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

Erratum in: J Am Heart Assoc. 2023 Jun 6;12(11):e027706. doi: 10.1161/JAHA.122.027706. Epub 2023 Jun 1.Free PMC article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10227232/Background: Homozygous familial hypercholesterolemia (HoFH) is a rare, treatment-resistant disorder characterized by earlyonset 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 lowdensity lipoprotein cholesterol levels were lower in adults than children (533 versus 776mg/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.Dr Martin is supported by grants/contracts from the American Heart Association (20SFRN35380046, 20SFRN35490003, 878924, and 882415), Patient‐Centered Outcomes Research Institute (PCORI) (ME‐2019C1‐15328), National Institutes of Health (NIH) (R01AG071032 and P01 HL108800), the David and June Trone Family Foundation, Pollin Digital Health Innovation Fund, and Sandra and Larry Small; Dr Knowles is supported by the NIH through grants P30 DK116074 (to the Stanford Diabetes Research Center), R01 DK116750, R01 DK120565, and R01 DK106236; and by a grant from the Bilateral Science Foundation. Dr Linton is supported by NIH grants P01HL116263, HL148137, HL159487, and HL146134.info:eu-repo/semantics/publishedVersio

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

A hydrogen-based burner concept for pilot-scale spray-flame synthesis of nanoparticles: Investigation of flames and iron oxide product materials

Nanoparticle synthesis in spray flames is a flexible method to produce materials with a wide range of compositions, morphologies, and properties. On the road to industrial application, the transfer from laboratory to pilot scale is an important intermediate step. In the present paper, nanoparticle synthesis based on spray combustion combined with a novel burner concept based on a fuel/air pilot flame ignited by an electrical heat ring is presented. When operating with H2, the burner concept allows nanoparticle production with a sustainable fuel. The temperature profile in the flame is one of the key factors determining the kinetics of precursor decomposition, particle formation, and growth. In this work, we have studied the gas-phase temperature in the reactive zone using non-intrusive multi-line NO-LIF temperature imaging. A solution of iron nitrate nonahydrate dissolved in ethanol was used as nanoparticle precursor mixture, atomized by a commercial two-fluid nozzle, and ignited by the premixed flame to synthesize iron-oxide nanoparticles. The burner can be operated at different conditions to direct the properties of the nanoparticles produced. To this goal, process conditions were varied in a targeted manner. In addition to variations in fuel gas and flow rates, the use of compressed air instead of pure O2 as a dispersion gas has also been investigated. The effects of these variations on temperature distribution and materials properties have been investigated. It has been determined that the dispersion gas mass flow has relatively small influence on the materials properties, while higher flame temperatures are advantageous to suppress the often-undesired liquid-to-particle synthesis pathway

Characterization of PCSK9 in the Blood and Skin of Psoriasis

© 2020 The Authors Mechanisms explaining the link between psoriasis, a proinflammatory condition, and cardiovascular disease are not fully known. PCSK9 is predominantly expressed in hepatocytes as a critical regulator of lipid metabolism, and clinical trials targeting PCSK9 reduce cardiovascular disease. Independent of its role in lipid metabolism, PCSK9 levels associate with endothelial dysfunction and predict cardiovascular events. We used two separate human psoriasis cohorts and the K14-Rac1V12−/+ murine model of psoriasis to investigate PCSK9 and cardiovascular risk in psoriasis. In both psoriasis cohorts (n = 88 and n = 20), PCSK9 levels were 20% and 13% higher than in age-, sex-, and cholesterol-matched controls, respectively (P \u3c 0.05 for each comparison) and correlated with PASI (r = 0.43, P \u3c 0.05). Despite no difference in hepatocyte expression, K14-Rac1V12−/+ mice demonstrated skin-specific PCSK9 staining, which was confirmed in human psoriatic lesional skin. In patients with psoriasis, PCSK9 levels correlated with impaired endothelial vascular health (e.g., early atherosclerosis, β = 4.5, P \u3c 0.01) and log converted coronary artery calcium score (β = 0.30, P = 0.01), which remained significant after adjustment for Framingham risk, body mass index, and active biologic use. Taken together, these findings suggest, independent of cholesterol, an association between circulating PCSK9 and early as well as advanced stages of atherosclerosis in psoriasis

The management of respiratory motion in radiation oncology report of AAPM Task Group 76.

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134989/1/mp9696.pd