You’ve heard all the usual health advice to keep your heart healthy or reduce your risk of cancer, but sometimes you are tempted by that mouth-watering piece of cake in the patisserie window or want to miss that workout for the day to catch your favourite TV show. And to be honest there is no harm in occasionally being a little lazy and treating yourself. But maybe you would find it easier to be healthy if you understand why taking such health precautions are good for you. In my previous post, you learned what causes heart attacks and strokes. Now here is how you can prevent them happening to you.
1) Ditch the lard
As mentioned in my previous post, fats are essential to start the atherosclerotic process. If there is too much ‘bad cholesterol’ (otherwise known as low density lipoproteins or LDL) and another type of fat call triglycerides, in your blood from all those hamburgers or a full English breakfast (red meat is particularly high in fat), they will deposit in curved or branching arteries triggering the immune response where macrophages initially consume the fats, clear them from the artery and break them down into cholesterol, which become a vital part of the cell membrane. However the amount of LDL eventually overwhelms macrophages, so they die and deposit in the artery wall contributing to the build up of the atherosclerotic plaque. And why in particular is LDL so dangerous? The clue is in the name, the particles are of a low density and thus are small enough to fit through the spaces between endothelial cells and deposit inside the artery wall, while also being more easily consumed by macrophages. The dying macrophages also contribute to the problem, as their cell membranes become part of the growing plaque increasing the level of cholesterol inside. And it’s not just the fat inside your arteries that creates problems. As more fat is consumed, the body primarily deposits the excess fat around the abdomen resulting in an increase in number and size of fat cells, called adipocytes, which are full of triglycerides and cholesterol. And crucially these adipocytes release chemicals, which increase the aggressive immune activity of macrophages, making them more likely to build up and cause damage in the artery wall.
2) Keep working out
The recommended amount is equivalent to half an hour everyday, my suggestion is to do as much as you can! Research suggests that physical activity; particularly aerobic exercise (such as running, cycling, swimming) can lead to better control of the production of inflammatory signals, which would normally mobilise the immune cells, such as macrophages, responsible for exacerbating atherosclerosis. In fact exercise stimulates the production of anti-inflammatory signals, which dampen down the potentially damaging inflammation, reduce adipocytes, help macrophages to expel cholesterol, reduce growth of the plaque, and in already advanced plaques it can increase the thickness of the fibrous cap (by promoting the growth of smooth muscle cells) therefore it is less likely to rupture and create a blood clot. So it is never too late to start exercising, even as you get older it could save your life!
3) Eat your five-a-day or even more!
Studies show that the more fruit and vegetables you eat, the lower your risk of suffering a heart attack or stroke, particularly with green leafy vegetables and fruits such as apples. Research is ongoing to establish exactly why fruit and vegetables are so beneficial. Early studies suggest a protein called sulforaphane – found in green vegetables such as broccoli – can suppress the activation of endothelial cells, thus it could reduce atherosclerosis by preventing the chain of events that start the disease process.
Earlier I mentioned the dangers of LDL or ‘bad cholesterol’. But there is also ‘good cholesterol’ otherwise called high density lipoproteins or HDL. And as you’ve probably guessed from the name, HDL is not dangerous to the artery wall like LDL because the particles are of a high density and are unable to squeeze in between the endothelial cells and deposit in the artery wall. In addition, HDL serves many benefits. HDL can reduce the inflammatory actions and the entry of macrophages into plaques while increasing their exit from atherosclerotic plaques, thus reducing the size of plaques even if they are already large in size. HDL also promotes the breakdown of cholesterol and its excretion by macrophages, thus reducing the fat content of plaques. So how can you increase your HDL levels? Foods that are known to increase HDL levels in the blood are: fish, high fibre foods (such as oats, fruit, vegetables, grains), nuts, legumes, yogurt, fruit juice, dark chocolate, garlic, and red wine (or dark grape juice if you don’t drink alcohol). And if you have been prescribed statins, keep taking them as they reduce LDL levels while increasing HDL in your blood, and have many anti-inflammatory benefits.
4) Don’t add salt to taste
A high intake of salt increases blood pressure, and the higher your blood pressure the higher your risk of suffering a heart attack or stroke. A higher salt concentration in your blood promotes the diffusion of fluid; primarily water, into the circulation increasing blood volume and thus increasing pressure and potentially damaging the blood vessel wall, particularly the endothelial cells. When pulses of blood are pumped around the body, the arteries need to expand and relax with each pulse of blood that moves through. But if the endothelial cells are damaged, they cannot send signals to stimulate the expansion of the vessel wall further increasing the pressure created by flowing blood and imposing stress on the cells. All of these events increase inflammation creating the conditions for atherosclerosis to begin and further increase blood pressure.
