Residual Cardiovascular Risk in Chronic Kidney Disease: Role of High-density Lipoprotein

Valentina Kon, Haichun Yang, Sergio Fazio

    Research output: Contribution to journalArticle

    21 Citations (Scopus)

    Abstract

    Although reducing low-density lipoprotein-cholesterol (LDL-C) levels with lipid-lowering agents (statins) decreases cardiovascular disease (CVD) risk, a substantial residual risk (up to 70% of baseline) remains after treatment in most patient populations. High-density lipoprotein (HDL) is a potential contributor to residual risk, and low HDL-cholesterol (HDL-C) is an established risk factor for CVD. However, in contrast to conventional lipid-lowering therapies, recent studies show that pharmacologic increases in HDL-C levels do not bring about clinical benefits. These observations have given rise to the concept of dysfunctional HDL where increases in serum HDL-C may not be beneficial because HDL loss of function is not corrected by or even intensified by the therapy. Chronic kidney disease (CKD) increases CVD risk, and patients whose CKD progresses to end-stage renal disease (ESRD) requiring dialysis are at the highest CVD risk of any patient type studied. The ESRD population is also unique in its lack of significant benefit from standard lipid-lowering interventions. Recent studies indicate that HDL-C levels do not predict CVD in the CKD population. Moreover, CKD profoundly alters metabolism and composition of HDL particles and impairs their protective effects on functions such as cellular cholesterol efflux, endothelial protection, and control of inflammation and oxidation. Thus, CKD-induced perturbations in HDL may contribute to the excess CVD in CKD patients. Understanding the mechanisms of vascular protection in renal disease can present new therapeutic targets for intervention in this population.

    Original languageEnglish (US)
    Pages (from-to)379-391
    Number of pages13
    JournalArchives of Medical Research
    Volume46
    Issue number5
    DOIs
    StatePublished - Jul 1 2015

    Fingerprint

    HDL Lipoproteins
    Chronic Renal Insufficiency
    Cardiovascular Diseases
    Lipids
    LDL Cholesterol
    Population
    Chronic Kidney Failure
    Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Therapeutics
    HDL Cholesterol
    Blood Vessels
    Dialysis
    Cholesterol
    Inflammation
    Kidney
    Serum

    Keywords

    • Cardiovascular disease
    • Cholesterol efflux
    • Chronic kidney disease
    • HDL
    • Residual cardiovascular risk
    • Statins

    ASJC Scopus subject areas

    • Medicine(all)

    Cite this

    Residual Cardiovascular Risk in Chronic Kidney Disease : Role of High-density Lipoprotein. / Kon, Valentina; Yang, Haichun; Fazio, Sergio.

    In: Archives of Medical Research, Vol. 46, No. 5, 01.07.2015, p. 379-391.

    Research output: Contribution to journalArticle

    @article{0bfe67b22c65476797093a2dcf69b24c,
    title = "Residual Cardiovascular Risk in Chronic Kidney Disease: Role of High-density Lipoprotein",
    abstract = "Although reducing low-density lipoprotein-cholesterol (LDL-C) levels with lipid-lowering agents (statins) decreases cardiovascular disease (CVD) risk, a substantial residual risk (up to 70{\%} of baseline) remains after treatment in most patient populations. High-density lipoprotein (HDL) is a potential contributor to residual risk, and low HDL-cholesterol (HDL-C) is an established risk factor for CVD. However, in contrast to conventional lipid-lowering therapies, recent studies show that pharmacologic increases in HDL-C levels do not bring about clinical benefits. These observations have given rise to the concept of dysfunctional HDL where increases in serum HDL-C may not be beneficial because HDL loss of function is not corrected by or even intensified by the therapy. Chronic kidney disease (CKD) increases CVD risk, and patients whose CKD progresses to end-stage renal disease (ESRD) requiring dialysis are at the highest CVD risk of any patient type studied. The ESRD population is also unique in its lack of significant benefit from standard lipid-lowering interventions. Recent studies indicate that HDL-C levels do not predict CVD in the CKD population. Moreover, CKD profoundly alters metabolism and composition of HDL particles and impairs their protective effects on functions such as cellular cholesterol efflux, endothelial protection, and control of inflammation and oxidation. Thus, CKD-induced perturbations in HDL may contribute to the excess CVD in CKD patients. Understanding the mechanisms of vascular protection in renal disease can present new therapeutic targets for intervention in this population.",
    keywords = "Cardiovascular disease, Cholesterol efflux, Chronic kidney disease, HDL, Residual cardiovascular risk, Statins",
    author = "Valentina Kon and Haichun Yang and Sergio Fazio",
    year = "2015",
    month = "7",
    day = "1",
    doi = "10.1016/j.arcmed.2015.05.009",
    language = "English (US)",
    volume = "46",
    pages = "379--391",
    journal = "Archives of Medical Research",
    issn = "0188-4409",
    publisher = "Elsevier Inc.",
    number = "5",

