Cardiovascular Disease

One person dies every 37 seconds in the United States from cardiovascular disease.  About 647,000 Americans die from heart disease each year—that's 1 in every 4 deaths. 


Why Take a Cardiovascular Hereditary DNA Assessment?

One person dies every 37 seconds in the United States from cardiovascular disease.
About 647,000 Americans die from heart disease each year—that's 1 in every 4 deaths. 


It’s not just a man’s disease. While 1 in 31 American women dies from breast cancer each year, heart disease is the leading cause of death for women in the United States according to the CDC, and fewer women than men survive their first heart attack according to AHA.


Many cardiac disorders can be inherited, including:

• arrhythmias,

• congenital heart disease,
• cardiomyopathy,

• and high blood cholesterol.


Coronary artery disease leading to heart attack, stroke, and heart failure can run in families, indicating inherited genetic risk factors inherited from your mother and father. If you know about your risk ahead of time, you may be able to get ahead of the problem, before it causes symptoms or becomes dangerous. 


Our Cardio Dx Hereditary DNA assessment examines 32 well-established cardiovascular disease genes for the purpose of identifying likely pathogenic variants (mutations) associated with hereditary cardiovascular conditions. When such a variant (or mutation) is inherited, development of symptoms is more likely.  Cardiovascular diseases tested for on this panel include, but are not limited to cardiomyopathies, arrhythmias, vascular & connective tissue diseases, and congenital heart. disease. This panel is designed for individuals with a personal and/or family history of. cardiovascular disease to help establish or confirm a diagnosis, assess risks, or guide. management.


Each of the conditions tested for is considered clinically actionable. Potential treatmentmoptions for some of our tested conditions include frequent screenings, medication, enzymenreplacement therapy, implantable devices, surgery, and lifestyle recommendations.  The complete assessment provides results that are very comprehensive which will allow your healthcare provider to determine a protocol, if required, that can mitigate or even prevent. certain symptoms from happening. On page 2 we have listed some of the more common cardiovascular diseases that may be hereditary.

Some Common Cardiovascular Diseases that May be Hereditary.


Cardiomyopathy- Every day your heart pumps the equivalent of 2,000 gallons of blood. throughout your body and creates enough energy to drive a truck 20 miles!  It’s no wonder the heart is the most important muscle in the body. But certain conditions can affect how well it. works. Weakening or disease of your heart muscle is called cardiomyopathy and occurs in the. lower chambers of the heart called ventricular cardiomyopathy.

Arrhythmias- A cardiac arrhythmia is any abnormal heart rate or rhythm. Tachycardia is a. common type of arrhythmia (abnormal heartbeat) that occurs when the heart beats too fast while. at rest. An adult's heart usually beats between 60 and 100 times per minute at rest. Tachycardia is. a heart rate over 100 beats per minute. In some cases, tachycardia doesn't cause any complications. In other cases, however, untreated tachycardia can cause serious complications,  such as stroke, heart failure, or death.


Congenital Heart Disease Congenital heart disease or defect is a problem with the structure of. the heart. It is present at birth. Congenital heart defects are the most common type of birth defect.  The defects can involve the walls of the heart, the valves of the heart, and the arteries and veins. near the heart. They can disrupt the normal flow of blood through the heart. The blood flow can. slow down, go in the wrong direction or to the wrong place, or be blocked completely.

Vascular and Connective tissues Disease significantly affects the aorta which is exposed to. high shear stress, or pressure from the constant flow of blood. The aorta is a very well designed. pipe that must convert chaotic flow into an organized stream. Two sites of chaos exist in the  aorta. The first is at the aortic root, where blood shoots out of the heart, and if the strength layer of the aorta is dysfunctional, the stress might internally break the aorta (a type A Dissection).  The second site of chaos is at the end of the aortic arch, where blood must loop around and head. downwards to supply blood to the abdomen and legs. The aorta  may tear at this juncture as well. a so-called type B Dissection). Many patients do not know that they may have this possibly inherited condition. Type A dissection is the more dangerous form, but chances of survival are. significantly improved with early detection and management.

