Viral Hepatitis in the United States Navy and Marine Corps

Two analyses of the Navy and Marine Corps experience with viral hepatitis are reported. The first is longitudinal in nature and shows that over the past 100 years the syndrome has been common and at a relatively steady rate of 100-400 cases/100,000 average strength/year. The second is an examination of cases in calendar year 1974 for demographic, geographic, and occupational patterns. There is a strong inverse relationship between disease occurrence and age. Each type of viral hepatitis shows a distinct geographic distribution. Navy personnel in health-related occupations had a greater risk of acquiring viral hepatitis than did other persons on active duty. Differences among other occupational groups were found, but valid interpretations could not be made because of the small numbers of cases in each category.     

The epidemiological aspects of viral hepatitides in Estonia]

The etiological structure of viral hepatitides among the adult population of Tallinn and the occurrence of markers of hepatitis B and hepatitis C virus infections in medical workers, addict introducing drugs intravenously and hemodialysis patients were studied. Changes in the etiological structure of viral hepatitides were established: they took the form of a decrease in the level of hepatitis A morbidity and the considerable growth of the role of hepatitides B and C, as well as the newly detected circulation hepatitis D virus. About one-third in the structure of morbidity in viral hepatitides were hepatitis cases without markers of hepatitis A, B or C viruses (non-A, non-B, non-C). The highest rates of hepatitis B virus infection (78.9%) and hepatitis C virus infection (82.5%) were detected among drug addicts. Their level of HBsAg was 8.8%. In the group of medical workers, 25% of the examinees, i.e. every fourth person, had markers of hepatitis B virus, while antibodies to hepatitis C virus were detected in 5% of cases. Among hemodialysis patients these rates were 21.4% and 10.7% respectively.     

The role of respiratory tract viruses in the etiology of obstructive bronchitis in infants

Out of 524 children with acute respiratory infections in 141 obstructive bronchitis was diagnosed (OZO). Seventy cases could be linked to viral infection. Viral infections tested (influenza virus A, B, parainfluenza typ 1-3, RSV, adenoviruses) were more frequently associated with OZO than other acute respiratory infections of unknown etiology. Majority infections induced by influenza virus A and parainfluenza virus typ 2 were accompanied by OZO symptoms. Of the highest risk of acquiring OZO despite of viral infection participation, were children of 4-12 months of age. OZO associated viral infections prevailed during autumn-winter season, while in spring-summer period undetermined factors were the major cause of OZO. In serum samples of children with OZO, despite of etiology of the disease, higher level of IgE was found than in a group of children without the symptoms. In the case of OZO of unestablished etiology the level of serum IgE was significantly higher than in the cases when viral etiology of the disease was found.     

Incidence of tuberculosis,hepatitis, brucellosis,and shigellosis in British medical laboratory workers.

A retrospective postal survey of 21 000 medical laboratory workers in England and Wales showed 18 new cases of pulmonary tuberculosis in 1971, a five-times increased risk of acquiring the disease compared with the general population. Technicians were at greatest risk, especially if they worked in morbid anatomy departments. Of the 35 cases of hepatitis, the technicians were again the occupational group most likely to acquire the disease. Microbiology staff were twice as likely to report shigellosis as those in other pathology divisions but only one case of brucellosis was reported in the whole laboratory population. A similar survey carried out in 1973 of 3000 Scottish medical laboratory workers corroborates the results from England and Wales. Medical laboratory workers continue to experience a considerable risk of developing an occupationally acquired infection. Improvements in staff safety and health care seem to be necessary.     

Sexual transmission of hepatitis C virus and its relation with hepatitis B virus and HIV.

