Social and Metabolic Characteristics Associated With Multiple DKA Admissions at a Large County Hospital.

Context: Diabetic ketoacidosis (DKA) is a preventable, deadly, and costly complication of type 1 diabetes mellitus (T1DM). Some individuals with T1DM have recurrent DKA admissions. Objective: We sought to characterize social factors that differ between patients with single vs multiple DKA admissions at an urban, safety-net hospital. Methods: We queried the electronic health records for T1DM patients admitted for DKA from 2019 to 2021. Admission laboratory values, demographic information, and detailed social histories were collected and analyzed statistically, including logistical regression. Results: A total of 243 patients were admitted for DKA, 64 of whom had multiple DKA admissions. There was no significant difference between the groups in their admission laboratory values, hospital length of stay, health-care payer status, history of homelessness, current employment, living alone, independence of activities of daily living, and barriers to discharge. T1DM patients with multiple DKA admissions had greater rates of substance use disorder (33.0% vs 60.9%; P < .001), especially with cannabis (6.7% vs 25.0%; P < .001), tobacco (26.3% vs 46.3%; P = .002), and psychoactive substance use (1.1% vs 6.3%; P = .043). Regression models of substance use showed increased risk with any substance use (odds ratio [CI] 3.17 [1.78-5.73]; P < .001) and cannabis (3.70 [1.55-8.83]; P = .003). Conclusion: We identified substance use as a possible predictor of T1DM patients at risk for multiple DKA admissions. Our findings identify a group of T1DM patients for whom interventions may help to decrease recurrence of DKA episodes within similar community hospital populations.

Contemporary Homozygous Familial Hypercholesterolemia in the United States: Insights From the CASCADE FH Registry.

Background Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by early-onset atherosclerotic and aortic valvular cardiovascular disease if left untreated. Contemporary information on HoFH in the United States is lacking, and the extent of underdiagnosis and undertreatment is uncertain. Methods and Results Data were analyzed from 67 children and adults with clinically diagnosed HoFH from the CASCADE (Cascade Screening for Awareness and Detection) FH Registry. Genetic diagnosis was confirmed in 43 patients. We used the clinical characteristics of genetically confirmed patients with HoFH to query the Family Heart Database, a US anonymized payer health database, to estimate the number of patients with similar lipid profiles in a "real-world" setting. Untreated low-density lipoprotein cholesterol levels were lower in adults than children (533 versus 776 mg/dL; P=0.001). At enrollment, atherosclerotic cardiovascular disease and supravalvular and aortic valve stenosis were present in 78.4% and 43.8% and 25.5% and 18.8% of adults and children, respectively. At most recent follow-up, despite multiple lipid-lowering treatment, low-density lipoprotein cholesterol goals were achieved in only a minority of adults and children. Query of the Family Heart Database identified 277 individuals with profiles similar to patients with genetically confirmed HoFH. Advanced lipid-lowering treatments were prescribed for 18%; 40% were on no lipid-lowering treatment; atherosclerotic cardiovascular disease was reported in 20%; familial hypercholesterolemia diagnosis was uncommon. Conclusions Only patients with the most severe HoFH phenotypes are diagnosed early. HoFH remains challenging to treat. Results from the Family Heart Database indicate HoFH is systemically underdiagnosed and undertreated. Earlier screening, aggressive lipid-lowering treatments, and guideline implementation are required to reduce disease burden in HoFH.

Sex-related differences in premature cardiovascular disease in familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is associated with an increased prevalence of premature atherosclerotic cardiovascular disease (ASCVD), however, little is known about sex-specific differences in premature ASCVD and its risk factors. OBJECTIVE: The present study seeks to assess the burden and risk factors for premature ASCVD among men and women with FH. METHODS: In this study we retrospectively examined sex-specific differences in ASCVD prevalence, risk factor burdens, and lipid treatment outcomes in 782 individuals with clinically or genetically confirmed FH treated in 5 U.S. lipid and genetics clinics. A generalized linear model using Binomial distribution with random study site effect and sex-stratified analysis was used to determine the strongest predictors of premature ASCVD, and lipid treatment outcomes. Covariates included age, sex, diabetes mellitus (DM), hypertension, and current smoking. RESULTS: Among the cohort, 98/280 men (35%) and 89/502 women (18%) had premature ASCVD (defined as <55 years in men and <65 years in women). Women with premature ASCVD had higher mean treated total cholesterol (216 vs. 179 mg/dl, p=<0.001) and LDL-C (135 vs. 109 mg/dl, p= 0.005). CONCLUSION: These data confirm that high percentages of women and men with FH develop premature ASCVD, and suggest that FH may narrow the observed sex difference in premature ASCVD onset. These data support more aggressive prevention and treatment strategies in FH, including in women, to reduce non-lipid risk factors and residual hypercholesterolemia.

