From Low-Fat, High-Carb to Insulin Resistance, Fatty Liver, and Heart Disease

I recently gave a talk at a meeting with colleagues, most of them cardiologists and endocrinologists, where I, among other things, discussed the current status of diet-heart hypothesis and the possible relationship between our fear of dietary fats and the obesity epidemic.

After the meeting, a senior colleague of mine, an old friend, and a mentor who I deeply respect, approached me and lambasted me for several points I had made during my talk.


He said that the mortality from heart disease had dropped dramatically for the last 30-40 years, mostly because we had managed to lower blood cholesterol by making changes to our diet. He was angry with me for asking the question whether our emphasis on low-fat food products could ultimately have steered us into an epidemic of obesity, metabolic syndrome, and diabetes.

During our discussion, I came to think of Dr. Tim Noakes’ words at the Foodloose Convention in Reykjavik last year where he touched upon the same issue. As a matter of fact, I had the privilege to speak at the same conference which gave me the opportunity to meet and talk with Tim for the first time.

Tim showed the slide above and said;

… the dietary guidelines changed in 1977 and in 1978 the obesity epidemic begins in the United States, and no one will take responsibility for that. And that’s the question you have to ask. You change the guidelines and why won’t you take responsibility for what happened? Why do you ignore it? And, why do you attack us for asking that question?

Yes, these were the words I remembered so vividly: … and, why do you attack us for asking that question?

The Macronutrient of Interest in Chronic Disease Is Carbohydrate, not Fat

Sixty years ago, American psychologist Leon Festinger described a phenomenon he called cognitive dissonance. He believed that we hold many cognitions about the world and ourselves; when they clash, a discrepancy is evoked, resulting in a state of tension known as cognitive dissonance (1).

Our powerful motive to maintain cognitive consistency can give rise to irrational and sometimes maladaptive behavior.

Festinger wrote:

A man with a conviction is a hard man to change. Tell him you disagree and he turns away. Show him facts or figures and he questions your sources. Appeal to logic and he fails to see your point. 

Well, I guess you’re assuming that I think my senior colleague and old mentor suffers from cognitive dissonance. And you’re right, I do. But, I also know he thinks I’ve completely gone off the rails.

So, how can a low-fat diet lead to an epidemic of obesity, metabolic syndrome, and diabetes? Let’s start by looking at three facts.

The first one is that a low-fat diet is also a high-carb diet. Of course, this does not imply that it is a diet composed of added sugars and refined carbohydrates. However, the energy has to come from somewhere and therefore a low-fat diet is usually synonymous with a high-carb diet.

The second fact is that according to recently published evidence, at least 50% of the adult population in the U.S. have insulin resistance, manifested as diabetes or prediabetes (2).

Finally, there is evidence from several studies on human metabolism showing that insulin resistance and high-carb diets make a destructive combination. And, remember, at least half of the U.S population is insulin resistant.

Let me quote Tim Noakes’ Reykjavik lecture again:

Insulin resistance is a benign condition. However, a high carbohydrate diet turns it into a killer.

Noakes believes that the macronutrient of interest in chronic disease is carbohydrate, not fat. He says:  

They completely got it wrong. Ancel Keys backed the wrong horse completely. But, this truth comes through understanding human metabolism, not epidemiology.

Insulin Resistance and High-Carb Diets – From Reaven to Noakes

Insulin resistance is defined as a diminished response to a given concentration of insulin. Initially, the pancreas responds by producing more insulin (compensatory hyperinsulinemia). For this reason, individuals with insulin resistance often have high levels of insulin in their blood (3).

Gerald M. Reaven professor emeritus in medicine at the Stanford University School of Medicine was the first to emphasize the role of insulin resistance and compensatory hyperinsulinemia in increasing the likelihood of developing the cluster of abnormalities commonly referred to as the metabolic syndrome (4).

The five conditions described below are used to define the metabolic syndrome. Three of them must be present in order to be diagnosed with the condition.

  • Abdominal obesity, defined as waist circumference > 40 inches (102 cm) in men and > 35 inches (88 cm) in women
  • A high triglyceride level in blood, defined as > 150 mg/dL (1.7 mmol/L)
  • A low HDL cholesterol level in blood, defined as < 40 mg/dL (1 mmol/L)
  • High blood pressure, defined as > 130/85 mmHg or drug treatment for elevated blood pressure
  • Elevated blood sugar, defined as fasting blood glucose >100 mg/dL (5.6 mo/L) or drug treatment for diabetes

The Role of Triglycerides

In his Reykjavik lecture, Tim Noakes summarized few of Reaven’s studies on the importance of triglycerides in patients with insulin resistance.

In a study published 1966, Reaven and colleagues examined the triglyceride response to low- and high-carbohydrate diets (5). They discovered that the majority of patients will increase their triglyceride concentration to a variable extent as a consequence of a high-carb diet.

Interestingly, they also found that the more insulin resistance present, the greater the subsequent rise in triglycerides following the ingestion of carbohydrates.

Reaven also suggested that endogenous hypertriglyceridemia is caused by increased triglyceride production by the liver (6). In other words, the liver is pumping triglycerides into the circulation. The higher the plasma insulin, the higher the liver production of triglycerides, the higher the blood levels of triglycerides.

Endogenous hypertriglyceridemia, which includes familial hypertriglyceridemia and idiopathic hypertriglyceridemia, is characterized by the increased level of very low-density lipoprotein (VLDL) and triglycerides in the blood (7).

Hence, insulin resistance, accompanied by hyperinsulinemia, may be an important cause of the enhanced triglyceride production by the liver following the ingestion of a diet high in carbohydrates.

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“It’s Not the Insulin Resistance per se that Is the Problem – It’s High-Carbohydrate Diets”

Reaven developed a model explaining the relationship between insulin resistance and cardiovascular disease (8).

He concluded that insulin resistance and hyperinsulinemia are common findings in apparently healthy individuals and associated with a number of abnormalities that significantly increase the risk of coronary artery disease. Among them are lipid abnormalities commonly termed atherogenic dyslipidemia because they tend to promote atherosclerosis which is believed to be the underlying cause of cardiovascular disease.

Several bad things seem to happen if we’re insulin resistant; weight gain, atherogenic dyslipidemia, visceral adiposity, endothelial dysfunction, hypertension, hyperuricemia, systemic inflammation, mitochondrial dysfunction, and impaired exercise performance.

Noakes believes Reaven’s biggest mistake was to not pinpoint high-carbohydrate diets as the culprit. However, Noakes refers to three papers published by Reaven’s group between 1987-1994 to emphasize that Raven knew that carbohydrate was the villain.

Noakes says:

So, Reaven understood that carbohydrates drive insulin secretion in the metabolic syndrome. Hence he had to conclude that restricting carbohydrate should be the key therapy for this condition. In 1987 he was heading into that conclusion because he published three papers in 1987, 1989 and 1994 all showing the benefits of low carbohydrate diets in people with insulin resistance.

The studies Noakes is referring to were performed on individuals with non-insulin dependent diabetes mellitus (NIDDM); a group that is highly representative for insulin resistance. Here are Reaven’s main conclusions from these three papers (9,10,11):

These results document that low-fat, high-carbohydrate diets, containing moderate amounts of sucrose, similar in composition to the recommendation of the ADA, have deleterious metabolic effects when consumed by patients with NIDDM for 15 days. Until it can be shown that these untoward effects are evanescent and that long-term ingestion of similar diets will result in beneficial metabolic changes, it seems prudent to avoid the use of low-fat, high-carbohydrate diets containing moderate amounts of sucrose (9).

