High Serum Cholesterol Levels Research Articles

High serum Cholesterol and Triglyceride levels in older adults: associations with sleep and nighttime behavior disorders at baseline and a prediction analysis of incidental cases at 12 months follow-up.

This study explored the association between dyslipidemia and sleep and nighttime behavior disorders (SNBD) in the elderly. ADNI population with complete Cholesterol, Triglyceride, SNBD, and neurocognitive data were included. Logistic regression was performed to study the association between dyslipidemia and SNBD at baseline and 12 months. Relevant confounders were adjusted for. Among the 2,216 included cases, 1,045 (47%) were females, and the median age was 73 (IQR: 68, 78). At baseline, 357 (16%) had SNBD, and 327 (18%) at 12 months; 187 were incident cases.There were more cases of baseline SNBD in the hypertriglyceridemia group than in those without (19% vs. 14%, p-value=0.003). Similarly, more follow-up SNBD cases had hypertriglyceridemia at baseline (21% vs. 16%, p-value=0.025). SNBD cases at baseline had significantly higher serum Triglyceride levels than those without (132 vs. 118mg/dL, p-value<0.001).Only hypertriglyceridemia was significantly associated with baseline SNBD (crude OR=1.43, 95%CI: 1.13,1.80, p-value=0.003), even after adjustment for confounding factors (adj.OR=1.36, 95%CI: 1.06,1.74, p-value=0.016) and (BMI-adj.OR=1.29, 95%CI: 1.00,1.66, p-value=0.048). None of the dyslipidemia forms did predict incident cases at 12 months. Hypertriglyceridemia, but not hypercholesterolemia, was associated with higher odds of SNBD. None of the dyslipidemia forms predicted incidental SNBD over 12 months.

Isolation of Lactobacillus acidophilus strain and its anti-obesity effect in a diet induced obese murine model.

Intestinal microbiota is a potential determinant of obesity, with probiotic bile salt hydrolase (BSH) as one of the key mechanisms in the anti-obesity effects. In this study, we present a Lactobacillus acidophilus GOLDGUT-LA100 (LA100) with high BSH activity, good gastric acid and bile salt tolerance, and a potential anti-obesity effect. LA100's anti-obesity effects were evaluated in a high-fat diet-induced, obese mouse model. LA100 administration alleviates high-fat diet-induced pathophysiological symptoms, such as body weight gain, high serum glucose and cholesterol level, hepatic lipid accumulation, and adipose inflammation. These results demonstrate concrete anti-obesity benefit in animal models and show promising applications in future clinical studies.

Contrasting Evidences Between High Cholesterol Levels and The Risk of Cardiovascular Disease: A Review

Introduction: The cholesterol hypothesis had been kept alive for decades by reviewers who used statistics that excluded the results from unsuccessful trials and ignored numerous contradictory observations. High dietary cholesterol intake had been associated with development of cardiovascular diseases (CVD) and mortality, for over several decades, without a direct link between the CVD and high serum cholesterol level. Hence, people avoided healthy cholesterol-rich diets due to the fear of developing CVD. The relationship between elevated plasma cholesterol and CVD and criteria for appropriate methods for screening patients with elevated cholesterol had remained a source of medical debates. Lack of decrease in overall mortality rates in patients without clinical coronary disease in whom aggressive lowering of cholesterol was achieved might have contributed to the lack of consensus on this most important issue.&#x0D; Methodology: With information derived from search engines, such as Elsevier, Springer, PubMed, Science Direct, Medline, Google Scholar and a library search for articles published in peer-reviewed journals.&#x0D; Results: Several research results showed that association between total serum cholesterol, its components and CVD is weak, absent or inverse implying that consuming healthy high cholesterol diets may not be harmful to health.&#x0D; Conclusion: This review provides evidence contrasting the links between elevated plasma cholesterol and CVD, and demonstrated that elevated cholesterol concentrations, rather, improve quality of life and life expectancy. In addition, most prevalent methods for cholesterol quantification in biological samples and foods, utilizing new technologies, such as Ambient Ionization Mass Spectrometry are summarized, along with other components of cholesterol.&#x0D; Keywords: Cholesterol, CVD, Quantification

Predictors of macrovascular complications in Al-Madinah Al-Munawara type 2 diabetes mellitus patients, Saudi Arabia: A cross-sectional study

