Markers of inflammation in relation to long-term cardiovascular mortality in patients with lower-extremity peripheral arterial disease

Urbonavičienė, Gražina; Frystyk, Jan; Flyvbjerg, Allan; Urbonavičius, Sigitas; Henneberg, E W; Lindholt, Jes Sanddal

doi:10.1016/j.ijcard.2011.03.030

Cited by 35 publications

(36 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although PAD without CLI and PAD with CLI likely share some of the proinflammatory profiles engendered by obesity, CLI may be the result of an accelerated or dose‐dependent inflammatory pathway that occurs to a higher burden of obesity 20, 21. Indeed, compared to patients with PAD without CLI, patients with PAD with CLI have been found to have higher circulating levels of inflammatory markers, including C‐reactive protein, several cytokines, and α‐defensin 10. Consequently, the association of obesity with PAD with CLI may be stronger than the association of obesity with PAD without CLI simply because CLI is a more severe form of PAD.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the association between obesity and CLI has not been reported previously. Given that CLI has some pathophysiological aspects that are unique from PAD, such as higher levels of inflammation and potential nonvascular contributions from nonhealing ulcers,10, 11 we hypothesized that any association between obesity and PAD would be magnified in CLI.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Associations of Obesity With Incident Hospitalization Related to Peripheral Artery Disease and Critical Limb Ischemia in the ARIC Study

Hicks

Yang

Ndumele

et al. 2018

JAHA

View full text Add to dashboard Cite

BackgroundWe conducted an analysis of data from the ARIC (Atherosclerosis Risk in Communities) study to assess the independent association of obesity with peripheral artery disease (PAD) and critical limb ischemia (CLI).Methods and ResultsAll black and white ARIC participants without prevalent PAD at baseline (1987–1989) were included. We used Cox proportional hazards models adjusting for potential confounders and then potential mediators to quantify the association between body mass index (BMI) and incident hospitalizations related to PAD without CLI and with CLI through 2013. Our analysis included 13 988 men and women followed for a median of 24 years. Incident PAD without CLI and PAD with CLI occurred in 373 and 201 participants, respectively. After adjusting for potential confounders, higher BMI at baseline was associated with increased risk of PAD without CLI when BMI was modeled continuously (hazard ratio per 1‐SD increment in BMI: 1.23; 95% confidence interval, 1.11–1.37) and with PAD with CLI regardless of whether BMI was modeled categorically (P<0.05) or continuously (hazard ratio per 1‐SD increment in BMI: 1.51; 95% confidence interval, 1.34–1.69). The associations of BMI with PAD without CLI and with CLI were attenuated after further accounting for potential mediators but remained significant for PAD with CLI when BMI was linearly modeled (hazard ratio per 1‐SD increment in BMI: 1.19; 95% confidence interval, 1.04–1.36). The positive association between BMI and PAD with CLI was stronger than the association between BMI and PAD without CLI for all models (P<0.001).ConclusionsIn the general population, BMI is positively associated with incident hospitalized PAD after adjusting for potential confounders, particularly its most severe form of CLI. Maintaining an optimal weight, in addition to controlling other cardiovascular risk factors, may play a role in reducing risk of PAD with CLI.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Associations of Obesity With Incident Hospitalization Related to Peripheral Artery Disease and Critical Limb Ischemia in the ARIC Study

Hicks

Yang

Ndumele

et al. 2018

JAHA

View full text Add to dashboard Cite

show abstract

“…Increased plasma levels of ␣-defensins are associated with acute myocardial infarction (15), cardiovascular mortality in patients with peripheral arterial disease (16), and chronic heart failure (17). ␣-Defensins stimulate foam cell formation (18), promote plaque instability (16), regulate aortic contractility, and acti-* This work was supported by National Institutes of Health Grants HL077760, HL805429, HL82545, and HL123912 and by Grant 930/04 from the Israeli Science Foundation. The authors declare that they have no conflicts of interest with the contents of this article.…”

mentioning

confidence: 99%

α-Defensins Induce a Post-translational Modification of Low Density Lipoprotein (LDL) That Promotes Atherosclerosis at Normal Levels of Plasma Cholesterol

