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Increased Prevalence of Chlamydophila Pneumoniae but Not Epstein–Barr Antibodies in Essential Hypertensives

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Increased Prevalence of Chlamydophila Pneumoniae but Not Epstein–Barr Antibodies in Essential Hypertensives Journal of Human Hypertension (2003) 17, 21–27 & 2003 Nature Publishing Group All rights reserved 0950-9240/03 $25.00 www.nature.com/jhh ORIGINAL ARTICLE Increased prevalence of Chlamydophila pneumoniae but not Epstein–Barr antibodies in essential hypertensives V Ch Pitiriga, V Th Kotsis, M-EK Alexandrou, VD Petrocheilou-Paschou, N Kokolakis, RN Zakopoulou and NA Zakopoulos Department of Clinical Therapeutics, Alexandra Hospital, University of Athens, National and Kapodistrial University, Athens, Greece Conflicting data exist regarding the relationship be- without antihypertensive medication were defined as tween Chlamydophila pneunoniae (C. pneumoniae) and hypertensives. Controls were free of any history or hypertension. In this study, both C. pneumoniae IgG and clinical evidence of hypertension, cardiovascular or IgA titres and Epstein–Barr virus antibody levels were pulmonary disease. Of the total participants, 77 hyper- measured in 146 sustained hypertensives defined by tensives (52.7%) and 10 normotensives (18.5%) had IgA 24 h ambulatory blood pressure monitoring (ABPM) and titres X40 (crosstabs Po0.000), whereas 76 hyperten- 54 normotensives. C. pneumoniae antibodies were sives (52.1%) and 15 normotensives (27.8%) had IgG measured by microimmunofluorescence test. IgGX80 titres X80, (crosstabs Po0.002). No difference was and IgAX40 were defined as elevated antibody titres. found in Epstein–Barr antibodies, between hyperten- Epstein–Barr antibodies were measured in order to sives and normotensives. In conclusion, C. pneumo- investigate whether a possible association exists be- niae, but not Epstein–Barr, antibody levels were found tween hypertension and other, similarly widespread in significantly higher in sustained hypertensives, sug- the general population, intracellular microorganisms. All gesting high frequency of chronic C. pneumoniae, participants underwent casual blood pressure (BP) infections in this specific group of patients. readings and 24 h ABPM. Subjects having mean 24 h Journal of Human Hypertension (2003) 17, 21–27. systolic/diastolic ambulatory BP4125/80 mmHg, with or doi:10.1038/sj.jhh.1001501 Keywords: C. pneumoniae; hypertension; infection; atherosclerosis; ABPM Introduction tension.13,14 This discrepancy may be the result of performing different serological methods (enzyme- Chlamydophila pneumoniae is an intracellular linked immunosorbent assay (ELISA), microimmuno- Gram negative bacterium that is currently recog- fluorescence (MIF); it could be traced in the nized as a significant respiratory pathogen. It can examination technicalities used to define hyperten- cause acute and chronic pulmonary infections such sion in those studies, or in the sampling procedure. as pneumonia, bronchitis, sinusitis and pharyngitis 1 In order to clarify whether there is a real in both adults and children. Several studies have association between C. pneumoniae and essential documented an association between serologic evi- hypertension, C. pneumoniae IgA and IgG antibody dence of C. pneumoniae infection and various forms 2–4 levels were determined in a selected population of of vascular disease, such as coronary heart disease, sustained hypertensives and in healthy normoten- carotid atherosclerotic lesions5,6 and ischaemic 7 sives. As a result of the existing controversy on cerebrovascular disease. However, a number of whether white-coat hypertension is a benign condi- studies have failed to establish such an associa- 8–12 tion or a pathophysiological entity leading to similar tion. complications with sustained hypertension,15,16 Similarly, in prior research efforts, conflicting white-coat hypertensives were excluded from this findings exist regarding the relation between study, to avoid possible methodological errors. In C. pneumoniae antibodies and essential hyper- order to identify correctly sustained hypertensives, all participants underwent 24 h ambulatory blood pressure monitoring (ABPM). Correspondence: Dr N Zakopoulos, Department of Clinical Therapeutics, Alexandra Hospital, Vas. Sofias and Lourou str Antibodies against Epstein–Barr virus (EBV IgM, 11528, Athens, Greece. E-mail: [email protected] EBV IgG, EB nuclear antigen (EBNA) IgG, EBV Received 2 June 2002; revised and accepted 11 October 2002 EA IgG were also measured to examine whether C. pneumoniae and Epstein–Barr infection in hypertension V Ch Pitiriga et al 22 a possible association between essential sustained number of years as a smoker times the average hypertension and infections concerns, except for number of smoked cigarettes. In regards to alcohol C. pneumoniae, and other intracellular micro- consumption, the