Baseline inflammatory status affects the prognostic impact of statins in patients with peripheral arterial disease

Background Statins bring favorable effects on the clinical prognosis of patients with atherosclerotic disease partly through their anti-inflammatory properties. However, this effect has not been fully verified in patients with peripheral arterial disease (PAD). We aimed to test whether statins exert different prognostic effects depending on the degrees of inflammation in patients with PAD. Methods This study was a sub-analysis of a multicenter prospective cohort of 2,321 consecutive patients with PAD who received endovascular therapy (EVT). After excluding patients without information on C-reactive protein (CRP) levels at the time of index EVT, 1,974 patients (1,021 statin users and 953 non-users) were ultimately analyzed. Enrolled patients were classified into four groups depending on CRP levels: low CRP (<0.1 mg/dL), intermediate-low CRP (0.1–0.3 mg/dL), intermediate-high CRP (0.3–1.0 mg/dL), and high CRP (>1.0 mg/dL). A composite of death, stroke, myocardial infarction, and major amputation as the primary endpoint was compared between statin users and non-users in each CRP category. Results Overall, statin users showed a significantly lower event rate than non-users (log-rank, p<0.001). However, statin therapy was associated with significantly lower event rates only in the intermediate-high- and high-CRP categories (p=0.02 and p=0.008, respectively). Multivariable Cox regression analysis revealed that statin use was independently associated with the primary endpoint only in the high-CRP category (adjusted hazard ratio: 0.64 [95% confidence interval: 0.41–0.98]). Conclusion Statins may exert favorable prognostic effects in patients with PAD and highly elevated CRP levels but not in those with low to moderate CRP levels. Condensed abstract This multicenter retrospective study compared the prognostic effects of statins among patients with peripheral arterial disease (PAD) presenting diverse baseline C-reactive protein (CRP) levels [low CRP (<0.1 mg/dL), intermediate-low CRP (0.1–0.3 mg/dL), intermediate-high CRP (0.3–1.0 mg/dL), and high CRP (>1.0 mg/dL)]. Multivariable analysis showed that statin use was independently associated with a lower rate of death, stroke, myocardial infarction, and major amputation only in the high-CRP category. This suggests that statins may have favorable prognostic effects in patients with PAD and active inflammation. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR No. UMIN000015100). ### Funding Statement This work was supported by the Vascular Disease Research Project of the Japan Research Promotion Society for Cardiovascular Diseases. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the Ethics Committee at Sakakibara Heart Institute (reference no. 14-023) and the committees of each participating facility. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author. * CAD : coronary artery disease CRP : C-reactive protein EVT : endovascular therapy PAD : peripheral artery disease