Limits...
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.

Show MeSH

Related in: MedlinePlus

Kaplan Meier survival curve for cardiovascular disease-related mortality by cytomegalovirus serostatus.Unadjusted Kaplan-Meier survival curves for cardiovascular disease (CVD)-related mortality by cytomegalovirus (CMV) serostatus for 14105 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 and diabetes status, follow-up time from exam to death from CVD was not significantly different between CMV seronegative and CMV seropositive subjects (Adjusted Wald F  = 2.66, p-value  = 0.1092. CMV = cytomegalovirus and MEC = mobile examination center.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3040745&req=5

pone-0016103-g002: Kaplan Meier survival curve for cardiovascular disease-related mortality by cytomegalovirus serostatus.Unadjusted Kaplan-Meier survival curves for cardiovascular disease (CVD)-related mortality by cytomegalovirus (CMV) serostatus for 14105 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 and diabetes status, follow-up time from exam to death from CVD was not significantly different between CMV seronegative and CMV seropositive subjects (Adjusted Wald F  = 2.66, p-value  = 0.1092. CMV = cytomegalovirus and MEC = mobile examination center.

Mentions: The unadjusted Kaplan-Meier survival curves for all-cause mortality by CMV serostatus are shown in Figures 1 and 2. Overall mean survival duration since time of exam for those CMV seropositive was 13.4 years (160.4±2.40 months) whereas mean survival duration was 14.5 years (173.5±3.15 months) for CMV seronegative subjects. Table S1. shows the HR and 95% CI from Cox proportional hazard models examining the association between CMV and all-cause/CVD-related mortality, mutually adjusted for hypothesized confounders. After adjusting for age, gender, race/ethnicity, country of origin, education level, BMI (kg/m2), smoking status and diabetes status, CMV seropositivity remained statistically significantly associated with all-cause mortality (HR 1.19, 95% CI: 1.01, 1.41) and follow-up time from exam to death from all causes was significantly different between CMV seronegative and CMV seropositive subjects (Adjusted Wald F  = 4.66, p-value  = 0.0358) in model 2. The effect of CMV on all-cause mortality was not further attenuated after controlling for CRP level (HR 1.19, 95% CI: 1.01, 1.40 versus HR 1.19, 95% CI: 1.01, 1.41). Although the magnitude of effect for CVD-related mortality was similar to that of all-cause mortality, the association between CMV and CVD-related mortality was not statistically significant in the fully adjusted model and follow-up time from exam to death from CVD-related mortality for those CMV seropositive versus seronegative was not statistically significantly different (Adjusted Wald F  = 2.66, p-value  = 0.1092). Similarly, adjustment for CRP level did not further attenuate the association between CMV and CVD-related mortality (HR 1.19, 95% CI: 0.95, 1.49 versus HR 1.19, 95% CI: 0.96, 1.49).


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 cardiovascular disease-related mortality by cytomegalovirus serostatus.Unadjusted Kaplan-Meier survival curves for cardiovascular disease (CVD)-related mortality by cytomegalovirus (CMV) serostatus for 14105 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 and diabetes status, follow-up time from exam to death from CVD was not significantly different between CMV seronegative and CMV seropositive subjects (Adjusted Wald F  = 2.66, p-value  = 0.1092. CMV = cytomegalovirus and MEC = mobile examination center.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0016103-g002: Kaplan Meier survival curve for cardiovascular disease-related mortality by cytomegalovirus serostatus.Unadjusted Kaplan-Meier survival curves for cardiovascular disease (CVD)-related mortality by cytomegalovirus (CMV) serostatus for 14105 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 and diabetes status, follow-up time from exam to death from CVD was not significantly different between CMV seronegative and CMV seropositive subjects (Adjusted Wald F  = 2.66, p-value  = 0.1092. CMV = cytomegalovirus and MEC = mobile examination center.
Mentions: The unadjusted Kaplan-Meier survival curves for all-cause mortality by CMV serostatus are shown in Figures 1 and 2. Overall mean survival duration since time of exam for those CMV seropositive was 13.4 years (160.4±2.40 months) whereas mean survival duration was 14.5 years (173.5±3.15 months) for CMV seronegative subjects. Table S1. shows the HR and 95% CI from Cox proportional hazard models examining the association between CMV and all-cause/CVD-related mortality, mutually adjusted for hypothesized confounders. After adjusting for age, gender, race/ethnicity, country of origin, education level, BMI (kg/m2), smoking status and diabetes status, CMV seropositivity remained statistically significantly associated with all-cause mortality (HR 1.19, 95% CI: 1.01, 1.41) and follow-up time from exam to death from all causes was significantly different between CMV seronegative and CMV seropositive subjects (Adjusted Wald F  = 4.66, p-value  = 0.0358) in model 2. The effect of CMV on all-cause mortality was not further attenuated after controlling for CRP level (HR 1.19, 95% CI: 1.01, 1.40 versus HR 1.19, 95% CI: 1.01, 1.41). Although the magnitude of effect for CVD-related mortality was similar to that of all-cause mortality, the association between CMV and CVD-related mortality was not statistically significant in the fully adjusted model and follow-up time from exam to death from CVD-related mortality for those CMV seropositive versus seronegative was not statistically significantly different (Adjusted Wald F  = 2.66, p-value  = 0.1092). Similarly, adjustment for CRP level did not further attenuate the association between CMV and CVD-related mortality (HR 1.19, 95% CI: 0.95, 1.49 versus HR 1.19, 95% CI: 0.96, 1.49).

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