Plasma Osteopontin Levels and Adverse Cardiovascular Outcomes in the PEACE Trial

Abdalrhim, Ahmed D.; Marroush, Tariq S.; Austin, Erin; Gersh, Bernard J.; Solak, Nusret; Rizvi, Syed; Bailey, Kent R.; Kullo, Iftikhar J.

doi:10.1371/journal.pone.0156965

Cited by 38 publications

(31 citation statements)

References 25 publications

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“…There is a clear association of OPN protein levels with atherosclerosis [6] and cardiovascular disease [41], and many studies have shown an association of higher OPN levels with CVE in several populations, including the NEFRONA cohort [5,42,43,44]. In our analysis, in agreement with previous reports, OPN levels increased progressively with the degree of renal function impairment [18], and were higher in patients with CVE.…”

Section: Discussionsupporting

confidence: 91%

The rs1126616 Single Nucleotide Polymorphism of the Osteopontin Gene Is Independently Associated with Cardiovascular Events in a Chronic Kidney Disease Cohort

Cambray

Galimudi

Božić

et al. 2019

JCM

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Chronic kidney disease (CKD) is associated with a higher risk of cardiovascular events (CVE), partly due to the higher burden of atherosclerosis. Circulating Osteopontin (OPN) levels have been also shown to have a potential role in the development of atherosclerosis. Indeed, CKD patients show an increase in circulating OPN levels, but their effect of CKD-related atherosclerosis is not clear. Polymorphisms in the OPN gene (SPP1) have been studied in atheromatous disease, but reported results show conflictive findings. Thus, the main aim of the present study is to analyze the influence of SPP1 polymorphisms in CVE in CKD patients, taking into account circulating OPN levels. We followed 559 healthy controls and 2445 CKD patients without previous CVE from the National Observatory of Atherosclerosis in Nephrology study (NEFRONA study). After 48 months of follow-up 206 CVE were recorded. Genotyping for rs9138, rs1126616, rs1126772, rs11730582 and rs28357094 polymorphisms of the SPP1 gene was performed along with the measurements of plasma OPN levels. The group of patients with CVE showed higher incidence of atherosclerotic plaque (90.3% vs 64.5%; p < 0.001) and higher OPN levels (p < 0.001) at baseline. Patients with the heterozygous genotype of the rs1126616 polymorphism showed a higher hazard ratio of having a CVE, even after adjustment for multiple potential confounders. After adjustment, OPN levels were no longer associated with the incidence of CVE. We found that the rs1126616 single nucleotide polymorphism (SNP) of the SPP1 gene is independently associated with a higher incidence of CVE in a cohort of CKD patients and that it could be used to predict CVE risk.

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Section: Discussionsupporting

confidence: 91%

The rs1126616 Single Nucleotide Polymorphism of the Osteopontin Gene Is Independently Associated with Cardiovascular Events in a Chronic Kidney Disease Cohort

Cambray

Galimudi

Božić

et al. 2019

JCM

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“…174,176 Interestingly, osteopontin deficiency ameliorates myocardial fibrosis and improves cardiac function, 177 indicating that osteopontin may emerge as an attractive biotarget in the treatment of cardiovascular disease. 178 In humans, plasma osteopontin levels appear to be lower in women, 179,180 and it is suggested that oestrogen suppresses osteopontin expression in the vascular tissue. 181 Currently, there is strong evidence highlighting the prognostic value of osteopontin in HF patients, [182][183][184] although sex-specific data are lacking.…”

