Vegetarian Diet in Patients With Ischemic Heart Disease

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Ischemic Heart Disease

Intervention / Treatment
-----------------
* Other: Vegetarian diet followed by meat diet or vice versa


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vegetarian - Meat<br>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<br>* 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.<br>|
| Active Comparator: Meat - Vegetarian<br>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<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |