Does a Mediterranean diet including wine improve long-term outcomes in high CVD risk?

In the Spanish PREDIMED trial, a Mediterranean diet including moderate wine consumption was associated with reduced risks of MACE and all-cause mortality in patients with high CVD risk, compared with poor diet compliance. However, these results could not be replicated in the younger and healthier SUN cohort.

This summary is based on the publication of Martínez-González MA, Bes-Rastrollo M, Sayon-Orea C, et al. - Wine consumption, Mediterranean diet, and cardiovascular risk in two Spanish cohorts. Eur Heart J. 2026 Feb 11:ehaf1081 [Online ahead of print]. doi: 10.1093/eurheartj/ehaf1081

Introduction and methods

Background

The beneficial effects of following a Mediterranean diet on CVD risk are well established [1]. For example, the intention-to-treat analysis of the PREDIMED (“PREvencion con DIeta MEDiterránea”) trial showed that patients with high CVD risk but no CVD who were randomized to a Mediterranean diet had a 30% lower risk of MACE over 4.8 years compared with those assigned to a low-fat control diet [2]. Interestingly, per-protocol analyses indicated the benefit increased with higher adherence [2]. While moderate consumption of wine is a key component of the Mediterranean diet, the role of alcohol, including wine, remains controversial [3-6].

Aim of the study

The authors examined the associations between adherence to the Mediterranean diet with or without moderate wine consumption and both MACE and all-cause mortality in PREDIMED participants and a younger cohort with longer follow-up (SUN cohort).

Methods

The PREDIMED trial was a multicenter RCT conducted in Spain in which 4282 women (aged 60–80 years) and 3165 men (aged 55–80 years) with high CVD risk (i.e., T2D or ≥3 major risk factors, such as smoking, hypertension, elevated LDL-c levels) but no CVD at enrollment were included. Participants were randomized in a 1:1:1 ratio to a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a low-fat control diet. Adherence to the Mediterranean diet was assessed annually using the validated 14-item Mediterranean Diet Adherence Screener, which includes a question on wine consumption. Moderate wine consumption (≥7 glasses/week) was scored as 1 wine point. Median wine consumption was 6.7 mL/day (IQR: 0–92.9).

To complement the PREDIMED trial results, data were extracted from the SUN (Seguimiento University of Navarra) study, a prospective, dynamic cohort study among Spanish university graduates that was initiated in 1999 and is still ongoing [7]. The present analysis included 10,554 participants aged ≥40 years (during the first 5 years of follow-up), who were followed up for 22 years. Their median wine consumption was 13.4 mL/day (IQR: 0–49.6).

Outcomes

The MACE endpoint was as a composite outcome of MI, stroke, or CV death. In addition, the occurrence of all-cause mortality was assessed. In the PREDIMED cohort, MACE incidence was recorded during the trial (median follow-up duration: 4.8 years; IQR: 2.8–5.8), while the incidence of all-cause mortality was tracked during the trial and the extended follow-up period (mean duration: 13.4 years).

Main results

PREDIMED cohort

• In multivariable-adjusted analysis, PREDIMED participants who complied with the Mediterranean diet but did not drink a moderate weekly amount of wine (i.e., 0 wine points) showed a similar MACE risk as the reference group of poor compliers with no wine point (adjusted HR: 0.84; 95%CI: 0.61–1.15).
• Only Mediterranean diet compliers who scored 1 wine point had a lower MACE risk compared with the reference group (adjusted HR: 0.55; 95%CI: 0.36–0.83).
• During 17-year follow-up, reduced risks of all-cause mortality compared with the reference group were observed for compliers with the Mediterranean diet but with no wine point (adjusted HR: 0.77; 95%CI: 0.68–0.87) and Mediterranean diet compliers who did drink ≥7 glasses of wine per week (adjusted HR: 0.67; 95%CI: 0.57–0.78).
• Likelihood ratio tests did not indicate the presence of supra-multiplicative interaction between Mediterranean diet compliance and the wine point for the risks of MACE and all-cause mortality (both P>0.05; 1 df).
• Exploratory dose–response analyses did not show a reduced mortality risk for death in PREDIMED participants who drank ≥3 glasses of wine per day versus abstention (adjusted HR: 0.81; 95%CI: 0.57–1.13).

SUN cohort

• In the SUN cohort, good compliance with the Mediterranean diet (excluding wine) did not alter MACE risk compared with overall poor compliance (adjusted HR: 0.77; 95%CI: 0.49–1.22). The same was true for good compliance in combination with moderate wine consumption (adjusted HR: 1.45; 95%CI: 0.74–2.83).
• For all-cause mortality, a nonsignificant trend toward a lower risk was observed in participants with both good Mediterranean diet compliance and 1 wine point compared with the reference group (adjusted HR: 0.54; 95%CI: 0.28–1.04).
• There was no multiplicative interaction between Mediterranean diet compliance and the wine point in relation to all-cause mortality risk (P=0.08).

Pooled cohorts

• In a pooled analysis of the PREDIMED and SUN cohorts, the combination of good Mediterranean diet compliance and moderate wine consumption was not associated with a lower MACE risk compared with the reference group (adjusted HR: 0.72; 95%CI: 0.51–1.03).
• However, a reduced all-cause mortality risk was observed in the overall good compliers compared with the reference group (adjusted HR: 0.66; 95%CI: 0.57–0.77).

Conclusion

In this analysis of the Spanish PREDIMED trial including an extended follow-up, good compliance with the Mediterranean diet including moderate wine consumption (i.e., ≥7 glasses/week) was associated with reduced risks of MACE and all-cause mortality compared with overall poor compliance among patients with high CVD risk but no CVD at enrollment. However, these results could not be replicated in the younger and healthier SUN cohort.

Find this article online at Eur Heart J.

References

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