Advertisement

Effect of Lipoprotein Apheresis on Progression of Carotid Intima-Media Thickness in Patients with Severe Hypercholesterolemia

      The extent of intervention effects on carotid intima-media thickness (CIMT) can predict the degree of atherosclerotic cardiovascular risk-reduction. We hypothesized that regular lipoprotein apheresis over the course of 10 years might slow down progression of CIMT in patients with severe hypercholesterolemia. This case series describes 10 Caucasian patients (mean age 60 ± 9 years, 70% female, 80% statin intolerant) with a severe hypercholesterolemia phenotype treated with lipoprotein apheresis between 2005 and 2020 (mean duration, 10 ± 4 years). The median pretreatment low-density lipoprotein cholesterol (LDL-C) level was 214 mg/100 ml (95% confidence interval, 145 to 248), lipoprotein(a) (Lp[a]), 26 mg/100 ml (15 to 109; 40% with Lp(a)>60 mg/100 ml). Three patients were diagnosed with a monogenic cause. The baseline mean CIMT was 850 ± 170 µm, and maximum CIMT was 1,040 ± 220 µm across the age range of 46 to 70 years. Acute effects of lipoprotein apheresis determined as a difference before and immediately after the procedure were estimated as a median of 72 ± 8% and 75 ± 7% reduction in the LDL-C and Lp(a) levels, respectively. Using the imputed trajectories, period-specific on-treatment time-weighted averages for LDL-C and Lp(a) were 141 mg/100 ml (interquartile range, 89 to 152; 38% reduction from the baseline) and 24 mg/100 ml (interquartile range, 12 to 119; 19% reduction from baseline), respectively. The number of patients with CIMT above their “vascular age” decreased from 80% to 30% over the treatment course. In conclusion, an increase in CIMT seen with advanced age and severe hypercholesterolemia was halted with lipoprotein apheresis with an estimated annual rate of change in mean common CIMT of −4 µm/y and maximum CIMT of −3 µm/y.

