Low Cholesterol Group Research Articles

Comprehensive assessment of the combined impact of dyslipidemia and inflammation on chronic kidney disease development: A prospective cohort study

There remains a limited comprehensive understanding of how dyslipidemia and chronic inflammation collectively contribute to the development of CKD. We aimed to identify clusters of individuals with five variables, including lipid profiles and C-reactive protein (CRP) levels, and to assess whether the clusters were associated with incident CKD risk. We used the Korean Genome and Epidemiology Study-Ansan and Ansung data. K-means clustering analysis was performed to identify distinct clusters based on total cholesterol, triglyceride, non-high-density lipoprotein (HDL)-C, HDL-C, and CRP levels. Cox proportional hazards models were used to examine the association between incident CKD risk and the different clusters. During the mean 10-year follow-up period, CKD developed in 1,645 participants (690 men and 955 women) among a total of 8,053 participants with a mean age of 51.8 years. Four distinct clusters were identified: C1, low cholesterol group (LC); C2, high HDL-C group (HC); C3, insulin resistance and inflammation group (IIC); and C4, dyslipidemia and inflammation group (DIC). Cluster 4 had a significantly higher risk of incident CKD compared to clusters 2 (HR 1.455 [95% CI 1.234-1.715]; p < 0.001) and cluster 1 (HR 1.264 [95% CI 1.067-1.498]; p = 0.007) after adjusting for confounders. Cluster 3 had a significantly higher risk of incident CKD compared to cluster 2 and 1. Clusters 4 and 3 had higher risk of incident CKD compared to clusters 2 and 1. The combination of dyslipidemia with inflammation or insulin resistance with inflammation appears to be pivotal in the development of incident CKD.

Association between intracerebral hemorrhage and cholesterol levels, and molecular mechanism underlying low cholesterol inhibiting autophagy in cerebral arterial smooth muscle cells leading to cell necrosis

BackgroundAn association between cholesterol and intracerebral hemorrhage (ICH) has been reported, but the mechanism is unclear. MethodsIn this cross-sectional study, participants aged 50–75 years were selected using multistage stratified cluster sampling. All samples completed a questionnaire (age, gender, medication, etc.) and were examined (blood lipid, height, blood pressure, etc.) for risk factors. Multivariable logistic regression was used to analyze the association between cholesterol levels and ICH risk, after adjusting for age, smoking, hypertension, and other factors. We cultured rat cerebral artery smooth muscle cells at different cholesterol concentrations. The autophagy pathway was identified by transcriptome sequencing. The results were then validated using real-time polymerase chain reaction and western blot. ResultsWe included 39,595 patients, among whom 286 had ICH. The study showed that a low level of low-density lipoprotein cholesterol (LDL-C) was a risk factor of ICH (odds ratio 2.912, 95% confidence interval 1.460–5.806; P = 0.002). Cell experiments showed that lower cholesterol levels could significantly induce rat cerebral artery smooth muscle cell necrosis. In low-cholesterol groups, expression of the autophagy marker LC3 protein was significantly decreased and p62 protein was significantly increased. In western blot and comparison with the control group, the low cholesterol PI3K/Akt/mTOR signaling pathway was significantly activated in the autophagy pathway, resulting in its inhibition, which in turn led to smooth muscle cell death. ConclusionLow cholesterol levels may inhibit autophagy through PI3K/Akt/mTOR signaling and induce arterial smooth muscle cell necrosis, thereby increasing the risk of ICH.

Associations of gut microbiota with dyslipidemia based on sex differences in subjects from Northwestern China.

