Lipoprotein(a) concentration, genetic variants, apo(a) isoform size, and cellular cholesterol efflux in patients with elevated Lp(a) and coronary heart disease submitted or not to lipoprotein apheresis: An Italian case-control multicenter study on Lp(a).

BACKGROUND: Coronary artery disease (CAD) risk is greater with higher plasma lipoprotein(a)[Lp(a)] concentrations or smaller apoisoform size and putatively with increased cellular cholesterol loading capacity (CLC). The relationship between Lp(a) and CLC is not known. Information on Lp(a) polymorphisms in Italian patients is lacking. OBJECTIVE: The objective of this study was to determine relationships between Lp(a) and CLC, the impact of lipoprotein apheresis (LA), and describe the genetic profile of Lp(a). METHODS: We conducted a multicenter, observational study in Italian patients with hyperLp(a) and premature CAD with (n = 18)/without (n = 16) LA in which blood samples were analyzed for Lp(a) parameter and CLC. Genetic profiling of LPA was conducted in patient receiving LA. RESULTS: Mean macrophage CLC of the pre-LA serum was significantly higher than that of normolipidemic controls (19.7 ± 0.9 µg/mg vs 16.01 ± 0.98 µg/mg of protein, respectively). After LA, serum macrophage CLC was markedly lower relative to preapheresis (16.1 ± 0.8 µg/mg protein; P = .003) and comparable with CLC of the normolipidemic serum. LA did not significantly affect average apo(a) isoform size distribution. No anthropometric or lipid parameters studied were related to serum CLC, but there was a relationship between CLC and the Lp(a) plasma concentration (P = .035). DNA analysis revealed a range of common genetic variants. Two rare, new variants were identified: LPA exon 21, c.3269C>G, p.Pro1090Arg, and rs41259144 p.Arg990Gln, c.2969G>A CONCLUSIONS: LA reduces serum Lp(a) and also reduces macrophage CLC. Novel genetic variants of the LPA gene were identified, and geographic variations were noted. The complexity of these polymorphisms means that genetic assessment is not a predictor of CAD risk in hyperLp(a).

Optical coherence tomography of retinal and choroidal layers in patients with familial hypercholesterolaemia treated with lipoprotein apheresis.

PURPOSE: Detect and quantify morpho-functional alterations of the retina and choroid in patients affected by familial hypercholesterolemia (FH) treated with lipoprotein apheresis (LA) using optic coherence tomography (OCT) and optic coherence tomography-angriography (OCTA). DESIGN: Observational study. SUBJECTS: To be diagnosed: A group of 20 patients (40 eyes) being clinically and genetically diagnosed as FH and under treatment (FH-Group)", for at least 2 years, was compared to a control group of 20 healthy subjects (40 eyes), with a normal lipid profile and no ocular disease (CT-Group). METHODS: Participants were studied with the slit lamp, binocular indirect fundoscopy, OCT and OCTA. MAIN OUTCOME MEASURES: Best corrected visual acuity (BVCA), spherical equivalent (SE), intraocular pressure (IOP), central macular thickness (CMT), choroidal thickness (CHT), retinal nerve fiber layer in four quadrants (RNFL (Superior = Sup; Inferior = Inf; Nasal = Nas Temporal = Temp), and the mean value across the four quadrants (RNFL G), foveal avascular zone (FAZ) and vascular density (VD). RESULTS: FH subjects had smaller RNFL superiorly (108 ±â€¯19,38 µm OD/111 ±â€¯16,56 µm OS FH-Group vs 127 ±â€¯7,42 µm OD/129 ±â€¯14,64 µm OS CT-Group; P < 0,001 for both OD and OS) and inferiorly (108 ±â€¯23,58 µm OD/115 ±â€¯17,33 µm OS FH-Group vs 128 ±â€¯18,15 µm OD/133 ±â€¯17,38 µm OS CT-Group; P = 0,002 OD; P = 0,001 OS). G RNFL was consequently smaller (93 ±â€¯12,94 µm OD/94 ±â€¯10,49 µm OS FH-Group vs 101 ±â€¯9,01 µm OD/101 ±â€¯10,20 µm OS CT-Group; P = 0,03 OD; P = 0,02 OS). FH subjects had a larger FAZ (0,31 ±â€¯0,08 mm2 OD/0,33 ±â€¯0,10 mm2 in OS FH-Group vs 0,21 ±â€¯0,05 mm2 OD/0,21 ±â€¯0,07 mm2 OS CT-Group; P < 0,001 OD; P = 0,002 OS). CONCLUSIONS: Early signs of retinal vessel damage in FH patients can be detected and quantified with OCT and OCTA.

