Did you know that many forms of cardiovascular disease are connected to gene variations and polymorphisms?
Our CardiaX Panel measures these variations, called Single Nucleotide Polymorphisms (SNPs), which are variations in a single nucleotide that occur at a specific position in the DNA sequence of an individual's genome.
SNPs can significantly impact how genes are expressed or regulated, and they can also affect how an individual responds to environmental factors, medications, or diseases.
The CardiaX test detects these gene variations associated with an increased risk of developing several cardiovascular conditions, including atherosclerosis, abnormal cholesterol production, hypertension, stroke, and even heart attack.
Use this downloadable Quick Guide to Interpreting CardiaX Panel Markers to detect heart disease and related conditions early and accurately so you can implement targeted clinical strategies based on your patient’s unique genetics.
In this handy guide, you’ll find the following for each genetic marker:
- Gene description and function
- Risks associations with polymorphisms or variations of that gene
- Clinical implications and recommendations specific to that marker
You’ll also find detailed guidelines on therapeutic lifestyle changes that can reduce your patient’s risk of developing cardiac conditions.
Advanced Predictive Markers
Advanced predictive markers are genetic variations strongly correlated with cardiovascular disease and are used to predict the likelihood of disease development.
These markers include genes involved in the regulation of inflammatory pathways and a gene that controls for vasoconstriction.
9p21
9p21 is a chromosomal region with 4 SNPs discovered in 2007 and is said to be a genetic revolution for cardiovascular disease.
It's integral to regulating inflammatory pathways and significantly correlated with adverse events independent of other lifestyle factors.
Risks Associated with Genetic Variations
- Increased risk of inflammation
- Plaque rupture
- Thrombosis
- Abdominal aortic aneurysm
- Atherosclerotic cardiovascular disease
- Congenital heart defects
- Myocardial infarction
- Diabetes mellitus
- Insulin resistance
Clinical Implications & Treatment Recommendations
- Aggressive early detection, prevention, and risk factor control
- Aggressive management of an anti-inflammatory diet and emphasis on plant-based foods
4q25
The 4q25 is a chromosomal region associated with 2 SNPs. This region contains several genes, including the PITX2 gene, which plays a critical role in the early development of several organs, including the heart.
Risks Associated with Genetic Variations
- Increased risk for atrial fibrillation
- Increased risk of ischemic stroke
Clinical Implications & Treatment Recommendations
- Incorporate therapeutic lifestyle changes
- Emphasize sodium restriction—less than 1500 mg per day
6p24.1
6p24.1 is a gene that codes for a potent vasoconstrictor peptide. It plays a role in regulating endothelial cells, which line the blood vessels and are critical for maintaining healthy cardiovascular function.
Risks Associated with Genetic Variations
- Increased risk for venous thrombosis
- Increased risk of congenital heart defect
Clinical Implications & Treatment Recommendations
- Early detection and preventative treatments
- Incorporate therapeutic lifestyle changes
- Emphasize lower fat and high fiber plant-based foods/fiber
Markers Related to Hypertension
High blood pressure, also known as hypertension, is a common condition in which the force of blood pushing against the artery walls is too high, making the heart work harder to pump blood and affecting the body’s arteries.
The CardiX markers below are related to hypertension:
ADR-B2
The receptor protein ADR-B2 binds with epinephrine to control smooth muscle relaxation.
Risks Associated with Genetic Variations
- Obesity
- Type 2 diabetes
- High blood pressure
- Ischemic stroke
- Idiopathic
- Thromboembolism
- Asthma
Clinical Implications & Treatment Recommendations
Incorporate therapeutic lifestyle changes for cardiometabolic disease risk reduction, such as weight loss, a reduced sodium and high-fiber diet, avoiding unhealthy fats, and aerobic exercise.
Corin
Corin is a key enzyme in the biosynthesis of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which regulates salt and water balance, intravascular volume, and blood pressure.
Risks Associated with Genetic Variations
- Increased risk of hypertension and preeclampsia in pregnant women
- Increased risk for cardiovascular disease and congestive heart failure
Clinical Implications & Treatment Recommendations
- Incorporate therapeutic lifestyle changes
- Optimize dietary sodium/potassium ratio
- Supplement with ACE inhibitors or Angiotensin blockers
- ACE inhibitors or Angiotensin blockers
CYP1A2
CYP1A2 is a gene responsible for 95% of caffeine metabolism in the liver. Genetic polymorphisms can result in increased or decreased caffeine metabolism. Slow metabolizers represent about half of the population.
