Associations of serologic markers of infection and inflammation with vascular disease events and mortality in American dialysis patients

Saint Louis University Center for Outcomes Research Salus Center, 2nd Floor, 3545 Lafayette Avenue, MO 63104, USA.
Clinical and Experimental Nephrology (Impact Factor: 2.02). 03/2006; 10(1):55-62. DOI: 10.1007/s10157-005-0392-5
Source: PubMed


Inflammatory markers predict cardiovascular risk and mortality in endstage renal disease. The relationship of chronic infections to inflammation and vascular disease events has not been reported among American dialysis patients.
We performed a cross-sectional and prospective study of a multiracial cohort of 97 chronic hemodialysis patients in California. Anti-Chlamydia pneumoniae IgA and IgG antibodies (Cp-IgA and Cp-IgG), anti-Helicobacter pylori antibodies (Hp-IgG), and highly sensitive C-reactive protein (hsCRP) levels were measured at enrollment. We ascertained the prevalence of atherosclerotic vascular (coronary artery, cerebrovascular, and peripheral vascular) disease (AVD) events, and observed participants for at least 1 year for incident events and mortality. We defined statistical significance as P < 0.01.
Elevated hsCRP levels (77%) and seropositivity to C. pneumoniae were common (Cp-IgA, 49%; Cp-IgG, 64%), whereas the seroprevalence of Hp-IgG was relatively low (25%). The hsCRP levels did not vary with infection status. In bivariate analysis, Cp-IgA and Cp-IgG were each associated with approximately fourfold higher odds of prevalent AVD (P < 0.01). Although anti-chlamydial antibodies maintained nearly significant associations with AVD after covariate adjustment (P < 0.05), antibodies did not predict outcomes over the period of observation. However, hsCRP was a nearly significant independent predictor of prevalent AVD (P = 0.02) and of mortality during follow-up (P = 0.01). We did not detect an association of Hp-IgG with any study outcome.
Our findings generalize a possible link between C. pneumoniae and prevalent atherosclerosis in American hemodialysis patients and confirm the importance of hsCRP as a prognostic indicator. Our work does not support H. pylori as an important mediator of cardiovascular risk in dialysis patients.

3 Reads
  • Source
    • "Inflammation (indicated by CRP level) and chronic C pneumoniae infection have been reported to play an important role in lower limb atherosclerosis and to correlate with the severity of the disease (Kaperonis et al., 2006). A possible link between C. pneumoniae and prevalent atherosclerosis was reported in American hemodialysis patients and confirmed the importance of hsCRP as a prognostic indicator (Lentine et al., 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Coronary artery disease (CAD) is the leading cause of death in many countries. The underlying mechanism of the chronic inflammatory process in atherosclerosis is still unknown. As a possible trigger, different viruses and bacteria may be associated with atherosclerotic diseases. The aim of this work was to investigate the association of chronic infection with C pneumoniae, H pylori and cytomegalovirus (CMV) infections and CAD. Fifty patients [20 with acute coronary artery disease (ACAD) and 30 with chronic coronary artery disease (CCAD)] in addition to 15 healthy individuals as a control group were involved in this study. The studied individuals were subjected to complete history taking, thorough physical examination, electrocardiography, echocardiography and coronary angiography (for patients). Assessment of blood glucose level, lipid profile and creatine kinase (CK) was performed. Determination of hsCRP was done by nephlemetry, while C pneumoniae-, H pylori- and CMV-specific IgG antibodies was done by enzyme immunoassay. Results showed that the levels of cholesterol, triglycerides, LDL-c and hsCRP were significantly higher, while HDL-c was significantly lower among patients compared to that of the controls. A significantly (P<0.05) higher perecentage of patients had C pneumoniae and H pylori-specific IgG antibodies as compared to that of the controls. Higher percentage of patients had CMV-specific IgG antibody, however, there was no significant difference between the 2 groups. The levels of C pneumoniae and H pylori-specific IgG antibodies were significantly (P<0.001) higher among patients with CAD when compared to that of the controls. CMV-specific IgG level in patients was higher compared to that of the controls, however, the difference was not statistically significant. Among acute CAD patients, C pneumoniae-specific IgG was positively correlated with hsCRP (P<0.05), cholesterol (p<0.01) and HDL-c (P<0.05), while H pylori-specific IgG was positively correlated with triglyceride level (P<0.05). Among patients with CCAD, hsCRP was negatively correlated with HDL-c (P<0.05). There was no significant correlation between the levels of CMV-specific IgG and lipid profile or hsCRP. In conclusion, the level of C pneumoniae and H pylori-specific IgG antibodies are elevated among CAD patients and their presence was associated with development of the disease. They were significantly correlated to cholesterol level. Moreover, C pneumoniae-specific IgG was significantly correlated with hsCRP among ACAD patients, suggesting an important role of these organisms in the development of CAD by altering lipid profile and induction of inflammation.
