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1.  Psychological distress as a risk factor for death from cerebrovascular disease 
Background:
Little is known about psychological risk factors in cerebrovascular disease. We examined the association between psychological distress and risk of death due to cerebrovascular disease.
Methods:
We obtained data from 68 652 adult participants of the Health Survey for England (mean age 54.9 [standard deviation 13.9] yr, 45.0% male sex) with no known history of cardiovascular diseases at baseline. We used the 12-item General Health Questionnaire (GHQ-12) to assess the presence of psychological distress. We followed participants for eight years for cause-specific death using linkage to national registers.
Results:
There were 2367 deaths due to cardiovascular disease during follow-up. Relative to participants with no symptoms of psychological distress (GHQ-12 score 0) at baseline, people with psychological distress (GHQ-12 score ≥ 4, 14.7% of participants) had an increased risk of death from cerebrovascular disease (adjusted hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.32–2.08) and ischemic heart disease (adjusted HR 1.59, 95% CI 1.34–1.88). There was also evidence of a dose–response effect with increasing GHQ-12 score (p for trend < 0.001 in all analyses). Associations were only marginally attenuated after we adjusted for possible confounders, including socioeconomic status, smoking and use of antihypertensive medications.
Interpretation:
Psychological distress was associated with increased risk of death due to cerebrovascular disease in a large population-representative cohort. These data suggest that the cardiovascular effects of psychological distress are not limited to coronary artery disease.
doi:10.1503/cmaj.111719
PMCID: PMC3447014  PMID: 22711734
2.  Low Socioeconomic Status and Psychological Distress as Synergistic Predictors of Mortality From Stroke and Coronary Heart Disease 
Psychosomatic Medicine  2013;75(3):311-316.
Background
The purpose of this study was to test whether lower socioeconomic status (SES) augments the effect of psychological distress on mortality from stroke or coronary heart disease (CHD).
Methods
We prospectively linked data from 66,500 participants 35 years or older in the Health Survey for England, selected using stratified random sampling from 1994 to 2004, and free of cardiovascular disease and cancer at baseline, with mortality records. The median follow-up time was 7.9 years. SES was indexed by occupational class, and psychological distress was assessed using the 12-item General Health Questionnaire (GHQ-12).
Results
After adjustment for demographic and clinical variables, both psychological distress and low SES were associated with increased mortality: the hazard ratios (HR) for one-category increase in low SES (three categories in total) were 1.15 for stroke-death (95% confidence interval [CI] = 1.00–1.31, p = .043) and 1.24 for CHD-death (95% CI = 1.09–1.41, p = .001); the HR for one-category increase in GHQ-12 (three categories in total) was 1.18 for stroke-death (95% CI = 1.07–1.30, p = .001) and 1.24 for CHD-death (95% CI = 1.13–1.36, p < .001). In stratified analyses, the strongest associations were found in the lowest SES categories: the HR for GHQ-12 toward stroke-death was 1.15 in high-SES participants (95% CI = 0.97–1.37, p = .107) and 1.31 in low-SES ones (95% CI = 1.13–1.51, p < .001); the HR for GHQ-12 toward CHD-death was 1.10 in high-SES participants (95% CI = 0.97–1.25, p = .129) and 1.33 in low-SES ones (95% CI = 1.19–1.48, p < .001).
Conclusions
People in low socioeconomic circumstances are more vulnerable to the adverse effect of psychological distress. This pattern should be taken into account when evaluating the association between psychosocial variables and health outcomes.
doi:10.1097/PSY.0b013e3182898e6d
PMCID: PMC4196790  PMID: 23533282
stroke; coronary heart disease; mortality; psychological distress; socioeconomic status
3.  Erectile Dysfunction Severity as a Risk Marker for Cardiovascular Disease Hospitalisation and All-Cause Mortality: A Prospective Cohort Study 
PLoS Medicine  2013;10(1):e1001372.
In a prospective Australian population-based study linking questionnaire data from 2006–2009 with hospitalisation and death data to June 2010 for 95,038 men aged ≥45 years, Banks and colleagues found that more severe erectile dysfunction was associated with higher risk of cardiovascular disease.
Background
Erectile dysfunction is an emerging risk marker for future cardiovascular disease (CVD) events; however, evidence on dose response and specific CVD outcomes is limited. This study investigates the relationship between severity of erectile dysfunction and specific CVD outcomes.
Methods and Findings
We conducted a prospective population-based Australian study (the 45 and Up Study) linking questionnaire data from 2006–2009 with hospitalisation and death data to 30 June and 31 Dec 2010 respectively for 95,038 men aged ≥45 y. Cox proportional hazards models were used to examine the relationship of reported severity of erectile dysfunction to all-cause mortality and first CVD-related hospitalisation since baseline in men with and without previous CVD, adjusting for age, smoking, alcohol consumption, marital status, income, education, physical activity, body mass index, diabetes, and hypertension and/or hypercholesterolaemia treatment. There were 7,855 incident admissions for CVD and 2,304 deaths during follow-up (mean time from recruitment, 2.2 y for CVD admission and 2.8 y for mortality). Risks of CVD and death increased steadily with severity of erectile dysfunction. Among men without previous CVD, those with severe versus no erectile dysfunction had significantly increased risks of ischaemic heart disease (adjusted relative risk [RR] = 1.60, 95% CI 1.31–1.95), heart failure (8.00, 2.64–24.2), peripheral vascular disease (1.92, 1.12–3.29), “other” CVD (1.26, 1.05–1.51), all CVD combined (1.35, 1.19–1.53), and all-cause mortality (1.93, 1.52–2.44). For men with previous CVD, corresponding RRs (95% CI) were 1.70 (1.46–1.98), 4.40 (2.64–7.33), 2.46 (1.63–3.70), 1.40 (1.21–1.63), 1.64 (1.48–1.81), and 2.37 (1.87–3.01), respectively. Among men without previous CVD, RRs of more specific CVDs increased significantly with severe versus no erectile dysfunction, including acute myocardial infarction (1.66, 1.22–2.26), atrioventricular and left bundle branch block (6.62, 1.86–23.56), and (peripheral) atherosclerosis (2.47, 1.18–5.15), with no significant difference in risk for conditions such as primary hypertension (0.61, 0.16–2.35) and intracerebral haemorrhage (0.78, 0.20–2.97).
Conclusions
These findings give support for CVD risk assessment in men with erectile dysfunction who have not already undergone assessment. The utility of erectile dysfunction as a clinical risk prediction tool requires specific testing.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Erectile dysfunction is the medical term used when a man is unable to achieve or sustain an erection of his penis suitable for sexual intercourse. Although a sensitive topic that can cause much embarrassment and distress, erectile dysfunction is very common, with an estimated 40% of men over the age of 40 years experiencing frequent or occasional difficulties. The most common causes of erectile dysfunction are medications, chronic illnesses such as diabetes, and drinking too much alcohol. Stress and mental health problems can also cause or worsen erectile dysfunction. There is also increasing evidence that erectile dysfunction may actually be a symptom of cardiovascular disease—a leading cause of death worldwide—as erectile dysfunction could indicate a problem with blood vessels or poor blood flow commonly associated with cardiovascular disease.
Why Was This Study Done?
Although previous studies have suggested that erectile dysfunction can serve as a marker for cardiovascular disease in men not previously diagnosed with the condition, few studies to date have investigated whether erectile dysfunction could also indicate worsening disease in men already diagnosed with cardiovascular disease. In addition, previous studies have typically been small and have not graded the severity of erectile dysfunction or investigated the specific types of cardiovascular disease associated with erectile dysfunction. In this large study conducted in Australia, the researchers investigated the relationship of the severity of erectile dysfunction with a range of cardiovascular disease outcomes among men with and without a previous diagnosis of cardiovascular disease.
What Did the Researchers Do and Find?
The researchers used information from the established 45 and Up Study, a large cohort study that includes 123,775 men aged 45 and over, selected at random from the general population of New South Wales, a large region of Australia. A total of 95,038 men were included in this analysis. The male participants completed a postal questionnaire that included a question on erectile functioning, which allowed the researchers to define erectile dysfunction as none, mild, moderate, or severe. Using information captured in the New South Wales Admitted Patient Data Collection—a complete record of all public and private hospital admissions, including the reasons for admission and the clinical diagnosis—and the government death register, the researchers were able to determine health outcomes of all study participants. They then used a statistical model to estimate hospital admissions for cardiovascular disease events for different levels of erectile dysfunction.
The researchers found that the rates of severe erectile dysfunction among study participants were 2.2% for men aged 45–54 years, 6.8% for men aged 55–64 years, 20.2% for men aged 65–74 years, 50.0% for men aged 75–84 years, and 75.4% for men aged 85 years and over. During the study period, the researchers recorded 7,855 hospital admissions related to cardiovascular disease and 2,304 deaths. The researchers found that among men without previous cardiovascular disease, those with severe erectile dysfunction were more likely to develop ischemic heart disease (risk 1.60), heart failure (risk 8.00), peripheral vascular disease (risk 1.92), and other causes of cardiovascular disease (risk 1.26) than men without erectile dysfunction. The risks of heart attacks and heart conduction problems were also increased (1.66 and 6.62, respectively). Furthermore, the combined risk of all cardiovascular disease outcomes was 1.35, and the overall risk of death was also higher (risk 1.93) in these men. The researchers found that these increased risks were similar in men with erectile dysfunction who had previously been diagnosed with cardiovascular disease.
What Do These Findings Mean?
These findings suggest that compared to men without erectile dysfunction, there is an increasing risk of ischemic heart disease, peripheral vascular disease, and death from all causes in those with increasing degrees of severity of erectile dysfunction. The authors emphasize that erectile dysfunction is a risk marker for cardiovascular disease, not a risk factor that causes cardiovascular disease. These findings add to previous studies and highlight the need to consider erectile dysfunction in relation to the risk of different types of cardiovascular disease, including heart failure and heart conduction disorders. However, the study's reliance on the answer to a single self-assessed question on erectile functioning limits the findings. Nevertheless, these findings provide useful information for clinicians: men with erectile dysfunction are at higher risk of cardiovascular disease, and the worse the erectile dysfunction, the higher the risk of cardiovascular disease. Men with erectile dysfunction, even at mild or moderate levels, should be screened and treated for cardiovascular disease accordingly.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001372.
Wikipedia defines erectile dysfunction (note that Wikipedia is a free online encyclopedia that anyone can edit)
MedlinePlus also has some useful patient information on erectile dysfunction
The Mayo Clinic has patient-friendly information on the causes of, and treatments for, erectile dysfunction, and also includes information on the link with cardiovascular disease
The National Heart Foundation of Australia provides information for health professionals, patients, and the general public about how to prevent and manage cardiovascular disease, including assessment and management of cardiovascular disease risk
doi:10.1371/journal.pmed.1001372
PMCID: PMC3558249  PMID: 23382654
4.  Combined Impact of Lifestyle-Related Factors on Total and Cause-Specific Mortality among Chinese Women: Prospective Cohort Study 
PLoS Medicine  2010;7(9):e1000339.
Findings from the Shanghai Women's Health Study confirm those derived from other, principally Western, cohorts regarding the combined impact of lifestyle-related factors on mortality.
Background
Although cigarette smoking, excessive alcohol drinking, obesity, and several other well-studied unhealthy lifestyle-related factors each have been linked to the risk of multiple chronic diseases and premature death, little is known about the combined impact on mortality outcomes, in particular among Chinese and other non-Western populations. The objective of this study was to quantify the overall impact of lifestyle-related factors beyond that of active cigarette smoking and alcohol consumption on all-cause and cause-specific mortality in Chinese women.
