Journal of clinical lipidology最新文献

{"title":"Familial Hypercholesterolemia Diagnosis and Management: Insights from the NIH Precision Medicine Initiative All of Us Study","authors":"","doi":"10.1016/j.jacl.2024.04.066","DOIUrl":"10.1016/j.jacl.2024.04.066","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>Limited data exist regarding familial hypercholesterolemia (FH) diagnosis and treatment in diverse populations.</p></div><div><h3>Objective/Purpose</h3><p>We sought to assess patient characteristics and current treatment patterns among individuals with FH and/or elevated low-density lipoprotein cholesterol (LDL-C) in a diverse real-world cohort within the United States.</p></div><div><h3>Methods</h3><p>We examined data from the NIH Precision Medicine Initiative All of Us Research Program, a cross-sectional study beginning in 2015 inclusive of historically underrepresented groups. Among participants with &gt;1 LDL-C measurement, we examined lipid-lowering medication utilization and treatment patterns among participants with and without FH diagnosis stratified by LDL-C. We additionally examined whether sex differences existed in treatment and diagnosis.</p></div><div><h3>Results</h3><p>Among 369,483 All of Us participants age ≥18 years, our study sample included 113,153 individuals who had at least one LDL-C measurement. Of these, 4018 (3.5%) had LDL-C ≥160 mg/dL, 733 (0.26%) had LDL-C ≥190 mg/dL, and 434 were diagnosed with FH (0.37%). Statin usage was found to be higher among men compared to women both in those with FH (84% vs. 70.3%, p=0.002) and without FH (54.2% vs. 39.2%, p&lt;0.001) irrespective of LDL-C measures. Women tended to have higher mean LDL-C levels compared to men (130.9 mg/dL vs. 105.8 mg/dL, p&lt;0.001 in those with FH and 106.9 mg/dL vs. 98.8 mg/dL p&lt;0.001 in those without FH). Participants with FH were also more likely to be on statin therapy (75.2% vs 44.8%, p-value &lt;0.001) with 18.4% on two or more types of lipid-lowering agents. Despite this, a higher percentage of FH participants had a history of &gt;1 major ASCVD event (19.4% vs 10.7%, p-value &lt;0.001), and exhibited higher mean LDL-C levels (121.9 mg/dL vs 103.9 mg/dL) compared to non-FH participants. Notably, only 30.5% of FH participants achieved the recommended LDL-C&lt;100 mg/dL compared to 45.7% of those without FH (p-value&lt;0.001). Furthermore, a majority (60.6%) of those already diagnosed with FH had LDL-C &lt;130 mg/dL, including those not taking a lipid-lowering drug (Figure 1), questioning whether FH is being incorrectly diagnosed in some patients.</p></div><div><h3>Conclusions</h3><p>This study highlights the under and possible inappropriate diagnosis of FH and inadequate treatment of those diagnosed with FH among a real-world population.</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":"141849947","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":"Unmasking the Silent Culprit: Lipoprotein(a) Elevation in a Previously Healthy Individual","authors":"","doi":"10.1016/j.jacl.2024.04.033","DOIUrl":"10.1016/j.jacl.2024.04.033","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>Lipoprotein A [(Lp(a)] has known atherogenic and thrombotic properties. We present a young patient with recurrent transient ischemic attacks (TIA) and ischemic stroke who was found to have hyperlipidemia and elevated Lp(a) levels. In patients with increased risk of atherosclerosis, screening guidelines recommend checking Lp(a) levels once. This case emphasizes the importance of obtaining Lp(a) levels in young patients with cardiovascular risk factors and appropriate medical therapy.</p></div><div><h3>Objective/Purpose</h3><p>Describe the importance of Lp (a) screening in young patients.</p></div><div><h3>Methods</h3><p>Medical record review.</p></div><div><h3>Results</h3><p>A 49-year-old African American male with a past medical history of anxiety and seizures presented with left sided numbness and paresthesia. Family history was remarkable for diabetes and hypertension. He was diagnosed with a TIA. His LDL-C was 214mg/dL. He was started on atorvastatin 40mg and aspirin 81mg. He continued on this regimen despite uncontrolled LDL-C. Five years later, the patient presented with visual disturbances and headache and was found to have a PCA stroke. A TTE with bubble was negative for PFO and ASD. Holter monitor was unrevealing for arrhythmia. He was started on ezetimibe 10mg and atorvastatin was increased to 80mg. </p><p>One year later, he presented with episodic dizziness. CTA head and neck revealed a basilar TIA.  