    Pakistan journal of pharmaceutical sciences 04/2011; 24(2):95-101. · 0.68 Impact Factor
  • Source
    • "In particular, both anti-CP IgG and IgA antibodies titers have been associated to progression of carotid atherosclerosis and ischemic heart disease (Kato et al. 2004; Wszola et al. 2006). However, in the clinical setting, together with a great deal of studies reporting the close association between CP infection and CVD, both in general and HD population (Lentine et al. 2006), conflicting evidence by observational and interventional studies also exists (Ieven and Hoymans 2005; O&apos;Connor et al. 2003). Some authors have proposed CP infection only having a subsidiary role in atherosclerosis development in HD patients (Kato et al. 2006). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Autoimmunity to heat shock protein 60 (HSP60) has been related to atherosclerosis. Chlamydia pneumoniae (CP), the most studied infectious agent implicated in promoting atherosclerosis, produces a form of HSP60, which can induce an autoimmune response, due to high antigenic homology with human HSP60 (hHSP60). In this study, we evaluated the correlations among anti-hHSP60 antibodies, CP infection, and cardiovascular disease (CVD) in a high-risk population, such as patients undergoing hemodialysis (HD). Thirty-two patients (67.9 ± 13.9 years; male/female, 23:9) on regular HD were enrolled. Global absolute cardiovascular risk (GCR) was assessed using the Italian CUORE Project's risk charts, which evaluate age, gender, smoking habits, diabetes, systolic blood pressure, and serum cholesterol. The occurrence of cardiovascular events during a 24-month follow-up was recorded. Seropositivity to CP and the presence of anti-hHSP60 antibodies were tested by specific enzyme-linked immunosorbent assays. Inflammation was assessed by measurement of C-reactive protein (CRP) serum levels. Fifteen healthy sex and age-matched (61.9 ± 9.5 years; male/female, 11:4) subjects were the control group. Fifteen of 32 patients resulted seropositive for CP. CP + patients were older than CP-, while they did not differ for GCR, CRP, and dialytic parameters. CVD incidence was significantly higher in CP+ (9 CP+ vs 2 CP-, p < 0.05). Cox analysis recognized that the incidence of CVD was independently correlated with seropositivity to CP (HR, 7.59; p = 0.01; 95% CI = 1.63-35.4). On the other hand, there were no significant differences in anti-hHSP60 levels among CP+, CP- and healthy subjects: 18.11 μg/mL (14.8-47.8), 31.4 μg/mL (23.2-75.3), and 24.72 μg/mL (17.7-41.1), respectively. Anti-hHSP60 did not correlate to GCR, CRP, and incidence of CVD. In conclusion, our data suggest that anti-hHSP60 autoimmune response is not related to CP infection and CP-related CVD risk in HD patients.
