Serum Low-Density Lipoprotein Cholesterol and Cardiovascular Disease Risk Across Chronic Kidney Disease Stages (Data from 1.9 Million United States Veterans).
In the general population, elevated low-density lipoprotein (LDL) cholesterol levels are an important risk factor for cardiovascular disease (CVD) and mortality; however, the association of LDL with mortality risk and cardiovascular events are less clear in chronic kidney disease (CKD). We sought to examine the relationship of LDL with mortality and rates of atherosclerotic cardiovascular disease (ASCVD) and non-atherosclerotic cardiovascular-related (non-ASCVD) hospitalizations across CKD stages. Our analytical cohort consisted of 1,972,851 United States veterans with serum LDL data between 2004 and 2006. Associations of LDL with all-cause and cardiovascular mortality across CKD stages were evaluated using Cox proportional hazard models with adjustment for demographics, comorbid conditions, smoking status, prescription of statins and non-statin lipid-lowering drugs, body mass index, albumin, high-density lipoprotein, and triglycerides. Associations between LDL and ASCVD and non-ASCVD hospitalizations were estimated using negative binomial regression models across CKD stages. The cohort consisted of 5% female, 14% Black, 29% diabetic, 33% statin-users, and 44% current smokers, with a mean patient age of 64 ± 14 years. Patients with high LDL (≥160 mg/dL) had a higher risk of all-cause and cardiovascular mortality as well as ASCVD and non-ASCVD hospitalization rates across all CKD stages compared with the reference (LDL 70 to <100 mg/dL). The associations with all-cause and cardiovascular mortality and ASCVD hospitalization rate were attenuated at higher CKD stages. These trends were reversed with amplification of the association of high LDL with non-ASCVD hospitalization at higher CKD stages. In conclusion, associations of LDL with mortality and both ASCVD and non-ASCVD hospitalizations are modified according to kidney disease stage.
Hashemi L
，Hsiung JT
，Arif Y
，Soohoo M
，Jackson N
，Gosmanova EO
，Budoff M
，Kovesdy CP
，Kalantar-Zadeh K
，Streja E
... -
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Serum triglycerides and mortality risk across stages of chronic kidney disease in 2 million U.S. veterans.
In the general population, elevated triglyceride (TG) levels are an important risk factor for cardiovascular disease and mortality. However, in chronic kidney disease, the association of serum TGs with mortality is less clear.
We sought to examine the association of TGs with mortality across chronic kidney disease (CKD) stages in a large cohort of U.S. veterans.
We examined 2,086,904 U.S. veterans with a TG measurement obtained between a baseline period of October 2004 and September 2006, with follow-up until December 2014 (median [interquartile range {IQR}]: 9.2 [6.5, 9.9] years). Associations of TGs with all-cause and cardiovascular mortality across CKD stages were evaluated using Cox proportional hazard models.
Patients were 64 ± 14 years old with a median (IQR) baseline TG of 129 [88, 193] mg/dL and estimated glomerular filtration rate of 76 [61, 91] mL/min/1.73 m2. More advanced CKD was associated with higher odds of TGs ≥ 240 mg/dL. Low levels of TGs < 80 mg/dL were associated with a higher risk of mortality across all stages, whereas TG levels ≥ 240 mg/dL were only associated with a higher risk of all-cause mortality in non-CKD and CKD stages 3A, 3B, and 4 (reference: TG 120 to <160 mg/dL). The relationship of higher TGs with mortality incrementally attenuated across worsening stages of CKD and attenuated to the null among patients with CKD stage 5/end-stage renal disease. Similar results were observed for cardiovascular mortality, in strata by age and diabetes, and further adjustment for high-density lipoprotein and low-density lipoprotein.
Associations of elevated TGs with all-cause and cardiovascular mortality were incrementally attenuated across more advanced stages of CKD.
Soohoo M
，Moradi H
，Obi Y
，Kovesdy CP
，Kalantar-Zadeh K
，Streja E
... -
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Lipids, Apolipoproteins, and Risk of Atherosclerotic Cardiovascular Disease in Persons With CKD.
