Vitamin E supplement use and the incidence of cardiovascular disease and all-cause mortality in the Framingham Heart Study: Does the underlying health status play a role?☆
Introduction
Several observational studies published in the 1990s suggested that higher vitamin E intake is associated with a significantly lower risk of cardiovascular disease (CVD) [1], [2], [3], [4]. The Nurses Health Study and the Health Professionals Follow-up Study for example showed that higher vitamin E intake from supplements for more than 2 years significantly reduced the relative risk for coronary heart disease (CHD) [1], [2]. Results from these studies were the catalyst for randomized controlled vitamin E intervention trials. The majority of these intervention trials, however, did not support the hypothesis derived from the observational studies [5], [6]. Recently, unexpectedly, two meta-analyses of vitamin E intervention trials of CVD, cancer, and other diseases, reported an increased relative risk of all-cause mortality. Further, two individual vitamin E intervention trials reported increased risk of heart failure [7], [8], [9], [10].
Previous observational studies of vitamin E supplement use and CVD focused on primary prevention and most excluded individuals with CVD at baseline, whereas the majority of the vitamin E intervention trials focused on secondary prevention and included individuals at high risk of CVD (e.g., patients with diabetes) or with pre-existing CVD. The meta-analyses, which are based on these intervention trials, therefore also mainly included individuals with pre-existing diseases.
Based on this major difference in design of the observational and intervention studies, we hypothesized that health effects of vitamin E supplement use vary, based on the underlying health status of individuals. Thus, the purpose of our study was to investigate both, primary and secondary prevention within an observational study. Specifically, we hypothesized that among individuals free of CVD we will observe a lower risk of CVD and all-cause mortality with vitamin E supplement use, and among individuals with pre-existing CVD, we will observe either no effect or harmful health effects.
To examine our hypothesis, we investigated the association between vitamin E supplement use and the risk of CVD and all-cause mortality in 4270 participants of the Framingham Heart Study, stratifying our analyses by presence versus absence of prevalent CVD. In secondary analyses, we investigated the association between the vitamin E supplement dose and duration of use and the risk of CVD and all-cause mortality.
The single entity vitamin E supplement use is from here on described as “vitamin E supplement use” and does not include vitamin E from other sources such as multivitamin supplements or dietary vitamin E intake.
Section snippets
Study sample
The Framingham Heart Study, a prospective, population-based study on risk factors for CVD, began in 1948 enrolling 5209 men and women [11]. Participants in the original cohort are examined every 2 years. Details of the study design and selection criteria for the original Framingham Heart Study have been described elsewhere [11]. The Framingham Offspring Study began in 1971 with the recruitment of 5124 men and women who were offspring and spouses of offspring of the above mentioned original
Results
By the end of the 10-year follow-up period, 756 of the 4270 participants experienced a CVD event (17.7%) and 611 participants had died of any cause (14.3%). In the “all participants” group, for CVD incidence and ACM, there were 79 (17%) and 67 (15%) cases in the vitamin E supplement group versus 677 (18%) and 544 (14%) in the non-vitamin E supplement group, respectively.
Discussion
We investigated the relations between supplemental vitamin E intake and risk of cardiovascular disease and all-cause mortality in the Framingham Heart Study, a large community-based observational study. Observational studies on vitamin E have generally investigated primary prevention, whereas intervention trials mainly focused on secondary prevention. The purpose of our study was to investigate both, primary and secondary prevention within an observational study, a novel systematic approach
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This work was supported by the following grants: NHLBI Contract NO1-HC-25195; 2 K 24 HL 04334 (for R.S.V.); NIH/NIDDK DK07651-17 and AHA 0735131N (for M.D.); this material is based upon work supported by the U.S. Department of Agriculture, under agreement No. 58-1950-4-401. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture.