Mayo Clinic conducted a meta-analysis of randomized controlled trials (RCTs) testing the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on coronary heart disease (CHD). The goal was to evaluate improvement in patients taking these 2 Omega-3 fatty acids. This sounds like it should be a good study. However, not everything is as it seems so lets dig in to this one and see if it pans out as they stated.
The title of the study was “A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk.”
The investigators searched medical literature databases including Ovid/Medline, PubMed, Embase, and the Cochrane Library for studies regarding EPA & DHA, either from food or from supplements associated with cardiovascular disease (myocardial infarction, sudden cardiac death, coronary death, and angina). They looked at studies from 1947 to 2015 and identified 18 randomized controlled trials (RCTs) & 16 prospective cohort studies.
They wanted to evaluate the association of Omega-3 intake with coronary heart disease (CHD). They also wanted to evaluate the effect of the dose of Omega-3s as well as the effect of EPA & DHA on specific outcomes such as heart attacks (myocardial infarction). Each identified study was required to report at least one of the following: myocardial infarction (heart attack – fatal or non-fatal), chest pain (angina), sudden cardiac death, & CHD incidence. The studies had to include outpatient adults at least 18 years of age with or without CHD. They grouped the studies based on Omega-3 intake levels of below 1 gram per day or above 1 gram per day.
There were 93,000 participants in the RCT data and 732,000 participants in the prospective cohort data. There were 2 trials for primary prevention (preventing a first CHD event) with 27,494 participants. There were 9 trials focusing on mixed prevention and 12 trials focusing on secondary prevention.
One of the problems with meta-analysis as a study type is that your conclusions are only as good as the studies in the meta-analysis. The problem here is that there is a very wide range of Omega-3 dosing (0.38 grams to 23.8 grams per day for the primary and mixed prevention groups). It is likely that beneficial effects of Omega-3s were not noticed in the trial where they only took 380mg of EPA+DHA (0.38 grams) daily. Conversely, 23.8 grams per day is quite a lot.
The authors of the trial did observe that higher doses of EPA+DHA had a “stronger impact” in those with elevated triglyceride levels compared to trials where the participants took less than 1 gram per day of EPA+DHA.
Prospective cohort trials did demonstrate statistically significant reductions in CHD. The number is the percentage reduction for that event in patients taking Omega-3s.
Any CHD event – 18%
Fatal CHD events – 23%
Coronary death – 18%
Sudden cardiac death – 47%
They noted that Omega-3s reduced triglycerides as well as reduced risk of CHD in patients with LDL cholesterol >130. They felt that the benefit in regards to LDL may have been due to the change in LDL to the larger LDL particle which is less atherogenic. They also stated that “Blood pressure is another well-documented CHD risk factor impacted favorably by n-3 LCPUFA administration.”
Their conclusion?
“Results indicate that EPA+DHA may be associated with reducing CHD risk, with a greater benefit observed among higher-risk populations in RCTs.” However, I believe that further review of their data demonstrates that their conclusion statement is understating the effect of Omega-3s.
For example, one of the studies was a food recall questionnaire asking participants how many servings of fish they ate on a weekly basis. The investigators then assigned an Omega-3 quantity based on what type of fish meat it was (dark meat fish, canned tuna, and other fish). One confounding factor noted was that there was an inverse relationship of fish intake and red/processed meats. In other words, those that ate more fish ate less red/processed meats. It should be noted that there is a huge potential for bias in a food/diet recall questionnaire. Regardless, the investigators stated “In this prospective cohort study of diabetic women, higher consumption of fish and ω-3 fatty acids was associated with a lower incidence of both CHD and total mortality, even after adjustment for established cardiovascular risk factors.”2
Here are some of the studies evaluated in the Mayo Clinic Omega-3 Study
The DART Trial3
Another trial was merely based on whether or not they received dietary recommendations. 2033 male participants who had recovered from a heart attack (myocardial infarction) were randomized to either receive or not receive dietary advice. If they did receive dietary advice it was in regards to one of 3 groups: reduced fat intake (and increase in ratio of polyunsaturated fat to saturated fat), increase the amount of dietary fatty fish, or increase the amount of cereal fiber. The investigators noted that “The subjects advised to eat fatty fish had a 29% reduction in 2 year all-cause mortality compared with those not so advised.”3 I have several issues with relying on this study. There may be a good correlation with dietary advice regarding fish intake and coronary heart disease but there is no way to confirm how much fish they ate, their Omega-3 Index levels, quality of fish, etc.
GISSI-Prevenzione Trial4
This trial consisted of 11,324 participants who had survived a recent heart attack. They were randomized to receive Vitamin E (alpha-tocopherol, 300mg daily), Omega-3 supplements (1 gram daily), both of these, or neither of these for 3-5 years. The investigators wanted to evaluate if these supplements made a difference in death, non-fatal heart attack (myocardial infarction), or stroke.
They discovered that vitamin E supplementation did not make a difference. However, Omega-3 supplementation did with a relative risk reduction of 15% by 4-way analysis. The results for the group taking Vitamin E and Omega-3 combined were similar to those taking Omega-3s alone.
The ORIGIN Trial5
This study is very interesting because they showed that “Daily supplementation with 1 g of n–3 fatty acids did not reduce the rate of cardiovascular events in patients at high risk for cardiovascular events.” 12,536 participants were randomized to receive 900mg of ethyl ester Omega-3 (EPA 465 mg and DHA 375 mg) or a placebo. The participants had impaired fasting glucose, impaired glucose tolerance, or diabetes. They also received ither insulin glargine or standard care. Their primary outcome measurement was death from cardiovascular disease.
Why did this study not show improvement with Omega-3s when so many other studies do show improvement? The answer is simple. Their placebo was 1 gram of olive oil which is well known to have cardiovascular disease protective benefits!
The JELIS Trial6
There were 18,645 Japanese participants with a total cholesterol level of 251 mg/dL or more who were randomized to receive a statin only or a combination of a statin plus EPA 1800mg. Primary endpoints were any major adverse coronary events (sudden cardiac death, heart attacks, unstable angina, angioplasty, stents, or coronary artery bypass grafting [CABG]).
There was a 19% reduction in these Major Adverse Coronary Events (MACE) in the EPA + statin group at the end of 4-6 years. This study shows that patients have lower risk of cardiovascular disease outcomes if they are on EPA in addition to a statin.
The OMEGA Trial7
The OMEGA trial was a multicenter trial in Germany and consisted of 3,851 participants. It was a randomized, placebo-controlled, double-blinded (RCDBT) trial. Participants were randomized between 3 & 14 days after a heart attack to receive either 1 g omega-3 ethyl esters (EPA 460 mg & DHA 380 mg) or a soft gelatin capsule containing 1 g olive oil. This is yet another trial using olive oil as a placebo inappropriately. Therefore, they didn’t notice any difference between the 2 groups.
The Framingham Heart Study has been an ongoing study, since 1948, attempting to identify common risk factors that contribute to cardiovascular disease. The study began with 5,209 men and women between the ages of 30-62 from the town of Framingham, Massachusetts. The study participants return every 2 years for detailed physical examinations, medical history, and lab tests.
The second generation of participants, the off-spring of the original participants, were enrolled in 1971. There were 5,124 of those. The “Omni Cohort” was enrolled in the Framingham Heart Study in 1994 after identifying the need to increase the diversity of the population. Framingham 3 began in 2002 with the enrollment of the grandchildren of the original participants, the third generation. The 2nd generation of the Omni Cohort was added in 2003. The majority of participants are caucasian.
The Framingham Heart Study has resulted in approximately 1,200 articles in different medical journals. Over the years, different diagnostic technologies have been added. Echocardiography, carotid artery ultrasound, cardiac MRI, and CT scans of the hart and coronary arteries are examples of some of the diagnostic technologies. Evaluations of the genetic profiles of all participants are also being evaluated.
Research Milestones of findings from the Framingham Heart Study are available on their website.
The Framingham Risk Score
The Framingham Risk Score is a 10-year calculation of risk for cardiovascular disease was formulated from the Framingham Heart Study. The Framingham Risk Score Calculator uses several factors in order to calculate the patient’s risk of developing cardiovascular disease within 10 years. Low intermediate, and high risk is based on the percent risk over 10 years.
Low Risk: <10% risk in the next 10 years
Intermediate Risk: 10-20% risk in the next 10 years
High Risk: >20% rusk in the next 10 years
The components of the risk calculator are:
Age
Gender
Systolic Blood Pressure
Treatment for hypertension (yes or no)
Smoking status
Diabetes
HDL
Total Cholesterol
The Framingham Risk Score (FRS) has driven cardiovascular disease risk screening for many years. I believe there are 2 problems with this. First, this screening is based on known risk factors and not the actual presence of disease. Second, it is based on epidemiology.
Epidemiologic data can be tricky because it tells us about issues in a given population. However, it does NOT necessarily indicate risk for a specific person.
6p24.1 Gene resides on Chromosome 6. Chromosome 6 represents about 6% of human DNA. Chromosome 6 contains numerous genes having to do with the immune response such as Human Leukocyte Antigen (HLA), Major Histocompatibility Complex (MHC), and many others.
6p24.1 is also called Phosphatase and Actin Regulator 1 (PHACTR1)1 and is most significantly expressed in the globus pallidus of the brain. The Genome-Wide Association Studies (GWAS) has revealed an association with coronary artery disease as well as migraines.2,3.
Aldosterone synthase is the enzyme that activates aldosterone. In fact, it is the only enzyme that can create aldosterone. Aldosterone synthase is encoded by the CYP11B2 gene on chromosome 8q22.2
Aldosterone synthase catalyzes the synthesis of aldosterone from deoxycorticosterone, a process that successively requires hydroxylation at positions 11 beta and 18 and oxidation at position 18
The presence of left ventricular hypertrophy worsens the prognosis of cardiovascular disease 1, 2. In arterial hypertension, left ventricular structure is determined by hemodynamic (e.g., blood pressure) and nonhemodynamic factors such as angiotensin II3, 4and aldosterone5, 6, 7. Aldosterone stimulates cardiac collagen synthesis and thus contributes to the development of cardiac fibrosis8, 9, 10. Aldosterone acts via the mineralocorticoid type I receptor, which has been found in both the rat heart 11, 12, 13and, more recently, in the human heart (14).
