The Hurdle of Access to Emerging Therapies and Potential Solutions in the Management of Dyslipidemias.

This review explores the many barriers to accessing lipid-lowering therapies (LLTs) for the prevention and management of atherosclerotic cardiovascular disease (ASCVD). Geographical, knowledge, and regulatory barriers significantly impede access to LLTs, exacerbating disparities in healthcare infrastructure and affordability. We highlight the importance of policy reforms, including pricing regulations and reimbursement policies, for enhancing affordability and streamlining regulatory processes. Innovative funding models, such as value-based pricing and outcome-based payment arrangements, have been recommended to make novel LLTs more accessible. Public health interventions, including community-based programs and telemedicine, can be utilized to reach underserved populations and improve medication adherence. Education and advocacy initiatives led by patient advocacy groups and healthcare providers play a crucial role in raising awareness and empowering patients. Despite the barriers to access, novel LLTs present a big opportunity to reduce the burden of ASCVD, emphasizing the need for collaborative efforts among policymakers, healthcare providers, industry stakeholders, and patient advocacy groups to address these barriers to improve access to LLTs globally.

Point-of-care testing compared to gold-standard laboratory methods in the measurement of serum lipids.

BACKGROUND: Cardiovascular disease is the leading cause of mortality worldwide, with dyslipidaemia being one of the major risk factors. Point-of-care testing (POCT) allows for the rapid measurement of serum lipids. The aim of this study was to assess the accuracy of serum lipid measurement by the Fujifilm™ NX700 POCT compared to a gold-standard clinical laboratory method (Medpace, Leuven, Belgium). METHODS: This was a prospective, observational study conducted at the Lipid Clinic at Charlotte Maxeke Johannesburg Academic Hospital from July to September 2022. Participants were known to have a lipid disorder, most commonly, familial hypercholesterolaemia. Samples sent for lipid measurement by standard laboratory methods were simultaneously measured by the Fujifilm™ NX700 POCT. RESULTS: Lipograms evaluating total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and calculated low-density lipoprotein cholesterol (LDL-C) were obtained from 115 participants. No statistically significant difference was noted between the parameters tested on the different platforms. The Fujifilm™ NX700 POCT correctly identified > 91% of serum lipid results as normal or abnormal, as defined by NCEP-ATP III criteria, and exhibited good sensitivity and specificity for each parameter. Lin's concordance correlation coefficient demonstrated a strong correlation for all parameters; TC (ρc = 0.9861), HDL-C (ρc = 0.95919), LDL-C (ρc = 0.98134) and TG (ρc = 0.92775). Bland-Altman plots identified low bias and a good level of agreement between the two test methods. CONCLUSION: The Fujifilm™ NX700 POCT compared favourably with gold-standard laboratory methods in the determination of serum lipid measurements, allowing for rapid screening at the primary healthcare level.

Targeting PCSK9 and Beyond for the Management of Low-Density Lipoprotein Cholesterol.

Reducing low-density lipoprotein cholesterol (LDL-C) levels is crucial to the prevention of atherosclerotic cardiovascular disease (ASCVD). However, many patients, especially those at very high ASCVD risk or with familial hypercholesterolemia (FH), do not achieve target LDL-C levels with statin monotherapy. The underutilization of novel lipid-lowering therapies (LLT) globally may be due to cost concerns or therapeutic inertia. Emerging approaches have the potential to lower LDL-C and reduce ASCVD risk further, in addition to offering alternatives for statin-intolerant patients. Shifting the treatment paradigm towards initial combination therapy and utilizing novel LLT strategies can complement existing treatments. This review discusses innovative approaches including combination therapies involving statins and agents like ezetimibe, bempedoic acid, cholesterol ester transfer protein (CETP) inhibitors as well as strategies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and angiopoietin-like protein 3 (ANGPTL3) inhibition. Advances in nucleic acid-based therapies and gene editing are innovative approaches that will improve patient compliance and adherence. These strategies demonstrate significant LDL-C reductions and improved cardiovascular outcomes, offering potential for optimal LDL-C control and reduced ASCVD risk. By addressing the limitations of statin monotherapy, these approaches provide new management options for elevated LDL-C levels.

Lp(a), oxidized phospholipids and oxidation-specific epitopes are increased in subjects with keloid formation.

