Psychological stress and cardiovascular disease: empirical demonstration of bias in a prospective observational study of Scottish men

Objectives: To examine the association between self perceived psychological stress and cardiovascular disease in a population where stress was not associated with social disadvantage. Design: Prospective observational study with follow up of 21 years and repeat screening of half the cohort 5 years from baseline. Measures included perceived psychological stress, coronary risk factors, self reported angina, and ischaemia detected by electrocardiography. Setting: 27 workplaces in Scotland. Participants: 5606 men (mean age 48 years) at first screening and 2623 men at second screening with complete data on all measures Main outcome measures: Prevalence of angina and ischaemia at baseline, odds ratio for incident angina and ischaemia at second screening, rate ratios for cause specific hospital admission, and hazard ratios for cause specific mortality. Results: Both prevalence and incidence of angina increased with increasing perceived stress (fully adjusted odds ratio for incident angina, high versus low stress 2.66, 95% confidence interval 1.61 to 4.41; P for trend <0.001). Prevalence and incidence of ischaemia showed weak trends in the opposite direction. High stress was associated with a higher rate of admissions to hospital generally and for admissions related to cardiovascular disease and psychiatric disorders (fully adjusted rate ratios for any general hospital admission 1.13, 1.01 to 1.27, cardiovascular disease 1.20, 1.00 to 1.45, and psychiatric disorders 2.34, 1.41 to 3.91). High stress was not associated with increased admission for coronary heart disease (1.00, 0.76-1.32) and showed an inverse relation with all cause mortality, mortality from cardiovascular disease, and mortality from coronary heart disease, that was attenuated by adjustment for occupational class (fully adjusted hazard ratio for all cause mortality 0.94, 0.81 to 1.11, cardiovascular mortality 0.91, 0.78 to 1.06, and mortality from coronary heart disease 0.98, 0.75 to 1.27). Conclusions: The relation between higher stress, angina, and some categories of hospital admissions probably resulted from the tendency of participants reporting higher stress to also report more symptoms. The lack of a corresponding relation with objective indices of heart disease suggests that these symptoms did not reflect physical disease. The data suggest that associations between psychosocial measures and disease outcomes reported from some other studies may be spurious

Limitations of adjustment for reporting tendency in observational studies of stress and self reported coronary heart disease

Recently, observational evidence has been suggested to show a causal association between various "psychosocial" exposures, including psychological stress, and heart disease. Much of this evidence derives from studies in which a self reported psychosocial exposure is related to an outcome dependent on the subjective experience of coronary heart disease (CHD) symptoms. Such outcomes may be measured using standard symptom questionnaires (like the Rose angina schedule). Alternatively they may use diagnoses of disease from medical records, which depend on an individual perceiving symptoms and reporting them to a health worker. In these situations, reporting bias may generate spurious exposure-outcome associations. For example if people who perceive and report their life as most stressful also over-report symptoms of cardiovascular disease then an artefactual association between stress and heart disease will result

The Strauss conjecture on asymptotically flat space-times

By assuming a certain localized energy estimate, we prove the existence portion of the Strauss conjecture on asymptotically flat manifolds, possibly exterior to a compact domain, when the spatial dimension is 3 or 4. In particular, this result applies to the 3 and 4-dimensional Schwarzschild and Kerr (with small angular momentum) black hole backgrounds, long range asymptotically Euclidean spaces, and small time-dependent asymptotically flat perturbations of Minkowski space-time. We also permit lower order perturbations of the wave operator. The key estimates are a class of weighted Strichartz estimates, which are used near infinity where the metrics can be viewed as small perturbations of the Minkowski metric, and the assumed localized energy estimate, which is used in the remaining compact set.Comment: Final version, to appear in SIAM Journal on Mathematical Analysis. 17 page

Shorter juvenile telomere length is associated with higher survival to spawning in migratory Atlantic salmon

The risk of mortality associated with a long-distance migration will depend on an animal's physiological state, as well as the prevailing ecological conditions. Here we assess whether juvenile telomere length, which in endotherms has been shown to be a biomarker of physiological state and expected lifespan, predicts whether wild Atlantic salmon Salmo salar successfully complete their marine migration. Over 1800 juvenile fish were trapped, measured, PIT-tagged and a tissue biopsy taken when migrating as juveniles down-river towards the sea. Survivors of the marine phase of the life cycle were then re-trapped and re-sampled when returning to the river to spawn as sexually mature adults, 1.5-2.5 years later. Most individuals experienced a reduction in telomere length during the marine migratory phase of their life cycle. While the relative rate of telomere loss was greater in males than females, telomere loss was unrelated to growth at sea. Contrary to expectations, salmon that had the shortest telomeres at the time of the outward migration had the greatest probability of surviving through to the return migration. This effect, independent of body size, may indicate a trade-off between investment in readiness for marine life (which favours high glucocorticoid levels, known to increase telomere attrition in other vertebrate species) and investment in telomere maintenance. Survival was also significantly influenced by the seasonal timing of outward migration, with the fish migrating downstream earliest in the spring having the highest probability of return. This study reveals that telomere length is associated with survival, although in ways that contrast with patterns seen in endotherms. This illustrates that while telomeres may be universally important for chromosome protection, the potential for telomere dynamics to predict performance may vary across taxa

Links between parental life histories of wild salmon and the telomere lengths of their offspring

The importance of parental contributions to offspring development and subsequent performance is self-evident at a genomic level; however, parents can also affect offspring fitness by indirect genetic and environmental routes. The life history strategy that an individual adopts will be influenced by both genes and environment; and this may have important consequences for offspring. Recent research has linked telomere dynamics (i.e. telomere length and loss) in early life to future viability and longevity. Moreover, a number of studies have reported a heritable component to telomere length across a range of vertebrates, though the effects of other parental contribution pathways have been far less studied. By using wild Atlantic salmon with different parental life histories in an experimental split-brood IVF mating design and rearing the resulting families under standardised conditions, we show that there can be significant links between parental life history and offspring telomere length (studied at the embryo and fry stage). Maternal life history traits, in particular egg size, were most strongly related to offspring telomere length at the embryonic stage, but then became weaker through development. In contrast, paternal life history traits, such as the father's growth rate in early life, had a greater association in the later stages of offspring development. However, offspring telomere length was not significantly related to either maternal or paternal age at reproduction, nor to paternal sperm telomere length. This study demonstrates both the complexity and the importance of parental factors that can influence telomere length in early life