Moderate Hypercholesterolemia Research Articles

Clinical, imaging and pathological features of hepatic carcinosarcoma in a sugar glider (Petaurus breviceps)

AbstractA 5‐year 6‐month‐old, neutered, male sugar glider (Petaurus breviceps) presented for lethargy. Plasma biochemistry revealed severely elevated alkaline phosphatase and moderate hypercholesterolemia. A heterogenous liver and a right abdominal mass were noted on abdominal ultrasonography. Computed tomography revealed an enlarged liver with ill‐defined hypoattenuating regions and a heterogenous mass arising from the caudate lobe. Cytology of the liver was consistent with low‐grade mixed lipid and hydropic vacuolar change and mild to moderate mixed to mature lymphocytic infiltrate. Liver biopsies were declined, and the patient was managed with silymarin and prednisolone. Serial bloodwork and abdominal ultrasonography revealed persistently elevated alkaline phosphatase and progressive heterogenous hepatomegaly and hepatic nodules. The sugar glider died over 2 years after original presentation. On postmortem examination, there was a poorly differentiated hepatic neoplasm, with immunohistochemistry most consistent with a carcinosarcoma. In future cases, hepatic biopsies could be considered for sugar gliders presenting with hepatic masses when cytology is unrewarding.

SAT330 Recurrence of Acth Independent Cushing Syndrome In Patient With Previously Operated On For Primary Bilateral Macronodular Adrenal Hyperplasia And Co-existence Of Papillary Thyroid Carcinoma

Abstract Disclosure: N. Vashakmadze: None. D. Nikoleishvili: None. Background: Cushing syndrome is a rare and usually sporadic endocrine disorder. Herein we describe a case of ACTH-independent Cushing syndrome and ACTH-dependent Cushing disease in non-identical twins. Moreover, recurrence of Cushing syndrome after 25 years of non-complete resection of adrenal glands and co-existence of papillary thyroid cancer. Clinical Case: A 57-year woman presented with hypertension, depression, easy bruising, proximal muscle weakness, fatigue, and facial plethora. According to the patient, Cushing’s syndrome caused by bilateral macronodular adrenal hyperplasia was diagnosed in 1997. Surgical treatment - left adrenalectomy and right adrenal gland resection was performed. She was receiving HRT during the first 6 months, since then she was not receiving HRT and her cortisol was normal. It is extremely interesting that her nonidentical twin sister was diagnosed with ACTH-dependent Cushing disease in 2006 and was successfully treated with transsphenoidal surgery. In 2019 patient was diagnosed with papillary thyroid cancer (PTC), thyroidectomy was performed and multifocal PTC pT1b(m)N0M0 was diagnosed. Patient received adjuvant therapy with 80 mCi of RAI. In 2019 cortisol and ACTH levels were routinely evaluated, ACTH was undetectable <3 ng/dl (N: 7.2-63); 1 mg dexamethasone suppression test showed no suppression of cortisol 116 ng/ml (N: <1.8 ng/ml). However, patient did not consult an endocrinologist with the results of the mentioned investigations. She admitted to our clinic in December 2022 with above-mentioned complains to determine the tactics of further investigation/treatment. The data obtained during our consultation was consistent to recurrence of Cushing syndrome: midnight salivary cortisol– 0.46 mcg/dl (0.02-0.34), ACTH– 4.2 ng/l (7.2-63), 1 mg of dexamethasone suppression test – 217 nmol/l (<50). CT showed right adrenal noduls (2.5 cm and 1.2 cm). These data confirmed the diagnosis of recurrence of Cushing’s syndrome and right adrenalectomy with steroid coverage and postoperative hormone replacement therapy was recommended. Other data showed normal OGTT, moderate hypercholesterolemia, taking into account Cushing’s syndrome and smoking, statins were initiated. DXA showed osteoporosis (forearm T-score = -3.9 SD). 25(OH)D3 – 22.35 ng/ml, Ca – 1.09 mmol/l (1.1-1.3). Denosumab, calcium and vitamin D supplements were started to the patient. In addition, TSH was markedly suppressed on 125 mcg LT4 therapy, TSH – 0.005 mIU/l (0.4-3.8); Tg <0.17 g/l, anti-Tg - N and neck ultrasound was normal, that is consistent with excellent response and the target TSH was established 0.5-2.0 mIU/l. The dose of LT4 was reduced to 100 mcg. Conclusion: To our knowledge existence of Cushing syndrome and Cushing disease in non-identical twins has not been reported yet. Also, co-existence of Cushing syndrome and thyroid cancer is rare, and no connection is established yet. Presentation: Saturday, June 17, 2023