Laboratory results showed LDL-C 140mg/dL. Lp(a) was obtained as prior workup had been equivocal and was 356.7nmol/L (ref. &lt;75nmol/L). He was started on PCSK9 therapy in addition to his other lipid lowering therapies.</p></div><div><h3>Conclusions</h3><p>This patient presented with stroke and was found to have an LDL-C above 200mg/dL which should have prompted aggressive medical therapy, lifestyle modifications and close follow-up. He remained on the same medications despite uncontrolled LDL-C. Elevated Lp(a) was discovered only after the patient had suffered multiple events. On average, African American patients have higher Lp(a) levels compared to Caucasian and Asian patients, however this patient's Lp(a) levels are significantly higher than what can be solely attributed to race. It is likely that obtaining Lp(a) during the first event could have changed his clinical course over the years. This case emphasizes the importance of timely Lp(a) screening and prompt intervention.</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":"141850134","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":"Pancreatitis Polygenic Risk Score is Associated with Acute Pancreatitis in Multifactorial Chylomicronemia Syndrome","authors":"","doi":"10.1016/j.jacl.2024.04.063","DOIUrl":"10.1016/j.jacl.2024.04.063","url":null,"abstract":"<div><h3>Study Funding</h3><p>This work was supported by the Cardiometabolic Health, Diabetes and Obesity Research Network (CMDO) from Le Fonds de recherche du Québec (FRQS). Luigi Bouchard received a Senior Research Scholar from the FRQS and is a member of the FRQS-Centre Hospitalier</p></div><div><h3>Background/Synopsis</h3><p>The most common cause of severe hypertriglyceridemia is multifactorial chylomicronemia syndrome (MCS). MCS is associated with an increased risk of acute pancreatitis (AP), but the risk is highly heterogenous between patients. The maximal concentration of triglycerides (TG) and the presence of a heterozygous rare pathogenic variant in a TG-related metabolism gene are known predictors of AP in MCS patients. Previous genome-wide association studies identified pancreatitis susceptibility genes. However, no study has assessed whether the accumulation of common variants in these pancreatitis susceptibility genes could help predict the risk of AP in MCS patients.</p></div><div><h3>Objective/Purpose</h3><p>To determine if a weighted polygenic risk score (PRS) including common variants in known pancreatitis susceptibility genes is associated with AP in MCS patients.</p></div><div><h3>Methods</h3><p>A total of 114 patients MCS underwent gene sequencing for the five canonical genes involved in TG metabolism (LPL, APOA5, APOC2, GPIHBP1, and LMF1). In addition, we genotyped eight single nucleotide polymorphisms (SNPs) in genes previously associated with pancreatitis (ABCG8, CLDN2, CTRB1/2, CTRC, PRSS1, PRSS2, SPINK1, and TWIST2). A weighted PRS was calculated to account for the phenotypic effect of each SNP locus.</p></div><div><h3>Results</h3><p>A high pancreatitis-PRS score (defined as ≥ 0.44 and representing the median PRS score) was associated with a 2.94-fold increased risk of AP (p=0.02) among patients with MCS. The association between the pancreatitis-PRS and AP remained statistically significant after correction for known predictors of acute pancreatitis, including age, sex, body mass index, diabetes, the maximal TG concentration and the presence of a heterozygous pathogenic rare variant in a TG-related metabolism gene (p=0.04). MCS patients with a high pancreatitis - PRS and heterozygous for a pathogenic rare variant in a TG metabolism-related gene had a 9.50-fold increased risk of AP (p=0.001), compared to those with a low-PRS and no pathogenic variant.