All things Cardiovascular and Atherosclerosis

Question 1

How many people are on statins in the US? Worldwide?

Answer 1

40 million Americans are on statins
200 million are on statins worldwide

Question 2

What drug types lower LDL?

Answer 2

Statins
Bile acid sequestrants
Niacin
Zetimibe
PCSK9 inhibitors
CETP inhibitors

Question 3

How do PCSK9 inhibitors work?

Answer 3

The liver is able to take up excess cholesterol from the blood. However, there is a receptor

Question 4

What are the most popular statins and how much do they cost per 30 days

Answer 4

Lipitor: $559 (generic Atorvastin: $20)
Lescol XL: $401 (generic Fluvastatin: $128)
Livalo: $339 patent expires 2024
Pravachol: $371 (generic Pravastatin $20)
Crestor: $294 (generic Rosuvastatin: $15)
Zocor: $173 (generic Simvastatin: $13)

Question 5

What percentage of people experience side-effects with statins?

Answer 5

5%-10% or less when compared to a placebo. This varies from study to study. A meta analysis of 176 studies and over 4m patients found the prevalance of statin intollerance at 9.1%, (Banach et 2022). However as many as 30% stop taking statins due to percieved side-effects (usually muscle aches) and up to 50% stop, reduce dose, or take infrequently due to percieved side-effects (the nocebo effect)

Question 6

What percentage of people are on statins?

Answer 6

According to an NHANES survey from 2012:
40-59 yrs old: 17%
60-74 yrs old: 43%
75+: 47%

Question 7

Cost of a cardiac event

Question 8

Downstream conditions

Answer 8

Hypertension > further damage to arteries
Stenosis > angina, peripheral vascular disease
Plaque rupture > thrombis > heart attack / stroke

Question 9

How much did Lipitor make in its prime? How does that compare to other blockbuster drugs from other years?

Answer 9

Lipitor made $13 billion in its biggest year in 2006. It was the top selling drug from 2001 - 2011 when it came off patent. Humira took over and grew from 7B to 21B in 2022. It goes off-patent in 2023.

Question 10

In 2006 when Lipitor made the most money, what percentage of people in the US and World were 65+? What will that number be by 2030? 2040 (I’m assuming when the patent runs out)?

Answer 10

12.4% (36.8 million people) were over 65 in 2005
17% (73 million people) will be over 65 in 2030
21.6% (80.8 million people) will be over 65 in 2040

https://acl.gov/sites/default/files/aging%20and%20Disability%20In%20America/2020Profileolderamericans.final_.pdf

Question 11

Hyperlipidemia

Answer 11

High levels of LDL or triglycerides

Question 12

Dyslipidemia

Answer 12

An imbalance or abnormal amount of lipids in the blood. This includes triglycerides, cholesterol, and/or fat phospholipids in the blood. Dyslepidemia is a risk factor for athersclerotic cardiovascular disease, cerebrovascular disease, and peripheral artery disease.

Question 13

Pharmacoeconomics and Pharmacoeconomic benefits

Answer 13

Pharmacoeconomics is the measuring of outcomes associated with the use of pharamceuticals in healthcare delivery.
Pharmacoeconomic benefits are the improvements in costs that a pharmaceutical causes in the delivery of healthcare

Question 14

Direct medical costs for patients with established cardiovascular diseasees

Answer 14

$18,953 mean with stdev of $39,036 in the US (2010 study that tracked 12,000 patients in Kaiser Permanented Northwest from 2000-2008). Inpatient costs accounted for 42.8% ($8,114). And the biggest cost difference were between people who had a second hospitalization vs those that didn’t ($62,755 vs $13,509) https://europepmc.org/article/med/20205493

Question 15

What would treatment with Cyclarity’s drug look like?

Answer 15

3-5 injections over 2-3 weeks, then not again for several years /decades

Question 16

What are the four main types of cardiovascular disease?

Answer 16

1. Coronary heart disease
2. Stroke
3. Peripheral arterial disease
4. Aortic disease

Question 17

What is the difference between cardiovascular disease and heart disease?