The human aldosterone synthase (CYP11B2) gene is located on chromosome 8, band 8q22, closely related to CYP11B1 15, 16. Gene variants of CYP11B2 have been associated with corticosterone methyloxidase II deficiency (17), and a chimeric 11-beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and arterial hypertension (18). One frequent polymorphism of the aldosterone synthase gene is located in the promoter region (−344 C/T). Another polymorphism is a gene conversion in intron 2 (19).
The −344 C/T polymorphism seems to be functionally relevant. Response to adrenocorticotropic hormone stimulation is reduced in the −344 CC genotype as compared with the TT genotype (20). Tetrahydroaldosterone excretion rate was found higher in the TT and CT genotypes than in the CC genotype (21). The C-allele has been found associated with elevated levels of plasma aldosterone, increased pulse wave velocity, and decreased baroreflex sensitivity 22, 23, but another study reports an elevated urinary aldosterone excretion in T-allele carriers (20). Blood pressure might also be influenced by the −344 C/T polymorphism. There are, however, inconsistent results about whether the T-allele 21, 24or the C-allele (20)is associated with arterial hypertension.
In a recent study, Kupari et al. (25)found an association between the −344 C/T polymorphism and left ventricular structure: the greater the number in C-alleles, the greater the left ventricular mass (LVM) and left ventricular end-systolic and end-diastolic diameter (25). In contrast, a most recent study by Schunkert et al. (26)could not confirm these findings in a larger study cohort. However, the pattern of cardiac morphology in subjects with the CC genotype in the study of Kupari et al. (25)is similar to that found in a state of volume load that can be the result of high dietary sodium intake 27, 28; consequently, a correlation between dietary sodium intake and LVM index was found in C-allele carriers only (25).
References
Mol. Cell. Endocrinol. 217 (1–2): 67–74.
Takeuchi, F., Yamamoto, K., Katsuya, T. et al. Reevaluation of the association of seven candidate genes with blood pressure and hypertension: a replication study and meta-analysis with a larger sample size. Hypertens Res35, 825–831 (2012).
Journal of the American College of Cardiology. 2001;37(3):878-884
The CardioHealth Platinum program is specifically designed for those who want to know all they can about their current and future risk of cardiovascular disease. It is the best of everything we have to offer for identifying cardiovascular disease as well as risk for cardiovascular disease. But these tests don’t just help diagnose things. They can also show us if our therapeutic treatment plan is working and gives us a change to adjust to make sure we get the results we want and need.
The CardioHealth Platinum is cost-effective and easy to complete. All blood work is drawn at Revolution Health & Wellness Clinic in Tulsa, Oklahoma. All testing (except the CAC discussed below) is also done at Revolution. Of course, we may find something that would need additional testing or therapy not available in our clinic. All of these tests can be completed in less than half a day.
Having measurements of risk factors AND disease process allows us to directly treat the disease process as well as the risk factors. More importantly, we can see if improving the risk factors is actually making a difference in the overall disease process.
We start off looking at risk factors. We capture as much information as we can in regards to your overall risk for cardiovascular disease. Certainly, we look at the 5 traditional risk factors but we do it in an exceptional way:
(1) Hypertension:
You may already know that your blood pressure should be <120 over <80. However, there is so much more that you should know about your blood pressure! We use the right machines and devices to measure your blood pressure in the most accurate way possible. Our testing is based on a thorough review of the medical literature so that we can give you the absolute best information about your blood pressure available.
We measure your blood pressure in ALL of your extremities. We check it with several different devices. We check your central blood pressure. And, finally, we check your 24-hour ambulatory blood pressure. These tests, together, provide the absolute best information you can get about your blood pressure at various times of day. This allows us to further evaluate your cardiovascular health and prescribe the absolute best interventions.
We also measure several labs to make sure we thoroughly understand the physiologic mechanisms behind your hypertension, if present. Knowing these mechanisms helps us further refine your therapy. Plasma Renin Activity and Aldosterone levels help us with this. These labs are run through your insurance so we do not charge for them.
CardiaX is a genetic test that evaluates your cardiovascular risk based on genetics. Several of these genes can help us understand your blood pressure and how it should be treated. Knowing your genetics enables us to focus our therapy on your specific reasons for blood pressure issues if they are present.
(2) Hyperlipidemia:
It is important to understand your lipid (cholesterol) levels. However, the standard lipid panel is woefully inadequate for assessing your cardiovascular disease risk. You need additional testing if you really want to understand how to be as healthy as possible. We add LDL-Particle, Lp(a), and sdLDL as part of our routine lipid assessment.
(3) Diabetes:
Many people think that if they are not “diabetic” then they doing well in regards to their blood sugar when it comes to cardiovascular disease. Nothing could be farther from the truth. In fact, risk for cardiovascular disease begins to increase when your A1c is higher than 5.1. There is evidence that risk for cardiovascular disease increases 1% for every 1 point above 75 is your fasting blood sugar. If you have actual diabetes then you have a real problem and you need to be VERY aggressive about getting it under control.
We measure several labs such as fasting blood sugar, insulin, HbA1c, pro-insulin, c-peptide, fructosamine, 1,5-anhydroglucitol, adiponectin, leptin, an others to ensure that your insulin sensitivity is optimal so that you can be as healthy as possible. Not only can we diagnose with this information but we can also track our progress so that we can measure the effectiveness of your therapy. That is absolutely critical.
(4) Obesity:
We define obesity by the body mass index (BMI). A BMI above from 25-30 is considered overweight and over 30 is considered obese. However, it isn’t really the BMI that matters. It is body composition. We need to measure and assess your body composition so that we can see percent body fat which is the real issue.
We measure this with the Bio-Electric Impedance Analysis (BIA). Our goal is to optimize your body composition as opposed to your BMI. This measurement is included in your CardioHealth Platinum.
(5) Tobacco/Smoking:
There is really nothing to measure here… If you smoke, quit. Whatever it takes. Do not smoke. Ever.
Other Risk Factors In The CardioHealth Platinum Program
There are numerous other labs that we routinely check in the CardioHealth Platinum program. The lab will bill your insurance for these labs so we do not charge for these at our clinic. We check a full hormone panel, thyroid labs, inflammatory markers, nutritional markers, and many others. Many of our patients are shocked at the amount of information they get from what we consider our ‘basic’ lab panel.
Nutritional deficiencies can play a significant role in cardiovascular disease. We measure serum levels of some nutrients. However, others are very difficult to measure. Additionally, we want to make sure that our cells are functioning at their highest level. The Spectracell Functional Intracellular Assay (FIA) of 31 nutrients provides excellent nutritional and cellular function information. It can be a game changer!
Heavy Metals, Toxins, and Infections
Each of these can significantly impair cellular function, increase inflammation, increase oxidative stress, decrease antioxidant ability, and simply wreak havoc. We have found heavy metals to be a significant cause of cellular disruption and they can frequently contribute to cardiovascular disease. We routinely test for these heavy metals in the CardioHealth Platinum program. Other toxins and infections can be measured if indicated at any point.
Heart Rate Variability (HRV) reflects the simultaneous affect of the sympathetic and parasympathetic nervous systems on the heart, which results in a beat-to-beat variability on an electrocardiographic (ECG) rhythm strip. A change in the normal autonomic regulation of heart rate may reflect the impact of a stressor on the body and can detect the early signs of pathologic developments or functional disorders, which may not be detected with routine physical or laboratory examinations.
It is well known that stress can greatly increase cardiovascular disease risk. We know that working to improve the physiologic response to stress can decrease this risk.
The HRV test is a routine part of the CardioHealth Platinum program which helps us understand your physiologic and emotional responses to stress which can impact your heart health. Knowing your autonomic responses can help us tailor our therapy.
PULS
This is, without question, one of the best tests I’ve seen in quite a while. It measures your risk of having a cardiovascular disease event within the next 5 years based on several serum markers. When these markers are elevated, there is a high correlation with unstable plaque in the arteries and this risk needs to be mitigated.
This test does not “diagnose” cardiovascular disease. It is simply a “check engine light” letting us know that there is a problem. Like many of the other tests mentioned previously, we can repeat this test to measure the effectiveness of our therapy to make sure it is working. When it is working we’ll see the score improve. Often, fairly quickly.
CardioHealth Platinum Disease Evaluation Tests
Evaluating actual cardiovascular disease appears to be vastly superior in our ability to predict heart attacks and strokes. Risk factors matter but it is more important to understand if you actually have cardiovascular disease. The following tests are included in the CardioHealth Platinum program.
Endothelial dysfunction is the first marker of cardiovascular disease. Given our poor diet, stress, inflammation, and exposure to toxins, most people have very poor endothelial function. How many people do you know who have erectile dysfunction? Maybe you have it yourself. Erectile dysfunction is caused by endothelial dysfunction. If those aren’t working to provide an erection then they aren’t working anywhere else either.
We can easily measure endothelial function in the clinic and results are available immediately. If your endothelial function isn’t good then cardiovascular disease is in your future. We need to get this treated as quickly as possible and there are several things that can help.
Arterial Elasticity
The second marker to show up in the presence of vascular dysfunction is a decrease in arterial elasticity. You want young, elastic arteries. As we age, and certainly in the setting of increased vascular damage, our arteries get stiffer. The CV Profile directly measures the arterial elasticity and helps us understand how healthy (or sick) your arteries may be. This is an excellent initial test to screen for the beginnings of cardiovascular disease.
DPA stands for Digital Pulsewave Analysis. It is another measurement of arterial stiffness as stiff arteries transmit a pulse wave much faster than a soft, elastic artery.
The Carotid Intima-Media Test (CIMT) is one of my favorite tests as it measures the wall of the artery itself as well as the presence of any plaque. This test is much more sensitive than the duplex doppler used by most physicians since it can detect the presence of ANY plaque, not just the ones blocking at least 60% of the artery.
Ankle-Brachial Index (ABI)
This test measures your blood pressure in your arms and legs and calculates your risk of having peripheral arterial disease (PAD). It is fairly simple to do and only takes a few minutes. Your blood pressure is measured with a doppler and a blood pressure cuff. You want a score of >0.9 to ensure good vascular health.
