Endothelial Microparticles as Potential Biomarkers of Endothelial Dysfunction
Condition: Endothelial Dysfunction
Study type: Observational

Summary: 
      Endothelial microparticles (EMP) have a promising role as a diagnostic and prognostic tool in
      the assessment of endothelial function. This study compares the levels of EMP in
      hypercholesterolaemia patients before and after treatment with statins and correlates it with
      the current method of assessing endothelial function using pulse wave analysis.

      The current available methods to assess endothelial function are tedious and not suitable to
      be applied clinically. Detecting EMP levels are simpler as it only involves routine blood
      taking which is better tolerated by patients.

      Outcome from this study will contribute to finding a potential diagnostic, prognostic and
      treatment assessment tool that is suitable to be used clinically. This will have a large
      impact in the management of cardiovascular-related disease that is prevalent worldwide and
      increasing in the developed countries.
    

Detailed description: 
      General study objective

      To evaluate EMP as a simple diagnostic tool in assessing endothelial function in
      hypercholesterolaemic patients.

      Specific objectives:

        1. To compare the levels of EMP ( Cluster of differentiation (CD)144, CD62e and CD31+/42-)
           in hypercholesterolaemics before and after statin.

        2. To correlate the levels of EMP with the assessment of endothelial function using pulse
           wave analysis (PWA) in hypercholesterolaemics before and after statin.

      Research design

      It is a clinical cohort study involving newly diagnosed hypercholesterolemic patients before
      and after intervention with statin.

      Sampling method and subject recruitment Consecutive sampling of sampling frame will be
      applied due to limited number of sample who could fulfill the criteria within the planned
      data collection period.

      Data collection method

      Screening

      Before acceptance into the study, all potential subjects will undergo a screening procedure.
      A signed written informed consent will be obtained from the subjects before screening
      procedure is performed. The screening procedure will include detailed history taking on
      medical history, physical examination and 5 ml venous blood sampling for fasting lipid
      profile (FLP) from the antecubital vein.

      Clinical study session

      Once the FLP results are obtained, appointment to attend the clinical study sessions will be
      arranged with the eligible subjects who fulfil the criteria.

      Newly diagnosed hypercholesterolaemia patients recruited will undergo clinical study.

      First visit

      The first visit will involve blood taking for baseline values, assessment with SphygmoCor and
      consultation by the treating physician.

      During the first visit, 10 ml of venous blood will be withdrawn from the antecubital vein
      followed by the assessment of endothelial function, augmentation index (AI) and central
      arterial pressure (CAP) using SphygmoCor.

      Venous blood is needed for baseline full blood count (FBC), renal function test (RFT), liver
      function test (LFT), fasting blood sugar (FBS), high sensitivity C-reactive protein (hs-CRP)
      and EMP.

      Assessment of endothelial function, AI and CAP using SphygmoCor .

      Physician consultation

      During the first visit, all patients will be seen by the treating physician (a Family
      Medicine Specialist) at the outpatient clinic (KRK) and advised for therapeutic life style
      changes (TLC) as recommended by the Malaysian Clinical Practice Guideline (CPG) for
      Hyperlipidaemia (2011). Patients will be on TLC for a minimum duration of 6 weeks before the
      next visit.

      Second visit

      The second visit will only involve blood taking for FLP (5 ml blood) after at least 6 weeks
      duration of TLC.

      Third visit

      Once the FLP results are obtained (in approximately a week), patients will then be seen by
      the treating physician in the clinic.

      Patients who do not achieve the targeted LDL level after TLC and indicated for treatment will
      be prescribed with statin by the attending physician.

      Patients who achieve the targeted LDL level after TLC will continue TLC and will be excluded
      from the study

      Fourth visit

      The fourth visit will be arranged with the patients 3 months later. 10 ml of blood will be
      withdrawn for EMP quantification, FLP, hs-CRP and LFT. This will be followed by the
      assessments of endothelial function, AI and CAP as explained above.

      Fourth visit marks the end of the Study 2. Thereafter, patients will continue their treatment
      at the KRK.

      The study duration for each subject will be approximately 5 months.

      Patients that miss follow-up or not compliant to the medication prescribed will be excluded
      from the study analysis. However, this will not compromise the treatment received by patients
      as they will continue to be treated in KRK.
    

Intervention name(s): HMG-CoA Reductase Inhibitor
Intervention type(s): Drug
Other intervention name(s): statin
Intervention MeSH terms: Hydroxymethylglutaryl-CoA Reductase Inhibitors
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Newly diagnosed hypercholesterolemia