Some Cardio Genes We Assess


The ACTA2 gene provides instructions for making a protein called smooth muscle alpha (α)-2
actin, which is part of the actin protein family. Actin proteins are important for cell movement
and the tensing (contraction) of muscles. Smooth muscle α-2 actin is found in smooth muscle cells. Smooth muscle α-2 actin contributes to the ability of these muscles to contract, which allows the arteries to maintain their shape instead of stretching out as blood is pumped through them. More than 30 ACTA2 gene mutations have been identified in people with familial thoracic aortic aneurysm and dissection (familial TAAD). This disorder involves problems with the aorta. The aorta can weaken and stretch, causing a bulge in the blood vessel wall (an aneurysm). Stretching of the aorta may also lead to a sudden tearing of the layers in the aorta wall (aortic dissection). Aortic aneurysm and dissection can cause life-threatening internal bleeding.


ACTC1 encodes cardiac muscle alpha actin. Alpha cardiac actin is the major protein of the thin filament in cardiac sarcomeres, which are responsible for muscle contraction and generation of force to support the pump function of the heart


ApoBs are proteins found in lipoprotein particles that are artery-clogging. The apoB-containing
lipoprotein particles that are the most damaging to our arteries include not only LDL cholesterol
but also remnants of chylomicrons and VLDL (very low density lipoproteins). All three – LDL,
VLDL, and chylomicrons – promote atherosclerosis-Atherosclerosis is a disease caused in large
part by the build-up of excess cholesterol within the artery wall, which leads to cholesterol-rich
deposits called plaque. When a plaque bursts or ruptures, blood clots form. They’re dangerous
because they can block blood flow to vital organs like the heart and brain.


The CACNA1S gene provides instructions for making the main piece (subunit) of a structure
called a calcium channel. Channels containing the CACNA1S protein are found in muscles used
for movement (skeletal muscles). These skeletal muscle calcium channels play a key role in a
process called excitation-contraction coupling, by which electrical signals (excitation) trigger
muscle tensing (contraction).


COL3A1 There are more than 500 mutations in the COL3A1 gene have been found to cause a
form of Ehlers-Danlos syndrome (EDS) called the vascular type. Ehlers-Danlos syndrome is a
group of disorders that affect the connective tissues that support the skin, bones, blood vessels,
and many other organs and tissues. Some rare types of EDS are characterized by
cardiovascular problems – the vascular type carries a risk of arterial rupture at a young age, and
in cardiac-valvular EDS there are severe progressive problems of the aortic and mitral valves.


The DSC2 gene provides instructions for making a protein called desmocollin-2. This protein is
found in many tissues, although it appears to be particularly important in the heart muscle and
skin. Desmocollin-2 is a major component of specialized structures called desmosomes.
These structures help hold neighboring cells together, which provides strength and stability to
tissues. Defects in DSC2 cause arrhythmogenic right ventricular dysplasia type 10, and
susceptibility to cardiomyopathy.


Mutations in the FBN1 gene, which provides instructions for making a protein called fibrillin-
Marfan syndrome is inherited in an autosomal dominant pattern. At least 25% of cases are due
to a new ( de novo ) mutation. Treatment is based on the signs and symptoms in each person.
Marfan syndrome is a disorder of the connective tissue. Connective tissue provides strength and
flexibility to structures throughout the body such as bones, ligaments, muscles, walls of blood
vessels, and heart valves.


GLA Currently, specific mutations are associated with the cardiac variant showing myocardial
hypertrophy that is clinically similar to HCM. Patients with FD are at risk for developing
cerebrovascular disease (CVD), cardiac sudden death, and renal failure, and these patients can
benefit from specific treatments.


TPM1 (Tropomyosin 1) is a Protein Coding gene. Diseases associated with TPM1 include
Cardiomyopathy, Familial Hypertrophic, 3 and Cardiomyopathy, Dilated, 1E. Among its related
pathways are Cardiac conduction and Dilated cardiomyopathy (DCM).


