A prospective study evaluates the relationship between regular antioxidant supplement use (vitamins C and E) and the risk of stroke in healthy and physically active men age 40-60. The study compares the risk of stroke among men who consumed antioxidant supplements for ≥5 years and among men who consumed antioxidant supplements for

Question

A prospective study evaluates the relationship between regular antioxidant supplement use (vitamins C and E) and the risk of stroke in healthy and physically active men age 40-60.  The study compares the risk of stroke among men who consumed antioxidant supplements for ≥5 years and among men who consumed antioxidant supplements for <5 years, as compared to a reference group of men who never consumed antioxidant supplements.  According to the study results, men who consumed antioxidant supplements for <5 years and men who consumed antioxidant supplements for ≥5 years have stroke relative risks of 0.95 (p = 0.45) and 0.75 (p < 0.01), respectively, when compared to the reference group.  The results of the study were adjusted to account for baseline differences related to healthy behaviors and overall health.  Which of the following factors most likely explains why the relative risk of stroke is lower with longer antioxidant use?

Quizplus · Accepted Answer

Antioxidant use for ≥5 years was associated with a statistically significant (p < 0.01) decreased risk of stroke (relative risk [RR] = 0.75 <1). By contrast, antioxidant use for <5 years demonstrated a nonstatistically significant (p > 0.05) smaller reduction in risk (RR = 0.95); in other words, antioxidant use for <5 years seems to have no benefit on stroke risk reduction. This discrepancy can be explained if reduction in stroke risk is associated with the duration of exposure to antioxidant supplementation; in other words, a minimum cumulative exposure to antioxidants may be necessary for the exposure to have a significant effect on stroke risk. This concept of accumulation effect can apply to both risk factors and risk reducers. The effect of exposure to risk factors may depend on the duration and intensity of the exposure; long-term exposure may be necessary well before an effect on the disease process is clinically evident (eg, lung cancer developing after decades of smoking exposure). Similarly, exposure to certain risk reducers must occur continuously over extended periods before disease outcome is affected. In this case, ≥5 years of continuous antioxidant use (risk reducer) were required to reveal their protective effect on stroke. (Choice B) Lead time is the time between the initial detection of a disease and a specific outcome or measured endpoint. Lead-time bias can occur when a test detects or diagnoses the disease at an earlier stage than another test without impacting the natural history of the disease. A study comparing disease survival times may then erroneously conclude that using the earlier-detection test prolongs survival, when in actuality the increased survival time is due solely to earlier detection of the disease. (Choice C) Observer bias occurs when an observer misclassifies data due to individual differences in interpretation or preconceived expectations regarding a study. It can be reduced by performing a double-blind study (ie, both observers and participants unaware of randomized parameters) and by having multiple observers encode and verify the recorded data. (Choice D) Diseases with a very low incidence rate in the population will also have a very low prevalence. According to the rare disease assumption, the odds ratio approximates RR when disease prevalence is low (eg, <10%). (Choice E) Selection bias can occur with inappropriate (ie, nonrandom) selection methods or through selective attrition of the study participants. Although selection bias is a possible limitation of the study (eg, individuals who take vitamins daily may be more likely to be already healthy), the fact that the study was limited to healthy, physically active men and that it adjusted for baseline differences should considerably reduce the effect of this potential bias. Educational objective: The concept of accumulation effect can be applied to disease pathogenesis and exposure to risk modifiers. Cumulative exposure to a risk factor or risk reducer must sometimes occur for prolonged periods before a clinically significant effect is detected.

A Prospective Study Evaluates the Relationship Between Regular Antioxidant Supplement