We examined the cross-sectional relationships of subclinical atherosclerosis – expressed by carotid intimal–medial thickness and coronary calcification – with antibodies to Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, herpes simplex virus, hepatitis A virus, and pathogen burden (number of positive pathogens). A random sample of 1056 individuals chosen from 5030 Multi-Ethnic Study of Atherosclerosis cohort participants were included. After multiple adjustment, no associations were found between atherosclerosis measures and either individual pathogens or pathogen burden. Interactions with inflammatory and endothelial function markers, demographic factors, BMI, high-density lipoprotein, diabetes, and smoking were also explored. The only interaction that was large, qualitative, statistically significant (P < 0.05) and in the expected direction was that between hepatitis A virus and soluble intercellular adhesion molecule-1 with regard to Agatston calcium score: the difference between hepatitis A virus-positive and hepatitis A virus-negative participants was −86 units in participants with soluble intercellular adhesion molecule-1 below the median, and +162 units in those with soluble intercellular adhesion molecule-1 equal or above the median. However, given the number of interactions that were explored, these results must be interpreted cautiously.
Findings from the present analyses do not provide support for an infectious etiology for subclinical atherosclerosis. However, the study’s limitations, which include its cross-sectional design and insufficient statistical power, suggest that inferences from its findings should be made cautiously.
atherosclerosis; infections; pathogens
Systemic inflammation is linked to cardiovascular risk, but the influence of persistent pathogens, which are conventionally dichotomously categorized, on circulating levels of inflammatory markers is not clear. Antibody levels of pathogens have not been examined in relation to inflammation.
Using data from a subsample of the Multi-Ethnic Study of Atherosclerosis, we examined circulating levels of interleukin-6 (IL-6), C-reactive protein (CRP) and fibrinogen in relation to five common persistent pathogens: cytomegalovirus, herpes simplex virus-1, Hepatitis A virus, Helicobacter pylori and Chlamydia pneumoniae. We tested the hypothesis that the number of seropositive pathogens (based on conventional cut-off points) would not be as sensitive a marker of inflammation as immune response measured by antibody levels to pathogens.
High antibody response to multiple pathogens showed graded and significant associations with IL-6 (p < 0.001), CRP (p = 0.04) and fibrinogen (p = 0.001), whereas seropositive pathogen burden did not. In multiple linear regression models, high antibody response to multiple pathogens maintained a positive association only with IL-6 (4.4% per pathogen exhibiting high antibody response, 95% CI 0.0-8.9).
High antibody response to pathogens was a more consistent marker of inflammatory outcomes compared to seropositivity alone and high antibody response to multiple pathogens was a stronger marker compared to any single pathogen.
Prospective studies have identified chronic inflammation as a risk factor for type 2 diabetes. However, it is not known whether infection by specific pathogens or having a greater “pathogen burden” is associated with diabetes. The aim of this study was to examine the cross-sectional relation of seropositivity to five pathogens (C. pneumoniae, cytomegalovirus, H. pylori, hepatitis A virus, herpes simplex virus) and prevalent diabetes.
Baseline data from a random sample of MultiEthnic Study of Atherosclerosis (MESA) participants (n=1,000; age: 45-84) were used. Diabetes was defined by ADA 2003 criteria, and “pathogen burden” by the number of pathogens (0–5) for which an individual was seropositive. Logistic regression was used to test differences in diabetes prevalence by seropositivity. Linear regression was used to explore associations between pathogen seropositivity and the inflammation markers CRP, IL-6, and fibrinogen.
Diabetes prevalence was 12.7%, while seropositivity for C. pnuemoniae was 76%, cytomegalovirus 77%, H. pylori 45%, hepatitis A 58%, and herpes simplex virus 85%. 72% were seropositive for ≥3 pathogens. In crude analyses, the prevalence of diabetes was higher among those with a pathogen burden ≥3, and with seropositivity to cytomegalovirus, H. pylori, hepatitis A, and herpes simplex virus. After adjustment for demographic covariates (particularly race) all associations became nonsignificant. Pathogen seropositivity was also not related to inflammation marker levels.
