Mild Hypercholesterolemia Research Articles

A Comparison of Dry Bean and Pea Consumption on Serum Cholesterol: A Randomized Controlled Trial in Adults with Mild Hypercholesterolemia

BackgroundDiets including pulses are associated with better cardiovascular profiles, including lipid, glycemia, and hemodynamics; however, evidence is lacking regarding the contributions of individual pulse varieties. ObjectivesThis randomized, controlled trial examined the effects of beans or peas individually, relative to rice, on LDL-cholesterol levels (primary outcome) and other indices of cardiovascular disease risk (secondary outcomes) at 6 wk in adults with mild hypercholesterolemia. MethodsThis randomized, controlled, single-blind, 3-arm parallel-group study was conducted in 2 Canadian cities (Edmonton, Alberta; Winnipeg, Manitoba). Participants (n = 60 per group) were randomly assigned to 6 wk of regular consumption of foods containing either 120 g (∼0.75 cups) of beans (mixture of black, great northern, navy, and pinto) or 120 g (∼0.75 cups) peas (mixture of yellow and green), or identical foods containing white, parboiled rice (control foods). LDL-cholesterol (primary outcome) and indices of lipid metabolism, glycemia, and hemodynamics (secondary outcomes) were assessed. ResultsMean LDL-cholesterol was lower in the bean group (−0.21; 95% CI: −0.39, −0.03) but not the pea group (−0.11; 95% CI: −0.29, 0.07) relative to rice after 6 wk. Non-HDL-cholesterol (−0.20; 95% CI: −0.40, −0.002) and total cholesterol (−0.28; 95% CI: −0.49, −0.06) were also lower in the bean compared with rice groups. No changes were noted in triglycerides (−0.07; 95% CI: −0.28, 0.14), glucose (0.02; 95% CI: −0.17, 0.14), insulin (4.94; 95% CI: −5.51, 11.38), or blood pressure (systolic: −1.39; 95% CI: −5.18, 2.40; diastolic: −1.89; 95% CI: −4.65, 0.88). Dietary fiber intake (grams per day or grams per 1000 kcal) was not correlated with LDL-cholesterol (grams per day: r2 = 0.209, P = 0.142; grams per 1000 kcal: r2 =0.126, P = 0.379) in the bean group. Gastrointestinal effects were transient and most often not related to the study foods. ConclusionsBeans, but not peas, lowered LDL-cholesterol, relative to rice, in adults with mild hypercholesterolemia. Fiber may not be responsible for the effect of beans, suggesting other phytochemicals may be the active component(s). Strategies incorporating 120 g of pulses in a meal are feasible for managing some cardiometabolic risk factors.This trial was registered at clinicaltrials.gov as NCT01661543.

LDL-Cholesterol-Lowering Effects of a Dietary Supplement Containing Onion and Garlic Extract Used in Healthy Volunteers.

Hypercholesterolemia plays a pivotal role in the development and progression of cardiovascular diseases, and its prevention seems to be a crucial healthcare strategy to ameliorate these conditions. Subjects with mild hypercholesterolemia are frequently advised against using cholesterol-lowering drugs due to potential side effects, with an emphasis instead on prioritizing dietary adjustments and lifestyle modifications as the primary strategy. In this context, the use of dietary supplements based on medicinal plants may be recommended as a complementary approach to managing elevated cholesterol levels. The aim of this study was to investigate the safety and potential therapeutic effectiveness of a standardized formulation containing extracts from garlic and onions in addressing the health concerns of individuals with slightly elevated cholesterol levels. A controlled, randomized, double-blind, two parallel-group study was conducted over 8 weeks, with clinical visits scheduled at baseline, weeks 2 and 4, as well as at the end of the study. The results revealed significant reductions in both low-density lipoprotein cholesterol and total cholesterol levels among participants who received the extract. Additionally, improvements in blood pressure, as well as in oxidative and inflammatory markers were observed, thus suggesting its potential as a valuable therapeutic intervention for managing mild hypercholesterolemia.

