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Cholesterol

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Ismail Munir

Overview

In 1769, French physician and chemist Fran&ccedil;ois Poulletier became the first person to obtain solid pure cholesterol from gallstones<a href="#accordion">[1]</a>.&nbsp;The compound was named &lsquo;cholesterine&rsquo;, derived from its ancient Greek counterparts &lsquo;chole&rsquo; (bile) and &lsquo;stereos&rsquo; (solid).

However, it wasn&rsquo;t until 1888 that Austrian botanist Friedrich Reinitzer was able to establish the molecule structure of the compound&nbsp;and it became known as cholesterol<a href="#accordion">[1]</a>.&nbsp;

The waxy substance is a type of lipid commonly present in all cells of the body. It not only helps form hormones but also protects nerves. Although the body can produce its own cholesterol with the help of the liver, the fat-like substance is also present in the food one consumes.&nbsp;

Excess consumption of foods containing cholesterol can lead to high levels in the blood. Moreover, foods high in saturated and trans fats cause the liver to produce more cholesterol. The increase in cholesterol increases one&rsquo;s risk of several diseases.&nbsp;

According to the World Health Organization (WHO), a third of ischemic heart diseases worldwide can be linked to high cholesterol levels, also called hypercholesterolemia<a href="#accordion">[2]</a>.&nbsp;Moreover, elevated cholesterol levels are responsible for approximately 2.6 million deaths<a href="#accordion">[2]</a>. In 2008, the global prevalence of elevated cholesterol among adults was estimated at 39%<a href="#accordion">[2]</a>.

However, high cholesterol levels are not the only possibility. In some people, cholesterol levels can also be low. Since the compound is important for cell functioning, low levels have been associated with increased criminal activity,&nbsp;anxiety, and depression<a href="#accordion">[3][4]</a>.

A study conducted among the Pakistani population found 63% of participants had lipid irregularities<a href="#accordion">[5]</a>. Approximately 9% of the women had high cholesterol levels compared to 7% of men.&nbsp;Another study analyzed lipid abnormalities in obese individuals and those with coronary heart disease (CHD)<a href="#accordion">[6]</a>.&nbsp;According to the results, 49.5% of the participants had higher-than-normal total cholesterol levels<a href="#accordion">[6]</a>.&nbsp;Thus, revealing the role of elevated cholesterol levels in causing obesity and CHD in Pakistan.&nbsp;

&nbsp;

Cholesterol travels in the circulatory system with the help of lipoproteins. These particles are formed from fat and protein.&nbsp;

Based on these lipoproteins, cholesterol is divided into: 
&nbsp;

<ul>
	<li>High-Density Lipoprotein (HDL) - Often called &lsquo;good&rsquo; cholesterol, HDL is responsible for removing low-density lipoprotein cholesterol from the bloodstream and taking it to the liver. The liver then removes it from the body. High HDL levels can decrease one&rsquo;s risk of heart disease.&nbsp; 
	&nbsp;</li>
	<li>Low-Density Lipoprotein (LDL) - LDL is also called &lsquo;bad&rsquo; cholesterol because it causes a buildup of plaque in the arteries. High LDL levels indicate a high risk of heart disease and stroke. 
	&nbsp;</li>
	<li>Very Low-Density Lipoprotein (VLDL) - Unlike LDL, VLDL helps carry triglycerides in the blood. However, it also leads to plaque buildup in the artery walls. Therefore, it&#39;s also called &lsquo;bad&rsquo; cholesterol.&nbsp;</li>
</ul>

&nbsp;

Signs And Symptoms

The cholesterol can combine with other substances in the blood and form plaques. These plaques then stick to the walls of the coronary arteries. As they build up, the artery wall hardens and the vessels narrow (<a href="https://www.merisehat.pk/disease/atherosclerosis" target="_blank">atherosclerosis</a>).&nbsp;

Atherosclerosis results in a reduction or obstruction of blood flow and can lead to coronary artery disease in people. Therefore, in most people chest pain due to blockage of a coronary artery may be the only symptom.&nbsp;

Furthermore, the majority of people are asymptomatic and only discover high cholesterol levels during routine blood testing.&nbsp;For low cholesterol, there is no chest pain but people may experience symptoms such as confusion, agitation, hopelessness, mood changes, or sleep disturbances. However, these symptoms can also arise from other causes.

