Association of Chlamydophila pneumoniae DNA in peripheral blood mononuclear cells and IgA antibody with atherosclerotic diseases.

An association has been demonstrated between Chlamydophila pneumoniae (C. pneumoniae) infection and atherosclerosis, but data on the relationship between C. pneumoniae DNA in peripheral blood mononuclear cells (PBMC) and antibodies to this organism are lacking. We investigated the C. pneumoniae DNA in PBMC by polymerase chain reaction (PCR) and C. pneumoniae IgG and IgA antibodies by enzyme-linked immunosorbent assay of 168 patients with atherosclerotic diseases and 27 controls (healthy control subjects). C. pneumoniae DNA was detected for 48/168 (29%) atherosclerosis patients, IgG for 79 (47%), and IgA for 98 (58%), whereas the corresponding numbers for the controls were 11 (41%), 13 (48%), and 7 (26%). There was no significant difference of the C. pneumoniae DNA positivity rate between the atherosclerosis patients and the controls. However, the C. pneumoniae IgA-positive rate was significantly higher for carotid atherosclerosis patients who had C. pneumoniae DNA in their PBMC than for those without it (74% vs. 18%, P < 0.05). Among the patients with coronary artery disease, the C. pneumoniae IgA antibody positive rate was significantly higher for the patients with DNA than for those without it (68% vs. 18%, P < 0.05). Our results suggest that a high C. pneumoniae IgA antibody titer and C. pneumoniae DNA positivity are associated with an increased risk of atherosclerotic diseases due to endovascular C. pneumoniae infection.

[AIDS-related Mycobacterium avium infection dissemination in a patient with endobronchial lesions associated with immune reconstitution inflammatory syndrome].

Highly active antiretroviral therapy (HAART) has dramatically decreased the incidence of HIV-1-associated morbidity and mortality. During the initial months of HAART, immune reconstitution inflammatory syndrome (IRIS), an adverse consequence of restoration of the pathogen-specific immune response, often occurred in terminal-stage in patients, with MAC infection the most frequently implicated in IRIS. In August 2004, a 26-year-old Japanese woman with fever and general lymphadenopathy was diagnosed with AIDS (HIV-1 RNA 5.7 x 10(5) copies/mL, CD4+ T cell count 10/microL) and disseminated Mycobacterium avium (M. avium) infection, for which antimycobacterial treatment was initiated. The M. avium infection responded well to two months of this treatment, and HAART was begun. Despite good virologic response to HAART (HIV-1 RNA <50 copies/mL), she contracted pulmonary disease with parenchymal lung changes, endobronchial lesions, and localized supraclavicular lymphadenitis, which are M. avium-associated IRIS. Good immunological response (CD4+ T cell count 136/microL) and a stronger antimycobacterial treatment helped her overcoming M. avium-associated IRIS without systemic corticosteroids or the discontinuation of HAART. The possibility of IRIS should always be watched for when treating AIDS patients with HAART and an antimycobacterial treatment regimen formulated that considers potential drug interactions with HAART.

Association of hyperhomocysteinemia and Chlamydia pneumoniae infection with carotid atherosclerosis and coronary artery disease in Japanese patients.

An elevated plasma level of homocysteine (Hcy) and infection by Chlamydia pneumoniae (C. pneumoniae) have been suggested as independent risk factors for carotid atherosclerosis (CA) and coronary artery disease (CAD), but the mechanisms involved are unclear. We investigated the correlation between positivity for antibody to C. pneumonia (anti-C. pneumoniae) and the Hcy level in patients with CA and CAD. The total plasma homocysteine (tHcy) concentration was determined in 99 patients with CA and 31 patients with CAD, as well as 119 controls with matched risk factors for atherosclerosis. The tHcy level was measured with a Bio-Rad microplate enzyme immunoassay. In the CAD group, the tHcy level (13.67 micromol/l) was significantly higher than that in other groups (CA group, 10.96 micromol/l; control group, 9.95 micromol/l; ANOVA, P = 0.0006). Positivity for anti-C. pneumoniae IgG was significantly more common in the CAD group (77.4%) than in the other groups (CA group, 53.5%; control group, 54.6%; ANOVA, P = 0.0490). There was no association between anti-C. pneumoniae IgA positivity or tHcy and conventional risk factors. However, anti-C. pneumoniae IgG positivity was significantly more common in subjects with higher tHcy levels than in those with low tHcy levels from each of the 3 groups. The CAD group had significantly higher tHcy levels, and tHcy was significantly associated with anti-C. pneumoniae IgG positivity. These findings indicate that elevation of tHcy is related to positivity for anti-C. pneumoniae IgG in patients with CAD.

