Cardiovascular Disease
Conditions
Keywords
fatty acids, cardiovascular disease, vascular function, microparticles
Brief summary
It is well established that diet plays an important role in both the development and progression of heart disease. Different types of dietary fat have varying effects on heart disease risk factors. The elasticity of an individual's blood vessels is strongly associated with heart disease risk and recent evidence suggests that dietary manipulation may influence elasticity of the blood vessels with dietary fat (including saturated, monounsaturated and polyunsaturated fatty acids) as a potentially important modulator. Substantial evidence exists on the effects of monounsaturated fats (type of fatty acids mainly found in olive and rapeseed oil), n-6 polyunsaturated fats (type of polyunsaturated fatty acids found in vegetable oils) and saturated fat (found mainly in animal derived products) on lipid levels. However, the influence of these dietary fats on the elasticity of blood vessels remains unclear.The main purpose of the DIVAS study is to determine the effects of the substitution of saturated fats with either n-6 polyunsaturated or monounsaturated fats on blood vessel elasticity and to determine the effects of these different dietary fats on other risk factors for heart disease including lipoproteins and inflammatory biomarkers.
Interventions
DIETARY_SUPPLEMENTSFA diet
Volunteers are following a high saturated fat diet for a 4-month period
DIETARY_SUPPLEMENTMUFA diet
Volunteers are following a high monounsaturated fat diet for a 4-month period
DIETARY_SUPPLEMENTn-6 PUFA diet
Volunteers are following a high n-6 polyunsaturated fat diet for a 4-month period
Sponsors
University of Reading
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Adults should have a relative risk (RR) of \> 1.5 of developing cardiovascular disease (CVD) based on presenting with at least one recognised risk factor for CVD: * total cholesterol (TC) \> 6.0 mmol/l * HDL cholesterol (HDLC) ≤ 1.0 mmol/l male, ≤ 1.3 mmol/l female * Glucose ≥ 6 mmol/l * Stage 1 hypertension or above i.e. a systolic BP ≥ 140 mmHg, diastolic BP ≥ 90 mmHg * BMI 28-35 kg/m2 * waist \>102 cm male or \> 84 cm female * Adults with a first degree relative with either a history of premature CVD - age of onset younger than 55 y in fathers, sons or brothers or younger than 65 y in mothers, daughters or sisters, or type 2 diabetes.
Exclusion criteria
* having suffered a myocardial infarction/stroke in the past 12 months * diabetic (diagnosed or fasting glucose \> 7 mmol/l) or suffer from other endocrine disorders * suffering from renal or bowel disease or have a history of choleostatic liver or pancreatitis * on drug treatment for hyperlipidaemia, hypertension, inflammation or hypercoagulation * no history of alcohol abuse * planning or on a weight reducing regime * taking any fish oil, fatty acid or vitamin and mineral supplements * pregnant, lactating or planning a pregnancy * smokers
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change in Flow Mediated Dilatation (FMD) | Baseline, 4 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular Risk Factors (Lipids, Inflammatory Markers, Indices of Insulin Resistance, Cell Microparticles, Endothelial Progenitor Cells) | 4 months | Data for fasting serum lipids (total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC:HDL-C ratio, low-density lipoprotein cholesterol (LDL-C), triacylglycerol (TAG)). |
| 24-hour Ambulatory Blood Pressure | 4 months | 24-hour, daytime and night-time measures of systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP; SBP-DBP) and heart rate (HR) |
| Vascular Stiffness by Pulse Wave Velocity (PWV), Pulse Wave Analysis (PWA) and Digital Volume Pulse (DVP) | 4 months | PWV (m/s) PWA produces Augmentation Index (AIx; %) DVP produces Stiffness Index (SI; m/s) and Reflection Index (RI; %) |
| Microvascular Reactivity (Laser Doppler Imaging With Iontophoresis) | 4 months | Laser Doppler imaging (LDI) with iontophoresis of acetylcholine (Ach; endothelium-dependent vasodilation) and sodium nitroprusside (SNP; endothelium-independent vasodilation). |
Countries
United Kingdom
Participant flow
Recruitment details
Recruited in three cohorts between November 2009 and June 2012.
