Journal of clinical lipidology最新文献

{"title":"Lipoprotein(a) screening for cardiac allograft vasculopathy among heart transplant recipients","authors":"Deepasree Bangaru-Raju MD,&nbsp;Dhivyashree Bangaru-Raju MD,&nbsp;Vi Nguyen PharmD,&nbsp;Shamim Khosrowjerdi BS,&nbsp;Sotirios Tsimikas MD,&nbsp;Jose Benjamin Cruz Rodriguez MD,&nbsp;Antoinette Birs MD,&nbsp;Andrew Kao MD","doi":"10.1016/j.jacl.2025.04.032","DOIUrl":"10.1016/j.jacl.2025.04.032","url":null,"abstract":"<div><h3>Background/Synopsis</h3><div>Lipoprotein(a) [Lp(a)] is a well-established inheritable risk factor of atherosclerotic cardiovascular disease (ASCVD) for which the National Lipid Association (NLA) recommends Lp(a) screening once in all adults. Heart transplant (HTx) recipients develop both cardiac allograft vasculopathy (CAV) hallmarked by a chronic but progressive coronary intimal thickening as well as atherosclerosis. While traditional ASCVD risk factors such as hypertension, diabetes, hyperlipidemia are stringently optimized among transplant recipients, the impact of Lp(a) on CAV development remains unknown.</div></div><div><h3>Objective/Purpose</h3><div>Elevated Lp(a), defined as level &gt; 50mg/dL, has been shown to confer development of ASCVD. The complex pathophysiology of early CAV is a result of both donor and recipients baseline risk factors, and post-transplant factors. This study aims to investigate the association of Lp(a) and early CAV development in HTx recipients.</div></div><div><h3>Methods</h3><div>A single-center, retrospective study analyzed 88 HTx recipients between 2015 to 2024 with measured Lp(a) and at least one post-HTx coronary angiogram with highly sensitive intravascular ultrasound (IVUS). The primary endpoint was CAV quantified by maximal intimal thickness (MIT) of 1mm and 1.5mm. Cox proportional hazard models were used to evaluate the association of elevated Lp(a) with MIT. The model was adjusted for key covariates: treated cytomegalovirus, rejection, LDL-cholesterol, high intensity statin use, donor ischemic time, BMI, and sex.</div></div><div><h3>Results</h3><div>A total of 24 (27.3%) of HTx recipients had an elevated Lp(a) &gt; 50 mg/dL; median Lp(a) was 17.5 [7.0, 34.0] and 91.5 [68.8, 128.5] mg/dL, respectively. Median follow-up time post HTx was 2.12 years [1.17, 4.04]. Baseline lipid profile and characteristics were similar between groups, Table 1. In univariate analysis, Lp(a) &gt; 50 mg/dL was not associated with MIT 1.5mm development (HR 1.9, 95% CI 0.49-7.60, p = 0.35), nor in multivariate analysis, (HR 2.36, 95% CI 0.45-12.4, p = 0.30; overall model p = 0.03). LDL-C &gt; 100 mg/dL was highly correlated with CAV outcomes (HR 4.7, p = 0.02).</div></div><div><h3>Conclusions</h3><div>Elevated Lp(a) was not associated with an increased risk for the early development of CAV as determined by IVUS. As elevated Lp(a) has been associated with increased long-term risk of angiographic disease, additional study is required to understand how cumulative exposure to elevated Lp(a) may contribute to this process. The complex relationship between Lp(a), the immune response to HTx, and CAV warrants further investigation.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Page e24"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168616","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":"Preliminary results of a multifaceted intervention to improve guideline-directed lipid-lowering therapy in patients with recent MI","authors":"Ning Rosenthal MD,&nbsp;Laney Jones PharmD,&nbsp;Cezary Wojcik MD,&nbsp;Ran Jin MD,&nbsp;Zachary Johnson BS,&nbsp;Leslie Carabuena MS,&nbsp;Edna Kavuma MPH,&nbsp;Rachel Mackey PhD","doi":"10.1016/j.jacl.2025.04.022","DOIUrl":"10.1016/j.jacl.2025.04.022","url":null,"abstract":"<div><h3>Funding</h3><div>This research (the LOGAN-CV study)was sponsored by Amgen Inc.</div></div><div><h3>Background/Synopsis</h3><div>Most patients with atherosclerotic cardiovascular disease (ASCVD) do not achieve guideline-recommended LDL-C &lt; 70 mg/dL. Effective interventions are urgently needed to reduce risk of recurrent CV events. Within the Premier, Inc. hospital network, we conducted a multicenter single-arm interventional study (LOGAN-CV) to improve lipid management in high-risk, post-myocardial infarction (MI) patients.