The Coronary Artery Calcium Score (CAC) is another excellent test that measure coronary artery disease directly. We do not perform this test in our clinic and the cost ($50-100) is not included in the program but it is an essential component of understanding your cardiovascular disease risk as deeply as possible. This is a non-invasive, pain-free, quick test that provides excellent information about cardiovascular disease in your coronary arteries.
CardioHealth Platinum Summary
The CardioHealth Platinum program is the most comprehensive cardiovascular screening program you’ll find anywhere in this area. Nobody in Oklahoma even comes close to being able to identify cardiovascular disease as early as we can with all of these tests. You may not want (or need) this much information so you may want to start with CardioHealth 101 or CardioHealth Advanced. However, you may want all of the peace of mind we can provide with the CardioHealth Platinum program.
Whichever program you choose, don’t wait another day. Your health is simply too important!
The CardioHealth Advanced program identifies cardiovascular disease far before the conventional medical approach “risk factors based” assessment. In fact, the conventional risk factor based evaluation for cardiovascular disease misses 50% of patients with cardiovascular disease.1 Doing things like regular doctor’s office visits, getting your cholesterol checked, making sure you aren’t diabetic and controlling your blood sugar, and not smoking are all good things. However, they don’t guarantee that you won’t have a heart attack. In fact, they can lead to a false sense of security!
If you want to know your REAL risk of cardiovascular disease then you need to dig deeper. You need additional testing. You need to know exactly where you are. This starts with the CardioHealth 101 program which consists of 3 simple, quick, and relatively inexpensive tests performed in our clinic. These 3 tests are:
These are great tests and an excellent place to start but that may not be enough for you. You may want more reassurance that your blood vessels are healthy. You simply may need more information. That is why we developed the CardioHealth Advanced Program.
What Is Included in the CardioHealth Advanced Program?
Everything in the CardioHealth 101 program
an EKG to assess for electrical abnormalities in your heart as well as abnormal heart beats and patterns
Central blood pressure assessment which is a much better reflection of the strain on your heart as well as your risk of cardiovascular disease
Labs assessing your kidney function, blood sugar, homocysteine, and lipids (cholesterol) – you need to be fasting for these labs.
COSEHC Score which calculates your risk of dying of cardiovascular disease within the next 5 years
An Ankle-Brachial Index (ABI) which checks for Peripheral Arterial Disease (PAD) or atherosclerosis in your abdominal aorta, iliac arteries, and arteries in your legs
Adding the CardioHealth Advanced program dramatically expands the amount of information we obtain about your cardiovascular health an risk for heart attack (or stroke). Plus, it only adds a small cost – not even half the cost of the CardioHealth 101. The price of the ABI alone covers the additional cost of the CardioHealth Advanced over the cost of the CardioHealth 101.
Of course, you can always start with the CardioHealth 101 and we can add the CardioHealth Advanced tests at any time. However, I firmly believe that the amount of additional information about your cardiovascular system makes the small price difference a non-issue.
The CardioHealth Advanced program is a lot more information and far less expensive than any other cardiovascular screening program than any other cardiovascular screening program out there. Certainly, there are less expensive tests but they don’t provide anywhere near the information and they don’t detect cardiovascular disease early enough.
While the CardioHealth Advanced screening is sufficient for most people, some of our patients want the absolute best they can get. If that is you then you need to look at the CardioHealth Platinum program.
Whichever program you choose, don’t wait another day to schedule your CardioHealth screening. You never know when cardiovascular disease may strike!
Atherosclerosis Without Cardiovascular Risk Factors
This study, a sub-population of the PESA study, clearly shows that Atherosclerosis Without Cardiovascular Risk Factors occurs far sooner than we often think. This paper, published in the Journal of the American College of Cardiology, is entitled “Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors.” It was conducted on a subset of participants in the larger PESA Study. The title implies that it doesn’t matter if your LDL is elevated or not, you still may be at risk for developing plaque in your arteries. In other words, we miss a lot of patients at risk for heart attacks when we are looking at the typical risk factors often described in traditional medicine.
We typically consider patients to be at low risk of cardiovascular disease and heart attacks if they don’t have the typical CardioVascular Risk Factors (CVRF) such as:
Smoking
Hypertension (BP >140/>90)
Fasting blood sugar >126 mg/dL
Total Cholesterol >240 mg/dL
LDL Cholesterol >160 mg/dL
HDL <40 mg/dL
In this paper, there was a sub-group of patients considered to have Optimal Risk Factors. This means that the patients were the “best of the best” so to speak, in regards to their risk factors for cardiovascular disease. The “optimal risk factors” were defined as follows:
Blood pressure <120/<80
Fasting glucose <100 mg/dL
Glycosylated Hemoglobin (A1c) <5.7%
Total cholesterol <200 mg/dL
The traditional approach to assessing risk for cardiovascular disease is based on RISK FACTORS as defined above. The question is “does assessing for these risk factors help prevent cardiovascular disease?” The authors of this study attempted to answer this question.
First, they assessed patients for the “typical cardiovascular risk factors” as defined above. The investigators then performed ultrasound to detect carotid, iliofemoral, and abdominal aortic plaque; coronary artery calcification (CAC) score; serum biomarkers; and lifestyle in order to detect atherosclerosis and cardiovascular disease.
In my experience, most cardiovascular disease evaluation is based on risk factors (as listed above) and symptoms. If you are considered very high risk then you MAY get some additional work-up but it is often difficult to get it approved my insurance. However, if you have symptoms then it is much more likely that insurance will cover the additional workup. The bottom line is that you don’t get worked up until you have disease so bad that you are seriously obstructing the artery. This simply makes ZERO sense!
What is even worse is that 68% of heart attacks occur in patients with less than 50% blockage2 in their arteries. These lesions probably wouldn’t show up on stress tests anyway! We are doing a TERRIBLE job at identifying cardiovascular disease early in its inception when it would be easiest to treat and monitor.
Atherosclerosis without Cardiovascular Risk Factors – Methods
As mentioned earlier, the group in this study is a sub-population from the Progression of Early Subclinical Atherosclerosis (PESA) Study. This population had CardioVascular Risk Factors (CVRF) below the current recommended thresholds. 4,184 participants were screened ranging from 40-54 years of age. Exclusion criteria were: known cardiovascular disease, actively being treated for cancer, or any disease where their life expectancy or ability to maintain study protocol were compromised. 4,027 (96.2%) participants had all of the required data available. 1,779 (42.5%) participants (50.3% were women) were in the CardioVascular Risk Factor (CVRF) Free population. 740 (41.6%) of those participants had CardioVascular Risk Factors at optimal levels.
At baseline, each participant went through a clinical interview, evaluations (lifestyle and activity), physical exam, EKG, and imaging studies. These were repeated at 3 and 6 years.
The study population had no CardioVascular Risk Factors as defined above. The study population represented 42.5% of the PESA study group in total. As mentioned above, there was another sub-group with “optimal” CardioVascular Risk Factors (CVRFs) which were also defined above. Other risk factors were defined as follows:
Family History of CVD: 1st-degree relative with clinical atherosclerosis (men <55 yrs of age, women <65 yrs of age)
Obesity: BMI >30 kg/m2
No tobacco use
The 10-year risk of atherosclerotic cardiovascular disease was calculated as follows:
Low: <5%
Intermediate: 5 to <7.5%
High: > 7.5%
The 30-Year Framingham Risk Scores (FRS) were calculated and classified as follows:
Low: <10%
Moderate: 10-20%
High: >20%
Blood samples were obtained and tested for:
Total Cholesterol
HDL
LDL (calculated by the Friedwald equation)
oxLDL
Triglycerides
Lp(a)
Glucose
Insulin
AbA1c
Cystatin C
Creatinine
hs-CRP
Fibrinogen
VCAM-1
P-selectin
Physical activity was monitored with an ActiTrainer accelerometer for 7 consecutive days. The PREDIMED Score was also calculated in order to assess Traditional Mediterranean Diet (TMD) compliance.
Assessment for Subclinical Atherosclerosis
Vascular Ultrasound (2D) and CT (non-contrast) performed as noted previously. Plaque was defined as a localized protrusions into the lumen of the artery with a thickness of either more than 0.5mm or 50% of the intima-media thickness (IMT). Diffuse intima-media thickness of >1.5mm.
The Coronary Artery Calcium Score (CAC) was obtained by the Agatston method. All of the CT scans were analyzed at Imaging Core Laboratory by blinded radiologists.
Subclinical Atherosclerosis was defined as either a CAC of >1 or vascular ultrasound score of >1. Participants were score as:
Even though there were no conventional CardioVascular Risk Factors, 49.7% of the participants had clinical atherosclerosis.
46.7% had peripheral vascular disease (PAD)
22.7% had plaque in their coronary arteries
17.2% had plaque in their abdominal aorta below the renal arteries
30.1% had plaque in the iliofemoral arteries.
11.1% had coronary artery calcium, most of them were mild (CAC of <100).
The extent of atherosclerosis analysis showed:
22.6% had Focal Atherosclerosis
20.9% had Intermediate Atherosclerosis
6.0% had Generalized Atherosclerosis
For participants in the Optimal CVRF group:
280 (37.8%) had atherosclerosis (peripheral plaques in 268, CAC in 43)
20.8% had Focal Atherosclerosis
13.8% had Intermediate Atherosclerosis
3.2% had Generalized Atherosclerosis
So, even though the risk factors were OPTIMAL, there was STILL cardiovascular disease present. We simply can’t trust these risk factors alone for evaluating your risk of having a heart attack!
Presence of Atherosclerosis Prediction (and multi-territorial extent)
There were significant associations between the extent of atherosclerosis as well as its presence with all measured variables except for Family History, Lp(a), Cystatin-C, hs-CRP, and Fibrinogen. VCAM-1 was not associated with the presence of plaque but was associated with its extent. Age, gender, HbA1c, and LDL were associated with the presence of disease in multivariable models. The extent of atherosclerosis was associated with the same variable as well as VCAM-1 and Cystatin-C.
Age, male gender, and LDL were associated with both the presence and extent of disease in the group with Optimal CVRFs.
There was a linear relationship with the presence of atherosclerosis and LDL. The higher the LDL, the more likely there was atherosclerosis. In the group with LDL of 60-70, the incident of atherosclerosis was 11%. However, incidence increased to 64% in the 150-160 group.