Methods and Findings
We used data from the Shanghai Women's Health Study, an ongoing population-based prospective cohort study in China. Participants included 71,243 women aged 40 to 70 years enrolled during 1996–2000 who never smoked or drank alcohol regularly. A healthy lifestyle score was created on the basis of five lifestyle-related factors shown to be independently associated with mortality outcomes (normal weight, lower waist-hip ratio, daily exercise, never exposed to spouse's smoking, higher daily fruit and vegetable intake). The score ranged from zero (least healthy) to five (most healthy) points. During an average follow-up of 9 years, 2,860 deaths occurred, including 775 from cardiovascular disease (CVD) and 1,351 from cancer. Adjusted hazard ratios for mortality decreased progressively with an increasing number of healthy lifestyle factors. Compared to women with a score of zero, hazard ratios (95% confidence intervals) for women with four to five factors were 0.57 (0.44–0.74) for total mortality, 0.29 (0.16–0.54) for CVD mortality, and 0.76 (0.54–1.06) for cancer mortality. The inverse association between the healthy lifestyle score and mortality was seen consistently regardless of chronic disease status at baseline. The population attributable risks for not having 4–5 healthy lifestyle factors were 33% for total deaths, 59% for CVD deaths, and 19% for cancer deaths.
Conclusions
In this first study, to our knowledge, to quantify the combined impact of lifestyle-related factors on mortality outcomes in Chinese women, a healthier lifestyle pattern—including being of normal weight, lower central adiposity, participation in physical activity, nonexposure to spousal smoking, and higher fruit and vegetable intake—was associated with reductions in total and cause-specific mortality among lifetime nonsmoking and nondrinking women, supporting the importance of overall lifestyle modification in disease prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
It is well established that lifestyle-related factors, such as limited physical activity, unhealthy diets, excessive alcohol consumption, and exposure to tobacco smoke are linked to an increased risk of many chronic diseases and premature death. However, few studies have investigated the combined impact of lifestyle-related factors and mortality outcomes, and most of such studies of combinations of established lifestyle factors and mortality have been conducted in the US and Western Europe. In addition, little is currently known about the combined impact on mortality of lifestyle factors beyond that of active smoking and alcohol consumption.
Why Was This Study Done?
Lifestyles in regions of the world can vary considerably. For example, many women in Asia do not actively smoke or regularly drink alcohol, which are important facts to note when considering practical disease prevention measures for these women. Therefore, it is important to study the combination of lifestyle factors appropriate to this population.
What Did the Researchers Do and Find?
The researchers used the Shanghai Women's Health Study, an ongoing prospective cohort study of almost 75,000 Chinese women aged 40–70 years, as the basis for their analysis. The Shanghai Women's Health Study has comprehensive baseline data on anthropometric measurements, lifestyle habits (including the responses to validated food frequency and physical activity questionnaires), medical history, occupational history, and select information from each participant's spouse, such as smoking history and alcohol consumption. This information was used by the researchers to create a healthy lifestyle score on the basis of five lifestyle-related factors shown to be independently associated with mortality outcomes in this population: normal weight, lower waist-hip ratio, daily exercise, never being exposed to spouse's smoking, and higher daily fruit and vegetable intake. The score ranged from zero (least healthy) to five (most healthy) points. The researchers found that higher healthy lifestyle scores were significantly associated with decreasing mortality and that this association persisted for all women regardless of their baseline comorbidities. So in effect, healthier lifestyle-related factors, including normal weight, lower waist-hip ratio, participation in exercise, never being exposed to spousal smoking, and higher daily fruit and vegetable intake, were significantly and independently associated with lower risk of total, and cause-specific, mortality.
What Do These Findings Mean?
This large prospective cohort study conducted among lifetime nonsmokers and nonalcohol drinkers shows that lifestyle factors, other than active smoking and alcohol consumption, have a major combined impact on total mortality on a scale comparable to the effect of smoking—the leading cause of death in most populations. However, the sample sizes for some cause-specific analyses were relatively small (despite the overall large sample size), and extended follow-up of this cohort will provide the opportunity to further evaluate the impact of these lifestyle-related factors on mortality outcomes in the future.
The findings of this study highlight the importance of overall lifestyle modification in disease prevention, especially as most of the lifestyle-related factors studied here may be improved by individual motivation to change unhealthy behaviors. Further research is needed to design appropriate interventions to increase these healthy lifestyle factors among Asian women.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000339
The Vanderbilt Epidemiology Center has more information on the Shanghai Women's Health Study
The World Health Organization provides information on health in China
The document Health policy and systems research in Chinacontains information about health policy and health systems research in China
The Chinese Ministry of Healthalso provides health information
doi:10.1371/journal.pmed.1000339
PMCID: PMC2939020  PMID: 20856900
5.  Natural Course of Recurrent Psychological Distress in Adulthood 
Journal of affective disorders  2010;130(3):454-461.
Background
The course of major depressive disorder is often characterized by progressing chronicity, but whether this applies to the course of self-reported psychological distress remains unclear. We examined whether the risk of self-reported psychological distress becomes progressively higher the longer the history of distress and whether prolonged history of distress modifies associations between risk markers and future distress.
Methods
Participants were British civil servants from the prospective Whitehall II cohort study (n=7934; 31.5% women, mean age 44.5 years at baseline) followed from 1985 to 2006 with repeat data collected in 7 study phases. Psychological distress was assessed with the 30-item General Health Questionnaire (GHQ). Sex, socioeconomic status, marital status, ethnicity, physical activity, alcohol consumption, smoking, and obesity were assessed as risk markers.
Results
Recurrent history of psychological distress was associated with a progressively increasing risk of future distress in a dose-response manner. Common risk markers, such as low socioeconomic status, non-White ethnicity, being single, and alcohol abstinence were stronger predictors of subsequent distress in participants with a longer history of psychological distress. Sex differences in psychological distress attenuated with prolonged distress history.
Limitations
The participants were already adults in the beginning of the study, so we could not assess the progressive chronicity of psychological distress from adolescence onwards.
Conclusions
These data suggest that self-reported psychological distress becomes more persistent over time and that a longer prior exposure to psychological distress increases sensitivity to the stressful effects of certain risk markers.
doi:10.1016/j.jad.2010.10.047
PMCID: PMC3062710  PMID: 21106248
Chronic distress; Kindling hypothesis; Longitudinal; Recurrence
6.  Psychological distress, physical illness, and risk of coronary heart disease 
Study objective: The aims of this study are to confirm the association between psychological distress and coronary heart disease (CHD) using an epidemiological community study with hospital admissions data and to examine if any association is explained by existing illness.
Design: Prospective cohort study modelling the association between psychological distress, measured using the 30 item general health questionnaire (GHQ), and hospital admissions data for CHD (ICD 410–414), using proportional hazards modelling adjusted for sociodemographic, CHD risk factors, and angina, bronchitis, diabetes, ischaemia, and stroke.
Setting: Two suburbs of Glasgow, Renfrew and Paisley, in Scotland.
Participants: 6575 men and women aged 45–64 years from Paisley.
Main: results: Five year CHD risk in distressed men compared with non-distressed men was 1.78 (95% confidence intervals (CI), 1.15 to 2.75) in age adjusted analysis, 1.78 (95% CI, 1.14 to 2.79) with sociodemographic and CHD risk factor adjustment, and 1.61 (95% CI 1.02 to 2.55) with additional adjustment for existing illness. Psychological distress was unrelated to five year CHD risk in women. In further analysis, compared with healthy, non-distressed men, distressed physically ill men had a greater risk of CHD than non-distressed physically ill men, a relative risk of 4.01 (95% CI 2.42 to 6.66) compared with 2.12 (95% CI 1.35 to 3.32).
Conclusion: The association of psychological distress with an increased risk of five year CHD risk in men could be a function of baseline physical illness but an effect independent of physical illness cannot be ruled out. Its presence among physically ill men greatly increases CHD risk.
doi:10.1136/jech.2004.019786
PMCID: PMC1732997  PMID: 15650146
7.  Association of Early Repolarization Pattern on ECG with Risk of Cardiac and All-Cause Mortality: A Population-Based Prospective Cohort Study (MONICA/KORA) 
PLoS Medicine  2010;7(7):e1000314.
In a population-based cohort study of middle-aged people in Central Europe, Stefan Kääb and colleagues find an association between electrocardiographic early repolarization pattern and mortality risk.
Background
Early repolarization pattern (ERP) on electrocardiogram was associated with idiopathic ventricular fibrillation and sudden cardiac arrest in a case-control study and with cardiovascular mortality in a Finnish community-based sample. We sought to determine ERP prevalence and its association with cardiac and all-cause mortality in a large, prospective, population-based case-cohort study (Monitoring of Cardiovascular Diseases and Conditions [MONICA]/KORA [Cooperative Health Research in the Region of Augsburg]) comprised of individuals of Central-European descent.
Methods and Findings
Electrocardiograms of 1,945 participants aged 35–74 y, representing a source population of 6,213 individuals, were analyzed applying a case-cohort design. Mean follow-up was 18.9 y. Cause of death was ascertained by the 9th revision of the International Classification of Disease (ICD-9) codes as documented in death certificates. ERP-attributable effects on mortality were determined by a weighted Cox proportional hazard model adjusted for covariables. Prevalence of ERP was 13.1% in our study. ERP was associated with cardiac and all-cause mortality, most pronounced in those of younger age and male sex; a clear ERP-age interaction was detected (p = 0.005). Age-stratified analyses showed hazard ratios (HRs) for cardiac mortality of 1.96 (95% confidence interval [CI] 1.05–3.68, p = 0.035) for both sexes and 2.65 (95% CI 1.21–5.83, p = 0.015) for men between 35–54 y. An inferior localization of ERP further increased ERP-attributable cardiac mortality to HRs of 3.15 (95% CI 1.58–6.28, p = 0.001) for both sexes and to 4.27 (95% CI 1.90–9.61, p<0.001) for men between 35–54 y. HRs for all-cause mortality were weaker but reached significance.
Conclusions
We found a high prevalence of ERP in our population-based cohort of middle-aged individuals. ERP was associated with about a 2- to 4-fold increased risk of cardiac mortality in individuals between 35 and 54 y. An inferior localization of ERP was associated with a particularly increased risk.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Cardiovascular diseases—disorders that affect the heart and the circulation—are the leading cause of death in the developed world. About half of cardiovascular deaths occur when the heart suddenly stops pumping (sudden cardiac arrest). The muscular walls of the four heart chambers contract in a set pattern to pump blood around the body. The heart's internal electrical system controls the rate and rhythm of these contractions and, if this system goes wrong, an abnormal heart beat or “arrhythmia” develops. Some arrhythmias—in particular, ventricular fibrillation in which the walls of the two lower heart chambers quiver or “fibrillate” instead of pumping—can cause sudden cardiac arrest and immediate loss of consciousness. Death follows within minutes in 95% of cases but immediate cardiopulmonary resuscitation (CPR; chest compression to pump the heart and inflation of the lungs by mouth-to-mouth resuscitation) can keep a person alive until a defibrillator can be used to restore the normal heart beat. People who survive sudden cardiac arrest can be given anti-arrhythmia drugs or have a pacemaker implanted to stabilize their heart beat.
Why Was This Study Done?
