All things Cardiovascular and Atherosclerosis Flashcards
How many people are on statins in the US? Worldwide?
40 million Americans are on statins
200 million are on statins worldwide
What drug types lower LDL?
Statins
Bile acid sequestrants
Niacin
Zetimibe
PCSK9 inhibitors
CETP inhibitors
How do PCSK9 inhibitors work?
The liver is able to take up excess cholesterol from the blood. However, there is a receptor
What are the most popular statins and how much do they cost per 30 days
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)
What percentage of people experience side-effects with statins?
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)
What percentage of people are on statins?
According to an NHANES survey from 2012:
40-59 yrs old: 17%
60-74 yrs old: 43%
75+: 47%
Cost of a cardiac event
Downstream conditions
Hypertension > further damage to arteries
Stenosis > angina, peripheral vascular disease
Plaque rupture > thrombis > heart attack / stroke
How much did Lipitor make in its prime? How does that compare to other blockbuster drugs from other years?
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.
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)?
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
Hyperlipidemia
High levels of LDL or triglycerides
Dyslipidemia
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.
Pharmacoeconomics and Pharmacoeconomic benefits
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
Direct medical costs for patients with established cardiovascular diseasees
$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
What would treatment with Cyclarity’s drug look like?
3-5 injections over 2-3 weeks, then not again for several years /decades
What are the four main types of cardiovascular disease?
- Coronary heart disease
- Stroke
- Peripheral arterial disease
- Aortic disease
What is the difference between cardiovascular disease and heart disease?
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
What is the difference between athersclerosis and cardiovascular disease?
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
According to Health and Human Services, what amount of healthcare spending is spent on cardiovascular disease?
1 out of every 6 healthcare dollars
What does atherosclerosis mean?
Athero = soft
sclerosis = hard
atheroscleromas = fatty deposits in artery wall
sclerosis = stiffening of the blood vessel wall
What areas does atherosclerosis affect?
Large and medium arteries
What causes athersclerosis (long answer from the beginning)
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.
What are the primary effects of athersclerosis
- Hypertension
- Stenosis (a narrowing due to plaque which reduces blood flow
- Plaque rupture
What is stenosis? How does aethersclerosis contribute to it? What can it lead to?
A narrowing due to plaque which reduces blood flow.
Athersclerosis narrows the artery.
Reduced blood flow can lead to angina and peripheral vascular disease
What is hypertension? What causes it in athersclerosis? Why is it bad?
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
What is a plaque rupture? What does it lead to?
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.
What are the non-modifiable risk factors for athersclerosis?
Age
Sex
Family history
What are the 6 modifiable risk factors for athersclerosis?
Drinking
Smoking
Obesity
Diet (high sugar, high trans fat)
Lack of exercise
Stress
Medical comorbidities that increase the risk of athersclerosis
Diabetes (1 & 2)
Hypertension
Chronic kidney disease
Inflammatory conditions (e.g. rhumatoid arthritis)
Atypical antipsychotics (e.g. for schizophrenia)
If you were a doctor considering athersclerosis as a possible diagnosis, what could you ask about?
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)
Define claudication
A condition of cramping pain in the legs brought on by exercise- usually due to obstruction of the arteries
