Category: Media

The Smart Watch: Telemetry For Humans?

GOOD nutrition, clean environments, accessibility to good healthcare and healthy lifestyles have increased human longevity. Nevertheless, the quest of increasing longevity is insatiable. As medical science pushes the boundaries of human lifespan, delving into the science of longevity can help us sieve through the reams of information and distil the essence of anti-ageing and cell preservation.

Cellular ageing

Cell ageing or cellular senescence is a physiological state with permanent cessation of the ability of the cell to replicate and accumulation of damaged DNA ( basic building blocks of genes), and this process is increased by ageing. This cellular senescence is marked by shortening of the protective terminal ends of the chromosomes which are called telomeres. Telomeres are like plastic caps at the ends of shoelaces, preventing them from being frayed and damaged. Shortening of the telomere is a sign of cellular senescence. In 1979, the first of the SIR (silent information regulator) proteins or sirtuins was reported. Over time more members of this protein group were found. In 1999, the publication of a study that reported that increased sirtuin activity could increase the lifespan of yeast cells by 70 per cent heralded a major breakthrough that accelerated the interest and research in sirtuins. Since then, there has been a growing body of evidence that the cell has a group of anti-ageing proteins, the sirtuins, that are essential for delaying cellular senescence and increasing the lifespan of organisms.

Anti-ageing proteins

Core to the science of anti-ageing is this group of proteins called sirtuins. In human cells, there are seven sirtuins (SIRT 1 to 7) with various roles within the cell. Three of these sirtuins (SIRT 3,4,5) control the generation of power for the needs of the cells and function in the mitochondria (power generator which produce the energy for the needs of the cell) with roles in cellular antioxidant balance and lipid metabolism. Another three sirtuins (SIRT 1, 6, 7) control the genetic framework in the cell and function in the cell nucleus (the central core of the genetic material in the cell) with roles in gene expression and DNA repair. There is one sirtuin (SIRT 2 mainly) which control the environmental processes within the cell and function in the cytoplasm (the liquid content within the cell). As an analogy, if the cell is a factory, the sirtuins are the executive management of the company directing and controlling all the aspects of the cell’s activities. They play important roles in maintaining the integrity of the cellular genetic structure, keeping the genetic material (chromatin) in a “wound up” protected state to reduce damage and in repairing damaged DNA.

Mechanisms of action

The main mechanisms of suppression of cellular senescence by sirtuin activity is via the actions of preventing telomere shortening or attrition, and promoting the repair of damaged DNA. Many proteins in the cells have a chemical tag called an acetyl group attached to it. One of the key ways in which sirtuins work is by the removal of the acetyl group from other molecules or proteins, thereby affecting the activity of the protein. This action has significant impact on the control centre of the cell, namely the activity of the genetic material or chromatin.

The basic building block of the genetic material, the DNA, is wrapped around groups of proteins called histones allowing the genetic material (chromatin) to be packed more compactly. When the histone protein has the acetyl group chemical tag , it causes the chromatin to be partially unwound and hence exposing the unwound DNA to be copied, thereby allowing the gene instruction to be passed to another cell or protein. As an analogy, it is as if a door to the office is opened and people are allowed to go into the office to copy instructions which are then passed to other offices. Once all the instructions are copied, the office door is closed. Hence, once the task is completed, the chromatin will not remain unwound as it will be more vulnerable to damage if it remains open.

Subsequently, the sirtuins can then remove the acetyl group from the histones which will then allow the chromatin to be closed by being “wound up” tightly, preventing DNA material from being copied and in effect silence the gene. Besides histones, sirtuins target other non-histone proteins such as proteins involved in copying genetic information and proteins that are involved in the repair of DNA. They are also known to regulate the production of the enzyme telomerase which is required for telomere elongation and maintenance of the integrity of the telomere. Most human cells have insufficient telomerase and hence there is progressive shortening of the telomere which is strongly indicative of progressive cellular ageing. Elongation of the chromosomal telomere is tantamount to reversing the biological clock.

Beneficial effects of sirtuin activity

Studies have shown that sirtuins have roles in the regulation of copying of gene information, modulation of energy production, prolongation of cell survival, reduction of DNA damage, reduction of cell damage and prolongation of longevity. Increased sirtuin activity in mammals has been associated with a delayed onset of age-related diseases and an increase in longevity. Sirtuins appear to be able to inhibit axonal (nerve fibre) degeneration, a process that often precedes the death of nerve cells as seen in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease.

It may also have protective effect on nerve cells, reducing processes that lead to the death o f nerve cells and the development of Alzheimer’s disease. Loss of sirtuin activity has been implicated in the development of cardiovascular and metabolic diseases including degeneration of arteries, acute damage to the heart muscle, thickening of the heart muscle, abnormal heart rhythms, high blood pressure, obesity, diabetes mellitus and abnormal lipid levels. While most of the studies have been done in animals, there is an increasing number of human studies.

There is presently an increasing body of evidence that shows increased sirtuin activity is indispensable for delaying cellular senescence and appears to protect the body against many age related diseases. In addition, studies support the role of sirtuins as anti-aging agents and potentially prolong longevity. Hence, lifestyle, dietary and pharmacological choices that increase sirtuin activity can potentially increase the anti-ageing effects and prolong longevity. These will be discussed in the next article where we will examine how we can make better decisions to increase our quality of life and lifespan.

Unravelling the holy grail of anti-ageing and longevity

GOOD nutrition, clean environments, accessibility to good healthcare and healthy lifestyles have increased human longevity. Nevertheless, the quest of increasing longevity is insatiable. As medical science pushes the boundaries of human lifespan, delving into the science of longevity can help us sieve through the reams of information and distil the essence of anti-ageing and cell preservation.

Cellular ageing

Cell ageing or cellular senescence is a physiological state with permanent cessation of the ability of the cell to replicate and accumulation of damaged DNA ( basic building blocks of genes), and this process is increased by ageing. This cellular senescence is marked by shortening of the protective terminal ends of the chromosomes which are called telomeres. Telomeres are like plastic caps at the ends of shoelaces, preventing them from being frayed and damaged. Shortening of the telomere is a sign of cellular senescence. In 1979, the first of the SIR (silent information regulator) proteins or sirtuins was reported. Over time more members of this protein group were found. In 1999, the publication of a study that reported that increased sirtuin activity could increase the lifespan of yeast cells by 70 per cent heralded a major breakthrough that accelerated the interest and research in sirtuins. Since then, there has been a growing body of evidence that the cell has a group of anti-ageing proteins, the sirtuins, that are essential for delaying cellular senescence and increasing the lifespan of organisms.