Monoglucosyl rutin, a flavonoid glycoside, improves low-density lipoprotein-cholesterol levels in healthy adults: A randomized controlled trial

Background: Atherosclerotic cardiovascular disease (ASCVD) continues to be a significant contributor to global mortality, impacting over 523 million individuals worldwide. Dyslipidemia stands as one of the foremost risk factors for ASCVD. Thus, prioritizing the reduction of low-density lipoprotein cholesterol (LDL-C) levels is essential in mitigating cardiovascular complications. Objective: This study aimed to evaluate the lipid-lowering activity of a dietary supplement containing monoglucosyl rutin (MR) in individuals with low to mild hypercholesterolemia. Methods: This was a randomized, placebo-controlled, double-blind, parallel-group study conducted from April 20 to December 24, 2022. The study population included 56 healthy Japanese adult participants with LDL-C levels between 120–139 mg/dL who were randomly allocated to either the MR or placebo groups (n = 28/group) using a computerized random number generator. 200 mg of MR or placebo divided into 3 tablets was given daily; participants were instructed to take 1 tablet with water after each meal for 12 weeks. The main focus was on measuring the serum LDL-C level as the primary outcome, with additional attention given to secondary outcomes such as serum high-density lipoprotein cholesterol (HDL-C), total cholesterol, and nonHDL-C levels. The study also evaluated the percentage of participants achieving serum LDL-C levels below 120 mg/dL after the 12-week intervention. Assessments were conducted after 4, 8, and 12 weeks of intervention. Results: There were 54 (27 in each group) participants in the per-protocol set (PPS) and 53 (placebo group, 26; MR group, 27) participants in the modified PPS (mPPS). A statistically significant group difference in serum LDL-C levels was observed (P < 0.05), with a 5.0% decrease from preintervention to after 12 weeks. The reduction in LDL-C levels coincided with (statistically significant?) decreases in total cholesterol levels, nonHDL-C levels, and the LDL-C/HDL-C ratio. During the study period, there was no adverse event or concern about the safety of MR. Conclusions: MR has potential as a preventive or therapeutic tool for improving improve long-term health and reducing cardiovascular morbidity. Keywords: monoglucosyl rutin, flavonoid glycoside, low-density lipoprotein cholesterol, hyperlipidemia, lipid profile Trial registration number: UMIN000047790

CLINICAL CHALLENGE: AORTITIS IN THE EMERGENCY DEPARTMENT

Abstract A 67 yo woman presented to the ED for a sustained episode of palpitations and acute chest pain. Past medical history: suspected psoriatic arthritis previously treated with steroids and hydroxychloroquine; previous suspicion of rheumatic polymyalgia and Horton arteritis, regressed with steroids; gastroesophageal reflux disease; mild hypercholesterolemia and a family history of premature coronary artery disease. In the ED the patient was hemodynamically stable. On physical examination: tachyarrhythmic heart sounds with no murmurs. The peripheral arterial pulses were preserved and symmetrical. The remaining physical examination was unremarkable. ECG: atrial fibrillation at 150 bpm. The D–dimer was increased, normal hs–troponin and normal haemoglobin. On echocardiography: normal biventricular structure and function; normal aortic root with dilatation of proximal ascending aorta (47 mm), without visible intimal flaps. The anterior wall of the proximal ascending aorta was thickened. A moderate circumferential pericardial effusion was present, without signs of hemodynamic impact. On suspicion of an acute aortic syndrome with possible intramural haematoma of an ascending aortic aneurism, an urgent CT scan was ordered. It showed a severe dilatation of ascending aorta (52 mm) involving of the proximal aortic arch. The anterior aortic wall was thickened (5 mm), without clear images of IMH, aortic dissection or penetrating ulcer. The pericardial effusion had a supra–fluid density without blood density. A repeated CT at 6 hours showed no changes. The case was suggestive of an inflammatory aetiology. The patient was admitted to the cardiac intensive care unit. A PET–CT scan showed signs of an inflammatory disease of the great vessels. A serological autoimmunity screening was negative. The patient was diagnosed with inflammatory aortitis (giant cell vs Takayasu arteritis) and started on high dose iv glucocorticoid therapy. Given the high risk of severe aortic complications, adjunctive therapy with tocilizumab was prescribed. The therapy was gradually tapered, with subsequent switch to oral steroids plus tocilizumab. At one and a half month of follow–up, a CT scan was repeated, documenting stable aortic diameters and the disappearance of the abnormal thickness and of the enhancement of the aortic wall. A follow–up PET–CT scan has been scheduled at 6 months time. An elective aortic intervention has been indicated after remission of the inflammatory phase.

Hypercalcaemia in a dog with hypothyroidism

AbstractA 5‐year‐old, entire, female Greenland dog was presented with polyuria and polydipsia. A mildly increased circulating concentration of ionised calcium, mild non‐regenerative anaemia, mild hypercholesterolemia and mild increases in liver enzyme activity were detected. Parathyroid hormone, plasma parathyroid hormone‐related protein and vitamin D were analysed in a blood sample, with all results below the lower limit of the reference range. Further investigation with abdominal ultrasonography, fine‐needle aspiration for cytology of the liver and spleen, thoracic radiography, adrenocorticotropic hormone‐stimulation and serum protein electrophoresis could not detect any disease. During the next months, the dog developed coat changes that clinically corresponded to an endocrinopathy. Analysis of thyroxine and thyroid‐stimulating hormone was performed. Thyroxine was less than 6 nmol/L and thyroid‐stimulating hormone was 1.5 µg/L, which indicated primary hypothyroidism. Treatment with l‐thyroxine resulted in normalisation of the hypercalcaemia. Moreover, the polyuria and alopecia resolved.

