Cardiovascular Effects and Benefits of Exercise

Matthew A. Nystoriak1, Aruni Bhatnagar1
1Division of Cardiovascular Medicine, Department of Medicine, Diabetes and Obesity Center, Institute of Molecular Cardiology, University of Louisville, Louisville, KY, United States

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2015, Underlying Cause of Death 1999-2013 on CDC WONDER Online Database, Released 2015. Data are From the Multiple Cause of Death Files, 1999-2013, as Compiled From Data Provided by the 57 Vital Statistics Jurisdictions Through the Vital Statistics Cooperative Program

Benjamin, 2017, Heart disease and stroke statistics-2017 update: a report from the American Heart Association, Circulation, 135, e146, 10.1161/CIR.0000000000000485

Roth, 2015, Demographic and epidemiologic drivers of global cardiovascular mortality, N Engl J Med., 372, 1333, 10.1056/NEJMoa1406656

Paffenbarger, 1986, Physical activity, all-cause mortality, and longevity of college alumni, N Engl J Med., 314, 605, 10.1056/NEJM198603063141003

Blair, 1996, Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women, JAMA, 276, 205, 10.1001/jama.1996.03540030039029

Stevens, 2002, Fitness and fatness as predictors of mortality from all causes and from cardiovascular disease in men and women in the lipid research clinics study, Am J Epidemiol., 156, 832, 10.1093/aje/kwf114

Hu, 2004, Adiposity as compared with physical activity in predicting mortality among women, N Engl J Med., 351, 2694, 10.1056/NEJMoa042135

Vella, 2017, Physical activity and adiposity-related inflammation: the MESA, Med Sci Sports Exerc., 49, 915, 10.1249/MSS.0000000000001179

Florido, 2018, Six-year changes in physical activity and the risk of incident heart failure: ARIC study, Circulation, 137, 2142, 10.1161/CIRCULATIONAHA.117.030226

Moholdt, 2018, Sustained physical activity, not weight loss, associated with improved survival in coronary heart disease, J Am Coll Cardiol., 71, 1094, 10.1016/j.jacc.2018.01.011

Caspersen, 1985, Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research, Public Health Rep., 100, 126

Haskell, 1984, The influence of exercise on the concentrations of triglyceride and cholesterol in human plasma, Exerc Sport Sci Rev., 12, 205, 10.1249/00003677-198401000-00009

Fuster, 1996, 27th Bethesda Conference: matching the intensity of risk factor management with the hazard for coronary disease events. Task Force 1. Pathogenesis of coronary disease: the biologic role of risk factors, J Am Coll Cardiol., 27, 964, 10.1016/0735-1097(96)00014-9

Leon, 2001, Response of blood lipids to exercise training alone or combined with dietary intervention, Med Sci Sports Exerc., 33, S528, 10.1097/00005768-200106001-00021

Kraus, 2002, Effects of the amount and intensity of exercise on plasma lipoproteins, N Engl J Med., 347, 1483, 10.1056/NEJMoa020194

Gordon, 1977, High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study, Am J Med., 62, 707, 10.1016/0002-9343(77)90874-9

Assmann, 1992, Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience). Prospective Cardiovascular Munster study, Am J Cardiol., 70, 733, 10.1016/0002-9149(92)90550-I

Schwartz, 2012, Effects of dalcetrapib in patients with a recent acute coronary syndrome, N Engl J Med., 367, 2089, 10.1056/NEJMoa1206797

Group, 2014, Effects of extended-release niacin with laropiprant in high-risk patients, N Engl J Med., 371, 203, 10.1056/NEJMoa1300955

Du, 2015, HDL particle size is a critical determinant of ABCA1-mediated macrophage cellular cholesterol export, Circ Res., 116, 1133, 10.1161/CIRCRESAHA.116.305485

Sarzynski, 2018, Effects of increasing exercise intensity and dose on multiple measures of HDL (High-Density Lipoprotein) function, Arterioscler Thromb Vasc Biol., 38, 943, 10.1161/ATVBAHA.117.310307

Lee, 1997, Physical activity, physical fitness and longevity, Aging, 9, 2, 10.1007/BF03340123

Sesso, 2000, Physical activity and coronary heart disease in men: the Harvard Alumni Health Study, Circulation, 102, 975, 10.1161/01.CIR.102.9.975

Blair, 2001, Physical fitness and activity as separate heart disease risk factors: a meta-analysis, Med Sci Sports Exerc., 33, 762, 10.1097/00005768-200105000-00013

