Lower Low-density Lipoprotein Cholesterol Levels Research Articles

Effect of atorvastatin calcium plus clopidogrel in the treatment of patients with transient ischemic attacks and its effect on blood lipids and platelets

Objective To explore the clinical effect of atorvastatin calcium combined with clopidogrel in the treatment of patients with transient ischemic attacks (TIAs) and its effect on blood lipids and platelets. Methods Low-density lipoprotein cholesterol (LDL-C)], platelet-related parameters [prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count (PLT)], incidence of cerebral infarction, and adverse reactions. Results The clinical outcomes of the experimental group patients were significantly better than those of the control group patients (p < 0.05). The experimental group exhibited notably lower levels of TG, TC, and LDL-C compared to the control group (p < 0.05). Platelet-related indices—PT, APTT, and PLT—showed no significant differences between groups before and after treatment (p > 0.05). The incidence of cerebral infarction was notably lower in the experimental group (p < 0.005), while the occurrence of adverse reactions showed no significant difference between groups (p > 0.05). Conclusion Atorvastatin calcium combined with clopidogrel demonstrates a positive impact on individuals with TIAs by significantly lowering levels of LDL, total cholesterol, and triglycerides. However, it is noteworthy that platelet-related indices did not exhibit significant differences between the experimental and control groups. While the observed improvements in blood lipids are attributed to the effects of atorvastatin, the combination with clopidogrel did not show a substantial influence on platelet-related parameters. Thus, the overall therapeutic impact, particularly on platelet-related indices, may require further investigation and clarification. Despite these nuances, our findings suggest potential benefits in reducing the risk of adverse reactions and cerebral infarction, supporting the consideration of this approach for wider clinical use.

Low-density lipoprotein cholesterol and the risk of hyperemesis gravidarum: a Mendelian randomization study

Objective The inconsistency in conclusions from early observational studies has sparked our interest in elucidating the relationship between lipid levels and susceptibility to hyperemesis gravidarum (HG). This study wishes to employed Mendelian randomization analysis to investigate the causal relationship between low-density lipoprotein cholesterol (LDL-C) and HG. Methods We employed Tow-Sample MR analysis to investigate the causal associations between LDL-C and HG. Specific variables were selected from GWAS database for MR analysis, using single nucleotide polymorphisms (SNPs) as our instruments. The threshold for significant SNPs as genetic instruments has been set at 5 × 10−8. F-statistic was employed to validate the strength of exposure instruments. The causality was mainly evaluated by Inverse Variance Weighted method (IVW). To address potential bias from the selection of genetic variants with pleiotropic effects, sensitivity analysis was performed by Cochrane Q-test, MR Egger, weighted median, MR-PRESSO and Leave-one-out methods. To validate the directionality of causal relationships, we employed Steiger test to filter SNPs. At last, we conducted reverse MR to exclude the causal impact of HG on LDL-C levels. Results Our MR results identified the effect of genetically predicted increased LDL-C levels on increased genetic susceptibility to HG (OR:1.30; 95%CI:1.03-1.65; p = 0.028). In reverse MR analyses, no evidence was found for causal effect of HG on LDL-C levels (OR:1.00; 95%CI:1.00-1.01; p = 0.163). Sensitivity analyses were used to confirm reliability. Conclusion This study may have provided evidence of genetically predicted increased LDL-C levels on increased genetic susceptibility to HG. Appropriate lowering LDL-C levels may serve as a preventive and treatment measure for HG.

Factors Associated with Non-attendance at a Follow-up Visit for Dyslipidemia Identified at Health Checkups: A Retrospective Cohort Study in a Japanese Prefecture.

Dyslipidemia increases the risk of cardiovascular and cerebrovascular diseases. Visiting a physician for follow-up is essential when dyslipidemia is detected during health checkups. We investigated factors associated with non-attendance at a follow-up visit for dyslipidemia. We conducted a retrospective cohort study using linked health checkups and medical claims data from individuals covered by National Health Insurance in Ibaraki Prefecture, Japan. Participants were 40-74 years old, underwent health checkups between April 2018 and March 2019, and had cholesterol levels exceeding the recommended levels to visit a physician. We excluded individuals who had visited physicians for dyslipidemia in the past year. We calculated the proportion of patients who had a follow-up visit with a physician within 180 days after their health checkup. Then, we investigated the demographic and clinical characteristics associated with non-attendance using a multivariable logistic regression model. Among 33,503 individuals (median age, 66 years [interquartile range, 59-69 years]; females, 58.8%) with dyslipidemia at the health checkup, 18.1% attended follow-up visits. Younger age, male sex, drinking habits, and lack of symptoms were associated with higher odds of non-attendance. Participants who underwent health checkups at public facilities, lacked other abnormal results at health checkups, and had not visited physicians for other diseases were less likely to attend a follow-up visit. Among those with elevated low-density lipoprotein cholesterol (LDL-C) levels, those with relatively lower LDL-C levels were less likely to attend. Systems that inform high-risk populations of non-attendance and encourage follow-up visits are warranted.