</div></div><div><h3>Objective/Purpose</h3><div>To evaluate whether a 1-year multifaceted intervention improves lipid-lowering therapy (LLT) intensification and LDL-C control in statin-treated adults who had an MI in the past year and had uncontrolled LDL-C.</div></div><div><h3>Methods</h3><div>Clinicians with patients who met inclusion criteria (age ≥ 21, acute MI, statin treatment, LDL-C ≥ 70 mg/dL) during the year prior to start of the intervention were recruited from 7 sites. Clinician-focused interventions included custom cholesterol guideline and LLT education modules and a personalized dashboard of LDL-C and LLT-related patient metrics. Index date is the end of clinician education and baseline is 12 months before the index. This preliminary analysis includes the 2 sites that have completed the 1-year intervention.</div></div><div><h3>Results</h3><div>The 2 completed sites had 15 clinicians and 126 patients. Mean patient age was 65.7 years (SD=13.4), 56% were women, 63% white, 29% black, 36% had diabetes, 41% had obesity, and 54% had hypertension (Table). Patients’ most recent MI occurred a mean of 4.5 months (SD=3.1) prior to index, with 31% receiving PCI, 7.1% receiving CABG, and 62% medical management only. At index, majority of patients were prescribed moderate- (25%) or high-intensity (73%) statin. Ezetimibe was prescribed in 13% (n=17) of patients in combination with moderate- (n=3) or high- (n=14) intensity statin. During the 1-year intervention, 10% of patients had 1 recurrent MI and 21% had 2 recurrent MIs. LLT intensification occurred in 17% of patients (8.7% statin intensification, 4.8% ezetimibe addition, 3.2% PCSK9i mAb addition) (Figure). Only 64% (n=80) patients had LDL-C tests ordered. Median (Q1, Q3) LDL-C decreased from 90 (78, 110) mg/dL at index (n=126) to 71 (54, 94) mg/dL at month 12 of follow up (n=79), and 40/126 (32%) patients reached LDL-C control (&lt;70 mg/dl) in an average of 5.4 (SD=3.2) months, and 16% reached LDL-C &lt;55 mg/dL in an average of 6.3 (SD=3.2) months.</div></div><div><h3>Conclusions</h3><div>During a 1-year, multifaceted intervention to improve lipid management in patients with recent MI and uncontrolled LDL-C, 32% of patients reached the guideline-recommended LDL-C of &lt; 70 mg/dL. Additional efforts to this intervention are needed to improve LDL-C testing and LDL-C control in these high-risk patients to prevent recurrent events.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Pages e15-e16"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144166974","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":"Associations of serum omega-6 polyunsaturated fatty acids with apolipoprotein B and atherogenic lipoprotein lipids","authors":"Carol Kirkpatrick PhD,&nbsp;Meredith Wilcox MPH,&nbsp;Liana Guarneiri PhD,&nbsp;Peter Attia MD,&nbsp;David Allison PhD,&nbsp;Kevin Maki PhD","doi":"10.1016/j.jacl.2025.04.086","DOIUrl":"10.1016/j.jacl.2025.04.086","url":null,"abstract":"<div><h3>Funding</h3><div>The Indiana University Foundation funded this research.</div></div><div><h3>Background/Synopsis</h3><div>Observational evidence supports associations between higher intakes of omega-6 polyunsaturated fatty acids (PUFAs) and reduced risk for atherosclerotic cardiovascular disease. Serum levels of total omega-6 PUFAs and linoleic acid (LA), the predominant dietary omega-6 PUFA, correlate with dietary LA intake.</div></div><div><h3>Objective/Purpose</h3><div>Aegis was a prospective cohort study that investigated immunological and other biomarker changes after incident severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This cross-sectional analysis of baseline data from the Aegis cohort examined the relationships between serum omega-6 PUFA (total and LA) levels and selected biomarkers of cardiovascular risk, including apolipoprotein B (apoB) and lipoprotein lipid concentrations.</div></div><div><h3>Methods</h3><div>Baseline fasting serum levels of omega-6 PUFAs, apoB, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides were assessed. Multivariate linear models were used to assess biomarker levels across quintile categories of serum fatty acids with body mass index (BMI), age, and sex as covariates.