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.
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.
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.
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).
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.
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 (rxy). 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 (rxy = 0.687) and with LDL‐Z (rxy = −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.
The main objective of this study was to determine plasma levels of PS and to study SNVs rs41360247, rs4245791, rs4148217, and rs11887534 of
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.
There is limited, and inconsistent, data on the prospective association between physical activity and surrogate markers of adiposity in older adults. We aim to determine the prospective association ...of leisure time physical activity (LTPA) with body mass index (BMI), waist circumference (WC) and the incidence of obesity.
This prospective analysis included 7144 individuals with a mean age of 67 ± 6.2 years, from the PREvención con DIeta MEDiterránea (PREDIMED) study. BMI and WC were measured and LTPA was recorded using the Minnesota Leisure Time Physical Activity Questionnaire. Exposure and outcome variables were calculated as cumulative average of repeated measurements.
Total LTPA was inversely associated (P < 0.001) with BMI and WC. The difference in BMI and WC between extreme quintiles of LTPA (Q1-Q5) was 2.1 kg/m2 (95% confidence interval (CI) 1.68; 2.49, P < 0.001) and 4.8 cm (CI 2.28; 7.25, P < 0.001), respectively. Low-intensity LTPA was inversely associated with BMI but not with WC, while moderate/vigorous LTPA showed an inverse relationship with BMI and WC. The hazard of general and abdominal obesity incidence decreased across quintiles of total and moderate/vigorous LTPA (P < 0.001 for both), whereas low-intensity LTPA was inversely associated with the incidence of general obesity (P < 0.001).
LTPA was inversely associated with BMI, WC and incidence of general and abdominal obesity. The finding that low-intensity LTPA was inversely related to BMI and the incidence of obesity is of particular importance because this level of physical activity could be a feasible option for many older adults.
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.
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.
A systematic search was performed using the scientific databases PubMed and Medline from 1989 to 2016.
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.
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.
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 (
= 0·015). A statistically significant association between PDQS and changes in depressive symptoms after 2-years follow-up was found (
(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.
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.
Optimize a simple and fast precipitation method to isolate sd-LDL particles and establish a reference interval in a Mediterranean population.
Forty-five serum samples were collected, and sd-LDL particles were isolated using a modified heparin-Mg
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.
The Passing-Bablok regression equation is
= 1.52 (0.72 to 1.73) + 0.07
(-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.
An optimization of the heparin-Mg
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.
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.
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