S N Pokrovsky1, O I Afanasieva2, M S Safarova3, T V Balakhonova4, Yu G Matchin5, I Y U Adamova2, G A Konovalov6, M V Ezhov3. 1. Laboratory of Atherosclerosis, Institute of Experimental Cardiology, Federal State Institution "Russian Cardiology Research and Production Center" of Ministry of Health of the Russian Federation, 15A, 3d Cherepkovskaya Street, Moscow 121552, Russia. Electronic address: Dr.Pokrovsky@mail.ru. 2. Laboratory of Atherosclerosis, Institute of Experimental Cardiology, Federal State Institution "Russian Cardiology Research and Production Center" of Ministry of Health of the Russian Federation, 15A, 3d Cherepkovskaya Street, Moscow 121552, Russia. 3. Atherosclerosis Department, Institute of Clinical Cardiology named after A.L. Myasnikov, Federal State Institution "Russian Cardiology Research and Production Center" of Ministry of Health of the Russian Federation, 15A, 3d Cherepkovskaya Street, Moscow 121552, Russia. 4. Ultrasound Laboratory, Institute of Clinical Cardiology named after A.L. Myasnikov, Federal State Institution "Russian Cardiology Research and Production Center" of Ministry of Health of the Russian Federation, 15A, 3d Cherepkovskaya Street, Moscow 121552, Russia. 5. Catheterization Laboratory, Institute of Clinical Cardiology named after A.L. Myasnikov, Federal State Institution "Russian Cardiology Research and Production Center" of Ministry of Health of the Russian Federation, 15A, 3d Cherepkovskaya Street, Moscow 121552, Russia. 6. Center of Extracorporeal Therapies, MEDSI Clinic, 3A, Georgian Lane, Moscow 123056, Russia.
Abstract
BACKGROUND: An elevated lipoprotein(a) (Lp(a)) level is observed in more than 30% of patients with stable ischemic heart disease (SIHD). We conducted an investigation of the effects of specific Lp(a) apheresis on the progression of atherosclerosis in SIHD patients with Lp(a) levels greater than 50 mg/dL. METHODS: We prospectively enrolled 15 patients diagnosed with SIHD based on symptom-driven coronary angiography findings, with Lp(a) ≥50 mg/dL and a low density lipoprotein cholesterol (LDL-C) ≤2.5 mmol/L, who were on long-term statin therapy. They underwent weekly Lp(a) apheresis using Lp(a) Lipopak® adsorption columns which contain monospecific sheep polyclonal antibodies against human Lp(a). Fifteen age and gender matched SIHD patients receiving atorvastatin monotherapy served as controls. At baseline and 18 months post-treatment, quantitative coronary angiography, intracoronary ultrasound with virtual histology and carotid ultrasound were performed. Lipid profile, including Lp(a), was measured at the scheduled visits, and before and after each apheresis procedure. Levels of high-sensitivity C-reactive protein (hsCRP), matrix metalloproteinases (MMP)-7 and 9, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and 2 were determined at baseline and at the end of the study period. RESULTS: Each specific Lp(a) apheresis procedure was carried out with two adsorption columns resulting in an average acute decrease in Lp(a) levels of 75% (from 110 ± 22 to 29 ± 16 mg/dL) without significant changes in other plasma components. Lp(a) reduction over the course of 18 months was associated with a decrease in the mean percent diameter stenosis of 5.05% and an increase in minimal lumen diameter of 14%; the mean total atheroma volume was reduced by 4.60 mm3 (p < 0.05 for all). There was a decrease in absolute common carotid intima-media thickness in the Lp(a) apheresis group of 0.07 ± 0.15 mm both from baseline and compared with the control group (p = 0.01). Levels of hsCRP were reduced by 40% in patients on Lp(a) apheresis without significant changes in the levels of other biomarkers at the end of the study. CONCLUSION: Reduction of the atherosclerotic burden in coronary and carotid arteries was observed in patients treated with specific Lp(a) apheresis and statin over 18 months compared with statin therapy alone. These findings support the atherogenic role of Lp(a) and reinforce the need to assess the effects of Lp(a)-lowering on cardiovascular events and mortality. Trial Registration Clinicaltrials.gov (NCT02133807).
BACKGROUND: An elevated lipoprotein(a) (Lp(a)) level is observed in more than 30% of patients with stable ischemic heart disease (SIHD). We conducted an investigation of the effects of specific Lp(a) apheresis on the progression of atherosclerosis in SIHD patients with Lp(a) levels greater than 50 mg/dL. METHODS: We prospectively enrolled 15 patients diagnosed with SIHD based on symptom-driven coronary angiography findings, with Lp(a) ≥50 mg/dL and a low density lipoprotein cholesterol (LDL-C) ≤2.5 mmol/L, who were on long-term statin therapy. They underwent weekly Lp(a) apheresis using Lp(a) Lipopak® adsorption columns which contain monospecific sheep polyclonal antibodies against humanLp(a). Fifteen age and gender matched SIHD patients receiving atorvastatin monotherapy served as controls. At baseline and 18 months post-treatment, quantitative coronary angiography, intracoronary ultrasound with virtual histology and carotid ultrasound were performed. Lipid profile, including Lp(a), was measured at the scheduled visits, and before and after each apheresis procedure. Levels of high-sensitivity C-reactive protein (hsCRP), matrix metalloproteinases (MMP)-7 and 9, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and 2 were determined at baseline and at the end of the study period. RESULTS: Each specific Lp(a) apheresis procedure was carried out with two adsorption columns resulting in an average acute decrease in Lp(a) levels of 75% (from 110 ± 22 to 29 ± 16 mg/dL) without significant changes in other plasma components. Lp(a) reduction over the course of 18 months was associated with a decrease in the mean percent diameter stenosis of 5.05% and an increase in minimal lumen diameter of 14%; the mean total atheroma volume was reduced by 4.60 mm3 (p < 0.05 for all). There was a decrease in absolute common carotid intima-media thickness in the Lp(a) apheresis group of 0.07 ± 0.15 mm both from baseline and compared with the control group (p = 0.01). Levels of hsCRP were reduced by 40% in patients on Lp(a) apheresis without significant changes in the levels of other biomarkers at the end of the study. CONCLUSION: Reduction of the atherosclerotic burden in coronary and carotid arteries was observed in patients treated with specific Lp(a) apheresis and statin over 18 months compared with statin therapy alone. These findings support the atherogenic role of Lp(a) and reinforce the need to assess the effects of Lp(a)-lowering on cardiovascular events and mortality. Trial Registration Clinicaltrials.gov (NCT02133807).
Authors: Dominik M Schulte; Georg H Waetzig; Harald Schuett; Marlies Marx; Berenice Schulte; Christoph Garbers; Juliane Lokau; Ann-Kathrin Vlacil; Juliane Schulz; Anna K Seoudy; Bernhard Schieffer; Philip Rosenstiel; Marcus Seeger; Matthias Laudes; Stefan Rose-John; Ulf Lützen; Karsten Grote; Stefan Schreiber Journal: Front Pharmacol Date: 2022-06-09 Impact factor: 5.988
Authors: María Del Prado Garrido; Ana Maria Borreguero; Francisco Javier Redondo; David Padilla; Manuel Carmona; María Jesús Ramos; Juan Francisco Rodriguez Journal: Materials (Basel) Date: 2022-08-30 Impact factor: 3.748
Authors: Daniel I Swerdlow; David A Rider; Arash Yavari; Marie Wikström Lindholm; Giles V Campion; Steven E Nissen Journal: Cardiovasc Res Date: 2022-03-25 Impact factor: 10.787