Association between cerebral infaction and increased serum
antibody levels in young adults. J Syrjanen, VV Valtonen, M Iivanainen,
T Hovi, M Malkamadi, PH Makela. Acta Neurol Scand 1986
Mar;73(3):273-278. "Increased antibody levels against several bacteria
were found in 15 of the 34 stroke patients (44%) under the age of 45
years, but in only six of the 68 controls (9%) (p less than 0.001).
Based on the serologic data, the most common preceding infections were
streptococcal, staphylococcal, and enterobacterial. There was no
relationship between viral antibodies and cerebral infarction. When the
clinical history of the patients was also taken into consideration,
stroke was found to be associated with a recent infection in 68% of the
patients, as compared with 26% for the second most common risk factor,
Preceding infection as an important risk factor for ischaemic
infarction in young and middle aged patients. J Syrjanen, VV Valtonen,
M Iivanainen, M Kaste, JK Huttunen. Br Med J (Clin Res Ed) 1988 Apr
23;296(6630):1156-1160. 54 consecutive patients under 50 years of age
with brain infarction and 54 randomly selected controls from the
community matched for sex and age. "Febrile infection was found in
patients during the month before the brain infarction significantly
more often than in controls one month before their examination (19 patients v three controls; estimated relative risk 9-0 (95% confidence interval 2-2 to 80.0))."
Anticardiolipin response and its association with infections
young and middle-aged patients with cerebral infarction. J Syrjanen, O
Vaarala, M Iivanainen, T Palosuo, VV Valtonen, K Aho. Acta Neurol Scand
1988 Nov;78(5):381-386. "To study further our recent observation on the
association between infection and cerebral infarction in young and
middle-aged patients we measured anticardiolipin response (IgG, IgM,
IgA) in paired sera from 54 consecutive patients with cerebral
infarction under 50 years of age and in 54 community controls matched
for sex and age. An elevated IgG-class ACA level or a significant
change in level as observed in 2 serial samples occurred in 15 (28%)
patients, but in only 4 (7%) controls (P less than 0.02)."
Dental infections in association with cerebral infarctions in
and middle-aged men. J Syrjanen, J Peltola, V Valtonen, M Iivanainen, M
Kaste, JK Huttunen. J Intern Med 1989 Mar;225(3):179-184. 40 patients
with ischaemic cerebral infarction under the age of 50, and 40 randomly
selected community controls matched for sex and age. "If severe dental
infections were combined with other probable bacterial infections there
were altogether 16 patients (40%) but only two controls (5%) who had
suffered from a probable bacterial infection within 1 month or at the
time of the stroke or when examined as a control (P less than 0.01)."
Infection as a risk factor for infarction and atherosclerosis. VV Valtonen. Ann Med 1991;23(5):539-543. (Review).Valtonen - Ann Med 1991 abstract / PubMed
Immunohematologic characteristics of infection-associated
infarction. SF Ameriso, VL Wong, FP Quismorio, M Fisher. Stroke 1991
Aug;22(8):1004-1009. Among 50 consecutive patients, "17 had symptoms of
infection beginning less than or equal to 1 month before the stroke (11
had upper respiratory tract infections, three urinary tract infections,
two subacute bacterial endocarditis, and one pneumonia). Compared with
patients without infection, patients with infection had significant
increases in fibrin D-dimer concentration (5.3 +/- 1.1 versus 4.7 +/-
0.9 log-transformed ng/ml, p less than 0.05) and cardiolipin
immunoreactivity, IgG isotype (1.8 +/- 1.3 versus 1.1 +/- 0.9
log-transformed phospholipid units, p less than 0.04), and, when
studied less than or equal to 2 days after the stroke, increased
fibrinogen levels (459 +/- 126 versus 360 +/- 94 mg/dl, p less than
Infection as a risk factor for cerebral infarction. J Syrjanen. Eur Heart J 1993 Dec;14 Suppl K:17-19. (Review).Syrjanen - Eur Heart J 1993 abstract / PubMed
Cytomegalovirus/herpesvirus and carotid atherosclerosis: the ARIC Study. PD Sorlie, E Adam, SL Melnick, A Folsom, T Skelton, LE Chambless, R Barnes, JL Melnick. J Med Virol 1994 Jan;42(1):33-37. In 340 matched case-control pairs from the Atherosclerosis Risk in Communities (ARIC) Study, "The case-control odds ratio for CMV antibodies was 1.55 (P = .03), for HSV 1.41 (P = .07), and for HSV2 0.91 (P = .63)."Sorlie - J Med Virol 1994 abstract / PubMed
Recent infection as a risk factor for cerebrovascular
Grau, F Buggle, S Heindl, C Steicjhen-Wiehn, T Banerjee, M Maiwald, M
Rohlfs, H Suhr, W Fiehn, H Becher, W Hache. Stroke 1995
Mar;26(3):373-379. 197 patients aged 18 to 80 years with acute
cerebrovascular ischemia and 197 randomly selected controls. "Infection
within 1 week before ictus or examination was significantly more common
among patients (38 of 197) than control subjects (10 of 197; odds ratio
[OR], 4.5; 95% confidence interval [CI], 2.1 to 9.7). Patients more
often had febrile and subfebrile infections (> or = 37.5 degrees
than control subjects (29 of 197 versus 5 of 197; OR, 7.0; 95% CI, 2.5
to 20). Respiratory tract infections were most common in both groups.
Bacterial infections dominated among patients but not among control
subjects. Infection increased the risk for cerebrovascular ischemia in
all age groups; this reached significance for patients aged 51 to 60
and 61 to 70 years."
Prospective relations between Helicobacter pylori infection,
coronary heart disease, and stroke in middle aged men. PH Whincup, MA
Mendall, IJ Perry, DP Strachan, M Walker. Heart 1996 Jun;75(6):568-572.
135 cases of myocardial infarction and 137 cases of stroke occurring
before December 1991 in men aged 40-59 years in 24 British towns, 136
controls. "95 of the myocardial infarction cases (70%) and 93 (68%) of
the stroke cases were seropositive for H pylori compared with 78 (57%)
of the controls (odds ratio for myocardial infarction 1.77, 95%
confidence interval (CI) 1.06 to 2.95, P = 0.03; odds ratio for stroke
1.57, 95% CI 0.95 to 2.60, P = 0.07)."
[Infectious diseases as a cause and risk factor for
ischemia]. AJ Grau, F Buggle, W Hacke. Nervenarzt 1996
Cohort study of cytomegalovirus infection as a risk factor for
carotid intimal-medial thickening, a measure of subclinical
atherosclerosis. FJ Nieto, E Adam, P Sorlie, H Farzadegan, JL Melnick,
GW Comstock, M Szklo. Circulation 1996 Sep 1;94(5):922-927. "CMV
antibody levels were higher among the 19 case subjects who had some
evidence of clinical disease (age-adjusted geometric mean, 7.8) than
among those without clinical disease (age-adjusted geometric mean,
7.3), although the difference was not statistically significant as a
result of the small sample size." CMV antibody levels were lower than
levels observed during 1974.
Impairments of the protein C system and fibrinolysis in
infection-associated stroke. RF Macko, SF Ameriso, A Gruber, JH
Griffin, JA Fernendez, R Barndt, FP Quismorio, JM Weiner, M Fisher.
Stroke 1996 Nov;27(11):2005-2011. 36 patients with acute ischemic
stroke and 81 controls. "We examined the hypothesis that patients with
brain infarction preceded by infection/inflammation within 1 week could
be identified by a distinctive procoagulant laboratory profile
characterized by abnormalities in the protein C system and endogenous
fibrinolysis... The stroke group had a lower mean level of the
circulating antithrombotic enzyme activated protein C (APC)
(4.33±0.34% [log-transformed percentage of control value,
mean±SD]) than community control subjects (4.51±0.27%,
P<.02) or hospitalized neurological patient controls
(4.57±0.31%, P<.005). The lowest circulating APC levels were
found in the stroke group with antecedent infection/inflammation within
1 week preceding index brain infarction (4.23±0.4%, n=12).
Within the stroke group, circulating APC levels were inversely related
to IgG isotype anticardiolipin antibody titers (r=-.55, P<.001).