Traditional Chinese medicine lowering lipid levels and cardiovascular events across baseline lipid levels among coronary heart disease: a meta-analysis of randomized controlled trials.

Dyslipidemia is a critical driver in the development of coronary heart disease (CHD), which further exacerbates the risk of major adverse cardiovascular events (MACEs). Chinese herbal medicine (CHM) plays an important role in the regulation of lipid levels and improvement of prognosis. However, few systematic reviews report whether the efficacy of CHM therapy for regulating lipid levels and lowering cardiovascular events is associated with baseline lipid levels. Randomized controlled trials assessing efficacy of CHM for lipid profiles and MACEs among patients with CHD were searched in six databases. Two authors independently extracted studies according to a predesigned form. Cochrane risk of bias tool and Grading of Recommendations Assessment, Development, and Evaluation system were used to assess the methodological quality of the included studies. The primary outcomes were blood lipid levels and MACEs including cardiovascular mortality, non-fatal myocardial infarction, revascularization, angina pectoris, heart failure, and non-fatal stroke across baseline lipid levels. The secondary outcomes were individual components of the primary outcomes. A total of 23 trials with 7,316 participants were included in this study. Altogether 377 cardiovascular events occurred in 3,670 patients in the CHM group, while 717 events occurred in 3,646 patients in the Western medicine-alone group. Compared with the Western medicine alone, additional CHM significantly lowered low-density lipoprotein cholesterol (LDL-C) [MD = -0.46, 95% CI (-0.60 to -0.32), P < 0.00001, I 2 = 96%]. The risk reduction in MACEs associated with CHM vs. Western medicine therapy was 0.52 [95% CI (0.47-0.58), P < 0.00001, I 2 = 0%], but varied by baseline LDL-C level (P = 0.03 for interaction). Triglycerides (TG) level was also significantly lowered by additional CHM vs. Western medicine alone [MD = -0.27, 95% CI (-0.34 to -0.20), P < 0.00001, I 2 = 81%], and risk reduction for MACEs also varied with baseline TG, with greater risk reduction in higher baseline TG subgroups (P = 0.03 for interaction). Similar results were observed with total cholesterol and high-density lipoprotein cholesterol. Compared with Western medicine alone, additional CHM was associated with lower risk of cardiovascular events and improvement of lipid profiles. Risk reduction for cardiovascular events was associated with baseline LDL-C and TG levels. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023425791.

Association of IL-18 gene polymorphisms with clinical aspects of hyperlipidemia in middle-aged and early people in the community.

Hyperlipidemia is notorious for causing coronary artery disease (CAD). IL-18 is a proinflammtory cytokine that contributes to the pathogenesis of CAD. Previous reports have revealed that genetic polymorphism of IL-18 is associated with its expression level as well as the susceptibility to CAD. In the present study, we aim to investigate the relationship between IL-18 single nucleotide polymorphisms (SNPs) and hyperlipidemia in the Han Chinese population in Taiwan. A total of 580 participants older than 30 were recruited from the community. We collected the demographics, self-reported disease histories, and lifestyles. We also assessed the levels of lipid profiles including total cholesterol (CHOL), triglyceride, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol. Two SNPs, rs3882891C/A (intron 5) and rs1946518A/C (promoter -607) of IL-18 were elucidated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Our results revealed that rs3882891 AA was associated with lower risk of hypercholesterolemia, higher CHOL and LDL-C in subjects (p=0.003, p=0.000 and p=0.005 separately), and rs1946518 CC was associated with hypercholesterolemia, higher CHOL and LDL-C as well (p=0.021, p=0.003 and p=0.001 separately) Furthermore, both SNPs were associated with IL-18 expression level, which was examined by Genotype-Tissue Expression (GTEx) Portal (p=0.042 and 0.016 separately). Finally, the haplotype of IL-18 was subsequently arranged in the order of rs3882891 and rs1946518. The result revealed that the AC haplotype of 2 IL-18 SNPs was also associated with lower risk of hypercholesterolemia, lower levels of CHOL and LDL-C (p=0.01, p=0.001 and 0.003). The current study is the first to report the association between IL-18 SNPs and hyperlipidemia in the Chinese Han population.

