Infections in Peripheral Arterial

Disease
Peripheral vascular disease (PVD), also known as peripheral artery disease
(PAD) or peripheral artery occlusive disease (PAOD), includes all diseases
caused by the obstruction of large arteries in the arms and legs. PVD can
result from atherosclerosis, inflammatory processes leading to stenosis, an
embolism or thrombus formation. It causes either acute or chronic ischemia
(lack of blood supply), typically of the legs.
Chlamydia pneumoniae DNA in the arterial wall of patients with peripheral
vascular disease. J Gutierrez, J Linares-Palomino, C Lopez-Espada, M
Rodriguez, E Ros, G Piedrola, MC del Maroto. Infection 2001
Aug;29(4):196-200. 71 PAOD patients vs. 50 varicose controls, p< 0.0001.
Gutierrez - Infection 2001 abstract / PubMed
Gutierrez / Doctor's Guide News 2001
Cystatin C and incident peripheral arterial disease events in the elderly:
results from the Cardiovascular Health Study. AM O'Hare, AB Newman, R Katz,
LF Fried, CO Stehman-Breen, SL Seliger, DS Siscovick, MG Shlipak. Arch
Intern Med 2005 Dec 12-26;165(22):2666-2670. "The association of cystatin
C, a novel marker of renal function, with risk for developing complications
related to peripheral arterial disease (PAD) has not been examined.
METHODS: We evaluated the hypothesis that a high cystatin C concentration
is independently associated with future PAD events among 4025 participants
in the Cardiovascular Health Study who underwent serum cystatin C
measurement at the 1992-1993 visit and who did not have PAD at baseline.
The association of cystatin C quintiles with time to first lower-extremity PAD
procedure (bypass surgery, angioplasty, or amputation) was evaluated using
multivariable proportional hazards models. Secondary analyses were
conducted using quintiles of serum creatinine level and estimated glomerular
filtration rate (eGFR). RESULTS: The annualized risk of undergoing a
procedure for PAD was 0.43% per year among participants in the highest
cystatin C quintile (>1.27 mg/L) compared with 0.21% per year or less in all
other quintiles. After multivariable adjustment for known risk factors for PAD,
elevated cystatin C levels remained associated with the outcome (hazard ratio,
2.5 for highest vs lowest quintile of cystatin C, 95% confidence interval,
1.2-5.1). The highest quintiles of serum creatinine level and eGFR were not
associated with future PAD events in either unadjusted or adjusted analyses.
CONCLUSION: Elevated concentrations of cystatin C were independently
predictive of incident PAD events among community-dwelling elderly
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patients."
O'Hare / Arch Intern Med 2005 full article
[Role of chronic infection and heat shock proteins in peripheral arterial
disease]. M Rabczyski, R Adamiec. Przegl Lek 2007;64(6):419-422. 31
patients with peripheral arterial disease or with diabetic macroangiopathy, 11
healthy volunteers. "Statistic analysis showed anti-C. pneumoniae IgG (p<
0.025) and anti-CMV IgG (p<0.0157) antibodies were signicantly more
frequent in both study groups in comparison with healthy controls. Antibodie
levels were also found signicantly higher than in controls. Mean
concentration of anti-C. pneumoniae IgG in the study group was 69.67574 vs.
18.59722 [AU/ml] in the control group (p<0.01). Analogical anti CMV IgG
levels in the study group were 337.6516 vs 121.3778 [AU/ml] in controls
(p<0.025). Similar changes in antibody concentration were noticed for the C.
pneumoniae IgA index. 0.835258 vs. 0.176333 (p< 0.005). Antibodies against
HSP 60/65 were present in signicantly higher titre (p<0.005). No signicant
dierences in antibody levels were detected beteween groups I and II. The
positive correlation between anti-C. pneumoniae Ig A (r=0.3910; p<0.03) and
anti HSP 60/65 antibodies titre, as well as anti-C. pneumoniae Ig G (r= 0.7151;
p<0.00009) and anti HSP 60/65 speaks for the heat shock protein involvement
in atherosclerotic plaque development."