Only the stroke group with infection/inflammation within 1 week had
elevated plasma C4b binding protein compared with control subjects
(141±61% versus 112±44%, P<.05). Stroke patients with
antecedent infection/inflammation had a distinctively lower ratio of
active tissue plasminogen activator to plasminogen activator inhibitor
(0.11±0.04, n=9) than other stroke patients (0.19±0.06,
n=9, P<.01) and control subjects (0.22±0.16, n=17,
Acute infection as a risk factor for ischemic stroke. LY Bova,
Bornstein, AD Korczyn. Stroke 1996 Dec;27(12):2204-2206. 182 patients
with acute ischemic strokes, versus 194 patients who had strokes at
least six months earlier. "The prevalence of acute infection in the
study group was significantly higher (44193/=24.2%) than in the control
group (19193/=9.7%; odds ratio, 2.93; 95% confidence interval, 1.64 to
5.26; P=.0002) and infection occurred mostly within 1 week before the
IS (41/44). Neither the severity of the IS nor the type of the
infection was significantly different in patients and control subjects."
Association of Chlamydial infection with cerebrovascular
MLJ Wimmer, R Sandmann-Strupp, P Saikku, RL Haberl. Stroke 1996
Dec;27(12):2207-2210. Antibodies to C pneumoniae in 58 consecutive
stroke patients and 52 hospital controls. "Twenty-seven patients
(46.6%) and 12 control subjects (23.1%) had raised IgA titers 1:16
(P=.018). IgG titers 1:32 were measured in 74.1% of the patients and
77% of control subjects (P=.623). Specific IgG antibodies in
circulating immune complexes, which were isolated by polyethylene
glycol precipitation, were elevated 1:8 in 24.1% of the patients and
7.7% of control subjects (P=.047). With the use of a conditional
logistic regression model, the odds ratios were 1.70 (95% confidence
interval [CI], 1.13 to 2.58) for elevated IgA titers, 1.91 (95% CI,
1.06 to 3.47) for the presence of immune complexes, and 1.96 (95% CI,
1.00 to 3.82) for the presence of both factors."
Association between acute cerebrovascular ischemia and chronic
recurrent infection. AJ Grau, F Buggle, C Ziegler, W Schwarz, J Meuser,
A-J Tasman, A Buhler, C Benesch, H Becher, W Hacke. Stroke 1997
Sep;28(9):1724-1729. 166 consecutive patients with acute
cerebrovascular ischemia and in 166 age- and sex-matched nonstroke
neurological patient controls. "Frequent (2 episodes in each of the 2
preceding years) or chronic bronchitis was associated with
cerebrovascular ischemia in age-adjusted multiple logistic regression
analysis (odds ratio, OR, 2.2; 95% confidence interval, CI, 1.04 to
4.6)... In age-adjusted multiple logistic regression analysis with
social status and established vascular risk factors, poor dental status
(TDI) was independently associated with cerebrovascular ischemia (OR,
2.6; 95% CI, 1.18 to 5.7)."
Helicobacter pylori infection: a risk factor for ischaemic
cerebrovascular disease and carotid atheroma. HS Markus, MA Mendall. J
Neurol Neurosurg Psychiatry 1998 Jan;64(1):104-107. 238 patients and
119 controls. "H pylori seropositivity was more common in cases (58.8%
v 44.5%, p=0.01). The odds ratio for cerebrovascular disease associated
with seropositivity was 1.78 (95% confidence interval (95% CI)
1.14-2.77), and this remained significant after controlling for other
risk factors including socioeconomic status (1.63 (95% CI 1.02-2.60). H
pylori seropositivity was associated with large vessel disease (odds
ratio 2.58 (95% CI 1.44-4.63), p=0.001) and lacunar stroke (odds ratio
2.21 (95% CI 1.12-4.38), p=0.02) but not stroke due to cardioembolism
or unknown aetiology (odds ratio 1.16 (95% CI 0.66-2.02), p=0.5)."
Recent bacterial and viral infection is a risk factor for
cerebrovascular ischemia: clinical and biochemical studies. AJ Grau, F
Buggle, H Becher, E Zimmermann, M Spiel, T Fent, M Maiwald, E Werle, M
Zorn, H Hengel, W Hacke. Neurology 1998 Jan;50(1):196-203.166
consecutive patients with acute cerebrovascular ischemia, versus
166 patients hospitalized for nonvascular and noninflammatory
neurologic diseases. "Infection within the preceding week was a risk
factor for cerebrovascular ischemia in univariate (odds ratio [OR] 3.1;
95% confidence interval (CI), 1.57 to 6.1) and age-adjusted multiple
logistic regression analysis (OR 2.9; 95% CI, 1.31 to 6.4). The OR of
recent infection and age were inversely related. Both bacterial and
viral infection contributed to increased risk. Infection elevated the
risk for cardioembolism and tended to increase the risk for
Chlamydia pneumoniae antibody titers are significantly
with acute stroke and transient cerebral ischemia. The West Birmingham
Stroke Project. PJ Cook, D Honeybourne, GYH Lip, DG Beevers, R Wise, P
Davies. Stroke 1998 Feb;29(2):404-410. 176 patients with stroke or
transient cerebral ischemia and 1518 controls. "13.6% of
stroke/transient ischemic attack (TIA) patients and 5.7% of control
subjects had antibody titers suggesting acute C pneumoniae
(re)infection, while 32.4% of stroke/TIA patients and 12.7% of control
subjects had titers suggesting previous infection (P<.05).
Stroke/TIA patients differed from control subjects in their levels of
acute and previous infection, with adjusted odds ratios of 4.2 (95% CI,
2.5 to 7.1) and 4.4 (95% CI, 3.0 to 6.5), respectively."
Role of infection as a risk factor for atherosclerosis,
infarction, and stroke. KJ Mattila, VV Valtonen, MS Nieminen, S
Asikainen. Clin Infect Dis 1998 Mar;26(3):719-734. (Review).
Bacterial infections and atherosclerosis. JB Muhlestein. J Investig Med 1998 Oct;46(8):396-402. (Review).Muhlestein - J Investig Med 1998 abstract / PubMed
Prospective study of herpes simplex virus, cytomegalovirus,
risk of myocardial infarction and stroke. PM Ridker, CH Hennekens, MJ
Stampfer, F Wang. Circulation 1998 Dec 22/29;98(25):2796-2799. 643
patients with first MI in a nested case-control study. "Specifically,
the relative risks for future MI and stroke were 0.94 (95% CI, 0.7 to
1.2) for HSV seropositivity and 0.72 (95% CI, 0.6 to 0.9) for CMV
seropositivity, after adjustment for other cardiovascular risk factors."
Chlamydia pneumoniae but not cytomegalovirus antibodies are
associated with future risk of stroke and cardiovascular disease: a
prospective study in middle-aged to elderly men with treated
hypertension. B Fagerberg, J Gnarpe, H Gnarpe, S Agewall, J Wikstrand.
Stroke 1999 Feb;30(2):299-305. 111 patients in intervention study.
"Elevations of any or both of the IgA or IgG titers to C pneumoniae at
entry or after 3.5 years were found in 84 cases (55%). Of those with
high titers at entry, 97% remained high at the 3.5 year reexamination.
After 6.5 years of follow-up, high titers to C pneumoniae at entry were
associated with an increased risk for future stroke (relative risk
[RR], 8.58; P=0.043; 95% CI, 1.07 to 68.82) and for any cardiovascular
event (RR, 2.69; P=0.042; 95% CI, 1.04 to 6.97)."
Association of cervical artery dissection with recent
Grau, T Brandt, F Buggle, E Orberk, J Mytilineos, E Werle, Conradt, M
Krause, R Winter, W Hacke. Arch Neurol 1999 Jul;56(7):851-856. 43
consecutive patients with acute CAD and 58 consecutive patients younger
than 50 years with acute cerebral ischemia from other causes (control
patients). "Recent infection was more common in patients with CAD
(25/43 [58.1%]) than in control patients (19/58 [32.8%]; P=.01).
Respiratory tract infection was preponderant in both groups. Recent
infection, but not the mechanical factors cough, sneezing, or vomiting,
was independently associated with CAD in multivariate analysis.
Investigation of serum antibodies against Chlamydia pneumoniae, smooth
muscle cells, endothelial cells, collagen types I through IV, and heat
shock protein 65 and assessment of serum alpha1-antitrypsin and HLA did
not contribute to the understanding of the pathogenesis of CAD."
