Effects of exercise on cardiovascular mortality
Data from Mora et al. We also argue that any negative effects of autonomic dysfunction are amplified by concurrent endothelial dysfunction and, indeed, there is some evidence for direct and deleterious interactions between elevated sympathetic nervous system activity and NO function Hijmering et al. Vitamins for Healthy Veins. Comments 0 Please log in to add your comment. One of the most powerful predictors of who became hypertensive was the blood pressure response to acute sympathoexcitatory stress at baseline Matthews et al. They go to organs and other tissues to supply nutrients. However, less than half of the improvement in the risk for coronary heart disease could be attributed to improvements in traditional risk factors Fig.
Energy Demands of Cardio Exercise
There are various indices of autonomic function; however, none of them is perfect, and none is as simple as obtaining a blood test for cholesterol or glucose or simply measuring blood pressure with a cuff. Additionally, many widely studied or used markers of autonomic function are subject to some debate regarding their underlying mechanisms Eckberg, ; Karemaker, For example, renal noradrenaline spillover correlates well with muscle sympathetic nerve activity in resting humans Wallin et al.
In spite of some of these limitations, we believe that enough information is available to begin to ask whether autonomic dysfunction is in fact the missing risk factor that is altered by exercise, and how it might interact with other risk factors. This shows that reduced heart rate variability is a marker of poor outcomes in middle-aged patients at risk for cardiovascular disease.
In subsequent sections, we will argue that poor heart rate variability is related to increased vascular stiffness as a result of poor endothelial function and reduced baroreflex function. A, B, C and D reflect specific outcomes as follows: A, coronary heart disease; B, myocardial infarction; C, fatal coronary heart disease; and D, total mortality. Diabetic subjects with any marker of reduced heart rate variability had increased morbidity and mortality.
Data from Liao et al. In the Studies of left ventricular dysfunction SOLVD trial of asymptomatic subjects with left ventricular dysfunction, individuals with resting noradrenaline levels above the median had double or triple the all-cause mortality, cardiovascular mortality, hospitalization for development of congestive heart failure and development of myocardial infarction or angina Benedict et al.
Thus, evidence of sympathetic activation in these patients appeared to be at best a poor prognostic sign and was probably a major contributor to their poor outcomes. In the Coronary artery risk development in young adults CARDIA study, young healthy subjects were followed for 15 years in an effort to understand factors that might predispose some individuals to develop hypertension.
One of the most powerful predictors of who became hypertensive was the blood pressure response to acute sympathoexcitatory stress at baseline Matthews et al. Individuals in the quartile with the largest increase in blood pressure developed hypertension at about five times the rate of individuals in the lowest quartile. This again suggests that there is an important link between the autonomic nervous system and cardiovascular risk factors in humans.
Less is known about how baseline levels of sympathetic activity interact with lipid and metabolic risk factors. Given the potent vasoconstricting effects of increased sympathetic traffic, how is normotension maintained in subjects with high sympathetic activity?
These two factors limit the blood pressure-raising effects of the high sympathetic activity in these subjects. In terms of hypertensive subjects, there is evidence both for and against a relationship between sympathetic activity and blood pressure.
By contrast, blood pressure typically rises with age and becomes more closely linked to sympathetic activity after the age of 40 Narkiewicz et al. Therefore, we have at best a modest relationship between increased baseline sympathetic activity and blood pressure along with limited data on how the sympathetic nervous system interacts with metabolic risk factors such as lipids and diabetes. However, there is at least a hint of what might be happening during ageing, especially in female subjects.
In an effort to understand how reduced endothelial function in combination with high MSNA might influence the cardiovascular system, we performed a systemic infusion of the nitric oxide synthase inhibitor N G -monomethyl- l -arginine l -NMMA and measured the effects on blood pressure and systemic haemodynamics in a group of healthy young men with widely varying baseline MSNA Charkoudian et al.
The idea was that there was at least some evidence that NO levels are higher in individuals with high baseline MSNA and that this NO buffers the blood pressure-raising effects of the high sympathetic activity.
While the 2—7 mmHg differences noted in the dose—response curves in Fig. Low- and moderate-dose nitric oxide synthase inhibition causes larger increases in blood pressure in the subset of subjects with high baseline levels of MSNA.
Data from Charkoudian et al. Based on epidemiological evidence, and observations similar to those outlined above, we propose that high levels of sympathetic activity will interact negatively with traditional risk factors in middle-aged subjects. This is likely to be made worse by weight gain, which has been shown to dramatically increase baseline levels of MSNA Fig. This means that as individuals enter their 40s and 50s, those with high MSNA or who those gain weight especially visceral fat may be at increased risk.