    Cell Stress and Chaperones 10/2010; 16(2):219-24. DOI:10.1007/s12192-010-0235-5 · 3.16 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: RESUMEN La enfermedad vascular periférica es una complicación fre-cuente en la población en hemodiálisis que contribuye a aumentar su morbi-mortalidad, al favorecer el estado in-flamatorio, la malnutrición y las complicaciones severas como la isquemia y la sepsis secundaria. El objetivo del es-tudio fue analizar la prevalencia de enfermedad vascular periférica en nuestra población en hemodiálisis, su reper-cusión en la mortalidad y su asociación con parámetros de inflamación y malnutrición. Fueron incluidos 220 pacientes prevalentes en hemodiálisis, del área perteneciente a nuestro centro hospitalario. Se realizó un estudio basal en el año 2001 y se siguieron durante 48 meses. La enferme-dad vascular periférica fue diagnosticada en función de los datos recogidos de las historias clínicas. Se clasificó en au-sencia, claudicación intermitente, úlceras o necrosis. De los 220 pacientes, el 39,5% padecía EVP. La clínica más fre-cuente fue claudicación intermitente (30%), seguida de úl-ceras (6,5%) y necrosis (3%). El 95% recibió tratamiento médico, el 0,5% fue tratado con angioplastia, el 2% con by-pass y se amputó al 2,5%. En el análisis univariante los pacientes con EVP eran más mayores, con mayor índice de Charlson, diabéticos, tenían niveles séricos más elevados de PCR, fibrinógeno y menores de albúmina y prealbúmi-na; con respecto a los libres de enfermedad. La supervi-vencia de los pacientes con EVP fue significativamente menor, analizando la curva Kaplan-Meier (log rank = 12,4; p < 0,000). En el análisis de Cox, los factores que se asocian de forma independiente a la mortalidad son la EVP (p = 0,034; OR = 2,10; IC [1,06 ; 4,23]), la edad (p = 0,001; OR=1,06; IC [1,03; 1,09]) y los niveles bajos de prealbúmina (p = 0,012; OR = 0,93; IC [0,89; 0,98]). La enfermedad vascu-lar periférica es una complicación frecuente en la pobla-ción en HD, que se asocia frecuentemente a un estado in-flamatorio y a un mayor riesgo de mortalidad. Su diagnóstico precoz, mediante interrogatorio dirigido o con exploraciones complementarias, es obligado para iniciar tratamiento. Palabras clave: Enfermedad vascular periférica. Hemodiálisis. Infla-mación. Mortalidad. SUMMARY Peripheral vascular disease (PVD) is a common disease among patients undergoing hemodialysis leading to increase morbidity and mortality with a high risk of inflammation and sepsis. The aim of the present study was to determinate PVD prevalence in our hemodialysis population and association with inflammation. The study sample consisted of 220 patients prevalents in hemo-dialysis. A basal study was made in 2001 and a follow up for 47 months. Data were collected retrospectively. PVD diagnosis was made attending to limb pulses and doppler in revisions. Diagno-sis was classified as rest pain, ischemic ulceration and gangrene. Among a total of 220 patients, 89 had prevalent PVD. Thirty per cent had rest pain, 6,5% had ischemic ulceration and 3% had gangrene. Ninety five per cent underwent medical treatment, 0,5% were treated by percutaneous transluminal angioplasty (PTA), 2% were treated with surgical revascularization and 2,5% were treated with amputation. Patients with PVD were older, with higher Charlson index, diabetes, they hay higher CRP and fibrinogen serum levels; and lower albumin and prealbumine serum levels. Survival PVD was decreased in Kaplan-Meier (log rank 012,4; p < 0,000). Adjusted Cox regression analysis revea-led that PVD (p = 0,034; OR = 2,10; IC [1,06; 4,23]) ; age (p = 0,001; OR = 1,06; IC [1,03; 1,09]) and low serum albumin levels (p = 0,012; OR = 0,93; IC [0,89; 0,98]) predicted significantly the risk of mortality. PVD is an independent mortality risk factor in hemodialysis patients. An early diagnosis and treatment are able with examination and doppler. In our sample, a few patients are treated with PTA or surgical revascularization. There is an asso-ciation between PVD and inflammation.
Show more