The beating heart generates tiny electric waves that can be detected by electrodes on the skin. The pattern of these waves (an electrocardiogram or ECG) provides information about the heart's health. One wave pattern that is often seen on ECGs is the “early repolarization pattern” (ERP), which some studies suggest is associated with an increased risk of cardiac death. Here, the researchers investigate the prevalence of ERP (the proportion of a population with ERP) and its association with death from heart-related problems (cardiac mortality) and from any cause (all-cause mortality) in the MONICA/KORA prospective, population-based case-cohort study. The MONICA Project (MONitoring of Trends and Determinants in CArdiovascular Disease) has studied cardiovascular disease in 10 million people in 21 countries; KORA denotes the study done in the Augsburg region of Germany. In a prospective study, specific baseline characteristics of the study's participants are determined and the participants are followed to see who experiences a predefined outcome. A case-cohort study investigates a randomly selected subcohort (subgroup) of the original participants of a study and any participants who experience the predefined outcome instead of all the participants.
What Did the Researchers Do and Find?
The researchers selected 1945 MONIKA/KORA participants aged 35–74 years from a source population of about 6,000 people using a case-cohort study design. They analyzed the ECGs (recorded in 1984–1985 or 1989–1990) of this subcohort and ascertained the cause of death for those participants who died during the 18.9 year average follow-up. The overall prevalence of ERP in the study was 13.1%, report the researchers, and ERP was associated with cardiac mortality, particularly among younger and male participants. Specifically, among men and women aged 35–54 years, having ERP was associated with a nearly doubled risk of cardiac death. Among men aged 35–54 years, having ERP was associated with an increase in the risk of cardiac death by 2.65-fold. An ERP localized to the bottom of the heart (inferior localization) was associated with an increased risk of cardiac death among both sexes by more than 3-fold and among men by more than 4-fold in this age group. Finally, ERP was also significantly associated with an increased risk of all-cause mortality but less strongly than with cardiac mortality.
What Do These Findings Mean?
These findings suggest that the prevalence of ERP among the middle-aged people in the MONICA/KORA study is high (and somewhat higher than previously reported). They also show a clear association between ERP and the risk of cardiac death among 35–54-year-old people, particularly among men, but because of the study design, these findings do not show that ERP actually causes cardiac death; it could simply be a susceptibility marker. The researchers note that the increased risk of cardiac death associated with ERP is of a similar size to that associated with some other ECG abnormalities. However, although it might be worth paying special attention to young people with an inferior localization of ERP, finding ERP in a person without symptoms and without a family history of sudden cardiac death should not lead to further investigations or any preventative therapy, they suggest, because the absolute risk of cardiac arrest in such people is very low.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000314.
The US National Heart Lung and Blood Institute provides information on cardiovascular conditions, including sudden cardiac arrest and on arrhythmias
The American Heart Association also information on sudden cardiac death and on arrhythmias
The German Cardiac Society (Deutsche Gesellschaft fr Kardiologie) and the German Heart Foundation (Deutsche Herzstiftung) provide further information (in German) on cardiovascular conditions
The Heart Rhythm Foundation provides information on all aspects of heart arrhythmia
The Fondation Leducq Alliance Against Sudden Cardiac Death provides information on sudden cardiac arrest
MedlinePlus provides links to other resources about cardiac arrest and arrhythmias (in English and Spanish)
The MedlinePlus Encyclopedia has a page on electrocardiograms (in English and Spanish)
The Nobel Foundation provides an interactive electrocardiogram game
More information about the MONICA project and the KORA Study or is available
doi:10.1371/journal.pmed.1000314
PMCID: PMC2910598  PMID: 20668657
8.  Combined Impact of Health Behaviours and Mortality in Men and Women: The EPIC-Norfolk Prospective Population Study 
PLoS Medicine  2008;5(1):e12.
Background
There is overwhelming evidence that behavioural factors influence health, but their combined impact on the general population is less well documented. We aimed to quantify the potential combined impact of four health behaviours on mortality in men and women living in the general community.
Methods and Findings
We examined the prospective relationship between lifestyle and mortality in a prospective population study of 20,244 men and women aged 45–79 y with no known cardiovascular disease or cancer at baseline survey in 1993–1997, living in the general community in the United Kingdom, and followed up to 2006. Participants scored one point for each health behaviour: current non-smoking, not physically inactive, moderate alcohol intake (1–14 units a week) and plasma vitamin C >50 mmol/l indicating fruit and vegetable intake of at least five servings a day, for a total score ranging from zero to four. After an average 11 y follow-up, the age-, sex-, body mass–, and social class–adjusted relative risks (95% confidence intervals) for all-cause mortality(1,987 deaths) for men and women who had three, two, one, and zero compared to four health behaviours were respectively, 1.39 (1.21–1.60), 1.95 (1.70–-2.25), 2.52 (2.13–3.00), and 4.04 (2.95–5.54) p < 0.001 trend. The relationships were consistent in subgroups stratified by sex, age, body mass index, and social class, and after excluding deaths within 2 y. The trends were strongest for cardiovascular causes. The mortality risk for those with four compared to zero health behaviours was equivalent to being 14 y younger in chronological age.
Conclusions
Four health behaviours combined predict a 4-fold difference in total mortality in men and women, with an estimated impact equivalent to 14 y in chronological age.
From a large prospective population study, Kay-Tee Khaw and colleagues estimate the combined impact of four behaviors--not smoking, not being physically inactive, moderate alcohol intake, and at least five vegetable servings a day--amounts to 14 additional years of life.
Editors' Summary
Background.
Every day, or so it seems, new research shows that some aspect of lifestyle—physical activity, diet, alcohol consumption, and so on—affects health and longevity. For the person in the street, all this information is confusing. What is a healthy diet, for example? Although there are some common themes such as the benefit of eating plenty of fruit and vegetables, the details often differ between studies. And exactly how much physical activity is needed to improve health? Is a gentle daily walk sufficient or simply a stepping stone to doing enough exercise to make a real difference? The situation with alcohol consumption is equally confusing. Small amounts of alcohol apparently improve health but large amounts are harmful. As a result, it can be hard for public-health officials to find effective ways to encourage the behavioral changes that the scientific evidence suggests might influence the health of populations.
Why Was This Study Done?
There is another factor that is hindering official attempts to provide healthy lifestyle advice to the public. Although there is overwhelming evidence that individual behavioral factors influence health, there is very little information about their combined impact. If the combination of several small differences in lifestyle could be shown to have a marked effect on the health of populations, it might be easier to persuade people to make behavioral changes to improve their health, particularly if those changes were simple and relatively easy to achieve. In this study, which forms part of the European Prospective Investigation into Cancer and Nutrition (EPIC), the researchers have examined the relationship between lifestyle and the risk of dying using a health behavior score based on four simply defined behaviors—smoking, physical activity, alcohol drinking, and fruit and vegetable intake.
What Did the Researchers Do and Find?
Between 1993 and 1997, about 20,000 men and women aged 45–79 living in Norfolk UK, none of whom had cancer or cardiovascular disease (heart or circulation problems), completed a health and lifestyle questionnaire, had a health examination, and had their blood vitamin C level measured as part of the EPIC-Norfolk study. A health behavior score of between 0 and 4 was calculated for each participant by giving one point for each of the following healthy behaviors: current non-smoking, not physically inactive (physical inactivity was defined as having a sedentary job and doing no recreational exercise), moderate alcohol intake (1–14 units a week; a unit of alcohol is half a pint of beer, a glass of wine, or a shot of spirit), and a blood vitamin C level consistent with a fruit and vegetable intake of at least five servings a day. Deaths among the participants were then recorded until 2006. After allowing for other factors that might have affected their likelihood of dying (for example, age), people with a health behavior score of 0 were four times as likely to have died (in particular, from cardiovascular disease) than those with a score of 4. People with a score of 2 were twice as likely to have died.
What Do These Findings Mean?
These findings indicate that the combination of four simply defined health behaviors predicts a 4-fold difference in the risk of dying over an average period of 11 years for middle-aged and older people. They also show that the risk of death (particularly from cardiovascular disease) decreases as the number of positive health behaviors increase. Finally, they can be used to calculate that a person with a health score of 0 has the same risk of dying as a person with a health score of 4 who is 14 years older. These findings need to be confirmed in other populations and extended to an analysis of how these combined health behaviors affect the quality of life as well as the risk of death. Nevertheless, they strongly suggest that modest and achievable lifestyle changes could have a marked effect on the health of populations. Armed with this information, public-health officials should now be in a better position to encourage behavior changes likely to improve the health of middle-aged and older people.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050012.
The MedlinePlus encyclopedia contains a page on healthy living (in English and Spanish)
The MedlinePlus page on seniors' health contains links to many sites dealing with healthy lifestyles and longevity (in English and Spanish)
The European Prospective Investigation into Cancer and Nutrition (EPIC) study is investigating the relationship between nutrition and lifestyle and the development of cancer and other chronic diseases; information about the EPIC-Norfolk study is also available
The US Centers for Disease Control and Prevention provides information on healthy aging for older adults, including information on health-related behaviors (in English and Spanish)
The UK charity Age Concerns provides a fact sheet about staying healthy in later life
The London Health Observatory, which provides information for policy makers and practitioners about improving health and health care, has a section on how lifestyle and behavior affect health
doi:10.1371/journal.pmed.0050012
PMCID: PMC2174962  PMID: 18184033
9.  Biomarker Profiling by Nuclear Magnetic Resonance Spectroscopy for the Prediction of All-Cause Mortality: An Observational Study of 17,345 Persons 
PLoS Medicine  2014;11(2):e1001606.
In this study, Würtz and colleagues conducted high-throughput profiling of blood specimens in two large population-based cohorts in order to identify biomarkers for all-cause mortality and enhance risk prediction. The authors found that biomarker profiling improved prediction of the short-term risk of death from all causes above established risk factors. However, further investigations are needed to clarify the biological mechanisms and the utility of these biomarkers to guide screening and prevention.
Please see later in the article for the Editors' Summary
Background
Early identification of ambulatory persons at high short-term risk of death could benefit targeted prevention. To identify biomarkers for all-cause mortality and enhance risk prediction, we conducted high-throughput profiling of blood specimens in two large population-based cohorts.
Methods and Findings
106 candidate biomarkers were quantified by nuclear magnetic resonance spectroscopy of non-fasting plasma samples from a random subset of the Estonian Biobank (n = 9,842; age range 18–103 y; 508 deaths during a median of 5.4 y of follow-up). Biomarkers for all-cause mortality were examined using stepwise proportional hazards models. Significant biomarkers were validated and incremental predictive utility assessed in a population-based cohort from Finland (n = 7,503; 176 deaths during 5 y of follow-up). Four circulating biomarkers predicted the risk of all-cause mortality among participants from the Estonian Biobank after adjusting for conventional risk factors: alpha-1-acid glycoprotein (hazard ratio [HR] 1.67 per 1–standard deviation increment, 95% CI 1.53–1.82, p = 5×10−31), albumin (HR 0.70, 95% CI 0.65–0.76, p = 2×10−18), very-low-density lipoprotein particle size (HR 0.69, 95% CI 0.62–0.77, p = 3×10−12), and citrate (HR 1.33, 95% CI 1.21–1.45, p = 5×10−10). All four biomarkers were predictive of cardiovascular mortality, as well as death from cancer and other nonvascular diseases. One in five participants in the Estonian Biobank cohort with a biomarker summary score within the highest percentile died during the first year of follow-up, indicating prominent systemic reflections of frailty. The biomarker associations all replicated in the Finnish validation cohort. Including the four biomarkers in a risk prediction score improved risk assessment for 5-y mortality (increase in C-statistics 0.031, p = 0.01; continuous reclassification improvement 26.3%, p = 0.001).
