Seasonal variations in vascular endothelial function and physical activity in men

Vascular endothelial function, which plays an important independent role in the onset of cardiovascular disease, often changes seasonally, with functional deterioration generally occurring during the winter. Physical activity is necessary for preventing cardiovascular disease and all-cause mortality, as it improves vascular endothelial and metabolic function; however, the amount of physical activity an individual gets also varies with the seasons. Changes in physical activity may induce seasonal variations in vascular endothelial function, although this hypothesis remains unconfirmed. An individual's sex can also affect their vascular endothelial function, habitual physical activity, and hormonal and metabolic function. Men have a higher risk of cardiovascular disease compared to women; therefore, clarifying the impact of physical activity on vascular endothelial function and its seasonality is important for managing men's health. The purpose of this article is to review the association between seasonal variations in vascular endothelial function and physical activity in men.

Vascular endothelial function; Physical activity; Seasonal variation; Hormonal function; Metabolic function

[1] Lerman A, Zeiher AM. Endothelial function: cardiac events. Circula-tion. 2005; 111: 363–368.

[2] Neunteufl T, Heher S, Katzenschlager R, Wolfl G, Kostner K, Maurer G, et al. Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. American Journal of Cardiology. 2000; 86: 207–210.

[3] Vanhoutte PM, Shimokawa H, Feletou M, Tang EH. Endothelial dysfunction and vascular disease - a 30th anniversary update. Acta Physiologica. 2017; 219: 22–96.

[4] Wilkinson IB, Cockcroft JR. Cholesterol, endothelial function and cardiovascular disease. Current Opinion in Lipidology. 1998; 9: 237–242.

[5] Gokce N, Keaney JF Jr., Hunter LM, Watkins MT, Menzoian JO, Vita JA. Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study. Circulation. 2002; 105: 1567–1572.

[6] Yeboah J, Folsom AR, Burke GL, Johnson C, Polak JF, Post W, et al. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation. 2009; 120: 502–509.

[7] Reckelhoff JF, Fortepiani LA. Novel mechanisms responsible for postmenopausal hypertension. Hypertension. 2004; 43: 918–923.

[8] Rosano GM, Sheiban I, Massaro R, Pagnotta P, Marazzi G, Vitale C, et al. Low testosterone levels are associated with coronary artery disease in male patients with angina. International Journal of Impotence Research. 2007; 19: 176–182.

[9] Dockery F, Bulpitt CJ, Donaldson M, Fernandez S, Rajkumar C. The relationship between androgens and arterial stiffness in older men. Journal of the American Geriatrics Society. 2003; 51: 1627–1632.

[10] Pearson LJ, Yandle TG, Nicholls MG, Evans JJ. Regulation of endothelin-1 release from human endothelial cells by sex steroids and angiotensin-II. Peptides. 2008; 29: 1057–1061.

[11] Kappert K, Bohm M, Schmieder R, Schumacher H, Teo K, Yusuf S, et al. Impact of sex on cardiovascular outcome in patients at high cardiovascular risk: analysis of the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects With Cardiovascular Disease (TRANSCEND) and the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET). Circulation. 2012; 126: 934–941.

[12] Yang XP, Reckelhoff JF. Estrogen, hormonal replacement therapy and cardiovascular disease. Current Opinion in Nephrology and Hypertension. 2011; 20: 133–138.

[13] Yang XC, Jing TY, Resnick LM, Phillips GB. Relation of hemostatic risk factors to other risk factors for coronary heart disease and to sex hormones in men. Arteriosclerosis and Thrombosis. 1993; 13: 467–471.

[14] Fares A. Winter cardiovascular diseases phenomenon. North Ameri-can Journal of Medical Sciences. 2013; 5: 266–279.

[15] Bjornerem A, Straume B, Oian P, Berntsen GK. Seasonal variation of estradiol, follicle stimulating hormone, and dehydroepiandrosterone sulfate in women and men. Journal of Clinical Endocrinology and Metabolism. 2006; 91: 3798–3802.