BACKGROUNDThe gut microbiota (GM) has been proven to play a role in the regulation of host lipid metabolism, which provides a new theory about the pathogenesis of dyslipidemia. However, the associations of GM with dyslipidemia based on sex differences remain unclear and warrant elucidation.AIMTo investigate the associations of GM features with serum lipid profiles based on sex differences in a Chinese population.METHODSThis study ultimately recruited 142 participants (73 females and 69 males) at Honghui Hospital, Xi’an Jiaotong University. The anthropometric and blood metabolic parameters of all participants were measured. According to their serum lipid levels, female and male participants were classified into a high triglyceride (H_TG) group, a high total cholesterol (H_CHO) group, a low high-density lipoprotein cholesterol (L_HDL-C) group, and a control (CON) group with normal serum lipid levels. Fresh fecal samples were collected for 16S rRNA gene sequencing. UPARSE software, QIIME software, the RDP classifier and the FAPROTAX database were used for sequencing analyses.RESULTSThe GM composition at the phylum level included Firmicutes and Bacteroidetes as the core GM. Different GM features were identified between females and males, and the associations between GM and serum lipid profiles were different in females and males. The GM features in different dyslipidemia subgroups changed in both female patients and male patients. Proteobacteria, Lactobacillaceae, Lactobacillus and Lactobacillus_salivarius were enriched in H_CHO females compared with CON females, while Coriobacteriia were enriched in L_HDL-C females. In the comparison among the three dyslipidemia subgroups in females, Lactobacillus_salivarius were enriched in H_CHO females, and Prevotellaceae were enriched in L_HDL-C females. Compared with CON or H_TG males, Prevotellaceae, unidentified_Ruminococcaceae, Roseburia and Roseburia_inulinivorans were decreased in L_HDL-C males (P value < 0.05), and linear discriminant analysis effect size analysis indicated an enrichment of the above GM taxa in H_TG males compared with other male subgroups. Additionally, Roseburia_inulinivorans abundance was positively correlated with serum TG and total cholesterol levels, and Roseburia were positively correlated with serum TG level. Furthermore, Proteobacteria (0.724, 95%CI: 0.567-0.849), Lactobacillaceae (0.703, 95%CI: 0.544-0.832), Lactobacillus (0.705, 95%CI: 0.547-0.834) and Lactobacillus_salivarius (0.706, 95%CI: 0.548-0.835) could distinguish H_CHO females from CON females, while Coriobacteriia (0.710, 95%CI: 0.547-0.841), Coriobacteriales (0.710, 95%CI: 0.547-0.841), Prevotellaceae (0.697, 95%CI: 0.534-0.830), Roseburia (0.697, 95%CI: 0.534-0.830) and Roseburia_inulinivorans (0.684, 95%CI: 0.520-0.820) could discriminate H_TG males from CON males. Based on the predictions of GM metabolic capabilities with the FAPROTAX database, a total of 51 functional assignments were obtained in females, while 38 were obtained in males. This functional prediction suggested that cellulolysis increased in L_HDL-C females compared with CON females, but decreased in L_HDL-C males compared with CON males.CONCLUSIONThis study indicates associations of GM with serum lipid profiles, supporting the notion that GM dysbiosis may participate in the pathogenesis of dyslipidemia, and sex differences should be considered.

Prognostic impacts of serum levels of C-reactive protein, albumin, and total cholesterol in patients with myelodysplastic syndromes.

Various systems for predicting the prognosis of patients with myelodysplastic syndromes (MDS) have been developed. However, associations between performance status (PS) and prognosis of MDS require further investigation. To objectively assess the impact of PS on survival, we examined laboratory findings associated with PS, including serum levels of C-reactive protein (CRP), albumin (ALB), and total cholesterol (CHOL). Patients (n = 123; male 86, female 37; median age 74 yrs.) diagnosed with MDS or myelodysplastic/myeloproliferative neoplasms at Kanazawa Medical University Hospital between 2010 and 2020 were enrolled and grouped by cutoff values determined by receiver operating characteristic analysis: 0.44mg/dL for CRP, 4.0g/dL for ALB, and 120mg/dL for CHOL. The median follow-up period was 17.6months. Kaplan-Meier analysis revealed that overall survival (OS) in the high CRP, low ALB, and low CHOL groups was significantly shorter than in the low CRP, high ALB, and high CHOL groups, respectively. Multivariable analysis revealed that elevated serum CRP was an independent prognostic risk factor independent of gender, bone marrow blast percentage, and cytogenetics.

