Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym SAMS (Statin-Associated Muscle Side Effects). These side effects are responsible for statin treatment discontinuation that results in increased cardiovascular risk. The National Lipid Association (NLA) has recently provided an updated definition of statin intolerance, and a distinction between complete and partial statin intolerance has been reported. The evaluation of symptom severity and the presence of muscle damage biomarker alterations make it essential to adopt a patient-centered approach aimed at obtaining a personalized therapeutic strategy. Firstly, it could be useful to administer a different statin, reduce the dosage or adopt an alternate dosage regimen. However, some patients are unable to tolerate any statin at every dosage, or despite taking statins at the maximum tolerated dose, they fail to achieve the recommended LDL-C target, and thus it is necessary to introduce a non-statin hypolipidemic treatment. Ezetimibe, proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as monoclonal antibodies (alirocumab and evolocumab) or RNA messenger silencing (inclisiran), bempedoic acid or nutraceuticals are non-statin lipid-lowering therapies that could be used as an alternative or in addition to statins to achieve an early and sustained LDL-C reduction in clinical practice. In this review, we evaluated SI management focusing on non-statin lipid lowering therapies and their implications in lipid lowering approaches in clinical practice.
BackgroundLong non‐coding RNAs (lncRNAs) could be attractive circulating biomarkers for cardiovascular risk stratification in subjects at high atherosclerotic cardiovascular disease risk such as familial hypercholesterolaemia (FH). Our aim was to investigate the presence of lncRNAs carried by high‐density lipoprotein (HDL) in FH subjects and to evaluate the associations of HDL‐lncRNAs with lipoproteins and mechanical vascular impairment assessed by pulse wave velocity (PWV).MethodsThis was a retrospective observational study involving 94 FH subjects on statin treatment. Biochemical assays, HDL purification, lncRNA and PWV analyses were performed in all subjects.ResultsLncRNA HIF1A‐AS2, LASER and LEXIS were transported by HDL; moreover, HDL‐lncRNA LEXIS was associated with Lp(a) plasma levels (p < .01). In a secondary analysis, the study population was stratified into two groups based on the Lp(a) median value. The high‐Lp(a) group exhibited a significant increase of PWV compared to the low‐Lp(a) group (9.23 ± .61 vs. 7.67 ± .56, p < .01). While HDL‐lncRNA HIF1A‐AS2 and LASER were similar in the two groups, the high‐Lp(a) group exhibited a significant downregulation of HDL‐lncRNA LEXIS compared to the low‐Lp(a) group (fold change −4.4, p < .0001). Finally, Lp(a) and HDL‐lncRNA LEXIS were associated with PWV (for Lp(a) p < .01; for HDL‐lncRNA LEXIS p < .05).ConclusionsLncRNA HIF1A‐AS2, LASER and LEXIS were transported by HDL; moreover, significant relationships of HDL‐lncRNA LEXIS with Lp(a) levels and PWV were found. Our study suggests that HDL‐lncRNA LEXIS may be useful to better identify FH subjects with more pronounced vascular damage.
Over the last three years, the Coronavirus-19 disease has been a global health emergency, playing a primary role in the international scientific community. Clinical activity and scientific research have concentrated their efforts on facing the pandemic, allowing the description of novel pathologies correlated to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), such as the Multisystemic Inflammatory Syndrome in Children and Adults (MIS-C, MIS-A). Conversely, this shift of attention to COVID-19 disease and its complications could, in some cases, have delayed and underestimated the diagnosis of diseases not associated with SARS-CoV-2, including rare diseases. Here we describe the diagnostic process that led to the definition of a rare vasculitis in a young woman with a recent clinical history of SARS-CoV-2.
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