental health-expert assessments of PD., (Copyright © 2018. Published by Elsevier B.V.)

Introduction: The therapeutic response to statins has a high interindividual variability with respect to reductions in plasma LDL-cholesterol (c-LDL) and increases in HDL cholesterol (c-HDL). Many studies suggest that there is a relationship between the rs20455 KIF6 gene variant (c.2155T> C, Trp719Arg) and a lower risk of cardiovascular disease in patients being treated with statins., Aim: The aim of this study was to investigate whether or not the c.2155T> C KIF6 gene variant modulates the hypercholesteremic effects of treatment with simvastatin, atorvastatin, or rosuvastatin., Materials and Methods: This was a prospective, observational and multicenter study. Three hundred and forty-four patients who had not undergone prior lipid-lowering treatment were recruited. Simvastatin, atorvastatin or rosuvastatin were administered. Lipid profiles and multiple clinical and biochemical variables were assessed before and after treatment., Results: The c.2155T> C variant of the KIF6 gene was shown to influence physiological responses to treatment with simvastatin and atorvastatin. Patients who were homozygous for the c.2155T> C variant (CC genotype, ArgArg) had a 7.0% smaller reduction of LDL cholesterol levels (p = 0.015) in response to hypolipidemic treatment compared to patients with the TT (TrpTrp) or CT (TrpArg) genotype. After pharmacological treatment with rosuvastatin, patients carrying the genetic variant had an increase in c-HDL that was 21.9% lower compared to patients who did not carry the variant (p = 0.008)., Conclusion: Being a carrier of the c.2155T> C variant of the KIF6 gene negatively impacts patient responses to simvastatin, atorvastatin or rosuvastatin in terms of lipid lowering effect. Increasing the intensity of hypolipidemic therapy may be advisable for patients who are positive for the c.2155T> C variant., Competing Interests: The authors have declared that no competing interests exist.