Rabczyski - Przegl Lek 2007 abstract / PubMed
[Clinical Summary] Symptomatic peripheral arterial disease in women:
nontraditional biomarkers of elevated risk. AD Pradhan, S Shrivastava, NR
Cook, N Rifai, MA Creager, PM Ridker. Circulation 2008 Feb
12;117(6):823-831. 12.3-year prospective study of 27,935 US female health
professionals > or = 45 years of age without diagnosed vascular disease at
baseline. sICAM-1 (adjusted HR, 4.0; 95% confidence interval, 1.9 to 8.6).
"Findings pertaining to novel biomarkers provide clinical confirmation of a
prominent role of endothelial activation and leukocyte recruitment in lower-
extremity arterial disease."
Pradhan - Circulation 2008 abstract / PubMed
Periodontitis may increase the risk of peripheral arterial disease. YW Chen, M
Umeda, T Nagasawa, Y Takeuchi, Y Huang, Y Inoue, T Iwai, Y Izumi, I
Ishikawa. Eur J Vasc Endovasc Surg 2008 Feb;35(2):153-158. 25 patients with
aorto-iliac and/or femoro-popliteal occlusive disease and 32 generally healthy
controls. PCR was used to identify Porphyromonas gingivalis, Treponema
denticola, Actinobacillus actinomycetemcomitans, Prevotella intermedia,
Cytomegalovirus (CMV), Chlamydia pneumoniae, and Helicobacter pylori in
tissue specimens, and serum IgG titres against the four bacteria were
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measured. "Periodontopathic bacteria were detected in 13/25 (52%)
atherosclerotic specimens. CMV or C. pneumoniae was detected in 1/25 (4%)
specimens; H. pylori was not detected from any of these specimens. Fontaine
grade III or IV patients showed higher detection frequency of P. gingivalis
than Fontaine grade II patients (57.1% vs 22.2%, P=0.09). After adjusting for
age, gender, diabetes and smoking, periodontitis increased 5-fold the risk of
having PAD (OR 5.45).... This association could result from the increased
concentration of serum inflammatory cytokines in those with periodontitis."
Chen - Eur J Vasc Endovasc Surg 2008 / PubMed
Markers of Chlamydia pneumoniae and human cytomegalovirus infection in
patients with chronic peripheral vascular disease and their relation to
inflammation, endothelial dysfunction and changes in lipid metabolism. PJ
Kraml, K Roubalov, M Bulvas, Z Sommerov, J PotoCkov, V Mandys, M Andel.
Folia Microbiol (Praha) 2008;53(6):551-557. "CPN genome was detected in 9
(47.4 %) patients by at least one PCR method. Serological markers of acute
CPN infection were found in 5 (26.3 %) subjects; each of them showed also
positivity in at least one of the PCR methods... Patients with laboratory markers
of acute CPN infection exhibited more pronounced alterations in lipid
metabolism and endothelial dysfunction."
Kraml - Folia Microbiol (Praha) 2008 abstract / PubMed
Cystatin C--a marker of peripheral atherosclerotic disease? J Arpegrd, J
Ostergren, U de Faire, LO Hansson, P Svensson. Atherosclerosis 2008
Aug;199(2):397-401. "Blood samples were analysed for serum Cystatin C, IL6,
CRP and creatinine in 103 males with peripheral arterial disease (PAD) and 96
controls matched for age and sex. "Cystatin C-concentration was higher in
PAD-patients compared to controls; 1.09+/-0.40 vs. 0.95+/-0.17 mg/L
(p<0.01). There was no difference in CCr; 81+/-27 vs. 82+/-22 mL/min or
eGFR; 76+/-21 vs. 79+/-14 mL/min. Cystatin C correlated to CCr, logIL-6 and
logCRP in both patients (r=-0.60, p<0.001), (r=0.35, p<0.001) and (r=0.30,
p<0.01) and controls (-0.44, p<0.001), (0.38, p<0.001) and (r=0.32, p<0.01),
respectively. In an analysis of covariance, corrected for difference in eGFR,
Cystatin C remained higher in PAD-patients compared to controls; 1.09 (C.I.