</div></div><div><h3>Results</h3><div>Analyses included 1894 participants for whom relevant biomarker data were available (65% female, mean age: 50 y, mean BMI: 29.0 kg/m², 62% Non-Hispanic White, 11% Black/African American, 7% Hispanic/Latino, 10% Asian, 10% mixed/other). The 20^th and 80^th percentiles for omega-6 PUFAs as a percentage of total circulating fatty acids were 38.5% and 42.8%, respectively, and for LA were 31.3% and 36.4%, respectively. Least squares geometric means (LSGMs) in mg/dL for serum omega-6 PUFA level quintile (Q)1 and Q5, respectively, were: apoB, 101 and 90.1 (P &lt; 0.001); LDL-C, 107 and 100 (P = 0.069); non-HDL-C, 140 and 117 (P &lt; 0.001); and triglycerides, 184 and 69.0 (P &lt; 0.001). LSGMs for serum LA level Q1 and Q5, respectively, were: apoB, 90.5 and 105; LDL-C, 93.8 and 118; non-HDL-C, 122 and 138; and triglycerides, 151 and 89.1 (all P &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>A higher serum total omega-6 PUFA level was linked to a more favorable lipid profile, with lower concentrations of apoB, non-HDL-C, and triglycerides. However, a higher serum LA concentration was associated with a lower triglyceride concentration but higher apoB, LDL-C, and non-HDL-C concentrations, highlighting potential differential relationships for specific omega-6 PUFAs.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Pages e62-e63"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168361","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":"Outcomes of hyperglycemic emergencies among African Americans compared to Caucasians: A large-scale nationwide analysis","authors":"Oluwatoyosi Awotorebi MD,&nbsp;Ikponmwosa Ogieuhi MD,&nbsp;Aseed Mestahiri MD,&nbsp;Godbless Ajenaghughrure MD,&nbsp;Derek Ugwendum MD,&nbsp;Karldon Nwaezeapu MD,&nbsp;Anuoluwa Oyetoran MD,&nbsp;Kayode Ogunniyi MBBS","doi":"10.1016/j.jacl.2025.04.069","DOIUrl":"10.1016/j.jacl.2025.04.069","url":null,"abstract":"<div><h3>Background/Synopsis</h3><div>Hyperglycemic emergencies, including diabetic ketoacidosis and hyperglycemic hyperosmolar states, remain critical contributors to morbidity and mortality among patients with diabetes. Although previous studies have highlighted racial disparities in diabetes care, limited large-scale data exist on in-hospital outcomes specifically comparing African Americans and Caucasians with hyperglycemic emergencies, particularly with mortality as a primary endpoint.</div></div><div><h3>Objective/Purpose</h3><div>To investigate whether African Americans differ from Caucasians in in-hospital mortality, critical interventions (mechanical ventilation, vasopressor use), and resource utilization (acute kidney injury [AKI], length of stay [LOS], total hospital charges [TOTCHG]) when hospitalized for hyperglycemic emergencies.</div></div><div><h3>Methods</h3><div>We analyzed a nationally representative administrative database, identifying adults (≥ 18 years) hospitalized primarily for hyperglycemic emergencies via ICD-10 codes. Our unweighted subpopulation (n=39,899) expanded to weighted totals of 129,115 admissions for Caucasians (Race=1) and 70,380 admissions for African Americans (Race=2). We employed survey-weighted logistic regression to assess mortality, mechanical ventilation, vasopressor use, and AKI, and linear regression to evaluate LOS and TOTCHG. Adjusted models controlled for age, Charlson Comorbidity Index, and sex.</div></div><div><h3>Results</h3><div>In unadjusted analyses, African Americans had lower odds of mortality (odds ratio [OR] ∼ 0.53), mechanical ventilation (OR ∼ 0.80), and vasopressor use (OR ∼ 0.62), yet exhibited higher odds of AKI (OR ∼ 1.39) compared to Caucasians. They also showed a modest increase in LOS (by ∼ 0.35 days) and hospital charges (by ∼ $1,936). After adjusting for covariates, African Americans remained significantly less likely to die in hospital (OR=0.61, p=0.002), require mechanical ventilation (OR=0.83, p=0.049), or need vasopressor support (OR=0.67, p=0.013), but were more likely to develop AKI (OR=1.54, p &lt; 0.001). They also experienced an additional 0.39 days of hospitalization (p &lt; 0.001) and incurred $2,190 higher charges (p=0.009) on average.