Background/aim Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia, which causes macrovascular complications that account for most of the morbidity, hospitalizations, and deaths. The goal of this study is to evaluate the relationship between macrovascular complications and associated risk factors in Al-Madinah Al-Munawara patients suffering from type 2 diabetes mellitus. Patients and methods This descriptive cross-sectional study involved 275 type 2 diabetes mellitus patients who resided in Al-Madinah Al-Munawara and visited the diabetic clinic at King Fahd Hospital on a regular basis. Participants in the study ranged in age from 20 to 65. Hemoglobin, glycated hemoglobin, serum calcium, fasting blood glucose, and lipid profile were analyzed. Results Out of 275 patients with type 2 diabetes mellitus, 113 have had macrovascular complications. A significant association (P&lt;0.05) has been observed between the age of the patients and different forms of macrovascular complications, which impact 62.7% of the elderly (41–65 years old). The prevalence of macrovascular complications was higher among females. Glycated hemoglobin levels positively correlated with the number of hospitalizations, high blood pressure, hemoglobin, and serum cholesterol levels. Macrovascular complications are positively correlated with age, sex, hypertension, and therapy type (P&lt;0.05), while physical activity has a negative significant effect on the appearance of macrovascular complications by multiple regression analysis. Conclusion In this study, diabetic macrovascular complications were prevalent. The age, sex of participants, and type of treatment were independent predictors of macrovascular complications. Hypertension has a significant positive effect on the appearance of macrovascular complications. Physically inactive patients have a higher risk of macrovascular complications.

Effect of the Association of Fixed Oils from Abelmoschus esculentus (L.) Moench, Euterpe oleracea Martius, Bixa orellana Linné and Chronic SM® on Atherogenic Dyslipidemia in Wistar Rats.

Dyslipidemia presents high levels of serum cholesterol and is characterized as a risk factor for cardiovascular diseases, especially for the development of atherosclerosis. E. oleracea oil (OFEO), A. esculentus oil (OFAE), B. orellana oil (OFBO), and Chronic SM® granules (CHR) are rich in bioactive compounds with the potential to treat changes in lipid metabolism. This study investigated the effects of treatments with oils from A. esculentus, E. oleracea, B. orellana, and Chronic SM® on Cocos nucifera L. saturated-fat-induced dyslipidemia. The chromatographic profile showed the majority presence of unsaturated fatty acids in the tested oils. The quantification of tocotrienols and geranylgeraniol in OFBO and CHR was obtained. Treatments with OFEO, OFAE, OFBO, and CHR were able to significantly reduce glycemia, as well as hypertriglyceridemia, total cholesterol, and LDL-cholesterol, besides increasing HDL-cholesterol. The treatments inhibited the formation of atheromatous plaques in the vascular endothelium of the treated rats. The obtained results suggest that the OFEO, OFAE, OFBO, and CHR exhibit antidyslipidemic effects and antiatherogenic activity.

Fatty Liver Index and mortality after myocardial infarction: A prospective analysis in the Alpha Omega Cohort.

Accumulating evidence shows that NAFLD might play a role in the etiology and progression of CVD, but little is known on the association of NAFLD and CVD mortality in patients with a history of a myocardial infarction (MI). Therefore, we studied the relationship of Fatty Liver Index (FLI), as indicator for non-alcoholic fatty liver disease (NAFLD), with 12-year risk of cardiovascular disease (CVD) and all-cause mortality in post-MI patients. We included 4165 Dutch patients from the Alpha Omega Cohort aged 60-80 years who had an MI ≤10 years prior to study enrolment. NAFLD was defined as FLI ≥60. Patients were followed for cause-specific mortality from enrolment (2002-2006) through December 2018. Hazard ratios for CVD and all-cause mortality were obtained by multivariable Cox regression using FLI <30 (indicating absence of NAFLD) as the reference. Baseline FLI as a continuous measure was studied with mortality using restricted cubic splines analyses. The median (IQR) FLI was 68 (48-84). Sixty percent of the patients had FLI ≥60, who were more likely to be male and more often had diabetes, high blood pressure, and high serum cholesterol levels. During 12 years of follow-up, 2042 deaths occurred of which 846 from CVD. Patients with NAFLD were at increased risk of CVD mortality (HR: 1.55 [1.19, 2.03]) and all-cause mortality (HR: 1.21 [1.03; 1.41]) compared to patients without NAFLD. Results remained consistent after excluding patients with obesity and diabetes. To conclude, the adverse association of FLI with CVD mortality was stronger in female than in male patients with conventional cut-off points. FLI ≥60, indicating NAFLD, was a predictor for CVD and all-cause mortality in post-MI patients, independent of other cardiometabolic risk factors. However, cut-off points might differ between male and female patients for predicting CVD mortality.

