Hypertriglyceridaemia - cause and effects
Research type
Research Study
Full title
Abnormal Lipids: therapeutic targets, genetic causes and associated neuropathy
IRAS ID
104413
Contact name
Handrean Soran
Contact email
Sponsor organisation
Central Manchester University Hospitals NHS Foundation Trust
Research 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 hypertriglyceridaemia is associated with more significant nerve damage.3) Genetic screening arm:
Several genetic mutations have been identified to cause hypertriglyceridaemia.
Deficiency of the enzyme lysosomal acid lipase (LAL) results in Cholesterol Ester Storage Disease (CESD) and hypercholesterolaemia, hypertriglyceridaemia, and abnormal lipid deposition in organs. We wish to identify genetic mutations associated with severe hypertriglyceridemia and the prevalence of LAL deficiency in patients attending our tertiary referral centre.REC name
North West - Greater Manchester Central Research Ethics Committee
REC reference
13/NW/0297
Date of REC Opinion
14 Jun 2013
REC opinion
Further Information Favourable Opinion