The results of this study indicate that high-carbohydrate diets lead to several changes in carbohydrate and lipid metabolism in patients with NIDDM that could lead to an increased risk of coronary artery disease, and that these effects persist for more than 6 weeks. Given these results, it seems reasonable to suggest that the routine recommendation of low-fat high-carbohydrate diets for patients with NIDDM be reconsidered (10).

In NIDDM patients, high carbohydrate diets compared with high monounsaturated fat diets caused persistent deterioration of glycemic control and accentuation of hyperinsulinemia, as well as increased plasma triglycerides and VLDL-cholesterol levels which may not be desirable (11).

Then Noakes says:

Why did he (Reaven) stop in 1994 doing low carbohydrate studies? The answer is that because he was at Stanford which is one of the most progressive cardiovascular groups. Had he came out in 1994 and said you must all eat a high-fat diet, his career would have ended overnight. And wisely he decided to continue researching without drawing attention to himself and that’s why that work is so fundamental but it has got lost.

Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease in the United States and other Western countries (12).

It is primarily triglycerides that accumulate in the liver in patients with NAFLD. Triglyceride accumulation may be due to an excessive importation of free fatty acids to the liver from adipose tissue. Excessive amounts of fatty acids may also be produced by the liver cells themselves due to an increased conversion of carbohydrates and proteins to triglycerides. Defective transport of fatty acids from the liver may also contribute to the accumulation of triglycerides in the liver.

A paper published 2016 suggests that the presence of NAFLD in people with insulin resistance is a key driver of atherogenic dyslipidemia so typical of the metabolic syndrome (13).

Patients with NAFLD are more likely to have high levels of apolipoprotein B and small LDL particles, regardless of similar body mass index and other clinical parameters. The authors speculate that this lipoprotein profile is driven mostly by liver fat content and insulin resistance and appears not to be worsened by obesity or the severity of liver disease. Hence, NAFLD may be a major link between insulin resistance, metabolic syndrome, and coronary heart disease.

In his Reykjavik lecture, Noakes said:

What they are showing for the first time is that the key driver of atherogenic dyslipidemia is NAFLD. And, how do you get NAFLD?  You get it from eating a high carbohydrate-diet feeding insulin resistance.

The Bottom Line

Noakes does an excellent job in explaining the clinical implications of the metabolic abnormalities underlying insulin resistance, visceral obesity, type 2 diabetes, and coronary heart disease, and how these may be fueled by high consumption of carbohydrates.

You’re either highly carbohydrate tolerant, normal or carbohydrate intolerant. If you’re tolerant, you’re probably an athlete, probably not overweight or obese, and you’ll probably not get these diseases, and you can eat pretty much what you like.

But if you’re carbohydrate intolerant, there’s only one way you can go; insulin resistance, expanding waistline, obesity, metabolic syndrome and type 2 diabetes await you.

Noakes says:

And that’s the point when we’re talking about nutrition. Nutrition is not the issue. It’s the patient. And you’ve got to fit the diet the patient. People just don’t seem to get it; If you’re insulin resistant you cannot eat carbohydrates.

Noakes is convinced that a low-carbohydrate diet is a key to the prevention and treatment of insulin resistance and all its associated conditions.

If he’s right, advising everybody to consume a low-fat, high-carbohydrate may be catastrophic because at least 50% of the adult population is insulin resistant. If we put all these insulin resistant people on a high-carb diet, we may have an epidemic of obesity, metabolic syndrome and type 2 diabetes.

Sounds familiar huh?



Who Wants To Live Forever

The famous song, Who Wants to Live Forever, performed by the British rock band, Queen was used for the scenes in the film Highlander, where Connor MacLeod must endure his beloved wife Heather growing old and dying while he, as an immortal, remains forever young. The scenes are both tragic and beautiful at the same time, and the passionate performance by Queen makes them a classic.

You feel strong sympathy for both Connor and Heather. He who has to say goodbye to the woman he loves and continue living and she who must bid farewell to life because old age and disease can’t be forever avoided.

Who Wants To Live Forever is also the title of Iceland Health Symposia’s next annual conference to be held in Reykjavik on September 8, 2017. Further information and registration can be found here.

Last year’s convention entitled Foodloose was a huge success. It was hosted by Dr. Maryanne Demasi and included speakers like Gary Taubes, Aseem Malhotra, Axel F. Sigurdsson, Tim Noakes, Denise Minger and Tommy Wood. You can find all the presentations from Foodloose here.

Noncommunicable Diseases (NCDs)

Noncommunicable diseases (NCDs) are disorders that are not caused by infectious agents and therefore not transmissible.

Due to the enormous progress in preventing and treating infectious disorders, NCDs have become the most common cause of death and disability worldwide. It is estimated that these diseases kill 40 million people each year, equivalent to 70% of all deaths globally.

Examples of NCD’s are cancers, diabetes, cardiovascular diseases such as coronary artery disease and stroke, and chronic respiratory diseases such as chronic obstructive pulmonary disease and asthma.

Cardiovascular diseases account for most NCD deaths, or 17.7 million people annually, followed by cancers (8.8 million), respiratory diseases (3.9 million), and diabetes (1.6 million)(1).

According to the World Health Organization,

These diseases are driven by forces that include rapid unplanned urbanization, globalization of unhealthy lifestyles and population aging. Unhealthy diets and a lack of physical activity may show up in people as raised blood pressure, increased blood glucose, elevated blood lipids and obesity. These are called metabolic risk factors that can lead to cardiovascular disease, the leading NCD in terms of premature deaths.

What NCD’s have in common is that they are to a large extent determined by our behaviors. Smoking, physical inactivity, unhealthy diet and the harmful use of alcohol are examples of factors that increase the risk of NCD’s.

Who Wants To Live Forever

The famous Queen song includes these words:

There’s no chance for us
It’s all decided for us
This world has only one sweet moment set aside for us

However, the Iceland Health Symposia’s approach is not that pessimistic and does not merely target longevity but also highlights the importance of being fit and healthy throughout the course of our lives:

One of modern society’s greatest achievements is the dramatic rise in the average global life expectancy. A baby born in the early 1900’s could not expect to live much beyond 50 years old, but people in many countries now live well into their 80’s and 90’s. As a consequence of this rapid change in our society, we have seen a major shift in the leading causes of death, with a corresponding increase in chronic diseases such as cancer, obesity, diabetes, and Alzheimer’s disease.

However, most of us not only want to have a long lifespan but also a long healthspan; to be fit and healthy throughout the course of our lives. As we move into this unprecedented era of human history, a question arises: how far can the human healthspan be extended, and what are the most effective ways to achieve longevity?

In September 2017, the Icelandic Health Symposium is bringing together some of the world’s best experts in health and longevity to help you discover:

What science has to say about the importance of lifestyle on our health and lifespan.

The extent to which our genes control our fate.

How to optimize our physical performance for longevity.

Lastly, but maybe even more importantly, you will learn how our species can achieve longevity in a way that harmonizes with nature, so both humans and our planet can have a long, sustainable future.

What better place to learn about the best ways to optimize your own health and longevity than Iceland? Home to some of the strongest and healthiest humans on the planet!

Who Wants To Live Forever – Host and Speakers

Tommy Wood

Dr. Tommy Wood will be hosting the conference.

Dr. Wood is a research scientist and Chief Medical Officer of Nourish Balance Thrive, an online-based company using advanced biochemical testing to optimize performance in athletes.Tommy has a bachelor’s degree in natural sciences from the University of Cambridge, a medical degree from the University of Oxford, and a PhD in physiology and neuroscience from the University of Oslo.

