Exercise Benefits in Cardiovascular Disease: New Findings
I know that I’m preaching to the converted here, but despite the knowledge that exercise is proven to reduce your risk of cardiovascular disease (CVD) as well as numerous other health benefits, physical inactivity remains highly prevalent worldwide. In the UK alone, around 39% (20 million people) fail to meet the minimum requirements for physical activity each week (Approximately 22 mins per day of moderate activity – such as brisk walking, plus 2 x strength sessions).
The British Heart Foundation (BHF) estimates that the average man in the UK spends the equivalent of 78 days each year sitting (74 for women) and of that time almost 30 hours a week are spent watching TV – according to Ofcom. Indeed Physical inactivity is now recognised by Kohl et al, (2012) as the fourth leading course of death worldwide, just behind prescription drugs, according to former leading Cochrane researcher (Peter C Gotzsche, 2016).
This current trend towards physical inactivity seems to begin in early adolescence (13-15 years) and leads to an increased risk of cardio-metabolic disorders later in life. Most large epidemiological studies demonstrate an inverse association with physical activity and CVD risk (in other words the more exercise you engage in – the lower the risk of adverse CVD). Also, higher levels of cardiorespiratory fitness (CRF) are strongly associated with good metabolic health, low levels of chronic disease and lower risk of premature death.
Regular physical activity is associated with well-known reductions in cardiovascular risk factors: American College of Sports Medicine (ACSM) Guidelines (10th Edition 2018)
- Reduction in systolic / diastolic blood pressure
- Increase HDL (good) cholesterol
- Decrease in Triglycerides (ciculating fats)
- Reduction in visceral (intra-abdominal) fat
- Reduced Insulin needs, improved insulin sensitivity of muscles
- Improved glucose tolerance (handling of glucose load by the body)
- Reduced platelet adhesiveness and aggregation (stickiness of blood platelets / clotting)
- Reduced inflammation
But perhaps more relevant to our community, analysis of data from UK Cardiac Rehab (CR) programmes shows that the current uptake for CR is only around 47% falling short of the 65% national targets (BHF, 2017) It is worth pointing out however that UK CR uptake far exceeds all other European countries (mean of 30%). So whilst we accept that you can’t outrun a bad diet, (Malhotra, 2017), and exercise alone cannot resolve the current twin epidemics of obesity and type 2 diabetes we currently face, it remains a powerful tool in preventing and improving cardiovascular disease outcomes. In a large meta-analysis that included 8440 patients in 32 trials, exercise training as part of cardiac rehabilitation programmes was associated with a 31% reduction in the mortality (death) rate in patients with stable CAD/myocardial infarction. (Joliffe et al, 2002, Cochrane library).
In some cases exercise may be more effective than drug therapy or cardiologic interventions. A 2004 randomised study published in the American Heart Association’s journal Circulation, compared the effects of a standard percutaneous coronary intervention (PCI with Stent) versus a 12-month programme of regular exercise (20 mins cycling per day) in 101 male patients aged ≤ 70 years patients with stable coronary artery disease (CAD). The researchers were interested in changes in clinical symptoms such as angina upon exercise, myocardial perfusion (flow of blood through the heart & vessels), cost-effectiveness, and worsening of cardiac disease or death.
The results demonstrated that the exercise training group attained superior event-free survival – in other words, they lived longer and suffered less cardiovascular events, in addition, exercise capacity improved at lower costs, notably owing to reduced rehospitalisation’s and repeat revascularizations.
What does this mean? Exercise training alone can be a safer, more effective strategy than cardiology interventions in patients with stable coronary artery disease (CAD) and retards the progression of CAD over time without the potential risks of undergoing an invasive medical procedure and subsequent restenosis of a stented artery. However, let’s not forget that there is no substitute for the acute heart attack patient that requires emergency lifesaving PCI / stenting.
We will now explore some new findings from the Exercise & Health Sciences. Much of the content of this article I have summarised from a comprehensive review on “Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors”. Faculty of Sports / Health Sciences, Universidad Europea de Madrid, Spain recently published (Carmen Fiuza-Luces et al, 2018).
- Regular exercise induces anti-atherogenic adaptations in vascular function and
structure, irrespective of traditional cardiovascular disease (CVD) risk factors.
- Regular exercise training improves cardiac parasympathetic regulation, thereby
conferring protection against malignant arrhythmias.
- Muscle-derived myokines are responsible for many of the beneficial effects of
exercise, particularly by promoting a healthy anti-inflammatory milieu.
