TY - JOUR
AU - Yoshimura,, Manabu
AB - Abstract To determine whether Chlamydia pneumoniae (C. pneumoniae) infection is associated with hypertension in Japanese adults, we measured serum levels of IgA (a marker of reinfection) and of IgG (a marker of previous infection) antibodies to C. pneumoniae by enzyme-linked immunosorbent assay in 112 adults including normotensive and untreated hypertensive subjects and in 117 hypertensive subjects who had been receiving treatment for more than 3 years. In 112 adults, positivity rate for IgA was lower (P < .01) in hypertensive than in normotensive or borderline hypertensive subjects. Positivity rates for IgA and IgG together, which indicate persistent infection of C. pneumoniae, were lower (P < .01) in hypertensive than in normotensive subjects. IgA levels were inversely correlated with systolic blood pressure (SBP) (r = 0.530, P = .0001) and with diastolic blood pressure (DBP) (r = 0.398, P = .0001). In the 117 hypertensive subjects treated with medication, positivity rate for IgA was lower (P < .01) in subjects with poor control than in those with good control. Positivity rates for IgA and IgG together were lower (P < 0.01) in the poor control group than in the good or fair control groups. IgA levels were correlated inversely with SBP and DBP. In both 112 adults and 117 hypertensive patients, levels of SBP or DBP were inversely associated with positivity rates for IgA and IgG together in multiple logistic regression analysis. The results suggest an inverse relationship between high blood pressure and C. pneumoniae infection in Japanese adults. Am J Hypertens 2001;14:20–26 © 2001 American Journal of Hypertension, Ltd. Hypertension, blood pressure, Chlamydia pneumoniae, reinfection Chlamydia pneumoniae (C. pneumoniae), the third species to be described in the genus Chlamydia,1 is an obligate intracellular pathogen that is a significant cause of human upper and lower respiratory tract disease.2,3 Several studies have implied an association between C. pneumoniae infection and cardiovascular diseases such as coronary artery disease,4–7 as well as cerebrovascular disease.8,9 Recently, an association between C. pneumoniae infection and severe essential hypertension was reported,10 although the precise mechanism underlying this association was not elucidated. Because hypertension is one of the most important risk factors for cardiovascular disease, a close relationship between C. pneumoniae infection and hypertension may affect the risk of cardiovascular disease in hypertensive patients. In the present study, we measured serum levels of IgA and IgG antibodies to C. pneumoniae in two groups of Japanese adults: one group consisted of normotensive and untreated hypertensive subjects and the other consisted of patients that had been continuously treated for hypertension for more than 3 years. We aimed to clarify the precise relationship between C. pneumoniae infection and blood pressure (BP) in Japanese adults by relating changes in positivity rates for IgA and IgG or serum IgA and IgG levels to BP. Methods This study was approved by the Committee for Human Research of Kyoto Prefectural University of Medicine, and all of the subjects provided informed consent for participation in this study. The relationship between C. pneumoniae infection and BP was investigated in the two protocols described below. Protocol 1 One hundred twelve outpatients were studied (aged 58 ± 10 [mean ± SD]) who came to the hospital for routine medical examination (Table 1). The subjects were 36 men (aged 59 ± 10 years) and 76 women (aged 57 ± 10 years). Subjects who had been treated for hypertension, diabetes mellitus, or other medical conditions, including cardiovascular, renal, and hepatic disorders, were excluded from the study. Each patient's BP was measured by nurses, with the patient sitting, during the morning (9:00 AM to 11:00 AM) with a standard sphygmomanometer on 3 different days. Blood pressure measurements were repeated at least three times on a given day and the mean of the last two measurements was taken as the actual BP for that day. The mean of BP measured on 3 different