A four-year review of orthodontic cases appearing before the General Dental Council Professional Conduct Committee.

OBJECTIVES: To evaluate the characteristics of orthodontic cases at the General Dental Council's (GDC) Professional Conduct Committee (PCC). DESIGN: Review of data from the GDC website for orthodontically related hearings or those involving orthodontic treatment providers during 2015-2018. SETTING: Observational descriptive study. METHODS: Data were accessed from the GDC website by a single researcher to retrieve orthodontic cases. The press office of the GDC was contacted to ensure all data were captured. For each case that met the inclusion criteria, demographic details of the registrant, the charges proved/not proved and final outcome of the case were recorded. RESULTS: A total of 23 registrant cases involved orthodontics and this was 8% of the total number of PCC hearings during 2015-2018. Nine (39%) of the registrants had a Membership in Orthodontics qualification although only 7 (30%) were registered as orthodontists on the UK GDC Specialist List in Orthodontics. Charges related to clinical assessment, consent and record keeping were mostly proved for dentists (13/16 hearings for each) whereas a poor standard of treatment and not cooperating with the GDC were mostly proved for orthodontists (4/7 hearings for each). Overall, conditions were imposed in 10 (44%) cases, erasure in 7 (30%) cases, suspension in 5 (22%) cases and a reprimand in 1 (4%) case. CONCLUSION: The GDC continue to view misdemeanours seriously and it would be prudent for registrants to be familiar with the nature of these hearings to reduce the risk of finding themselves in such a predicament.

Revival of sun-and-beach tourism through the lens of regulatory and risk dimensions of environmental sustainability.

Environmental sustainability is essential in tourism literature, and sun-and-beach tourism (SBT) is one of the most popular subsections of the tourism field. The appropriate policies and strategies during the COVID-19 pandemic to revive SBT growth through the lens of the regulatory dimension (RED) and risk dimension (RID) of environmental sustainability are gaining timely ground to conduct this research. The current study examined the nexus between SBT, RED, and RID utilizing three novel indexes (i.e., weighted sun-and-beach tourism index, weighted regulatory dimension index, and weighted risk dimension index) by employing the principal component analysis within the framework of six stages of empirical estimation strategy. These three novel indexes combine the most commonly used SBT, RED, and RID indicators. This research tested the CSD and homogeneous, then employed the second generation CIPS-CADF panel unit root test, used an AMG estimator, and employed the panel Toda-Yamamoto (PTY) causality test. The findings revealed that the RED positively influences SBT while the RID mitigates SBT. Results also indicate bidirectional causality between SBT, RID, and RED. In other words, changes in RID and RED have predictive power for the SBT, which further highlights the role of SBT on the RID and RED. Therefore, concerned authorities can focus on environmental sustainability design initiatives and appropriate policy/strategy implications to boost SBT.

In vitro fertilization and hypertriglyceridemic pancreatitis: Case report.

Few cases of hypertriglyceridemic pancreatitis have been reported in women during a vitro fertilization treatment (IVF) cycle. Here, we describe a 41-year-old woman with primary infertility and a history of acute pancreatitis (of unknown etiology) who was started on high dose ethinyl estradiol to prepare for transfer of cryopreserved embryos. She subsequently presented with nausea, vomiting, and abdominal pain to an emergency room and was found to have hypertriglyceridemic pancreatitis. Her hospitalization involved a prolonged intensive care unit stay in which she underwent three sessions of plasmapheresis. Eventually, with discontinuation of ethinyl estrogen, aggressive intravenous fluid hydration, plasmapheresis, a low-fat diet, and gemfibrozil, she had resolution of severe hypertriglyceridemia and all symptoms related to acute pancreatitis. Our case highlights the possibility that ethinyl estradiol, a commonly used form of estrogen for endometrial preparation during IVF cycles, may cause severe hypertriglyceridemia and acute pancreatitis in certain predisposed individuals. Only seven cases of hypertriglyceridemic pancreatitis during in vitro fertilization have been previously reported, and only one of these prior cases experienced pancreatitis during transfer of cryopreserved embryos like our patient. Our case, along with the few prior reported cases, demonstrate hypertriglyceridemic pancreatitis can occur during IVF. Further work is needed to understand the effects of exogenous estrogen on lipids for women undergoing IVF.

