Infections Cause Stroke

The vast majority of studies have found associations between infections and cerebrovascular disease (stroke). The pathogens implicated include bacteria such as Chlamydia pneumoniae, Helicobacter pylori, and dental pathogens; and viruses. People in less wealthy classes are more to be infected; and smokers are more likely to be in the less wealthy classes. Therefore, the stage is set for confounding by infection, which is not eliminated by adjusting for proxy variables.

All of the anti-smokers' studies blaming smoking for causing strokes, including the Surgeon General reports and the SAMMEC, simply ignore the role of infection and stonewall the issue of confounding by infection. Therefore, they are not reputable studies, and supposed authorities who use them as such are guilty of fraud and deceit.

Association between cerebral infaction and increased serum bacterial 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, ethanol intoxication."

Syrjanen - Acta Neurol Scand 1986 abstract / PubMed

Preceding infection as an important risk factor for ischaemic brain 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))."

Syrjanen - Br Med J (Clin Res Ed) 1988 abstract / PubMed
Syrjanen - Br Med J (Clin Res Ed) 1988 full article / PubMed Central

Anticardiolipin response and its association with infections in 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)."

Syrjanen - Acta Neurol Scand 1988 abstract / PubMed

Dental infections in association with cerebral infarctions in young 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)."

Syrjanen - J Intern Med 1989 abstract / PubMed

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 cerebral 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 0.05)."

Ameriso - Stroke 1991 abstract / PubMed
Ameriso / Stroke 1991 full article (pdf, 7 pp)

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 ischemia. AJ 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 C) 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."

Grau - Stroke 1995 abstract / PubMed
Grau / Stroke 1995 full article

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)."

Whincup - Heart 1996 abstract / PubMed
Whincup - Heart 1996 full article / PubMed Central

[Infectious diseases as a cause and risk factor for cerebrovascular ischemia]. AJ Grau, F Buggle, W Hacke. Nervenarzt 1996 Aug;67(8):639-649. Review.

Grau - Nervenarzt 1996 abstract / PubMed

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.

Nieto / Circulation 1996 full article

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, P<.02)."

Macko / Stroke 1996 full article

Acute infection as a risk factor for ischemic stroke. LY Bova, NM 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."

Bova / Stroke 1996 full article

Association of Chlamydial infection with cerebrovascular disease. 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."

Wimmer / Stroke 1996 full article

Association between acute cerebrovascular ischemia and chronic and 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)."

Grau / Stroke 1997 full article

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)."

Markus / J Neurol Neurosurg Psychiatry 1998 full article

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 arterioarterial embolism."

Grau - Neurology 1998 abstract / PubMed
Grau / Neurology 1998 full article

Chlamydia pneumoniae antibody titers are significantly associated 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."

Cook / Stroke 1998 full article

Role of infection as a risk factor for atherosclerosis, myocardial infarction, and stroke. KJ Mattila, VV Valtonen, MS Nieminen, S Asikainen. Clin Infect Dis 1998 Mar;26(3):719-734. (Review).

Mattila - Clin Infect Dis 1998 abstract / PubMed

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, and the 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."

Ridker / Circulation 1998 full article

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)."

Fagerberg - Stroke 1999 abstract / PubMed

Association of cervical artery dissection with recent infection. AJ 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."

Grau - Arch Neurol 1999 abstract / PubMed

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 was 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."

Nagaraja - J Assoc Physicians India 1999 abstract / PubMed

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 do 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."

Glader - Stroke 1999 abstract / PubMed

Multiple infections in carotid atherosclerotic plaques. B Chiu. Am 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."

Chiu - Am Heart J 1999 abstract / PubMed

[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?]

Wiedermann - A Am Coll Cardiol 1999 abstract / PubMed

Fever and infection soon after ischemic stroke. AJ Grau, F Buggle, P 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."

Grau - J Neurol Sci 1999 abstract / PubMed

Previous infection and other risk factors for acute cerebrovascular 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)."

Becher - J Epidemiol Biostat 2000 abstract / PubMed

[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 stroke fatality.

Czlonkowska - Neurol Neurochir Pol 2000 abstract / PubMed

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 intracranial 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 and influenza."

Lanska - Stroke 2000 abstract / PubMed
Lanska / Stroke 2000 full article

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)."

Song - Yonsei Med J 2000 abstract / PubMed

Chlamydia pneumoniae and the risk of first ischemic stroke: The 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 Hispanics."

Elkind - Stroke 2000 abstract / PubMed
Elkind / Stroke 2000 full article

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)."

Mayr - Circulation 2000 abstract / PubMed
Mayr / Circulation 2000 full article

Chlamydia pneumoniae DNA in non-coronary atherosclerotic plaques and 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."

Berger - J Lab Clin Med 2000 abstract / PubMed

Are morphological or functional changes in the carotid artery wall 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)."

Espinola-Klein - Stroke 2000 abstract / PubMed
Espinola-Klein / Stroke 2000 full article

Recent infection as a risk factor for intracerebral and subarachnoid 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."

Kunze - Cerebrovascular Dis 2000 abstract / PubMed

Identification of periodontal pathogens in atheromatous plaques. VI 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 target species."

Haraszthy - J Periodontol 2000 abstract / PubMed

[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.

Kawashima - Rinsho Shinkeigaku 2000 abstract / PubMed

Detection of Helicobacter pylori in human carotid atheosclerotic 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."

Ameriso - Stroke 2001 abstract / PubMed
Ameriso / Stroke 2001 full article

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 pneumoniae and 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, p<0.0001)" in 147 in-patients.