Mild untreated hypercholesterolaemia affects mechanical properties of the Achilles tendon but not gastrocnemius muscle

Tendon xanthoma and altered mechanical properties have been demonstrated in people with familial hypercholesterolaemia. However, it is unclear whether mild, untreated hypercholesterolaemia alters musculotendinous mechanical properties and muscle architecture. We conducted a case-control study of adults aged 50 years and over, without lower limb injury or history of statin medication. Based on fasting low-density lipoprotein (LDL) cholesterol levels, 6 participants had borderline high LDL (>3.33 mmol/L) and 6 had optimal LDL cholesterol (<2.56 mmol/L). Using shear wave elastography, shear wave velocity (SWV) of the Achilles tendon and gastrocnemius medialis muscle (a proxy for stiffness), along with muscle fascicle length and pennation angle were measured under four passive tensile loads (0, 0.5, 1.0, 1.5 kg) applied via a pulley system. Differences between groups were found for tendon SWV but not muscle SWV, fascicle length or pennation angle. Participants with hypercholesterolaemia showed greater SWV (mean difference, 95 % CI: 2.4 m/s, 0.9 to 4.0, P = 0.024) compared to the control group across all loads. These findings suggest that adults with mild hypercholesterolaemia have increased tendon stiffness under low passive loads, while muscle was not affected. Future research is needed to confirm findings in a larger cohort and explore the impact of hypercholesterolaemia on tendon fatigue injury and tendinopathy.

Physiologic Effects of Isolated or Synthetic Dietary Fiber in Children: A Scoping Review

BackgroundFiber is an integral part of a healthy diet. Studies have shown that the fiber intake in children is below adequate amounts, leading to adverse health outcomes. ObjectivesThis study aimed to perform a scoping review to assess the available evidence for the impact of isolated and synthetic dietary fiber on children’s health outcomes. MethodsA systematic literature search was conducted in Ovid Medline, Ovid Global Health, Embase, and Cochrane Library via Wiley to identify randomized controlled trials (RCTs) in healthy children aged 1–18 y at baseline who consumed added, isolated, or synthetic dietary fiber. The outcomes of interest were categorized based on the Food and Drug Administration’s guidance for industry on nondigestible carbohydrates and the Vahouny Fiber Symposium criteria, which included reduced fasting blood, glucose, total and/or LDL cholesterol concentrations, attenuation of postprandial glycemia/insulinemia, increased fecal bulk/laxation, reduced transit time, weight loss/reduction in adiposity, reduced energy intake from food consumption, increased satiety, bone health/enhanced mineral absorption, and blood pressure. We also cataloged additional reported outcomes. ResultsOf 3837 randomized controlled parallel or crossover trials screened at the abstract level, 160 were eligible for full-text review, and 32 included for data extraction. This scoping review presents analysis of data from 32 RCTs in children who were healthy, overweight/obese or had mild hypercholesterolemia. Inulin-type fructans (41%) and psyllium (22%) were the most frequently administered fiber types, with weight/adiposity, markers of lipid metabolism (41%), and bone-related markers (38%) being the most frequently reported health outcomes. Only a few RCTs have investigated the effects of laxation (9%), and none specifically studied the impact of fiber on reducing postprandial glycemia/insulinemia. ConclusionsThis scoping review demonstrates sufficient evidence for conducting systematic reviews and meta-analyses for several outcomes. Evidence gaps remain on the impact of isolated fibers on outcomes such as laxation, colonic transit time, and postprandial glycemia/insulinemia in children.

Distinct Microbial Taxa Are Associated with LDL-Cholesterol Reduction after 12 Weeks of Lactobacillus plantarum Intake in Mild Hypercholesterolemia: Results of a Randomized Controlled Study.

