Video summary
The video introduces the field of cardiogenetics and its critical role in understanding how genetic factors influence cardiovascular health. Hosted by Dr. Juan McGuire, the discussion features Dr. Silvana Miskovic, an expert in preventive genetics who explains that while humans carry approximately 2,000 genetic defects, recent advancements since 2005 have allowed scientists to identify specific genes linked to common conditions. These include coronary artery disease, familial hypercholesterolemia, hypertension, cardiomyopathy, and atrial fibrillation. Dr. Miskovic notes that while there are around 30,000 known gene variants, only a few hundred to low thousands have strong evidence connecting them directly to cardiovascular diseases, highlighting the precision required in modern genetic analysis.
A significant portion of the conversation focuses on the practical aspects of genetic testing, including sample collection and reliability. Dr. Miskovic emphasizes that saliva samples are often preferred for their non-invasive nature, yet they provide DNA quality comparable to blood or oral swabs. Modern technologies like next-generation sequencing offer high analytical accuracy of around 99% and sensitivity between 95% and 99%, making them highly effective tools for screening. The discussion illustrates how these tests can reveal specific polymorphisms that affect lipid metabolism, homocysteine levels, and the risk of sudden cardiac death, providing a detailed genetic profile that goes beyond simple blood work.
The video also underscores the importance of interpreting genetic data within a broader clinical context rather than relying solely on laboratory results. Dr. Miskovic explains that their "cardiovascular sensor" combines quantitative analysis with qualitative, psychologically friendly visual presentations to help patients understand their risks, such as the impact of omega-3 fatty acids or the need for specific vitamin supplements like B6 and B12. Crucially, she stresses that the final interpretation and medical recommendations must always come from a qualified physician who considers the patient's overall health, rather than automated lab reports which may lack necessary scientific nuance or personalized advice.
Ultimately, the podcast concludes by defining the standards for appropriate genetic testing, which must include the analysis of relevant genes, high-performance technology, adequate counseling, and interpretation grounded in scientific literature. The segment transitions from general cardiogenetics to pharmacogenetics, setting the stage for how these genetic insights can be used to tailor medication regimens for safety and efficacy. By integrating genetic data with clinical judgment, healthcare providers can significantly reduce adverse drug reactions and create personalized preventive programs that lower the risk of cardiovascular diseases, marking a pivotal shift toward safer and more effective medical treatments.
Read the full video transcript
Welcome to the Texas Heart Institute
educational programs and podcast series
on the latest advances in
cardiogenetics.
My name is Juan McGuire.
I'm a clinical professor of cardiology
at Baylor College of Medicine and
interventional cardiologist at Texas
Heart Institute Baylor St. Luke's
Medical Center in Houston, Texas.
How genes influence our health?
Most of our genetic mutations and
defects are inherited from our parents.
Some of the genes, however, are altered
by the environment and could have a far
harmful effect on our health.
The best known cause of environmental
mutations is radioactivity, but there
are many others.
It is estimated that each person carries
about 2,000 genetic defects, which may
in some cases cause various illnesses.
Thanks to the latest genetic testing
technologies, it is now possible to
analyze specific genes to determine
genetic traits that are linked to
various diseases.
Based on genetic analysis, it is
possible to develop a preventive program
that significantly reduces the risk of
various cardiovascular diseases.
Every person reacts differently to
medications.
According to estimates, approximately 7%
of patients suffer from severe adverse
reactions to drugs,
and about 0.4% suffer fatal
consequences.
Adverse reactions to drugs are the fifth
most common frequent cause of death in
developed world.
In most cases, these reactions are
determined by inherited genetic
variations,
environmental factors, and also certain
drug interactions.
Our first podcast in this series is on
cardiogenetics.
Our guest today is Dr. Silvana Miskovic
from Split, Croatia.
Dr. Miskovic graduated from the Medical
School of Zagreb
in 1999 in Split, Croatia.
She holds a degree in sports medicine
and in human genetics from European
School of Genetic Medicine Bologna,
Italy.
She has published extensively on this
topic and is an author of a book Genetic
Counseling and Practice.
Since 2005, she's working in the field
of immunology, oncology, and preventive
genetics at the polyclinic Analiza in
Split, Croatia. Dr. Miskovic, welcome to
this
podcast.
