Cardiovascular disease (CVD) is associated with high levels of low-density lipoprotein (LDL)
cholesterol and low levels of high-density lipoprotein (HDL) cholesterol.
CVD results from 'hardening of the arteries' when there is a build-up of cholesterol in the
walls of blood vessels. LDL is the main carrier of cholesterol in the body. LDL particles are
responsible for transporting cholesterol that is deposited in vessel walls. LDL particles can
also be altered in structure and turn into an irritant to the vessel walls. The body responds
to the irritating effect of LDL by producing substances that result in inflammation. This
sequence of events eventually leads to the vessels becoming permanently damaged. HDL has a
protective role in CVD. It is associated with the enzyme paraoxonase which protects the body
from the damaging effects of altered LDL particles.
Nicotinic acid (niacin) has the ability to lower LDL levels and raise HDL levels thus
reducing the incidence of CVD. Our study aims to show that niacin not only has good effects
on cholesterol levels but is also able to reduce inflammation. Niacin is often poorly
tolerated due to flushing side effect. Tredaptive is a formulation that combines niacin with
laropiprant, an agent that reduces flushing hence improving tolerability and compliance.
Patients who are receiving cholesterol-lowering medication and whose LDL levels have not
reached the recommended target are recruited to the study. The study will be conducted at the
Manchester Royal Infirmary. The study has two consecutive 16 week periods. In each period
patients will be randomised to either tredaptive or placebo. They will attend for 5
monitoring visits. Apart from the first visit, fasting blood samples will be taken from them
during all subsequent visits.