Effect of n-3 Fatty Acid Supplementation in Hyperlipidemic Patients Taking Statins, on Lipid Profile, Including Small Dense LDL: A Randomized, Placebo-controlled, Double-blind Trial.

This study is a parallel randomised, double-blind placebo - controlled trial which was conducted in Istanbul, Turkey.

BACKGROUND

Cardiovascular disease (CVD) has been, and still is the number 1 cause of deaths all over the world. According to the World Health Organisation (WHO), 1 of every 3 death was caused by CVD in 2012. Heart disease and stroke were the No. 1 and No. 2 killers worldwide, according to American Heart Association. In Turkey, it is even worse, 40% of all deaths were caused by CVD. Such high prevalence naturally brings a huge disease burden and in many countries there are ongoing research to mitigate CVD risk.

It is essential to highlight that CVD is not a single disease, it is actually a family of diseases that mostly cause by a common pathology named "atherosclerosis". Atherosclerosis is plaque formation in artery walls which leads a reduced lumen diameter, causing organ damage or clinical events like myocardial infarction (MI), angina or stroke. One of the two reasons of atherosclerosis is hyperlipidemia, which is the theme of this study. Atherosclerosis and lipids are evident to be related; the elevations in circulating LDL cholesterol level plays a central role in atherogenesis, given the fact that they cause the formation of fatty plaque. Therefore, in all clinical guidelines, LDL level is the primary target to prevent atherosclerosis.However, more recent studies have revealed that LDL is structurally heterogeneous based on its size and density. There are large, buoyant LDL particles and small, dense LDL particles, which are believed to be more atherogenic. Individuals that have a large amount of small and dense LDL particles are at an increased risk of CV events, regardless of their total LDL level. In studies, small and dense LDL profile was associated with a three-fold to seven-fold increase in risk of CVD as they:1- Have the increased ability to penetrate arterial wall. 2- Are readily oxidized.

The main therapeutic approach to treat small&dense LDL is using drugs that lower serum triglyceride (TG) levels, as they also cause a change in the LDL size profile to larger, less dense and, therefore, less atherogenic species. Most commonly used such drugs are statins. Apart from statins, there is strong evidence that omega-3 fatty acids also have a beneficial effect in lowering TGs. However, their effect on small, dense LDL has not been studied enough yet. If omega-3 fatty acids have a beneficial effect in changing LDL profile to less dense and larger particles, omega-3 supplementation will be quite effective for patients with hyperlipidemia. Given the fact that statin use is the gold standard in all clinical guidelines, this study will not compare statins with omega-3 fatty acids and instead, compare statin monotherapy to the combined use of statin and omega-3 supplements to investigate whether omega-3 fatty acids have a supportive role to statin.