Seropositivity to Cytomegalovirus, Inflammation, All-Cause and Cardiovascular Disease-Related Mortality in the United States

Abstract

BackgroundStudies 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 FindingsData come from subjects ≥25 years of age who were tested for CMV and CRP level and were eligible for mortality follow-up on December 31st, 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/SignificanceCMV 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.

How does cytomegalovirus factor into diseases of aging and vaccine responses, and by what mechanisms?

“…The European Prospective Investigation into Cancer (EPIC) study identified an association between higher levels of CMV-IgG and ischemic heart disease (with a hazard ratio of 1.4 when compared to seronegativity). Simanek et al reported significant associations between CMV infection and both CVD and CVD-related mortality in the US population (Simanek et al 2009(Simanek et al , 2011. Similarly, Roberts et al showed that CMV was associated with CVD mortality in a predominantly Latino population living in the US and that these associations were partly mediated by IL-6 (Roberts et al 2010).…”

“…The association between CMV infection and atherosclerotic cardiovascular disease (CVD) is well-known from the literature (Blankenberg et al 2001;Gkrania-Klotsas et al 2012;Muhlestein et al 2000;Roberts et al 2010;Simanek et al 2009Simanek et al , 2011Spyridopoulos et al 2016). Since immunological processes are key features of atherosclerosis, it has been postulated that CMV infection increases cardiovascular mortality via immunological mechanisms.…”

Cytomegalovirus‐Productive Infection Is Associated With Acute Coronary Syndrome

“…Data on the involvement of HHVs in human atherosclerosis are far less conclusive13 and are predominantly based on epidemiological studies. These data do not allow assessment of actual viral infection in patients because antibodies (and cell‐associated DNA) may provide evidence of past infections rather than infections that are active at the time of analysis 14, 15…”

Association of anti‐gangliosides antibodies and anti‐CMV antibodies in Guillain–Barré syndrome

“…Furthermore, serials of investigations indicated that AGA can be found in the serum of patients with CMV‐IgG positive (Caudie et al., 2002; Sivadon et al., 2005; Yuki, Yoshino, Sato, & Miyatake, 1990). Meanwhile, Simanek AM and co‐workers provided evidence that the CMV reaction had the relationship with chronic inflammation (Simanek et al., 2011). Therefore, we investigated the relationship between AGA and CMV‐IgG in patients with GBS in our study.…”