TNNT2 Cardiac muscle troponin T is a protein that in humans is encoded by the TNNT2 gene.
Cardiac TnT is the tropomyosin-binding subunit of the troponin complex, which is located on the
thin filament of striated muscles and regulates muscle contraction in response to alterations in
intracellular calcium ion concentration


TNN13 Approximately 10 mutations in the TNNI3 gene have been found to cause familial
restrictive cardiomyopathy, which is characterized by stiffening of the heart muscle. Most of
these mutations change single amino acids in the cardiac troponin I protein, which impairs the
protein's function


TMEM43 This gene belongs to the TMEM43 family. Defects in this gene are the cause of
familial arrhythmogenic right ventricular dysplasia type 5 (ARVD5), also known as
arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5). Arrhythmogenic right
ventricular dysplasia is an inherited disorder, often involving both ventricles, and is characterized
by ventricular tachycardia, heart failure, sudden cardiac death, and fibrofatty replacement of
cardiomyocytes. This gene contains a response element for PPAR gamma (an adipogenic
transcription factor), which may explain the fibrofatty replacement of the myocardium, a
characteristic pathological finding in ARVC


TGFBR2 At least nine TGFBR2 gene mutations have been identified in people with familial
thoracic aortic aneurysm and dissection (familial TAAD). This disorder involves problems with
the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the
body. The aorta can weaken and stretch, causing a bulge in the blood vessel wall (an aneurysm).
Stretching of the aorta may also lead to a sudden tearing of the layers in the aorta wall (aortic
dissection). Aortic aneurysm and dissection can cause life-threatening internal bleeding.


SMAD3 Thoracic aortic aneurysms and dissections are a main feature of connective tissue
disorders, such as Marfan syndrome and Loeys-Dietz syndrome. We delineated a new syndrome
presenting with aneurysms, dissections and tortuosity throughout the arterial tree in association
with mild craniofacial features and skeletal and cutaneous anomalies. In contrast with other
aneurysm syndromes, most of these affected individuals presented with early-onset osteoarthritis.
We mapped the genetic locus to chromosome 15q22.2-24.2 and show that the disease is caused
by mutations in SMAD3.


SCN5A A few mutations in the SCN5A gene have been found to cause progressive familial
heart block. This condition alters the normal beating of the heart and can lead to fainting
(syncope) or sudden cardiac arrest and death. The SCN5A gene mutations change single amino
acids in the SCN5A protein.


The RYR2 gene provides instructions for making a protein called ryanodine receptor 2. This
protein is part of a family of ryanodine receptors, which form channels that transport positively
charged calcium atoms (calcium ions) within cells. For the heart to beat normally, the cardiac
muscle must tense (contract) and relax in a coordinated way. This cycle of muscle contraction
and relaxation results from the precise control of calcium ions within myocytes. In response to
certain signals, the RYR2 channel releases calcium ions from the sarcoplasmic reticulum into the
surrounding cell fluid (the cytoplasm). The resulting increase in calcium ion concentration
triggers the cardiac muscle to contract, which pumps blood out of the heart. Calcium ions are
then transported back into the sarcoplasmic reticulum, and the cardiac muscle relaxes. In this
way, the release and reuptake of calcium ions in myocytes produces a regular heart rhythm.
Mutations of the Cardiac Ryanodine Receptor (RyR2) Gene in Familial Polymorphic Ventricular
Tachycardia. Familial polymorphic ventricular tachycardia is an autosomal-dominant, inherited
disease with a relatively early onset and a mortality rate of approximately 30% by the age of 30


The RYR-1 gene provides instructions for production of the RYR-1 receptor. The RYR-1
receptor is a channel in the sarcoplasmic reticulum in skeletal muscle cells that regulates the flow
of calcium, a critical component of muscle contraction. Mutations in the RYR-1 gene have also been associated with susceptibility to malignant hyperthermia (MH), a severe and potentially
fatal reaction to certain types of anesthesia (sedating or paralyzing drugs given by a doctor for
medical/surgical procedures). Anyone with an RYR-1 gene mutation should take “malignant
hyperthermia precautions” if anesthesia is required for a medical/surgical procedure. In addition,
there are case reports of “wake MH”–i.e. an episode of MH that is unrelated to the administration
of anesthesia.
The PRKAG2 gene


The PRKAG2 gene provides instructions for making one part (the gamma-2 subunit) of a larger
enzyme called AMP-activated protein kinase (AMPK). This enzyme helps sense and respond to
energy demands within cells. It is active in many different tissues, including heart (cardiac)
muscle and muscles used for movement (skeletal muscles). The enzyme may also regulate the
activity of certain ion channels in the heart. These channels, which transport positively charged
atoms (ions) into and out of heart muscle cells, play critical roles in maintaining the heart's
normal rhythm.


