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 c Show more
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
The APOE p.(Leu167del) variant has been identified as a rare cause of autosomal dominant hypercholesterolemia. A comprehensive phenotypic profile of carriers remains undefined, and its frequency has n Show more
The APOE p.(Leu167del) variant has been identified as a rare cause of autosomal dominant hypercholesterolemia. A comprehensive phenotypic profile of carriers remains undefined, and its frequency has not been systematically studied. To characterize the phenotypic differences between p.(Leu167del) carriers among individuals with primary hypercholesterolemia and those with familial hypercholesterolemia (FH), and to estimate the variant's frequency in different populations. Phenotypic differences were assessed from the Lipid Unit cohort of the Hospital Universitario Miguel Servet (HUMS, n = 6489). The allele frequency of the p.(Leu167del) variant was estimated using data from the HUMS and Aragon Workers Health Study (AWHS, n = 5678), a cohort of working adults, and international cohorts: GnomAD (n ≈ 807,162), TOPMed (n ≈ 180,000), 100 K Genomes Project (n ≈ 85,000). To characterize the profile of carriers, data from the HUMS cohort and a systematic review of the published literature were also used. Carriers showed significantly higher high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and non-HDL cholesterol and lower lipoprotein(a) [Lp(a)] concentrations compared to noncarriers with primary hypercholesterolemia. In comparison with FH patients carrying LDL receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK9) variants, carriers displayed higher triglycerides and HDL cholesterol but lower LDL cholesterol and Lp(a). The APOE p.(Leu167del) frequency is approximately 1 in 12,000 individuals in the general population and about 2.5% of FH. The study confirmed the association of APOE p.(Leu167del) with hypercholesterolemia but with lower LDL cholesterol than subjects with FH. These findings support p.(Leu167del) as a cause of FH and its inclusion in the genetic screening for FH, particularly in Caucasian populations. Show less
Apolipoprotein (apo) C-III is involved in several processes that increase triglyceride levels, inflammation, and insulin resistance. Four of its proteoforms have been the focus of several studies and Show more
Apolipoprotein (apo) C-III is involved in several processes that increase triglyceride levels, inflammation, and insulin resistance. Four of its proteoforms have been the focus of several studies and have shown differential associations with cardiovascular risk biomarkers, mostly lipids. However, there are other proteoforms of apoC-III that have not yet been investigated in detail. The aim of this study was to evaluate the associations of seven apoC-III proteoforms with a comprehensive set of biomarkers, including lipid metabolism, inflammation, and glucose homeostasis. Seven apoC-III proteoforms (apoC-III Three proteoform ratios (apoC-III While apoC-III is positively associated with biomarkers of cardiometabolic risk, the proportions of three apoC-III proteoforms show opposite associations, independent of total apoC-III concentrations. Measuring not only apoC-III but also the proportions of apoC-III proteoforms can provide valuable information since individuals with similar levels of total apoC-III could display opposite lipid profiles depending on the proportion of apoC-III proteoforms. Show less