- Exercise can improve myocardial regeneration capacity, in part through stimulation
of circulating angiogenic cells.
- Loss of muscle strength and mass is a forgotten hallmark of, and in fact, a risk factor
for CVD that can be largely reversed with resistance (strength) training, including
in elderly individuals.
- Regular exercise can promote a healthy gut microbiota while protecting the
permeability and function of the gut barrier.
Anti-atherogenic Vascular Adaptations
Vascular structure and function can be improved as a result of the repetitive shear stresses from exercise placed upon the walls of arteries leading to adaptations that reduce build-up of atherosclerosis (plaque).
Endothelial (inner lining of artery wall) dysfunction has an important role in the development of atherosclerosis (plaque in artery) including increased risk of plaque rupture that causes sudden heart attacks. Statins are typically prescribed post MI (heart attack) to help restore normal vascular endothelial function, but exercise can also provide similar benefits. In a 2015 meta-analysis aerobic exercise intensity was shown to improve vascular endothelial function in a dose-dependent manner (Ashor et al, 2015). The “shear stress” induced by moderate intensity exercise stimulates vasodilatation (widening of vessel) via an increase in a powerful substance called Nitric Oxide (NO).
Studies show that regular exercise training is associated with increased coronary artery size and capacity to dilate more effectively (Nguyen et al, 2011) Remodelling of artery walls in response to exercise training – including a decrease in wall thickness and increases in luminal diameter, creates a reserve capacity so that even when atherosclerosis narrows a vessel – blood flow is not limited.
Regardless of blood cholesterol levels, exercise training increases the collagen and elastin content of the atherosclerotic plaque. The advantage of a thicker, fibrous coronary plaque is that it is less likely to suddenly rupture with devastating consequences (Shimada et al, 2011) Elastin makes the blood vessels more flexible / better able to expand and contract as required during stress or physical exertion.
Collateral Blood Vessels
Aerobic exercise training increases the development of collateral (accessory) blood vessels which may help bypass a clot or lessen the extent of damage to the myocardium (heart muscle) incurred following a heart attack. Another important benefit of reduced vascular stiffness as we age is that vital organs are protected by good blood flow – reducing the possibility of oxygen deprived (Ischaemic) events potentially damaging the brain, kidneys and indeed the heart – reducing the risk of heart failure in later life (Seals et al, 2008)
Autonomic (Nervous System) Balance
A leading cause of sudden cardiac death in patients with coronary artery disease is “Ventricular Fibrillation” or VF. This occurs when the hearts electrical system suddenly loses its natural rhythm and becomes chaotic and is no longer able to pump blood out and maintain adequate perfusion of vital organs or indeed its own coronary circulation. Beyond improvements to blood flow to the heart, regular exercise protects against life-threatening arrhythmias (irregular heart rhythms). Heart Rate Variability (HRV) is a measure of balance of the autonomic nervous system which includes the sympathetic and parasympathetic divisions. Low HRV is associated impaired cardiovascular health and increased mortality in patients following heart attacks or in those with Heart failure. Exercise improves the “calming” effect of the parasympathetic division, via output from the vagus nerve and reducing the “excitable” sympathetic division – thus protecting against fatal arrhythmias (Villafaina et al, 2017).
Chronic systemic inflammation is now a recognised CVD risk factor as highlighted by Dr Aseem Malhotra’s BJSM review (2017) discussed in the previous edition of our magazine. Messenger cells known as “cytokines” that are pro-inflammatory have been associated with increases in risk of coronary heart disease and type 2 diabetes. Exercise training produces an anti-inflammatory effect, lowering markers of inflammation such as C-Reactive protein (CRP).
A less known function of skeletal muscle is its inherent endocrine capacity, able to release substances known as myokines into the bloodstream during muscle contractions. These myokines are able to exert a myriad of local and systemic (whole body) benefits – including decreased inflammation and insulin resistance, both of which are important in protecting arteries against progression of atherosclerosis, (narrowing of arteries) and helping to stabilize plaques and thus preventing sudden rupture causing a heart attack.
Irisin is another novel type of myokine that appears to protect against development of CVD and is found in larger amounts in the blood of individuals that engage in regular aerobic exercise – such as brisk walking or running. Irisin has also been found present in twice the amount of centenarians (people that live to 100 yrs) compared with young adults experiencing early heart attacks. Emanuele et al (2014). Irisin also helps to dilate blood vessels via a nitric oxide mediated mechanism, protecting the endothelium (inner artery lining) from injury.