A consensus document of the Diabetes working group of the Spanish Society of Arteriosclerosis (SEA) is presented, based on the latest studies and conceptual changes that have appeared. It presents the cardiovascular risk in type 2 diabetes mellitus (T2DM) and the action guidelines for the prevention and treatment of cardiovascular disease (CVD) associated with T2DM. The importance of lipid control, based on the objective of LDL-C and non-HDL-C when there is hypertriglyceridemia, and the blood pressure control in the prevention and treatment of CVD is evaluated. The new hypoglycemic drugs and their effects on CVD are reviewed, as well as the treatment and control guidelines of hyperglycemia. Likewise, the use of antiplatelet agents is considered. Emphasis is placed on the importance of global and simultaneous action on all risk factors to achieve a significant reduction in cardiovascular events. This supplement is sponsored by Laboratorios Esteve, S.A., (Copyright © 2018 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Objective: The relationship between atherothrombotic cardiovascular disease (ATCD) and localised infections in teeth, including caries and chronic apical periodontitis (CAP) has not been studied much and is not well defined., Method: A systematic search was performed using the scientific databases PubMed and Medline from 1989 to 2016., Results: A significant relationship was observed with ATCD in 10 out of 10 studies addressing the degree of oral hygiene, in 14 of 17 that included loss of teeth, in 6 of 12 that analysed caries and in 11 of 15 that included CAP. However, there was a huge methodological heterogeneity., Conclusions: It can be concluded that there is an association between CAP and ATCD. Patients with ATCD present a worse oral hygiene status and fewer teeth., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Background: High serum concentrations of small dense low-density lipoprotein cholesterol (sd-LDL-c) particles are associated with risk of cardiovascular disease (CVD). Their clinical application has been hindered as a consequence of the laborious current method used for their quantification., Objective: Optimize a simple and fast precipitation method to isolate sd-LDL particles and establish a reference interval in a Mediterranean population., Materials and Methods: Forty-five serum samples were collected, and sd-LDL particles were isolated using a modified heparin-Mg 2+ precipitation method. sd-LDL-c concentration was calculated by subtracting high-density lipoprotein cholesterol (HDL-c) from the total cholesterol measured in the supernatant. This method was compared with the reference method (ultracentrifugation). Reference values were estimated according to the Clinical and Laboratory Standards Institute and The International Federation of Clinical Chemistry and Laboratory Medicine recommendations. sd-LDL-c concentration was measured in serums from 79 subjects with no lipid metabolism abnormalities., Results: The Passing-Bablok regression equation is y = 1.52 (0.72 to 1.73) + 0.07 x (-0.1 to 0.13), demonstrating no significant statistical differences between the modified precipitation method and the ultracentrifugation reference method. Similarly, no differences were detected when considering only sd-LDL-c from dyslipidemic patients, since the modifications added to the precipitation method facilitated the proper sedimentation of triglycerides and other lipoproteins. The reference interval for sd-LDL-c concentration estimated in a Mediterranean population was 0.04-0.47 mmol/L., Conclusion: An optimization of the heparin-Mg 2+ precipitation method for sd-LDL particle isolation was performed, and reference intervals were established in a Spanish Mediterranean population. Measured values were equivalent to those obtained with the reference method, assuring its clinical application when tested in both normolipidemic and dyslipidemic subjects., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Introduction and Objectives: Despite the recognized clinical benefit of statins on cardiovascular prevention, providing correct management of hypercholesterolaemia, possible adverse effects of their use cannot be disregarded. Previously published data shows that there is a risk of developing diabetes mellitus or experiencing changes in glucose metabolism in statin-treated patients. The possible determining factors are the drug characteristics (potency, dose), patient characteristics (kidney function, age, cardiovascular risk and polypharmacy because of multiple disorders) and the pre-diabetic state., Methods: In order to ascertain the opinion of the experts (primary care physicians and other specialists with experience in the management of this type of patient) we conducted a Delphi study to evaluate the consensus rate on diverse aspects related to the diabetogenicity of different statins, and the factors that influence their choice., Results: Consensus was highly significant concerning aspects such as the varying diabetogenicity profiles of different statins, as some of them do not significantly worsen glucose metabolism. There was an almost unanimous consensus that pitavastatin is the safest statin in this regard., Conclusions: Factors to consider in the choice of a statin regarding its diabetogenicity are the dose and patient-related factors: age, cardiovascular risk, diabetes risk and baseline metabolic parameters (which must be monitored during the treatment), as well as kidney function.

Background: The APOE Christchurch (APOECh) is a rare variant (c.543C>A) in codon 154. It was first described in an E2 patient with type III dyslipidemia, and thus initially called E2Ch. Its prevalence and the lipid profile of carriers remain unclear., Methods: E2, E3, and E4 screening for the APOE gene was performed by PCR-RFLP. The rare APOECh variant was firstly found after detecting an unexpected 109 base-pair band in the high-resolution agarose gel electrophoresis leading to a genotype misinterpretation: the presence of APOECh alters the restriction-bands pattern. To confirm the Ch variant, a second PCR-RFLP method was specifically designed to detect this variant and Sanger sequencing was also performed for all positive samples., Results: We identified 12 unrelated subjects for the APOECh among a cohort of 2,560 patients: nine E3/E3Ch, two E3Ch/E4, and one E2/E3Ch or E2Ch/E3. The frequency of the variant is 0.4% in our study population, which represents the highest percentage published so far. If there is a 109 bp band, it is easy to recognize the presence of the variant. However, in APOE routine genotyping, an E4Ch allele is indistinguishable from a standard E3. Therefore, E4Ch alleles might be underrepresented in the results., Conclusion: We recommend APOE exon 4 sequencing to unequivocally detect the common three variants E2, E3, and E4 and the rare variants as well, to find out the real role they play in atherosclerosis and to estimate its real frequency which is nowadays unclear, in part by the small number of cases identified., (© 2016 Wiley Periodicals, Inc.)