</div></div><div><h3>Conclusions</h3><div>In this large, nationally representative cohort, African Americans demonstrated lower in-hospital mortality and decreased use of critical interventions compared to Caucasians despite a heightened risk of AKI and modestly increased LOS and costs. These findings highlight the complex interplay between disease severity, comorbid burden, and possible underlying systemic or biological factors. Further investigation into social determinants, baseline health status, and patterns of care is warranted to optimize management and reduce inequities in hyperglycemic emergency outcomes.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Page e52"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168567","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":"Ketogenic diets exacerbating dyslipidemia: The role of lipid testing, genetic testing and advanced cardiac imaging","authors":"Robert Fishberg MD,&nbsp;Loba Alam MD","doi":"10.1016/j.jacl.2025.04.038","DOIUrl":"10.1016/j.jacl.2025.04.038","url":null,"abstract":"<div><h3>Background/Synopsis</h3><div>Low carb/high fat ketogenic diets (LCHF/KD) have gained recent popularity in the United States for its benefits on weight loss and type 2 diabetes mellitus management. However, it can potentially exacerbate significant dyslipidemia, particularly in those with certain genetic predispositions. Individual response to ketogenic diets varies largely based on the quantity and composition of the diet as well as individual genetics.</div></div><div><h3>Objective/Purpose</h3><div>The hyper-response of dyslipidemia from a LCHF/KD has not been widely reported in the medical literature. In this article, we present three patients, and compare them to an additional eleven patients we found on a PubMed literature search, all of whom developed severe hyperlipidemia in response to LCHF/KDs, and in whom such a diet should have been otherwise contraindicated.</div></div><div><h3>Methods</h3><div>We studied a series of 3 patients along with 11 patients found on literature search (Table 1) all of whom underwent exacerbation of hyperlipidemia after initiation of a ketogenic diet. We compared age, sex, past medical history, medications, LDL levels pre- and post- ketogenic diet, genetic testing, and availability of imaging among our patients with those reported in the literature.</div></div><div><h3>Results</h3><div>Compared to the 11 patients found in the literature search, our patients were of similar age, had similar levels of hyperlipidemia exacerbation, and similar genetic mutations (apolipoprotein gene mutations) (Table 2). All 3 of our patients underwent cardiovascular risk screening with imaging and had cholesterol hyper-absorbance testing. One of our patients was found to be a cholesterol hyper-absorber and responded well to ezetimibe therapy.</div></div><div><h3>Conclusions</h3><div>Dyslipidemia is caused by various genetic factors including familial hypercholesterolemia (FH), caused by mutations in either LDL receptor, apolipoprotein B(ApoB) or proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. Additionally, less commonly known genetic factors of dyslipidemia include apolipoprotein E (ApoE) variants. We recommend that all patients initiate ketogenic diet with an appropriate health care provider and have their baseline and routine lipid panel monitored. If there is a significant increase in their lipid profile, they should also undergo genetic testing, coronary CT angiogram for early detection of atherosclerosis as well as to establish clinically relevant plaque stages, and initiate lipid lowering therapy when clinically indicated. A suggested algorithm for patients initiating ketogenic diet is included in Figure 1.