Association between Iron Indices and Dyslipidemia among Patients with Iron Deficiency Anaemia: A Cross-sectional Study

Introduction: Iron Deficiency Anaemia (IDA) is a major public health problem in India. Iron plays a role in hepatic lipogenesis, being an integral part of some enzymes and transporters involved in lipid metabolism. Since information on the association between iron metabolism and dyslipidemia in adults is limited, it is important to assess the lipid status in iron-deficient patients. Aim: To study the association of iron indices with the lipid profile among patients with iron deficiency anaemia. Materials and Methods: This hospital-based cross-sectional study was conducted at the Department of Paramedical and Health Sciences, Parul Institute of Paramedical and Health Sciences, Faculty of Medicine, Parul University, Vadodara, Gujarat, India, from December 2022 to May 2023. In the present study, 100 IDA patients aged between 25-45 years were included. All the participants underwent different tests including Total Cholesterol (TC), Triglyceride (TG), High Density Lipoprotein-Cholesterol (HDL-C), and Low Density LipoproteinCholesterol (LDL-C). Furthermore, the association between IDA patients and lipid levels was analysed. The data were statistically analysed using Pearson’s correlation test and Chi-square test. Results: In the present study, out of a total of 100 patients, 38 were males and 62 were females. The majority of IDA patients had lower levels of TC, TG, and LDL-C. Low levels of TC and LDL were found in 52 (83.87%) of females and 30 (78.94%) of males. A total of 28 (73.68%) of males and 52 (83.87%) of females had lower values for TG levels. In contrast to TC and TG, a substantial correlation between Haemoglobin (Hb) levels and HDL-C and LDL-C was found. However, Hb had a positive association with TG, HDL-C, and LDL-C and a negative correlation with TC. These results also suggest a substantial correlation between Serum Iron (SI) and TC, TG, and HDL-C, but not a significant correlation with LDL-C. Conclusion: When observed for dyslipidemia, IDA patients showed significantly lower levels of TC, TG, and HDL-C with respect to their SI levels.

Extracellular vesicle-mediated delivery of CRISPR/Cas9 ribonucleoprotein complex targeting proprotein convertase subtilisin-kexin type 9 (Pcsk9) in primary mouse hepatocytes.

The loss-of-function of the proprotein convertase subtilisin-kexin type 9 (Pcsk9) gene has been associated with significant reductions in plasma serum low-density lipoprotein cholesterol (LDL-C) levels. Both CRISPR/Cas9 and CRISPR-based editor-mediated Pcsk9 inactivation have successfully lowered plasma LDL-C and PCSK9 levels in preclinical models. Despite the promising preclinical results, these studies did not report how vehicle-mediated CRISPR delivery inactivating Pcsk9 affected low-density lipoprotein receptor recycling in vitro or ex vivo. Extracellular vesicles (EVs) have shown promise as a biocompatible delivery vehicle, and CRISPR/Cas9 ribonucleoprotein (RNP) has been demonstrated to mediate safe genome editing. Therefore, we investigated EV-mediated RNP targeting of the Pcsk9 gene ex vivo in primary mouse hepatocytes. We engineered EVs with the rapamycin-interacting heterodimer FK506-binding protein (FKBP12) to contain its binding partner, the T82L mutant FKBP12-rapamycin binding (FRB) domain, fused to the Cas9 protein. By integrating the vesicular stomatitis virus glycoprotein on the EV membrane, the engineered Cas9 EVs were used for intracellular CRISPR/Cas9 RNPdelivery, achieving genome editing with an efficacy of ±28.1% in Cas9 stoplight reporter cells. Administration of Cas9 EVs in mouse hepatocytes successfully inactivated the Pcsk9 gene, leading to a reduction in Pcsk9 mRNA and increased uptake of the low-density lipoprotein receptor and LDL-C. These readouts can be used in future experiments to assess the efficacy of vehicle-mediated delivery of genome editing technologies targeting Pcsk9. The ex vivo data could be a step towards reducing animal testing and serve as a precursor to future in vivo studies for EV-mediated CRISPR/Cas9 RNP delivery targeting Pcsk9.