days was taken as a representative BP. According to the guidelines of the World Health Organization (WHO),11 the subjects were classified as normotensive (NT, systolic blood pressure [SBP] ≤140 mm Hg and diastolic blood pressure [DBP] ≤90 mm Hg), borderline hypertensive (BHT, SBP <160 mm Hg and DBP <95 mm Hg but SBP between 141 and 159 mm Hg or DBP between 91 and 94 mm Hg), or hypertensive (HT, SBP ≥160 mm Hg or DBP ≥95 mm Hg). All hypertensive subjects in this group were at WHO stages I or II. Blood was collected after an overnight fast, and serum was obtained by centrifugation. Serum concentrations of total protein, total cholesterol, HDL cholesterol, triglycerides, and uric acid were measured with an automatic analyzer (Ektachem 700 analyzer; Eastman Kodak, Rochester, NY). Former smoking or alcohol histories were checked by a questionnaire to the participants. Smoking habit was classified as follows: 0, no smoking; +1, less than 20 cigarettes per day; +2, 21–40 cigarettes per day; plus;3, more than 41 cigarettes per day. Alcohol consumption was classified as follows: 0, no alcohol consumption, +1, less than 20 g of alcohol per day; plus;2, 21–50 g of alcohol per day; +3, more than 51 g of alcohol per day. Table 1 Clinical characteristics of protocol 1 participants . NT . BHT . HT . No. (female, male) 48 (31, 17) 29 (20, 9) 35 (25, 10) Age (yr) 58 ± 2 57 ± 2 58 ± 2 Systolic BP (mm Hg) 131 ± 1 149 ± 1 170 ± 2 Diastolic BP (mm Hg) 77 ± 1 86 ± 1 95 ± 1 Body mass index 22 ± 0.4 23 ± 0.5 23 ± 0.5 Smoking habit 0 25 (52%) 13 (45%) 15 (43%) +1 16 (33%) 11 (38%) 15 (43%) +2 6 (13%) 4 (14%) 4 (11%) +3 1 (2%) 1 (3%) 1 (3%) Alcohol consumption 0 23 (48%) 13 (45%) 17 (49%) +1 16 (33%) 8 (28%) 13 (37%) +2 7 (15%) 7 (24%) 3 (8%) +3 2 (4%) 1 (3%) 2 (6%) Serum total cholesterol (mmol/L) 5.25 ± 0.13 5.30 ± 0.16 5.38 ± 0.13 Serum HDL cholesterol (mmol/L 1.43 ± 0.05 1.40 ± 0.08 1.48 ± 0.08 Serum triglycerides (mmol/L) 12.0 ± 1.0 12.7 ± 1.3 11.6 ± 0.7 Serum uric acid (μmol/L) 271 ± 12 266 ± 18 266 ± 12 . NT . BHT . HT . No. (female, male) 48 (31, 17) 29 (20, 9) 35 (25, 10) Age (yr) 58 ± 2 57 ± 2 58 ± 2 Systolic BP (mm Hg) 131 ± 1 149 ± 1 170 ± 2 Diastolic BP (mm Hg) 77 ± 1 86 ± 1 95 ± 1 Body mass index 22 ± 0.4 23 ± 0.5 23 ± 0.5 Smoking habit 0 25 (52%) 13 (45%) 15 (43%) +1 16 (33%) 11 (38%) 15 (43%) +2 6 (13%) 4 (14%) 4 (11%) +3 1 (2%) 1 (3%) 1 (3%) Alcohol consumption 0 23 (48%) 13 (45%) 17 (49%) +1 16 (33%) 8 (28%) 13 (37%) +2 7 (15%) 7 (24%) 3 (8%) +3 2 (4%) 1 (3%) 2 (6%) Serum total cholesterol (mmol/L) 5.25 ± 0.13 5.30 ± 0.16 5.38 ± 0.13 Serum HDL cholesterol (mmol/L 1.43 ± 0.05 1.40 ± 0.08 1.48 ± 0.08 Serum triglycerides (mmol/L) 12.0 ± 1.0 12.7 ± 1.3 11.6 ± 0.7 Serum uric acid (μmol/L) 271 ± 12 266 ± 18 266 ± 12 NT = normotensive subjects; BHT = borderline hypertensive subjects; HT = hypertensive subjects; BP = blood pressure; HDL = high density lipoprotein. Classification of smoking habit or alcohol consumption was described in the Methods. Open in new tab Table 1 Clinical characteristics of protocol 1 participants . NT . BHT . HT . No. (female, male) 48 (31, 17) 29 (20, 9) 35 (25, 10) Age (yr) 58 ± 2 57 ± 2 58 ± 2 Systolic BP (mm Hg) 131 ± 1 149 ± 1 170 ± 2 Diastolic BP (mm Hg) 77 ± 1 86 ± 1 95 ± 1 Body mass index 22 ± 0.4 23 ± 0.5 23 ± 0.5 Smoking habit 0 25 (52%) 13 (45%) 15 (43%) +1 16 (33%) 11 (38%) 15 (43%) +2 6 (13%) 4 (14%) 4 (11%) +3 1 (2%) 1 (3%) 1 (3%) Alcohol consumption 0 23 (48%) 13 (45%) 17 (49%) +1 16 (33%) 8 (28%) 13 (37%) +2 7 (15%) 7 (24%) 3 (8%) +3 2 (4%) 1 (3%) 2 (6%) Serum total cholesterol (mmol/L) 5.25 ± 0.13 5.30 ± 0.16 5.38 ± 0.13 Serum HDL cholesterol (mmol/L 1.43 ± 0.05 1.40 ± 0.08 1.48 ± 0.08 Serum triglycerides (mmol/L) 12.0 ± 1.0 12.7 ± 1.3 11.6 ± 0.7 Serum uric acid (μmol/L) 271 ± 12 266 ± 18 266 ± 12 . NT . BHT . HT . No. (female, male) 48 (31, 17) 29 (20, 9) 35 (25, 10) Age (yr) 58 ± 2 57 ± 2 58 ± 2 Systolic BP (mm Hg) 131 ± 1 149 ± 1 170 ± 2 Diastolic BP (mm Hg) 77 ± 1 86 ± 1 95 ± 1 Body mass index 22 ± 0.4 23 ± 0.5 23 ± 0.5 Smoking habit 0 25 (52%) 13 (45%) 15 (43%) +1 16 (33%) 11 (38%) 15 (43%) +2 6 (13%) 4 (14%) 4 (11%) +3 1 (2%) 1 (3%) 1 (3%) Alcohol