*This introduction section also provides very important information about skin cholesterol. Unless you have a thorough understanding of cholesterol including current cholesterol biomarkers, framingham risk assessment, and Candadian cholesterol epidemiology it is advised that you go through this section of the website first as these concepts are a prerequisite to understanding concepts discussed in the SKIN CHOLESTEROL section.
What is Cholesterol?
Cholesterol is a waxy, fat-like substance found in all cells if the body. Most of the time when someone talks about cholesterol in the medical community it is with a negative connotation making cholesterol seem like a bad thing. This is a very common misconception and cholesterol actually plays a very essential role in our bodies and we could not live without it [1].
Cholesterol is used in the body to make:[1]
The body has the ability to form cholesterol to perform all these daily functions however cholesterol is also taken in through our diet. In particular, animal products are a significant source of dietary cholesterol.[2] Cholesterol only becomes a problem when there are elevated levels of it in the body. We will talk more about what is considered an elevated cholesterol level later on. The file below provides an extensive list of foods and their cholesterol content to help you get an idea of the relative cholesterol content in common foods. (1,2)
Cholesterol is used in the body to make:[1]
- Sex hormones such as progesterone and estrogen in women and testosterone in men
- Cortisol which is involved in regulating blood glucose levels and is involved in anti-inflammatory pathways
- Aldosterone production which is essential for retaining salt and water in the body
- Vitamin D which is essential for calcium absorption and bone health
- Bile which is essential for absorbing fat-containing foods and fat soluble vitamins (A,D,E,K)
The body has the ability to form cholesterol to perform all these daily functions however cholesterol is also taken in through our diet. In particular, animal products are a significant source of dietary cholesterol.[2] Cholesterol only becomes a problem when there are elevated levels of it in the body. We will talk more about what is considered an elevated cholesterol level later on. The file below provides an extensive list of foods and their cholesterol content to help you get an idea of the relative cholesterol content in common foods. (1,2)
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Blood Cholesterol
When you traditionally hear someone talking about cholesterol they are most likely referring to blood cholesterol levels. In the blood, cholesterol is carried by molecules called lipoproteins. A lipid panel(cholesterol blood test) is typically done annually in patients with high cholesterol and requires the patient to fast for 12 hours prior to the test. When a lipid panel is done the following values are typically reported:[3]
LDL: This is often referred to as "bad cholesterol". LDL carries cholesterol from the liver to cells all around the body. When there is too much cholesterol, it results in a build up of excess LDL in the blood and can increase your risk of cardiovascular disease.
HDL: This is often referred to as good cholesterol. HDL performs the opposite role of LDL and takes cholesterol from cells back to the liver where it is broken down or excreted from the body via bile.
TG: Most fat in the body exists in the form of triglycerides (TG) and also is present in the blood as plasma lipids (blood fat). TG's are the end product of dietary fat digestion. The primary reason why fasting is required before a lipid panel is because TG levels in particular can become elevated after a meal.
Total Cholesterol: This is simply the total cholesterol level however, it is not a simple addition of the above values. It is calculated with a weighted formula using LDL, HDL, and TG levels as variables. Total cholesterol alone does not provide sufficient clinical information and it is important to look at the individual components.
ApoB: This is a molecule present on LDL molecules. Its complete function or role is not as strongly established as the other markers, however it is used to guide therapy in some cases in the guidelines. ApoB is not yet uniformly available as a funded lab test in many provinces.
What About Skin Cholesterol?
Skin cholesterol makes up 11% of the total cholesterol in the body (3). In some conditions such as familial hypercholesterolemia where people have very high blood lipids, xanthomas may form which look like small sores or bumps on the skin and are made up of fat deposits under the skin. Our bodies skin ages in parallel with vascular connective tissue which is the logic behind studying it as a predictor of cardiovascular disease. It is important to note that when we measure skin cholesterol levels, we are not measuring LDL, HDL or TG; skin cholesterol is a separate and independent bio-marker from these blood tests. Skin cholesterol is used in conjunction with and does not replace standard blood cholesterol testing. This will be discussed in more detail in the skin cholesterol section of the website.
When you traditionally hear someone talking about cholesterol they are most likely referring to blood cholesterol levels. In the blood, cholesterol is carried by molecules called lipoproteins. A lipid panel(cholesterol blood test) is typically done annually in patients with high cholesterol and requires the patient to fast for 12 hours prior to the test. When a lipid panel is done the following values are typically reported:[3]
LDL: This is often referred to as "bad cholesterol". LDL carries cholesterol from the liver to cells all around the body. When there is too much cholesterol, it results in a build up of excess LDL in the blood and can increase your risk of cardiovascular disease.
