Effect Of Omega 3 On Cardiovascular Disease Biology Essay


In the United States, as of 2006 there were approximately 81 million people with some form of Cardiovascular Disease (CVD) as reported by The American Heart Association. (1) In that group, roughly 831,000 Americans died from complications of Cardiovascular Disease. (1) And, about half of that number died as the result of Coronary heart disease (CAD). (1) The numbers for new or recurrent myocardial infarction (MI) in the U.S are estimated at 1.2 million, with 40% being fatal and new or recurrent stroke is about 700,000, with a death rate of about 275,000 a year. (2)

Cardiovascular disease takes on many forms, such as high blood pressure (HTN), stroke, heart failure (HF), peripheral arterial disease (PAD) and coronary heart disease (CAD). (2, 3) CAD is the result of collection of fatty deposits on the inner wall of arteries, called Atherosclerosis. This collection of fat leads to a narrowing of the coronary arteries. It's the narrowing of the coronary arteries that places patients in a higher risk of angina and myocardial infarction. Many times these deposits start out as streaking in adolescence and develop into larger deposits later in life. This collection is many times the result of poor diet.

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Dyslipidemia is the elevation of cholesterol or triglycerides, or both, or it can be due to a low HDL (high density lipoproteins) in the blood stream. This elevation in the amount of lipid in the blood has two causes; either primary (the results of genetics, in that patients are predisposed to having elevated lipids though no fault of their own) or secondary (due to diet or lifestyle).

Omega-3 is a group of unsaturated fatty acids, made up of Alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA).

Clinical Case Presentation.

LH is a 60 year old Caucasian female that presents to an outpatient family practice clinic for a regularly scheduled yearly well check up.

LH is G2P2, with history of menopause. Past medical history includes psoriasis and osteoarthritis. Past surgical history includes breast augmentation, Abdominoplasty and Liposuction, and two Dilatation & Curettage for Uterine Fibroids. She is allergic to Mobic and Relafen. Current medications include Methotrexate, Folic Acid, Celebrex, Multivitamin, Enteric Coated Fish Oil Capsules, Testosterone Cream, Estrace Vaginal Cream, and Glucosamine & Chondroitin. Family history; Father, alive at 83, with history Anemia, Hypertension (HTN), Insulin dependent Diabetes, Bilateral knee replacement, Myocardial Infarction (MI), and quadruple coronary artery bypass graft (CABG). Her mother, deceased at 79, with history of Type II Diabetes, HTN and breast cancer. Her uncle is alive, with history of CABG and chronic obstructive pulmonary disease (COPD). Brother is a alive, with history of Hypertension. LH is married, in a monogamous relationship, former registered nurse, now stay-at-home mother. Past social history includes occasional alcohol use, no tobacco use, regular exercise, including resentence training and running, and a regular diet, containing based on fruits and vegetables with some deep fried foods. Her current body mass index (BMI) is 25.8, with is slightly overweight.

The patient's last Lipid Panel is: Total Cholesterol 175, High Density Lipoprotein Cholesterol (HDL-C) 48, Low Density Lipoprotein Cholesterol (LDL-C) 110, and Triglycerides 110

This particular patient has been on fish oil since 2007. The enteric coated capsules have proven better, with fewer side effects such as "fishy breath" and "burping." She was placed on fish oil for elevated lipids 2007, along with strong family history of HTN, diabetes, heart disease, and MI.

Clinical Question

In patients with dyslipidemia and history of cardiovascular disease, is utilization of omega-3 more effective at lowering lipid levels than lifestyle modifications?


A PubMed search was conducted in August 2009 using the terms; "omega-3", "heart disease" and "prevention", which yielded 703 results. Additional PubMed searches with terms "cardiovascular disease", "dyslipidemia" and "lifestyle modification." Then Cochrane library, using the terms "omega-3", "heart disease", and "prevention", which yielded 12 results. PubMed was searched again in February 2010 using the terms "lifestyle modification" and "coronary heart disease," with limits for "humans, clinical trial and randomized controlled trial," which yielded 52 results.


Study #1: Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia.

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This study was performed in the United Kingdom at the University of Wales College of Medicine in 1998. The objective of the study was to determine the effect on large artery function with marine omega-3 in patients, who have a documented history of hypercholesterolemia.