Preceding infection as a risk factor of stroke in the young. D
Nagaraja, R Christopher, M Tripathi, MV Kumar, ER Valli, SA Patil. J
Assoc Physicians India 1999 Jul;47(7):673-675. Sixty consecutive
patients aged 40 years or less. "Evidence of infection was noted in 26
(43.3%) of patients and 6 controls (p < 0.001). History of fever
elicited in 23 patients and 3 controls while 15 patients were febrile
on examination at admission. Signs of local infection was observed in
14 patients and one control. The commonest site of infection was
respiratory tract. Cultures were positive in 11 patients, commonest
being beta haemolytic streptococci in six from throat."
Lack of association of infectious agents with risk of future myocardial infarction and stroke. Definitive evidence disproving the infection/coronary artery disease hypothesis? SE Epstein, J Zhu. Circulation 1999 Sep 28;100(13):1366-1368. (Editorial).Epstein / Circulation 1999 full article
Association of periodontal infections with atherosclerotic and pulmonary diseases. FA Scannapieco, RJ Genco. J Periodontal Res 1999 Oct;34(7):340-345. (Review).Scannapieco - J Periodontal Res 1999 abstract / PubMed
Chlamydia pneumoniae antibodies and high lipoprotein(a) levels
not predict ischemic cerebral infarctions: results from a nested
case-control study in northern Sweden. CA Glader, B Stegmayr, J Boman,
H Stenlund, L Weinehall, G Hallmans, GH Dahlen. Stroke 1999
Oct;30(10):2013-2018. 101 cases, 201 matched controls. "[P]lasma Lp(a)
was unable to predict ischemic cerebral infarctions in either women or
men. The proportion of individuals with positive C pneumoniae-specific
IgG or IgA titers did not differ between cases and controls. Antibody
titers were unable to predict a future stroke. The proportion of
individuals with a positive C pneumoniae IgG titer in combination with
a high Lp(a) level did not differ significantly between cases and
controls... However, selection bias and a recent C pneumoniae epidemic
may have influenced the results."
Multiple infections in carotid atherosclerotic plaques. B
Heart J 1999 Nov;138(5 Pt 2):S534-S536. "Immunostainings for C
pneumoniae, cytomegalovirus, herpes simplex virus-1, P gingivalis, and
S sanguis were positive in the carotid plaques. From 1 to 4 organisms
were found in the same specimen. The micro-organisms were
immunolocalized in plaque shoulders and lymphohistiocytic infiltrate,
associated with ulcer and thrombus formation, and adjacent to areas of
strong labeling for apoptotic bodies."
[Infection, atherosclerosis and acute ischemic cerebrovascular disease]. A Grau, F Buggle. Rev Neurol 1999 Nov 1-15;29(9):847-851. (Review).Grau - Rev Neurol 1999 abstract / PubMed
Association of endotoxemia with carotid atherosclerosis and
cardiovascular disease: prospective results from the Bruneck Study. CJ
Wiedermann, S Kiechl, S Dunzendorfer, P Schratzberger, G Egger, F
Oberhollenzer, J Willeit. J Am Coll Cardiol 1999 Dec;34(7):1975-81.
"Notably, smokers with low endotoxin levels and nonsmokers did not
differ in their atherosclerosis risk, whereas smokers with high levels
almost invariably developed new lesions." [Note the anti-smoker
contortions. What about nonsmokers with high levels? And does this
purport that nonsmokers never develop new lesions?]
Fever and infection soon after ischemic stroke. AJ Grau, F
Schnitzler, M Spiel, C Lichy, W Hacke. J Neurol Sci 1999 Dec
15;171(2):115-120. 119 consecutive patients. "Fever within 48 h after
stroke was observed in 30 (25.2%) patients. The probable cause of fever
was infective or chemical aspiration pneumonia (n=12), other
respiratory tract infection (n=7), urinary tract infection (n=4), viral
infections (n=3) or insufficiently defined (n=5). (One patient had two
potential causes of fever.) In thirteen of these patients, infection
was most probably acquired before stroke."
Previous infection and other risk factors for acute
ischaemia: attributable risks and the characterisation of high risk
groups. H Becher, A Grau, K Steindorf, F Buggle, W Hacke. J Epidemiol
Biostat 2000;5(5):277-283. 83 female and 114 male cases, and matched
controls. "Recent infections showed a relative risk of 4.3 (95% CI
1.8-10.5) and an attributable risk of 0.15 (95% CI 0.09-0.21)."
[The relationship between immunological parameters with
etiopathogenesis and clinical course of stroke]. A Czlonkowska, G
Gromadzka. Neurol Neurochir Pol 2000;34(3 Suppl):13-26. Elevated total
WBC was an independent stroke risk factor and predictor of 30-days
Frequency of coexistence of cytomegalovirus and Chlamydia pneumoniae in atherosclerotic plaques. HB Qavi, JL Melnick, E Adam, ME DeBakey. Cent Eur J Public Health 2000 May;8(2):71-73. CMV and/or C pneumoniae DNA were found in 71% of 17 carotid atherosclerotic plaques.Qavi - Cent Eur J Public Health 2000 abstract / PubMed
Risk factors for peripartum and postpartum stroke and
venous thrombosis. DJ Lanska, RJ Kryscio. Stroke 2000
Jun;31(6):1274-1282. 183 peripartum strokes, 170 cases of peripartum
intracranial venous thrombosis, 975 cases of stroke and 864 cases of
intracranial venous thrombosis during pregnancy and the puerperium.
"Covariates that were strongly and significantly associated with both
peripartum and postpartum intracranial venous thrombosis included
cesarean delivery, hypertension, and infections other than pneumonia
Serologic and histopathologic study of Chlamydia pneumoniae
infection in atherosclerosis: a possible pathogenetic mechanism of
atherosclerosis induced by Chlamydia pneumoniae. YG Song, HM Kwon, JM
Kim, BK Hong, DS Kim, AJ Huh, KH Chang, HY Kim, TS Kang, BK Lee, DH
Choi, YS Jang, HS Kim. Yonsei Med J 2000 Jun;41(3):219-327. "The
seropositive rate of anti-Chlamydia pneumoniae IgG was higher in the
disease group (Group I, 59.8%, n = 254) than in the negative control
group (Group III, 47.4%, n = 97) (p = 0.041), but the anti-Chlamydia
pneumoniae IgA was not different in seropositivity between the two
groups (Group I, 64.6%; Group III, 57.7%). The simultaneous
seropositive rates of both IgG and IgA were 56.7% in Group I and 43.3%
in Group III (p = 0.033)."
Chlamydia pneumoniae and the risk of first ischemic stroke:
Northern Manhattan Stroke Study. MS Elkind, IF Lin, JT Grayston, RL
Sacco. Stroke 2000 Jul;31(7):1521-1525. 89 cases and 89 controls.
"Elevated C pneumoniae IgA titers were significantly associated with
risk of ischemic stroke after adjusting for other stroke risk factors
(adjusted OR 4. 51, 95% CI 1.44 to 14.06). IgG titers were less
strongly associated with stroke risk (adjusted OR 2.59, 95% CI 0.87 to
7.75). The association of IgA with stroke risk was detected in both
younger and older groups, in men and women, and in whites, blacks, and
Infections, immunity, and atherosclerosis: associations of
antibodies to Chlamydia pneumoniae, Helicobacter pylori, and
cytomegalovirus with immune reactions to heat-shock protein 60 and
carotid or femoral atherosclerosis. M Mayr, S Kiechl, J Willeit, G
Wick, Q Xu. Circulation 2000 Aug 22;102(8):833-839. 826 random
subjects. "C pneumoniae seropositivity emerged as a significant risk
predictor. Antibody titers against cytomegalovirus were not a marker
for prevalence or incidence of atherosclerosis in this population.
Further infection parameters added to the predictive value of
chlamydial serology in risk assessment: Mean odds ratios for the
prevalence of carotid atherosclerosis were 4.2 and 6.3 for seropositive
subjects with elevated C-reactive protein levels and clinical evidence
for chronic respiratory infection, respectively. For subjects with all
3 infection parameters, the odds ratio of carotid atherosclerosis
reached 10.3 (P<0.0001)."
