Lowering C-reactive protein with statins after an ischemic stroke avoids mortality and readmissions. A prospective cohort study

Arévalo-Lorido, José Carlos; Carretero-Gómez, Juana; Fernández-Recio, José María; Álvarez-Oliva, A.; Gutiérrez-Montaño, Concepción; Najarro-Díez, Francisco; Martín-Sánchez, Maria Josefa

doi:10.3109/07853890.2015.1010227

Cited by 14 publications

(12 citation statements)

References 30 publications

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“…Prospective evidence provided by the JUPITER trial (justification for the use of statins in primary prevention: an intervention trial evaluating rosuvastatin) demonstrated that rosuvastatin-treated patients with normal LDL-C levels, but elevated baseline CRP levels, showed highly significant (− 44%) reduction in adverse cardiovascular events [ 14 , 19 ], suggesting additional benefits of CRP reduction, and further demonstrating an inflammatory component in CVD risk [ 16 ]. Notably, either previous or early initiation of CRP lowering by statin therapy, after an ischemic stroke, improves the survival and readmission rates [ 25 ]. Thus, CRP is a marker of inflammation and atherosclerosis that may play an active role in the atherogenic process [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Gemcabene, a first-in-class lipid-lowering agent in late-stage development, down-regulates acute-phase C-reactive protein via C/EBP-δ-mediated transcriptional mechanism

Srivastava¹,

Cornicelli

Markham

et al. 2018

Mol Cell Biochem

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Inflammation plays a key role in setting the stage leading to atherosclerosis progression, and high-sensitivity C-reactive protein (CRP) has been recognized as a predictor of cardiovascular risk. As a monotherapy and in combination with statins, gemcabene markedly reduced CRP in humans. Present investigation was undertaken to understand the mechanism of CRP reduction. In human hepatoma cells, gemcabene inhibited IL-6 plus IL-1β-induced CRP production in a concentration-dependent manner, reaching 70% inhibition at 2 mM. In TNF-α-stimulated primary human coronary artery endothelial cells, both CRP and IL-6 productions were reduced by 70% at 2 mM gemcabene concentration. To investigate the mechanism of gemcabene-mediated reduction of CRP, transfection studies were performed with human CRP regulatory sequences in luciferase/β-gal system that showed 25-fold increase in IL-6- and IL-6 plus IL-1β-stimulated CRP transcription. Luciferase activity was reduced by 50% by gemcabene, suggesting transcriptional down-regulation of CRP. Site-directed mutagenesis of human CRP promoter revealed that the overlapping downstream C/EBP and NF-κB binding sites are important for gemcabene-mediated CRP transcription. Gel shift assays identified the transcription factor that binds to the downstream CRP promoter as C/EBP-δ. In conclusion, gemcabene decreases CRP by C/EBP-δ and NF-κB-mediated transcriptional mechanism and suppresses IL-6 and IL-1β-induced CRP production.

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Section: Introductionmentioning

confidence: 99%

Gemcabene, a first-in-class lipid-lowering agent in late-stage development, down-regulates acute-phase C-reactive protein via C/EBP-δ-mediated transcriptional mechanism

Srivastava¹,

Cornicelli

Markham

et al. 2018

Mol Cell Biochem

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“…Statin treatments could lower Hs-CRP levels in ischemic stroke patients. Several studies with small samples have shown that statin treatment lowered the level of Hs-CRP in patients with any stroke history 9 , 18 ) , but this is the first to show anti-inflammatory effects of statins in a randomized larger-scale trial of chronic ischemic stroke patients. These findings support the recommendation in current guidelines of statin treatments for the prevention of stroke recurrence 19 ) .…”

Section: Discussionmentioning

confidence: 81%

Reduction in High-Sensitivity C-Reactive Protein Levels in Patients with Ischemic Stroke by Statin Treatment: Hs-CRP Sub-Study in J-STARS