A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Cholesterol-Lowering Effect of BBR 4401 in Adults with Moderate Hypercholesterolemia

A randomized, double-blind, placebo-controlled trial was designed to assess the efficacy of the parabiotic Bifidobacterium breve IDCC 4401, named BBR 4401, for lowering cholesterol levels. The 66 subjects (per protocol set, n = 60) with low-density lipoprotein-cholesterol (LDL-C) levels between 100 mg/dL and 150 mg/dL were enrolled after a 4-week run-in period (e.g., no probiotics, low cholesterol diet and no food affecting lipid profiles). The two groups were prescribed 1 × 1010 (low-dose) and 1 × 1011 CFU (high-dose), whereas the placebo group was prescribed 97% (w/w) of maltodextrin for 4 weeks. The compliance rates exceeded 97% in the subjects who completed the study. Comparison of the mean changes from baseline between the placebo group and test groups after the 12 weeks of BBR 4401 consumption showed a statistically significant reduction in LDL-C (up to −10.8%, p-value = 0.008) and apolipoproteinB (up to −8.1%, p-value = 0.008). Meanwhile, there were no clinically significant changes in vital signs, clinical pathology tests or electrocardiograms and no significant adverse events were reported during the study period. Concerning bowel habits, the consumption of BBR 4401 alleviated defecation strain, distension and watery feces in the high-dose group. Thus, BBR 4401 may be a safe and functional food for adults with moderate hypercholesterolemia.

Capillary Dynamics Regulate Post-Ischemic Muscle Damage and Regeneration in Experimental Hindlimb Ischemia.

This study aimed to show the significance of capillary function in post-ischemic recovery from the perspective of physiological parameters, such as blood flow, hemoglobin oxygenation and tissue regeneration. Muscle-level microvascular alterations of blood flow and hemoglobin oxygenation, and post-ischemic myofiber and capillary responses were analyzed in aged, healthy C57Bl/6J mice (n = 48) and aged, hyperlipidemic LDLR-/-ApoB100/100 mice (n = 69) after the induction of acute hindlimb ischemia using contrast ultrasound, photoacoustic imaging and histological analyses, respectively. The capillary responses that led to successful post-ischemic muscle repair in C57Bl/6J mice included an early capillary dilation phase, preceding the return of arterial driving pressure, followed by an increase in capillary density that further supported satellite cell-induced muscle regeneration. Initial capillary enlargement was absent in the LDLR-/-ApoB100/100 mice with lifelong moderate hypercholesterolemia and led to an inability to recover arterial driving pressure, with a resulting increase in distal necrosis, chronic tissue damage and a delay in the overall recovery after ischemia. To conclude, this manuscript highlights, beyond arterial collateralization, the importance of the proper function of the capillary endothelium in post-ischemic recovery and displays how post-ischemic capillary dynamics associate beyond tissue blood flow to both hemoglobin oxygenation and tissue regeneration.

Effects of TOTUM-070, a polyphenol-rich compound, on LDL-cholesterol in subjects with moderate hypercholesterolemia (the heart study): A randomized, double-blind, placebo-controlled trial

Effects of TOTUM-070, a polyphenol-rich compound, on LDL-cholesterol in subjects with moderate hypercholesterolemia (the heart study): A randomized, double-blind, placebo-controlled trial

P362 SHORT TERM EFFECTIVENESS OF A NOVEL NUTRACEUTICAL FOR THE MANAGEMENT OF HYPERCHOLESTEROLEMIA IN PATIENTS WITH LOW TO MODERATE CARDIOVASCULAR RISK: A MULTICENTER PRIMARY CARE OBSERVATIONAL