Chlamydia pneumoniae DNA in non-coronary atherosclerotic
circulating leukocytes. M Berger, B Schroder, G Daeschlein, W
Schneider, A Busjahn, I Buchwalow, FC Luft, H Haller. J Lab Clin Med
2000 Sep;136(3):194-200. Plaques from 130 patients who underwent
surgery for carotid stenosis, aneurysm, or peripheral vascular disease,
and circulating leukocytes from 60 patients and 51 normal controls. "C.
pneumoniae antibody titers, C-reactive protein, fibrinogen, leukocyte
count, cholesterol, and diabetes were not associated with C. pneumoniae
DNA. Although immunostaining of plaque and PCR results were highly
correlated, we found no relationship between C. pneumoniae DNA in
plaques and that in circulating leukocytes."
Are morphological or functional changes in the carotid artery
associated with Chlamydia pneumoniae, Helicobacter pylori,
cytomegalovirus, or herpes simplex virus infection? C Espinola-Klein,
HJ Rupprecht, S Blankenberg, C Bickel, H Kopp, G Rippin, G Hafner, U
Pfeifer, J Meyer. Stroke 2000 Sep;31(9):2127-2133. 504 patients.
"Seropositivity for C pneumoniae was an independent predictor for a
combined end point of highest category of IMT and carotid artery
stenosis (OR 1.8, 95% CI 1.1 to 3.1; adjusted) for IgG titers.
Independently, CMV increased the risk for the combined end point (OR
1.7, 95% CI 1.1 to 2.8; adjusted) for IgG titers and for IgA titers (OR
2.3, 95% CI 1.1 to 4.9; adjusted)."
Recent infection as a risk factor for intracerebral and
hemorrhages. AK Kunze, A Annecke, F Wigger, C Lichy, F Buggle, H
Schnippering, P Schnitzler, AJ Grau. Cerebrovasc Dis 2000
Sep-Oct;10(5):352-358. 56 consecutive patients with ICH, 44 consecutive
patients with SAH, and 56 and 44 neurological control patients.
"Infection within 4 weeks was associated with SAH independently of
hypertension and smoking (p = 0.049). There was no significant
association between infection and ICH."
Identification of periodontal pathogens in atheromatous
Haraszthy, JJ Zambon, M Trevisan, M Zeid, RJ Genco. J Periodontol 2000
Oct;71(10):1554-1560. "Eighty percent of the 50 endarterectomy
specimens were positive in 1 or more of the PCR assays. Thirty-eight
percent were positive for HCMV and 18% percent were positive for C.
pneumoniae. PCR assays for bacterial 16S rDNA also indicated the
presence of bacteria in 72% of the surgical specimens. Subsequent
hybridization of the bacterial 16S rDNA positive specimens with
species-specific oligonucleotide probes revealed that 44% of the 50
atheromas were positive for at least one of the target periodontal
pathogens. Thirty percent of the surgical specimens were positive for
B. forsythus, 26% were positive for P. gingivalis, 18% were positive
for A. actinomycetemcomitans, and 14% were positive for P. intermedia.
In the surgical specimens positive for periodontal pathogens, more than
1 species was most often detected. Thirteen (59%) of the 22 periodontal
pathogen-positive surgical specimens were positive for 2 or more of the
[Chlamydia pneumoniae antibody titers in patients with acute
ischemic stroke]. N Kawashima, J Kawada. Rinsho Shinkeigaku 2000
Nov;40(11):1063-1068. Stroke patients (n=91) were more likely to have
active C. pneumoniae infection.
Detection of Helicobacter pylori in human carotid
plaques. SF Ameriso, EA Fridman, RC Leiguarda, GE Sevlever. Stroke 2001
Feb;32(2):385-391. "H pylori DNA was found in 20 of 38 atherosclerotic
plaques. Ten of the H pylori DNA-positive plaques also showed
morphological and immunohistochemical evidence of H pylori infection.
None of 7 normal carotid arteries was positive for H pylori."
Chronic infections and the risk of carotid atherosclerosis: prospective results from a large population study. S Kiechl, G Egger, M Mayr, CJ Wiedermann, E Bonora, F Oberhollenzer, M Muggeo, Q Xu, G Wick, W Poewe, J Willeit. Circulation 2001 Feb 27;103(8):1064-1070. "[A]ny chronic infection versus none," odds ratio 4.08 (2.42-6.85), P<0.0001.Kiechl - Circulation 2001 abstract / PubMed
An association between an antibody against Chlamydia
common carotid atherosclerosis. R Kawamoto, T Doi, H Tokunaga, I
Konishi. Intern Med 2001 Mar;40(3):208-213. IgG for C. pneumoniae "was
a significant independent contributing factor (R2=0.3465,
in 147 in-patients.
Enhanced progression of early carotid atherosclerosis is
Chlamydia pneumoniae (Taiwan acute respiratory) seropositivity. D
Sander, K Winbeck, J Klingelhofer, T Etgen, B Conrad. Circulation 2001
Mar 13;103(10):1390-1395. In 272 consecutive patients, "Cp-seropositive
patients showed a significantly enhanced progression of the IMT even
after adjustment for other cardiovascular risk factors (0.12 mm/y [95%
CI 0.11 to 0.14] versus 0.07 mm/y [0.05 to 0.09]; P:<0.005).
Patients with increased C-reactive protein (>/=0.5 mg/dL) and Cp
seropositivity showed the most pronounced IMT progression."
Presence of Chlamydia pneumoniae in human symptomatic and asymptomatic carotid atherosclerotic plaque. R LaBiche, D Koziol, TC Quinn, C Gaydos, S Azhar, G Ketron, S Sood, TJ DeGraba. Stroke 2001 Apr;32(4):855-860. "[H]igh serum anti-chlamydial IgA levels (>/=1:128) were associated with occurrence of symptomatic disease (P=0.03; odds ratio, 2.86; 95% CI, 1.12 to 7.28)."LaBiche - Stroke 2001 abstract / PubMed
Chlamydia pneumoniae in atherosclerotic carotid artery
prevalence among heavy smokers. N Dobrilovic, L Vadlamani, M Meyer, CB
Wright. Am Surg 2001 Jun;67(6):589-593. "Forty-two (70.0%) of the 60
plaques that were evaluated tested positive for the presence of C.
pneumoniae DNA by polymerase chain reaction analysis. In the sample
defined as being from heavy smokers (greater than 15-pack-year history)
33 (94.3%) of 35 plaques tested positive whereas two (5.7%) tested
negative." 9 (36.0%) of the 25 nonsmokers were positive.
Increased CD8(+) T cells associated with Chlamydia pneumoniae
symptomatic carotid plaque. ZD Nadareishvili, DE Koziol, B Szekely, C
Ruetzler, R LaBiche, R McCarron, TJ DeGraba. Stroke 2001
Sep;32(9):1966-1972. 14 plaques (5 symptomatic and 9 asymptomatic)
positive for C pneumoniae. "Although all patients with symptomatic
disease show a modest elevation in the concentration of intraplaque
lymphocytes, a preferential increase in CD8+ class I-restricted T cells
is observed in symptomatic carotid plaque positive for C pneumoniae."
Chlamydia pneumoniae in atherosclerotic middle cerebral artery. D Virok, Z Kis, L Karai, L Intzedy, K Burian, A Szabo, B Ivanyi, E Gonczol. Stroke 2001 Sep;32(9):1973-1976. CP was found in 5/15 atherosclerotic cerebral arteries vs 0/4 otherwise healthy victims of trauma.Virok - Stroke 2001 abstract / PubMed
The significance of Chlamydia pneumoniae in symptomatic
stenosis. C Katsenis, E Kouskouni, L Kolokotronis, D Rizos, P
Dimakakos. Angiology 2001 Sep;52(9):615-619. "Twenty of 35 patients
(57.1%) had increased titers of IgG antibodies to C. pneumoniae...
Sixty-five percent (13/20) of the patients with increased IgG
antibodies to C. pneumoniae, 87.5% (7/8) with IgG + IgM, and 100% with
IgG + IgM + positive polymerase chain reaction were symptomatic."
