Extra-Virgin Olive Oil and Additional Cardiovascular Outcomes in the PREDIMED Trial: An Outcome-Wide Perspective.

Background And Aims: Olive oil, increasingly consumed in the U.S., has been inversely associated with cardiovascular disease (CVD) risk. However, previous studies did not assess a broad spectrum of CVD outcomes, incorporated repeated annual dietary assessments, or distinguished between polyphenol-rich EVOO and common olive oil (COO), which lacks these compounds.

Methods: We assessed 7,102 high-risk participants from the PREDIMED trial (57.5% women; aged 55-80 years), all free of CVD at baseline. Olive oil consumption was assessed annually, and cumulative average intakes of EVOO and COO were calculated. The primary outcome was a composite of myocardial infarction, stroke, peripheral arterial disease, heart failure, atrial fibrillation, or cardiovascular death, whichever occurred first. Individual outcomes were also evaluated. Time-dependent Cox models were adjusted for major confounders, including trial intervention arm.

Results: Over a median follow-up of 4.7 years, 621 participants experienced at least one CVD event. Participants in the highest tertile of cumulative EVOO intake (mean: 49.2 g/day) had a 25% lower risk of the composite outcome (HR: 0.75; 95% CI: 0.60 to 0.94), with significant reductions in several individual CVD outcomes. In the decile analysis, the highest (mean: 60.9 g/day) versus lowest decile had a 48% lower risk (HR: 0.52; 95% CI: 0.35 to 0.79). COO consumption was not significantly associated with CVD risk when mutually adjusted for EVOO (HR: 0.93; 95% CI: 0.87 to 1.00).

Conclusions: High consumption of EVOO is associated with a substantial reduction in the risk of an outcome-wide composite of CVD events among high-risk individuals. In contrast, COO, which lacks polyphenols, showed weaker associations, highlighting the importance of differentiating olive oil types in CVD prevention strategies.

Trial Registration: This trial was registered in the ISRCTN registry (ISRCTN 35739639): https://www.isrctn.com/ISRCTN35739639.