The potential role of cholesterol in Parkinson's disease neuropathology: perpetrator or victim.

Parkinson's disease (PD) is a neurodegenerative disease characterized by deposition of α-synuclein and aggregation of Lewy bodies. Cholesterol is involved with PD neuropathology in bidirectional ways that could be protective or harmful. Thus, the objective of the present review was to verify the potential role of cholesterol in PD neuropathology. Deregulation of ion channels and receptors induced by cholesterol alteration suggests a possible mechanism for the neuroprotective effects of cholesterol against PD development. However, high serum cholesterol level increases PD risk indirectly by 27-hydroxycholesterol which induces oxidative stress, inflammation, and apoptosis. Besides, hypercholesterolemia triggers the accumulation of cholesterol in macrophages and immune cells leading to the release of pro-inflammatory cytokines with progression of neuroinflammation subsequently. Additionally, cholesterol increases aggregation of α-synuclein and induces degeneration of dopaminergic neurons (DN) in the substantia nigra (SN). Hypercholesterolemia may lead to cellular Ca2+ overload causing synaptic and the development of neurodegeneration. In conclusion, cholesterol has bidirectional effects on PD neuropathology and might be protective or harmful.

Kadar Kolesterol Darah Total Pada Pasien Rawat Jalan Laki – Laki Usia 40 Sampai Dengan 70 Tahun Di Rumah Sakit TNI AU LANUD Sam Ratulangi Manado

The type of fat that is best known by parents or the public that can cause disease is cholesterol. According to Yogendra Kumar, 2021, normal total cholesterol levels in the blood are in the range of 140-200 mg/dl, while high total cholesterol levels are between 200-400 mg/dl. Men aged 40 years and over with high serum cholesterol levels, namely cholesterol &gt; 200 mg/dL and LDL cholesterol &gt; 130 mg/dL, have a high risk of stroke and coronary heart disease (CHD). Based on WHO data for 2015, Yusvita and Shinta (2018) reported that globally there were 17.7 million deaths due to heart and blood vessel disease. Data collection was carried out based on the results of blood cholesterol examination in every man aged 40 to 70 years. This research approach is descriptive. The samples taken amounted to 30 people according to the criteria and are willing to be respondents. This research method uses total sampling. From the results of the study it was found that high total cholesterol levels were &gt; 200 mg/dl at ages 40-55 years with 6 respondents out of 12, while those aged 56-70 years only amounted to 4 respondents out of 8. This shows that the percentage of ages 40-55 and 56-70 is not much different or the same. Total blood cholesterol levels in men aged 40 years to 70 years have normal values ​​or &gt; 200 mg/dl with a percentage of 60% and 40% having high value or &gt; 200 mg/dl from 30 respondents or outpatients who were sampled . High total blood cholesterol levels or &gt; 200 mg/dl have a risk of stroke and coronary heart disease, while normal total blood cholesterol levels or &lt; 200 mg/dl have a low risk. This basic research is expected to be a reference for further or other research and can be useful for readers, especially men aged 40 to 70 years.

Cardiovascular Mortality in 10 Cohorts of Middle-Aged Men Followed-Up 60 Years until Extinction: The Seven Countries Study.

To investigate mortalities from three major groups of cardiovascular diseases (CVDs) in a pooled cohort and followed up until extinction. Ten cohorts of men (N = 9063) initially aged 40-59, in six countries, were examined and followed-up for 60 years. The major CVD groups were coronary heart disease (CHD), cerebrovascular diseases (STROKE) and other heart diseases of uncertain etiology (HDUE). Death rates from CHD were higher in countries with high serum cholesterol levels (USA, Finland and The Netherlands) and lower in countries with low cholesterol levels (Italy, Greece and Japan), but the opposite was observed for STROKE and HDUE, which became the most common CVD mortalities in all countries during the last 20 years of follow-up. Systolic blood pressure and smoking habits were, at an individual level, the common risk factors for the three groups of CVD conditions, while serum cholesterol level was the most common risk factor only for CHD. Overall, death rates for the pooled CVDs were 18% higher in North American and Northern European countries, while CHD rates were 57% higher in the same countries. Differences in lifelong CVD mortalities across different countries were smaller than expected due to the different rates of the three groups of CVD, and the indirect determinant of this seemed to be baseline serum cholesterol levels.