C-reactive protein levels and viable Chlamydia pneumoniae in carotid artery atherosclerosis. SC Johnston, LM Messina, WS Browner, MT Lawton, C Morris, D Dean. Stroke 2001 Dec 1;32(12):2748-2752. 18/48 (38%) carotid endarterectomy specimens had viable C pneumoniae; and C-reactive protein levels were higher in these patients.Johnston - Stroke 2001 abstract / PubMed
Active and passive smoking, chronic infections, and the risk of carotid atherosclerosis: prospective results from the bruneck study. S Kiechl, P Werner, G Egger, F Oberbollenzer, M Mayr, Q Xu, W Poewe, J Willett. Stroke 2002 Sep;33(9):2170-2176. The bottom line of this study is that "Remarkably [sic], current and ex-smokers faced an increased atherosclerosis risk only in the presence of chronic infections (odds ratios [95% CIs], 3.3 [1.8 to 6.2] and 3.4 [1.8 to 6.3]; P<0.001 each)." The same held true for passive smoking as well. This is only "remarkable" to deluded true believers of the lie that smoking causes heart disease. It is not remarkable to those who realize that the anti-smokers have purposely used defective studies all along, to falsely blame smoking for heart disease that is really caused by infection. In addition, "current, past, and nonsmokers without infections did not differ substantially in their estimated risk burden." Despite this, the deluded authors cling to their ossified prejudices by claiming that "the pro-atherogenic effects of cigarette smoking are mediated in part by the chronic infections found in smokers" [sic - these infections are also found in non-smokers, who have NO reduced risk of heart disease; they merely succomb a few years later, which is best attributable to less exposure to the relevant infections.] - and they ludicrously proclaim that "A better understanding of the pathogenetic mechanisms of smoking [sic - rather than the pathogenetic mechanisms of INFECTION, as any rational person would conclude!] may offer novel clues for disease prevention supplementary to the primary goal of achieving long-term abstinence." And then, the vile and despicable American Heart Association proclaims in its viciously dishonest press release that "Cigarette smoking turns the entire body into a breeding ground for infection." (Science Daily Sep. 6, 2002.)Kiechl - Stroke 2002 abstract / PubMed
Impact of infectious burden on progression of carotid atherosclerosis. C Espinola-Klein, HJ Rupprecht, S Blankenberg, C Bickel, H Kopp, A Victor, G Hafner, W Prellwitz, W Schlumberger, J Meyer. Stroke 2002 Nov;33(11):2581-2586. "Elevated IgA antibodies against C. pneumoniae (P<0.04) and IgG antibodies against Epstein-Barr virus (P<0.01) and herpes simplex virus type 2 (P<0.04) were associated with progression of atherosclerosis... Infectious burden, divided into 0 to 3, 4 to 5, and 6 to 8 seropositives, was significantly associated with progression of atherosclerosis, with odds ratios of 1.8 (95% confidence interval, 1.1 to 2.9) for 4 to 5 and 3.8 (95% CI, 1.6 to 8.8) for 6 to 8 compared with 0 to 3 seropositives after adjustment."Espinola-Klein - Stroke 2002 abstract / PubMed
Infection and risk of ischemic stroke: differences among
subtypes. A Paganini-Hill, E Lozano, G Fischberg, M Perez Barreto, K
Rajamani, SF Ameriso, PN Heseltine, M Fisher. Stroke 2003
Feb;34(2):452-457. 233 cases and 363 controls aged 21 to 89 in Los
Angeles. "[P]atients with a recent respiratory tract infection suffered
more often from large-vessel atherothromboembolic or cardioembolic
stroke than did patients without infection (48% vs 24%, P=0.07). The
age- and sex-adjusted relative risk estimate for these subtypes was
1.75 (95% CI, 0.86 to 3.55). The risk was notably high for those
without stroke risk factors: 4.15 (95% CI, 1.22 to 14.1) for
normotensives, 2.71 (95% CI, 1.04 to 7.06) for nondiabetics, and 1.74
(95% CI, 0.74 to 4.07) for nonsmokers."
Increased risk of atherosclerosis is confined to CagA-positive
Helicobacter pylori strains: prospective results from the Bruneck
study. M Mayr, S Kiechl, MA Mendall, J Willeit, G Wick, Q Xu. Stroke.
2003 Mar;34(3):610-615. "Common carotid artery intima-media
thickness-both absolute values and changes between 1995 and 2000-were
significantly enhanced in subjects seropositive to CagA but not in
those infected with CagA-negative H pylori strains. There was a clear
dose-response relation between anti-CagA antibodies and both
intima-media thickness and atherosclerosis risk. Notably, the risk of
atherosclerosis associated with CagA seropositivity was amplified by
elevated C-reactive protein levels."
AAN: Chlamydia Pneumoniae a Risk Factor for Stroke. By Charlene Laino. Doctor's Guide 2003 Apr 7. Re MS Elkind et al, Antibodies to Chlamydia Pneumoniae Are Associated with Risk of Ischemic Stroke, presented at the 55th Annual Meeting of the American Academy of Neurology. Of 218 patients with their first stroke, "[P]atients with high IgG levels were 60% more likely to have had a stroke than those with normal levels, and individuals with IgA titers were 50% more likely to have had a stroke." The effect was stronger using higher cutoff levels.Elkind / Doctor's Guide 2003 article
Leukocyte count as an independent predictor of recurrent
events. AJ Grau, AW Boddy, DA Dukovic, F Buggle, C Lichy, T Brandt, W
Hacke; CAPRIE Investigators. Stroke 2004 May;35(5):1147-1152. "The
leukocyte count measured by chance within 7 days (mean 4±2)
before a recurrent event was significantly higher than individual
baseline values (n=211; +0.46±2.37x109/L, P=0.005) (Figure 1).
The neutrophil count mainly contributed to increased leukocyte counts
(+0.41±2.24x109/L, P=0.009). Leukocyte counts assessed at
earlier time points before recurrent ischemia, and last values in
patients without a second event were not different from baseline.
Differences to baseline were higher in patients tested within 8 days
before a recurrent event than in those tested earlier before an event
Risk of myocardial infarction and stroke after acute infection
vaccination. L Smeeth, SL Thomas, AJ Hall, R Hubbard, P Farrington, P
Vallance. N Engl J Med 2004 Dec 16;351(25):2611-2608. 19,063 persons
with a first stroke who received influenza vaccine from the United
Kingdom General Practice Research Database. "There was no increase in
the risk of myocardial infarction or stroke in the period after
influenza, tetanus, or pneumococcal vaccination. However, the risks of
both events were substantially higher after a diagnosis of systemic
respiratory tract infection and were highest during the first three
days (incidence ratio for myocardial infarction, 4.95; 95 percent
confidence interval, 4.43 to 5.53; incidence ratio for stroke, 3.19; 95
percent confidence interval, 2.81 to 3.62). The risks then gradually
fell during the following weeks. The risks were raised significantly
but to a lesser degree after a diagnosis of urinary tract infection.
The findings for recurrent myocardial infarctions and stroke were
similar to those for first events."
Association of serum-soluble heat shock protein 60 with
atherosclerosis: clinical significance determined in a follow-up study.
Q Xiao, K Mandal, G Schett, M Mayr, G Wick, F Oberhollenzer, J Willeit,
S Kiechl, Q Xu. Stroke 2005 Dec;36(12):2571-6. "RESULTS: sHSP60 levels
measured in 1995 and 2000 were highly correlated (r=0.40;
indicating consistency over a 5-year period. Circulating HSP60 levels
were significantly correlated with antilipopolysaccharide and
anti-HSP60 antibodies. It was also elevated in subjects with chronic
infection (top quintile group of HSP60, among subjects with and without
chronic infection: 23.8% versus 17.0%; P=0.003 after adjustment for age
and sex). HSP60 levels were significantly associated with early
atherogenesis, both in the entire population (multivariate odds ratio,
for a comparison between quintile group V versus I+II: 2.0 [1.2 to 3.5]
and the subgroup free of atherosclerosis at the 1995 baseline: 3.8 [1.6
to 8.9]). The risk of early atherogenesis was additionally amplified
when high-sHSP60 and chronic infection were present together."
Detection of Chlamydia pneumoniae and Helicobacter pylori in
atherosclerotic plaques of carotid artery by polymerase chain reaction.