Conclusions
Biomarker associations with cardiovascular, nonvascular, and cancer mortality suggest novel systemic connectivities across seemingly disparate morbidities. The biomarker profiling improved prediction of the short-term risk of death from all causes above established risk factors. Further investigations are needed to clarify the biological mechanisms and the utility of these biomarkers for guiding screening and prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
A biomarker is a biological molecule found in blood, body fluids, or tissues that may signal an abnormal process, a condition, or a disease. The level of a particular biomarker may indicate a patient's risk of disease, or likely response to a treatment. For example, cholesterol levels are measured to assess the risk of heart disease. Most current biomarkers are used to test an individual's risk of developing a specific condition. There are none that accurately assess whether a person is at risk of ill health generally, or likely to die soon from a disease. Early and accurate identification of people who appear healthy but in fact have an underlying serious illness would provide valuable opportunities for preventative treatment.
While most tests measure the levels of a specific biomarker, there are some technologies that allow blood samples to be screened for a wide range of biomarkers. These include nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. These tools have the potential to be used to screen the general population for a range of different biomarkers.
Why Was This Study Done?
Identifying new biomarkers that provide insight into the risk of death from all causes could be an important step in linking different diseases and assessing patient risk. The authors in this study screened patient samples using NMR spectroscopy for biomarkers that accurately predict the risk of death particularly amongst the general population, rather than amongst people already known to be ill.
What Did the Researchers Do and Find?
The researchers studied two large groups of people, one in Estonia and one in Finland. Both countries have set up health registries that collect and store blood samples and health records over many years. The registries include large numbers of people who are representative of the wider population.
The researchers first tested blood samples from a representative subset of the Estonian group, testing 9,842 samples in total. They looked at 106 different biomarkers in each sample using NMR spectroscopy. They also looked at the health records of this group and found that 508 people died during the follow-up period after the blood sample was taken, the majority from heart disease, cancer, and other diseases. Using statistical analysis, they looked for any links between the levels of different biomarkers in the blood and people's short-term risk of dying. They found that the levels of four biomarkers—plasma albumin, alpha-1-acid glycoprotein, very-low-density lipoprotein (VLDL) particle size, and citrate—appeared to accurately predict short-term risk of death. They repeated this study with the Finnish group, this time with 7,503 individuals (176 of whom died during the five-year follow-up period after giving a blood sample) and found similar results.
The researchers carried out further statistical analyses to take into account other known factors that might have contributed to the risk of life-threatening illness. These included factors such as age, weight, tobacco and alcohol use, cholesterol levels, and pre-existing illness, such as diabetes and cancer. The association between the four biomarkers and short-term risk of death remained the same even when controlling for these other factors.
The analysis also showed that combining the test results for all four biomarkers, to produce a biomarker score, provided a more accurate measure of risk than any of the biomarkers individually. This biomarker score also proved to be the strongest predictor of short-term risk of dying in the Estonian group. Individuals with a biomarker score in the top 20% had a risk of dying within five years that was 19 times greater than that of individuals with a score in the bottom 20% (288 versus 15 deaths).
What Do These Findings Mean?
This study suggests that there are four biomarkers in the blood—alpha-1-acid glycoprotein, albumin, VLDL particle size, and citrate—that can be measured by NMR spectroscopy to assess whether otherwise healthy people are at short-term risk of dying from heart disease, cancer, and other illnesses. However, further validation of these findings is still required, and additional studies should examine the biomarker specificity and associations in settings closer to clinical practice. The combined biomarker score appears to be a more accurate predictor of risk than tests for more commonly known risk factors. Identifying individuals who are at high risk using these biomarkers might help to target preventative medical treatments to those with the greatest need.
However, there are several limitations to this study. As an observational study, it provides evidence of only a correlation between a biomarker score and ill health. It does not identify any underlying causes. Other factors, not detectable by NMR spectroscopy, might be the true cause of serious health problems and would provide a more accurate assessment of risk. Nor does this study identify what kinds of treatment might prove successful in reducing the risks. Therefore, more research is needed to determine whether testing for these biomarkers would provide any clinical benefit.
There were also some technical limitations to the study. NMR spectroscopy does not detect as many biomarkers as mass spectrometry, which might therefore identify further biomarkers for a more accurate risk assessment. In addition, because both study groups were northern European, it is not yet known whether the results would be the same in other ethnic groups or populations with different lifestyles.
In spite of these limitations, the fact that the same four biomarkers are associated with a short-term risk of death from a variety of diseases does suggest that similar underlying mechanisms are taking place. This observation points to some potentially valuable areas of research to understand precisely what's contributing to the increased risk.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001606
The US National Institute of Environmental Health Sciences has information on biomarkers
The US Food and Drug Administration has a Biomarker Qualification Program to help researchers in identifying and evaluating new biomarkers
Further information on the Estonian Biobank is available
The Computational Medicine Research Team of the University of Oulu and the University of Bristol have a webpage that provides further information on high-throughput biomarker profiling by NMR spectroscopy
doi:10.1371/journal.pmed.1001606
PMCID: PMC3934819  PMID: 24586121
10.  Higher levels of psychological distress are associated with a higher risk of incident diabetes during 18 year follow-up: results from the British household panel survey 
BMC Public Health  2012;12:1109.
Background
Reviews have shown that depression is a risk factor for the development of type 2 diabetes. However, there is limited evidence for general psychological distress to be associated with incident diabetes. The aim of the present study was to test whether persons who report higher levels of psychological distress are at increased risk to develop type 2 diabetes during 18 years follow up, adjusted for confounders.
Methods
A prospective analysis using data from 9,514 participants (41 years, SD=14; 44% men) of the British Household Panel Survey. The General Health Questionnaire 12 item version was used to assess general psychological distress, diabetes was measured by means of self-report. Cox proportional hazards regression models were used to calculate the multivariate-adjusted hazard ratio (HR) of incident diabetes during 18 years follow up, comparing participants with low versus high psychological distress at baseline (1991).
Results
A total of 472 participants developed diabetes 18 year follow up. Those with a high level of psychological distress had a 33% higher hazard of developing diabetes (HR=1.33, 95% CI 1.10–1.61), relative to those with a low level of psychological distress, adjusted for age, sex, education level and household income. After further adjustment for differences in level of energy, health status, health problems and activity level, higher psychological distress was no longer associated with incident diabetes (HR=1.10, 95% CI 0.91-1.34).
Conclusions
Higher levels of psychological distress are a risk factor for the development of diabetes during an 18 year follow up period. This association may be potentially mediated by low energy level and impaired health status.
doi:10.1186/1471-2458-12-1109
PMCID: PMC3551824  PMID: 23259455
Type 2 diabetes; Psychological distress; Prospective; Risk factor; British household panel survey
11.  Marital status, gender and cardiovascular mortality: Behavioural, psychological distress and metabolic explanations☆ 
Social Science & Medicine (1982)  2009;69(2):223-228.
The intermediate processes through which the various unmarried states can increase the risk of subsequent cardiovascular disease mortality are incompletely understood. An understanding of these processes and how they may vary by gender is important for understanding why marital status is strongly and robustly associated with subsequent cardiovascular disease. In a prospective study of 13,889 Scottish men and women (mean age 52.3, Standard Deviation: 11.8 yrs, range 35–95, 56.1% female) without a history of clinically diagnosed cardiovascular disease, we examined the extent to which health behaviours (smoking, alcohol, physical activity), psychological distress (General Health Questionnaire-12 item) and metabolic dysregulation (obesity levels, and the presence of hypertension and diabetes) account for the association between marital status and cardiovascular mortality. There were 258 cardiovascular deaths over an average follow up of 7.1 (Standard Deviation = 3.3) years. The risk of cardiovascular mortality was greatest in single, never married men and separated/divorced women compared with those that were married in gender stratified models that were adjusted for age and socio-economic group. In models that were separately adjusted, behavioural factors explained up to 33%, psychological distress explained up to 10% and metabolic dysregulation up to 16% of the relative change in the hazard ratios in the observed significant associations between marital status and cardiovascular mortality. Behavioural factors were particularly important in accounting for the relationship between being separated/divorced and cardiovascular mortality in both men and women (33% and 21% of the relative change in the hazard ratios, respectively). The findings suggest that health behaviour, psychological distress and metabolic dysregulation data have varying explanatory power for understanding the observed relationship between cardiovascular disease mortality and unmarried states.
doi:10.1016/j.socscimed.2009.05.010
PMCID: PMC2852675  PMID: 19501442
Cardiovascular disease; Health behaviour; Marital status; Distress; UK; Scotland; Gender
12.  Long-Term Exposure to Silica Dust and Risk of Total and Cause-Specific Mortality in Chinese Workers: A Cohort Study 
PLoS Medicine  2012;9(4):e1001206.
A retro-prospective cohort study by Weihong Chen and colleagues provides new estimates for the risk of total and cause-specific mortality due to long-term silica dust exposure among Chinese workers.
Background
Human exposure to silica dust is very common in both working and living environments. However, the potential long-term health effects have not been well established across different exposure situations.
Methods and Findings
We studied 74,040 workers who worked at 29 metal mines and pottery factories in China for 1 y or more between January 1, 1960, and December 31, 1974, with follow-up until December 31, 2003 (median follow-up of 33 y). We estimated the cumulative silica dust exposure (CDE) for each worker by linking work history to a job–exposure matrix. We calculated standardized mortality ratios for underlying causes of death based on Chinese national mortality rates. Hazard ratios (HRs) for selected causes of death associated with CDE were estimated using the Cox proportional hazards model. The population attributable risks were estimated based on the prevalence of workers with silica dust exposure and HRs. The number of deaths attributable to silica dust exposure among Chinese workers was then calculated using the population attributable risk and the national mortality rate. We observed 19,516 deaths during 2,306,428 person-years of follow-up. Mortality from all causes was higher among workers exposed to silica dust than among non-exposed workers (993 versus 551 per 100,000 person-years). We observed significant positive exposure–response relationships between CDE (measured in milligrams/cubic meter–years, i.e., the sum of silica dust concentrations multiplied by the years of silica exposure) and mortality from all causes (HR 1.026, 95% confidence interval 1.023–1.029), respiratory diseases (1.069, 1.064–1.074), respiratory tuberculosis (1.065, 1.059–1.071), and cardiovascular disease (1.031, 1.025–1.036). Significantly elevated standardized mortality ratios were observed for all causes (1.06, 95% confidence interval 1.01–1.11), ischemic heart disease (1.65, 1.35–1.99), and pneumoconiosis (11.01, 7.67–14.95) among workers exposed to respirable silica concentrations equal to or lower than 0.1 mg/m3. After adjustment for potential confounders, including smoking, silica dust exposure accounted for 15.2% of all deaths in this study. We estimated that 4.2% of deaths (231,104 cases) among Chinese workers were attributable to silica dust exposure. The limitations of this study included a lack of data on dietary patterns and leisure time physical activity, possible underestimation of silica dust exposure for individuals who worked at the mines/factories before 1950, and a small number of deaths (4.3%) where the cause of death was based on oral reports from relatives.
Conclusions
Long-term silica dust exposure was associated with substantially increased mortality among Chinese workers. The increased risk was observed not only for deaths due to respiratory diseases and lung cancer, but also for deaths due to cardiovascular disease.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Walk along most sandy beaches and you will be walking on millions of grains of crystalline silica, one of the commonest minerals on earth and a major ingredient in glass and in ceramic glazes. Silica is also used in the manufacture of building materials, in foundry castings, and for sandblasting, and respirable (breathable) crystalline silica particles are produced during quarrying and mining. Unfortunately, silica dust is not innocuous. Several serious diseases are associated with exposure to this dust, including silicosis (a chronic lung disease characterized by scarring and destruction of lung tissue), lung cancer, and pulmonary tuberculosis (a serious lung infection). Moreover, exposure to silica dust increases the risk of death (mortality). Worryingly, recent reports indicate that in the US and Europe, about 1.7 and 3.0 million people, respectively, are occupationally exposed to silica dust, figures that are dwarfed by the more than 23 million workers who are exposed in China. Occupational silica exposure, therefore, represents an important global public health concern.
Why Was This Study Done?
Although the lung-related adverse health effects of exposure to silica dust have been extensively studied, silica-related health effects may not be limited to these diseases. For example, could silica dust particles increase the risk of cardiovascular disease (diseases that affect the heart and circulation)? Other environmental particulates, such as the products of internal combustion engines, are associated with an increased risk of cardiovascular disease, but no one knows if the same is true for silica dust particles. Moreover, although it is clear that high levels of exposure to silica dust are dangerous, little is known about the adverse health effects of lower exposure levels. In this cohort study, the researchers examined the effect of long-term exposure to silica dust on the risk of all cause and cause-specific mortality in a large group (cohort) of Chinese workers.
What Did the Researchers Do and Find?
The researchers estimated the cumulative silica dust exposure for 74,040 workers at 29 metal mines and pottery factories from 1960 to 2003 from individual work histories and more than four million measurements of workplace dust concentrations, and collected health and mortality data for all the workers. Death from all causes was higher among workers exposed to silica dust than among non-exposed workers (993 versus 551 deaths per 100,000 person-years), and there was a positive exposure–response relationship between silica dust exposure and death from all causes, respiratory diseases, respiratory tuberculosis, and cardiovascular disease. For example, the hazard ratio for all cause death was 1.026 for every increase in cumulative silica dust exposure of 1 mg/m3-year; a hazard ratio is the incidence of an event in an exposed group divided by its incidence in an unexposed group. Notably, there was significantly increased mortality from all causes, ischemic heart disease, and silicosis among workers exposed to respirable silica concentrations at or below 0.1 mg/m3, the workplace exposure limit for silica dust set by the US Occupational Safety and Health Administration. For example, the standardized mortality ratio (SMR) for silicosis among people exposed to low levels of silica dust was 11.01; an SMR is the ratio of observed deaths in a cohort to expected deaths calculated from recorded deaths in the general population. Finally, the researchers used their data to estimate that, in 2008, 4.2% of deaths among industrial workers in China (231,104 deaths) were attributable to silica dust exposure.
What Do These Findings Mean?
These findings indicate that long-term silica dust exposure is associated with substantially increased mortality among Chinese workers. They confirm that there is an exposure–response relationship between silica dust exposure and a heightened risk of death from respiratory diseases and lung cancer. That is, the risk of death from these diseases increases as exposure to silica dust increases. In addition, they show a significant relationship between silica dust exposure and death from cardiovascular diseases. Importantly, these findings suggest that even levels of silica dust that are considered safe increase the risk of death. The accuracy of these findings may be affected by the accuracy of the silica dust exposure estimates and/or by confounding (other factors shared by the people exposed to silica such as diet may have affected their risk of death). Nevertheless, these findings highlight the need to tighten regulations on workplace dust control in China and elsewhere.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001206.
The American Lung Association provides information on silicosis
The US Centers for Disease Control and Prevention provides information on silica in the workplace, including links to relevant US National Institute for Occupational Health and Safety publications, and information on silicosis and other pneumoconioses
The US Occupational Safety and Health Administration also has detailed information on occupational exposure to crystalline silica
What does silicosis mean to you is a video provided by the US Mine Safety and Health Administration that includes personal experiences of silicosis; Dont let silica dust you is a video produced by the Association of Occupational and Environmental Clinics that identifies ways to reduce silica dust exposure in the workplace
The MedlinePlus encyclopedia has a page on silicosis (in English and Spanish)
The International Labour Organization provides information on health surveillance for those exposed to respirable crystalline silica
The World Health Organization has published a report about the health effects of crystalline silica and quartz
doi:10.1371/journal.pmed.1001206
PMCID: PMC3328438  PMID: 22529751
13.  Intake of B vitamins in childhood and adult life in relation to psychological distress among women in a British birth cohort 
Public health nutrition  2008;12(2):166-174.
Background
Lower levels of B vitamins (particularly folate, vitamin B12 and vitamin B6) may be associated with psychological distress. Little is known about the impact of childhood nutrition on psychological distress in adult life.
Objective
We investigated whether prospectively measured childhood and adult dietary intakes of thiamin, riboflavin, niacin, folate, vitamin B6 and vitamin B12 were related to the psychological distress of women in mid-age, taking into account socio-economic, behavioural and lifestyle factors.
Design
Prospective data were collected from a cohort of 636 British women followed up since their birth in 1946. Participants completed a 28-item, scaled version of the General Health Questionnaire (GHQ-28) to measure psychological distress at age 53 years. Dietary intakes in childhood (at age four) were determined by 24 h recall and in adulthood (at age 36, 43 and 53 years) by a 5 d food record.
Results
Low dietary vitamin B12 intake at age 53 was associated with higher psychological distress at that age. Women in the lowest third of vitamin B12 intake in adulthood had a higher GHQ-28 score compared with those in the highest third (percentage change, adjusted regression coefficient, 21 (95 % CI 3, 39)). There were no other significant associations between dietary B vitamin intake in childhood or adulthood and psychological distress in the cohort.
Conclusions
Overall, there is evidence that intake of vitamin B12 at age 53 is related to adult psychological distress but there is no evidence for the effects of other adult B vitamin intakes or childhood intakes on psychological distress.
doi:10.1017/S1368980008002413
PMCID: PMC2748268  PMID: 18503720
Mental health; General Health Questionnaire; Depression; Diet; Life-course nutrition; Vitamin B12; B vitamins
14.  Red Blood Cell Transfusion and Mortality in Trauma Patients: Risk-Stratified Analysis of an Observational Study 
PLoS Medicine  2014;11(6):e1001664.
Using a large multicentre cohort, Pablo Perel and colleagues evaluate the association of red blood cell transfusion with mortality according to the predicted risk of death for trauma patients.
Please see later in the article for the Editors' Summary
Background
Haemorrhage is a common cause of death in trauma patients. Although transfusions are extensively used in the care of bleeding trauma patients, there is uncertainty about the balance of risks and benefits and how this balance depends on the baseline risk of death. Our objective was to evaluate the association of red blood cell (RBC) transfusion with mortality according to the predicted risk of death.
Methods and Findings
A secondary analysis of the CRASH-2 trial (which originally evaluated the effect of tranexamic acid on mortality in trauma patients) was conducted. The trial included 20,127 trauma patients with significant bleeding from 274 hospitals in 40 countries. We evaluated the association of RBC transfusion with mortality in four strata of predicted risk of death: <6%, 6%–20%, 21%–50%, and >50%. For this analysis the exposure considered was RBC transfusion, and the main outcome was death from all causes at 28 days. A total of 10,227 patients (50.8%) received at least one transfusion. We found strong evidence that the association of transfusion with all-cause mortality varied according to the predicted risk of death (p-value for interaction <0.0001). Transfusion was associated with an increase in all-cause mortality among patients with <6% and 6%–20% predicted risk of death (odds ratio [OR] 5.40, 95% CI 4.08–7.13, p<0.0001, and OR 2.31, 95% CI 1.96–2.73, p<0.0001, respectively), but with a decrease in all-cause mortality in patients with >50% predicted risk of death (OR 0.59, 95% CI 0.47–0.74, p<0.0001). Transfusion was associated with an increase in fatal and non-fatal vascular events (OR 2.58, 95% CI 2.05–3.24, p<0.0001). The risk associated with RBC transfusion was significantly increased for all the predicted risk of death categories, but the relative increase was higher for those with the lowest (<6%) predicted risk of death (p-value for interaction <0.0001). As this was an observational study, the results could have been affected by different types of confounding. In addition, we could not consider haemoglobin in our analysis. In sensitivity analyses, excluding patients who died early; conducting propensity score analysis adjusting by use of platelets, fresh frozen plasma, and cryoprecipitate; and adjusting for country produced results that were similar.
Conclusions
The association of transfusion with all-cause mortality appears to vary according to the predicted risk of death. Transfusion may reduce mortality in patients at high risk of death but increase mortality in those at low risk. The effect of transfusion in low-risk patients should be further tested in a randomised trial.
Trial registration
www.ClinicalTrials.gov NCT01746953
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Trauma—a serious injury to the body caused by violence or an accident—is a major global health problem. Every year, injuries caused by traffic collisions, falls, blows, and other traumatic events kill more than 5 million people (9% of annual global deaths). Indeed, for people between the ages of 5 and 44 years, injuries are among the top three causes of death in many countries. Trauma sometimes kills people through physical damage to the brain and other internal organs, but hemorrhage (serious uncontrolled bleeding) is responsible for 30%–40% of trauma-related deaths. Consequently, early trauma care focuses on minimizing hemorrhage (for example, by using compression to stop bleeding) and on restoring blood circulation after blood loss (health-care professionals refer to this as resuscitation). Red blood cell (RBC) transfusion is often used for the management of patients with trauma who are bleeding; other resuscitation products include isotonic saline and solutions of human blood proteins.
Why Was This Study Done?
Although RBC transfusion can save the lives of patients with trauma who are bleeding, there is considerable uncertainty regarding the balance of risks and benefits associated with this procedure. RBC transfusion, which is an expensive intervention, is associated with several potential adverse effects, including allergic reactions and infections. Moreover, blood supplies are limited, and the risks from transfusion are high in low- and middle-income countries, where most trauma-related deaths occur. In this study, which is a secondary analysis of data from a trial (CRASH-2) that evaluated the effect of tranexamic acid (which stops excessive bleeding) in patients with trauma, the researchers test the hypothesis that RBC transfusion may have a beneficial effect among patients at high risk of death following trauma but a harmful effect among those at low risk of death.
What Did the Researchers Do and Find?
The CRASH-2 trail included 20,127 patients with trauma and major bleeding treated in 274 hospitals in 40 countries. In their risk-stratified analysis, the researchers investigated the effect of RBC transfusion on CRASH-2 participants with a predicted risk of death (estimated using a validated model that included clinical variables such as heart rate and blood pressure) on admission to hospital of less than 6%, 6%–20%, 21%–50%, or more than 50%. That is, the researchers compared death rates among patients in each stratum of predicted risk of death who received a RBC transfusion with death rates among patients who did not receive a transfusion. Half the patients received at least one transfusion. Transfusion was associated with an increase in all-cause mortality at 28 days after trauma among patients with a predicted risk of death of less than 6% or of 6%–20%, but with a decrease in all-cause mortality among patients with a predicted risk of death of more than 50%. In absolute figures, compared to no transfusion, RBC transfusion was associated with 5.1 more deaths per 100 patients in the patient group with the lowest predicted risk of death but with 11.9 fewer deaths per 100 patients in the group with the highest predicted risk of death.
What Do These Findings Mean?
