MedEvidence Magazine | The Cholesterol Edition

MAGAZINE

EDITION 2 | ENCOREDOCS.COM

THE CHOLESTEROL EDITION

ARE YOU 1 OF 29 MILLION AMERICANS WITH HIGH CHOLESTEROL?

Published by ENCORE Research Group

The Cholesterol Edition

TABLE OF CONTENTS 3 BREAKTHROUGHS IN CHOLESTEROL MANAGEMENT

4-5 CHOLESTEROL 101

6-7 5 THINGS TO KNOW ABOUT Lp(a)

8 HEART HEALTHY RECIPE

9 ENCORE EXPERIENCE | PATIENT TESTIMONIALS

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3 | Breakthroughs in Cholesterol Management

BREAKTHROUGHS IN CHOLESTEROL MANAGEMENT As we get past the COVID pandemic, we are fortunate we have these new incredible technologies to battle an even larger source of death and disability -Cardiovascular Disease.

For some patients, managing cholesterol creates a challenge. Statins are a safe and standard treatment, but many people have very high levels of cholesterol that require more than statin drugs alone. Others cannot easily tolerate statins. Nonetheless, treating cholesterol saves lives and avoids heart attacks and strokes.

Thankfully, the future is here. New breakthroughs can change the way we maintain healthy cholesterol levels due to continued research and clinical trial participants. We outline some of these exciting technologies below.

Antisense oligonucleotides (ASOs) ASOs are short, synthetic single stranded fragments of RNA that can reduce, restore or modify protein expression. ASOs have been designed specifically to target high levels of LDL (bad cholesterol) in the bloodstream in a different way than current medications.

Firstly, ASOs targets the source of the disease resulting in a higher chance of success compared to therapies targeting downstream pathways. Secondly, ASOs are not metabolized by cytochrome P450 as most other drugs are. This significantly reduces the chance of one drug interacting with another drug which could potentially cause more harm than good.

Small interfering RNA (SiRNAs)

SiRNAs are another type of RNA therapy that is being used in clinical trials to reduce the risks of cardiovascular disease. Unlike ASOs, which are single-stranded oligodeoxynucleotides, siRNAs are double-stranded RNA molecules. SiRNAs are used in the silencing of disease-causing genes, in this case the genes involved in creating cardiovascular diseases. It has made great progress.

Adnectins

Michael Koren, MD, FACC, FAPCR, CPI CEO and Medical Director, Jacksonville Center for Clinical Research

Adnectins are a class of drugs used to target proteins.

Adnectins can be rapidly developed to bind proteins or other necessary targets. Currently, adnectins are being used in clinical trials to bind with a human protein called PCSK9. This binding blocks the interactions between PCSK9 and LDL (bad cholesterol) receptors. As a result, the levels of LDL cholesterol in the body are lowered.

These technologies hold the potential to not only better manage cholesterol levels and thereby reducing heart attack and stroke risk, but many other conditions as well.

The Cholesterol Edition

DID YOU

KNOW?

Having high blood cholesterol raises the risk for heart disease, the leading cause of death, and for stroke, the fifth leading cause of death.

High cholesterol may have no symptoms.

Many people don’t know that their cholesterol is too high. A simple blood test can check cholesterol levels.

Using cholesterol-lowering medications has contributed to a substantial decrease in the prevalence of high cholesterol over the past 25 years.

5 | Cholesterol 101

The Nutrition List

CHEAT SHEET Lowering cholesterol can be difficult, and food labels can be confusing. It is time we simplify it for you and make your trip to the grocery store easy, stress-free and full of healthy choices!

It is important to check the polyunsaturated and monounsaturated fats. Look for foods that are higher in monounsaturated fats.

Check the calories to make sure you're keeping to your daily calorie budget based on your desired goal. Talk to your doctor or dietitian if you are unsure.

Always look at the serving size.

It can be much smaller than you think!

Check the carbs!

Eating more than 60% of your daily calories from carbohydrates may increase cholesterol levels.

The American Heart Association recommends a sugar limit of no more than 100 calories per day (less that 10% of total calories) for women and 150 calories per day (less that 10% of total calories) for men.

