Hypertriglyceridaemia: Therapeutic Targets, Genetic Causes, and Associated Neuropathy
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.
• Therapeutic target arm
‣ Statin treated patients with and without hypertriglyceridemia.
⁃ Statin treated patients with type 2 diabetes.
⁃ Statin treated patients with CKD stages 4 and 5.
• Nerve function arm
• •Patients known to have severe hypertriglyceridaemia (defined as triglyceride \>5.5 mmol/l) but not known to have diabetes and matched controls.
• Genetic screening arm
‣ Patients with a documented triglyceride level of more than 10 mmol/l at any time.
⁃ Criteria for screening for FH and LAL deficiency include non-obese patients (BMI \<30) with low HDL-C (\<1.0 mmol/l male and \<1.3 mmol female), high triglycerides \>1.7 mmol/l, high total cholesterol \>6.2 or LDL cholesterol \>4.7 mmol/l; patients with raised liver alanine aminotransferase (ALT) (1.5 x above ULN) but no metabolic or viral disease or alcohol excess and patients diagnosed with NAFLD with or without hyperlipidaemia.