Higher plasma CXCL12 levels predict incident myocardial infarction and death in chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort study

Mehta, Nehal N.; Matthews, Gregory J.; Krishnamoorthy, Parasuram; Shah, Rhia; McLaughlin, Charles W.; Patel, Parth; Budoff, Matthew J.; Chen, Jing; Wolman, M; Go, Alan S.; He, Jiang; Kanetsky, Peter A.; Master, Stephen R.; Rader, Daniel J.; Raj, Dominic S.; Gadegbeku, Crystal A.; Shah, Rachana; Schreiber, M. Fernanda; Fischer, Michael J.; Townsend, Raymond R.; Kusek, John W.; Feldman, Harold I.; Foulkes, Andrea S.

doi:10.1093/eurheartj/eht481

Cited by 44 publications

(35 citation statements)

References 30 publications

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“…It stays in accordance with the observation derived from a prospective cohort of CKD patients that SDF-1alpha/CXCL12 is an independent predictor of death or myocardial infarction [5]. In addition to its prohypertrophic effect on the myocardium, it stimulates LDL-oxLDL uptake into the platelets, resulting in pro-oxidative, thrombogenic effects in platelets and clot structure that favors adverse events [12,13].…”

Section: Cxcl12 In Cardiomyocyte Dysfunction and Apoptosissupporting

confidence: 88%

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CXCL12 in Patients with Chronic Kidney Disease and Healthy Controls: Relationships to Ambulatory 24-Hour Blood Pressure and Echocardiographic Measures

et al. 2018

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Background/Aims: Chronic kidney disease is a pro-inflammatory condition where the interplay between different regulatory pathways and immune cells mediates an unfavorable remodeling of the vascular wall and myocardial hypertrophy. These mechanisms include the action of CXCL12. The aim of this study is to evaluate the association between serum CXCL12 with left ventricular hypertrophy (LVH) and blood pressure control in chronic kidney disease (CKD) patients. Methods: This single-center observational study involved 90 stable CKD stage 1–5 patients (including 33 renal transplant recipients) and 25 healthy age- and sex-matched control subjects. CXCL12 was quantified by ELISA. 24-h ambulatory blood pressure monitoring was performed in 90 patients and 25 healthy controls. Left ventricular mass index (LVMI) was calculated based on the transthoracic echocardiography measurements in 27 patients out of the CKD population and in the whole control group. Results: CXCL12 correlated significantly with LVMI by multivariate regression analysis (coefficient B = 0.33, p = 0.02) together with age (B = 0.30, p = 0.03) and gender (B = 0.41, p = 0.003). A positive correlation was observed between CXCL12 and average 24-h systolic blood pressure (SBP) (rho = 0.35, p = 0.001), daytime SBP (rho = 0.35, p = 0.001), and nocturnal SBP (rho = 0.30, p = 0.002). Nocturnal hypertension was frequent (46% of CKD patients). Conclusions: The results of our study point towards a link between CXCL12 and LVH as well as blood pressure control among patients with CKD, supporting the thesis that CXCL12 may be regarded as a new potential uremic toxin.

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Section: Cxcl12 In Cardiomyocyte Dysfunction and Apoptosissupporting

confidence: 88%

“…Secretion of CXCL12 may be induced in the cardiomyocytes by the renin-angiotensin-aldosterone (RAA) system in the failing heart [4]. Importantly, its serum concentration was reported to increase in CKD patients [5].…”

Section: Introductionmentioning

confidence: 99%

CXCL12 in Patients with Chronic Kidney Disease and Healthy Controls: Relationships to Ambulatory 24-Hour Blood Pressure and Echocardiographic Measures

et al. 2018

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“…The MI and mortality events were assessed as previously described 19 , including review of detailed hospital records by two physician adjucators. Participants were followed annually in person with interim telephone calls until death, withdrawal from study, lost to follow-up, or June 30, 2009, when data were locked for this analysis.…”

Section: Methodsmentioning

confidence: 99%

Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Shah

Matthews

Shah

et al. 2015

American Journal of Kidney Diseases

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Background Cardiometabolic disease is a major cause of morbidity and mortality in persons with chronic kidney disease (CKD). Fractalkine (CX3CL1) is a potential mediator of both atherosclerosis and metabolic disease. Studies on the relationship of CX3CL1 with risk of CVD events and metabolic traits are lacking, particularly in the high-risk setting of CKD. Study Design Cross-sectional and longitudinal observational analysis. Setting & Participants Adults with CKD from 7 US sites participating in the Chronic Renal Insufficiency Cohort (CRIC) Study. Predictor Quartiles of plasma CX3CL1 levels at baseline. Outcomes Baseline estimated glomerular filtration rate (eGFR) from a creatinine- and cystatin C–based equation, prevalent and incident CVD, diabetes, metabolic syndrome and its criteria, homeostatic model assessment of insulin resistance, hemoglobin A1C, myocardial infarction, all-cause mortality, and the composite outcome of myocardial infarction/all-cause mortality. Results Among 3687 participants, baseline CX3CL1 levels were positively associated with several CVD risk factors and metabolic traits, lower eGFR, and higher levels of inflammatory cytokines as well as prevalent CVD (OR, 1.09; 95% CI, 1.01–1.19; p=0.03). Higher CX3CL1 was also associated with prevalent diabetes (OR, 1.26; 95% CI, 1.16–1.38; p<0.001) in adjusted models. During a mean follow up of 6 years, there were 352 deaths, 176 myocardial infarctions, and 484 with composite outcomes. In fully-adjusted models, 1-SD higher CX3CL1 increased the hazard for all-cause mortality (1.11; 95% CI, 1.00–1.22; p=0.02) and the composite outcome (1.09; 95% CI, 1.00–1.19; p=0.04). Limitations Study design did not allow evaluation of changes over time, correlation with progression of phenotypes, or determination of causality of effect. Conclusions Circulating CX3CL1 may contribute to both atherosclerotic CVD and diabetes in a CKD cohort. Further studies are required to establish mechanisms through which CX3CL1 affects pathogenesis of atherosclerosis and diabetes.

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“…CXCL12 CXC chemokine ligand-12 regeneration of ischemic tissue through the regulation of hematopoietic progenitor cells and is upregulated at the sites of vascular injury and platelet activation. Another study found that in chronic kidney disease (CVD), baseline plasma levels of CXCL12 were associated with known cardiovascular (CV) risk factors, prevalent CV disease, as well as incident MI/ death after adjustment for traditional CV risk factors and measures of CKD, suggesting that plasma CXCL12 levels may be atherogenic [28]. In this study, we firstly assessed the serum CXCL12 levels with regard to their accuracy to predict functional outcome and mortality in patients with AIS within 6 months in the Chinese sample.…”

Section: Discussionmentioning

confidence: 99%

Elevated Serum Levels of CXC Chemokine Ligand-12 Are Associated with Unfavorable Functional Outcome and Mortality at 6-Month Follow-up in Chinese Patients with Acute Ischemic Stroke

Chen

Lian

et al. 2016

Mol Neurobiol

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The aim of this study was to examine whether the circulating CXC chemokine ligand-12 (CXCL12) level can predict a 6-month outcome in Chinese patients with acute ischemic stroke (AIS). In a prospective study, CXCL12 levels were measured on admission in the serum of 304 consecutive patients with AIS. The prognostic value of CXCL12 to predict the functional outcome and mortality within 1 year was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. A receiver operating characteristic (ROC) curve was used to evaluate the accuracy of serum CXCL12 in predicting functional outcome and mortality. Patients with an unfavorable outcome and non-survivors had significantly increased CXCL12 levels on admission (P < 0.0001 and P < 0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that CXCL12 (≥12.4 ng/mL; third quartile) was an independent predictor of functional outcome (odds ratio [OR] = 8.81; 95 % confidence interval [CI] 4.92-24.79) and mortality (OR = 10.15; 95 %CI 2.44-27.98). The area under the receiver operating characteristic curve of CXCL12 was 0.84 (95 % CI 0.76-0.92) for functional outcome and 0.87 (95 % CI 0.80-0.93) for mortality. Circulating CXCL12 serum levels at admission is a useful and complementary biomarker to predict functional outcome and mortality 6 months after acute ischemic stroke.

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Higher plasma CXCL12 levels predict incident myocardial infarction and death in chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort study

Abstract: In CKD, higher plasma CXCL12 was associated with CVD risk factors and prevalent CVD as well as the hazard of incident MI and death. Further studies are required to establish if plasma CXCL12 reflect causal actions at the vessel wall and is a tool for genomic and therapeutic trials.

Cited by 44 publications

References 30 publications

CXCL12 in Patients with Chronic Kidney Disease and Healthy Controls: Relationships to Ambulatory 24-Hour Blood Pressure and Echocardiographic Measures

CXCL12 in Patients with Chronic Kidney Disease and Healthy Controls: Relationships to Ambulatory 24-Hour Blood Pressure and Echocardiographic Measures

Serum Fractalkine (CX3CL1) and Cardiovascular Outcomes and Diabetes: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Elevated Serum Levels of CXC Chemokine Ligand-12 Are Associated with Unfavorable Functional Outcome and Mortality at 6-Month Follow-up in Chinese Patients with Acute Ischemic Stroke

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