Association between Metabolic Syndrome and the Number of Remaining Teeth in Postmenopausal Women: A Cross-Sectional Analysis Using the Korean National Health and Nutritional Examination Survey.

There are very few studies on metabolic syndrome (MetS) and oral health in postmenopausal women. The purpose of this cross-sectional study was to determine the association between MetS and its components and the number of remaining teeth in postmenopausal women in Korea. The study selected 3320 menopausal women (40–79 years old) from those who participated in the seventh Korea National Health and Nutrition Survey (2016–2018). Multiple regression and multiple logistic regression analyses were performed to determine the association between MetS and its components and the number of remaining teeth. According to the multiple regression analysis, the regression coefficient (B) values were −1.62 (p < 0.05), −1.31 (p < 0.05), −1.60 (p < 0.05), and −2.28 (p < 0.05) in the hypertension group, hyperglycemia group, low high-density lipoprotein (HDL) cholesterol group, and MetS prevalence group, respectively. This indicates that the number of remaining teeth was lower in the MetS prevalence group as compared to the non-prevalence groups. As observed in the multiple logistic regression analysis, the odds ratio of the number of remaining teeth (less than 20) was higher in the MetS prevalence group (1.82 (p < 0.05)) as compared to the non-prevalence groups (1.25 (p < 0.05) in the abdominal obesity group, 1.50 (p < 0.05) in the hypertension group, 1.36 (p <0.05) in the hyperglycemia group, and 1.72 (p < 0.05) in the low HDL cholesterol group). Therefore, our results indicate that abdominal obesity, hypertension, diabetes, dyslipidemia, and prevalence of MetS are associated with tooth loss in postmenopausal women.

High-density Lipoprotein Cholesterol and the Risk of Future Retinal Artery Occlusion Development: A Nationwide Cohort Study

To evaluate the association between high-density lipoprotein (HDL) cholesterol levels and the future risk of retinal artery occlusion (RAO). Population-based cohort study. This study used data provided by the Korean National Health Insurance Service. A total of 9,316,212 individuals aged > 40 years who participated in the Korean National Health Screening Program in 2013 or 2014 were included. Data on risk factors - including age, sex, income level, systemic comorbidities, behavioral factors, and baseline lipid profiles - were collected from health screening results and claims data. Patients were followed up until December 2018 and incident cases of RAO were identified using registered diagnostic codes from claims data. A prospective association between HDL cholesterol level and incident RAO was investigated using the multivariable-adjusted Cox proportional hazard model. During an average follow-up period of 4.93 years, 9878 patients were newly diagnosed with RAO. Compared with those with low HDL cholesterol levels (< 40 mg/dL), patients with high HDL cholesterol levels (≥ 60 mg/dL) had a lower risk of future RAO development, with a hazard ratio (95% CI) of 0.78 (0.73-0.83) in the age-adjusted and sex-adjusted model and 0.88 (0.83-0.95) in the full-adjusted model. The younger subgroup (< 60 years) had an HR of 0.81 in the high HDL cholesterol group compared with the low HDL cholesterol group, while the older subgroup (≥ 60 years) had an HR of 0.93 (P for interaction=.012). A low HDL cholesterol level is an independent risk factor for the development of RAO.

High cholesterol concentrations as well as low cholesterol concentrations are associated with mortality at 28 days in sepsis: a retrospective cohort study.