OBJECTIVE--To determine the extent of transmission of hepatitis C virus in sexual partners of intravenous drug misusers and to examine the relation between the prevalences of HIV, hepatitis B virus, and hepatitis C virus infections in homosexual men and intravenous drug misusers and their sexual partners. DESIGN--Serum samples collected between 1984 and 1988 were tested for hepatitis B virus markers and antibodies against hepatitis C virus by enzyme linked immunosorbent assay (ELISA) and for HIV antibody by enzyme immune analysis and western blotting. SETTING--Large referral university hospital with an external AIDS clinic in the metropolitan area of Barcelona, Spain. SUBJECTS--243 Intravenous drug misusers, 143 of their regular heterosexual partners, and 105 homosexual men. MAIN OUTCOME MEASURES--Prevalences of hepatitis C virus, hepatitis B virus, and HIV infections. RESULTS--In all, 178 of the 243 (73%) intravenous drug misusers, 16 out of 143 (11%) of their partners, and 17 of the 105 (16%) homosexual men had antibodies against hepatitis C virus. The presence of hepatitis C virus infection was unrelated to sex, age, the presence of HIV or hepatitis B virus infections, or the Centers for Disease Control stage of HIV. In sexual partners of intravenous drug misusers there were strong correlations between the presence of hepatitis C virus infection and that of HIV (p = 0.001) and hepatitis B virus (p = 0.013) infections. CONCLUSIONS--Intravenous drug misusers have a high risk of acquiring hepatitis C virus, hepatitis B virus, and HIV infections, but the presence of hepatitis C virus infection seems to be unrelated to the presence of the other two viruses. Homosexual men have a high prevalence of HIV and hepatitis B virus infections with a low prevalence of hepatitis C virus infection, the presence of which is not related to that of the other two infections. Conversely, heterosexual partners of intravenous drug misusers have low prevalences of the three virus infections, but the presence of hepatitis C virus infection correlates significantly with the presence of HIV and hepatitis B infections. The rate of sexual transmission of hepatitis C virus seems to be low, even in partners of people known to be seropositive for this virus.     

Genotoxic evaluation of workers employed in pesticide production

Pesticides are widely used throughout the world in agriculture to protect crops and in public health to control diseases. Nevertheless exposure to pesticides can represent a potential risk to humans. Pesticide manufacturing unit workers are prone to possible occupational pesticide exposure. Therefore, this study was performed to evaluate the genotoxic effect of pesticide exposure in these workers. In the present investigation 54 pesticide workers and an equal number of control subjects were assessed for genome damage in blood lymphocytes utilizing the chromosomal aberration analysis and the buccal epithelial cell by adopting the micronucleus test. The results suggested that pesticide workers had a significantly increased frequency of chromosomal aberrations when compared with controls (mean+/-S.D., 8.43+/-2.36 versus 3.32+/-1.26; P<0.05). Similarly, the pesticides exposed workers showed a significant increase in micronucleated cells compared with controls (1.24+/-0.72 versus 0.32+/-0.26; P<0.05). Analysis of variance revealed that occupational exposure to pesticides had a significant effect on frequency of micronuclei (P<0.05), whereas smoking, age, gender and alcohol consumption had no significant effect on genetic damage (P>0.05). However, no association was found between years of exposure, smoking, age, gender, alcohol consumption and higher levels of genetic damage as assessed by the chromosomal aberration assay (P>0.05). Our findings indicate that occupational exposure to pesticides could cause genome damage in somatic cells.     

Genetic polymorphism in the manganese superoxide dismutase gene is associated with an increased risk for hepatocellular carcinoma in HCV-infected Moroccan patients

Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide. The main risk factors for its development are hepatitis B and C virus infections. Hepatitis B and C viruses induce chronic inflammation and oxidative stress that could predispose a cell to mutagenesis and proliferation. Manganese superoxide dismutase (MnSOD) catalyses the detoxification of free radicals, thus playing a crucial role in the protection against damage. A valine (Val) to alanine (Ala) substitution at amino acid 9, mapping within the mitochondrion-targeting sequence of the MnSOD gene, has been associated with an increased cancer risk. The aim of our study was to investigate a possible association of the Val/Ala-MnSOD polymorphism and HCC development in Moroccan patients. Genotypes were determined by means of PCR and RFLP analysis in 96 patients with HCC and 222 control subjects matched for age, sex, and ethnicity. Homozygous Ala/Ala carriers were 31% in the cases and 18% in the controls, which corresponds to an odds ratio (OR) of 2.89, with a 95% confidence interval (CI) of 1.47-5.68. Stratification into subgroups based on HCV infection status revealed an even more increased risk for homozygous Ala/Ala carriers with hepatitis C infection (38.2% in the cases versus 14.8% in the control subjects OR, 5.09; 95% CI, 1.76-14.66). Our findings provide further evidence of an association between the Ala-9Val MnSOD polymorphism and HCC occurrence in hepatitis C virus-infected Moroccan patients.     

