Editorial Social Network and Stroke Risk Size Matters Graeme J. Hankey, MD See related article, p 2868. umans are social animals. The quality and quantity of our relationships with other humans (social network) underpin our happiness and success.1 A social network structure also provides functional social support. It assists us emotionally and physically, informs and educates us, and improves our health-related choices and behaviors.2 But does it protect us from stroke? Several epidemiological studies have reported small social network and limited social support to be associated with an increased incidence of mortality, coronary heart disease, cancer, and mood disorders,3–13 but only 4 studies have examined the association with stroke and the results are conflicting.5,6,14,15 In the first study, of 2603 members of a US health maintenance organization, there was no difference in the 15-year incidence of stroke among those in the lowest versus highest tertile of social network indices.5 However, in the second study, of 32 624 US male health professionals, socially isolated men had an increased risk of stroke (relative risk, 2.21; 95% confidence interval [CI], 1.12–4.35), which was dose-dependent (P for trend=0.008).6 A subsequent study of 629 women with suspected myocardial infarction also found a higher rate of stroke among more socially isolated women than those with more social relationships (adjusted hazards ratio [HR], 2.7; 95% CI, 1.1–6.7).14 Finally, among 44 152 Japanese men and women, those lacking someone to share intimate personal feelings and secrets had a higher incidence of stroke (adjusted HR, 1.18; 95% CI, 1.01–1.37).15 Having no friends (adjusted HR, 0.98; 95% CI, 0.80–1.20) and no esteem support (adjusted HR, 1.16; 95% CI, 0.99–1.37) were not associated with a higher incidence of stroke, however; nor was low social support (HR, 1.11; 95% CI, 0.89–1.37).15 In this issue of Stroke, Nagayoshi et al16 report that a small social network was associated with a 44% increased risk of stroke (HR, 1.44; 95% CI, 1.02–2.04) compared with a large social network in the Atherosclerosis Risk in Communities (ARIC) study. This result incorporates adjustment for the
H
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the School of Medicine and Pharmacology, The University of Western Australia, Perth, Australia; and Department of Neurology, Sir Charles Gairdner Hospital, Perth, Australia. Correspondence to Graeme J. Hankey, MD, School of Medicine and Pharmacology, The University of Western Australia, Perkins Institute of Medical Research, QEII Medical Centre, Perth 6009, Australia. E-mail [email protected] (Stroke. 2014;45:2853-2854.) © 2014 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.114.006798
higher likelihood of being black, male, unmarried, unemployed, less educated, diabetic, a smoker, and scoring highly on the vital exhaustion measure among the 380 participants (2.8%) with a small social network compared with a large social network.16 The association appeared to be partly mediated by perceived social support and vital exhaustion (fatigue, irritability, and feelings of demoralization) but not inflammation (high-sensitivity C-reactive protein). There was no significant increase in the incidence of stroke among the few participants (0.5%) who perceived a lack of social support compared with those with high social support (HR, 1.59; 95% CI, 0.75–3.36).16 The internal validity of the ARIC study results is supported by the rigorous study methodology. A large cohort (n=13 686) of community-dwelling, biracial, middle-aged, stroke-free men and women were recruited prospectively from sampling 4 US communities and underwent a standardized baseline assessment of candidate variables (social network by the 10-item Lubben Social Network Scale, and perceived social support by a 16-item Interpersonal Support Evaluation List-Short Form) and covariates.16 After a median of 18.6 years follow-up, a large number (n=905) of incident stroke outcomes were adjudicated according to a standardized definition of stroke. The limitations of the study include measurement of social network and support based on self-report and at one point in time only, probable incomplete ascertainment of stroke outcome events (hospitalized or fatal strokes reported by participants and proxys), and limited statistical power to evaluate the effect of a perceived lack of social support on stroke risk because of its low prevalence (0.5%) in the study population. The external validity of the ARIC study results is supported by their consistency with other studies.6,14,15 The results of the first study of 2603 health maintenance organization members5 may also have been consistent if the authors of that study had not defined a small social network as a score