Low serum cholesterol is known to be associated with poor prognosis in sepsis patients. On the other hand, there have been few studies on the association between high serum cholesterol, one of the major risk factors for cardiovascular adverse events, and prognosis of sepsis patients. We investigated the relationship between the serum total cholesterol concentration and outcome of sepsis patients. We conducted a multicenter retrospective cohort study at the emergency departments (EDs) of three urban tertiary teaching hospitals. Patients were divided into three groups according to the initial serum total cholesterol concentration: low cholesterol (cholesterol <120 mg/dL), normal cholesterol (cholesterol 120-200 mg/dL), and high cholesterol (cholesterol >200 mg/dL). Multivariable Cox proportional hazard regression model was used to identify the independent association between the serum total cholesterol concentrations and mortality at 28 days. A total of 4,512 patients were included in the final analysis. The mortality at 28 days of the low, normal, and high cholesterol groups were 24.1%, 14.5%, and 20.5%, respectively (P<0.001). Both the low and high cholesterol groups had a higher risk of death than the normal cholesterol group (low cholesterol group [hazard ratio (HR), 1.46; 95% confidence interval (CIs), 1.25-1.71] and high cholesterol group (HR, 1.57; 95% CI, 1.14-2.16). Both low and high serum total cholesterol concentrations were associated with higher mortality at 28 days in sepsis patients.

Total cholesterol concentration predicts the effect of plasmapheresis on hypertriglyceridemic acute pancreatitis: a retrospective case\u2013control study

BackgroundWhat kind of patients with hypertriglyceridemic acute pancreatitis (HLAP) might benefit from plasmapheresis (PP) remains unknown. The objective of this study is to determine the predict function of total cholesterol (TC) on the Triglyceride (TG)-lowing effect in patients on either non-PP or PP therapy.MethodsPatients were categorized into high total cholesterol (HTC)/low total cholesterol (LTC) groups based on TC level of 12.4 mmol/L. The primary outcome was TG reduction to below 500 mg/dL within 48 h. Linear mixed-effect model and logistic regression analyses were used to assess the association of TC level and TG-lowing efficacy in different therapy groups.ResultsCompared with LTC group, patients with HTC showed more severe imaging manifestations (p < 0.001) and higher APACH II scores (p = 0.036). Deaths occurred only in HTC groups. Significant interaction of time sequence with the 2 TGs-lowing therapy groups on TG level was only found in HTC group (p < 0.001). In patients with elevated TC level, primary outcome occurred in 66.67% of patients in the PP group, and 27.91% in the non-PP group. After adjustment for age, gender, CT grade and APACH II score, the odd ratio remain significant (OR 5.47, 95% confidence interval [CI] 1.84–16.25, p = 0.002). Furthermore, in patients with lower TC level, no significant difference was found in primary outcome between PP group and non-PP group (81.25% versus 62.30%, adjusted OR 2.05; 95% CI 0.45–9.40; p = 0.353).ConclusionsTC could be a potential biomarker to predict the effects of TG-lowing therapy in patients with HLAP.

A Combination of Blood Pressure and Total Cholesterol Increases the Lifetime Risk of Coronary Heart Disease Mortality: EPOCH-JAPAN.

Aim: Lifetime risk (LTR) indicates the absolute risk of disease during the remainder of an individual's lifetime. We aimed to assess the LTRs for coronary heart disease (CHD) mortality associated with blood pressure (BP) and total cholesterol levels in an Asian population using a meta-analysis of individual participant data because no previous studies have assessed this risk.Methods: We analyzed data from 105,432 Japanese participants in 13 cohorts. Apart from grade 1 and 2–3 hypertension groups, we defined “normal BP” as systolic/diastolic BP < 130/< 80 mmHg and “high BP” as 130–139/80–89 mmHg. The sex-specific LTR was estimated while considering the competing risk of death.Results: During the mean follow-up period of 15 years (1,553,735 person-years), 889 CHD deaths were recorded. The 10-year risk of CHD mortality at index age 35 years was ≤ 0.11%, but the corresponding LTR was ≥ 1.84%. The LTR of CHD at index age 35 years steeply increased with an increase in BP of participants with high total cholesterol levels [≥ 5.7 mmol/L (220 mg/dL)]. This risk was 7.73%/5.77% (95% confidence interval: 3.53%–10.28%/3.83%–7.25%) in men/women with grade 2–3 hypertension and high total cholesterol levels. In normal and high BP groups, the absolute differences in LTRs between the low and high total cholesterol groups were ≤ 0.25% in men and ≤ 0.40% in women.Conclusions: High total cholesterol levels contributed to an elevated LTR of CHD mortality in hypertensive individuals. These findings could help guide high-risk young individuals toward initiating lifestyle changes or treatments.