Atherosclerosis without Cardiovascular risk factors? Discussion:
The traditional approach to evaluating your risk for cardiovascular disease is based on risk factors. This type of evaluation is simply not effective. Do YOU want to know if you have cardiovascular disease? Are you okay with the fact that your doctor may miss it half of the time?
I’m not okay with this!
It is NOT okay that we miss so many potential heart attacks. I want to know for sure that I am at risk or I’m not. This is why we developed the CardioHealth 101, Advanced, and Platinum screening programs. These assessments for cardiovascular disease evaluate, not only your risk factors but also your actual disease. We use similar testing (and many more of them) to accurately and comprehensively evaluated your risk for actually having a heart attack.
There are many reasons for the multiple findings in this study. LDL was associated with increase risk of atherosclerosis as well as age and gender. Regardless of the CAUSE of atherosclerosis, which is not LDL, its presence is NOT clearly defined by the current recommendations for these risk factors. It is important that we look at the disease process and work to limit the effect of each step.
Additionally, it is important that we are more aggressive with risk and disease screening as early as possible and aggressively intervene when disease is identified we can clearly get atherosclerosis without cardiovascular risk factors.
The Rasmussen Center Score provides a validated risk prediction of having a cardiovascular disease event. Traditional screening for cardiovascular disease is woefully inadequate and identified no better than 50% of patients at risk of having a heart attack.1
The traditional approach to cardiovascular disease risk reduction has been 2-pronged. First, for patients who have already had a cardiovascular event, aggressive intervention is imposed. This is called “secondary prevention” as we are trying to prevent a 2nd heart attack or other cardiovascular event. Secondly, we screen who are considered to be “healthy” for cardiovascular disease “risk factors” and manage these with medications and lifestyle changes if they are considered abnormal.
We need a better way to differentiate those at low risk vs. high risk. The Rasmussen Score for Cardiovascular Disease is a much better test and more accurately identifies patients at risk for cardiovascular disease.
The Rasmussen Score for Cardiovascular Disease is a panel of 10 tests which are easily performed. These tests assess coronary vascular disease and are better able to predict future cardiovascular events such as heart attacks and strokes.
Rasmussen Score for Cardiovascular Disease Methods
Questionnaires were mailed out to 1400 patients who had been previously screened at the Rasmussen Center for Cardiovascular Disease Prevention. The primary focus of the questionnaire was morbid events (heart attack, angina, stroke, CABG, stents, heart failure, and peripheral vascular disease) occurring after their screening tests. 613 questionnaires were returned completed.
There are 10 tests in the Rasmussen Score for Cardiovascular Disease. Arterial elasticity is measured with the CV Profiler and provides the C1 and C2 elasticity index. The scores are age adjusted and are displayed in the table below.
Rasmussen Score for Cardiovascular Disease Scoring System
Each test listed above is scored as Normal, Borderline, or Abnormal. Normal has a score of 0, Borderline = 1, and Abnormal =2. Therefore, if you assign a number to each test then the score ranges from 0 (no evidence of disease) to 20 (strong evidence of disease).
Scores of 0-2 were considered to be absent of cardiovascular disease. A score ranging from 3-5 were considered as evidence of early disease and a score of >6 were considered to have advancing cardiovascular disease.
Results
35 participants experienced a cardiovascular event as defined above between their screening and when they filled out their questionnaires. 26 of these events occurred within the “Advanced Disease” group with a score of >6. 8 events occurred in the “Early Disease” group with a score of between 3 & 5. 1 event occurred in the “no disease” group with a score of 0-2.
Of note, >10% of the morbid events occurred in patients considered to be low-risk by the Framingham Risk Score (FRS). These patients were not identified by the FRS and would, therefore, not been candidates for preventive therapy. The authors stated “Because so few individuals exhibited risk factors in the high-risk category, it is clear that traditional FRS classification is not an adequate discriminator in this population.”
The Hazard Ratio (HR) for the Rasmussen Score for Cardiovascular Disease was greater than the HR for the Framingham Risk Score (FRS).
28% of the participants had a Rasmussen Score for Cardiovascular Disease of 0-2 and there were no cardiovascular events in 6 years of follow up. There was 1 participant in this group that had an event at 8 years but it was noted that his score had increased to 7. These participants were encouraged to follow a healthy lifestyle and return in 5-10 years.
35% of the participants had a score of 3-5 (early disease group) and they had an increased likelihood of having an event but the risk was only 5% after about 4 years. However, 37% of the participants had a score of >6 (advanced disease) and 15% of those participants had an event by 6 years.
Participants in the Early Disease group received more aggressive recommendations and medications were recommended based on current guidelines and asked to return in 3 years for repeat screening. The Advanced Disease group were nearly always treated with medications and asked to return in 1 year.
As is common in the literature, cholesterol and blood pressure measurements do not necessarily discriminate patients who will or will not have an event. The traditional approach of risk-factor based evaluation should be replaced with the early disease assessment as it appears to be much more discriminating.
Discussion
Abnormalities in the cardiovascular system exhibit far before a cardiovascular event. Therefore, if we can screen for and identify these abnormalities and work to reduce them then we should be able to reduce cardiovascular disease events. The Rasmussen Score for Cardiovascular Disease is much more sensitive for cardiovascular disease risk and will allow us to identify more patients at an earlier stage where our efforts are both better and more cost effective.
This testing takes approximately 1 hour to perform and costs approximately $600. Some of the testing may be covered by insurance. The return on investment of this modest-cost testing should be quite high.
EVERYONE needs to get a CardioHealth 101! Why? Because cardiovascular Disease is the #1 cause of death of men and women. In fact, 2200 people die from cardiovascular disease every day!1 This is equivalent to four 747 airplanes crashing into the ground every day. There is 1 heart attack every 40 seconds.2 Every 37 seconds, someone dies from cardiovascular disease.3
What is even scarier is that most people have absolutely no idea if they have cardiovascular disease. In many cases, the first sign of a heart IS a heart attack. There is often no warning.
On top of that, going to your doctor often doesn’t help. Looking at the 5 traditional risk factors (hypertension, hyperlipidemia, obesity, diabetes, and tobacco use) only catches 50% of people who will have a heart attack. That means we miss 50% of people who will have a heart attack!
Are you scared you may have a heart attack? We have the answer for you.
Enter CardioHealth 101
We have the answer to the question of whether or not you will have a heart attack. CardioHealth 101 is a simple battery of 3 tests performed in the clinic. These 3 tests take approximately 30 minutes and costs less than 2 months worth of your favorite gourmet coffee. What a small price to pay for such peace of mind!
You don’t have to be a patient of Revolution. You don’t have to change doctors. You can simply schedule for the CardioHealth 101 program and get the most sensitive testing for detecting cardiovascular disease available.
With the knowledge gained from the CardioHealth 101 testing you’ll either sleep well knowing that you don’t have concern for cardiovascular disease or you’ll know that you need additional testing or therapy.
Who Should Get the CardioHealth 101?
In short, virtually everyone would benefit from the information in the CardioHealth 101. However, the medical literature suggests that anyone meeting any of the following criteria should have this testing:
Men over 45 years of age
Women over 55 years of age
Hypertension
Hyperlipidemia
Obesity
Diabetes
Metabolic Syndrome
What are the 3 tests?
These 3 tests were researched and hand-picked based on their ability to evaluate arterial structure and function. We know that endothelial dysfunction is the first abnormality in cardiovascular disease. It precedes hypertension (and other vascular issues) by decades.
Either of these tests evaluate endothelial function. You cannot get cardiovascular disease without endothelial dysfunction. Therefore, if you have a healthy endothelium then you can feel pretty good about having pretty healthy arteries.
However, if your Endothelix or EndoPAT show endothelial dysfunction then you need to work on improving it. If you ignore an abnormal endothelial function test, over time, you are facing an increased risk for cardiovascular disease. You should begin a treatment regimen to improve your endothelial function. Additionally, you can repeat your endothelial function test to make sure that your treatment regimen is working.
The Computerized Arterial Pulse Wave Analysis device, by Hypertension Diagnostics, Inc, provides the CV Profile which measures arterial elasticity. Arterial elasticity is the second finding in cardiovascular disease behind endothelial dysfunction.
This test only takes a few minutes and results are available immediately. Results are reported for C1 and C2 arterial elasticity index. This is a measure of arterial function and health.
Carotid Intima-Media Thickness (CIMT)
The CIMT is un ultrasound of the carotid arteries which evaluates the thickness of the intima and media layers of the carotid artery as well as plaque within the artery. There are other cardiovascular disease screening programs using a different kind of carotid ultrasound called a duplex doppler. However, a duplex doppler is not nearly sensitive enough and there is a big difference between it and a CIMT.
The CIMT test is also a simple, painless, non-invasive test performed in the clinic by one of our trained technicians. Performing a CIMT test takes less than 5 minutes and we’ll typically have your results in 2-3 days.
The CIMT test not only evaluates the presence or absence of plaque in the carotid artery but also assesses the Intima-Media thickness which correlates well with vascular disease. The Mayo Clinic summarized the value of carotid IMT in its March, 2009 edition of the Mayo Clinic “Proceedings” magazine in which it stated the following: “Conclusion – A CIMT evaluation can detect subclinical vascular disease in young to middle-aged patients with low FRS and CACS of zero. These findings have important implications for vascular disease screening and the implementation of primary–prevention strategies.”4
Summary
These tests are a good idea for virtually anyone but especially for those who have one of the indications listed above suggesting a higher risk for cardiovascular disease. Remember, cardiovascular disease is common and needs to be detected early when treatment is much for effective and much less expensive!
The CardioHealth 101 assessment is an excellent place to start. However, you may want more advanced testing. If so, check out the CardioHealth Advanced & CardioHealth Platinum programs.
Call the clinic today to schedule your CardioHealth 101 assessment.
References
NEJM 2011;365:2098
Vascular Biology in Clinical Practice, Oct. 2000; Mark C. Houston, MD
Heron, M. Deaths: Leading causes for 2017. National Vital Statistics Reports;68(6). Accessed November 19, 2019.
J. Am. Coll. Cardiol. 2010;56;e50-el03 originally published on line Nov 15, 2010.
Prevention is a primary focus at our Tulsa Integrative Medicine clinic. Unfortunately, the first symptom of a heart attack, for most people, is… a heart attack. The Coronary Artery Calcium Score (CAC) is an important test that helps detect cardiovascular disease much earlier than most common cardiovascular tests.