Applying an LDL-C threshold-based approach to identify individuals with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) remains underdiagnosed and undertreated. The optimal electronic health record (EHR) screening strategy for FH is unclear. OBJECTIVE: To evaluate an LDL-C threshold-based approach of identifying patients with FH from the EHR to determine the optimal LDL-C range for FH consideration. METHODS: Individuals from UT Southwestern Medical Center with an LDL-C level ≥190mg/dL at any time were enrolled in an FH registry. These 5,786 patients were divided into four categories of LDL-C (190- 219, 220 - 249, 250 - 299, and ≥ 300mg/dL) with 100 individuals randomly selected for manual chart review in each category. Chart review included 1) the presence of secondary causes of dyslipidemia, 2) diagnosis of possible/definite FH by modified Simon Broome criteria, and 3) probable/definite FH by modified Dutch Lipid Clinic Network (DLCN) criteria. RESULTS: Of the 400 individuals with an LDL-C level ≥190mg/dL (mean age 52 years ± 14), the presence of secondary causes increased across each LDL-C category (p < 0.001) with the greatest prevalence in those ≥ 300mg/dL (52%). The prevalence of possible/probable or definite FH also varied by LDL-C category, with the highest prevalence of FH by Simon Broome criteria in the 220 - 249mg/dL category (52%) and by DLCN criteria in the 250 - 299mg/dL category (46%). CONCLUSIONS: Among those with LDL-C ≥ 190mg/dL, the prevalence of secondary causes increased markedly with higher LDL-C, while the diagnosis of FH has a parabolic relationship. Patients with intermediate LDL-C (220 - 299mg/dL) may be the optimal group to prioritize for FH screening.

Nonalcoholic Fatty Liver Disease and Cardiovascular Risk: A Scientific Statement From the American Heart Association.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition that is believed to affect >25% of adults worldwide. Unless specific testing is done to identify NAFLD, the condition is typically silent until advanced and potentially irreversible liver impairment occurs. For this reason, the majority of patients with NAFLD are unaware of having this serious condition. Hepatic complications from NAFLD include nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. In addition to these serious complications, NAFLD is a risk factor for atherosclerotic cardiovascular disease, which is the principal cause of death in patients with NAFLD. Accordingly, the purpose of this scientific statement is to review the underlying risk factors and pathophysiology of NAFLD, the associations with atherosclerotic cardiovascular disease, diagnostic and screening strategies, and potential interventions.

Genetic Lipid Disorders Associated with Atherosclerotic Cardiovascular Disease: Molecular Basis to Clinical Diagnosis and Epidemiologic Burden.

Genetic lipid disorders, ranging from common dyslipidemias such as familial hypercholesterolemia, lipoprotein (a), and familial combined hyperlipidemia to rare disorders including familial chylomicronemia syndrome and inherited hypoalphalipoproteinemias (ie, Tangier and fish eye diseases), affect millions of individuals in the United States and tens of millions around the world and are often undiagnosed in the general population. Clinicians should take into consideration the potential of inherited lipid disorders or syndromes when severe derangements in lipid parameters are observed. Patients' combined genotype and phenotype should be evaluated in conjunction with a host of environmental factors impacting their risk of atherosclerotic cardiovascular disease.

Evaluation of a Chair-Mounted Passive Trunk Orthosis: A Pilot Study on Able-Bodied Subjects.

Trunk stability is important for adequate arm function due to their kinematic linkage. People with Duchenne muscular dystrophy (DMD) can benefit from trunk-assistive devices for seated daily activities, but existing devices limit trunk movement to forward bending. We developed a new trunk orthosis that has spring and pulley design. This study evaluated orthosis performance with 40 able-bodied subjects under with and without orthosis condition in 20 seated tasks for trunk rotation, forward bending, and side bending movements. Subjects adopted static posture in specific trunk orientation while their muscle activity was recorded. They also rated the subjective scales of perceived exertion and usability. A percent change in muscle activity for each task, due to orthosis use, is reported. Significant muscle activity reductions up to 31% and 65% were observed in lumbar and thoracic erector spinae muscles, respectively. Using three-way ANOVA, we found these reductions to be specific to the task direction and the choice of upper limb that is used to perform the asymmetric tasks. A total of 70% participants reported acceptable usability and ~1-point increase in exertion was found for maximum voluntary reaching with the orthosis. The outcomes of this study are promising, though tested on able-bodied subjects. Hence, orthosis mounted on wheelchairs should be further evaluated on DMD patients.