The PKP2 gene provides instructions for making a protein called plakophilin 2. This protein is
found primarily in cells of the myocardium, which is the muscular wall of the heart. Within these
cells, plakophilin 2 is one of several proteins that make up structures called desmosomes. These
structures form junctions that attach cells to one another. Desmosomes provide strength to the
myocardium and are involved in signaling between neighboring cells.


The PCSK9 gene provides instructions for making a protein that helps regulate the amount of
cholesterol in the bloodstream. Cholesterol is a waxy, fat-like substance that is produced in the
body and obtained from foods that come from animals. The PCSK9 protein controls the number
of low-density lipoprotein receptors, (LDL) which are proteins on the surface of cells. These
receptors play a critical role in regulating blood cholesterol levels.


The MUTYH (MYH) gene provides instructions for making an enzyme called MYH glycosylase,
which is involved in the repair of DNA. This enzyme corrects particular errors that are made
when DNA is copied (DNA replication) in preparation for cell division.


The MYBPC3 gene provides instructions for making cardiac myosin binding protein C (cardiac
MyBP-C), which is found in heart (cardiac) muscle cells. In these cells, cardiac MyBP-C is
associated with a structure called the sarcomere, which is the basic unit of muscle contraction.
Sarcomeres are made up of thick and thin filaments. The overlapping thick and thin filaments
attach to each other and release, which allows the filaments to move relative to one another so
that muscles can contract. Regular contractions of cardiac muscle pump blood to the rest of the


Mutations in the LMNA gene, which encodes the two major lamin A and C isoforms, cause a
diverse range of diseases, called laminopathies, including dilated cardiomyopathy, associated
with a poor prognosis and high rate of sudden death due to conduction defect and early
ventricular arrhythmia.


The LDLR gene provides instructions for making a protein called the low-density lipoprotein
receptor. This receptor binds to particles called low-density lipoproteins (LDLs), which are the
primary carriers of cholesterol in the blood. Cholesterol is a waxy, fat-like substance that is
produced in the body and obtained from foods that come from animals. Low-density lipoprotein
receptors play a critical role in regulating the amount of cholesterol in the blood.. The number of
low-density lipoprotein receptors on the surface of liver cells determines how quickly cholesterol
is removed from the bloodstream.


KCNQ1 gene mutations increases the risk of an abnormal heart rhythm that can cause syncope
or sudden death. The KCNQ1 gene mutations associated with short QT syndrome change single
amino acids in the KCNQ1 protein. The mutations alter the function of ion channels made with
the KCNQ1 protein, increasing the channels' activity.


Mutations in the KCNH2 gene can cause Romano-Ward syndrome, which is the most common
form of a heart condition called long QT syndrome. Mutations in this gene account for
approximately 25 percent of cases of Romano-Ward syndrome. Romano–Ward syndrome is
the most common form of congenital Long QT syndrome (LQTS), a genetic heart condition that
affects the electrical properties of heart muscle cells. Those affected are at risk of abnormal heart
rhythms which can lead to fainting, seizures, or sudden death.

Conditions Suggesting a Cardiovascular Hereditary DNA Assessment

1. Breathlessness even at rest or especially with physical exertion
2. Shortness of breath or trouble breathing
3. Swelling of the legs, ankles and feet
4. Swelling in the abdomen and veins in the neck
5. Undiagnosed dry hacking cough or wheezing
6. Chronic fatigue
7. Heartbeat that feel rapid or irregular
8. Chest discomfort, pressure, pounding or fluttering
9. Dizziness, lightheadedness and fainting
10. Chest pain, especially after physical exertion or heavy meals
11. Long-term high blood pressure
12. Use of cocaine, amphetamines or anabolic steroids
13. Metabolic disorders, such as obesity, thyroid disease or diabetes
14. Nutritional deficiencies of essential vitamins or minerals, such as thiamin
(vitamin B-1)
15. Heart attack
16. Heart valve problems
17. Any diagnosed cardiovascular disease
18. Stent


Any one of the conditions 1 through 15 suggest a patient and their family can benefit from a cardiovascular DNA assessment, especially if the patient has more than one condition, or a bloodline family member was diagnosed with cardiovascular disease.


Conditions 16 through 18 strongly suggests a patient and their family can benefit from a cardiovascular DNA assessment.

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