[16] Santi D, Spaggiari G, Granata ARM, Setti M, Tagliavini S, Trenti T, et al. Seasonal Changes of Serum Gonadotropins and Testosterone in Men Revealed by a Large Data Set of Real-World Observations Over Nine Years. Frontiers in Endocrinology. 2019; 10: 914.

[17] Smith RP, Coward RM, Kovac JR, Lipshultz LI. The evidence for seasonal variations of testosterone in men. Maturitas. 2013; 74: 208–212.

[18] Dannenberg AL, Keller JB, Wilson PW, Castelli WP. Leisure time physical activity in the Framingham Offspring Study. Description, seasonal variation, and risk factor correlates. American Journal of Epidemiology. 1989; 129: 76–88.

[19] Shephard RJ, Aoyagi Y. Seasonal variations in physical activity and implications for human health. European Journal of Applied Physiology. 2009; 107: 251–271.

[20] Honda H, Igaki M, Komatsu M, Tanaka S. Association between Physical Activity and Seasonal Variations in Metabolic and Vascular Function in Adults. Endocrines. 2021; 2: 150–159.

[21] Skaug EA, Aspenes ST, Oldervoll L, Morkedal B, Vatten L, Wisloff U, et al. Age and gender differences of endothelial function in 4739 healthy adults: the HUNT3 Fitness Study. European Journal of Preventive Cardiology. 2013; 20: 531–540.

[22] Dengel DR, Jacobs DR, Steinberger J, Moran AM, Sinaiko AR. Gender differences in vascular function and insulin sensitivity in young adults. Clinical Science. 2011; 120: 153–160.

[23] Sarabi M, Millgard J, Lind L. Effects of age, gender and metabolic factors on endothelium-dependent vasodilation: a population-based study. Journal of Internal Medicine. 1999; 246: 265–274.

[24] Pabbidi MR, Kuppusamy M, Didion SP, Sanapureddy P, Reed JT, Sontakke SP. Sex differences in the vascular function and related mechanisms: role of 17β-estradiol. American Journal of Physiology: Heart and Circulatory Physiology. 2018; 315: H1499–H1518.

[25] Widlansky ME, Vita JA, Keyes MJ, Larson MG, Hamburg NM, Levy D, et al. Relation of season and temperature to endothelium-dependent flow-mediated vasodilation in subjects without clinical evidence of cardiovascular disease (from the Framingham Heart Study). American Journal of Cardiology. 2007; 100: 518–523.

[26] Iwata M, Miyashita Y, Kumagai H. Seasonal variation of endothelium-dependent flow-mediated vasodilation measured in the same subjects. American Journal of Cardiovascular Disease. 2012; 2: 111–115.

[27] Yoneyama K, Nakai M, Higuma T, Teramoto K, Watanabe M, Kaihara T, et al. Weather temperature and the incidence of hospitalization for cardiovascular diseases in an aging society. Scientific Reports. 2021; 11: 10863.

[28] Ndzie Noah ML, Adzika GK, Mprah R, Adekunle AO, Adu-Amankwaah J, Sun H. Sex-Gender Disparities in Cardiovascular Diseases: The Effects of Estrogen on eNOS, Lipid Profile, and NFATs During Catecholamine Stress. Frontiers in Cardiovascular Medicine. 2021; 8: 639946.

[29] Papakonstantinou NA, Stamou MI, Baikoussis NG, Goudevenos J, Apostolakis E. Sex differentiation with regard to coronary artery disease. Journal of Cardiology. 2013; 62: 4–11.

[30] Moreau KL, Hildreth KL, Meditz AL, Deane KD, Kohrt WM. Endothelial function is impaired across the stages of the menopause transition in healthy women. Journal of Clinical Endocrinology and Metabolism. 2012; 97: 4692–4700.

[31] Stanhewicz AE, Wenner MM, Stachenfeld NS. Sex differences in endothelial function important to vascular health and overall cardiovascular disease risk across the lifespan. American Journal of Physiology: Heart and Circulatory Physiology. 2018; 315: H1569–H1588.

[32] Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019; 140: e563–e595.

[33] Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal. 2018; 39: 3021–3104.