    }

    TY - JOUR

    T1 - Residual Cardiovascular Risk in Chronic Kidney Disease

    T2 - Role of High-density Lipoprotein

    AU - Kon, Valentina

    AU - Yang, Haichun

    AU - Fazio, Sergio

    PY - 2015/7/1

    Y1 - 2015/7/1

    N2 - Although reducing low-density lipoprotein-cholesterol (LDL-C) levels with lipid-lowering agents (statins) decreases cardiovascular disease (CVD) risk, a substantial residual risk (up to 70% of baseline) remains after treatment in most patient populations. High-density lipoprotein (HDL) is a potential contributor to residual risk, and low HDL-cholesterol (HDL-C) is an established risk factor for CVD. However, in contrast to conventional lipid-lowering therapies, recent studies show that pharmacologic increases in HDL-C levels do not bring about clinical benefits. These observations have given rise to the concept of dysfunctional HDL where increases in serum HDL-C may not be beneficial because HDL loss of function is not corrected by or even intensified by the therapy. Chronic kidney disease (CKD) increases CVD risk, and patients whose CKD progresses to end-stage renal disease (ESRD) requiring dialysis are at the highest CVD risk of any patient type studied. The ESRD population is also unique in its lack of significant benefit from standard lipid-lowering interventions. Recent studies indicate that HDL-C levels do not predict CVD in the CKD population. Moreover, CKD profoundly alters metabolism and composition of HDL particles and impairs their protective effects on functions such as cellular cholesterol efflux, endothelial protection, and control of inflammation and oxidation. Thus, CKD-induced perturbations in HDL may contribute to the excess CVD in CKD patients. Understanding the mechanisms of vascular protection in renal disease can present new therapeutic targets for intervention in this population.

    AB - Although reducing low-density lipoprotein-cholesterol (LDL-C) levels with lipid-lowering agents (statins) decreases cardiovascular disease (CVD) risk, a substantial residual risk (up to 70% of baseline) remains after treatment in most patient populations. High-density lipoprotein (HDL) is a potential contributor to residual risk, and low HDL-cholesterol (HDL-C) is an established risk factor for CVD. However, in contrast to conventional lipid-lowering therapies, recent studies show that pharmacologic increases in HDL-C levels do not bring about clinical benefits. These observations have given rise to the concept of dysfunctional HDL where increases in serum HDL-C may not be beneficial because HDL loss of function is not corrected by or even intensified by the therapy. Chronic kidney disease (CKD) increases CVD risk, and patients whose CKD progresses to end-stage renal disease (ESRD) requiring dialysis are at the highest CVD risk of any patient type studied. The ESRD population is also unique in its lack of significant benefit from standard lipid-lowering interventions. Recent studies indicate that HDL-C levels do not predict CVD in the CKD population. Moreover, CKD profoundly alters metabolism and composition of HDL particles and impairs their protective effects on functions such as cellular cholesterol efflux, endothelial protection, and control of inflammation and oxidation. Thus, CKD-induced perturbations in HDL may contribute to the excess CVD in CKD patients. Understanding the mechanisms of vascular protection in renal disease can present new therapeutic targets for intervention in this population.

    KW - Cardiovascular disease

    KW - Cholesterol efflux

    KW - Chronic kidney disease

    KW - HDL

    KW - Residual cardiovascular risk

    KW - Statins

    UR - http://www.scopus.com/inward/record.url?scp=84938053462&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84938053462&partnerID=8YFLogxK

    U2 - 10.1016/j.arcmed.2015.05.009

    DO - 10.1016/j.arcmed.2015.05.009

    M3 - Article

    C2 - 26009251

    AN - SCOPUS:84938053462

    VL - 46

    SP - 379

    EP - 391

    JO - Archives of Medical Research

    JF - Archives of Medical Research

    SN - 0188-4409

    IS - 5

    ER -