Alongside his career in medicine and research, Tommy has published and spoken on multiple topics surrounding functional and holistic approaches to health, including examining the root causes of disease (such as multiple sclerosis and insulin resistance) using engineering techniques.

He holds positions as the Chief Scientific Officer, and President-elect of Physicians for Ancestral Health is a Director of the British Society of Lifestyle Medicine, and a member of the Lifestyle Medicine Global Alliance advisory board

Ben Greenfield 

Ben Greenfield is the author of the New York Times Bestseller “Beyond Training“. His balanced approach to fitness, nutrition, and health comes from his extensive experience in the fitness and wellness industry as one of the country’s leading personal trainers and wellness consultants. In 2008, Ben was nominated by the NSCA as America’s top personal trainer, and in 2013 and 2014, Ben was voted as one of the top 100 most influential individuals in health and fitness.

He is currently the founder and owner of Greenfield Fitness Systems, a company that develops innovative and cutting-edge fitness and nutrition services and solutions to help people reach their physical and mental performance goals, whether that be to defy aging and achieve longevity, cross the finish line of an Ironman triathlon, or simply shed a few pounds.

Bryan Walsh

Dr. Bryan Walsh has been studying human physiology and nutrition for over 25 years and has been educating others in health for 20 of those years. When he isn’t teaching, he spends his time pouring over the latest research and synthesizing his findings into practical information for health practitioners to use with their clients. He has lectured to members of the healthcare industry around the world and consistently receives positive feedback in his seminars and courses.

Dr. Walsh is best known for his expertise in biochemistry and human physiology and his unparalleled ability to educate on these topics. As such, he has been sought out to consult with multiple companies, academic institutions, and wellness organizations.

Dr. Walsh is a Scientific Advisor at Lifetime Fitness, where he designs laboratory panels and interpretation methods as well as provides ongoing education for the professional staff. He is a licensed, board-certified Naturopathic Doctor and has been seeing patients throughout the U.S. for the past decade.

Diana Rodgers

Diana Rodgers, RD, LDN, NTP is a “real food” nutritionist and writer living on a working organic farm in Carlisle, Massachusetts. She runs a clinical nutrition practice, has written two books, hosts the Sustainable Dish Podcast, and speaks internationally about human nutrition, sustainability, animal welfare and social justice. Her work has been featured in The Los Angeles Times, The Boston Globe, Outside Magazine, Edible Boston, and Mother Earth News.

Dominic D’Agostino

Dr. Dominic D’Agostino is an Associate Professor in the Department of Molecular Pharmacology and Physiology at the University of South Florida Morsani College of Medicine. He is also a Visiting Senior Research Scientist at the Institute for Human and Machine Cognition (IHMC). His laboratory develops and tests metabolic-based strategies for targeting CNS oxygen toxicity (seizures), epilepsy, neurodegenerative diseases, brain cancer and metastatic cancer. To investigate the mechanism of these pathologies, he uses a variety of in vivo and

His laboratory develops and tests metabolic-based strategies for targeting CNS oxygen toxicity (seizures), epilepsy, neurodegenerative diseases, brain cancer and metastatic cancer. To investigate the mechanism of these pathologies he uses a variety of in vivo and in-vitro techniques, including radio-telemetry (EEG, EMG), electrophysiology, fluorescence microscopy, confocal microscopy, atomic force microscopy (AFM), biochemical assays and in vivo bioluminescence imaging.  They have adopted many of these techniques for use inside hyperbaric chambers, which allows them to manipulate oxygen concentrations (from hypoxia to hyperbaric oxygen).

Dr. Agostino’ current project is to identify cellular mechanisms of seizures from CNS oxygen toxicity and to develop mitigation strategies against it. His efforts have focused specifically on measuring brain EEG, neuronal excitability, reactive oxygen species (ROS) production and biomarkers of oxidative stress.

The main focus of his lab over the last ten years has been understanding the anticonvulsant and neuroprotective mechanism of the ketogenic diet and ketone metabolite supplementation. The shift in brain metabolism (from glucose to ketones) reduces neuronal hyperexcitability, oxidative stress and enhances brain metabolism. This approach can be used to treat a wide variety of pathologies linked pathophysiologically to metabolic dysregulation, including cancer.  Other areas of interest include researching drugs that cancer-specific metabolic.  His research is supported by the Office of Naval Research (ONR), Department of Defense (DoD), private organizations and foundations.

Doug McGuff

Doug McGuff, MD became interested in exercise at an early age when he first read Arthur Jones’ Nautilus Training Bulletin No. 2. His interest in exercise and biology led him into a career in medicine.

In 1989, he graduated from the University of Texas Medical School at San Antonio and went on to train in Emergency Medicine at the University of Arkansas for Medical Sciences at Little Rock where he served as Chief Resident. From there, Dr. McGuff served as Faculty in the Wright State University Emergency Medicine Residency and was a staff Emergency Physician at Wright-Patterson AFB Hospital.

In 1995, Dr. McGuff moved to Seneca, South Carolina where he joined Blue Ridge Emergency Physicians with whom he continues to practice full-time emergency medicine.

Throughout his career, Dr. McGuff maintained his interest in high-intensity exercise. Doug realized a lifelong dream when he opened Ultimate Exercise in November 1997, where he and his instructors continue to explore the limits of exercise through their personal training of clients.

In addition to his work at Ultimate Exercise, Dr. McGuff is a full-time practicing emergency physician who lives in Seneca, South Carolina with his wife of 30 years, Wendy, and their children Eric and Madeline.

Rangan Chatterjee

Dr.Chatterjee, 38, is the star of the new BBC One series Doctor in The House, which sees the GP live with three different families in their homes for a month at a time. He scrutinizes them at work, at play, shopping for food and cooking, eating and sleeping.

After qualifying from Edinburgh University Medical School in 2001, Dr. Chatterjee spent his first six years in hospital medicine. He completed his internal medicine examinations gaining Membership of the Royal College of Physicians.

However, He soon realized that his passion was in connecting with people and building relationships, so he made the decision to move to General Practice. He didn’t want to spend his whole career seeing problems in one single specialty. To him, the whole body is connected, and so it was a natural decision for him to move to General Practice.

Within a few years, it became clear to him that he was only really helping about 20% of the patients that were coming in to see him. So he began searching for solutions.

He soon became aware of where the gaps in his training were. For acute problems such as trauma, infections or catastrophic events like heart attacks, the medical training from Edinburgh University Medical School was superb.

However, for the majority of problems seen on a day to day basis – headaches, joint pain, gut problems, indigestion, weight gain, stress, diabetes and skin problems – He realized that the training was lacking in certain areas.

There was a key turning point Dr. Chatterjee‘s life when his son was six months old. He nearly died from a preventable vitamin deficiency. Modern medicine saved his life but taught him nothing in terms of how to prevent the long-term complications from his condition.

Dr. Chatterjee immersed himself in nutritional science and came across new research that was not being utilized in conventional medical care. In his mind doctors are practicing a type of medicine suitable for acute care but not as relevant for the new epidemic of chronic lifestyle-driven conditions.

Since then, Dr. Chatterjee has studied Movement Science, Stress Reduction, Ancestral Health, Nutrition and Functional Medicine. He has also completed a BSc Honours Degree in Immunology. This has proven invaluable in navigating the exciting new field of mucosal health and the gut microbiome.

Dr. Chatterjee currently works as an NHS GP in Oldham where he looks after a deprived and socially isolated patient population. He also works privately one day per week where he sees patients for 60–90 minutes so that he can delve deeper into what is causing their problem. When he sees patients today, he uses a hybrid approach, integrating all of his experience and research from these different areas. He also draws from his personal experience both as a father and caring for his own father who was ill for 15 years.

