The Hellenic Postprandial Lipemia Study (HPLS)
Condition: Coronary Heart Disease; Dyslipidemia
MeSH terms: Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Dyslipidemias; Hyperlipidemias
Study type: Observational

Summary: 
      Coronary heart disease (CHD) is the leading cause of death worldwide. The disease is
      characterized by a high mortality rate (about 40%) and a course continuously altered by
      lifestyle, gene polymorphisms and therapeutic treatment. Fasting concentration of blood
      lipids and lipoproteins only partially express the complex relation between dyslipidemia and
      CHD. Following the indication stated nearly 40 years ago by Zilversmit, there is now
      accumulating evidence that postprandial lipemia plays an important role in the atherogenic
      process [ref Kolovou], particularly that most hours of the day are spent in the postprandial
      state. Furthermore, the increases in blood glucose and triglycerides (TGs) following meals
      stimulate oxidative stress, impair endothelial function, and rises the inflammatory factors
      that lead to atherosclerosis. Previous studies reported on postprandial lipemia in subjects
      with obesity, metabolic syndrome, diabetes mellitus, elderly, patients with CHD and others.
      However, currently the estimation of cardiovascular disease risk is based on fasting blood
      values of triglycerides (TGs) and inflammatory markers. The effect of postprandial
      atherogenic factors on the initiation and progression of atherosclerosis is actually not
      known.The Hellenic Postprandial Lipemia Study (HPLS) was designed to study the consequences
      of postprandial lipemia in CRP as inflammatory marker in high-risk adults. Furthermore, the
      HPLS study will investigate whether hypolipidemic, hypoglycemic or antihypertensive
      medication may lessen the exaggerated postprandial lipemia as well as the rest abnormal
      postprandial metabolism. Finally, the HPLS study is intending to evaluate the influence of
      gene polymorphisms involved in lipid and glucose metabolism on postprandial lipemia and
      cardiovascular outcomes.
    

Detailed description: 
      The study aims to recruit 1200 patients that are characterized either as high risk or
      very-high risk for Coronary Heart Disease. It is assumed that an equal number of high risk
      and very high risk patients will be included in the study. Patients will be invited to
      participate in the study from outpatient clinics in the 14 centers in Athens, Greece.

      The study will be approved by the institution ethics committee and informed consent will be
      obtained from all participating patients.

      Participating patients will have recently (up to 15 days) been initiated in one of the
      following dislipidemic treatments:

        -  Simvastatin up to 40 mg,

        -  Atorvastatin up to 80 mg,

        -  Rosuvastatin up to 40 mg,

        -  Statin intolerant subjects receiving colesevelam up to 3.75 g/day or fenofibrate 145
           mg/day.

      All patients should have received the above treatments as initial treatment for dyslipidemia
      with the exception of statin intolerant patients. All patients at the time of their inclusion
      in the study will have been evaluated for gene polymorphisms as part of their dyslipidemic
      profile evaluation. Furthermore patients will have been characterized as high risk or very
      high risk according to the SCORE level of risk, calculated using the Greek version of
      low-risk regions charts.

      Each center will recruit 50 very high and 50 high risk patients. Each site will include 10
      consecutive high risk and 10 very high risk patients for each treatment group as described
      above. The following data will be collected for each patient:

        -  Personal and demographic details

        -  Family and personal medical history (including smoking, hypertension, hyperlipidemia and
           glucose metabolism, as well as cardiovascular disease history)

        -  Past measurements of blood pressure,

        -  Diabetes and lipids,

        -  Diagnostic procedures undertaken (coronary or other angioplasty, Coronary artery by-pass
           surgery),

        -  Measurements of blood pressure,

        -  Weight, height, waist and hip circumference. Body mass index (BMI) will be calculated as
           weight/height2

        -  The SCORE level of risk will be also calculated using the Greek version of low-risk
           regions charts.

      Each subject will have to complete 2 Lipotest meals with the first one given at the beginning
      of the study and the second one after at least 3 months of hypolipidemic treatment. Before
      and 4 hours after the meals blood samples will be collected. After that, subjects will be
      followed annually for 3 years.

      Lipotest Meal The Lipotest meal is a diagnostic standardized meal recognized by Hellenic Drug
      Organization (EOF, National Drug Organization). A single serving, provided in a sachet, is
      comprised of 115 g powder that is rehydrated by adding 150 ml water.

