Search

Copyright of Herz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Internist is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims: Several the use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) for patients at high/very high cardiovascular risk who are inadequately treated with maximally tolerated lipid-lowering therapies (LLTs). Objectives: We assessed the effectiveness and safety of the PCSK9i alirocumab and evolocumab in a single-center clinical practice for up to 68 weeks. Methods: In this prospective, open-label study conducted in Germany, 635 enrolled patients were treated with alirocumab [75 or 150 mg every 2 weeks (Q2W)] or evolocumab (140 mg Q2W) according to European Society of Cardiology/European Atherosclerosis Society guidelines (low-density lipoprotein cholesterol [LDL-C] > 1.81/2.59 mmol/L (70/100 mg/dL), depending on cardiovascular risk]. Investigators were able to adjust LLTs, including PCSK9i, according to their own clinical judgment. The primary effectiveness endpoint was LDL-C reduction from baseline to week 68. Results: At baseline, approximately 50% of patients were statin intolerant, and approximately 90% reported a history of cardiovascular disease. LDL-C reductions remained generally unchanged from weeks 4 to 68 in each treatment group. At week 68, LDL-C mean percentage changes from baseline were − 41.7% (alirocumab 75 mg Q2W), − 53.7% (alirocumab 150 mg Q2W), and − 54.1% (evolocumab 140 mg Q2W). LDL-C reduction was 7.1% greater in patients receiving statins than in those not receiving statins because of statin intolerance (P < 0.0001). PCSK9i consistently improved levels of other lipoproteins throughout. Overall, 47.1% of patients reported adverse events at week 68. Conclusions: Consistent with clinical trial findings, alirocumab and evolocumab improved lipid levels in a real-world setting in patients with high baseline LDL-C levels despite receiving maximally tolerated LLTs. PCSK9i were generally well-tolerated. [ABSTRACT FROM AUTHOR]

Epidemiological, clinical, and experimental evidence has accumulated during the last decades suggesting that high-density lipoproteins (HDLs) may protect from atherosclerosis and its clinical consequences. However, more than 55 years after the first description of the link between HDL and heart attacks, many facets of the biochemistry, function, and clinical significance of HDL remain enigmatic. This applies particularly to the completely unexpected results that became available from some recent clinical trials of nicotinic acid and of inhibitors of cholesteryl ester transfer protein (CETP). The concept that raising HDL cholesterol by pharmacological means would decrease the risk of vascular disease has therefore been challenged. [ABSTRACT FROM AUTHOR]

High levels of low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] are associated with early morbidity and mortality caused by cardiovascular disease (CVD). There are hints that a reduction of LDL-C levels beyond currently advocated targets, and the use of drugs that also have Lp(a)-lowering potential, could provide further clinical benefit. Today, LDL apheresis is the only available treatment option to achieve further lowering of apolipoprotein-B (apo-B)-containing lipoproteins, especially Lp(a). Mipomersen is currently being studied in patients with mild to severe hypercholesterolaemia as add-on therapy to other lipid-lowering therapy, as monotherapy in patients who are intolerant of HMG-CoA reductase inhibitors (statins) and who are at high risk for CVD. Patients affected by homozygous or heterozygous familial hypercholesterolaemia (FH), which are inherited autosomal co-dominant disorders characterized by a marked elevation of serum LDL-C concentration, remain a clinical challenge, especially when their CVD risk is aggravated by additionally elevated Lp(a) levels. Mipomersen is a 20-mer oligonucleotide [2′-O-(2-methoxy) ethyl-modified oligonucleotide], a second-generation antisense oligonucleotide (AOS), complementary to the coding region for human-specific apo-B-100 messenger RNA (mRNA). Mipomersen inhibits apo-B-100 synthesis and is consequently a new treatment strategy to lower apo-B-containing lipoproteins like LDL-C and Lp(a) in patients at high risk for CVD not on target or intolerant to statins. This article focuses on mipomersen and gives an overview of the current status of mipomersen as a promising treatment option. Recent studies have shown a decrease in LDL-C levels of 22--42.2% and in Lp(a) of 19.6-31.1% from baseline, depending on study design. Dose-dependent reductions of very low-density lipoprotein cholesterol (VLDL-C) and triglyceride levels have also been observed. Although the short-term efficacy and safety of mipomersen have been proven, side effects like injection-site reactions (up to 90-100%), increased liver enzymes, cephalgias, nasopharyngitis, myalgia, nausea and fatigue must be mentioned and critically discussed. Furthermore, we need more data on the long-term side effects, especially regarding the long-term potential for hepatic steatosis. Data on cardiovascular outcomes with mipomersen are also not yet available. [ABSTRACT FROM AUTHOR]

Rare monogenic hyperchylomicronemia is caused by loss-of-function mutations in genes involved in the catabolism of triglyceride-rich lipoproteins, including the lipoprotein lipase gene, LPL. Clinical hallmarks of this condition are eruptive xanthomas, recurrent pancreatitis and abdominal pain. Patients with LPL deficiency and severe or recurrent pancreatitis are eligible for the first gene therapy treatment approved by the European Union. Therefore the precise molecular diagnosis of familial hyperchylomicronemia may affect treatment decisions. We present a 57-year-old male patient with excessive hypertriglyceridemia despite intensive lipid-lowering therapy. Abdominal sonography showed signs of chronic pancreatitis. Direct DNA sequencing and cloning revealed two novel missense variants, c.1302A>T and c.1306G>A, in exon 8 of the LPL gene coexisting on the same allele. The variants result in the amino-acid exchanges p.(Lys434Asn) and p.(Gly436Arg). They are located in the carboxy-terminal domain of lipoprotein lipase that interacts with the glycosylphosphatidylinositol-anchored HDL-binding protein (GPIHBP1) and are likely of functional relevance. No further relevant mutations were found by direct sequencing of the genes for APOA5, APOC2, LMF1 and GPIHBP1. We conclude that heterozygosity for damaging mutations of LPL may be sufficient to produce severe hypertriglyceridemia and that chylomicronemia may be transmitted in a dominant manner, at least in some families. [ABSTRACT FROM AUTHOR]

The article presents a clinical utility gene card for hyperlipoproteinemia, type II. Key characteristics of the disease are provided, including the name of the analysed genes or DNA/chromosome segments, mutational spectrum, and analytical validation. It explores the test characteristics of hyperlipoproteinemia, type II as well as looks at its clinical utility.