consumption 0 23 (48%) 13 (45%) 17 (49%) +1 16 (33%) 8 (28%) 13 (37%) +2 7 (15%) 7 (24%) 3 (8%) +3 2 (4%) 1 (3%) 2 (6%) Serum total cholesterol (mmol/L) 5.25 ± 0.13 5.30 ± 0.16 5.38 ± 0.13 Serum HDL cholesterol (mmol/L 1.43 ± 0.05 1.40 ± 0.08 1.48 ± 0.08 Serum triglycerides (mmol/L) 12.0 ± 1.0 12.7 ± 1.3 11.6 ± 0.7 Serum uric acid (μmol/L) 271 ± 12 266 ± 18 266 ± 12 NT = normotensive subjects; BHT = borderline hypertensive subjects; HT = hypertensive subjects; BP = blood pressure; HDL = high density lipoprotein. Classification of smoking habit or alcohol consumption was described in the Methods. Open in new tab Protocol 2 One hundred seventeen outpatients (68 ± 12 years [mean ± SD]) who were treated for hypertension for more than 3 years were studied (Table 2). The subjects were 56 men (aged 66 ± 13 years) and 61 women (aged 69 ± 11 years). All subjects in this group were classified as WHO stages I or II. Blood pressure measurements were performed as described for protocol 1, and the mean of BP measured every month for 1 year before measurement of serum antibodies to C. pneumoniae was taken as the representative BP. Hypertension was treated with calcium antagonists, diuretics, β-blockers, and angiotensin I converting enzyme inhibitors. Depending on the level of BP on treatment, the subjects were divided into a good control group (SBP ≤ 140 mm Hg and DBP ≤ 90 mm Hg), a fair control group (SBP < 160 mm Hg and DBP < 95 mm Hg but SBP between 141 and 159 mm Hg or DBP between 91 and 94 mm Hg), and a poor control group (SBP ≥ 160 mm Hg or DBP ≥ 95 mm Hg). Serum concentrations of total protein, total cholesterol, HDL cholesterol, triglycerides, and uric acid were measured as described in protocol 1. The degrees of smoking habit and alcohol consumption were checked and classified as described in protocol 1. Table 2 Clinical characteristics of protocol 2 participants . Good Control . Fair Control . Poor Control . No. (female, male) 69 (37, 32) 29 (15, 14) 19 (9, 10) Age (yr) 68 ± 1 68 ± 3 66 ± 2 Systolic BP (mm Hg) 121 ± 2 147 ± 1 173 ± 3 Diastolic BP (mm Hg) 72 ± 1 80 ± 1 94 ± 1 Body mass index 22 ± 0.3 24 ± 0.6 23 ± 0.7 Smoking habit 0 31 (45%) 15 (52%) 8 (42%) +1 26 (38%) 9 (31%) 6 (32%) +2 10 (14%) 4 (14%) 3 (16%) +3 2 (3%) 1 (3%) 2 (10%) Alcohol consumption 0 38 (55%) 14 (48%) 9 (47%) +1 18 (26%) 7 (24%) 6 (32%) +2 13 (19%) 6 (21%) 3 (16%) +3 0 2 (7%) 1 (5%) Serum total cholesterol (mmol/L) 5.20 ± 0.10 5.49 ± 0.16 5.56 ± 0.18 Serum HDL cholesterol (mmol/L) 1.40 ± 0.03 1.48 ± 0.08 1.46 ± 0.08 Serum triglycerides (mmol/L) 13.6 ± 0.8 15.1 ± 1.2 16.1 ± 1.5 Serum uric acid (μmol/L) 301 ± 12 289 ± 18 271 ± 18 . Good Control . Fair Control . Poor Control . No. (female, male) 69 (37, 32) 29 (15, 14) 19 (9, 10) Age (yr) 68 ± 1 68 ± 3 66 ± 2 Systolic BP (mm Hg) 121 ± 2 147 ± 1 173 ± 3 Diastolic BP (mm Hg) 72 ± 1 80 ± 1 94 ± 1 Body mass index 22 ± 0.3 24 ± 0.6 23 ± 0.7 Smoking habit 0 31 (45%) 15 (52%) 8 (42%) +1 26 (38%) 9 (31%) 6 (32%) +2 10 (14%) 4 (14%) 3 (16%) +3 2 (3%) 1 (3%) 2 (10%) Alcohol consumption 0 38 (55%) 14 (48%) 9 (47%) +1 18 (26%) 7 (24%) 6 (32%) +2 13 (19%) 6 (21%) 3 (16%) +3 0 2 (7%) 1 (5%) Serum total cholesterol (mmol/L) 5.20 ± 0.10 5.49 ± 0.16 5.56 ± 0.18 Serum HDL cholesterol (mmol/L) 1.40 ± 0.03 1.48 ± 0.08 1.46 ± 0.08 Serum triglycerides (mmol/L) 13.6 ± 0.8 15.1 ± 1.2 16.1 ± 1.5 Serum uric acid (μmol/L) 301 ± 12 289 ± 18 271 ± 18 Abbreviations as in Table 1. Classification of smoking habit or alcohol consumption was described in the Methods. Open in new tab Table 2 Clinical characteristics of protocol 2 participants . Good Control . Fair Control . Poor Control . No. (female, male) 69 (37, 32) 29 (15, 14) 19 (9, 10) Age (yr) 68 ± 1 68 ± 3 66 ± 2 Systolic BP (mm Hg) 121 ± 2 147 ± 1 173 ± 3 Diastolic BP (mm Hg) 72 ± 1 80 ± 1 94 ± 1 Body mass index 22 ± 0.3 24 ± 0.6 23 ± 0.7 Smoking habit 0 31 (45%) 15 (52%) 8 (42%) +1 26 (38%) 9 (31%) 6 (32%) +2 10 (14%) 4 (14%) 3 (16%) +3 2 (3%) 1 (3%) 2 (10%) Alcohol consumption 0 38 (55%) 14 (48%) 9 (47%) +1 18 (26%) 7 (24%) 6 (32%) +2 13 (19%) 6 (21%) 3 (16%) +3 0 2 (7%) 1 (5%) Serum total cholesterol (mmol/L) 5.20 ± 0.10 5.49 ± 0.16 5.56 ± 0.18 