A strong sense of coherence associated with reduced risk of anxiety disorder among women in disadvantaged circumstances: British population study.

OBJECTIVE: Many patients receiving medical treatment for anxiety relapse or do not improve. Research has therefore been turning to coping mechanisms as a way to decrease anxiety rates. Previously, we showed that living in a deprived area significantly increases the risk of anxiety in women, but not in men. The objective of this study is to assess whether sense of coherence (coping mechanism) buffers the influence of area deprivation on women's risk of generalised anxiety disorder using data from the European Prospective Investigation of Cancer-Norfolk. DESIGN: Large, population study. SETTING: UK population-based cohort. PARTICIPANTS: 30 445 people over the age of 40 years were recruited through general practice registers in England. Of these, 20 919 completed a structured health and lifestyle questionnaire used to assess generalised anxiety disorder and sense of coherence. Area deprivation was measured using 1991 Census data, and sense of coherence and anxiety were examined in 1996-2000. 10 183 women had data on all variables. MAIN OUTCOME MEASURE: Past-year generalised anxiety disorder defined according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. RESULTS: In this study, 2.6% (260/10 183) of women had generalised anxiety disorder. In those with a strong sense of coherence, area deprivation was not significantly associated with anxiety (OR 1.29, 95% CI 0.77 to 2.17). However, among women with a weak sense of coherence, those living in deprived areas were almost twice as likely to have generalised anxiety disorder compared with those living in more affluent areas (OR 1.99, 95% CI 1.37 to 2.91). CONCLUSION: The number of women living in deprived conditions is large worldwide, and significant numbers are affected by generalised anxiety disorder. Sense of coherence moderates the association between area deprivation and anxiety in women; therefore, interventions targeting coping mechanisms may need to be considered for people with anxiety.

Cumulative social risk exposure in childhood and smoking and excessive alcohol use in adulthood.

BACKGROUND: Social inequalities in adult smoking and excessive alcohol intake may be associated with exposure to multiple childhood social risk factors across different domains of risk within the household. METHODS: We used data from a cross-sectional cohort study of adults (40-75 years) in 1993-97 living in England (N = 19466) to examine the association between clusters of childhood social risks across different domains with adult smoking and excessive alcohol use. Participants reported exposure to six childhood social risk factors, current smoking behaviour and alcohol intake. Factor analysis was used to identify domains of social risk. We created a childhood cumulative domain social risk score (range 0-2) from summing the total number of domains. RESULTS: Factor analysis identified two domains of childhood social risk within the household: maladaptive family functioning (parental unemployment, substance misuse, physical abuse) and parental separation experiences : maternal separation, divorce, being sent away from home). Compared to those children with risk exposure in no single domain, children with risk exposure in both domains (i.e. maladaptive family functioning, parental separation experiences) had a higher prevalence of adult smoking [men: Prevalence ratio (PR) = 1.74, 95% confidence intervals (CI): 1.35-2.26; women: PR = 1.71 95% CI: 1.34-2.18]. There was a trend association between the number of childhood social risk domains and adult smoking (both sexes: P < 0.001) and excessive alcohol use (men: P <0.008). CONCLUSIONS: Further work is needed to understand if addressing cumulative risk exposure to maladaptive family functioning and parental separation experiences can reduce social inequalities in adult smoking and excessive alcohol intake.

Social adversity experience and blood pressure control following antihypertensive medication use in a community sample of older adults.

BACKGROUND: Psychosocial stress is a risk factor for hypertension and has been shown to affect response to treatment for psychiatric illnesses. PURPOSE: We investigate the relationship between a history of social adversity experience and blood pressure control following antihypertensive medication use. METHODS: A total of 1,186 participants selected from the European Prospective Investigation into Cancer-Norfolk study (531 men and 655 women, aged 42 to 80 years) had attended two health checks at which blood pressure measurements were taken; were taking antihypertensive medication at the second, but not the first health check; and had completed a questionnaire assessment of their social and psychological circumstances which included details of traumatic experiences in childhood and of adverse life events, long-term difficulties, and perceived stress in adulthood. RESULTS: Experience of recent loss events in adulthood was associated with a smaller reduction in systolic blood pressure after starting hypertension treatment (ß = 1.78, 95 % confidence interval 0.15-3.40, per life event), independently of age, sex, preexisting health conditions, cigarette smoking history, alcohol consumption, physical activity, and obesity. CONCLUSION: Results from this study suggest that stress caused by recent losses may be associated with reduced effectiveness of treatment for hypertension. Subject to replication, these findings may help determine the specific physiological mechanisms by which medication treatment effectiveness is affected by stress.