Probiotic microbes such as Lactobacillus may reduce serum total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol. The objective of this study was to assess the effect of Lactobacillus plantarum strains CECT7527, CECT7528, and CECT7529 (LP) on the serum lipids, cardiovascular parameters, and fecal gut microbiota composition in patients with mild hypercholesterolemia. A randomized, double-blinded, placebo-controlled clinical trial with 86 healthy adult participants with untreated elevated LDL cholesterol ≥ 160mg/dl was conducted. Participants were randomly allocated to either placebo or LP (1.2 × 109CFU/d) for 12weeks. LDL, HDL, TC, and triglycerides (TG), cardiovascular parameters (blood pressure, arterial stiffness), and fecal gut microbiota composition (16S rRNA gene sequencing) were assessed at baseline and after 12weeks. Both groups were comparable regarding age, sex, and LDL-C at baseline. LDL-C decreased (mean decrease - 6.6mg/dl ± - 14.0mg/dl, Ptime*group = 0.006) in the LP group but not in the placebo group. No effects were observed on HDL, TG, or cardiovascular parameters or overall gut microbiota composition. Responders to LP intervention (> 5% LDL-C reduction) were characterized by higher BMI, pronounced TC reduction, higher abundance of fecal Roseburia, and lower abundance of Oscillibacter. In conclusion, 12weeks of L. plantarum intake moderately reduced LDL-C and TC as compared to placebo. LDL-C-lowering efficacy of L. plantarum strains may potentially be dependent on individual difference in the gut microbiota. Trial registration: DRKS00020384, dated 07/01/2020.

GLUCOMANNAN AND RED RICE EXTRACT REDUCE BLOOD LIPID LEVELS IN OVERWEIGHT PATIENTS

Objective: This study aims to explore the changes in blood lipid levels, body composition, and blood pressure in healthy middle-aged overweight people with mild hypercholesterolemia following the 45-day intake of a dietary supplement containing both glucomannan and red rice extract. Design and method: The survey was designed as a single-arm non-randomized, non-blind intervention study. 31 study participants consumed a dietary supplement containing dietary fibers (Konjak glucomannan, E425ii) and red rice extract (Monascus purpureus) for 45 days. Participants were asked not to change their current diet. Their body weight, body composition, and blood pressure were measured every two weeks. Blood lipids were tested at the beginning and at the end of the intervention. Results: After 45 days, there was a significant decrease in total cholesterol (by 16-18%), LDL cholesterol (by 20-24%), and triglyceride levels (by 11-23%) in both genders. In addition, women lost on average about 1 kilogram of body weight, 1.5 kilograms in body fat, and decreased their body mass index by 0.5 kg/m2. No changes in body composition were observed among men, but their systolic pressure decreased by six mmHg on average. Conclusions: Concurrent use of glucomannan and red yeast rice extract resulted in a significant reduction in blood lipid levels in both genders. It could be a safe and effective treatment option for the population of healthy middle-aged overweight people with mild hypercholesterolemia.

Effects of Monacolin K in Nondiabetic Patients with NAFLD: A Pilot Study.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver condition with significant risk of progression to steatohepatitis and cirrhosis. Therapeutic strategies in NAFLD include lifestyle changes mainly related to dietary interventions and use of drugs or nutritional components that could improve plasma lipid profiles and insulin sensitivity and decrease the local inflammatory response. In this study, we tested the effects of monacolin K, an inhibitor of HMCoA reductase. In a prospective, uncontrolled, open study, we treated 24 patients with NAFLD and mild hypercholesterolemia with 10 mg/day of monacolin K. At baseline and after 26 weeks, we measured in plasma liver tests, lipids, malondialdehyde, and oxidized glutathione, and assessed biochemical steatosis scores, liver elastography, and body composition with bioimpedance analysis. Monacolin K significantly reduced plasma alanine aminotransferase, cholesterol, triglycerides and the homeostatic model assessment (HOMA) index that indicated improved insulin sensitivity. No significant changes were found in body fat mass and visceral fat, nor in liver elastography, while the fatty liver index (FLI) was significantly decreased. Plasma levels of both malondialdehyde and oxidized glutathione were markedly reduced by monacolin K treatment, suggesting a reduction in oxidative stress and lipid peroxidation. In summary, this pilot study suggests possible benefits of monacolin K use in NAFLD patients that could be linked to a reduction in oxidative stress. This hypothesis should be further investigated in future studies.