      Graphical Abstract

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Johri AM
        • Nambi V
        • Naqvi TZ
        • Feinstein SB
        • Kim ESH
        • Park MM
        • Becher H
        • Sillesen H.
        Recommendations for the assessment of carotid arterial plaque by ultrasound for the characterization of atherosclerosis and evaluation of cardiovascular risk: from the American Society of Echocardiography.
        J Am Soc Echocardiogr. 2020; 33: 917-933
        • Stein JH
        • Fraizer MC
        • Aeschlimann SE
        • Nelson-Worel J
        • McBride PE
        • Douglas PS.
        Vascular age: integrating carotid intima-media thickness measurements with global coronary risk assessment.
        Clin Cardiol. 2004; 27: 388-392
        • Fernández-Friera L
        • Peñalvo JL
        • Fernández-Ortiz A
        • Ibañez B
        • López-Melgar B
        • Laclaustra M
        • Oliva B
        • Mocoroa A
        • Mendiguren J
        • Martínez de Vega V
        • García L
        • Molina J
        • Sánchez-González J
        • Guzmán G
        • Alonso-Farto JC
        • Guallar E
        • Civeira F
        • Sillesen H
        • Pocock S
        • Ordovás JM
        • Sanz G
        • Jiménez-Borreguero LJ
        • Fuster V
        Prevalence, vascular distribution, and multiterritorial extent of subclinical atherosclerosis in a middle-aged cohort: the PESA (Progression of Early Subclinical Atherosclerosis) study.
        Circulation. 2015; 131: 2104-2113
        • Kusters DM
        • Wiegman A
        • Kastelein JJ
        • Hutten BA.
        Carotid intima-media thickness in children with familial hypercholesterolemia.
        Circ Res. 2014; 114: 307-310
        • Rampersaud E
        • Bielak LF
        • Parsa A
        • Shen H
        • Post W
        • Ryan KA
        • Donnelly P
        • Rumberger JA
        • Sheedy 2nd, PF
        • Peyser PA
        • Shuldiner AR
        • Mitchell BD.
        The association of coronary artery calcification and carotid artery intima-media thickness with distinct, traditional coronary artery disease risk factors in asymptomatic adults.
        Am J Epidemiol. 2008; 168: 1016-1023
        • Luirink IK
        • Wiegman A
        • Kusters DM
        • Hof MH
        • Groothoff JW
        • de Groot E
        • Kastelein JJP
        • Hutten BA.
        20-year follow-up of statins in children with familial hypercholesterolemia.
        N Engl J Med. 2019; 381: 1547-1556
        • van Bergen En Henegouwen K
        • Hutten BA
        • Luirink IK
        • Wiegman A
        • de Groot E
        • Kusters DM.
        Intima-media thickness in treated and untreated patients with and without familial hypercholesterolemia: a systematic review and meta-analysis.
        J Clin Lipidol. 2022; 16: 128-142
        • Stein JH
        • Korcarz CE
        • Hurst RT
        • Lonn E
        • Kendall CB
        • Mohler ER
        • Najjar SS
        • Rembold CM
        • Post WS
        American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine.
        J Am Soc Echocardiogr. 2008; 21: 93-190
        • Bots ML
        • Evans GW
        • Riley WA
        • Grobbee DE.
        Carotid intima-media thickness measurements in intervention studies: design options, progression rates, and sample size considerations: a point of view.
        Stroke. 2003; 34: 2985-2994
        • Ezhov MV
        • Safarova MS
        • Afanasieva OI
        • Pogorelova OA
        • Tripoten MI
        • Adamova IY
        • Konovalov GA
        • Balakhonova TV
        • Pokrovsky SN.
        Specific lipoprotein(a) apheresis attenuates progression of carotid intima-media thickness in coronary heart disease patients with high lipoprotein(a) levels.
        Atheroscler Suppl. 2015; 18: 163-169
        • Vergeer M
        • Zhou R
        • Bots ML
        • Duivenvoorden R
        • Koglin J
        • Akdim F
        • Mitchel YB
        • Huijgen R
        • Sapre A
        • de Groot E
        • Sijbrands EJ
        • Pasternak RC
        • Gagné C
        • Marais AD
        • Ballantyne CM
        • Isaacsohn JL
        • Stalenhoef AF
        • Kastelein JJ.
        Carotid atherosclerosis progression in familial hypercholesterolemia patients: a pooled analysis of the ASAP, ENHANCE, RADIANCE 1, and CAPTIVATE studies.
        Circ Cardiovasc Imaging. 2010; 3: 398-404
        • van den Munckhof ICL
        • Jones H
        • Hopman MTE
        • de Graaf J
        • Nyakayiru J
        • van Dijk B
        • Eijsvogels TMH
        • Thijssen DHJ.
        Relation between age and carotid artery intima-medial thickness: a systematic review.
        Clin Cardiol. 2018; 41: 698-704
        • Willeit P
        • Tschiderer L
        • Allara E
        • Reuber K
        • Seekircher L
        • Gao L
        • Liao X
        • Lonn E
        • Gerstein HC
        • Yusuf S
        • Brouwers FP
        • Asselbergs FW
        • van Gilst W
        • Anderssen SA
        • Grobbee DE
        • Kastelein JJP
        • Visseren FLJ
        • Ntaios G
        • Hatzitolios AI
        • Savopoulos C
        • Nieuwkerk PT
        • Stroes E
        • Walters M
        • Higgins P
        • Dawson J
        • Gresele P
        • Guglielmini G
        • Migliacci R
        • Ezhov M
        • Safarova M
        • Balakhonova T
        • Sato E
        • Amaha M
        • Nakamura T
        • Kapellas K
        • Jamieson LM
        • Skilton M
        • Blumenthal JA
        • Hinderliter A
        • Sherwood A
        • Smith PJ
        • van Agtmael MA
        • Reiss P
        • van Vonderen MGA
        • Kiechl S
        • Klingenschmid G
        • Sitzer M
        • Stehouwer CDA
        • Uthoff H
        • Zou ZY
        • Cunha AR
        • Neves MF
        • Witham MD
        • Park HW
        • Lee MS
        • Bae JH
        • Bernal E
        • Wachtell K
        • Kjeldsen SE
        • Olsen MH
        • Preiss D
        • Sattar N
        • Beishuizen E
        • Huisman MV
        • Espeland MA
        • Schmidt C
        • Agewall S
        • Ok E
        • Aşçi G
        • de Groot E
        • Grooteman MPC
        • Blankestijn PJ
        • Bots ML
        • Sweeting MJ
        • Thompson SG
        • Lorenz MW
        PROG-IMT and the Proof-ATHERO Study Groups. Carotid intima-media thickness progression as surrogate marker for cardiovascular risk: meta-analysis of 119 clinical trials involving 100 667 patients.
        Circulation. 2020; 142: 621-642
        • Cherepanov D
        • Bentley TGK
        • Hsiao W
        • Xiang P
        • O'Neill F
        • Qian Y
        • Yurgin N
        • Beenhouwer D.
        Real-world cardiovascular disease burden in patients with atherosclerotic cardiovascular disease: a comprehensive systematic literature review.
        Curr Med Res Opin. 2018; 34: 459-473
        • Tuzcu EM
        • Kapadia SR
        • Tutar E
        • Ziada KM
        • Hobbs RE
        • McCarthy PM
        • Young JB
        • Nissen SE.
        High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults: evidence from intravascular ultrasound.
        Circulation. 2001; 103: 2705-2710
        • Safarova MS
        • Kullo IJ.
        My approach to the patient with familial hypercholesterolemia.
        Mayo Clin Proc. 2016; 91: 770-786
        • Thompson RC
        • Allam AH
        • Lombardi GP
        • Wann LS
        • Sutherland ML
        • Sutherland JD
        • Soliman MA
        • Frohlich B
        • Mininberg DT
        • Monge JM
        • Vallodolid CM
        • Cox SL
        • Abd el-Maksoud G
        • Badr I
        • Miyamoto MI
        • el-Halim Nur el-Din A
        • Narula J
        • Finch CE
        • Thomas GS
        Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations.
        Lancet. 2013; 381: 1211-1222
        • Stein JH
        • Douglas PS
        • Srinivasan SR
        • Bond MG
        • Tang R
        • Li S
        • Chen W
        • Berenson GS.
        Distribution and cross-sectional age-related increases of carotid artery intima-media thickness in young adults: the Bogalusa Heart Study.
        Stroke. 2004; 35: 2782-2787