Thompson, 2003, Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity), Circulation, 107, 3109, 10.1161/01.CIR.0000075572.40158.77

Hambrecht, 1993, Various intensities of leisure time physical activity in patients with coronary artery disease: effects on cardiorespiratory fitness and progression of coronary atherosclerotic lesions, J Am Coll Cardiol., 22, 468, 10.1016/0735-1097(93)90051-2

Hambrecht, 2003, Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase, Circulation, 107, 3152, 10.1161/01.CIR.0000074229.93804.5C

Pynn, 2004, Exercise training reduces neointimal growth and stabilizes vascular lesions developing after injury in apolipoprotein e-deficient mice, Circulation, 109, 386, 10.1161/01.CIR.0000109500.03050.7C

Laufs, 2005, Physical inactivity increases oxidative stress, endothelial dysfunction, and atherosclerosis, Arterioscler Thromb Vasc Biol., 25, 809, 10.1161/01.ATV.0000158311.24443.af

Matsumoto, 2010, Regular exercise training prevents aortic valve disease in low-density lipoprotein-receptor-deficient mice, Circulation, 121, 759, 10.1161/CIRCULATIONAHA.109.892224

Ginsberg, 2000, Insulin resistance and cardiovascular disease, J Clin Invest., 106, 453, 10.1172/JCI10762

Lewis, 1997, Fatty acid regulation of very low density lipoprotein production, Curr Opin Lipidol., 8, 146, 10.1097/00041433-199706000-00004

Borggreve, 2003, Alterations in high-density lipoprotein metabolism and reverse cholesterol transport in insulin resistance and type 2 diabetes mellitus: role of lipolytic enzymes, lecithin:cholesterol acyltransferase and lipid transfer proteins, Eur J Clin Invest., 33, 1051, 10.1111/j.1365-2362.2003.01263.x

Steinberg, 1994, Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release, J Clin Invest., 94, 1172, 10.1172/JCI117433

Zeng, 1996, Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells, J Clin Invest., 98, 894, 10.1172/JCI118871

Potenza, 2005, Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production, Am J Physiol Heart Circ Physiol., 289, H813, 10.1152/ajpheart.00092.2005

Marasciulo, 2006, Endothelin-1: the yin and yang on vascular function, Curr Med Chem., 13, 1655, 10.2174/092986706777441968

Beckman, 2002, Diabetes and atherosclerosis: epidemiology, pathophysiology, and management, JAMA, 287, 2570, 10.1001/jama.287.19.2570

Wang, 2003, Insulin affects vascular smooth muscle cell phenotype and migration via distinct signaling pathways, Diabetes, 52, 2562, 10.2337/diabetes.52.10.2562

Schleicher, 1997, Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging, J Clin Invest., 99, 457, 10.1172/JCI119180

Sell, 2012, Molecular basis of arterial stiffening: role of glycation - a mini-review, Gerontology, 58, 227, 10.1159/000334668

Wallberg-Henriksson, 1982, Increased peripheral insulin sensitivity and muscle mitochondrial enzymes but unchanged blood glucose control in type I diabetics after physical training, Diabetes, 31, 1044, 10.2337/diacare.31.12.1044

Trovati, 1984, Influence of physical training on blood glucose control, glucose tolerance, insulin secretion, and insulin action in non-insulin-dependent diabetic patients, Diabetes Care, 7, 416, 10.2337/diacare.7.5.416

Koivisto, 1986, Physical training and insulin sensitivity, Diabetes Metab Rev, 1, 445, 10.1002/dmr.5610010407

Newsom, 2013, A single session of low-intensity exercise is sufficient to enhance insulin sensitivity into the next day in obese adults, Diabetes Care, 36, 2516, 10.2337/dc12-2606

Richter, 1982, Muscle glucose metabolism following exercise in the rat: increased sensitivity to insulin, J Clin Invest., 69, 785, 10.1172/JCI110517

Craig, 1987, Adipocyte insulin resistance: effects of aging, obesity, exercise, and food restriction, J Appl Physiol., 62, 95, 10.1152/jappl.1987.62.1.95

Zheng, 2015, Vascular function, insulin action, and exercise: an intricate interplay, Trends Endocrinol Metab., 26, 297, 10.1016/j.tem.2015.02.002