Abstract Purpose: Increasing evidence reinforces the benefits of reduction of low–density lipoprotein (LDL–C) levels on cardiovascular outcomes. Different targets are suggested based on cardiovascular risk (CVR). According to the current European guidelines, a goal of LDL–C≤ 115mg/dL is desirable for patients with low–moderate CVR. However, a high percentage of these patients are far from this target. Nutraceuticals are “food supplements” that may help to achieve this goal in this population. In this retrospective analysis, we evaluate the effects of dietary supplementation with a novel monacolin/berberine/bergamot nutraceutical formulation on plasma lipid levels of subjects with low–moderate hypercholesterolemia who are not treated with conventional drug or other dietary supplements. Patients and Methods 526 adult patients with hypercholesterolemia were retrospectively selected from the database of participant family practitioners according to prespecified criteria. All selected patients had a baseline and 30–day value of total cholesterol (TC), LDL–C, high–density lipoprotein cholesterol, triglycerides, C–reactive protein, and transaminases and have started a dietary supplementation with this novel nutraceutical. Similarly, 104 subjects with comparable clinical features but not treated with any supplements were also selected. Results At 30–day, the administration of nutraceuticals was associated with a significant reduction of LDL–C (124 ± 14 vs. 100 ± 13 mg/dL, Δ 24.5mg, p–value <0.0001) and TC levels (210 ± 56 vs. 187 ± 60, p–value < 0.0001), in the absence of a significant change of transaminase levels. No side effects were reported in the database during the observation period. Conclusion This novel nutraceutical is an effective dietary supplement to achieve a significant and early LDL–C reduction.

A polyphenol-rich compound reduces LDL-cholesterol in subjects with moderate hypercholesterolemia (the HEART study): A randomized, double-blind, placebo-controlled trial

A polyphenol-rich compound reduces LDL-cholesterol in subjects with moderate hypercholesterolemia (the HEART study): A randomized, double-blind, placebo-controlled trial

Nutraceutical alternatives to red yeast rice extract/monacolin K for moderate hypercholesterolaemia: Current evidence and knowledge gaps: Nutraceuticals and hypercholesterolaemia

The nutraceutical approach to moderate hypercholesterolaemia is an interesting option in the context of appropriate conditions associated with low cardiovascular risk, and red yeast rice (RYR) extract is one of the most utilized products in this field. Monacolin k, its main active component, reduces serum LDL-C levels via inhibition of β-Hydroxy β-methylglutaryl-CoA reductase, similarly to statins. In 2011, EFSA approved the claim regarding monacolin k from RYR extract and maintenance of normal cholesterol levels. However, in 2018, EFSA issued a warning about potential adverse effects of this nutraceutical and, in 2022, the European Commission published a Regulation with several limitations of its use. Therefore, current research and development efforts are aiming at assessing efficacy and safety of other known and novel nutraceutical products which may benefit patients with moderate hypercholesterolaemia. These active agents range from phytosterols, probiotics and berberine to bergamot, cabbage and artichoke extracts and soy protein. Moreover, plant extracts from traditional medicine, for example from African countries, are also a subject of study in this direction. The full clinical exploitation of many of them, however, still requires robust clinical evidence, which should be the objective of future research.

Short-Term Effect of Nutraceutical Fruit Juices on Lipid Metabolism in Patients with Acquired Hypercholesterolemia.

The crucial role of dyslipidaemia, especially hypercholesterolemia, in the development of atherosclerosis-related cardiovascular diseases has been extensively documented in genetic, pathologic, observational and intervention studies. The European guidelines for dyslipidaemia management include the possible use of lipid-lowering nutraceuticals to support a relatively large number of natural compounds. In this context, we have conducted a study to investigate whether dietary supplementation with a functional nutraceutical beverage, containing a standardized polyphenolic fraction from fruit, red yeast rice, phytosterols, and berberine complexed with β-cyclodextrin, could positively affect serum lipid concentration in 14 subjects with hypercholesterolemia. After 12 weeks of treatment, dietary supplementation with this nutraceutical combination was associated with significant improvements in total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B, compared to baseline. Compliance was excellent and no adverse effects were reported. In conclusion, this study demonstrates that 100 mL of a functional beverage containing lipid-lowering nutraceuticals safely leads to significant improvements in serum lipids in subjects with moderate hypercholesterolemia. Future research is needed to unravel the role that the polyphenols contained in fruit extracts play in the reduction of cholesterolemia and in cardiovascular disease prevention.