Monascus purpureus for statin and ezetimibe intolerant heterozygous familial hypercholesterolaemia patients: A clinical study.

BACKGROUND: Hypercholesterolaemia is a major risk factor for cardiovascular disease and requires effective therapy in affected patients. Statins, the mainstay of lipid-lowering therapy, can cause side effects, including myalgia, in some patients. Ezetimibe, is frequently used as an add-on therapy for statins, and is also used as a monotherapy in statin-intolerant patients, however elevations in liver transaminases can occur. We examined the lipid-lowering efficacy of the natural fungal product Monascus purpureus (MP), which contains the natural statin monacolin K. METHODS: Fifty-five patients with familial hypercholesterolaemia who had discontinued statins due to muscle symptoms. Patients were placed on a lipid-lowering diet cholesterol-lowering diet (1500-1800 kcal daily, 30% lipids, 19% proteins and 52% carbohydrates). MP was added to the diet at a dose of 300 mg (providing monacolin K 10 mg). Patients were followed for 12 months. Lipid profiles and adverse event data were collected in the normal course of patient care. RESULTS: After 6 months of treatment with MP and diet therapy, statistically significant changes in low-density lipoprotein cholesterol were evident (-17% for males, -16% for females; p < 0.005) Levels fell to -24% and -27% respectively at 12 months. No patients experienced elevated serum aminotransferases or C-reactive protein levels. CONCLUSIONS: MP is a viable option for lipid-lowering therapy in statin-intolerant patients with hypercholesterolaemia, with good efficacy and safety profiles.

Management of homozygous familial hypercholesterolemia in real-world clinical practice: A report of 7 Italian patients treated in Rome with lomitapide and lipoprotein apheresis.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare, genetically determined condition of highly elevated low-density lipoprotein cholesterol (LDLC) levels. If untreated, patients do not typically survive beyond the second decade of life. Traditional lipid-lowering therapies (statins and ezetimibe) are largely ineffective in HoFH patients, and extracorporeal lipoprotein apheresis (LA) forms the mainstay of treatment. Lomitapide is a microsomal triglyceride transfer protein inhibitor approved for the treatment of HoFH as an adjunct to LA. We undertook to examine the efficacy and safety of lomitapide in 7 HoFH patients treated with LA in the Lipid Clinic and Therapeutic Apheresis Unit in Rome, Italy outside a clinical trial setting. METHODS: Seven patients with genetically determined HoFH were treated with lomitapide in the normal course of their therapy. All patients received LA either weekly or biweekly. Lomitapide was administered according to the approved European Union prescribing information. LDLC levels, liver enzymes, and hepatic fat were monitored. Length of follow-up varied between 12 and 50 weeks. RESULTS: After titration, lomitapide doses ranged from 10 to 30 mg/d for most (5/7) patients. One patient received lomitapide 60 mg/d and another 5 mg/d. Three patients achieved LDLC reductions of >50%. The patient on the lowest lomitapide dose did not gain significant benefit. Gastrointestinal adverse events (AEs) were managed via alterations to dietary fat intake. CONCLUSION: Lomitapide is an effective adjunct to LA in patients with HoFH. AEs are manageable; gastrointestinal AEs can be managed with a low-fat eating plan.