My traditional medical training taught me to work up cardiovascular disease as follows: If the patient isn’t having active chest pain or shortness of breath with exertion then my tests included a standard lipid (cholesterol) panel, A1c and blood sugar, blood pressure, and maybe an EKG. If those tests were normal then we were basically done.
As I’ve stated many times, this approach misses 50% of people who will have a heart attack.1
It is essential that we are more aggressive in looking for cardiovascular disease BEFORE there is advanced disease. We have to be much more comprehensive in our testing and screening. Tests such as EndoPAT, Endothelix, CIMT, CV Profiler, and many others are much more sensitive for detecting cardiovascular disease in its very early stages where it is much easier and more cost effective to treat.
In talking about the traditional approach to cardiovascular disease, if a patient does have chest pain, shortness of breath, or any other symptom of cardiovascular disease then a stress test is often ordered, which is very appropriate by the way. However, these stress tests are often not positive until there is at least 60-70% blockage of the coronary artery. The most interesting thing to me is that 68% of heart attacks occur in arteries with less than 50% blockage.2
National guidelines recommend the use of population-based risk algorithms, such as the Pooled Cohort Risk Assessment Equations, to determine atherosclerotic cardiovascular risk (ASCVD). “These risk algorithms are remarkably effective in predicting risk in populations, but have limitations in predicting individual risk,” says R Todd Hurst, M.D., director of the Heart Health and Performance Program at Mayo Clinic’s campus in Phoenix/Scottsdale, Arizona. “The best illustration of these limitations is that the majority of CVD events (up to 75 percent) occur in low- and intermediate-risk populations.”
Cardiovascular Disease is the #1 cause of death. However, 80% of cardiovascular disease is preventable. Here are our recommendations for how to improve cardiovascular disease and risk. This is the program we recommend for:
Coronary Heart Disease
Angina (chest pain)
Coronary Artery plaque prevention, plaque regression, and prevention of plaque rupture
Stabilization of plaque
Reduction of the Coronary Artery Calcium (CAC)
Lifestyle Recommendations
These are baseline and everyone should be following these guidelines. They apply to all aspects of health and, certainly, to cardiovascular disease as well.
Ideal body weight and composition: Men 16% body fat or less. Women 22 % body fat or less. BMI between 18.5 and 24.9. Waist circumference: Men < 36 inches. Women < 30 inches.
Sleep: 8 hours per night with good sleep habits.
Avoid all tobacco products. Limit alcohol (1-2 servings/day for men, 1 for women)
Mediation prayer, religion, spirituality and faith.
Caffeine: If you are a slow metabolizer, then avoid caffeine. If you are a fast metabolizer, it is OK to drink. You’ll learn if you are a fast or slow metabolizer on the CardiaX test.
Avoid all artificial sweeteners. Use only Erythrytol (Swerve), Allulose, or Stevia.
Nutritional Recommendations to Improve Cardiovascular Disease
Water: 50% of body weight (pounds) in ounces of filtered or distilled water per day. If you weigh 150 pounds that is 75 ounces of water, herbal teas, broths daily. No plastic.
Tea: 16 ounces of decaffeinated green tea per day and 8 oz of white tea per day
Detox + elimination diet, then anti-inflammatory, blood sugar regulating protocol with high-fiber foods and cruciferous vegetables: broccoli, cauliflower, Brussels sprouts, and cabbage
Supplement Recommendations to Improve the Cardiovascular Disease Process:
Many people (physicians included) will look at HDL and think their levels look good (or bad) simply by the number. However, it isn’t so much the LEVEL of your HDL. What really matters is HDL functionality. Ideally, you’ll have good levels with high functionality. This program helps improve HDL number and function.
Lifestyle Recommendations
Exercise: Gradual increase over 2 months to 60 minutes 6 d/wk. 40 minutes resistance and 20 minutes interval aerobics.
Ideal body weight and composition: Men 16% body fat or less. Women 22 % body fat or less. BMI between 18.5 and 24.9. Waist circumference: Men < 36 inches. Women < 30 inches.
Sleep: 8 hours per night with good sleep habits.
Avoid all tobacco products. Limit alcohol (1-2 servings/day for men, 1 for women)
Mediation prayer, religion, spirituality and faith.
Caffeine: If slow metabolizer, then avoid. If fast metabolizer, it is OK to drink. You’ll learn if you are a fast or slow metabolizer on the CardiaX test.
Avoid all artificial sweeteners. Use only Erythrytol (Swerve), Allulose, or Stevia.
Fruits and Vegetables: 10-12 servings/d of fruits (4 servings) and multicolor non-starchy vegetables (8 servings)
Water: 50% of body weight (pounds) in ounces of filtered or distilled water per day. If you weigh 150 pounds that is 75 ounces of water, herbal teas, broths daily. No plastic.
Tea: 16 ounces of decaffeinated green tea per day and 8 oz of white tea per day
Pomegranate: ¼ cup of pomegranate seeds or 6 oz of pomegranate juice per day
Genetic differentiation is what makes us unique. It also changes our risk for certain diseases. In regards to cardiovascular disease, one gene stands out as having a consistent association with increased risk of coronary heart disease, heart attacks (MI) and atherosclerosis. That gene is 9p21.
4 separate studies reported the association between 9p21 and cardiovascular disease within weeks of each other in 2007.16 Eight different single nucleotide polymorphisms (SNPs) have been identified to associate with increased risk of cardiovascular disease.
It is interesting to note that the association of 9p21 to cardiovascular disease is independent of other risk factors. 9p21 doesn’t seem to have any effect on cholesterol, hypertension, diabetes or markers of inflammation. Because of this, the mechanism by which 9p21 increases risk is poorly understood.8,9 Another interesting point is that the atherogenic 9p21 Single Nucleotide Polymorphism (SNP) maps to a segment of the chromosome with no known protein coding genes.
The 9p21 Gene is associated with:
Coronary artery disease (CAD)9,11,17
Heart attacks (myocardial infarction [MI])8,18
Abdominal aortic aneurysms7
Intracrandial aneurysms7
Peridontitis19
Stroke6
Approximately 21% of individuals in the population are homozygous for this SNP meaning that both of their genes have the higher risk variant. Their estimated risk of suffering heart attack is 1.64 times compared to those without the high-risk SNP. In looking this SNP in the setting of early-onset heart attacks, the risk is doubled8.
How Does 9p21 Increase Heart Attack Risk?
Initially, the 9p21 SNP didn’t make sense. However, more information has come out which, at least partially, explains why 9p21 increases risk for cardiovascular disease.
Signal Transducer and Activator of Transcription 1 (STAT1) is a transcription factor protein. This means that it helps turn certain genes on and off. It is activated by several ligands such as IL-6, TNFa, PDGF, and many others.20 STAT1 has a key role in many gene expressions that cause survival of the cell, viability or pathogen response. It plays a very important role in inflammation. Inflammation is a major contributor to atherosclerosis and angiogenesis in endothelial tissue.
There are 33 gene enhancers located in the 9p21 region that are implicated in inflammatory pathways.1 The interaction of 9p21 with STAT1, CDKN2A/B, and INF-g increase the genetic susceptibility to coronary heart disease and the response to inflammatory signaling in vascular cells.10 STAT1 is a downstream effector of the pathway that mediates response to inflammation, which is associated with angiogenesis12 and atherosclerosis pathogenesis13 in endothelial tissue. Thus, in endothelial tissues, the biological effects of the rs10811656 and rs10757278 risk alleles disrupting the ECAD9 STAT1 binding site might be augmented during activation of the inflammatory response.
Two SNPs located in one of these enhancers disrupt a binding site for STAT1, a signal transduction protein that regulates inflammation. This enhancer locus physically interacts with the CDKN2A/B locus and an interval downstream of IFNA21, The gene that encodes interferon-γ in human vascular endothelial cells. The activation of interferon-γ affects transcriptional regulation of the 9p21 locus, including STAT1 binding, suggesting a link between genetic susceptibility to coronary artery disease and response to inflammatory signaling in vascular cells. Yet another driver of disease may be the aforementioned noncoding RNA element ANRIL.
How To Improve Your Risk If you Have 9p21
Obviously, you can’t change your genetics any more than a leopard can change its spots. The good news is that you CAN change whether or not this gene is causing a problem and increasing your risk.
A study by Ron et al. evaluated 8,114 participants from the global INTERHEART Study and assessed 4 different 9p21 SNPs. They evaluated the association of 9p21 with MI in those participants who ate a “prudent” diet vs those who ate less fruits and vegetables. They discovered that those who ate high amounts of the prudent diet virtually negated their risk of MI associated with their higher risk due to 9p21 (odds ratio = 1.02). The FINRISK Study revealed similar findings.15
Another trial evaluated the association of Sugar Sweetened Beverages (SSB) and 9p21. They found a clear and strong association between MI and SSB in those with 9p21. Those who drank the most SSB (highest tertile) had an odds ratio of 1.45 (45% increased risk of MI) compared to those in the lowest intake (lowest tertile) with an odds ratio of 0.96 (4% reduced risk of MI).21
As with so many things in medicine, a healthy lifestyle can make all the difference. The Traditional Mediterranean Diet (TMD) and the DASH-2 diet have been shown to be beneficial for improving health. The principles within these nutritional approaches appear to extend to patients at higher risk of cardiovascular disease because of the 9p21 gene. The principles behind these nutritional approaches are outlined in our Revolution Nutrition Plan.
References
Nature. 2011 Feb 10; 470(7333): 264–268.
Roberts R. Genetics of premature myocardial infarction. Curr Atheroscler Rep. 2008 Jun;10(3):186-93.
Shen GQ1, Rao S, Martinelli N, Li L, Olivieri O, Corrocher R, Abdullah KG, Hazen SL, Smith J, Barnard J, Plow EF, Girelli D, Wang QK.Association between four SNPs on chromosome 9p21 and myocardial infarction is replicated in an Italian population. Genome-wide single nucleotide polymorphism (SNP) association studies recently identified four SNPs (rs10757274, rs2383206, rs2383207, and rs10757278) on chromosome 9p21 were associated with myocardial infarction (MI) with odd ratio of 1.24, 1.31, 1.26, and 1.28.
