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      Triggering of Sudden Death from Cardiac Causes by Vigorous Exertion

      , , , , ,
      New England Journal of Medicine
      Massachusetts Medical Society

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          Abstract

          Retrospective and cross-sectional data suggest that vigorous exertion can trigger cardiac arrest or sudden death and that habitual exercise may diminish this risk. However, the role of physical activity in precipitating or preventing sudden death has not been assessed prospectively in a large number of subjects. We used a prospective, nested case-crossover design within the Physicians' Health Study to compare the risk of sudden death during and up to 30 minutes after an episode of vigorous exertion with that during periods of lighter exertion or none. We then evaluated whether habitual vigorous exercise modified the risk of sudden death that was associated with vigorous exertion. In addition, the relation of vigorous exercise to the overall risk of sudden death and nonsudden death from coronary heart disease was assessed. During 12 years of follow-up, 122 sudden deaths were confirmed among the 21,481 male physicians who were initially free of self-reported cardiovascular disease and who provided information on their habitual level of exercise at base line. The relative risk of-sudden death during and up to 30 minutes after vigorous exertion was 16.9 (95 percent confidence interval, 10.5 to 27.0; P<0.001). However, the absolute risk of sudden death during any particular episode of vigorous exertion was extremely low (1 sudden death per 1.51 million episodes of exertion). Habitual vigorous exercise attenuated the relative risk of sudden death that was associated with an episode of vigorous exertion (P value for trend=0.006). The base-line level of exercise was not associated with the overall risk of subsequent sudden death. These prospective data from a study of U.S. male physicians suggest that habitual vigorous exercise diminishes the risk of sudden death during vigorous exertion.

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          Most cited references36

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          Final report on the aspirin component of the ongoing Physicians' Health Study. Steering Committee of the Physicians' Health Study Research Group.

          The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial designed to determine whether low-dose aspirin (325 mg every other day) decreases cardiovascular mortality and whether beta carotene reduces the incidence of cancer. The aspirin component was terminated earlier than scheduled, and the preliminary findings were published. We now present detailed analyses of the cardiovascular component for 22,071 participants, at an average follow-up time of 60.2 months. There was a 44 percent reduction in the risk of myocardial infarction (relative risk, 0.56; 95 percent confidence interval, 0.45 to 0.70; P less than 0.00001) in the aspirin group (254.8 per 100,000 per year as compared with 439.7 in the placebo group). A slightly increased risk of stroke among those taking aspirin was not statistically significant; this trend was observed primarily in the subgroup with hemorrhagic stroke (relative risk, 2.14; 95 percent confidence interval, 0.96 to 4.77; P = 0.06). No reduction in mortality from all cardiovascular causes was associated with aspirin (relative risk, 0.96; 95 percent confidence interval, 0.60 to 1.54). Further analyses showed that the reduction in the risk of myocardial infarction was apparent only among those who were 50 years of age and older. The benefit was present at all levels of cholesterol, but appeared greatest at low levels. The relative risk of ulcer in the aspirin group was 1.22 (169 in the aspirin group as compared with 138 in the placebo group; 95 percent confidence interval, 0.98 to 1.53; P = 0.08), and the relative risk of requiring a blood transfusion was 1.71. This trial of aspirin for the primary prevention of cardiovascular disease demonstrates a conclusive reduction in the risk of myocardial infarction, but the evidence concerning stroke and total cardiovascular deaths remains inconclusive because of the inadequate numbers of physicians with these end points.
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            The case-crossover design: a method for studying transient effects on the risk of acute events.

            M Maclure (1991)
            A case-control design involving only cases may be used when brief exposure causes a transient change in risk of a rare acute-onset disease. The design resembles a retrospective nonrandomized crossover study but differs in having only a sample of the base population-time. The average incidence rate ratio for a hypothesized effect period following the exposure is estimable using the Mantel-Haenszel estimator. The duration of the effect period is assumed to be that which maximizes the rate ratio estimate. Self-matching of cases eliminates the threat of control-selection bias and increases efficiency. Pilot data from a study of myocardial infarction onset illustrate the control of within-individual confounding due to temporal association of exposures.
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              Estimation of a common effect parameter from sparse follow-up data.

              Breslow (1981, Biometrika 68, 73-84) has shown that the Mantel-Haenszel odds ratio is a consistent estimator of a common odds ratio in sparse stratifications. For cohort studies, however, estimation of a common risk ratio or risk difference can be of greater interest. Under a binomial sparse-data model, the Mantel-Haenszel risk ratio and risk difference estimators are consistent in sparse stratifications, while the maximum likelihood and weighted least squares estimators are biased. Under Poisson sparse-data models, the Mantel-Haenszel and maximum likelihood rate ratio estimators have equal asymptotic variances under the null hypothesis and are consistent, while the weighted least squares estimators are again biased; similarly, of the common rate difference estimators the weighted least squares estimators are biased, while the estimator employing "Mantel-Haenszel" weights is consistent in sparse data. Variance estimators that are consistent in both sparse data and large strata can be derived for all the Mantel-Haenszel estimators.
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                Author and article information

                Journal
                New England Journal of Medicine
                N Engl J Med
                Massachusetts Medical Society
                0028-4793
                1533-4406
                November 09 2000
                November 09 2000
                : 343
                : 19
                : 1355-1361
                Article
                10.1056/NEJM200011093431902
                11070099
                ff4ef243-c545-443a-a845-7c7992c8940c
                © 2000
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