Lipoprotein(a) and risk of coronary, cerebrovascular, and peripheral artery disease: the EPIC-Norfolk prospective population study.

OBJECTIVE: Although the association between circulating levels of lipoprotein(a) [Lp(a)] and risk of coronary artery disease (CAD) and stroke is well established, its role in risk of peripheral arterial disease (PAD) remains unclear. Here, we examine the association between Lp(a) levels and PAD in a large prospective cohort. To contextualize these findings, we also examined the association between Lp(a) levels and risk of stroke and CAD and studied the role of low-density lipoprotein as an effect modifier of Lp(a)-associated cardiovascular risk. METHODS AND RESULTS: Lp(a) levels were measured in apparently healthy participants in the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort. Cox regression was used to quantify the association between Lp(a) levels and risk of PAD, stroke, and CAD outcomes. During 212 981 person-years at risk, a total of 2365 CAD, 284 ischemic stroke, and 596 PAD events occurred in 18 720 participants. Lp(a) was associated with PAD and CAD outcomes but not with ischemic stroke (hazard ratio per 2.7-fold increase in Lp(a) of 1.37, 95% CI 1.25-1.50, 1.13, 95% CI 1.04-1.22 and 0.91, 95% CI 0.79-1.03, respectively). Low-density lipoprotein cholesterol levels did not modify these associations. CONCLUSIONS: Lp(a) levels were associated with future PAD and CAD events. The association between Lp(a) and cardiovascular disease was not modified by low-density lipoprotein cholesterol levels.

Genetic determinants of lipid homeostasis.

Circulating levels of blood lipids are heritable risk factors for atherosclerosis and heart disease, and are the target of therapeutic intervention. Studies of monogenic disorders and - more recently - genome-wide association studies have identified several important genetic determinants of blood lipid levels. These have the potential to provide new drug targets to alter blood lipid levels and may improve prediction of cardiovascular disease. Better functional validation of lipid loci is required to clarify the biological role of proteins encoded by specific genomic regions and understand how they influence lipid metabolism and confer disease risk.

Educational attainment and mean leukocyte telomere length in women in the European Prospective Investigation into Cancer (EPIC)-Norfolk population study.

BACKGROUND: Telomere length has been postulated as a marker of biological aging. Recent evidence has suggested that educational attainment but not social class is associated with telemore length. METHODS: We investigated the associations between educational attainment, social class and relative mean telomere length in an ethnically homogeneous population of 4441 women, aged 41-80 years. Mean telomere length was measured using high-throughput quantitative Real Time PCR. RESULTS: Educational attainment (p=0.015) but not social class (p=0.61) was associated with mean telomere length in these data. This association was independent of social class and of systolic blood pressure, high-density lipoprotein cholesterol, cigarette smoking, body mass index, glycated hemoglobin, plasma vitamin C and physical activity (p=0.014), and was not attenuated through additional adjustment for measures of social adversity, including those experienced during childhood (p=0.006). CONCLUSIONS: Our results, at least for women, provide support for the findings previously reported in this journal that lower educational attainment, but not social class, is associated with shorter telomere length.

A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol.

Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ∼25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79×10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.

Life stress, emotional health, and mean telomere length in the European Prospective Investigation into Cancer (EPIC)-Norfolk population study.

We investigated the association between psychological stress, emotional health, and relative mean telomere length in an ethnically homogeneous population of 4,441 women, aged 41-80 years. Mean telomere length was measured using high-throughput quantitative real-time polymerase chain reaction. Social adversity exposure and emotional health were assessed through questionnaire and covariates through direct measurement and questionnaire. This study found evidence that adverse experiences during childhood may be associated with shorter telomere length. This finding remained after covariate adjustment and showed evidence of a dose-response relationship with increasing number of reported childhood difficulties associated with decreasing relative mean telomere length. No associations were observed for any of the other summary measures of social adversity and emotional health considered. These results extend and provide support for some previous findings concerning the association of adverse experience and emotional health histories with shorter telomere length in adulthood. Replication of these findings in longitudinal studies is now essential.