Relationships of the Surface Charge of Low-Density Lipoprotein (LDL) with the Serum LDL-Cholesterol and Atherosclerosis Levels in a Japanese Population: The DOSANCO Health Study.

This study investigated the associations of the surface charge of low-density lipoprotein (LDL) with the serum LDL-cholesterol and atherosclerosis levels in a community-based Japanese population. The study had a cross-sectional design and included 409 community residents aged 35-79 years who did not take medications for dyslipidemia. The potential electric charge of LDL and the zeta potential, which indicate the surface charge of LDL, were measured by laser Doppler microelectrophoresis. The correlations of the zeta potential of LDL (-mV) with the serum LDL-cholesterol levels (mg/dL), cardio-ankle vascular index (CAVI), and serum high-sensitivity C-reactive protein (hsCRP) levels (log-transformed values, mg/L) were examined using Pearson's correlation coefficient (r). Linear regression models were constructed to examine these associations after adjusting for potential confounding factors. A total of 201 subjects with correctly stored samples were included in the primary analysis for zeta potential measurement. An inverse correlation was observed between the LDL zeta potential and the serum LDL-cholesterol levels (r=-0.20; p=0.004). This inverse association was observed after adjusting for sex, age, dietary cholesterol intake, smoking status, alcohol intake, body mass index, and the serum levels of the major classes of free fatty acids (standardized β=-6.94; p=0.005). However, the zeta potential of LDL showed almost no association with CAVI or the serum hsCRP levels. Similar patterns were observed in the 208 subjects with compromised samples as well as all the original 409 subjects. A higher electronegative surface charge of LDL was associated with lower serum LDL-cholesterol levels in the general Japanese population.

Investigating the association of the effect of genetically proxied PCSK9i with mood disorders using cis-pQTLs: A drug-target Mendelian randomization study.

PCSK9-inhibitors (PCSK9i) are new drugs recently approved to lower LDL-cholesterol levels. However, due to the lack of long-term clinical data, the potential adverse effects of long-term use are still unknown. The PCSK9 genetic locus has been recently implicated in mood disorders and hence we wanted to assess if the effect of PCSK9i that block the PCSK9 protein can lead to an increase in the incidence of mood disorders. We used genetically-reduced PCSK9 protein levels (pQTLs) in plasma, serum, cerebrospinal fluid as a proxy for the effect of PCSK9i. We performed Mendelian randomization analyses using PCSK9 levels as exposure and mood disorder traits major depressive disorder, mood instability, and neuroticism score as outcomes. We find no association of PCSK9 levels with mood disorder traits in serum, plasma, and cerebrospinal fluid. We can conclude that genetically proxied on-target effect of pharmacological PCSK9 inhibition is unlikely to contribute to mood disorders.

EFEKTIVITAS PEMBERIAN JELLY PORANG (Amorphophallus Muelleri) KOMBINASI JAMBU BIJI (Psidium Guajava) TERHADAP KADAR KOLESTEROL LDL PADA PASIEN HIPERKOLESTEROLEMIA

Hypercholesterolemia sufferers tend to be experienced at the age of 45-59 years and over 60 years. Hypercholesterolemia is caused by several factors, namely lifestyle, diet and physical activity. Guava and Porang tubers are one alternative to lower LDL cholesterol levels. Combination guava porang jelly is a snack made from porang flour and guava which is high in fiber and vitamin C. This study is an experimental quasy research. The subjects of the study amounted to 20 people consisting of 10 treatment groups and 10 control groups. The data collected were the intake of fat, fiber and vitamin C obtained by the method of recall of food consumption 1x24 hours before and during the intervention 4 times. Examination of LDL cholesterol levels using the CHOD-PAP method. Data were tested with the Mann-Whitney test to look at the effect of treatment on LDL cholesterol levels between the control group and the intervention group. The treatment group of LDL cholesterol levels before and during the study also decreased by 19,5 mg/dl while the control group by 7,7 mg/dl. There was no significant difference in LDL cholesterol levels after the intervention. However, there was a decrease in LDL cholesterol levels decreased by 19,5 mg/dl in the treatment group and 7,7 mg/dl in the control group.

