Part 1 of 3: The Hypertension Series

Our health is a dynamic, complex, chaotic, nonlinear system. To make sense of this system, it’s critical that we learn to understand its language, which means we need to crack two interplaying codes: our genes and our environments. Unraveling the mysterious asymmetry and complexity in our biological systems raises an important question — can we ever break the uncrackable enigma of human health?

Just like any system of interconnected parts, our health possesses many quantitative and qualitative variables such as blood pressure, heart rate, sleep quantity, blood glucose levels, mood, the number and types of pathogens that reside within us, the red blood cell count, and so on. All of these variables constitute different measurable parts of our health and play a major role in predicting risk of health problems in the future. Both our genes and our environments interact in unique ways to bring about changes in these variables, which may differ from person to person. 

Blood pressure, or the pressure of flowing blood against the walls of our blood vessels, is a very important indicator. Not only is it the most well-characterized parameter in scientific literature, it can also be easily accessed by people without the need of a doctor. Recently, the continuous monitoring of vital signs has become a magnet attracting medical device companies by the dozen, from established titans like Omron to newcomers like BioBeat. Walking the streets in virtually any city, it doesn’t take much time to spot a person sporting a watch or wristband that can track blood pressure or heart rate. 

It can be an empowering feeling to have access to such data points – but knowing this information without the proper context can be dangerous when it comes to your health. Before bringing up the numbers in dinner conversations or running to your doctor at its slightest increase, it is important to be aware of how these variables play out in our body and why they have the effects you see.

In the first part of Nano’s hypertension three part-series, we hope to give you an appreciation of all the biological and environmental players that control the two numbers jumping out at you when you check your blood pressure. 

Why should you care about hypertension?

Hypertension, or elevated blood pressure, is an increasing cause for concern in the United States. In January 2018, the American Heart Association (AHA) reported that over 103 million American adults had high blood pressure, a number that represents nearly half of the adult population (AHA). Such staggering rates of hypertension place a significant burden on healthcare systems, particularly with respect to costs. For example, in the United States alone, individuals with hypertension have almost double the outpatient cost, and triple the prescription medication cost of those without hypertension (Kirkland et al, 2018).

Hypertension can have a profound impact on your life because it is a risk factor for multiple types of cardiovascular disease. According to the CDC, about seven in 10 people with chronic heart failure have hypertension, and heart failure costs the U.S.  over $30.7 billion each year (CDC). Tragically, about half of those who develop heart failure do not live more than five years beyond their diagnosis (CDC). 

The biology behind this life-threatening condition is remarkably straightforward: hypertension means the heart has to physically work harder to pump blood. As the hypertensive heart increases heart rate and contractile force, it thickens and enlarges. This triggers a vicious cycle in which the heart’s pumping efficiency decreases, so  it has to work harder to sustain blood flow. 

Risk factors related to hypertension extend far beyond just heart failure. Arterial damage due to hypertension can lead to stroke (and possibly dementia), kidney failure (due to injury of vessels going to and from the kidneys), eye damage (due to leaky blood vessels near the retina and optic nerve damage). Literally, unchecked hypertension can impair the body from head to toe.

The list of potential causes for hypertension is as long as the ocean is deep. Science points to everything from aging, drug use and infection to genetics, poor diet/lifestyle choices and the environment. In one way or another, each of these  potential causal factors influences on a range of biochemical pathways within our bodies that can either elevate heart rate, constrict blood vessels, increase blood volume or do something else that raises blood pressure. 

Let’s focus on two potent risk factors for hypertension: particulate matter in the environment, and genetic predispositions to hypertension susceptibility. The proliferation of miniature and wearable devices that can conduct real-time detection of particulate matter in the air, coupled with the vast array of personal genetic testing available on the market (23andme, Helix, NebulaGenomics, etc.) is bringing this previously elusive information to a bigger  audience. Integrating such information with real-time monitoring of heart rate represents the new frontier for diagnostics, and an understanding of basic biochemical principles underlying the science at play is the foundation for exploring it.

Player 1: Genetics

As we uncover more and more about the meaning and implications of the biochemical code  within our DNA, the importance of incorporating genetics into our analysis of health and disease has become increasingly clear. This is even despite the fact that all humans bear upwards of 99% genomic similarity! Of course, when considering the enormous size and scope of the human genome, conducting detailed investigations of even 1% of it is a massive undertaking – but a very worthwhile one.

Most of the 1% variation in human genomes can be attributed to single nucleotide polymorphisms, or SNPs. These are essentially mutations to DNA that can:
a) have no effect
b) produce a nonfunctional protein, or
c) produce an overactive or “poisonous” protein. 

The latter two situations can be deadly, since those kinds of SNPs can have outsized effects on the body’s maintenance of proper internal conditions. The number of SNPs can differ from person to person, with the presence of specific SNPs letting us know if we are susceptible to certain diseases.

Player 2: Environment

Besides genetics, our environment is also fundamental to our existence and dictates our vulnerability to diseases. While you may think that our external surroundings are stationary, it has recently been proven that this is far from the truth. In fact, we can pick up environmental factors in our morning strolls, at work or even on vacations. Imagine a cloud of such factors following us everywhere we go, shedding off when necessary or picking up new external matter on our journey through life. Unfortunately, we do not know much about our environmental profiles, the way we do about our individual genetic profiles. 

In 2018, researchers found that every human being walks around with his or her own unique environmental cloud, also known as the exposome cloud, which is the equivalent of a genetic SNP (Jiang et al, 2018). We are exposed to thousands of pan-domain species such as pathogens or even beneficial bacteria, chemical compounds, such as insecticides and carcinogens, particulate matter and so much more. Researchers called it a personalized exposome cloud, which continuously interacts with us. Sometimes, the cloud may sense a change in our lifestyle or behavior, and find a good opportunity to attack or protect our health. 

The environmental matter can have direct effects in our bodies through a process known as epigenetic changes – that eventually turns some of our genes on or off. Such a change at the micro-level can have a huge impact on the macro-level. Why? Because what differentiates a cell in say, our brain from a cell in our liver are the genes that our body has turned on. Our cells automatically know how to do that, based on rules learned during early development in the womb. Therefore, you can see how having environmental matter tinkering with such delicate regulatory processes, can accelerate the manifestation of a disease in our bodies. The exposome cloud is a new phenomenon in our understanding of diseases and it is only a matter of time before we can create holistic profiles out of genetic and environmental data to characterize diseases. 

It is virtually impossible to escape contact with outside air, which we encounter on a daily basis, whether it is on our way to work or even a casual stroll in our neighborhoods. Without realizing, we are constantly inhaling air that contains the tiny inconspicuous remnants of burned materials, dust, soot, industrial smoke, agricultural waste, regular cigarette smoke or construction activities, which together constitute particulate matter (PM). Even if we were to hypothetically sit at home all day, our indoor environments can still be infiltrated with ambient air particles. They are everywhere. Don’t be fooled by their size – they can create serious mayhem in our bodies! 

Due to the rise of urbanization and industrialization in the past two centuries, air pollution has now become a significant public health concern. About 4.2 million deaths occur every year as a result of exposure to ambient air pollution (WHO). PM is one of the major harmful components associated with air pollution. It consists of coarse (PM10) and fine (PM2.5) particles. While both kinds of particles can be easily inhaled into our lungs, only the fine particles are small enough to penetrate small airways and inflict major damage to our lungs and cardiovascular systems.

It is no surprise that about 24% of all deaths from stroke and 25% of all deaths from ischaemic heart disease are due to poor air quality (WHO). After conducting a highly controlled study, researchers found that with every 10 μg/m3 increase (that’s the equivalent of less than a quarter of a tiny raindrop) of PM2.5 concentrations, the incidence risk of hypertension is raised by 11% (Huang et al, 2019). Results like these should alert us to be more cognizant of our invisible, yet possibly harmful external environment.

Clearly, the risks posed by hypertension cannot be ignored. That being said, it’s about as complex and multidimensional an issue as anyone could imagine, especially as it can affect the body in so many different ways. The curiosity to better understand the causes and effects of hypertension has stimulated a flurry of research to unravel its mysteries, which we shall explore in greater detail next week. Stay tuned!

 

American Heart Association. (n.d.). Health Threats From High Blood Pressure. Retrieved July 8, 2019, from https://www.heart.org/en/health-topics/high-blood-pressure/health-threats-from-high-blood-pressure

American Heart Association News. (2018, January 31). More than 100 million Americans have high blood pressure, AHA says. Retrieved July 8, 2019, from https://www.heart.org/en/news/2018/05/01/more-than-100-million-americans-have-high-blood-pressure-aha-says

Centers for Disease Control. (n.d.). Heart Failure Fact Sheet|Data & Statistics|DHDSP|CDC. Retrieved July 12, 2019, from https://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_heart_failure.htm

Centers for Disease Control. (n.d.). High Blood Pressure Facts. Retrieved July 12, 2019, from https://www.cdc.gov/bloodpressure/facts.htm

Huang, K., Yang, X., Liang, F., Liu, F., Li, J., Xiao, Q., Chen, J., Liu, X., Cao, J., Shen, C., Yu, L., Lu, F., Wu, X., Zhao, L., Wu, X., Li, Y., Hu, D., Huang, J., Liu, Y., Lu, X. and Gu, D. (2019). Long-Term Exposure to Fine Particulate Matter and Hypertension Incidence in China. Hypertension, 73(6), pp.1195-1201.

Jiang, C., Wang, X., Li, X., Inlora, J., Wang, T., Liu, Q. and Snyder, M. (2018). Dynamic Human Environmental Exposome Revealed by Longitudinal Personal Monitoring. Cell, 175(1), pp.277-291.e31.

Kirkland, E. B., Heincelman, M., Bishu, K. G., Schumann, S. O., Schreiner, A., Axon, R. N., . . . Moran, W. P. (2018). Trends in Healthcare Expenditures Among US Adults With Hypertension: National Estimates, 2003–2014. Journal of the American Heart Association, 7(11). doi:10.1161/jaha.118.008731

World Health Organization. (2019). Ambient air pollution: Health impacts. [online] Available at: https://www.who.int/airpollution/ambient/health-impacts/en/ [Accessed 22 Jul. 2019].