HDL: This is often referred to as good cholesterol. HDL performs the opposite role of LDL and takes cholesterol from cells back to the liver where it is broken down or excreted from the body via bile.
TG: Most fat in the body exists in the form of triglycerides (TG) and also is present in the blood as plasma lipids (blood fat). TG's are the end product of dietary fat digestion. The primary reason why fasting is required before a lipid panel is because TG levels in particular can become elevated after a meal.
Total Cholesterol: This is simply the total cholesterol level however, it is not a simple addition of the above values. It is calculated with a weighted formula using LDL, HDL, and TG levels as variables. Total cholesterol alone does not provide sufficient clinical information and it is important to look at the individual components.
ApoB: This is a molecule present on LDL molecules. Its complete function or role is not as strongly established as the other markers, however it is used to guide therapy in some cases in the guidelines. ApoB is not yet uniformly available as a funded lab test in many provinces.
What About Skin Cholesterol?
Skin cholesterol makes up 11% of the total cholesterol in the body (3). In some conditions such as familial hypercholesterolemia where people have very high blood lipids, xanthomas may form which look like small sores or bumps on the skin and are made up of fat deposits under the skin. Our bodies skin ages in parallel with vascular connective tissue which is the logic behind studying it as a predictor of cardiovascular disease. It is important to note that when we measure skin cholesterol levels, we are not measuring LDL, HDL or TG; skin cholesterol is a separate and independent bio-marker from these blood tests. Skin cholesterol is used in conjunction with and does not replace standard blood cholesterol testing. This will be discussed in more detail in the skin cholesterol section of the website.
Canadian Hyperlipidemia Guidelines [4]
The Canadian Hyperlipidemia Guidelines guide treatment initiation and management of patients with high cholesterol. It is important to understand these guidelines as these are the go to reference for healthcare professionals. The guidelines are updated every couple of years; the latest update to the guidelines was in 2012 and before that was in 2009. Some of the key points in the latest 2012 update are summarized below:
Screening
Screening
Treatment
Stratifying patients by risk
Stratifying patients by risk
FRS = Framingham Risk Score.
Figure 3: Targets of therapy are based on patient risk category (above)
Figure 3: Targets of therapy are based on patient risk category (above)
In terms of drug treatment, statins remain the 1st line therapy for patients with elevated LDL levels and are associated with a 25-30% relative risk reduction of Cardiovascular events in clinical trials.[4]
Skin Cholesterol in the Guidelines
It is important to note that Canadian hyperlipidemia guidelines do not mention or endorse skin cholesterol testing in any way. This is because skin cholesterol is a very new bio-marker and is not in wide-spread use yet or been tested in randomized trials on a large scale. As you will see later in the next section of the site, there is some very promising evidence for skin cholesterol as a predictor of cardiovascular risk and more research is still being done. Thus, it is very possible that skin cholesterol testing may be integrated into the guidelines in the near future.
The full 2012 Canadian Hyperlipidemia Guidelines can be downloaded from below:
Skin Cholesterol in the Guidelines
It is important to note that Canadian hyperlipidemia guidelines do not mention or endorse skin cholesterol testing in any way. This is because skin cholesterol is a very new bio-marker and is not in wide-spread use yet or been tested in randomized trials on a large scale. As you will see later in the next section of the site, there is some very promising evidence for skin cholesterol as a predictor of cardiovascular risk and more research is still being done. Thus, it is very possible that skin cholesterol testing may be integrated into the guidelines in the near future.
The full 2012 Canadian Hyperlipidemia Guidelines can be downloaded from below:
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2012_update_of_the_canadian_cardiovascular_society_guidelines_for_the_diagnosis_and_treatment_of_dyslipidemia_for_the_prevention_of_cardiovascular_disease_in_the_adult..pdf | |
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Framingam Risk Calculations
The Framingham Risk Calculator is a well validated tool to assess a patients cardiovascular risk. This tool was validated by a study with 6000 patients between ages 30-59 years old who were free of cardiovascular disease at baseline[5]. These patients underwent biannual examinations and were followed for 20 years for development of cardiovascular disease (defined as coronary death, myocardial infarction, coronary insufficiency, angina, ischemic stroke, hemorrhagic stroke, transient ischemic attack, peripheral artery disease, heart failure). The study identified the following risk factors to be most strongly associated with cardiovascular disease:[5][6]
1. Cigarette Smoking
2. Elevated Blood Pressure
3. Diabetes mellitus
4. Advancing age
5. Elevated total (and LDL) cholesterol
6. Low serum HDL cholesterol
Some of the key strengths of the Framingham risk calculator are that it has more external validation than any other cardiovascular risk estimation tool and it was derived using a North American population.[7] The Framingham uses age, gender, total cholesterol, HDL cholesterol, smoking status, and blood pressure to calculate a 10 year-risk. The calculator can be accessed at the link below:
Framingham Risk Calculator
For individuals between 30-59 years of age without diabetes and a positive history of premature cardiovascular disease in a first degree relative (men < 55 and women < 65 years of age), the Risk Score should be doubled.[8]
Skin Cholesterol + Framingham
Some of the studies looking at the effectiveness of skin cholesterol as a biomarker for cardiovascular used skin cholesterol levels in conjunction with Framingham Risk Scores. The results showed that. This is discussed in more detail in the evidence section of the skin cholesterol section of the website.