Background and Objectives: This post hoc study analysed the perception of the relevance of chronic kidney disease (CKD) in dyslipidaemia screening and the choice of statin among primary care physicians (PCPs) and other specialists through a Delphi questionnaire., Methods: The questionnaire included 4blocks of questions concerning dyslipidaemic patients with impaired carbohydrate metabolism. This study presents the results of the impact of CKD on screening and the choice of statin., Results: Of the 497 experts included, 58% were PCPs and 42% were specialists (35, 7% were nephrologists). There was consensus by both PCPs and specialists, with no difference between PCPs and specialists, that CKD patients should undergo a dyslipidaemia screening and that the screening should be part of routine clinical practice. However, there was no consensus in considering the estimated glomerular filtration rate (eGFR) (although there was consensus among PCPs and nephrologists), or considering albuminuria when selecting a statin, or in determining albuminuria during follow-up after having initiated treatment with statins (although there was consensus among the nephrologists)., Conclusions: The consensus to analyse the lipid profile in CKD patients suggests acknowledgment of the high cardiovascular risk of this condition. However, the lack of consensus in considering renal function or albuminuria, both when selecting a statin and during follow-up, suggests a limited knowledge of the differences between statins in relation to CKD. Thus, it would be advisable to develop a guideline/consensus document on the use of statins in CKD., (Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Statins are the cornerstone of cardiovascular prevention for general population, and in patients with type 2 diabetes mellitus (T2DM). However, statin therapy predisposes to type 2 diabetes, particularly in patients with predisposition to this condition. Some statins have been associated with increases in blood glucose in patients with or without DM2, and others have shown to have neutral effects, varying from one another their glucose or diabetogenic capacity. In many statin trials the incidence of DM2 has not been systematically evaluated and others the power to detect differences between statins is lacking. Evidence highest quality available comes from the meta-analysis of controlled clinical trials. The only controlled clinical trial to evaluate the incidence of new-onset T2DM is the J-PREDICT conducted with pitavastatin in patients with abnormal glucose tolerance. Preliminary results of this study show that pitavastatin is associated with a significant decrease in the incidence of de novo T2DM compared to only modification lifestyle. Therefore, pitavastatin may be an appropriate therapeutic alternative of choice to reduce vascular risk in patients with T2DM or at risk of presenting it., (Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.)

Pandemics of metabolic síndrome, obesity, and type 2 diabetes is a major challenge for the next years and supported the grat burden of cardiovascular diseases. The R3i (Residual Risk Reduction initiative) has previously highlighted atherogenic dyslipidaemia as an important and modifiable contributor to the lipid related residual cardiovascular risk. Atherogenic dyslipidaemia is defined as an imbalance between proatherogenic triglycerides-rich apoB-containing lipoproteins and antiatherogenic AI containing lipoproteins. To improve clinical management of atherogenic dyslipidaemia a despite of lifestyle intervention includes pharmacological approach, and fibrates is the main option for combination with a statin to further reduce non-HDL cholesterol., (Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.)

Introduction: Evaluating the therapeutical adherence as well as the patient' satisfaction with the treatment should be considered to optimize lipidic control. The REINA Study evaluates the grade of satisfaction in dyslipidemic patients treated with pitavastatin., Methods: The current study was observational, descriptive, transversal and multi-centric with patients from our country only. The following data were collected in each case: Morisky-Green test and TSQM-9 for patients older than 18 years old, with dyslipidemia treated with pitavastatin in the last 12 weeks., Results: We studied 6,489 patients (60.0% males) from Primary Health (52.7%) and Specialised Health (47.3%), with age (mean) = 60.9 ± 11.2 years by aleatory sampling. 72.3% of patients achieved an adequate control with 2mg/day of pitavastatin. General satisfaction with the treatment was 73.20 points (95% CI: 58.17-87.23). Patients who followed the treatment (65%) showed better data of satisfaction with the drug (77.70 [95% CI: 65.20-90.20]), of global satisfaction (75.00 [95% CI: 61.50-88.50]) and their satisfaction with the drug efficiency was higher (72.50 [95% CI: 57.70-87.30]) than in the patients who did not finish the treatment (72.70 [95% CI: 59.30-85.74]; 68.5 [95% CI: 53.20-83.80] and 67.80 [95% CI: 53.70-81.90], respectively), P < .0001, without any difference between the two primary care systems., Conclusions: The validation of the satisfaction is a crucial indicator in the evaluation of the services offered in health. Patients with the highest grade of satisfaction present better therapeutical adherence, and such a relation is bidirectional. The individuals who are satisfied and who followed the treatment obtained better clinical results. Pitavastatin is an effective therapeutic alternative for patients with dyslipidemia., (Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.)