</p></div><div><h3>Conclusions</h3><p>This is the first study to show that the accumulation of common variants in known pancreatitis susceptibility genes is associated with AP in MCS patients. MCS patients with both a high pancreatitis-PRS score and a heterozygous pathogenic rare variant in a TG-related metabolism gene have higher risk of AP, similar to what is seen in monogenic form of severe hypertriglyceridemia. Genetic testing, including both rare and common variants, could help clinicians to identify MCS patients who may be at higher risk of acute pancreatitis and who may","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":"141949547","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":"Patients Admitted with Acute pancreatitis and Dyslipidemia Affected by Non-Alcoholic Fatty Liver Disease are Associated with Worse Clinical Outcomes","authors":"","doi":"10.1016/j.jacl.2024.04.057","DOIUrl":"10.1016/j.jacl.2024.04.057","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>Individuals with NAFLD may have alterations in lipid metabolism, insulin resistance, and an increased risk of dyslipidemia, all of which can contribute to the development of acute pancreatitis. Dyslipidemia, particularly elevated triglycerides and low-density lipoprotein cholesterol (LDL-C), is often seen in individuals with NAFLD. Insulin resistance and metabolic syndrome are common underlying factors.</p></div><div><h3>Objective/Purpose</h3><p>There is limited scientific evidence of clinical outcomes of NAFLD in patients admitted with acute pancreatitis &amp; dyslipidemia. 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 acute pancreatitis &amp; dyslipidemia with NAFLD. The primary outcome was inpatient mortality. The secondary outcomes were cardiogenic shock, cardiac arrest, gastrointestinal bleeding (GIB), 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 574,269 hospitalizations with acute pancreatitis and dyslipidemia where 29,324 (5.1%) had NAFLD. NAFLD and non-NAFLD cohorts were with mean age of 61.5 vs. 60 yrs; males 54.5% vs 56.2%; Caucasians 65.0% both; HTN 49% vs 56%; HF 18.8% vs 12%; obesity 27% vs 24%; Metabolic Syndrome 9.6% vs 8.7%; DKA 3.9% vs 4.9%; AF 24.4% vs 23.5%; AKI 38% vs 21.8%; obesity 30.3% vs 29.3%; ACS 6.6% vs 2.8%; acute respiratory failure 17.8% vs 6.4%; history of stroke 0.9% vs 0.4%; COPD 15% vs 13.5%; alcohol use 19.9% vs 18.5%, respectively. NAFLD cohort had significantly higher mortality and worse clinical outcomes (Table 1).</p></div><div><h3>Conclusions</h3><p>NAFLD group demonstrated significantly higher mortality, worse clinical outcomes and resource utilization. Patients were older, obese, female, same Caucasian population, with more frequent HF, AF, ACS and alcohol use. NAFLD is associated with greater risk for cardiovascular events, renal failure, GIB, and ICU care. NAFLD is an important predictor of adverse outcomes in acute pancreatitis &amp; dyslipidemia 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":"141843512","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":"†Evaluation of Chenodeoxycholic Acid Treatment in Adult Patients with Cerebrotendinous Xanthomatosis: A Randomized, Placebo-Controlled Phase 3 Study","authors":"","doi":"10.1016/j.jacl.2024.04.069","DOIUrl":"10.1016/j.jacl.2024.04.069","url":null,"abstract":"<div><h3>Study Funding</h3><p>Mirum Pharmaceuticals, Inc.</p></div><div><h3>Background/Synopsis</h3><p>Cerebrotendinous xanthomatosis (CTX) is a rare metabolic disorder of bile acid synthesis caused by biallelic pathogenic variants in the CYP27A1 gene, encoding the sterol 27-hydroxylase enzyme, which leads to abnormal bile acid synthesis and toxic accumulation of cholestanol, bile alcohols and other metabolites. Chenodeoxycholic acid (CDCA) treatment is considered the standard-of-care for CTX.</p></div><div><h3>Objective/Purpose</h3><p>We evaluated the efficacy and safety of CDCA on biomarkers of CTX in the first Phase 3, randomized withdrawal, double-blind (DB), placebo (PBO)-controlled, two-period x two-treatment cross-over study with rescue medication (RESTORE).