M Kaplan, SS Yavuz, B Cinar, V Koksal, MS Kut, F Yapici, H Gercekoglu,
MM Demirtas. Int J Infect Dis 2006 Mar;10(2):116-123. "C. pneumoniae
DNA was detected in 16 of 52 (30.8%) atherosclerotic plaques and 1 of
52 (1.9%) macroscopically healthy ascending aorta wall specimens (P
< 0.001). H. pylori DNA was detected in 9 of 52 (17.3%)
atherosclerotic plaques and none of the controls (P = 0.003)."
Seropositivity to Chlamydia pneumoniae is associated with risk of first ischemic stroke. MS Elkind, ML Tondella, DR Feikin, BS Fields, S Homma, MR Di Tullio. Stroke 2006 Mar;37(3):790-5. "Elevated C pneumoniae IgA titers were associated with increased risk of ischemic stroke after adjusting for hypertension, diabetes mellitus, current cigarette use, atrial fibrillation, and levels of high-density lipoprotein and low-density lipoprotein (adjusted OR, 1.5; 95% CI, 1.0 to 2.2)." [Note- UN-adjusted odds ratios should be presented, because adjustment is a fraud -cast.]Elkind et al. - Stroke 2006 abstract / PubMed
Elevated levels of anti-Chlamydia pneumoniae IgA and IgG
in young adults with ischemic stroke. B Piechowski-Jóźwiak, A
Mickielewicz, Z Gaciong, H Berent, H Kwieciński. Acta Neurol Scand 2007
Sep;116(3):144-149. 94 patients (<55 years) with ischemic
stroke and 103 controls. "Mean IgA and IgG indices were higher in
stroke patients vs controls (IgA: 1.40 vs 0.56; P < 0.001; IgG:
vs. 0.78; P < 0.003). The IgA seropositivity was associated with
stroke risk (11.92; 5.94-23.92; P < 0.001) as well as IgG
seropositivity was (2.31; 1.15-4.61; P < 0.016). Seropositivity
assessed with combined IgA and IgG indices was associated with
increased stroke risk (OR 9.35; 95% CI 4.78-18.29; P < 0.0001).
After controlling for age and sex, the IgA seropositivity yielded a
significantly adjusted OR for stroke (8.95; 4.44-18.07; P <
while IgG seropositivity did not (0.85; 0.53-1.63)."
Recent respiratory infection and risk of cardiovascular
case-control study through a general practice database. TC Clayton, M
Thompson, TW Meade. Eur Heart J 2008 Jan;29(1):96-103. 11 155 MI cases
and 9208 stroke cases, with 326 and 260 respiratory infections during
the month preceding the index date, respectively. "There was strong
evidence of an increased risk of both events in the 7 days following
infection, for MI adjusted odds ratio (OR) 2.10 (95% confidence
interval 1.38-3.21), for stroke OR 1.92 (95% confidence interval
1.24-2.97). The strength of these associations fell over time. The
associations for MI occurred at all levels of initial underlying
Chlamydia pneumoniae seropositivity in aetiological subtypes
brain infarction and carotid atherosclerosis: a case control study. S
Alamowitch, J Labreuche, PJ Touboul, F Eb, P Amarenco; GENIC
Investigators. J Neurol Neurosurg Psychiatry 2008 Feb;79(2):147-151.
483 brain infarction cases and 483 controls. "IgA seropositivity
increased the BI risk in patients without hypertension (adjusted OR
2.79, 95% CI 1.15 to 6.74)."
Chlamydia pneumoniae antibodies in various subtypes of
stroke in Indian patients. VC Bandaru, V Laxmi, M Neeraja, S Alladi, AK
Meena, R Borgohain, AS Keerthi, S Kaul. J Neurol Sci 2008 Sep
15;272(1-2):115-122. "Seventy two out of 200 ischemic stroke patients
(36%) had positive C. pneumoniae antibodies (IgG or IgA), compared to
35 out of 200 controls (17.5%) (p<0.0001). IgG antibody was
in 64/200 (32%) ischemic stroke patients, compared to 34/200 (17%)
controls (p<0.0001) and IgA was positive in 20/200 (10%)
stroke patients compared to 1/200 (0.5%) controls (p<0.0001).
Logistic regression analysis showed statistically significant
association between C. pneumoniae antibody positivity and ischemic
stroke, thereby establishing it as an independent risk factor.
Prevalence of C. pneumoniae antibodies was significantly higher in all
stroke subtypes (except the stroke of undetermined etiology) compared
The influence of oseltamivir treatment on the risk of stroke after influenza infection. M Madjid, S Curkendall, WA Blumentals. Cardiology 2009;113(2):98-107. "The oseltamivir cohort comprised 49,238 patients and the comparison cohort 102,692 patients. Oseltamivir was associated with a 28% reduction in risk of stroke/TIA in the 6 months after influenza [hazard ratio (HR) 0.72; 95% CI 0.62-0.82] and with significant reductions after 1 and 3 months. In patients <65 years of age, there was a 34% risk reduction with oseltamivir after 6 months (HR 0.66; 95% CI 0.56-0.77) and also significant reductions after 1 and 3 months. In those aged > or =65 years, there was a 51% reduction in risk after 1 month (HR 0.49; 95% CI 0.27-0.91)."Madjid - Cardiology 2009 full article / PubMed Central
Seroprevalence of Chlamydia pneumoniae antibodies in stroke in
young. VC Bandaru, DB Boddu, V Laxmi, M Neeraja, S Kaul. Can J Neurol
Sci 2009 Nov;36(6):725-730. 120 patients and 120 controls aged less
than 45 years with acute ischemic stroke. "We found C. pneumoniae
antibodies in 29.1% (35/120) stroke patients and in 12.5% (15/120)
control subjects (p=0.002). C. pneumoniae IgG antibodies were found in
27.5 % (33/120) of stroke patients and 12.5% (15/120) of controls
(p=0.006). IgA antibodies were observed in 5% (6/120) of strokes and
none in control group (p=0.03). After adjustment of all risk factors C.
pneumoniae IgG seropositivity showed odds ratio of 2.6; 95% Confidence
Chlamydia pneumoniae seropositivity in adults with acute ischemic stroke: A case-control study. NK Rai, R Choudhary, R Bhatia, MB Singh, M Tripathi, K Prasad, MV Padma. Ann Indian Acad Neurol 2011 Apr;14(2):93-97. 51 patients, 48 controls. "The IgA seropositivity was significantly associated with AIS (unadjusted odds ratio 3.1; 95% CI 1.38, 6.96; P = 0.005), whereas IgG (unadjusted OR 0.44; 95% CI 0.18, 1.09; P = 0.07) and IgM (unadjusted OR 1.1; 95% CI 0.36, 3.3; P = 0.88) were not. There was no difference in IgA or IgG positivity in different stroke subtypes. On multivariate analysis after adjusting for sex, hypertension, diabetes mellitus, smoking and alcohol, the IgA seropositivity yielded an adjusted OR for stroke (4.72; 95% CI 1.61, 13.83; P = 0.005), while IgG seropositivity did not (OR 0.25; 95% CI 0.08, 0.83; P = 0.23)."Rai - Ann Indian Acad Neurol 2011 full article / PubMed Central
Association of Chlamydia pneumoniae serology and ischemic stroke. ZN Hasan. South Med J 2011 May;104(5):319-321. 50 patients, 40 controls. "Eighteen (36%) patients with ischemic stroke have positive IgA, in comparison with 6 (15%) among the control group (OR 3.18; CI 1.12-9.04; P = 0.03). This translates into the fact that there was a more than three-fold risk of developing ischemic stroke in those with Chlamydia pneumoniae infection compared to those who without. The IgG seropositivity was increased in patients with ischemic stroke, but it did not reach statistical significance (OR = 2.32; CI = 0.97-5.58; P = 0.078)."Hasan - South Med J 2011 abstract / PubMed
Human cytomegalovirus linked to stroke in a chinese
Huang, LP Yu, XC Yang, F Zhang, YR Chen, F Feng, XS Qian, J Cai. CNS
Neurosci Ther 2012 Jun;18(6):457-460. 200 patients and 200 controls in
the Stroke Hypertension Investigation in Genetics (SHINING) study.
"HCMV seropositivity was higher in the stroke group than in controls
(55.0% vs. 23.5%; P < 0.0001). The presence of HCMV DNA
the risk of stroke (unadjusted odds ratio [OR], 3.98; 95% confidence
interval [CI], 2.59 to 6.11; P < 0.0001). Risks were also
for the subtypes ischemic stroke (unadjusted OR, 4.01; 95% CI,
2.57-6.24; P < 0.0001) and hemorrhagic stroke (unadjusted OR,
95% CI, 1.64-8.78; P= 0.0018)." Results were similar after adjustment.
Association of serum anti-periodontal pathogen antibody with ischemic stroke. N Hosomi, S Aoki, K Matsuo, K Deguchi, H Masugata, K Murao, N Ichihara, H Ohyama, H Dobashi, T Nezu, T Ohtsuki, O Yasuda, H Soejima, H Ogawa, Y Izumi, M Kohno, J Tanaka, M Matsumoto. Cerebrovasc Dis 2012;34(5-6):385-392. 132 patients with acute ischemic stroke, 77 with no previous stroke, compared in levels of serum antibodies against Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg) and Prevotella intermedia (Pi). "The serum-antibody level of Pi was significantly higher in atherothrombotic-stroke patients than in patients with no previous stroke (p = 0.0035). Detectable serum anti-Pg antibody was significantly associated with atrial fibrillation (overall χ(2) = 35.5, R(2) = 0.18, n = 209, p < 0.0001; anti-Pg antibody: OR 4.36, 95% CI 1.71-12.10, p = 0.0017), and detectable serum anti-Pi antibody was significantly associated with bulb/ICA atherosclerosis after controlling for the statistically selected associated factors (overall χ(2) = 46.1, R(2) = 0.18, n = 209, p < 0.0001; anti-Pg antibody: OR 16.58, 95% CI 3.96-78.93, p < 0.0001). The levels of serum anti-Pi antibody were significantly associated with atherothrombotic stroke with the statistically selected associated factors excluding bulb/ICA atherosclerosis (overall χ(2) = 77.0, R(2) = 0.44, n = 129, p < 0.0001; anti-Pi antibody: OR 23.6, 95% CI 2.65-298.2, p = 0.008). However, when we included bulb/ICA atherosclerosis in this model, the levels of serum anti-Pi antibody were no longer significantly associated with atherothrombotic stroke (overall χ(2) = 98.0, R(2) = 0.56, n = 129, p < 0.0001; anti-Pi antibody: p = 0.107)."Hosomi - Cerebrovasc Dis 2012 abstract / PubMed
Dental prophylaxis and periodontal treatment are protective factors to ischemic stroke. YL Lee, HY Hu, N Huang, DK Hwang, P Chou, D Chu. Stroke 2013 Apr;44(4):1026-1030. 510,762 PD patients with periodontal disease and 208,674 without. "The stroke IR of the non-PD subjects was 0.32%/year. In the PD group, subjects who received dental prophylaxis had the lowest stroke IR (0.14%/year); subjects with intensive treatment or tooth extraction had a higher stroke IR (0.39%/year); and subjects without PD treatment had the highest stroke IR (0.48%/year; P<0.001). After adjustment for confounders, the dental prophylaxis and intensive treatment groups had a significant lower hazard ratios for stroke than the non-PD group (hazard ratio=0.78 and 0.95; 95% confidence interval=0.75-0.81 and 0.91-0.99, respectively), whereas the PD without treatment group had a significant higher hazard ratio for stroke (1.15; 95% confidence interval=1.07-1.24), especially among the youngest (20-44) age group (hazard ratio=2.17; 95% confidence interval=1.64-2.87) after stratifying for age."Lee - Stroke 2013 abstract / PubMed
Influenza and pneumococcal vaccination and risk of stroke or transient ischaemic attack-Matched case control study. AN Siriwardena, Z Asghar, CA Coupland. Vaccine 2014 Mar 10;32(12):1354-1361. 26,784 cases of stroke and 20,227 cases of TIA with equal numbers of matched controls. "Influenza vaccination within-season was associated with 24% reduction in stroke risk (adjusted OR 0.76, 95% CI 0.72 to 0.80) but no reduction in TIA (1.03, 0.98 to 1.09). Stroke risk was significantly lower with early (September to mid-November: 0.74, 0.70 to 0.78) but not later influenza vaccination (mid-November onwards: 0.92, 0.83 to 1.01)... Pneumococcal vaccination was not associated with a reduction in risk of stroke (0.98, 0.94 to 1.00) or TIA (1.15, 1.08 to 1.23)."Siriwardena - Vaccine 2014 abstract / PubMed
Anti-cytomegalovirus antibody levels are associated with carotid atherosclerosis and inflammatory cytokine production in elderly Koreans. SJ Jeong, NS Ku, SH Han, JY Choi, CO Kim, YG Song, JM Kim. Clin Chim Acta 2015 Mar 20;445:65-69. 71 patients. "Multivariate logistic regression analysis revealed three independent risk factors of high IMT: higher levels of anti-HCMV antibody (odds ratio [OR] 1.04, p=0.003), Framingham score (OR 1.14, p=0.018), and levels of IL-1β (OR 2.96, p=0.013). Anti-HCMV antibody levels had a significantly positive correlation with max-IMT (r=0.523, p<0.001), free T4 levels (r=0.315, p=0.021), and Log(TNF-α) (r=0.562, p<0.001) in multivariate correlation analysis."Jeong - Clin Chim Acta 2015 abstract / PubMed
Relationship between Cnm-positive Streptococcus mutans and cerebral microbleeds in humans. F Miyatani, N Kuriyama, I Watanabe, R Nomura, K Nakano, D Matsui, E Ozaki, T Koyama, M Nishigaki, T Yamamoto, T Mizuno, A Tamura, K Akazawa, A Takada, K Takeda, K Yamada, M Nakagawa, M Ihara, N Kanamura, RP Friedland, Y Watanabe. Oral Dis 2015 Oct;21(7):886-893. 139 subjects. "Fifty-one subjects were identified as Cnm-positive S. mutans carriers (36.7%), with cerebral microbleeds being detected in 43 (30.9%). A significantly larger number of subjects carried Cnm-positive S. mutans in the cerebral microbleeds (+) group. S. mutans with Cnm collagen-binding ability was detected in 39 (28.1%) of all subjects, and the adjusted odds ratio for cerebral microbleeds in the Cnm positive group was 14.4. Regarding the presence of cerebral microbleeds, no significant differences were noted in the number of remaining teeth, dental caries, or in classic arteriosclerosis risk factors."Miyatani - Oral Dis 2015 abstract / PubMed
Association of serum immunoglobulin-G to Porphyromonas gingivalis with acute cerebral infarction in the Chinese population. Z Zhang, N Ma, Y Zheng, L Zhang. J Indian Soc Periodontol 2015 Nov-Dec;19(6):628-632. 88 patients, 40 controls. "P. gingivalis IgG antibody levels were significantly higher in acute cerebral infarction cases than in healthy controls (mean ± standard deviation, 11.06 ± 1.49 vs. 9.15 ± 1.70, P < 0.001)."Zhang - J Indian Soc Periodontol 2015 full article / PubMed Central
Human Cytomegalovirus Increases the Risk of Future Hemorrhagic But Not Ischemic Stroke - A Nested Case-Control Study. L Zheng, Z Sun, Z Sun, X Zhang, K Jing, J Li, D Hu, Y Sun. Circ J 2016 Sep 23;80(10):2235-2239. 300 cases, 300 controls. "HCMV DNA was detected in 38 of 300 samples from stroke patients and in 17 of 300 control samples (12.7% vs. 5.7%; P=0.023). Seropositivity for HCMV DNA increased the risk of incident stroke (unadjusted OR, 1.437; 95% confidence interval (CI), 1.023-2.020, P=0.037) and adjustment for other potential cardiovascular confounders only slightly changed the OR (1.464; 95% CI, 1.003-2.137, P=0.048)."Zheng - Circ J 2016 abstract / PubMed
Viral and parasitic pathogen burden and the association with stroke in a population-based cohort. BD Pearce, A Bracher, JL Jones, D Kruszon-Moran. Int J Stroke 2017 Jan 1:1747493017729269. 13,904 subjects in NHANES III. "In multivariable logistic regression models, the positive association of serological evidence of prior infection with stroke prevalence remained significant after adjustment for other significant risk factors (odds ratio = 1.4, p = 0.01) but was only significant among those aged 20-59 (odds ratio = 2.0, p = 0.005) and not among those aged 60-69 ( p = 0.78) or 70 and older ( p = 0.43)."Pearce - Int J Stroke 2017 abstract / PubMed