Lifestyle behaviours and quality-adjusted life years in middle and older age.

OBJECTIVE: to examine the relationship between combined lifestyle behaviours and quality-adjusted life years (QALYs) in a general population. METHODS: a population-based study was conducted in 13,358 men and women who participated in the European Prospective Investigation into Cancer (EPIC)-Norfolk (baseline 1993-97). A score of 1 was given to each of non-smoking, physically not inactive, moderate alcohol consumption (1-14 units) and consumption of at least five portions of fruit and vegetables (vitamin C level ≥50 µmol/l). Short-Form Six-Dimension (SF-6D) health utility index scores were derived from the SF-36. QALYs were estimated up to follow-up (July 2007). RESULTS: a total of 13,358 men and women were eligible to be included in the study (aged 40-79 years at baseline). A total of 12,921 people were alive at follow-up (117, 784 person-years). Mean follow-up period was ∼11.5 years. 437 (4.4% of men and 2.4% of women) died. The death rate was 6.5 times higher in people with health behaviour score 0 compared with those who scored 4 (8.4 versus 1.3%). People with higher scores had significantly higher QALYs. CONCLUSION: our findings support the view that modifiable lifestyle factors are an important component in health improvement.

Mastery is associated with cardiovascular disease mortality in men and women at apparently low risk.

OBJECTIVE: We examine the prospective relationship between mastery, where limited mastery is defined as the inability to control negative emotions (and perceiving stressful experiences as beyond personal control), and cardiovascular disease (CVD) mortality particularly among individuals at apparently low CVD risk. DESIGN: Prospective population-based study of 19,067 men and women, aged 41-80 years with no previous heart disease or stroke at baseline assessment. MAIN OUTCOME MEASURES: Primary outcome measure CVD mortality. RESULTS: A total of 791 CVD deaths were recorded up to June 2009 during a median 11.3 person-years of follow-up. Limited perceived mastery over life circumstances was associated with an increased risk of CVD mortality, independently of biological, lifestyle, and socioeconomic risk factors (hazard ratio 1.11 per SD decrease in mastery score, 95% confidence interval 1.01-1.21). This association was more pronounced among those participants apparently at low CVD risk (p = .01 for test of interaction according to the number of CVD risk factors at baseline). CONCLUSIONS: Limited perceived control over life circumstances is associated with an increased risk of CVD mortality, independently of classical cardiovascular risk factors, and particularly among those at apparently low risk. Future attention should be given to this potentially modifiable personal characteristic, through the design of preliminary intervention studies, to reduce cardiovascular risk.

Physical functional health predicts the incidence of coronary heart disease in the European Prospective Investigation into Cancer-Norfolk prospective population-based study.

BACKGROUND: Little is known about the relationship between physical functional health and long-term risk of coronary heart disease (CHD) independently of known risk factors in a general population. METHODS: Men and women aged 40-79 years at baseline who completed a health and lifestyle questionnaire and attended a health examination during 1993-97 participating in the European Prospective Investigation into Cancer-Norfolk who were free of myocardial infarction (MI), stroke and cancer were included. Eighteen months later, physical functional health was assessed using physical component summary (PCS) scores of Short-Form 36-item questionnaire (SF-36). The incidence of CHD was ascertained by death certification and hospital record linkage up to March 2008. RESULTS: A total of 14,222 men and women were included in the study. There were 389 incident CHD (total person-years = 126,896 years). People who reported better physical functional health had significantly lower risk of CHD. Using Cox proportional hazard models adjusting for age, sex, body mass index, cholesterol, systolic blood pressure, smoking, alcohol consumption, physical activity, diabetes, family history of MI, social class and aspirin usage, it was found that men and women who were in the top quartile of SF-36 PCS had half the risk of CHD [relative risk (RR) = 0.46; 95% confidence interval (CI) = 0.32-0.65] compared with the people in the bottom quartile. The relationships remained essentially unchanged after excluding incident CHD within the first 2 years of follow-up (RR = 0.48; 95% CI = 0.33-0.70). CONCLUSIONS: Physical functional health predicts subsequent CHD risk independently of known risk factors in a general population. People with poor physical functional health may benefit from targeted preventive interventions.

