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Abstrac t: Background: Long 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). Methods: This 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. Results: LncRNA 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). Conclusions: LncRNA 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. [ABSTRACT FROM AUTHOR]

The classic description of diabetic kidney disease (DKD) involves progressive stages of glomerular hyperfiltration, microalbuminuria, proteinuria, and a decline in the estimated glomerular filtration rate (eGFR), leading to dialysis. In recent years, this concept has been increasingly challenged as evidence suggests that DKD presents more heterogeneously. Large studies have revealed that eGFR decline may also occur independently from the development of albuminuria. This concept led to the identification of a new DKD phenotype: non-albuminuric DKD (eGFR < 60 mL/min/1.73 m2, absence of albuminuria), whose pathogenesis is still unknown. However, various hypotheses have been formulated, the most likely of which is the acute kidney injury-to-chronic kidney disease (CKD) transition, with prevalent tubular, rather than glomerular, damage (typically described in albuminuric DKD). Moreover, it is still debated which phenotype is associated with a higher cardiovascular risk, due to contrasting results available in the literature. Finally, much evidence has accumulated on the various classes of drugs with beneficial effects on DKD; however, there is a lack of studies analyzing the different effects of drugs on the various phenotypes of DKD. For this reason, there are still no specific guidelines for therapy in one phenotype rather than the other, generically referring to diabetic patients with CKD. [ABSTRACT FROM AUTHOR]