FREQUENCY OF METABOLIC SYNDROME IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS PRESENTING AT A PUBLIC SECTOR TERTIARY CARE HOSPITAL OF LAHORE: A CROSS- SECTIONAL STUDY

Background and Objective: Metabolic syndrome is characterized by central obesity, deranged lipid profile, high blood pressure and abnormally high levels of blood sugar. It is an independent risk factor for cardiovascular disease. Systemic Lupus Erythematosus (SLE) is an autoimmune disease that can affect joints, skin, brain, lungs, kidneys, and blood vessels. The extent to which metabolic syndrome is frequent in our population is less known. The objective of this study was to assess the frequency of metabolic syndrome amongst SLE patients. Methods: This cross-sectional study was undertaken in a public sector tertiary care hospital of Lahore from February 2021 through August 2021, including 110 confirmed SLE cases. After institutional approval and taking an informed consent, blood pressure, fasting and random blood sugar levels and fasting lipid profile were measured. Central obesity was assessed using waist circumference. Data were transferred to SPSS 21 for descriptive and inferential analyses. Frequencies were determined using numbers and percentages. Results: Of 110 SLE patients, 14 (12.3%) were males and 96 (87.7%) were females. Mean age of SLE patients was 42.9± 9.9 years. Mean BMI was 28.7±4.7 kg/m2. The frequency of metabolic syndrome in studied SLE patients was 37/110 (33.6%). Conclusion: Systemic lupus erythematosus patients had abnormally high serum triglyceride and cholesterol levels, diabetes mellitus, central obesity, high levels of fasting plasma glucose and hypertension. Therefore, one-third of SLE patients may have metabolic syndrome in our population.

Leptin and other Biochemical Investigations in the Serum of Type 2 Diabetes Mellitus Patients

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia and insulin resistance, and serious health consequences can be developed from T2DM such as in the eye (diabetic retinopathy), the renal (diabetic nephropathy), the cardiovascular system (hypertension), etc. Leptin is one of the regulators that released by the adipose tissue, which involved in mediating inflammatory processes, and related to oxidative stress. This article was made to examine the level of leptin in T2DM patients and its association with lipid profile and glycaemia status in T2DM patients. Also, the possibility of using leptin in the prognosis of T2DM was investigated. The study was included 60 T2DM patients and 30 normal glycemic non-diabetic control. The results have shown a significant high levels of serum leptin, glucose, HbA1c, triglycerides, and cholesterol in T2DM patients with significant low level of high-density lipoprotein, when compared to control. Leptin has shown to be involved in the pathophysiology of type 2 diabetes mellitus. The T2DM patients were contained a significant high levels of leptin in their serum compared to the normal glycemic people without T2DM disease. Furthermore, leptin was correlated significantly with the percentage of HbA1c in T2DM patients, which indicates a major part of influence between leptin and insulin resistance development in T2DM patients. Moreover, lipids were altered significantly in T2DM patients, but the results have revealed no significant involvement of leptin with this alteration. Based on these findings, we suggest the use of leptin in the prognosis of risks in T2DM patients.

Innovative therapeutic strategies for cardiovascular disease.

As a significant non-communicable disease, cardiovascular disease is the leading cause of death for both men and women, comprises almost twenty percent of deaths in most racial and ethnic groups, can affect greater than twenty-five million individuals worldwide over the age of twenty, and impacts global economies with far-reaching financial challenges. Multiple factors can affect the onset of cardiovascular disease that include high serum cholesterol levels, elevated blood pressure, tobacco consumption and secondhand smoke exposure, poor nutrition, physical inactivity, obesity, and concurrent diabetes mellitus. Yet, addressing any of these factors cannot completely eliminate the onset or progression of cardiovascular disorders. Novel strategies are necessary to target underlying cardiovascular disease mechanisms. The silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), a histone deacetylase, can limit cardiovascular injury, assist with stem cell development, oversee metabolic homeostasis through nicotinamide adenine dinucleotide (NAD+) pathways, foster trophic factor protection, and control cell senescence through the modulation of telomere function. Intimately tied to SIRT1 pathways are mammalian forkhead transcription factors (FoxOs) which can modulate cardiac disease to reduce oxidative stress, repair microcirculation disturbances, and reduce atherogenesis through pathways of autophagy, apoptosis, and ferroptosis. AMP activated protein kinase (AMPK) also is critical among these pathways for the oversight of cardiac cellular metabolism, insulin sensitivity, mitochondrial function, inflammation, and the susceptibility to viral infections such as severe acute respiratory syndrome coronavirus that can impact cardiovascular disease. Yet, the relationship among these pathways is both intricate and complex and requires detailed insight to successfully translate these pathways into clinical care for cardiovascular disorders.

