High Blood Cholesterol

Cholesterol is a waxy, fatty substance found in the cell walls of various organs in our body, from the nervous system to the liver to the heart. Our body uses cholesterol to make hormones, bile acids, vitamin D and other substances.

The liver produces most of the cholesterol found in the body; the rest of the cholesterol comes from the food we eat. Dietary cholesterol comes only from foods of animal origin, such as liver and other meats, seafood, egg yolks (but not the whites, which have no cholesterol), and whole milk dairy products including butter, cream and cheese.

Cholesterol circulates in the bloodstream in compounds known as lipoproteins, which are combinations of cholesterol and protein. There are two main types of lipoproteins:

Low-density lipoprotein (LDL)

Commonly known as “bad” cholesterol as they carry cholesterol to tissues via blood vessels and arteries. This “bad” cholesterol can build up with other substances in the inner walls of arteries and cause narrowing and hardening of the blood vessels, a condition known as atherosclerosis. The fatty deposits may also come loose and cause blood clots, resulting in a stroke or a heart attack.

High-density lipoprotein (HDL)

Also known as “good” cholesterol as they remove LDL cholesterol from the tissues to the liver, where it is metabolised and removed from the body.

Human beings are generally born with low cholesterol levels which increase with age and eating habits. The LDL cholesterol levels of human newborns are at 30 to 70 mg/dL and typically rise above 100 mg/dL by age 20. While most of one’s blood cholesterol still comes from his own production in the liver, dietary consumption patterns do shape the cholesterol level, particularly with a cholesterol-rich and fatty diet.

What is High Blood Cholesterol?

High blood cholesterol occurs when your levels of total cholesterol or LDL cholesterol is too high, while HDL cholesterol is abnormally low.

Classification of Total, LDL and HDL Cholesterol and Triglyceride Levels

Total Blood Cholesterol (mmol/L [mg/dL])
<5.2 (200)	Desirable
5.2 – 6.1 (200 – 239)	Borderline high
≥6.2 (240)	High

LDL Cholesterol (mmol/L [mg/dL])
<2.6 (100)	Optimal
2.6 – 3.3 (100 – 129)	Desirable
3.4 – 4.0 (130 – 159)	Borderline high
4.1 – 4.8 (160 – 189)	High
≥4.9 (190)	Very high

HDL Cholesterol (mmol/L [mg/dL])
<1.0 (40)	Low
1.0 – 1.5 (40 – 59)	Desirable
≥1.6 (60)	Optimal

Triglyceride (mmol/L [mg/dL])
<1.7 (150)	Optimal
1.7 – 2.2 (150 – 199)	Desirable
2.3 – 4.4 (200 – 399)	High
≥4.5 (400)	Very high

According to the National Population Health Survey 2024, the prevalence of high blood cholesterol among Singaporeans decreased from 31.9% in 2021-2022 to 30.5% in 2023-2024. The mean LDL-cholesterol level among the newly diagnosed was 4.6 mmol/L.

High blood cholesterol level is a major risk factor of heart disease and plays a significant role in the development of atherosclerotic disease. People above 40–50 years old develop high blood cholesterol as a result of environmental factors and typically develop heart disease by the age of 70, that is 20 years of exposure to high blood cholesterol.

Patients who are born with genetically high blood cholesterol conditions (for example homozygous familial hypercholesterolemia) can even develop coronary artery disease in their teenage years (average 12.5 years).

Desirable Cholesterol Levels

Cholesterol in mmol/L (mg/dl)	Average Adult (without known coronary risk factors)	Adult with heart disease/diabetes/other coronary risk factors
LDL Cholesterol	< 3.4 (130)	< 2.6 (100)
HDL Cholesterol	≥ 1.0 (40)	≥ 1.0 (40)
Total Cholesterol	< 5.2 (200)	< 4.1 (160)

Symptoms

High blood cholesterol has no symptoms and we will not know when the level is high. High blood cholesterol increases your risk for heart disease.

Causes of High Cholesterol

The two main factors of high blood cholesterol are genetics and lifestyle.

