Lipoprotein Apheresis Acutely Reverses Coronary Microvascular Dysfunction in Patients With Severe Hypercholesterolemia

Melinda D. Wu, Federico Moccetti, Eran Brown, Brian P. Davidson, Tamara (Tami) Atkinson, J. Todd Belcik, George Giraud, Paul Duell, Sergio Fazio, Hagai Tavori, Sotirios Tsimikas, Jonathan Lindner

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objectives: The study evaluated whether lipoprotein apheresis produces immediate changes in resting perfusion in subjects with severe hypercholesterolemia, and whether there is a difference in the response between peripheral and coronary microcirculations. Background: Lipoprotein apheresis is used in patients with severe hypercholesterolemia to reduce plasma levels of low-density lipoprotein cholesterol. Methods: Quantitative contrast-enhanced ultrasound perfusion imaging of the myocardium at rest and skeletal muscle at rest and during calibrated contractile exercise was performed before and immediately after lipoprotein apheresis in 8 subjects with severe hypercholesterolemia, 7 of whom had a diagnosis of familial hypercholesterolemia. Myocardial perfusion imaging was also performed in 14 normal control subjects. Changes in myocardial work and left ventricular function were assessed by echocardiography. Ex vivo ovine coronary and femoral artery ring tension assays were assessed in the presence of pre- and post-apheresis plasma. Results: Apheresis acutely decreased low-density lipoprotein cholesterol (234.9 ± 103.2 mg/dl vs. 67.1 ± 49.5 mg/dl; p < 0.01) and oxidized phospholipid on apolipoprotein B-100 (60.2 ± 55.2 nmol/l vs. 47.0 ± 24.5 nmol/l; p = 0.01), and acutely increased resting myocardial perfusion (55.1 [95% confidence interval: 77.2 to 73.1] vs. 135 [95% confidence interval: 81.2 to 189.6] IU/s; p = 0.01), without changes in myocardial work. Myocardial longitudinal strain improved in those subjects with reduced pre-apheresis function. Skeletal muscle perfusion at rest and during contractile exercise was unchanged by apheresis. Acetylcholine-mediated dilation of ex vivo ovine coronary but not femoral arteries was impaired in pre-apheresis plasma and was completely reversed in post-apheresis plasma. Conclusions: Lipoprotein apheresis produces an immediate improvement in coronary microvascular function, which increases myocardial perfusion and normalizes endothelial-dependent vasodilation. These changes are not observed in the periphery. (Acute Microvascular Changes With LDL Apheresis; NCT02388633).

Original languageEnglish (US)
JournalJACC: Cardiovascular Imaging
DOIs
StateAccepted/In press - Jan 1 2018

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Blood Component Removal
Hypercholesterolemia
Lipoproteins
Perfusion
Femoral Artery
LDL Cholesterol
Sheep
Skeletal Muscle
Confidence Intervals
Exercise
Apolipoprotein B-100
Hyperlipoproteinemia Type II
Myocardial Perfusion Imaging
Perfusion Imaging
Microcirculation
Left Ventricular Function
Vasodilation
Acetylcholine
Echocardiography
Dilatation

Keywords

  • apheresis
  • contrast ultrasound
  • familial hypercholesterolemia
  • myocardial contrast echocardiography

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Lipoprotein Apheresis Acutely Reverses Coronary Microvascular Dysfunction in Patients With Severe Hypercholesterolemia. / Wu, Melinda D.; Moccetti, Federico; Brown, Eran; Davidson, Brian P.; Atkinson, Tamara (Tami); Belcik, J. Todd; Giraud, George; Duell, Paul; Fazio, Sergio; Tavori, Hagai; Tsimikas, Sotirios; Lindner, Jonathan.

In: JACC: Cardiovascular Imaging, 01.01.2018.

Research output: Contribution to journalArticle

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abstract = "Objectives: The study evaluated whether lipoprotein apheresis produces immediate changes in resting perfusion in subjects with severe hypercholesterolemia, and whether there is a difference in the response between peripheral and coronary microcirculations. Background: Lipoprotein apheresis is used in patients with severe hypercholesterolemia to reduce plasma levels of low-density lipoprotein cholesterol. Methods: Quantitative contrast-enhanced ultrasound perfusion imaging of the myocardium at rest and skeletal muscle at rest and during calibrated contractile exercise was performed before and immediately after lipoprotein apheresis in 8 subjects with severe hypercholesterolemia, 7 of whom had a diagnosis of familial hypercholesterolemia. Myocardial perfusion imaging was also performed in 14 normal control subjects. Changes in myocardial work and left ventricular function were assessed by echocardiography. Ex vivo ovine coronary and femoral artery ring tension assays were assessed in the presence of pre- and post-apheresis plasma. Results: Apheresis acutely decreased low-density lipoprotein cholesterol (234.9 ± 103.2 mg/dl vs. 67.1 ± 49.5 mg/dl; p < 0.01) and oxidized phospholipid on apolipoprotein B-100 (60.2 ± 55.2 nmol/l vs. 47.0 ± 24.5 nmol/l; p = 0.01), and acutely increased resting myocardial perfusion (55.1 [95{\%} confidence interval: 77.2 to 73.1] vs. 135 [95{\%} confidence interval: 81.2 to 189.6] IU/s; p = 0.01), without changes in myocardial work. Myocardial longitudinal strain improved in those subjects with reduced pre-apheresis function. Skeletal muscle perfusion at rest and during contractile exercise was unchanged by apheresis. Acetylcholine-mediated dilation of ex vivo ovine coronary but not femoral arteries was impaired in pre-apheresis plasma and was completely reversed in post-apheresis plasma. Conclusions: Lipoprotein apheresis produces an immediate improvement in coronary microvascular function, which increases myocardial perfusion and normalizes endothelial-dependent vasodilation. These changes are not observed in the periphery. (Acute Microvascular Changes With LDL Apheresis; NCT02388633).",
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author = "Wu, {Melinda D.} and Federico Moccetti and Eran Brown and Davidson, {Brian P.} and Atkinson, {Tamara (Tami)} and Belcik, {J. Todd} and George Giraud and Paul Duell and Sergio Fazio and Hagai Tavori and Sotirios Tsimikas and Jonathan Lindner",
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AU - Wu, Melinda D.

