Secondary Prevention of Atherosclerosis Through Chlamydia pneumoniae Eradication (SPACE Trial): A Randomised Clinical Trial in Patients with Peripheral Arterial Disease

Vainas, Tryfon; Stassen, Frank R. M.; Schurink, Geert-Willem; Tordoir, Jan H.M.; Welten, R.J.Th.J.; Akker, L.H.J.M. van den; Kurvers, H. A. J. M.; Bruggeman, Cathrien A.; Kitslaar, Peter J.E.H.M.

doi:10.1016/j.ejvs.2005.01.001

Cited by 29 publications

(15 citation statements)

References 53 publications

(74 reference statements)

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“…[175][176][177][178] Four studies enrolled Ϸ1300 patients; 3 of the 4 studies demonstrated no benefit in peripheral artery disease-related outcomes among antibiotic recipients. In the absence of evidence supporting improved outcomes, there has been no recommendation from professional societies for antibiotic therapy in the absence of sepsis for patients with MI, unstable angina, peripheral artery disease, or asymptomatic coronary artery disease.…”

Section: Direct Mechanisms: Bacteremia and Vascular Infection By Perimentioning

confidence: 99%

Periodontal Disease and Atherosclerotic Vascular Disease: Does the Evidence Support an Independent Association?

Lockhart

Bolger²,

Papapanou³

et al. 2012

Circulation

890

814

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Abstract-A link between oral health and cardiovascular disease has been proposed for more than a century. Recently, concern about possible links between periodontal disease (PD) and atherosclerotic vascular disease (ASVD) has intensified and is driving an active field of investigation into possible association and causality. The 2 disorders share several common risk factors, including cigarette smoking, age, and diabetes mellitus. Patients and providers are increasingly presented with claims that PD treatment strategies offer ASVD protection; these claims are often endorsed by professional and industrial stakeholders. The focus of this review is to assess whether available data support an independent association between ASVD and PD and whether PD treatment might modify ASVD risks or outcomes. It also presents mechanistic details of both PD and ASVD relevant to this topic. The correlation of PD with ASVD outcomes and surrogate markers is discussed, as well as the correlation of response to PD therapy with ASVD event rates. Methodological issues that complicate studies of this association are outlined, with an emphasis on the terms and metrics that would be applicable in future studies. Observational studies to date support an association between PD and ASVD independent of known confounders. They do not, however, support a causative relationship. Although periodontal interventions result in a reduction in systemic inflammation and endothelial dysfunction in short-term studies, there is no evidence that they prevent ASVD or modify its outcomes. (Circulation. 2012;125:2520-2544.)

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Section: Direct Mechanisms: Bacteremia and Vascular Infection By Perimentioning

confidence: 99%

Periodontal Disease and Atherosclerotic Vascular Disease: Does the Evidence Support an Independent Association?

Lockhart

Bolger²,

Papapanou³

et al. 2012

Circulation

890

814

View full text Add to dashboard Cite

show abstract

“…Intriguingly the results of the large randomized placebo-controlled clinical trials did not support the infectious agent hypothesis, consequently it was largely concluded that C. pneumoniae was not an important cofactor in AS and that efforts to treat C. pneumoniae with antimicrobials could not alter disease outcomes [40–42]. However, the following observations could not be ignored.…”

Section: Endothelial Response To Injurymentioning

confidence: 99%

Bacterial Invasion of Vascular Cell Types: Vascular Infectology and Atherogenesis

Kozarov

2011

Future Cardiol.

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To portray the chronic inflammation in atherosclerosis, leukocytic cell types involved in the immune response to invading pathogens are often the focus. However, atherogenesis is a complex pathological deterioration of the arterial walls, where vascular cell types are participants with regards to deterioration and disease. Since other recent reviews have detailed the role of both the innate and adaptive immune response in atherosclerosis, herein we will summarize the latest developments regarding the association of bacteria with vascular cell types: infections as a risk factor for atherosclerosis; bacterial invasion of vascular cell types; the atherogenic sequelae of bacterial presence such as endothelial activation and blood clotting; and the identification of the species that are able to colonize this niche. The evidence of a polybacterial infectious component of the atheromatous lesions opens the doors for exploration of the new field of vascular infectology and for the study of atherosclerosis microbiome.

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“…Thus, the data presented here fit a model of systemic infection with an intermediate step where bacterial strains, once in the circulation, are internalized by phagocytic cells, at which stage selected species avoid immediate killing and spread and colonize distant sites. Bacterial internalization may also account for the resistance to antibiotic treatment observed in large randomized placebo-controlled clinical trials for the secondary prevention of cardiovascular events 32) . To address the study limitations, the true causative role of this species in vascular pathologies using in vitro and in vivo models must be further investigated.…”

Section: Persistence In Phagocytesmentioning

confidence: 99%

Cultivation of Enterobacter Hormaechei from Human Atherosclerotic Tissue

Rafferty

Dolgilevich

Kalachikov

et al. 2011

JAT

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Aim:To determine whether culturable bacterial strains are present in human atheromatous tissue and to investigate their properties using culture, quantitative PCR, metagenomic screening, genomic and biochemical methods. Methods: We analyzed femoral atherosclerotic plaque and five pairs of diseased and healthy arterial tissue for the presence of culturable bacteria using cell cultures and genomic analysis. Results: Gram negative aerobic bacilli were cultivated from the plaque tissue. Ribosomal 16S DNA amplification and sequencing identified the isolates as Enterobacter hormaechei. The isolate was resistant to ampicillin, cefazolin, and erythromycin. A circular 10kb plasmid was isolated from the strain. Antibiotic protection assays of the isolate demonstrated invasive ability in a human monocytic cell line. To extend the study, five matched pairs of diseased and healthy aortic tissue were analyzed via quantitative PCR. Eubacterial 16S rDNA was detected in all specimens, however, E. hormaechei DNA was detected in surprisingly high numbers in two of the diseased tissues only. Conclusions: While it is well documented that inflammation is an important risk factor for vascular pathophysiology, the association of bacteria with atherosclerosis has not been clearly established, in large part due to the inability to isolate live bacteria from atheromatous tissue. This is the first study providing direct evidence of Enterobacter spp. associated with atheromatous tissues. The data suggest that chronic infection with bacteria may be an under-reported etiologic factor in vascular pathogenesis. Importantly, characterization of the clinical isolate supports a model of atherogenesis where systemic dissemination of bacteria to atherosclerotic sites may occur via internalization in phagocytic cells. J Atheroscler Thromb, 2011; 18:72-81.

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Secondary Prevention of Atherosclerosis Through Chlamydia pneumoniae Eradication (SPACE Trial): A Randomised Clinical Trial in Patients with Peripheral Arterial Disease

Abstract: A short-term course of azithromycin offers no benefits for survival or ankle pressure in PAD-patients.

Cited by 29 publications

References 53 publications

Periodontal Disease and Atherosclerotic Vascular Disease: Does the Evidence Support an Independent Association?

Periodontal Disease and Atherosclerotic Vascular Disease: Does the Evidence Support an Independent Association?

Bacterial Invasion of Vascular Cell Types: Vascular Infectology and Atherogenesis

Cultivation of Enterobacter Hormaechei from Human Atherosclerotic Tissue

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