1. 1. Genetics

Some patients are born with high blood cholesterol levels (familial hypercholesterolemia) and have a strong family history of premature coronary artery disease (men developing disease at <50 years old and women at <60 years old).

Familial Hypercholesterolemia

Familial Hypercholesterolemia (FH) is an inherited high blood cholesterol condition passed down through families, caused by one or more abnormal genes. In FH patients, the liver is unable to remove excess LDL cholesterol, resulting in exposure to extremely high levels of blood cholesterol from young age.

FH affects 1 in 300 people, which translates to approximately 20,000 patients in Singapore. However, more than 90% are unaware of this condition and remain undiagnosed.

The condition is suspected when:

1. 1. • Adults have LDL-C of 190 mg/dL (>4.9 mmol/L) and children >155 mg/dL (>4.0mmol/L)
      • Family history of high blood cholesterol level, premature coronary artery disease (male: <55 years old; female: < 65 years old) and stroke etc.

It can be confirmed by genetic testing although the types of mutations do not matter when it comes to treatment strategies.

FH can lead to early heart disease, the leading cause of death in Singapore. If left untreated, men with FH have a 50% risk of having heart disease by age of 50; women with FH have a 30% risk of having heart disease by age of 60.

Early diagnosis can allow affected individuals and their family members to start treatment early and ultimately reduce the risk of getting an early heart attack. Screening of family members or cascade screening is recommended following diagnosis of any index case of FH. Such patients will always need medications to control their blood cholesterol levels and close surveillance of their health conditions.

1. 1. Unhealthy lifestyle

Unhealthy lifestyle factors such as poor dietary habits, obesity, lack of exercise, smoking and excessive alcohol consumption contribute to high blood cholesterol.

Dietary cholesterol comes only from foods of animal origin, including meat, seafood, poultry, egg yolks and diary products. Studies have shown that compared to dietary cholesterol, fats in our diet have a larger effect on blood cholesterol levels. Limit or avoid consuming too much saturated fats (found in fatty cuts of meat, coconut oil, coconut cream, palm oil, full-fat diary products) and trans fat (found in cakes, cookies, processed foods, deep-fried foods and products containing vegetable-shortening and hydrogenated/partially hydrogenated oils).

Too much alcohol can also cause an increase in levels of blood cholesterol and triglycerides, another fat component in the blood.

1. 1. Ageing

Ageing can cause blood cholesterol levels to be raised because the liver is less able to remove the bad cholesterol from the body.

1. 1. Other Medical Conditions

Some medical conditions such as diabetes mellitus, chronic kidney disease and hypothyroidism can also cause one’s cholesterol level to be elevated.

While some medicines may raise blood cholesterol levels (for example steroids, beta-blockers, diuretics etc), their impact is limited and may be easily reversed. You can discuss with your personal physician regarding the alternative treatments available.

Complications of Uncontrolled High Blood Cholesterol

Heart disease, stroke and peripheral artery disease (blockage of arteries in the lower limbs)

The higher the levels and the longer a patient’s exposure to an elevated blood cholesterol level, the higher the risk of cardiovascular disease.

As blood cholesterol builds up in the coronary arteries of the heart over time, it results in “plaque” formation, which narrows blood vessels and hardens the arteries, a condition known as atherosclerosis. When the arteries that supply blood to your heart become narrowed (generally more than 70% diameter narrowing), blood flow to the heart becomes compromised, and coronary artery disease is the result. When the same disease process affects the brain, it results in cerebrovascular disease.

As the disease process advances, blood clot formation may occur within the arteries and block off the blood supply to the heart and brain, resulting in what is known clinically as acute myocardial infarction (heart attack) or stroke if it involves the brain (‘brain attack’).

Among close to 12,000 cases of heart attacks in Singapore in 2020, high blood cholesterol level was the second most common risk factor, after high blood pressure, found in 73.3% of patients.

Patients who have established heart disease are at the highest risk of developing recurrent events, the incidence being about 20% in the ensuing 5 years. It is important that the LDL cholesterol of these patients be lowered to at least below 70mg/dL (or 1.8mmol/L).

When to see a doctor?