Some anabolic (building up) myokines such as IL-4, IL-6, IL-7 are involved in muscle growth and maintenance. Given that sarcopenia (wasting of muscle mass) is commonly associated with CVD especially in the elderly and is often associated with higher levels of visceral fat (another CVD risk factor) it is important to consider the role of resistance exercise. Low muscle strength is associated with CVD development and mortality (death). For example a measure of baseline handgrip strength was associated with CVD events and hospitalization in patients (average age 64 yrs) as well as diabetes (Hamaski et al, 2017).
The strength of skeletal muscle is largely dependent on it mass and therefore low muscle mass is associated with coronary artery calcification in “healthy” middle-aged adults and with increased CVD mortality in individuals with known CVD risk factors ≥65 years (Spahillari et al, 2016). Conversely having larger biceps is an independent predictor of survival in patients aged ≥ 70 years. Also studies have shown higher muscle mass may protect against ischaemic stroke (Minn et al, 2017).
Accelerated sarcopenia is prevalent among patients with Heart Failure (HFpEF) and can promote the development of this condition via cardiac dysfunction and remodelling (Yamamoto et al, 2017). Another downside to sarcopenia is myokine dysregulation resulting in systemic inflammation which may induce microvascular coronary artery endothelial inflammation and reduce nitric oxide (potent vasodilator) bio-availability.
Glucose Intolerance and Insulin Resistance
As skeletal muscle acts as a reservoir for dietary glucose disposal, loss of muscle tissue contributes to both insulin resistance (when the cells become resistant to the effects of the hormone insulin – that is released by the pancreas in response to rising blood glucose from consumption of dietary carbohydrates and sugar) and abnormal blood glucose levels. Both insulin resistance and hyperglycaemia are associated with endothelial and mitochondrial (energy production units within cells) dysfunction and with an enlarged heart (LV Hypertrophy).
What is the relevance?
A decline in muscle mass and function in an ageing population with CVD (worse in diabetics) is associated with early disability, frailty, increase risk of falls, dependence on nursing homes etc. I have mentioned this before in previous issues of the Take Heart Magazine but feel it’s important to reiterate that the preservation of functional capacity (performing of tasks and activities required for daily living) is an essential component of weekly physical activities.
Despite its incredible therapeutic role, resistance or strength training remains largely ignored by both healthcare providers and patients that are perhaps unaware of its benefits. It is especially important for patients with diabetes, coronary artery disease, and following a stroke as meta-analysis shows (Mehta et al, 2012). Resistance training can be commenced even during the 90’s or near end of life and result in significant gains in strength. Other benefits associated with increase muscle strength include; a reduction in visceral fat (abdominal fat), decreased blood pressure and triglycerides. Decreased body fat and increased muscle mass is also associated with improvements of resting metabolic rate, which will help maintain healthy metabolic function and weight (Artero et al, 2012)
Effects of exercise on the Gut
Recent findings are beginning to discover the importance of the role of the gut microbiota in health and disease including CVD. Although the research is in its infancy, an unhealthy gut microbiota may worsen CVD via a number of mechanisms including; an increased production of the microbial metabolite TMAO, endotoxaemia (increased Lipopolysaccharides in the blood) and relocation to carotid artery plaques, increased bodyfat, decreased HDL cholesterol and increased blood pressure. Yang et al (2017). The good news is that independent of diet, regular exercise can modulate the gut microbiota towards a healthy phenotype. Possible mechanisms that result in improved general health include an increase in healthy bacterial diversity, increasing faecal concentrations of short chain fatty acids such as butyrate (associated with good gut health) and increase in the amount of healthy gut bacteria, as well as a decrease in microorganisms associated with obesity and metabolic diseases. Yang et al (2017) Endotoxins leaked into the circulation have been shown to increase systemic inflammation which may begin the process of atherosclerosis and may be an important factor in the development of type 2 diabetes and metabolic syndrome (Kallio et al, 2015). In summary exercise can improve a healthy gut microbiota whilst protecting the intestinal barrier independent of diet.
As I have elucidated to before, regular physical activity / structured exercise induces a myriad of physiological adaptations within the body that benefits human cardiovascular health either directly or indirectly. Many of these benefits appear to be independent of traditional risk factors for CVD such as cholesterol, glucose levels, blood pressure and obesity. The fascinating discovery of the powerful effects of skeletal muscle secreting myokines opens up a milieu of additional cardiovascular benefits not understood previously. But perhaps most important is the consideration that, compared with most drugs, exercise is largely free of adverse effects, and its benefits are dependent on the dose and intensity. It is a timely reminder that Exercise is Medicine in the management of cardiovascular disease.