These findings show that RBC transfusion is associated with an increase in all-cause deaths among patients with trauma and major bleeding with a low predicted risk of death, but with a reduction in all-cause deaths among patients with a high predicted risk of death. In other words, these findings suggest that the effect of RBC transfusion on all-cause mortality may vary according to whether a patient with trauma has a high or low predicted risk of death. However, because the participants in the CRASH-2 trial were not randomly assigned to receive a RBC transfusion, it is not possible to conclude that receiving a RBC transfusion actually increased the death rate among patients with a low predicted risk of death. It might be that the patients with this level of predicted risk of death who received a transfusion shared other unknown characteristics (confounders) that were actually responsible for their increased death rate. Thus, to provide better guidance for clinicians caring for patients with trauma and hemorrhage, the hypothesis that RBC transfusion could be harmful among patients with trauma with a low predicted risk of death should be prospectively evaluated in a randomised controlled trial.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001664.
This study is further discussed in a PLOS Medicine Perspective by Druin Burch
The World Health Organization provides information on injuries and on violence and injury prevention (in several languages)
The US Centers for Disease Control and Prevention has information on injury and violence prevention and control
The National Trauma Institute, a US-based non-profit organization, provides information about hemorrhage after trauma and personal stories about surviving trauma
The UK National Health Service Choices website provides information about blood transfusion, including a personal story about transfusion after a serious road accident
The US National Heart, Lung, and Blood Institute also provides detailed information about blood transfusions
MedlinePlus provides links to further resources on injuries, bleeding, and blood transfusion (in English and Spanish)
More information in available about CRASH-2 (in several languages)
doi:10.1371/journal.pmed.1001664
PMCID: PMC4060995  PMID: 24937305
15.  Immediate Risk for Cardiovascular Events and Suicide Following a Prostate Cancer Diagnosis: Prospective Cohort Study 
PLoS Medicine  2009;6(12):e1000197.
Katja Fall and Fang Fang and colleagues find that men newly diagnosed with prostate cancer are at increased risk of cardiovascular events and suicide.
Background
Stressful life events have been shown to be associated with altered risk of various health consequences. The aim of the present study was to investigate whether the emotional stress evoked by a prostate cancer diagnosis increases the immediate risks of cardiovascular events and suicide.
Methods and Findings
We conducted a prospective cohort study by following all men in Sweden who were 30 y or older (n = 4,305,358) for a diagnosis of prostate cancer (n = 168,584) and their subsequent occurrence of cardiovascular events and suicide between January 1, 1961 and December 31, 2004. We used Poisson regression models to calculate relative risks (RRs) and 95% confidence intervals (CIs) of cardiovascular events and suicide among men who had prostate cancer diagnosed within 1 y to men without any cancer diagnosis. The risks of cardiovascular events and suicide were elevated during the first year after prostate cancer diagnosis, particularly during the first week. Before 1987, the RR of fatal cardiovascular events was 11.2 (95% CI 10.4–12.1) during the first week and 1.9 (95% CI 1.9–2.0) during the first year after diagnosis. From 1987, the RR for cardiovascular events, nonfatal and fatal combined, was 2.8 (95% CI 2.5–3.2) during the first week and 1.3 (95% CI 1.3–1.3) during the first year after diagnosis. While the RR of cardiovascular events declined, the RR of suicide was stable over the entire study period: 8.4 (95% CI 1.9–22.7) during the first week and 2.6 (95% CI 2.1–3.0) during the first year after diagnosis. Men 54 y or younger at cancer diagnosis demonstrated the highest RRs of both cardiovascular events and suicide. A limitation of the present study is the lack of tumor stage data, which precluded possibilities of investigating the potential impact of the disease severity on the relationship between a recent diagnosis of prostate cancer and the risks of cardiovascular events and suicide. In addition, we cannot exclude residual confounding as a possible explanation.
Conclusions
Men newly diagnosed with prostate cancer are at increased risks for cardiovascular events and suicide. Future studies with detailed disease characteristic data are warranted.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Prostate cancer—a type of tumor that develops in a walnut-sized structure in the male reproductive system—is the commonest cancer (excluding skin cancer) among men in developed countries. In the USA and the UK, for example, one in six men will develop prostate cancer during their lifetime. Most prostate cancers develop in elderly men and, because these tumors usually grow relatively slowly, many men die with prostate cancer rather than as a result of it. Nevertheless, some prostate cancers are fast-growing and aggressive and prostate cancer is the second leading cause of cancer-related death among men. The symptoms of prostate cancer include problems urinating and excessive urination during the night. Nowadays, however, most prostate cancers are detected before they produce any symptoms by measuring the amount of a protein called the prostate-specific antigen (PSA) in the blood.
Why Was This Study Done?
Widespread PSA screening was introduced 20 years ago in the hope that early detection of prostate cancer would save lives. But, although many more prostate cancers are detected nowadays, the number of prostate cancer deaths has not changed significantly. Experts are divided, therefore, about whether the potential benefits of PSA screening outweigh its risks. Treatments for prostate cancer (for example, surgical removal of the prostate) may be more effective if they are started early but they can cause impotence and urinary incontinence, so should men be treated whose cancer might otherwise never affect their health? In addition, receiving a diagnosis of prostate cancer is stressful and there is growing evidence that stressful life events can increase an individual's risk of becoming ill or dying from a heart attack, stroke, or other “cardiovascular” events and of becoming mentally ill. In this study, therefore, the researchers investigate whether men diagnosed with prostate cancer in Sweden have increased risks of cardiovascular events and suicide during the first week and first year after their diagnosis.
What Did the Researchers Do and Find?
The researchers identified nearly 170, 000 men diagnosed with prostate cancer between 1961 and 2004 among Swedish men aged 30 years or older by searching the Swedish Cancer Register. They obtained information on subsequent fatal and nonfatal cardiovascular events and suicides from the Causes of Death Register and the Inpatient Register (in Sweden, everyone has a unique national registration number that facilitates searches of different health-related Registers). Before 1987, men with prostate cancer were about 11 times as likely to have a fatal cardiovascular event during the first week after their diagnosis as men without prostate cancer; during the first year after their diagnosis, men with prostate cancer were nearly twice as likely to have a cardiovascular event as men without prostate cancer (a relative risk of 1.9). From 1987, the relative risk of combined fatal and nonfatal cardiovascular events associated with a diagnosis of prostate cancer was 2.8 during the first week and 1.3 during the first year after diagnosis. The relative risk of suicide associated with a diagnosis of prostate cancer was 8.4 during the first week and 2.6 during the first year after diagnosis throughout the study period. Finally, men younger than 54 years at diagnosis had higher relative risks of both cardiovascular events and suicide.
What Do These Findings Mean?
These findings suggest that men newly diagnosed with prostate cancer have an increased risk of cardiovascular events and suicide. Because there is no information on tumor size or aggressiveness in the Cancer Register, the researchers could not look at the relationship between disease severity and the likelihood of a cardiovascular event or suicide. Furthermore, because of the study design, men who received a diagnosis of prostate cancer may have had additional characteristics in common that contributed to their increased risk of cardiovascular events and suicide. Nevertheless, these findings strongly suggest that the stress of the diagnosis itself rather than any subsequent treatment has deleterious effects on the health of men receiving a diagnosis of prostate cancer. Thus, strategies should be developed to reduce the risks of cardiovascular events and suicide—increased clinical and psychological monitoring—after a diagnosis of prostate cancer, particularly among young men, and this new information should be considered in the ongoing debate about the risks and benefits of PSA screening.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000197.
The US National Cancer Institute provides information on all aspects of prostate cancer, (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on prostate cancer, including Prostate Cancer Screening, A Decision Guide (some information in multiple languages)
The UK National Health Service Choices Web site provides detailed information on prostate cancer
The UK-based Samaritans charity provides confidential nonjudgmental emotional support, 24 hours a day, for people who are experiencing feelings of distress or despair, including those which could lead to suicide
Outside the UK, Befrienders provides information on help lines for those experiencing distress
doi:10.1371/journal.pmed.1000197
PMCID: PMC2784954  PMID: 20016838
16.  Are Sitting Occupations Associated with Increased All-Cause, Cancer, and Cardiovascular Disease Mortality Risk? A Pooled Analysis of Seven British Population Cohorts 
PLoS ONE  2013;8(9):e73753.
Background
There is mounting evidence for associations between sedentary behaviours and adverse health outcomes, although the data on occupational sitting and mortality risk remain equivocal. The aim of this study was to determine the association between occupational sitting and cardiovascular, cancer and all-cause mortality in a pooled sample of seven British general population cohorts.
Methods
The sample comprised 5380 women and 5788 men in employment who were drawn from five Health Survey for England and two Scottish Health Survey cohorts. Participants were classified as reporting standing, walking or sitting in their work time and followed up over 12.9 years for mortality. Data were modelled using Cox proportional hazard regression adjusted for age, waist circumference, self-reported general health, frequency of alcohol intake, cigarette smoking, non-occupational physical activity, prevalent cardiovascular disease and cancer at baseline, psychological health, social class, and education.
Results
In total there were 754 all-cause deaths. In women, a standing/walking occupation was associated with lower risk of all-cause (fully adjusted hazard ratio [HR] = 0.68, 95% CI 0.52–0.89) and cancer (HR = 0.60, 95% CI 0.43–0.85) mortality, compared to sitting occupations. There were no associations in men. In analyses with combined occupational type and leisure-time physical activity, the risk of all-cause mortality was lowest in participants with non-sitting occupations and high leisure-time activity.
Conclusions
Sitting occupations are linked to increased risk for all-cause and cancer mortality in women only, but no such associations exist for cardiovascular mortality in men or women.
doi:10.1371/journal.pone.0073753
PMCID: PMC3784430  PMID: 24086292
17.  Association between Class III Obesity (BMI of 40–59 kg/m2) and Mortality: A Pooled Analysis of 20 Prospective Studies 
PLoS Medicine  2014;11(7):e1001673.
In a pooled analysis of 20 prospective studies, Cari Kitahara and colleagues find that class III obesity (BMI of 40–59) is associated with excess rates of total mortality, particularly due to heart disease, cancer, and diabetes.
Please see later in the article for the Editors' Summary
Background
The prevalence of class III obesity (body mass index [BMI]≥40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity.
Methods and Findings
In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19–83 y at baseline, classified as obese class III (BMI 40.0–59.9 kg/m2) compared with those classified as normal weight (BMI 18.5–24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976–2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40–44.9, 45–49.9, 50–54.9, and 55–59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7–7.3), 8.9 (95% CI: 7.4–10.4), 9.8 (95% CI: 7.4–12.2), and 13.7 (95% CI: 10.5–16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report.
Conclusions
Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The number of obese people (individuals with an excessive amount of body fat) is increasing rapidly in many countries. Worldwide, according to the Global Burden of Disease Study 2013, more than a third of all adults are now overweight or obese. Obesity is defined as having a body mass index (BMI, an indicator of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) of more than 30 kg/m2 (a 183-cm [6-ft] tall man who weighs more than 100 kg [221 lbs] is obese). Compared to people with a healthy weight (a BMI between 18.5 and 24.9 kg/m2), overweight and obese individuals (who have a BMI between 25.0 and 29.9 kg/m2 and a BMI of 30 kg/m2 or more, respectively) have an increased risk of developing diabetes, heart disease, stroke, and some cancers, and tend to die younger. Because people become unhealthily fat by consuming food and drink that contains more energy (kilocalories) than they need for their daily activities, obesity can be prevented or treated by eating less food and by increasing physical activity.
Why Was This Study Done?