A large residual risk for atherosclerotic cardiovascular disease (ASCVD) remains in the setting of chronic kidney disease (CKD) despite treatment with statins. We sought to evaluate the associations of lipid and apolipoprotein levels with risk for ASCVD in individuals with CKD.
Prospective cohort study.
Adults aged 21 to 74 years with non-dialysis-dependent CKD at baseline enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in 7 clinical study centers in the United States.
Baseline total cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo-B), HDL-C, and apolipoprotein AI (Apo-AI) values stratified into tertiles.
A composite ASCVD event of myocardial infarction or ischemic stroke.
Multivariable Cox proportional hazards regression to estimate the risk for ASCVD for each tertile of lipoprotein predictor.
Among 3,811 CRIC participants (mean age, 57.7 years; 41.8% white), there were 451 ASCVD events during a median follow-up of 7.9 years. There was increased ASCVD risk among participants with VLDL-C levels in the highest tertile (HR, 1.28; 95% CI, 1.01-1.64), Apo-B levels in the middle tertile (HR, 1.30; 95% CI, 1.03-1.64), HDL-C levels in the middle and lowest tertiles (HRs of 1.40 [95% CI, 1.08-1.83] and 1.77 [95% CI, 1.35-2.33], respectively), and Apo-AI levels in the middle and lowest tertiles (HRs of 1.77 [95% CI, 1.02-1.74] and 1.77 [95% CI, 1.36-2.32], respectively). LDL-C level was not significantly associated with the ASCVD outcome in this population (HR, 1.00 [95% CI, 0.77-1.30] for the highest tertile).
Associations based on observational data do not permit inferences about causal associations.
Higher VLDL-C and Apo-B levels, as well as lower HDL-C and Apo-AI levels, are associated with increased risk for ASCVD. These findings support future investigations into pharmacologic targeting of lipoproteins beyond LDL-C, such as triglyceride-rich lipoproteins, to reduce residual risk for ASCVD among individuals with CKD.
Bajaj A
，Xie D
，Cedillo-Couvert E
，Charleston J
，Chen J
，Deo R
，Feldman HI
，Go AS
，He J
，Horwitz E
，Kallem R
，Rahman M
，Weir MR
，Anderson AH
，Rader DJ
，CRIC Study Investigators
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Association of Serum Triglycerides and Renal Outcomes among 1.6 Million US Veterans.
Previous studies have suggested that metabolic syndrome (MetS) components are associated with renal outcomes, defined as a decline in kidney function or reaching end-stage renal disease (ESRD). Elevated triglycerides (TGs) are a component of MetS that have been reported to be associated with renal outcomes. However, the association of TGs with renal outcomes in chronic kidney disease (CKD) patients independent of the other components of the MetS remains understudied.
We examined 1,657,387 patients with data on TGs and other components of MetS in 2004-2006 and followed up until 2014. Patients with ESRD on renal replacement therapy were excluded. We examined time to ESRD, estimated glomerular filtration rate (eGFR) slope (renal function decline), and time to incident CKD (eGFR <60 mL/min/1.73 m2) among baseline normal kidney function (non-CKD) patients, using Cox or logistic regression, adjusted for clinical characteristics and MetS components. We also stratified analyses by the number of MetS components.
The cohort was on average 64 years old and comprised 5% females, 15% African Americans, and 24% with nondialysis-dependent CKD. Among non-CKD patients, the adjusted relationship of TGs with time to incident CKD was strong and linear. Compared to TGs 120-<160 mg/dL, higher TGs were associated with a faster renal function decline across all CKD stages. Elevated TGs ≥240 mg/dL were associated with a faster time to ESRD among non-CKD and CKD stages 3A-3B, while the risk gradually declined to null or lower in CKD stages 4-5. Models were robust after MetS component adjustment and stratification.
Independent of MetS components, high TGs levels were associated with a higher incidence of CKD and a faster renal function decline, yet showed no or inverse associations with time to ESRD in CKD stages 4-5. Examining the effects of TGs-lowering interventions on incident CKD and kidney preserving therapy warrants further studies including clinical trials.
Soohoo M
，Hashemi L
，Hsiung JT
，Moradi H
，Budoff MJ
，Kovesdy CP
，Kalantar-Zadeh K
，Streja E
... -
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