1. Cigarette Smoking
2. Elevated Blood Pressure
3. Diabetes mellitus
4. Advancing age
5. Elevated total (and LDL) cholesterol
6. Low serum HDL cholesterol
Some of the key strengths of the Framingham risk calculator are that it has more external validation than any other cardiovascular risk estimation tool and it was derived using a North American population.[7] The Framingham uses age, gender, total cholesterol, HDL cholesterol, smoking status, and blood pressure to calculate a 10 year-risk. The calculator can be accessed at the link below:
Framingham Risk Calculator
For individuals between 30-59 years of age without diabetes and a positive history of premature cardiovascular disease in a first degree relative (men < 55 and women < 65 years of age), the Risk Score should be doubled.[8]
Skin Cholesterol + Framingham
Some of the studies looking at the effectiveness of skin cholesterol as a biomarker for cardiovascular used skin cholesterol levels in conjunction with Framingham Risk Scores. The results showed that. This is discussed in more detail in the evidence section of the skin cholesterol section of the website.
Cholesterol in Canada
Percentage of Canadian adults with unhealthy levels of LDL and HDL by age group[9]
Note: All data presented are from fasting respondents and do not account for the impact of lipid adjusting therapy.
Source: Canadian Health Measures Survey, 2007 to 2009
Percentage of Canadians without a regular medical doctor, by sex, household population aged 12 or older (2003 to 2010)[10]
Source: Canadian Health Measures Survey, 2007 to 2009
Percentage of Canadians without a regular medical doctor, by sex, household population aged 12 or older (2003 to 2010)[10]
Source: Canadian Community Health Survey, 2003, 2005, 2007, 2008, 2009, 2010.
Percentage of Canadians without a regular medical doctor, by age group and sex, household population aged 12 or older in 2010 [10]
Percentage of Canadians without a regular medical doctor, by age group and sex, household population aged 12 or older in 2010 [10]
Source: Canadian Community Health Survey, 2010.
In 2010, there were 4.4 million Canadians without a regular doctor. 82.2% of Canadians in this group reported that they had a usual place to go when they were sick or in need of health advice with 61.8% reported using a walk-in clinic.[10]
1 in 3 deaths in Canada is due to heart attack or stroke.[11]
There is one cardiac arrest every 12 minutes in Canada. [11]
There are 70,00 heart attacks in Canadians every year. [11]
There are over 45, 00 cardiac arrests in Canada annually. [11]
At least 25% of coronary patients have sudden death or nonfatal heart attacks without prior symptoms.[11]
What does this mean? How does it relate to skin cholesterol testing?
Patients who do not have a family physician are likely not getting regular blood work or cardiovascular risk assessments. These patients only visit the doctor when they are sick so receive limited global assessment of their health. Furthermore, most patients are between 20-34 years of age which is very crucial period where patients have a significant ability to incorporate positive lifestyle changes and decrease their risk of cardiovascular disease when they are older. These patients can benefit greatly from a skin cholesterol test which is accompanied by education about modifiable cardiovascular risk factors. This will be discussed in more detail later on in the site.
In 2010, there were 4.4 million Canadians without a regular doctor. 82.2% of Canadians in this group reported that they had a usual place to go when they were sick or in need of health advice with 61.8% reported using a walk-in clinic.[10]
1 in 3 deaths in Canada is due to heart attack or stroke.[11]
There is one cardiac arrest every 12 minutes in Canada. [11]
There are 70,00 heart attacks in Canadians every year. [11]
There are over 45, 00 cardiac arrests in Canada annually. [11]
At least 25% of coronary patients have sudden death or nonfatal heart attacks without prior symptoms.[11]
What does this mean? How does it relate to skin cholesterol testing?
