Effect of Fish Oil (Omega-3 Fatty Acids) on Arteries

Phase 3

Terminated

Conditions: Heart Disease
Hypertension
Diabetes
Cardiovascular Disease
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Vascular Diseases

Interventions: Drug: Placebo
Drug: Omega-3

Registration Number: NCT00935766

Lead Sponsor: Denver Health and Hospital Authority

Brief Summary: The overall objective of LUCHAR Specific Aims 4.1 and 4.2 is to assess the additional contribution of cardiovascular disease (CVD) risk markers to traditional biomedical risk factors in the prediction of pre-clinical CVD. Specific Aim 4.3 will test the impact of omega-3 fatty acid supplementation on risk markers and pre-clinical markers of CVD in Hispanic patients.

Specific Aim 4.3: Conduct a randomized, placebo-controlled trial of the effect of omega-3 fatty acid supplementation on vascular function as measured by brachial artery reactivity (BAR) and on circulating inflammatory markers.

Hypotheses:

1. Daily omega-3 fatty acid supplementation will improve vascular function in subjects at high risk for CVD.

2. Daily omega-3 fatty acid supplementation will reduce inflammatory protein panel scores in subjects at high risk for CVD.

Detailed Description: Omega-3 fatty acids reduce triglycerides (TG) in a manner similar to fibric acids by lowering hepatic TG release, reducing VLDL production, stimulating lipoprotein lipase and enhancing TG clearance. Although statins are widely utilized among DH patients, our overall population, even those with CHD, have fairly low levels of LDL-cholesterol (Krantz et al, 2004). This likely reflects our population that is predominantly Latino with a high incidence of metabolic syndrome. Among our patients, we often achieve LDL-c NCEP targets, yet secondary goals for non-HDL, HDL, and TG are rarely achieved. This is an unmet opportunity given the strong independent contribution of non-HDL (McQueen et al, 2008), HDL (D'Agostino et al, 2008) and TG (Nordestgaard et al, 2007, Tirosh et al, 2007) to CHD risk, which may be particularly important in Latino populations.

The study drug (LOVAZA) improves the TC/HDL ratio which is the strongest predictor of CHD events based on the \~30,000 patient Interheart study noted above. LOVAZA has no hepatic P450 effects and for that matter no meaningful clinical adverse effects, making it advantageous for use in a population with multiple co-morbidities who are at risk for drug-drug interactions and have difficulty with medication adherence. Given the high incidence of insulin resistance among DH's predominately Latino CHD population, and strong lipid (Harris et al, 1997; Davidson et al 2007) as well outcome data in CHD (GISSI investigators, 1999) this agent has potential clinical utility in our population.

To date, improved outcomes in non-CHD populations have not been demonstrated prospectively with LOVAZA. Although recent data suggest promising effects on inflammatory makers such as LpPLA2, the impact of LOVAZA on pre-clinical markers of atherosclerosis such as BAR and CIMT have not been well characterized particularly among Latinos. Moreover, changes in inflammatory markers have been limited and more expansive evaluations are currently available. Against this background we assessed whether LOVAZA might improve atherosclerotic risk via improvement in flow mediated dilation of the brachial artery as well as through reduction in a comprehensive inflammatory marker panel.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 76

Inclusion Criteria

Diagnosis of HTN
Hispanic or Non-Hispanic White
Age > 18
One additional CVD risk factor
- Age > 55 for males or >65 for females
- DM
- Dyslipidemia O TC >220 or O LDL >130 or O on statin therapy
- Current smoker
- Chronic kidney disease defined as GFR <60 ml/min/1.72m2
- BMI > 30 kg/m2
- Positive microalbuminuria -Able to sign consent form and willing to complete 12-month follow- up period.

Exclusion criteria used for SA3/4 will also apply for Aim 4.3. These include factors rendering assessment of endothelial function unreliable, such as:

Clinically manifest CVD (including angina, myocardial infarction, surgical or percutaneous coronary revascularization, stroke, cerebrovascular revascularization, peripheral vascular disease, heart failure, or valvular heart disease
Electrocardiographic evidence of prior myocardial infarction
Known valvular heart disease of at least moderate severity
Known left ventricular systolic dysfunction (LVEF < 0.50)
End-stage renal disease
History of inflammatory disease or vasculitis (including rheumatoid arthritis, systemic lupus erythematosis, Raynaud phenomenon, or other connective tissue disease/vasculitides)
Corticosteroid therapy
Active substance abuse
Projected life-expectancy <12 months due to comorbid condition
Plans to move away from the Denver area within 12 months
Previous trauma or surgery of the brachial artery
Upper arm circumference exceeding 42 cm.

Additional exclusion criteria for participation in Aim 4.3 include:

Pregnancy or breast-feeding
Known sensitivity or allergy to fish
Known sensitivity or allergy to omega-3 fatty acid supplements
Taking omega-3 fatty acid supplements in the last 2 weeks- may participate after 2 week washout
Triglycerides > 500 mg/dL.
Alanine aminotransferase (ALT) levels above 3x upper limit of normal
Not a good candidate for participation based on the opinion of the investigators.
Current therapy with a fibric acid derivative

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sugar Pill	Placebo	4 tabs of placebo dependent on randomization
Omega 3	Omega-3	omega-3-acid ethyl esters and instructed to take 4 1 mg capsules daily

Primary Outcome Measures

Name	Time	Method
Change in Pulse Wave Velocity in Active vs. Placebo-treated Patients.	Baseline, 3 months	We conducted a prospective, randomized; double-blinded study of omega-3 fatty acids among 60 Latino and White hypertensive patients at risk for CVD. Patients received either 4-g omega-3 fatty acids or matched placebo daily. The principal outcome measure was change in brachial-ankle PWV. .

Secondary Outcome Measures