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Keep Out The Rain

cvd umbrella

It has been well established that cardiovascular disease (CVD) is a condition that leads to chronic symptoms that are generally thought of as a primary disease. However, vascular injury leads to subsequent disease such as metabolic disease, obesity, high blood pressure and kidney disease. There are several contributing factors starting a person on the path of having cardiovascular disease. Some of these include:

  1. Oxidative (ox)stress—potentially results in DNA damage
  2. Increased low density lipid (LDL) that can become oxidized into oxLDLs
  3. Overeating/over-nutrition leads to hormonal imbalances and subsequently obesity and/or metabolic disease
  4. Distress/Eustress is controversial, but the body does not know the difference and they can both lead to shear stress due to increased blood flow through laminar areas of the vascular system.
  5. Toxins that come produced within the body (endobiotics) or enter the body from outside source (xenobiotics). Environmental effects have strong impacts on how the body responds. It is important to manage the things that are within one’s control such as smoking, exercise, and consuming a well-balanced diet.

With people livings becoming busier, it is easy to miss the warning signs. A slight weight gain here or a headache there. What then can be done about the progression of CVD and other disease states such as hypertension? I am glad you asked. Controlling hypertension for example can be maintained by making lifestyle changes consisting of exercising at least 150 minutes per week, modifying one’s diet to potentially include the dash diet, and reducing stress levels. This sounds like a lot but planning ahead is key. Often times I find myself going to a fast food restaurant because I have gotten too hungry to cook, or because I have not had time to go shopping. When I plan ahead and purchase my food for a week and pack healthy snacks, I evade the urge to go for those french fries (my go-to weapon against hunger). Additionally, I find I am less stressed if I spend some time performing rigorous exercises or get moving throughout the day. I attempt at least 250 steps every hour and 10,000 steps over the course of the day.

However, the symptoms are not the same for everyone, thus one should know what to look for to identify vascular disease early as well as forming a trusting relationship with a primary care provider because, “You’re the Cure”!! Let’s keep this conversation going. Follow me on Twitter (@AnberithaT) or on my site. I will take a deeper look at each of these topics and discuss what, if anything, can be done to combat or control these symptoms.

 

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Getting To The Heart of Long-Term Space Travel

During my last years in graduate school, I learned that the coolest experiment to ever be conduct was about to take flight – literally. In the genetics world, twin studies have been a classical tool used to study the nature vs. nurture effect of any given trait or disorder in humans. With the ever-increasing interest in understanding how long-term space travel affects humans, exploring this idea would obviously benefit from controlled twin studies, but what are the chances that NASA could actually find identical twins that are both qualified enough to be astronauts?

Turns out not as low as you would think!

Mark and Scott Kelly are twin brothers who joined NASA in 1996 and already had many spaceflights under their belts before the idea of a twin study even popped in to anyone’s head. However, in 2015, NASA jumped at their opportunity to perform what I think, is the coolest science experiment to have ever been executed. To get a better understanding of how being in space for an extended period of time, the NASA Twin Study would monitor an outstanding number of biological variables in both brothers before, during and after Scott’s 1-year long stay at the International Space Station, while Mark stayed on Earth.

While that alone makes for a pretty outstanding story, the best part of this experiment was truly how collaborative and integrative the studies were. The study was coordinated by NASA’s Human Research program, and over 84 researchers across 12 different universities performed the insane amount of work to analyze 10 different biological areas, including:

  • Biochemistry
  • Cognition
  • Epigenomics
  • Gene Expression
  • Immune
  • Metabolomics
  • Microbiome
  • Proteomics
  • Physiology
  • Telomeres
NASA Twin Study experimental design via Garrett-Bakelman et al., Science 364, 144 (2019)

NASA Twin Study experimental design via Garrett-Bakelman et al., Science 364, 144 (2019)

