Journal of clinical lipidology最新文献

{"title":"†Role of Epigenetic Regulation and Sp1 Rranscription Factor on DP1 Receptor Expression in Osteoarthritis","authors":"Sami G Alsabri","doi":"10.1016/j.jacl.2024.04.108","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.04.108","url":null,"abstract":"","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141851066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes And Mortality in Heart Failure And Chronic Kidney Disease Patients Admitted With Non-Variceal Upper Gastrointestinal Bleeding","authors":"","doi":"10.1016/j.jacl.2024.04.050","DOIUrl":"10.1016/j.jacl.2024.04.050","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>Chronic kidney disease (CKD) is a major risk factor for cardiovascular disease. Non-variceal upper gastrointestinal bleeding (NVUGIB) can be associated with various medical conditions, including heart failure (HF) and CKD. CKD and HF has been shown to further increase cardiovascular risks.</p></div><div><h3>Objective/Purpose</h3><p>Nevertheless, there is limited scientific evidence of clinical outcomes of NVUGIB in patients with CKD &amp; HF. Hence, we sought to investigate this population.</p></div><div><h3>Methods</h3><p>We queried National Inpatient Sample between 2017-2020 for adult patients who were hospitalized with NVUGIB and had CKD &amp; HF. The primary outcome was inpatient mortality. The secondary outcomes were cardiogenic shock, cardiac arrest, acute kidney injury (AKI), intubation, length of stay (LOS) and total hospital charge. Multivariable logistic regression analysis was used to estimate clinical outcomes. P-value &lt; 0.05 was significant.</p></div><div><h3>Results</h3><p>There were 3,349,779 hospitalizations with NVUGIB and 459,980 (13.7%) had CKD &amp; HF. HF &amp; CKD and non-HF &amp; CKD cohorts were with mean age of 74 vs. 66 yrs; males 46.9% vs 53.1%; Caucasians 63.5% vs 66.6%; HTN 8% vs 39%; dyslipidemia 53.3% vs 37.2%; PE 3.9% vs 4.9%; DM 56% vs 30.4%; AF 24.4% vs 23.5%; obesity 19.5% vs 13.3%; AF 50.2% vs 21.1%; history of stroke 2.0% both, COPD 33.5% vs 18.4%; alcohol use 3% vs 13.8%, respectively. HF &amp; CKD cohort had significantly higher mortality and worse clinical outcomes (Table 1).</p></div><div><h3>Conclusions</h3><p>HF &amp; CKD cohort demonstrated significantly higher mortality, worse clinical outcomes and resource utilization. Patients were older, obese, female, fewer Caucasians, with more frequent dyslipidemia, DM, AF and COPD. HF &amp; CKD is associated with greater risk for cardiovascular events, renal failure, GIB, and ICU care. HF &amp; CKD is an important predictor of adverse outcomes in NVUGIB population. Further research is necessary to describe long-term outcomes.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoprotein(a)’s Prediction of Cardiovascular Disease Events When Accessed via Electronic Health Records","authors":"","doi":"10.1016/j.jacl.2024.04.090","DOIUrl":"10.1016/j.jacl.2024.04.090","url":null,"abstract":"<div><h3>Study Funding</h3><p>Kaneka Pharma America: “Lipoprotein(a) Testing at URMC and Referral to Preventive Cardiology Program\".</p></div><div><h3>Background/Synopsis</h3><p>Lipoprotein(a) (Lp(a)) is a cholesterol-containing, genetically determined molecule in our blood. Studies show that an elevated level of Lp(a) can independently predict an increased risk of atherosclerotic cardiovascular disease (ASCVD) events. There are currently no FDA-approved drugs to reduce Lp(a) and cardiovascular disease event risk.</p></div><div><h3>Objective/Purpose</h3><p>Using the electronic health record (EHR) from the University of Rochester Medical Center (URMC), we determined how well Lp(a) levels predict future cardiovascular disease events currently and over time.</p></div><div><h3>Methods</h3><p>Data were collected from the URMC EHR database of patients &gt;= 18 years with and without at least one Lp(a) measurement from January 1st, 2011 to August 1st 2023 . Cox regression analysis was performed to investigate the effect of Lp(a) level on ASCVD events, while adjusting for several demographic factors and previous ASCVD event status. The Lp(a) level was dichotomized into a normal-level group (&lt;=30 mg/dL) and a high-level group (&gt;30 mg/dL).