Effect on carotid atherosclerosis of probucol plus levofloxacin for Chlamydia pneumoniae infection.

To investigate the effect of levofloxacin on carotid atherosclerosis, patients with hypercholesterolemia whose carotid atherosclerosis was not improved by probucol therapy (500 mg/day) for 24 months were enrolled. All patients were seropositive for anti C. pneumoniae IgA and/or IgG. Carotid atherosclerosis was evaluated by ultrasonic measurement of the maximum intima-media thickness (Max-IMT). All subjects were prescribed three courses of levofloxacin (each course, 400 mg/day for 2 weeks, followed by 14 days off drug treatment). At 12 months after combined therapy with probucol and levofloxacin, Max-IMT was significantly decreased compared with the value before treatment (P < 0.01). These results suggest that the combination therapy was effective for improving carotid atherosclerosis in C. pneumoniae-seropositive patients.

Association between fast-migrating low-density lipoprotein subfraction as characterized by capillary isotachophoresis and intima-media thickness of carotid artery.

BACKGROUND: A mildly modified LDL subfraction that is characterized by an increased negative charge exists in plasma. This electronegative LDL separated by ion-exchange chromatography has been shown to be inflammatory and its proportion is increased in patients with hyperlipidemia and diabetes mellitus. The present study examined the association between the level of fast (f)-migrating LDL subfraction characterized by capillary isotachophoresis (cITP) and carotid-artery intima-media thickness (CA-IMT). METHODS AND RESULTS: This study included 469 subjects who underwent a physical examination. CA-IMT was determined by high-resolution B-model ultrasonoraphy. Levels of charge-based LDL subfractions were measured by cITP on a Beckman P/ACE MDQ system. An increased serum LDL-C level and cITP fLDL level were associated with increased CA-IMT after adjusting for age. The extent of the associations between cITP fLDL and CA-IMT and between LDL-C and CA-IMT were similar as assessed by a receiver-operating characteristic curve analysis. LDL-C, triglyceride, and remnant-like particle cholesterol levels were independently correlated with cITP fLDL, and the LDL-C level had the strongest correlation with cITP fLDL. The association between the cITP fLDL level and CA-IMT was significant in the high LDL-C stratum but not in the low stratum, indicating that it is modified by the LDL-C level. The high-LDL-C-high-fLDL group had the highest relative risk for a high CA-IMT among the groups with each combination of LDL-C and cITP fLDL level. CONCLUSION: The cITP fLDL level was associated with CA-IMT and its combination with the LDL-C level is a stronger indicator for a high CA-IMT.

Pravastatin improves insulin resistance in dyslipidemic patients.

To evaluate the effect of pravastatin on both lipid and glucose metabolism, twenty-two consecutive dyslipidemic patients treated with pravastatin at 10 mg/day for one year were enrolled in this study. The meal test, which consisted of 115 g of cookies (energy 560 kcal; glucose 75 g; protein 7 g; fat 24 g), was conducted before and after one year of treatment. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR), by the area under the IRI curve (AUC-IRI), and by the formula AUC-IRI x AUC-PG. After one year of treatment with pravastatin, the plasma glucose (PG), immunoreactive insulin (IRI) and C-peptide levels were unchanged after fasting and at 120 minutes after the meal test; however, PG, IRI and C-peptide levels at 60 minutes after the meal were all significantly decreased from baseline (p < 0.05). AUC-IRI and AUC-IRI x AUC-PG were also significantly decreased (p < 0.05). HOMA-IR was reduced by 26.8%, but the reduction was not significant. The triglyceride (TG) level was decreased after fasting and increased at 60 and 120 minutes after the meal test, but not significantly. This study demonstrated that pravastatin not only reduced serum lipids, but also improved the glucose metabolism, including insulin resistance, of dyslipidemic patients.