Following demographic adjustments, no associations were observed between infection by several pathogens and diabetes status, suggesting no etiologic role for them in the occurrence of diabetes.
diabetes; infection; pathogen; seropositivity
Sex differences in cardiovascular disease mortality are more pronounced among non-Hispanic whites than other racial/ethnic groups, but it is unknown whether this variation is present in the earlier subclinical stages of disease. The authors examined racial/ethnic variation in sex differences in coronary artery calcification (CAC) and carotid intimal media thickness at baseline in 2000–2002 among participants (n = 6,726) in the Multi-Ethnic Study of Atherosclerosis using binomial and linear regression. Models adjusted for risk factors in several stages: age, traditional cardiovascular disease risk factors, behavioral risk factors, psychosocial factors, and adult socioeconomic position. Women had a lower prevalence of any CAC and smaller amounts of CAC when present than men in all racial/ethnic groups. Sex differences in the prevalence of CAC were more pronounced in non-Hispanic whites than in African Americans and Chinese Americans after adjustment for traditional cardiovascular disease risk factors, and further adjustment for behavioral factors, psychosocial factors, and socioeconomic position did not modify these results (for race/sex, Pinteraction = 0.047). Similar patterns were observed for amount of CAC among adults with CAC. Racial/ethnic variation in sex differences for carotid intimal media thickness was less pronounced. In conclusion, coronary artery calcification is differentially patterned by sex across racial/ethnic groups.
calcification, physiologic; continental population groups; coronary vessels; sex; social class
The overall burden of prior infections may contribute to atherosclerosis and stroke risk. We hypothesized that serological evidence of common infections would be associated with carotid plaque thickness in a multi-ethnic cohort.
Antibody titers to five common infectious microorganisms (i.e. Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, and herpesvirus 1 and 2) were measured among stroke-free community participants, and a weighted index of infectious burden (IB) was calculated based on Cox models previously derived from for the association of each infection with stroke risk. High-resolution carotid duplex Doppler studies were used to assess maximum carotid plaque thickness (MCPT). Weighted least squares regression was used to measure the association between IB and MCPT after adjusting for other risk factors.
Serological results for all five infectious organisms were available in 861 participants with MCPT measurements available (mean age 67.2+/−9.6 yrs). Each individual infection was associated with stroke risk after adjusting for other risk factors. The IB index (n=861) had a mean of 1.00 ± standard deviation 0.35, median 1.08. Plaque was present in 52% of participants (mean 0.90+/−1.04 mm). IB was associated with MCPT (adjusted increase in MCPT 0.09 mm, 95% confidence interval 0.03–0.15 mm, per standard deviation increase of IB).
A quantitative weighted index of infectious burden, derived from the magnitude of association of individual infections with stroke, was associated with carotid plaque thickness in this multi-ethnic cohort. These results lend support to the notion that past or chronic exposure to common infections, perhaps by exacerbating inflammation, contributes to atherosclerosis. Future studies are needed to confirm this hypothesis and to define optimal measures of infectious burden as a vascular risk factor.
The pathophysiological mechanisms that underlie health disparities by socioeconomic status and race/ethnicity are poorly understood. Promising new research suggests that the burden of persistent infection may influence adult disease risk and mortality. This article examines how multiple persistent infections cluster within individuals and how this clustering varies by socioeconomic position and race/ethnicity in U.S. adults.
We analyze data from the National Health and Nutrition Examination Survey III (N = 19,275) for adults aged 17–90 years. The clustering of infections within individuals is studied using tetrachoric correlations. Multiple indicator multiple cause models are used to analyze the infection burden construct as measured by seropositivity to Helicobacter pylori, cytomegalovirus, herpes simplex virus-1, and hepatitis B, focusing on the burden's distribution by socioeconomic position and race/ethnicity. The results are corroborated using ordered logistic regression for a commonly used count index of individual infections.
Seroprevalence of individual persistent infections is positively correlated, suggesting common factors related to exposure or susceptibility. Education, income, and race/ethnicity are strong and significant independent predictors of infection burden in U.S. adults in all models.
The disproportionate burden of persistent infections among disadvantaged groups across all ages may be one biologic pathway by which low socioeconomic position is related to increased rates of morbidity and mortality in the United States.
Socioeconomic; Race; Ethnic; United states; Adults; Infection; Biomarkers
Socioeconomic status (SES) is inversely associated with coronary heart disease (CHD) risk. Cumulative pathogen burden may also predict future CHD. The hypothesis was tested that lower SES is associated with a greater pathogen burden, and that pathogen burden accounts in part for SES differences in cardiovascular risk factors.
This was a cross‐sectional observational study involving the clinical examination of 451 men and women aged 51–72 without CHD, recruited from the Whitehall II epidemiological cohort. SES was defined by grade of employment, and pathogen burden by summing positive serostatus for Chlamydia pneumoniae, cytomegalovirus and herpes simplex virus 1. Cardiovascular risk factors were also assessed.
Pathogen burden averaged 1.94 (SD) 0.93 in the lower grade group, compared with 1.64 (0.97) and 1.64 (0.93) in the intermediate and higher grade groups (p = 0.011). Pathogen burden was associated with a higher body mass index, waist/hip ratio, blood pressure and incidence of diabetes. There were SES differences in waist/hip ratio, high‐density lipoprotein‐cholesterol, fasting glucose, glycated haemoglobin, lung function, smoking and diabetes. The SES gradient in these cardiovascular risk factors was unchanged when pathogen burden was taken into account statistically.