Anti-ageing proteins

Core to the science of anti-ageing is this group of proteins called sirtuins. In human cells, there are seven sirtuins (SIRT 1 to 7) with various roles within the cell. Three of these sirtuins (SIRT 3,4,5) control the generation of power for the needs of the cells and function in the mitochondria (power generator which produce the energy for the needs of the cell) with roles in cellular antioxidant balance and lipid metabolism. Another three sirtuins (SIRT 1, 6, 7) control the genetic framework in the cell and function in the cell nucleus (the central core of the genetic material in the cell) with roles in gene expression and DNA repair. There is one sirtuin (SIRT 2 mainly) which control the environmental processes within the cell and function in the cytoplasm (the liquid content within the cell). As an analogy, if the cell is a factory, the sirtuins are the executive management of the company directing and controlling all the aspects of the cell’s activities. They play important roles in maintaining the integrity of the cellular genetic structure, keeping the genetic material (chromatin) in a “wound up” protected state to reduce damage and in repairing damaged DNA.

Mechanisms of action

The main mechanisms of suppression of cellular senescence by sirtuin activity is via the actions of preventing telomere shortening or attrition, and promoting the repair of damaged DNA. Many proteins in the cells have a chemical tag called an acetyl group attached to it. One of the key ways in which sirtuins work is by the removal of the acetyl group from other molecules or proteins, thereby affecting the activity of the protein. This action has significant impact on the control centre of the cell, namely the activity of the genetic material or chromatin.

The basic building block of the genetic material, the DNA, is wrapped around groups of proteins called histones allowing the genetic material (chromatin) to be packed more compactly. When the histone protein has the acetyl group chemical tag , it causes the chromatin to be partially unwound and hence exposing the unwound DNA to be copied, thereby allowing the gene instruction to be passed to another cell or protein. As an analogy, it is as if a door to the office is opened and people are allowed to go into the office to copy instructions which are then passed to other offices. Once all the instructions are copied, the office door is closed. Hence, once the task is completed, the chromatin will not remain unwound as it will be more vulnerable to damage if it remains open.

Subsequently, the sirtuins can then remove the acetyl group from the histones which will then allow the chromatin to be closed by being “wound up” tightly, preventing DNA material from being copied and in effect silence the gene. Besides histones, sirtuins target other non-histone proteins such as proteins involved in copying genetic information and proteins that are involved in the repair of DNA. They are also known to regulate the production of the enzyme telomerase which is required for telomere elongation and maintenance of the integrity of the telomere. Most human cells have insufficient telomerase and hence there is progressive shortening of the telomere which is strongly indicative of progressive cellular ageing. Elongation of the chromosomal telomere is tantamount to reversing the biological clock.

Beneficial effects of sirtuin activity

Studies have shown that sirtuins have roles in the regulation of copying of gene information, modulation of energy production, prolongation of cell survival, reduction of DNA damage, reduction of cell damage and prolongation of longevity. Increased sirtuin activity in mammals has been associated with a delayed onset of age-related diseases and an increase in longevity. Sirtuins appear to be able to inhibit axonal (nerve fibre) degeneration, a process that often precedes the death of nerve cells as seen in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease.

It may also have protective effect on nerve cells, reducing processes that lead to the death o f nerve cells and the development of Alzheimer’s disease. Loss of sirtuin activity has been implicated in the development of cardiovascular and metabolic diseases including degeneration of arteries, acute damage to the heart muscle, thickening of the heart muscle, abnormal heart rhythms, high blood pressure, obesity, diabetes mellitus and abnormal lipid levels. While most of the studies have been done in animals, there is an increasing number of human studies.

There is presently an increasing body of evidence that shows increased sirtuin activity is indispensable for delaying cellular senescence and appears to protect the body against many age related diseases. In addition, studies support the role of sirtuins as anti-aging agents and potentially prolong longevity. Hence, lifestyle, dietary and pharmacological choices that increase sirtuin activity can potentially increase the anti-ageing effects and prolong longevity. These will be discussed in the next article where we will examine how we can make better decisions to increase our quality of life and lifespan.

Belly fat is the biggest enemy in fight against obesity

A combination of a healthy diet and exercise can get rid of the extra kilos and decrease the risk of developing diabetes

My patients have been complaining of weight loss or weight gain since the circuit breaker was initiated. Those who have lost weight were very concerned that they had an illness of sorts. Some of them had lost substantial weight – 5-8kg. We did the necessary and made sure there were no sinister causes. So, what had happened to my patients who lost substantial weight? Well, I figured out that they had change in lifestyle; there was a change in diet with eating and cooking more at home. Those who previously travelled extensively had stopped eating and drinking on planes, and had to give up entertaining or being entertained. All this resulted in a healthier diet; cooking at home involved healthier ingredients, produce and oils. The other big change is exercise.

With so much time on our hands and working from home, most of my patients ended up doing more exercise. Some started with walking, graduated to running and high intensity interval training. The gyms were closed and so quite a few ended up with cycling. There  was also a lot of online yoga, Pilates and aerobics being done. Underneath all these changes in lifestyle, there were also mental changes. There is loss with all that has happened – loss of liberty, loss of travel, loss of connection, loss of relationships, economic loss. And some of the losses would be only realised somewhere in the future. With such loss, a grief reaction was inevitable and there would be denial, anger, bargaining, sadness and finally acceptance. Some of my patients, without realising it, had slipped into depression or a milder form of it called dysthymia.