[34] Makinen TM, Mantysaari M, Paakkonen T, Jokelainen J, Palinkas LA, Hassi J, et al. Autonomic nervous function during whole-body cold exposure before and after cold acclimation. Aviation Space and Environmental Medicine. 2008; 79: 875–882.

[35] Mourot L, Bouhaddi M, Regnard J. Effects of the cold pressor test on cardiac autonomic control in normal subjects. Physiological Research. 2009; 58: 83–91.

[36] Maruhashi T, Soga J, Fujimura N, Idei N, Mikami S, Iwamoto Y, et al. Relationship between flow-mediated vasodilation and cardiovascular risk factors in a large community-based study. Heart. 2013; 99: 1837–1842.

[37] Cuspidi C, Ochoa JE, Parati G. Seasonal variations in blood pressure: a complex phenomenon. Journal of Hypertension. 2012; 30: 1315–1320.

[38] Alperovitch A, Lacombe JM, Hanon O, Dartigues JF, Ritchie K, Ducimetiere P, et al. Relationship between blood pressure and outdoor temperature in a large sample of elderly individuals: the Three-City study. Archives of Internal Medicine. 2009; 169: 75–80.

[39] Tan KC, Chow WS, Ai VH, Metz C, Bucala R, Lam KS. Advanced glycation end products and endothelial dysfunction in type 2 diabetes. Diabetes Care. 2002; 25: 1055–1059.

[40] Williams SB, Goldfine AB, Timimi FK, Ting HH, Roddy MA, Simonson DC, et al. Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation. 1998; 97: 1695–1701.

[41] Kershenbaum A, Kershenbaum A, Tarabeia J, Stein N, Lavi I, Rennert G. Unraveling seasonality in population averages: an examination of seasonal variation in glucose levels in diabetes patients using a large population-based data set. Chronobiology International. 2011; 28: 352–360.

[42] Tseng CL, Brimacombe M, Xie M, Rajan M, Wang H, Kolassa J, et al. Seasonal patterns in monthly hemoglobin A1c values. American Journal of Epidemiology. 2005; 161: 565–574.

[43] Walker BR, Best R, Noon JP, Watt GC, Webb DJ. Seasonal variation in glucocorticoid activity in healthy men. Journal of Clinical Endocrinology and Metabolism. 1997; 82: 4015–4019.

[44] Sohmiya M, Kanazawa I, Kato Y. Seasonal changes in body composi-tion and blood HbA1c levels without weight change in male patients with type 2 diabetes treated with insulin. Diabetes Care. 2004; 27: 1238–1239.

[45] Gordon DJ, Trost DC, Hyde J, Whaley FS, Hannan PJ, Jacobs DR Jr., et al. Seasonal cholesterol cycles: the Lipid Research Clinics Coronary Primary Prevention Trial placebo group. Circulation. 1987; 76: 1224–1231.

[46] Grimes DS, Hindle E, Dyer T. Sunlight, cholesterol and coronary heart disease. QJM: An International Journal of Medicine. 1996; 89: 579–589.

[47] Kamezaki F, Sonoda S, Tomotsune Y, Yunaka H, Otsuji Y. Seasonal variation in metabolic syndrome prevalence. Hypertension Research. 2010; 33: 568–572.

[48] Hadaegh F, Harati H, Zabetian A, Azizi F. Seasonal variability of serum lipids in adults: Tehran Lipid and Glucose Study. Medical Journal of Malaysia. 2006; 61: 332–338.

[49] Ignarro LJ. Nitric oxide as a unique signaling molecule in the vascular system: a historical overview. Journal of Physiology and Pharmacology. 2002; 53: 503–514.

[50] Ando J, Yamamoto K. Effects of shear stress and stretch on endothelial function. Antioxid Redox Signal. 2011; 15: 1389–1403.

[51] Qiu S, Cai X, Yin H, Sun Z, Zugel M, Steinacker JM, et al. Exercise training and endothelial function in patients with type 2 diabetes: a meta-analysis. Cardiovascular Diabetology. 2018; 17: 64.