Helgadottir A1, Thorleifsson G, Magnusson KP, Grétarsdottir S, Steinthorsdottir V, Manolescu A, Jones GT, Rinkel GJ, Blankensteijn JD, Ronkainen A, Jääskeläinen JE, Kyo Y, Lenk GM, Sakalihasan N, Kostulas K, Gottsäter A, Flex A, Stefansson H, Hansen T, Andersen G, Weinsheimer S, Borch-Johnsen K, Jorgensen T, Shah SH, Quyyumi AA, Granger CB, Reilly MP, Austin H, Levey AI, Vaccarino V, Palsdottir E, Walters GB, Jonsdottir T, Snorradottir S, Magnusdottir D, Gudmundsson G, Ferrell RE, Sveinbjornsdottir S, Hernesniemi J, Niemelä M, Limet R, Andersen K, Sigurdsson G, Benediktsson R, Verhoeven EL, Teijink JA, Grobbee DE, Rader DJ, Collier DA, Pedersen O, Pola R, Hillert J, Lindblad B, Valdimarsson EM, Magnadottir HB, Wijmenga C, Tromp G, Baas AF, Ruigrok YM, van Rij AM, Kuivaniemi H, Powell JT, Matthiasson SE, Gulcher JR, Thorgeirsson G, Kong A, Thorsteinsdottir U, Stefansson K.The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Study population included 16732 controls, 2836 individuals diagnosed with Abdominal Aortic Aneurysm, Results indicate that rs10757278-G is associated with Abdominal Aortic Aneurysm has an odd ratio of 1.31.
Genomics of Cardiovascular Disease. NEJM 2011;365:2098-109
Anderson CD, Biffi A, Rost NS, Cortellini L, Furie KL, Rosand J. Chromosome 9p21 in ischemic stroke: population structure and meta-analysis. Stroke2010;41:1123–1131
Helgadottir A, Thorleifsson G, Magnusson KP, et al. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet2008;40:217–224
Helgadottir A, Thorleifsson G, Manolescu A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science2007;316:1491–1493
McPherson R, Pertsemlidis A, Kavaslar N, et al. A common allele on chromosome 9 associated with coronary heart disease. Science2007;316:1488–1491
Visel A, Zhu Y, May D, et al. Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. Nature2010;464:409–412
Circulation. 2008, 117: 1675-1684.
Cancer Res. 2006 Apr 1; 66(7):3649-57.
Am Heart J. 1999 Nov; 138(5 Pt 2):S419-20.
J Am Coll Cardiol 2014;63:2234-45.
Do R, Xie C, Zhang X, et al. The effect of chromosome 9p21 variants on cardiovascular disease may be modified by dietary intake: evidence from a case/control and a prospective study. PLoS Med 201;8:e1001106.
There is a killer lurking within your body and you probably don’t even know its there.
Cardiovascular disease is the #1 cause of death in the United States for men and women. It kills more people than all forms of cancer combined. In 2010, there were 788,000 deaths caused by cardiovascular disease in the United States. Cardiovascular disease accounts for 1/3 of all deaths in the country.1
The annual cost of heart disease is over $320 billion dollars. In order to understand the implications of this number, let’s break it down a little further. That is 2200 deaths from cardiovascular disease EVERY DAY! Can you imagine a Boeing 747 filled with people, crashing into the ground every 4 and a half hours? Just imagine the outcry. Do you think you’d EVER get on a 747 jet? Not on your life!
Most people have no idea they have cardiovascular disease. It is a silent killer.
You’ve got to listen to John’s story. He never thought he’d have a heart attack. He even received frequent stress tests, got his cholesterol checked, and went to his doctor. He thought he was doing everything right.
Did you hear him and his wife? They thought they were protected because of eating “healthy”, exercising regularly, going to the doctor, getting cholesterol checked, etc. But they missed it!
In fact, more than 50% of people having a heart attack have normal cholesterol.2 Also, more than half the people studied have cardiovascular disease even if they aren’t diabetic, obese, and don’t smoke.3 The point is that many people have a false sense of security because they think they are health.
In case you think that heart attacks are only in men or only in people over the age of 65, here is Andrea’s story. She is 42 years old and had no idea she had cardiovascular disease. That is, until she had a heart attack. Her story is another one where she thought she was healthy and was blindsided by cardiovascular disease.
Just consider Bob Harper. This guy was a celebrity personal trainer on NBC’s “The Biggest Loser.” He was 51 years old and extremely fit. He also thought he was healthy. He went to the gym in February, 2017 and was working out with some friends. At the end of his workout he collapsed. It took about a minute for those around him to figure out there was a real problem. Fortunately, there was a medical student in the gym who began performing CPR and an AED was placed on his chest. He was “shocked” a couple of times and taken to the hospital. Their actions saved his life.
I had the opportunity to meet Bob Harper once several years ago. 2013 to be exact.
It is amazing that he had no idea that he had any cardiovascular disease whatsoever yet fell over, unconscious due to a massive heart attack. If he had been at home alone he would be dead and there would have been no way to prevent it. Identifying cardiovascular disease BEFORE it is a problem is the ONLY solution! If you listen to the videos, note that they say over and over to get checked out by a physician.
The problem is that traditional screening isn’t enough.
We think that if you don’t smoke, aren’t diabetic, aren’t obese, have normal blood pressure, and have normal cholesterol then you are low risk for cardiovascular disease. The stories above tell a different story. As mentioned above, traditional cardiovascular disease evaluation is marginal at best. We miss 50% of all people at risk for cardiovascular disease by measuring the 5 traditional risk factors for heart attack and stroke. This is what we call the Coronary Heart Disease Gap. The traditional approach has reached a plateau with what it can do to identify and prevent cardiovascular disease. We will never get better unless we begin to look at things differently and use different tools and parameters.
The Progression of Early Subclinical Atherosclerosis (PESA) Study[3]
The PESA study evaluated 4,184 people without conventional conventional cardiovascular risk factors (CVRFs). This means that these people didn’t smoke, had blood pressure less than 140/90 (and not on medication), non-diabetic fasting blood sugar, LDL less than 160, and an HDL of greater than or equal to 40. They even had a subgroup of “optimal cardiovascular risk factors” where blood pressure was less than 120/80, fasting blood sugar was less than 100, A1c was less than 5.7%, and total cholesterol was less than 200.
They evaluated these patients with ultrasound of the carotid, iliofemoral, and abdominal plaques; coronary artery calcification score (CACS), serum biomarkers, and lifestyle. They found that 49.7% of these participants had subclinical atherosclerosis (plaque in their arteries). In their conclusion, they stated “Many CVRF-free middle-aged individuals have atherosclerosis. LDL-C, even at levels currently considered normal, is independently associated with the presence and extent of early systemic atherosclerosis in the absence of major CVRFs.”
We clearly aren’t doing enough to identify and treat cardiovascular disease. It is a huge problem and nobody is immune. I don’t want to have a heart attack so I started making some changes for myself. Then, I attended a lecture by Dr Mark Houston, a National expert in integrative cardiology. His lecture changed my life and I knew I needed to change my approach to cardiovascular medicine. I received his Integrative Cardiology Certification after a year of intensive education and study.
Through this program I developed this CardioHealth Programs. These programs are unlike anything else available in Oklahoma. This testing is simply not available anywhere else in this area. This is the most comprehensive cardiovascular evaluation program available and I believe EVERYONE should get this testing at least once.
Are you scared that you could have a heart attack? Does the fact that the traditional “risk based” approach to screening misses 50% of people with cardiovascular disease? If so, then THIS is the program for you!
The CardioHealth Platinum program is the best cardiovascular disease screening program in this area.
Includes everything in the CardioHealth 101 and CardioHealth Advanced plus…
These programs evaluate your risk factors for cardiovascular disease, genetic predisposition, cardiovascular function, and structural cardiovascular disease. They evaluate the health of your cardiovascular system across the entire paradigm of cardiovascular disease. This type of evaluation allows us to identify cardiovascular disease at its earliest point. When we identify a cardiovascular problem and its underlying cause we are able to accurately intervene as well as track our progress. You owe it to yourself and your family to know your risk and work to decrease your risk. Schedule your CardioHealth assessment today!
If you want to know how to comprehensively address cardiovascular disease, decrease its presence, or prevent it from occurring then read about how to Improve Cardiovascular Disease.
Sachdeva A, Cannon CP, Deedwania PC, Labresh KA, Smith SC Jr, Dai D, Hernandez A, Fonarow GC. Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J. 2009 Jan;157(1):111-117.e2. doi: 10.1016/j.ahj.2008.08.010. Epub 2008 Oct 22.
Leticia Fernández-Friera, Valentín Fuster, Beatriz López-Melgar, Belén Oliva, José M. García-Ruiz, José Mendiguren, Héctor Bueno, Stuart Pocock, Borja Ibáñez, Antonio Fernández-Ortiz and Javier Sanz. Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors. Journal of the American College of Cardiology. Volume 70, Issue 24, December 2017DOI: 10.1016/j.jacc.2017.10.024
There is a killer lurking within your body and you probably don’t even know its there.
Cardiovascular disease is the #1 cause of death in the United States for men and women. It kills more people than all forms of cancer combined.
In 2010, there were 788,000 deaths caused by cardiovascular disease in the United States. Cardiovascular disease accounts for 1/3 of all deaths in the country.1 The annual costs of heart disease is over $320 billion dollars.
In order to understand the implications of this number, let’s break it down a little further. That is 2200 deaths from cardiovascular disease EVERY DAY! Can you imagine a Boeing 747 filled with people, crashing into the ground every 4 and a half hours? Just imagine the outcry. Do you think you’d EVER get on a 747 jet? Not on your life!
Most people have no idea they have cardiovascular disease. It seems to be a silent killer.
John’s Story
You’ve got to listen to John’s story. He never thought he’d have a heart attack. He even received frequent stress tests, got his cholesterol checked, and went to his doctor. He thought he was doing everything right.
Did you hear him and his wife? They thought they were protected because of eating “healthy”, exercising regularly, going to the doctor, getting cholesterol checked, etc. But they missed it!
In fact, more than 50% of people having a heart attack have normal cholesterol.2 Also, more than half the people studied have cardiovascular disease even if they aren’t diabetic, obese, and don’t smoke.3
The point is that many people have a false sense of security because they think they are health.
