• Hypercholesterolemia is a condition characterized by very high levels of cholesterol in the blood
  • Many patients with high cholesterol levels can’t tolerate statins due do side effects
  • Bempedoic acid is a safe and efficient drug to reduce LDL cholesterol

Introduction Hypercholesterolemia is a condition characterized by very high levels of cholesterol in the blood [1]. Cholesterol is a fat-like, essential substance which is produced in the body as well as obtained from many foods such as egg yolks, meat, fish, dairy products etc [1]. It is found in two forms: Low-density lipoprotein (LDL), the unhealthy type of cholesterol, and high-density lipoprotein (HDL), the healthy type one [5]. Body finds LDL cholesterol as a very crucial substance because since:
1.Contributes to the  structure of cell wall – cholesterol is an important structural component which gives the cell membrane support to hold the cell together[2].
2.Allows body to produce vitamin D- Cholesterol and vitamin D have a very interesting relationship, since the enzyme called DHCR7, which converts a substance called 7DHC into cholesterol can be turned into vitamin D by UV light [3].
3. Cholesterol is a precursor of steroid hormones such as: progesterone, androgens, estrogens, as well as cortisol which promotes gluconeogenesis and helps on fat and protein degradation[4].
On the other side, high LDL cholesterol can cause serious health problems  such as: Atherosclerosis- condition of stiffening and hardening of the arteries due to buildup of LDL, if this happens on a coronary artery heart muscle can’t get supplied. This leads to hear attack [6]. Stomach pain- high amount of cholesterol can cause gallstones formation [7]. Stroke- high cholesterol can block normal flow to the brain and cause stroke [8].


Fig.1 Difference between normal artery and artery with plaque build-up.
Image adapted from [9].

Statistics It is estimated that high cholesterol causes 2.6 million deaths (4.5% of total), and 29.7 million disability adjusted life years (2% in total of DALYS) [10]. Data collected from Center for Disease Control and Prevention (CDC) state that 73.5 million or 31.7% of adults in USA have high levels of LDL, and are twice the risk for heart disease rather than other people with normal levels[10]. The most concerning part is that only 48.1% of them are receiving treatment to lower it [10]. Latest data from WHO claim that the prevalence of elevated total cholesterol was highest in Europe (54% for both sexes), followed by America ( 48% for both sexes), whereas region of Africa (22.6%)  and South East Asian Region (29.0%) showed the lowest percentage[11]. Referring to income level of the country, in high-income countries over 50% of adults had high total cholesterol, more than twice the level of the low-income countries[11].

Fig 2. Global Health observatory data about raised cholesterol in WHO Regions.
Image adapted from [11].

Diagnosing and Medications – High cholesterol has no symptoms, the only way to detect it if you have it or not is blood test [12]. In order to have the most accurate measurements, it is recommended to not eat or drink anything (except water) for 9 to 12 hours before the test is done [12]. Children and young adults with no risk of heart disease are tested between 9 and 11, and again between the ages 17 and 19 [12].Meanwhile, children and people with family history of cholesterol, diabetes or high blood pressure are required to follow more-frequent tests [13].Basing on the levels of “bad” cholesterol the risk of hypercholesterolemia is named as low, moderate or high. These levels vary by age, weight and gender and are interpreted based on general guidelines and treated by lowering cholesterol drugs[13].

Treatment – The main treatment of hypercholesterolemia is by statin drugs [14]. These drugs work by inhibiting the enzyme 3-hydroxy-3 methyl glutaryl coenzyme A reductase[14] This inhibition results in upregulation of LDL cholesterol receptors and greater clearance of LDL cholesterol [14].Despite the fact that statins have shown a great impact on plaque stabilization, reduction of platelet activation, anticoagulation as well as vasodilation, they tend to show various side effects such as : muscle pain, headache, vomiting, drowsiness, diarrhea as well as difficulty sleeping[15]. In addition to this, statins may interact with other drugs that the patient may be taking for example with antibiotics, antifungals, anti-arrhythmic drugs [16].These interactions may increase statins side effects and make very patients unable to take them[16].