Mild hypercholesterolemia impacts achilles sub-tendon mechanical properties in young rats

BackgroundHypercholesterolemia is associated with tendon pathology, but the reasons underpinning this relationship are not well understood. Cholesterol can accumulate in the tendon non-collagenous matrix which may affect both global and local tissue mechanics. Changes to the local strain environment within tendon may have significant implications for mechanosensitive tenocytes. Here, we investigated the association between elevated blood cholesterol and presence of tendon lipids in the Achilles tendon. We expected lipids to be localised in the proteoglycan-rich inter-sub-tendon matrix (ISTM), therefore we also sought to examine the impact of this on the biomechanical and viscoelastic properties of the ISTM.MethodsThe Achilles tendons of 32 young wild-type (SD) and 32 apolipoprotein E knock-out rats (ApoE−/−) were harvested at 15.6 ± 2.3 weeks of age. 32 specimens underwent histological examination to assess the distribution of lipids throughout sub-tendons and ISTM. The remaining specimens were prepared for biomechanical testing, where the ISTM between the gastrocnemius and soleus sub-tendons was subjected to shear load mechanical testing. A sub-set of tests were video recorded to enable a strain analysis.ResultsApoE−/− serum cholesterol was double that of SD rats (mean 2.25 vs. 1.10 mg/ml, p < 0.001) indicating a relatively mild hypercholesterolemia phenotype. Nonetheless, we found histological evidence of esterified lipids in the ISTM and unesterified lipids in the sub-tendons, although the location or intensity of staining was not appreciably different between rat strains. Despite a lack of observable histological differences in lipid content between groups, there were significant differences in the mechanical and viscoelastic behaviour of the Achilles sub-tendon matrix.ConclusionEven slightly elevated cholesterol may result in subtle changes to tendon biomechanical properties and hence injury risk. The young age of our cohort and the mild phenotype of our ApoE−/− rats are likely to have limited our findings and so we also conclude that the ApoE−/− rat model is not well suited for investigating the biomechanical impact of tendon xanthomas on Achilles sub-tendon function.

The impact of mild hypercholesterolemia on injury repair in the rat patellar tendon.

Hypercholesterolemia is associated with tendon pathology and injury prevalence. Lipids can accumulate in the tendon's extracellular spaces, which may disrupt its hierarchical structure and the tenocytes physicochemical environment. We hypothesized that the tendon's ability to repair after injury would be attenuated with elevated cholesterol levels, leading to inferior mechanical properties. Fifty wild-type (sSD) and 50 apolipoprotein E knock-out rats (ApoE-/ - ) were given a unilateral patellar tendon (PT) injury at 12 weeks old; the uninjured limb served as a control. Animals were euthanized at 3-, 14,- or 42-days postinjury and PT healing was investigated. ApoE-/ - serum cholesterol was double that of SD rats (mean: 2.12 vs. 0.99 mg/mL, p < 0.001) and cholesterol level was related to the expression of several genes after injury; notably rats with higher cholesterol demonstrated a blunted inflammatory response. There was little physical evidence of tendon lipid content or differences in injury repair between groups, therefore we were not surprised that tendon mechanical or material properties did not differ between strains. The young age and the mild phenotype of our ApoE-/ - rats might explain these findings. Hydroxyproline content was positively related to total blood cholesterol, but this result did not translate to observable biomechanical differences, perhaps due to the narrow range of cholesterol levels observed. Tendon inflammatory and healing activity is modulated at the mRNA level even with a mild hypercholesterolemia. These important initial impacts need to be investigated as they may contribute to the known consequences of cholesterol on tendons in humans.

Enterococcus faecium R-026 combined with Bacillus subtilis R-179 alleviate hypercholesterolemia and modulate the gut microbiota in C57BL/6 mice.

Probiotics have been demonstrated to lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in individuals with mild hypercholesterolemia. Our previous study found that intervention with Bacillus subtilis R-179 and Enterococcus faecium R-026, well-known probiotics, improved obesity-associated dyslipidemia through ameliorating the gut microbiota, but similar studies on hypercholesterolemia have not been reported to date. Here, we investigated the therapeutic effect of live combined B. subtilis R-179 and E. faecium R-026 (LCBE) in a C57BL/6 mouse model of hypercholesterolemia. A total of 40 mice were administered with a high-cholesterol diet (containing 1.2% cholesterol) to establish a state of hypercholesterolemia for 4 weeks. Then, mice were divided into one model group (group M) and three treatment groups (n=10 per group), which were administered with LCBE at 0.023g/mouse/day (group L) or 0.230g/mouse/day (group H), or atorvastatin 0.010g/kg/day (group A), for 5 weeks while on a high-cholesterol diet. LCBE at high doses significantly alleviated the symptoms of group M and reduced serum TC, LDL-C, and lipopolysaccharide (LPS). LCBE improved liver steatosis and adipocyte enlargement caused by a high-cholesterol diet. In addition, the administration of LCBE regulated the change in gut microbiota and diversity (Shannon index). Compared with group M, the relative abundance of Actinobacteriota, Colidextribacter, and Dubosiella dramatically decreased in the treatment groups, which were positively correlated with serum TC and LPS. These findings indicated that the mechanism of action of LCBE in treating hypercholesterolemia may be modulation of the gut microbiota. In conclusion, LCBE ameliorated lipid accumulation, reduced inflammation, and alleviated the gut microbiota imbalance in hypercholesterolemic mice. These findings support the probiotic role of LCBE as a clinical candidate for the treatment of hypercholesterolemia.

Positive effects of ketogenic diet on weight control in children with obesity due to Prader-Willi syndrome.

Prader-Willi Syndrome (PWS) is the most common genetic cause of obesity. Prevention and management of obesity, which represents the main cause of morbidity and mortality in these patients, is essential. Ketogenic diet (KD) is used in the treatment of various disorders, however knowledge of its effect in PWS is lacking. The present study assesses the characteristics of patients with PWS who were on KD. This is a retrospective, cross-sectional descriptive study investigating the subjects with PWS, who had received KD for at least 6 months. Ten patients with PWS[median age 52.5 (47-77)months]complied with KD. The median treatment period was 16.5 [11-52]months. Of the daily calorie, 75%-85% were from fat, and 15%-25% from protein + carbohydrate. The baseline body weight standard deviation (SD)score before diet therapy was 2.10 [-1.11-4.11], whereas it was 0.05 [-0.92-1.2]at final evaluation (p = .007). The baseline median BMI SD score before diet therapy was 3.05 [-0.21-3.72], whereas it was 0.41 [-0.87-1.57]at final evaluation (p = .002). The height SD score remained unchanged. Mild hypercholesterolaemia was the most common biochemical abnormality during treatment with KD. Our results indicate that KD might have a favourable effect on weight management in PWS.

219 ISOLATED CORONARY OSTIAL STENOSIS DUE TO RECURRENT AORTIC WALL THROMBOSIS

Abstract Background Coronary ostial lesions are a rare entity and isolated coronary ostial stenosis is even less frequent. Diffuse coronary artery atherosclerosis is the main cause for the non-isolated stenosis, based on old post-mortem series and histological analysis of tissue removed during atherectomies. Case presentation A 49-year-old woman suffering from mild non-familial hypercholesterolemia reported to her family physician repeated episodes of chest pain related to exercise. During a cardiological outpatient evaluation, 12 lead electrocardiogram (ECG) and echocardiography turned out normal. During a stress test she had recurrent chest pain coupled with ECG ischemic changes (diffuse ST segment elevation). She was immediately referred to the emergency department where the ECG was back to normal and the troponin dosage within normal range. Coronary angiography was performed: non-selective cannulation revealed some irregularities of the aortic wall profile at the level of the right coronary ostium, with inability to visualize the right coronary artery. The selective cannulation of the left main coronary artery (LMCA), left anterior descending (LAD) and left circumflex branches showed a critical ostial stenosis at the origin of the LMCA without any other relevant lumen restriction, in a left-dominant pattern of coronary circulation. A suspicion of LAD dissection was raised when a laminar flux was observed at its origin. At the end of the procedure, the patient suddenly collapsed. The recorded rhythm was initially bradycardia, evolving to episodes of ventricular tachycardia for which multiple shocks were applied. Despite the resuscitation efforts, the patient never recovered. Autopsy was performed at the local hospital. At gross analysis, a non-uniform pale-tan thickening at the level of the sino-tubular junction was evident with involvement of both the right and left coronary ostia. Histological examination allowed to ascribe the thickening to recurrent thrombosis, without any underlying inflammatory process at the level of the aortic wall and with only minimal atherosclerotic plaques. No coronary artery dissection nor significant stenosis was present in all the coronary tree. Regarding the ventricular myocardium, one focus of replacement-type fibrosis was identified at subendocardial level in the infero-septal wall coupled with a small spot of loose connective tissue rich in hemosiderin-laden macrophages in the same region, consistent with an area of subacute ischemic damage. Conclusion Several series reported a higher frequency of isolated coronary ostial stenosis in women versus men. In fact, female sex along with hypertriglyceridemia have been recognized as independent risk factors for ostial lesions. The case herein reported highlights the diagnostic relevance of the autopsy investigation together with clinicopathological correlation, particularly in cases where the definite diagnosis can't be achieved in vivo.