These were all characterised by weight loss, insomnia, loss of drive, loss of pleasure and libido with depressed mood. Some felt hopelessness with loss of focus and concentration as well. As we move into a lull phase of the pandemic in our nation, we still have to contend with the economic losses and unemployment ahead, with possibility of resurgence of the virus at any time. The prior losses, current bleakness and future potential losses have been instrumental in affecting our mental state. What about those who had gained weight? The majority had increased their intake for various reasons and had not matched it with exercise. One of the biggest drivers of ill health in today’s world is being overweight and obesity. We use body mass index (BMI) of 25 and above for overweight and 30 and above for obesity. For Asians, we actually found that we are worse off at those criteria and we use 23 and above for overweight and 27 and above for obesity.

Our local obesity rate is about 10 per cent of our population. Depot for fat cells The biggest enemy in our battle is the presence of visceral fat. Visceral fat is also known as “belly” fat and is different from fat on your thighs and buttocks. The visceral fat is actually deposited in the omentum – an apron that surrounds our intestines. The omentum is actually the transparent skin that gives the meat sausage its shape. It is also the biggest depot for fat cells. This fat is different because it generates cytokines; these are proteins that are generated by the immune system. You may have heard of the role of cytokines in desperately ill Covid-19 patients undergoing a “cytokine storm”. We know that these cytokines, including proteins named interleukins, tumour necrosis factor, adiponectin and leptin,  are powerful drivers of insulin resistance and inflammation and ultimately leading to an increased risk of diabetes, hypertension, heart disease, stroke and even cancer.

How does one know that he or she has visceral fat? A simple tape measure of the waist circumference around the navel and a measurement of 80cm and above for women or that of 90cm and above for men is indicative. So, how did we know all this? In 1986, there were more than 100,000 patients in Da Qing with prediabetes and they were subjected to diet, exercise and combination of both for six years. The outcome was that those who did nothing went on to develop diabetes, while those who went on a diet reduced their chance of diabetes by 31 per cent, those who exercised by 46 per cent and those who did both diet and exercise by 42 per cent. In the same year, a study of more than 40,000 nurses over the next eight years by Harvard showed that women with obesity, a high waist-to-hip ratio and a waist circumference of 92cm and above were more 11 times more likely to develop diabetes.

So, what do we have to do about visceral fat? We have to make sure our sugar levels do not spike as our insulin levels will also mirror such a spike to get rid of the sugar. The insulin works like a key and opens all the cell doors in your body so that the sugar load in your blood will move into cells to burn for energy. Avoid a sugar spike The main driver of visceral fat formation is actually the high insulin level. So in this case a sky high level of insulin is the “bad boy”. Hence, we have to eat carbohydrates that don’t give us a sugar spike.  These include healthier options such as cooked oatmeal as opposed to instant oatmeal, glass noodles, Japanese noodles like soba and udon and Italian pastas. The ones to avoid are white rice, white bread, potato and yellow noodles. Fruits are also high in sugar and these include pineapple, mango, melons, banana, grapes, lychee and longans. The idea then is to eat carbohydrates that turn slowly to sugar.

These are called Low Glycemic Index (GI) foods. Hence, the quality of the carbohydrates and the amount of the carbohydrates also matters. When you factor both quality and quantity of the carbohydrates you get something called Glycemic Load (GL). When you attach a glucose monitor onto your arm that measure your blood sugar levels every 15 minutes for a period of two weeks, we get nice graphs of your sugar peaks and troughs. When you annotate these beautiful graphs with the foods you eat, you get something called a Glycemic Response (GR). We have analysed patients with such graphs using machine learning tools software and found some interesting findings. We found that sometimes what you think is healthy may not be so. I used to eat oatmeal with blueberries every morning and thought that was extremely healthy. It turned out that it spiked my blood sugar sky high.

I have a patient whose sugar spiked through the roof every time he ate any kind of bread including wholemeal. The message is clear, each individual’s GR is different; pretty much like a thumbprint. You may have to attach a glucose monitor to find out. The final analysis is that we think that there are certain foods that you are eating and these are likely to be your favourite, and hence frequently consumed, foods that are really affecting your GR and making you pile on visceral fat. You can boil all this down to an adage: there are foods you want to eat, there are foods you should eat, but ultimately you have to figure out which foods you can eat.

A Checklist Before Exercising To Prevent Sudden Cardiac Death

If you are deciding on starting an exercise programme to get yourself fit and healthy, you should tick off some boxes to ensure that you reduce your risk of sudden cardiac death (SCD). SCD is sudden unexpected death caused by the onset of a life-threatening heart rhythm (sudden cardiac arrest). In Singapore, it is estimated that about 1,000 individuals die of SCD every year. A 2017 Singapore study on SCD reported that the median age of SCD victims was about 47 years in males and more than 50 years for women. The largest cause of natural death in many developed countries including the USA is sudden cardiac death (SCD). SCD accounts for about half of heart-related deaths in the USA. It is also the most frequent medical cause of sudden death in athletes.

In SCD, there is a malfunction of the electrical system in the heart and the heart rhythm suddenly becomes very fast and irregular. This life-threatening heart rhythm (ventricular fibrillation or VF) will cause the pumping chambers (ventricles) of the heart to “quiver” instead of pumping blood to the body. This will result in a large drop in blood pressure, severe reduction of blood flow to the brain, loss of consciousness and death if no emergency measures are instituted. In the USA, if sudden cardiac arrest occurs outside a hospital, the one-year survival rate after hospital discharge is only about 10 per cent.

Heart attack does not equal sudden cardiac death In coronary artery disease (CAD), the coronary or heart artery is gradually narrowed and when the artery suddenly gets completely blocked (usually by a blood clot), a heart attack occurs resulting in damage to the heart muscle. This may result in instability of the heart rhythm and the development of VF. If VF occurs, and emergency measures are not instituted immediately, SCD ensues. However, not all heart attacks result in life-threatening heart rhythms. Hence, SCD can occur in seemingly “normal” individuals without any symptoms or warning in the absence of heart attacks. Causes of sudden cardiac death Coronary artery disease (CAD) is the most common cause of SCD and accounts for about 80 per cent of all SCD.