No evidence that social stress is associated with breast cancer incidence.

Women commonly attribute the experience of stress as a contributory cause of breast cancer. The purpose of this study is to investigate the associations between a history of social stress and breast cancer risk. A total of 11,467 women with no prior history of breast cancer, participants in the European Prospective Investigation into Cancer (EPIC)-Norfolk population-based prospective cohort study, completed a comprehensive assessment of lifetime social adversity exposure. Summary measures of social adversity were defined according to difficult circumstances in childhood, stressful life events and longer-term difficulties in adulthood, derived measures representing the subjective 'impact' of life events and associated 'stress adaptive capacity', and perceived stress over a 10-year period. Incident breast cancers were identified through linkage with cancer registry data. During 102,514 (median 9) person-years of follow-up, 313 incident breast cancers were identified. No associations were observed between any of the summary social adversity measures and subsequent breast cancer risk, with or without adjustment for age, menopausal status, parity, use of menopausal hormones, age at menarche, age at first birth, family history of breast cancer, physical activity, social class, body mass index, height, and alcohol intake. This study found no evidence that social stress exposure or individual differences in its experience are associated with the development of breast cancer. These findings may aid strategies designed to meet the psychosocial and emotional needs of breast cancer survivors and may be interpreted in a positive way in the context of commonly voiced beliefs that the experience of stress is a contributory cause of their disease.

The Short-Form Six-Dimension utility index predicted mortality in the European Prospective Investigation into Cancer-Norfolk prospective population-based study.

OBJECTIVE: To examine the relationship between the Short-Form Six-Dimension (SF-6D) and mortality. STUDY DESIGN AND SETTING: Participants were 17,736 men and women aged 40-79 years at baseline who lived in Norfolk, UK, and had no known cardiovascular disease or cancer, and completed the anglicized Short-Form 36 (SF-36)-item during 1996-2000 in the European Prospective Investigation into Cancer-Norfolk prospective population study. The SF-36 data were converted to SF-6D. The relationship between SF-6D and all-cause and cause-specific mortality were examined. RESULTS: One thousand and seventy deaths occurred during a total of 115,255 person years of follow-up (mean 6.5 years). Lower SF-6D was associated with increased risk of all-cause mortality in men and women. A decrease of 1 standard deviation (0.12 point) in SF-6D was associated with a 35% increase in all-cause mortality (hazards ratio = 1.35; 95% CI: 1.26, 1.45) after controlling for age, gender, body mass index, systolic blood pressure, cholesterol, diabetes, smoking, and social class. Similar results were observed for cardiovascular, cancer, and other causes of deaths. CONCLUSION: Poor health utility measured by the SF-6D predicted increased risk of all-cause and cause-specific mortality in men and women. The present study provides the first evidence of the sensitivity of the SF-6D in predicting mortality in an apparently healthy population.

Effect of age and sex on the relationship between different socioeconomic indices and self-reported functional health in the EPIC-Norfolk population-based study.

BACKGROUND: The relationship between different social-economic indices and physical and mental functional health of older people compared with younger people is unclear. OBJECTIVE: To examine the effect of age and sex on the relationship between various social-economic indices and self-reported functional health. METHODS: A population-based cross-sectional study was conducted in 19,088 participants of European Prospective Investigation into Cancer (EPIC)-Norfolk, UK, ages 40-79 years at baseline. The independent relationships between three different socioeconomic indices; occupational social class, education and residential area deprivation, and functional health measured by anglicized version of 36-item short form questionnaire (UK SF-36), were compared between older (>or=65 years) and younger (<65 years) men and women. RESULTS: Residential area deprivation was significantly associated with poor physical and mental functional health independent of social class and education, and consistent in both age groups in men and women. A low level of education in younger men and being in low social class in younger women were associated with poorer physical functional health compared with their respective older counterparts. Social class had a significantly greater effect in older women compared with younger women. CONCLUSION: Commonly used socioeconomic indices have differing associations with functional health depending the age and sex of an individual. Residential area deprivation predicts poor functional health in all age and sex groups. This may have implications for health policy.

No association between APOE and major depressive disorder in a community sample of 17,507 adults.

