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 Disease

Literature - 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

Background

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 [3]. 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.

Methods

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.

Outcomes

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.

Main results

  • 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.

Conclusion

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.

References

1. Authors/Task Force Members, Guidelines ESCCfP and Societies ESCNC. ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Atherosclerosis. 2019;2019(290):140–205. doi: 10.1016/j.atherosclerosis.2019.08.014

2. Adhyaru BB, Jacobson TA. New cholesterol guidelines for the management of atherosclerotic cardiovascular disease risk: a comparison of the 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines with the 2014 National Lipid Association recommendations for patient-centered management of dyslipidemia. Endocrinol Metab Clin North Am. 2016;45:17–37. doi: 10.1016/j.ecl.2015.09.002

3. Sarnak MJ, Amann K, Bangalore S, Cavalcante JL, Charytan DM, Craig JC, Gill JS, Hlatky MA, Jardine AG, Landmesser U, et al. Chronic kidney disease and coronary artery disease: JACC State-of-the-art review. J Am Coll Cardiol. 2019;74:1823–1838. doi: 10.1016/j.jacc.2019.08.1017

4. Wanner C, Krane V, Marz W, Olschewski M, Mann JF, Ruf G, Ritz E, German D, Dialysis Study I. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353:238–248. doi: 10.1056/NEJMoa043545

5. Fellstrom BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, Chae DW, Chevaile A, Cobbe SM, Gronhagen-Riska C, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360:1395–1407. doi: 10.1056/NEJMoa0810177

6. Massy ZA, de Zeeuw D. LDL cholesterol in CKD—to treat or not to treat? Kidney Int. 2013;84:451–456. doi: 10.1038/ki.2013.181

7. Messow CM, Isles C. Meta-analysis of statins in chronic kidney disease: who benefits? QJM. 2017;110:493–500. doi: 10.1093/qjmed/hcx040

Find this article online at J Am Heart Assoc.

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