You should seek a doctor’s consultation when your LDL cholesterol level is higher than 160mg/dL (4.1 mmol/l).

Should your doctor consider you to be at moderate risk for heart attacks because of your concurrent risk factors such as diabetes mellitus, hypertension, kidney disease etc; or if you already have established cardiovascular disease, he will prescribe you medicines, which you should not resist taking. These medicines can lower your chance of heart attack by 30% to 40% and are safe with a low incidence of short- or long-term side effects. They are literally lifesaving medicines.

Most guidelines would recommend that cholesterol-lowering therapies be started in the following 4 groups of people:

1. Established atherosclerotic cardiovascular disease (ASCVD) – that is the person has pre-existing blockages of the coronary (heart), cerebral (brain) or any arteries in the body circulatory system
2. Diabetes mellitus, especially those with a prolonged duration of more than 10 years
3. LDL cholesterol level of >190 mg/dL (4.9 mmol/L)
4. People with no established cardiovascular disease, but have multiple risk factors that increase their chances of developing the condition in future.

In addition, if you have higher risk features such as strong family history, smoking history, obesity or have diabetes mellitus or hypertension. Your doctor may want to check your blood cholesterol level more regularly and be more aggressive in treatment.

Routine health screening

It is recommended for men and women aged 40 years and older to routinely screen for lipid disorders. This can be carried out even as young as 18 years of age if a person has other risk factors such as a family history of premature coronary death, smoking, obesity, diabetes mellitus etc.

Managing High Blood Cholesterol

Lowering blood cholesterol levels prevents disease in both normal people without any established cardiovascular disease (primary prevention) as well as in high-risk patients who have previous heart attacks, strokes, or have undergone coronary stenting or coronary artery bypass operations (secondary prevention).

Dietary cholesterol and fat restriction can at best lower blood cholesterol by up to 20%. The rest of your blood cholesterol (80%) comes from your own body production in the liver. Therefore, it is not surprising that to lower cholesterol to target levels, one will have to rely on a combination of lifestyle changes and medications.

Lifestyle Changes

There are a number of lifestyle changes in the form of diet and exercise that can be undertaken first to control bad cholesterol levels. These include:

1. 1. Reduce consumption of bad fats

Foods rich in saturated fat and trans fat such as fatty cuts of meat, coconut oil, coconut cream, palm oil, full-fat dairy products, baked products, deep-fried food can raise LDL cholesterol levels, increasing our risk for cardiovascular disease.

Replace them with foods higher in monounsaturated and polyunsaturated fats, such as extra virgin olive oil, sunflower, flaxseed, corn, olives or soybean, which have been shown to reduce LDL-C levels.

Fish — such as salmon, tuna, sardines, Spanish mackerel and herrings can be an excellent source of protein, and they contain unsaturated fats, such as Omega-3 fatty acids, which is beneficial for the body.

Focus on a low-fat diet. Take lean proteins such as fresh lean meat (e.g., chicken breast), fish and add more soluble fibre to your diet from fruit, vegetables, and whole-grains like oatmeal.

Follow the Singapore Heart Foundation’s ‘Heart Smart Eating Plate’ to get a balanced diet, maximise nutrient intake and practice portion control to prevent excessive weight gain and reap benefits for your heart.

1. 1. Exercise Regularly

Aim for 150 – 300 minutes of moderate-intensity aerobic physical activity each week. Incorporate muscle and bone strengthening activities (e.g., weight training, pilates, body weight calisthenics) at least 2 times per week.

Regular physical activity may increase HDL modestly and contribute to the reduction of LDL cholesterol and triglycerides.

It is advised for people with abnormally high cholesterol levels to engage in regular moderate-intensity exercise for more than 30 min/day, even if they are not overweight. This is for enhancement of their overall health and to improve the control of other concurrent cardiovascular risk factors such as high blood pressure and diabetes mellitus.

1. 1. Reduce alcohol intake

Alcohol is high in calories and sugar and has a potent effect on triglycerides. If you drink, do so in moderation. Have no more than one standard drink a day for women and two drinks a day for men.

