In this study, we found that LAR was associated with all-cause mortality and cardiovascular events in PD patients. PD patients with low LAR were older, had less hypertension; decreased levels of albumin, TC, HDL-C, and LDL-C; and increased levels of TG, apo B and ferritin. Moreover, low LAR patients had higher all-cause mortality and cardiovascular events. Therefore, the LAR can be used as a significant important risk indicator for PD patients.
PD is an effective renal replacement therapy for patients with advanced CKD. However, dyslipidemia is common in PD patients. Patients with advanced CKD are characterized by increased levels of TG, mainly due to decreased lipolysis of TG-rich lipoproteins, accompanied by lower levels of HDL-C[29, 30]. These dyslipidemias are present in patients with advanced CKD and in CKD patients treated with PD[31, 32]. The main manifestation is a decrease in HDL, HDL-C and HDL-2/HDL-3 and an increase in TC, intermediate-density lipoprotein, chylomicron remnants, HDL triglyceride, LDL triglyceride, and lipoprotein lipase activity.
LDL-C is a strong predictor of coronary heart disease. Decreasing LDL-C levels is considered to be the main therapeutic target for the treatment of hypercholesterolemia and this approach can reduce the incidence of major atherosclerotic events in patients with advanced CKD [33, 34]. Related studies have shown that reducing serum LDL-C levels can effectively reduce the risk of ischemic stroke, myocardial infarction and coronary artery death. Massy ZA et al. have shown that half of CKD patients have an LDL-C that exceeds the recommended target, and a significant proportion do not receive treatment, thus increasing the morbidity and mortality of CKD patients due to coronary heart disease and stroke. However, other studies have found that there is no significant correlation between the level of LDL-C and the prognosis of atherosclerotic CVD in CKD. Tani S et al. found that a low LDL-C level in patients with coronary artery disease and advanced kidney disease was associated with a poor prognosis. Our study showed that after adjusting for age, sex, BMI, eGFR, CCI, diabetes, hypertension, premorbid CVD, hemoglobin, albumin, alkaline phosphatase, phosphorus, iPTH, ferritin, HDL-C, TC, and lipid-lowering medication, the LDL-C levels were not significantly associated with all-cause mortality or cardiovascular events. Therefore, further research is required to resolve this controversy.
Apo B is the main structural lipoprotein of LDL, VLDL, medium density lipoprotein and lipoprotein A. Each particle has one apo B, so the measurement of apo B is used to determine the exact number of atherogenic lipoprotein particles[18, 39]. The trapping of apo B lipoprotein particles within the arterial wall plays an important role in initiating and driving the atherosclerotic process. A study found that low apo B levels may be an effective marker of left ventricular hypertrophy in PD patients . In addition, other studies have shown that apo B levels are higher in PD patients than in hemodialysis and normal subjects and that a high apo B level increases the risk of coronary heart disease in PD patients. Current evidence suggests that apo B measures the risk of atherosclerosis caused by apolipoprotein more accurately than LDL-C or non-HDL-C . However, the predictive ability of apolipoprotein B is not always better than that of non-HDL-C. Di Angelantonio E  and Benn M  showed that non-HDL-C and apo B have the same predictive ability. A cross-sectional study showed that higher apo B is associated with the prevalence of coronary heart disease. Lamprea-Montealegre JA et al. showed that higher apo B is associated with an increased risk of atherosclerotic vascular events in patients with CKD. In the fully adjusted model, apo B was positively correlated with CVD-related mortality. However, our study showed that apo B was not significantly associated with all-cause mortality or cardiovascular events.
LDL particles can be divided into large and low-density LDL particles (diameter >25 nm) and small and dense LDL (diameter <25 nm)[49, 50]. Small and dense low-density lipoprotein particles have higher arterial wall permeability, lower LDL receptor binding affinity, a longer plasma half-life and lower oxidative stress resistance[11, 51-53]. St-Pierre AC et al. showed that in patients with LDL particle sizes of 25.5 nm or smaller, the incidence of coronary heart disease increased significantly with increasing serum LDL-C levels. Similarly, some patients may have the same LDL-C level, but patients may have more or smaller LDL particles, and their risk may be higher. The LAR indirectly determines the size of the LDL particles. Some studies have shown that the LAR can distinguish between large loose LDL and small dense LDL, and the latter leads to a significant increase in the incidence of coronary heart disease[56-58]. Therefore, LAR is an independent predictor of coronary heart disease [13, 59, 60]. Rabizadeh S et al. showed that LAR≤1.2 can independently predict coronary heart disease. Bae JC et al. used LAR as an alternative indicator of LDL particle size and found that LAR had a significant negative correlation with the incidence of CKD, especially when LAR ≤ 1.29 . Tani et al. showed that in male patients treated with statins, the LAR in patients with coronary heart disease was significantly lower . This finding is similar to our findings, which show that all-cause mortality and cardiovascular events increased significantly when LAR<1.04. The reason may be that low LAR is mainly characterized by small and dense LDL particles. Since each particle can only contain one apo B, an increase in serum apo B may indicate that there are a large number of LDL particles in the blood circulation, thus increasing the risk of cardiovascular events. This has been confirmed in several studies[56, 57, 62]. Previous studies have shown that the level of plasma apo B-cholesterol may better reflect the number of atherogenic granules than the concentration of LDL-C. Although our study shows that apo B levels alone do not predict all-cause mortality and cardiovascular events, as an alternative to LDL-C particle size alone, a lower LAR in PD patients may play an important role in predicting all-cause mortality and cardiovascular events.
Our study also has some limitations. For example, this is a retrospective study with a small sample size, followed by no assessment of the effects of inflammatory cells and inflammatory factors, as well as the impact of some unknown factors on blood lipid levels in PD patients. Although lipid-lowering drugs were adjusted in the risk model, this factor was not taken into account in the grouping of LAR, indicating improvements are necessary in future studies.