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Page e28"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167933","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":"Management of complex lipid disorders in a community lipid clinic setting","authors":"Carol Ko MS,&nbsp;Arthur Loussararian MD,&nbsp;Christine Coy MS,&nbsp;Shih-Ting Chiu PhD,&nbsp;Sainaz Mumtaz,&nbsp;Fatima El-Haj-Ibrahim,&nbsp;Sandra Brown MS,&nbsp;William Miyamoto BA,&nbsp;Grace Miyamoto BA,&nbsp;Michael Miyamoto MD","doi":"10.1016/j.jacl.2025.04.012","DOIUrl":"10.1016/j.jacl.2025.04.012","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background/Synopsis&lt;/h3&gt;&lt;div&gt;The management of patients with complex lipid disorders, including genetic dyslipidemias and treatment intolerance and resistance commonly occurs largely within specialized clinics in academic medical centers. Many patients who could benefit from such specialized services are cared for in community settings within primary care practices, however.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective/Purpose&lt;/h3&gt;&lt;div&gt;To report the experience of a specialized lipid clinic in a community setting, with a focus on treatment efficacy and the detection of genetic dyslipidemias in a challenging patient cohort.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Patients from a large, multispecialty practice were referred to our lipid clinic, identified based on factors including intolerance to lipid medical therapy, difficulty reaching lipid targets, and/or suspicion of genetic dyslipidemias. Management was provided by a multidisciplinary team including lipid specialist physicians, genetic counselors, and a nutritionist, with support from a pharmacy team. Outcomes included baseline and follow up lipid measurements and the results of lipid genetic testing.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In the first year of our lipid clinic experience, 61 patients were seen (40 female [66%], mean age 62y). Comorbid conditions included ASCVD (23%), hypertension (40%) and diabetes (12%). Statin intolerance was deemed to be present in 53% of patients at presentation, and 40% of patients were on no lipid-lowering medication at their first visit. Total and LDL cholesterol were both significantly reduced at a mean follow up of 6 months (total - 237 to 190 mg/dL; LDL - 151 to 107 mg/dL; both p&lt;0.001). Lipid genetic testing was performed in 37 (61%), with pathogenic FH genetic variants found in 10 (27% positive rate, LDLR 8, APOB 2, all heterozygous). Follow up genetic counseling was offered, with appropriate recommendations for cascade (family) lipid screening and genetic testing. LDL levels were effectively reduced even in patients with statin intolerance and/or on no lipid-lowering medication at baseline, and those with genetically-confirmed FH (Table). In-clinic lipid nutrition counseling was performed for 22 (36%) patients. The proportion of patients without any lipid-lowering therapy decreased from 41% to 16%. Pharmacy prior authorizations and/or appeals were required for 21 patients (34%), of which 20 were successful.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Effective lipid management can be achieved in a multidisciplinary community lipid clinic for patients with highly complex lipid conditions with high baseline rates of medical therapy intolerance and/or those with genetic dyslipidemias. In addition, our observations suggest the possibility that, despite very high baseline LDL levels, those with genetic confirmation of FH may derive particular benefit from such management, perhaps related to the availability of relevant genetic insights reinforcing compliance and","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Page e8"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167939","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":"One size doesn't fit all: A dose-dependent twist in PCSK9 monoclonal antibody therapy","authors":"Erik Kelly MD,&nbsp;Athul Rajesh MD","doi":"10.1016/j.jacl.2025.04.040","DOIUrl":"10.1016/j.jacl.2025.04.040","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background/Synopsis&lt;/h3&gt;&lt;div&gt;Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies are important therapeutic options for LDL cholesterol (LDL-C) lowering in patients with high cardiovascular risk. While PCSK9 monoclonal antibody non-responders have been well-characterized, a differential effect to once monthly versus biweekly dose formulations has not been described in the literature. We present the case of a 77-year-old woman with hypercholesterolemia and statin intolerance who demonstrated superior LDL-C lowering with once monthly PCSK9 monoclonal antibody therapy compared with biweekly formulations.