They knew they probably wouldn’t have a shot like this again and took advantage it. I was ecstatic in April when I saw the published results of the study since I’ve been following this experiment for years. Obviously, I was most interested in how cardiovascular function was impacted by long-term space travel. It’s been well known that the gravity-free environment of space takes some pressure of the heart from working so hard, but since the heart is a muscle, this lack of use causes a decrease in muscle mass. To combat this loss of muscle mass, astronauts typically spend ~ 2.5 hours exercising on the International Space Station! The heart also changes shape in space becoming more circular rather than elongated. Luckily, these changes return to normal once the astronaut returns to space, but what does spending a year in space do to your heart and vasculature? Here are the main cardiovascular changes from this study:

  • Cardiac output increased by of 10% while moderate decreases in systolic and mean arterial pressure were observed (these findings are consistent with previous studies)
  • The carotid intima-media thickness increased while Scott was in space and remained thicker 4 days after landing.
  • Inflammatory cytokines and chemokines were increased during all spaceflight timepoints and returned to normal after landing.
  • Urine levels of Collagen alpha-1(III) chain (COL3A1) and collagen alpha-1(I) chain (COL1A1) proteins were increased compared with preflight values, and these returned to baseline levels postflight.
  • An increase in the ratio of plasma levels of apoliprotein B (APOB; a major constituent of LDL particles) to apolipoprotein A1 [APOA1; a major constituent of high-density lipoprotein (HDL) particles] during the last 6 months of the mission in space. This ratio came back to baseline once Scott returned to Earth.

One of the most important take-home messages is that many of the variables analyzed either stayed the same or returned back to baseline once Scott came back to Earth, suggesting the effects of being in space for a year, on the heart in particular, is temporary and reversible. Obviously, the results of this study are limited because only one set of twins was analyzed so it’s hard to definitively say that these results represent how a year in space affects all of us – but it gives great insight into the biological effects of long-term space travel.

While I only focused on the cardiovascular results here, this study has an insane amount of information that is definitely worth reading, particularly since there were some variables, such as telomere length and DNA damage that changed during Scott’s time in space, but never returned back to his normal levels. That SpaceX flight might not be the best idea *just* yet.

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Polygenic Scores in Cardiovascular Disease 

For many decades, we knew that cardiovascular disease and several of its risk factors are heritable. This justifies why we often ask our patients about their family history, but is that truly the best measure for someone’s genetic liability to develop a disease?

Diseases such as myocardial infarction, type 2 diabetes, and atrial fibrillation are called complex traits. This is because their genetic liability comes from the summation of weak effects of many single nucleotide variations across the 3 billion nucleotides in our genome. This is different from monogenic diseases such as hypertrophic cardiomyopathy, which is due to a single but highly potent nucleotide variation in the cardiac sarcomere gene.

Owing to multiple large genome-wide association studies, a better understanding of the human genome and advances in statistical genomics methods, this polygenic liability of disease could now be measured in a single individual to predict where he or she falls on the genetic risk spectrum of disease. Over the past year, two high profile papers in Nature Genetics and JACC showed that polygenic scores can accurately predict coronary artery disease, as well as other diseases such as Type 2 Diabetes and Atrial Fibrillation.

A polygenic score is a number that is normally distributed in the population. Where your score is located on that bell-shaped curve determines your risk or protection from disease. While most of us will be in the middle, the unlucky person who happens to be in the upper tail of the distribution will carry several fold increased risk of CAD compared to the rest of us. This could be your 45 year-old patient, non-smoker with an LDL of 120mg/dL and no clinical risk factors who presents with a STEMI. On the other hand, I always wonder whether my 95 year-old grandpa who died of lung cancer with the cigarette in his mouth but a healthy heart actually was on the bottom tail of the CAD polygenic score distribution?