Kawamoto - Intern Med 2001 abstract / PubMed
Kawamoto / Intern Med 2001 full article (pdf, 6pp)

Enhanced progression of early carotid atherosclerosis is related to 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."

Sander - Circulation 2001 abstract / PubMed
Sander / Circulation 2001 full article

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 plaques: high 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.

Dobrilovic - Am Surg 2001 abstract / PubMed

Increased CD8(+) T cells associated with Chlamydia pneumoniae in 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."

Nadareishvili - Stroke 2001 abstract / PubMed
Nadareishvili /d Stroke 2001 full article

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 carotid 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."

Katsenis - Angiology 2001 abstract / PubMed

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
Kiechl / Science Daily 2002

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 stroke 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."

Paganini-Hill - Stroke 2003 abstract / PubMed
Paganini-Hill / Stroke 2003 full article

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."

Mayr et al. - Stroke 2003 abstract / PubMed

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 ischemic 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 (P<0.05)."

Grau - Stroke 2004 abstract / PubMed
Grau / Stroke 2004 full article

Risk of myocardial infarction and stroke after acute infection or 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."

Smeeth - N Engl J Med 2004 abstract / PubMed
Smeeth / N Engl J Med 2004 full article

Association of serum-soluble heat shock protein 60 with carotid 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; P<0.001), 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."

Xiao et al. - Stroke 2005 abstract / PubMed

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)."

Kaplan et al. - Int J Infect Dis 2006 abstract / PubMed

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 antibodies 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: 0.85 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 < 0.002), while IgG seropositivity did not (0.85; 0.53-1.63)."

Piechowski-Jóźwiak - Acta Neurol Scand 2007 abstract / PubMed

Recent respiratory infection and risk of cardiovascular disease: 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 cardiovascular risk."

Clayton - Eur Heart J 2008 abstract / PubMed

Chlamydia pneumoniae seropositivity in aetiological subtypes of 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)."

Alamowitch. - J Neurol Neurosurg Psychiatry 2008 abstract / PubMed

Chlamydia pneumoniae antibodies in various subtypes of ischemic 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 positive in 64/200 (32%) ischemic stroke patients, compared to 34/200 (17%) controls (p<0.0001) and IgA was positive in 20/200 (10%) ischemic 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 to controls."

Bandaru - J Neurol Sci 2008 abstract / PubMed

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 Interval 1.2-5.6."

Bandaru - Can J Neurol Sci 2009 abstract / PubMed

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
Rai / Ann Indian Acad Neurol 2011 full article

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 population. ZR 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 increased 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 increased for the subtypes ischemic stroke (unadjusted OR, 4.01; 95% CI, 2.57-6.24; P < 0.0001) and hemorrhagic stroke (unadjusted OR, 3.80; 95% CI, 1.64-8.78; P= 0.0018)." Results were similar after adjustment.

Huang - CNS Neurosci Ther 2012 abstract / PubMed

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
Boehme / Ann Clin Transl Neurol 2018 full article

Oral Bacterial Signatures in Cerebral Thrombi of Patients With Acute Ischemic Stroke Treated With Thrombectomy. O Patrakka, JP Pienimäki, S Tuomisto, J Ollikainen, T Lehtimäki, PJ Karhunen, M Martiskainen. J Am Heart Assoc 2019 Jun 4;8(11):e012330. "Bacterial DNA was detected in 84% (n=63) of aspired thrombi, and 16% (n=12) of samples were considered bacterial DNA negative. DNA of Streptococcus species, mainly the S mitis group, was found in 79% (n=59) of samples. The median relative amount of Streptococcus species DNA was 5.10-fold higher compared with the control blood samples from the same patients. All thrombi were negative for both P gingivalis and A actinomycetemcomitans."

Patrakka - J Am Heart Assoc 2019 abstract / PubMed


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 48.1% for those with CD4+CD28- counts of >8.0% (p = 0.003, Cochran linear 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."

Nadareishvili - Neurology 2004 abstract / PubMed

Chlamydia pneumoniae in foci of "early" calcification of the tunica 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."

Bobryshev - Am J Physiol Heart Circ Physiol 2006 abstract / PubMed

Unchecked CD70 expression on T cells lowers threshold for T cell 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 CD4(+)CD28(-) T cells functioned by lowering the threshold for T cell activation."

Lee - J Immunol 2007 abstract / PubMed

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

Cross-Reactivity as a Mechanism Linking Infections to Stroke. G Lucchese, A Flöel, B Stahl. Front Neurol 2019 May 14;10:469. "The resulting data demonstrate massive peptide sharing between infectious pathogens-such as Chlamydia pneumoniae, Streptococcus pneumoniae, Tannerella forsythia, Haemophilus influenzae, Influenza A virus, and Cytomegalovirus-and human proteins related to risk of ischemic and hemorrhagic stroke."

Lucchese - Front Neurol 2019 full article / PubMed Central
Lucchese / Front Neurol 2019 full article

New Test For C-Reactive Protein Identifies Patients With 11-Fold Higher Risk For Stroke

New Blood Test May Improve Risk Assessment for Ischemic Stroke in 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."

Ballantyne et al / Arch Intern Med 2005 full article
DGNews, Nov. 29, 2005 / Doctors Guide

Varicella Zoster Virus May Be An Underdiagnosed Cause of Stroke

Although herpes zoster is common in the elderly, none of these studies has considered its possible role in stroke.

VZV and Stroke

See Also:

Confounding By Infection
"Bad Habits" Do Not Explain Higher Death Rates in the Poor
How the Public Was Brainwashed About Heart Disease
Dental Infections Cause Heart Disease
CMV & other infections cause heart disease


cast 06-18-19