Serum HDL cholesterol (mmol/L) 1.40 ± 0.03 1.48 ± 0.08 1.46 ± 0.08 Serum triglycerides (mmol/L) 13.6 ± 0.8 15.1 ± 1.2 16.1 ± 1.5 Serum uric acid (μmol/L) 301 ± 12 289 ± 18 271 ± 18 . Good Control . Fair Control . Poor Control . No. (female, male) 69 (37, 32) 29 (15, 14) 19 (9, 10) Age (yr) 68 ± 1 68 ± 3 66 ± 2 Systolic BP (mm Hg) 121 ± 2 147 ± 1 173 ± 3 Diastolic BP (mm Hg) 72 ± 1 80 ± 1 94 ± 1 Body mass index 22 ± 0.3 24 ± 0.6 23 ± 0.7 Smoking habit 0 31 (45%) 15 (52%) 8 (42%) +1 26 (38%) 9 (31%) 6 (32%) +2 10 (14%) 4 (14%) 3 (16%) +3 2 (3%) 1 (3%) 2 (10%) Alcohol consumption 0 38 (55%) 14 (48%) 9 (47%) +1 18 (26%) 7 (24%) 6 (32%) +2 13 (19%) 6 (21%) 3 (16%) +3 0 2 (7%) 1 (5%) Serum total cholesterol (mmol/L) 5.20 ± 0.10 5.49 ± 0.16 5.56 ± 0.18 Serum HDL cholesterol (mmol/L) 1.40 ± 0.03 1.48 ± 0.08 1.46 ± 0.08 Serum triglycerides (mmol/L) 13.6 ± 0.8 15.1 ± 1.2 16.1 ± 1.5 Serum uric acid (μmol/L) 301 ± 12 289 ± 18 271 ± 18 Abbreviations as in Table 1. Classification of smoking habit or alcohol consumption was described in the Methods. Open in new tab Serologic study of C. pneumoniae infection The levels of serum IgA and IgG antibodies to C. pneumoniae were determined by a specific enzyme-linked immunosorbent assay (ELISA) kit (HITAZYME C. pneumoniae, Hitachi Chemical Co., Ltd., Tokyo, Japan)12,13; this ELISA method detects antibodies to the chlamydial outer membrane complex, which has been isolated from purified elementary bodies of C. pneumoniae YK-41 strain.14 The levels of IgA and IgG to C. pneumoniae in each sample were expressed as the IgA or IgG index. The IgA index was determined by calculating the corrected optical density (OD) (405 nm) of the IgA sample divided by the IgA cutoff value, and the IgG index by calculating the corrected OD (405 nm) of the IgG sample divided by the IgG cutoff value. ThecorrectedOD (405 nm) ofasample=OD (405 nm) ofsample×referencevalueofapositivecontrol/meanOD (405 nm) ofthepositivecontrol. Thecutoffvalue=meanOD (405 nm) ofanegativecontrol×referencevalueofthepositivecontrol/themeanOD (405 nm) ofthepositivecontrol+0.20. Index values more than 1.10 were scored as positive for IgA or IgG antibodies, whereas those below 1.10 were scored as negative. Detection rates of IgG and IgA antibodies to C. pneumoniae by this ELISA method were compared with the microimmunofluorescence method: sensitivity was 90.4% in IgG and 84.6% in IgA, and specificity was 89.9% in IgG and 86.7% in IgA.13 In addition, the rates of agreement between the ELISA method and Western blotting analysis were 80.0% in IgG and 87.5% in IgA.12 Statistical analysis Values are expressed as mean ± SEM. The Statistical Analysis Software (SAS; SAS Inc., Cary, NC) system was used for statistical analyses. Differences in continuous variables between groups was evaluated by the Wilcoxon rank-sum test, and differences in categoric data between groups was evaluated by χ2 test. Simple regression analysis was used to assess the relationship between antibody levels to C. pneumoniae and BP. Multiple regression method was used when evaluating the effect of a continuous or categoric covariates on a dichotomous outcome (positivity rates for IgA and IgG together). Odds ratios, their corresponding confidence intervals, and standardized estimates were then calculated from the logistic regression parameter estimates; positive values of standardized estimates indicate positive correlation, and the negative values indicate inverse correlation between clinical parameters and positivity rates for IgA and IgG together. P < .05 was considered statistically significant. Results Protocol 1 Clinical characteristics of the study participants subdivided by BP did not differ with respect to age, body mass index, or serum concentrations of total cholesterol, HDL cholesterol, triglycerides, or uric acid (Table 1). Positivity rates for IgA and IgG antibodies to C. pneumoniae in the subjects in protocol 1 were 58.9% (66 of 112 patients) and 53.6% (60 of 112 patients), respectively, and the positivity rate for IgA and IgG together was 42.0% (47 of 112 patients). Positivity rate for IgA was lower in the HT group than in the NT or