What is interesting is that in a recent Australian study on SCD in the young (published in October 2020 in the Circulation: Cardiovascular Quality and Outcomes journal) the most common cause of SCD in those 35 years or younger was CAD. accounting for 40 per cent of SCD. If this is further segmented into different age groups, CAD accounted for 50 per cent of SCD in those aged 26 years to 35 years. In those 5 years and below, inflammation of the heart muscle (myocarditis) was the main cause of SCD and in those 6 to 15 years, myocarditis accounted for 25 per cent of SCD. Other than CAD and myocarditis, the other two main underlying causes of SCD were:
* those who die from an electrical malfunction (arrhythmia) with a structurally normal heart but no other cause found (otherwise known as sudden arrhythmic death syndrome or SADS)
* those with a structurally abnormal heart (swollen heart such as dilated cardiomyopathy or abnormal thickening of the heart muscle such as hypertrophic cardiomyopathy).

Less common causes of SCD include tear of the aorta (aortic dissection), heart valve disease and congenital heart disease. Sudden cardiac death in athletes The SCD profile is different in competitive athletes with most SCDs occurring during intense exertion, and the  common causes of SCD being SADS, heart muscle disease and coronary anomaly (abnormal heart artery). In one study, it was reported that in competitive athletes, SCD was due to SADS in 42 per cent of the cases followed by heart muscle disease (40 per cent). An American College of Cardiology article in December 2019 stated that recent data from the National Collegiate Athletic Association suggested that the most common finding at autopsy for SCD cases was a structurally normal heart (25 per cent), implying that abnormal heart rhythm is likely to be the most common cause of SCD. The second commonest cause was coronary anomaly followed by hypertrophic cardiomyopathy.

This is different from Italian studies, where the most common cause of SCD in athletes was arrhythmogenic right ventricular cardiomyopathy (ARVC), which accounted for about 25 per cent. ARVC is a genetically inherited heart muscle disease where the right ventricle muscle wall has been replaced with abnormal scar tissue causing electrical instability and an increased disposition to VF. The risk of VF is increased by exercise. Generally, in athletes, the data is consistent that electrical malfunction of the heart, heart muscle disease and abnormal heart artery are the three commonest causes of SCD, unlike the general population where CAD is the commonest cause of SCD. Checklist to reduce risk of sudden cardiac death As the consequences of SCD are often devastating, preventing SCD is a key priority.

This means that we need to identify those at risk of SCD. As CAD is the main cause of SCD even for the young , identifying those at risk of CAD is one of the best ways to prevent SCD. Check out this pre-exercise risk identifier list before you embark on vigorous exercise:
* Do you have risk factors for CAD such as high cholesterol, smoking, hypertension, diabetes mellitus, or family history of heart disease?
* Did you have significant damage to your heart because of a previous heart attack or did you have a heart attack within the last 6 months?
* Did you have a previous episode of sudden cardiac arrest?
* Do you have a family history of sudden cardiac arrest or SCD?
* Do you have pre-existing abnormal heart rhythms?
* Do you have unexplained fainting episodes?
* Do you have exertional chest tightness or shortness of breath?
* Are you on medication that can potentially increase your risk of abnormal heart rhythm such as diuretics (can cause abnormally low blood potassium or magnesium levels) or rhythm controlling drugs?
* Do you have a history of congenital heart disease?

If your answer is yes to any of the questions above, you should seek your doctor’s advice before embarking on your exercise programme.

Pre-exercise screening
Both the American Heart Association and the European Society of Cardiology (ESC) advocate pre-participation screening (PPS) of young athletes as intense athletic activity can trigger SCD or disease progression in susceptible individuals. While both recommend a thorough medical and physical examination, only the ESC recommends a routine 12-lead electrocardiogram (ECG) to detect underlying electrical abnormalities or heart muscle disease. However, it is important to understand the limitations of the ECG. For example, the ECG is normal in most individuals with congenital coronary anomalies, in 5 to 10 per cent of those with hypertrophic cardiomyopathy, and in most individuals with catecholaminergic polymorphic ventricular tachycardia (life-threatening heart rhythm).

Those athletes with abnormal findings during the PPS will require further assessment. In addition, the American Heart Association recommends that for men who are 40 years and older and women who are 50 years and older, an exercise stress test may also be required depending on the assessment by their doctor. If heart problems are identified or suspected during the screening, the individual should be referred to a heart specialist for further evaluation before embarking on an exercise programme. As CAD accounts for about 80 per cent of SCD, it means that ticking off the boxes before embarking on exercise and getting appropriate medical advice can prevent SCD in most high-risk individuals.

An eye test can save your life

Modern medicine works by finding evidence to support one or more differential diagnosis at a particular point in time. Sometimes the evidence can come from seemingly unrelated parts of our body. The eye is unique in being the only organ in our body that allows a direct visualisation of its nerve and blood vessels. This offers a peephole view of the state of our health. As such, an eye test is a golden opportunity not to be missed, to gauge our overall physical wellbeing.

Starting from the eyelid and the internal content of the eyeball, all the way to the layers of its walls as well as the six muscles responsible for eye movements, all are closely connected to the rest of our body via their blood supply and innervations. One could say the eye is the “crystal ball” that can foretell our health, providing early clues that should be acted on with appropriate follow-up tests and actions, not just for sight, but also for life-preservation. Several recent examples come to my mind.

First is a very fit patient who had a persistent blurring of vision when reading in one eye and no obvious general health issues. I made a diagnosis of macula swelling secondary to blockage of a branch retina vein at the back of the eye, supported by a thorough eye examination and eye scans. Treatment with eye injections and laser was successful in restoring eyesight. Closing the case after eyesight restoration would be like missing the forest for the trees, as it is usually the underlying cardiovascular health that is the root cause of the eye disease. In fact, in a 2016 meta-analysis endorsed by the American Heart Association and American Stroke association, blockage of the retina vein was found to be associated with a 120 per cent to 450 per cent increase in the risk of stroke, depending on age.

The bigger picture

Recognising the possible bigger picture from a single problem of blurring of eyesight can indeed prompt health-seeking behaviour and ultimately save your life. In fact, my patient is contemplating a career switch from a very stressful job that is felt to be contributing to episodic blood pressure spikes, which almost certainly caused the vein occlusion in the eye.

Another is a patient with a complex intraocular lens problem who also suffered from intractable diabetes and severe diabetic eye disease. A previous cataract surgery in a neighbouring country many years ago could not stand the test of time and the inserted artificial lens implant had become wobbly, to the point of causing terrible visual distortions with every movement. After a rather “heroic” eye surgery lasting several hours, we treated both the dislocated lens implant and detached retina, but subsequent recovery of sight seemed slower than expected.