5) Don’t give in to your sweet tooth
There is no doubt about the association between high sugar intake and cardiovascular disease, but we still don’t really know why this is the case. Studies performed so far suggest that high blood glucose levels can increase inflammation, promote the entry of macrophages into the artery wall and possibly interfere with the expulsion of cholesterol by macrophages. It also appears that LDL is increased in diabetics, thus sugar and cholesterol may work together to promote atherosclerosis. While more studies are needed to firm up these conclusions, the link between diabetes and cardiovascular disease is very clear so don’t tickle you sweet tooth too often!
6) Limit the booze
Early studies demonstrate that light drinking (up to the recommended 2-3 units of alcohol a day) reduces atherosclerosis, and the risk of strokes and heart attacks, but consuming higher amounts of alcohol on a regular basis increases atherosclerosis significantly. But a recent small-scale study published by New Scientist  showed that when regular social drinkers gave up alcohol for a month, they experienced a large drop in liver fat, blood glucose and cholesterol, and improved their sleep quality and concentration, although more scientific evidence is needed to back up these results. So you can still enjoy that tipple, but only in moderation.
Any questions? Please comment below
Ten years ago when my father was hospitalised after suffering a heart attack, the nurses gave him a video to watch about heart attacks. The video detailed the symptoms and treatment given, and when addressing the cause of heart attacks, the narrator stated that it is not really known, all is known is that a blood clot arises blocking the artery’s blood flow from reaching the heart, thus starving the heart muscle of vital nutrients and oxygen for survival and ultimately damaging the heart. While the latter is true, the events prior to blood clot formation have been well known for years, in fact centuries! A more accurate statement would have been that it is not fully understood how the various symptoms of a heart attack, such as vomiting and excessive sweating, occur. Nonetheless as an A-level student, this deepened my curiosity into the cause of heart attacks ultimately leading me to undertake a PhD on atherosclerosis – which I will define later in this post.
If you watched the second episode of the recent “Watermen: A Dirty Business” series on BBC Two, you will have seen how drains are often blocked because hundreds of litres of cooking fat is poured down household sinks every week. Over time the fat builds up inside the pipework, particularly at joints and bends, eventually blocking the pipes and causing the rather unpleasant consequence of sewage spewing out onto the roads! The process of fat blocking our sewage pipes is reminiscent of what happens in our own arteries.
So what is the disease inside our arteries that can have such deadly consequences? Firstly it is important to clear up a couple of terms which can cause confusion, even to me! Arteriosclerosis refers to the hardening and thickening of the arterial walls. The middle layer of the artery wall (the tunica media) primarily consists of smooth muscle cells, which contract and relax, like our muscles, to create an elastic effect so that each time the heart pumps, the artery wall expands and constricts to allow pulses of blood to flow through. Hardening of the artery wall means this elasticity is lost and blood pressure increases in the artery. The subsequent narrowing of the artery reduces the ability of blood to flow to the intended tissues.
Hardening can occur for several reasons; calcium deposits can build up in the tunica media. Or a process called intimal hyperplasia can occur (please don’t worry too much about the jargon!) where smooth muscle cells multiply excessively and move towards the inner layer of the artery wall. ‘Intimal’ refers to the innermost layer of the artery – the intima, and ‘hyperplasia’ refers to the excess reproduction or multiplication of cells. Additionally the smooth muscle cells produce proteins such as collagen and elastic fibres further hardening and clogging up the artery.
But the main type of arteriosclerosis causing major problems in the human population, and primarily responsible for heart attacks and strokes, is atherosclerosis. It is a disease that takes decades to develop and inflict its potent consequences on us but by the time we know it’s happening, it is often too late. So what exactly is atherosclerosis? As you read the next part, watch this video which may help you visualise the disease (video created by 3FX medical animation inc.):
Just like the fatty sewage pipes, atherosclerosis begins at bends and branches of arteries. Blood pressure can be high in these regions, and the blood tends to slow down or swirl around causing the cells lining the inside of the artery (called endothelial cells) to become ‘activated’ setting off a chain of events. Firstly ‘lipids’ including cholesterol – particularly low density lipoproteins, more commonly known as ‘bad cholesterol’ - deposit in the artery wall in between the endothelial cells; hence why you should stay away from those pesky fast food outlets! But atherosclerosis is not simply a fatty plaque that blocks your artery. As these lipids slowly build up in the artery, our immune system is called to action by the active endothelial cells and sends in cells called macrophages to consume, break down and dispose of these lipids, and initially they are successful. But over time the amount of lipid building up can become excessive and overwhelm the macrophages, so these cells consume surplus lipid and become immobile, just like if you eat too much chocolate cake and feel so sick you can’t move! The macrophages eventually die and add to the material building up in the artery wall. There are many other types of immune cell that become involved and contribute to the problem but macrophages are the main protagonist (and incidentally the main cell of interest in my research!)