Monogenic and polygenic causes of low and extremely low LDL-C levels in patients referred to specialty lipid clinics: Genetics of low LDL-C.

BACKGROUND: In clinical setting, current standard-of-care does not include genetic testing for patients with low (<50 mg/dL) and extremely low (<20 mg/dL) levels of serum low-density lipoprotein-cholesterol (LDL-C). OBJECTIVE: We aimed identify the underlying molecular cause - both monogenic and polygenic - of low and extremely low LDL-C levels in a cohort of patients presenting to specialty lipid clinics. METHODS: Whole exome sequencing was done in patients with low or extremely low LDL-C not due to any secondary causes. RESULTS: Nine patients (4 women), ranging in age from 25 to 63 years old, with low or extremely low LDL-C levels were evaluated. Median LDL-C was 16 mg/dL (range undetectable - 43), total cholesterol 82 mg/dL (42 - 101), triglycerides 35 mg/dL (19-239), and high-density lipoprotein-cholesterol 45 mg/dL (24-81). Of nine patients, two carried known pathogenic variants in APOB (one stop-gain, one deletion; LDL-C range undetectable -10 mg/dL); three patients had novel APOB heterozygous mutations (two frameshift deletions and one splice site; LDL-C range undectable-13 mg/dL); two had heterozygous APOB frameshift deletions previously reported as variants of unknown significance (LDL-C 18 mg/dL in both patients); one (LDL-C 43 mg/dL) had two heterozygous mutations in PCSK9, both previously reported to be benign; and one patient (LDL-C 16 mg/dL) had the APO E2/E2 genotype along with several variants of unknown significance in genes associated with triglycerides. No patients had an LDL-C polygenic risk score below the 5th percentile (range 26th percentile to 93rd percentile). CONCLUSION: We found APOB mutations to be the most common molecular defect in patients presenting to lipid clinics with low or extremely low LDL-C . Whether clinical genetic testing and LDL-C polygenic risk scores have any utility - other than diagnostic purposes - for such patients remains unclear. In addition, further efforts may be needed to better reclassify pathogenicity of variants of unknown significance.

Racial Disparities in Modifiable Risk Factors and Statin Usage in Black Patients With Familial Hypercholesterolemia.

Background Black men and women are at higher risk for, and suffer greater morbidity and mortality from, atherosclerotic cardiovascular disease (ASCVD) compared with adults of European Ancestry (EA). Black patients with familial hypercholesterolemia are at particularly high risk for ASCVD complications because of lifelong exposure to elevated levels of low-density-lipoprotein cholesterol. Methods and Results This retrospective study analyzed ASCVD prevalence and risk factors in 808 adults with heterozygous familial hypercholesterolemia from 5 US-based lipid clinics, and compared findings in Black versus EA patients. Multivariate logistic regression models were used to determine the strongest predictors of ASCVD as a function of race. No significant difference was noted in the prevalence of ASCVD in Black versus EA patients with familial hypercholesterolemia (39% versus 32%, respectively; P=0.15). However, Black versus EA patients had significantly greater prevalence of modifiable risk factors, including body mass index (mean, 32±7 kg/m2 versus 29±6 kg/m2; P<0.001), hypertension (82% versus 50%; P<0.001), diabetes (39% versus 15%; P<0.001), and current smoking (16% versus 8%; P=0.006). Black versus EA patients also had significantly lower usage of statins (61% versus 73%; P=0.004) and other lipid-lowering agents. In a fully adjusted multivariate model, race was not independently associated with ASCVD (odds ratio, 0.92; 95% CI, 0.60-1.49; P=0.72). Conclusions The strongest predictors of ASCVD in Black patients with familial hypercholesterolemia were hypertension and cigarette smoking. These data support wider usage of statins and other lipid-lowering therapies and greater attention to modifiable risk, specifically blood pressure management and smoking cessation.

A proof-of-concept study of cascade screening for Familial Hypercholesterolemia in the US, adapted from the Dutch model.