Patients who do not have a family physician are likely not getting regular blood work or cardiovascular risk assessments. These patients only visit the doctor when they are sick so receive limited global assessment of their health. Furthermore, most patients are between 20-34 years of age which is very crucial period where patients have a significant ability to incorporate positive lifestyle changes and decrease their risk of cardiovascular disease when they are older. These patients can benefit greatly from a skin cholesterol test which is accompanied by education about modifiable cardiovascular risk factors. This will be discussed in more detail later on in the site.
Current Limitations and Challenges
Now that you have an understanding of some of the basic concepts, now we will talk about some of the limitations and challenges that we are currently facing in the current health care environment when it comes to cholesterol screening and management.
Screening
A retrospective cohort analysis of 5688 patients admitted with their first MI to 96 acute care hospitals in Ontario was conducted in 2004-2005. Rates of screening for diabetes and hyperlipidemia according to the guidelines were calculated and the screening rates were stratified by age, sex, socioeconomic status, and number of primary care visits in the past 5 years. The study found that among the 5688 eligible patients, 27.1% did not receive serum cholesterol screening in the 5 years preceding their MI and 27.5% of patients did not receive a fasting blood glucose or glucose tolerance test in the 3 years before their MI.[12]
Skin cholesterol tests can be used as a screening tool
In Canada where all Candians have access to free healthcare services, it is quite an alarming statistic that more than a quarter of Canadians were never even screened for cholesterol in the past 5 years before their first heart attack. Skin cholesterol testing clinics provide an excellent opportunity for pharmacists to get involved and help identify patients who are at an elevated risk of cardiovascular disease early on. These patients can then be referred for further testing and be put on medications to decrease their risk.
LDL
In the general population LDL is an important marker of coronary risk however its usefulness in patient with chronic kidney disease is not as clear.
A study looking at the Association between LDL-C and Risk of Myocardial Infarction was conducted in 836, 060 patients who were followed from 2002-2009[13]. During the median follow up at 48 months, 7762 patients were hospitalized for myocardial infarction, with incidence highest among participants with the lowest eGFR. The hazard ratios of myocardial infarction associated with LDL ≥4.9 compared with 2.6-3.39 mmol/L in participants with varying eGFR are summarized below:
eGFR = 15-59.9 ml/min per 1.73 m2; HR = 2.06 (1.59-2.67)
eGFR = 60-89.9 ml/min per 1.73 m2; HR = 2.30 (2.00-2.65)
eGFR ≥ 90 ml/min per 1.73 m2; HR = 3.01 (2.46, 3.69).
In conclusion, the association between higher LDL-C and risk of myocardial infarction is weaker for people with lower baseline eGFR even despite the fact that they have a higher absolute risk of myocardial infarction. Therefore, increased LDL may be less useful as a marker of coronary risk among people with CKD than it is the general population.
Although LDL is currently considered the gold standard, it is not a perfect biomarker and has several limitations. It is important to understand that no biomarker is perfect for all patients. Alternative biomarkers may prove to be more useful in specific patient populations where LDL levels are less clinically significant. Skin Cholesterol is one of several biomarkers which are currently being studied and it may prove to have similar properties and be more significant in certain populations.
Physician-led Cardiovasular Risk Assessment
Recent Canadian survey of physicians suggests that physician understanding and use of cardiovascular risk assessment is suboptimal. 846 Canadian primary care physicians were surveyed and the survey revealed that only 70% of physicians used the Framingham Risk Score, 30% could not identify the thresholds for high risk patients, 44% correctly used a positive family history to double the risk score.[14]
In a separate analysis, it was estimated that preventive services are only offered in 11%-33% of primary care visits.[15]
Pharmacists can play a big role in cardiovascular risk assessment. One of the ways this can be done is by doing a skin cholesterol test. This can be complemented with a Framingham risk calculation and a discussion of modifiable risk factors which are essential for all patients to understand.
Compliance
When it comes to compliance, the numbers speak for themselves (they are not good).
Skin cholesterol testing clinics provide an excellent opportunity for the pharmacist to educate the patient and put their cardiovascular risk into perspective for them. This is very important as there are so many patients who are not convinced they need treatment. The specifics on how to do this will be discussed further under the clinic day section of the website
Framingham Risk Scores
Framingham Risk Scores are one of the best and most validated tools we have however there are still several limitations:[17]
Combining Framingham Risk Scores with skin cholesterol may be more valuable than either one alone as has been suggested in clinical trials. This evidence is discussed further in the skin cholesterol section of the site.