Work-Related Psychological Injury Is Associated with Metabolic Syndrome Components in Apparently Healthy Workers

Objective

The aim of this study was to evaluate the association between psychological damage caused by common occupational trauma and metabolic syndrome (MES).

Method

571 workers from 20 small Italian companies were invited to fill in the Psychological Injury Risk Indicator (PIRI) during their routine medical examination at the workplace.

Results

Compared to workers with no psychological injury, workers with a high PIRI score had a significantly increased risk of having at least one metabolic syndrome component (adjusted hazards ratio, 1.8; 95% confidence interval, 1.2 to 2.6). There was a significant increase in the risk of hypertriglyceridemia in male workers (OR 2.53 CI95% 1.03-6.22), and of hypertension in female workers (OR 2.45 CI95% 1.29-4.66).

Conclusion

Psychological injury related to common occupational trauma may be a modifiable risk factor for metabolic syndrome.     

Serosurveillance of Vaccine Preventable Diseases and Hepatitis C in Healthcare Workers from Lao PDR

Background and Aims

Healthcare workers (HCW) have an increased risk of exposure to infectious diseases and are a potential source of infections for their patients. The Lao People’s Democratic Republic (Lao PDR) has no national policy regarding HCW vaccinations and routine vaccination coverage is low within the general population. This cross-sectional serostudy determines the level of exposure and risk of infection in Lao HCW against 6 vaccine preventable diseases and hepatitis C.

Methods

1128 HCW were recruited from 3 central, 2 provincial and 8 district hospitals. Sera were tested by ELISA for the presence of antibodies and antigens to hepatitis B, hepatitis C, measles, rubella, varicella zoster, tetanus and diphtheria.

Results

Only 53.1% of the HCW had protective anti-hepatitis B surface antigen antibodies (anti-HBs) with 48.8% having anti-hepatitis B core antibodies (anti-HBc), indicating previous exposure and 8.0% were hepatitis B surface antigen carriers. 3.9% were hepatitis C seropositive. Measles and rubella antibodies were detected in 95.4% and 86.2% of the HCW, with 11.9% of females being unprotected against rubella. Antibodies against varicella zoster, tetanus and diphtheria were detected in 95%, 78.8% and 55.3%, respectively. Seroprevalence varied according to age, gender and number of children.

Conclusion

An unacceptably high proportion of Lao HCW remain susceptible to infection with hepatitis B, diphtheria, tetanus and rubella. Furthermore, a high number of healthcare workers are chronically infected with hepatitis B and C viruses. These data emphasize the need for a robust HCW vaccination policy in addition to increased awareness within this subpopulation.     

Micronucleus frequency is increased in peripheral blood lymphocytes of nuclear power plant workers

Nuclear power plant workers are exposed to ionizing radiation at relatively low doses and for prolonged periods of time. To investigate the extent of genetic damage in these workers, a group of 133 nuclear power plant workers and 39 healthy controls were compared using the cytokinesis-block micronucleus assay. The frequency of micronuclei was significantly increased in peripheral lymphocytes of nuclear power plant workers (20.5 +/- 9.7% compared to 13.7 +/- 5.9%). A significant dose-response relationship was observed between micronucleus (MN) frequency and both the accumulated dose and the duration of employment (P < 0.01 for both variables after adjusting for age, gender and cigarette smoking) with an evident leveling off for exposures over 200 mSv. Accumulated dose and duration of employment were significantly correlated but exerted independent effects on MN frequency. For non-occupational parameters, age was significantly associated with the frequency of micronuclei, while gender was not. Smoking habit showed no overall effect, whereas increased chromosome damage was evident in smokers of more than 20 cigarettes per day. In conclusion, a dose-related association between MN frequency and exposure to ionizing radiation was evident in nuclear power plant workers, encouraging the application of the cytokinesis-block micronucleus assay in biomonitoring studies of human populations with prolonged exposure to ionizing radiation.     