1.04-1.14) vs. 0.96 (C.I. 0.90-1.01). CONCLUSION: Cystatin C-concentration,
corrected for differences in eGFR, IL-6 and CRP values, is higher in
PAD-patients compared to controls. Our finding suggests that Cystatin C may
be an independent marker of atherosclerotic disease apart from its relation to
kidney function."
Arpegrd - Atherosclerosis 2008 abstract / PubMed
A biomarker panel for peripheral arterial disease. ET Fung, AM Wilson, F
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Zhang, N Harris, KA Edwards, JW Olin, JP Cooke. Vasc Med 2008
Aug;13(3):217-24. 197 individuals with both coronary artery disease and
peripheral arterial disease; 81 with CAD only; and 262 with no
hemodynamically significant disease. "Among the plasma markers tested, beta
2 microglobulin (beta2M) and cystatin C had the highest correlation with ABI
[ankle-brachial index], and higher than any of the conventional risk
factors of age, smoking status, and diabetes status. A biomarker panel score
derived from beta2M, cystatin C, hsCRP, and glucose had an increased
association with PAD status (OR = 12.4, 95% confidence interval (CI) 6.6-23.5
for highest vs lowest quartile), which was still significant after adjusting for
known risk factors (OR = 7.3, 95% CI 3.6-14.9 for highest vs lowest quartile)."
Fung - Vasc Med 2008 abstract / PubMed
The human protease inhibitor cystatin C is an activating cofactor for the
streptococcal cysteine protease IdeS. B Vincents, R Vindebro, M Abrahamson,
U von Pawel-Rammingen. Chem Biol 2008 Sep 22;15(9):960-968. "Human
cystatin C is considered the physiologically most important inhibitor of
endogenous papain-like cysteine proteases. We present here an unexpected
function of cystatin C. Instead of acting as an inhibitor, cystatin C acts as a
facultative, endogenous cofactor for the papain-like IgG-cleaving enzyme IdeS
of the human pathogen Streptococcus pyogenes. IdeS activity is not dependent
on cystatin C, but is significantly enhanced in the presence of cystatin C. We
report a protease inhibitor that accelerates the activity of its putative target
protease and a unique example of how a host protease inhibitor is "hijacked"
by a bacterial protease to increase its activity. This finding has important
implications for the view on protease-inhibitor interactions, and is relevant to
consider in the therapeutic use of protease inhibitors."
Vincents - Chem Biol 2008 abstract / PubMed
[Comment re Vincents] Friend or foe? Turning a host defense protein into a
pathogen's accomplice. A Shen, M Bogyo. Chem Biol 2008 Sep
22;15(9):879-880. "Cystatins are cysteine protease inhibitors that are at the
front-line of defense against pathogens that secrete proteases as virulence
factors. In this issue, Vincents et al. (2008) reveal how the bacterial protease
IdeS from Streptococcus pyogenes hijacks normal cystatin C function to
convert it into a cofactor that enhances proteolytic destruction of host-defense
antibodies."
Shen - Chem Biol 2008 abstract / PubMed
Kidney function estimated from serum creatinine and cystatin C and peripheral
arterial disease in NHANES 1999-2002. E Selvin, A Kttgen, J Coresh. Eur
Heart J 2009 Aug;30(15):1918-1925. 3089 subjects. "Glomerular filtration
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rate estimated using cystatin C was more strongly associated with PAD
compared with eGFR using serum creatinine before and after multivariable
adjustment. Further, after adjustment for cystatin C, kidney function based on
serum creatinine was no longer significantly associated with PAD. However,
cystatin C remained significantly associated with PAD even after adjustment
for GFR estimated by serum creatinine. Compared with optimal kidney function
(eGFR(serum creatinine) >or=60, eGFR(cystatin C) >90), the odds ratio for
PAD was 3.11 (95% confidence interval 1.26-7.64) for preclinical CKD
(eGFR(serum creatinine) >or=60, eGFR(cystatin C) <76.7) and 5.07
(3.01-8.52) for 'confirmed' CKD (eGFR(serum creatinine) <60, eGFR(cystatin
C) <60)."