ASSOCIATION BETWEEN MATERNAL SERUM LIPID PROFILE AT LATE GESTATION WITH NEONATAL MACROSOMIA

Background &#x0D; Macrosomia is a serious health problem that is highly prevalent and can negatively affect neonatal and maternal outcomes. Pregnant women and neonates can be negatively influenced by dyslipidemia (high maternal serum lipids) which also results in the development of fetal macrosomia..&#x0D; Objectives &#x0D; The current study aimed to determine how maternal lipid profile during the third trimester of pregnancy correlated with fetal birthweight. &#x0D; Patients and Methods&#x0D; A prospective cohort study was conducted in Sulaimani Maternity Teaching Hospital over eight months, starting from the 1st of September 2018 till the 30th of April 2019. The study included 123 pregnant with a viable singleton pregnancy, gestational age &gt; 32 weeks, delivered between 37 and 42 weeks of gestational age, and women suffering from thyroid disorders and hypertension. For all women, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and serum triglycerides (TG) were measured. In addition, the women were followed up until their childbirth, and the correlation between the mothers’ lipid profile and their neonates’ weight was measured..&#x0D; Results&#x0D; The mean age ± SD (standard deviation) of the studied women was 31.10± 3.65 years, ranging from (25 to 38) years. Regarding their parity, 78% of women were multiparous (have 2-4 children), and the remaining (22%) were primipara. Among the 123 participating women, 23 (18.7%) delivered macrosomic babies (weight &gt; 4kg), and 100 (81.3%) delivered babies with normal birth weight. Fifteen women (12.2%) have high cholesterol levels, and all delivered macrosomic newborns, with a statistically significant association (P=0.001) between macrosomia and maternal cholesterol level. Also, the prevalence of macrosomia was significantly higher among women with high serum triglyceride levels (P=0.001). &#x0D; Conclusion&#x0D; There is a significant association between increased risk of macrosomia and high serum cholesterol and triglycerides levels during pregnancy.

Role of predictable biomarkers in early detection of cardiovascular events in Chronic Kidney Disease III and IV

Abstract This comes about because of a lack of predicted biomarkers in the risk analysis of CVD events in chronic kidney disease (CKD) patients. The present study aimed to determine the clinical utility of independent, predictable biomarkers such as serum creatinine, estimated Glomerular Filtration Rate (eGFR), high sensitive C-Reactive protein (hsCRP), fibrinogen and lipid profile as early predictors of CVD in CKD at stage III/IV. Methods. This is a case-control study that includes a sample size of 100 patients of cases and 100 patients of controls who were recruited from November 2020 to April 2021, from the Nephrology department of the Visakhapatnam tertiary care teaching hospital, and present with chronic kidney disease – stage III/IV. The subjects’ general conditions (age, gender, height, weight, systolic blood pressure, diastolic blood pressure, and smoking history); underlying diseases (coronary heart disease and diabetes mellitus) were recorded. Fasting venous blood samples were collected under aseptic conditions from the study group after taking informed consent. The measurement of serum creatinine was performed by modification of kinetic Jaffe reaction. The Cockcroft-Gault equation was used to calculate eGFR in both cases and controls. CRP testing was done with a Cobas C311 analyzer, using immunoturbidimetric assay. The Fibroquant kit from Tulip was employed to measure fibrinogen levels in blood samples, and enzymatic methods were applied for lipid profile analysis. Results. In this study, higher mean values of hsCRP (34.28 mg/dl), increased serum creatinine levels (2.876 mg/dl), reduced eGFR (28.37 mls/min), high levels of serum fibrinogen (291.6 mg/dl), and cholesterol (214.5 mg/dl), HDL (28.34 mg/dl), TG (162.1 mg/dl), VLDL (32.41 mg/dl) and LDL (153.77 mg/dl) were found to be independent predictors of assessment of CV events in patients with CKD stages III and IV as determined by Chi-square test. Conclusion. A prompt and accurate assessment of cardiovascular risk in CKD patients would enable more aggressive and focused treatment of the individuals who are most in need of preventive interventions to decrease incident rates.

Western diet–induced mouse model of non-alcoholic fatty liver disease associated with metabolic outcomes: Features of gut microbiome-liver-adipose tissue axis

ObjectivesNon-alcoholic fatty liver disease (NAFLD) has a growing epidemiologic and economic burden. It is associated with Western diet (WD) patterns, and its pathogenesis involves metabolic disorders (obesity, dyslipidemia, hyperglycemia, and diabetes) and gut dysbiosis, features that are usually neglected or not reproduced by most animal models. Thus, we established a 6-mo WD-induced NAFLD mouse model associated with metabolic disorder, investigating its main features at the gut microbiome–liver-adipose tissue axis, also evaluating the correlations of gut dysbiosis to the other disease outcomes. MethodsMale C57 BL6 mice received a high-fat (30% lard and 0.2% cholesterol, ∼57% calories) and sucrose-rich (20%) chow, and a high-sugar solution (23.1 and 18.9 g/L of D-fructose and D-glucose) for 6 mo. ResultsThe model featured high serum cholesterol levels, glucose intolerance, and hyperinsulinemia. WD intervention resulted in extensive macro/microvesicular liver steatosis and pericellular fibrosis—resembling human disease—accompanied by hepatic stellate cell activation and CD68+ macrophage infiltration, increased protein levels of proinflammatory p65-nuclear factor-κB, interleukin-6 and tumor necrosis factor-α, with decreased antioxidant regulator Nrf2. Mice showed clear obesity with adipocyte hypertrophy, and CD68+macrophage/mast cell infiltration in adipose tissue while a reduction in number of goblet cells was also observed in the small intestine. Moreover, the pyrosequencing of the 16 S ribosomal RNA of gut cecal content showed decreased bacterial diversity, enriched Firmicutes and Proteobacteria, decreased Bacteroidetes and Fusobacteria, and increased ratio of Firmicutes to Bacteroidetes. Bacteroidetes and Bacteroides had the highest number of significant correlations with liver–adipose tissue axis outcomes. In silico analysis of gut microbiome in NAFLD obese patients revealed a depletion in Bacteroides, which also correlated to disease outcomes. ConclusionThis mice model gathered suitable phenotypical alterations in gut–liver–adipose tissue axis that resembled NAFLD associated with metabolic disorders in humans and may be considered for preclinical investigation.

Hypolipidemic trials in the elderly - a recent historic standpoint

In spite of the first trials on the effect of cholesterol reduction and its beneficial impact on morbidity and mortality in the elderly many have already proven the antecipated positive results. The high risk attributable to the elderly is a guarantee for an effort in primary prevention, especially when a high level of serum cholesterol is combined with other risk factors linked to coronary artery disease. There are elements of similarity for primary prevention in the elderly over 65 years of age, compared to middle-aged patients. This consideration opened the need for scientific evidence with confirmed levels of evidence. The first studies were WOSCOPS, AFCAPS/TEXCAPS, Heart Protection Study, PROSPER, ALLHAT (Antihipertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial-Lipid Lowering Trial), REVERSAL, Health Study, ASCOT (Anglo Scandinavian Cardiac Outcomes), MIRACL, Post CABG, AVERT, ACCESS, ASSET, ATGOAL, CHALLENGE, CURVES, BELLS, ARBITER, NASDAC, PROVE-IT and DEBATE. Positive evidences were shown from the first to the last trial recalled in this historical beginning.

Abstract P3132: High-salt Diet Increases Blood Cholesterol: Potential Role Of Hepatic Enzyme CYP51