The artery tries to tackle this problem by expanding outwards to increase the diameter of the artery, and by moving smooth muscle cells from the wall to the surface of what is now a developing atherosclerotic plaque. The smooth muscle cells create a ‘cap’ at the surface separating blood flow from the plaque as exposure of dead cells to flowing blood can trigger the formation of a blood clot. Eventually the artery cannot expand any further and so the growing plaque begins to constrict blood flow. The growing plaque can be enough to obstruct blood flow. Narrowing of the artery also causes the flowing blood to exert force on the cap and weaken it eventually causing it to burst open or rupture. A blood clot will then form on the surface, which may or may not block blood flow in the artery. If blood flow is blocked in the coronary arteries supplying blood to heart muscle, a heart attack occurs and some of the heart muscle can die. Alternatively blocking blood flow to part of the brain, either by a blood clot or part of a plaque dislodging and blocking the small blood vessels in the brain, leads to a stroke.
So atherosclerosis is an extremely complex process with many different factors involved, hence why it is so difficult to treat. Research is vital to fully understand this disease and improve existing treatments. Much like cancer, which is so difficult to treat because cancer in each patient can be caused by a different mutation in a different gene, thus we cannot use a ‘one size fits all’ drug.
Now that you know what atherosclerosis is, I will explore how you can reduce your risk of suffering from a heart attack or stroke in my next post.
An annual sum of approximately £2.8 billion is spent on academic medical research in the UK – £1.2 billion of which is sourced from medical charities . Despite only being a fraction of the amount spent on medical research in the US, the UK is second only to the US in terms of research output, with more articles and citations per researcher than any other country . But how much research with a medical aim is actually converted into a benefit for patients? Is it all money well spent? These are the questions being asked as we endure an economic downturn, while patients seek the next miracle cure.
When it comes to investigating a medical problem, the mind-set of a scientist can be somewhat different to what a layperson might expect. They are often driven by their fascination in the mechanisms of disease. But often their sources of funding are either the government or charities relying on the generosity of members of the public. These sources award funding to researchers with the hope that they will make the next discovery or innovation to improve prevention, diagnosis or treatment of disease and ultimately save lives. One could, however, argue that extensive work is necessary to fully understand the problem before any steps towards translational research can be made. So are scientists doing enough to translate their findings to the clinic? And hence do they justify the funding they receive?
Perhaps herein lies a problem with the way scientific research is recognised. Scientists build their reputation on a myriad of publications, ideally in high impact factor journals, and the ability to attract large grants. Hence we often see publication of a research paper as the end point of a research project. The peer-review process is important to judge the quality of the study and whether its results and conclusions are reliable. Thus it is necessary to ensure the safety and efficacy of any potential therapeutics in question. Unfortunately, at times the peer-review system can be flawed, as journal editors prioritise studies with positive results, particularly on so-called “trendy topics,” such as the use of stem cells in regenerative medicine. This can lead to controversies such as the recent Nature publication claiming that exposing adult cells to an acidic environment converts them to 'totipotent' stem cells . Its credibility is now under investigation and a subsequent questionnaire given to stem cell researchers by New Scientist led to a small proportion of scientists admitting they had felt pressure from their peers to submit incomplete data for publication and even falsify data, which in some cases has been published despite the peer review process, although it must be emphasised that the proportion of scientists making these claims is extremely small . Negative data is often ignored even though it could be highly informative on the efficacy of a particular treatment or understanding the pathogenesis of disease. Hence researchers choose not to submit a paper showing negative data as they are resigned to believe it will never be accepted for publication. While initiatives such as the Journal for Negative Results in Biomedicine  aim to counteract this problem, they have yet to gain widespread recognition.
