Association between circulating proprotein convertase subtilisin/kexin type 9 levels and prognosis in patients with severe chronic kidney disease

Laust Dupont Rasmussen; Morten Bøttcher; Per Ivarsen; Hanne Skou Jørgensen; Mette Nyegaard; Henriette Buttenschøn; Camilla Gustafsen; Simon Glerup; Hans Erik Bøtker; My Svensson; Simon Winther

doi:10.1093/ndt/gfy257

Association between circulating proprotein convertase subtilisin/kexin type 9 levels and prognosis in patients with severe chronic kidney disease

Laust Dupont Rasmussen, Morten Bøttcher, Per Ivarsen, Hanne Skou Jørgensen, Mette Nyegaard, Henriette Buttenschøn, Camilla Gustafsen, Simon Glerup, Hans Erik Bøtker, My Svensson, Simon Winther

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

8 Citations (Scopus)

Abstract

Background: Chronic kidney disease is a risk factor for premature development of coronary atherosclerosis and mortality. A high level of proprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently recognized cardiovascular risk factor and has become the target of effective inhibitory treatment. In 167 kidney transplantation candidates, we aimed to: (i) compare levels of PCSK9 with those of healthy controls, (ii) examine the association between levels of PCSK9 and low-density lipoprotein cholesterol (LDL-c) and the degree of coronary artery disease (CAD) and (iii) evaluate if levels of PCSK9 predict major adverse cardiac events (MACE) and mortality.

Methods: Kidney transplant candidates (n = 167) underwent coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) before transplantation. MACE and mortality data were extracted from the Western Denmark Heart Registry, a review of patient records and patient interviews. A group of 79 healthy subjects were used as controls.

Results: Mean PCSK9 levels did not differ between healthy controls and kidney transplant candidates. In patients not receiving lipid-lowering therapy, PCSK9 correlated positively with LDL-c (rho = 0.24, P < 0.05). Mean PCSK9 was similar in patients with and without obstructive CAD at both CCTA and ICA. In a multiple regression analysis, PCSK9 was associated with neither LDL-c (β=-6.45, P = 0.44) nor coronary artery calcium score (β=2.17, P = 0.84). During a follow-up of 3.7 years, PCSK9 levels were not associated with either MACE or mortality.

Conclusions: The ability of PCSK9 levels to predict cardiovascular disease and prognosis does not seem to apply to a cohort of kidney transplant candidates.

Original language	English
Article number	gfy257
Journal	Nephrology Dialysis Transplantation
Volume	35
Issue	4
Pages (from-to)	632-639
Number of pages	8
ISSN	0931-0509
DOIs	https://doi.org/10.1093/ndt/gfy257
Publication status	Published - 2020

Keywords

PCSK9
coronary artery disease
kidney transplant candidates
low-density lipoprotein cholesterol
major adverse cardiac events

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10.1093/ndt/gfy257

Cite this

Rasmussen, L. D., Bøttcher, M., Ivarsen, P., Jørgensen, H. S., Nyegaard, M., Buttenschøn, H., Gustafsen, C., Glerup, S., Bøtker, H. E., Svensson, M., & Winther, S. (2020). Association between circulating proprotein convertase subtilisin/kexin type 9 levels and prognosis in patients with severe chronic kidney disease. Nephrology Dialysis Transplantation, 35(4), 632-639. Article gfy257. https://doi.org/10.1093/ndt/gfy257

@article{86530d2b3612428794cb2e9c3c89a74e,

title = "Association between circulating proprotein convertase subtilisin/kexin type 9 levels and prognosis in patients with severe chronic kidney disease",

abstract = "Background: Chronic kidney disease is a risk factor for premature development of coronary atherosclerosis and mortality. A high level of proprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently recognized cardiovascular risk factor and has become the target of effective inhibitory treatment. In 167 kidney transplantation candidates, we aimed to: (i) compare levels of PCSK9 with those of healthy controls, (ii) examine the association between levels of PCSK9 and low-density lipoprotein cholesterol (LDL-c) and the degree of coronary artery disease (CAD) and (iii) evaluate if levels of PCSK9 predict major adverse cardiac events (MACE) and mortality.Methods: Kidney transplant candidates (n = 167) underwent coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) before transplantation. MACE and mortality data were extracted from the Western Denmark Heart Registry, a review of patient records and patient interviews. A group of 79 healthy subjects were used as controls.Results: Mean PCSK9 levels did not differ between healthy controls and kidney transplant candidates. In patients not receiving lipid-lowering therapy, PCSK9 correlated positively with LDL-c (rho = 0.24, P < 0.05). Mean PCSK9 was similar in patients with and without obstructive CAD at both CCTA and ICA. In a multiple regression analysis, PCSK9 was associated with neither LDL-c (β=-6.45, P = 0.44) nor coronary artery calcium score (β=2.17, P = 0.84). During a follow-up of 3.7 years, PCSK9 levels were not associated with either MACE or mortality.Conclusions: The ability of PCSK9 levels to predict cardiovascular disease and prognosis does not seem to apply to a cohort of kidney transplant candidates.",

keywords = "PCSK9, coronary artery disease, kidney transplant candidates, low-density lipoprotein cholesterol, major adverse cardiac events",

author = "Rasmussen, {Laust Dupont} and Morten B{\o}ttcher and Per Ivarsen and J{\o}rgensen, {Hanne Skou} and Mette Nyegaard and Henriette Buttensch{\o}n and Camilla Gustafsen and Simon Glerup and B{\o}tker, {Hans Erik} and My Svensson and Simon Winther",