Risks Associated with Genetic Variations
- Fast metabolizers have decreased risk of hypertension and myocardial infarction
- Slow metabolizers have moderately increased risk for:
- Hypertension
- Myocardial infarction
- Congenital heart defects
- Tachycardia
- Stiff aorta
- Pulse wave velocity
- Aortic insufficiency
- Vascular inflammation
- Increased catecholamines
Clinical Implications & Treatment Recommendations
Slow metabolizers should consume no more than 200 mg of caffeine daily.
Possible caffeine sources to watch out for include:
- Coffee, tea, soda, and other caffeinated beverages
- Chocolate
- Medications
CYP11B2
CYP11B2 is a gene responsible for aldosterone synthesis in the adrenal glands. Polymorphisms are associated with increased aldosterone.
Risks Associated with Genetic Variations
- Higher aldosterone levels increase blood pressure
- Increased risk for hypertension and aldosterone enzyme disorder
Clinical Implications & Treatment Recommendations
- Spironolactone treatment for resistant
- Incorporate therapeutic lifestyle changes to reduce hypertension
ACE I/D
ACE I/D is an enzyme found in the lungs that is a major player in the speed and regulation of the renin-angiotensin-aldosterone system (RAAS).
Risks Associated with Genetic Variations
- Insertion/deletion genomics
- Stimulated RAAS
- Increased risk for cardiovascular disease and myocardial infarction
- Higher salt sensitivity
- Increased risk of hypertension with sodium intake
Clinical Implications & Treatment Recommendations
- Incorporate therapeutic lifestyle changes to reduce hypertension and cardiometabolic disease risk
- Low sodium/DASH diet
CYP4F2
CYP4F2 codes for an enzyme that starts the process of inactivating and degrading Leukotriene B4, a potent mediator of inflammation.
Risks Associated with Genetic Variations
- Decreased degradation of Leukotriene B4
- Higher levels of Leukotriene B4
- Increased inflammation
- Increased risk of hypertension and myocardial infarction
Clinical Implications & Treatment Recommendations
- Incorporate therapeutic lifestyle changes to reduce hypertension and cardiometabolic disease risk
- DASH diet
AGTR1
AGTR1 is involved in the regulation of blood pressure and renal function.
Risks Associated with Genetic Variations
Variations directly affect the RAAS system, which controls blood pressure, depending on potassium intake.
Clinical Implications & Treatment Recommendations
- Use ACE inhibitors and angiotensin blockers to control hypertension
- Incorporate therapeutic lifestyle changes to reduce hypertension
- Optimize sodium: potassium ratio in the diet
Markers Related to Dyslipidemia and Metabolic Disease
Dyslipidemia is a condition where there is an imbalance of lipids in the body, including cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, and high-density lipoprotein (HDL).
This condition can be influenced by environmental or genetic factors and cause severe cases of cardiovascular disease.
Metabolic disease or syndrome encompasses various conditions that co-occur, putting individuals at risk for heart disease, stroke, and type 2 diabetes.
The CardiX markers below are related to dyslipidemia and metabolic disease:
ADRB2
ADRB2 interacts with epinephrine and adrenaline to indirectly control smooth muscle relaxation and bronchodilation.
Risks Associated with Genetic Variations
- Obesity and type 2 diabetes
- High blood pressure
- Ischemic stroke
- Idiopathic thromboembolism
- Asthma
Clinical Implications & Treatment Recommendations
- Incorporate therapeutic lifestyle changes to lower high blood pressure
- A diet rich in plant-based foods
ApoE
ApoE is a gene that codes for Apolipoprotein E, produced primarily by the liver and brain.
ApoE-containing lipoproteins transport lipids (fats) from the diet to other tissues for storage and transport cholesterol from those tissues to the liver for excretion.
Genetic variation influences susceptibility to dietary fat and other lifestyle factors.