Andrea’s Story
In case you think that heart attacks are only in men or only in people over the age of 65, here is Andrea’s story. She is 42 years old and had no idea she had cardiovascular disease. That is, until she had a heart attack. Her story is another one where she thought she was healthy and was blindsided by cardiovascular disease.
Bob Harper
Just consider Bob Harper. This guy was a celebrity personal trainer on NBC’s “The Biggest Loser.” He was 51 years old and extremely fit. He also thought he was healthy. He went to the gym in February, 2017 and was working out with some friends. At the end of his workout he collapsed. It took about a minute for those around him to figure out there was a real problem. Fortunately, there was a medical student in the gym who began performing CPR and an AED was placed on his chest. He was “shocked” a couple of times and taken to the hospital. Their actions saved his life.
I had the opportunity to meet Bob Harper once several years ago. 1993 to be exact.
It is amazing that he had no idea that he had any cardiovascular disease whatsoever yet fell over dead due to a massive heart attack. If he had been at home alone he would be dead and there would have been no way to prevent it. Identifying cardiovascular disease BEFORE it is a problem is the ONLY solution! If you listen to the videos, note that they say over and over to get checked out by a physician.
The problem is that traditional screening isn’t enough.
Heart Disease “Gap”
We think that if you don’t smoke, aren’t diabetic, aren’t obese, have normal blood pressure, and have normal cholesterol then you are low risk for cardiovascular disease. The stories above tell a different story.
As mentioned above, traditional cardiovascular disease evaluation is marginal at best. We miss 50% of all people at risk for cardiovascular disease by measuring the 5 traditional risk factors for heart attack and stroke. This is what we call the Coronary Heart Disease Gap. The traditional approach has reached a plateau with what it can do to identify and prevent cardiovascular disease. We will never get better unless we begin to look at things differently and use different tools and parameters.
The Progression of Early Subclinical Atherosclerosis (PESA) Study3
The PESA study evaluated study 4,184 people without conventional CVRFs. This means that these people didn’t smoke, had blood pressure less than 140/90 (and not on medication), non-diabetic fasting blood sugar, LDL less than 160, and an HDL of greater than or equal to 40. They even had a subgroup of “optimal cardiovascular risk factors” where blood pressure was less than 120/80, fasting blood sugar was less than 100, A1c was less than 5.7%, and total cholesterol was less than 200.
They evaluated these patients with ultrasound of the carotid, iliofemoral, and abdominal plaques; coronary artery calcification score (CACS), serum biomarkers, and lifestyle. They found that 49.7% of these participants had subclinical atherosclerosis (plaque in their arteries). In their conclusion, they stated “Many CVRF-free middle-aged individuals have atherosclerosis. LDL-C, even at levels currently considered normal, is independently associated with the presence and extent of early systemic atherosclerosis in the absence of major CVRFs.“
The Executive Cardiovascular Evaluation Program (ECEP)
We clearly aren’t doing enough to identify and treat cardiovascular disease. It is a huge problem and nobody is immune. I don’t want to have a heart attack so I started making some changes for myself. Then, I attended a lecture by Dr Mark Houston, a National expert in integrative cardiology. His lecture changed my life and I knew I needed to change my approach to cardiovascular medicine. I received his Integrative Cardiology Certification after a year of intensive education and study.
Through this program I developed this Executive Cardiovascular Evaluation Program. This program is unlike anything available in Oklahoma. This testing is simply not available anywhere else in this area. This is the most comprehensive cardiovascular evaluation program available and I believe EVERYONE should get this testing at least once.
So, what is the Executive Cardiovascular Evaluation Program?
Extended Office Visit to review all results and develop a plan
This program evaluates your risk factors for cardiovascular disease, genetic predisposition, cardiovascular function, and structural cardiovascular disease. It evaluates the health of your cardiovascular system across the entire paradigm of cardiovascular disease.
This type of evaluation allows us to identify cardiovascular disease at its earliest point. When we identify a cardiovascular problem and what is causing it we are able to accurately intervene as well as track our progress.
You owe it to yourself and your family to know your risk and work to decrease your risk.
Schedule your Executive Cardiovascular Evaluation assessment today!
Sachdeva A, Cannon CP, Deedwania PC, Labresh KA, Smith SC Jr, Dai D, Hernandez A, Fonarow GC. Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J. 2009 Jan;157(1):111-117.e2. doi: 10.1016/j.ahj.2008.08.010. Epub 2008 Oct 22.
Leticia Fernández-Friera, Valentín Fuster, Beatriz López-Melgar, Belén Oliva, José M. García-Ruiz, José Mendiguren, Héctor Bueno, Stuart Pocock, Borja Ibáñez, Antonio Fernández-Ortiz and Javier Sanz. Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors. Journal of the American College of Cardiology. Volume 70, Issue 24, December 2017DOI: 10.1016/j.jacc.2017.10.024
When it comes to cardiovascular disease, CardiaX is incredibly important for understanding your risk of developing cardiovascular disease as well as hypertension.
Cardiovascular disease is the #1 killer of men and women in the US and in the world. Our Tulsa Functional Medicine clinic focuses on identifying the underlying cause for illness and disease as well as your individual risk for future problems.
Not only does the CardiaX gentic test help us identify a potential problem, it also helps us understand how to optimally treat it.
Consider this case:
A 44 year old black male with a history of hypertension for 20 years. He is on 4 medications (amlodipine 5mg, ramipril 10mg, indapamide 1.25mg, and metoprolol 100mg) and his blood pressure is STILL 168/102 and he has some lower extremity edema.
His labs showed a high urine aldosterone and potassium. His plasma renin activity (PRA) was low at 0.42. His endothelial function test (Endopat) was low at 1.52. His CardiaX genetics showed that he was CYP4A11 homozygote abnormal.
He was started on Amiloride 10mg per day. This is an older medication that is just not used much anymore at all.
In 8 weeks he was only taking Amiloride 10mg and amlodipine 5mg per day. He had no edema and his endothelial function (Endopat) was 1.95 (near normal). Oh, and his blood pressure was 122/84!
This is a real case and underscores how understanding your genetics and treating them appropriately can dramatically alter the course of the disease process. His CYP4A11 is a specific genetic alteration with specific implications. The ONLY medication that works in this case is amiloride.
Why YOU need a CardiaX Lab:
CardiaX is a genetics labs evaluating your genetics for 21 different Single Nucleotide Polymorphisms (SNPs). Each of these 21 SNPs were identified through research as both pertaining to cardiovascular disease or hypertension AND are modifiable. That doesn’t mean that we can change the gene itself but we CAN change the expression of the gene and reduce its impact.
Each of these genes play a role in cardiovascular disease. The case above gives an example of how knowing the genetics can change the way we treat your risk for cardiovascular disease.
It is an excellent test and EVERYONE should know their genetics and have this test read by a physician who understands the implications of these specific genes.
It is a once in a lifetime test – you’ll never have to do it again because your genetics will never change.
Who should get a CardiaX lab?
My first answer is that everyone should get it. However, more specifically, anyone who has any of the following concerns should get the CardiaX genetic evaluation:
This gene is commonly associated with increased risk of cardiovascular disease.
Aggressive early detection, prevention and risk factor control is essential.
The following heart healthy lifestyle changes are recommended to increase HDL cholesterol levels: increase intake of monounsaturated fats, daily cardiovascular exercise, fruits high in fiber, and increased intake of fatty fish high in omega-3 fatty acids. Also, eliminate sugar sweetened beverages (SSB).
aka Phosphatase & Actin Regulator 1 (PHACTR1). Mostly expressed in the brain (globus pallidus). It is a protein which regulates the reorganization of the cytoskeleton. Associated with migraines and CAD. Induces by NRP and VEGF through NRP-1 and VEGF-R1 receptors. Thus, it is thought to play a role in cell motility and vascular morphogenesis.
Early identification, prevention and risk factor control is extremely important in the context of heart disease.
Emphasize a lower fat, higher fiber diet based on whole plant sources and unrefined foods. High fiber, low-fat diets, combined with exercise, reduce the risk of Venous Thrombosis.
4q25
Excess sodium intake has been linked to hypertension in some individuals. This can increase risk for atrial fibrillation.
Consider limiting sodium intake to <1500mg/day.
To reduce risk of stroke, limit intake of saturated and trans fats, and increase intake of monounsaturated fats from high-omega-3 source fish, such as salmon.
1q25
encodes for glutamine synthase, an enzyme that converts glutamate to glutamine. This SNP is significantly associated with CHD in diabetic patients (OR 1.36) but not in patients without diabetes (OR 0.99).
This C mutation has been associated with an increased effect in diabetics.
Tight control of blood glucose is an important clinical target. Consider glutathione precursors for treatment.
Diet changes should focus on an increase in fiber and reduced intake of refined sugar.
CYP11B2
Polymorphisms in this gene control aldosterone levels.
Higher aldosterone leads to higher blood pressure.
Spironolactone is considered the best treatment option in these patients (ACEI or ARB), especially in resistant hypertensive patients. Aldosterone breakthrough on ARB and ACEI may be more common with the TT allele.
TT variant results in highest aldosterone levels followed by CT, and then CC.
Low sodium, heart healthy diets such as DASH and Mediterranean and selective angiotensin receptor antagonists have been shown to help reduce hypertension.
CYP4F2
Myocardial infarction, or heart attack, occurs due to inadequate blood flow or lack of oxygen which damages heart muscle. Avoiding smoking, reducing blood cholesterol and increasing physical activity can all help in maintaining good heart health. The DASH diet is recommend as it has been shown to reduce risk of heart attack
Myocardial infarction, or heart attack, occurs due to inadequate blood flow or lack of oxygen which damages heart muscle.
Avoiding smoking, reducing blood cholesterol and increasing physical activity can all help in maintaining good heart health.
The DASH diet is recommend as it has been shown to reduce risk of heart attack
ApoC3
It damages your HDL and makes it dysfunctional and the LDL more atherogenic. It is an independent risk factor for CVD. The ratio of HDL/ApoC3 or VLDL/ApoC3 is a better CHD risk predictor than ApoA or ApoB. It antagonizes ApoE and inhibits clearance of TRL from the circulation. It increases TG and sdLDL. It inhibits Lipoprotein Lipase and clearance of LDL. It promotes vascular inflammation, stimulates NfKb, increases CAMs, activates monocytes and endothelial cells. High responder to endotoxin. Role in pancreatic B cell biology and DM1.