[52] Jakicic JM, Kraus WE, Powell KE, Campbell WW, Janz KF, Troiano RP, et al. Association between Bout Duration of Physical Activity and Health: Systematic Review. Medicine & Science in Sports & Exercise. 2019; 51: 1213–1219.

[53] Higueras-Fresnillo S, Cabanas-Sanchez V, Lopez-Garcia E, Esteban-Cornejo I, Banegas JR, Sadarangani KP, et al. Physical Activity and Association Between Frailty and All-Cause and Cardiovascular Mortality in Older Adults: Population-Based Prospective Cohort Study. Journal of the American Geriatrics Society. 2018; 66: 2097–2103.

[54] Kodama S, Tanaka S, Heianza Y, Fujihara K, Horikawa C, Shimano H, et al. Association between physical activity and risk of all-cause mortality and cardiovascular disease in patients with diabetes: a meta-analysis. Diabetes Care. 2013; 36: 471–479.

[55] Black MA, Cable NT, Thijssen DH, Green DJ. Impact of age, sex, and exercise on brachial artery flow-mediated dilatation. American Journal of Physiology: Heart and Circulatory Physiology. 2009; 297: H1109–1116.

[56] Pierce GL, Eskurza I, Walker AE, Fay TN, Seals DR. Sex-specific effects of habitual aerobic exercise on brachial artery flow-mediated dilation in middle-aged and older adults. Clinical Science. 2011; 120: 13–23.

[57] Seals DR, Nagy EE, Moreau KL. Aerobic exercise training and vascular function with ageing in healthy men and women. Journal of Physiology. 2019; 597: 4901–4914.

[58] Guthold R, Stevens GA, Riley LM, Bull FC. Worldwide trends in insufficient physical activity from 2001 to 2016: a pooled analysis of 358 population-based surveys with 1.9 million participants. The Lancet Global Health. 2018; 6: e1077–e1086.

[59] Kudo N, Nishide R, Mizutani M, Ogawa S, Tanimura S. Association between the type of physical activity and metabolic syndrome in middle-aged and older adult residents of a semi-mountainous area in Japan. Environmental Health and Preventive Medicine. 2021; 26: 46.

[60] Tyrovolas S, Chalkias C, Morena M, Kalogeropoulos K, Tsakountakis N, Zeimbekis A, et al. High relative environmental humidity is associated with diabetes among elders living in Mediterranean islands. Journal of Diabetes & Metabolic Disorders. 2014; 13: 25.

[61] Juna CF, Cho YH, Ham D, Joung H. Associations of Relative Humidity and Lifestyles with Metabolic Syndrome among the Ecuadorian Adult Population: Ecuador National Health and Nutrition Survey (ENSANUT-ECU) 2012. International Journal of Environmental Research and Public Health. 2020; 17: 9023.

[62] Togo F, Watanabe E, Park H, Shephard RJ, Aoyagi Y. Meteorology and the physical activity of the elderly: the Nakanojo Study. International Journal of Biometeorology. 2005; 50: 83–89.

[63] Chan CB, Ryan DA, Tudor-Locke C. Relationship between objective measures of physical activity and weather: a longitudinal study. The International Journal of Behavioral Nutrition and Physical Activity. 2006; 3: 21.

[64] Pivarnik JM, Reeves MJ, Rafferty AP. Seasonal variation in adult leisure-time physical activity. Medicine and Science in Sports and Exercise. 2003; 35: 1004–1008.

[65] Uitenbroek DG. Seasonal variation in leisure time physical activity. Medicine and Science in Sports and Exercise. 1993; 25: 755–760.

[66] Hoaas H, Zanaboni P, Hjalmarsen A, Morseth B, Dinesen B, Burge AT, et al. Seasonal variations in objectively assessed physical activity among people with COPD in two Nordic countries and Australia: a cross-sectional study. International Journal of Chronic Obstructive Pulmonary Disease. 2019; 14: 1219–1228.

[67] Klompstra L, Jaarsma T, Stromberg A, van der Wal MHL. Seasonal variation in physical activity in patients with heart failure. Heart and Lung. 2019; 48: 381–385.