Answer 17

Cardiovascular disease is an umbrella term for diseases that involve the narrowing or obstruction of blood vesels, so this includes atherosclerosis, coronary artery disease (CAD), and cerebrovascular disease.

Heart disease may result in problems of the heart but that aren’t associated with blocked blood vessels (e.g. arrhythmias, inflammatory heart disease, and other heart conditions

Question 18

What is the difference between athersclerosis and cardiovascular disease?

Answer 18

Athersclerosis is upstream of cardiovascular disease. Cardiovascular disease occurs when athersclerosis leads to an established disease / adverse event such as:
* Stroke
* Heart attack
* Peripheral artery disease
* Aortic disease

Question 19

According to Health and Human Services, what amount of healthcare spending is spent on cardiovascular disease?

Answer 19

1 out of every 6 healthcare dollars

Question 20

What does atherosclerosis mean?

Answer 20

Athero = soft
sclerosis = hard
atheroscleromas = fatty deposits in artery wall
sclerosis = stiffening of the blood vessel wall

Question 21

What areas does atherosclerosis affect?

Answer 21

Large and medium arteries

Question 22

What causes athersclerosis (long answer from the beginning)

Answer 22

Oxidized cholesterol (such as 7 ketocholesterol) carried by ApoB protein (a protein that carries cholesterol in the blood stream) gets lodged in the artery wall. Monocytes that adhere to the arterial wall differentiate into macrophages and try to eat the oxidized cholesterol but are unable to break it down. Over time this leads to the macrophage becoming a foam cell, attracting other macrophages which also become foam cells, causing fibrosis as a part of the immune response and forming a plaque that pertrudes narrows the artery at the site of the plaque, decreasing blood flow and increasing blood pressure.

Question 23

What are the primary effects of athersclerosis

Answer 23

1. Hypertension
2. Stenosis (a narrowing due to plaque which reduces blood flow
3. Plaque rupture

Question 24

What is stenosis? How does aethersclerosis contribute to it? What can it lead to?

Answer 24

A narrowing due to plaque which reduces blood flow.
Athersclerosis narrows the artery.
Reduced blood flow can lead to angina and peripheral vascular disease

Question 25

What is hypertension? What causes it in athersclerosis? Why is it bad?

Answer 25

Increased blood pressure from stiff arterial walls.
1. The plaques themselves are less flexible than the arterial walls
2. Plaques become calcified
3. Plaques promote fibrosis, which is less flexible than the arterial wall

Increased blood pressure further damages the arterial wall and increases the chance for more plaques to begin to develop

Question 26

What is a plaque rupture? What does it lead to?

Answer 26

A plaque rupture occurs when some of the athersclerotic plaque breaks off and travels downstream. This break off is called a thrombus and eventually will get lodged somewhere and will either block flow completely or partially called Ischemia. This is the main cause of Acute Coronary Syndrome, i.e. heart attack.

Question 27

What are the non-modifiable risk factors for athersclerosis?

Answer 27

Age
Sex
Family history

Question 28

What are the 6 modifiable risk factors for athersclerosis?

Answer 28

Drinking
Smoking
Obesity
Diet (high sugar, high trans fat)
Lack of exercise
Stress

Question 29

Medical comorbidities that increase the risk of athersclerosis

Answer 29

Diabetes (1 & 2)
Hypertension
Chronic kidney disease
Inflammatory conditions (e.g. rhumatoid arthritis)
Atypical antipsychotics (e.g. for schizophrenia)

Question 30

If you were a doctor considering athersclerosis as a possible diagnosis, what could you ask about?

Answer 30

Break it down into symptoms (chest pain, intermittent claudication), non-modifiable risk factors (age, sex, family history) and modifiable risk factors (smoking, drinking, diet, exercise- including exercise tolerance, stress, lack of sleep)

Question 31

Define claudication

Answer 31

A condition of cramping pain in the legs brought on by exercise- usually due to obstruction of the arteries