Screening
A retrospective cohort analysis of 5688 patients admitted with their first MI to 96 acute care hospitals in Ontario was conducted in 2004-2005. Rates of screening for diabetes and hyperlipidemia according to the guidelines were calculated and the screening rates were stratified by age, sex, socioeconomic status, and number of primary care visits in the past 5 years. The study found that among the 5688 eligible patients, 27.1% did not receive serum cholesterol screening in the 5 years preceding their MI and 27.5% of patients did not receive a fasting blood glucose or glucose tolerance test in the 3 years before their MI.[12]
Skin cholesterol tests can be used as a screening tool
In Canada where all Candians have access to free healthcare services, it is quite an alarming statistic that more than a quarter of Canadians were never even screened for cholesterol in the past 5 years before their first heart attack. Skin cholesterol testing clinics provide an excellent opportunity for pharmacists to get involved and help identify patients who are at an elevated risk of cardiovascular disease early on. These patients can then be referred for further testing and be put on medications to decrease their risk.
LDL
In the general population LDL is an important marker of coronary risk however its usefulness in patient with chronic kidney disease is not as clear.
A study looking at the Association between LDL-C and Risk of Myocardial Infarction was conducted in 836, 060 patients who were followed from 2002-2009[13]. During the median follow up at 48 months, 7762 patients were hospitalized for myocardial infarction, with incidence highest among participants with the lowest eGFR. The hazard ratios of myocardial infarction associated with LDL ≥4.9 compared with 2.6-3.39 mmol/L in participants with varying eGFR are summarized below:
eGFR = 15-59.9 ml/min per 1.73 m2; HR = 2.06 (1.59-2.67)
eGFR = 60-89.9 ml/min per 1.73 m2; HR = 2.30 (2.00-2.65)
eGFR ≥ 90 ml/min per 1.73 m2; HR = 3.01 (2.46, 3.69).
In conclusion, the association between higher LDL-C and risk of myocardial infarction is weaker for people with lower baseline eGFR even despite the fact that they have a higher absolute risk of myocardial infarction. Therefore, increased LDL may be less useful as a marker of coronary risk among people with CKD than it is the general population.
Although LDL is currently considered the gold standard, it is not a perfect biomarker and has several limitations. It is important to understand that no biomarker is perfect for all patients. Alternative biomarkers may prove to be more useful in specific patient populations where LDL levels are less clinically significant. Skin Cholesterol is one of several biomarkers which are currently being studied and it may prove to have similar properties and be more significant in certain populations.
Physician-led Cardiovasular Risk Assessment
Recent Canadian survey of physicians suggests that physician understanding and use of cardiovascular risk assessment is suboptimal. 846 Canadian primary care physicians were surveyed and the survey revealed that only 70% of physicians used the Framingham Risk Score, 30% could not identify the thresholds for high risk patients, 44% correctly used a positive family history to double the risk score.[14]
In a separate analysis, it was estimated that preventive services are only offered in 11%-33% of primary care visits.[15]
Pharmacists can play a big role in cardiovascular risk assessment. One of the ways this can be done is by doing a skin cholesterol test. This can be complemented with a Framingham risk calculation and a discussion of modifiable risk factors which are essential for all patients to understand.
Compliance
When it comes to compliance, the numbers speak for themselves (they are not good).
- Around 50% of patients will discontinue lipid drug therapy within one year.[15]
- As few as 25% of those treated for primary prevention will continue therapy after 2 years.[15]
- Most patients stop treatment because they are unconvinced of the need for treatment. [16]
Skin cholesterol testing clinics provide an excellent opportunity for the pharmacist to educate the patient and put their cardiovascular risk into perspective for them. This is very important as there are so many patients who are not convinced they need treatment. The specifics on how to do this will be discussed further under the clinic day section of the website
Framingham Risk Scores
Framingham Risk Scores are one of the best and most validated tools we have however there are still several limitations:[17]
- Short-term risk estimates over 10 years are very sensitive to a patients age and older individuals are more likely to be targeted for therapy
- Risk categories that are widely used (Low Risk: 10%, Intermediate Risk: 10%-19%, and High Risk: >20%) are completely arbitrary and have been chosen by consensus rather than by scientific evidence.
- There are no randomized controlled trials which showing optimal outcomes based on therapy guided by Framingham Risk Scores
- Does not take into account family history or socio-economic position
- Overestimation of risk in patients with diabetes
- Not validated in patients > 75 years of age
Combining Framingham Risk Scores with skin cholesterol may be more valuable than either one alone as has been suggested in clinical trials. This evidence is discussed further in the skin cholesterol section of the site.