Higher DHA levels reduce protective impact of EPA on major adverse CV events
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Higher levels of eicosapentaenoic acid were associated with reductions in major adverse events, in particular improved survival, according to a presentation at the American College of Cardiology Scientific Session.
The researchers also found that higher levels of docosahexaenoic acid (DHA), when adjusted for eicosapentaenoic acid (EPA) and comorbidities, increased risk for major adverse CV events, and when EPA and DHA are combined, higher DHA levels counteract the benefit of EPA.
Researchers analyzed 987 patients who underwent angiography and were enrolled in the INSPIRE registry (mean age, 62 years; 57% men; 41% with obesity, 42% with severe CAD).
The primary endpoint of major adverse CV events, defined as all-cause death, MI, stroke and HF hospitalization at 10 years, occurred in 31.5% of patients, Viet T. Le, MPAS, PA, researcher and cardiovascular physician assistant at the Intermountain Heart Institute, Salt Lake City, said during a presentation.
In the unadjusted EPA-only model, patients in the highest quartile of EPA level were less likely to have a major adverse CV event compared with others (HR vs. lowest quartile = 0.48; P < .0001; HR vs. middle quartiles = 0.71; P = .02), driven by reduced risk for death (P < .0001), according to the researchers.
“As we adjusted for DHA and DHA plus those comorbidities, CAD, [chronic obstructive pulmonary disease] and HF, we see that higher EPA is much more protective, and when adjusted, dose dependence becomes even more apparent. Quartile 4 being the most protected, even when adjusted for DHA and DHA and comorbidities,” Le said during the presentation.
“When we look at unadjusted DHA, DHA alone was not associated with major adverse CV events either way, whether it was less likely or more likely and may suggest inert benefits. And DHA adjusted for EPA and EPA with comorbidities, when we adjusted for EPA higher DHA, increases risk of major adverse CV events, both adjusted for comorbidities and adjusted for EPA alone,” Le said.
Those with EPA/DHA ratio greater than 1 had a 27% rate of 10-year major adverse CV events compared with 37% for those with a ratio of 1 or less (adjusted HR = 0.69; 95% CI, 0.55-0.86; P = .0012), the researchers found.
“When given in combination, the net impact of higher doses of EPA is blunted by the negative effect of DHA,” Le said.
Le said the findings might help explain the discrepancies in clinical trial results, and they raise further concerns regarding the use of combination EPA/DHA preparations for CV risk reduction.
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Le VT, et al. Highlighted Original Research: Prevention and Health Promotion and the Year in Review. Presented at: American College of Cardiology Scientific Session; May 15-17, 2021 (virtual meeting).
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