Kitagawa

Hosomi

Nagai

et al. 2017

JAT

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Aims: The pleiotropic effects of statins on recurrent stroke remain unclear. We investigated the effects of pravastatin on high-sensitivity C-reactive proteins (Hs-CRP) in ischemic stroke, and explored the impact of Hs-CRP on recurrent stroke and vascular events.Methods: This randomized open-label trial was ancillary to the J-STARS trial. One thousand and ninety-five patients with non-cardiogenic ischemic stroke were assigned to the pravastatin (n = 545) or control groups (n = 550). The primary and secondary endpoints were serum Hs-CRP reduction and stroke recurrence, including both ischemic and hemorrhagic ones, respectively. Onset of vascular events and each stroke subtype in relation to Hs-CRP levels were also determined.Results: In the pravastatin treatment group, Hs-CRP levels (median 711 µg/L, IQR 344–1500) significantly decreased 2 months later (median 592 µg/L, IQR 301–1390), and they remained significantly lower until the end of the study. However, in the control group, baseline Hs-CRP levels were similar to those 2 months later. The reduction of Hs-CRP levels from the baseline to 2 months in the pravastatin group was statistically significant compared with the control (p = 0.007). One SD increase in log-transformed Hs-CRP increased the risk of stroke recurrence (HR 1.17, 95% CI 0.97–1.40) and vascular events (HR 1.30, 95% CI 1.12–1.51). With an Hs-CRP cut-off of 1000 µg/L, higher Hs-CRP significantly increased the risk of recurrent stroke (HR 1.50, 95% CI 1.03–2.17) and vascular events (HR 1.68, 95% CI 1.23–2.29).Conclusion: In non-cardiogenic ischemic stroke, pravastatin treatment may reduce vascular inflammation as assessed by Hs-CRP, and higher Hs-CRP levels appeared to increase the risk of recurrent stroke and vascular events.

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“…Previous studies have looked at the association between statins and perioperative and long-term mortality following AAA repair [31][32][33] but there is scant data on the effect of statins upon readmission. Statins have been reported to reduce all-cause readmissions and length of stay following sepsis 34 or ischemic stroke with respect to mortality and readmissions, 35 although this has remained an underinvestigated area.…”

Section: Discussionmentioning

confidence: 99%

Cohort study of risk factors for 30-day readmission after abdominal aortic aneurysm repair

Bath

Smith

Kruse

et al. 2019

Vasa

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Abstract. Background: We conducted a retrospective cohort study of thirty-day readmission after abdominal aortic aneurysm (AAA) repair. Patients and methods: Inpatients (2009–2016) undergoing elective AAA repair were selected from the multicenter Cerner Health Facts® database using ICD-9 procedure codes. We identified characteristics associated with 30-day readmission with chi-square analysis and logistic regression. Results: 4,723 patients undergoing elective AAA procedures were identified; 3,101 endovascular aneurysm repairs (EVAR) and 1,622 open procedures. Readmission differed by procedure type (6.5 % EVAR vs. 9.3 % open, p =.0005). Multivariable logistic regression found that patients undergoing EVAR were less likely to be readmitted (OR 0.71, 95 % CI 0.54–0.92) than patients undergoing open repair. The following risk factors were associated with 30-day readmission following any AAA repair: surgical site infection during the index admission (OR 2.79, 95 % CI 1.25–6.22), age (OR 1.03, 95 % CI 1.01–1.05), receipt of bronchodilators (OR 1.34, 95 % CI 1.06–1.70) or steroids (OR 1.45, 95 % CI 1.04–2.02), serum potassium > 5.2 mEq/L (OR 1.89, 95 % CI 1.16–3.06), and higher Charlson co-morbidity scores (OR 1.12, 95 % CI 1.04–1.21). Subgroup analysis revealed that age (OR 1.02, 95 % CI 1.01–1.04), higher Charlson comorbidity scores (OR 1.20, 95 % CI 1.09–1.33), and receipt of post-operative bronchodilators (OR 1.39, 95 % CI 1.03–1.88) were risk factors for 30-day readmission following EVAR. After open procedures, readmission was associated with surgical site infection during the index admission (OR 2.91, 95 % CI 1.17–7.28), chronic heart failure (OR 2.18, 95 % CI 1.22–3.89), and receipt of post-operative steroids (OR 1.92, 95 % CI 1.24–2.96). The most common infections were pneumonia after open procedures and urinary tract infection after EVAR. Conclusions: The risk factor most associated with 30-day readmission after elective AAA repair was surgical site infection. Awareness of these risk factors and vulnerable groups may help identify high-risk patients who could benefit from increased surveillance programs to reduce readmission.

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Lowering C-reactive protein with statins after an ischemic stroke avoids mortality and readmissions. A prospective cohort study

Abstract: Therapy with statins, either previous or early initiation, after an ischemic stroke, could improve the survival and readmission rates by lowering both cholesterol and hsCRP levels.

Cited by 14 publications

References 30 publications

Gemcabene, a first-in-class lipid-lowering agent in late-stage development, down-regulates acute-phase C-reactive protein via C/EBP-δ-mediated transcriptional mechanism

Gemcabene, a first-in-class lipid-lowering agent in late-stage development, down-regulates acute-phase C-reactive protein via C/EBP-δ-mediated transcriptional mechanism

Reduction in High-Sensitivity C-Reactive Protein Levels in Patients with Ischemic Stroke by Statin Treatment: Hs-CRP Sub-Study in J-STARS

Cohort study of risk factors for 30-day readmission after abdominal aortic aneurysm repair

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