</p></div><div><h3>Methods</h3><p>A 24-week randomized withdrawal, DB, crossover study with a 30-day safety follow-up was conducted in adult patients (≥16 years of age) with CTX who received 250 mg CDCA TID for two 8-week open label (OL) periods of the study and either blinded CDCA or PBO for two 4-week DB periods. Eligible participants had a clinical diagnosis of CTX with biochemical confirmation, no known malabsorption or GI conditions, and not on cholic acid and/or medication impacting bile acid absorption. The primary endpoint was change in the urinary bile alcohol biomarker 5β-cholestane-3α,7α,12α,23S,25-pentol (23S-pentol) from Baseline (BL) to the end of each DB treatment period. Key secondary efficacy endpoints included: percent changes in plasma cholestanol and 7α-hydroxy-4-cholesten-3-one (7αC4) at end of each DB period and proportion of patients requiring rescue medication (CDCA) during the DB periods. Safety parameters were also assessed.</p></div><div><h3>Results</h3><p>The analysis included 14 participants with a median (min, max) age at enrollment of 41.5 (16, 55) years, the majority were white males, and all had a clinical diagnosis of CTX with biochemical confirmation. CDCA withdrawal after the OL treatment period resulted in a statistically significant 20-fold increase (95% CI: 10.3, 43.5 p&lt;0.0001) in urine 23S-pentol (ng/mL), a 2.8-fold increase (95% CI: 1.5, 5.2; p=0.0083) in plasma cholestanol (µg/mL), and a 50-fold increase (95% CI: 25.0, 66.7; p&lt;0.0001) in plasma 7αC4 (ng/mL; placebo relative to CDCA). A significant proportion of participants on PBO (61.5% [95% CI: 31.6, 86.1]; p=0.0006) required blinded rescue medication during the DB withdrawal periods. Most commonly reported TEAEs on CDCA were diarrhea (n=5) and headache (n=3) with the majority mild to moderate in severity and not considered treatment related.</p></div><div><h3>Conclusions</h3><p>Withdrawal of CDCA treatment led to significant increases in CTX biomarkers. CDCA treatment is well-tolerated and can effectively suppress abnormal bile acid synthesis in CTX, preventing accumulation of cholestanol and bile alcohols. This underscores the potential for CDCA to help CTX patients avoid disease progr","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":"141839097","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":"Discrepancies in Prescribing Practices for SGLT2 Inhibitors Between Sexes","authors":"","doi":"10.1016/j.jacl.2024.04.044","DOIUrl":"10.1016/j.jacl.2024.04.044","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>In recent years, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated significant benefits in both cardiovascular and renal outcomes, which has resulted in increased provider utilization and inclusion into society guidelines. As the use of SGLT2i expands, variations in prescribing practices may arise.</p></div><div><h3>Objective/Purpose</h3><p>To identify variations in prescribing practices in SGLT2i among patients of different sex with either congestive heart failure (CHF) or chronic kidney disease (CKD).</p></div><div><h3>Methods</h3><p>A cross-sectional analysis of all patients prescribed SGLT2i between 2018 and 2023 within the Northwell Health system in New York State was conducted. Demographic data, including race, sex, ICD-10 codes for CHF and CKD, and last documented GFR, were retrieved from the electronic medical record. Patients were considered to have CKD with an appropriate indication for SGLT2i if they had an ICD-10 code for CKD or a GFR between 30 and 60. This data was then compared to the prevalence of CHF and CKD in men and women as reported in the Medicare Current Beneficiaries Survey (MCBS) of Fall 2021.</p></div><div><h3>Results</h3><p>From 2018 to 2023, of the 11,290 patients were prescribed SGLT2i, 12.7% had CHF and 10.5% had CKD. Of the patients with CHF, 27.6% were women, and of the patients with CKD, 33.9% were women. Within MCBS, women comprised 48.9% of patients with CHF and 51.9% of patients with CKD.</p></div><div><h3>Conclusions</h3><p>While according to MCBS, CHF and CKD affect men and women in approximately equal proportions, our data suggests that less women were prescribed SGLT2i. This discrepancy may represent different prevalence of CHF and CKD in men and women in New York State, contraindications to SGLT2i that are more likely to be present in women, or a systematic bias. Alternatively, prescribers may be hesitant to prescribe SGLT2i to women, given the FDA warning regarding increased risk of genitourinary infections. Ultimately, this study reveals a potential underlying bias in prescribing practices for SGLT2i between men and women that would benefit from further study and enhanced clinician awareness.