Class III obesity (extreme, or morbid, obesity), which is defined as a BMI of more than 40 kg/m2, is emerging as a major public health problem in several high-income countries. In the US, for example, 6% of adults are now morbidly obese. Because extreme obesity used to be relatively uncommon, little is known about the burden of disease, including total and cause-specific mortality (death) rates, among individuals with class III obesity. Before we can prevent and treat class III obesity effectively, we need a better understanding of the health risks associated with this condition. In this pooled analysis of prospective cohort studies, the researchers evaluate the risk of total and cause-specific death and the years of life lost associated with class III obesity. A pooled analysis analyzes the data from several studies as if the data came from one large study; prospective cohort studies record the characteristics of a group of participants at baseline and follow them to see which individuals develop a specific condition.
What Did the Researchers Do and Find?
The researchers included 20 prospective (mainly US) cohort studies from the National Cancer Institute Cohort Consortium (a partnership that studies cancer by undertaking large-scale collaborations) in their pooled analysis. After excluding individuals who had ever smoked and people with a history of chronic disease, the analysis included 9,564 adults who were classified as class III obese based on self-reported height and weight at baseline and 304,011 normal-weight adults. Among the participants with class III obesity, mortality rates (deaths per 100,000 persons per year) during the 30-year study period were 856.0 and 663.0 in men and women, respectively, whereas the mortality rates among normal-weight men and women were 346.7 and 280.5, respectively. Heart disease was the major contributor to the excess death rate among individuals with class III obesity, followed by cancer and diabetes. Statistical analyses of the pooled data indicate that the risk of all-cause death and death due to heart disease, cancer, diabetes, and several other diseases increased with increasing BMI. Finally, compared with having a normal weight, having a BMI between 40 and 59 kg/m2 resulted in an estimated loss of 6.5 to 13.7 years of life.
What Do These Findings Mean?
These findings indicate that class III obesity is associated with a substantially increased rate of death. Notably, this death rate increase is similar to the increase associated with smoking among normal-weight people. The findings also suggest that heart disease, cancer, and diabetes are responsible for most of the excess deaths among people with class III obesity and that having class III obesity results in major reductions in life expectancy. Importantly, the number of years of life lost continues to increase for BMI values above 50 kg/m2, and beyond this point, the loss of life expectancy exceeds that associated with smoking among normal-weight people. The accuracy of these findings is limited by the use of self-reported height and weight measurements to calculate BMI and by the use of BMI as the sole measure of obesity. Moreover, these findings may not be generalizable to all populations. Nevertheless, these findings highlight the need to develop more effective interventions to combat the growing public health problem of class III obesity.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001673.
The US Centers for Disease Control and Prevention provides information on all aspects of overweight and obesity (in English and Spanish)
The World Health Organization provides information on obesity (in several languages); Malri's story describes the health risks faced by an obese child
The UK National Health Service Choices website provides information about obesity, including a personal story about losing weight
The Global Burden of Disease Study website provides the latest details about global obesity trends
The US Department of Agriculture's ChooseMyPlate.gov website provides a personal healthy eating plan; the Weight-Control Information Network is an information service provided for the general public and health professionals by the US National Institute of Diabetes and Digestive and Kidney Diseases (in English and Spanish)
MedlinePlus provides links to other sources of information on obesity (in English and Spanish)
doi:10.1371/journal.pmed.1001673
PMCID: PMC4087039  PMID: 25003901
18.  Physical distress is associated with cardiovascular events in a high risk population of elderly men 
Background
Self-reported health perceptions such as physical distress and quality of life are suggested independent predictors of mortality and morbidity in patients with established cardiovascular disease. This study examined the associations between these factors and three years incidence of cardiovascular events in a population of elderly men with long term hyperlipidemia.
Methods
We studied observational data in a cohort of 433 men aged 64–76 years from a prospective, 2 × 2 factorial designed, three-year interventional trial. Information of classical risk factors was obtained and the following questionnaires were administered at baseline: Hospital Anxiety and Depression Scale, Physical Symptom Distress Index and Life Satisfaction Index. The occurrence of cardiovascular death, myocardial infarction, cerebrovascular incidences and peripheral arterial disease were registered throughout the study period. Continuous data with skewed distribution was split into tertiles. Hazard ratios (HR) were calculated from Cox regression analyses to assess the associations between physical distress, quality of life and cardiovascular events.
Results
After three years, 49 cardiovascular events were registered, with similar incidence among subjects with and without established cardiovascular disease. In multivariate analyses adjusted for age, smoking, systolic blood pressure, serum glucose, HADS-anxiety and treatment-intervention, physical distress was positively associated (HR 3.1, 95% CI 1.2 – 7.9 for 3rd versus 1st tertile) and quality of life negatively associated (HR 2.6, 95% CI 1.1–5.8 for 3rd versus 1st tertile) with cardiovascular events. The association remained statistically significant only for physical distress (hazard ratio 2.8 95% CI 1.2 – 6.8, p < 0.05) when both variables were evaluated in the same model.
Conclusion
Physical distress, but not quality of life, was independently associated with increased risk of cardiovascular events in an observational study of elderly men predominantly without established cardiovascular disease.
Trial Registration
Trial registration: NCT00764010
doi:10.1186/1471-2261-9-14
PMCID: PMC2667171  PMID: 19331677
19.  Psychological distress and chronic obstructive pulmonary disease in the Renfrew and Paisley (MIDSPAN) study 
Background
This study examined whether psychological distress might be a predictor of chronic obstructive pulmonary disease (COPD).
Method
The relation between psychological distress at baseline, measured by the general health questionnaire (GHQ), and chronic bronchitis three years later, as measured by the Medical Research Council (MRC) bronchitis questionnaire and forced expiratory flow in one second (FEV1), was examined in 1682 men and 2203 women from the Renfrew and Paisley (MIDSPAN) study. The analyses were run on men and women separately and adjustments were made for age, socioeconomic position, and lung function at baseline (FEV1). People with chronic diseases at baseline were then excluded to give a “healthy” baseline cohort. The effect of psychological distress on individual components of the MRC bronchitis questionnaire and FEV1 was also assessed.
Results
In multivariate analyses of the whole cohort baseline psychological distress in women was associated with reduced FEV1 at follow up (OR 1.31 95% CI 1.0 to 1.73) after adjustment. In women, in the healthy cohort, psychological distress was associated with chronic bronchitis (OR 2.00, 95% CI 1.16 to 3.46), symptoms of bronchial infection (OR 2.14, 95% CI 1.44 to 3.19), symptoms of breathlessness (OR 3.02, 95% CI 1.99 to 4.59), and reduced FEV1 (OR 1.62, 95% CI 1.13 to 2.32). In men psychological distress predicted symptoms of bronchial infection (OR 2.09, 95% CI 1.28 to 3.42).
Conclusion
This study supports research suggesting that psychological distress is associated with COPD and shows that psychological distress predicts COPD in women. The robustness of the association and the exact mechanism requires further investigation.
doi:10.1136/jech.2005.042150
PMCID: PMC2566028  PMID: 16905724
psychological distress; GHQ; chronic obstructive pulmonary disease; MIDSPAN study
20.  Quality of Life in GERD and Barrett’s Esophagus is Related to Gender and Manifestation of Disease 
Introduction
Gastroesophageal reflux disease (GERD) is a common condition that impacts patients’ health-related quality of life (HRQoL). The HRQoL of Barrett’s esophagus (BE) has been less well studied. Furthermore, it is unknown to what extent BE patients suffer from psychological distress as a result of carrying a diagnosis of a premalignant condition. We sought to compare BE and GERD (stratified by erosive (ERD) and non-erosive reflux disease (NERD)) with regards to HRQoL and psychological impact.
Methods
In this single-center study of subjects presenting for elective upper endoscopy, consecutive patients with BE and GERD were enrolled. Participants completed questionnaires assessing generic HRQoL (Medical Outcomes Study Short Form-36: SF-36), disease-specific HRQoL (Gastrointestinal Quality of Life Index: GIQLI), a measure of psychological distress (the Revised Hopkins Symptom Checklist: SCL-90R) and a patient-centered assessment of impact of disease severity (the GERD health-related quality of life measure: GERD HRQL).
Results
Patients with BE had the lowest symptom severity compared to those with NERD or ERD (GERD HRQL: 13.7 vs. 18 and 15.9 respectively, p<0.01). Those with BE also had better disease-specific quality of life compared to NERD or ERD patients (GIQLI: 137.2 vs. 124.3 and 131.0 respectively, p<0.001). After adjusting for potential confounding variables including symptom severity and gender, BE patients continued to demonstrate better disease-specific HRQoL, scoring 12.2 points higher on the GIQLI than NERD patients (95% CI 5.1 – 19.3) and 16.3 points higher than ERD patients (95% CI 5.4 – 27.3), as well as better generic HRQoL, scoring 4.8 points higher on the SF-36 physical component summary than NERD patients (95% CI 0.8 – 8.8) and 7.1 points higher than ERD patients (95% CI 1.2–13.1). There were no significant differences between groups in psychological distress, as demonstrated by the SCL-90R global severity index, though BE patients scored lower on the somatization domain compared to NERD and ERD patients. When stratified by gender, females with NERD and BE had worse disease-specific HRQoL than males.
Conclusions
Patients with BE have better generic and disease-specific HRQoL when compared to patients with NERD and ERD. This difference is only partially attributable to lower symptom severity amongst BE patients. Psychological distress did not differ significantly amongst groups. Female gender was associated with worsened HRQoL regardless of GERD disease manifestation. Though more precise instruments may aid in detecting any HRQoL decrements in BE patients due to perceived cancer risk or fear of developing or dying from cancer, we were unable to demonstrate an additional decrement in HRQoL due to cancer risk in subjects with BE.
doi:10.1038/ajg.2009.504
PMCID: PMC3073722  PMID: 19755967
Barrett esophagus; Gastroesophageal reflux; Erosive esophagitis; Non-erosive esophagitis; Quality of Life; Gender
21.  Psychological Distress and Mortality: Are Women More Vulnerable?* 
Does psychological distress increase mortality risk? If it does, are women more vulnerable than men to the effect of distress on mortality? Drawing from cumulative disadvantage theory, these questions are addressed with data from a 20-year follow-up of a national sample of adults ages 25−74. Event history analyses were performed to examine mortality from general and specific causes for men and women. Findings reveal that the effect of psychological distress on all-cause mortality was nonlinear for men. Moderate amounts of distress were associated with lower mortality risk, but high levels of distress raised men's mortality risk. Moreover, the curvilinear relationship between distress and mortality varied by cause of death for men and women. Men with high levels of psychological distress were more vulnerable to ischemic heart disease mortality. Women with high levels of distress were more vulnerable to cancer mortality.
PMCID: PMC2637996  PMID: 17066774
22.  The contribution of psychological distress to socio-economic differences in cause-specific mortality: a population-based follow-up of 28 years 
BMC Public Health  2011;11:138.
Background
Psychological factors associated with low social status have been proposed as one possible explanation for the socio-economic gradient in health. The aim of this study is to explore whether different indicators of psychological distress contribute to socio-economic differences in cause-specific mortality.
Methods
The data source is a nationally representative, repeated cross-sectional survey, "Health Behaviour and Health among the Finnish Adult Population" (AVTK). The survey results were linked with socio-economic register data from Statistics Finland (from the years 1979-2002) and mortality follow-up data up to 2006 from the Finnish National Cause of Death Register. The data included 32451 men and 35420 women (response rate 73.5%). Self-reported measures of depression, insomnia and stress were used as indicators of psychological distress. Socio-economic factors included education, employment status and household income. Mortality data consisted of unnatural causes of death (suicide, accidents and violence, and alcohol-related mortality) and coronary heart disease (CHD) mortality. Adjusted hazard ratios were calculated using the Cox regression model.
