Thyroid Status and Death Risk in US Veterans With Chronic Kidney Disease

Background: Chronic kidney disease (CKD) patients have a higher cardiovascular (CV) disease and mortality risk, elevated triglycerides (TG), and decreased high density lipoproteins (HDL). Post-hoc analysis of trials examining use of fibrate (Fib) or niacin (Nia) therapy in lowering CV outcome risk have failed to show benefit in mild to moderate kidney disease. These analyses were criticized for their study design or small sample size. We sought to examine if Fib or Nia use is associated with lower mortality risk in US veterans across CKD stages. Methods: In a retrospective cohort analysis, we identified male veterans who initiated Fib or Nia, with a high TG ≥150 mg/dL or low HDL ≤40 mg/dL between 2004-2014, and matched them on CKD stage and TG and HDL levels to unexposed men. We examined the association of Fib or Nia use (ref: unexposed) with 12-month all-cause mortality risk across CKD stage strata using an adjusted Cox proportional hazards model. Propensity scores (PS) included baseline demographics, comorbidities and lab measures and high-dimensional propensity scores (HDPS) included over 100 covariates for each drug and stage analysis. PS and HDPS analyses included score adjustment and matching. Results: The cohort had a mean±SD age of 64±12 years, and 30% had CKD stage 3A and higher. There were 69,295 Fib, 87,727 Nia, and 114,411 unexposed patients, respectively. Patient characteristics were similar across drug groups within each CKD stage. With covariate adjustment, both Fib and Nia were associated with a lower death risk compared to unexposed men in lower CKD stages (Figure A and B). Among those with CKD stage 4/5, Fib and Nia were associated with a higher death risk (HR[95%CI]: 1.43[1.15, 1.78] and 1.17[0.97,1.40], respectively). Those on Fib or Nia and in end-stage renal disease had a null association with mortality. Associations were similar for each CKD stage in PS and HDPS analyses, yet Fib and Nia were no longer associated with a lower death risk for CKD stage 3A and 3B patients. Conclusion: Mortality associations of Fib and Nia among male veterans with high TG and low HDL varied across CKD stage, where CKD stage 4/5 patients had a higher mortality risk, even in PS and HDPS analyses. While covariate balance was met, further studies are needed to examine the mechanisms for this higher observed risk in late-stage CKD patients.

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Abstract 14430: Effect Modification of Statin Therapy on the Relationship of Low-density Lipoprotein Cholesterol With Incident CKD in Us Veterans

Circulation ◽

10.1161/circ.142.suppl_3.14430 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Jui-Ting Hsiung ◽

Maria Marroquin ◽

Kamyar Kalantar-Zadeh

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Us Veterans ◽

The Impact ◽

Statin Use

Background: Studies suggests that in the general population, hyperlipidemia may confer higher risk of developing chronic kidney disease (CKD). But, there is conflicting data as to whether statins can protect renal function or slow renal degradation. We sought to examine the impact of statins on the association of low-density lipoprotein cholesterol (LDL) and risk of incident CKD. Methods: Our cohort included 1,439,756 US veterans without chronic kidney disease (CKD), but with LDL measured between 2004-2006, who were followed until 2014. Incident CKD was defined as over 3 estimated glomerular filtration rate (eGFR) measurements <60 mL/min/1.73m 2 at least 90 days apart. Patients with a statin prescription at the time of LDL measurement were identified. Cox models were used to estimate the associations between LDL with incident CKD. Model adjustments include demographics, comorbidities, smoking status, prescription of fibrate or niacin, body mass index, albumin, high-density lipoprotein cholesterol, and triglycerides. Results: The cohort included 5% females, 16% African Americans, 26% diabetics, and 30% statin-users, with a mean age of 60±13 years. The median [IQR] of LDL and eGFR were 109 [88,133] mg/dL and 83 [72,94] mL/min/1.73m 2 , respectively. A J-shaped association between LDL and incident CKD were observed in both those on statin and not on a statin after adjustment. Low LDL (<70 mg/dL) was associated with a higher risk of incident CKD compared to the reference (LDL 70-<100 mg/dL) regardless of statin use. High LDL ≥160 mg/dL was associated with the highest of risks of incident CKD (HR: 1.08, 95% CI: 1.04, 1.13, and HR: 1.10, 95% CI: 1.07, 1.12, for statin use and no statin use, respectively). Conclusion: Both high and low LDL were associated with higher incident CKD risk independent of statin use in this US veteran cohort. Further studies are needed to understand how to manage cardiovascular disease risk by lowering LDL while simultaneously reducing risk of CKD.

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