Improvement in cardiometabolic risk markers following an oatmeal diet is associated with gut microbiota in mildly hypercholesterolemic individuals

Cardiovascular diseases have been the leading cause of death worldwide for decades. Some animal studies have indicated that oatmeal could improve gut microbiota and cardiometabolic risk markers. However, vivo evidence remained limited, especially in individuals with mild hypercholesterolemia. Our purpose was to explore the beneficial effects of oatmeal on serum lipids, oxidative stress and inflammation levels, and their correlations with gut microbiota and short-chain fatty acids (SCFAs) in mildly hypercholesterolemic individuals. The study was a randomized, single-blind, placebo-controlled trial. A total of 62 qualified participants were randomly divided into control group and oatmeal group with a 45-day follow-up. 16S rDNA and Gas-Chromatography Mass Spectrometry were employed respectively to measure the changes in gut microbiota and SCFAs at the start and the end of the intervention period. Cardiometabolic risk markers were assayed via commercial kits. The results suggested that oatmeal could significantly decrease serum total cholesterol (TC) (−8.59 %, p = 0.013), low density lipoprotein cholesterol (LDL-c) (−12.97 %, p = 0.004) and non-high density lipoprotein cholesterol (non-HDL-c) (−10.98 %, p = 0.040) level. In terms of oxidative stress, oatmeal significantly increased serum total antioxidant capacity (T-AOC) (21.98 %, p < 0.001), superoxide dismutase (SOD) (15.53 %, p = 0.044) levels and decreased concentration of malondialdehyde (MDA) (−19.11 %, p = 0.033) compared with control group. While no significant effect was observed in inflammatory factors. SCFAs results indicated that oatmeal could significantly increase serum acetic acid, propionic acid and valeric acid. The results of 16S rDNA showed that there was a significant difference in the alteration of β-diversity between groups throughout the whole trial. Oatmeal resulted in the increases of Akkermansia, Dialister, Faecalibacterium, Barnesiella, Agathobacter, Lactobacillus and the decrease of Ruminococcaceae-MK4A214-group. Correlation analysis further suggested that the lipids regulation effect of oatmeal may be mainly mediated by Lactobacillus and Dialister, as well as some SCFAs (e.g., acetic acid and propionic acid), while Barnesiella and Akkermansia may play a crucial role in ameliorating oxidative stress level. In conclusion, despite of its small sample size, the present study is the first clinical trial performed in Chinese individuals with mild hypercholesterolemia to explore the effects of oatmeal on serum lipids, oxidative stress, inflammation levels, and gut microbiota. The results demonstrated that oatmeal could induce some beneficial changes in serum lipids, oxidative stress, gut microbiota composition and SCFAs. Correlation analysis further extended our understanding of the role of gut microbiota and SCFAs in improving cardiometabolic risk markers.

Leu22_Leu23 Duplication at the Signal Peptide of PCSK9 Promotes Intracellular Degradation of LDLr and Autosomal Dominant Hypercholesterolemia.

PCSK9 (Proprotein convertase subtilisin/kexin type 9) regulates LDL-C (low-density lipoprotein cholesterol) metabolism by targeting LDLr (LDL receptor) for lysosomal degradation. PCSK9 gain-of-function variants cause autosomal dominant hypercholesterolemia by reducing LDLr levels, the D374Y variant being the most severe, while loss-of-function variants are associated with low LDL-C levels. Gain-of-function and loss-of-function activities have also been attributed to variants occurring in the PCSK9 signal peptide. Among them, L11 is a very rare PCSK9 variant that seems to increase LDL-C values in a moderate way causing mild hypercholesterolemia. Using molecular biology and biophysics methodologies, activities of L8 and L11 variants, both located in the leucine repetition stretch of the signal peptide, have been extensively characterized in vitro. L8 variant is not associated with increased LDLr activity, whereas L11 activity is increased by ≈20% compared with wt PCSK9. The results suggest that the L11 variant reduces LDLr levels intracellularly by a process resulting from impaired cleavage of the signal peptide. This would lead to less efficient LDLr transport to the cell membrane and promote LDLr intracellular degradation. Deletion of a leucine in the signal peptide in L8 variant does not affect PCSK9 activity, whereas the leucine duplication in the L11 variant enhances LDLr intracellular degradation. These findings highlight the importance of deep in vitro characterization of PCSK9 genetic variants to determine pathogenicity and improve clinical diagnosis and therapy of inherited familial hypercholesterolemia disease.