Mood-related phenotypes are commonly comorbid with, and have been implicated in the development of, neurological disorders. APOE is a major susceptibility gene for neurodegeneration. Recent evidence from case-control studies has suggested that the apoE 2 allele is associated with major depressive disorder (MDD). However, evidence from large-scale community-based studies is limited. APOE was genotyped for 17,507 men and women, aged 41-80 years, participating in the European Prospective Investigation into Cancer-Norfolk study, who had also completed a psychosocial assessment that included measures of emotional health status defined by MDD, psychological distress (as represented by the Mental Health Inventory, MHI-5), and by an assessment of neuroticism. No associations were found between APOE genotypes and measures either of past-year or lifetime MDD, or of emotional health defined according to the MHI-5 or by neuroticism. Data from this large-scale, community-based, study are not supportive of an association between either MDD or associated measures of emotional state and APOE genotype. These findings suggest that the association between APOE and MDD risk is more modest than has been previously reported.

Major depression, C-reactive protein, and incident ischemic heart disease in healthy men and women.

OBJECTIVE: To investigate how C-reactive protein (CRP) and major depressive disorder (MDD) relate to each other and to incident ischemic heart disease (IHD). Studies have shown that both depression and raised CRP concentration predict IHD and that elevated CRP is linked with increased risk of depression. METHODS: A prospective case-control study of healthy men and women, aged 45 to 79 years, was undertaken within the United Kingdom European Prospective Investigation into Cancer (EPIC)-Norfolk study. CRP concentration was measured for 726 (fatal or nonfatal) IHD cases and 1688 matched controls who completed a baseline MDD self-assessment, defined by restricted Diagnostic and Statistical Manual of Mental Disorders, 4th Edition diagnostic criteria. RESULTS: Past-year MDD was associated with increased CRP concentration levels (4.31 mg/L for participants who reported episodes of MDD in the past year versus 3.65 mg/L for those who did not; p = .003), and the odds ratio for incident IHD associated with higher CRP concentration was 2.02 (comparing the top versus bottom quartile of CRP; 95% Confidence Interval (CI) = 1.52-2.68), adjusted for cigarette smoking, diabetes, systolic blood pressure, body mass index, and cholesterol. The association between past-year MDD and IHD was independent of CRP (odds ratio = 1.55; 95% CI = 1.01-2.37, with adjustments as above, and additionally for CRP). CONCLUSIONS: Evidence from this study is supportive of an association between MDD and CRP although it suggests that CRP does not account for the association between MDD and future IHD.

Depression and ischemic heart disease mortality: evidence from the EPIC-Norfolk United Kingdom prospective cohort study.

OBJECTIVE: The authors investigated the association between major depressive disorder, including its clinical course, and mortality from ischemic heart disease. METHOD: This was a prospective cohort study of 8,261 men and 11,388 women 41-80 years of age who were free of clinical manifestations of heart disease and participated in the Norfolk, U.K., cohort of the European Prospective Investigation Into Cancer. The authors conducted a cross-sectional assessment of major depressive disorder during the period 1996-2000 and ascertained subsequent deaths from ischemic heart disease through linkage with data from the U.K. Office for National Statistics. RESULTS: As of July 31, 2006, 274 deaths from ischemic heart disease were recorded over a total follow-up of 162,974 person-years (the median follow-up period was 8.5 years). Participants who had major depression during the year preceding baseline assessment were 2.7 times more likely to die from ischemic heart disease over the follow-up period than those who did not, independently of age, sex, smoking, systolic blood pressure, cholesterol, physical activity, body mass index, diabetes, social class, heavy alcohol use, and antidepressant medication use. This association remained after exclusion of the first 6 years of follow-up data. Consideration of measures of major depression history (including recency of onset, recurrence, chronicity, and age at first onset) revealed recency of onset to be associated most strongly with ischemic heart disease mortality. CONCLUSIONS: Major depression was associated with an increased risk of ischemic heart disease mortality. The association was independent of established risk factors for ischemic heart disease and remained undiminished several years after the original assessment.

Healthy lifestyle choices: could sense of coherence aid health promotion?

