Cholesterol
Your liver regulates cholesterol production and metabolism. Dietary saturated fats and cholesterol decrease the activity of LDL receptors and impair the ability of the liver to remove LDL from the blood. Cholesterol is carried in your bloodstream by lipoproteins. There are two important cholesterol-carrying lipoproteins in the blood.
High-density lipoprotein cholesterol (HDL-C) normally makes up about 20-30 % of the total cholesterol carried in the blood. High-density lipoproteins (HDL) pick up cholesterol from the walls of the arteries and take it back to the liver for recycling or for excretion into bile.
A low level of HDL-C is associated with an increased risk for cardiovascular disease. However, a high level of HDL-C is also associated with increased risk of cardiovascular disease. For this reason, the total cholesterol/HDL-C ratio is no longer used for risk prediction.
Low density lipoprotein cholesterol (LDL-C) usually makes up about 60-70 % of the total cholesterol carried in the blood. LDL-C delivers cholesterol to the walls of your arteries. This build up is known as plaque and it causes thickening of the walls of the arteries (atherosclerosis). Over time, the cholesterol-rich plaque bulges into the lumen of the artery, accumulating more and more LDL-C. Eventually, the arteries become so narrowed that blood flow is slowed down or blocked. When this happens, you may suffer angina (chest tightness or discomfort in your left arm or jaw due to poor blood flow in the heart muscle). If a cholesterol-rich plaque ruptures, the artery may become completely blocked by a blood clot and you may suffer a heart attack.
Intensive reduction of LDL-C reduces the cholesterol content of plaque, increased plaque stability and a reduced likelihood of plaque rupture. Overall, this reduces the risk for a heart attack. In addition, lowering LDL-C by statin therapy appears to improve the ability of blood vessels to dilate, improving blood flow to the heart.
Non-HDL-cholesterol
If we subtract HDL-C from the total cholesterol we will have a measure of the amount of apoB-containing lipoprotein particles that transport cholesterol to the walls of the arteries. This measure is termed non-HDL cholesterol (non-HDL-C). Non-HDL-C is a better marker of risk of heart disease AND the best cardiovascular risk predictor.
Triglycerides
High levels of blood triglycerides (TG), are also a risk factor for heart disease if non-HDL-C levels (total cholesterol – HDL-C) levels are elevated. Fasting blood triglyceride levels above 10 mmol/L increase your risk of pancreatitis (a serious inflammation of the pancreas). To avoid pancreatitis, severely elevated triglyceride levels require treatment even if you have no other risk factors for heart disease. Successful treatment requires optimal blood sugar control if you have diabetes, weight loss, alcohol and refined carbohydrate restriction and avoidance of oral estrogen and retinoids.
Lipoprotein(a)
Lipoprotein(a) – also known as Lp(a) – is a cholesterol- carrying particle in your bloodstream that is genetically determined (inherited). High levels of Lp(a) promote cholesterol build-up in your arteries and calcification of the aortic valve. Lp(a) levels greater than 100 nmol/L are associated with an increase in the risk of heart disease and stroke. The risk increases proportional to the level of Lp(a). Because Lp(a) levels are dependent on genetics, lifestyle changes have no effect on reducing Lp(a). Your Lp(a) measurement can help your doctor determine whether earlier treatment of other heart disease risk factors is indicated. An Lp(a) above 100 nmol/L may indicate that a LDL-C lowering drug is warranted even if you have a borderline elevation in LDL-C.
New therapies that effectively lower Lp(a) (Pelacarsen, Olpasiran, Lepodisiran) are currently undergoing clinical trials.