BACKGROUND: The Dutch cascade screening model for FH was the most successful of such programs in the world. It remains unclear whether aspects of the Dutch model (i.e. direct engagement with FH probands and relatives outside usual healthcare settings) are feasible in the US. This is especially important since prior attempts at cascade screening in the US have had very low screening rates (<10% of families screened). METHODS: We conducted a multi-site single-arm proof-of-concept study in which the US-based FH Foundation (a 501c3 research and advocacy organization) directly engaged with FH probands and relatives similar to the approach taken by the Dutch "Foundation for Tracing FH." RESULTS: Eleven unrelated probands with genetically confirmed FH were enrolled. Mean age was 43 years; 82% were women, and 82% were of European ancestry. Prior to enrolling into the study, only 2 families (18% screening rate) were screened for FH with both lipid measurements and genetic testing. Two probands declined cascade screening due to fear over genetic discrimination. Nine total relatives engaged with the FH Foundation. Mean age was 43 years and 44% were women. Seven of those relatives (from 6 families; 55% screening rate) consented to be screened for FH with lipid measurement and genetic testing. The two additional relatives - men ages 39 and 49 - agreed to lipid measurements but not genetic testing, each noting he would like to think more about genetic testing. CONCLUSIONS: Our proof-of-concept study demonstrates the feasibility of the FH Foundation engaging FH probands and their relatives outside the usual healthcare settings for cascade screening, similar to the Dutch model. We found only 18% of families had already been screened, and after engaging with the FH Foundation, 55% of families were willing to participate in cascade screening. These findings suggest the methods described here may improve cascade screening rates in the US.

Implications of Islamic Governance towards Psychosocial Work Stressors and Work Productivity.

This is a cross-sectional study, using multivariate regression analysis, to explore the relationship of Islamic governance on psychosocial work stressors and work productivity in healthcare settings. The results revealed that Islamic governing components that are culturally assimilating were significantly related to positive aspects of psychosocial work stressors and increased productivity. Organisational goals that are re-directed towards the Maqasid, i.e. higher order of objectives in Islam, had direct benefits in reducing work-family conflict, promoting general health, increasing job satisfaction and improving commitment to work. Benefits, challenges and recommendations for future studies to expand the field of Islamic governance in organisational and cross-disciplinary healthcare research were discussed.

Children with Heterozygous Familial Hypercholesterolemia in the United States: Data from the Cascade Screening for Awareness and Detection-FH Registry.

OBJECTIVE: To describe enrollment characteristics of youth in the Cascade Screening for Awareness and Detection of FH Registry. STUDY DESIGN: This is a cross-sectional analysis of 493 participants aged <18 years with heterozygous familial hypercholesterolemia recruited from US lipid clinics (n = 20) between April 1, 2014, and January 12, 2018. At enrollment, some were new patients and some were already in care. Clinical characteristics are described, including lipid levels and lipid-lowering treatments. RESULTS: Mean age at diagnosis was 9.4 (4.0) years; 47% female, 68% white and 12% Hispanic. Average (SD) highest Low-density lipoprotein cholesterol (LDL-C) was 238 (61) mg/dL before treatment. Lipid-lowering therapy was used by 64% of participants; 56% were treated with statin. LDL-C declined 84 mg/dL (33%) among those treated with lipid-lowering therapy; statins produced the greatest decline, 100 mg/dL (39% reduction). At enrollment, 39% had reached an LDL-C goal, either <130 mg/dL or ≥50% decrease from pre-treatment; 20% of those on lipid-lowering therapy reached both goals. CONCLUSIONS: Among youth enrolled in the Cascade Screening for Awareness and Detection of FH Registry, diagnosis occurred relatively late, only 77% of children eligible for lipid-lowering therapy were receiving treatment, and only 39% of those treated met their LDL-C goal. Opportunities exist for earlier diagnosis, broader use of lipid-lowering therapy, and greater reduction of LDL-C levels.

A regional analysis of payer and provider views on cholesterol management: PCSK9 inhibitors as an illustrative alignment model.