Results
In unnatural mortality, psychological distress accounted for some of the employment status (11-31%) and income level (4-16%) differences among both men and women, and for the differences related to the educational level (5-12%) among men; the educational level was associated statistically significantly with unnatural mortality only among men. Psychological distress had minor or no contribution to socio-economic differences in CHD mortality.
Conclusions
Psychological distress partly accounted for socio-economic disparities in unnatural mortality. Further studies are needed to explore the role and mechanisms of psychological distress associated with socio-economic differences in cause-specific mortality.
doi:10.1186/1471-2458-11-138
PMCID: PMC3053248  PMID: 21356041
23.  Increased mortality risk in women with depression and diabetes mellitus 
Archives of general psychiatry  2011;68(1):42-50.
Context
Both depression and diabetes have been associated with an increased risk of all-cause and cardiovascular diseases (CVD) mortality. However, data evaluating the joint effects of these two conditions on mortality are sparse.
Objectives
To evaluate the individual and joint effects of depression and diabetes on all-cause and CVD mortality in a prospective cohort study.
Design, Settings and Participants
A total of 78282 female participants in the Nurses' Health Study aged 54-79 years at baseline in 2000 were followed until 2006. Depression was defined as having self-reported diagnosed depression, treatment with antidepressant medications, or a score indicating severe depressive symptomatology, i.e., a five-item Mental Health Index score ≤52. Self-reported type 2 diabetes was confirmed using a supplementary questionnaire.
Main outcome measures
All-cause and CVD-specific mortality.
Results
During 6 years of follow-up (433066 person-years), 4654 deaths were documented, including 979 deaths from CVD. Compared to participants without either condition, the age-adjusted relative risks (95% confidence interval, CI) for all-cause mortality were 1.76 (1.64-1.89) for women with depression only, 1.71 (1.54-1.89) for individuals with diabetes only, and 3.11 (2.70-3.58) for those with both conditions. The corresponding age-adjusted relative risks of CVD mortality were 1.81 (1.54-2.13), 2.67 (2.20-3.23), and 5.38 (4.19-6.91), respectively. These associations were attenuated after multivariate adjustment for other demographic variables, body mass index, smoking status, alcohol intake, physical activity, and major comorbidities (including hypertension, hypercholesterolemia, heart diseases, stroke and cancer) but remained significant, with the highest relative risks for all-cause and CVD mortality found in those with both conditions (2.07 [95% CI, 1.79-2.40] and 2.72 [95% CI, 2.09-3.54], respectively). Furthermore, the combination of depression with a long duration of diabetes (i.e., >10 years) or insulin therapy was associated with particularly higher risk of CVD mortality after multivariate adjustment (relative risk=3.22 and 4.90, respectively).
Conclusions
Depression and diabetes are associated with significantly increased risk of all-cause and CVD mortality. The coexistence of both conditions identifies particularly high-risk women.
doi:10.1001/archgenpsychiatry.2010.176
PMCID: PMC3081788  PMID: 21199964
depression; diabetes; prospective cohort study; morbidity
24.  Olive oil intake and risk of cardiovascular disease and mortality in the PREDIMED Study 
BMC Medicine  2014;12:78.
Background
It is unknown whether individuals at high cardiovascular risk sustain a benefit in cardiovascular disease from increased olive oil consumption. The aim was to assess the association between total olive oil intake, its varieties (extra virgin and common olive oil) and the risk of cardiovascular disease and mortality in a Mediterranean population at high cardiovascular risk.
Methods
We included 7,216 men and women at high cardiovascular risk, aged 55 to 80 years, from the PREvención con DIeta MEDiterránea (PREDIMED) study, a multicenter, randomized, controlled, clinical trial. Participants were randomized to one of three interventions: Mediterranean Diets supplemented with nuts or extra-virgin olive oil, or a control low-fat diet. The present analysis was conducted as an observational prospective cohort study. The median follow-up was 4.8 years. Cardiovascular disease (stroke, myocardial infarction and cardiovascular death) and mortality were ascertained by medical records and National Death Index. Olive oil consumption was evaluated with validated food frequency questionnaires. Multivariate Cox proportional hazards and generalized estimating equations were used to assess the association between baseline and yearly repeated measurements of olive oil intake, cardiovascular disease and mortality.
Results
During follow-up, 277 cardiovascular events and 323 deaths occurred. Participants in the highest energy-adjusted tertile of baseline total olive oil and extra-virgin olive oil consumption had 35% (HR: 0.65; 95% CI: 0.47 to 0.89) and 39% (HR: 0.61; 95% CI: 0.44 to 0.85) cardiovascular disease risk reduction, respectively, compared to the reference. Higher baseline total olive oil consumption was associated with 48% (HR: 0.52; 95% CI: 0.29 to 0.93) reduced risk of cardiovascular mortality. For each 10 g/d increase in extra-virgin olive oil consumption, cardiovascular disease and mortality risk decreased by 10% and 7%, respectively. No significant associations were found for cancer and all-cause mortality. The associations between cardiovascular events and extra virgin olive oil intake were significant in the Mediterranean diet intervention groups and not in the control group.
Conclusions
Olive oil consumption, specifically the extra-virgin variety, is associated with reduced risks of cardiovascular disease and mortality in individuals at high cardiovascular risk.
Trial registration
This study was registered at controlled-trials.com (http://www.controlled-trials.com/ISRCTN35739639). International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.
doi:10.1186/1741-7015-12-78
PMCID: PMC4030221  PMID: 24886626
Olive oil; Cardiovascular; Mortality; Mediterranean Diet; PREDIMED
25.  Socioeconomic Factors and All Cause and Cause-Specific Mortality among Older People in Latin America, India, and China: A Population-Based Cohort Study 
PLoS Medicine  2012;9(2):e1001179.
Cleusa Ferri and colleagues studied mortality rates in over 12,000 people aged 65 years and over in Latin America, India, and China and showed that chronic diseases are the main causes of death and that education has an important effect on mortality.
Background
Even in low and middle income countries most deaths occur in older adults. In Europe, the effects of better education and home ownership upon mortality seem to persist into old age, but these effects may not generalise to LMICs. Reliable data on causes and determinants of mortality are lacking.
Methods and Findings
The vital status of 12,373 people aged 65 y and over was determined 3–5 y after baseline survey in sites in Latin America, India, and China. We report crude and standardised mortality rates, standardized mortality ratios comparing mortality experience with that in the United States, and estimated associations with socioeconomic factors using Cox's proportional hazards regression. Cause-specific mortality fractions were estimated using the InterVA algorithm. Crude mortality rates varied from 27.3 to 70.0 per 1,000 person-years, a 3-fold variation persisting after standardisation for demographic and economic factors. Compared with the US, mortality was much higher in urban India and rural China, much lower in Peru, Venezuela, and urban Mexico, and similar in other sites. Mortality rates were higher among men, and increased with age. Adjusting for these effects, it was found that education, occupational attainment, assets, and pension receipt were all inversely associated with mortality, and food insecurity positively associated. Mutually adjusted, only education remained protective (pooled hazard ratio 0.93, 95% CI 0.89–0.98). Most deaths occurred at home, but, except in India, most individuals received medical attention during their final illness. Chronic diseases were the main causes of death, together with tuberculosis and liver disease, with stroke the leading cause in nearly all sites.
Conclusions
Education seems to have an important latent effect on mortality into late life. However, compositional differences in socioeconomic position do not explain differences in mortality between sites. Social protection for older people, and the effectiveness of health systems in preventing and treating chronic disease, may be as important as economic and human development.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, half of all deaths occur in people aged 60 or older. Yet mortality among older people is a neglected topic in global health. In high income countries, where 84% of people do not die until they are aged 65 years or older, the causes of death among older people and the factors (determinants) that affect their risk of dying are well documented. In Europe, for example, the leading causes of death among older people are heart disease, stroke, and other chronic (long-term) diseases. Moreover, as in younger age groups, having a better education and owning a house reduces the risk of death among older people. By contrast, in low and middle income countries (LMICs), where three-quarters of deaths of older people occur, reliable data on the causes and determinants of death among older people are lacking, in part because many LMICs have inadequate vital registration systems—official records of all births and deaths.
Why Was This Study Done?
In many LMICs, chronic diseases are replacing communicable (infectious) diseases as the leading causes of death and disability—health experts call this the epidemiological transition (epidemiology is the study of the distribution and causes of disease in populations)—and the average age of the population is increasing (the demographic transition). Faced with these changes, which occur when countries move from a pre-industrial to an industrial economy, policy makers in LMICs need to introduce measures to improve health and reduce deaths among older people. However, to do this, they need reliable data on the causes and determinants of death in this section of the population. In this longitudinal population-based cohort study (a type of study that follows a group of people from a defined population over time), researchers from the 10/66 Dementia Research Group, which is carrying out population-based research on dementia, aging, and non-communicable diseases in LMICs, investigate the patterns of mortality among older people living in Latin America, India, and China.
What Did the Researchers Do and Find?
Between 2003 and 2005, the researchers completed a baseline survey of people aged 65 years or older living in six Latin American LMICs, China, and India. Three to five years later, they determined the vital status of 12,373 of the study participants (that is, they determined whether the individual was alive or dead) and interviewed a key informant (usually a relative) about each death using a standardized “verbal autopsy” questionnaire that includes questions about date and place of death, and about medical help-seeking and signs and symptoms noted during the final illness. Finally, they used a tool called the InterVA algorithm to calculate the most likely causes of death from the verbal autopsies. Crude mortality rates varied from 27.3 per 1,000 person-years in urban Peru to 70.0 per 1,000 person-years in urban India, a three-fold difference in mortality rates that persisted even after allowing for differences in age, sex, education, occupational attainment, and number of assets among the study sites. Compared to the US, mortality rates were much higher in urban India and rural China; much lower in urban and rural Peru, Venezuela, and urban Mexico; but similar elsewhere. Although several socioeconomic factors were associated with mortality, only a higher education status provided consistent independent protection against death in statistical analyses. Finally, chronic diseases were the main causes of death; stroke was the leading cause of death at all the sites except those in rural Peru and Mexico.
What Do These Findings Mean?
These findings identify the main causes of death among older adults in a range of LMICs and suggest that there is an association of education with mortality that extends into later life. However, these findings may not be generalizable to other LMICs or even to other sites in the LMICs studied, and because some of the information provided by key informants may have been affected by recall error, the accuracy of the findings may be limited. Nevertheless, these findings suggest how health and mortality might be improved in elderly people in LMICs. Specifically, they suggest that efforts to ensure universal access to education should confer substantial health benefits and that interventions that target social and economic vulnerability in later life and promote access to effectively organized health care (particularly for stroke) should be considered.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001179.
The World Health Organization provides information on mortality around the world and projections of global mortality up to 2030
The 10/66 Dementia Research Group is building an evidence base to inform the development and implementation of policies for improving the health and social welfare of older people in LMICs, particularly people with dementia; its website includes background information about demographic and epidemiological aging in LMICs
Wikipedia has a page on the demographic transition (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Information about the InterVA tool for interpreting verbal autopsy data is available
The US Centers for Disease Control and Prevention has information about healthy aging
doi:10.1371/journal.pmed.1001179
PMCID: PMC3289608  PMID: 22389633

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