As a result of the severe diabetic eye disease, in this case, the optic nerve is no longer able to provide clues to possible brain diseases. However, due to complaints of headache and my impression that there could be more to the case, I ordered a brain magnetic resonance imaging (MRI). The result was a sizeable brain tumour that fortunately was still operable, and the final outcome of the case was thankfully a happy ending.

Many patients ask me why their eyes look “smaller” and their eye colour seems to become lighter as they age. The answer is a ring of deposit of oily (lipid) material around the cornea, which is the perceived “black of eye”. The scientific parlance is arcus senilis (pardon the language please) and may indicate a rise in the blood cholesterol level of the body, so it is highly recommended to undergo tests and treatment to manage the cholesterol level.

More than meets the eye

And if becoming senile and demented is a concern, new research also indicated that studying the retina blood vessels may give clues to early Alzheimer’s disease, although diagnosis still needs to be supplemented by neurological tests and brain imaging.

Dry eye disease can be associated with an underlying thyroid problem, and new research has also indicated an association with a lack of Vitamin D which is not rare even in sunny Singapore. I have sent many patients, some even pre-operatively before their planned cataract or laser refractive surgery for blood tests for the above, if suspicion index is high.

Sometimes these tests do turn out to be positive. Proper treatment can then improve their eye symptoms such as eye tiredness and irritation, and improve their general wellbeing too.

I always make it a point to inform young (and sometimes older) patients who sign up for Lasik surgeries which rid them of refractive errors like myopia and astigmatism, if I find any tell-tale signs suspicious of glaucoma, at the risk of sounding like nagging.

One of the associated causes for glaucoma is snoring (sleep apnoea). This may sound innocent enough, but if the end result of continuous neglect is the possibility of complete blindness, my sincere advice is to please get the snoring treated, by the ear nose and throat specialist, as believe me, blindness from glaucoma is real, irreversible and very terrible.

The English poet William Blake once wrote in his famous Auguries of Innocence: To see a world in a grain of sand, and heaven in a wild flower. So too, a quick check of the eyes can reveal more than, well, meets the eye. It may not be possible to hold infinity in the palm of the hand, but here’s wishing that we safely go through the world!

Getting a flu shot is a good idea right now

The year-end and the yuletide season will be soon upon us. Ordinarily we would be gearing to go travelling and some of us would be headed to cold temperatures in the northern part of the globe. However, this has been anything but an ordinary year. We have been beset by a once-in-a-centenary event of a pandemic. As we speak, the pandemic has claimed its one millionth victim and shows no signs of abating. We are all resigned to tracking with bated breath the progress of the 11 Covid-19 vaccines in Phase 3 human trials as there seems to be no other way to stop the onslaught of the coronavirus. Yet we should not be so helpless; we can still do our part by getting our influenza (flu) vaccines. The influenza vaccine is important at this juncture in our fight against the pandemic.

We should first understand that influenza attacks vulnerable groups especially in winter. We do not have a winter season but up to recently we have had a mobile population that travelled extensively for leisure and business; and we used to have 20 million visitors annually. Despite being at the Equator and having tropical climate, we are also an air-conditioned nation. All these factors can make us more susceptible to influenza and its spread. The more vulnerable among us include young children, those who are pregnant and seniors, especially those with chronic diseases and ailments.

Risk to vulnerable groups
Influenza vaccines are recommended for these groups and in the midst of the pandemic, it is imperative that we get them vaccinated to avoid the difficulty of telling apart the Covid-19 infection from the common cold or influenza when patients present with respiratory illnesses. We can also prevent hospitalisation or events related to flu that may increase the risk of the vulnerable groups to Covid-19. We are often asked which flu vaccine we need to take. There are two flu vaccines in a calendar year. The Northern Hemisphere vaccine is available around this time of the year while the Southern Hemisphere vaccine is available in March. The names of Northern and Southern refer to the winter seasons that are critical to patients who contract influenza. The winter season tends to exacerbate the influenza and lead to complications and ultimately the demise of the vulnerable patients. As a result we tend to vaccinate prior to the arrival of winter.

We also need to understand the logistics of producing a flu vaccine. The initial research is to figure out what flu strains will be active in the winter ahead. This involves some degree of “crystal balling” to identify the strains the vaccine should be effective against. Sometimes the prediction is correct and sometimes it is not. It takes, on an average, five months for the pharmaceutical firms to produce, ship and have a vaccine made available. We will usually offer the vaccine that is currently available. Sometimes because the pharmaceutical firms have to make an educated guess as to which flu strains will be causing problems in the winter ahead, we have a situation where if one takes the prevailing vaccine, there is still a chance that we have to take the next vaccine that comes out six months later. So you may hear of people taking two flu vaccines within six months of each other. Fortunately we have guidance on this from our Ministry of Health.

While we are in the midst of a pandemic, we should look back at history. We had the infamous Spanish flu pandemic in 1918 that spawned the H1N1 virus that came from birds. There were smaller pandemics in 1957 (H2N2), 1968 (H3N2) and the recent H1N1 in 2009. I was fascinated by the stories of scientists who discovered the genome of the Spanish flu by exhuming the bodies of Inuit natives who died in 1918. The lung tissue of these bodies was well preserved by the permafrost in Alaska. The scientists managed to extract the RNA of the virus from the preserved lung tissue, decipher it and reconstruct the actual virus at the CDC Laboratories in Atlanta, Georgia. As for the 1957 flu pandemic, my Italian patient in his 70s recall contracting the flu in 1957 as a young boy and told me that he was so ill that he was in bed for three weeks.

Global fight
We are always faced with mutating flu strains and the latest is a swine flu strain in China. This strain is H1N1 and has been spreading since 2016 in the Chinese pig herd. They have found that about 10 per cent of swine workers have been exposed to the virus. So far there has been no human-to-human spread but the local and global authorities are watching this virus like a hawk. This siege is the reality in our global and united fight against viral threats. One of the key battles is the speed of a vaccine against a novel virus. The vaccines take a long time to be produced and in the H1N1 pandemic in 2009, it took 26 weeks for a vaccine to be produced and shipped. We can technically reduce this lead time to 12 weeks but that will need a lot of resources and international cooperation.