A Review of Low-Density Lipoprotein-Lowering Diets in the Age of Anti-Sense Technology.

This narrative review discusses an important issue, the primary role of diet in reducing low-density lipoprotein cholesterol (LDLc) concentrations in polygenic hypercholesterolemia. Two effective drugs, statins, and ezetimibe, that lower LDLc > 20% are relatively inexpensive and potential competitors to strict dieting. Biochemical and genomic studies have shown that proprotein convertase subtilisin kexin type 9 (PCSK9) plays an important role in low-density lipoprotein (LDL) and lipid metabolism. Clinical trials have demonstrated that inhibitory monoclonal antibodies of PCSK9 dose-dependently lower LDLc up to 60%, with evidence of both regression and stabilization of coronary atherosclerosis and a reduction in cardiovascular risk. Recent approaches using RNA interference to achieve PCSK9 inhibition are currently undergoing clinical evaluation. The latter presents an attractive option of twice-yearly injections. They are, however, currently expensive and unsuitable for moderate hypercholesterolemia, which is largely due to inappropriate patterns of eating. The best dietary approach, the substitution of saturated fatty acids by polyunsaturated fatty acids at 5% energy, yields > 10% lowering of LDLc. Foods such as nuts and brans, especially within a prudent, plant-based diet low in saturates complemented by supplements such as phytosterols, have the potential to reduce LDLc further. A combination of such foods has been shown to lower LDLc by 20%. A nutritional approach requires backing from industry to develop and market LDLc-lowering products before pharmacology replaces the diet option. Energetic support from health professionals is vital.

Short-Term Dietary Calcium Fortification Increases Fecal Saturated Fat Content and Reduces Serum Lipids in Men

The effect of dietary calcium on fecal fatty acid excretion and serum lipids was tested in a randomized, single-blind metabolic study in 13 healthy men with moderate hypercholesterolemia. A low calcium base diet containing 34% of energy from fat, 13% from saturated fatty acids, 240 mg cholesterol/d and 410 mg Ca/d was compared with a fortified version in which calcium citrate malate was added to orange juice, (550 mg) muffins (750 mg), and two tablets (500 mg) for a total calcium intake of 2200 mg/d. Fecal collections (72 h, d 8, 9, 10) and blood from fasting subjects for lipids and lipoproteins (d 9, 10, 11) were obtained. The percentage of dietary saturated fat excreted per day increased from 6 to 13% with calcium fortification. There was no change in fecal bile acid excretion. The high Ca diet significantly reduced total cholesterol 6% (5.99 to 5.66 mmol/L), LDL cholesterol 11% (4.13 to 3.67 mmol/L), and apolipoprotein B concentrations 7% when compared with the low Ca diet (P < 0.05). There was no change in HDL cholesterol or apolipoprotein A1 concentrations. Urinary calcium excretion increased from 146 to 230 mg/d when the high Ca diet was consumed. Calcium fortification was effective in lowering total and LDL cholesterol concentrations and may be an effective adjunct to cholesterol-lowering diet therapy.

Α Randomized, Placebo-Controlled Trial to assess the Efficacy and Safety of a Novel Nutraceutical Combination of Monacolin K and Bergamot extract in subjects with Mild to Moderate Hypercholesterolemia

Α Randomized, Placebo-Controlled Trial to assess the Efficacy and Safety of a Novel Nutraceutical Combination of Monacolin K and Bergamot extract in subjects with Mild to Moderate Hypercholesterolemia

551 RAPID RELATIVE EFFECTIVENESS OF A NOVEL NUTRACEUTICAL FOR THE MANAGEMENT OF HYPERCHOLESTEROLEMIA: A MULTICENTER PRIMARY CARE EXPERIENCE IN A LARGE POPULATION OF PATIENTS AT LOW TO MODERATE CARDIOVASCULAR RISK