BACKGROUND: Multiple barriers exist for appropriate use of the proprotein convertase subtilisin/kexin type 9 enzyme inhibitors (PCSK9i) in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH) with inadequately controlled hypercholesterolemia despite standard therapies. Among these barriers, high payer rejection rates and inadequate prior authorization (PA) documentation by providers hinder optimal use of PCSK9i. OBJECTIVES: To (a) identify and discuss provider and payer discordances on barriers to authorization and use of PCSK9i based on clinical and real-world evidence and (b) align understanding and application of clinical, cost, safety, and efficacy data of PCSK9i. METHODS: Local groups of 3 payers and 3 providers met in 6 separate locations across the United States through a collaborative project of AMCP and PRIME Education. Responses to selected pre- and postmeeting survey questions measured changes in attitudes and beliefs regarding treatment barriers, lipid thresholds for considering PCSK9i therapy, and tactics for improving PA processes. Statistical analysis of inter- and intragroup changes in attitudes were performed by Cox proportional hazards test and Fisher's exact test for < 5 variables. RESULTS: The majority of providers and payers (67%-78%) agreed that high patient copayments and inadequate PA documentation were significant barriers to PCSK9i usage. However, payers and providers differed on beliefs that current evidence does not support PCSK9i cost-effectiveness (6% providers, 56% payers; P = 0.003) and that PA presents excessive administrative burden (72% providers, 44% payers; P = 0.09) Average increases pre- to postmeeting were noted in provider beliefs that properly documented PA forms expedite access to PCSK9i (22%-50% increase) and current authorization criteria accurately distinguish patients who benefit most from PCSK9i (6%-22%). Payers decreased in their belief that current authorization criteria accurately distinguish benefiting patients (72%-50%). Providers and payers increased in their belief that PCSK9i are cost-effective (44%-61% and 28%-50%, respectively) and were more willing to consider PCSK9i at the low-density lipoprotein cholesterol threshold of > 70 mg/dL for patients with ASCVD (78%-83% and 44%-67%, respectively) or FH (22%-39% and 22%-33%). Payers were more agreeable to less stringent PA requirements for patients with FH (33%-72%, P = 0.019) and need for standardized PA requirements (50%-83%, P = 0.034); these considerations remained high (89%) among providers after the meeting. Most participants supported educational programs for patient treatment adherence (83%) and physician/staff PA processes (83%-94%). CONCLUSIONS: Provider and payer representatives in 6 distinct geographic locations provided recommendations to improve quality of care in patients eligible for PCSK9i. Participants also provided tactical recommendations for streamlining PA documentation processes and improving awareness of PCSK9i cost-effectiveness and clinical efficacy. The majority of participants supported development of universal, standardized patient eligibility criteria and PA forms. DISCLOSURES: The study reported in this article was part of a continuing education program funded by an independent educational grant awarded by Sanofi US and Regeneron Pharmaceuticals to PRIME Education. The grantor had no role in the study design, execution, analysis, or reporting. AMCP received grant funding from PRIME to assist in the study, as well as in writing the manuscript. McCormick, Bhatt, Bays, Taub, Caldwell, Guerin, Steinhoff, and Ahmad received an honorarium from PRIME for serving as faculty for the continuing education program. McCormick, Bhatt, Bays, Taub, Caldwell, Guerin, Steinhoff, and Ahmad were involved as participants in the study. Bhatt discloses the following relationships: Advisory board: Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, PhaseBio, PLx Pharma, Regado Biosciences; Board of directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data monitoring committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); Site co-investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded research: FlowCo, Merck, Novo Nordisk, Takeda. Bays' research site has received research grants from 89Bio, Acasti, Akcea, Allergan, Alon Medtech/Epitomee, Amarin, Amgen, AstraZeneca, Axsome, Boehringer Ingelheim, Civi, Eli Lilly, Esperion, Evidera, Gan and Lee, Home Access, Janssen, Johnson and Johnson, Lexicon, Matinas, Merck, Metavant, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, Selecta, TIMI, and Urovant. Bays has served as a consultant/advisor for 89Bio, Amarin, Esperion, Matinas, and Gelesis, and speaker for Esperion. McCormick, Caldwell, Guerin, Ahmad, Singh, Moreo, Carter, Heggen, and Sapir have nothing to disclose.

Estimating health state utilities associated with a rare disease: familial chylomicronemia syndrome (FCS).