Although serological signs of infection with common pathogens are more frequent in lower SES groups, their distribution across the social gradient does not match the linear increases in CHD risk present across higher, intermediate and lower SES groups. Additionally, pathogen burden does not appear to mediate SES differences in cardiovascular risk profiles.
Persistent pathogens have been proposed as risk factors for stroke; however, the evidence remains inconclusive. Mexican Americans have an increased risk of stroke especially at younger ages, as well as a higher prevalence of infections caused by several persistent pathogens.
Findings Using data from the Sacramento Area Latino Study on Aging (n = 1621), the authors used discrete-time regression to examine associations between stroke risk and (1) immunoglobulin G antibody levels to Helicobacter pylori (H. pylori), Cytomegalovirus, Varicella Zoster Virus, Toxoplasma gondii and Herpes simplex virus 1, and (2) concurrent exposure to several pathogens (pathogen burden), defined as: (a) summed sero-positivity, (b) number of pathogens eliciting high antibody levels, and (c) average antibody level. Models were adjusted for socio-demographics and stroke risk factors. Antibody levels to H. pylori predicted incident stroke in fully adjusted models (Odds Ratio: 1.58; 95% Confidence Interval: 1.09, 2.28). No significant associations were found between stroke risk and antibody levels to the other four pathogens. No associations were found for pathogen burden and incident stroke in fully adjusted models.
Our results suggest that exposure to H. pylori may be a stroke risk factor in Mexican Americans and may contribute to ethnic differences in stroke risk given the increased prevalence of exposure to H. pylori in this population. Future studies are needed to confirm this association.
To assess whether markers of acculturation (birthplace, number of U.S. generations) and socioeconomic status (SES) are associated with carotid artery plaque, internal carotid intima-media thickness (IMT), and albuminuria, in four racial/ethnic groups.
Using Multi-Ethnic Study of Atherosclerosis data (n = 6,716; age: 45-84) and race-specific binomial regression models, we computed prevalence ratios, adjusted for demographics and traditional cardiovascular risk factors.
The adjusted U.S. to foreign-born prevalence ratio (99% CI) for carotid plaque was 1.20 (0.97, 1.39) in Whites, 1.91 (0.94, 2.94) in Chinese, 1.62 (1.28, 2.06) in Blacks, and 1.23 (1.15, 1.31) in Hispanics. Greater carotid plaque prevalence was also found among Whites, Blacks, and Hispanics with more generations of US residence (p<0.001). Lower educational attainment and/or income were associated with greater carotid plaque prevalence in Whites and Blacks. Similar associations were observed with IMT. There was also some evidence of an inverse association between albuminuria and SES, in Whites and Hispanics.
Greater U.S. acculturation and lower SES were associated with a higher prevalence of carotid plaque and IMT, while little association was found with albuminuria.
Many studies document racial variation, gender differences, and socioeconomic status (SES) patterning in cardiovascular disease (CVD) risk factors but few studies have investigated heterogeneity in SES differences by race/ethnicity or gender. Using data from the Multi-Ethnic Study of Atherosclerosis (N = 6,814) and stratified regression models, we investigated race/ethnic differences in the SES patterning of diabetes, hypertension, smoking, and body mass index (BMI). Inverse socioeconomic gradients in hypertension, diabetes, smoking, and BMI were observed in White and Black women but associations were weaker or absent in Hispanic and Chinese women (except in the case of diabetes for Hispanic women). Even greater heterogeneity in social patterning of risk factors was observed in men. In White men all four risk factors were inversely associated with socioeconomic position, although often associations were only present or were stronger for education than for income. The inverse socioeconomic patterning was much less consistent in men of other races/ethnic groups, and higher SES was associated with higher BMI in non-White men. These findings have implications for understanding the causes of social patterning, for the analysis of SES adjusted race/ethnic differences, and for the targeting of interventions.
Cardiovascular disease; risk factors; socioeconomic status; race; ethnicity
We assessed associations of herpes simplex virus types 1 and 2 (HSV-1 and -2), cytomegalovirus (CMV), and human herpesvirus 8 (HHV-8) infection with subclinical coronary atherosclerosis in 291 HIV-infected men in the Multicenter AIDS Cohort Study. Coronary artery calcium (CAC) was measured by non-contrast coronary CT imaging. Markers for herpesviruses infection were measured in frozen specimens collected 10-12 years prior to case identification. Multivariable logistic regression models and ordinal logistic regression models were performed. HSV-2 seropositivity was associated with coronary atherosclerosis (adjusted odds ratio [AOR] =4.12, 95% confidence interval [CI] =1.58-10.85) after adjustment for age, race/ethnicity, cardiovascular risk factors, and HIV infection related factors. Infection with a greater number of herpesviruses was associated with elevated CAC levels (AOR=1.58, 95% CI=1.06-2.36). Our findings suggest HSV-2 may be a risk factor for subclinical coronary atherosclerosis in HIV-infected men. Infection with multiple herpesviruses may contribute to the increased burden of atherosclerosis.
