Association of Low-Density Lipoprotein Cholesterol Levels During Statin Treatment With Cardiovascular and Renal Outcomes in Patients With Moderate Chronic Kidney Disease

Abstract

Background The benefit of low-density lipoprotein cholesterol (LDL-C) levels in chronic kidney disease populations remains unclear. This study evaluated the cardiovascular and renal outcomes in patients with stage 3 chronic kidney disease with different LDL-C levels during statin treatment. Methods and Results There were 8500 patients newly diagnosed as having stage 3 chronic kidney disease under statin treatment who were identified from the Chang Gung Research Database and divided into 3 groups according to their first LDL-C level after the index date: <70 mg/dL, 70 to 100 mg/dL, and >100 mg/dL. Inverse probability of treatment weighting was performed to balance baseline characteristics. Compared with the LDL-C ≥100 mg/dL group, the 70≤LDL-C<100 mg/dL group exhibited significantly lower risks of major adverse cardiac and cerebrovascular events (6.8% versus 8.8%; subdistribution hazard ratio [SHR], 0.76 [95% CI, 0.64-0.91]), intracerebral hemorrhage (0.23% versus 0.51%; SHR, 0.44 [95% CI, 0.25-0.77]), and new-onset end-stage renal disease requiring chronic dialysis (7.6% versus 9.1%; SHR, 0.82 [95% CI, 0.73-0.91]). By contrast, the LDL-C <70 mg/dL group exhibited a marginally lower risk of major adverse cardiac and cerebrovascular events (7.3% versus 8.8%; SHR, 0.82 [95% CI, 0.65-1.02]) and a significantly lower risk of new-onset end-stage renal disease requiring chronic dialysis (7.1% versus 9.1%; SHR, 0.76 [95% CI, 0.67-0.85]). Conclusions Among patients with stage 3 chronic kidney disease, statin users with 70≤LDL-C<100 mg/dL and with LDL-C <70 mg/dL had similar beneficial effect in the reduction of risks of major adverse cardiac and cerebrovascular events and new-onset end-stage renal disease compared with those with LDL-C >100 mg/dL. Moreover, the 70≤LDL-C<100 mg/dL group seemed to have a lowest risk of intracerebral hemorrhage, although the incidence was low.

Keywords: cardiovascular disease; chronic kidney disease; low‐density lipoprotein cholesterol; statin; stroke.

Figure 1. Patient inclusion–exclusion flowchart.

CKD3 indicates stage 3 chronic kidney disease; and LDL, low‐density lipoprotein.

Figure 2. The cumulative event rate of MACCE (A), ischemic stroke (B), new‐onset ESRD requiring dialysis, (C) and hepatitis‐related hospitalization (D) in patients with stage 3 chronic kidney disease by different LDL‐C levels after statin treatment in the GBM‐IPTW–adjusted cohort.

ESRD indicates end‐stage renal disease; GBM‐IPTW, generalized boosted modeling‐inverse probability of treatment weighting; HR, hazard ratio; LDL, low‐density lipoprotein; LDL‐C, low‐density lipoprotein cholesterol; MACCE, major adverse cardiac and cerebrovascular event; and SHR, subdistribution hazard ratio.

Figure 3. The relationship between LDL level and the risk of MACCEs, in which LDL was treated as a restricted cubic spline.

The LDL‐C level of 70 mg/dL was used as the referent. The solid red line is the estimate, and the dashed blue lines are the 95% CIs of the estimate. LDL indicates low‐density lipoprotein; LDL‐C, low‐density lipoprotein cholesterol; and MACCEs, major adverse cardiac and cerebrovascular events.