Latest research – Statins, take your side effects and go home. The future is bright for people unable to take statins due to their side effects such as muscle pain or bad interactions with other medications[17]. A study from Imperial College London’s School of Public Health led by Professor Kausik Ray shows that Bempedoic acid is a safe and very efficient oral medication for LDL cholesterol reduction  [17]. Data from a 52-week trial where 2230 patients where involved, of whom 1488 received bempedoic acid and 742 received placebo confirm that Bempedoic Acid can be the solution to reduce high level of LDL. Furthermore, it can be considered as a great option for people  unable to take statins due to their side effects[18].
Even though Bempedoic Acid has the same mechanism of action as statins, it can get activated just in liver because muscle cells don’t express the acyl- coA synthetase( the enzyme required to activate Bempedoic Acid) as liver does [18]. Thus, treatment with Bempedoic acid would be unlikely to cause adverse effects on muscular system such as muscle spasms, arthralgia and myalgia [18].

In conclusion, Bempedoic Acid is a safe and efficient cholesterol lowering drug for people unable to take statins due to side effects.

COPYRIGHT: This article is the property of We Speak Science, a non-profit institution co-founded by Dr. Detina Zalli and Dr. Argita Zalli. The article is written by Rexhep Sahatçiu, University of Prishtina, Kosovo.

References:
[1]. Johns Hopkins Medicine- High cholesterol prevention, treatment and research https://www.hopkinsmedicine.org/health/conditions-and-diseases/high-cholesterol/high-cholesterol-prevention-treatment-and-research [2].The role of cholesterol in the cell membrane https://www.livestrong.com/article/80925-role-cholesterol-cell-membrane/ [3].Health Line- the cholesterol and vitamin d relationship https://www.healthline.com/health/high-cholesterol/vitamin-d-relationship#vitamin-d [4]. Important derivatives of cholesterol https://www.ncbi.nlm.nih.gov/books/NBK22339/ [5] Harvard Health Publishing https://www.health.harvard.edu/blog/understanding-cholesterol-hdl-vs-ldl-2018041213608 [6] The role of Lipids and Lipoproteins in Atherosclerosis https://www.ncbi.nlm.nih.gov/books/NBK343489/ [7] Mayo clinic data- Gallstones https://www.mayoclinic.org/diseases-conditions/gallstones/symptoms-causes/syc-20354214
[8] National stroke association- Medical Risk Factors https://www.stroke.org/understand-stroke/preventing-a-stroke/medical-risk-factors/ [9]Johns Hopkins Medicine –Atherosclerosis https://www.hopkinsmedicine.org/health/conditions-and-diseases/atherosclerosis [10]  WHO- Global Health Observatory data https://www.who.int/gho/ncd/risk_factors/cholesterol_text/en/ [11] Risk factors of cholesterol https://www.who.int/gho/ncd/risk_factors/cholesterol_text/en/ [12] Mayo Clinic data – high cholesterol  https://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/diagnosis-treatment/drc-20350806 [13] News medical data- hypercholesterolemia diagnosis https://www.news-medical.net/health/Hypercholesterolemia-Diagnosis.aspx [14] US National Library of Medicine- Emerging treatments for hypercholesterolemia https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187606/ [15] WebMD- Side effects of Statins https://www.webmd.com/cholesterol-management/side-effects-of-statin-drugs#1 [16] Verywell health- statin drug interactions https://www.verywellhealth.com/statin-side-effects-and-drug-interactions-698202 [17] Sciene daily – New cholesterol lowering drug could help patients unable to take statins https://www.sciencedaily.com/releases/2019/03/190313185417.htm  [18] The new England Journal of Medicine-  Safety and efficacy of Bempedoic Acid. https://www.nejm.org/doi/full/10.1056/NEJMoa1803917