[68] Gil MCC, Koolhaas C, Franco O, Schoufour J. Seasonality of physical activity, sedentary behavior and nighttime sleep duration in middle aged and elderly population of the Rotterdam Study. Maturitas. 2017; 103: 94.

[69] Ferguson T, Curtis R, Fraysse F, Lagiseti R, Northcott C, Virgara R, et al. Annual, seasonal, cultural and vacation patterns in sleep, sedentary behaviour and physical activity: a systematic review and meta-analysis. BMC Public Health. 2021; 21: 1384.

[70] Werneck AO, Baldew SS, Miranda JJ, Diaz Arnesto O, Stubbs B, Silva DR, et al. Physical activity and sedentary behavior patterns and sociodemographic correlates in 116,982 adults from six South American countries: the South American physical activity and sedentary behavior network (SAPASEN). The International Journal of Behavioral Nutrition and Physical Activity. 2019; 16: 68.

[71] Plasqui G, Westerterp KR. Seasonal variation in total energy expen-diture and physical activity in Dutch young adults. Obesity Research. 2004; 12: 688–694.

[72] Yasunaga A, Togo F, Watanabe E, Park H, Park S, Shephard RJ, et al. Sex, age, season, and habitual physical activity of older Japanese: the Nakanojo study. Journal of Aging and Physical Activity. 2008; 16: 3–13.

[73] Hopkins ND, Stratton G, Tinken TM, Ridgers ND, Graves LE, McWhannell N, et al. Seasonal reduction in physical activity and flow-mediated dilation in children. Medicine and Science in Sports and Exercise. 2011; 43: 232–238.

[74] Honda H, Igaki M, Komatsu M, Tanaka S. Seasonal variations on endothelium-dependent flow-mediated vasodilation in adults with type 2 diabetes and nondiabetic adults with hypertension and/or dyslipidaemia who perform regular exercise. Endocrinology, Diabetes & Metabolism. 2021; 4: e00168.

[75] Fahrner CL, Hackney AC. Effects of endurance exercise on free testosterone concentration and the binding affinity of sex hormone binding globulin (SHBG). International Journal of Sports Medicine. 1998; 19: 12–15.

[76] Vingren JL, Kraemer WJ, Ratamess NA, Anderson JM, Volek JS, Maresh CM. Testosterone physiology in resistance exercise and training: the up-stream regulatory elements. Sports Medicine. 2010; 40: 1037–1053.

[77] Kraemer WJ, Hakkinen K, Newton RU, McCormick M, Nindl BC, Volek JS, et al. Acute hormonal responses to heavy resistance exercise in younger and older men. European Journal of Applied Physiology and Occupational Physiology. 1998; 77: 206–211.

[78] Linnamo V, Pakarinen A, Komi PV, Kraemer WJ, Hakkinen K. Acute hormonal responses to submaximal and maximal heavy resistance and explosive exercises in men and women. Journal of Strength and Conditioning Research. 2005; 19: 566–571.

[79] Kraemer WJ, Hakkinen K, Newton RU, Nindl BC, Volek JS, McCormick M, et al. Effects of heavy-resistance training on hormonal response patterns in younger vs. older men. Journal of Applied Physiology. 1999; 87: 982–992.

[80] Grandys M, Majerczak J, Duda K, Zapart-Bukowska J, Kulpa J, Zoladz JA. Endurance training of moderate intensity increases testosterone concentration in young, healthy men. International Journal of Sports Medicine. 2009; 30: 489–495.

[81] Hiruntrakul A, Nanagara R, Emasithi A, Borer KT. Effect of endurance exercise on resting testosterone levels in sedentary subjects. Central European Journal of Public Health. 2010; 18: 169–172.

[82] Bjornerem A, Straume B, Midtby M, Fonnebo V, Sundsfjord J, Svartberg J, et al. Endogenous sex hormones in relation to age, sex, lifestyle factors, and chronic diseases in a general population: the Tromso Study. Journal of Clinical Endocrinology and Metabolism. 2004; 89: 6039–6047.

[83] Fahey TD, Rolph R, Moungmee P, Nagel J, Mortara S. Serum testos-terone, body composition, and strength of young adults. Medicine and Science in Sports. 1976; 8: 31–34.