Neutralizing antibodies to enterovirus 71 in Belém, Brazil

Non-polio enteroviruses (Coxsackievirus A, Coxsackievirus B, Echovirus and EV 68-72) which belong to the enterovirus (EV) genus, Picornaviridae family, may be responsible for acute flaccid paralysis, aseptic meningitis, myocarditis, hepatitis, pleurodinia, neonatal sepsis, hand, foot and mouth disease (HFMD) even though 50-80% of infections are asymptomatic. EV 71 has been responsible for outbreaks and epidemics of HFMD and acute neurologic disease justifying its study in our country. The aim of this study was to detect neutralizing antibodies (NtAb) to EV 71 in individuals up to 15 years of age living in Belém, State of Pará, northern Brazil. Serum samples from 238 patients attending the Virology Sector of Evandro Chagas Institute in Belém, Brazil, were analyzed using microneutralization tests that included RD cells and BrCr strain. Overall 40.8% (97/238) of tested samples had NtAb to EV 71. Regarding the distribution per age group, 85.2% (92/108) of patients aged 0-3 years had no NtAb to this virus and 69.2% of those 12 to 15 years of age were seropositive. These results confirm that EV 71 infection occurs in the city of Belém; and that a high rate of individuals in this study were infected aged 3 years and over and, when aged 15 years nearly 70% had EV 71 NtAb.     

Risk factors associated with exposure to Crimean-Congo haemorrhagic fever virus in animal workers and cattle,and molecular detection in ticks,South Africa

Crimean-Congo haemorrhagic fever (CCHF) is a severe tick-borne viral zoonosis endemic to parts of Africa, Europe, the Middle East and Central Asia. Human cases are reported annually in South Africa, with a 25% case fatality rate since the first case was recognized in 1981. We investigated CCHF virus (CCHFV) seroprevalence and risk factors associated with infection in cattle and humans, and the presence of CCHFV in Hyalomma spp. ticks in central South Africa in 2017–18. CCHFV IgG seroprevalence was 74.2% (95%CI: 64.2–82.1%) in 700 cattle and 3.9% (95%CI: 2.6–5.8%) in 541 farm and wildlife workers. No veterinary personnel (117) or abattoir workers (382) were seropositive. The prevalence of CCHFV RNA was significantly higher in Hyalomma truncatum (1.6%) than in H. rufipes (0.2%) (P = 0.002). Seroprevalence in cattle increased with age and was greater in animals on which ticks were found. Seroprevalence in cattle also showed significant geographic variation. Seroprevalence in humans increased with age and was greater in workers who handled livestock for injection and collection of samples. Our findings support previous evidence of widespread high CCHFV seroprevalence in cattle and show significant occupational exposure amongst farm and wildlife workers. Our seroprevalence estimate suggests that CCHFV infections are five times more frequent than the 215 confirmed CCHF cases diagnosed in South Africa in the last four decades (1981–2019). With many cases undiagnosed, the potential seriousness of CCHF in people, and the lack of an effective vaccine or treatment, there is a need to improve public health awareness, prevention and disease control.     

Innate detection of hepatitis B and C virus and viral inhibition of the response

Viral hepatitis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) infections poses a significant burden to the public health system. Although HBV and HCV differ in structure and life cycles, they share unique characteristics, such as tropism to infect hepatocytes and association with hepatic and extrahepatic disorders that are of innate immunity nature. In response to HBV and HCV infection, the liver innate immune cells eradicate pathogens by recognizing specific molecules expressed by pathogens via distinct cellular pattern recognition receptors whose triggering activates intracellular signalling pathways inducing cytokines, interferons and anti‐viral response genes that collectively function to clear infections. However, HBV and HCV evolve strategies to inactivate innate signalling factors and as such establish persistent infections without being recognized by the innate immunity. We review recent insights into how HBV and HCV are sensed and how they evade innate immunity to establish chronicity. Understanding the mechanisms of viral hepatitis is mandatory to develop effective and safe therapies for eradication of viral hepatitis.     

Is Universal HBV Vaccination of Healthcare Workers a Relevant Strategy in Developing Endemic Countries? The Case of a University Hospital in Niger

Background

Exposure to hepatitis B virus (HBV) remains a serious risk to healthcare workers (HCWs) in endemic developing countries owing to the strong prevalence of HBV in the general and hospital populations, and to the high rate of occupational blood exposure. Routine HBV vaccination programs targeted to high-risk groups and especially to HCWs are generally considered as a key element of prevention strategies. However, the high rate of natural immunization among adults in such countries where most infections occur perinatally or during early childhood must be taken into account.