Study Design: This is a prospective, placebo-controlled, randomized, double-blinded, parallel-group study. The study lasted for 120 days. 30 subjects were chosen from the Lipid Clinic at the University Hospital of Wales. All of the subjects have a confirmed diagnosis of hypercholesterolemia after a low-fat diet for three months. Hypercholesterolemia as defined by the study is patients with a serum total cholesterol >6.5 mmol/liter. Subjects on antilipid medication that had stable cholesterol levels, remained on the same dose and drug during the study. Exclusion for the study; active smokers, recent smokers (in the past 2 years), diabetes, hypertension, patients on hormone supplements, vasoactive medications, vitamins, antioxidants, or fish oils, or subjects with a clinical history of coronary, cerebral or peripheral vascular disease. From this, the 30 recruited subjects were randomly assigning to two groups of 15 participants; one group received marine omega-3 fatty acids in 2 1-gram capsules twice a day for 120 days and the other group received a placebo, made of corn oil, in 2 1-gram capsules twice a day for 120 days. The marine omega-3capsules contained EPA and DHA, and produced from whole-body fish oil, with a combined concentration of both fatty acids as 85%., along with 4 IU of vitamin E per capsule. The placebo contained no vitamin E. (3)

Study Conduct: Patients in the study were required to submit to a physical examination at base line, day 0, and at day 120, along with venous blood sampling and flow-mediated brachial artery dilation on the same days. Flow-mediated dilation was measured by ultrasonic wall tracking. The purpose of ultrasonic wall tracking was to determine the "end-diastolic" diameter for each beat, along with measuring blood pressure. Brachial artery blood flow was calculated by the internal brachial artery diameter and multiplying the mean blood velocity. All studies in the trial were performed in the morning with at room temperature of 21C to 23 C; patients fasted for the night before and were required to be supine for 15 minutes with arm held outstretched on pneumatic cushion. Patients were asked to abstain from coffee for 12 hours before the study. "Measurements were made at baseline, during hand hyperemia, and after sublingual glycerol trinitrate (GTN) and endothelium-independent vasodilator. Hand uremia performed by placing a pediatric sphygmomanometer cuff at the wrist and inflating cuff to a systolic pressure of + 50 mm HG for 5 minutes. Blood flow was recorded every 15 seconds, starting 15 seconds before inflation and 90 seconds after, while brachial artery diameter was measured every 10 seconds at 60-70 seconds. "Flow-mediated dilation was defined as brachial artery diameter at 60 to 70 seconds after cuff release minus baseline diameter. GTN spray was a dose of 400 micrograms, and measurements were repeated 3 minutes after sublingual. Serum concentrations of the following:

Lipid panel:

Total cholesterol

High-density lipoprotein (HDL) cholesterol

Low-density lipoprotein (LDL) cholesterol

Very low density lipoprotein (VLDL) cholesterol




Liver function


Were collected from patients who were fasting.

Study Results: The two subject groups, control and experimental groups, were comparable at the beginning of the study. And, all but two in the control finished the study. Brachial artery blood for all groups, before and after treatment, was similar. However, Flow-mediated dilation increased after omega-3 treatment over placebo. For serum levels, triglyceride levels dropped for subjects taking omega-3, but omega-3 had no effect on VLDL, LDL, HDL, or total cholesterol.

Study Criteria: The strength of the study was it was a double-blinded, placebo controlled study. The study's subjects were picked with specific inclusion and exclusion criteria. However, the size of the population was extremely small, 30 subjects. Second, the time of trial was only four months. Validity of the results and its significance is questionable. The study should have included a larger number of subjects, with longer trial period.

Levels of Evidence: 2a

Study #2: The Triglyceride-Lowering Effects of a Modest Dose of Docosahexaenoic Acid Alone Versus in Combination with Low Dose Eicosapentaenoic Acid in Patients with Coronary Artery Disease and Elevated Triglycerides.

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This study was performed with the objective to determine if Docosahexaenoic acid (DHA) compared with the combination of Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) in patients with Coronary artery disease (CAD) at lowering elevated triglycerides.

Study Design: This is a prospective, randomized, double-blind study. 116 subjects were enrolled in the study, from 853 that were invited to participate. Subjects were invited based on the following criteria; history of CAD (defined as acute myocardial infarction, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, and/or a cardiac catheterization showing >50% occlusion of one or more coronary vessels), subjects with two consecutive triglyceride levels between 200 and 750 mg/dl, a LDL-C level less 100 mg/dL, and thyroid stimulating hormone (TSH) level within normal limits (0.32-5.50 IU/ml) in the past year were considered for enrollment. Exclusions for the study included, "pregnant or breast feeding, documented history of alcoholism within the previous year, glycosylated hemoglobin (HbA1C) > 8.5% within the past six months, taking omega-3 fatty acid supplements in doses of greater than 400mg DHA per day, receiving >5mg prednisone (or equivalent) per day, hospitalized for any reason with the previous two months, and failure to provide written informed consent." (4) For medications, patients using statins, thiazide, diuretics, beta-blockers, estrogen, levothyroxine, and/or oral corticosteroids were permitted into the study if they continued on the same dose of medication starting from the 2 months before starting the study.

Study Conduct: Patients in the study who meet initial entry criteria were mailed invitation letters and consent forms, and with the collection of sign consent, the subjects' medical records were obtained and reviewed for eligibility. Each potential study subject who meets criteria had the following serum levels collected:

Baseline fasting lipid (FLP)

Alanine aminotransferase (ALT)

Creatine kinase (CK)

Fasting blood glucose (FBG)

TSH (if not performed in the last year)

HB1AC (for subjects with history of diabetes, if not performed in the past 6 months)

If the subjects meet entry requirements, then that subject was enrolled and randomized. Subjects in the trial were randomly given 1000 mg/day of DHA or 1252 mg/day (1000 mg of DHA) of DHA + EPA for eight weeks using a computer generated list of random numbers. All products in the study had the same lot number, and participants and investigators were not allowed to know the treatment allocation. Supplements were mailed to subjects by an independent mailer not associated with the study, and supplements were labeled as either "Supplement A" or "Supplement B." Subjects were told to maintain their current diet, exercise habits, and alcohol intake throughout the eight-week trial period. At the end of the eight weeks, serum FLP, ALT, CK, and FBG levels were collected, along with a standardized telephone questionnaire administered as a follow-up to assess how study participants tolerated the supplements and the adequacy of the study blinding. The questionnaire was performed by an individual separate from the trial. (2)

Study Results: 116 subjects were used in the study, based on defined inclusion and exclusion criteria, along with willingness to participate. The mean age was 69 years, and 70% were men, and over 90% were on a statin and aspirin therapy. For the two groups, base line triglycerides were similar. In both groups, triglyceride levels dropped, but more in the DHA group (21.8%) vs. the DHA + EPA group (18.3%). And, 24.6 % of the DHA group achieved their goal of a serum triglyceride level of <150 mg/dl, vs. 10.2% in the DHA + EPA group. LDL levels did change, and HDL levels changed in both groups, more in the DHA group. Both groups experienced an increase in ALT over base line, more in the DHA + EPA than the DHA group. One subject stopped taking the supplement due to gastrointestinal upset, and many subjects reported a fishy taste.

Study Criteria: This study had several strengths, including a large collection of possible subjects used in the study, clearly defined perimeters for selection of subjects, computerized selections of subjects, and a large number of subjects. The study was a controlled trial, and subjects were randomly placed in control vs. experimental groups, and supplements were distributed by individuals not involved in the study.

The study had several weaknesses. Primarily, the length the study was only eight weeks. There was no reference of why only eight weeks was chosen or its significance. The results of the study may have been different if a longer period had been chosen. Second, there was no control group in the study. It results would cared more validity if the two study groups had a placebo group to compare to.

Levels of Evidence:2a

Study #3: Effects of fish-oil ingestion on cardiovascular risk factors in hyperlipidemic subjects in Israel: a randomized, double-blind crossover study.

This study was performed in Israel. The objective the study was to determine the effect on serum lipids, apolipoproteins, and platelet function/hemorheologic variables in patients with high linoleic acid intake (with potential benefit in cardiovascular risk factors) with fish supplement vs. vegetable oil.

Study Design: This is a randomized, controlled, double-blinded, crossover fashion study. The study lasted a total of 20 weeks. 27 patients were chosen at the Lipid Clinic of the Beilinson Medical Center. All subjects chosen had a serum triglyceride level of >2.8 mmol/L while on standard lipid-lowering diet, with no hypolipidemic drug for the past 2 months or more before the trial. Second, no subject could have a history of serious illness or operation during the 3 months before the study. Subjects were required to sign an informed-consent from the hospital Helsinki Committee. Subjects were defined into phenotypes by the World Health Organization, consisting of clinical characteristics; Diabetes mellitus, Hypertension, smokers, Ischemic heart disease, and Peripheral vascular disease. Patients in the study were randomly separated in two groups.