Detection of specific Chlamydia pneumoniae and cytomegalovirus antigens in human carotid atherosclerotic plaque in a Chinese population. J Cao, Y Mao, B Dong, W Guan, J Shi, S Wang. Oncotarget 2017 Jul 18;8(33):55435-55442. "In the group of 25 carotid atherosclerotic specimens, the detection rate of the Cpn-specific antigens was 84.0% (21/25). In the control group, the detection rate was 13.3% (2/15) in the ascending aortic intima. Thus, the between-group difference was significant (P<0.01). The CMV-specific antigen detection rate was 72.0% (18/25) using the same experimental group specimens, and the detection rate was zero in the control group."Cao - Oncotarget 2017 abstract / PubMed
Influenza-like illness as a trigger for ischemic stroke. Boehme AK, J Luna, ER Kulick, H Kamel, MSV Elkind. Ann Clin Transl Neurol 2018 Mar 14;5(4):456-463. 36,975 strokes, of which 554 (1.5%) had at least 1 influenza-like illness in the past year. " the odds of ischemic stroke was greatest in the first 15 days post ILI (OR: 2.88, 95% CI: 1.86-4.47). The strength of the relationship decreased as the time from ILI increased, and was no longer significant after 60 days. There was a significant interaction (P = 0.017) with age and ILI; the odds of stroke associated increased 7% with each 10-year decrease in age (OR per 10-year age decrease 1.07, 95% CI: 1.03-1.35)."Boehme - Ann Clin Transl Neurol 2018 full article / PubMed Central
Emergence of a CD4+CD28- granzyme B+, cytomegalovirus-specific T cell subset after recovery of primary cytomegalovirus infection. EM van Leeuwen, EB Remmerswaal, MT Vossen, AT Rowshani, PM Wertheim-van Dillen, RA van Lier, IJ ten Berge. J Immunol 2004 Aug 1;173(3):1834-1841. "In this study, we show that in primary CMV infections, CD4(+)CD28(-) T cells emerge just after cessation of the viral load, indicating that infection with CMV triggers the formation of CD4(+)CD28(-) T cells. In line with this, we found these cells only in CMV-infected persons. CD4(+)CD28(-) cells had an Ag-primed phenotype and expressed the cytolytic molecules granzyme B and perforin. Importantly, CD4(+)CD28(-) cells were to a large extent CMV-specific because proliferation was only induced by CMV-Ag, but not by recall Ags such as purified protein derivative or tetanus toxoid. CD4(+)CD28(-) cells only produced IFN-gamma after stimulation with CMV-Ag, whereas CD4(+)CD28(+) cells also produced IFN-gamma in response to varicella-zoster virus and purified protein derivative. Thus, CD4(+)CD28(-) T cells emerge as a consequence of CMV infection."van Leeuwen / J Immunol 2004 full article
Elevated pro-inflammatory CD4+CD28- lymphocytes and stroke
recurrence and death. ZG Nadareishvili, H Li, V Wright, D Maric, S
Warach, JM Hallenbeck, J Dambrosia, JL Barker, AE Baird. Neurology 2004
Oct 26;63(8):1446-1451. 106 patients followed for one year; 10
recurrent strokes and 17 deaths occurred. "Stroke recurrence/death
rates were significantly associated with increasing CD4+CD28- counts,
rising from 14.2% in patients with CD4+CD28- levels of <1.0 to
for those with CD4+CD28- counts of >8.0% (p = 0.003, Cochran
test of trend). Higher CD4+CD28- counts were also present in patients
with a history of prior stroke (p = 0.03). After adjustment for age,
admission NIH Stroke Scale score, prior stroke, and atrial
fibrillation, CD4+CD28- counts of >8.0% were associated with a
cumulative hazard ratio of 5.81 (95% CI: 1.58 to 21.32) for stroke
recurrence or death."
Chlamydia pneumoniae in foci of "early" calcification of the
media in arteriosclerotic arteries: an incidental presence? YV
Bobryshev, RS Lord, D Tran. Am J Physiol Heart Circ Physiol 2006
Apr;290(4):H1510-9. In carotid artery segments obtained by
endarterectomy from 60 patients, "Medial calcification occurred in 10
of 17 (58.8%) C. pneumoniae double-positive arterial specimens, but no
medial calcification was observed in any of 22 C. pneumoniae
double-negative arterial specimens. Electron microscopy indicated C.
pneumoniae in smooth muscle cells (SMCs) in foci of medial
calcification. Medial SMCs showing damage to the cytoplasm and basement
membrane contained the structures with the appearance of elementary,
reticulate, and aberrant bodies of C. pneumoniae."
Unchecked CD70 expression on T cells lowers threshold for T
activation in rheumatoid arthritis. WW Lee, ZZ Yang, G Li, CM Weyand,
JJ Goronzy. J Immunol 2007 Aug 15;179(4):2609-2615. Expression of CD70
was the most striking difference between CD4(+)CD28(-) and
CD4(+)CD28(+) T cells; and "CD70 on bystander
cells functioned by lowering the threshold for T cell activation."
Expansion of the NKG2C+ Natural Killer-Cell Subset Is Associated With High-Risk Carotid Atherosclerotic Plaques in Seropositive Patients for Human Cytomegalovirus. JE Martínez-Rodríguez, J Munné-Collado, R Rasal, E Cuadrado, L Roig, A Ois, A Muntasell, T Baro, F Alameda, J Roquer, M López-Botet. Arterioscler Thromb Vasc Biol 2013 Nov;33(11):2653-2659. 40 CMV+ patients with CAP, with 15 nonatherosclerotic strokes and 11 healthy subjects as controls. "High-risk CAP (n=16), defined as carotid stenosis >50% with ipsilateral neurological symptomatology in the previous 180 days, compared with non-high-risk CAP had higher %NKG2C+ NK cells (29.5±22.4% versus 16.3±13.2%; P=0.026; odds ratio, 1.053; 95% confidence interval, 1.002-1.106; P=0.042), with a corresponding reduction in the NKG2A+ NK subset (31.7±17.8% versus 41.8±15.8%; P=0.072). The proportions of NKG2C+ NK cells in high-risk CAP were inversely correlated with the CD4+/CD8+ ratio (RSpearman=-0.629; P=0.009) and directly with high-sensitivity C-reactive protein levels (RPearson=0.591; P=0.012), consistent with higher subclinical systemic inflammation."Martínez-Rodríguez - Arterioscler Thromb Vasc Biol 2013 abstract / PubMed
Human Cytomegalovirus Up-Regulates Endothelin Receptor Type B: Implication for Vasculopathies? KC Yaiw, AA Mohammad, H Costa, C Taher, S Badrnya, A Assinger, V Wilhelmi, S Ananthaseshan, A Estekizadeh, B Davoudi. Open Forum Infect Dis 2015 Dec 24;2(4):ofv155. "Human CMV is capable of upregulating both ETBR mRNA and protein expression in ECs and SMCs. The ETBR was also abundantly expressed in ECs, foam cells, and SMCs, and, more importantly, in HCMV-positive cells in human carotid plaques."Yaiw - Open Forum Infect Dis 2015 full article / PubMed Central
New Blood Test May Improve Risk Assessment for Ischemic Stroke
Middle Aged Adults. DGNews, Nov. 29, 2005. Re: C Ballantyne, R
Hoogeveeen, H Bang, et al. Lipoprotein-associated phospholipase A2,
high-sensitivity C-Reactive Protein, and Risk for Incident Ischemic
Stroke in Middle-aged Men and Women in the Atherosclerosis Risk in
Communities (ARIC) Study. Arch Intern Med 2005;165:1-7. "Individuals
with the highest levels of both Lp-PLA2 and CRP had an 11.38-fold (95%
CI 3.13-41.41) increased risk of suffering an ischemic stroke during
the study, compared to individuals with the lowest levels of Lp-PLA2
and CRP. Notably, LDL-cholesterol levels did not differ between
incident stroke cases and non-cases and, in fully adjusted models,
LDL-cholesterol, HDL-cholesterol and triglycerides were not associated
with increased risk for stroke consistent with previous reports."
Although herpes zoster is common in the elderly, none of these studies has considered its possible role in stroke.VZV and Stroke