Vegetarian Diet in Patients With Ischemic Heart Disease (VERDI)

Vegetarian Diet in Patients With Ischemic Heart Disease: An Open-label, Randomized, Prospective Crossover Study

Open label, 4 week randomized, cross-over study to compare the effect of a vegetarian diet to a conventional (meat containing) diet based on the Swedish average meat consumption on a range of parameters with prognostic importance for cardiovascular disease.The study will be conducted in patients diagnosed with ischemic heart disease. We hypothesize that patients will benefit from a vegetarian diet as assessed by multiple risk markers for this type of disease with a primary focus on changes in oxidized LDL cholesterol.

Study Overview

• Status: Completed
• Conditions: Ischemic Heart Disease
• Intervention / Treatment: Other: Vegetarian diet followed by meat diet or vice versa

Detailed Description

Background

Cardiovascular disease is the leading cause of death globally. Ischemic heart disease (IHD) contributes the most to this statistic and since 1990 the global burden of IHD has increased. It is estimated that 50 000 Swedish patients are hospitalized every year due to IHD. The risk of developing IHD is to a large extent determined by the existence and state of several modifiable risk factors including dietary habits, smoking, hypertension, diabetes mellitus, hyperlipidemia, high apolipoprotein B/ apolipoprotein A1-ratio, abdominal obesity, physical inactivity, alcohol consumption and psychosocial factors. High levels of oxidative stress, oxidized LDL cholesterol and the microbial metabolite trimethylamine N-oxide TMAO have been suggested to be associated with development of IHD.

A plant-based (vegetarian) diet may provide cardiovascular health benefits through various mechanisms. Clinical studies suggest that a vegetarian diet has positive effects on low-density lipoprotein (LDL) cholesterol, oxidized LDL cholesterol, total cholesterol, triglycerides, apolipoprotein B, body mass index (BMI), inflammatory markers, blood pressure, arterial intima-media thickness, insulin sensitivity, glycated hemoglobin, (HbA1c) and fasting glucose levels. Through positive impacts on risk factors that a vegetarian diet is associated with a lowered incidence and mortality of IHD and an overall reduced mortality.

A weakness of several prior long-term controlled studies comparing vegetarian and meat-containing diets is the lack of well-defined control diets leading to study heterogeneity. For example, some of the subjects on meat-containing diets consume great quantities of red meat, others eat substantial amounts of processed meat products and some eat mostly white meat and fish complicating interpretation of outcome. In cross-sectional or observational cohort studies comparing long-term vegetarians to long-term omnivores, results may be influenced by other lifestyle choices besides the studied diet, such as smoking and exercise.Furthermore, the participants in many previous studies were often healthy volunteers and not patients with overt cardiovascular disease.

Purpose

The objective is to perform an open label, 4 week randomized, cross-over study to compare the effect of a vegetarian diet to a conventional (meat containing) diet based on the Swedish average meat consumption on a range of parameters with prognostic importance for cardiovascular disease: lipids, inflammation, oxidative stress, BMI, HbA1c, apolipoprotein B/apolipoprotein A1-ratio, gut microbiota, endothelial function and quality of life. The study will be conducted in patients diagnosed with STEMI (ST-segment elevation myocardial infarction), non-STEMI (non-ST-segment elevation myocardial infarction) or angina pectoris and treated by percutaneous coronary intervention (PCI).

Hypothesis

The study hypothesis is that patients diagnosed with IHD can benefit from a vegetarian diet as assessed by multiple risk markers for this type of disease with a primary focus on changes in oxidized LDL cholesterol.