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective/Purpose&lt;/h3&gt;&lt;div&gt;To describe a case of superior LDL-C lowering with once monthly PCSK9 monoclonal antibody therapy compared with biweekly formulations.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Literature review and retrospective review of electronic health records.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A 77-year-old female with coronary atherosclerosis (90th percentile coronary calcium score) and hypercholesterolemia presented to our lipid clinic for evaluation. The patient experienced myalgias and gastrointestinal side effects to multiple statins, ezetimibe, and bile acid sequestrants. The patient declined bempedoic acid due to concerns about potential side effects.&lt;/div&gt;&lt;div&gt;Her off-treatment lipid testing revealed total cholesterol 186, HDL 64, LDL 114, triglycerides 40, apolipoprotein B 79 and lipoprotein(a) 45 nmol/L. She was initiated on evolocumab 140 mg biweekly, resulting in a modest LDL-C reduction from 114 mg/dL to 106 mg/dL over six months. Given the suboptimal response, she was transitioned to alirocumab 150 mg biweekly. Her LDL-C remained suboptimal at 101 mg/dL after three months. Timing of lab draws and injection technique were confirmed to be accurate.&lt;/div&gt;&lt;div&gt;Genetic testing revealed no pathogenic mutations related to cholesterol metabolism. Following a two-month treatment hiatus, she was prescribed evolocumab 420 mg monthly. This resulted in a more robust LDL-C reduction to 88 mg/dL, sustained over the following year. No other medication or lifestyle changes occurred over this timeframe.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;This case illustrates a differential effect to once monthly versus biweekly PCSK9 monoclonal antibody formulations. It is notable that even with the evolocumab 420 mg monthly formulation, LDL-C lowering was less than what would be expected based on clinical trial data. However the LDL-C lowering was nearly double the biweekly formulations. While mechanisms of PCSK9 monoclonal antibody resistance are well-established, the variable response based on dosage formulation is not reported. This case illustrates that some PCSK9 monoclonal antibody “non-responders” may have more robust LDL-C lowering with an alternative dosing formulation. Further research is warranted to better understand the mechanisms and clinical implications of such formulation-dependen","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Pages e29-e30"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167943","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":"Impact of protein-calorie malnutrition on outcomes in patients admitted with acute pancreatitis: Insights from the National Inpatient Sample","authors":"Godbless Ajenaghughrure MD,&nbsp;Fernando Mateo MD,&nbsp;Sila Mateo Faxas MD,&nbsp;Muayad Alzamara MD,&nbsp;Amin Eshghabadi MD,&nbsp;Fayaz Khan MD,&nbsp;M Kenan Rahima MD","doi":"10.1016/j.jacl.2025.04.094","DOIUrl":"10.1016/j.jacl.2025.04.094","url":null,"abstract":"<div><h3>Background/Synopsis</h3><div>Acute pancreatitis (AP) is a common and potentially life-threatening condition, with malnutrition being an important prognostic factor. Protein-calorie malnutrition (PCM) may exacerbate morbidity, mortality, and resource utilization in AP patients.</div></div><div><h3>Objective/Purpose</h3><div>We analyzed a large national dataset 2017-2021 to assess the impact of PCM on in-hospital outcomes in AP admissions.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study using the National Inpatient Sample (NIS) from 2017 to 2021. Adult patients with AP were identified and stratified based on the presence or absence of PCM. The primary endpoint was inpatient mortality, while secondary endpoints included gastrointestinal bleeding, cardiogenic shock, cardiac arrest, intubation, and hospital resource utilization. Multivariable logistic regression analysis and Poisson regression were utilized to estimate clinical outcomes, with a significance threshold of P &lt; 0.05.