What is Hypercholesterolaemia ?
Hyperlipidemia or hypercholesterolaemia is defined as an excess amount of lipoprotein in the blood. This can be caused by excess production of lipoprotein, especially when the amount of fats consumed is high, or defective removal of lipoproteins, or a combination of these two.
Lipoprotein :- Lipoproteins are macromolecules of lipids that circulate in the plasma. The various types of lipoproteins are separated by density.
The largest and least dense of those lipoproteins are the chylomicrons.
As you move down the list from VLDLs to HDLs, the lipoproteins become smaller and more dense.
Each lipid is made up of :-
The least dense lipoproteins contain the highest proportion of triglyceride to apoprotein ratio.
Therefore, HDL has the least amount of triglyceride and the most amount of apoprotein. LDL and HDL are the most relevant in clinical practice.
There are certain factors that place individuals at increased risk of having elevated cholesterol levels.
Advanced age and male gender are associated with increased risk of hypercholesterolemia. In addition, positive family history, tobacco use, hypertension, and diabetes are all associated with similar increased risk.
Finally, there are several genetic disorders of lipid metabolism.
Listed here are several of the more common types of genetically inherited disorders that lead to elevated cholesterol levels:-
1) Familial hypercholesterolaemia: in it there’s a defect in the gene that encodes for the LDL receptor, which leads to reduced clearances of LDL from the circulation. A defect in the apoB-100 ligand on the LDL particle impairs binding of LDL to its receptor, also leading to reduced clearance of LDL from the circulation in familial defective apolipoprotein B-100.
2) PCSK9 gene mutation:- it leads to reduced expression of the LDL receptor and, therefore, increased LDL in the circulation.
3)Familial combined hyperlipidemia:- it is associated with overproduction of apoB-100. This leads to increased levels of apoB, triglycerides, and reduced HDL. And this disorder is associated with a threefold increased risk of coronary heart disease.
4) Hyper apo beta lipoproteinemia:- it is a disorder in which there’s overproduction of apoB.
5)polygenic hypercholesterolemia:- in it there are multiple abnormalities in LDL metabolism leading to elevated total cholesterol.
6) small, dense LDL disorder:- it is associated with increased triglycerides and apoB.
Patients with hyperlipidemia may be completely asymptomatic without any evidence of elevated cholesterol on examination. However, there are certain physical findings that, when present, should be suggestive of elevated cholesterol. For example:-
- On skin examination, xanthomas can be seen. These are cutaneous or even subcutaneous papules, plaques, or nodules that are made up of lipid-laden histiocytes.
- These can be seen within tendons, at extensor surfaces of joints, pressure areas, within skinfolds or scars, or even on eyelids.
- Gray-white corneal rings, also called arcus corneae, can be seen.
- Lipemia retinalis is a cream-colored discoloration of the retinal vessels that’s associated with elevated chylomicrons.
- Other possible manifestations include pancreatitis, which is most commonly associated with very high triglyceride levels
- As well as aortic stenosis and the metabolic syndrome.
- Atherosclerosis is the most dreaded but common manifestation of hypercholesterolemia.
There are multiple health agencies that publish guidelines for screening for hyperlipidemia. In general, screening should begin once an individual is in his or her 20s. A lipid profile should be obtained approximately once every five years.
However, those with borderline elevated cholesterol levels should have a lipid profile checked more frequently, approximately once every one to two years. In addition, individuals being treated for hypercholesterolemia need to have follow-up labs checkups to determine the efficacy of the interventions implemented. Goal lipid levels vary depending on medical comorbidities.
In assessing an individual patient, one must determine the patient’s risk for coronary heart disease. While previous myocardial infarction, known atherosclerosis, and angina can be considered indicative of coronary heart disease, other disorders can be considered equivalent.
Non-coronary forms of atherosclerotic disease include :-
- peripheral arterial disease,
- abdominal aortic aneurysm,
- symptomatic carotid artery stenosis
- chronic kidney disease with creatinine levels of above 1.5.
Risk factors that are crucial in establishing an individual’s risk also include :-
- Old age
- Gender( males are more prone to hyper lipedema)
- Smoking history
- Low HDL level
- Low activity level
An HDL level below 40 is considered a significant risk factor, a level above 60 is considered protective and is counted as a negative risk factor.
An individual’s risk should be calculated using the Framingham Risk Score, which utilizes data from the Framingham Heart Study in order to determine the 10-year risk of having a cardiovascular event. Online calculators can help to use patient information and to determine this Framingham Risk Score.
Interventions for elevated cholesterol fall into three categories–
- Dietary changes
- Increased exercise
- Oral medications.
Decreased intake of saturated fats is the primary dietary recommendation. Exercise can help to raise HDL and even lower triglycerides. But it does not have much effect on LDL levels.
Treatment of hypercholesterolaemia
Many types of drugs can help to reduce cholesterol levels:-
1)Bile acid resins bind bile acids and help to upregulate LDL receptors. They can cause constipation and abdominal discomfort, but are helpful in achieving a reduction in LDL of approximately 10% to 20%.
2)Nicotinic acid, also known as niacin, decreases hepatic synthesis of VLDL, increases synthesis of HDL, and inhibits glycolysis in adipose tissue, and increases lipase activity. While this is helpful in reducing LDL and increasing HDL, use is often limited by the severe side effects of flushing.
3) HMG-CoA reductase inhibitors, more commonly known as statins, inhibit the rate-limiting enzyme in the synthesis of cholesterol.
4)Fibric acid derivatives increase lipolysis and decrease VLDL synthesis, and are effective in reducing LDL and triglyceride levels.
5)Fish oil is another agent that helps to decrease synthesis of VLDL.
6)Statins are the most evidence-based medications for hypercholesterolemia. They’re very effective in reducing LDL by up to 60% and have been shown to prevent cardiac events. However, the most life-threatening and limiting side effects of statin therapy include myositis and even rhabdomyolysis.
Note:- All patients on statin therapy should have liver function test and creatinine kinase levels monitored for signs of muscle injury.
LDL goal depends on an individual’s risk factors for coronary heart disease.
Dietary changes, increased exercise, and smoking cessation should all be recommended whenever the LDL level is above goal.
However, the decision of when to initiate lipid-lowering medication is dependent on the number of risk factors that a patient has and their Framingham Risk Score.
In summary, hypercholesterolaemia is a significant disease due to the medical implication, especially the risk of cardiovascular disease. A patient should be evaluated to determine his individual risk of coronary heart disease. And this risk helps to determine when lifestyle changes alone can help to meet LDL goal or whether lipid-lowering medication is needed.