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

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 m 2 ), 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.

Association of circulating PCSK9 concentration with cardiovascular metabolic markers and outcomes in stable coronary artery disease patients with or without diabetes: a prospective, observational cohort study

“…Body mass index (BMI) was determined as body weight (kg) divided by body height (m 2 ). Non-high-density lipoprotein cholesterol (non-HDL-C) was calculated as TC minus HDL-C, triglyceride-rich lipoprotein was calculated as non-HDL-C minus LDL-C as the previous study showed [23]. The value of atherogenic index of plasma was defined as the base 10 logarithm of the ratio of the concentration of TG to HDL-C, the lipoprotein combine index (LCI) was defined as the ratio of TC × TG × LDL-C to HDL-C [24].…”

Acute kidney injury leading to CKD is associated with a persistence of metabolic dysfunction and hypertriglyceridemia

“…However, genetic mutations that lead to similar lipid profiles are not associated with the development of CKD ( Lanktree et al., 2018 ). Patients with CKD and dyslipidemia are at high risk of cardiovascular complications, and a recent post hoc analysis of the Study of Heart and Renal Protection (SHARP) trial data has shown that high triglycerides are independently associated with worse cardiovascular outcomes ( Lamprea-Montealegre et al., 2020 ). Our data suggest that the presence of CKD alone may generate this abnormal lipid profile, which, along with the accumulation of uremic endothelial toxins such as indoxyl sulfate, may provide insights into the close association between CKD and cardiovascular disease ( Lano et al., 2020 ; Provenzano et al., 2019 ).…”

Triglycerides to High-Density Lipoprotein Cholesterol Ratio Predicts Chronic Renal Disease in Patients without Diabetes Mellitus (STELLA Study)

“…In our study, we did not consider apolipoproteins B or A1 since many previous studies have reported on them and also a clear superiority of apolipoproteins over traditional lipids in their association with eGFR or CKD has not been suggested [ 10 ]. Recently, a TG/HDL-C ratio was comprised of the potential risk factors for atherosclerotic vascular events in CKD [ 15 ]. In agreement, in our study we noted a significant unadjusted association of a high TG/HDL-C ratio with manifested hypertension and the patients with a higher TG/HDL-C ratio had significantly higher blood pressure and arterial stiffening in comparison to the group of patients with a lower TG/HDL-C ratio.…”

“…The TG to HDL-C (TG/HDL-C) ratio has been already included in the potential indices for an increased risk of atherosclerotic vascular events in CKD [ 15 ], although a few studies considered its role on the chronic renal disease until now.…”