Introduction and Objectives: Although atherogenic dyslipidemia is a recognized cardiovascular risk factor, it is often underassessed and thus undertreated and poorly controlled in clinical practice. The objective of this study was to reach a multidisciplinary consensus for the establishment of a set of clinical recommendations on atherogenic dyslipidemia to optimize its prevention, early detection, diagnostic evaluation, therapeutic approach, and follow-up., Methods: After a review of the scientific evidence, a scientific committee formulated 87 recommendations related to atherogenic dyslipidemia, which were grouped into 5 subject areas: general concepts (10 items), impact and epidemiology (4 items), cardiovascular risk (32 items), detection and diagnosis (19 items), and treatment (22 items). A 2-round modified Delphi method was conducted to compare the opinions of a panel of 65 specialists in cardiology (23%), endocrinology (24.6%), family medicine (27.7%), and internal medicine (24.6%) on these issues., Results: After the first round, the panel reached consensus on 65 of the 87 items discussed, and agreed on 76 items by the end of the second round. Insufficient consensus was reached on 3 items related to the detection and diagnosis of atherogenic dyslipidemia and 3 items related to the therapeutic goals to be achieved in these patients., Conclusions: The external assessment conducted by experts on atherogenic dyslipidemia showed a high level of professional agreement with the proposed clinical recommendations. These recommendations represent a useful tool for improving the clinical management of patients with atherogenic dyslipidemia. A detailed analysis of the current scientific evidence is required for those statements that eluded consensus., (Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.)

Background: Factors related to hyperhomocystinemia in the pediatric population of our geographical area with a parental history of premature coronary disease (PCD) are not well known., Objectives: To evaluate the possible association between plasma total homocysteine (tHcy), the B vitamins involved in its metabolism (folate, vitamin B12 and B6), and 677C T polymorphism of methylenetetrahydrofolate reductase (MTHFR) in a group of children with a parental history of PCD., Methods: A cross-sectional analytical study of 80 children (aged 5-18 years old) with a parental history of PCD was performed. Values found in these children were compared with reference values for similar age groups. Plasma tHcy and vitamin B6 were evaluated by high-performance liquid chromatography with fluorometric detection. Folate and vitamin B12 concentrations were determined by radioimmunoassay. Detection of 677C T polymorphism of MTHFR was performed using polymerase chain reaction amplification and Hinfl digestion. Statistical analysis was performed using the SPSS program, version 10.0. Concentrations of tHcy and vitamins were compared using the Mann-Whitney U-test and Spearman's correlation coefficient. The association between phenotype, hyperhomocystinemia and low vitamin concentrations was analyzed using the chi-squared test. ResultsPlasma tHcy values in the children aged more than 10 years with a parental history of PCD were significantly higher (p < 0.001) than the reference values. Vitamin B12 levels were significantly lower (p 0.015), but neither folate nor vitamin B6 levels differed from the reference values. A negative correlation (p < 0.0001) was observed between tHcy and folate (r 0.47) and between tHcy and vitamin B12 levels (r 0.51). Eighty percent of the children with the TT genotype of MTHFR showed hyperhomocystinemia. Suboptimal vitamin B levels were also associated with the TT genotype of MTHFR., Conclusions: Hyperhomocystinemia detected in children with a parental history of PCD is associated with the TT genotype of MTHFR and with low folate levels. Because hyperhomocystinemia can be corrected by vitamin B supplementation, tHcy determination is recommended in the offspring of patients with PCD.