Use of Green Tea Extract (Camellia sinensis) Orally to Prevent Dyslipidemia in Female Rats (Rattus norvegicus) Fed A High-Fat Diet

One of the significant danger factors for cardiovascular disease and stroke is dyslipidemia. According to long-term prospective epidemiological research, coronary heart disease is less common in those with good lipid profiles who lead better lives. In this study, on a high-fat diet, female wistar rats (Rattus norvegicus) will be tested and analyzed to see if green tea extract (Camellia sinensis) can prevent dyslipidemia when given orally. Compared to a control group that received only distilled water, the trial group that received 5 milliliters of green tea extract (Camellia sinensis) had significantly lower total and LDL cholesterol levels and higher HDL cholesterol levels. This treatment was more effective in lowering cholesterol overall. The components found in green tea (Camellia sinensis), including tannins, steroids, alkaloids, saponins, and flavonoids, can induce this. When certain bioactive substances are off, the body can bring them back into normalcy. These results suggest that white wistar rats (Rattus norvegicus), given a high-fat diet, can benefit from green tea (Camellia sinensis) extract to avoid dyslipidemia. Your lipid profile can be improved by ingesting green tea extract. The primary polyphenol in tea, catechin, is responsible for this transformation. Therefore, the Camellia sinensis plant, from which green tea is made, is a valuable plant that can halt or slow the progression of several ailments, including hypertension, metabolic disorders, and cardiovascular disorders.

Sex-dependent relationship of polymorphisms in CLOCK and REV-ERBα genes with body mass index and lipid levels in children

Circadian rhythms, which are governed by a circadian clock, regulate important biological processes associated with obesity. SNPs in circadian clock genes have been linked to energy and lipid homeostasis. The aim of our study was to evaluate the associations of CLOCK and REV-ERBα SNPs with BMI and plasma lipid levels in pre-pubertal boys and girls. The study sample population comprised 1268 children aged 6–8 years. Information regarding anthropometric parameters and plasma lipid concentrations was available. Genotyping of CLOCK SNPs rs1801260, rs4580704, rs3749474, rs3736544 and rs4864548 and REV-ERBα SNPs rs2017427, rs20711570 and rs2314339 was performed by RT-PCR. The CLOCK SNPs rs3749474 and rs4864548 were significantly associated with BMI in girls but no in boys. Female carriers of the minor alleles for these SNPs presented lower BMI compared to non-carriers. A significant association of the REV-ERBα SNP rs2071570 with plasma total cholesterol, LDL-cholesterol and Apo B in males was also observed. Male AA carriers showed lower plasma levels of total cholesterol, LDL-cholesterol and Apo B levels as compared with carriers of the C allele. No significant associations between any of the studied REV-ERBα SNPs and plasma lipid levels were observed in females. In summary, CLOCK and REV-ERBα SNPs were associated with BMI and plasma lipid levels respectively in a sex-dependent manner. Our findings suggest that sex-related factors may interact with Clock genes SNPs conditioning the effects of these polymorphisms on circadian alterations.

Assessing the impact of physical activity on bone density, cardiopulmonary function, and metabolic health in stroke survivors.

Stroke survivors often face motor impairments leading to decreased physical activity, which can, in turn, result in secondary health-related issues like cardiovascular and pulmonary impairment and osteoporosis. This research finds out the impact of physical activity on bone mineral density, cardiopulmonary health, and metabolic status in stroke survivors. The goal is to generate knowledge to inform rehabilitation strategies, emphasizing the significant role of regular exercise in enhancing the health of individuals recovering from stroke. This study was conducted using a cross-sectional study design, and involved 100 stroke survivors selected through stratified random sampling. Physical activity was measured using the validated Stroke-Specific Physical Activity Questionnaire. Health outcomes were assessed through various means: bone mineral density via the OSTEOKJ3000 ultrasonic bone densitometer; resting heart rate and blood pressure via an automated monitor; lipid profiles through the CardioChek PA analyzer; Hb1Ac levels via the A1CNow + System; and respiratory parameters through a spirometer. Statistical analysis revealed bone mineral density is positively correlated with physical activity (R = 0.53, P < .001). Additionally, an association was found between physical activity and improved cardiopulmonary function (resting heart rate r = -0.45, P < .001; forced expiratory volume in one second R = 0.30, P = .0023; forced vital capacity R = 0.28, P = .0041). Moreover, higher physical activity levels correlated with lower low-density lipoprotein cholesterol levels (r = -0.35, P = .0007), higher high-density lipoprotein cholesterol levels (R = 0.33, P = .0012), and better glycaemic control (HbA1c r = -0.40, P = .0002). This study highlights the significant benefits of physical activity for stroke survivors, showing positive impacts on bone density, cardiopulmonary function, and metabolic health. It underscores the need to include regular exercise in rehabilitation strategies to mitigate secondary health complications and enhance the overall health of stroke survivors. Future research should continue investigating the potential benefits of physical activity in this population.