Satchidananda Panda

Dr. Panda is a Professor at the Salk Institute. He has authored nearly 100 scientific and popular articles on the topic of circadian rhythm in health and disease.

His discoveries are among the top ten breakthroughs of the year by the Science magazine, and he is considered as one of the top 50 influential scientists in the book “Brain Trust”.

Research in Dr. Panda’s lab has shown daily light exposure pattern, and a daily eating-fasting cycle can have a profound impact on the prevention and prognosis of diseases of aging.

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19 Important Causes of Shortness of Breath – Dyspnea Explained

Estimated reading time: 16 minutes

Shortness of breath, also known as dyspnea is a symptom that describes a sense of breathing discomfort or difficulty in breathing. It is often expressed as feeling out of breath or suffering from breathlessness.

It is estimated that up to 7-8 percent of patients presenting to emergency rooms complain of dyspnea (1). In half of these cases, it is the primary reason for their visit.

The American Thoracic Society (ATS) defines dyspnea as “a term used to characterize a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity. The experience derives from interactions among multiple physiological, psychological, social, and environmental factors, and may induce secondary physiological and behavioral responses” (1)

Although such a broad and complex definition is of little use in individual cases, it reflects the complexity of the issue and the multiplicity of factors that may be involved when a patient complains of dyspnea. These factors may vary from normal physiological responses to an underlying heart or lung disorder or may reflect a psychological disorder such as anxiety. Furthermore, dyspnea is frequently influenced by environmental factors such as air quality, temperature, and altitude.

Contrary to many other medical symptoms, shortness of breath is an entirely normal phenomenon in particular situations, such as during heavy exercise. Hence, it may be challenging for the individual and the clinician to determine if dyspnea is due to an underlying disease or just merely reflects a healthy response to physical effort. Obviously, an inactive person is more likely to experience shortness of breath than someone who is in good physical shape.

Normally we are unaware of the act of breathing at rest, and although we may become conscious of breathing during mild to moderate exercise, no discomfort is experienced. However, during strenuous exercise, we may become unpleasantly aware of our breathing, but we will feel reasonably assured that the sensation will be transitory and is appropriate to the level of exercise.

The words used by patients describing dyspnea may provide insight into the underlying cause. Examples of verbal expressions used are: “cannot get enough air“, “air does not go all the way down“, “smothering feeling in the chest“, “tightness in the chest“, “fatigue in the chest“, and a “choking sensation“.

The subjectivity of dyspnea is one of the main challenges facing the clinician whose task is to determine the diagnosis and assess the severity of the underlying condition

The causes of dyspnea may fall into three broad categories; respiratory system dyspnea, cardiovascular system dyspnea, and dyspnea due to other causes.

Different Types of Dyspnea

Dyspnea is considered acute when it develops suddenly (over hours to days) and chronic when it is present during longer periods (weeks or months).

Most often patients complain of dyspnea on physical exertion. Sudden and unexpected dyspnea at rest may indicate a serious underlying medical disorder or may be due to anxiety.

Intermittent dyspnea associated with cold air or animal dander may suggest asthma. Work-related dyspnea may indicate occupational asthma. Dyspnea following upper respiratory tract infections may indicate asthma or chronic obstructive pulmonary disease (COPD).

Dyspnea when lying down, usually in the supine position is called orthopnea. The patient may use multiple pillows or choose to sleep in the sitting position to feel better. The situation is typical of heart failure

Nocturnal episodes of dyspnea (paroxysmal nocturnal dyspnea) may also be a sign of heart failure. The patient experiences sudden attacks of shortness of breath, which most often occur at night, and awakens him/her from sleep.

Trepopnea describes an unusual situation in which the patient experiences shortness of breath while lying on the left or right side. Platypnea is dyspnea that only occurs in the upright position.

Respiratory System Dyspnea

1. Asthma

Asthma is the most common reason for presenting to the emergency room with shortness of breath (2). It is a disease that affects about 5% of the population.

Asthma is a condition in which the airways narrow and swell and produce extra mucus. This can cause shortness of breath, wheezing, tightness in the chest, and a nonproductive cough.

Some patients with asthma have infrequent attacks or have symptoms during certain conditions, such as when exercising, while others have more frequent or chronic symptoms.

Allergy-induced asthma is triggered by airborne substances such as pollen, spores, dust mites and pet dander. Other allergic symptoms such as watery eyes and runny nose are common.

Exercise-induced asthma is typically provoked by exercise and often gets worse when the air is cold and dry.

Occupational asthma is usually triggered by workplace irritants such as chemical fumes or dust.

2. Chronic Obstructive Pulmonary Disease (COPD)

Chronic obstructive pulmonary disease, or COPD, refers to a group of diseases that cause airflow blockage leading to shortness of breath, cough, mucus (sputum) production and wheezing. It includes emphysema, chronic bronchitis, and in some cases asthma.

Tobacco smoke is the leading cause of the development and progression of COPD in the United States (3). Genetic factors, exposure to air pollutants, and respiratory infections also play a role.

COPD was the third leading cause of death in the United States in 2014 (4).

Emphysema and chronic bronchitis are the two most common conditions that contribute to COPD.

Chronic bronchitis is inflammation of the lining of the bronchial tubes leading to shortness of breath, a daily cough and mucus production.

Emphysema is a condition in which the alveoli (air sacs) at the end of the smallest air passages of the lungs are destroyed. Hence, the exchange of oxygen and carbon dioxide between the blood and the lungs becomes impaired. As the air gets trapped in the alveoli, the lungs become hyperinflated.

Tobacco smoke is the leading cause of the development and progression of chronic obstructive pulmonary disease (COPD) in the United States

3. Interstitial Lung Disease (ILD)

The term interstitial lung disease (ILD) refers to a broad category of lung diseases rather than a distinct disease entity. It includes a variety of illnesses with different underlying causes. These disorders are grouped together because of similarities in their clinical presentations, radiographic appearance, and physiologic features (5).

The abnormalities that characterize ILD involve the lung interstitium (the area between the capillaries and the alveolar space)  to a greater extent than the alveolar spaces or airways. The interstitium supports the delicate relation between the alveoli and capillaries, allowing an efficient gas exchange.

The lungs may be initially injured by external exposure (e.g., asbestos, drugs, moldy hay), an underlying autoimmune disease (e.g., rheumatoid arthritis) or some unknown agent (idiopathic pulmonary fibrosis).

The resulting inflammatory response triggers a repair process in the lungs. If the exposure persists or if the repair process is incomplete, the lungs may be permanently damaged. Increased interstitial tissue typically replaces the normal capillaries, alveoli, and normal interstitium.

Lung function may become severely reduced in ILD. Gas exchange is impaired, and the work of breathing is increased because of decreased lung compliance.

Shortness of breath and a nonproductive cough are the most common reasons patients seek medical attention.

Examples of ILD’s are hypersensitivity pneumonitis, sarcoidosis, idiopathic pulmonary fibrosis, and cryptogenic organizing pneumonia (COP) which is the revised nomenclature for bronchiolitis obliterans organizing pneumonia (BOOP).

Therapy depends on the underlying disease and may consist of immunosuppressive drugs and avoidance of disease-inducing exposures.

4. Pulmonary Embolism

Pulmonary embolism is a blockage in one or both of the pulmonary arteries within the lungs. It is caused by blood clots that travel from the lower extremities, through the right heart chambers, and lodge in the lungs (6).

In most cases, a blood clot in the deep veins of the leg, called deep vein thrombosis (DVT), is the underlying cause of pulmonary embolism. Painful swelling of one leg, ankle or feet should raise the suspicion of DVT.