Uh,
when did we start to identify the factor
of specific genes or cardiovascular
conditions?
>> The starting of identification of
specific genes in cardiovascular
diseases is started after 2005.
Uh, when genome-wide association is
started and transferred the complete
field of genetic investigation.
Uh, in this period, the uh,
investigators remove from
um, analyzing the rare inherited
cardiovascular diseases and trying to
identify genetic variation that are
association with a different type of uh,
genetic disease genetic cardiovascular
diseases.
>> Thank you very much. So, Silvana, how
many relevant genes so far have been
identified in the
diseases.
>> Uh
dear professor, when you ask me that
question, the
the answer is lots of
Um
when we including the all relevant
relevant functional evidence-based of
expression studies, rare variants
studies, or pathways analysis,
uh
the number of the gene or gene variant
is around a 30,000.
Uh but when you ask me about the
relevant genes connected with the strong
evidence with the cardiovascular
disease, the number of genes is around
uh
hundreds to low thousands.
>> Very good.
So, this is interesting. We already have
quite a bit of information. So, what are
the most uh important conditions that we
have already identified as far as
cardiovascular conditions are concerned?
>> Uh the most important conditions are
coronary artery disease, familial
hypercholesterolemia,
uh arterial hypertension,
uh dilatative or hypertrophic
cardiomyopathy,
atrial fibrillation, uh syndrome of
prolonged QT interval,
uh myocardial infarction, and I think
the heart failure.
>> Very interesting. So, another important
uh topic is uh what is required to
obtain adequate sample
for
well,
genetic or cardiogenetic
testing. I know there are several
options available. Well, what is the
most reliable uh
uh well, sample that we can obtain to
get meaningful information?
>> Uh
we have three type of samples. That is
is blood, oral swab, and saliva sample.
Uh the Uh the saliva sample we use in
our clinic because it's a non-invasive
testing without the discomfort of the
patient, and the saliva contains cells
which provide us a DNA
molecules which is adequate for uh any
type of genetic testing, especially
cardiogenetic testing.
>> Excellent, Silvana. So, how reliable and
sensitive is genetic testing depending
on the type of the sample that we can
obtain?
>> Uh the new method of
of genetic
technology such as
next generation sequencing
have high analytical accuracy around the
99%
and the sensitivity around
95 to 94
95 to 99%.
>> Excellent, Silvana. So, here we have one
of the examples of the test on one of
the patients
that you analyzed. And can you explain
the information that is provided in this
table related to genetic variations and
polymorphism
that affects cardiovascular system? I
hope you can see this image.
>> Yes, I see this image.
Uh that is a table or some picture of
more than 20 relevant genes including
with a high
evidence
to connection with the cardiovascular
diseases.
Uh you can see the name of the gene, the
relevant polymorphism based of
scientific publication, and also the
genotype of that patient.
Uh genotype is a picture of our alleles
that we
from our parents. Uh
for example, the first two gene are
connected with a high risk of heart
disease. Um APOA5
is connected with the lipid metabolism,
while the
methylenetetrahydrofolate gene is
connected with the homocysteine
metabolism.
>> Very good. So, can you explain also the
information that's provided in this
following table
on again another studied patient with
some genetic variations and polymorphism
that affects cardiovascular system. And
here is so-called cardiovascular sensor.
Maybe you can mention what did it mean
cardiovascular sensor?
>> Uh okay, the cardiovascular sensor is
one type of our genetic test that we
perform in our clinic. Uh in this
picture, you can see two genes connected
with a high risk of heart disease. Uh
that is a cadherin 13 and coronary heart
disease susceptibility to eight gene.
Uh
you see the name, the relevant
polymorphism connected with the
scientific
references. Also, you see the three
possible genotype population prevalence
and results of our patient. For example,
when we speak about the cadherin 13, uh
this patient is a carrier of a GG
genotype
uh with a population prevalency of 59%
and also this GG genotype is connected
with high risk of
uh heart disease uh in compared with a
TT genotype.