The association of repeatedly measured low-density lipoprotein cholesterol and all-cause mortality and cardiovascular disease in dyslipidemic patients: A longitudinal study

Background and aimsThis study aimed to evaluate the association between very low levels of low-density lipoprotein (LDL) cholesterol and subsequent clinical outcomes among dyslipidemic patients. MethodsA retrospective longitudinal study was conducted at a large teaching hospital in Tokyo, Japan, from 2005 to 2018. We included all dyslipidemic adult patients who were followed up at the department of endocrinology. The primary outcome was all-cause mortality and the secondary outcome was cardiovascular disease. We compared the development of these outcomes according to LDL cholesterol categories through longitudinal analyses adjusting for potential confounders. ResultsWe included total of 4485 dyslipidemic patients. The mean patient age (standard deviation) was 58.4 (12.2) years, and 2286 patients were men. During a median follow-up of 5.3 (interquartile range 2.2–9.6) years, 252 (5.7%) patients died (25[0.6%] were cardiovascular deaths) and 912 (20.3%) patients developed cardiovascular diseases. Multivariable longitudinal analyses showed that the very low LDL cholesterol group (<60 mg/dl) had significantly higher all-cause mortality than the normal LDL cholesterol group (100–140 mg/dl) (odds ratio[OR] 1.96, 95%confidence interval [CI]:1.22–3.16). Among high-risk patients for atherosclerotic cardiovascular disease (ASCVD), very low LDL cholesterol was significantly associated with increased all-cause mortality (OR 2.61, 95%CI: 1.12–6.10) but decreased incidence of cardiovascular disease (OR 0.47, 95%CI: 0.23–0.93). ConclusionsVery low LDL cholesterol is associated with increased all-cause mortality but not statistically associated with cardiovascular disease incidence among dyslipidemic patients, regardless of risk. When patients were stratified according to ASCVD risk, this association was more obvious among high-risk patients.

Association of microalbuminuria and high–normal 24-hour urinary albumin excretion with metabolic syndrome and its components in the general Chinese population: cross-sectional study

ObjectiveMicroalbuminuria (MAU) has been described as a risk factor for metabolic syndrome (MetS). However, the association between MetS components with MAU and 24-hour urinary albumin excretion (UAE) has not been...

Plasma endoxifen and 4-hydroxytamoxifen levels in CYP2D6(C100T) carrying breast cancer patients and association with serum cholesterol

Breast cancer patients with high cholesterol biosynthesis signature had poorer therapeutic outcome. Cytochrome P450 (CYP) 2D6 is crucial in the oxidation of tamoxifen to generate active metabolites, 4-hydroxytamoxifen and endoxifen. CYP2D6 variants with C100T substitution encode null or poor functional proteins. This study aims to examine the association of C100T genotypes and serum lipid levels with plasma drug levels in patients. Plasma tamoxifen concentration was positively associated with serum triglyceride concentration, adjusting for age and C100T genotype. Overweight (body mass index >24.0) patients with high serum cholesterol (≥200 mg/dL) had increased risks of ineffective endoxifen levels (<5.97 ng/mL). Compared to the low-cholesterol group, the high-cholesterol group had a lower 4-hydroxytamoxifen or endoxifen level in T/T carriers. In T/T carriers, the high-cholesterol group had an increased risk of an ineffective endoxifen level. Metastasis, hot flash/flushing, and high alanine transaminase did not relate to plasma 4-hydroxytamoxifen or endoxifen levels. Results indicate that C100T and high serum cholesterol are risk factors of ineffective endoxifen levels in Taiwanese breast cancer patients. These findings warrant further studies of a large hypercholesterolemic population to examine the outcome of increased doses of tamoxifen.