These individuals will also be likely to have reduced vasodilator function as a result of endothelial dysfunction associated with the metabolic syndrome, sedentary lifestyle and high levels of oxidative stress that limit the ability of NO to cause vasodilatation. As noted previously, almost all of the major cardiovascular risk factors are associated with reduced endothelial function. In addition to reduced endothelial function, there might be increased circulating vasoconstrictor substances and increased vasoconstrictor responsiveness that will further contribute to vascular dysfunction as middle-aged individuals drift into the cardiovascular disease phenotype Nielsen et al.
Data from Gentile et al. All of these factors together then contribute to a vicious cycle of high sympathetic outflow, reduced vasodilator function and cardiovascular disease that would self amplify over time Fig.
In the endurance exercise-trained state or with high levels of physical activity, endothelial function and parasympathetic tone augmented heart rate variability are enhanced. Large conducting vessels remain compliant, and the effects of high sympathetic outflow, when present, are buffered. These positive interactions may account for observations showing that exercise is more protective against cardiovascular risk than predicted by its effects on traditional risk factors.
With physical inactivity, there is a loss of endothelial function during middle age, a potential accumulation of risk factors, and increased vessel stiffness. These effects of physical inactivity permit the effects of high sympathetic tone to be more fully expressed while parasympathetic tone is progressively lost. These negative interactions may account for observations showing that physical inactivity is a more potent cardiovascular risk factor than widely appreciated.
There is strong evidence to suggest that exercise training can keep the autonomic nervous system healthy. For example, exercise is protective against age-related reductions in baroreflex function in humans Monahan et al.
In this context, endurance-trained older subjects have baroreflex function that is similar to moderately active young subjects. This improvement in baroreflex function, which on a population basis is likely to manifest as improved heart rate variability, could be the result of both greater blood vessel distensibility and better signal transduction in barosensitive areas of the carotid sinus and aortic arch, or it could also represent improved or maintained central integration in the brainstem cardiovascular centres.
However, the key point is that moderate exercise, endurance training and high levels of physical activity are highly protective against age-associated baroreflex dysfunction.
Finally, exercise training can clearly reduce muscle sympathetic nerve activity in patients with congestive heart failure Fraga et al. Since exercise is also protective against weight gain and visceral obesity, it is likely to blunt the age-associated rise in MSNA. There are also important confirmatory and mechanistic data from animal studies to show that exercise training limits sympathoexcitation and favours sympathoinhibition in the brainstem cardiovascular centres. For example, Mueller has shown that the increases in arterial pressure and lumbar sympathetic nerve activity are blunted when bicuculline is injected into the rostral ventrolateral medulla.
Additionally, the reductions in heart rate during the pressor response are greater in exercise-trained animals. These data imply strong central nervous system effects of exercise on the autonomic nervous system that favour sympathoinhibition and enhanced vagal outflow.
In summary, we have tried to be provocative in this paper and used an impressionistic approach to integrate key data about exercise and the risk factor gap in cardiovascular disease. In this context, autonomic dysfunction is clearly a marker of poor outcomes in large populations of middle-aged humans. Autonomic dysfunction, including sympathetic activation, is also a marker of bad outcomes in patients with various risk factors for cardiovascular disease.
We also argue that any negative effects of autonomic dysfunction are amplified by concurrent endothelial dysfunction and, indeed, there is some evidence for direct and deleterious interactions between elevated sympathetic nervous system activity and NO function Hijmering et al. In the context of the above ideas, we believe there is a vicious cycle between autonomic dysfunction and endothelial dysfunction that can largely be prevented or ameliorated by exercise training.
We also believe that this vicious cycle explains why exercise is more protective than it should be based on its effects on traditional risk factors for cardiovascular disease.
Therefore, our global hypothesis is that the risk factor gap can be explained by the following effects of exercise and physical activity on the cardiovascular system. National Center for Biotechnology Information , U. Journal List J Physiol v. Published online Sep 7. This review was presented at The Journal of Physiology Symposium on Physiological regulation linked with physical activity and health , which took place at the 36th International Congress of Physiological Sciences in Kyoto, Japan on 31 July It was commissioned by the Editorial Board and reflects the views of the authors.
Received Jul 28; Accepted Aug This article has been cited by other articles in PMC. Abstract In humans, exercise training and moderate to high levels of physical activity are protective against cardiovascular disease.
Along the lines outlined above, we will briefly review the following topics. We will discuss the impact of exercise on morbidity and mortality. We will compare exercise with traditional drug-based and other interventions that alter risk factors and improve outcomes.
We will then ask questions about what might explain the risk factor gap and make arguments that exercise and physical activity improve endothelial function and also preserve or improve autonomic function. We will conclude by suggesting that a vicious cycle that promotes cardiovascular disease exists between inactivity and endothelial dysfunction that can be prevented or ameliorated by exercise. Open in a separate window. Differences in sudden death cardiovascular mortality in physically active London bus conductors vs.
