Chronic kidney disease, lipids and apolipoproteins, and coronary heart disease: The ARIC Study☆
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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An abstract of this manuscript was presented as a poster in the 2012 American Society of Nephrology Scientific Sessions.