This sets a dangerous precedent for many reasons. Several groups may come up with the same idea that a particular protein may be detrimental in cancer for example. However if a group has already carried out a study, which showed no effect, the rest of the scientific community will never know. Thus other groups will waste time and resources on a study, which has already been performed, possibly many times over. What is of great concern is that therapies that have no beneficial effect in treating disease may still be produced and given to patients because studies showing a beneficial effect have been published while studies showing no benefit have not. Ben Goldacre brilliantly explains the publication bias of clinical trials in his recent TedMed talk . Publication bias has been extensively studied with regard to clinical trials but less attention has been paid to basic scientific studies, which experience the same kind of discrimination and whose results are the first step in producing potential therapies.
But with success in publishing comes a greater chance of success with grant applications, as having a good track record proves your ability to produce high quality science. Recently there has been a developing trend towards awarding larger grants to more prominent scientists over a longer period of time in an effort to inspire greater discoveries. But could such an initiative change scientists’ motivation towards obtaining larger amounts of funding rather than producing sound science that is ultimately beneficial to the public? A recent study in Canada suggests researchers receiving additional funding were not more productive . It appears that awarding smaller grants to more researchers boosts productivity.
The inability to translate biomedical research findings could be attributed to the increasing divide between researchers and clinicians, which is a relatively recent phenomenon. While clinicians performed early research, the emergence of molecular biology 40 years ago led to specialised research by biomedical scientists, who have greatly increased the understanding of disease in recent decades, but it appears few have meaningful collaborations with clinicians or industry. This is possibly due to reluctance among basic scientists to delve into the clinical situation while clinicians, whose time is occupied with patients, have difficulty not only performing research but also just keeping in touch with the latest literature, which is increasingly complex.
Fortunately this problem is being realised by more individuals in the scientific community. Funding organisations are making a concerted effort to encourage multi-disciplinary research enforcing collaborations between biomedical scientists, engineers and clinicians. The National Institutes of Health (NIH) in the US have created a translational research initiative, pumping funding into the creation of numerous Clinical and Translational Science Centres (CTSCs) across the country. These research centres are at the early stages of their development in many cases but have still yielded some positive signs thus far. Much of the research conducted in CTSCs is driven towards drug development and there have been many drug targets identified which have led to drug development and even the initiation of clinical trials for example against cancer, neurological diseases, and cardiac disorders (through the advancement of regenerative medicine). However it is not clear what proportion of research within CTSCs has been successful in achieving a translational output.
Similar efforts have been seen in the UK with the creation of specialist research centres such as the British Heart Foundation Centres of Research Excellence and MRC (Medical Research Council) UK Centre in Allergic Mechanisms of Asthma. These facilities provide scientists with state-of-the-art facilities, renewed sources of funding and a stronger platform to foster multi-disciplinary collaborations. There has been a strong initiative to bring academics closer to the clinical setting with the creation of the National Institute of Health Research (NIHR), acting as a bridge between basic research and the delivery of improvements to the clinic. The NIHR has several aims: funding research for the benefit of patients, such as public health research or the development of innovative medical technologies; increasing the reliability and open access to medical research literature to better inform patients, clinicians, and policy-makers in their decision making with regards to medical practice; and improving the healthcare infrastructure. Various teams have also been set up to facilitate partnerships with industry to develop pharmaceuticals, medical technologies, and improvements in the healthcare environment.
It is evident that the increasing need to translate basic scientific research to the clinical setting is being recognised by funding agencies and national healthcare institutions. The increase in funding and provision of modern research facilities is encouraging for the future of medicine. Scientific developments over the next decade will be the true testament of the success of current translational research programmes.
This post is an updated version (as of March 2014) of what was originally published on the Oxbridge Biotech Roundtable Review in July 2013.
 Association of Medical Research Charities (AMRC) http://www.amrc.org.uk/home/
 International Comparative Performance of the UK Research Base – 2011. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/32489/11-p123-international-comparative-performance-uk-research-base-2011.pdf
 Stem cell scientists reveal 'unethical' work pressures http://www.newscientist.com/article/dn25281-stem-cell-scientists-reveal-unethical-work-pressures.html#.Uzcltdxg42w
 Journal of Negative Results in Biomedicine http://www.jnrbm.com
 What doctors don’t know about the drugs they prescribe by Ben Goldacre, TedMed 2012. http://www.ted.com/talks/ben_goldacre_what_doctors_don_t_know_about_the_drugs_they_prescribe.html
 Big Science vs. Little Science: How Scientific Impact Scales with Funding, (2013), Jean-Michel Fortin, David J. Currie, PLOS One 8(6): e65263.
Dr. Anusha Seneviratne
My research is funded by the British Heart Foundation. To donate click sponsor me below.
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