Methodology/Principal Findings

We conducted a cross sectional study in 207 personnel of 4 occupational groups (medical, paramedical, cleaning staff, and administrative) in Niamey’s National Hospital, Niger, in order to assess the prevalence of HBV markers, to evaluate susceptibility to HBV infection, and to identify personnel who might benefit from vaccination. The proportion of those who declared a history of occupational blood exposure ranged from 18.9% in the administrative staff to 46.9% in paramedical staff. Only 7.2% had a history of vaccination against HBV with at least 3 injections. Ninety two percent were anti-HBc positive. When we focused on170 HCWs, only 12 (7.1%) showed no biological HBV contact. Twenty six were HBsAg positive (15,3%; 95% confidence interval: 9.9%–20.7%) of whom 8 (32%) had a viral load >2000 IU/ml.

Conclusions/Significance

The very small proportion of HCWs susceptible to HBV infection in our study and other studies suggests that in a global approach to prevent occupational infection by bloodborne pathogens, a universal hepatitis B vaccination of HCWs is not priority in these settings. The greatest impact on the risk will most likely be achieved by focusing efforts on primary prevention strategies to reduce occupational blood exposure. HBV screening in HCWs and treatment of those with chronic HBV infection should be however considered.     

Spread of hepatitis virus as a threat to national security

Information on viral hepatitis A, B and C morbidity in Russia is presented. A distinct trend to decreased viral hepatitis B and C morbidity in 2001-2002 in comparison with the 1990-ies is noted. Nevertheless, there is still unfavorable prognosis regarding high hepatitis B morbidity among the population of reproductive age, as well as among adolescents, which increases the risk for children at an early age. In addition, a new specific feature of hepatitis A spread is observed: morbidity in this infection is shifted to older age groups. The role of vaccinal prophylaxis in the decrease of hepatitis A and B morbidity, virus safety of blood and its components, the quality of the diagnostics of chronic hepatitis, especially hepatitis C, are discussed. The complex of measures for the prophylaxis of viral hepatitis is proposed.     

Is Midlife Occupational Physical Activity Related to Disability in Old Age? The SNAC-Kungsholmen Study

Objectives

Leisure-time physical activity (PA) has been established to be related to more years lived without disability. However, less is known about the relationship between occupational PA and disability in old age. The aim of the study was 1) to investigate whether midlife occupational PA is related to late-life disability, and 2) to test the hypothesis that the association differs according to the occupational categories of blue and white collar work.

Methods

The study population was derived from the Swedish National Study on Aging and Care, and consisted of a random sample of 1804 subjects aged 72 and above. The association of occupational PA during the longest held occupation with disability in old age was determined using logistic regression.

Results

There was no significant relationship between occupational PA and disability in personal or instrumental activities of daily living (ADL) after controlling for demographic and health-related factors. However, in stratified analyses moderate levels of occupational PA was associated with a lower odds ratio of dependency in personal ADL amongst white collar workers, compared to low level of occupational PA (OR = 0.34 95% C1 0.12–0.98).

Conclusions

Moderate levels of midlife occupational PA were associated with a decreased risk of personal ADL disability in old age among white collar workers, but not among blue collar workers. Our results highlight the importance of encouraging white collar workers to engage in physical activity during or outside work hours.     

Simultaneous detection of waterborne viruses by multiplex real-time PCR

Norovirus, Rotavirus group A, the Hepatitis A virus, and Coxsackievirus are all common causes of gastroenteritis. Conventional diagnoses of these causative agents are based on antigen detection and electron microscopy. To improve the diagnostic potential for viral gastroenteritis, internally controlled multiplex real-time polymerase chain reaction (PCR) methods have been recently developed. In this study, individual real-time PCRs were developed and optimized for specific detections of Norovirus genogroup I, Norovirus genogroup II, Rotavirus group A, the Hepatitis A virus, and Coxsackievirus group B1. Subsequently, individual PCRs were combined with multiplex PCR reactions. In general, multiplex real-time PCR assays showed comparable sensitivities and specificities with individual assays. A retrospective clinical evaluation showed increased pathogen detection in 29% of samples using conventional PCR methods. Prospective clinical evaluations were detected in 123 of the 227 (54%) total samples used in the multiplex real-time PCR analysis. The Norovirus genogroup II was found most frequently (23%), followed by Rotavirus (20%), the Hepatitis A virus (4.5%), Coxsackievirus (3.5%), and Norovirus genogroup I (2.6%). Internally controlled multiplex real-time PCR assays for the simultaneous detection of Rotavirus, Coxsackievirus group B, the Hepatitis A virus, and Norovirus genogroups I and II showed significant improvement in the diagnosis of viral gastroenteritis.     