Selvin - Eur Heart J 2009 abstract / PubMed
White blood cell count predicts all-cause mortality in patients with suspected
peripheral arterial disease. FA Arain, M Khaleghi, KR Bailey, BD Lahr, TW
Rooke, IJ Kullo. Am J Med 2009 Sep;122(9):874.e1-7. 56 deaths / 242 patients.
"Patients in the top tertile of WBC count and CRP level had a relative risk of
mortality of 3.37 (confidence interval [CI], 1.56-7.27) and 2.12 (CI, 0.97-4.62),
respectively. However, only the WBC count contributed incrementally to
prediction of mortality. Inferences were similar when analyses were limited to
patients with peripheral arterial disease (ABI<0.9, n = 114)."
Arain - Am J Med 2009 abstract / PubMed
Infections in Buerger's Disease
Buerger's disease (thromboangiitis obliterans) "is dierent from Peripheral
Arterial Disease or PAD, because it is not caused by atherosclerosis (plaque)
buildup that causes a narrowing of the artery. Instead TAO is caused by
inammation of the artery wall, along with the development of clots in the
small and medium sized arteries of the arms or legs causing the arteries to
become blocked. Without blood ow below the inamed artery or clots, the
ngers, toes, and skin tissue do not receive adequate blood. This usually leads
to enormous pain at rest or with exercise, plus sores may develop and may be
slow to heal." (Buergers Disease : What is it? Vascular Disease Foundation,
accessed 3/9/09.)
Oral bacteria in the occluded arteries of patients with Buerger disease. T Iwai,
Y Inoue, M Umeda, Y Huang, N Kurihara, M Koike, I Ishikawa. J Vasc Surg
2005 Jul;42(1):107-115. "Fouteen male patients with a smoking history who
had developed characteristics of Buerger disease before the age of 50 years
were included in this study. Occluded arteries, including superficial femoral (n
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= 4), popliteal (n = 2), anterior tibial (n = 4), and posterior tibial (n = 4)
arteries, were removed and studied. A periodontist performed a periodontal
examination on each patient and collected dental plaque and saliva samples
from them at the same time. The polymerase chain reaction method was
applied to detect whether seven species of periodontal bacteria--
Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola,
Campylobacter rectus, Actinobacillus actinomycetemcomitans, Prevotella
intermedia , and Prevotella nigrescens--were present in the occluded arteries
and oral samples. In addition, arterial specimens from seven control patients
were examined by polymerase chain reaction analysis. RESULTS: DNA of oral
bacteria was detected in 13 of 14 arterial samples and all oral samples of
patients with Buerger disease. Treponema denticola was found in 12 arterial
and all oral samples. Campylobacter rectus, Porphyromonas gingivalis,
Prevotella intermedia, Tannerella forsythensis, and Prevotella nigrescens were
found in 14% to 43% of the arterial samples and 71% to 100% of the oral
samples. A pathologic examination revealed that arterial specimens showed the
characteristics of an intermediate-chronic-stage or chronic-stage lesion of
Buerger disease. All 14 patients with Buerger disease had moderate to severe
periodontitis. None of the control arterial samples was positive for periodontal
bacteria. CONCLUSIONS: This is the first study to identify oral
microorganisms in the lesions of Buerger disease. Our findings suggest a
possible etiologic link between Buerger disease and chronic infections such as
oral bacterial infections."
Iwai - J Vasc Surg 2005 abstract / PubMed
See Also:
The Lie That Secondhand Smoke Causes Heart Disease
Chlamydia pneumoniae causes heart disease
CMV Causes Rheumatoid Arthritis
CMV Impairs Immunity
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