Olver, 2017, A chronic physical activity treatment in obese rats normalizes the contributions of ET-1 and NO to insulin-mediated posterior cerebral artery vasodilation, J Appl Physiol., 122, 1040, 10.1152/japplphysiol.00811.2016

Kim, 1995, Effects of endurance training on gene expression of insulin signal transduction pathway, Biochem Biophys Res Commun., 210, 766, 10.1006/bbrc.1995.1725

Houmard, 1999, Effect of short-term exercise training on insulin-stimulated PI 3-kinase activity in human skeletal muscle, Am J Physiol., 277, E1055, 10.1152/ajpendo.1999.277.6.E1055

Kirwan, 2000, Regular exercise enhances insulin activation of IRS-1-associated PI3-kinase in human skeletal muscle, J Appl Physiol, 88, 797, 10.1152/jappl.2000.88.2.797

Richter, 1989, Effect of exercise on insulin action in human skeletal muscle, J Appl Physiol., 66, 876, 10.1152/jappl.1989.66.2.876

Goodyear, 1990, Contractile activity increases plasma membrane glucose transporters in absence of insulin, Am J Physiol., 258, E667, 10.1152/ajpendo.1990.258.4.E667

Gao, 1994, Additive effect of contractions and insulin on GLUT-4 translocation into the sarcolemma, J Appl Physiol., 77, 1597, 10.1152/jappl.1994.77.4.1597

Hotamisligil, 1994, Tumor necrosis factor alpha inhibits signaling from the insulin receptor, Proc Natl Acad Sci USA., 91, 4854, 10.1073/pnas.91.11.4854

del Aguila, 1999, TNF-alpha impairs insulin signaling and insulin stimulation of glucose uptake in C2C12 muscle cells, Am J Physiol., 276, E849

Del Aguila, 2000, Muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase in human skeletal muscle, Am J Physiol Endocrinol Metab., 279, E206, 10.1152/ajpendo.2000.279.1.E206

Kirwan, 2003, Insulin signalling, exercise and cellular integrity, Biochem Soc Trans., 31, 1281, 10.1042/bst0311281

Shepherd, 1987, Circulatory response to exercise in health, Circulation, 76, VI3

Fagard, 2001, Exercise characteristics and the blood pressure response to dynamic physical training, Med Sci Sports Exerc., 33, S493, 10.1097/00005768-200106001-00018

Hardy, 2015, Reducing the blood pressure-related burden of cardiovascular disease: impact of achievable improvements in blood pressure prevention and control, J Am Heart Assoc., 4, e002276, 10.1161/JAHA.115.002276

Cox, 1996, Exercise and weight control in sedentary overweight men: effects on clinic and ambulatory blood pressure, J Hypertens., 14, 779, 10.1097/00004872-199606000-00015

Bacon, 2004, Effects of exercise, diet and weight loss on high blood pressure, Sports Med., 34, 307, 10.2165/00007256-200434050-00003

Fagard, 2006, Exercise is good for your blood pressure: effects of endurance training and resistance training, Clin Exp Pharmacol Physiol., 33, 853, 10.1111/j.1440-1681.2006.04453.x

Niebauer, 1996, Cardiovascular effects of exercise: role of endothelial shear stress, J Am Coll Cardiol., 28, 1652, 10.1016/S0735-1097(96)00393-2

Dominiczak, 1995, Nitric oxide and its putative role in hypertension, Hypertension, 25, 1202, 10.1161/01.HYP.25.6.1202

Kim, 2007, Influence of endothelial nitric oxide synthase gene polymorphisms (-786T>C, 4a4b, 894G>T) in Korean patients with coronary artery disease, Thromb Res., 119, 579, 10.1016/j.thromres.2006.06.005

Cruz-Gonzalez, 2009, Association between -T786C NOS3 polymorphism and resistant hypertension: a prospective cohort study, BMC Cardiovasc Disord., 9, 35, 10.1186/1471-2261-9-35

Zago, 2010, Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people, Eur J Appl Physiol., 110, 825, 10.1007/s00421-010-1568-6

Kuru, 2009, Effect of exercise training on resistance arteries in rats with chronic NOS inhibition, J Appl Physiol., 107, 896, 10.1152/japplphysiol.91180.2008

Wilund, 2007, Is the anti-inflammatory effect of regular exercise responsible for reduced cardiovascular disease?, Clin Sci., 112, 543, 10.1042/CS20060368