How does exercise compare with other interventions that reduce cardiovascular disease? What about NO and endothelial function? Therefore, what can we say about the exercise risk factor gap? Exercise is roughly as effective as statins in preventing cardiovascular disease. The changes in traditional risk factors associated with exercise training are modest compared with the impact of medications, with the possible exception of pre- diabetes.
Physical activity and exercise can have a profound influence on either preserving endothelial function in the face of various risk factors and aging or improving it when used as a therapeutic intervention. However, is the improvement in endothelial function alone enough to explain the exercise effect? Or is there something else? Does the autonomic nervous system contribute to the risk factor gap? The endothelial cells lining the arteries are active in maintaining normal blood vessel tone—the tension in the walls of arteries—and the chemical, growth and immunological processes that occur in the blood vessels.
Smooth muscle cells in the walls of the arteries also regulate blood pressure and contribute to vascular function Figure 1. In vascular disease, atherosclerosis causes the artery walls to thicken and narrow, making the blood vessels susceptible to blockage and decreasing their flexibility.
If platelets, small blood cells that trigger blood clotting, form a clot where the blood vessel narrows or branches, blood flow is reduced or prevented.
If a blood vessel is blocked, a heart attack or stroke follows. With reduced circulation, blood flow in the veins leading to the heart may back up, causing fluid to build up in other parts of the body.
Figure 2 shows how plaque builds up in a normal artery to narrow it and decrease blood flow. The atherosclerosis disease process includes the binding of cholesterol-rich lipoproteins in the inner lining of the artery endothelium , inflammation of the artery, formation of foam cells that lead to plaque formation and calcification of the arterial wall. Atherosclerosis is generally accepted as an inflammatory disease.
Vascular disease that affects the heart is commonly known as coronary heart disease, that affecting the brain as cerebrovascular disease and that affecting the limbs principally the legs as peripheral vascular disease.
What health conditions are associated with vascular disease? Many vascular disorders are associated with the atherosclerotic buildup of plaque, which is formed from cholesterol, fat, calcium and other substances in the blood. Atherosclerosis is by far the most common cause of vascular disease. The long-held view underlying vascular disease risk told us that consumption of total fat, saturated fat and dietary cholesterol raised total and low-density lipoprotein cholesterol bad cholesterol levels in the blood, thereby causing cardiovascular disease.
But the famous Framingham Heart Study showed there are many factors affecting the chance of developing heart disease, stroke and vascular disease—including smoking, stress, unhealthy diet, lack of exercise, high blood pressure, high blood cholesterol, low levels of high-density lipoprotein cholesterol good cholesterol , diabetes, advancing age, being overweight, family history of premature heart disease, high blood triglycerides and others.
Dietary habits contribute to many of these factors and can be effective in reducing their contribution to vascular disease. In particular, the quality of fat we eat, including the omega-3 fatty acids from fish, can reduce the impact of several of these factors. Early observations on diet and vascular disease. Over two decades ago, investigators reported that deaths from coronary heart disease were more than 50 percent lower among people who consumed at least 30 grams of fish per day than among those who did not eat fish.
Even before that, it was known that native Arctic populations, whose diet was rich in sea animals, were free of heart disease, thanks in part to the long-chain omega-3 fatty acids omega-3s they consumed.
Population studies and clinical trials indicated that dietary fish oils favorably modified various risk factors and had the potential to reduce vascular disease progression, the chance of dying from heart disease and the possibility of sudden cardiac death.
In elderly individuals, eating tuna or other broiled or baked fish was associated with a lower chance of experiencing ischemic stroke. Other studies found that the consumption of omega-3s reduced the chance of vascular disease, heart attack, inflammation, heart arrhythmias, sudden cardiac death, atherosclerosis and ischemic, but not hemorrhagic, stroke. In the secondary prevention of cardiovascular disease—that is, prevention following the occurrence of an initial coronary incident—studies have largely concluded that the consumption of fish or omega-3s significantly reduces the chance of another heart attack or major cardiac event.
The American Heart Association and many other professional groups have recommended the consumption of at least two fish meals a week to reduce the chance of heart disease. They note, too, that the plant-based omega-3 alpha-linolenic acid has only weak effects on heart disease and does not affect as many factors as the omega-3s in seafood.
The precise mechanisms for how omega-3s affect vascular disease are becoming better understood. Long-chain omega-3s are key components of cell membranes where they affect the communication within and between cells. By partially replacing their corresponding omega-6 counterparts in membranes, omega-3s can dampen the effect of omega-6s on inflammation and heart arrhythmias.
In vascular endothelial cells, omega-3s have numerous anti-inflammatory effects, especially at the sites where plaque accumulates.
Omega-3 fatty acids affect all stages of vascular disease, including alterations in blood lipids and lipoproteins, blood pressure, platelet adhesiveness, relaxation of the arteries which eases blood flow and lowers blood pressure , changes in the electrical properties of the heart and alterations in gene expression.