</p></div><div><h3>Results</h3><p>From January 1st, 2011 to August 1st, 2023, we identified 2,698 patients with at least one Lp(a). Among these individuals, 1,594 did not have an ASCVD event after a baseline Lp(a), while 611 individuals did have an ASCVD event after an Lp(a) baseline measurement. The remaining individuals did not have data on ASCVD status. The mean Lp(a) level was 48 mg/dL among all patients, 45.2 mg/dL among patients without an ASCVD event, and 55.2 mg/dL among patients with an ASCVD event. The normal Lp(a) level range in the URMC lab is &lt;30 mg/dL. Among patients without ASCVD history at baseline, the hazard of an ASCVD event in the high Lp(a) level group is 1.44 times the hazard for the normal Lp(a) level group, with a p-value of 0.008. For patients with a previous ASCVD event, the hazard of an ASCVD event in the high Lp(a) level group is 0.87 times the hazard for the normal Lp(a) level group but not at a statistically significant level (p-value = 0.206).</p></div><div><h3>Conclusions</h3><p>The level of Lp(a) has a varied effect on the hazard of a future ASCVD event. While high Lp(a) level increased the hazard of future ASCVD event for patients with no ASCVD history, high Lp(a) level does not significantly affect the hazard of future ASCVD event for patients with an ASCVD history. It is vital to measure Lp(a) levels to make active steps toward prevention of ASCVD events in the future.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141840768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study Design of a Phase 3 Randomized Controlled Trial Evaluating the Efficacy and Safety of Pegozafermin in Patients with Severe Hypertriglyceridemia","authors":"","doi":"10.1016/j.jacl.2024.04.086","DOIUrl":"10.1016/j.jacl.2024.04.086","url":null,"abstract":"<div><h3>Study Funding</h3><p>89bio, Inc.</p></div><div><h3>Background/Synopsis</h3><p>Severe hypertriglyceridemia (SHTG; defined as greater than or equal to 500 mg/dL) increases the risk of acute pancreatitis, non-alcoholic fatty liver disease and cardiovascular disease. Currently available medications often do not reduce triglycerides to desired levels, highlighting the need for new therapeutic options. Fibroblast growth factor 21 (FGF21) is an endogenous hormone, mainly secreted by the liver, which functions as a master metabolic regulator of lipid and glucose metabolism, as well as energy expenditure. Pegozafermin (PGZ), a long acting FGF21 analog, is in development for the treatment of SHTG and non-alcoholic steatohepatitis. Previous Phase 2 data demonstrated PGZ significantly reduced TGs and hepatic steatosis and improved atherogenic lipoprotein particles and glycemic control, with a good safety and tolerability profile. These promising results led to the design of the first Phase 3 trial of PGZ for the treatment of SHTG.</p></div><div><h3>Objective/Purpose</h3><p>To determine the effect of Pegozafermin on fasting serum triglyceride levels in subjects with Severe Hypertriglyceridemia (TG greater than or equal to 500 to less than or equal to 2000 mg/dL) after 26 weeks of treatment.</p></div><div><h3>Methods</h3><p>ENTRUST is a global 52-week Phase 3, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of pegozafermin in patients with SHTG. Approximately 360 patients aged 22 years old or older, with baseline triglycerides between 500 and 2000 mg/dL and receiving background standard-of-care lipid-modifying therapy will be randomized in a 3:3:2 ratio to weekly subcutaneous injections of PGZ 30 mg, PGZ 20 mg, or placebo. Exclusion criteria include uncontrolled or newly diagnosed T2DM, T1DM, symptomatic gallstone/biliary disease, uncontrolled hypertension, or an acute pancreatitis event within 6 months. The primary endpoint will be percent change in fasting serum TGs from baseline after 26 weeks of PGZ/placebo treatment. Key secondary endpoints include changes in serum lipids, lipoproteins, glycemic control, liver steatosis and safety. Final efficacy analysis will be based on 52 weeks of treatment.