      The powder and water are mixed to homogeneity (2-3 minutes with a hand held mixer), and then
      refrigerated to form a mousse. All ingredients are food grade and are stable for a period of
      24hours after preparation as proved by antioxidant tests The ingredients' composition of
      Lipotest is hydrogenated vegetable fat, glucose syrup solids, milk proteins, sugar,
      emulsifiers (lactic and acetic acid esters of monoglycerides and diglycerides, cocoa powder
      (20-22% fat content), defatted cocoa powder (10-12% fat content), and flavorings.

      On a per serving basis, Lipotest provides 832 kcal (42% FDA Daily reference value (DRV) for
      adults, and 42% of the European Guideline Daily Amount, GDA), 10 g protein (20% DRV, 20%
      GDA), 25 g of carbohydrates (8.3% DRV, 10% GDA) of which simple sugars comprise 14.3 g (no
      DRV, 16% GDA), 2.1 g fiber (8.4% DRV), 0.15 g salt (2.5% DRV for sodium), and 75 g fat (115 %
      DRV, 109% GDA), all of which is fully saturated (375% DRV and GDA) through hydrogenation of
      vegetable fat. Fat used is coconut oil named Cegepal VF HC 77 and Lamequick 6068 both from
      Cognis, which are fully approved for use in food applications and are in powder form.

      Oral fat loading The meal will be administrated in the morning after 12-h overnight fast.
      Subjects will eat meal within 20 min and will be instructed to keep physical activity to a
      minimum, refrain from smoking and fast during the 4 h of the test. Blood samples will be
      withdrawn at 0 and 4 h for determination of TGs concentration. The meal will be administrated
      twice, before any treatment (visit 1) and 3 months after treatment with hypolipidemic,
      hypoglycemic or antihypertensive drugs (visit 2).

      Collection of blood and biomarker analyses All laboratory tests will be carried out at as
      part of everyday clinical practice and will be covered by the patient insurance.

      Serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and TG
      concentrations will be measured from both fasting and postprandial blood samples and plasma
      glucose concentrations will be measured from true fasting blood samples only.

      Inflammatory marker analysis Plasma will be analyzed for hs-C-reactive protein (CRP)
      according to everyday clinical practice and will be covered by the patient insurance.

      Study Duration 18 months recruitment period. 3 years follow up for every patient.

      Subject Participation Duration 36 Months 1200 very high and high risk for CHD patients

      Number of Participating Sites 14 clinics in 12 Hospitals

      Investigational Product: Not Applicable Investigational Product Dosage & Administration: Not
      Applicable

      Concomitant Medication All patients will receive concomitant medication in accordance to the
      everyday practice of their treating physician.

      Safety Evaluation All adverse events will be recorded in accordance to all applicable laws
      and regulations concerning medications prescribed according to their approved summary of
      product characteristics.

      Statistical Analysis Continuous variables will be described using means and standard
      deviations. Comparisons of continuous variables will be performed using the Student's t-test
      or the Mann-Whitney-U test for parametric and non-parametric data, respectively. Categorical
      variables will be expressed as absolute (N) or relative (%) frequencies and will be analyzed
      for associations using the chi-square test. The Paired t-test will be used to compare changes
      within the groups of variables and the Bonferroni test will be used to compare the changes
      between the groups, as a method for their post hoc comparisons Univariate and multivariate
      stepwise linear regression analyses will be performed in order to identify independent
      predictors for CRP and other dependent variables.

      Survival analysis will be performed to elucidate potential predictors of MACE using both
      fasting and postprandial values of the studies variables and gene polymorphisms.

      All tests will be two-sided. P-value will be considered statistically significant if <0.05.
      Data will be analyzed using STATA™ statistical software (Version 9.0, Stata Corporation,
      College Station, TX 77845, USA).

      Ethical Considerations The Ethics Committee of the each participating Hospital will approve
      the non interventional study. All participants will sign the written informed consent prior
      to participation in the study. The information protection rules in the National Institute for
      Health and Welfare (former National Public Health Institute to 2009) will be followed
      throughout the study.
    

Observational model: Other
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The study aims to recruit 1200 patients that are characterized either as high risk or
        very-high risk for Coronary Heart Disease. It is assumed that an equal number of high risk
        and very high risk patients will be included in the study. Patients will be invited to
        participate in the study from outpatient clinics in the 14 centers in Athens, Greece.