Canadians for Health Research conference

Dentists were surveyed regarding a history of hepatitis and the presence in the blood of hepatitis B surface antigen (HBsAg) and antibody (anti-HBs) to determine whether they were at high risk of exposure to hepatitis B virus. Of 288 Canadian dentists 5.2% gave a history of hepatitis after graduation. This proportion is similar to that for 1462 Ontario dentists (6.3%) and that for 3162 accountants (5.1%) who had previously completed a mailed questionnaire. One dentist (0.3%) was HBsAg-positive and 42 (14.6%) were anti-HBs-positive. Of 210 healthy volunteer blood donors matched for age, sex and ethnic origin with the group of dentists none was HBsAg-positive and 2.9% significantly fewer (P less than 0.005), were anti-HBs-positive. Among Ontario blood donors 0.3% were HBsAg-positive and 3% were anti-HBs-positive. Thus, in Canada, dentists are not at increased risk of acquiring clinical hepatitis or becoming carriers, but they are more likely than other groups to have anti-HBs in the blood. Among dentists from outside Canada a higher proportion had a history of hepatitis (10.3%) and were HBsAg-positive (1.6%), but approximately the same proportion were anti-HBs-positive (15.9%).     

Prevalence of HIV,Hepatitis B and C Infections and an Assessment of HCV-Genotypes and Two IL28B SNPs among People Who Inject Drugs in Three Regions of Nepal

As part of a comprehensive health care programme for people who use drugs in Nepal, HIV and viral hepatitis B and C status—including risk factors, HCV-genotypes and co-infections—as well as two IL28B Single-nucleotide polymorphisms (SNPs) were assessed for a random sample of 401 people who inject drugs in three regions of Nepal: mid-western Terrai (Nepalgunj), the eastern region (Dharan, Biratnagar) and the central region (Kathmandu, Lalitpur and Chitwan). Individuals were included who showed at least a minimum of health care seeking behaviour. This latter criterion was defined by being registered with any organisation offering health services. The average age of the participants was 30.5 yrs, and the average length of intravenous drug use was 8.5 yrs. The prevalence rates of HBsAg, anti-HIV antibodies and HCV-RNA were 3.5%, 13.8% and 41.9%, respectively. Spontaneous HCV clearance was evident in 16% of all of those who tested positive for anti-HCV antibodies. Independent risk factors for HCV-RNA positivity were age, gender, geographical region, duration of injecting drug use, history of imprisonment and HIV co-infection. In the age group ≤24 yrs, the rate of spontaneous HCV clearance was 43.5%. Overall, 59.8% of HCV infections were caused by HCV genotype 3 and 40.2% by HCV genotype 1. No other HCV genotypes were identified in this study. The IL28B SNP rs12979860 and rs8099917 were identified in 122 patients, and 75.4% of all participants had both favourable genotypes rs12979860 C/C and rs8099917 T/T.     

The Relation of Ambulatory Heart Rate with All-Cause Mortality among Middle-Aged Men: A Prospective Cohort Study

The aim of this study was to investigate the association between average 24-hour ambulatory heart rate and all-cause mortality, while adjusting for resting clinical heart rate, cardiorespiratory fitness, occupational and leisure time physical activity as well as classical risk factors. A group of 439 middle-aged male workers free of baseline coronary heart disease from the Belgian Physical Fitness Study was included in the analysis. Data were collected by questionnaires and clinical examinations from 1976 to 1978. All-cause mortality was collected from the national mortality registration with a mean follow-up period of 16.5 years, with a total of 48 events. After adjustment for all before mentioned confounders in a Cox proportional hazards regression analysis, a significant increased risk for all-cause mortality was found among the tertile of workers with highest average ambulatory heart rate compared to the tertile with lowest ambulatory heart rate (Hazard ratio = 3.21, 95% confidence interval: 1.22–8.44). No significant independent association was found between resting clinic heart rate and all-cause mortality. The study indicates that average 24-hour ambulatory heart rate is a strong predictor of all-cause mortality independent from resting clinic heart rate, cardiorespiratory fitness, occupational and leisure time physical activity and other classical risk factors among healthy middle-aged workers.