BACKGROUND: Keloid formation following trauma or surgery is common among darkly pigmented individuals. Since lipoprotein(a) [Lp(a)] has been postulated to have a putative role in wound healing, and also mediates atherosclerotic cardiovascular disease, it was assessed whether Lp(a), its associated oxidized phospholipids and other oxidation-specific biomarkers were associated with keloid formation. METHODS: This case-control study included darkly pigmented individuals of African ancestry, 100 with keloid scarring and 100 non-keloid controls. The lipid panel, hsCRP, Lp(a), oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB), IgG and IgM apoB-immune complexes and IgG and IgM autoantibodies to a malondialdehyde mimotope (MDA-mimotope) were measured. Immunohistochemistry of keloid specimens was performed for both Lp(a) and OxPL staining. RESULTS: Cases and controls were well matched for age, sex and lipid profile. Mean Lp(a) (57.8 vs. 44.2 mg/dL; P = 0.01, OxPL-apoB 17.4 vs. 15.7 nmol/L; P = 0.009) and IgG and IgM apoB-immune complexes and IgG and IgM MDA-mimotope levels were significantly higher in keloid cases. Keloid tissue stained strongly for OxPL. CONCLUSION: Darkly pigmented individuals of African ancestry with keloids have higher plasma levels of Lp(a), OxPL-apoB and oxidation-specific epitopes. The commonality of excessive wound healing in keloids and chronic complications from coronary revascularization suggests avenues of investigation to define a common mechanism driven by Lp(a) and the innate response to oxidized lipids.

ANGPTL3 as a Drug Target in Hyperlipidemia and Atherosclerosis.

PURPOSE OF REVIEW: Elevated low-density lipoprotein cholesterol (LDL-C) and triglyceride-rich lipoproteins (TRLs) or remnants are important risk factors for the development of atherosclerotic cardiovascular disease (ASCVD). The ongoing challenge of not being able to achieve recommended LDL-C targets despite maximally tolerated lipid-lowering therapy (LLT) has led to the development of novel therapeutic agents including angiopoietin-like 3 (ANGPTL3) inhibitors. RECENT FINDINGS: ANGPTL3 is a glycoprotein produced by the liver that inhibits lipoprotein lipase and endothelial lipase. Data from genetic and clinical studies have shown that a lower ANGPTL3 level is associated with lower plasma LDL-C, triglyceride (TG), and other lipoproteins. Pharmacological inactivation of ANGPTL3 with the monoclonal antibody, evinacumab, results in a 50% reduction in LDL-C, even in patients with homozygous familial hypercholesterolemia (HoFH). The safe and effective targeted delivery of nucleic acid-based therapies will shape the future of the lipid arena. ANGPTL3 is a novel target in lipoprotein metabolism, targeting not only LDL-C via an LDL-receptor (LDLR) independent mechanism but also TRLs and carries a significant promise for further ASCVD risk reduction.

Dyslipidemia in South African patients with hypothyroidism.

Background: Overt hypothyroidism leads to increased cardiovascular risk, primarily through effects the disorder has on lipids. Most studies investigating lipids in the setting of hypothyroidism, have been performed in predominantly Caucasians in North America and Europe. Different patterns and prevalence of dyslipidemia have been described; one study reporting dyslipidemia in 90% of patients with hypothyroidism. The prevalence of dyslipidemia in overt hypothyroidism among the ethnically diverse predominantly black South African population is unknown. Methodology: A retrospective case-control study evaluating lipid profiles of an ethnically diverse cohort of patients with overt hypothyroidism (TSH > 10 mIU/L) attending two academic hospitals in Johannesburg, South Africa from September 2006-September 2016. Patients with primary or secondary causes for dyslipidemia and those taking lipid-lowering therapy were excluded. Results: Two hundred and six patients with hypothyroidism were included and compared to 412 euthyroid controls matched for sex, ethnicity, and age. Most hypothyroid patients were female (n = 180;67.5 %). Median TSH was similar across all ethnic groups (p = 0.09). Median TC, TG and LDL-C were higher in hypothyroid patients (p < 0.01). Normal lipid profiles were found in 29.44 % of all hypothyroid patients. However, a greater proportion, 47 of 124 (37.90 %), black African patients with hypothyroidism had a normal lipid profile. Conclusion: Dyslipidemia is less common in black African patients with hypothyroidism. This is probably due to this population group being in an earlier stage of epidemiologic transition. Those with hypothyroidism were at greater overall cardiovascular risk based on TC/HDL-C ratio but did not reach high risk atherogenic profiles reported in previous studies.

A Severe Case of Molluscum Contagiosum Immune Reconstitution Inflammatory Syndrome in a Patient with Human Immunodeficiency Virus.

Paradoxical immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-positive patients initiating antiretroviral treatment (ART) is caused by restored immunity to specific antigens, resulting in worsening of a pre-existing infection. Molluscum contagiosum (MC) is commonly noted in HIV-positive individuals but ART alone is usually sufficient to bring about resolution. We present a rare case of severe MC-IRIS that worsened despite immune reconstitution. LEARNING POINTS: Molluscum contagiosum is a common opportunistic infection which can have severe manifestations in immunocompromised individuals.Antiretroviral treatment alone is usually sufficient to clear the infection, however refractory cases can persist despite immune reconstitution.Failure to improve or worsening immune reconstitution inflammatory syndrome should raise suspicion for additional immunological dysfunction.Surgery, cytodestructive therapies and chemotherapeutic agents can be considered in extensive, persistent disease.