There are three variations (alleles) of Apo E2, E3, and E4, and individuals carry two alleles for a variety of genetic combinations:
- E2/2
- E2/3
- E2/4
- E3/3
- E3/4
- E4/4
Risks Associated with Genetic Variations
ApoE e4 genotype is found in 25% of the population and predisposes an individual to:
- Elevated levels of LDL cholesterol and triglycerides
- Increased risk of atherosclerosis
- Affected absorption rates
- Higher serum LDL
- Delayed clearance
- Increased cardiovascular disease risk with smoking and alcohol intake
- Reduced ability to repair vascular endothelium due to the inability to activate the Apo E2 receptor to produce nitric oxide
- Lowered response to statin
- Increased risk of congenital heart defects, cardiovascular disease, myocardial infarction, Alzheimer's disease, and dementia
Clinical Implications & Treatment Recommendations
- Individualized omega-3 treatment/supplementation
- A diet low in trans fats, refined oils, and conventional saturated fats
- Avoid refined, high-glycemic foods
- A diet high in plant-based foods and fiber
- Apo E4 specific recommendations:
- Avoid smoking and alcohol
- Daily physical activity is particularly critical for Apo E4’s
- May need to combine statins with other lipid-lowering agents, as Apo E4’s are less responsive to statin therapy
SCARB1
SCARB1 is a liver protein receptor involved in HDL (high-density lipoprotein) clearance.
Risks Associated with Genetic Variations
Prevents HDL from attaching to receptors for breakdown, leading to decreased HDL clearance and elevated levels of dysfunctional (nonprotective) HDL.
Clinical Implications & Treatment Recommendations
- Incorporate therapeutic lifestyle changes
- Exercise
- Moderate alcohol
- Healthy fats and oils
1q25
1q25 is a chromosome that's important in:
- Cell proliferation and signaling
- Inhibition of apoptosis
- Insulin and glucose metabolism
- Incretin
- Enterocyte health
- Endothelial cell metabolism
Risks Associated with Genetic Variations
Variations in the position of the 1q25 chromosome result in:
- Reduced expression of glutamine synthase, which converts glutamic acid to glutamine
- Higher risk for diabetes and insulin resistance
Clinical Implications & Treatment Recommendations
- Optimize diet for glycemic control with:
- Exercise
- Low sugar/high fiber
- Low glycemic index
- Consider glutathione supplementation
ApoA1
ApoA1 is a gene that provides instructions for making Apo A1 Lipoprotein.
Found on HDL lipoprotein and is involved with a reaction called cholesterol esterification that converts cholesterol to a form that can be fully integrated into HDL and transported through the bloodstream.
Risks Associated with Genetic Variations
- Impaired reverse cholesterol transport
- Dyslipidemia risk
Clinical Implications & Treatment Recommendations
- Incorporate therapeutic lifestyle changes
- Increase in omega-3’s
- Moderate alcohol consumption
ApoA2
ApoA2 is a gene that provides instructions for making Apo A2 lipoprotein, the second most abundant high-density lipoprotein particle.
Risks Associated with Genetic Variations
Increased risk for obesity, dyslipidemia, and diabetes.
Clinical Implications & Treatment Recommendations
Incorporate therapeutic lifestyle changes.
ApoC3
ApoC3 protein is a component of VLDL. It inhibits lipoprotein lipase and hepatic lipase and is thought to delay the catabolism of triglyceride-rich particles.
Risks Associated with Genetic Variations
Gene variation results in increased levels of ApoC3, which can cause:
- Hypertriglyceridemia
- Dyslipidemia
- Congenital heart defects
- Non-alcoholic fatty liver disease
Clinical Implications & Treatment Recommendations
Aggressive management and treatment of lipids.
Markers Related to Detoxification and Methylation
Detoxification is the process of removing toxins from the body and is essential in preventing cardiovascular disease. When genetic variants inhibit detoxification, there is a greater risk of developing heart conditions.
Methylation is a critical cellular process that occurs in the body a billion times per second and aids in processing nutrients and molecules to support numerous body systems (including detoxification).
Genetic variants inhibiting methylation can increase the risk of developing heart-related conditions.
