[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › Lipoproteins, cardiovascular risk and lipid-lowering strategy # Lipoproteins, cardiovascular risk and lipid-lowering strategy How fats travel in the blood, why LDL and lipoprotein(a) build up in arteries, and how treatment is matched to a person's risk. Updated Nov 12, 2026 Cholesterol and triglycerides cannot dissolve in blood, so they travel in lipoprotein particles. Particles carrying apolipoprotein B, above all LDL, enter artery walls and drive atherosclerosis. Lipid-lowering treatment is chosen by the person's overall cardiovascular risk rather than by the cholesterol number alone, and the more LDL is lowered, the more risk falls. ## Key points - Chylomicrons carry dietary fat from the gut; VLDL carries fat made in the liver; lipoprotein lipase strips their triglycerides, leaving remnants and, from VLDL, LDL. - LDL is cleared mainly by liver LDL receptors; PCSK9 destroys these receptors, and statins raise their number. - HDL carries cholesterol back to the liver, but drugs that raise HDL have not reduced events. - Lipoprotein(a) is an LDL-like particle with apolipoprotein(a); its level is mostly inherited and barely changes with lifestyle. - Treatment intensity follows risk: people with established atherosclerotic disease, diabetes with other risk, very high LDL or familial hypercholesterolaemia get the most intense lowering. ## The lipoprotein particles - Chylomicrons: made in the intestine with apoB-48; carry dietary triglyceride and cholesterol. Lipoprotein lipase on capillary walls, activated by apoC-II, releases fatty acids to muscle and fat; the remnants are taken up by the liver through apoE. - VLDL: made in the liver with apoB-100; carries triglyceride made from excess calories, sugar and alcohol. Lipolysis turns it into IDL and then LDL. - LDL: the main cholesterol carrier; each particle has one apoB-100, which binds the LDL receptor on liver cells for clearance. - HDL: built from apoA-I; collects cholesterol from cells (through ABCA1) and returns it to the liver directly or via CETP transfer to apoB particles. - Lipoprotein(a): an LDL particle with apolipoprotein(a) attached to its apoB-100; it promotes both atherosclerosis and, through its resemblance to plasminogen, possibly thrombosis. ## How LDL is controlled Liver cells make cholesterol through the HMG-CoA reductase pathway and take up LDL through LDL receptors. When cell cholesterol falls, SREBP-2 switches on more receptors, so blood LDL drops; this is how statins work, and why ezetimibe (which blocks intestinal cholesterol uptake via NPC1L1) and bempedoic acid add to them. PCSK9 binds the receptor and sends it to be destroyed instead of recycled: antibodies such as evolocumab and alirocumab, and the siRNA inclisiran, block PCSK9 and lower LDL further. Familial hypercholesterolaemia, caused by variants in LDLR, APOB or PCSK9 and affecting roughly one person in every 200 to 250, gives high LDL from birth and early heart disease. ## Triglycerides and HDL High triglycerides come from obesity, insulin resistance, diabetes, alcohol, some drugs and genetic defects in lipolysis. Very high levels risk acute pancreatitis; moderate elevation marks remnant particles that also add to atherosclerosis. Fibrates (PPAR-alpha agonists) and omega-3 fatty acids lower triglycerides, and icosapent ethyl is approved to reduce cardiovascular events in selected high-risk patients already on a statin. Low HDL marks risk, but raising HDL with niacin or CETP inhibitors did not reduce events, so HDL is not a treatment target. ## Lipoprotein(a) Lp(a) levels are set mainly by variation in the LPA gene, and NHLBI describes elevated Lp(a) as likely the leading inherited cardiovascular risk factor, with an estimated 20 to 30 percent of people worldwide having raised levels. Because levels are stable, a single measurement is generally enough; it helps explain heart disease in young people or in families, and pushes doctors to control other risk factors more tightly. Statins do not lower it, PCSK9 inhibitors lower it modestly, apheresis removes it, and drugs that block its production are in trials. ## Risk assessment and treatment targets Guidelines group patients by risk. Secondary prevention (after a heart attack, stroke or with peripheral artery disease) and familial hypercholesterolaemia justify the most intense LDL lowering. In primary prevention, risk calculators combine age, sex, blood pressure, cholesterol, diabetes and smoking to estimate risk over the next years, and risk enhancers such as chronic kidney disease, family history, inflammatory disease, high Lp(a) or coronary calcium can tip the decision. The response to treatment is checked by the percentage fall in LDL and, in many guidelines, by LDL goals that are lower the higher the risk; non-HDL cholesterol or apoB help when triglycerides are high. - Lifestyle for everyone: less saturated and trans fat, more fibre, activity, weight control, no tobacco. - First drug: a statin, at high intensity in the highest-risk groups. - If LDL stays above goal: add ezetimibe, then a PCSK9 inhibitor, or use bempedoic acid when statins are not tolerated. - A repeat lipid test after starting or changing treatment, together with a check on adherence, shows whether the goal is reached. ## Memory aid B is for Bad: every apoB particle (LDL, VLDL remnants, Lp(a)) can enter the artery wall. ## Test yourself Think of the answer, then tap the question to see it. ## What enzyme releases fatty acids from chylomicrons and VLDL, and what activates it? Lipoprotein lipase on capillary walls, activated by apolipoprotein C-II. ## How do PCSK9 inhibitors lower LDL? PCSK9 sends LDL receptors to be destroyed; blocking it lets receptors recycle to the liver surface and clear more LDL from the blood. ## Why is lipoprotein(a) usually measured only once? Its level is set mostly by the LPA gene and changes little over life or with lifestyle, so one value describes inherited risk. ## Why is HDL not a treatment target? Low HDL marks risk, but drugs that raised HDL, such as niacin and CETP inhibitors, did not reduce cardiovascular events. ## Which patients receive the most intense LDL lowering? Those with established atherosclerotic disease, familial hypercholesterolaemia or other very high-risk profiles, such as diabetes with organ damage. [Add to my cards (5)](https://durgical.app/estudiar/?add=/en/pharmacology/topics/lipoproteins-cardiovascular-risk-and-lipid-lowering-strategy/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## Example drugs - [Atorvastatin](https://durgical.com/en/pharmacology/atorvastatin/) - [Rosuvastatin](https://durgical.com/en/pharmacology/rosuvastatin/) - [Ezetimibe](https://durgical.com/en/pharmacology/ezetimibe/) - [Evolocumab](https://durgical.com/en/pharmacology/evolocumab/) - [Alirocumab](https://durgical.com/en/pharmacology/alirocumab/) - [Inclisiran](https://durgical.com/en/pharmacology/inclisiran/) - [Fenofibrate](https://durgical.com/en/pharmacology/fenofibrate/) - [Icosapent ethyl](https://durgical.com/en/pharmacology/icosapent-ethyl/) ## Connections ## Related classes 6 - [Statins](https://durgical.com/en/pharmacology/classes/statins/) - [Cholesterol absorption inhibitors](https://durgical.com/en/pharmacology/classes/cholesterol-absorption-inhibitors/) - [PCSK9 inhibitors](https://durgical.com/en/pharmacology/classes/pcsk9-inhibitors/) - [Bile acid sequestrants](https://durgical.com/en/pharmacology/classes/bile-acid-sequestrants/) - [Fibrates](https://durgical.com/en/pharmacology/classes/fibrates/) - [Prescription omega-3 fatty acids](https://durgical.com/en/pharmacology/classes/prescription-omega-3-fatty-acids/) [← All of pharmacology](https://durgical.com/en/pharmacology/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [Blood Cholesterol - Treatment | NHLBI, NIH](https://www.nhlbi.nih.gov/health/blood-cholesterol/treatment) (National Heart, Lung, and Blood Institute, 2026); [Lipoprotein(a): What to know about elevated levels](https://www.nhlbi.nih.gov/news/2024/lipoproteina-what-know-about-elevated-levels) (National Heart, Lung, and Blood Institute, 2024); [Familial hypercholesterolemia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/familial-hypercholesterolemia/) (MedlinePlus Genetics (U.S. National Library of Medicine), 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/topics/lipoproteins-cardiovascular-risk-and-lipid-lowering-strategy/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/topics/lipoproteins-cardiovascular-risk-and-lipid-lowering-strategy/