</p></div><div><h3>Results</h3><p>The study was initiated in June 2023 and has an estimated primary completion date of August 2025. NCT05852431.</p></div><div><h3>Conclusions</h3><p>ENTRUST is a pivotal Phase 3 clinical trial designed to confirm the efficacy and safety of PGZ in the treatment of SHTG. Expected clinical benefits include significant reductions of triglycerides and hepatic steatosis, as well as other metabolic improvements.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141848042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obicetrapib Alone and with Ezetimibe Reduces Non-HDL-C by Enhanced LDL-Receptor-Mediated VLDL Clearance and Increased Net Fecal Sterol Excretion","authors":"","doi":"10.1016/j.jacl.2024.04.085","DOIUrl":"10.1016/j.jacl.2024.04.085","url":null,"abstract":"<div><h3>Study Funding</h3><p>NewAmsterdam Pharma.</p></div><div><h3>Background/Synopsis</h3><p>Obicetrapib is a selective cholesteryl ester transfer protein (CETP) inhibitor currently in clinical development for the treatment of hypercholesterolemia and reduction of cardiovascular risk that strongly reduces apolipoprotein B (ApoB) and low-density lipoprotein cholesterol (LDL-C) and concomitantly increases plasma high-density lipoprotein cholesterol (HDL-C). Ezetimibe reduces absorption of biliary and dietary cholesterol from the small intestine, thereby reducing LDL-C levels.</p></div><div><h3>Objective/Purpose</h3><p>The current study was carried out to elucidate the mechanism of action responsible for the observed decrease in non-HDL-C by obicetrapib monotherapy and in combination with ezetimibe in a translational mouse model for hyperlipidemia and atherosclerosis.</p></div><div><h3>Methods</h3><p>Female ApoE*3-Leiden.CETP transgenic mice were fed a Western diet with 0.05% w/w cholesterol (equivalent to daily human intake) or this diet containing obicetrapib alone (2 mg/kg/day), ezetimibe alone (1 mg/kg/day) or the combination of obicetrapib and ezetimibe.</p></div><div><h3>Results</h3><p>Obicetrapib, ezetimibe and the combination thereof reduced total plasma cholesterol levels (-42%, -23% and -62%), mainly attributed to a decrease in non-HDL-C levels (-61%, -24% and -80%). Obicetrapib alone and in combination with ezetimibe nearly completely blocked CETP activity (-99% and -100%) resulting in increased HDL-C (+260% and +245%) and ApoA1 levels (98% and 81%). Obicetrapib, ezetimibe and to a larger extent the combination thereof enhanced clearance of VLDL-like particles (half-life: -44%, -23% and -57%) and enhanced hepatic LDL receptor expression (+63% and +74%). Fecal analysis demonstrated increased bile acid excretion in obicetrapib-treated mice (+41%) and increased neutral sterol excretion in ezetimibe-treated mice, which was even more pronounced in combination with obicetrapib (+68% and +100%), resulting in a net fecal sterol loss.</p></div><div><h3>Conclusions</h3><p>Obicetrapib alone and the combination with ezetimibe reduce non-HDL-C levels by increased VLDL lipolysis, increased VLDL clearance and elevated LDL receptor levels accompanied by an enhanced fecal bile acid and neutral sterol excretion.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141842648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"†Synergistic Effect of Obicetrapib and Ezetimibe on Circulating LDL Particles","authors":"","doi":"10.1016/j.jacl.2024.04.102","DOIUrl":"10.1016/j.jacl.2024.04.102","url":null,"abstract":"<div><h3>Study Funding</h3><p>NewAmsterdam Pharma.</p></div><div><h3>Background/Synopsis</h3><p>The oral selective cholesteryl ester transfer protein (CETP) inhibitor, obicetrapib, is in development for dyslipidemia in patients unable to achieve sufficient low-density lipoprotein cholesterol (LDL-C) lowering with other lipid-lowering medications. Previous Phase 1 and 2 trials evaluated obicetrapib as monotherapy, in combination with statins and on top of high-intensity statins (HIS).</p></div><div><h3>Objective/Purpose</h3><p>In this study we tested the efficacy and safety of obicetrapib in combination with ezetimibe on top of HIS.