Just like the systolic blood pressure and the LDL cholesterol, polygenic scores are continuous measures of risk that require drawing cut-offs in order to practically classify patients and treat accordingly.  Defining those thresholds and determining how we act on them will be key for the successful implementation of those scores in clinical care. Anytime we draw thresholds to use in screening or treatment, there will be issues of sensitivity, specificity, outcomes, and value. After all, even cutoffs for risk factors that we’ve understood for decades, such as blood pressure and LDL cholesterol, continue to be debated from one guideline update to the other. The power of the polygenic scores is their wide availability and low cost (around $50 once for all diseases) as well as their ability to classify risk at an early stage in life (practically from birth) before clinical risk factors start appearing, which creates an opportunity to target disease early on before it develops.

The journey to clinical implementation of polygenic scores in cardiovascular disease still requires several steps. First, the current predictive ability of those scores declines in populations of non-European ancestry.  Development of scores that carry similar predictive ability across different ethnicities will be crucial to avoid widening healthcare disparities.  Second, prospective trials testing specific thresholds and interventions will be necessary to prove that implementation of those scores can lead to positive outcomes. For example, would targeting lower LDL thresholds in people with high polygenic scores reduce their risk of CAD?  Third, behavioral psychology studies could inform how young and healthy people react to information regarding their score. Ideally, you would want someone with higher score to engage in good lifestyle activities to mitigate his/her risk but also someone with a low score to not get falsely reassured and pick up poor lifestyle choices.  Fourth, clinical trials of existing and new therapies could be better informed with polygenic score stratification to pick up missed opportunities of benefit. One example would be that people at the upper tail of risk could benefit from treatment that when applied to the average population does not show a benefit.

Precision medicine in cardiovascular disease is happening and polygenic scores are one opportunity to prevent disease early on by targeting specific people at risk. Unlike the heritability informed by a positive family history which rarely changes management, the quantitative aspects of polygenic scores and our ability to validate their impact on outcomes prospectively and in different settings will change how we care for patients in the near future.

 

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Eat smarter- How to boost your cardiovascular health and lower your blood pressure with functional foods – Watermelon

It’s finally summer. Warmer temperatures and local Farmer’s markets motivate us to eat lots of fresh fruits and greens. A healthy summer diet maintains our health and can be even supportive in the management of various diseases. For example, some patients with treated blood pressure are able to taper off blood pressure medications by eating not only healthier but also smarter, losing weight and exercising more.

American Heart Association guidelines recommend eating 9 servings of fresh fruit and vegetables per day. Although reasonable, it is often difficult to implement these recommendations into one’s busy life. In addition to consuming more fruits and greens, is it possible to eat smarter and implement more so-called functional foods to positively affect blood pressure and ultimately cardiovascular health?

One of my friends brought my attention to the beneficial effects of watermelon. Since then I am hooked. For me, watermelon in the form of juice works best – either in the office or during work outs to help with next day muscle soreness.

Watermelons are sweet and popular fruits of summer, originating from sub-Saharan Africa, usually consumed fresh in slices, diced in fruit salads, or as juice. They contain more than 90% of water and are low in fat. Against popular belief watermelons are neither high caloric nor do they have high sugar levels. They contain approximately 6-7 g total sugars which is half of total sugars found in apples, bananas, mangos, sweet cherries, kiwis, pineapples etc., and comparable to blackberries, blueberries, grapefruits, and oranges, just to name a few.

Studies have shown that watermelon can lower blood pressure and improve arterial compliance. Watermelons seem to work like an anti-aging remedy on arteries. But how does watermelon reduce blood pressure and make arteries “younger”?

Watermelon contains three functional important bioactive components: lycopene, arginine and citrulline. These are potent antioxidants and converted into nitric oxide, the principal vasodilatory molecule produced by endothelial cells, the inner layer of your arteries. For decades, doctors have prescribed nitroglycerin which gets converted to nitric oxide in patients with chronic angina to dilate heart arteries and relieve chest pain.  

A variety of factors can reduce the production of nitric oxide and ultimately lead to increased arterial stiffness and higher blood pressure levels such as aging, unhealthy diets, and poor exercise habits. Many people reach for arginine supplements, but the body does not absorb it well. Citrulline on the other hand is easy absorbed and converted into arginine and ultimately nitric oxide.

