EPA and DHA in blood cell membranes from acute coronary syndrome patients and controls
Introduction
The omega-3 fatty acids (FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are currently recommended by the American Heart Association for reducing the risk for coronary heart disease (CHD) [1]. Multiple lines of evidence (epidemiological, mechanistic, and clinical trial) support the view that these FAs reduce risk for death from CHD [2]. But, the association between these FA and the risk for non-fatal cardiac events (i.e., myocardial infarction, unstable angina) remains poorly defined. Although in two cohort studies of only men [3], [4], there was no relationship between fish intake (a surrogate for EPA + DHA intake) and myocardial infarction risk, higher fish intake was significantly associated with reduced risk for myocardial infarction in women [5]. In randomized controlled trials with oily fish [6] and with EPA + DHA supplements [7], significant reductions in death were observed, but the risk for myocardial infarction was not significantly impacted by these interventions. Other studies have also produced conflicting findings [8], [9], [10], [11]. Thus despite extensive inquiry about the association between EPA and DHA and non-fatal coronary events, significant uncertainty remains.
To help clarify the association between EPA + DHA and non-fatal coronary events, we designed a case-control study to determine if the level of EPA + DHA (expressed as a percent of total FA in blood cell membranes) is reduced in patients admitted to the hospital with an acute coronary syndrome [ACS; acute myocardial infarction or unstable angina] compared to controls. In addition, we also sought to determine the extent to which this relationship was independent of other potential risk factors associated with ACS.
Section snippets
Selection of cases
Cases were drawn from a prospective registry of patients with a confirmed diagnosis of either acute myocardial infarction [12] or unstable angina [13] as previously described [14]. In brief, all consecutive patients admitted to two hospitals associated with the University of Missouri-Kansas City School of Medicine (Truman Medical Center and Saint Luke's Hospital) were prospectively screened for an ACS. Patients presenting with suggestive cardiac symptoms, diagnostic electrocardiogram (EKG)
Case-control differences
Because of prospective matching, the age, sex, and race distributions of the cases and the controls were virtually identical (Table 1). Cases had a greater proportion of diabetic subjects, current smokers and individuals with no college education. Cases were also more likely to be taking aspirin and/or statins, and to have a family history of premature CHD. Serum total, LDL and HDL cholesterol were all lower in cases whereas triglycerides were higher. Cases were also more likely to have a
Discussion
Although there is a growing consensus favoring a mortality benefit for increased long-chain omega-3 FA intake [2], [17], there is considerably less agreement regarding the association of EPA + DHA with a beneficial effect on non-fatal cardiovascular events. In the present case-control study we provide evidence that individuals with lower EPA + DHA in red blood cell membranes are more likely to be ACS cases than those with higher levels. By measuring this biomarker, an indicator of patients’
Conclusion
A reduced blood cell membrane EPA + DHA content is independently associated with increased odds of ACS case status. The prognostic and/or diagnostic value of this marker, as it relates to ACS, and the extent to which modification of the EPA + DHA content (by diet or supplementation) will alter risk for ACS are both currently unknown and warrant further study.
Acknowledgements
The authors wish to express their appreciation to Karen Nugent, Amy Shipman and Mary Baston for their important contributions in data collection and sample processing, and to Philip Jones for statistical advice. Finally, we are indebted to Dr. James Crockett and the Saint Luke's Hospital Foundation for providing funding for this study.
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