&nbsp;

Causes

Although high cholesterol levels are more common, it is also possible for the levels to fall below the normal range. Both conditions result from a variety of diseases.&nbsp; 
&nbsp;

The most common causes of high cholesterol are: 
&nbsp;

<ul>
	<li>Diet - An unhealthy diet of foods high in saturated fats can increase one&rsquo;s cholesterol level. Examples include red meat, fried food, processed food, chocolates, and dairy products. 
	&nbsp;</li>
	<li>Lifestyle - Regular exercise can help lower LDL levels and increase HDL levels. Moreover, it can also help lose weight. Therefore, a sedentary lifestyle is associated with high cholesterol levels. 
	&nbsp;</li>
	<li>Smoking - Smoking can lower HDL levels and cause high cholesterol.&nbsp; 
	&nbsp;</li>
	<li>Genetics - Familial hypercholesterolemia is an inherited disorder that runs in families. It prevents the body from removing LDL from the blood and leads to high cholesterol levels.&nbsp; 
	&nbsp;</li>
	<li>Weight - Being overweight or <a href="https://www.merisehat.pk/disease/obesity" target="_blank">obese </a>can also increase one&rsquo;s cholesterol and triglyceride levels. 
	&nbsp;</li>
	<li>Medical Conditions - <a href="https://www.merisehat.pk/disease/diabetes-type-1-and-2" target="_blank">Diabetes</a>, <a href="https://www.merisehat.pk/disease/hiv-61" target="_blank">HIV</a>/<a href="https://www.merisehat.pk/disease/aids" target="_blank">AIDS</a>, <a href="https://www.merisehat.pk/disease/hypothyroidism" target="_blank">hypothyroidism</a>, and chronic kidney disease can also lead to high cholesterol levels. 
	&nbsp;</li>
	<li>Medications - These include drugs for acne, hypertension, cancer, arrhythmias, and immunosuppressive medications.&nbsp; 
	&nbsp;</li>
</ul>

The most common causes of low cholesterol are:

<ul>
	<li><a href="https://www.merisehat.pk/disease/anemia" target="_blank">Anemia</a></li>
	<li>Malnutrition&nbsp;</li>
	<li>Thyroid abnormalities</li>
	<li>Liver disease</li>
	<li>Family history of low cholesterol levels</li>
</ul>

&nbsp;

Diagnosis

The CDC recommends cholesterol testing every 5 years for adults (20 years or older) with a low risk for cardiovascular disease<a href="#accordion">[7]</a>. However, more frequent testing is required for people with cardiovascular risk factors. Men aged 45-65 years and women aged 55-65 years should undergo cholesterol screening every 1-2 years while people over 65 should opt for annual screening tests.&nbsp;

Doctors might ask you to fast for 9-12 hours before the lipid profile test. The lipid profile test measures: 
&nbsp;

Total Cholesterol - This is the total amount of cholesterol in the blood, including HDL and LDL cholesterol.

<ul>
	<li>&lt; 200 mg/dl - Normal</li>
	<li>&gt; 240 mg/dL - High</li>
	<li>200-239 mg/dl - Borderline high<a href="#accordion">[8]</a> 
	&nbsp;</li>
</ul>

LDL Cholesterol - For people who are at risk of coronary artery disease (CAD) or who have diabetes, the ideal LDL levels are less than 100 mg/dl.&nbsp;

Those who have stents or a history of heart attacks and angina, their LDL levels should be below 70 mg/dl.

<ul>
	<li>130-159 mg/dl - Borderline high</li>
	<li>160-189 mg/dl - High<a href="#accordion">[8]</a> 
	&nbsp;</li>
</ul>

HDL Cholesterol - Since HDL is good cholesterol, high levels (60 mg/dl or more) are considered good, whereas levels below 40 mg/dl are considered unhealthy and mean that the person is at risk for heart disease and stroke<a href="#accordion">[8]</a>. 
&nbsp;

Triglycerides - Triglycerides are another type of lipid present in the blood.

<ul>
	<li>&lt; 150 mg/dl - Normal&nbsp;</li>
	<li>&gt; 200 mg/dl - High</li>
	<li>150-199 mg/dl &ndash; Borderline high<a href="#accordion">[8]</a></li>
</ul>

Due to the rising obesity epidemic, the American Academy of Pediatrics recommends screening all children between 9-11 years&nbsp;and repeating the test every 5 years<a href="#accordion">[8][9]</a>. 
&nbsp;

Moreover, screening for children should begin at 2 years of age if:

<ul>
	<li>Their parents or grandparents have high total cholesterol levels (240mg/dl or higher)</li>
	<li>Their parents or grandparents have a history of heart attack, stroke, or other cardiovascular diseases</li>
	<li>There is an unknown family medical history as happens in the case of adoption 
	&nbsp;</li>
</ul>

Following are the normal cholesterol levels in children<a href="#accordion">[9]</a>:

Normal&nbsp;

<ul>
	<li>Total cholesterol &lt; 170 mg/dl&nbsp;</li>
	<li>LDL &lt; 110 mg/dl 
	&nbsp;</li>
</ul>

Borderline&nbsp;

<ul>
	<li>Total cholesterol 170-199 mg/dl&nbsp;</li>
	<li>LDL 110-129 mg/dl 
	&nbsp;</li>
</ul>

High&nbsp;

<ul>
	<li>Total cholesterol &gt; 200 mg/dl</li>
	<li>LDL &gt; 130 mg/dl</li>
</ul>

&nbsp;

Treatment

Doctors may prescribe a combination of lifestyle changes and medications to help lower cholesterol levels.&nbsp;Treatment is typically recommended if the cholesterol levels are high or borderline high, the person is overweight, or if the person has a family history of heart disease.

&nbsp;

<h5>Lifestyle Modifications&nbsp;</h5>

A healthy diet comprising lean protein, high fiber, vegetables, and foods containing omega-3 fatty acids is often recommended.&nbsp;Besides, it&rsquo;s better if the person avoids deep-fried foods, processed and packaged items, baked goods, and high-fat dairy products.&nbsp;

Regular exercise, stress management, quitting smoking, and limiting alcohol intake are other lifestyle modifications that are prescribed to lower cholesterol.&nbsp; 
&nbsp;

<h5>Medications&nbsp;</h5>

When lifestyle changes are not able to bring cholesterol levels down, doctors might prescribe several medications. These include:

<ul>
	<li>Statins - Drugs such as rosuvastatin, Fluvastatin, and lovastatin block the liver from producing cholesterol.&nbsp;</li>
	<li>Cholesterol Absorption Inhibitors - Drugs such as ezetimibe help reduce cholesterol by limiting cholesterol absorption.&nbsp;</li>
	<li>Niacin - Niacin reduced the production of LDL and VLDL cholesterol. It is mostly recommended for people who can&rsquo;t take statins.</li>
	<li>PCSK9 Inhibitors - These drugs lower cholesterol by helping the liver absorb more LDL cholesterol. Examples include evolocumab and alirocumab.&nbsp;</li>
	<li>Fibrates - These reduce the liver&rsquo;s production of VLDL and help remove triglycerides from the blood.&nbsp;</li>
	<li>Bile Acid Sequestrants - Cholestyramine and colesevelam reduce cholesterol levels by causing the liver to make more bile acids.&nbsp;</li>
	<li>Omega-3 Fatty Acids - These over-the-counter supplements lower triglyceride levels.&nbsp; 
	&nbsp;</li>
</ul>

In the case of low-cholesterol levels, doctors prescribe the treatment based on the underlying cause. Depending on the mental health evaluation, antidepressants are also prescribed to the individual.

&nbsp;

High cholesterol can lead to several complications, such as:

<ul>
	<li><a href="https://www.merisehat.pk/disease/atherosclerosis" target="_blank">Atherosclerosis</a></li>
	<li>Heart attack</li>
	<li>Chest pain (<a href="https://www.merisehat.pk/disease/angina" target="_blank">angina</a>)</li>
	<li><a href="https://www.merisehat.pk/disease/stroke" target="_blank">Stroke</a></li>
	<li><a href="https://www.merisehat.pk/disease/hypertension-57" target="_blank">Hypertension</a></li>
	<li>Chronic Kidney Disease</li>
	<li>Peripheral Vascular Disease</li>
	<li>Gallstones</li>
</ul>

