Effect of renal impairment on atherosclerosis: Only partially mediated by homocysteine

J. David Spence, Bradley L. Urquhart, Heejung Bang

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background Cardiovascular risk and plasma total homocysteine (tHcy) are high in patients with renal failure. High tHcy may account for a substantial part of the increased risk. We assessed mediation by tHcy of the association of estimated glomerular filtration rate (eGFR CKD/EPI) with carotid total plaque area (TPA) and carotid stenosis. Methods TPA and carotid stenosis were measured by ultrasound. Multiple linear regression was used to assess the effects of eGFR and/or tHcy after adjustment for age, sex, systolic blood pressure (SBP), smoking, LDL, HDL and weight. Results Complete data were available for 1967 patients. eGFR decreased, and TPA and total stenosis increased linearly with age. After adjustment [age, sex, SBP, smoking (in pack years), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and weight], eGFR and tHcy were independently associated with TPA (P < 0.01), but when both were added to the model, their significance was attenuated (P = 0.06 for eGFR, 0.03 for tHcy). Mediation analysis showed that tHcy seems to contribute to a significant mediation of the association of eGFR with TPA but not stenosis; after adjustment for the set of risk factors listed above, tHcy still demonstrated significant mediation on TPA (P = 0.03), but not on stenosis (P = 0.16). Conclusions tHcy accounts for a significant part, but not all of the effect of renal impairment on atherosclerosis. Other uremic toxins including metabolic products of the intestinal microbiome may explain residual effects of renal failure on atherosclerosis. Therapeutic approaches arising from that hypothesis are discussed.

Original languageEnglish (US)
Pages (from-to)937-944
Number of pages8
JournalNephrology Dialysis Transplantation
Volume31
Issue number6
DOIs
StatePublished - Jun 24 2016

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Homocysteine
Atherosclerosis
Kidney
Blood Pressure
Pathologic Constriction
Carotid Stenosis
HDL Lipoproteins
LDL Lipoproteins
Renal Insufficiency
Smoking
Social Adjustment
Weights and Measures
Glomerular Filtration Rate
Linear Models

Keywords

  • TMAO

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Effect of renal impairment on atherosclerosis : Only partially mediated by homocysteine. / Spence, J. David; Urquhart, Bradley L.; Bang, Heejung.

In: Nephrology Dialysis Transplantation, Vol. 31, No. 6, 24.06.2016, p. 937-944.

Research output: Contribution to journalArticle

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N2 - Background Cardiovascular risk and plasma total homocysteine (tHcy) are high in patients with renal failure. High tHcy may account for a substantial part of the increased risk. We assessed mediation by tHcy of the association of estimated glomerular filtration rate (eGFR CKD/EPI) with carotid total plaque area (TPA) and carotid stenosis. Methods TPA and carotid stenosis were measured by ultrasound. Multiple linear regression was used to assess the effects of eGFR and/or tHcy after adjustment for age, sex, systolic blood pressure (SBP), smoking, LDL, HDL and weight. Results Complete data were available for 1967 patients. eGFR decreased, and TPA and total stenosis increased linearly with age. After adjustment [age, sex, SBP, smoking (in pack years), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and weight], eGFR and tHcy were independently associated with TPA (P < 0.01), but when both were added to the model, their significance was attenuated (P = 0.06 for eGFR, 0.03 for tHcy). Mediation analysis showed that tHcy seems to contribute to a significant mediation of the association of eGFR with TPA but not stenosis; after adjustment for the set of risk factors listed above, tHcy still demonstrated significant mediation on TPA (P = 0.03), but not on stenosis (P = 0.16). Conclusions tHcy accounts for a significant part, but not all of the effect of renal impairment on atherosclerosis. Other uremic toxins including metabolic products of the intestinal microbiome may explain residual effects of renal failure on atherosclerosis. Therapeutic approaches arising from that hypothesis are discussed.

AB - Background Cardiovascular risk and plasma total homocysteine (tHcy) are high in patients with renal failure. High tHcy may account for a substantial part of the increased risk. We assessed mediation by tHcy of the association of estimated glomerular filtration rate (eGFR CKD/EPI) with carotid total plaque area (TPA) and carotid stenosis. Methods TPA and carotid stenosis were measured by ultrasound. Multiple linear regression was used to assess the effects of eGFR and/or tHcy after adjustment for age, sex, systolic blood pressure (SBP), smoking, LDL, HDL and weight. Results Complete data were available for 1967 patients. eGFR decreased, and TPA and total stenosis increased linearly with age. After adjustment [age, sex, SBP, smoking (in pack years), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and weight], eGFR and tHcy were independently associated with TPA (P < 0.01), but when both were added to the model, their significance was attenuated (P = 0.06 for eGFR, 0.03 for tHcy). Mediation analysis showed that tHcy seems to contribute to a significant mediation of the association of eGFR with TPA but not stenosis; after adjustment for the set of risk factors listed above, tHcy still demonstrated significant mediation on TPA (P = 0.03), but not on stenosis (P = 0.16). Conclusions tHcy accounts for a significant part, but not all of the effect of renal impairment on atherosclerosis. Other uremic toxins including metabolic products of the intestinal microbiome may explain residual effects of renal failure on atherosclerosis. Therapeutic approaches arising from that hypothesis are discussed.

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