AU - Moccetti, Federico

AU - Brown, Eran

AU - Davidson, Brian P.

AU - Atkinson, Tamara (Tami)

AU - Belcik, J. Todd

AU - Giraud, George

AU - Duell, Paul

AU - Fazio, Sergio

AU - Tavori, Hagai

AU - Tsimikas, Sotirios

AU - Lindner, Jonathan

PY - 2018/1/1

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N2 - Objectives: The study evaluated whether lipoprotein apheresis produces immediate changes in resting perfusion in subjects with severe hypercholesterolemia, and whether there is a difference in the response between peripheral and coronary microcirculations. Background: Lipoprotein apheresis is used in patients with severe hypercholesterolemia to reduce plasma levels of low-density lipoprotein cholesterol. Methods: Quantitative contrast-enhanced ultrasound perfusion imaging of the myocardium at rest and skeletal muscle at rest and during calibrated contractile exercise was performed before and immediately after lipoprotein apheresis in 8 subjects with severe hypercholesterolemia, 7 of whom had a diagnosis of familial hypercholesterolemia. Myocardial perfusion imaging was also performed in 14 normal control subjects. Changes in myocardial work and left ventricular function were assessed by echocardiography. Ex vivo ovine coronary and femoral artery ring tension assays were assessed in the presence of pre- and post-apheresis plasma. Results: Apheresis acutely decreased low-density lipoprotein cholesterol (234.9 ± 103.2 mg/dl vs. 67.1 ± 49.5 mg/dl; p < 0.01) and oxidized phospholipid on apolipoprotein B-100 (60.2 ± 55.2 nmol/l vs. 47.0 ± 24.5 nmol/l; p = 0.01), and acutely increased resting myocardial perfusion (55.1 [95% confidence interval: 77.2 to 73.1] vs. 135 [95% confidence interval: 81.2 to 189.6] IU/s; p = 0.01), without changes in myocardial work. Myocardial longitudinal strain improved in those subjects with reduced pre-apheresis function. Skeletal muscle perfusion at rest and during contractile exercise was unchanged by apheresis. Acetylcholine-mediated dilation of ex vivo ovine coronary but not femoral arteries was impaired in pre-apheresis plasma and was completely reversed in post-apheresis plasma. Conclusions: Lipoprotein apheresis produces an immediate improvement in coronary microvascular function, which increases myocardial perfusion and normalizes endothelial-dependent vasodilation. These changes are not observed in the periphery. (Acute Microvascular Changes With LDL Apheresis; NCT02388633).

AB - Objectives: The study evaluated whether lipoprotein apheresis produces immediate changes in resting perfusion in subjects with severe hypercholesterolemia, and whether there is a difference in the response between peripheral and coronary microcirculations. Background: Lipoprotein apheresis is used in patients with severe hypercholesterolemia to reduce plasma levels of low-density lipoprotein cholesterol. Methods: Quantitative contrast-enhanced ultrasound perfusion imaging of the myocardium at rest and skeletal muscle at rest and during calibrated contractile exercise was performed before and immediately after lipoprotein apheresis in 8 subjects with severe hypercholesterolemia, 7 of whom had a diagnosis of familial hypercholesterolemia. Myocardial perfusion imaging was also performed in 14 normal control subjects. Changes in myocardial work and left ventricular function were assessed by echocardiography. Ex vivo ovine coronary and femoral artery ring tension assays were assessed in the presence of pre- and post-apheresis plasma. Results: Apheresis acutely decreased low-density lipoprotein cholesterol (234.9 ± 103.2 mg/dl vs. 67.1 ± 49.5 mg/dl; p < 0.01) and oxidized phospholipid on apolipoprotein B-100 (60.2 ± 55.2 nmol/l vs. 47.0 ± 24.5 nmol/l; p = 0.01), and acutely increased resting myocardial perfusion (55.1 [95% confidence interval: 77.2 to 73.1] vs. 135 [95% confidence interval: 81.2 to 189.6] IU/s; p = 0.01), without changes in myocardial work. Myocardial longitudinal strain improved in those subjects with reduced pre-apheresis function. Skeletal muscle perfusion at rest and during contractile exercise was unchanged by apheresis. Acetylcholine-mediated dilation of ex vivo ovine coronary but not femoral arteries was impaired in pre-apheresis plasma and was completely reversed in post-apheresis plasma. Conclusions: Lipoprotein apheresis produces an immediate improvement in coronary microvascular function, which increases myocardial perfusion and normalizes endothelial-dependent vasodilation. These changes are not observed in the periphery. (Acute Microvascular Changes With LDL Apheresis; NCT02388633).

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