</p></div><div><h3>Methods</h3><p>ROSE2 enrolled men and women without current clinically manifest cardiovascular disease who had LDL-C &gt;70 mg/dL and triglycerides &lt;400 mg/dL, while taking HIS. Participants continued their HIS and were randomized to obicetrapib 10 mg + ezetimibe 10 mg (n=40), obicetrapib 10 mg (n=39), or placebo (n=40) for 12 weeks. Endpoints included the LDL-C response to combination therapy vs. placebo (primary), and non-high-density lipoprotein cholesterol (non-HDL-C), nuclear magnetic resonance-assessed lipoprotein particles (-P), apolipoprotein B (ApoB), lipoprotein (a) [Lp(a)], small dense (sd)LDL-C, other lipid biomarkers and safety.</p></div><div><h3>Results</h3><p>Obicetrapib monotherapy and with ezetimibe, respectively, significantly (all P&lt;0.05) reduced LDL-C (43.5 and 63.4%), non-HDL-C (37.5 and 55.6%), ApoB (24.2 and 34.4%), total LDL-P (54.8 and 72.1%), small LDL-P (92.7 and 95.4%), sdLDL-C (30.9 and 44.4%), and Lp(a) (47.2 and 40.2%), and increased HDL-C (142 and 136%). Obicetrapib was well tolerated, with no dose-related adverse events or clinically significant changes in vital signs, electrocardiograms, hematology or biochemistry. The tremendous lowering of LDL particles with obicetrapib + ezetimibe suggests a synergistic effect perhaps due to an additional mechanism of action (MoA) for CETP inhibition; it upregulates LDL receptors (as previous studies have indicated), but also increases cholesterol removal through transintestinal cholesterol excretion (TICE). Ezetimibe meanwhile prevents reuptake of the excreted cholesterol removed via the inhibition of Niemann-Pick C1-like 1 (Figure).</p></div><div><h3>Conclusions</h3><p>Obicetrapib monotherapy, in combination with HIS, and with HIS plus ezetimibe is safe, well-tolerated and produces robust reductions in LDL-C, LDL particles, sdLDL-C, and Lp(a). ROSE2 obicetrapib monotherapy results concur with findings across the phase 1/2 development program, while combination therapy results support a synergistic effect of obicetrapib + ezetimibe on circulating LDL particles, consistent with the drugs’ known and hypothesized MoAs.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141844055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid lowering Injectable Clinic-Novel Idea for Improving Compliance with Twice Yearly Dosing of Inclisiran","authors":"","doi":"10.1016/j.jacl.2024.04.017","DOIUrl":"10.1016/j.jacl.2024.04.017","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>Inclisiran is a first-in-class small interfering ribonucleic acid (siRNA) which prevents hepatic PCSK9 production. It is indicated as an adjunct to diet or in combination with other cholesterol-lowering medications for adults with Heterozygous familial hypercholesterolemia, clinical atherosclerotic cardiovascular disease and expanded indication for primary prevention for patients with high LDL and without a history of cardiovascular disease. It is administered every 6 months (after initial and 3-month doses) providing a convenient approach to lower LDL cholesterol in a clinic setting. If a scheduled administration is missed by less than 3 months inclisiran should be given as soon as possible and continued the regular schedule. If it is missed by more than 3 months inclisiran dosing schedule should be restarted again.</p></div><div><h3>Objective/Purpose</h3><p>A dedicated clinic was started under the supervision of Dr. Sarah Qureshi to provide team-based care for the patients who were started on inclisiran in the practice to improve compliance.</p></div><div><h3>Methods</h3><p>Clinic lead was responsible for facilitating the clinic by coordinating with the physicians, pharmacists scheduler and clinic nurse. After the first dose of inclisiran was prescribed by the physician, the specialty pharmacists will obtain insurance approval. After the approval was obtained, the patient was notified and a clinic visit was scheduled. Inclisiran was administered at the clinic visit and the patient was educated by the clinic nurse about the side effects. A telephone visit was done 1 week prior to next injection for any side effects and prescribing the medicine. Monthly meetings were conducted to review patient's clinical progress.