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High Prevalence of Chlamydia Pneumoniae Antibodies and Increased High-Sensitive C-Reactive Protein in Patients with Vascular Dementia

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http://www.medscape.com/viewarticle/502525

High Prevalence of Chlamydia Pneumoniae Antibodies and Increased High-Sensitive C-Reactive Protein in Patients with Vascular Dementia

Hideki Yamamoto; Takuya Watanabe; Akira Miyazaki; Takashi Katagiri; Tsunenori Idei; Takashi Iguchi; Masaru Mimura; Kunitoshi Kamijima J Am Geriatr Soc. 2005; 53 (4): 583-589. ©2005 Blackwell Publishing

Abstract and Introduction

Abstract

Objectives: To determine the relationships between Chlamydia pneumoniae infection, carotid atherosclerosis, and dyslipidemia in patients with vascular dementia (VaD) and Alzheimer's disease (AD).Design: Case control study.Setting: Showa University Karasuyama Hospital, Tokyo, Japan.Participants: One hundred twenty-four elderly subjects: 31 with VaD, 61 with AD, and 32 age-matched controls without dementia.Mesurements: Presence of antibodies to C. pneumoniae (immunoglobulin G (IgG) and IgA), the serum concentrations of high-sensitive C-reactive protein (hs-CRP) and atherogenic lipoproteins, and the carotid artery intima-media thickness (IMT) and plaques were determined.Results: Age; body mass index; systolic and diastolic blood pressures; and fasting plasma glucose, hemoglobin A1c, high-density lipoprotein cholesterol, and apolipoprotein A-I, B, and E concentrations did not differ significantly between the three groups, but the mean IMT and frequency of atherosclerotic plaques in the carotid arteries, as well as the serum concentrations of low-density lipoprotein cholesterol (LDL-C), lipoprotein(a), and lipid peroxides were significantly greater in VaD patients than in AD patients or nondemented controls. Hs-CRP concentrations and prevalence of C. pneumoniae IgG and IgA antibodies also were significantly higher in VaD patients than in AD patients and nondemented controls. Multiple logistic regression analysis revealed that carotid IMT and plaques, LDL-C, lipid peroxides, hs-CRP, and IgG and IgA C. pneumoniae seropositivity were independent risk factors for VaD.Conclusion: These results suggest that carotid atherosclerosis, atherogenic lipoproteins, and C. pneumoniae infection (as documented by the IgG and IgA seropositivity together with increased hs-CRP) may be VaD risk factors.

Introduction

Well-known independent risk factors for atherosclerosis include hypertension, smoking, diabetes mellitus, and hypercholesterolemia; yet these do not explain all forms of atherosclerosis.[1] In addition to a response-to-injury model, the presence of inflammatory cell infiltrates in atherosclerotic plaques suggests immune-mediated inflammatory disease, possibly caused by infectious agents.[2] An elevated serum concentration of high-sensitive C-reactive protein (hs-CRP), an inflammatory marker, is a powerful predictor of cardiovascular disease, including stroke, coronary artery disease, and peripheral arterial disease.[3–5]

Chlamydia pneumoniae ( C. pneumoniae ), which commonly causes asymptomatic acute respiratory tract infection followed by lifelong chronic infection, has been particularly associated with incipient and advanced atherosclerosis.[6,7] C. pneumoniae has been detected in atherosclerotic lesions in coronary arteries, in abdominal aortic aneurysms, in atherosclerotic carotid arteries, and most recently in specimens from atherosclerotic middle cerebral arteries using methods including immunohistochemistry, in situ hybridization, amplification of genomic material using polymerase chain reaction (PCR), and electron microscopy.[8–10] Several studies demonstrated higher titers of specific anti- C. pneumoniae antibodies in patients with cerebrovascular disease than in controls,[11–13] and a prospective study indicated that high antibody titers to C. pneumoniae were associated with increased risk of future stroke.[14]

Previous investigations have shown close relationships between vascular dementia (VaD) and atherogenic dyslipidemia (high prevalence of small dense low-density lipoprotein cholesterol (LDL-C) and high concentrations of LDL-C, lipoprotein(a), and lipid peroxides) and a unique pattern of nootrophic antiapoptosis factors (low levels of insulin-like growth factor-1 and high levels of hepatocyte growth factor),[15,16] but chronic C. pneumoniae infection and VaD have not been closely investigated in search of an association.

This study sought to determine whether C. pneumoniae infection, as indicated by immunoglobin G (IgG) and IgA antibodies to C. pneumoniae together with hs-CRP, was a risk factor for VaD. Atherogenic dyslipidemia parameters and atherosclerosis, as evidenced by carotid artery intima-media thickness (IMT) and plaque prevalence, also were assessed for VaD risk.