The influence of lifestyle modification on carotid artery intima-media thickness in a suburban Japanese population.

To evaluate the influence of lifestyle modification with and without lipid-lowering drug therapy on the carotid arterial wall, we did a 2 year prospective ultrasound study of carotid intima-media thickness (IMT) in 1390 male and female residents of a suburban Japanese town. According to total cholesterol (TC) level at baseline, subjects were classified into a lifestyle modification alone group (TC >/= 220 mg/dl, n = 437), a lifestyle modification with lipid-lowering drug group (TC >/= 220 mg/dl, n = 159), and a control group (TC < 220 mg/dl, n = 794). After 2 years of follow-up, both sexes of both treatment groups showed significant reductions of TC, low-density lipoprotein cholesterol (LDL-C), and IMT, although TC continued over 220 mg/dl in some subjects in the lifestyle modification group. The reduction of TC and LDL-C was significantly higher in the lifestyle modification with lipid-lowering drug group than in the lifestyle modification alone group. Although the IMT reduction was not statistically different between the treatment groups of either sex, the reduction of IMT was greater in the lifestyle modification with lipid-lowering drug group than in the lifestyle modification alone group. Our results indicate that comprehensive lifestyle modification can reduce carotid IMT in the general population, with or without the use of lipid-lowering drugs and that cholesterol reduction is of benefit even when TC level remain above the recommended level.

Carotid atherosclerosis and cardiovascular risk factors: a comparison of residents of a rural area of Okinawa with residents of a typical suburban area of Fukuoka, Japan.

Areas of Japan are known worldwide for the longevity of their residents. Okinawa has the highest longevity in Japan and a low rate of death due to cardiovascular disease. We investigated carotid atherosclerotic (CA) risk factors in islands of I city in Okinawa prefecture and compared them with K town, a suburban area of Fukuoka prefecture in Kyushu, to determine the relationship between cardiovascular risk factors and carotid atherosclerosis. We investigated conventional cardiovascular risk factors in 1078 I city residents (375 men, mean age 63.7 and 703 women, mean age 60.0) in 2000 and 2364 K town residents (676 men, mean age 57.1 and 1688 women, mean age 53.0) in 1999. Carotid atherosclerosis was assessed by mean intima-media thickness (IMT) by B-mode ultrasound. The mean IMT was significantly lower in the residents of I city than in those of K town (P < 0.05). Total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) levels and smoking rate were also lower in I city than in K town. Body mass index (BMI) and triglyceride (TG) level were higher in I city than in K town. In I city, multiple regression analysis found independent relationships between carotid atherosclerosis and age, sex (male), hypertension, LDL cholesterol, high-density-lipoprotein cholesterol (HDL-C), and diabetes. The lower mean IMT is probably related to a lower lifetime burden of atherosclerotic risk factors, which may in turn be related to the longevity of Okinawa residents. BMI was not a cardiovascular risk factor, although LDL cholesterol was a common important risk factor.

Association of Chlamydia pneumoniae antibody with the cholesterol-lowering effect of statins.

To investigate the association between Chlamydia pneumoniae (C. pneumoniae) infection and atherosclerosis, we compared the effect of lipid-lowering drugs on carotid intima-media thickness (IMT) between patients who were positive and negative for C. pneumoniae antibodies. A total of 165 asymptomatic hypercholesterolemic patients were randomized to probucol (500 mg per day, n = 82) or pravastatin (10 mg per day, n = 83) and followed for 2 years. The 2-year change of IMT in the common carotid artery was the primary endpoint, while mean IMT change and major cardiovascular events were secondary endpoints. C. pneumoniae antibodies (IgA and IgG) were measured by enzyme-linked immunosorbent assay. The 50 patients without C. pneumoniae antibodies showed significant reduction of IMT progression (-19%), while no significant change of IMT was noted in the 115 antibody-positive patients (-6%). Significant inverse associations were found between the reduction of IMT progression and the C. pneumoniae IgA- and IgG-antibody index (P < 0.01 and 0.01, respectively). No significant differences in the reduction of serum total-cholesterol and LDL-cholesterol were found between antibody-positive and -negative patients. There was no significant difference of efficacy between probucol and pravastatin. These observations suggest that C. pneumoniae infection reduces the effect of lipid-lowering therapy on carotid atherosclerosis and that this organism may play a role in the progression of atherosclerosis.

