Clinical Trial: Hypertriglyceridaemia - Cause and Effects

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Hypertriglyceridaemia: Therapeutic Targets, Genetic Causes, and Associated Neuropathy

Brief Summary:

  1. At target LDL-C levels, apoB100 concentrations will be higher than recommended levels in the following populations:

    1. Tertiary centre lipid clinic patients with raised TG treated with statins.
    2. Patients with type 2 diabetes treated with statins.
    3. Patients with Chronic Kidney disease (CKD) stages 4 and 5 treated with statins.
  2. Despite achieving LDL-C and non-HDL-C targets, a significant number of statin-treated patients have residual cardiovascular risk related to raised hsCRP. The relationship between hsCRP and Lp-PLA2 (markers of inflammation) and LDL particle number measured by apoB100 is stronger than that of measured and calculated LDL and non-HDL. In statin treated patients there will be higher levels of hs-CRP and Lp-PLA2 in patients achieving LDL targets but not apo B targets.
  3. We hypothesise that non-diabetic patients with severe hypertriglyceridaemia (fasting serum triglyceride >5.5 mmol/l) have evidence of greater nerve damage compared with matched controls.
  4. LAL deficiency is underdiagnosed in patients with severe hypertriglyceridaemia, low HDL-C, hyperlipidaemias, non alcoholic fatty liver disease and idiopathic high liver enzymes.

Detailed Summary:

Fats are present in the body in the form of lipid particles containing cholesterol and triglycerides. Lipid particles can deposit in blood vessels, forming atheromas, blocking blood vessels and leading to heart attacks and strokes. These harmful particles are termed 'atherogenic' particles. Low density lipoprotein (LDL) is the major atherogenic particle. Each atherogenic particle has a protein associated with it called apolipoprotein B (apoB). Cholesterol, triglycerides, and apoB levels can be measured in the laboratory. In this study we focus on patients with raised levels of triglycerides (hypertriglyceridaemia).

We will recruit patients with hypertriglyceridaemia to look at (1) therapeutic targets, (2) genetic causes, and (3) associated neuropathy in these patients.

  1. Therapeutic target arm:

    LDL-cholesterol (LDL-C) is the primary target for lipid-lowering drugs. A drug (commonly a statin) is effective when it lowers LDL-C. Patients with diabetes, chronic kidney disease and hypertriglyceridaemia on statins may have normal levels of LDL-C; but because the size of LDL particles in these patients is smaller, they may in fact have raised levels of apoB and therefore remain at cardiovascular risk. Thus, measurement of apoB may be a better target for treatment because it measures 'atherogenic' particle numbers. Since atheromatous disease is an inflammatory disease, we will also investigate if residual risk may be correlated with inflammatory markers, such as hsCRP and Lp-PLA2.

  2. Hypertriglyceridaemia and nerve function arm:

    We aim to demonstrate that severe hypertriglyc
    Sponsor: Central Manchester University Hospitals NHS Foundation Trust

    Current Primary Outcome: Measurement of ApoB in specified patient populations to gauge cardiovascular risk. [ Time Frame: 1 day. ]

    Residual risk due to the presence of sd-LDL and reflected in a discrepancy between apoB and cholesterol indices is correlated with hs-CRP.


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: Central Manchester University Hospitals NHS Foundation Trust

    Dates:
    Date Received: July 10, 2014
    Date Started: January 2014
    Date Completion: February 2025
    Last Updated: January 28, 2016
    Last Verified: January 2016