There are several risk factors for DVT. Among them are inherited disorders of blood clotting, prolonged bed rest, injury or surgery, pregnancy, birth control pills, smoking, and some forms of cancer.

Sitting for extended periods of time such as during long flights may also increase the risk of DVT because the leg muscles are not contracting. The leg muscles play a significant role in pumping the blood through the veins. The most effective preventive measure is to contract the leg muscles, either while sitting or by walking when possible (7).

The most common symptoms of pulmonary embolism include shortness of breath, cough, and sometimes chest pain that gets worse when breathing (pleuritic pain)(8). Signs of DVT in one or both legs may be found.

5. Pneumothorax

A pneumothorax is when air builds up in the pleural sac, between the outside of the lung and the inside the chest wall (9). The air can come from the lung or from outside the body if there is a chest injury. A large pneumothorax may compress the lung causing it to collapse.

Although pneumothorax caused by leaks of air from the lungs is more common in people with a lung condition, it can occur in individuals who are otherwise completely healthy (spontaneous pneumothorax).

Spontaneous pneumothorax is far more common in men than women. It often occurs in people between 20 and 40 years old, often in tall individuals and is commonly associated with underweight.

Patients with spontaneous pneumothorax present with sudden onset of chest pain that gets worse by breathing in (pleuritic pain)(8). The pain is often associated with shortness of breath. A routine chest radiograph usually confirms the diagnosis.

6. Pulmonary Hypertension

Pulmonary hypertension is a disease caused by elevated pressure (hypertension) in the pulmonary arteries (10).

Pulmonary hypertension is a rare condition that can affect people of all ages. However, it is more common in people who have an underlying heart or lung condition.

The walls of the pulmonary arteries may become thickened and stiff, and can’t expand as well to allow blood through. The reduced blood flow makes it harder for the right side of the heart to pump blood through the arteries. Subsequently, right-sided heart failure may develop.

The main symptoms of pulmonary hypertension are shortness of breath, tiredness, dizziness, palpitations (11) and leg edema (7).

Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease characterized by elevated pulmonary artery pressure with no apparent cause (12). IPAH is also termed precapillary pulmonary hypertension and was previously termed primary pulmonary hypertension. Untreated IPAH may lead to right-sided heart failure.

7. Pneumonia

Patients with pneumonia often experience shortness of breath. In patients over age 65, it is the primary symptom in the majority of cases (13).

Patients with pneumonia also typically have fever and a productive cough. Some may experience chest pain that gets worse on inspiration (pleuritic pain)(8).

8. Lung cancer

Many patients with lung cancer experience shortness of breath. It may be due to the tumor itself or to another underlying lung- or heart disease.

Other symptoms associated with lung cancer are coughing, chest pain, and coughing up blood (hemoptysis).

9. Noncardiogenic Pulmonary Edema/Adult Respiratory Distress Syndrome (ARDS)

ARDS can complicate a broad range of conditions such as sepsis, shock, trauma, and toxic inhalations. It is characterized by rapidly progressive dyspnea, hypoxia and bilateral infiltrates on chest radiograph.

High altitude pulmonary edema (HAPE) is a form of noncardiogenic pulmonary edema that typically occurs in people who have ascended rapidly to elevations over 2500 meters (8000 feet).

The main symptoms are a nonproductive cough, shortness of breath on exertion, and fatigue, often occurring two to four days after ascending to a high altitude. It may progress quickly to dyspnea at rest.

 

High altitude pulmonary edema (HAPE) is a form of noncardiogenic pulmonary edema that typically occurs in people who have ascended rapidly to elevations over 2500 meters (8000 feet)

10. COVID-19

COVID-19 is a disease caused by an infection with a recently discovered type of coronavirus. This virus and disease were unknown before the outbreak began in Wuhan, China, in December 2019.

Symptoms of COVID-19 may appear two to 14 days after exposure. According to the WHO, the most common symptoms are fever, tiredness and a dry cough. Some patients may also have a runny nose, sore throat, nasal congestion and aches and pains or diarrhoea. Some report losing their sense of taste and/or smell.

The severity of COVID-19 symptoms can range from very mild to severe. Some people have no symptoms. People who are older or have existing chronic medical conditions, such as heart or lung disease or diabetes, may be at higher risk of serious illness.

Shortness of breath is a common and sometimes serious manifestation of Covid-19, and it can occur on its own, without a cough.

When it comes to COVID-19, shortness of breath is thought to be due to the development of pneumonia, an inflammation of the lungs caused by the coronary virus.

Cardiovascular System Dyspnea

11. Acute Coronary Syndrome (ACS)

The term acute coronary syndrome covers a range of conditions associated with a sudden reduction in blood flow to the heart muscle. It includes conditions such as ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) (14). The underlying mechanism usually involves the rupture of an atherosclerotic plaque in a coronary artery with superimposed blood clotting (thrombosis), thereby blocking blood supply (15).

ACS and acute heart attack are one and the same and should always be treated as an emergency.

Patients with ACS typically experience pressure, fullness or tightness in the chest (8). Sometimes there is searing pain that may radiate to the back, neck, jaw, shoulders and arms, particularly the left arm.

Many patients complain of shortness of breath, and in some cases, dyspnea is the sole complaint.

12. Angina Pectoris

The term angina pectoris or angina is used to describe chest pain or discomfort, often felt like a pressure or a squeezing sensation in the chest (16). The pain may radiate to the shoulders, arms, neck, jaw or the back region between the shoulder blades. Often, the patient also experiences shortness of breath and sometimes it is the only symptom. In these

Often, the patient also experiences shortness of breath and sometimes it is the only symptom. In these cases, the dyspnea is defined as an anginal equivalent.

Angina pectoris is not a disease. It is a symptom, usually caused by inadequate blood flow in a coronary artery resulting in insufficient supply of oxygen-rich blood to an area of the heart muscle. Hence, in most cases, angina reflects underlying coronary artery disease (17).

Typically, a patient with angina will experience no symptoms at rest. However, during exercise, the oxygen demands of the heart muscle will increase. If blood supply in a coronary artery is limited, usually because of an atherosclerotic plaque, angina will occur. If the patient stops exercising, oxygen supply will again meet demands, and angina will resolve.

13. Heart Failure

Heart failure occurs when the heart muscle is weakened and cannot pump enough blood to meet the body’s needs for blood and oxygen. In some cases, the pumping capacity of the heart muscle is preserved but left ventricle is stiff with decreased compliance and impaired relaxation, which leads to increased filling pressure in the left ventricle.

Heart failure is caused by an underlying heart disease that has caused damage to the heart muscle and/or an increased stiffness of the left ventricle. Coronary heart disease, hypertension, valvular disorders and dilated cardiomyopathy are the most common causes of heart failure.

Heart failure frequently presents with shortness of breath on exertion, orthopnea, and paroxysmal nocturnal dyspnea.

Heart failure affects between 1–2% of the general United States population and occurs in 10% of those over 65 years old (18). 

Chronic heart failure is a common cause of dyspnea during daily activities.

Acute heart failure or acute worsening of a chronic heart failure may cause fluid to accumulate in the lungs (pulmonary edema). Pulmonary edema is a common cause of dyspnea in the emergency department.

Patients with chronic heart failure often have fatigue, diminished exercise tolerance, and fluid retention.

14. Valvular Heart Disease

Valvular heart disease may cause shortness of breath. Such dyspnea is particularly common among the elderly.

The most common valvular diseases causing dyspnea are aortic valve stenosis and mitral insufficiency (19).