case and control subjects were organisms. It was chosen among others, based classified as abstainers and heavy drinkers on the fact that, like C. pneumoniae, infections (men460 g/day; women440 g/day alcohol intake, by EBV are frequently observed in the Hellenic with reference to the suggestions of the Italian population. Alcohol Society19). Blood glucose, cholesterol, tri- glycerides, HDL, LDL, C-reactive protein were determined. Materials and methods In all, 14 hypertensives refused to participate. Three hypertensives and one control were excluded Hypertensives were selected among patients con- because they did not meet the serologic criteria secutively referred to the Outpatient University (IgGX512). Eventually, 146 hypertensive patients Hypertension Center of the Department of Clinical Fusing antihypertensive medication or notFand Therapeutics at Alexandra University Hospital of 54 normotensive controls were included in the Athens. They were included in the sample if all of study. All participants gave informed consent before the following criteria were met: (a) mean 24 h entering the study. systolic/diastolic ambulatory BP4125/80 mmHg (in accordance with WHO 1999)17 and (b) history of hypertension (BP4140/90 mmHg, based on three sphygmomanometer measurements during each Clinic BP measurements examination, repeated in three different exami- BP was measured three times using a mercury nations in 1 month duration). The former criteria sphygmomanometer (standard cuff applied around for sustained hypertensives is in compliance with the nondominant arm and systolic and diastolic the existing literature, according to which the 24 h values identified from the first and fifth phase of ABPM is a highly reproducible procedure, adequate Korotkoff sounds). During the measurements, the to establish the long-term hypertensive status of an 17,18 study participants remained seated with the arm individual. placed at the heart level. The three initial BP values Controls were selected among healthy subjects were averaged to obtain a single systolic and proceeding to the hospital for routine medical diastolic ‘clinic’ value. check-up, including ECG, chest radiograph, echo- cardiography and ABPM. In the control subjects, the following criteria were met: (a) no history of hypertension, based on previous and past BP ABPM measurements (subjects who reported even once in their life BP values X140/90 mmHg were excluded), All participants underwent 24 h ABPM that was (b) no history of antihypertensive therapy, (c) BP performed using oscillometric Spacelabs 90209 measurements by sphygmomanometer at the out- equipment (Spacelabs, Redmond, Washing- patient unit o140/90 mmHg on the first and second ton, USA). The monitoring equipment was visit (on the next day) and mean 24 h ambulatory BP applied at the end of the medical visit. The o125/85 mmHg. device was set to obtain automatic BP readings at Finally, all participants were enrolled only if they 15-min intervals. The monitoring was always had no evidence (history, physical examination, performed on a working day and the subjects were ECG, chest radiograph, echocardiography) of other instructed to act and work as usual. Eventually, coexisting cardiovascular or pulmonary disease; no 80–96 pairs of systolic and diastolic BP values/ evidence (history, physical examination, previous patient/24 h values and times were fed into a PC/ laboratory tests provided by the patients) of second- Pentium II computer. No subject having fewer than ary hypertension (Cushing’s, Conn’s syndrome, three readings per hour, in any of the 24 h, was pheochromocytoma, etc) immunodeficiency, hyper- included in the study. The accuracy of the ABPM gammaglobulinaemia, autoimmune disease, diabetes system was tested against mercury sphygmoman- mellitus; normal results of serum urea, creatinine, ometer readings, both before each patient was electrolytes, plasma renin activity at rest and after leaving the hospital and on the following day when exercise, urinary excretion of catecholamines; he returned. and normal renal imaging studies (radionuclide renogram, intravenous pyelography or ultra- sound scan). Definition of white-coat hypertension Body weight and height were measured as body surface area (BSA). Occupation, residence, educa- It was defined as the combination of raised clinic tion, alcohol abuse, smoking habits, hyperlipidae- BP (4140 mmHg systolic and/or 90 mmHg diastolic mia, obesity and diabetes mellitus were recorded in BP) with average daytime ambulatory BPo135/ each subject. ‘Cigarette-years’ were calculated as the 85 mmHg.20 Journal of Human Hypertension C. pneumoniae and Epstein–Barr infection in hypertension V Ch Pitiriga et al 23 Serologic analyses reference tests are as follows: for EBV IgM ELISA test 97.4 and 98.3%, respectively; for EBV IgG Venus blood was drawn at the entry for the ELISA test 78.1 and 90.9%, respectively; for
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