Phytosterols: Potential Therapeutic Effects and Challenges in Food Industry.

Increases in serum total and low-density lipoprotein (LDL) cholesterol are known as hypercholesterolemia, and it is a significant risk factor for the emergence of cardiovascular illnesses. Any action strategy for lowering serum cholesterol is supported by lifestyle changes. Phytosterols are organic substances from the triterpene family. Phytosterols can lower serum LDL cholesterol levels because of their structural resemblance to cholesterol. Phytosterols are used to enrich or fortify a broad spectrum of food products. Phytosterols are quickly oxidized, just like cholesterol and unsaturated fatty acids. The utilization of free phytosterols for the manufacture of functional meals is highlighted in this chapter, which also focuses on the therapeutic effects of phytosterols and their technological concerns in the industrial field.

Ezetimibe and atherosclerotic cardiovascular disease: a systematic review and meta-analysis

IntroductionIndividuals diagnosed with atherosclerotic cardiovascular disease (ACD) are exposed to an increased risk of cardiovascular events. Reducing low-density lipoprotein cholesterol (LDL-C) levels has been established as an effective approach to mitigate these risks. However, a comprehensive and up-to-date meta-analysis investigating the LDL-C-lowering effectiveness and the impact on coronary atherosclerotic plaque compositions of Ezetimibe has been lacking.MethodsWe conducted a systematic review by meticulously analyzing databases such as MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials that evaluated the efficacy of ezetimibe in lowering LDL-C levels and its influence on coronary atherosclerotic plaques among individuals with ACD. This review encompassed studies available until August 1, 2023. In our analysis, we employed the weighted mean difference (WMD) as the aggregated statistical measure, accompanied by the corresponding 95% confidence interval (CI).ResultsWe encompassed a total of 20 eligible studies. Our findings unveiled that the combined therapy involving ezetimibe alongside statins led to a more substantial absolute decrease in LDL-C in comparison to using statins alone. This difference in means amounted to (−14.06 mg/dl; 95% CI −18.0 to −10.0; p = 0.0001). Furthermore, upon conducting subgroup analyses, it became evident that the intervention strategies proved effective in diminishing the volume of dense calcification (DC) in contrast to the control group.ConclusionsOur study findings indicate that the inclusion of ezetimibe in conjunction with statin therapy leads to a modest yet meaningful additional reduction in LDL-C levels when compared to using statins in isolation. Importantly, the introduction of ezetimibe resulted in a significant decrease in the volume of DC. However, it is worth noting that further investigation is warranted to delve deeper into this phenomenon.

High diet quality indices associated with lower risk of lipid profile abnormalities in Taiwanese kidney transplant recipients

Cardiovascular disease (CVD) and its risk factors seem to be linked with deteriorated graft function and persists as the major cause of mortality in kidney transplant recipients (KTRs). Diet quality is associated with CVD prevention in the healthy population, however, less study focuses on KTRs. The study aimed to determine the association between diet quality indices and lipid profile abnormalities as risk factors for CVD in KTRs. This prospective study enrolled 106 KTRs who had functioning allografts from September 2016. Lipid profiles included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG) and were based on the National Cholesterol Education Program Adult Treatment Panel III recommendations. Three-day dietary data were collected by a well-trained registered dietitian. The Alternative Healthy Eating Index-Taiwan (AHEI-Taiwan), Alternative Healthy Eating Index-2010 (AHEI-2010), and Healthy Eating Index-2015 (HEI-2015) scores were calculated and divided into quartiles and compared accordingly. KTRs’ mean LDL-C, HDL-C, TC, and TG levels were 119.8 ± 36.6 mg/dL, 52.0 ± 17.9 mg/dL, 205.8 ± 43.9 mg/dL, and 160.2 ± 121.6 mg/dL, respectively. Compared with the lowest quartile, only the highest quartile of AHEI-Taiwan had lower TC and LDL-C levels. After adjustment for age, gender, energy, Charlson comorbidity index, transplant duration, and dialysis duration, logistic regression analysis revealed that the highest quartile of AHEI-Taiwan had 82% (odds ratio [OR], 0.18; 95% confidence interval [CI] 0.04–0.72, p < 0.05) lower odds of high TC and 88% (OR 0.12; 95% CI 0.03–0.58, p < 0.05) lower odds of high LDL-C, and the highest quartile of HEI-2015 had 77% (OR 0.23; 95% CI 0.05–0.95, p < 0.05) lower odds of high LDL-C. Higher adherence to a healthy diet as per AHEI-Taiwan and HEI-2015 guidelines associated with lower risk of lipid profile abnormalities in KTRs.