Typical symptoms of aortic valve stenosis include diminished physical performance, episodes of collapse, syncope, and dizziness, and, sometimes, chest pain resembling angina pectoris.

Auscultation usually points to the diagnosis because a rough systolic heart murmur can be heard over the aortic valve.

Echocardiography is the definitive diagnostic study.

15. Cardiac Arrhythmia

Irregular or abnormal heart rhythm may cause dyspnea (10). Examples are atrial fibrillation and atrial flutter (20), ventricular tachycardia, and second and third-degree heart block.

These arrhythmias may often be associated with underlying cardiovascular diseases such as coronary artery disease, cardiomyopathy or heart failure.

Dyspnea Due to Other Causes

16. Anemia

Anemia that develops gradually often presents with exertional dyspnea, fatigue, weakness, and palpitations (21).

17. Obesity

Obesity may interfere with the normal expansion of the lungs causing dyspnea and hypoxia. This applies in particular if there is massive abdominal girth.

Based on data from the Third National Health and Nutrition Examination Survey, obese participants were 2.66 times more likely to experience dyspnea when walking up a hill compared with matched non-obese participants (22).

18. Hyperventilation and Anxiety

Patients with anxiety and hyperventilation commonly experience shortness of breath and breathing difficulties.

Hyperventilation from anxiety is a diagnosis of exclusion in the emergency department after organic causes of dyspnea have been excluded (23).

19. Deconditioning

Cardiovascular fitness is determined by the ability of the heart to increase maximal cardiac output and by the ability of the peripheral muscles to utilize energy efficiently for aerobic metabolism (24).

Fitter individuals experience less dyspnea for any given workload than sedentary people.

Deconditioning is defined as the multiple, potentially reversible changes in body systems brought about by physical inactivity and disuse. Such changes often have significant functional and clinical consequences.

Deconditioning commonly occurs in two situations: (1) a sedentary lifestyle, which is common in older people even in the absence of significant disease or disability and may result in a slow, chronic decline in physical fitness; and (2) bed or chair rest during an acute illness, which can lead to disastrously rapid physical decline (25).

Due to deconditioning, sedentary people may experience shortness of breath with seemingly trivial tasks.

In a study of obese adolescents with or without a diagnosis of asthma, breathlessness was primarily due to cardiopulmonary deconditioning (26).

How to Determine the Cause of Dyspnea

History and Physical Examination

History is of particular importance when determining the cause of dyspnea. The onset, character, duration, periodicity and severity of the symptoms are all important factors.

Physical examination may also provide important clues. Tachycardia (rapid pulse) may accompany anemia, heart failure, and pulmonary embolism. Distention of the jugular veins and peripheral edema may be consistent with heart failure. Cardiac murmurs may suggest underlying valvular disorders. Decreased breath sounds and wheezing may indicate COPD.

Diagnostic Studies

Initial testing should include pulse oximetry, complete blood count, basic metabolic panel, chest radiography, electrocardiography (ECG), and commonly, spirometry (27).

A chest radiograph is important in evaluating patients with dyspnea. It may show signs of heart failure, pneumonia, interstitial lung disease or lung tumor.

However, a negative chest radiograph does not rule out lung disease. For example, patients with asthma and pulmonary embolism may have normal radiographic findings.

An ECG may reveal arrhythmias such as atrial fibrillation (28). It may show sign of coronary artery disease and prior myocardial infarction may be discovered.

Spirometry is helpful for detecting airflow obstruction. Hence it may help diagnose asthma, COPD, and interstitial lung disease.

Brain natriuretic peptide (BNP) is a cardiac neurohormone secreted by the myocardium (29). BNP and its prohormone, N-terminal pro-BNP can be measured in blood.

In patients with dyspnea, plasma N-terminal pro-BNP concentrations are increased in left ventricular dysfunction and heart failure but not in lung disease (30) Hence, BNP and N-terminal pro-BNP levels can be used to distinguish between respiratory and cardiovascular causes of dyspnea.

D-dimer is a marker of fibrin degradation in the blood. Plasma levels of d-dimer are directly related to the severity of pulmonary emboli. A negative test can contribute to excluding pulmonary embolism in patients with low pretest probability (31).

Several more advanced studies such as echocardiography, computed tomography (CT scan), ventilation-perfusion scanning, and stress testing may provide additional information.

The Bottom Line

Shortness of breath (dyspnea) is a common symptom associated with multiple disease conditions, some of which are of serious nature.

Many cases of dyspnea are associated with diseases of the heart and lungs. Anemia, anxiety disorders, deconditioning, and obesity may also cause dyspnea.

Asthma, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), pulmonary hypertension, coronary heart disease, valvular disorders, and heart failure are examples of diseases that may cause chronic dyspnea.

Acute dyspnea may be due to an acute asthma attack, acute worsening of COPD or heart failure, pneumothorax, pulmonary embolism, COVID-19, acute coronary syndrome, and arrhythmias such as atrial fibrillation. Hence, acute dyspnea should be treated as a medical emergency.



Artificially Sweetened Beverages and the Risk of Stroke and Dementia

Estimated reading time: 5 minutes

I’m often asked which is worse for health, sugar- or artificially sweetened beverages. My most common response is to recommend skipping both and choose water.

In the era of fructose phobia and the apparent association between high fructose consumption and the risk of metabolic syndrome and diabetes, many tend to prefer artificially sweetened beverages (1,2).

However, recently published scientific evidence suggests that this may be a wrong approach and that artificially sweetened soft drinks may indeed cause more harm than those containing sugar.


The main advantage of artificially sweetened beverages is typically considered to be the lack of calories compared with sugars such as sucrose or fructose.

Five “non-nutritive” artificial, sweeteners used in soft drink production have FDA approval; saccharin, acesulfame, aspartame, neotame, and sucralose. Stevia, a natural extract from the plant Stevia rebaudiana, was approved by the FDA in 2008. These synthetic substances are hundreds to thousands of times more potent than sucrose and evoke an intense sensation of sweetness in trace amounts (3).

Artificially Sweetened Beverages and the Risk of Stroke and Dementia

A recently published paper by Matthew P. Pase PhD and coworkers from Boston University School of Medicine suggests that high consumption of artificially sweetened soft drinks may be associated with increased risk of both stroke and dementia (4). In fact, it is the first study to suggest that artificially sweetened beverages, but not sugar-sweetened beverages, may be associated with risk of stroke and dementia, including Alzheimer’s disease.

Cumulative consumption of artificially sweetened beverages and event-free survival of stroke (A) and dementia (B). Green, red, and blue lines denote intake of 0/wk, 6/wk, and 1/d, respectively. DOI: https://doi.org/10.1161/STROKEAHA.116.016027

The investigators studied 2.888 participants from the Framingham Heart Study Offspring Cohort between 1991 and 2001. The mean age was 62 years, 55% were women. Beverage intake was quantified using food-frequency questionnaires. During the ten year follow-up period, 82 cases of incident stroke were observed and 81 cases of incident dementia, 63 of which were consistent with Alzheimer’s disease.

After adjustments for age, sex, education, caloric intake, diet quality, physical activity, and smoking, higher recent and higher cumulative intake of artificially sweetened soft drinks were associated with an increased risk of ischemic stroke, all-cause dementia, and Alzheimer’s disease dementia.

Those who consumed artificially sweetened soft drinks daily were approximately three times more likely to develop stroke or dementia compared to those who consumed no artificially sweetened beverages. Sugar-sweetened beverages were not associated with stroke or dementia.

The Bottom Line

The Nurses Health Study and Health Professionals Follow-Up Study found that greater consumption of both sugar-sweetened and low-calorie sodas was associated with a significantly higher risk of stroke (5).