Clinical relevance

During the last decades the global mortality from IHD has remained unchanged regardless of development of new invasive and pharmacological treatments. Despite the fact that the prevalence and mortality from IHD have decreased in this country since 1990 and that the decrease most likely is due to lifestyle changes, IHD remains the leading cause of death in Sweden.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Örebro, Sweden
    • Regionorebrolan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Stable ischemic heart disease and previous percutaneous coronary intervention (PCI.
• Under optimal medical treatment including aspirin and cholesterol lowering drugs (statins)

Exclusion Criteria:

• PCI treatment during the last 30 days
• Inability to provide informed consent
• Already following a vegetarian or a vegan diet
• Known vitamin B deficiency
• Known food allergy
• Previous obesity surgery or gastric bypass surgery
• Life expectancy <1 year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Vegetarian - Meat; 4 weeks of vegetarian diet followed by 4 weeks of 'wash out' (no intervention) and 4 weeks of meat-containing diet	Other: Vegetarian diet followed by meat diet or vice versa; Half the patients will follow either a vegetarian diet for 6 weeks and the other half will adhere to or a meat-based diet for six weekd. This is followed by a 4 week period where patients eat their usual diet. Thereafter patients initially randomized to a vegetarian diet will follow a meat-based diet for six weeks while the patients initially randomized to meat will follow a vegetarian diet for six weeks.
ACTIVE_COMPARATOR: Meat - Vegetarian; 4 weeks of meat-containing diet followed by 4 weeks of 'wash out' (no intervention) and 4 weeks of vegetarian diet	Other: Vegetarian diet followed by meat diet or vice versa; Half the patients will follow either a vegetarian diet for 6 weeks and the other half will adhere to or a meat-based diet for six weekd. This is followed by a 4 week period where patients eat their usual diet. Thereafter patients initially randomized to a vegetarian diet will follow a meat-based diet for six weeks while the patients initially randomized to meat will follow a vegetarian diet for six weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in oxidative stress evaluated by oxidized LDL cholesterol changes	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in cardiovascular risk profile according to the Framingham Risk Score		4 weeks
Changes in biomarkers of inflammation	Markers: hs-CRP (high sensitivity C-reactive protein), IL-6 (interleukin 6), TNF-α (tumor necrosis factor α), interferon gamma (IFN-γ).	4 weeks
Changes in biomarkers of lipid status	Markers: total cholesterol, LDL-cholesterol, TGA (triacylglycerides), apolipoprotein B, apolipoprotein A1, HDL cholesterol.	4 weeks
Changes in HbA1c		4 weeks
Changes in TMAO levels in plasma	TMAO: trimethylamine N-oxide assessed by stable isotope dilution high-performance liquid chromatography.	4 weeks
Changes in gut microbiota	Assessment of: Bacteroides, Prevotella, Bacteroides-Prevotella, Bacteroides thetaiotaomicron, Clostridium clostridioforme and Faecalibacterium prausnitzii and 16S rRNA profiling and next-generation sequencing to analyze the gut microbiome.	4 weeks

Collaborators and Investigators

• Sponsor: Region Örebro County
• Collaborators: Göteborg University; Swedish University of Agricultural Sciences
• Investigators: Principal Investigator: Demir Djekic, MD, Region Örebro county

Publications and helpful links

General Publications

• Djekic D, Shi L, Brolin H, Carlsson F, Sarnqvist C, Savolainen O, Cao Y, Backhed F, Tremaroli V, Landberg R, Frobert O. Effects of a Vegetarian Diet on Cardiometabolic Risk Factors, Gut Microbiota, and Plasma Metabolome in Subjects With Ischemic Heart Disease: A Randomized, Crossover Study. J Am Heart Assoc. 2020 Sep 15;9(18):e016518. doi: 10.1161/JAHA.120.016518. Epub 2020 Sep 6.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2017
• Primary Completion (ACTUAL): October 1, 2018
• Study Completion (ACTUAL): June 1, 2019

Study Registration Dates

• First Submitted: October 20, 2016
• First Submitted That Met QC Criteria: October 21, 2016
• First Posted (ESTIMATE): October 24, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 12, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Ischemia
• Other Study ID Numbers: Regionorebrolan

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No