Introduction: The increased consumption of dietary fat has been well established to lead to cardiovascular disease via the elevation of lipids in serum. High blood pressure is also commonly associated with high serum cholesterol levels, but the relationships among blood pressure, dietary sodium intake and serum cholesterol have not been fully elucidated. Hypothesis: An increase in the intake of salt causes an elevation of serum cholesterol through the activation of hepatic enzymes critical to cholesterol synthesis. Methods: Dahl salt-sensitive rats (n=6) were fed a high-salt (HS) diet (8% NaCl) from 7 weeks of age to induce hypertension. Rats fed a normal-salt (NS) diet (0.3% NaCl; n=6) served as controls. Blood pressure was measured non-invasively using a tail artery cuff. Blood was withdrawn from 6-hour fasting HS and NS-fed rats to check serum cholesterol levels. Low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very-low density lipoprotein (VLDL) cholesterols were measured. Gene expression array and western blot were performed in liver protein extracts from HS and NS-fed rats. Results: Systolic blood pressure was elevated in HS-fed rats compared to NS-fed rats at 16 weeks of age (225±23 vs. 156±18 mmHg, p=0.0002). Serum fasting cholesterol was higher in hypertensive rats compared to normotensive rats (194±49 vs. 102±12 mg/dL, p=0.0013). LDL cholesterol was higher in HS-fed rats compared to NS-fed rats (83±9 vs. 60±10 mg/dL, p=0.0024), while HDL and VLDL cholesterol were not. Hepatic cholesterol synthesis gene array revealed significant up-regulation of 3 genes in hypertensive rats in comparison to normotensive rats ( Apoa1 fold change [FC] 2.84, p&lt;0.0001; Tm7sf2 FC 2.45, p=0.0004; Cyp51 FC 2.44, p=0.0002). Western blot of hepatic protein extracts showed a definitive increase in CYP51 in HS-fed rats compared to NS-fed rats (normalized against GAPDH, 2.7-fold increase, p=0.0018). Conclusions: A high-salt diet increased serum cholesterol levels, potentially via activation of liver enzyme CYP51, which is crucial for the synthesis of cholesterol in the liver. Further research is warranted to investigate the mechanisms of how high-salt diets can increase CYP51 in the liver.

Ezetimibe and Cancer: Is There a Connection?

The high level of serum cholesterol caused by the excessive absorption of cholesterol can lead to hypercholesteremia, thus promoting the occurrence and development of cancer. Ezetimibe is a drug that reduces cholesterol absorption and has been widely used for the treatment of patients with high circulating cholesterol levels for many years. Mechanistically, ezetimibe works by binding to NPC1L1, which is a key mediator of cholesterol absorption. Accumulating data from preclinical models have shown that ezetimibe alone could inhibit the development and progression of cancer through a variety of mechanisms, including anti-angiogenesis, stem cell suppression, anti-inflammation, immune enhancement and anti-proliferation. In the past decade, there has been heated discussion on whether ezetimibe combined with statins will increase the risk of cancer. At present, more and more evidence shows that ezetimibe does not increase the risk of cancers, which supports the role of ezetimibe in anti-cancer. In this review, we discussed the latest progress in the anti-cancer properties of ezetimibe and elucidated its underlying molecular mechanisms. Finally, we highlighted the potential of ezetimibe as a therapeutic agent in future cancer treatment and prevention.

Correlation of lipid profile with C3d and Carotid Intima-Media thickness in Type 2 Diabetic patients

Background: Complement activation occurs in the vessel's wall as serum lipids start to get deposited, marking the beginning of atherosclerosis formation. Carotid intima-media thickness (IMT) is a widely used tool for detecting atherosclerosis. This study objective was to correlate lipid profile with C3d levels and Carotid IMT in type 2 Diabetic patients. Methodology: This case-control study comprised 120 male and female participants between 35 to 65 years of age. Of them, 90 type 2 diabetes patients were stratified according to the diabetes duration into four groups, Group A (n=30) &lt;5 years of diabetic, Group B (n=30) 5-10 years of diabetic, Group C (n=30) &gt;10 years diabetic and non-diabetic subjects healthy controls in Group D (n=30). The Anthropometric measurements (height, weight, and BMI), serum C3d level, carotid intima-media thickness (carotid IMT) &amp;, serum levels of Cholesterol, Triglycerides, Low-density lipoprotein (LDL), and High-density lipoprotein (HDL) were evaluated. Results: In Type 2 Diabetic patients with moderate to high levels of serum Cholesterol, the C3d levels were found to be significantly raised (10.58 ±3.87 µg/ml and 15.37 ± 2.51 µg/ml, respectively), but Carotid IMT was increased in patients with high Cholesterol (0.98 ± 0.11 mm). Patients with moderate to high levels of Triglycerides had C3d 11.03 ± 3.85 µg/ml and 13.66 ± 4.30 µg/ml, respectively, but Carotid IMT was observed to be raised in patients with higher triglycerides levels (1.00 ± 0.11 mm). Also, in patients with moderate to high serum LDL C3d were 10.26 ± 3.10 µg/ml and 13.14 ± 4.08 µg/ml, respectively, whereas Carotid IMT was increased in patients with high levels of LDL (0.93 ± 0.13 mm). The C3d (12.12 ± 4.42 µg/ml) and Carotid IMT (0.90 ± 0.13 mm) levels were increased as HDL decreased significantly. Conclusion: Serum C3d can be used as an early marker of atherosclerosis formation, which increases as lipid levels exceed the normal range in diabetic type 2 patients compared to carotid IMT detected in patients with higher lipid parameters.

MO245: Risk Factors for Venous Thrombosis in ANTI-PLA2R + VE AND−VE Primary Membranous Nephropathy: A 6-YEAR Retrospective Analysis

Abstract BACKGROUND AND AIMS Venous thrombosis (VT) is an established cause of increased morbidity and mortality amongst patients with nephrotic syndrome. Previous studies suggest primary membranous nephropathy (PMN) to be associated with the highest risk of developing VT amongst all nephrotic diseases. Antibodies to the phospholipase A2 receptor (anti-PLA2R) is identified as a pathogenic marker to the disease activity of PMN, and considered a strong prognostic marker toward disease progression and treatment response. Recent evidence cites the potential of anti-PLA2R as an independent risk factor of VT in PMN. Nevertheless, the pathophysiology of VT for anti-PLA2R + ve and –ve PMN is not fully known. Whether the common risk factors of VT remain as significant within the anti-PLA2R + ve and –ve PMN context is also not convincingly elucidated of yet. Our study aimed to evaluate and compare risk factors for VT in patients with anti-PLA2R + ve and –ve PMN. METHOD This is a retrospective analysis of patients diagnosed with PMN between October 2015 and September 2021. Patients included are age ≥18 years, have biopsy-diagnosed PMN and anti-PLA2R direct immunofluorescence assay testing following PMN diagnosis. Patients excluded were those with secondary causes of membranous nephropathy, history of previous immunosuppression, kidney transplantation before or following PMN diagnosis, or where iatrogenic causes such as major surgery or prolonged immobilization led to VT. Study patients were screened until 28 November 2021 for any VT event and were grouped between those with anti-PLA2R + ve and −ve test results. Demographic and clinical parameters from age, gender, presence of co-morbidities and common risk factors associated with increased risk of VT (hypertension, diabetes mellitus, atrial fibrillation, CHA2DS2-VASC ≥ 3, BMI &amp;gt;30, malignant disease, hormonal treatment and contraceptive pill use), serum and urine biochemical test results at PMN diagnosis (albumin, 24-h proteinuria, proteinuria/albumin ratio, creatinine, eGFR, cholesterol, triglycerides and IgG) were collected. The comparison of demographic and clinical parameters for patients with and without VT in each of the anti-PLA2R + ve and –ve groups was conducted through chi-squared, t and Mann–Whitney U tests. Multivariate regression analysis determined the significance of association between each parameter and VT event occurrence. RESULTS Seventy patients with PMN were included in this study, of which 39 patients are anti-PLA2R + ve and 31 patients are anti-PLA2R−ve. Eight patients (20.5%) had VT in the anti-PLA2R + ve group during follow-up whilst this was the case for four patients (12.9%) in the anti-PLA2R−ve group. In both groups, patients with VT were found to have higher serum cholesterol levels (P &amp;lt; 0.05). Lower serum albumin levels, and greater 24-h proteinuria and proteinuria/albumin ratio was observed in patients with VT within the anti-PLA2R−ve group (P &amp;lt; .05). Full results from the multivariate regression analysis are presented in Tables 1 and 2. Serum cholesterol is demonstrated to be significantly associated with VT in the anti-PLA2R + ve (OR 1.42, 95% confidence interval (CI) 1.12–1.72) and anti-PLA2R−ve groups (OR 1.45, 95% CI 1.15–1.76), respectively. Serum albumin (OR 0.72, 95% CI 0.49–0.96), 24-h proteinuria (OR 1.33, 95% CI 1.03–1.63) and proteinuria/albumin ratio (OR 1.32, 95% CI 1.04–1.59) are shown to be significantly associated with VT within the anti-PLA2R−ve group. CONCLUSION There is supporting evidence that serum cholesterol, albumin and proteinuria may all present as important markers of risk prediction for VT in patients with PMN, though this will require further validation in prospective multi-center studies with larger patient samples. Close monitoring of these markers, and early intervention in response to hypercholesterolemia, hypoalbuminemia and proteinuria with consideration of anti-PLA2R status should ensue as part of primary prevention strategies to reduce VT incidence in the PMN population.