Elsevier

Atherosclerosis

Volume 234, Issue 1, May 2014, Pages 42-46
Atherosclerosis

Chronic kidney disease, lipids and apolipoproteins, and coronary heart disease: The ARIC Study

https://doi.org/10.1016/j.atherosclerosis.2014.02.006Get rights and content

Highlights

  • CKD is associated with higher levels of ApoB/A1 levels.

  • ApoB/A1 is associated with CHD incidence in individuals with CKD.

  • NonHDLc/HDLc is associated with CHD with a similar magnitude to that of ApoB/A1.

Abstract

Background

Chronic kidney disease (CKD) is associated with elevated apolipoprotein B to A-1 ratio (ApoB/A1). It is not known whether these markers are more strongly associated with the risk of coronary heart disease (CHD) in CKD compared to traditionally measured lipids and lipoprotein cholesterol ratios.

Methods

We studied the association of lipids and apolipoproteins including non-HDL-cholesterol to HDL-cholesterol ratio (NonHDLc/HDLc) and ApoB/A1 with incident CHD in 10,137 individuals free of CHD at baseline (visit four) in the Atherosclerosis Risk in Communities (ARIC) study. An estimated glomerular filtration rate of 15 to <60 ml/min/1.73 m2 based on a cystatin C measurement was used to define CKD (Stage 3–4). Cox proportional hazards regression models were used to determine the association of lipids and apolipoprotein measurements with the risk of CHD in those with and without CKD after adjustment for demographic and known clinical cardiovascular risk factors.

Results

CKD was present in 1217 (12%) individuals free of CHD at baseline. The median follow-up time was 11.1 years. A CHD event developed in 498 out of 8920 individuals without CKD (incidence rate: 5.2 events per 1000 person-years) and in 138 out of 1217 individuals with CKD (incidence rate: 12.0 events per 1000 person–years; P < 0.001). Those with CKD had a lower concentration of ApoA1: median (in g/L) and interquartile range (IQR) = 1.40 (1.38–1.42) vs. 1.48 (1.47–1.49) P < 0.001; and a higher ApoB/A1 = 0.75 (0.73–0.77) vs. 0.71 (0.70–0.72) P < 0.001; than those without CKD (eGFR ≥ 60 ml/min/1.73 m2). Among individuals with CKD, ApoB/A1 and NonHDLc/HDLc were both associated with the risk of CHD: hazard ratios (HR) and 95% confidence intervals (CI) per one standard deviation increase = 1.22 (1.02–1.46) for ApoB/A1 and 1.30 (1.07–1.57) for NonHDLc/HDLc with no significant differences detected (P for interaction >0.1) when comparing these estimates to those of participants without CKD.

Conclusions

Although CKD is associated with a lower ApoA1 concentration and with a higher ApoB/A1, we found no evidence that these apolipoproteins are more strongly associated with CHD incidence in CKD compared to NonHDLc/HDLc.

Introduction

Apolipoproteins B (ApoB) and A-1 (ApoA1) have been shown to be strong and independent predictors of cardiovascular disease in the general population [1], [2]. Given that the apolipoprotein B to A-1 ratio (ApoB/A1) is closely associated with the total number of atherogenic and anti-atherogenic lipid particles in plasma [3], it may be a better marker of the cardiovascular disease risk than conventional lipid measurements [4]. Controversy exists, however, regarding the need to recommend the routine introduction of apolipoprotein measurements in clinical practice.

Clinical guidelines do not currently recommend the measurement of apolipoproteins for cardiovascular risk assessment in the general population [5], [6]. Non-high density lipoprotein cholesterol (NonHDLc), which is estimated by subtracting high density lipoprotein cholesterol (HDLc) from total cholesterol, correspond closely to measurements of ApoB and HDLc to that of ApoA1 [6]. However, the advantage of the apolipoprotein measurements may be better observed in populations with elevated numbers of small LDL particles and triglyceride rich lipoproteins [7].

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease [8], [9]. A pattern of dyslipidemia characterized by elevations in the number of small low density lipoprotein (small LDL) and very low density lipoprotein (VLDL) particles and reduced numbers of HDL particles is more common in CKD than in the general population [10]. In addition, the concentration of ApoA1 is reduced [11] and the ApoB/A1 ratio is elevated in CKD [12]. It is not known whether, in CKD patients, the abnormal concentrations of apolipoproteins are more strongly related to coronary heart disease (CHD) risk than conventional lipid measurements.

Thus, we investigated in a large multi-center cohort study whether apolipoprotein concentrations were more strongly associated with CHD than concentrations of lipids and lipoprotein cholesterols in individuals with CKD.

Section snippets

Study population

The Atherosclerosis Risk in Communities (ARIC) study is a population-based cohort study of atherosclerosis and its clinical complications in 15,792 adult men and women aged 45–64 selected from four US communities [13]. Baseline examinations occurred from 1987 though 1989 (visit1) with re-examinations in 1990–1992, 1993–1995, and 1996–1998 (visit 4). At visit 4, participants had cystatin C, apolipoproteins B and A-1, and lipid and lipoprotein cholesterol measurements. In this study, we used

Results

CKD (eGFR 15 to <60 ml/min/1.73 m2) was present in 1217 participants (12%) at baseline (Table 1). Participants with CKD were more likely to be older, female, white, and to be using a lipid-lowering medication relative to those without CKD. Similarly, the prevalence of diabetes and hypertension, and levels of hs-CRP were higher for those with CKD. In those with CKD, 1073 (88%) individuals had moderate CKD (eGFR 30 to <60 ml/min/1.73 m2), and 144 individuals had severe CKD (eGFR 15 to

Discussion

Although CKD is associated with higher ratios of ApoB/A1, the association of ApoB/A1 with CHD in individuals with CKD was similar in magnitude to that observed for NonHDLc/HDLc. Furthermore, the association of CKD with CHD was similarly attenuated when adjusting for ApoB/A1 and NonHDLc/HDLc, meaning that the contributions of ApoB/A1 and NonHDLc/HDLc to the risk of CHD in CKD were similar. Taken together, our results advance in the knowledge of lipid abnormalities present in CKD and in their

Acknowledgments

The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts, (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). The authors thank the staff and participants of the ARIC study for their important contributions.

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