Uh when we speak about the coronary
heart disease
susceptibility to eight,
uh, you see the patient is a carrier of
GC GC genotype. Uh, the population
prevalence of that genotype is 45%
and that genotype is connected with 1.47
higher risk
>> [snorts]
>> uh, higher risk of heart diseases in
compared with a GG genotype. Uh, in the
lower part of this picture, you you can
see the references.
Uh, I think the all genetic test
including the cardiovascular sensor must
have the scientific publication or
scientific reference because they give
us credibility when we speak about
about
genotype, about the polymorphism and
results of our patient.
>> Very good. This is very meaningful and
very important information in screening
our patients for cardiovascular
diseases.
And here is a another example of
cardiogenetics and cardiovascular risk
risk factors. It's a like a summary of
all the tests that you have done in one
of your patients and can you describe
what are your findings as far as those
risk factors are concerned?
>> Uh, that is the graphically presentation
of cardiovascular risk
in in the patient. You can see the four
target point in our cardiovascular
sensor.
The lipid metabolism, homocysteine
metabolism,
risk of sudden cardiac death and uh
it's missing the risk of heart disease.
Uh this type of um
presentation is a base of
psychological effect that we know that
lots of people easily remember images
and also the colors than the numbers.
Uh
in this slide, you can see
uh that our patient uh have the
um little uh risk for high LDL
cholesterol. Uh
little risk uh of
uh low
uh HDL cholesterol with a positive
effect of omega-3 fatty acids on HDL
cholesterol. Uh based of a genetic base
of genetic
uh
investigation,
uh that patient doesn't have any problem
with the triglycerides.
Also, also, you can see uh that patient
have uh high increased risk for high
level of homocysteine in the blood
without without the positive effect of a
vitamin B2. Uh for example, in this
patient, we can prescribe the metal
forms of vitamin B6, B12, and metal
folic acid. Uh also, you can see the
connection between aspirin and arterial
thrombosis in the side of the protection
of the patient, but unfortunately, this
uh this patient
uh have increased risk of sudden cardiac
death uh due to prolonged QT interval.
>> So, this is very interesting and
meaningful information for the lay
public because they can comprehend that
easily. It's a qualitative assessment
rather than quantitative, but you can
also provide as in previous slides you
have shown also quantitative
risk from the publications that were
previously done.
>> Absolutely.
>> Now, there is a also this information of
a summary of affected genes that
contribute to various conditions that
you have already
mentioned as far as uh
uh the risk concerned related to
coronary disease and uh
a heart attack. Uh but there are also
the variables that are included there
that uh
affect uh
cardiovascular conditions as you have
mentioned previously. Any other comments
on it?
>> Uh absolutely not because in um our
cardiovascular sensors we combine uh
two important part.
Um
quantified analysis is connected with
us with the physicians and also the
quality analysis based on psychological
effect uh for our patients.
>> One thing that's really important that
uh I appreciate and I think it's uh very
important that when you provide uh your
genetic analysis
you always mention that the final
interpretation
decision and recommendation is uh
based on a professional opinion of the
physician that's taking care of the
patient, not the lab. And uh that that
is very important because there are some
other labs that either don't give
recommendations or make recommendations
that are not necessarily absolutely
scientifically based.
>> Absolutely. In our laboratory
uh the major part is the
communication between the physicians and
also the our patients.
>> Very good. So, there are a few other
questions that are very important for
any practicing physician and also our
patients. There are many genetic testing
facilities available worldwide.
What should the most appropriate genetic
testing include?
>> Uh the most appropriate genetic
testing must include
analysis of relevant gene, the analysis
of
genetic variants connected with that
type of disease,
high analytical performance based on
high accuracy, and also
high sensitivity, adequate genetic
counseling, and interpretation based on
scientific references.
>> Excellent. So, what does your lab's
report include when you
when when we request a pharmacogenetic
and genetic testing in general?
>> Uh when we ask about the
pharmacogenetic,
our laboratory include analysis of 14
14 genes.
Patient, also the analysis of relevant
polymorphisms and also analysis of a
gene type of the patient.
>> Thank you very much
for this information.
Uh we
Dr. Mishkovich, we are greatly
appreciative uh
of your participation in this
podcast series on the cardiogenetics.
And the next program will be on
pharmacogenetics, which is actually a
continuation of um
the analysis that you routinely perform
on the samples that are sent to your
lab.