A standard drink refers to:

1. • ⅔ can (220ml) of beer
   • One glass (100ml) of wine
   • One glass (30ml) of spirit

Medical Treatment

The medications for high blood cholesterol can broadly be divided into 2 categories: (1) Oral cholesterol medications (2) Injectables.

Oral Medicine

1. 1. Statins

Statins are the most commonly prescribed medications to lower blood cholesterol and decrease your risk of dying especially if you’re in one of the high-risk groups. It is the first-line therapy for patients with high blood cholesterol. The examples of statins used extensively in Singapore include simvastatin, lovastatin, atorvastatin and rosuvastatin.

They work in the liver to prevent blood cholesterol from forming and reduce the amount of blood cholesterol circulating in the blood. They are most effective at lowering LDL (bad) cholesterol, but also help to lower triglycerides and raise HDL cholesterol. This drug class has unfortunately received the most misinformation on social media but is proven to be effective in preventing heart attacks, strokes and death, even among low-risk patients.

They are well tolerated although a few patients may complain of side effects.

Some patients (about 5%) may experience statin-associated side-effects such as muscle aches, and about 5% of these patients may discontinue medication owing to adverse effects. Liver inflammation can occur in a small number of patients (<1%). These are rare and can often be overcome by lowering the dose or switching to another statin without the need to stop the medicine completely. Patient education is important because many patients do not understand the risk of LDL-C and heart disease, have a strong belief in lifestyle modification alone, or have unfounded fears of statin-associated side-effects and are concerned with cost.

1. 1. Ezetimibe

A common medicine that is often prescribed with statin to lower bad cholesterol is ezetimibe. This medicine works by preventing the absorption of blood cholesterol from the gut. The combination of statin and ezetimibe can bring about a 50% reduction in the LDL level (‘bad’ cholesterol).

1. 1. Oral Fibrates

Those patients with high triglyceride levels can benefit from taking oral fibrates, examples include fenofibrate and gemfibrozil. Should this therapy be insufficient, one can also add on prescription-strength Omega-3 fatty acid (fish oil) at higher doses than those marketed as supplements.

Injectables

A new class of injectables have emerged in recent years which provide an alternative for patients who are unable to achieve target LDL-C levels, statin-intolerant, or are unable to adhere to regular therapies. Injectables have the advantage of improving patients’ drug compliance.

The injectables can be used in combination with oral medicines to lower LDL-C. Oral medicines alone can lower LDL-C cholesterol levels by 65% but in combination with injectables, this can rise to 85%. The downside is that it is a costly medicine.

1. 1. PCSK9 inhibitors

PCSK9 inhibitors are monoclonal antibodies administered subcutaneously every 2 weeks. These drugs are highly effective and together with statins, may lower LDL cholesterol by as much as 85%. Examples include alirocumab and evolocumab.

These drugs can cause side effects such as itching, swelling, pain, or bruising at the injection site; and are also costly.

1. 1. Inclisiran

The latest class of drugs approved in Singapore for the treatment of high blood cholesterol is inclisiran. This is one of the first of a completely new class of cholesterol-lowering injectables known as ‘gene silencing drugs’. It turns off, or ‘silences’, the gene PCSK9, which in turn boosts the liver’s ability to remove harmful blood cholesterol from the blood.

The biggest advantage of this medicine is that it can be administered just once every 6 months which will greatly improve patient compliance.

Summary

To manage high blood cholesterol effectively, you cannot rely on medications alone without making lifestyle changes. Likewise, lifestyle changes should not be viewed as an alternative therapy to medicines but rather as complementary.

Although statins and other cholesterol-lowering medications are highly effective, they are never meant to be the only means to manage high blood cholesterol. One will still need to stay away from a diet that is high in saturated fat, trans fats and cholesterol and stick with a heart-healthy diet.

LDL-C levels can be lowered by 10% to 20% after three to six months of diet and exercise modification. Coupled with medications, the reduction may be observed earlier at 2 months.

This article is contributed by Prof Tan Huay Cheem, Chairman, Singapore Heart Foundation. He is also the Senior Consultant Cardiologist at the National University Hospital and Professor of Medicine with Yong Loo Lin School of Medicine, National University of Singapore.