A 2011 statement from the American Heart Association and American Diabetes Association concluded that when used judiciously, non-nutritive sweeteners (including very low-calorie sweeteners, artificial sweeteners, and non-caloric sweeteners) might help with weight loss or control, and could also have beneficial metabolic effects (6).

So clearly, the discussion about artificially and sugar-sweetened beverages has typically focused on the energy issue. And of course, the soft drink producers highlight the lack of calories as the main benefit of artificially sweetened beverages.

According to Coca-Cola; Diet Coke is the most popular calorie-free soft drink in America. It’s the original sparkling beverage for those who want great flavor without the calories – a drink for those with great taste.

According to Pepsi; Pepsi Zero Sugar or Pepsi Max is the only soda with zero calories and maximum Pepsi taste.

Interestingly, the study by Pase and coworkers also found that diabetes mellitus, which is a known risk factor for dementia, was more prevalent in those who regularly consumed artificially sweetened soft drinks.

On the other hand, it should be pointed out that this was an observational study and therefore can not determine whether there is a causal relationship between artificially sweetened soft drink intake and diabetes and stroke or dementia.

However, the fact that those who consumed artificially sweetened soft drinks daily, but not those who consumed sugar-sweetened beverages, were approximately three times more likely to develop stroke or dementia is intriguing.

About 25 percent of children and more than 41 percent of adults in the United States reported consuming foods and beverages containing low-calorie sweeteners such as aspartame, sucralose, and saccharin in a recent nationwide nutritional survey (7). Those numbers represent a 200 percent increase in the consumption of artificially sweetened beverages for children and a 54 percent jump for adults from 1999 to 2012.

These numbers highlight the potential implications of the hair-raising results presented by Pase and coworkers.

Unfortunately, in my opinion, the study has some methodological flaws. The limited number of events is clearly a problem. Furthermore, no adjustments were made for multiple statistical testing. Hence it can not be rule out that some of the findings are due to chance alone.

Another study by the same group, published online in Alzheimer’s and Dementia on March 5, shows a link between consumption of both sugar-sweetened and artificially sweetened beverages and reduction in brain volume in a middle-aged cohort (8). In the cross-sectional study, the sugary drinks, which included both soda and fruit juice, were also associated with worse episodic memory.

Apparently, the jury’s still out on the issue which is worse, sugar-sweetened or artificially sweetened. So, why not skip both and stick with water.




17 Important Causes of Chest Pain

Chest pain is a common symptom associated with a variety of underlying causes.

More than six million people visit hospital emergency departments in the United States each year because of chest pain (1).


The cause of chest pain may vary from life-threatening conditions to those that are relatively harmless.

Chest pain is most commonly caused by disorders of muscles, ligaments, tendons, and bones. Such pain is often called musculoskeletal pain and is usually harmless.

Digestive disorders are also a common cause of chest ache.

It is practical to classify the underlying conditions causing chest pain into;

  • cardiac (heart conditions)
  • pulmonary (lung conditions)
  • gastrointestinal (caused by digestive disorders)
  • musculoskeletal (disorders of muscles, ligaments, tendons, and bones)
  • psychiatric
  • other

Nowadays, all chest pain is regarded as suspected heart disease until proven otherwise.

Actually, most emergency departments have chest pain units, a fast-track service for patients with chest pain.

History Is a Key Factor

History and physical examination are of crucial importance when determining the cause of chest pain.

The character or quality of pain is essential. Sometimes, there may be only a vague discomfort. In other cases, the pain may be sharp, ripping or tearing, or just a feeling of pressure, fullness, or tightness in the chest.

The localization of the pain may also help determine its origin.

Pain in the middle of the chest may be caused by heart disease or digestive disorders. In contrast, right or left sided chest pain often originates from the ribs or muscles and tendons in the chest cage.

Chest pain may also radiate to other parts of the body. For example, pain due to coronary artery disease may radiate to the neck, jaw, and arms.

In addition, knowing the onset of pain is helpful. An abrupt onset may suggest pneumothorax and aortic dissection.

Chest ache that lasts only for a few seconds is unlikely to be caused by coronary artery disease. The same is true for pain that is consistent over weeks to months (2).

Furthermore, if and how the pain may be provoked is of importance.

For example, so-called pleuritic chest pain typically worsens with respiration. Such pain is often left or right sided.

Chest pain provoked by exertion is typical of angina pectoris (3).

Pain made worse by swallowing is likely of esophageal origin.

Chest ache associated with body position or specific movements is likely to originate from muscles and tendons. In addition, such pain is often well-localized and associated with tenderness on palpation (pushing on the spot).

Cardiac Causes – Heart Conditions Causing Chest Pain

1. Heart Attack/Acute Coronary Syndrome (ACS)/

Acute heart attack and acute coronary syndrome (ACS) are different terms used to describe the same phenomenon.

ACS covers a range of conditions associated with a sudden obstruction of blood flow in a coronary artery. Patients with ACS typically experience pressure, fullness, or tightness in the chest. Sometimes there is searing pain that may radiate to the back, neck, jaw, shoulders, and arms, particularly the left arm.

The pain usually lasts more than a few minutes.

If there is a complete blockage of a coronary artery, the pain may last for several hours. Moreover, it may be associated with shortness of breath, cold sweats, dizziness or weakness, nausea, and vomiting.

ACS should always be treated as an emergency.

2. Angina Pectoris

Angina pectoris is often described as a pressure or a squeezing sensation in the chest. The discomfort may radiate to the shoulders, arms, neck, jaw, or the back region between the shoulder blades.

Angina pectoris is not a disease. It is a symptom usually caused by inadequate blood flow in a coronary artery. Hence, in most cases, angina reflects underlying coronary artery disease (3).

Typically, a patient with angina will experience no symptoms at rest. However, during exercise, the oxygen demands of the heart muscle will increase. If blood supply in a coronary artery is limited, usually because of blockage in a coronary artery, angina will occur. If the patient stops exercising, the oxygen supply will again meet demands, and angina will resolve.

3. Aortic Dissection

Aortic dissection occurs when there is a tear in the inner layer of the aorta (the large blood vessel branching off the heart).

The tear causes the inner and middle layers of the wall of the aorta to become separated. This may cause the outer wall of the aorta to rupture, causing fatal bleeding.

Aortic dissection

Patients with acute aortic dissection usually present suddenly with severe, sharp pain in the chest. The pain sometimes radiates to the back (4).

Aortic dissection is relatively rare. It is a medical emergency and always needs immediate treatment.

4. Pericarditis

Pericarditis is an inflammation (swelling) of the pericardium. The pericardium is a thin membrane or sac surrounding the heart.

In most cases, a viral infection is responsible.

The primary symptom may be a sudden, sharp, and stabbing pain behind the sternum (breastbone). However, sometimes there may only be a dull ache.

The pain of pericarditis typically worsens when lying down or breathing in (pleuritic pain). Moreover, it may often get better when sitting up and leaning forward.

Pericarditis is usually not a serious condition and hospital admission is seldom required.

Symptoms usually resolve within a week. However, some patients experience recurring symptoms lasting longer than three months.

5. Stress Cardiomyopathy (Takotsubo)

Stress cardiomyopathy, also called the broken heart syndrome, apical ballooning syndrome, or takotsubo cardiomyopathy was first described in 1990 in Japan.

The symptoms of  stress cardiomyopathy mimic those of an acute heart attack. However, it is an entirely different disorder and is not caused by blocked coronary arteries.

Patients with stress cardiomyopathy experience sudden, intense chest pain.

An emotionally stressful event usually precipitates the pain, hence the term “broken heart syndrome.”