Comparison of laboratory features between low high-density lipoprotein cholesterol group and both low high-density lipoprotein cholesterol and high triglycerides group

Aim: Aim of the study was to compare laboratory features between groups with different types of dyslipidemia among middle-aged Lithuanian adults participating in Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program from 2009 to 2015.

Dietary cholesterol-induced transcriptome differences in the intestine, hepatopancreas, and muscle of Oriental River prawn Macrobrachium nipponense

Cholesterol is an important nutrient for crustaceans. In this study, we performed comparative transcriptome analyses to explore the transcriptome differences in the intestine, hepatopancreas, and muscle of Macrobrachium nipponense fed either a low cholesterol (LC) or high cholesterol (HC) diet (2.8 or 17.1g cholesterol per kg diet). High-throughput RNA-Seq was conducted, resulting in 7.65, 5.88, and 7.59G clean bases from the intestine, hepatopancreas, and muscle of the LC group, respectively, and 7.59, 6.73, and 6.70G clean bases from the same tissues of the HC group. Assembly of clean reads resulted in 230,946 unigenes. The following enriched pathways were identified: xenobiotic and drug metabolism by cytochrome P450; chloroalkane and chloroalkene degradation; metabolic and biosynthetic pathways; fatty acid metabolism and biosynthesis; and immune-related pathways. To the best of our knowledge, this is the first study to describe how functional unigenes and biosynthetic and metabolic pathways are affected by dietary cholesterol in aquatic crustaceans. Thus, these results contribute to our understanding of the molecular mechanisms underlying the cholesterol requirement of crustaceans.

Preoperative cholesterol level as a new independent predictive factor of survival in patients with metastatic renal cell carcinoma treated with cyto-reductive nephrectomy

BackgroundThe obesity and lipid metabolism were previously proposed to be related with the clinical outcomes of metastatic renal cell carcinoma (mRCC). We tried to investigate the relationship between preoperative cholesterol level (PCL) and survival outcomes in patients with mRCC.MethodsWe analysed the data of 244 patients initially treated with cyto-reductive nephrectomy after being diagnosed with mRCC. Patients were stratified into two groups according to the PCL cut-off level of 170 mg/dL. The postoperative survival rates were compared using Kaplan-Meier analysis and the possible predictors of patients’ cancer-specific survival (CSS) and overall survival (OS) were tested using multivariate Cox-proportional hazard models.ResultsThe low cholesterol group showed significantly worse postoperative CSS (p = 0.013) and OS (p = 0.009) than the high cholesterol group. On multivariate analysis, low PCL was revealed as an independent predictor of worse CSS (hazard ratio [HR], 2.162; 95% CI, 1.221–3.829; p = 0.008) and OS (HR, 2.013; 95% CI, 1.206–3.361; p = 0.007). Subsequent subgroup analysis showed that these results were maintained in the clear cell subgroup but not in the non-clear cell subgroup.ConclusionDecreased PCL was significantly correlated with worse survival outcomes in patients with mRCC treated with cytoreductive nephrectomy. The underlined mechanism is still uncharted and requires further investigation.

Preoperative Cholesterol Level Is Associated With Worse Pathological Outcomes and Postoperative Survival in Localized Renal Cell Carcinoma Patients: A Propensity Score-Matched Study.