Abstract Backgroud In the last few years increasing evidence have reinforced the benefits of low-density lipoprotrein (LDL-C) levels reduction on cardiovascular outcome. Different targets have been suggested based on the cardiovascular risk (CVR). A goal of LDL-C less of 115mg/dL is desiderable for patients at low to moderate CVR according the current european guidelines. However, an high percentage of patients at low to moderate CVR are far from this target. Nutraceuticals are “food supplements” that may help to achieve this goal in this population. The aim of this retrospective analysis was to evaluate the effects of dietary supplementation with a novel nutraceutical formulation on plasma lipid levels in subjects with low to moderate hypercholesterolemia who are not on treatment with conventional drug and/or with other dietary supplements. Methods Adult patients with hypercholesterolemia were retrospectively selected from the database of participant family practitioners. All patients had a baseline evaluation already recorded, including family and medical history, physical examination, and blood test that included total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), C-reactive protein (CRP), and transaminases (AST and ALT) and have started a dietary supplementation with nutraceuticals. After this selection, a total of 504 patients under this novel nutraceutical (given 1 tablet daily at dinner) with blood test at 30-days already performed, were identified. Similarly, 108 subjects with comparable clinical features but not treated with any supplements were also selected. Results At 30-day of follow-up, the use of this novel dietary supplement was associated with significant reduction of LDL-C 124 ± 16 vs. 100 ± 13 mg/dL, p-value &amp;lt;0.001) and TC levels (210 ± 56 vs. 187 ± 60, p-value &amp;lt; 0.0001), in absence of a significant changes of transaminase levels (AST: 30 ± 6 vs. 30 ± 6 U/L, p-value 0.198; ALT: AST: 30 ± 6 vs. 30 ± 6 U/L, p-value 0.325) and in CRP (3.9 ± 1.5 vs. 3.9 ± 1.4 mg/dL, p-value 0.889). No side effects were reported in the database along to the observation period. Conclusion This novel nutraceutical formulation is an effective dietary supplement in obtaining a significant and early reduction of LDL-C in patients with hypercholesterolemia at low to moderate cardiovascular risk.

Abstract 14188: An Unexpected Cause of Anterior ST Segment Elevation After Coronary Intervention

Background: ST elevation (STE) in V1 to V3 is traditionally labeled as anteroseptal infarction due to occlusion of the LAD proximal to the septal branches. An important and uncommon cause for similar ECG findings is an isolated RV myocardial infarction due to occlusion of the proximal RCA and/or its branches. We present a case of anteroseptal ST elevation after jailing of a conus branch during percutaneous coronary intervention (PCI) to the RCA. CASE: 89-year-old female with history of moderate aortic stenosis (AS), hypertension, hypercholesterolemia, and prior stroke presented with progressive dyspnea on exertion and 3 days of chest tightness. Initial echocardiogram showed an EF of 64% and severe AS with peak velocity of 4.27 m/s, mean gradient of 45 mmHg and aortic valve area of 0.43 cm 2 . Coronary angiography showed severe stenosis of the proximal RCA successfully treated with intravascular lithotripsy and drug-eluting stent deployment with jailing of the conus branch. The LAD and LCX had mild nonobstructive disease. Patient developed chest pain after the procedure with new STE in V1 to V3. She was taken for emergent cardiac angiogram due to suspected occlusion of the LAD however this showed unchanged anatomy with patent stent in the RCA and no new severe stenosis or occlusion of the left coronary arteries. There was no flow in the jailed conus branch that was not intervened on due to small vessel size. A repeat echocardiogram showed new mild RV dilatation with unchanged EF and normal LV wall motion. Patient had resolution of the chest pain and STE within 2 hours and was discharged home in stable condition. Conclusion: Occlusion of a conus branch artery with associated isolated RV myocardial infarction is an uncommon cause of STE in anteroseptal leads. High index of suspicion is important to anticipate and manage potential complications like ventricular arrhythmias and RV failure.