in the lowest tertile, because this may have been too crude a subcategorization if the prevalence of a small social network was well below one third, as observed in the ARIC study.16 Overall, the totality of published evidence suggests that a small social network is a risk factor for incident stroke. The association is reasonably strong, consistent, specific, and plausible. The potential mechanisms by which social interaction and relationships may reduce stroke risk include behavioral, social, psychological, and physiological pathways. Individuals with a small social network and support are predisposed to adverse health behaviors (eg, cigarette smoking, alcohol and other drug abuse, poor diet, sedentary lifestyle) and suboptimal health service utilization and adherence to medical recommendations.2 Small social network is also associated with psychological stress, activation of the neuroendocrine system,
Downloaded from http://stroke.ahajournals.org/ by guest on April 13, 2015 2853
2854 Stroke October 2014 upregulation of chronic inflammation, and endothelial and platelet dysfunction.17,18 Nevertheless, it is not possible to prove a causal relationship between small social network and stroke from observational studies.19 The results above may reflect residual confounding by failure to accurately measure and adequately adjust for factors such as diet, mood, health service utilization, and other complex social and environmental exposures that may have differed between the comparison groups (small versus large social network) and the outcome (stroke). The results may also reflect bias, such as reverse causality bias whereby lifestyle choices and health-related behaviors may have determined social networks. More robust techniques for assessing causal associations between social network and stroke are needed. Randomized controlled trials are problematic in this context.20 However, observational Mendelian randomization studies may be possible.21 Although the genetic and biological mechanisms underlying social networking are not well understood, the neuropeptides oxytocin and arginine vasopressin are brain signaling molecules that encode proteins that regulate a suite of social behaviors relevant to social bonding.22,23 Genetic polymorphisms in oxytocin pathway genes (eg, CD38 [rs12644506]) may influence social integration and other social behaviors.24 To perform Mendelian randomization, such genetic variants require 3 key features: first, to be allocated to individuals randomly (ie, at conception); second, to be associated with the risk factor (social network); and third, to affect outcome (stroke) only via the risk factor and not other biological pathways.21 While awaiting more definitive studies of a causal association between social network and stroke risk, it would be appropriate to encourage health professionals to consider social network size and quality as a possible causal and modifiable risk factor for stroke, to help individuals at risk of stroke to become more socially engaged and to advocate for more community resources to facilitate social networks.
Disclosures None.
References 1. Takagi D, Kondo K, Kawachi I. Social participation and mental health: moderating effects of gender, social role and rurality. BMC Public Health. 2013;13:701. 2. Watt RG, Heilmann A, Sabbah W, Newton T, Chandola T, Aida J, et al. Social relationships and health related behaviors among older US adults. BMC Public Health. 2014;14:533. 3. Durkheim E. Suicide. New York: Free Press; 1951. 4. House JS, Landis KR, Umberson D. Social relationships and health. Science. 1988;241:540–545. 5. Vogt TM, Mullooly JP, Ernst D, Pope CR, Hollis JF. Social networks as predictors of ischemic heart disease, cancer, stroke and hypertension: incidence, survival and mortality. J Clin Epidemiol. 1992;45:659–666.
6. Kawachi I, Colditz GA, Ascherio A, Rimm EB, Giovannucci E, Stampfer MJ, et al. A prospective study of social networks in relation to total mortality and cardiovascular disease in men in the USA. J Epidemiol Community Health. 1996;50:245–251. 7. Eng PM, Rimm EB, Fitzmaurice G, Kawachi I. Social ties and change in social ties in relation to subsequent total and cause-specific mortality and coronary heart disease incidence in men. Am J Epidemiol. 2002;155:700–709. 8. Sinokki M, Hinkka K, Ahola K, Koskinen S, Kivimäki M, Honkonen T, et al. The association of social support at work and in private life with mental health and antidepressant use: the Health 2000 Study. J Affect Disord. 2009;115:36–45. 9. Barth J, Schneider S, von Känel R. Lack of social support in the etiology and the prognosis of coronary heart disease: a systematic review and meta-analysis. Psychosom Med. 2010;72:229–238. 