BHT groups, and was lower in the BHT group than in the NT group (Fig. 1). Positivity rates for IgG or for IgA and IgG together were lower in the HT group than in the NT group, and were lower in the BHT group than in the NT group (Fig. 1). The index of IgA and IgG was lower in the HT and BHT groups than in the NT group (Table 3). The IgA index was correlated inversely with SBP (r = 0.530, P = .0001, n = 112) and with DBP (r = 0.398, P = .0001, n = 112), and the IgG index was also correlated inversely with SBP (r = 0.368, P = .0001, n = 112) and with DBP (r = 0.219, P = .02, n = 112). In multiple logistic regression analysis, SBP and DBP was inversely associated with positivity rate for IgA and IgG together (Table 4). Table 3 Differences in the index of IgA and IgG in Protocol 1 and Protocol 2 . IgA Index . IgG Index . Protocol NT (n = 48) 1.921 ± 0.116 1.756 ± 0.114 BHT (n = 29) 1.129 ± 0.112** 1.297 ± 0.195* HT (n = 35) 0.929 ± 0.097** 0.971 ± 0.144** Protocol 2 Good control (n = 69) 1.813 ± 0.109 1.512 ± 0.103 Fair control (n = 29) 1.456 ± 0.164 1.307 ± 0.112 Poor control (n = 19) 0.994 ± 0.157††‡ 0.971 ± 0.144††‡ . IgA Index . IgG Index . Protocol NT (n = 48) 1.921 ± 0.116 1.756 ± 0.114 BHT (n = 29) 1.129 ± 0.112** 1.297 ± 0.195* HT (n = 35) 0.929 ± 0.097** 0.971 ± 0.144** Protocol 2 Good control (n = 69) 1.813 ± 0.109 1.512 ± 0.103 Fair control (n = 29) 1.456 ± 0.164 1.307 ± 0.112 Poor control (n = 19) 0.994 ± 0.157††‡ 0.971 ± 0.144††‡ Abbreviations as in Table 1. * P < 0.05, ** P < .01, compared with NT group; †† P < .01, compared with good control group, ‡ P < .05, compared with fair control group. Open in new tab Table 3 Differences in the index of IgA and IgG in Protocol 1 and Protocol 2 . IgA Index . IgG Index . Protocol NT (n = 48) 1.921 ± 0.116 1.756 ± 0.114 BHT (n = 29) 1.129 ± 0.112** 1.297 ± 0.195* HT (n = 35) 0.929 ± 0.097** 0.971 ± 0.144** Protocol 2 Good control (n = 69) 1.813 ± 0.109 1.512 ± 0.103 Fair control (n = 29) 1.456 ± 0.164 1.307 ± 0.112 Poor control (n = 19) 0.994 ± 0.157††‡ 0.971 ± 0.144††‡ . IgA Index . IgG Index . Protocol NT (n = 48) 1.921 ± 0.116 1.756 ± 0.114 BHT (n = 29) 1.129 ± 0.112** 1.297 ± 0.195* HT (n = 35) 0.929 ± 0.097** 0.971 ± 0.144** Protocol 2 Good control (n = 69) 1.813 ± 0.109 1.512 ± 0.103 Fair control (n = 29) 1.456 ± 0.164 1.307 ± 0.112 Poor control (n = 19) 0.994 ± 0.157††‡ 0.971 ± 0.144††‡ Abbreviations as in Table 1. * P < 0.05, ** P < .01, compared with NT group; †† P < .01, compared with good control group, ‡ P < .05, compared with fair control group. Open in new tab Positivity rates for IgA (A), IgG (B), or both IgA and IgG (C) antibodies to Chlamydia pneumoniae in normotensive (NT), borderline hypertensive (BHT), or untreated hypertensive (HT) subjects (protocol 1). **P < .01. Figure 1. Open in new tabDownload slide Figure 1. Open in new tabDownload slide Table 4 Multiple logistic regression analyses between clinical parameters and positivity rate for IgA and IgG together in subjects of Protocol 1 and Protocol 2 . Protocol 1 . Protocol 2 . . Odds Ratio (95% CI) . Standardized Estimate . P . Odds Ratio (95%) CI) . Standardized Estimate . P . Age 1.12 −0.08 .78 1.05 –0.03 .53 (0.87–1.21) (0.91–1.08) Sex 1.33 +0.23 .69 1.15 +0.27 .73 (0.75–3.63) (0.88–2.32) Systolic blood pressure 0.17 −3.27 <.01 0.25 −2.94 <.01 (0.02–0.41) (0.07–0.62) Diastolic blood pressure 0.14 −2.85 <.01 0.31 −1.79 <.01 (0.04–0.67) (0.11–0.71) Body mass index 0.92 −0.11 .51 0.98 −0.13 .45 (0.78–1.35) (0.71–1.27) Smoking habit 1.34 +0.36 .93 1.21 +0.28 .64 (0.83–2.21) (0.79–2.52) Alcohol consumption 1.05 +0.21 .52 1.32 +0.19 .43 (0.52–1.97) (0.78–2.46) Serum total protein 1.04 +0.38 .62 1.27 +0.32 .48 (0.64–3.43) (0.65–2.83) Serum total cholesterol 1.18 −0.23 .88 0.89 −0.17 .33 (0.86–1.53) (0.71–1.49) Serum HDL cholesterol 0.92 –0.16 .72 0.89 −0.14 .67 (0.88–1.11) (0.73–1.34) Serum triglycerides 0.97 −0.21 .43 0.91 −0.29 .65 (0.87–1.21) (0.72–1.28) . Protocol 1 . Protocol 2 . . Odds Ratio (95% CI) . Standardized Estimate . P . Odds Ratio (95%) CI) . Standardized Estimate . P . Age 1.12 −0.08 .78 1.05 –0.03 .53 (0.87–1.21) (0.91–1.08) Sex 1.33 +0.23 .69 1.15 +0.27 .73 (0.75–3.63) (0.88–2.32) Systolic blood pressure 0.17 −3.27 <.01 0.25 −2.94 <.01 (0.02–0.41) (0.07–0.62) Diastolic blood pressure 0.14 −2.85 <.01 0.31 −1.79 <.01 (0.04–0.67) (0.11–0.71) Body mass index 0.92 −0.11 .51 0.98 −0.13 .45 (0.78–1.35) (0.71–1.27) Smoking habit 1.34 +0.36 .93 1.21 +0.28 .64 (0.83–2.21) (0.79–2.52) Alcohol consumption 1.05 +0.21 .52 1.32 +0.19 .43 (0.52–1.97) (0.78–2.46) Serum total protein 1.04 +0.38 .62 1.27 +0.32 .48 (0.64–3.43) (0.65–2.83) Serum total cholesterol 1.18 −0.23 .88 0.89 −0.17 .33 (0.86–1.53) (0.71–1.49) Serum HDL cholesterol 0.92 –0.16 .72 0.89 −0.14 .67 (0.88–1.11) (0.73–1.34) Serum triglycerides 0.97 −0.21 .43 0.91 −0.29 .65 (0.87–1.21) (0.72–1.28) CI = confidence interval; other abbreviations as in Tables 1, 2, and 3. Open in new tab Table 4 Multiple logistic regression analyses between clinical parameters and positivity rate for IgA and IgG together in subjects of Protocol 1 and Protocol 2 . Protocol 1 . Protocol 2 . . Odds Ratio (95% CI) . Standardized Estimate . P . Odds Ratio (95%) CI) . Standardized Estimate . P . Age 1.12 −0.08 .78 1.05 –0.03 .53 (0.87–1.21) (0.91–1.08) Sex 1.33 +0.23 .69 1.15 +0.27 .73 (0.75–3.63) (0.88–2.32) Systolic blood pressure 0.17 −3.27 <.01 0.25 −2.94 <.01 (0.02–0.41) (0.07–0.62) Diastolic blood pressure 0.14 −2.85 <.01 0.31 −1.79 <.01 (0.04–0.67) (0.11–0.71) Body mass index 0.92 −0.11 .51 0.98 −0.13 .45 (0.78–1.35) (0.71–1.27) Smoking habit 1.34 +0.36 .93 1.21 +0.28 .64 (0.83–2.21) (0.79–2.52) Alcohol consumption 1.05 +0.21 .52 1.32 +0.19 .43 (0.52–1.97) (0.78–2.46) Serum total protein 1.04 +0.38 .62 1.27 +0.32 .48 (0.64–3.43) (0.65–2.83) Serum total cholesterol 1.18 −0.23 .88 0.89 −0.17 .33 (0.86–1.53) (0.71–1.49) Serum HDL cholesterol 0.92 –0.16 .72 0.89 −0.14 .67 (0.88–1.11) (0.73–1.34) Serum triglycerides 0.97 −0.21 .43 0.91 −0.29 .65 (0.87–1.21) (0.72–1.28) . Protocol 1 . Protocol 2 . . Odds Ratio (95% CI) . Standardized Estimate . P . Odds Ratio (95%) CI) . Standardized Estimate . P . Age 1.12 −0.08 .78 1.05 –0.03 .53 (0.87–1.21) (0.91–1.08) Sex 1.33 +0.23 .69 1.15 +0.27 .73 (0.75–3.63) (0.88–2.32) Systolic blood pressure 0.17 −3.27 <.01 0.25 −2.94 <.01 (0.02–0.41) (0.07–0.62) Diastolic blood pressure 0.14 −2.85 <.01 0.31 −1.79 <.01 (0.04–0.67) (0.11–0.71) Body mass index 0.92 −0.11 .51 0.98 −0.13 .45 (0.78–1.35) (0.71–1.27) Smoking habit 1.34 +0.36 .93 1.21 +0.28 .64 (0.83–2.21) (0.79–2.52) Alcohol consumption 1.05 +0.21 .52 1.32 +0.19 .43 (0.52–1.97) (0.78–2.46) Serum total protein 1.04 +0.38 .62 1.27 +0.32 .48 (0.64–3.43) (0.65–2.83) Serum total cholesterol 1.18 −0.23 .88 0.89 −0.17 .33 (0.86–1.53) (0.71–1.49) Serum HDL cholesterol 0.92 –0.16 .72 0.89 −0.14 .67 (0.88–1.11) (0.73–1.34) Serum triglycerides 0.97 −0.21 .43 0.91 −0.29 .65 (0.87–1.21) (0.72–1.28) CI = confidence interval; other abbreviations as in Tables 1, 2, and 3. Open in new tab Protocol 2 Clinical characteristics of the hypertensive patients by the level of BP control did not differ according to age, body mass index, or serum concentrations of total cholesterol, HDL cholesterol, triglycerides, or uric acid (Table 2). The positivity rates for IgA and IgG antibodies to C. pneumoniae in the subjects studied in protocol 2 were 62.4% (73 of 117 patients) and 55.6% (65 of 117 patients), respectively, and positivity rate for IgA and IgG together was 45.3% (53 of 117 patients). The positivity rate for IgA was lower in the poor control group than in the good control group, and were lower in the fair control group than in the good control group (Fig. 2). Positivity rates for IgG or for IgA and IgG together were lower in the poor control group than in the good or fair control groups (Fig. 2). The index of IgA and IgG was lower in the poor control group than in the good or fair control groups (Table 3). The IgA index was correlated inversely with SBP (r = 0.312, P = .0006, n = 117) and with DBP (r = 0.349, P = .0001, n = 117), and the IgG index was also correlated inversely with SBP (r = 0.310, P = .0007, n = 117) and with DBP (r = 0.414, P = .0001, n = 117). Systolic and diastolic blood pressure was inversely associated with positivity rate for