A universal flu vaccine is still light years away. The comparison is the ongoing vaccine race for the Covid-19 vaccine. We had the published genome of the Covid-19 virus on the weekend of Jan 11/12 this year. As of today we have 11 vaccines in Phase 3 trials and five approved for limited use. These five include four Chinese vaccines and one Russian vaccine. In the midst of this pandemic while we wait for the Covid-19 vaccine, we must act and mobilise the population to get vaccinated against influenza. The latest flu vaccine is now here and I myself have taken it. While the use of face masks has reduced the incidence of influenza, it is still a good idea to approach your family doctor for a flu shot for all the reasons I have outlined above.

One reason is that it can help in differentiating the Covid-19 infection from the common cold or influenza when patients show symptoms of respiratory illnesses.

Should cholesterol lowering medication be started in the young?

Earlier treatment of elevated cholesterol results, even for children when indicated, results in better outcomes

While the general perception is that strokes only occur in the elderly, over the years, there has been a gradual increase in the prevalence of strokes in the young. Recently, a young patient of mine, who is in his 20s with multiple risk factors for heart disease and stroke, was found to have near complete occlusion of one of his major arteries in the brain, the middle cerebral artery (MCA). The MCA provides blood supply to the part of the brain that controls power, sensation and speech. A stroke involving this artery will not only result in severe disability but can also be life threatening.

Stroke in the young

Severe narrowing of an artery within the skull is termed as intracranial stenosis and encompasses narrowing of the brain arteries. Intracranial stenosis is a common cause of stroke and is particularly prevalent in Asians. In a 2017 study on young Chinese with intracranial stenosis published in the Annals of Translational Research, it was found that in about 80 per cent of those with unilateral blockage of the MCA, the underlying cause was attributable to atherosclerosis. Atherosclerosis is the condition where there is narrowing of the arterial wall (plaque formation) due to the build-up of fat, cholesterol, calcium, and other substances found in the arterial wall. While atherosclerosis remains the main cause of blockage of brain arteries in the young, there are also other causes such as vessel malformation (Moyamoya disease), inflammation of vessels (vasculitis), abnormal arterial wall growth (fibromuscular dysplasia), tear of the artery (arterial dissection); however, these are more prevalent in young females.

Earlier studies showed that for those with significant intracranial stenosis, there was about a one-in-eight chance of getting a stroke or even death within a one- to two-year period even with medical treatment. A more recent publication on the Oxford Vascular Study in May 2020 in Lancet Neurology demonstrated that the risk of intracranial stenosis stroke for those on intensive medical therapy was lower when compared to previous studies, being 5.6 per cent one-year risk (compared to 9.4 per cent in VISSIT, a study on treatment of intracranial stenosis) and 5.6 per cent two-year risk (compared to 14.1 per cent in SAMMPRIS, a study on treatment of intracranial stenosis). The better outcomes in the Oxford Vascular Study may be explained by better medical treatment available in more recent years. In the Chinese Intracranial Atherosclerosis (CICAS) Study, the highest rate of recurrent stroke was seen in those with three or more risk factors.

The major risk factors include high cholesterol level, diabetes mellitus, smoking and high blood pressure. Hence, optimal control of risk factors is essential in those with intracranial stenosis.

Atherosclerosis in children and young adults

While it may come as a surprise to many that the young can develop significant blockage of arteries, the data proving that atherosclerosis is prevalent in the young has been around for some time. Autopsy data from young men with a mean age of 22 years who died during the Korean war showed that more than 70 per cent of them had atherosclerosis in their heart arteries. A similar study on young Americans who perished in the Vietnam war showed that 45 per cent had atherosclerosis and 5 per cent had severe heart artery atherosclerosis. Studies on younger cohorts showed evidence of early onset atherosclerosis in children. A study of young American motor accident victims showed that more than 50 per cent of children aged 10 to 14 years have evidence of early atherosclerosis. In the Bogalusa Heart Study, early atherosclerosis (presence of fatty streaks in the heart arteries) was present in about 50 per cent of those aged from two to 15 years.

Never too young for prevention

Cholesterol remains the single most important risk factor for stroke and heart disease. While it is almost unthinkable in the past to consider starting children on cholesterol-lowering drugs (statins), there is now almost universal agreement that in those with familial hypercholesterolaemia (genetically high cholesterol levels), treatment should commence at a young age. The European Atherosclerosis Society (EAS) consensus panel and the latest American College of Cardiology-American Heart Association (ACC-AHA) guidelines for familial hypercholesterolemia recommend that statins be commenced from as young as eight years (EAS) to 10 years (ACC-AHA) of age. In October 2019, the New England Journal of Medicine published a 20-year follow-up study of children with familial hypercholesterolemia who were started on statin medication at an age of eight to 18 years.

Their results were compared with their affected parents with familial hypercholesterolemia who were only given statins much later in their lives. At the end of the follow-up period, 99 per cent of young patients receiving statins had cardiovascular disease-free survival compared to 74 per cent for their affected parents. This meant that earlier commencement of statin therapy in these at-risk young patients resulted in better long-term outcomes. The latest consensus from the EAS and the International Society of Atherosclerosis (ISA) is that it is not a hypothesis but a fact that LDL cholesterol (“bad” cholesterol) is a major determinant of atherosclerosis. The development of atherosclerosis in arteries is not just dependent on the absolute LDL cholesterol level but also by the cumulative exposure of the arterial wall to LDL cholesterol.

Hence, preventing the development of atherosclerosis not only embodies the concept of “the lower the better” with respect to the LDL cholesterol level, but also a newer concept that “the younger the better”, meaning earlier treatment of elevated cholesterol results in better outcomes.

