Lower LDL‐c levels associated with CV and renal benefits in moderate CKD under statin treatment
Association of Low‐Density Lipoprotein Cholesterol Levels During Statin Treatment With Cardiovascular and Renal Outcomes in Patients With Moderate Chronic Kidney DiseaseLiterature - Yen CL, Fan PC, Lee CC, et al. - J Am Heart Assoc. 2022 Oct 4;11(19):e027516. doi: 10.1161/JAHA.122.027516
Introduction and methods
Current lipid management guidelines of major American and European medical societies recommend lower target LDL‐c levels with advancing CKD stages [1,2]. This is mainly based on higher CVD risks from early to advanced CKD found in observational studies . However, clinical trials and meta-analyses have indicated a potentially weaker association between CVD risk and LDL‐c level in patients with advanced CKD stages than in other high-risk populations [4-7].
Aim of the study
The study aim was to evaluate CV and renal outcomes in statin-treated patients with stage 3 CKD across different LDL‐c levels.
In this large-scale observational study, data from 8500 patients with newly diagnosed stage 3 CKD who received statin treatment were collected from the Chang Gung Research Database, a large, comprehensive medical database in Taiwan, for the period from 2001 through 2018. Based on their first LDL‐c level data within 3 months after the index date, patients were divided into the following 3 groups: <70 mg/dL, 70–99 mg/dL, and ≥100 mg/dL . To balance the baseline characteristics of these observational data, inverse probability of treatment weighting was performed.
The primary endpoint was the occurrence of major adverse cardiac and cerebrovascular events (MACCE), defined as the composite outcome of acute MI, ischemic stroke, or CV death. Secondary endpoints were all‐cause mortality, CV death, acute MI, ischemic stroke, intracerebral hemorrhage, new‐onset end‐stage renal disease (ESRD) requiring chronic dialysis, noninfectious hepatitis–related hospitalization, and rhabdomyolysis‐related hospitalization.
- At 3-year follow-up, the group with an LDL-c level 70–99 mg/dL (n=3086) showed a lower risk of MACCE (6.8% vs. 8.8%; HR: 0.76; 95%CI: 0.64–0.91), ischemic stroke (2.7% vs. 4.8%; subdistribution HR (SHR): 0.56; 95%CI: 0.47–0.66), intracerebral hemorrhage (0.23% vs. 0.51%; SHR: 0.44; 95%CI: 0.25–0.77), and new‐onset ESRD requiring chronic dialysis (7.6% vs. 9.1%; SHR: 0.82; 95%CI: 0.73–0.91) compared with the group with LDL‐c ≥100 mg/dL (n=3770).
- The group with LDL‐c <70 mg/dL (n=1644) exhibited a reduced risk of ischemic stroke (2.9% vs. 4.8%; SHR: 0.60; 95%CI: 0.51–0.72) and new‐onset ESRD requiring chronic dialysis (7.1% vs. 9.1%; SHR: 0.76; 95%CI: 0.67–0.85) and a trend towards a lower risk of MACCE (7.3% vs. 8.8%; HR: 0.82; 95%CI: 0.65–1.02), compared with the LDL‐c ≥100 mg/dL group.
- A Cox model with LDL-c level as a restricted cubic spline showed that the relationship between LDL-c level and MACCE risk was generally linear (P for nonlinearity>0.05) and a higher LDL-c level was associated with a higher MACCE risk at a proportional scale. When an LDL-c level of 70 mg/dL was used as the reference level, LDL-c ≥106 mg/dL was associated with a significantly greater MACCE risk.
- Subgroup analyses indicated that the beneficial effect of low LDL‐c levels on the occurrence of MACCE was more pronounced in patients ≤65 years of age and in those with proteinuria. As for the incidence of ESRD, the protective effect of low LDL‐c levels seemed to be more evident in patients <65 years of age, those with comorbid DM or hypertension, and those with proteinuria.
Among Taiwanese statin-treated patients with stage 3 CKD, patients with LDL-c levels 70–99 mg/dL and those with LDL‐c<70 mg/dL had decreased risks of ischemic stroke and new‐onset ESRD requiring chronic dialysis compared with patients with LDL‐c ≥100 mg/dL. Patients with LDL-c levels 70–99 mg/dL also had reduced risks of MACCE , a trend that–albeit slightly less pronounced–was also seen in patients with LDL‐c <70 mg/dL. According to the authors, setting a LDL‐c target of <70 mg/dL may prove to be slightly more beneficial in patients ≤65 years of age and in those with proteinuria.