Fleenor, 2010, Arterial stiffening with ageing is associated with transforming growth factor-beta1-related changes in adventitial collagen: reversal by aerobic exercise, J Physiol., 588, 3971, 10.1113/jphysiol.2010.194753

Carter, 2015, Sympathetic neural adaptations to exercise training in humans, Auton Neurosci., 188, 36, 10.1016/j.autneu.2014.10.020

Breisch, 1986, Exercise-induced cardiac hypertrophy: a correlation of blood flow and microvasculature, J Appl Physiol., 60, 1259, 10.1152/jappl.1986.60.4.1259

Borlaug, 2009, Contractility and ventricular systolic stiffening in hypertensive heart disease insights into the pathogenesis of heart failure with preserved ejection fraction, J Am Coll Cardiol., 54, 410, 10.1016/j.jacc.2009.05.013

Burelle, 2004, Regular exercise is associated with a protective metabolic phenotype in the rat heart, Am J Physiol Heart Circ Physiol., 287, H1055, 10.1152/ajpheart.00925.2003

Riehle, 2014, Insulin receptor substrates are essential for the bioenergetic and hypertrophic response of the heart to exercise training, Mol Cell Biol., 34, 3450, 10.1128/MCB.00426-14

Gibb, 2017, Exercise-induced changes in glucose metabolism promote physiological cardiac growth, Circulation, 136, 2144, 10.1161/CIRCULATIONAHA.117.028274

McMullen, 2004, The insulin-like growth factor 1 receptor induces physiological heart growth via the phosphoinositide 3-kinase(p110alpha) pathway, J Biol Chem., 279, 4782, 10.1074/jbc.M310405200

Kim, 2008, Insulin-like growth factor I receptor signaling is required for exercise-induced cardiac hypertrophy, Mol Endocrinol., 22, 2531, 10.1210/me.2008-0265

Bostrom, 2010, C/EBPbeta controls exercise-induced cardiac growth and protects against pathological cardiac remodeling, Cell, 143, 1072, 10.1016/j.cell.2010.11.036

Bezzerides, 2016, CITED4 induces physiologic hypertrophy and promotes functional recovery after ischemic injury, JCI Insight, 1, e85904, 10.1172/jci.insight.85904

Wilkins, 2004, Calcineurin/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy, Circ Res., 94, 110, 10.1161/01.RES.0000109415.17511.18

Ferguson, 2001, Cardiac performance in endurance-trained and moderately active young women, Med Sci Sports Exerc., 33, 1114, 10.1097/00005768-200107000-00008

Esch, 2007, Diastolic ventricular interactions in endurance-trained athletes during orthostatic stress, Am J Physiol Heart Circ Physiol., 293, H409, 10.1152/ajpheart.00928.2006

Moore, 1993, Chronic exercise alters contractility and morphology of isolated rat cardiac myocytes, Am J Physiol., 264, C1180, 10.1152/ajpcell.1993.264.5.C1180

Wisloff, 2002, Aerobic exercise reduces cardiomyocyte hypertrophy and increases contractility, Ca2+ sensitivity and SERCA-2 in rat after myocardial infarction, Cardiovasc Res., 54, 162, 10.1016/S0008-6363(01)00565-X

Diffee, 2003, Altered single cell force-velocity and power properties in exercise-trained rat myocardium, J Appl Physiol., 94, 1941, 10.1152/japplphysiol.00889.2002

Kemi, 2008, Exercise-induced changes in calcium handling in left ventricular cardiomyocytes, Front Biosci., 13, 356, 10.2741/2685

Natali, 2002, Different regional effects of voluntary exercise on the mechanical and electrical properties of rat ventricular myocytes, J Physiol., 541, 863, 10.1113/jphysiol.2001.013415

Kemi, 2010, Mechanisms of exercise-induced improvements in the contractile apparatus of the mammalian myocardium, Acta Physiol., 199, 425, 10.1111/j.1748-1716.2010.02132.x

Wisloff, 2001, Increased contractility and calcium sensitivity in cardiac myocytes isolated from endurance trained rats, Cardiovasc Res., 50, 495, 10.1016/S0008-6363(01)00210-3

Marionneau, 2008, Distinct cellular and molecular mechanisms underlie functional remodeling of repolarizing K+ currents with left ventricular hypertrophy, Circ Res., 102, 1406, 10.1161/CIRCRESAHA.107.170050