Lowered by fibrates (30%), statins (20%), testosterone, low carbohydrate diets, and weight loss.
Reducing lipid levels (Total-C and LDL-C) are the goal for treatments of this condition.
Exercise, red wine and increased intake of monounsaturated fatty acids can help increase HDL levels, which will help reduce LDL-C.
Exercise >150 minutes per week.
Omega 3 supplementation has been shown to improve HDL. Whole food, plant based, high fiber diets have also been shown to reduce LDL-C.
Alternatively, cholesterol lowering medication can be considered.
COMT
Use of vitamin E and aspirin should be based on COMT polymorphisms.
Individuals who are homozygous for the enzyme’s high-activity valine form, the “val/vals,” have been shown to have lower levels of catecholamines compared to individuals who are homozygous for the enzyme’s low-activity methionine form; the “met/mets,” the val/met heterozygotes are in between.
Give aspirin or vitamin E to met/met (A/A), but neither to val/met(G/A) or val/val (G/G).
ACE I/D
Blood pressure is controlled by the renin-angiotensin system (RAS) which is directly affected by the ACE I/D polymorphism.
Variant D carriers make more ACE protein which results in a more active RAS system than that of variant I carriers. Variant D carriers will have a heightened sensitivity to sodium intake and a higher risk for hypertension with increased sodium intake.
Reducing sodium intake is recommended.
Avoiding smoking, reducing blood cholesterol and increasing physical activity can all help in maintaining good heart health.
The DASH diet (Dietary Approaches to Stop Hypertension) is also recommended which has been shown to reduce heart attack risk by 18%.
ApoE
APOE genotype contributes to the inter-individual variability observed in the metabolic response to an Omega-3 PUFA supplementation, especially serum lipids and glucose.
N3 PUFA supplementation was associated with a decrease of plasma triglyceride levels (p = 0.0002) as well as with an increase of fasting glucose (FG) levels but within normal levels(p = 0.02) in all phenotypes
APOE genotype was associated with increased FG (p = 0.001) and decreased C-reactive protein levels (p = 0.03) after supplementation.
Total-C, LDL-C, and Apo-B levels were higher in subjects carrying the APOE4 allele, intermediate in homozygotes for the APOE3 allele, and lower in carriers of the APOE2 allele.
MTHFR
Methylation supplementation is recommended for individuals who carry the mutations of the MTHFR genes.
Mutations in the MTHFR gene lead to accumulation of homocysteine in the body which increases risk for cardiovascular disease.
The most important nutrients that help lower homocysteine levels are folate, vitamins B12, B6 and B2, zinc and trimethylglycine (TMG).
CYP1A2
Caffeine is exclusively metabolized by CYP1A2 to paraxanthine, theobromine and theophylline.
Avoid caffeine if you are a slow metabolizer.
Polyphenols, chlorogenic acid and dihydro-caffeic acid increase eNOS and lower blood pressure.
Dietary changes such as DASH diet or Mediterranean diet are recommended for heart health and normal blood pressure.
Increasing potassium intake and reducing sodium intake have also been shown to lower blood pressure
SCARB1
Variant of SCARB1 changes a hepatic receptor protein from glycine to serine. Increased blood levels of HDL due to inability of HDL to attach to hepatic receptor for break down, disposal and recirculation. The HDL is not protective (dysfunctional). Increased risk of CHD by 49% in black males and 24% higher in white males.
Frequency: Chinese (3%), Blacks (8%), Latinos/whites (12%)
Because dysfunctional HDL does not appropriately assist in reverse cholesterol transport, avoid high saturated and trans fat foods to reduce Total-C level.
Eating fish high in omega 3 fatty acids have shown to decrease triglycerides and LDL cholesterol, as well as improve blood vessel elasticity, which reduces the risk for blood clots.
Oils with a higher polyunsaturated fat content, such as avocado, olive or safflower, contain more omega-6 fatty acids have been shown to reduce LDL cholesterol levels
NOS3
The 3 mutations in NOS3 gene lead to decreased production of Nitrous oxide or impede its travel to the cell membrane. Nitric oxide precursors can be used as supplements to compensate for these mutations.
Alternatively, exercise helps vascular endothelium release nitrous oxide, which relaxes arteries and increases blood flow.
Plant foods, particularly beets and leafy greens like kale, Swiss chard, arugula, and spinach, are rich in dietary nitrates and nitrites—compounds that stimulate the production of Nitrous oxide in the body.
ADR-B2
B2 adrenergic receptor. DASH diet increases PRA & Aldosterone levels in response to decreases in BP which can counteract the BP lowering effect of the diet. Adding an ACEi, ARB, or DRI improves BP response to the DASH diet in GG genotype due to the reflex increase in PRA.
Dietary interventions such as DASH diet or Mediterranean diet are recommended for reducing blood pressure.
A whole foods plant based diet is high in dietary fiber which can help reduce blood pressure.
High fiber, low-fat diets, combined with exercise, reduce the risk of Venous Thrombosis.
Corin
a serine protease that is the key enzyme in the biosynthesis of ANP and BNP which regulate salt and water balance, intravascular volume, and blood pressure. Corin is reduced in patients with CHF. The SNP is more common in blacks and may account for the increase in salt sensitive HTN & CVD.
Corin is a serine protease which is a key enzyme in the bio-synthesis of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) which regulate sodium and fluid balance, intravascular volume and blood pressure.
Mutations in corin genes lead to increased risk for sodium-sensitive hypertension.
Maintaining a healthy weight is important to avoid hypertension and other heart conditions.
Regular exercise, combined with a heart healthy diet rich in fiber, can help control blood pressure.
Reducing sodium intake and increasing potassium intake from vegetables has been shown to reduce blood pressure.
Pregnant women with risk for pre-eclampsia should consult with their physician and dietitian
GSHPx
Polymorphisms in glutathione peroxidase have been shown to increase the risk of cardiovascular disease due to decreased GSH-Px enzyme activity.
Supplementation of selenium and glutathione is recommended.
Food and specific nutrients as listed in the supplementary form can also be considered to reduce hypertension, CHD and MI risk.
Apo A1
Polymorphism in this gene is associated with Dyslipidemia due to impaired reverse cholestrol transport.
Reduced intake of high saturated and trans fat foods increases HDL-C and reduces LDL-C. A whole foods plant based diet, low in unhealthy fats, may help improve lipid levels. Exercise >150 minutes per week, may increase HDL levels. Higher HDL levels help remove bad cholesterol from the body. Emphasize nuts, fish and other foods containing omega-3 fatty acids to improve the ratio of LDL cholesterol to HDL cholesterol. Moderate use of alcohol has been linked with higher levels of HDL in some individuals.
Apo A2
Reduced intake of high saturated and trans fat foods increases HDL-C and reduces LDL-C.
A whole foods plant based diet, low in unhealthy fats, may help improve lipid levels. Exercise >150 minutes per week, may increase HDL levels. Higher HDL levels help remove bad cholesterol from the body.
Emphasize nuts, fish and other foods containing omega-3 fatty acids to improve the ratio of LDL cholesterol to HDL cholesterol.
Moderate use of alcohol has been linked with higher levels of HDL in some individuals.
CYP 4A11
One of the CYP450 enzymes. Hydroxylates MCFAa such as laurate and myristate. Metabolizes AA to 20-hydroxyeicosatetraenoic acid (20-HETE) by an Omega oxidation Rxn. 20-HETE regulates blood flow, vascularization, BP, and kidney tubule absorption of ions in rodents and possibly humans.
Amiloride is used with other diuretics as listed in the supplementary form to treat hypertension, heart failure, or extra fluid in the body (edema).
Amiloride also helps to treat or prevent low blood potassium levels caused by other diuretics.
Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.
AGTR1
AGTR1 polymorphisms directly affect the RAAS system which controls blood pressure, depending on dietary potassium intake.
ACE inhibitors and angiotensin receptor inhibitors can be used to reduce high blood pressure and risk for heart failure.
Lowering sodium and increasing potassium intake has been shown to help reduce blood pressure.
References
Shen GQ1, Rao S, Martinelli N, Li L, Olivieri O, Corrocher R, Abdullah KG, Hazen SL, Smith J, Barnard J, Plow EF, Girelli D, Wang QK.Association between four SNPs on chromosome 9p21 and myocardial infarction is replicated in an Italian population. Genome-wide single nucleotide polymorphism (SNP) association studies recently identified four SNPs (rs10757274, rs2383206, rs2383207, and rs10757278) on chromosome 9p21 were associated with myocardial infarction (MI) with odd ratio of 1.24, 1.31, 1.26, and 1.28.
Helgadottir A1, Thorleifsson G, Magnusson KP, Grétarsdottir S, Steinthorsdottir V, Manolescu A, Jones GT, Rinkel GJ, Blankensteijn JD, Ronkainen A, Jääskeläinen JE, Kyo Y, Lenk GM, Sakalihasan N, Kostulas K, Gottsäter A, Flex A, Stefansson H, Hansen T, Andersen G, Weinsheimer S, Borch-Johnsen K, Jorgensen T, Shah SH, Quyyumi AA, Granger CB, Reilly MP, Austin H, Levey AI, Vaccarino V, Palsdottir E, Walters GB, Jonsdottir T, Snorradottir S, Magnusdottir D, Gudmundsson G, Ferrell RE, Sveinbjornsdottir S, Hernesniemi J, Niemelä M, Limet R, Andersen K, Sigurdsson G, Benediktsson R, Verhoeven EL, Teijink JA, Grobbee DE, Rader DJ, Collier DA, Pedersen O, Pola R, Hillert J, Lindblad B, Valdimarsson EM, Magnadottir HB, Wijmenga C, Tromp G, Baas AF, Ruigrok YM, van Rij AM, Kuivaniemi H, Powell JT, Matthiasson SE, Gulcher JR, Thorgeirsson G, Kong A, Thorsteinsdottir U, Stefansson K.The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Study population included 16732 controls, 2836 individuals diagnosed with Abdominal Aortic Aneurysm, Results indicate that rs10757278-G is associated with Abdominal Aortic Aneurysm has an odd ratio of 1.31.