Abu‐Fanne¹,

Maraga²,

Abd‐Elrahman

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Approximately one-half of the patients who develop clinical atherosclerosis have normal or only modest elevations in plasma lipids, indicating that additional mechanisms contribute to pathogenesis. In view of increasing evidence that inflammation contributes to atherogenesis, we studied the effect of human neutrophil ␣-defensins on low density lipoprotein (LDL) trafficking, metabolism, vascular deposition, and atherogenesis using transgenic mice expressing human ␣-defensins in their polymorphonuclear leukocytes (Def ؉/؉ ). Accelerated Def Atherosclerosis and its thrombotic sequel, "atherothrombosis," are likely to remain the predominant cause of death in "developed" countries for decades to come. The etiology of this syndrome is multifactorial, and current predictors provide an incomplete estimate of the risk and opportunity for intervention. In a pooled analysis of over 87,000 persons with diagnosed coronary heart disease, one in five lacked any of the conventional risk factors: hypertension, smoking, high cholesterol, or diabetes (1). Furthermore, half of all cardiovascular events occur in patients with normal lipid levels (2). These data reveal the need to identify and mitigate as yet undescribed, but clinically relevant, risk factors for cardiovascular disease beyond those targeted in current practice.This problem is compounded by the lack of animal models that closely simulate human disease. Animal models used to study atherosclerosis, including its hyperlipidemic (3, 4) and inflammatory (5) components, are often characterized by striking elevations in plasma cholesterol, reaching plasma concentrations of 1500 -2200 mg/dl in LDLR Ϫ/Ϫ and 400 -450 mg/dl in ApoE Ϫ/Ϫ mice fed a high fat diet (3, 4), and most of the cholesterol is found in the VLDL fraction (3, 4). Neither these levels of lipids nor this distribution of lipoproteins is representative of findings in the vast majority of patients with atherosclerosis. Thus, there continues to be a need for new models to identify novel risk factors and novel approaches to intervention.We have identified human ␣-defensins 1-4, also known as human neutrophil peptides (HNPs), 2 as potentially having a role in the development of atherosclerosis. ␣-Defensins are antimicrobial proteins that constitute ϳ5% of the total protein in polymorphonuclear leukocytes (PMNs). ␣-Defensins are released from a subset of azurophilic granules when the PMNs are activated by a variety of agonists (6, 7). ␣-Defensins are abundant in human atherosclerotic coronary and carotid arteries (8, 9), and there is a significant correlation between the deposition of ␣-defensins in skin tissue and the severity of coronary artery disease (10). ␣-Defensins inhibit the degradation of low density lipoprotein (LDL) and Lp(a) by vascular cells (11), increase their binding and retention in extracellular matrix (12), and inhibit tissue-type plasminogen activator (tPA)-mediated fibrinolysis (13, 14).These observations have been confirmed and extended by others. Increased plasma levels of ␣-defensins are assoc...

show abstract

“…In a group of type-1 diabetic patients, with a 10-year-follow-up-period of cardiovascular end-points, elevated baseline plasma -defensin levels were an independent predictor for cardiovascular morbidity and mortality (Joseph et al, 2008). In a recent study, the risk of cardiovascular mortality was significantly increased with elevated plasma -defensin levels in patients admitted for elective lower extremity artery surgery (Urbonaviciene et al, 2011). Surprisingly, patients with high -defensin levels combined with high hs-CRP levels had a five time increased risk of cardiovascular death compared to patients in whom only one or none of the peptides was elevated.…”

Section: Possible Link Between -Defensins and Ihdmentioning

confidence: 99%

Inflammatory Biomarkers in Ischemic Heart Disease

Bjerre¹

2012

Novel Strategies in Ischemic Heart Disease

View full text Add to dashboard Cite

Markers of inflammation in relation to long-term cardiovascular mortality in patients with lower-extremity peripheral arterial disease

Cited by 35 publications

References 34 publications

Associations of Obesity With Incident Hospitalization Related to Peripheral Artery Disease and Critical Limb Ischemia in the ARIC Study

Associations of Obesity With Incident Hospitalization Related to Peripheral Artery Disease and Critical Limb Ischemia in the ARIC Study

α-Defensins Induce a Post-translational Modification of Low Density Lipoprotein (LDL) That Promotes Atherosclerosis at Normal Levels of Plasma Cholesterol

Inflammatory Biomarkers in Ischemic Heart Disease

Contact Info

Product

Resources

About