Promene serumskih lipida i telesne mase nakon primene dijetetskog suplementa sa glukomananom i ekstraktom crvenog pirinča u maloj interventnoj studiji

Glucomannan and red rice extract combined in a dietary supplement could exhibit a synergistic effect in lowering blood lipid levels. We aim to explore the changes in blood lipid levels, and body composition in healthy middle-aged overweight people with mild hypercholesterolemia following the 45-day intake of a dietary supplement containing glucomannan and red rice extract. We present a single-arm non-randomized, non-blind intervention study. In total, 31 participants consumed a dietary supplement containing glucomannan dietary fibers (Konjak glucomannan, E425ii, 4 grams) and red rice extract (Monascus purpureus, 1 gram) for 45 days, without changes in their current diet. Body weight and composition were measured every two weeks. Blood lipids were tested at the beginning and the end of the intervention. After 45 days, there was a significant decrease in total cholesterol (by 16-18%), LDL cholesterol (by 20-24%), and triglyceride levels (by 11-23%) in both genders. In addition, women lost on average about 1 kilogram of body weight, 1.5 kilograms in body fat, and decreased their body mass index by 0.5 kg/m2. In men, body composition did not change. Concurrent use of glucomannan and red yeast rice extract resulted in a significant reduction in blood lipid levels in both genders. It could be a safe and effective treatment option for the population of healthy middle-aged overweight people with mild hypercholesterolemia. Trial registry information. Study protocol was registered under ChiCTR1800016300.

Artichoke and Bergamot Phytosome Alliance: A Randomized Double Blind Clinical Trial in Mild Hypercholesterolemia.

Botanicals are natural alternatives to pharmacological therapies that aim at reducing hypercholesterolemia. In this context, despite bergamot being effective in modulating lipid profile, some subjects failed to achieve a satisfactory response to supplementation. The aim of this study was to evaluate whether the association of 600 mg of bergamot phytosome® (from Citrus Bergamia Risso) and 100 mg of artichoke leaf standardized dry extract (from Cynara cardunculus L.) can be an alternative in patients with mild hypercholesterolemia who are poor responders to bergamot in a 2-month randomized placebo-controlled trial. Sixty overweight adults were randomized into two groups: 30 were supplemented and 30 received a placebo. The metabolic parameters and DXA body composition were evaluated at the start, after 30 and 60 days. Between the two groups, total and LDL cholesterol in the supplemented group (compared to placebo) showed significant decreases overtime. A significant reduction of waist circumference and visceral adipose tissue (VAT) was recorded in the supplemented group (compared to placebo), even in subjects who did not follow a low-calorie diet. In conclusion, the synergism between Citrus Bergamia polyphenols and Cynara cardunculus extracts may be an effective option and may potentially broaden the therapeutic role of botanicals in dyslipidemic patients.

Long-term effects with policosanol on lipid profile according to hypercholesterolemia severity in older patients

Background: End-point based studies have demonstrated a direct relationship between coronary disease and elevated serum levels of low density lipoprotein cholesterol (LDL-C) and total cholesterol, as well as the benefits of lowering LDL-C with statins on clinical end-points. Policosanol is a mixture of very long chain fatty alcohols purified from sugar cane wax, with dislipidemia controlling effects, proved in numerous clinical assays in which patients with different conditions were included. The efficacy and tolerability of policosanol in the elderly have been also investigated in several clinical trials, being effective, safe and well tolerated. Objectives: To investigate the effects of policosanol treatment during three years on lipid profile with a proportional intensity to the initial dislipidemia severity in older hypercholesterolemic patients. Methods: The present analysis was obtained from the data of all patients treated with policosanol included in a previous prevention study. One thousand, ford hundred seventy old patients of both sexes, between 60 to 85 years old, with type II hypercholesterolemia, and ³ 1 non-lipid coronary risk factors, were randomized in two groups and treated with policosanol or placebo, during three years. Significant changes on lipid profile with a proportional intensity to the initial dislipidemia severity were considered primary efficacy variables. The analysis was done by Intention-to-treat method. Results: An analysis of the response intensity show that after treatment, reductions of LDL-C, total cholesterol and triglycerides were greater, and according to the initial hypercholesterolemia severity, so that, patients with severe hypercholesterolemia showed the better responses, followed by moderate and mild hypercholesterolemia. An opposite pattern, however, was observed for HDL-C serum concentration. Triglycerides did not respond in the same way. The frequency of vascular serious adverse events was lower in the policosanol group (15 events) compared with those on placebo group (49 events). There were 109 patients who experienced serious adverse events: 83 (11.3 %) in placebo and 26 (3.5 %) in policosanol group (p&lt;0.0001). Twenty-three deaths occurred up to study completion: 19 patients belonging to placebo group (2.6 %) and 4 to the policosanol group (0.5 %). Conclusions: The treatment with policosanol produce positive changes on serum lipid profile according to hypercholesterolemia severity and with a significant lower amount of vascular serious adverse events, mortality, and frequency of total adverse events in older patients.