</p></div><div><h3>Results</h3><p>A total of 204 were prescribed inclisiran from July 26, 2021 - December 31, 2023. 152 patients are on schedule. 52 patients stopped follow up in the clinic:</p><ul><li><span>○</span><span><p>29 refused when contacted to come for the initial injection.</p></span></li><li><span>○</span><span><p>8 patients stopped after one dose (6 after the 1st dose, 1 after the 2nd dose and 1 after the 3rd dose).</p></span></li><li><span>○</span><span><p>3 patients moved on to different clinic.</p></span></li><li><span>○</span><span><p>2 were non responders and switched to other PCSK9 inhibitors.</p></span></li><li><span>○</span><span><p>2 stopped due to terminal care.</p></span></li><li><span>○</span><span><p>3 rejected by insurance.</p></span></li><li><span>○</span><span><p>5 were unreachable.</p></span></li></ul></div><div><h3>Conclusions</h3><p>Team-based care for twice yearly dosing of Inclisiran improves adherence to therapy, monitoring of side effects with minimal effort from the prescribing physician.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141852270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"^Improving Risk Stratification in Severe Hypercholesterolemia: Provider Recommendations for Developing a Program to Communicate ASCVD Risk","authors":"","doi":"10.1016/j.jacl.2024.04.037","DOIUrl":"10.1016/j.jacl.2024.04.037","url":null,"abstract":"<div><h3>Study Funding</h3><p>Research reported in this abstract was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number: R01HL159182.</p></div><div><h3>Background/Synopsis</h3><p>Genetic studies suggest that severe hypercholesterolemia (defined as LDL-C &gt;190mg/dL) can be categorized into four subtypes: monogenic familial hypercholesterolemia (FH), polygenic hypercholesterolemia, elevated lipoprotein(a), and severe hypercholesterolemia with or without a positive family history in the absence of a genetic cause. This information has the potential to improve atherosclerotic cardiovascular disease (ASCVD) risk stratification of individuals affected with severe hypercholesterolemia. By improving understanding and management of the subtypes, health systems can reduce the burden of ASCVD morbidity and mortality in this high-risk population.</p></div><div><h3>Objective/Purpose</h3><p>Due to the complexity and heterogeneity of the severe hypercholesterolemia phenotype, we assessed the readiness and needs of providers who communicate ASCVD risk information to affected individuals.</p></div><div><h3>Methods</h3><p>Semi-structured interviews were conducted via videoconference with providers who care for patients with severe hypercholesterolemia. Interviewers described the four classification subtypes to participants and invited responses to hypothetical scenarios involving communication with a patient with each subtype. Interviewers also asked participants how they would respond to a scenario in which a risk stratification tool included genomic information. Participants were compensated after interviews were completed.</p></div><div><h3>Results</h3><p>Interviews were completed with 11 providers (5 primary care providers (PCPs), 3 cardiology specialists, and 3 genetic counselors) from a single integrated healthcare system. Four patterns from provider interviews emerged about managing each subtype (see Table 1). First, providers described how they would treat and talk with patients across subtypes, which revealed key differences between clinical professions. Most PCPs described a lack of knowledge about the differences among subtypes but expressed interest in understanding and following treatment recommendations for each subtype. Second, providers recommended varying communication resources they and their patients would need to effectively talk about and address the ASCVD risks of each subtype. Next, most PCPs and genetic counselors responded with positive reactions to an ASCVD risk stratification tool that incorporates genomic information, however, cardiology specialists expressed hesitancy to trust this such a tool. Finally, providers gave recommendations for how to implement a program including the genomics informed risk stratification tool to better care for patients with each subtype.