Early detection

While prevention remains the cornerstone of management, there will be invariably some at-risk young people who may get a stroke. Understanding the symptoms is a key step in early detection and management. Patients with significant intracranial stenosis can present with symptoms of a transient insufficiency in blood flow to the brain (transient ischemic attack) or a stroke. While symptoms such as weakness of one side of the body, slurring of speech, and numbness of one side of the body are easily recognised as an evolving stroke, other symptoms such as severe headache, changes in vision and severe dizziness or a spinning sensation (vertigo) are less well recognised as symptoms of stroke. While ultrasound of the neck (carotid) arteries is commonly used to assess the risk of stroke, it has its limitations. In the CICAS Study, only 20 per cent of those with intracranial stenosis had co-existing neck carotid artery disease, which means that the absence of disease in the neck carotid arteries does not mean that there is no significant intracranial stenosis.

For patients with symptoms, an MRI of the brain and brain arteries can provide confirmation. In an acute stroke, a CT scan of the neck and brain arteries is usually performed at the Emergency Department to help the doctor make a decision on therapeutic choices. In summary, evolving lifestyle and dietary changes have resulted in the development of atherosclerosis in children and young adults. Elevated LDL cholesterol remains the key driver of atherosclerosis and early management, even for children when indicated, can lead to better cardiovascular disease-free outcomes.

The havoc wreaked by the pandemic across the world

Let’s hope that a vaccine will put an end to all this misery and Singapore will be among the first to launch it

It has been six months since the first imported case of Covid-19 virus landed on our shores. The first imported case was diagnosed on Jan 23, 2020, and the first local case was on Feb 4, 2020. We have since come far with 54,797 cases as of yesterday. The community cases have come down to a trickle, averaging about two cases daily in the last week. The migrant worker cases still average about 300-odd cases daily in the last week.

This is really due to the ongoing effort to achieve clearance of the dormitories so the workers can go back to work. There is a herculean effort going on to swab all migrant workers by the day we go to print. To get a better understanding of the situation, I turned to my medical colleagues. These colleagues had founded Crisis Relief Alliance, an NGO that usually does overseas relief missions but could not turn its back on the outbreak in our dormitories at home. My colleagues in full battle order had ventured into the smaller factory dormitories to see, assess and help out.

They had helped to assess the ground situation to feedback to the relevant authorities, distributed fruits regularly to boost morale of the workers and prior to Hari Raya Haji had handed out new clothes, prayer mats and dates obtained from generous donors. There are more than a thousand of these factory dormitories housing anywhere from 20 to 200 migrant workers on their premises. The best way to describe these premises is that if a floor in a factory is empty, you house your workers there. The conditions are basic and spartan with bunk beds and the proximity of these bunk beds has led to rapid transmission.

The toilets are common and the kitchen is shared. Most foreign media have decried them as squalid but I liken them to my bunk bed in the overseas army camps during my National Service days three decades ago. The NGO has visited more than a hundred factory dormitories and the conditions in their premises vary. I have found that the majority of the bosses of these premises have treated their staff well and most workers have been working for the same boss for five to 20 years. Their salaries are paid on time, they received three catered meals daily and all had Internet access or data cards that allowed them to communicate with their loved ones back home.

As for the workers’ fears, they were not worried about the virus as the medical care here is world class, but they were more concerned about the economic damage and the loss of their jobs. In a sense, their fears and emotions are very much aligned with the rest of the population. On the subject of the economic fallout, we have seen devastation to global economies, with our own economy savaged by the virus. The downturn has caused GDP to drop by more than 40 per cent quarter on quarter, and total trade figures contracted by 25 per cent in May 2020. This has prompted a rescue budget totalling 20 per cent of our GDP, probably one of the largest globally in percentage terms.

We have seen our 19 million tourist annual arrivals tumble to a trickle, our airport and our national airline suffer huge downturns. We have really taken for granted in the past that we are truly a global city. The rest of the world has not fared well; we have seen the experience of nations that have done well in the first wave, now felled by the ferocity of the pandemic. We are dismayed by what has happened in Hong Kong and Australia.

Hong Kong is now in the midst of a lockdown and Melbourne is in a state of nightly curfew. Even China, with its herculean efforts in containing the Wuhan/Hubei situation, is now experiencing fresh outbreaks in Beijing, Dalian and Xinjiang. The lessons learnt from these nations is that the virus is unforgiving and penetrates through loopholes created by exemptions from testing, breakdown in quarantine procedures and unexpected contamination of packaging of frozen foods.

As for other nations, we gape in amazement at the politicisation of wearing masks in the US, along with sidelining of experts like Dr Anthony Fauci, a giant figure in the field of medicine. In my weekly Zoom meetings with my Indian colleagues, I hear their struggles about fighting the pandemic without essential resources of Covid-19 swabs or antibody test kits. You can imagine trying to diagnose a Covid-19 patient clinically and telling it apart from other viral or bacteria infections.

In Brazil, the leadership continues to pillory the use of masks, social distancing and promoting the use of hydroxychloroquine without merit; all in a defiant show of maschismo. As the sideshow continues in a desperate spiral of death and misery, this pandemic has really sharply outlined the differences between the first world nations and the rest. The cost of a Covid PCR swab test is estimated to be a hundred US dollars. That has already put a lot of countries out of the league of massive testing.

The next is the much-vaunted vaccine. At the last count we have more than a hundred vaccines in the race with four entering the Phase 3 clinical trials. There are many ways to make a vaccine and the tried and tested method is to use a dead virus or a weakened but live virus. Other ways involved the use of an innocuous virus like a common cold virus to carry the viral genes into the body of the host as in the Oxford vaccine.

The new methods include using messenger RNA or DNA fragments. The messenger RNA is interesting as seen in the Modena vaccine. The DNA is our genetic code and stays in the cell nucleus as it is important to the survival of our species. The DNA sequences when deciphered are able to transcribe proteins. After the DNA helix structure unravels itself to allow messenger RNA to dock alongside to copy the sequences, the messenger RNA then leaves the nucleus to arrive at the protein making sites in the cell cytoplasm.

The vaccine approach is to embed messenger RNA with viral sequences. However, the thought of messenger RNA being able to travel into every cell nucleus in the body gives me some discomfort. In a rush to market, there is talk of reduced liability of vaccine manufacturers for side effects and complications. The regulatory bar may have to be raised higher for novel vaccine approaches as opposed to traditional methods. As for the economics of the vaccine, the US and EU have already put down their interest in the Big Pharma vaccine race. The Chinese, on the other hand, is taking the approach of the vaccine as a global common good.

