Long-term impact of mediterranean diet on cardiovascular disease prevention: A systematic review and meta-analysis of randomized controlled trials

Background: Dietary modification plays a pivotal role in the prevention of cardiovascular disease (CVD), with particular emphasis on the potential benefits associated with adopting a Mediterranean diet (MedDiet). Numerous observational studies have explored the impact of the MedDiet on CVD prevention, addressing both primary and secondary prevention. However, a substantial portion of the primary evidence comes from specific Randomized Controlled Trials (RCTs), such as the Lyon Diet Heart Study, the Indo-Mediterranean Diet Heart Study, the PREDIMED Study, and the recent CORDIOPREV Study. To provide a comprehensive assessment of the long-term clinical effects, we conducted a meta -analysis, systematically synthesizing findings from RCTs to better understand the preventive impact of MedDiet on cardiovascular health. Methods: We searched for RCTs exploring the efficacy of MedDiet on CVD prevention from inception until January 2024, utilizing databases such as MEDLINE (via PubMed), Google Scholar, the Cochrane Library, ClinicalTrials.gov, and the ScienceDirect portal. Statistical analysis used RevMan 5.4 with a random -effects model, presenting dichotomous outcomes as odds ratios (OR) with a 95 % confidence interval (CI) and assessing heterogeneity using the I 2 test. Results: Our analysis incorporated four RCTs involving a total of 10,054 participants, with an average age of 57 years and a mean follow-up duration ranging from 2 to 7 years. In our pooled analysis, the composite endpoint of major adverse cardiovascular events (MACE) demonstrated a statistically significant reduction in incidence in participants on MedDiet versus control diet with an OR of 0.52 (95 % CI: 0.32 to 0.84, p = 0.008; I 2 = 87 %). Additionally, our study revealed a notable decrease in the incidence of cardiovascular events, both myocardial infarction (MI) and stroke in the the MedDiet group, with an OR of 0.62 (95 % CI: 0.41 to 0.92, p = 0.02; I 2 = 56 %) and 0.63 (95 % CI: 0.48 to 0.87, p = 0.002; I 2 = 0 %), respectively. However, no statistically significant change in the rate of revascularization was observed, with an OR of 0.74 (95 % CI: 0.30 to 1.27, p = 0.06; I 2 = 16 %). Concerning mortality rates, MedDiet significantly reduced the risk of cardiovascular death with an OR of 0.54 (95 % CI: 0.31 to 0.94, p = 0.03; I 2 = 55 %), while no significant change was noted in all -cause mortality, with an OR of 0.77 (95 % CI: 0.51 to 1.15, p = 0.20; I 2 = 58 %). Conclusion: MedDiet serves as an effective intervention for both primary and secondary prevention of CVD, demonstrating a substantial and long-term impact in reducing the incidence of MACE, MI, stroke, and cardiovascular -related mortality while showing no observed effect on allcause mortality. Nevertheless, it is essential to acknowledge the current limitations in available clinical trial evidence, emphasizing the need for additional trials to substantiate and strengthen these findings.