👤 Nuria Amigo

Lipoprotein(a) (Lp(a)) is a proatherogenic particle that is considered an important cardiovascular risk modifier due to its association with atherosclerotic cardiovascular disease (ASCVD) as well as calcific aortic valve stenosis (CAVS). Data on the clinical burden associated with elevated lipoprotein(a) levels in patients at high and very high cardiovascular risk remain limited. We evaluated the prevalence of ASCVD and LDL-C target achievement in subjects with high and very high elevated Lp(a) levels referred to a lipid unit. In this retrospective study, 1755 subjects were evaluated; 265 with Lp(a) ≥240nmol/L were included. The population was divided into two groups: high Lp(a) (240-429nmol/L, n=216) and very high Lp(a) (≥430nmol/L, n=49). ASCVD prevalence was 58% in the very high group and 48% in the high group (p=0.23). Age and statin intensity were higher in the very high Lp(a) group. LDL-C target achievement was low in both groups: 20.0% and 25.4% of very high-risk patients reached <55mg/dL as well as 18.2% and 17.2% of high-risk patients reached <70mg/dL in very high and high Lp(a) groups, respectively. Subjects with elevated Lp(a) levels showed a high prevalence of ASCVD and low LDL-C target attainment despite high-intensity statin therapy. These findings support the need for Lp(a) screening and additional lipid-lowering strategies in high-risk patients. Show less

Atherosclerotic cardiovascular disease is the main cause of mortality worldwide and is strongly influenced by circulating low-density lipoprotein (LDL) cholesterol levels. Only a few genes causally related to plasma LDL cholesterol levels have been identified so far, and only 1 gene, Using next-generation sequencing, we identified a novel dominant rare variant in the Family members carrying the We identified and characterized a novel rare variant in the Show less

Next generation sequencing (NGS) has expanded the diagnostic paradigm turning the focus to the growth plate. The aim of the study was to determine the prevalence of variants in genes implicated in skeletal dysplasias in probands with short stature and mild skeletal anomalies. Clinical and radiological data were collected from 108 probands with short stature and mild skeletal anomalies. A customized skeletal dysplasia NGS panel was performed. Variants were classified using ACMG recommendations and Sherloc. Anthropometric measurements and skeletal anomalies were subsequently compared in those with or without an identified genetic defect. Heterozygous variants were identified in 21/108 probands (19.4%). Variants were most frequently identified in ACAN (n = 10) and IHH (n = 7) whilst one variant was detected in COL2A1, CREBBP, EXT1, and PTPN11. Statistically significant differences (P < 0.05) were observed for sitting height/height (SH/H) ratio, SH/H ratio standard deviation score (SDS), and the SH/H ratio SDS >1 in those with an identified variant compared to those without. A molecular defect was elucidated in a fifth of patients. Thus, the prevalence of mild forms of skeletal dysplasias is relatively high in individuals with short stature and mild skeletal anomalies, with variants in ACAN and IHH accounting for 81% of the cases. An elevated SH/H ratio appears to be associated with a greater probability in detecting a variant, but no other clinical or radiological feature has been found determinant to finding a genetic cause. Currently, we cannot perform extensive molecular studies in all short stature individuals so detailed clinical and radiological phenotyping may orientate which are the candidate patients to obtain worthwhile results. In addition, detailed phenotyping of probands and family members will often aid variant classification. Show less