</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":"141839384","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":"Tailored Therapeutic Strategies for the Management of Chylomicronemia Syndrome","authors":"","doi":"10.1016/j.jacl.2024.04.031","DOIUrl":"10.1016/j.jacl.2024.04.031","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>Severe hypertriglyceridemia (HTG), greater than 1,000 mg/dL, is frequently due to a pathological accumulation of circulating chylomicrons, termed chylomicronemia. This can lead to plasma hyperviscosity with decreased perfusion, manifesting as acute pancreatitis, impaired cognition, and neuropathy. Given the lack of established guidelines, managing symptomatic chylomicronemia underscores the necessity for personalized expert care.</p></div><div><h3>Objective/Purpose</h3><p>To review the unusual presentations and inpatient management of chylomicronemia syndrome.</p></div><div><h3>Methods</h3><p>We present two cases of symptomatic, severe HTG, each managed with different treatment modalities.</p></div><div><h3>Results</h3><p>Case 1: A 35-year-old man, with a history of uncontrolled T2DM, hypertension (HTN), and HTG, presented with a persistent, throbbing headache (HA). His exam was unremarkable. Clinical investigation revealed severe HTG (9,157 mg/dL; normal 30-150) with normal abdominal and brain imaging. Inpatient management included nothing by mouth (NPO), intravenous (IV) fluids, and insulin infusion, which led to a gradual decline in TG to 1,341 mg/dL. HA resolution occurred after 7 days of therapy. The patient was educated on a very low-fat diet, strict glycemic control, lipid lowering therapy compliance, and scheduled outpatient follow-up.</p><p>Case 2: A 43-year-old woman, with a history of uncontrolled T2DM, HTN, and pancreatitis due to HTG, presented with a HA and abdominal pain one week after running out of her medications. Her exam was notable for a blood pressure of 180/96 mmHg, eruptive xanthomas on the extensor surfaces of the extremities, and abdominal tenderness. She was diagnosed with HTG-induced acute pancreatitis, supported by a TG of 5,307 mg/dL, elevated lipase levels (86 U/L; normal 5-55), and CT findings of an edematous pancreas with surrounding fat stranding. The patient was made NPO and treated with IV fluids and insulin infusion. On the 5th day of admission, due to persistently elevated TG and an ongoing HA, plasmapheresis was initiated. After a single session, TG decreased from 2,048 mg/dL to 534 mg/dL, and the patient's symptoms resolved. Prior to discharge, she was restarted on atorvastatin, fenofibrate, and omega-3 acid ethyl esters.</p></div><div><h3>Conclusions</h3><p>Managing severe, symptomatic HTG includes NPO status, insulin infusion, and oral lipid lowering therapies; often requiring prolonged hospitalization. Plasmapheresis, though costly and invasive, offers a rapid reduction in TG, symptom resolution, and prevention of HTG-associated complications. Future studies on these treatment modalities can aid in developing inpatient management guidelines for chylomicronemia syndrome.</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":"141853326","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":"Unique Case of Familial Hypobetalipoproteinemia (FHBL)","authors":"","doi":"10.1016/j.jacl.2024.04.073","DOIUrl":"10.1016/j.jacl.2024.04.073","url":null,"abstract":"<div><h3>Background/Synopsis</h3><p>RG is a 43-year-old male with fatty liver disease, found to have low total and low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) levels.</p></div><div><h3>Objective/Purpose</h3><p>To review a clinical scenario where making the proper lipid/lipoprotein diagnosis explains the background common coincident condition (fatty liver).</p></div><div><h3>Methods</h3><p>Patient was seen in the office at Lipid Clinic at Penn for further evaluation.</p></div><div><h3>Results</h3><p>RG is a 43-year-old obese male is referred to lipid clinic for further evaluation after initial presentation of abnormal liver function tests and very low cholesterol. There is a longstanding &gt;15 years history of abnormal liver function tests and radiographic suspicion of fatty liver disease and liver biopsy showing moderate macrovesicular steatosis with mild steatohepatitis.