year = "2020",

doi = "10.1093/ndt/gfy257",

language = "English",

volume = "35",

pages = "632--639",

journal = "Nephrology Dialysis Transplantation",

issn = "0931-0509",

publisher = "Oxford University Press",

number = "4",

}

Rasmussen, LD , Bøttcher, M , Ivarsen, P , Jørgensen, HS, Nyegaard, M, Buttenschøn, H , Gustafsen, C , Glerup, S , Bøtker, HE, Svensson, M & Winther, S 2020, 'Association between circulating proprotein convertase subtilisin/kexin type 9 levels and prognosis in patients with severe chronic kidney disease', Nephrology Dialysis Transplantation, vol. 35, no. 4, gfy257, pp. 632-639. https://doi.org/10.1093/ndt/gfy257

Association between circulating proprotein convertase subtilisin/kexin type 9 levels and prognosis in patients with severe chronic kidney disease. / Rasmussen, Laust Dupont ; Bøttcher, Morten ; Ivarsen, Per et al.
In: Nephrology Dialysis Transplantation, Vol. 35, No. 4, gfy257, 2020, p. 632-639.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Association between circulating proprotein convertase subtilisin/kexin type 9 levels and prognosis in patients with severe chronic kidney disease

AU - Rasmussen, Laust Dupont

AU - Bøttcher, Morten

AU - Ivarsen, Per

AU - Jørgensen, Hanne Skou

AU - Nyegaard, Mette

AU - Buttenschøn, Henriette

AU - Gustafsen, Camilla

AU - Glerup, Simon

AU - Bøtker, Hans Erik

AU - Svensson, My

AU - Winther, Simon

PY - 2020

Y1 - 2020

N2 - Background: Chronic kidney disease is a risk factor for premature development of coronary atherosclerosis and mortality. A high level of proprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently recognized cardiovascular risk factor and has become the target of effective inhibitory treatment. In 167 kidney transplantation candidates, we aimed to: (i) compare levels of PCSK9 with those of healthy controls, (ii) examine the association between levels of PCSK9 and low-density lipoprotein cholesterol (LDL-c) and the degree of coronary artery disease (CAD) and (iii) evaluate if levels of PCSK9 predict major adverse cardiac events (MACE) and mortality.Methods: Kidney transplant candidates (n = 167) underwent coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) before transplantation. MACE and mortality data were extracted from the Western Denmark Heart Registry, a review of patient records and patient interviews. A group of 79 healthy subjects were used as controls.Results: Mean PCSK9 levels did not differ between healthy controls and kidney transplant candidates. In patients not receiving lipid-lowering therapy, PCSK9 correlated positively with LDL-c (rho = 0.24, P < 0.05). Mean PCSK9 was similar in patients with and without obstructive CAD at both CCTA and ICA. In a multiple regression analysis, PCSK9 was associated with neither LDL-c (β=-6.45, P = 0.44) nor coronary artery calcium score (β=2.17, P = 0.84). During a follow-up of 3.7 years, PCSK9 levels were not associated with either MACE or mortality.Conclusions: The ability of PCSK9 levels to predict cardiovascular disease and prognosis does not seem to apply to a cohort of kidney transplant candidates.

AB - Background: Chronic kidney disease is a risk factor for premature development of coronary atherosclerosis and mortality. A high level of proprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently recognized cardiovascular risk factor and has become the target of effective inhibitory treatment. In 167 kidney transplantation candidates, we aimed to: (i) compare levels of PCSK9 with those of healthy controls, (ii) examine the association between levels of PCSK9 and low-density lipoprotein cholesterol (LDL-c) and the degree of coronary artery disease (CAD) and (iii) evaluate if levels of PCSK9 predict major adverse cardiac events (MACE) and mortality.Methods: Kidney transplant candidates (n = 167) underwent coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) before transplantation. MACE and mortality data were extracted from the Western Denmark Heart Registry, a review of patient records and patient interviews. A group of 79 healthy subjects were used as controls.Results: Mean PCSK9 levels did not differ between healthy controls and kidney transplant candidates. In patients not receiving lipid-lowering therapy, PCSK9 correlated positively with LDL-c (rho = 0.24, P < 0.05). Mean PCSK9 was similar in patients with and without obstructive CAD at both CCTA and ICA. In a multiple regression analysis, PCSK9 was associated with neither LDL-c (β=-6.45, P = 0.44) nor coronary artery calcium score (β=2.17, P = 0.84). During a follow-up of 3.7 years, PCSK9 levels were not associated with either MACE or mortality.Conclusions: The ability of PCSK9 levels to predict cardiovascular disease and prognosis does not seem to apply to a cohort of kidney transplant candidates.

KW - PCSK9

KW - coronary artery disease

KW - kidney transplant candidates

KW - low-density lipoprotein cholesterol

KW - major adverse cardiac events

UR - http://www.scopus.com/inward/record.url?scp=85075842280&partnerID=8YFLogxK

U2 - 10.1093/ndt/gfy257

DO - 10.1093/ndt/gfy257

M3 - Journal article

C2 - 30137516

SN - 0931-0509

VL - 35

SP - 632

EP - 639

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

IS - 4

M1 - gfy257

ER -

Association between circulating proprotein convertase subtilisin/kexin type 9 levels and prognosis in patients with severe chronic kidney disease

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