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Dyspnea has not been widely used as a proxy measure of fitness. Because dyspnea score is simple to obtain, it could be a screening tool for identifying individuals with low fitness and increased mortality risk. The aim was to study how baseline dyspnea, and changes in it, predicts all-cause mortality.The prospective Finnish Twin Cohort includes all same-sex twin pairs born in Finland before 1958. Dyspnea was measured with a four-question modified Medical Research Council scale. The level and change in dyspnea between 1975 and 1981 were used as the baseline predictors. Altogether, 21,379 twin individuals (8672 complete twin pairs) had answered dyspnea questions in 1975 and 1981. Cox proportional hazards model was used for mortality analysis starting from the 1981 response date until December 31, 2010.Increased mortality was observed among individuals with persistent dyspnea (dyspnea in 1975 and 1981); full covariate adjusted HR of death was 1.41 (95% confidence interval, 1.31–1.52), whereas the HR for dyspnea developers and those with dyspnea remission were 1.16 (1.05–1.25) and 1.07 (0.97–1.19), respectively, compared with asymptomatic individuals. Among healthy subjects at 1981 baseline, the corresponding HR values were 1.34 (1.16–1.54), 1.15 (0.97–1.37), and 1.05 (0.89–1.23). Within-pair analyses of death discordant pairs showed a fully adjusted HR for persistent dyspnea of 1.47 (1.23–1.77) for all twin pairs and 2.64 (1.21–5.74) for healthy monozygotic pairs.Persistent dyspnea predicts increased mortality during a 28-yr follow-up even among individuals without clinically overt disease known to associate with dyspnea. The dyspnea score, which can be easily obtained and correlates with fitness outcomes, could be a screening tool for identifying unfit individuals at an increased mortality risk.