We all wait in anticipation of the latest trials in the hope that a vaccine will put an end to all this misery. The last vaccine that was only 50 per cent effective did indeed wipe out polio. Interestingly, Singapore was one of the first countries in the world to launch the polio vaccine for all of her children in 1959. We were also one of the first countries in the world to launch Hepatitis B vaccination in 1987. It is with cautious optimism that I hope we will once again take the lead in such an endeavour.

10 ways to lower your blood pressure without medication

Making changes to your lifestyle will help give you a healthy head start in life

Can you lower your blood pressure without taking medication? The answer is yes. If you have abnormally elevated blood pressure (BP) or hypertension, you may want to consider non-pharmacological measures initially rather than commencing on drug therapy immediately. Here are 10 ways to lower your BP without taking medication.

  1. Exercise

It has been shown that after a single session of moderate intensity aerobic exercise of a duration of 10 minutes or more, the BP can be reduced by 5 to 7 mmHg in people with high blood pressure. The good news is that this BP reduction can be sustained for up to 24 hours after the exercise session. This BP reduction is termed as post-exercise hypotension or PEH. The exercise should preferably be 30 minutes a day or a total of 150 minutes or more of exercise per week. Evidence shows that PEH benefits occur more with aerobic exercises such as walking, jogging, cycling or swimming as compared to dynamic resistance training using weights or resistance machines. In terms of exercise intensity, it should be at least be the equivalent of brisk walking which would increase your heart rate and breathing but does not make you feel out of breath.

  1. Cut salt intake

There is strong evidence that reduction of salt or sodium intake will result in a reduction of blood pressure. For those with high BP, they should not take more than 2,400 mg of salt per day which is equivalent to about 1 teaspoon of table salt. If the salt intake can be further reduced to 1,500 mg per day, there can be as much as 7 mmHg reduction in the systolic blood pressure and 3 mmHg in the diastolic blood pressure. The reduction in salt intake not only decreases the blood pressure but it is also associated with reduction in cardiovascular morbidity and mortality.

  1. Weight reduction

Studies in diverse populations have consistently shown a nearly linear relationship between body mass index and systolic and diastolic BP. Data from the long term US Framingham Heart Study estimated that about three-quarters of high BP in men and two-thirds of high BP in women can be ascribed to excess weight gain. The increased fat accumulation in the abdomen in obese individuals can result in an increase in the pressure within the abdomen to as high as 40 mm Hg. This not only results in compression on the kidney but also increases the pressure within the kidney and the kidney vessels. These changes have been associated with the development of high blood pressure and chronic kidney disease. It has been shown that keeping your BMI below 25 kg/m2 is effective in preventing the development of high blood pressure. It is estimated that a weight reduction of about 10 kg can potentially reduce the systolic blood pressure by 5 to 20 mmHg.

  1. Stop smoking

There is some controversy about the impact of smoking in blood pressure. Nevertheless, it is known that smoking causes various adverse cardiovascular problems and acts synergistically with high blood pressure to increase the risk of heart artery disease, heart attacks, sudden cardiac death, and stroke. Hence, for those with hypertension, smoking cessation is advocated.

  1. Treat obstructive sleep apnoea

In recent years it has been shown that obstruction of the upper airway during sleep, a condition termed as obstructive sleep apnoea or OSA, may actually contribute to elevation in BP, poor control of hypertension and even hypertension that is resistant to drug therapy. OSA leads to poor sleep quality and a sleep duration of less than or equal to five hours per night has been shown to significantly increase risk for hypertension in patients 60 years of age or younger. Treatment of OSA may improve the blood pressure control.

  1. Eat potassium-rich foods

It has been shown that potassium can decrease both the systolic and diastolic BP possibly by causing the body to remove more salt in the urine and by relaxing the walls of the blood vessels. However excessive potassium supplements can be harmful and is generally not encouraged by doctors. Hence, instead of taking potassium supplements, the American Heart Association advises that eating potassium rich foods may help to manage the blood pressure. These foods may include dried apricots, spinach, tomatoes, avocados, mushrooms, prunes or a fat-free yoghurt or milk.

  1. Eat magnesium-rich foods

Review of trials on magnesium supplementation concluded that consumption of 300 mg of magnesium a day can cause a modest reduction of diastolic BP but has no significant impact on the systolic BP. However, excessive consumption of magnesium from supplements may cause diarrhoea. There are currently no known adverse effects of magnesium intake from food. It is best to get magnesium from foods that include dark leafy green vegetables, nuts, unrefined grains and legumes.

  1. Consume cocoa

An analysis of more than 30 studies on cocoa have shown that consumption of cocoa was associated with about 2 mm Hg lowering of both systolic and diastolic BP. Hence the consumption of dark chocolate or cocoa products can be beneficial and this benefit is mediated through chemical compounds in the cocoa products called flavanols and it is believed that the blood pressure lowering of these chemicals are related to their ability to widen the blood vessels through a chemical called nitrate oxide.

  1. Take folate supplement

Studies have shown that the intake of folate, which is a type of Vitamin B, among patients with high blood pressure or hypertension may reduce the risk of stroke and aid in stroke prevention in patients with hypertension. Hence, for those with high blood pressure, consumption of folic acid may help to reduce the risk of stroke.

  1. Reduce stress

While researchers are not certain about the relationship between stress and the development of hypertension, they are clear that stress can cause significant transient elevation of blood pressure. It is possible that long-term stress can result in frequent, temporary spikes in blood pressure that can damage the blood vessels, heart and kidneys. Stress management includes getting sufficient sleep, adopting relaxation techniques such as meditation or yoga, widening your social circle by participating in support groups or classes, improving on time management, resolving stressful situations amicably, caring for yourself by doing the things you enjoy and asking for help when you need it.

These 10 ways to lower your blood pressure can make a difference to your life. Research has shown that a reduction in systolic blood pressure of 5 mmHg can reduce death from stroke by about 14 per cent, death from heart disease by 9 per cent and death from all causes by 7 per cent. Recent data show that lowering blood pressure to ideal targets reduced the risk of heart attack, stroke, heart failure, and cardiovascular death by 25 per cent. So, if your blood pressure is high, these lifestyle measures can help you to lower your blood pressure and give you a healthy head start in life.