**11. Epidemiology**

More than 30% of worldwide deaths are thought to be cardiovascular based and the frequency tends to increase due to changes in lifestyle and prolonged life. According to AHA 2016 statistics, in the United States, one in every 42 seconds loses his/her life due to cardiovascular reasons [19]. In Europe, the cardiovascular mortality rate is 4.1 million a year. A total of 1.8 million deaths, in other words 20% of all deaths, are due to ischemic heart disease. This is followed by cerebrovascular events with an annual death of 1.1 million. According to ESC data, 1.5 million deaths before the age of 75 and 710,000 deaths before the age of 65 are cardiovascular sources; half is due to coronary artery disease [20]. Deaths in all age groups, 51% of women and 42% of men are cardiovascular.

## **12. Coronary artery disease and cholesterol**

Acute coronary syndrome is a clinical event that occurs when the coronary blood flow is reduced by thrombus on the rupture plaque and the myocardial oxygen requirement cannot be met. Acute coronary syndrome is broad spectrum which contains STEMI, nonSTEMI, unstable angina pectoris, and sudden cardiac death. In many cases, the thrombosis process begins with plaque rupture. Up to 25% of cases of acute coronary syndromes can begin with plaque erosion. Lymphocyte and macrophage activation and the inflammatory response is accompanied by atherothrombosis. There are clinical differences according to coronary collateral reserve and obstruction severity. This process occurs after a plaque rupture and is called Type 1 MI.

Atherosclerotic plaques that play an essential role in acute coronary syndrome are divided according to their structural characteristics: Plaque structure is with thin fibrous cap, dense necrotic core, high inflammatory cell density, and low smooth muscle content; it is called vulnerable plaque. Vulnerable plaque increases with hypertension, diabetes mellitus, elevated LDL, decreased HDL, and elevated ACE. Conversely, stabilized plaques with thick fibrous caps, poor necrotic cells, and dense extracellular matrix with low inflammatory content are observed in individuals with low risk factors (**Figure 1**).

**Figure 1.** Structural differences between vulnerable and stable plaques.

In a meta-analysis involving 90,056 patients, a reduction of 38.6 mg/dl in LDL was shown to be associated with a 20% reduction in major cardiovascular events [21]. In MIRACLE study: increased plaque stability with statin therapy reduces death, incidence of acute coronary syndrome and frequency of recurrent coronary ischemia [13]. In the PROVE IT TIMI-22 trial, atorvastatin 80 mg and pravastatin 40 mg were compared and it was determined that highdose statin therapy was more effective than low-dose statin therapy in reducing cardiovascular events. The 2017 ESC STEMI guidelines recommended that high-dose statin therapy was independent of cholesterol level. In the FOURIER study, it has been shown that the addition of the evolocumab in patient with LDL level ≥ 70 mg/dl, despite the use of high dose statin, is associated with a decrease in cardiovascular deaths [22].