Watermelon provides these artery-bioactive compounds and studies indicate beneficial influence on cardiovascular health. For example, one study showed that higher lycopene levels improve arterial compliance. Watermelon bioactive compounds also seem to be anti-inflammatory and to positively impact cholesterol levels including lowering of the so-called “bad” LDL cholesterol without impacting the “good” HDL cholesterol.

In addition, watermelon is also a good food source of glutamine and Vitamin C, both of which display antioxidant properties and have been shown to enhance arterial dilation. Studies that have examined the effects of watermelon on vascular function support the notion that this functional food may improve blood pressure and arterial stiffness. 

As recommended by the American Heart Association guidelines for the detection, prevention, management and treatment of high blood pressure, a healthy lifestyle is an integral part of health maintenance and high blood pressure should be treated with lifestyle changes and in some patients with medication.

So, as long as the watermelon season lasts, let’s be health smart and add it to our diet: fresh in slices, diced in fruit salads, or as juice and take advantage of this natural remedy.

References:

  1. Vlachopoulos C, Xaplanteris P, Aboyans V, Brodmann M, Cífková R, Cosentino F, et al. The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society. Atherosclerosis. 2015; 241(2): 507–532.
  2. Seals DR, Kaplon RE, Gioscia-Ryan RA, LaRocca TJ. You’re only as old as your arteries: translational strategies for preserving vascular endothelial function with aging. Physiology (Bethesda). 2014; 29(4):250–264.
  3. Ellis AC, Dudenbostel T, Locher JL, Crowe-White K. Modulating Oxidative Stress and Inflammation in Elders: The MOXIE Study. J Nutr Gerontol Geriatr. 2016 Oct-Dec;35(4):219-242.
  4. Figueroa A, Sanchez-Gonzalez MA, Perkins-Veazie PM, Arjmandi BH. Effects of watermelon supplementation on aortic blood pressure and wave reflection in individuals with prehypertension: a pilot study. Am J Hypertens. 2011; 24(1):40–44.
  5. Figueroa A, Sanchez-Gonzalez M, Wong A, Arjmandi B. Arterial stiffness and blood pressure are reduced after watermelon supplementation in obese with prehypertension and hypertension. The FASEB Journal. 2012; 26:385.
  6. Figueroa A, Wong A, Hooshmand S, Sanchez-Gonzalez MA. Effects of watermelon supplementation on arterial stiffness and wave reflection amplitude in postmenopausal women. Menopause. 2013; 20(5):573–577.

Tanja Dudenbostel Headshot

Tanja Dudenbostel is an Internist, Hypertension Specialist within Cardiology at the University of Alabama at Birmingham where I divide my time as an Assistant Professor between clinical research and seeing patients in cardiology.

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Weight Loss And Exercise: A Remedy For A Better Functioning HDL

We all know that weight loss and exercise are essential for a better health. A healthy life style reduces cardiovascular risk, obesity, and Type 2 Diabetes. In a previous post, I briefly touched upon the idea that weight loss and exercise make HDL, or our “good cholesterol,” better at reducing cholesterol circulating the bloodstream. In the latest issue of the ATVB journal, in the translational section, a new study from Baker Heart and Diabetes Institute in Melbourne, Australia looked at this specific idea. They asked how does weight loss and exercise affect HDL in patients. So I thought it would be interesting to share the results from this study.

The study examined 95 patients with metabolic syndrome and compared them to healthy individuals. Metabolic syndrome patients have characteristics that include obesity, high blood glucose levels, hypertension and/or dyslipidemia. These patients tend to have dysfunctional HDL, and its level fail to predict the possibility of future cardiovascular events. In the study, patients were divided into 3 groups. The first group had to reduce their caloric intake by 600 calories a day. The second group also reduced their caloric intake by 600 calories and, in addition, had to exercise for 3-4 sessions of about 30 minutes each. The third group kept their usual dietary and exercise patterns. The patients were monitored for 12 weeks and tested at the beginning and at the end of the study. Both groups resulted in similar weight loss. However, the researchers found evidence that the group of patients that followed both healthier diets and an exercise regimen had the most change in HDL capacity to excrete cholesterol.