10. Stringhini S, Berkman L, Dugravot A, Ferrie JE, Marmot M, Kivimaki M, et al. Socioeconomic status, structural and functional measures of social support, and mortality: The British Whitehall II Cohort Study, 1985-2009. Am J Epidemiol. 2012;175:1275–1283. 11. Ikeda A, Kawachi I, Iso H, Iwasaki M, Inoue M, Tsugane S. Social support and cancer incidence and mortality: the JPHC study cohort II. Cancer Causes Control. 2013;24:847–860. 12. Barger SD. Social integration, social support and mortality in the US National Health Interview Survey. Psychosom Med. 2013;75:510–517. 13. Hill PL, Weston SJ, Jackson JJ. Connecting social environment variables to the onset of major specific health outcomes. Psychol Health. 2014;29:753–767. 14. Rutledge T, Linke SE, Olson MB, Francis J, Johnson BD, Bittner V, et al. Social networks and incident stroke among women with suspected myocardial ischemia. Psychosom Med. 2008;70:282–287. 15. Ikeda A, Iso H, Kawachi I, Yamagishi K, Inoue M, Tsugane S; JPHC Study Group. Social support and stroke and coronary heart disease: the JPHC study cohorts II. Stroke. 2008;39:768–775. 16. Nagayoshi M, Everson-Rose SA, Iso H, Mosley TH Jr, Rose KM, Lutsey PL. Social network, social support, and risk of incident stroke: Atherosclerosis Risk in Communities Study. Stroke. 2014;45:2868–2873. 17. Yang YC, McClintock MK, Kozloski M, Li T. Social isolation and adult mortality: the role of chronic inflammation and sex differences. J Health Soc Behav. 2013;54:183–203. 18. Non AL, Rimm EB, Kawachi I, Rewak MA, Kubzansky LD. The effects of stress at work and at home on inflammation and endothelial dysfunction. PLoS One. 2014;9:e94474. 19. Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58:295–300. 20. Berkman LF, Blumenthal J, Burg M, Carney RM, Catellier D, Cowan MJ, et al; Enhancing Recovery in Coronary Heart Disease Patients Investigators (ENRICHD). Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA. 2003;289:3106–3116. 21. Burgess S, Butterworth A, Malarstig A, Thompson SG. Use of Mendelian randomisation to assess potential benefit of clinical intervention. BMJ. 2012;345:e7325. 22. Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M. Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat Rev Neurosci. 2011;12:524–538. 23. Ebstein RP, Knafo A, Mankuta D, Chew SH, Lai PS. The contributions of oxytocin and vasopressin pathway genes to human behavior. Horm Behav. 2012;61:359–379. 24. Chang SC, Glymour MM, Rewak M, Cornelis MC, Walter S, Koenen KC, et al. Are genetic variations in OXTR, AVPR1A, and CD38 genes important to social integration? Results from two large U.S. cohorts. Psychoneuroendocrinology. 2014;39:257–268. Key Words: Editorial ◼ epidemiology ◼ risk factors ◼ stroke
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Social Network and Stroke Risk: Size Matters Graeme J. Hankey Stroke. 2014;45:2853-2854; originally published online August 19, 2014; doi: 10.1161/STROKEAHA.114.006798 Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://stroke.ahajournals.org/content/45/10/2853
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Stroke is online at: http://stroke.ahajournals.org//subscriptions/
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H
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. From the School of Medicine and Pharmacology, The University of Western Australia, Perth, Australia; and Department of Neurology, Sir Charles Gairdner Hospital, Perth, Australia. Correspondence to Graeme J. Hankey, MD, School of Medicine and Pharmacology, The University of Western Australia, Perkins Institute of Medical Research, QEII Medical Centre, Perth 6009, Australia. E-mail [email protected] (Stroke. 2014;45:2853-2854.) © 2014 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.114.006798
higher likelihood of being black, male, unmarried, unemployed, less educated, diabetic, a smoker, and scoring highly on the vital exhaustion measure among the 380 participants (2.8%) with a small social network compared with a large social network.16 The association appeared to be partly mediated by perceived social support and vital exhaustion (fatigue, irritability, and feelings of demoralization) but not inflammation (high-sensitivity C-reactive protein). There was no significant increase in the incidence of stroke among the few participants (0.5%) who perceived a lack of social support compared with those with high social support (HR, 1.59; 95% CI, 0.75–3.36).16 The internal validity of the ARIC study results is supported by the rigorous study methodology. A large cohort (n=13 686) of community-dwelling, biracial, middle-aged, stroke-free men and women were recruited prospectively from sampling 4 US communities and underwent a standardized baseline assessment of candidate variables (social network by the 10-item Lubben Social Network Scale, and perceived social support