The stressful event could, for example, be the death of a loved one, breakup of a relationship, domestic abuse, devastating financial losses, or a natural disaster (5).

Stress cardiomyopathy is also characterized by a severely decreased contraction of a part of the heart muscle.

However, although the heart muscle’s function may be severely affected during the initial phase, recovery is usually complete.

Pulmonary Causes – Lung Conditions Causing Chest Pain

6. Pulmonary Embolism

Pulmonary embolism is a blockage in one or both of the arteries within the lungs. It is caused by blood clots that travel from the lower extremities, through the right heart chambers, and lodge in the lungs. Pulmonary embolism can be life-threatening (6).

In most cases, a blood clot in the leg’s deep veins, called deep vein thrombosis (DVT), is the underlying cause.

Sitting for extended periods, such as during long flights, may increase DVT risk (7).

Shortness of breath is the most common symptom. Cough is also relatively common and some patients have chest pain that gets worse when breathing (pleuritic pain).

A pneumothorax is when air builds up between the outside of the lung and the inside the chest wall. This may lead to a collapse of the lung.

7. Pneumothorax

A pneumothorax is when air builds up between the outside of the lung and the inside the chest wall (8). The air can come from the lung or from outside the body if there is a chest injury. A large pneumothorax may compress the lung, causing it to collapse.

Pneumothorax caused by leaks of air from the lungs usually occurs in people with a lung condition. However, it can also occur in people who are otherwise entirely healthy (spontaneous pneumothorax).

Spontaneous pneumothorax is far more common in men than in women. It often occurs in people between 20 and 40 years old  and is most common in tall individuals.

The pneumothorax pain is usually sudden in onset and gets worse by breathing in (pleuritic pain).

The treatment of pneumothorax depends on its size and whether it’s expanding.  A small pneumothorax may not need any treatment as it will heal on its own. However, a large pneumothorax will need to be drained using a syringe or a chest tube.

8. Pneumonia, Asthma, and Chronic Obstructive Lung Disease (COPD)

Pneumonia may cause chest pain. The pain often gets worse on inspiration (pleuritic pain). However, many patients with pneumonia don’t have chest pain.

Patients with pneumonia often have a fever and a productive cough as well.

Patients with asthma and chronic obstructive lung disease (COPD) typically suffer from shortness of breath. However, during worsening of these disorders, patients often describe chest tightness that may sometimes be interpreted as chest pain.

9. Pleuritis (Pleurisy)

Pleuritis or pleurisy is an inflammation (swelling) of the membranes (pleurae) covering the lungs (9)

The chief symptom associated with pleurisy is a sharp, stabbing pain in the chest. Patients often experience chest pain when breathing (pleuritic pain).

The most common underlying cause is a viral infection.

Treatment of pleuritis depends on the underlying cause. Paracetamol and NSAID’s such as ibuprofen may help relieve the pain.

10. Lung Cancer

Patients with lung cancer often complain of chest pain. The pain is usually located on the same side as the tumor.

Other symptoms include cough, hemoptysis (coughing blood), and shortness of breath.

Also, chest ache associated with lung cancer often gets worse with deep breathing, coughing, or laughing (10).

11. Pulmonary Hypertension

Pulmonary hypertension is a condition caused by elevated pressure (hypertension) in the pulmonary arteries (11).

Although shortness of breath is the main symptom of pulmonary hypertension, some patients may experience chest pain. The pain is usually most pronounced during exertion.

Gastrointestinal Causes – Digestive Disorders Causing Chest Pain

12. Gastroesophageal Reflux Disease (GERD)

Gastroesophageal reflux disease (GERD) is a common cause of chest discomfort (12).

GERD is a chronic digestive disease that occurs when stomach acid or, occasionally, stomach content flows back (reflux) into the esophagus. The reflux irritates and may damage the lining of the esophagus, causing the disease.

Most people can manage the symptoms of GERD with lifestyle changes and over-the-counter medications. But some patients may need prescription drugs, or even surgery, to reduce symptoms.

Most healthy people experience acid reflux and heartburn once in a while. However, when these symptoms occur at least twice each week or interfere with daily life, GERD should be suspected.

The chest pain associated with GERD is often described as squeezing or burning. It is usually located behind the sternum (substernal pain). Sometimes it radiates to the back, neck, jaw, or arms. It is usually relieved by antacids.

Most people can manage the symptoms of GERD with lifestyle changes and over-the-counter medications. Nevertheless, some patients may need prescription drugs, or even surgery, to reduce symptoms.

13. Esophagitis

The term esophagitis describes an inflammation or swelling of the esophagus.

Heartburn is the most common symptom of esophagitis. Other common symptoms include upper abdominal discomfort, nausea, bloating, and fullness.

Musculoskeletal Causes of Chest Pain

The term musculoskeletal is used to describe pain associated with muscles, ligaments, bones, and tendons.

14. Musculoskeletal Chest Pain

A large proportion of chest pain is caused by underlying conditions of muscles, ligaments, bones, and tendons.

This type of pain is usually referred to as musculoskeletal pain.

The chest wall contains a range of bony and soft tissue structures, including the spine. Hence, it may be difficult to pinpoint the exact source of pain in an individual patient.

Musculoskeletal conditions may cause both left and right-sided chest pain. Sometimes the pain gets worse when breathing.

The ache is often associated with body position or specific movements. Furthermore, it is usually well localized and associated with tenderness when pushing on the spot.

Psychiatric Causes of Chest Pain

15. Anxiety Chest Pain and Panic Disorder

Chest pain may be a symptom of anxiety (13).

Anxiety chest pain is often described as a sharp, stabbing sensation. The pain often starts suddenly and is usually not related to physical exertion.

Sometimes, however, there may be a less sharp, dull ache in the chest that is more persistent.

Panic disorder is an anxiety disorder characterized by recurrent unexpected panic attacks (14).

Panic attacks are sudden episodes of extreme fear or distress, often associated with chest pain and fast heartbeat. The patient may also experience palpitations (15), sweating, shortness of breath (16), and numbness.

Patients with panic attacks often suffer from constant fear about having further attacks. Thus, they ususllay try to avoid places or circumstances where attacks have occurred before.

It has been suggested that approximately one-quarter of patients seeking chest pain treatment have panic disorder (17). Notwithstanding, panic disorders often go unrecognized and untreated, leading to frequent return visits to emergency departments.

Fortunately, panic disorder is treatable, and quality of life can be improved by psychological methods and drug therapy (18,19).

Other Causes of Chest Pain

16. Chest Pain Related to Drug Abuse

Several illegal drugs can have adverse effects on the heart, ranging from abnormal heart rate to heart attacks.

Cocaine is an illegal drug most often associated with visits to hospital emergency departments in the United States.

Cocaine use has been related to both chest pain and heart attacks.

Chest pain may be the presenting symptom of herpes zoster (shingles). The diagnosis may be tricky because the pain usually precedes the rash.

17. Herpes Zoster

Herpes zoster (shingles) is an infection caused by the varicella-zoster virus, the same virus which causes chickenpox.

The chickenpox virus may remain dormant in the nervous system for years. In herpes zoster, it becomes activated again.

Herpes zoster is characterized by a red skin rash that can cause pain and burning. Typically it occurs as a stripe of blisters on one side of the body, often on the torso, neck, or face.

Most cases of herpes zoster clear up within two to three weeks. Approximately 1 in 3 people in the United States will have herpes zoster at some point in their life (22).

Chest pain may be the presenting symptom of herpes zoster. The diagnosis may be tricky because the pain usually precedes the rash.

The article was initially published in 2017.

It was revised, updated and republished January 17, 2021.




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