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Cardiovascular

Do people who feel more tired die sooner?

Basu N, Yang X, Luben RN, et al. · BMC medicine · 2016

Open access · cc by · source: Europe PMC

Middle-aged and older adults who reported the most fatigue were more likely to die over the next 16 years, mainly from heart and circulatory disease, even after accounting for many other health factors.

Study at a glance

Design
Cohort — Prospective population cohort: fatigue measured once with the four-item SF-36 vitality scale, then deaths tracked by national death-certificate linkage; Cox models compared highest vs lowest fatigue quartile with stepwise adjustment for confounders and candidate mechanisms.
N
N=18101 · 18,101 of the 25,639 baseline attendees who had complete SF-36 vitality data; 4397 deaths occurred during follow-up. Models excluding baseline cardiovascular disease or cancer used a smaller subset.
Population
Middle-aged and older adults (40-79 at baseline) from general-practice registers in Norfolk, UK, recruited 1993-1997.
Outcome
All-cause mortality, plus cardiovascular and cancer mortality, by quartile of self-reported fatigue.

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Key findings

There were 4397 deaths over an average of 16.6 years. After excluding people with prior heart attack, stroke or cancer and adjusting for confounders, the most fatigued quarter had about a 40% higher risk of death than the least fatigued (hazard ratio 1.40); adding thyroid function reduced this to 1.26, while CRP barely changed it. The extra risk was concentrated in cardiovascular deaths (adjusted hazard ratio 1.45), with no clear increase in cancer deaths, and an excess all-cause risk remained even in the fully adjusted model (hazard ratio 1.24).

Methodology

The researchers used the EPIC-Norfolk cohort, which recruited adults aged 40 to 79 from GP lists in eastern England between 1993 and 1997. Around 18 months after baseline, 18,101 participants answered four questions about energy and tiredness, and they were split into quarters from least to most fatigued. Deaths were followed through national records until 2013, and the team added confounders (such as age, smoking, depression and physical activity) and possible biological mechanisms (thyroid hormone, C-reactive protein, haemoglobin) to the models one at a time.

Limitations

This is observational, so it shows fatigue marks higher risk, not that fatigue itself causes death or that treating tiredness would extend life. Fatigue and every covariate were measured only once, and only 40-45% of invited people joined the cohort, with about 30% of them missing the fatigue questions. 'High fatigue' here simply means the most tired quarter of a general population over one month, so the results cannot be applied to chronic fatigue syndrome, where symptom duration was not measured. The labelling of confounders versus mechanisms was decided by a simple statistical rule, and after full adjustment the cardiovascular-death estimate was no longer statistically clear.

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