Effects of treatment with monacolin K, berberine and coenzyme Q10 on lipid metabolism in patients with moderate cardiovascular risk

ObjectiveThe use of nutritional supplements to treat hypercholesterolemia is gradually increasing, however further studies on their efficacy and safety are required. Patients and methodsThe present clinical trial included patients with moderate hypercholesterolemia and cardiovascular risk who were treated either with a nutraceutical preparation containing 3.75mg of monacolin K, 515mg of berberine and 50mg of coenzyme Q10 per tablet (Lipok®) or with a placebo. The clinical and laboratory variables were analyzed at baseline and at three and six months. None of the patients was diabetic, and none was being treated with lipid-lowering drugs or with any other nutritional supplements affecting lipid metabolism. ResultsIn patients of the intervention group and of the placebo group, baseline LDL-C was 134.7mg/dL (14.4) and 138.7mg/dL (15.2), respectively. At three months after treatment start, LDL-C had decreased by 26.1mg/dL (−32.4 to 19.7) and increased by 4.5mg/dL (−1.5 to 10.5) in the respective groups. In the intervention group, a similar decrease in non-HDL-C and total cholesterol was observed, while no significant changes were observed in either group for HDL-C, triglycerides and lipoprotein(a). A good tolerance and safety profile was observed. ConclusionIn conclusion, this study demonstrates that the combination of monacolin K, berberine and coenzyme Q10 is effective and safe for treating hypercholesterolemia in patients with a moderate degree of excess LDL-C and cardiovascular risk.

Effect of Dietary Supplementation with Eufortyn® Colesterolo Plus on Serum Lipids, Endothelial Reactivity, Indexes of Non-Alcoholic Fatty Liver Disease and Systemic Inflammation in Healthy Subjects with Polygenic Hypercholesterolemia: The ANEMONE Study.

We aimed to evaluate if dietary supplementation with a nutraceutical compound (Eufortyn® Colesterolo Plus) containing standardized bergamot polyphenolic fraction phytosome (Vazguard®), artichoke extract (Pycrinil®), artichoke dry extract. (Cynara scolymus L.), Q10 phytosome(Ubiqosome®) and zinc, could positively affect serum lipids concentration, systemic inflammation and indexes of non-alcoholic fatty liver disease (NAFLD) in 60 healthy subjects with polygenic hypercholesterolemia. Participants were adhering to a low-fat, low-sodium Mediterranean diet for a month before being randomly allocated to 8-week treatment with 1 pill each day of either Eufortyn® Colesterolo Plus or placebo. Dietary supplementation with Eufortyn® Colesterolo Plus was associated with significant improvement in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), high-sensitivity C-reactive protein (hs-CRP) and endothelial reactivity (ER) in comparison with baseline, and with significant reductions in waist circumference, TC, LDL-C, LDL-C/HDL-C, lipid accumulation product and fatty liver index compared to placebo. The study shows that dietary supplementation with standardized bergamot polyphenolic fraction phytosome, artichoke extracts, Q10 phytosome and zinc safely exerts significant improvements in serum lipids, systemic inflammation, indexes of NAFLD and endothelial reactivity in healthy subjects with moderate hypercholesterolemia.

Effects of an Optimized Aged Garlic Extract on Cardiovascular Disease Risk Factors in Moderate Hypercholesterolemic Subjects: A Randomized, Crossover, Double-Blind, Sustainedand Controlled Study.

The consumption of aged black garlic (ABG) has been related to improvements in several cardiovascular disease (CVD) risk factors. However, the extent of the beneficial effects depends on the garlic aging process and the amount and type of chemical compounds accumulated. The main objective of this study was to assess the effect of daily intake of a well-characterized ABG extract with a standardized S-allyl-L-cysteine (SAC) yield in combination with dietary recommendations regarding CVD risk factors in individuals with moderate hypercholesterolemia. Sixty-seven hypercholesterolemic individuals with low-density lipoprotein cholesterol levels ≥115 mg/dL were randomized in a crossover, double-blind, sustained, and controlled intervention study. The participants consumed 250 mg (1.25 mg SAC)/tablet/day ABG or a placebo for 6 weeks, with 3 weeks of washout. Blood and pulse pressure and other CVD risk biomarkers were determined at the beginning and end of each intervention. At 6 weeks, ABG extract reduced diastolic blood pressure (DBP) (mean (95% CI) −5.85 (−10.5; −1.3) mm Hg) compared to the placebo, particularly in men with a DBP > 75 mm Hg. The consumption of an improved ABG extract with 1.25 mg of SAC decreased DBP, particularly in men with moderate hypercholesterolemia. The potential beneficial effects of ABG may contribute to obtaining an optimal DBP.