Lipid metabolism has been suggested to be associated with clinical outcomes of renal cell carcinoma (RCC). In this study, we aimed to investigate the relationship between preoperative cholesterol level (PCL) and postoperative outcomes of patients with localized RCC. We retrospectively analyzed the data of 5022 patients surgically treated for nonmetastatic RCC. According to the receiver operating curve of PCL for cancer-specific mortality, we stratified the patients into 2 groups by using a cutoff value of 161 mg/dL. The propensity scores for having low PCL were calculated, and the low PCL group was matched with the high PCL group at a 1:2 ratio. The oncological profiles and postoperative survival of patients were compared. A low cholesterol level was significantly associated with adverse pathologic findings, such as higher pathologic stage (P< .001) and large tumor size (P= .002). Furthermore, the low cholesterol group showed significantly worse progression-free, cancer-specific, and overall survival (all P values< .001) compared with the high cholesterol group. Multivariate analysis exhibited a higher PCL as an independent predictor of better progression-free (P< .001), cancer-specific (P= .018), and overall survival (P= .001) after matching. Subgroup analysis according to tumor histology revealed that PCL had a significant relationship with patients' survival in clear cell RCC, but not in non-clear cell RCC. Decreased PCL was significantly associated with worse pathologic outcomes and also inferior postoperative survival in patients with localized RCC; however, those relationships were significant only in clear cell subtypes.

Associations of high HDL cholesterol level with all-cause mortality in patients with heart failure complicating coronary heart disease.

The aim of the present study was to evaluate the association between HDL cholesterol level and all-cause mortality in patients with ejection fraction reduced heart failure (EFrHF) complicating coronary heart disease (CHD).A total of 323 patients were retrospectively recruited. Patients were divided into low and high HDL cholesterol groups. Between-group differences and associations between HDL cholesterol level and all-cause mortality were assessed.Patients in the high HDL cholesterol group had higher HDL cholesterol level and other lipid components (P <0.05 for all comparison). Lower levels of alanine aminotransferase (ALT), high-sensitivity C-reactive protein (Hs-CRP), and higher albumin (ALB) level were observed in the high HDL cholesterol group (P <0.05 for all comparison). Although left ventricular ejection fraction (LVEF) were comparable (28.8 ± 4.5% vs 28.4 ± 4.6%, P = 0.358), mean mortality rate in the high HDL cholesterol group was significantly lower (43.5% vs 59.1%, P = 0.007). HDL cholesterol level was positively correlated with ALB level, while inversely correlated with ALT, Hs-CRP, and NYHA classification. Logistic regression analysis revealed that after extensively adjusted for confounding variates, HDL cholesterol level remained significantly associated with all-cause mortality although the magnitude of association was gradually attenuated with odds ratio of 0.007 (95% confidence interval 0.001–0.327, P = 0.012).Higher HDL cholesterol level is associated with better survival in patients with EFrHF complicating CHD, and future studies are necessary to demonstrate whether increasing HDL cholesterol level will confer survival benefit in these populations of patients.

Efficacy of Statin Therapy in Inducing Coronary Plaque Regression in Patients with Low Baseline Cholesterol Levels.

Aim: The efficacy of statin therapy in inducing coronary plaque regression may depend on baseline cholesterol levels. We aimed to determine the efficacy of statin therapy in inducing coronary plaque regression in statin-naïve patients with low cholesterol levels using serial intravascular ultrasound (IVUS) data from the treatment with statin on atheroma regression evaluated by virtual histology IVUS (TRUTH) study.Methods: The TRUTH study is a prospective, multicenter trial, comparing the efficacies of pitavastatin and pravastatin in coronary plaque regression in 164 patients. All patients were statin-naïve and received statin therapy only after study enrollment. The primary endpoint was the observation of coronary plaque progression, despite statin therapy.Results: Serial IVUS data, at baseline and after an 8-month follow-up, were available for 119 patients. The patients were divided into three groups based on non-high-density lipoprotein cholesterol (HDL-C) levels—low: ≤ 140 mg/dl, n = 38; moderate: 141–169 mg/dl, n = 42; and high: ≥ 170 mg/dl, n = 39. Coronary plaque progression was noted in the low cholesterol group, whereas plaque regression was noted in the moderate and high cholesterol groups [%Δplaque volume: 2.3 ± 7.4 vs. − 2.7 ± 10.7 vs. − 3.2 ± 7.5, p = 0.004 (analysis of variance)]. After adjusting for all variables, a low non-HDLC level (≤ 140 mg/dl) was identified as an independent predictor of coronary plaque progression [odds ratio, 3.7; 95% confidence interval, 1.5–9.1, p = 0.004].Conclusion: Serial IVUS data analysis indicated that statin therapy was less effective in inducing coronary plaque regression in patients with low cholesterol levels but more effective in those with high cholesterol levels at baseline.University Hospital Medical Information Network (UMIN) (UMIN ID: C000000311).