</p></div><div><h3>Conclusions</h3><p>To design and implement a program to identify and manage severe hyper","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141838485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"†Interaction of AI-Enabled Quantitative Coronary Plaque Analysis Volumes on Coronary CT Angiography, FFRCT, and Clinical Outcomes: A Retrospective Analysis of the ADVANCE Registry","authors":"W. Huey, James Dundas, Timothy A. Fairbairn, Nicholas Ng, Vida Sussman, Ilana Guez, Rachael Rosenblatt, L. Koweek, P. Douglas, M. Rabbat, G. Pontone, K. Chinnaiyan, B. de Bruyne, Jeroen Bax, T. Amano, K. Nieman, C. Rogers, H. Kitabata, Neils P Sand, Tomohiro Kawasaki, S. Mullen, Hitoshi Matsuo, Manesh R Patel, B. Nørgaard, Amir Ahmadi, G. Tzimas, J. Leipsic","doi":"10.1016/j.jacl.2024.04.119","DOIUrl":"https://doi.org/10.1016/j.jacl.2024.04.119","url":null,"abstract":"","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141852865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Testing Results in a Preventative Cardiology and Inherited Lipid Disorders Clinic","authors":"","doi":"10.1016/j.jacl.2024.04.068","DOIUrl":"10.1016/j.jacl.2024.04.068","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>Genetic testing for inherited lipid disorders can facilitate diagnosis, treatment, and family cascade screening. Of the known monogenic dyslipidemias, familial hypercholesteremia (FH) is the most common. FH is caused by inherited pathogenic variants in LDLR, APOB, PCSK9, and LDLRAP1 and is characterized by significantly elevated LDL cholesterol and increased risk for coronary artery disease (CAD). There are limitations to genetic testing and potential insurance implications, thus a shared decision model including a physician and genetic counselor provides optimal decision-making for the patient.</p></div><div><h3>Objective/Purpose</h3><p>Describe real-world experience of genetic testing at a lipid clinic with involvement of a genetic counselor.</p></div><div><h3>Methods</h3><p>Electronic health record (EHR) data from October 2021 to December 2023 was reviewed for all patients referred to the Inherited Lipid Disorders Clinic at the University of Pennsylvania for genetic counseling and testing.</p></div><div><h3>Results</h3><p>A total of 350 patients were referred for genetic testing. Approximately 72% (n=253) were for FH, 13% for other dyslipidemia, 5% for high triglycerides/chylomicronemia syndrome, 3% for partial lipodystrophy, and 5% for cascade screening following positive genetic testing in a family member. Following communication with the genetic counselor, genetic testing orders were placed for 310 patients who agreed to testing, of which 77% (n=239) completed testing. Results for these patients revealed 51 pathogenic variants, 27 positive (but not diagnostic) variants, 72 variants of uncertain significance (VUS), and 128 negative results. Among the 178 FH patients who completed testing, 17% of these patients had genetic testing confirm the diagnosis of FH with pathogenic variants in LDLR, APOB, PCSK9, or LDLRAP1, while 10% of patients were found to have a VUS in one of these 4 genes. Among the 19 hypertriglyceridemia patients, 9 completed testing and 1 pathogenic variant in LPL was detected. Of the 10 patients with partial lipodystrophy, 7 completed testing and 1 pathogenic variant in LMNA was detected. Meanwhile, of the 17 patients referred for cascade screening, 14 completed testing which showed a pathogenic LDLR variant in 8 patients and 1 patient with an LMNA variant. The genetic counselor informed all patients of results.</p></div><div><h3>Conclusions</h3><p>A high proportion of patients (68%) referred to the lipid clinic for genetic testing completed testing with at-home kits. The majority of patients referred for testing were those with suspected FH. Incorporation of a genetic counselor in the program provides patients with a comprehensive education on the risks and benefits of genetic testing.</p></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}