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.

Abstract 12303: Management of Severe and Moderate Hypercholesterolemia in Young Adults

Introduction: Cardiovascular guidelines advise statin therapy for adults aged 20-75 years with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL with a goal of lowering LDL-C by ≥50%. Further, early-life accumulation of cholesterol exposure increases future cardiovascular risk independent of total cumulative cholesterol exposure, highlighting the importance of LDL-C management in young adults. However, real-world management of hypercholesterolemia in young adults is not well described. Methods: Using the Mass General Brigham clinical data registry, we isolated 2 cohorts of patients with hypercholesterolemia who had cholesterol testing on ≥2 occasions and were 20-39 years old at the time of a qualifying LDL-C value between 2005-2018: those with LDL-C ≥190 mg/dL (Cohort 1) and LDL-C 160-&lt;190 mg/dL (Cohort 2). Follow-up LDL-C values were extracted through 2019. Primary endpoints were 50% reduction in LDL-C for Cohort 1 and 30% reduction for Cohort 2. Results: Cohort 1 (severe hypercholesterolemia) included 5,475 patients (37.9% female, mean [SD] age 32.6 [5.1] years at qualifying LDL-C), and Cohort 2 (moderate hypercholesterolemia) included 12,608 patients (39.6% female, mean [SD] age 32.6 [5.1] years). In Cohort 1, 1,638 individuals (29.9%) achieved ≥50% LDL-C reduction overall (31.7% of men vs. 27.1% of women, P&lt;0.001; Figure ) over median (IQR) 7.8 (4.5-11.3) years of follow-up. The youngest individuals were less likely to achieve 50% LDL-C reduction (e.g., 20-24 years old: 24.8% vs. 35-39 years old: 32.7%; P trend &lt;0.001). In Cohort 2, 4,515 individuals (35.8%) achieved ≥30% LDL-C reduction over median (IQR) 7.5 (4.2-11.1) years of follow-up. Conclusions: In a large, integrated healthcare system, &lt;30% of young adults with severe hypercholesterolemia achieved guideline-directed LDL-C-lowering over 8 years of follow-up. These findings highlight the need for strategies to promote guideline-recommended cholesterol management in young adults.

Replacing Saturated Fat with Polyunsaturated Fat Modulates Peripheral Blood Mononuclear Cell Gene Expression and Pathways Related to Cardiovascular Disease Risk Using a Whole Transcriptome Approach.

The aim of this study is to explore the molecular mechanisms underlying the effect of replacing dietary saturated fat (SFA) with polyunsaturated fat (PUFA) on cardiovascular disease (CVD) risk using a whole transcriptome approach. Healthy subjects with moderate hypercholesterolemia (n = 115) are randomly assigned to a control diet (C-diet) group or an experimental diet (Ex-diet) group receiving comparable food items with different fatty acid composition for 8 weeks. RNA isolated from peripheral blood mononuclear cells (PBMCs) at baseline and after 8 weeks of intervention is analyzed by microarray technology (n = 95). By use of a linear regression model (n = 92), 14 gene transcripts are differentially altered in the Ex-diet group compared to the C-diet group. These include transcripts related to vascular smooth muscle cell proliferation, low-density lipoprotein receptor folding, and regulation of blood pressure. Furthermore, pathways mainly related to immune response and inflammation, signal transduction, development, and cytoskeleton remodeling, gene expression and protein function, are differentially enriched between the groups. Replacing dietary SFA with PUFA for 8 weeks modulates PBMC gene expression and pathways related to CVD risk in healthy subjects with moderate hypercholesterolemia.