Aims: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder with no currently approved therapies. Treatments are in development, and cost-utility analyses will be needed to examine their value. These models will require health state utilities representing FCS. Therefore, the purpose of this study was to estimate utilities for FCS and an associated episode of acute pancreatitis (AP).Methods: Because it is not feasible to gather a large enough sample of patients with this extremely rare condition to complete standardized preference-based measures, vignette-based methods were used to estimate utilities. In time trade-off interviews, general population participants in the UK and Canada valued health state vignettes drafted based on literature review, clinician input, and interviews with patients. Four health states described variations of FCS. A fifth health state, describing AP, was added to one of the other health states to evaluate its impact on utility.Results: A total of 308 participants provided utility data (208 UK; 100 Canada). Mean utilities for FCS health states ranged from 0.46 to 0.83, with higher triglycerides, more severe symptoms, and a history of AP associated with lower utility values. The disutility (i.e. utility decrease) of AP ranged from -0.17 to -0.25, with variations depending on the health state to which it was added. Utility means were similar in the UK and Canada.Conclusions: The vignette-based approach is useful for estimating utilities of a rare disease. The health state utilities derived in this study would be useful in models examining cost-effectiveness of treatments for FCS.

The evaluation and management of patients with LDL-C ≥ 190 ​mg/dL in a large health care system.

OBJECTIVES: Patients with severe hyperlipidemia (low-density lipoprotein-cholesterol (LDL-C) ≥190 â€‹mg/dL) have a significantly increased risk of cardiovascular disease (CVD) and are more likely to have familial hypercholesterolemia (FH). We sought to determine how often health care providers recognize the implications of and adjust therapy for an LDL-C ≥190 â€‹mg/dL. METHODS: We conducted a retrospective review of patients with an LDL-C measurement in the medical record of a large health care system between November 2015 and June 2016. Patients were restricted to those with LDL-C ≥190 â€‹mg/dL and without secondary causes of dyslipidemia, with sensitivity analyses for those with LDL-C ≥220 â€‹mg/dL. RESULTS: Of 27,963 patients, 227 had LDL-C ≥190 â€‹mg/dL. Only 21% were on a statin at the time of LDL-C measurement. More than 90% had a follow-up clinic visit, but 41% had no change in treatment. FH was only included in the differential for 14%. The presence/absence of a family history of dyslipidemia, myocardial infarction, and premature CVD were documented in 26%, 29%, and 31%. Only 20.7% and 22.1% had documentation of the presence or absence of tendinous xanthomas or corneal arcus, respectively. Among those without prior specialist care (cardiologist or endocrinologist), only 13% were referred. These measures were only slightly better for those with LDL-C ≥220 â€‹mg/dL. CONCLUSION: In a large health care system, the possibility of FH was rarely acknowledged in those with residual LDL-C ≥190 â€‹mg/dL, few were referred to specialists, and therapeutic adjustments were suboptimal. Additional efforts are required to understand barriers to improving the evaluation and management of patients with LDL-C ≥190 â€‹mg/dL.

Longitudinal low density lipoprotein cholesterol goal achievement and cardiovascular outcomes among adult patients with familial hypercholesterolemia: The CASCADE FH registry.

BACKGROUND AND AIMS: There are limited data from the US on outcomes of patients in specialty care for familial hypercholesterolemia (FH). METHODS: CASCADE FH Registry data were analyzed to assess longitudinal changes in medication usage, in low density lipoprotein cholesterol (LDL-C) levels, and the rate of major adverse cardiovascular events (MACE (myocardial infarction, coronary revascularization, stroke or transient ischemic attack) in adults with FH followed in US specialty clinics. RESULTS: The cohort consisted of 1900 individuals (61% women, 87% Caucasian), with mean age of 56 ±â€¯15 years, 37% prevalence of ASCVD at enrollment, mean pretreatment LDL-C 249 ±â€¯68 mg/dl, mean enrollment LDL-C 145 mg/dl and 93% taking lipid lowering therapy. Over follow up of 20 ±â€¯11 months, lipid lowering therapy use increased (mean decrease in LDL-C of 32 mg/dl (p < 0.001)). Only 48% of participants achieved LDL-C < 100 mg/dl and 22% achieved LDL-C < 70 mg/dl; ASCVD at enrollment was associated with greater likelihood of goal achievement. MACE event rates were almost 6 times higher among patients with prior ASCVD compared to those without (4.6 vs 0.8/100 patient years). Also associated with incident MACE were markers of FH severity and conventional ASCVD risk factors. CONCLUSIONS: With care in FH specialized clinics, LDL-C decreased, but LDL-C persisted >100 mg/dl in 52% of patients. High ASCVD event rates suggest that adults with FH warrant designation as having an ASCVD risk equivalent. Earlier and more aggressive therapy of FH is needed to prevent ASCVD events.