</div></div><div><h3>Results</h3><div>A total of 2,172,229 AP hospitalizations were included, of which 201,870 (9.3%) had PCM. Patients with PCM were older and had a higher prevalence of White (64.2%) and Black (16.4%) individuals compared to the non-PCM group. Mortality was significantly higher in the PCM group (6.5% vs. 1.8%, adjusted OR 3.34, 95% CI 3.18–3.51, P &lt; 0.001). Other complications such as gastrointestinal bleeding (8.9% vs. 3.8%, OR 2.44), cardiac arrest (1.8% vs. 0.7%), cardiogenic shock (1.0% vs. 0.3%, OR 3.08), and intubation (9.7% vs. 2.7%, OR 3.70) were markedly more frequent in the PCM group (all P &lt; 0.001).</div><div>Resource utilization was substantially higher among patients with PCM, with a mean length of stay of 12.3 days (vs. 4.8 days, rate ratio 2.54, P &lt; 0.001) and a mean total cost of $38,674 (vs. $13,591, cost ratio 2.81, P &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>Protein-calorie malnutrition is a strong independent predictor of worse outcomes and higher resource utilization in patients with acute pancreatitis, leading to increased mortality and complications. Early identification and management of malnutrition should be a priority in hospitalized AP patients to mitigate adverse outcomes and reduce healthcare costs. Nutritional interventions integrated into AP care may improve both clinical and economic outcomes.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Pages e67-e68"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167950","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":"† VERVE-102, a clinical stage in vivo base editing medicine, leads to potent and precise inactivation of PCSK9 in preclinical studies","authors":"Ellen Rohde PhD,&nbsp;Richard Lee PhD,&nbsp;Anne Marie Mazzola MS,&nbsp;Colin Platt PhD,&nbsp;Taiji Mizoguchi MD,&nbsp;Kim Pendino PhD,&nbsp;Alexandra Chadwick PhD,&nbsp;Amit Khera MD,&nbsp;Scott Vafai MD,&nbsp;Sekar Kathiresan MD,&nbsp;Troy Lister PhD,&nbsp;Joseph Biedenkapp PhD,&nbsp;Patrick Flight PhD","doi":"10.1016/j.jacl.2025.04.095","DOIUrl":"10.1016/j.jacl.2025.04.095","url":null,"abstract":"<div><h3>Background/Synopsis</h3><div>Lipid lowering therapies reduce the risk of major adverse cardiovascular events, but the requirement for lifelong adherence contributes to poor real-world LDL-C control. Gene editing therapies that inactivate the PCSK9 gene in the liver may enable permanent LDL-C lowering after a single infusion. VERVE-102 is a clinical-stage in vivo base editing medicine. The RNA components of VERVE-102 are an mRNA encoding an adenine base editor (ABE) and a guide RNA that targets PCSK9. These components are delivered to hepatocytes by a GalNAc-lipid nanoparticle (LNP) where they are intended to permanently inactivate PCSK9 and lower LDL-C with a single A-to-G base pair change. The addition of a GalNAc targeting ligand to the LNP is expected to provide an additional route for LNP uptake in hepatocytes that is not dependent on the low-density lipoprotein receptor (LDLR), which may be deficient in familial hypercholesterolemia.</div></div><div><h3>Objective/Purpose</h3><div>Here we describe the translational research supporting ongoing clinical development of VERVE-102.</div></div><div><h3>Methods</h3><div>Editing potency and risk for off-target editing with VERVE-102 were evaluated in primary human hepatocytes (PHH) in vitro. Mouse and non-human primate (NHP) models were used to characterize in vivo editing, including biodistribution of editing across tissues, risk for germline transmission, editing efficiency and durability in the liver, and the impact of LDLR deficiency on editing potency.</div></div><div><h3>Results</h3><div>Increasing doses of VERVE-102 led to saturating PCSK9 editing and corresponding near complete elimination of PCSK9 protein secretion in PHH in vitro. There was no evidence for clinically relevant off-target editing in PHH across a panel of ∼6000 candidate sites. Biodistribution studies of editing across tissue types in NHPs showed high specificity for the liver, and there was no evidence for germline transmission of Pcsk9 edits in the offspring of VERVE-102 treated mice. In NHPs, a single infusion of VERVE-102 (3 mg/kg) led to durable mean reductions of 80% and 62% in blood PCSK9 and LDL-C, respectively. Editing efficiency was not dependent on LDLR in Ldlr knockout mouse models.