Moderate-intensity statin plus ezetimibe vs high-intensity statin according to baseline LDL-C in the treatment of atherosclerotic cardiovascular disease: A post-hoc analysis of the RACING randomized trial

Background and aimsWhether the effect of a combination strategy rather than increasing doses of one drug to lower low-density lipoprotein cholesterol (LDL-C) levels is consistent across baseline LDL-C levels remains uncertain. MethodsIn the RACING trial, which showed a non-inferiority of moderate-intensity statin with ezetimibe (rosuvastatin 10 mg with ezetimibe 10 mg) to high-intensity statin (rosuvastatin 20 mg) for the primary outcome (3-year composite of cardiovascular death, major cardiovascular event, or stroke), the heterogeneity in treatment effect according to baseline LDL-C levels was assessed for the primary and secondary outcomes (clinical efficacy and safety). ResultsOf 3780 participants, 2817 participants (74.5%) had LDL-C <100 mg/dL, and 963 participants (25.5%) had LDL-C ≥100 mg/dL. The treatment effect of combination therapy versus high-intensity statin monotherapy was similar among the lower LDL-C subset (8.8% vs. 10.2%; hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.67 to 1.08, p = 0.19) and the higher LDL-C subset (10.8% vs. 9.6 %; HR 1.14, 95% CI 0.76 to 1.7, p = 0.53) without a significant interaction (interaction p = 0.22). Of the secondary outcomes, the 1-, 2-, and 3-year achievement of LDL-C <70 mg/dL was greater in the combination therapy group regardless of baseline LDL-C levels. ConclusionsAmong ASCVD patients, there was no heterogeneity in the effect of moderate-intensity statin plus ezetimibe combination therapy in the higher and lower baseline LDL-C levels for the 3-year composite of cardiovascular outcomes.

Elevated remnant cholesterol in atherosclerotic cardiovascular disease in diabetes: a population-based prospective cohort study

Abstract Background Elevated remnant cholesterol is observationally and causally associated with increased risk of atherosclerotic cardiovascular disease (ASCVD) in the general population; the association in individuals with diabetes is not known. Purpose We tested the hypothesis that elevated remnant cholesterol is associated with increased risk of peripheral artery disease, myocardial infarction, ischemic stroke, and any ASCVD in individuals with diabetes. Methods We studied 4,569 individuals with diabetes and 102,674 individuals without diabetes from the Copenhagen General Population Study (2003-2015). In those with diabetes, during up to 15 years of follow-up, 236 were diagnosed with peripheral artery disease, 234 with myocardial infarction, 226 with ischemic stroke, and 498 with any ASCVD in national Danish health registries. Remnant cholesterol was calculated from a standard lipid-profile as total cholesterol minus HDL cholesterol minus LDL cholesterol. Results Individuals with diabetes had higher levels of remnant cholesterol, but lower levels of LDL cholesterol, compared to individuals without diabetes (Figure 1). Statin use could explain the lower levels of LDL cholesterol but did not associate with levels of remnant cholesterol. Multivariable adjusted hazard ratios (95% confidence interval) per doubling of remnant cholesterol and LDL cholesterol were 1.8 (1.2-2.5) and 0.9 (0.6-1.2) for peripheral artery disease, 1.8 (1.3-2.6) and 1.0 (0.7-1.4) for myocardial infarction, 1.6 (1.1-2.3) and 1.1 (0.8-1.6) for ischemic stroke, and 1.7 (1.4-2.2) and 0.9 (0.7-1.1) for any ASCVD, respectively. Excess risk conferred by diabetes was 2.5-fold for peripheral artery disease, 1.6-fold for myocardial infarction, 1.4-fold for ischemic stroke, and 1.6-fold for any ASCVD. Elevated remnant cholesterol explained 14% (95% confidence interval: 6-23%) of excess risk of PAD; corresponding numbers were 26% (10-41%) for myocardial infarction, 34% (5-64%) for ischemic stroke, and 24% (12-36%) for any ASCVD (Figure 2). LDL cholesterol was lower in individuals with diabetes than in individuals without diabetes and could therefore not explain excess risk. Conclusions Elevated remnant cholesterol was associated with increased risk of ASCVD in individuals with diabetes and explained 24% of their excess risk of ASCVD. Clinical trials should determine if remnant cholesterol lowering can prevent ASCVD in individuals with diabetes.

