Introduction
The Lyon Diet Heart Study (LDHS) stands as a cornerstone in the field of nutritional cardiology, significantly influencing the recognition and recommendation of the Mediterranean diet for cardiovascular health. Conducted in Lyon, France, between 1992 and 1996, this randomized, single-blind secondary prevention trial investigated the impact of a Mediterranean-type diet on the recurrence rate of myocardial infarction (MI). The study's remarkable findings, including a surprising 73% reduction in major cardiac events, have drawn considerable attention from medical and scientific communities. This article delves into the design, results, and implications of the LDHS, examining its methodologies, dietary intervention, and lasting impact on cardiovascular disease prevention.
Background and Objectives
Dietary trials often face the challenge of potential biases due to the infeasibility of double-blind designs. The Lyon Diet Heart Study addressed this limitation through a specific design aimed at minimizing investigator and attending physician bias. The primary objective was to test the hypothesis that a Mediterranean-type diet could prevent recurrences after a first myocardial infarction.
Study Design and Methods
Participants
The study involved 605 patients under 70 years old who had survived a first myocardial infarction within the previous six months. These patients were recruited at the University Hospital of Lyon, France.
Randomization and Blinding
Participants were randomized into either a control group, following a prudent Western-type diet, or a Mediterranean diet group. A unique aspect of the study design was that patients and their physicians were not fully informed about the comparative nature of the trial during recruitment. Only patients assigned to the experimental group signed a second informed consent, agreeing to modify their diet and adopt a Mediterranean-type α-linolenic acid-rich diet. This approach aimed to reduce potential biases related to awareness of the treatment assignment.
Dietary Intervention
The intervention group was encouraged to follow a Mediterranean-type diet rich in α-linolenic acid. Dietary habits were assessed in the experimental group using 24-hour recall and food frequency questionnaires to avoid influencing the behavior of the control participants.
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Bias Control
To evaluate potential biases, drug usage was monitored to assess attending physician bias, and a questionnaire was used to evaluate investigator bias. Specific scores were used to assess how patients appreciated their participation and whether this participation resulted in significant changes in their way of living.
Key Findings
Reduction in Cardiac Events
An intermediate analysis after 27 months of follow-up revealed a striking protective effect in the Mediterranean diet group. The study examined three composite outcomes (COs):
- CO 1: Cardiac death and nonfatal myocardial infarction
- CO 2: CO 1 plus major secondary end points (unstable angina, stroke, heart failure, pulmonary or peripheral embolism)
- CO 3: CO 2 plus minor events requiring hospital admission
The Mediterranean diet group experienced significant reductions in all three composite outcomes:
- CO 1: 14 events versus 44 in the prudent Western-type diet group (P=0.0001)
- CO 2: 27 events versus 90 (P=0.0001)
- CO 3: 95 events versus 180 (P=0. 0002)
Adjusted risk ratios ranged from 0.28 to 0.53, indicating a substantial protective effect of the Mediterranean diet.
Traditional Risk Factors
The study also assessed the impact of traditional risk factors on recurrence. Total cholesterol (1 mmol/L increase associated with an 18% to 28% increased risk), systolic blood pressure (1 mm Hg increase associated with a 1% to 2% increased risk), leukocyte count (adjusted risk ratios ranging from 1.64 to 2.86 with count >9x10(9)/L), and female sex (adjusted risk ratios, 0.27 to 0. The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infarction, confirming previous intermediate analyses. Major traditional risk factors, such as high blood cholesterol and blood pressure, were shown to be independent and joint predictors of recurrence, indicating that the Mediterranean dietary pattern did not alter, at least qualitatively, the usual relationships between major risk factors and recurrence.
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Long-Term Effects
The protective effect of the Mediterranean dietary pattern was maintained up to 4 years after the first infarction, confirming previous intermediate analyses.
Implications and Significance
Cardioprotective Diet
The results of the Lyon Diet Heart Study strongly suggest that a comprehensive strategy to decrease cardiovascular morbidity and mortality should primarily include a cardioprotective diet. The study demonstrated that the Mediterranean diet could significantly reduce the risk of recurrent cardiac events in patients who had experienced a myocardial infarction.
Comprehensive Strategy
The study emphasized that a cardioprotective diet should be associated with other means aimed at reducing modifiable risk factors.
Impact on Clinical Practice
The LDHS has had a profound impact on clinical practice, influencing dietary recommendations for cardiovascular disease prevention. The Mediterranean diet is now widely recognized as a heart-healthy dietary pattern, and its adoption is encouraged for both primary and secondary prevention of cardiovascular events.
The Mediterranean Diet: Beyond the Name
While the intervention in the LDHS was termed a "Mediterranean diet," it is important to consider its specific components. The diet emphasized increased consumption of:
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- Fruits
- Vegetables
- Fish
- α-linolenic acid-rich foods (e.g., canola oil, flaxseed)
It also encouraged reduced consumption of:
- Red meat
- Saturated fats
Challenges and Considerations
Single-Blind Design
The single-blind design of the LDHS, while innovative in addressing biases in dietary trials, is a limitation. The lack of complete blinding could potentially introduce some degree of bias, although the study implemented measures to minimize this.
Generalizability
While the LDHS provided compelling evidence for the benefits of the Mediterranean diet in a French population, the generalizability of these findings to other populations may warrant further investigation.
Contemporary Perspectives and Future Directions
Nutritional Ketosis and Cardiovascular Risk Factors
Emerging research has explored the impact of very low carbohydrate diets resulting in nutritional ketosis on cardiovascular risk factors. Studies have shown that such diets can lead to improvements in various risk markers, including normalization of the atherogenic lipoprotein profile (ALP).
LDL Cholesterol and Atherosclerosis
While LDL cholesterol is considered causal in atherosclerosis, it may not solely inform risk assessment. Measures reflective of the number of particles, like LDL particle number and ApoB, and non-HDL-C are better markers of risk than LDL-C and are included in practice guidelines.
Future Research
The impact of nutritional ketosis on cardiovascular outcomes like heart attack, stroke, and hospitalization or death from a cardiovascular cause remains an open question. Future research, such as a 10-year trial among newly diagnosed patients with T2D using ketogenic nutrition therapy, could provide valuable insights into primary prevention.