herpesvirus; HSV-2; atherosclerosis; HIV-1/AIDS; risk factors
Recent work in biodemography has suggested that life-time exposure to infection and inflammation may be important determinants of later-life morbidity and mortality. Early exposure to infections during critical periods can predispose individuals to chronic disease, in part through the reallocation of energy away from development needed for immune and inflammatory responses. Furthermore, markers of inflammation are known to vary by socioeconomic status in adults and may contribute to overall socioeconomic health inequalities, but little is known about how the sources of this inflammation over the life course. This paper uses novel biomarker data from the Third National Health and Nutrition Examination Survey (NHANES III) to test the association of the burden of common chronic infections (Helicobacter pylori (H. pylori), cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), hepatitis A and hepatitis B) with height-for-age and asthma/chronic respiratory conditions in U.S. children ages 6 and older, and the association of these chronic infections to children’s socioeconomic status. A higher burden of infection is found to be associated with lower height-for-age as well as an increased likelihood of asthma net of race/ethnicity, family income, and parental education. Children with lower family income, lower parental education, and non-white race/ethnicity have a higher likelihood of infection with several individual pathogens as well as the overall burden of infection. Differential exposure and/or susceptibility to infections may be one mechanism through which early social factors get embodied and shape later life health outcomes.
health inequalities; infections; children; NHANES III; socioeconomic status(SES); USA; lifecourse; biomarkers
Studies about associations of infections with herpes viruses and other pathogens, such as Chlamydia pneumoniae (CP) and Helicobacter pylori (HP) with cardiovascular disease (CVD), diabetes mellitus (DM), frailty and/or mortality are conflicting. Since high levels of antibodies against these pathogens occur in the elderly, the role of these pathogens in morbidity and mortality of vulnerable elderly was explored.
Blood samples of 295 community dwelling psycho-geriatric patients were tested for IgG antibodies to herpes simplex virus type 1 and 2, varicella zoster virus, Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpes virus type 6 (HHV6), CP and HP. Frailty was defined with an easy-to-use previously described frailty risk score. Relative risks (RR) with 95% confidence intervals were calculated to evaluate associations between CVD, DM, frailty and pathogens. Pathogens as a predictor for subsequent mortality were tested using Kaplan Meier analyses and Cox proportional hazard models. The mean age was 78 (SD: 6.7) years, 20% died, 44% were defined as frail, 20% had DM and 49% had CVD. Presence of CMV antibody titers was associated with frailty, as shown by using both qualitative and quantitative tests, RR ratio 1.4 (95% CI: 1.003-2.16) and RR ratio 1.5 (95% CI: 1.06-2.30), respectively. High IgG antibody titers of HHV6 and EBV were associated with DM, RR ratio 3.3 (95% CI: 1.57-6.49). None of the single or combined pathogens were significantly associated with mortality and/or CVD.
Prior CMV infection is associated with frailty, which could be in line with the concept that CMV might have an important role in immunosenescence, while high IgG titers of HHV6 and EBV are associated with DM. No association between a high pathogen burden and morbidity and/or mortality could be demonstrated.
Herpes viruses; Cytomegalovirus; Frailty; Diabetes mellitus; Morbidity; Mortality
To determine if cynical hostility is associated with alterations in diurnal profiles of cortisol. Hostility has been linked to cardiovascular disease but the biological mechanisms mediating this association remain unknown.
Up to 18 measures of salivary cortisol taken over three days were obtained from each of 936 participants in the Multi-Ethnic Study of Atherosclerosis (MESA). Cynical hostility was measured using an 8-item subscale of the Cook-Medley Hostility scale. Cortisol profiles were modeled using regression spline models incorporating random parameters for subject-specific effects. Models were adjusted for race, sex, age, socioeconomic position, and lifestyle factors. The association of cynical hostility with key features of the cortisol diurnal profile, both in the full sample and important subsamples, was examined.
Waking cortisol levels as well as the extent of the morning surge in cortisol levels did not differ significantly across tertiles of cynical hostility. However respondents in the lowest tertile of cynical hostility experienced a 22% sharper decline in salivary cortisol (age-and sex-adjusted slope of −.49 μg/dl per hour) than respondents in the highest tertile (−.40 μg/dl per hour, p for difference=.0004). Intertertile differences in these parameters remained unaltered after further adjustment for potential confounders. This pattern of differences in cortisol diurnal profile tended to be related in a dose-response way to level of cynical hostility, and persisted in stratified analyses.