Carotid artery lesions and atherosclerotic risk factors in Japanese hemodialysis patients.

To determine the prevalence and severity of carotid artery lesions and which risk factors might be responsible for atherosclerosis in end-stage renal disease (ESRD) patients, we tested for carotid atherosclerosis (CA) by ultrasonography and compared the CA prevalence with well-known or suspected atherosclerotic risk factors in 226 hemodialysis (HD) patients and 2410 healthy residents of Japan. The CA prevalence was higher in the HD patients than in the healthy residents. Univariate analysis showed that HD patients with CA had a higher frequency of diabetes mellitus and left ventricular hypertrophy, and were significantly older, had significantly higher systolic blood pressure and pulse pressure, and lower albumin levels than those without. Multivariate analysis showed that age, pulse pressure, phosphorus, duration of HD, and diabetes mellitus were independent, significant predictors for CA in the HD patients. Neither Chlamydia pneumoniae seropositivity nor elevated homocysteine level was independently, significantly associated with CA. Our results suggest that HD patients had more advanced CA than the healthy residents. CA in the HD patients may be associated not only with several conventional risk factors but also with non-conventional risk factors such as phosphorus and the HD procedure itself.

Chlamydia pneumoniae seropositivity and early carotid atherosclerosis in a suburban Japanese population.

To evaluate the association between Chlamydia pneumoniae (C. pneumoniae) infection and carotid atherosclerosis (CA), we investigated CA assessed by carotid B-mode ultrasound and known or suspected atherosclerotic risk factors including C. pneumoniae IgG and IgA antibodies in 2410 residents (mean age 54.5+/-13.6 years, 697 men) of a suburban Japanese town. CA was found in 30.1% of men and in 14.0% of women, IgG in 59.4% and in 51.4%, and IgA in 36.9% and in 32.4%, respectively. In univariate analysis, most conventional atherosclerotic risk factors and IgA antibody were significantly associated with CA in both sexes, but not IgG. In multivariate logistic regression analysis, independent risk factors for CA were confirmed with age and triglycerides (TG) in men and age, systolic blood pressure, pack-years of smoking, and low-density lipoprotein cholesterol (LDL-C) in women, but not IgG and IgA in either sex. These results do not support C. pneumoniae infection as an important risk factor for CA in this Japanese population.

Effects of probucol and pravastatin on common carotid atherosclerosis in patients with asymptomatic hypercholesterolemia. Fukuoka Atherosclerosis Trial (FAST).

OBJECTIVES: This study investigated the effect of reducing serum lipids on carotid artery intima-media thickness (IMT) in asymptomatic patients with hypercholesterolemia from Fukuoka, Japan. BACKGROUND: Carotid atherosclerosis is a strong, independent predictor of morbidity and mortality in patients with coronary heart disease (CHD). METHODS: A total of 246 asymptomatic hypercholesterolemic patients (mean age 66 years) were randomized to receive either probucol (500 mg/day, n = 82) or pravastatin (10 mg/day, n = 83) or to enter a control group (diet alone, n = 81); they were followed for two years. The change in IMT in the common carotid artery was the primary end point measure, and the incidence of major cardiovascular events was the secondary measure. RESULTS: Over the two-year period, serum low-density lipoprotein (LDL) cholesterol was significantly reduced in the pravastatin group (36%), the probucol group (29%) and the control group (12%) (p < 0.0001, p < 0.0001 and p < 0.05, respectively). After two years, the probucol and pravastatin groups showed a significant reduction in IMT (-13.9% and -13.9% and p < 0.01 and p < 0.01, respectively), but there was significant IMT thickening (23.2%; p < 0.05) in the control group. Probucol reduced the rate of IMT increase, independently of its reduction of LDL or high-density lipoprotein cholesterol. Moreover, there was a significantly lower incidence of cardiac events in the probucol group (2.4%) than in the control group (13.6%) (p = 0.0136). CONCLUSIONS: Probucol reduced cholesterol levels and stabilized plaque, leading to a lower incidence of cardiac events in these hypercholesterolemic patients.