IgA and IgG together in multiple logistic regression analysis (Table 4). Positivity rates for IgA (A), IgG (B), or both IgA and IgG (C) antibodies to Chlamydia pneumoniae in subjects in the good control, fair control, or poor control groups (protocol 2). *P < .05, **P < .01. Figure 2. Open in new tabDownload slide Figure 2. Open in new tabDownload slide Discussion Positivity rates for IgA or IgG to C. pneumoniae in this study were 54% to 59% in the subjects studied in protocol 1, and were 56% to 62% in the subjects studied in protocol 2. Because the positivity rates for serum antibodies to C. pneumoniae in Western countries are reportedly 50% to 60%,2,15 the prevalence of C. pneumoniae infection does not appear to be different between Japan and Western countries. In this study, in the subjects including untreated hypertension, positivity rates for IgA or IgG, either alone or together, were inversely proportional to SBP and DBP. In addition, in the subjects who had been receiving continuous medical treatment for hypertension, positivity rates for IgA or IgG, either alone or together, were also inversely proportional to controlled levels of SBP or DBP. These findings suggest that BP levels but not hypertension itself are associated with infectiousness of C. pneumoniae in Japanese adults. C. pneumoniae infection in humans is characterized by multiple repeated infections.16 After acute C. pneumoniae infection, IgG antibody titers increase and do not decrease for several years, whereas IgA antibody titers disappear slowly.17 In reinfection, the response of both IgA and IgG is prominent, and elevated levels of IgA and IgG together are thought to be a marker of chronic persistent infection of C. pneumoniae,18,19 although this hypothesis is not proven. As described above, this ELISA method detects antibodies to the chlamydial outer membrane complex, which is produced in infected monocytes/macrophages and presented in the cell surface or released into the circulation from these cells.12–14 Therefore, the simultaneous serum occurrence of IgA and IgG antibodies to C. pneumoniae is expected to mainly indicate the repeated or persistent infection of C. pneumoniae to monocytes/macrophages in the blood. We need to refer to the points that differences in age, sex, obesity, nutritional state, former histories of smoking or alcohol, or lipid metabolism, which are thought to affect BP, may confound the analysis of the association between the infectiousness of C. pneumoniae and BP. Multiple logistic regression analysis, however, showed a significant association of SBP or DBP with positivity rate for IgA and IgG together, but no association of other clinical parameters such as age, sex, body mass index, smoking habit, alcohol consumption, or serum concentrations of total protein, total cholesterol, HDL cholesterol, and triglycerides with positivity rate for IgA and IgG together. Therefore, levels of BP are thought to be associated with the persistent infection of C. pneumoniae, not confounded by other factors such as obesity, smoking habit, alcohol intake, or lipid metabolism. Alterations in immune function have been reported in hypertensive patients, although the precise connection between hypertension and immune function is not clear.20 Studies using spontaneously hypertensive rats (SHR) have shown a significant reduction in circulating T cells in the peripheral blood, in immature T cells in the thymus, and in the blastogenic response to phytohemagglutinin A and concanavalin A.21–23 Further studies have revealed that the decrease in the T-cell population of SHR is related to CD8+ T cells, which include suppresser T cells as well as cytotoxic T cells,24, but CD8+ T cells are not likely to affect chlamydial infection.25 In primary murine pneumonia from the mouse pneumonitis agent, depletion of CD4+ T cells leads to an increase in mortality and a decrease in production of interferon-γ,25 which is the major cytokine produced by T-helper 1 cells (CD4+ T cells) and which plays a role in protection from chlamydial infection.26 However, there is no evidence that hypertensive patients have increased function and