Cynical hostility is associated with the declining phase of the awakening cortisol response. The implications of this for cardiovascular and other health outcomes remain to be determined.
Cortisol rhythms; cynical hostility; regression splines; random effects; cortisol awakening response
The mechanisms underlying socioeconomic inequalities in mortality from cardiovascular diseases (CVD) are largely unknown. We studied the contribution of childhood socioeconomic conditions and adulthood risk factors to inequalities in CVD mortality in adulthood.
The prospective GLOBE study was carried out in the Netherlands, with baseline data from 1991, and linked with the cause of death register in 2007. At baseline, participants reported on adulthood socioeconomic position (SEP) (own educational level), childhood socioeconomic conditions (occupational level of respondent’s father), and a broad range of adulthood risk factors (health behaviours, material circumstances, psychosocial factors). This present study is based on 5,395 men and 6,306 women, and the data were analysed using Cox regression models and hazard ratios (HR).
A low adulthood SEP was associated with increased CVD mortality for men (HR 1.84; 95% CI: 1.41-2.39) and women (HR 1.80; 95%CI: 1.04-3.10). Those with poorer childhood socioeconomic conditions were more likely to die from CVD in adulthood, but this reached statistical significance only among men with the poorest childhood socioeconomic circumstances. About half of the investigated adulthood risk factors showed significant associations with CVD mortality among both men and women, namely renting a house, experiencing financial problems, smoking, physical activity and marital status. Alcohol consumption and BMI showed a U-shaped relationship with CVD mortality among women, with the risk being significantly greater for both abstainers and heavy drinkers, and among women who were underweight or obese. Among men, being single or divorced and using sleep/anxiety drugs increased the risk of CVD mortality. In explanatory models, the largest contributor to adulthood CVD inequalities were material conditions for men (42%; 95% CI: −73 to −20) and behavioural factors for women (55%; 95% CI: -191 to −28). Simultaneous adjustment for adulthood risk factors and childhood socioeconomic conditions attenuated the HR for the lowest adulthood SEP to 1.34 (95% CI: 0.99-1.82) for men and 1.19 (95% CI: 0.65-2.15) for women.
Adulthood material, behavioural and psychosocial factors played a major role in the explanation of adulthood SEP inequalities in CVD mortality. Childhood socioeconomic circumstances made a modest contribution, mainly via their association with adulthood risk factors. Policies and interventions to reduce health inequalities are likely to be most effective when considering the influence of socioeconomic circumstances across the entire life course and in particular, poor material conditions and unhealthy behaviours in adulthood.
Cardiovascular diseases; Socioeconomic status; Health behaviour; Life course epidemiology; Mortality determinants
Hypertension, myocardial infarction, atherosclerosis, arrhythmias and valvular heart disease, coagulopathies and stroke, collectively known as cardiovascular diseases (CVDs), contribute greatly to the mortality, morbidity and economic burden of illness in Canada and in other countries. It has been estimated that over four million Canadians have high blood pressure, a comorbid condition that doubles or triples the risk of CVD. According to the Heart and Stroke Foundation of Canada, CVDs caused 36% of deaths in 2001 and were responsible for 18% of the total hospital costs in Canada. The majority of Canadians exhibit at least one CVD-related risk factor, such as tobacco smoking, physical inactivity, diabetes, obesity, hypertension, a lack of daily fruit and vegetable consumption, and psychosocial factors, making these people more prone to developing a serious CVD-related illness in the future. It is therefore important that CVD-related causes and concerns be addressed. Given the scope and prevalence of CVDs, it is obvious that a population health approach – ‘prevention is better than cure’ – would be the most appropriate model to adopt to deal with this ubiquitous health problem and to reduce the costs of hospitalization, long-term medication and rehabilitation. The focus of the present review is to evaluate and compare the results of epidemiological, experimental and clinical studies, reporting on the influence of physical activity, dietary intervention, obesity and cigarette smoking on cardiovascular health and the prevention of CVDs. The prophylactic measures must be dealt with collectively because there is overwhelming evidence that the occurrence of CVDs can be reduced by approximately 80% by making lifestyle modifications. The preventive strategies against CVDs must be targeted at a primary health promotion level before some of the important underlying causes of CVD seriously afflict a person or a population at large. Such preventive approaches would help in reducing not only employee absenteeism but also the hospital and drug costs burdening the health care systems of both developed and developing countries.