The CardiX markers below are related to detoxification and methylation:
MTHFR
Methylene Tetrahydrofolate Reductase (MTHFR) is an enzyme that catalyzes the methylation (activation) of folic acid to L methyl folate, which is involved in:
- Homocysteine clearance
- The formation of tetrahydrobiopterin (BH4), an important cofactor of neurotransmitter production, nitric oxide synthesis, and ammonia detoxification
There are two SNPs possible, 677 and 1298.
Risks Associated with Genetic Variations
Increased risk for:
- Endothelial dysfunction
- Hypertension
- Thrombosis
- Cardiovascular disease
- Congenital heart defects
- Myocardial infarction
- Hyper-homocysteinemia
- Neurological conditions such as depression and anxiety
Clinical Implications & Treatment Recommendations
- Methylation treatment as appropriate
- Emphasize foods high in dietary folate, vitamins B12, B6, and B2, zinc
- Consider TMG (trimethylglycine) or betaine supplementation
GSHPx
The Glutathione Peroxidase (GSHPx) enzyme is a master detoxifier. Increased levels of GSHPx can help lower blood pressure and decrease the risk of myocardial infarction, left ventricular hypertrophy (LVH), and congestive heart failure (CHF).
Risks Associated with Genetic Variations
Low levels of GSHPx are associated with the following:
- Decreased enzyme activity
- Impaired detoxification
- Increased risk of cardiovascular disease
Clinical Implications & Treatment Recommendations
- Supplementation with selenium and glutathione
- Incorporate therapeutic lifestyle changes
- High antioxidant diet
NOS3
Nitric Oxide Synthase 3 (NOS3) synthesizes nitric oxide from L-arginine. Nitric oxide is an essential molecule to quench free radicals. There are three possible polymorphisms.
Risks Associated with Genetic Variations
Polymorphisms can lead to decreased production of NOS and less nitric oxide availability, resulting in higher free radical accumulation.
Clinical Implications & Treatment Recommendations
- Nitric oxide precursor supplements
- Upregulate nitric oxide with exercise (very important)
- A diet high in dietary nitrates, which act as precursors to nitric oxide (leafy greens, beets)
COMT
Catechol-o-Methyltransferase (COMT) is an enzyme that breaks down neurotransmitters.
COMT is particularly prominent in the region of the brain that processes:
- Personality
- Abstract thinking
- Emotion
- Aggressive behavior
- Short-term memory
Risks Associated with Genetic Variations
Variations result in reduced enzyme activity, leading to elevated norepinephrine and prolonged sympathetic nervous system stimulation.
It may be the root cause of aggression, anger, hostility, and increased risk of hypertension.
Clinical Implications & Treatment Recommendations
- Evaluate the use of Vitamin E and aspirin based on COMT mutation
- Give aspirin or Vitamin E to met/met (A/A-homozygous mutant)
- No aspirin or Vitamin E val/met(G/A) nor val/val (G/G-homozygous wild)
Recommended Therapeutic Lifestyle Changes
The following therapeutic lifestyle changes can significantly reduce patient risk of cardiac disease and related conditions.
Lifestyle Modifiers
- Tobacco cessation
- Exercise according to ACSM guidelines
- Adequate hydration with clean water
- Stress management
- Sleep hygiene
Diet Recommendations
- Limit refined carbohydrates from dietary sugar and processed grains
- Maximize plant-based fiber with a wide range of vegetables and fruits in a range of colors
- Optimize dietary sodium and potassium ratio
- Incorporate healthy dietary oils and fats as appropriate for energy requirements
- Non-refined/expeller pressed oils such as olive and avocado oil
- Foods that supply unsaturated fats, including olives, avocado, raw nuts and seeds, natural nut butters, and nut milks
- Omega-3 fats from oily fish and plant-based sources
- Saturated fats in moderation from high-quality sources such as grass-fed butter, game meats, eggs, grass-fed beef, organic dark meat chicken, cheese, coconut oil, and coconut milk
- NO hydrogenated or partially hydrogenated oils (trans fats)
- Consume high-quality protein as appropriate for energy requirements
- Consider prebiotic and probiotic food sources
- Choose organic foods recommended by the Environmental Working Group
Don't wait for heart conditions to strike before taking action.
With CardiaX genetic testing and therapeutic lifestyle changes, you can help your patients stay one step ahead to protect their heart health.
By detecting genetic variations early on, you can provide personalized guidance to your patients and help them make informed decisions about their health.