[84] Pullinen T, Mero A, Huttunen P, Pakarinen A, Komi PV. Resistance exercise-induced hormonal responses in men, women, and pubescent boys. Medicine and Science in Sports and Exercise. 2002; 34: 806–813.

[85] Baker JR, Bemben MG, Anderson MA, Bemben DA. Effects of age on testosterone responses to resistance exercise and musculoskeletal variables in men. Journal of Strength and Conditioning Research. 2006; 20: 874–881.

[86] Hakkinen K, Pakarinen A, Kraemer WJ, Newton RU, Alen M. Basal concentrations and acute responses of serum hormones and strength development during heavy resistance training in middle-aged and elderly men and women. Journals of Gerontology. Series A: Biological Sciences and Medical Sciences. 2000; 55: B95–105.

[87] Hakkinen K, Pakarinen A, Newton RU, Kraemer WJ. Acute hormone responses to heavy resistance lower and upper extremity exercise in young versus old men. European Journal of Applied Physiology and Occupational Physiology. 1998; 77: 312–319.

[88] Cumming DC, Wall SR. Non-sex hormone-binding globulin-bound testosterone as a marker for hyperandrogenism. Journal of Clinical Endocrinology and Metabolism. 1985; 61: 873–876.

[89] Hayashi T, Yamada T. Association of bioavailable estradiol levels and testosterone levels with serum albumin levels in elderly men. Aging Male. 2008; 11: 63–70.

[90] Ryu OH, Lee S, Yoo HJ, Choi MG. Seasonal variations in glycemic con-trol of type 2 diabetes in Korean women. Journal of Endocrinological Investigation. 2014; 37: 575–581.

[91] Ma Y, Olendzki BC, Li W, Hafner AR, Chiriboga D, Hebert JR, et al. Seasonal variation in food intake, physical activity, and body weight in a predominantly overweight population. European Journal of Clinical Nutrition. 2006; 60: 519–528.

[92] Nadif R, Goldberg S, Gourmelen J, Ozguler A, Goldberg M, Zins M, et al. Seasonal variations of lipid profiles in a French cohort. Atherosclerosis. 2019; 286: 181–183.

[93] Ramirez-Jimenez M, Morales-Palomo F, Ortega JF, Moreno-Cabanas A, Guio de Prada V, Alvarez-Jimenez L, et al. Effects of Exercise Train-ing during Christmas on Body Weight and Cardiometabolic Health in Overweight Individuals. International Journal of Environmental Research and Public Health. 2020; 17: 4732.

[94] Stevenson JL, Krishnan S, Stoner MA, Goktas Z, Cooper JA. Effects of exercise during the holiday season on changes in body weight, body composition and blood pressure. European Journal of Clinical Nutrition. 2013; 67: 944–949.

[95] Cano A, Ventura L, Martinez G, Cugusi L, Caria M, Deriu F, et al. Analysis of sex-based differences in energy substrate utilization during moderate-intensity aerobic exercise. European Journal of Applied Physiology. 2021. (in press)

[96] Davis SN, Galassetti P, Wasserman DH, Tate D. Effects of gender on neuroendocrine and metabolic counterregulatory responses to exercise in normal man. Journal of Clinical Endocrinology and Metabolism. 2000; 85: 224–230.

[97] Bouchard DR, Beliaeff S, Dionne IJ, Brochu M. Fat mass but not fat-free mass is related to physical capacity in well-functioning older individuals: nutrition as a determinant of successful aging (NuAge)–the Quebec Longitudinal Study. Journals of Gerontology. Series A: Biological Sciences and Medical Sciences. 2007; 62: 1382–1388.

[98] Doherty TJ. The influence of aging and sex on skeletal muscle mass and strength. Current Opinion in Clinical Nutrition and Metabolic Care. 2001; 4: 503–508.

[99] Poehlman ET, Toth MJ, Bunyard LB, Gardner AW, Donaldson KE, Colman E, et al. Physiological predictors of increasing total and central adiposity in aging men and women. Archives of Internal Medicine. 1995; 155: 2443–2448.