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Genetic factors contribute to risk factors for cardiovascular disease, such as blood lipids, blood pressure, obesity, diabetes, and may also influence dietary choices, physical activity, and responses to stress. The most robust genetic variant associated with myocardial infarction (MI) is the 9p21 variant, which may raise the risk of MI by up to 40% in those who carry 2 copies of the gene. The investigators recently found that among those who carry the 9p21 variant, the risk of MI may be "turned off" if individuals eat a diet high in fruits and vegetables. The investigators seek to determine how a "prudent" or "anti-inflammatory" diet interacts with the 9p21 risk allele to alter the risk of MI.
Cardiovascular disease (CVD) is the leading cause of death globally. The majority of CVD is explained by conventional risk factors including cigarette smoking, abnormal lipids, high blood pressure, obesity, diabetes, and health behaviours including dietary intake, physical activity, and psychosocial stressors. Genetic factors contribute to the development of these risk factors, and directly to CVD through other novel pathways. Since the advent of high throughput chip-based genotyping, more than 30 genetic variants have been found to be associated with myocardial infarction. The most robust genetic variant which has been consistently associated with myocardial infarction and other forms of arterial disease is the 9p21 variant. This genetic variant located on Chromosome 9 is common in the population, with 50% of people carrying one copy of the risk allele, and an additional 25% of the population carrying two copies of the risk allele. Compared with those with no copies of the risk allele, the risk of myocardial infarction with one copy of the risk allele is 15-20% higher, and the increased risk among carriers of 2 risk alleles is 20-40%. To date the exact mechanism by which the 9p21 variant increases the risk of myocardial infarction is unknown, although some data suggests that other genes and pathways associated with cell proliferation and inflammation are involved. Recently we made the observation that among carriers of the 9p21 variant, the risk of MI may be "turned off" if individuals consumed a diet high in fruits and vegetables. However the "mechanism" underlying this interaction is unknown. We seek to discover how a "Prudent" (i.e. anti-inflammatory) diet interacts with the 9p21 risk allele(s) to alter the risk of myocardial infarction.
We postulate that a "Prudent" diet (i.e. a diet high in fruits, vegetables, whole grains, non-processed foods) in comparison to a "Western" or "inflammatory diet" (eg, a typical North American diet high in saturated fats and processed foods) will differentially alter the gene expression (measured by RNA) of the 9p21 locus, change the epigenetic marks in this region, and alter several inflammatory markers suspected to mediate the effect of 9p21 on CVD risk (eg, hs-CRP, IF-alpha21, IFN-γ , interleukin 1-alpha, interleukin 1-beta, and interleukin 6) among people with one or two copies of the risk allele compared to people without the risk allele.
The proposed study offers an unique approach to studying dietary relationships with endpoints believed to be influenced by 9p21 gene variants. Rather than testing nutritional supplements, our results will be generalizable to the setting of most dietary counseling practices, which aim to alter dietary patterns, not specific nutrients. This trial will help us to unravel the basis for gene-diet interactions and gain a greater understanding of how inflammation is linked to the development of atherosclerosis, CVD, and possibly some cancers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Typical Western Diet | Active Comparator | The comparator dietary pattern ("Typical Western Diet") approximates the inflammatory dietary pattern typically consumed by North Americans. It contains refined grains, processed foods, dairy fat, meats, sugar and high glycemic index foods, and few fruits, nuts, legumes, and vegetables. The fruits and vegetables are highly processed (e.g. juices) and lower in micronutrients than those in the intervention diet. The saturated fat content of this diet does not meet national guidelines for health. The polyunsaturated fat:saturated fat ratio is ~0.5 (low). |