Section: Potential Heart Failure Biomarkers: Growth Differentiation Fmentioning

confidence: 99%

Sex‐related differences in contemporary biomarkers for heart failure: a review

Suthahar

Meems

et al. 2020

European J of Heart Fail

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The use of circulating biomarkers for heart failure (HF) is engrained in contemporary cardiovascular practice and provides objective information about various pathophysiological pathways associated with HF syndrome. However, biomarker profiles differ considerably among women and men. For instance, in the general population, markers of cardiac stretch (natriuretic peptides) and fibrosis (galectin‐3) are higher in women, whereas markers of cardiac injury (cardiac troponins) and inflammation (sST2) are higher in men. Such differences may reflect sex‐specific pathogenic processes associated with HF risk, but may also arise as a result of differences in sex hormone profiles and fat distribution. From a clinical perspective, sex‐related differences in biomarker levels may affect the objectivity of biomarkers in HF management because what is considered to be ‘normal’ in one sex may not be so in the other. The objectives of this review are, therefore: (i) to examine the sex‐specific dynamics of clinically relevant HF biomarkers in the general population, as well as in HF patients; (ii) to discuss the overlap between sex‐related and obesity‐related effects, and (iii) to identify knowledge gaps to stimulate research on sex‐related differences in HF.

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“…It is reported that sustained weight maintenance after weight loss improved cardiovascular mortality, however rebound exacerbated them in diabetic patients [22]. It is also reported that sustained high concentrations of blood osteopontin are poor prognostic factors such as cardiovascular disease, kidney disease and all-cause mortality [13][23]. The reduction in osteopontin concentration due to weight maintenance after weight loss may contribute to the improvement of prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…Constant production of osteopontin by these T cells causes chronic inflammation and/or pathological tissue remodeling [8] [10] [11]. An epidemiological study showed that the blood level of osteopontin was correlated with the prevalence of aging-related diseases such as cardiovascular disease and cardiac failure [13]. These osteopontin-producing T cells that are characterized by increased expression of programmed death-1 (PD-1).…”

Section: Introductionmentioning

confidence: 99%

Influence of long term administration of tofogliflozin on chronic inflammation of visceral adipose tissue in mice with obesity induced by a high-fat diet

et al. 2019

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We previously found that senescence of cluster of differentiation 4 (CD4) T cells is accelerated in the visceral adipose tissue (VAT) of mice with diet-induced obesity (DIO) due to a high-fat diet (HFD), and that these senescent-associated T cells cause chronic inflammation of visceral adipose tissue through secretion of osteopontin, provoking systemic insulin resistance. In this study, we examined whether the development of chronic inflammation and senescence-associated T cells in VAT of DIO mice was improved by long-term weight loss after switching to normal chow (NC) or by administration of a sodium glucose cotransporter 2 inhibitor (tofogliflozin). Wild-type mice were fed an HFD for 26 weeks from 4 weeks old. At 30 weeks of age, half of these DIO mice were switched to NC with or without 0.005% tofogliflozin for 38 weeks. The other mice remained on the HFD with or without 0.005% tofogliflozin for 38 weeks. When DIO mice were switched to NC, their weight decreased to that of mice kept on NC since weaning. After 38 weeks (68 weeks of age), chronic inflammation of the VAT subsided with disappearance of senescence-associated T cells. In the HFD groups, the carbohydrate intake per mouse was half or less of that in the NC group, and urinary glucose excretion by the effect of tofogliflozin was lower in the HFD mice than in the NC mice. Mice that remained on the HFD showed no improvement in chronic inflammation in VAT, possibly because urinary glucose excretion was not sufficiently promoted by tofogliflozin due to the low carbohydrate intake. Thus, no improvement in glucose metabolism or weight loss was observed in these mice.

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Plasma Osteopontin Levels and Adverse Cardiovascular Outcomes in the PEACE Trial

Cited by 38 publications

References 25 publications

The rs1126616 Single Nucleotide Polymorphism of the Osteopontin Gene Is Independently Associated with Cardiovascular Events in a Chronic Kidney Disease Cohort

The rs1126616 Single Nucleotide Polymorphism of the Osteopontin Gene Is Independently Associated with Cardiovascular Events in a Chronic Kidney Disease Cohort

Sex‐related differences in contemporary biomarkers for heart failure: a review

Influence of long term administration of tofogliflozin on chronic inflammation of visceral adipose tissue in mice with obesity induced by a high-fat diet

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