Cardiovascular disease; Diabetes; Diet; Exercise; Obesity; Smoking cessation
Recent publications have suggested that infective pathogens might play an important role in the pathogenesis of atherosclerosis. This review focuses on these microorganisms in the process of atherosclerosis. The results of in vitro studies, animal studies, tissue studies, and serological studies will be summarised, followed by an overall conclusion concerning the strength of the association of the microorganism with the pathogenesis of atherosclerosis. The role of the bacteria Chlamydia pneumoniae and Helicobacter pylori, and the viruses human immunodeficiency virus, coxsackie B virus, cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and measles virus will be discussed.
Key Words: atherosclerosis • Chlamydia pneumoniae • Helicobacter pylori
Coronary artery disease (CAD) occurs at an earlier age in South Asians compared with other ethnic groups. Infection and inflammation show a positive association with the disease.
To investigate the association of infection and inflammatory markers with premature CAD in the Indian Atherosclerosis Research Study population.
Antibody titres for Chlamydia pneumoniae, cytomegalovirus (CMV), Helicobacter pylori, herpes simplex virus and levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), fibrinogen and secretory phospholipase A2, were measured in 866 individuals (433 CAD patients and matched controls). All individuals were followed-up for recurrent cardiac events for four years. ANOVA was used to study the association of infection and inflammation with CAD.
The present study found that the odds of CAD occurrence was 2.42 (95% CI 1.26 to 4.64; P<0.008), with all four infections and increased in the presence of hsCRP (OR 4.67 [95% CI 1.43 to 15.25]); P=0.011). Only anti-CMV antibody levels were a significant risk factor for CAD occurrence (OR 2.23 [95% CI 1.20 to 4.15]; P=0.011) and recurrent cardiac events (OR 1.94 [95% CI 0.85 to 4.45]; P=0.015). Mean values of the inflammatory biomarkers IL-6 (P=0.035), fibrinogen (P=0.014), hsCRP (P=0.010) and secretory phospholipase A2 (P=0.002) increased with CMV antibody levels. Incorporating hsCRP and IL-6 in the risk prediction models significantly increased the OR to 2.56 (95% CI 1.16 to 5.63; P=0.019) with a c statistic of 0.826.
Pathogen burden, especially CMV infection in combination with inflammatory markers, is a significant predictor of CAD risk in the young Indian population.
Coronary artery disease; C-reactive protein; Cytomegalovirus; Inflammatory markers; Pathogen burden
Occupation has been linked to cardiovascular disease (CVD) incidence and mortality, but few studies have investigated occupation in relation to early atherosclerotic disease. This study examined associations between various occupational characteristics and carotid artery intima-media thickness (IMT) in a multi-ethnic sample.
The Multi-Ethnic Study of Atherosclerosis (MESA) recruited 6814 adults aged 45e84 years and free of clinical CVD (response rate 60%, 51% female). Questionnaire data were used to determine occupational group (managerial/professional, sales/office, service, blue-collar), psychosocial job characteristics (ie, job demands, job control) and other sociodemographic information.
Common carotid artery (CCA)-IMT was greater for blue-collar jobs than for management/professional jobs (mean difference=0.012 mm, p=0.049) after adjustment for age, sex, race, place of birth (US or foreign born) and CVD risk factors. Compared to management/professional jobs, internal carotid artery (ICA)-IMT was greater for sales/office, service and blue-collar jobs (mean difference=0.071 mm, p<0.001; 0.057 mm, p=0.009; and 0.110 mm, p<0.001, respectively) after adjustment for age, sex, race and place of birth. The difference between blue-collar jobs and management/professional jobs remained significant after additional adjustment for CVD risk factors, income and education (mean difference=0.048 mm, p=0.045). Higher levels of control at work were associated with thinner CCA-IMT (mean difference=‒0.009 mm, p=0.016, adjusted for age, sex, race and place of birth) but not with ICA-IMT. Job demands had no significant association with IMT.
Blue-collar jobs and low levels of job control were associated with the development of subclinical atherosclerosis.
An abnormally high ankle brachial index (ABI) is associated with increased all-cause and cardiovascular mortality. The relationship of obesity to incident high-ABI has not been characterized. We investigated the hypothesis that increased obesity—quantified by body weight, BMI, waist circumference, and waist-to-hip-ratio—is positively associated with a high-ABI (ABI ≥ 1.3) and with mean ABI increases over a four year follow-up. Prevalence and incidence ratios for a high-ABI were obtained for 6540 and 5045 participants respectively in the Multi-Ethnic Study of Atherosclerosis (MESA), using log-binomial regression models adjusted for demographic, cardiovascular, and inflammatory/novel risk factors. Linear regression was used to analyze mean ABI change. Both prevalence and incidence of a high-ABI were significantly higher for the highest versus the lowest quartile of every baseline measure of obesity, with weight and BMI demonstrating the highest incidence ratios (2.7 and 2.4, respectively). All prevalence and incidence ratios were positive and graded across obesity quartiles, and were persistent in the subpopulation without diabetes. Among those with normal baseline ABI values, one MESA-standard deviation increase in every baseline measure of obesity was associated with significant increases in mean ABI values. In conclusion, we observed an independent, positive and graded association of increasing obesity to both prevalent and incident high-ABI, and to mean increases in ABI values over time. Weight and BMI seemed to be at least as strongly, if not more strongly, associated with a high-ABI than were measures of abdominal obesity.
obesity; anthropometric measures; peripheral vascular disease; ankle-brachial index; epidemiology
Chronic infections could be contributing to the socioeconomic gradient in chronic diseases. Although chronic infections have been associated with increased levels of inflammatory cytokines and cardiovascular disease, there is limited evidence on how infections affect risk of diabetes.
RESEARCH DESIGN AND METHODS
We examined the association between serological evidence of chronic viral and bacterial infections and incident diabetes in a prospective cohort of Latino elderly. We analyzed data on 782 individuals aged >60 years and diabetes-free in 1998–1999, whose blood was tested for antibodies to herpes simplex virus 1, varicella virus, cytomegalovirus, Helicobacter pylori, and Toxoplasma gondii and who were followed until June 2008. We used Cox proportional hazards regression to estimate the relative incidence rate of diabetes by serostatus, with adjustment for age, sex, education, cardiovascular disease, smoking, and cholesterol levels.
Individuals seropositive for herpes simplex virus 1, varicella virus, cytomegalovirus, and T. gondii did not show an increased rate of diabetes, whereas those who were seropositive for H. pylori at enrollment were 2.7 times more likely at any given time to develop diabetes than seronegative individuals (hazard ratio 2.69 [95% CI 1.10–6.60]). Controlling for insulin resistance, C-reactive protein and interleukin-6 did not attenuate the effect of H. pylori infection.
We demonstrated for the first time that H. pylori infection leads to an increased rate of incident diabetes in a prospective cohort study. Our findings implicate a potential role for antibiotic and gastrointestinal treatment in preventing diabetes.
Although cardiovascular morbidity and mortality are increased in rheumatoid arthritis, little is known about the burden of subclinical coronary atherosclerosis in these patients.
Using computed tomography, coronary artery calcification was measured in 195 men and women with rheumatoid arthritis aged 45 to 84 years without clinical cardiovascular disease and compared with 1,073 controls without rheumatoid arthritis enrolled in the Baltimore cohort of the Multi-Ethnic Study of Atherosclerosis.
The prevalence of coronary calcification (Agatston score > 0) was significantly higher in men, but not women, with rheumatoid arthritis after adjusting for sociodemographic and cardiovascular risk factors (prevalence ratio = 1.19; P = 0.012). Among participants with prevalent calcification, those with rheumatoid arthritis had adjusted mean Agatston scores 53 units higher than controls (P = 0.002); a difference greater for men than women (P for interaction = 0.017). In all analyses, serum IL-6 attenuated the association between rheumatoid arthritis and coronary calcification, suggesting its role as a potential mediator of enhanced atherosclerosis. Notably, increasing severity of rheumatoid arthritis was associated with a higher prevalence and extent of coronary calcification among both men and women with rheumatoid arthritis, and for all age categories. The largest percentage difference in coronary arterial calcification between rheumatoid arthritis patients and their nonrheumatoid arthritis counterparts was observed in the youngest age category.
Increasing rheumatoid arthritis disease severity was associated with a higher prevalence and greater extent of coronary artery calcification, potentially mediated through an atherogenic effect of chronic systemic inflammation. Gender and age differences in association with coronary calcification suggest that preventive measures should be emphasized in men with rheumatoid arthritis, and considered even in younger rheumatoid arthritis patients with low levels of traditional cardiovascular risk factors.
The metabolic syndrome together with insulin resistance and their consequences are basic factors in pathogenesis of atherosclerosis. Chronic infections with herpes simplex virus type 1 (HSV-1), cytomegalovirus (CMV), and Chlamydia pneumoniae are associated with the development of atherosclerosis and coronary heart disease. The infectious aspects of metabolic syndrome have not been investigated.
In a cross-sectional, population-based study, we used National Cholesterol Education Program (NCEP)-Adult Treatment Panel (ATP)-III criteria in 1791 subjects, aged 25 years and over, selected by cluster random sampling in three Iranian ports in the northern Persian Gulf. Sera were analyzed for IgG antibodies to Chlamydia pneumoniae, HSV-1, Helicobacter pylori (H. pylori) and CMV using ELISA.