BACKGROUND: A research framework based on the personal characteristic defined by a sense of coherence (SOC) focuses on the effective use of resources to maintain good health. OBJECTIVES: To test the hypothesis that individual differences in SOC are associated with healthier lifestyle choices independently of social class and education. DESIGN AND SETTING: Cross sectional. Population based cohort study recruited through 35 general practice registers. Reported dietary intakes of alcohol, fruit and vegetables, fibre, saturated fat, non-discretionary salt (sodium), and total sugars were assessed by food frequency questionnaire. Current cigarette smoking, physical inactivity, and SOC were assessed through questionnaires. PARTICIPANTS: 7,863 men and 10,424 women. Residents of Norfolk (UK). RESULTS: Compared with participants with the weakest SOC, those with the strongest were 28% less likely to be current smokers (odds ratio 0.72 (95% confidence interval (CI), 0.58 to 0.89)), 36% less likely to be physically inactive (0.64 (0.55 to 0.75)), and reportedly consumed on average 63 g/day more fruit and vegetables (95% CI, 46 to 80), and 1.2 g/day more fibre (0.8 to 1.6). These associations were independent of age, sex, social class, and education. For physical inactivity and consumption of fruit, vegetables, and fibre, these differences exceeded those observed between the extremes of social class and education. CONCLUSIONS: Individual differences in SOC are associated with healthy lifestyle choices independently of social class and education, and may therefore aid the design of future health promotion interventions.

Self-reported mental health-related quality of life and mortality in men and women in the European Prospective Investigation into Cancer (EPIC-Norfolk): a prospective population study.

OBJECTIVE: To explore the relationship between self-reported mental functional health and mortality. METHODS: Participants included 17,777 men and women aged 40 to 79 years at baseline who lived in Norfolk, UK, and had no known cardiovascular disease or cancer, and completed the anglicized Short Form 36-item questionnaire (UK SF-36) during 1996 to 2000 in the European Prospective Investigation into Cancer-Norfolk prospective population study. We examined the relationship between mental functional health derived from the mental component summary scores of the SF-36 and mortality from all causes, cardiovascular disease, cancer, and other causes during an average 6.5-year follow-up. RESULTS: There were 1065 deaths during a total of 115,550 person-years of follow-up. Impaired mental health-related quality of life was associated with increased risk of all-cause mortality in men and women. A decrease of 1 SD (10 points) in SF-36 mental component summary scores was associated with a 14% increase in all-cause mortality (hazards ratio = 1.14; 95% Confidence Interval: 1.07, 1.21) after controlling for age, gender, body mass index, systolic blood pressure, cholesterol, alcohol consumption, diabetes, smoking, social class, and physical functional health. CONCLUSION: Poor self-reported mental functional health is related to increased risk of all-cause mortality in men and women. Interpretation of this association requires further investigation.

Adaptation to social adversity is associated with stroke incidence: evidence from the EPIC-Norfolk prospective cohort study.

BACKGROUND AND PURPOSE: Laboratory-based studies have suggested that individual differences in cardiovascular reactivity and stress adaptive capacity are associated with stroke incidence. We test the hypothesis that sense of coherence (SOC), a marker of social stress adaptive capacity, is associated with incident stroke in a population-based prospective cohort study. METHODS: A total of 20,629 participants, aged 41 to 80 years, in the UK European Prospective Investigation into Cancer (EPIC)-Norfolk study, who had not previously experienced a stroke, completed assessments that included SOC and details of their experience of life events during adulthood. An index of adaptation was constructed from responses to questions concerning over 80,000 adverse life events. RESULTS: During 145,000 person-years of follow-up (mean 7.1 years), 452 participants experienced either a fatal or nonfatal stroke event. A strong (as opposed to a weak) SOC was associated with a reduced rate of stroke incidence (rate ratio 0.76; 95% CI, 0.60 to 0.96) after adjustment for age, sex, pre-existing myocardial infarction, diabetes, hypertension treatment, family history of stroke, cigarette smoking, systolic blood pressure, obesity, social class, education, hostility and depression. No sex difference in this association was observed. Measures of social adversity occurrence and impact were not associated with stroke incidence, whereas faster reported adaptation to adverse event exposure was associated with a reduced rate of stroke incidence (rate ratio 0.89; 95% CI, 0.81 to 0.98; per standard deviation change in adaptation score, adjusted for age and sex). CONCLUSIONS: Stress adaptive capacity is a potentially important candidate risk factor for stroke.