</div></div><div><h3>Conclusions</h3><div>Gene editing treatments may have the potential to lower blood LDL-C for a lifetime after a single course of treatment. Here we demonstrate that VERVE-102 leads to potent and precise PCSK9 inactivation in PHH and animal models and provide nonclinical proof-of-concept for LDL-C lowering. A first-in-human clinical trial of VERVE-102 (NCT06164730) is ongoing.</div><div><strong>Previously Published:</strong> Abstract is original but the content will be an encore of a presentation originally given at the European Atherosclerosis Society Congress.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Page e68"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167951","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":"Behavioral risk factors and biomarkers of cardiovascular health in transgender and nonbinary individuals","authors":"Caroline Ong MD,&nbsp;Eugenia Gianos MD,&nbsp;Karina Ziskovich BA,&nbsp;Tung Ming Leung PhD,&nbsp;Leonid Poretsky MD,&nbsp;Natalie Cusano MD,&nbsp;Alaina Berruti BS","doi":"10.1016/j.jacl.2025.04.067","DOIUrl":"10.1016/j.jacl.2025.04.067","url":null,"abstract":"<div><h3>Background/Synopsis</h3><div>Research exploring the cardiovascular health (CVH) of transgender and nonbinary individuals remains limited, and there is evidence that gender affirming hormone therapy (GAHT) may impact CVH. Moreover, the Gender Minority Stress and Resilience Model highlights the mental and physical health consequences of unique stressors that affect these individuals. Together, these factors place an ever-increasing importance on the role of CVH risk assessment within this population.</div></div><div><h3>Objective/Purpose</h3><div>To characterize behavioral risk factors and biomarkers of CVH among transgender and nonbinary individuals and to assess the role of mental health in modulating these risk factors.</div></div><div><h3>Methods</h3><div>Individuals ages 18 or older who identify as transgender male/female (TGM/TGF) or nonbinary (NB) were recruited. The Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder-2 (GAD-2) were used to assess symptoms of depression and anxiety. Self-reported intake of specific food groups was converted to a score of 0-16, with higher diet scores reflecting larger quantities of potato chips, butter, fast-food, and soda and fewer quantities of fruits, vegetables, and beans. Weekly exercise was assessed using the International Physical Activity Questionnaire and converted to Metabolic Equivalent Tasks (METs). Diet scores, weekly METs, Body Mass Index (BMI), hemoglobin A1c (HbA1c), total cholesterol (TC), and low-density lipoprotein (LDL) levels were compared between those who screened positive on both the PHQ-2 and GAD-2 and those who screened negative. Unadjusted Mann-Whitney and Chi-square tests were performed; a p-value of under 0.05 was considered statistically significant.</div></div><div><h3>Results</h3><div>Seventy-eight participants were included: 24 TGM, 42 TGF, and 12 NB. Ages ranged from 18-69. 77% (n=60) of participants were on GAHT. Twenty-eight participants screened positive on both the PHQ-2 and GAD-2, and 34 participants screened negative for both. Participants who screened positive had less healthy diets than those who screened negative (average diet score 7.3 vs 6.0; p=0.0456). These participants also tended to be less likely to surpass the American Heart Association's recommended 600 weekly METs (57% of participants (n=16) vs 79% of participants (n=29); p=0.0584) and less likely to attain recommended levels of CVH biomarkers (Figure 1).</div></div><div><h3>Conclusions</h3><div>Our data highlight an important trend in which participants with symptoms of anxiety and depression had less healthy diets and were less likely to meet exercise and biomarker goals. With less than 50% of either group attaining target BMI or LDL levels, our data also underscore the significant overall CVH risk in this population.</div></div>","PeriodicalId":15392,"journal":{"name":"Journal of clinical lipidology","volume":"19 3","pages":"Pages e50-e51"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144168737","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}