Association of LDL cholesterol levels and all cause mortality in a real world analysis using data from an international network

Abstract Background Current cholesterol guidelines have recommended low low-density lipoprotein cholesterol (LDL-C) treatment targets for secondary prevention of cardiovascular disease. However, recent studies have suggested that very low or very high levels of LDL-C may be associated with increased mortality and other adverse outcomes. The association between LDL-C levels and mortality remains to be determined. Methods and Results This cohort study included data from a large multinational electronic health record network (TriNetX) of patients aged 18 years or older with coronary artery disease. LDL-C levels were divided into 4 categories: &amp;lt;30 (cohort 1), 30-50 (cohort 2), 50-70 (cohort 3), and 70-100 (cohort 4). Deaths were ascertained by linkage to death records in the last 10 years before the analysis. Five-year Kaplan-Meier curves and hazard ratios were calculated. We identified 1,136,600 patients, of whom 36,060 had LDL-C &amp;lt;30 mg/dL, 282,500 had LDL-C &amp;lt;50 mg/dL, 255,964 had LDL-C 50-70 mg/dL and 596,136 had LDL-C 70-100 mg/dL. Comparative analyzes were performed on the cohorts (cohort 1 vs. cohort 2, cohort 2 vs. cohort 3, and cohort 3 vs. cohort 4) after propensity score matching. After adjustment, individuals of cohort 2 (n = 36,004), compared with those of cohort 1 (n = 36,004), had higher all-cause mortality (HR 1.086; CI 95% 1.064-1.109, p &amp;lt;0.0001), individuals of cohort 3 (n = 244,908), compared to those of cohort 2 (n = 270,359), had higher risk of all-cause mortality (HR 1.063; 95% CI 1.055-1.1071, p &amp;lt;0.0001), and induviduals of cohort 4 (n = 254,465), compared with those of cohort 3 (n = 254,465), had lower risk of all-cause mortality (HR 0.937; CI 95% 0.929-0.944, p &amp;lt;0.0001). Conclusions Lower LDL-C levels are associated with a reduced risk of all-cause mortality in patients with coronary artery disease.

PSRC1 rs599839 G allele may promote protection from coronary artery disease in a Madeira Island population

Abstract Previous research associates the PSRC1 gene on the chromosomal locus 1p13.3 with coronary artery disease (CAD). Specifically, the A wild allele of the PSRC1 rs599539 A&amp;gt;G was identified as a risk allele for CAD, and the mutated G minor allele with a reduced risk of CAD. However, the underlying genetic mechanism is not yet fully understood and is controversial in other populations. Aim To investigate the association of rs599839 A&amp;gt;G variant with CAD risk and lipid profile in a Portuguese population from Madeira Island. Materials and Methods We performed a case-control study including 3161 participants, 1724 patients with CAD (78.7% male) and 1437 controls (76.3% male). Coronary patients were recruited from the Madeira Central Hospital, and controls were from the normal population. PSRC1 was genotyped by TaqMan allelic discrimination assay (Applied Biosystems, 7300 Real-Time PCR). Pearson´s Chi-squared test evaluated the association between CAD-genotypes and the t Student test for genotypes-lipid levels. Results PSRC1 rs599839 A&amp;gt;G variant was within Hardy -Weinberg equilibrium. The wild dominant model (AA+AG) conferred a trend for CAD risk (OR=1.16; p=0.414), and the mutated dominant model (GG+GA) presented slight protection for CAD susceptibility. However, the minor G (protector) allele was associated with low levels of total cholesterol (p=0.003) and LDL-cholesterol (p=0.004). Conclusions This finding is consistent with previous reports indicating a decrease in LDL-C and total cholesterol levels in carriers of the minor allele G of rs599839. Recent research refers that this allele could affect PSRC1 expression, resulting in lower levels of LDL cholesterol and reduced risk of CAD. In contrast, the A wild allele is associated with high LDL levels. PSRC1, lipid, and CAD risk is a complex topic involving genetic, epigenetic and environmental factors.