Upon looking at the details of the study, the researchers first observed that metabolic syndrome patients had smaller HDL particles with different composition, and lesser ability to get rid of cholesterol easily. With diet and exercise, the size of HDL particles in those patients got bigger and their ability to function in cholesterol efflux assay improved making these particles overall better in excreting blood cholesterol.

Despite the small sample size of the study, these results are promising in providing a better understanding of how life style changes can impact HDL function and overall reduce risk for CVD and Type 2 Diabetes. For me personally, this study make me wonder if exercise alone would effect HDL function, since it has become apparent that while exercise is important, exercise alone without appropriate dietary changes are not sufficient to lead to weight loss. Can exercise alone improve HDL composition and function? While this study does not provide an answer to my question, I am sure more studies will come out to address this question specifically. So until we know more, keep those healthy salads and spinning classes coming.

Dalia Gaddis Headshot

Dalia Gaddis is a postdoctoral fellow at the La Jolla Institute for Allergy and Immunology. She has a Ph.D. in microbiology and immunology. She is currently working on understanding the interactions between the immune system and atherosclerosis development. 

 

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Can Increasing HDL Reduce Heart Disease? An Issue Of Constant Debate!

A couple of years ago I was fortunate to attend the HDL workshop that followed the ATVB council conference, which was held in San Francisco. The workshop’s main focus was to discuss and debate high-density lipoproteins (HDL), or what is commonly known as “the good cholesterol,” and how it influences heart disease.
 
You may ask, “HDL-cholesterol is good for your heart, so why dedicate two days to discuss what is already know?!” Here is where it gets interesting. While we look forward to lab results showing high HDL-cholesterol levels and low levels of LDL-cholesterol (bad cholesterol) as an indication of reduced risk for cardiovascular disease, the actual answer to the benefits of HDL for cardiovascular disease is far from a simple yes or no. Yes, having high HDL-cholesterol indeed reduces the risk of heart disease, but this does not hold true for patients with metabolic conditions like diabetes, or chronic inflammation like chronic kidney disease.  In fact, multiple clinical studies that aimed at increasing levels of HDL-cholesterol have failed to reduce cardiovascular events. It is now becoming evident that just increasing the quantity of HDL-cholesterol alone is not sufficient to ensure cardiovascular free events.
 
Scientists are discovering that there is more to HDL-cholesterol than its concentration. The size of these HDL molecules, their composition, and their ability to remove lipids from the blood stream for excretion are more indicative of HDL protective function.  In addition, scientists are also finding that HDL has other compelling properties that can lower cardiovascular risk indirectly. HDL can reduce inflammation, protects from cell death and promotes wound healing. HDL also had antithrombotic effects (prevents blood clots formation), all of which would decrease the possibility of a cardiovascular incident.
 
So why not measure for the functionality of HDL rather than its mere concentration to determine one’s risk for cardiovascular disease? This was a topic for discussion at the HDL workshop. The methods used to measure HDL functionality are far from being standardized for use in clinical settings. More work is needed to find techniques that can be used routinely and reliably across clinical laboratories.
 
It is worth to note that the increase in HDL-cholesterol levels that are triggered by life style changes: healthy diets and physical exercise, does in fact correlate with reduced risk of cardiovascular disease. Researchers think life style change does not only increase HDL-cholesterol but also has an effect on its function and on other metabolic parameters. So until science figures a more clinically feasible way to measure HDL functionality, it would still be a good practice to continue whatever healthy diet and exercise regimen you are on and to aim to keep those HDL-cholesterol numbers high and those LDL-cholesterol numbers low.

Dalia Gaddis Headshot

Dalia Gaddis is a postdoctoral fellow at the La Jolla Institute for Allergy and Immunology. She has a Ph.D. in microbiology and immunology. She is currently working on understanding the interactions between the immune system and atherosclerosis development.