numbers of CD4+ T cells.25,26 The importance of the systemic BP for airway blood flow has been reported in other studies.27,28 The increase in mucosal blood flow in the airway parallels the increase in systemic BP, and increased bronchial mucosal blood flow causes enhanced plasma exudation in the airway.28 Because plasma exudate contains many inflammatory mediator cells such as monocytes/macrophages, the increased mucosal blood flow induced by hypertension may play a role in the inhibition of C. pneumoniae infection by promoting the clearance of C. pneumoniae from the airway. Further clinical and experimental studies are needed to clarify the involvement of the immune system in C. pneumoniae infection in hypertensive patients. The results of this study are not consistent with those of the study by Cook et al,10 which showed a close association between C. pneumoniae infection and hypertension. The precise basis for these discrepant results is not clear, but differences in the hypertensive subjects studied may be one of the reasons. The subjects in our study had benign hypertension (WHO stages I–II), whereas the subjects studied by Cook et al10 appeared to have more severe hypertension. Racial differences may also be involved in these discrepancies; Asian people comprised only 14.6% of the subjects studied by Cook et al. To ascertain whether the inverse relationship between C. pneumoniae infection and BP is peculiar to Japanese adults, we need further studies in other Asian countries. Laurila et al29 reported that serum triglyceride and total cholesterol concentrations are higher in subjects with chronic C. pneumoniae infection than in subjects with no antibodies, and that HDL cholesterol concentrations and the ratio of HDL cholesterol to total cholesterol are decreased in subjects with chronic infection. C. pneumoniae lipopolysaccharide reportedly can mimic the effects of tumor necrosis factor-α, which increases serum concentrations of triglycerides but decreases serum concentrations of HDL cholesterol.16,17 In our present study, however, levels of antibodies to C. pneumoniae were not associated with a serum lipid profile known to be a risk factor for atherosclerosis. Other studies could not find an association between C. pneumoniae infection and changes in serum lipids.9 Because serum lipid levels are affected by many factors, it may be difficult to demonstrate a constant association between serum lipids and C. pneumoniae infection. Results in the present study suggest that high BP inhibits reinfection or chronic infection of C. pneumoniae in Japanese adults, although the precise mechanism underlying this relationship between BP and C. pneumoniae infection is not clear. If BP is involved in the genesis of repeated or chronic infection of C. pneumoniae, it may offer new insights into the mechanism of infectiousness of C. pneumoniae in adults. We need further investigation to determine whether the inverse relationship between BP and C. pneumoniae infection seen in this study is limited to C. pneumoniae or can be extended to the infections from other pathogens, including C. trachomatis or various bacteria. References 1. Graystone JT , Kuo C-C, Campbell LA, Wang S-P: Chlamydia pneumoniae sp. nov. for Chlamydia sp. Strain TWAR . Int J Syst Bacteriol 1989 ; 39 : 88 – 90 . Google Scholar Crossref Search ADS WorldCat 2. Grayston JT : Infections caused by Chlamydia pneumoniae strain TWAR . 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Google Scholar Crossref Search ADS PubMed WorldCat Author notes * This study was supported in part by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Science and Culture of Japan (#09672362). © 2001 by the American Journal of Hypertension, Ltd. American Journal of Hypertension, Ltd.
TI - Inverse association of Chlamydia pneumoniae infection with high blood pressure in Japanese adults
JF - American Journal of Hypertension
DO - 10.1016/S0895-7061(00)01230-9
DA - 2001-01-01
UR - https://www.deepdyve.com/lp/oxford-university-press/inverse-association-of-chlamydia-pneumoniae-infection-with-high-blood-x00gn9rWyu
SP - 20
EP - 26
VL - 14
IS - 1
DP - DeepDyve
ER -