by a 16-item Interpersonal Support Evaluation List-Short Form) and covariates.16 After a median of 18.6 years follow-up, a large number (n=905) of incident stroke outcomes were adjudicated according to a standardized definition of stroke. The limitations of the study include measurement of social network and support based on self-report and at one point in time only, probable incomplete ascertainment of stroke outcome events (hospitalized or fatal strokes reported by participants and proxys), and limited statistical power to evaluate the effect of a perceived lack of social support on stroke risk because of its low prevalence (0.5%) in the study population. The external validity of the ARIC study results is supported by their consistency with other studies.6,14,15 The results of the first study of 2603 health maintenance organization members5 may also have been consistent if the authors of that study had not defined a small social network as a score in the lowest tertile, because this may have been too crude a subcategorization if the prevalence of a small social network was well below one third, as observed in the ARIC study.16 Overall, the totality of published evidence suggests that a small social network is a risk factor for incident stroke. The association is reasonably strong, consistent, specific, and plausible. The potential mechanisms by which social interaction and relationships may reduce stroke risk include behavioral, social, psychological, and physiological pathways. Individuals with a small social network and support are predisposed to adverse health behaviors (eg, cigarette smoking, alcohol and other drug abuse, poor diet, sedentary lifestyle) and suboptimal health service utilization and adherence to medical recommendations.2 Small social network is also associated with psychological stress, activation of the neuroendocrine system,
Downloaded from http://stroke.ahajournals.org/ by guest on April 13, 2015 2853
2854 Stroke October 2014 upregulation of chronic inflammation, and endothelial and platelet dysfunction.17,18 Nevertheless, it is not possible to prove a causal relationship between small social network and stroke from observational studies.19 The results above may reflect residual confounding by failure to accurately measure and adequately adjust for factors such as diet, mood, health service utilization, and other complex social and environmental exposures that may have differed between the comparison groups (small versus large social network) and the outcome (stroke). The results may also reflect bias, such as reverse causality bias whereby lifestyle choices and health-related behaviors may have determined social networks. More robust techniques for assessing causal associations between social network and stroke are needed. Randomized controlled trials are problematic in this context.20 However, observational Mendelian randomization studies may be possible.21 Although the genetic and biological mechanisms underlying social networking are not well understood, the neuropeptides oxytocin and arginine vasopressin are brain signaling molecules that encode proteins that regulate a suite of social behaviors relevant to social bonding.22,23 Genetic polymorphisms in oxytocin pathway genes (eg, CD38 [rs12644506]) may influence social integration and other social behaviors.24 To perform Mendelian randomization, such genetic variants require 3 key features: first, to be allocated to individuals randomly (ie, at conception); second, to be associated with the risk factor (social network); and third, to affect outcome (stroke) only via the risk factor and not other biological pathways.21 While awaiting more definitive studies of a causal association between social network and stroke risk, it would be appropriate to encourage health professionals to consider social network size and quality as a possible causal and modifiable risk factor for stroke, to help individuals at risk of stroke to become more socially engaged and to advocate for more community resources to facilitate social networks.
Disclosures None.
References 1. Takagi D, Kondo K, Kawachi I. Social participation and mental health: moderating effects of gender, social role and rurality. BMC Public Health. 2013;13:701. 2. Watt RG, Heilmann A, Sabbah W, Newton T, Chandola T, Aida J, et al. Social relationships and health related behaviors among older US adults. BMC Public Health. 2014;14:533. 3. Durkheim E. Suicide. New York: Free Press; 1951. 4. House JS, Landis KR, Umberson D. Social relationships and health. Science. 1988;241:540–545. 5. Vogt TM, Mullooly JP, Ernst D, Pope CR, Hollis JF. Social networks as predictors of ischemic heart disease, cancer, stroke and hypertension: incidence, survival and mortality. J Clin Epidemiol. 1992;45:659–666.
