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Low-Fat vs. Mediterranean Diet for Secondary Prevention

A study of stable coronary heart disease patients comparing the Mediterranean diet to a low-fat diet over a seven-year follow-up showed the Mediterranean diet was superior at preventing major cardiovascular events.

By Michael H. Crawford, MD

Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco

SYNOPSIS: A study of stable coronary heart disease patients comparing the Mediterranean diet to a low-fat diet over a seven-year follow-up showed the Mediterranean diet was superior at preventing major cardiovascular events.

SOURCE: Delgado-Lista J, Alcala-Diaz JF, Torres-Peña JD, et al. Long-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): A randomized controlled trial. Lancet 2022;399:1876-1885.

Low-fat and Mediterranean diets have been shown to be effective for the primary prevention of cardiovascular disease (CVD), but there is little information on their effectiveness for secondary prevention. Researchers at a single center in Spain studied patients with established coronary heart disease (CHD) ages 20-75 years and who were free of vascular events for at least six months.

The authors excluded patients unable to follow dietary instructions and those with other severe illnesses with a shorter expected survival than the duration of the diet study. Patients were randomized to a low-fat (LF) or Mediterranean (Med) diet. The authors were blinded, and patients were instructed not to discuss their diet with the physicians conducting the study. Patients saw dietitians separately, who instructed them in their assigned diets. The Med diet consisted of ≥ 35% of calories as fat, 15% protein, and 50% carbohydrates. The LF diet was < 30% fat, 15% protein, and 55% complex carbohydrates. Both diets limited cholesterol consumption to < 300 mg/day, and physical activity was not promoted. Intense follow-up and dietary coaching were provided to all subjects. The primary outcome was a composite of major CVD events for seven years.

From 2009 to 2012, researchers recruited 1,002 patients (mean age = 60 years; 83% men). By the end of the study in 2018, by an intention-to-treat analysis, 17% experienced the primary endpoint in the Med group and 22% in the LF group (HR, 0.75; 95% CI, 0.56-0.99). The rate per 1,000 person years was 28 in the Med group vs. 38 in the LF group (P = 0.039). These findings were more evident in men (16% Med vs. 23% LF; HR, 0.70; 95% CI, 0.49-0.92; P = 0.013). None of the individual components of the primary composite endpoint were statistically different between the two diets, despite numerical superiority for the Med diet. Sensitivity analyses based on clinical characteristics of the patients supported the main findings. The authors concluded that in patients with known CHD, a Med diet was superior for preventing major CVD events over seven years.


This was a unique study in several ways. Since it was a secondary prevention study, it would have been unethical to include a control diet group, so investigators chose two diets that have been recommended for secondary prevention based on their efficacy in primary prevention. It is remarkable they found a significant difference, especially since it was a relatively long-term study where one would expect diet fatigue. Patients maintained a > 80% adherence rate throughout the study by intensive dietitian consultations and group meetings, similar to Alcoholics Anonymous. Also, both diets were objectively effective. The Med diet increased total fat intake from 37% to 41% of total caloric intake because of an increase in olive oil, nuts, and oily fish, as directed. The LF diet increased complex carbohydrate intake from 42% to 46% and reduced fats from 37% to 32% of caloric intake. Both diets increased fiber intake because of greater consumption of fruit, vegetables, and legumes. Both diets decreased red meat intake, sweet beverage consumption, and fatty spreads. Thus, it is unsurprising major vascular events were lower than researchers expected.

Mortality was < 8% compared to about 20% in other similar study populations without diet interventions. In addition, this was accomplished without differences in lipid levels or blood glucose. Of course, 87% of patients were on statins. Finally, a subgroup analysis showed the beneficial results were not altered by considering only those with LDL cholesterol < 100 mg/dL, those younger than age 70 years, or those with > 80% diet adherence.

There were limitations. It was conducted in Spain, where the Mediterranean diet likely would be more acceptable. Also, the diet intervention was intense and may not be realistic in other settings. It was underpowered for women, but that is because the authors did not try to weight it for women. The study ended because the authors had reached a statistically significant endpoint, but the seven-year follow-up is longer than most studies of diet in CVD. Some would fault this work for occurring only in a single center, but this allowed investigators to tightly control the dietary interventions. Although 138 patients dropped out during the study, researchers followed 85% of these patients in the medical record for the intention-to-treat analysis.