&nbsp;

A person could be at risk of high cholesterol given their:

<ul>
	<li>Increasing age (in women, the risk increases after menopause)</li>
	<li><a href="https://www.merisehat.pk/disease/obesity" target="_blank">Obesity</a></li>
	<li>Smoking</li>
	<li>An unhealthy diet comprising saturated and trans fats</li>
	<li>Sedentary lifestyle</li>
	<li>Family history of high cholesterol</li>
	<li><a href="https://www.merisehat.pk/disease/diabetes-type-1-and-2" target="_blank">Type 2 diabetes&nbsp;</a></li>
	<li><a href="https://www.merisehat.pk/disease/hypothyroidism" target="_blank">Hypothyroidism&nbsp;</a></li>
	<li>Chronic kidney disease</li>
</ul>

&nbsp;

Risk factors for low cholesterol include:

<ul>
	<li>Family history of low cholesterol levels</li>
	<li>Cholesterol-lowering medications such as statins</li>
	<li>Untreated clinical depression</li>
</ul>

&nbsp;

The following measures can help manage cholesterol levels:

<ul>
	<li>Regular checkups</li>
	<li>A healthy, balanced diet</li>
	<li>30-minute exercise daily</li>
	<li>Stress management</li>
	<li>Smoking cessation</li>
</ul>

&nbsp;

Key Points

<ul>
	<li>Cholesterol is a type of lipid produced by the liver. The fat-like substance is an integral part of cells; it not only helps form hormones but also protects nerves.&nbsp;</li>
	<li>Cholesterol travels in the circulatory system with the help of lipoproteins. Based on these lipoproteins, cholesterol can be divided into high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL) cholesterol.&nbsp;</li>
	<li>High HDL levels can decrease one&rsquo;s risk of heart disease while high LDL and VLDL levels are associated with heart diseases and stroke.&nbsp;</li>
	<li>Total cholesterol levels of more than 240 mg/dl, LDL levels between 160-189 mg/dl, HDL levels below 40 mg/dl, and triglyceride levels above 150 mg/dl are all associated with an increased risk of heart disease and stroke.</li>
	<li>High cholesterol levels can result from an unhealthy lifestyle, certain diseases, inherited diseases, and certain medications.&nbsp;</li>
	<li>High cholesterol levels can lead to atherosclerosis, stroke, angina, gallstones, and <a href="https://www.merisehat.pk/disease/hypertension-57" target="_blank">hypertension</a>.&nbsp;</li>
	<li>Low cholesterol levels are rare but can develop due to anemia, malnutrition, liver disease, and a family history of the condition.&nbsp;</li>
	<li>Low cholesterol levels are commonly associated with mental health disorders, such as <a href="https://www.merisehat.pk/disease/depression" target="_blank">depression </a>and <a href="https://www.merisehat.pk/disease/anxiety" target="_blank">anxiety</a>.&nbsp;</li>
	<li>Both high and low levels of cholesterol pose risks to a person&rsquo;s health. A healthy diet, daily physical activity, stress management, limiting alcohol intake, and quitting smoking can all help prevent these health risks.&nbsp;</li>
</ul>

&nbsp;

[1] Endo A. A historical perspective on the discovery of statins. Proc Jpn Acad Ser B Phys Biol Sci. 2010;86(5):484-493.

[2] Indicator metadata registry details. World Health Organization.

[3] Golomb BA, Stattin H, Mednick S. Low cholesterol and violent crime. Journal of Psychiatric Research. 2000;34(4-5):301-309.

[4] Fiedorowicz JG, Haynes WG. Cholesterol, mood, and vascular health: Untangling the relationship: Does low cholesterol predispose to depression and suicide, or vice versa?. Curr Psychiatr. 2010;9(7):17-A.

[5] Zaid M, Hasnain S. Plasma lipid abnormalities in Pakistani population: trends, associated factors, and clinical implications. Braz J Med Biol Res. 2018;51(9):e7239.

[6] Shabana, Shahid SU, Sarwar S. The abnormal lipid profile in obesity and coronary heart disease (CHD) in Pakistani subjects. Lipids Health Dis. 2020;19(1):73.