To Test or Not To Test: Clinical Issues in Genetic Sequencing

The sequencing of the human genome, completed in 2003, opened the doors to providing genetic information for research, and, most recently, made it available directly to the public. Availability of highly precise and efficient sequencers (such as the ones from Illumina) resulted in minituarization of the genetic information, making it available and affordable to look for single-nucleotide polymorphisms, or SNPs, and their association with various diseases. However, as illustrated by the story of the 23and Me, the path to making such information available on-demand is complicated by regulatory and ethical dilemmas. The role of genetic information in clinical decision making is uncertain.

Recently, the New England Journal of Medicine reported on the results of an opinion poll in a case of a hypothetical patient seeking genetic sequencing because of a strong family history of malignancy. The majority of the responders favored genetic testing (60%), with mixed responses as to the extent of such testing to be performed. The authors called for genetic consultations to be carried out by trained geneticists. However, in real-life clinical practice, the statistical and population information provided by such genetic consultations is simply not enough.

As a cardiologist focused on bringing the practice of functional medicine into traditional cardiology domain, I rely on several genetic tests for a variety of reasons. The decisions to test are highly individualized, and have to be made based on patient’s history, objective findings and preferences. In one case, a patient with a distant history of atrial fibrillation sought advice. After normal physical exam and normal echocardiogram, we opted to run a genetic test that may help to determine his risk of atrial fibrillation and stroke. His one and only episode of atrial fibrillation occurred previously while he was treated for hypothyroidism, and has not recurred. Thus, genetic results would be of value in determining if indeed an elevated risk of atrial fibrillation existed independently of hypothyroidism, a reversible condition that could cause atrial fibrillation when untreated.  Detection of a carrier state associated with an elevated risk of atrial fibrillation and stroke would  result in more aggressive surveillance, and, possibly, earlier  treatment.

The decisions get more complicated when genetic testing that identifies a predisposition or likelihood of a disease must be carried out in a context of early disease diagnostic testing. The genetic predisposition as well as early disease may be modified by environmental and lifestyle influences. A patient this week reported that her father died of a massive myocardial infarct in his 40s. How should we proceed? In addition to history, physical exam, electrocardiogram, echocardiogram and possibly a stress test, we can consider imaging for subclinical atherosclerosis, such as obtaining a coronary calcium score. Addition of genetic testing to gauge probability of early myocardial infarction and vascular disease independently of traditional risk factors may be of value if the calcium score is greater than zero. In such circumstances, once sub-clinical disease is identified, a patient who carries a genetic variant forecasting an increased risk of heart disease and its complications may benefit from more aggressive attempt at disease stabilization and risk factor reduction, with supplements, medications, and lifestyle changes. In contrast, for patients with a score of zero (identifying a situation with no discernible vascular disease), detection of a carrier state associated with an increased risk may prompt more aggressive screening, and even result in over-testing.

The applicability of genetic testing is limited by patient acceptance and insurance reimbursement. Many patients view genetic testing as delivering an irreversible verdict, a final “say” about disease and illness. Yet, in most instances, genetic testing presents an opportunity for a change, focused and early intervention, and a possibility for a lifelong commitment to prevention.

Medication Safety is Top Priority for NIH

Despite scarcity of funds, NIH announced generous awards that would allow medication testing using human tissue chips. In this unique system, human tissue is arranged on experimental framework material  to mimick interplay of various organs in a body, and determine safety of drugs under development.

This represents one of many advances toward safety and tolerability of medications. At the Over 50 fair today, I gave a talk on the genetic testing for the cytochrome P450 polymorphisms. This system is responsible for processing nearly all of the drugs that are used in clinical practice. The lecture was well attended, and numerous questions at the end were reflective of  the intense interest drug testing and safety generates. The test is performed by swabbing a Q tip inside a patient’s cheek. Results are available in about 2 weeks. Over 280 medications can currently be assessed for safety based on personal genetic variability of the cytochrome P 450 system.

So far, the “med-tuning” using the personalized genetic testing for common alleles of the P 450 system has exceeded my expectations. In one instance, a patient of mine on multiple medications was found to be hypotensive. I stopped one of his blood pressure drugs, and his blood pressure improved. When the genetic testing results became available, the discontinued drug was the safest one for him! I now have the opportunity to readjust his medications so that he achieves optimal blood pressure and heart rate control using the safest medications based on his genetic profile. In another instance, I stopped a water pill for a patient who became dehydrated in a hot climate. Before restarting it, I tested this patient’s P450 system. The drug appeared to be safe for him, and no substitution was needed. He was counselled to maintain his fluid intake in warm weather, and to resume this medications.

The genetic testing for medication safety is an important piece of the medications selection puzzle, and allows a truly personalized approach. Of course, it does not shed light on possible effects (and side-effects) of medications under extenuating circumstances such as diseased states, dehydration, fever. The tissue chip research supported by the NIH will add significantly to the understanding of complex organ- medication interactions.

I encourage all of my patients on at least one medication to have a genetic test for safety and side-effects profiles. All of my patients receive a color-coded hard copy of their results to use as needed during doctors appointments or hospital admissions. Over 100,000 deaths occur annually due to medication toxicity, and the annual cost exceed 182 billion. Medicare and most major carriers cover the test. I negotiated a significant discount for the test for those of our patients not covered by insurance. This simple test, performed once, may be a life-saver!

Is Your Health an Accident?

According to the National Institutes of Health (NIH), the burden of chronic diseases is tremendous:

It is estimated that 3 in 4 adults over age 65 and 1 in 15 children suffer from two or more chronic medical conditions — such as diabetes mellitus, chronic kidney disease, hypertension, and chronic pain. As patients develop more chronic conditions, they are likely to use more health care services and suffer negative outcomes such as unnecessary hospitalizations, adverse drug reactions, declining functional status, and mortality. These growing problems emphasize the need for more research to improve health outcomes of patients with multiple chronic conditions.

NIH recently awarded over $19 million to various health care systems over 5 years to address management of chronic conditions. Here is the issue, though: promoting research into improving situation of patients with multiple chronic conditions does not address the fact of how miserably we failed at preventing these very same conditions from occurring. It perpetuates the notion of health as an accident. After all, with nearly 75% of adults over 65 and almost 10% of all children afflicted with two or more chronic conditions, one would certainly take it as a norm that nearly everyone should be experiencing these outcomes!

Nothing can be further from the truth. Health is not an accident. Many of my patients take great pride in their daily efforts directed at preserving their vitality, wellness and freedom from disease. No, do not expect medical insurance companies to pay physicians or help patients to meaningfully engage in such preventive efforts. This decision is up to you. Ask yourself: do you want to be one of the statistic referenced above? Or do you want to commit to a path of wellness that promotes more than accidental health?

At the Integrative Cardiology Center of Long Island, we have created cutting-edge,  one-of-a-kind programs that help you in your quest. Contact us to learn more, sign up for the newsletter, or return to this blog for more.

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