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Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States.

Simanek AM, Dowd JB, Pawelec G, Melzer D, Dutta A, Aiello AE - PLoS ONE (2011)

Bottom Line: After adjusting for multiple confounders, CMV seropositivity remained statistically significantly associated with all-cause mortality (HR 1.19, 95% CI: 1.01, 1.41).The association between CMV and CVD-related mortality did not achieve statistical significance after confounder adjustment.CRP did not mediate these associations.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, Center for Social Epidemiology and Population Health, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.

ABSTRACT

Background: Studies have suggested that CMV infection may influence cardiovascular disease (CVD) risk and mortality. However, there have been no large-scale examinations of these relationships among demographically diverse populations. The inflammatory marker C-reactive protein (CRP) is also linked with CVD outcomes and mortality and may play an important role in the pathway between CMV and mortality. We utilized a U.S. nationally representative study to examine whether CMV infection is associated with all-cause and CVD-related mortality. We also assessed whether CRP level mediated or modified these relationships.

Methodology/principal findings: Data come from subjects ≥ 25 years of age who were tested for CMV and CRP level and were eligible for mortality follow-up on December 31(st), 2006 (N = 14153) in the National Health and Nutrition Examination Survey (NHANES) III (1988-1994). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and CVD-related mortality by CMV serostatus. After adjusting for multiple confounders, CMV seropositivity remained statistically significantly associated with all-cause mortality (HR 1.19, 95% CI: 1.01, 1.41). The association between CMV and CVD-related mortality did not achieve statistical significance after confounder adjustment. CRP did not mediate these associations. However, CMV seropositive individuals with high CRP levels showed a 30.1% higher risk for all-cause mortality and 29.5% higher risk for CVD-related mortality compared to CMV seropositive individuals with low CRP levels.

Conclusions/significance: CMV was associated with a significant increased risk for all-cause mortality and CMV seropositive subjects who also had high CRP levels were at substantially higher risk for both for all-cause and CVD-related mortality than subjects with low CRP levels. Future work should target the mechanisms by which CMV infection and low-level inflammation interact to yield significant impact on mortality.

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Kaplan-Meier survival curve for all-cause mortality by combined cytomegalovirus serostatus and c-reactive protein level.Unadjusted Kaplan-Meier survival curves for all-cause mortality by combined cytomegalovirus (CMV) serostatus and C-reactive Protein (CRP) level for 14011 subjects, ≥25 years of age, in the National Health and Nutrition Examination Survey (NHANES) III from 1988–2006. After adjusting for age, gender, race/ethnicity, country of origin, education level, BMI (kg/m2), smoking status, diabetes status and non-steroidal anti-inflammatory drug use, follow-up time from exam to death from all-causes for CMV seropositive individuals with high CRP level was significantly different from CMV seropositive individuals with low CRP level (Adjusted Wald F  = 36.19, p<0.0001). CMV = cytomegalovirus, CRP = C-reactive Protein and MEC = mobile examination center. High CRP level: ≥0.3 mg/dL.
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pone-0016103-g003: Kaplan-Meier survival curve for all-cause mortality by combined cytomegalovirus serostatus and c-reactive protein level.Unadjusted Kaplan-Meier survival curves for all-cause mortality by combined cytomegalovirus (CMV) serostatus and C-reactive Protein (CRP) level for 14011 subjects, ≥25 years of age, in the National Health and Nutrition Examination Survey (NHANES) III from 1988–2006. After adjusting for age, gender, race/ethnicity, country of origin, education level, BMI (kg/m2), smoking status, diabetes status and non-steroidal anti-inflammatory drug use, follow-up time from exam to death from all-causes for CMV seropositive individuals with high CRP level was significantly different from CMV seropositive individuals with low CRP level (Adjusted Wald F  = 36.19, p<0.0001). CMV = cytomegalovirus, CRP = C-reactive Protein and MEC = mobile examination center. High CRP level: ≥0.3 mg/dL.

Mentions: Figures 3 and 4 show the unadjusted Kaplan-Meier survival curves for all-cause and CVD-related mortality by the four different permutations of CMV serostatus and CRP level. The overall mean survival times from exam to mortality for each combination of CMV serostatus and CRP level were 14.7 years (176.0±3.20 months) for CMV seronegative individuals with low CRP, 13.8 years (165.6±3.49 months) for CMV seronegative individuals with high CRP, 13.8 years (165.5±2.46 months) for CMV seropositive individuals with low CRP and 12.5 years (150.0±3.49 months) for CMV seropositive individuals with high CRP.


Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States.

Simanek AM, Dowd JB, Pawelec G, Melzer D, Dutta A, Aiello AE - PLoS ONE (2011)

Kaplan-Meier survival curve for all-cause mortality by combined cytomegalovirus serostatus and c-reactive protein level.Unadjusted Kaplan-Meier survival curves for all-cause mortality by combined cytomegalovirus (CMV) serostatus and C-reactive Protein (CRP) level for 14011 subjects, ≥25 years of age, in the National Health and Nutrition Examination Survey (NHANES) III from 1988–2006. After adjusting for age, gender, race/ethnicity, country of origin, education level, BMI (kg/m2), smoking status, diabetes status and non-steroidal anti-inflammatory drug use, follow-up time from exam to death from all-causes for CMV seropositive individuals with high CRP level was significantly different from CMV seropositive individuals with low CRP level (Adjusted Wald F  = 36.19, p<0.0001). CMV = cytomegalovirus, CRP = C-reactive Protein and MEC = mobile examination center. High CRP level: ≥0.3 mg/dL.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3040745&req=5

pone-0016103-g003: Kaplan-Meier survival curve for all-cause mortality by combined cytomegalovirus serostatus and c-reactive protein level.Unadjusted Kaplan-Meier survival curves for all-cause mortality by combined cytomegalovirus (CMV) serostatus and C-reactive Protein (CRP) level for 14011 subjects, ≥25 years of age, in the National Health and Nutrition Examination Survey (NHANES) III from 1988–2006. After adjusting for age, gender, race/ethnicity, country of origin, education level, BMI (kg/m2), smoking status, diabetes status and non-steroidal anti-inflammatory drug use, follow-up time from exam to death from all-causes for CMV seropositive individuals with high CRP level was significantly different from CMV seropositive individuals with low CRP level (Adjusted Wald F  = 36.19, p<0.0001). CMV = cytomegalovirus, CRP = C-reactive Protein and MEC = mobile examination center. High CRP level: ≥0.3 mg/dL.
Mentions: Figures 3 and 4 show the unadjusted Kaplan-Meier survival curves for all-cause and CVD-related mortality by the four different permutations of CMV serostatus and CRP level. The overall mean survival times from exam to mortality for each combination of CMV serostatus and CRP level were 14.7 years (176.0±3.20 months) for CMV seronegative individuals with low CRP, 13.8 years (165.6±3.49 months) for CMV seronegative individuals with high CRP, 13.8 years (165.5±2.46 months) for CMV seropositive individuals with low CRP and 12.5 years (150.0±3.49 months) for CMV seropositive individuals with high CRP.

Bottom Line: After adjusting for multiple confounders, CMV seropositivity remained statistically significantly associated with all-cause mortality (HR 1.19, 95% CI: 1.01, 1.41).The association between CMV and CVD-related mortality did not achieve statistical significance after confounder adjustment.CRP did not mediate these associations.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology, Center for Social Epidemiology and Population Health, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.

ABSTRACT

Background: Studies have suggested that CMV infection may influence cardiovascular disease (CVD) risk and mortality. However, there have been no large-scale examinations of these relationships among demographically diverse populations. The inflammatory marker C-reactive protein (CRP) is also linked with CVD outcomes and mortality and may play an important role in the pathway between CMV and mortality. We utilized a U.S. nationally representative study to examine whether CMV infection is associated with all-cause and CVD-related mortality. We also assessed whether CRP level mediated or modified these relationships.

Methodology/principal findings: Data come from subjects ≥ 25 years of age who were tested for CMV and CRP level and were eligible for mortality follow-up on December 31(st), 2006 (N = 14153) in the National Health and Nutrition Examination Survey (NHANES) III (1988-1994). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and CVD-related mortality by CMV serostatus. After adjusting for multiple confounders, CMV seropositivity remained statistically significantly associated with all-cause mortality (HR 1.19, 95% CI: 1.01, 1.41). The association between CMV and CVD-related mortality did not achieve statistical significance after confounder adjustment. CRP did not mediate these associations. However, CMV seropositive individuals with high CRP levels showed a 30.1% higher risk for all-cause mortality and 29.5% higher risk for CVD-related mortality compared to CMV seropositive individuals with low CRP levels.

Conclusions/significance: CMV was associated with a significant increased risk for all-cause mortality and CMV seropositive subjects who also had high CRP levels were at substantially higher risk for both for all-cause and CVD-related mortality than subjects with low CRP levels. Future work should target the mechanisms by which CMV infection and low-level inflammation interact to yield significant impact on mortality.

Show MeSH
Related in: MedlinePlus