Added Sugars

The new nutrition label requires "added sugar".

Be sure not to overlook it!

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The Cholesterol Edition

5 THINGS TO KNOW A B O U T Lp ( a ) Lipoprotein(a), or Lp(a), is an independent risk factor for atherosclerotic cardiovascular disease.

Cardiovascular disease is the leading cause of death in both men and women in the US and globally. You may have heard of LDL cholesterol, or “bad cholesterol,” as a risk factor for heart disease, but Lp(a) can be just as dangerous. Lp(a) flies under the radar of many physicians. This is because the awareness of Lp(a) is still very low. Very little is understood about the protein and the treatment options are limited.

W H A T I S Lp(a) Lp(a), pronounced “LP little a,” is a protein that is attached to LDL cholesterol. It is composed of an LDL-like particle, but it has a second protein coiled around it. Recent studies have shown that people born with elevated Lp(a) can be two to four times as likely to have a heart attack or serious cardiac related risk.

Lp(a) is present in 20% of the population.

Lp(a) UNIQUE RISK FACTORS Lp(a) is unique because it is a completely genetic risk factor.

Meaning, having an elevated Lp(a) is almost entirely determined by the genes you inherit. There is no evidence that a healthy lifestyle will lower your Lp(a). However, that does not mean those with high levels shouldn’t practice healthy habits. Reducing other risk factors that are determined by quality of health can still reduce the overall risk of heart disease.

Another risk factor that sets Lp(a) apart is that it is an independent risk factor. It has been linked to heart disease in younger adults who are otherwise healthy and have no prior cardiovascular risks. Elevated Lp(a) has affected the lives of many who are otherwise healthy. For example, Tennis legend Arthur Ashe, had his first heart attack at age 36. Bob Harper, a celebrity fitness trainer was also affected and nearly died of a heart attack at age 52.

WHO SHOULD BE TESTED? Studies show that there is a higher risk of a cardiovascular event if Lp(a) levels start to rise above 30 mg/dl. There is a greater risk at levels 50 mg/dl and higher. An estimated one in seven people are at or above this threshold. You should be tested for Lp(a) if: you’ve had a cardiac event but your cholesterol levels are normal you have a family member with heart disease at an early age you've had a cardiovascular event despite normal lipid levels you have a family history of elevated Lp(a) you have aortic valvular disease at an early age As mentioned, Lp(a) is a genetically mediated risk factor.

“This means it runs in families,” Albert Lopez, MD, DO, FASPC, internal physician and lipid specialist in Jacksonville, FL states. “Those individuals that have it, you have a 50% chance of giving to your children.” Dr. Lopez believes there should be cascade screening, meaning asking family members if they have it and then getting tested.

NO FDA APPROVED REMEDIES FOR Lp(a) Currently there are no FDA approved remedies for elevated Lp(a). Statins, a widely known and used therapy that lowers LDL cholesterol does not reduce Lp(a) and has been shown to sometimes result in a slight increase. One therapy that has been shown to work is apheresis. This process filters a patient’s blood by circulating it through a machine and removing Lp(a) particles. However, this process is reserved for high-risk patients because it is extremely expensive, requires weekly visits and involves risks. After stopping apheresis, the Lp(a) levels begin to rise again.

7 | Lp(a)

N E W A D V A N C E M E N T S I N S C I E N C E R E G A R D I N G Lp(a) Luckily, there are new drugs on the horizon that could potentially help those suffering from elevated Lp(a) levels. “What is exciting is that we are in totally nerd, sci-fi treatments now,” Dr. Lopez says. “We can actually stop your genes from making this protein by using a little snip that crinkles it up and doesnt let it read.” In other words, new studies are using gene silencing techniques to achieve a large and durable reduction of Lp(a).

“THOSE INDIVIDUALS WITH ELEVATED LP(A) HAVE A 50% CHANCE OF GIVING IT TO THEIR CHILDREN.”

- DR. ALBERT LOPEZ PRINCIPAL INVESTIGATOR

The Cholesterol Edition

Know Your Lipid Panel!