6. Kawachi I, Colditz GA, Ascherio A, Rimm EB, Giovannucci E, Stampfer MJ, et al. A prospective study of social networks in relation to total mortality and cardiovascular disease in men in the USA. J Epidemiol Community Health. 1996;50:245–251. 7. Eng PM, Rimm EB, Fitzmaurice G, Kawachi I. Social ties and change in social ties in relation to subsequent total and cause-specific mortality and coronary heart disease incidence in men. Am J Epidemiol. 2002;155:700–709. 8. Sinokki M, Hinkka K, Ahola K, Koskinen S, Kivimäki M, Honkonen T, et al. The association of social support at work and in private life with mental health and antidepressant use: the Health 2000 Study. J Affect Disord. 2009;115:36–45. 9. Barth J, Schneider S, von Känel R. Lack of social support in the etiology and the prognosis of coronary heart disease: a systematic review and meta-analysis. Psychosom Med. 2010;72:229–238. 10. Stringhini S, Berkman L, Dugravot A, Ferrie JE, Marmot M, Kivimaki M, et al. Socioeconomic status, structural and functional measures of social support, and mortality: The British Whitehall II Cohort Study, 1985-2009. Am J Epidemiol. 2012;175:1275–1283. 11. Ikeda A, Kawachi I, Iso H, Iwasaki M, Inoue M, Tsugane S. Social support and cancer incidence and mortality: the JPHC study cohort II. Cancer Causes Control. 2013;24:847–860. 12. Barger SD. Social integration, social support and mortality in the US National Health Interview Survey. Psychosom Med. 2013;75:510–517. 13. Hill PL, Weston SJ, Jackson JJ. Connecting social environment variables to the onset of major specific health outcomes. Psychol Health. 2014;29:753–767. 14. Rutledge T, Linke SE, Olson MB, Francis J, Johnson BD, Bittner V, et al. Social networks and incident stroke among women with suspected myocardial ischemia. Psychosom Med. 2008;70:282–287. 15. Ikeda A, Iso H, Kawachi I, Yamagishi K, Inoue M, Tsugane S; JPHC Study Group. Social support and stroke and coronary heart disease: the JPHC study cohorts II. Stroke. 2008;39:768–775. 16. Nagayoshi M, Everson-Rose SA, Iso H, Mosley TH Jr, Rose KM, Lutsey PL. Social network, social support, and risk of incident stroke: Atherosclerosis Risk in Communities Study. Stroke. 2014;45:2868–2873. 17. Yang YC, McClintock MK, Kozloski M, Li T. Social isolation and adult mortality: the role of chronic inflammation and sex differences. J Health Soc Behav. 2013;54:183–203. 18. Non AL, Rimm EB, Kawachi I, Rewak MA, Kubzansky LD. The effects of stress at work and at home on inflammation and endothelial dysfunction. PLoS One. 2014;9:e94474. 19. Hill AB. The environment and disease: association or causation? Proc R Soc Med. 1965;58:295–300. 20. Berkman LF, Blumenthal J, Burg M, Carney RM, Catellier D, Cowan MJ, et al; Enhancing Recovery in Coronary Heart Disease Patients Investigators (ENRICHD). Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA. 2003;289:3106–3116. 21. Burgess S, Butterworth A, Malarstig A, Thompson SG. Use of Mendelian randomisation to assess potential benefit of clinical intervention. BMJ. 2012;345:e7325. 22. Meyer-Lindenberg A, Domes G, Kirsch P, Heinrichs M. Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine. Nat Rev Neurosci. 2011;12:524–538. 23. Ebstein RP, Knafo A, Mankuta D, Chew SH, Lai PS. The contributions of oxytocin and vasopressin pathway genes to human behavior. Horm Behav. 2012;61:359–379. 24. Chang SC, Glymour MM, Rewak M, Cornelis MC, Walter S, Koenen KC, et al. Are genetic variations in OXTR, AVPR1A, and CD38 genes important to social integration? Results from two large U.S. cohorts. Psychoneuroendocrinology. 2014;39:257–268. Key Words: Editorial ◼ epidemiology ◼ risk factors ◼ stroke
Downloaded from http://stroke.ahajournals.org/ by guest on April 13, 2015
Social Network and Stroke Risk: Size Matters Graeme J. Hankey Stroke. 2014;45:2853-2854; originally published online August 19, 2014; doi: 10.1161/STROKEAHA.114.006798 Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://stroke.ahajournals.org/content/45/10/2853
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Stroke is online at: http://stroke.ahajournals.org//subscriptions/
Downloaded from http://stroke.ahajournals.org/ by guest on April 13, 2015