Cholesterol-induced inflammation and macrophage accumulation in adipose tissue is reduced by a low carbohydrate diet in guinea pigs.

BACKGROUND/OBJECTIVESThe main objective of this study was to evaluate the effects of a high cholesterol (HC) dietary challenge on cholesterol tissue accumulation, inflammation, adipocyte differentiation, and macrophage infiltration in guinea pigs. A second objective was to assess whether macronutrient manipulation would reverse these metabolic alterations.MATERIALS/METHODSMale Hartley guinea pigs (10/group) were assigned to either low cholesterol (LC) (0.04g/100g) or high cholesterol (HC) (0.25g/100g) diets for six weeks. For the second experiment, 20 guinea pigs were fed the HC diet for six weeks and then assigned to either a low carbohydrate (CHO) diet (L-CHO) (10% energy from CHO) or a high CHO diet (H-CHO) (54% CHO) for an additional six weeks.RESULTSHigher concentrations of total (P < 0.005) and free (P < 0.05) cholesterol were observed in both adipose tissue and aortas of guinea pigs fed the HC compared to those in the LC group. In addition, higher concentrations of pro-inflammatory cytokines in the adipose tissue (P < 0.005) and lower concentrations of anti-inflammatory interleukin (IL)-10 were observed in the HC group (P < 0.05) compared to the LC group. Of particular interest, adipocytes in the HC group were smaller in size (P < 0.05) and showed increased macrophage infiltration compared to the LC group. When compared to the H-CHO group, lower concentrations of cholesterol in both adipose and aortas as well as lower concentrations of inflammatory cytokines in adipose tissue were observed in the L-CHO group (P < 0.05). In addition, guinea pigs fed the L-CHO exhibited larger adipose cells and lower macrophage infiltration compared to the H-CHO group.CONCLUSIONSThe results of this study strongly suggest that HC induces metabolic dysregulation associated with inflammation in adipose tissue and that L-CHO is more effective than H-CHO in attenuating these detrimental effects.

High Cholesterol Levels Are Associated with Improved Long-term Survival after Acute Ischemic Stroke

Prior statin treatment and high admission cholesterol have been associated with favorable outcome after ischemic stroke (IS), a paradox not completely explained. The aim of this study was to investigate the effect of admission cholesterol levels and the impact of statin treatment on short- and long-term survival after IS. Consecutive patients admitted in 2006 and 2010 were included in the study. Total cholesterol of 4.6mmol/L or more was defined as high. Logistic regression analysis was performed to assess predictors of 1-month mortality, and Cox proportional hazard regression analysis was applied to investigate predictors of long-term mortality. Of 190 patients included in the final analysis, 21 (11%) died within 1 month and 61 (32%) died during 7 years of observation. Low cholesterol was associated with older age, lower blood pressure (BP), presence of angina, and higher risk of death. Three-month, 1-year, and 5-year survival rates were 100%, 98%, and 84%, respectively, in high cholesterol patients, compared with 92%, 87%, and 57% in low cholesterol group (P=.0001 with the log-rank test). Mortality risk was increased for patients with low cholesterol (hazard ratio: 1.97; 95% confidence interval [CI]: 1.05-3.69), after adjustment for age and admission National Institutes of Health Stroke Scale score. After further adjustment for angina and admission BP, the effect of cholesterol on mortality risk was still obvious, yet attenuated (hazard ratio: 1.87; 95% CI: .94-3.32). High admission cholesterol may be associated with increased long-term survival after IS. Future studies on the temporal profile of cholesterol levels and stroke outcome would be of interest.