</p><p>Genetic testing confirmed a pathogenic variant in the APOB gene associated with a diagnosis of autosomal dominant familial hypobetalipoproteinemia (FHBL). FHBL is primarily caused by pathogenic changes in the APOB gene but it has also been associated with pathogenic variants in other genes, including ANGPTL3 and PCSK9.</p><p>This condition is associated with a low risk of developing atherosclerotic cardiovascular disease (ASCVD) and high risk for development of fatty liver disease.</p><p>RG has coronary artery calcium score (CACS) = 0. He was counseled on natural history and inheritance pattern of this condition. There is no pharmacologic treatment required, but he was advised to supplement with fat-soluble vitamins and follow up with his primary team for ongoing care of liver disease.</p></div><div><h3>Conclusions</h3><p>Familial hypobetalipoproteinemia (FHBL) is a monogenic lipid disorder, characterized by low total and LDL-C. This condition is due to mutations in APOB gene that disrupts normal apoB protein synthesis. This condition is typically well-tolerated, but can be a cause of fatty liver disease and even cryptogenic cirrhosis. It is important to identify the correct cause of fatty liver disease since it may be reversible and because patients regularly report feeling accused by health professional when questioned about alcohol consumption or other lifestyle transgressions as a cause of their disease. Clarification of the diagnosis will enable proper lifestyle counseling and care.</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":"141851917","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":"†Not Published","authors":"","doi":"10.1016/j.jacl.2024.04.082","DOIUrl":"10.1016/j.jacl.2024.04.082","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":"141846438","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":"Detecting familial hypercholesterolemia: An observational study leveraging mandatory universal pediatric total cholesterol screening in Slovakia","authors":"","doi":"10.1016/j.jacl.2024.03.009","DOIUrl":"10.1016/j.jacl.2024.03.009","url":null,"abstract":"<div><h3>BACKGROUND</h3><p>In Slovakia, a mandatory national universal pediatric total cholesterol (TC) screening program is in place to identify cases of familial hypercholesterolemia (FH). However, the program's effectiveness has not been systematically assessed.</p></div><div><h3>OBJECTIVE</h3><p>This study aimed to estimate the prevalence of FH among parents of children that had elevated TC levels identified during screening.</p></div><div><h3>METHODS</h3><p>This prospective, non-interventional, observational study enrolled parents of 11-year-old children who underwent TC screening in 23 selected pediatric outpatient clinics between 2017 and 2018. FH was diagnosed using the Dutch Lipid Clinic Network (DLCN) criteria and targeted next-generation sequencing. The primary objective was to estimate the proportion of children with a TC level of &gt;188 mg/dL (&gt;4.85 mmol/L) who had a parent with a confirmed diagnosis of FH.</p></div><div><h3>RESULTS</h3><p>A total of 112 parents of 56 children with an elevated TC level were enrolled. Five children (8.9%) had a parent in whom FH was genetically confirmed. Without genetic analysis, all five parents would only be diagnosed with “possible FH” by DLCN criteria. Of parents, 83.9% (<em>n</em> = 94/112) had an low-density lipoprotein cholesterol (LDL-C) level of &gt;116 mg/dL (&gt;3 mmol/L), but only 5.3% (<em>n</em> = 5/94) received lipid-lowering therapy. Among the five parents with genetically confirmed FH, all had an LDL-C level &gt;116 mg/dL (&gt;3 mmol/L), with a mean (±SD) of 191 (±24) mg/dL (4.94 [±0.61] mmol/L). Only two of these parents received lipid-lowering therapy.</p></div><div><h3>CONCLUSIONS</h3><p>The present study demonstrates the significance of mandatory universal pediatric TC screening in identifying families with FH and other at-risk families in need of lipid-lowering therapy.</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":"https://www.sciencedirect.com/science/article/pii/S193328742400045X/pdfft?md5=af875b614ccb454856438e2af864164c&pid=1-s2.0-S193328742400045X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140400383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}