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. 2020 Jan 7;15(1):47-60.
doi: 10.2215/CJN.07320619. Epub 2019 Dec 12.

Apolipoprotein B, Triglyceride-Rich Lipoproteins, and Risk of Cardiovascular Events in Persons with CKD

Julio Alejandro Lamprea-Montealegre  1   2 , Natalie Staplin  3   4 , William G Herrington  3   4 , Richard Haynes  3   4 , Jonathan Emberson  3   4 , Colin Baigent  3   4 , Ian H de Boer  1   5 ; SHARP Collaborative Group
Affiliations

Apolipoprotein B, Triglyceride-Rich Lipoproteins, and Risk of Cardiovascular Events in Persons with CKD

Julio Alejandro Lamprea-Montealegre et al. Clin J Am Soc Nephrol. .

Abstract

Background and objectives: Triglyceride-rich lipoproteins may contribute to the high cardiovascular risk of patients with CKD. This study evaluated associations of apo-B and markers of triglyceride-rich lipoproteins with cardiovascular events in people with CKD.

Design, setting, participants, & measurements: Analyses were conducted in 9270 participants with CKD in the Study of Heart and Renal Protection (SHARP): 6245 not on dialysis (mean eGFR 26.5 ml/min per 1.73 m2), and 3025 on dialysis when recruited. Cox regression methods were used to evaluate associations of lipids with incident atherosclerotic and nonatherosclerotic vascular events, adjusting for demographics and clinical characteristics. Hazard ratios (HRs) were calculated per 1 SD higher level for apo-B, HDL cholesterol, LDL cholesterol, triglyceride-rich lipoprotein cholesterol (i.e., total cholesterol minus LDL cholesterol minus HDL cholesterol), non-HDL cholesterol, log triglyceride, and log ratio of triglyceride to HDL cholesterol.

Results: During a median follow-up of 4.9 years (interquartile range, 4.0-5.5 years), 1406 participants experienced at least one atherosclerotic vascular event. In multivariable adjusted models, positive associations with atherosclerotic vascular events were observed for apo-B (HR per 1 SD, 1.19; 95% confidence interval, 1.12 to 1.27), triglycerides (1.06; 1.00 to 1.13), the ratio of triglyceride to HDL cholesterol (1.10; 1.03 to 1.18), and triglyceride-rich lipoprotein cholesterol (1.14; 1.05 to 1.25). By contrast, inverse associations with nonatherosclerotic vascular events were observed for each of these lipid markers: apo-B (HR per 1 SD, 0.92; 0.85 to 0.98), triglycerides (0.86; 0.81 to 0.92), the ratio of triglyceride to HDL cholesterol (0.88; 0.82 to 0.94), and triglyceride-rich lipoprotein cholesterol (0.85; 0.77 to 0.94).

Conclusions: Higher apo-B, triglycerides, ratio of triglyceride to HDL cholesterol, and triglyceride-rich lipoprotein cholesterol concentrations were associated with increased risk of atherosclerotic vascular events in CKD. Reducing triglyceride-rich lipoproteins using novel therapeutic agents could potentially lower the risk of atherosclerotic cardiovascular disease risk in the CKD population.

Keywords: HDL cholesterol; LDL cholesterol; apolipoproteins; cardiovascular disease; cardiovascular diseases; cholesterol; chronic kidney disease; chronic renal insufficiency; demography; follow-up studies; glomerular filtration rate; humans; lipids; lipoprotein cholesterol; lipoprotein triglyceride; lipoproteins; low density lipoprotein triglyceride; renal dialysis; risk factors; triglycerides.

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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Association between usual lipid values and the risk of atherosclerotic vascular events. HRs adjusted for age, sex, ethnicity, treatment allocation, prior diabetes, prior vascular disease, smoking, body mass index, eGFR, and albuminuria are quoted (above squares) with numbers of events (below). Average HR (95% CI) throughout the range of values studied (i.e., assuming a log-log-linear relationship for triglycerides and triglyceride to HDLc ratio, and log-linear relationships for all other lipids), corresponding to about 1 SD differences in usual lipid values. 95% CI, 95% confidence interval; HDLc, HDL cholesterol; HR, hazard ratio; LDLc, LDL cholesterol; TG, triglyceride; TRL, triglyceride-rich lipoprotein; TRL cholesterol, total cholesterol minus LDLc minus HDLc.
Figure 2.
Figure 2.
Effect of allocation to simvastatin plus ezetimibe on major atherosclerotic events, by level of baseline lipids. Participants with missing baseline values of lipids are excluded from the subgroup analyses, but are included in the overall result. TG, triglyceride; TRL, triglyceride-rich lipoprotein; TRL cholesterol, total cholesterol minus LDL cholesterol minus HDL cholesterol.
Figure 3.
Figure 3.
Association between usual lipid values and the risk of nonatherosclerotic vascular events. HRs adjusted for age, sex, ethnicity, treatment allocation, prior diabetes, prior vascular disease, smoking, body mass index, eGFR, and albuminuria are quoted (above squares) with numbers of events (below). Average HR (95% CI) throughout the range of values studied (i.e., assuming a log-log-linear relationship for triglycerides and triglyceride to HDLc ratio, and log-linear relationships for all other lipids), corresponding to about 1 SD differences in usual lipid values. HDLc, HDL cholesterol; LDLc, LDL cholesterol; TG, triglyceride; TRL, triglyceride-rich lipoprotein; TRL cholesterol, total cholesterol minus LDLc minus HDLc.
Figure 4.
Figure 4.
Association between usual lipid values and the risk of nonatherosclerotic vascular events, stratified by levels of CRP. HRs adjusted for age, sex, ethnicity, treatment allocation, prior diabetes, prior vascular disease, smoking, body mass index, eGFR, and albuminuria are quoted (above squares) with numbers of events (below). Average HR (95% CI) throughout the range of values studied (i.e., assuming a log-log-linear relationship for triglycerides and triglyceride to HDLc ratio, and log-linear relationships for all other lipids), corresponding to about 1 SD differences in usual lipid values. CRP, C-reactive protein; HDLc, HDL cholesterol; LDLc, LDL cholesterol; TG, triglyceride; TRL, triglyceride-rich lipoprotein; TRL cholesterol, total cholesterol minus LDLc minus HDLc.
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Comment in

  • Lipids and Cardiovascular Risk with CKD.
    Afshinnia F, Pennathur S. Afshinnia F, et al. Clin J Am Soc Nephrol. 2020 Jan 7;15(1):5-7. doi: 10.2215/CJN.13531119. Epub 2019 Dec 12. Clin J Am Soc Nephrol. 2020. PMID: 31846933 Free PMC article. No abstract available.

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