Knowing your cholesterol numbers is an important step towards understanding your risk for multiple diseases. To screen for high cholesterol, your doctor will order blood work including a lipid panel. A lipid panel is a collection of blood tests that show the amount of lipids or fat in the blood. Having elevated cholesterol levels can lead to increased risk of heart attack and stroke.

What are Triglycerides?

Triglycerides are one type of fat (lipid) in blood.

They are used to store and move fat in the bloodstream. Excess calories, especially from carbohydrates, can cause your liver to increase the production of triglycerides. When there is an excess of triglycerides in the body, they can be stored in the liver or in fat cells to supply the body with energy when it is required. This is a natural process that provides a sustained source of energy for the body, particularly between meals, as triglycerides are a stored energy source.

Once High Triglycerides are Spotted: If high triglycerides are identified in your tests, many changes in lifestyle, diet and medications can help control it. Using multiple techniques is the best way to reduce risks. When it comes to diet, it is recommended that people with high triglycerides drink alcohol only in moderation or, in some cases, not at all. Exercise, avoiding sugars and refined carbohydrates and weight loss are very good steps.

Finally, several different medications can be used to reduce elevated triglycerides. These include statins, fibrates, fish oil and niacin. It is also important to note that some medication can raise your triglyceride levels. For instance, some birth control pills, steroids, HIV medications, and beta-blockers may increase these levels.

High Triglycerides Levels Can Harm More Than The Heart Elevated triglyceride levels can raise the risk of heart disease. Diseases associated with high triglycerides include many cardiovascular diseases: hardening of arteries, heart attacks, strokes and vascular disease.

Beware, high triglycerides can harm more than just your heart. Diseases also associated with high triglycerides include certain liver conditions (NAFLD or NASH), Diabetes Type 2, hypothyroidism and even Alzheimer’s Disease.

According to the American Academy of Dermatology Association, high triglycerides even cause skin disorders.

Checking your triglyceride levels may help you decide the next steps. A 12 hour fast is preferential prior to the lipid test to get the most accurate result.

Triglycerides to HDL Cholesterol Ratio Triglycerides to HDL cholesterol (the “good” cholesterol) ratio represents an easy to measure parameter to identify an individual’s increased cardiometabolic risk. Research has shown that people with the highest ratio of triglycerides to HDL cholesterol have 16 times the risk of heart attack as those with the lowest ratio of triglycerides to HDL. Simply take your TG level and divide by your HDL level.

Ideally your goal is <1. So the lower your TGs or the higher your HDL, the smaller your ratio becomes.

Check your TG/HDL ratio on your next lipid panel.

9 | ENCORE Experience

EXPERIENCE

BUDDY

LP(a) Trial Participant This has been a great experience and I would recommend it to anyone.

Buddy Webster is a participant in a Lp(a) trial at ENCORE Research Group. Lipoprotein(a), or Lp(a), is an independent risk factor for cardiovascular disease. This means that there is nothing a person can do to prevent high levels of Lp(a). It is completely genetic. However, Buddy is motivated to change that for future generations and hopefully be a part of finding the cure.

“A little over a year and a half ago my little brother died of heart related issues,” Buddy says. “My father also died of these same issues.” Because there are few ways to predict elevated Lp(a) levels, family history motivated Buddy to take the offense when it came to his heart health. “I would not be here if I did not have the family history. I would have never moved in the direction to go get checked.” Once checked, Buddy found out his Lp(a) levels were five times higher than normal, so his doctor told him about ENCORE Research’s clinical trial.

Buddy decided to join the clinical trial as a way to spread the word about Lp(a) and help others. “Being in a clinical trial makes you feel good because you are helping the youth and advancing society,” He said.

“That’s the way I look at it. I am doing something to help improve medicine for future generations.

The Cholesterol Edition

So, How do I Enroll in a Clinical Trial?

Enrolling in a clinical trial is easy. Simply scan the QR code above or call 904-730-0166.

11 | Word Search

CHOLESTEROL TERMINOLOGY ENCORE Word Search

ATHEROSCLEROSIS BLOOD CHOLESTEROL FIBRATES HDL

HEART HYPERCHOLESTEROLEMIA HYPERTENSION LDL LIPID

LIPOPROTEIN MEDICATION PLAQUE STATINS TRIGLYCERIDES

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