Biffi, 2008, Relation between training-induced left ventricular hypertrophy and risk for ventricular tachyarrhythmias in elite athletes, Am J Cardiol., 101, 1792, 10.1016/j.amjcard.2008.02.081

Yang, 2010, Homeostatic regulation of electrical excitability in physiological cardiac hypertrophy, J Physiol., 588, 5015, 10.1113/jphysiol.2010.197418

Yang, 2012, Exercise training and PI3Kalpha-induced electrical remodeling is independent of cellular hypertrophy and Akt signaling, J Mol Cell Cardiol., 53, 532, 10.1016/j.yjmcc.2012.07.004

Buick, 1980, Effect of induced erythrocythemia on aerobic work capacity, J Appl Physiol Respir Environ Exerc Physiol., 48, 636, 10.1152/jappl.1980.48.4.636

Weight, 1992, 'Sports anemia'–a real or apparent phenomenon in endurance-trained athletes?, Int J Sports Med., 13, 344, 10.1055/s-2007-1021278

Mairbaurl, 2013, Red blood cells in sports: effects of exercise and training on oxygen supply by red blood cells, Front Physiol., 4, 332, 10.3389/fphys.2013.00332

Semenza, 2009, Regulation of oxygen homeostasis by hypoxia-inducible factor 1, Physiology, 24, 97, 10.1152/physiol.00045.2008

Bonsignore, 2002, Circulating hematopoietic progenitor cells in runners, J Appl Physiol., 93, 1691, 10.1152/japplphysiol.00376.2002

Morici, 2005, Supramaximal exercise mobilizes hematopoietic progenitors and reticulocytes in athletes, Am J Physiol Regul Integr Comp Physiol., 289, R1496, 10.1152/ajpregu.00338.2005

Dufaux, 1989, Plasma elastase-alpha 1-antitrypsin, neopterin, tumor necrosis factor, and soluble interleukin-2 receptor after prolonged exercise, Int J Sports Med., 10, 434, 10.1055/s-2007-1024939

Ostrowski, 1999, Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans, J Physiol., 515, 287, 10.1111/j.1469-7793.1999.287ad.x

Suzuki, 2000, Circulating cytokines and hormones with immunosuppressive but neutrophil-priming potentials rise after endurance exercise in humans, Eur J Appl Physiol., 81, 281, 10.1007/s004210050044

Van Craenenbroeck, 2008, A maximal exercise bout increases the number of circulating CD34+/KDR+ endothelial progenitor cells in healthy subjects. Relation with lipid profile, J Appl Physiol., 104, 1006, 10.1152/japplphysiol.01210.2007

Ribeiro, 2017, Effects of resistance exercise on endothelial progenitor cell mobilization in women, Sci Rep., 7, 17880, 10.1038/s41598-017-18156-6

Green, 2017, Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli, Physiol Rev., 97, 495, 10.1152/physrev.00014.2016

Hallen, 1996, K+ balance in humans during exercise, Acta Physiol Scand., 156, 279, 10.1046/j.1365-201X.1996.187000.x

Radegran, 2001, Role of adenosine in exercise-induced human skeletal muscle vasodilatation, Acta Physiol Scand., 171, 177, 10.1046/j.1365-201x.2001.00796.x

Sarelius, 2010, Control of muscle blood flow during exercise: local factors and integrative mechanisms, Acta Physiol., 199, 349, 10.1111/j.1748-1716.2010.02129.x

Sun, 1994, Short-term daily exercise activity enhances endothelial NO synthesis in skeletal muscle arterioles of rats, J Appl Physiol., 76, 2241, 10.1152/jappl.1994.76.5.2241

Huonker, 2003, Size and blood flow of central and peripheral arteries in highly trained able-bodied and disabled athletes, J Appl Physiol., 95, 685, 10.1152/japplphysiol.00710.2001

Joyner, 2015, Regulation of increased blood flow (hyperemia) to muscles during exercise: a hierarchy of competing physiological needs, Physiol Rev., 95, 549, 10.1152/physrev.00035.2013

Laughlin, 2017, Vascular cell transcriptomic changes to exercise training differ directionally along and between skeletal muscle arteriolar trees, Microcirculation, 24, e12336, 10.1111/micc.12336

Taddei, 2000, Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes, Circulation, 101, 2896, 10.1161/01.CIR.101.25.2896

Feigl, 1983, Coronary physiology, Physiol Rev., 63, 1, 10.1152/physrev.1983.63.1.1