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| Prudent Diet | Experimental | The experimental dietary pattern ("Prudent Diet") is based on intakes of foods hypothesized to have beneficial effects on inflammation and long-term health. This dietary pattern includes micronutrient and macronutrient levels consistent with healthy eating in epidemiological studies and randomized controlled trials. The diet is constructed with low-fat dairy products, fish, chicken, and lean meats to minimize saturated fat and increase protein and calcium. The diet is rich in fruits, vegetables, whole grains, nuts, legumes, and seeds that are good sources of potassium, magnesium, and dietary fiber. This diet provides a 'favorable' macronutrient profile that is low in saturated fat, has a polyunsaturated/saturated fat ratio of ~1.0 (high), and low in high glycemic index carbohydrates. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Prudent Diet | Other | This intervention lasts 2 weeks (14 days). |
| |
| Measure | Description | Time Frame |
|---|---|---|
| gene expression measuring ANRIL production | baseline and 2 weeks | |
| epigenetic marks | baseline and 2 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| high-sensitivity C-reactive protein | Biomarker of inflammation | baseline and 2 weeks |
| interferon-alpha-21 | Biomarker of inflammation |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sonia S Anand, MD, PhD | McMaster University; Hamilton Health Sciences Center; Population Health Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| McMaster University | Hamilton | Ontario | L8S 4K1 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21295845 | Background | Anand SS, Yusuf S. Stemming the global tsunami of cardiovascular disease. Lancet. 2011 Feb 12;377(9765):529-32. doi: 10.1016/S0140-6736(10)62346-X. Epub 2011 Feb 4. No abstract available. | |
| 22129254 | Background | O'Donnell CJ, Nabel EG. Genomics of cardiovascular disease. N Engl J Med. 2011 Dec 1;365(22):2098-109. doi: 10.1056/NEJMra1105239. No abstract available. |
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Because sensitive genetic material was collected as part of this pilot study, data from this study will not be shared.
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| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D007249 | Inflammation |
| D050171 | Dyslipidemias |
| D006943 | Hyperglycemia |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D000072001 | Diet, Healthy |
| ID | Term |
|---|---|
| D004032 | Diet |
| D009747 | Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
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| Typical Western Diet |
| Other |
This intervention lasts 2 weeks (14 days). |
|
| baseline and 2 weeks |
| interferon-gamma | Biomarker of inflammation | baseline and 2 weeks |
| interleukin-1-alpha | Biomarker of inflammation | baseline and 2 weeks |
| total cholesterol | lipid risk factor for cardiovascular disease | baseline and 2 weeks |
| low-density lipoprotein-cholesterol | lipid risk factor for cardiovascular disease | baseline and 2 weeks |
| high-density lipoprotein-cholesterol | lipid risk factor for cardiovascular disease | baseline and 2 weeks |
| apolipoprotein-B | lipid risk factor for cardiovascular disease | baseline and 2 weeks |
| fasting glucose | indicator of insulin resistance | baseline and 2 weeks |
| systolic blood pressure | mmHg | baseline and 2 weeks |
| diastolic blood pressure | mmHg | baseline and 2 weeks |
| interleukin-6 | Biomarker of inflammation | baseline and 2 weeks |
| 17478681 | Background | McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds DA, Pennacchio LA, Tybjaerg-Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC. A common allele on chromosome 9 associated with coronary heart disease. Science. 2007 Jun 8;316(5830):1488-91. doi: 10.1126/science.1142447. Epub 2007 May 3. |
| 22022235 | Background | Do R, Xie C, Zhang X, Mannisto S, Harald K, Islam S, Bailey SD, Rangarajan S, McQueen MJ, Diaz R, Lisheng L, Wang X, Silander K, Peltonen L, Yusuf S, Salomaa V, Engert JC, Anand SS; INTERHEART investigators. The effect of chromosome 9p21 variants on cardiovascular disease may be modified by dietary intake: evidence from a case/control and a prospective study. PLoS Med. 2011 Oct;8(10):e1001106. doi: 10.1371/journal.pmed.1001106. Epub 2011 Oct 11. |
| 19364995 | Background | Mente A, de Koning L, Shannon HS, Anand SS. A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Arch Intern Med. 2009 Apr 13;169(7):659-69. doi: 10.1001/archinternmed.2009.38. |
| 11010931 | Background | Hu FB, Rimm EB, Stampfer MJ, Ascherio A, Spiegelman D, Willett WC. Prospective study of major dietary patterns and risk of coronary heart disease in men. Am J Clin Nutr. 2000 Oct;72(4):912-21. doi: 10.1093/ajcn/72.4.912. |
| D009750 | Nutritional and Metabolic Diseases |
| D044882 | Glucose Metabolism Disorders |