Participants by arm
| Arm | Count |
|---|---|
| High Saturated Fat Diet SFA diet: Volunteers followed a high saturated fat diet for a 4-month period | 65 |
| High Monounsaturated Fat Diet MUFA diet: Volunteers followed a high monounsaturated fat diet for a 4-month period | 64 |
| High n-6 Polyunsaturated Fat Diet n-6 PUFA diet: Volunteers followed a high n-6 polyunsaturated fat diet for a 4-month period | 66 |
| Total | 195 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Re-located | 0 | 1 | 0 |
| Overall Study | Unable to comply | 0 | 0 | 2 |
| Overall Study | Weight loss | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | High Saturated Fat Diet | High Monounsaturated Fat Diet | High n-6 Polyunsaturated Fat Diet |
|---|---|---|---|---|
| 24-hour Diastolic Blood Pressure (DBP) | 75 mm Hg STANDARD_DEVIATION 7 | 75 mm Hg STANDARD_DEVIATION 8 | 74 mm Hg STANDARD_DEVIATION 6 | 76 mm Hg STANDARD_DEVIATION 8 |
| 24-hour Systolic Blood Pressure (SBP) | 122 mm Hg STANDARD_DEVIATION 11 | 121 mm Hg STANDARD_DEVIATION 12 | 121 mm Hg STANDARD_DEVIATION 10 | 124 mm Hg STANDARD_DEVIATION 11 |
| Age, Continuous | 44 years STANDARD_DEVIATION 10 | 45 years STANDARD_DEVIATION 9 | 43 years STANDARD_DEVIATION 11 | 45 years STANDARD_DEVIATION 10 |
| Body Mass Index (BMI) | 26.7 kg/m^2 STANDARD_DEVIATION 4 | 26.7 kg/m^2 STANDARD_DEVIATION 4.4 | 26.3 kg/m^2 STANDARD_DEVIATION 3.9 | 27.0 kg/m^2 STANDARD_DEVIATION 3.7 |
| Fasting Glucose | 5.05 mmol/L STANDARD_DEVIATION 0.44 | 5.09 mmol/L STANDARD_DEVIATION 0.43 | 5.00 mmol/L STANDARD_DEVIATION 0.45 | 5.05 mmol/L STANDARD_DEVIATION 0.44 |
| Fasting High-Density Lipoprotein Cholesterol (HDL-C) | 1.48 mmol/L STANDARD_DEVIATION 0.37 | 1.45 mmol/L STANDARD_DEVIATION 0.33 | 1.48 mmol/L STANDARD_DEVIATION 0.39 | 1.51 mmol/L STANDARD_DEVIATION 0.38 |
| Fasting Low-Density Lipoprotein Cholesterol (LDL-C) | 3.73 mmol/L STANDARD_DEVIATION 0.98 | 3.67 mmol/L STANDARD_DEVIATION 0.93 | 3.71 mmol/L STANDARD_DEVIATION 0.88 | 3.81 mmol/L STANDARD_DEVIATION 1.13 |
| Fasting Total Cholesterol (TC) | 5.46 mmol/L STANDARD_DEVIATION 1.09 | 5.38 mmol/L STANDARD_DEVIATION 0.98 | 5.43 mmol/L STANDARD_DEVIATION 1.07 | 5.57 mmol/L STANDARD_DEVIATION 1.27 |
| Fasting Triacylglycerol (TAG) | 1.25 mmol/L STANDARD_DEVIATION 0.67 | 1.31 mmol/L STANDARD_DEVIATION 0.77 | 1.18 mmol/L STANDARD_DEVIATION 0.53 | 1.26 mmol/L STANDARD_DEVIATION 0.67 |
| Ratio of TC:HDL-C | 3.87 STANDARD_DEVIATION 1.1 | 3.92 STANDARD_DEVIATION 1.2 | 3.85 STANDARD_DEVIATION 0.99 | 3.85 STANDARD_DEVIATION 1.12 |
| Region of Enrollment United Kingdom | 195 participants | 65 participants | 64 participants | 66 participants |
| Sex: Female, Male Female | 110 Participants | 36 Participants | 37 Participants | 37 Participants |
| Sex: Female, Male Male | 85 Participants | 29 Participants | 27 Participants | 29 Participants |
| Waist Circumference | 90.9 cm STANDARD_DEVIATION 12 | 92.1 cm STANDARD_DEVIATION 12.1 | 88.2 cm STANDARD_DEVIATION 10.3 | 92.1 cm STANDARD_DEVIATION 13.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 67 | 0 / 66 | 0 / 69 |
| serious Total, serious adverse events | 0 / 67 | 0 / 66 | 0 / 69 |
Outcome results
Primary
Percent Change in Flow Mediated Dilatation (FMD)
Time frame: Baseline, 4 months
Population: Number of participants analyzed: n=171. n=24 were images of poor quality that could not be analyzed successfully.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Saturated Fat Diet | Percent Change in Flow Mediated Dilatation (FMD) | -0.39 post-occlusion diameter change as % | Standard Error 0.24 |
| High Monounsaturated Fat Diet | Percent Change in Flow Mediated Dilatation (FMD) | -0.07 post-occlusion diameter change as % | Standard Error 0.32 |
| High n-6 Polyunsaturated Fat Diet | Percent Change in Flow Mediated Dilatation (FMD) | -0.08 post-occlusion diameter change as % | Standard Error 0.31 |
Comparison: To detect a 2% inter-group difference in FMD (primary outcome) using a SD of 2.3, 90% power and 5% significance level, n=171 participants were required (n=57 per group), increasing to n=228 to include a 25% dropout rate.p-value: 0.238General Linear Model Univariate Analysis
p-value: 0.021General Linear Model Univariate Analysis
p-value: >0.05General Linear Model Univariate Analysis
p-value: >0.05General Linear Model Univariate Analysis
Secondary
24-hour Ambulatory Blood Pressure
24-hour, daytime and night-time measures of systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP; SBP-DBP) and heart rate (HR)
Time frame: 4 months
Secondary
Cardiovascular Risk Factors (Lipids, Inflammatory Markers, Indices of Insulin Resistance, Cell Microparticles, Endothelial Progenitor Cells)
Data for fasting serum lipids (total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC:HDL-C ratio, low-density lipoprotein cholesterol (LDL-C), triacylglycerol (TAG)).
Time frame: 4 months
Secondary
Microvascular Reactivity (Laser Doppler Imaging With Iontophoresis)
Laser Doppler imaging (LDI) with iontophoresis of acetylcholine (Ach; endothelium-dependent vasodilation) and sodium nitroprusside (SNP; endothelium-independent vasodilation).
Time frame: 4 months
Secondary
Vascular Stiffness by Pulse Wave Velocity (PWV), Pulse Wave Analysis (PWA) and Digital Volume Pulse (DVP)
PWV (m/s) PWA produces Augmentation Index (AIx; %) DVP produces Stiffness Index (SI; m/s) and Reflection Index (RI; %)
Time frame: 4 months