In multiple logistic regression analysis, of the infectious agents, CMV [OR = 1.81 (1.05–3.10); p = 0.03], H. pylori [OR = 1.50 (1.12–2.00); p = 0.007] and Chlamydia pneumoniae [OR = 1.69 (1.27–2.25); p < 0.0001] showed a significant association with the metabolic syndrome in men and HSV-1 [OR = 1.95 (1.22–3.11); p = 0.005], H. pylori [OR = 1.45 (1.09–1.94); 0.01] and Chlamydia pneumoniae [OR = 1.65 (1.23–2.21); p = 0.001] in women.
The metabolic syndrome, which occurs very frequently in the general population, has a significant association with prior infection with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus and herpes simplex virus type 1. Hypothesis about participation of infection in pathogenesis of metabolic syndrome should be investigated.
The increasing burden of cardiovascular diseases (CVD) in the ageing population of industrialized nations requires an intensive search for means of reducing this epidemic. In order to improve prevention, detection, therapy and prognosis of cardiovascular diseases on the population level in Eastern Germany, it is necessary to examine reasons for the East-West gradient of CVD morbidity and mortality, potential causal mechanisms and prognostic factors in the elderly.
Psychosocial and nutritional factors have previously been discussed as possible causes for the unexplained part of the East-West gradient. A reduced heart rate variability appears to be associated with cardiovascular disease as well as with psychosocial and other cardiovascular risk factors and decreases with age. Nevertheless, there is a lack of population-based data to examine the role of heart rate variability and its interaction with psychosocial and nutritional factors regarding the effect on cardiovascular disease in the ageing population. There also is a paucity of epidemiological data describing the health situation in Eastern Germany. Therefore, we conduct a population-based study to examine the distribution of CVD, heart rate variability and CVD risk factors and their associations in an elderly East German population. This paper describes the design and objectives of the CARLA Study.
For this study, a random sample of 45–80 year-old inhabitants of the city of Halle (Saale) in Eastern Germany was drawn from the population registry. By the end of the baseline examination (2002–2005), 1750 study participants will have been examined. A multi-step recruitment strategy aims at achieving a 70 % response rate.
Detailed information is collected on own and family medical history, socioeconomic, psychosocial, behavioural and biomedical factors. Medical examinations include anthropometric measures, blood pressure of arm and ankle, a 10-second and a 20-minute electrocardiogram, a general physical examination, an echocardiogram, and laboratory analyses of venous blood samples. On 200 participants, a 24-hour electrocardiogram is recorded. A detailed system of quality control ensures high data quality. A follow-up examination is planned.
This study will help to elucidate pathways to CVD involving autonomic dysfunction and lifestyle factors which might be responsible for the CVD epidemic in some populations.
Lack of sleep has been associated with an increased risk for cardiovascular disease (CVD) and all-cause mortality, but the mechanisms are not fully understood. Prior research has often been conducted in select populations and has not consistently adjusted for confounders, especially psychosocial factors.
The aims of this study were to assess the association between sleep habits and established risk factors for CVD and to evaluate potential interactions by race and gender.
Participants were part of a CVD screening and educational outreach program in New York City. Free-living men older than 40 years and women older than 50 years (n = 371, mean age = 60 years, 57% women, 60% racial/ethnic minorities) were systematically assessed for CVD risk (including traditional, lifestyle, and psychosocial risk factors) and completed a standardized questionnaire regarding sleep habits (including sleep duration and snoring). Lipids were analyzed by validated finger-stick technology. Stress at work and at home was assessed using a validated screening tool from the INTERHEART study. Associations between participants’ sleep habits and CVD risk factors/demographic factors were assessed using multivariable logistic regression.
The proportion of participants who reported sleeping less than 6 hours per night on average was 28%, and 52% of participants reported snoring. Sleeping less than 6 hours per night was significantly (P < .05) associated with female gender, being single, increased stress at home, increased financial stress, and low-density lipoprotein cholesterol (LDL-C) level. Gender modified the association between sleep duration and LDL-C level (P = .04): Sleeping less than 6 hours per night was significantly associated with reduced LDL-C level among women and increased LDL-C level among men. Snoring was significantly associated with low high-density lipoprotein cholesterol (HDL-C) level (<40 mg/dL for men/<50 mg/dL for women), being married, increased stress at work and at home, less than 30 minutes of exercise per day, less than 5 servings of fruits and vegetables per day, and being overweight/obese (body mass index ≥25 kg/m2). The association between snoring and low HDL-C level remained significant in logistic regression models adjusted for demographic confounders (odds ratio, 1.83; 95% confidence interval, 1.06–3.19) but not after adjustment for body mass index greater than 25 kg/m2.
Sleeping less than 6 hours per night was associated with several traditional and psychosocial CVD risk factors, and snoring was associated with low HDL-C level, likely mediated through overweight/obesity. These data may have significance for health care providers to identify individuals who may be at increased CVD risk based on sleep habits.
cardiovascular disease; psychosocial; risk factors; sleep; snoring