Heiss, 1976, Studies on the regulation of myocardial blood flow in man. I: Training effects on blood flow and metabolism of the healthy heart at rest and during standardized heavy exercise, Basic Res Cardiol., 71, 658, 10.1007/BF01906411

Barnard, 1980, Effects of intensive exercise training on myocardial performance and coronary blood flow, J Appl Physiol Respir Environ Exerc Physiol., 49, 444, 10.1152/jappl.1980.49.3.444

Tomanek, 1970, Effects of age and exercise on the extent of the myocardial capillary bed, Anat Rec., 167, 55, 10.1002/ar.1091670106

Thomas, 1985, Effects of acute and chronic exercise on myocardial ultrastructure, Med Sci Sports Exerc., 17, 546, 10.1249/00005768-198510000-00007

White, 1998, Exercise training in swine promotes growth of arteriolar bed and capillary angiogenesis in heart, J Appl Physiol., 85, 1160, 10.1152/jappl.1998.85.3.1160

Mobius-Winkler, 2016, Coronary Collateral growth induced by physical exercise: results of the impact of intensive exercise training on coronary collateral circulation in patients with stable coronary artery disease (EXCITE) trial, Circulation, 133, 1438, 10.1161/CIRCULATIONAHA.115.016442

DiCarlo, 1989, Daily exercise enhances coronary resistance vessel sensitivity to pharmacological activation, J Appl Physiol., 66, 421, 10.1152/jappl.1989.66.1.421

Bowles, 1998, Exercise training increases K+-channel contribution to regulation of coronary arterial tone, J Appl Physiol., 84, 1225, 10.1152/jappl.1998.84.4.1225

Laughlin, 2001, Training induces nonuniform increases in eNOS content along the coronary arterial tree, J Appl Physiol., 90, 501, 10.1152/jappl.2001.90.2.501

Durand, 2015, Acute exertion elicits a H2O2-dependent vasodilator mechanism in the microvasculature of exercise-trained but not sedentary adults, Hypertension, 65, 140, 10.1161/HYPERTENSIONAHA.114.04540

Robinson, 2016, Improved arterial flow-mediated dilation after exertion involves hydrogen peroxide in overweight and obese adults following aerobic exercise training, J Hypertens., 34, 1309, 10.1097/HJH.0000000000000946

Simpson, 2003, Walking trends among U.S. adults: the Behavioral Risk Factor Surveillance System, 1987-2000, Am J Prev Med., 25, 95, 10.1016/S0749-3797(03)00112-0

Wen, 2011, Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study, Lancet, 378, 1244, 10.1016/S0140-6736(11)60749-6

O'Keefe, 2012, Potential adverse cardiovascular effects from excessive endurance exercise, Mayo Clin Proc., 87, 587, 10.1016/j.mayocp.2012.04.005

Roberts, 2017, Fifty men, 3510 marathons, cardiac risk factors, and coronary artery calcium scores, Med Sci Sports Exerc., 49, 2369, 10.1249/MSS.0000000000001373

Laddu, 2017, 25-Year physical activity trajectories and development of subclinical coronary artery disease as measured by coronary artery calcium: the Coronary Artery Risk Development in Young Adults (CARDIA) study, Mayo Clin Proc., 92, 1660, 10.1016/j.mayocp.2017.07.016

Aengevaeren, 2017, Relationship between lifelong exercise volume and coronary atherosclerosis in athletes, Circulation, 136, 138, 10.1161/CIRCULATIONAHA.117.027834

Merghani, 2017, Prevalence of subclinical coronary artery disease in masters endurance athletes with a low atherosclerotic risk profile, Circulation, 136, 126, 10.1161/CIRCULATIONAHA.116.026964

Howden, 2018, Reversing the cardiac effects of sedentary aging in middle age-a randomized controlled trial: implications for heart failure prevention, Circulation, 137, 1549, 10.1161/CIRCULATIONAHA.117.030617

Mora, 2007, Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms, Circulation, 116, 2110, 10.1161/CIRCULATIONAHA.107.729939

Fernandez, 2018, Physical activity, immune system, and the microbiome in cardiovascular disease, Front Physiol., 9, 763, 10.3389/fphys.2018.00763

Fiuza-Luces, 2018, Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors, Nat Rev Cardiol., 10.1038/s41569-018-0065-1

Boldyrev, 2013, Physiology and pathophysiology of carnosine, Physiol Rev., 93, 1803, 10.1152/physrev.00039.2012