Loneliness, social isolation, cardiovascular disease and mortality: a synthesis of the literature and conceptual framework

To conduct a systematic review and develop a conceptual framework on the mechanisms linking loneliness, social isolation, health outcomes and mortality. Electronic databases were systematically searched (PubMed, MEDLINE, Scopus and EMBASE) from inception to October 2018 followed by manual searching to identify research on loneliness, social isolation and mortality in adults published in the English language. Articles were assessed for quality and synthesised into a conceptual framework using meta-ethnographical approaches. A total of 122 articles were included. These collated observational designs examining mediators and moderations of the association in addition to qualitative studies exploring potential mechanisms were included. A framework incorporating 18 discrete factors implicated in the association between loneliness, social isolation and mortality was developed. Factors were categorised into societal or individual, and sub-categorised into biological, behavioural and psychological. These findings emphasise the complex multidirectional relationship between loneliness, social isolation and mortality. Our conceptual framework may allow development of more holistic interventions, targeting many of the interdependent factors that contribute to poor outcomes for lonely and socially isolated people.

Emotional loneliness is associated with mortality among mentally intact nursing home residents with and without cancer: a five-year follow-up study.

Supporting papers Original research and reviews exploring the link between loneliness/social isolation and mortality
Loneliness and social isolation as risk factors for mortality: a meta-analytic review Social isolation, loneliness, and all-cause mortality in older men and women A Prospective Study of Social Isolation, Loneliness, and Mortality in Finland Loneliness, social isolation, their synergistic interaction, and mortality Reported loneliness rather than social isolation is a risk factor for 10-year mortality in older men Social isolation: a predictor of mortality comparable to traditional clinical risk factors Loneliness, health, and mortality in old age: a national longitudinal study Does the mortality risk of social isolation depend upon socioeconomic factors? Loneliness, health and mortality Loneliness, social networks, and mortality: 18 years of follow-up Situational versus chronic loneliness as risk factors for all-cause mortality. Among elderly men, feelings of loneliness are associated with increased 10-year mortality risk, independent of social isolation and medical and psychiatric conditions Older people who report loneliness have increased risk of mortality and functional decline Effect of loneliness on mortality after retirement. Increased risk of mortality associated with social isolation in older men: only when feeling lonely? Results from the Amsterdam Study of the Elderly (AMSTEL) Suffering from loneliness indicates significant mortality risk of older people Social isolation and loneliness as risk factors for myocardial infarction, stroke and mortality: UK Biobank cohort study of 479 054 men and women Emotional loneliness is associated with mortality among mentally intact nursing home residents with and without cancer: a five-year follow-up study. Feelings of Loneliness and Living Alone as Predictors of Mortality in the Elderly: The PAQUID Study. Impact of loneliness and depression on mortality: results from the Longitudinal Ageing Study Amsterdam Relationship of depression, anxiety, and social isolation to chronic heart failure outpatient mortality Extreme social isolation, use of community-based senior support services, and mortality among African American elderly women. Loneliness and All-Cause, Cardiovascular, and Noncardiovascular Mortality in Older Men: The Zutphen Elderly Study The feeling of loneliness prior to coronary artery bypass grafting might be a predictor of shortand long-term postoperative mortality Combined effects of job strain and social isolation on cardiovascular disease morbidity and mortality in a random sample of the Swedish male working population Social isolation and mortality in ischemic heart disease. A 10-year follow-up study of 150 middleaged men All-cause mortality and multimorbidity in older adults: The role of social support and loneliness Social isolation, health literacy, and mortality risk: Findings from the English Longitudinal Study of Ageing Social isolation and all-cause mortality: a population-based cohort study in Denmark Heartbeat: Social isolation is associated with increased mortality after acute myocardial infarction or stroke Association of loneliness with all-cause mortality: A meta-analysis. The Pathophysiology of Perceived Social Isolation: Effects on Health and Mortality. Co-existence of social isolation and homebound status increase the risk of all-cause mortality Social Isolation and Mortality in US Black and White Men and Women. Loneliness, social isolation and risk of cardiovascular disease in the English Longitudinal Study of Ageing Loneliness and all-cause mortality in community-dwelling elderly Singaporeans Social isolation, cognitive decline, and cardiovascular disease risk Depression, isolation, social support, and cardiovascular disease in older adults Does social isolation predict hospitalization and mortality among HIV+ and uninfected older veterans? Type A behaviour, social support, and coronary risk: interaction and significance for mortality in cardiac patients Older Adults' Social Relationships and Health Care Utilization: A Systematic Review Whites but Not Blacks Gain Life Expectancy from Social Contacts An overview of systematic reviews on the public health consequences of social isolation and loneliness Gender-specific secondary prevention? Differential psychosocial risk factors for major cardiovascular events Role of social factors on cell death, cerebral plasticity and recovery after stroke Social networks, social support, and burden in relationships, and mortality after breast cancer diagnosis in the Life After Breast Cancer Epidemiology (LACE) study Socioeconomic status, structural and functional measures of social support, and mortality: The British Whitehall II Cohort Study, 1985-2009 Positive life orientation predicts good survival prognosis in old age Long-term effect of social relationships on mortality in patients with congestive heart failure Predictors of cognitive decline and mortality of aged people over a 10-year period Towards a suicide free society: identify suicide prevention as public health policy Longitudinal study of psychiatric symptoms, disability, mortality, and emigration among Bosnian refugees Characteristics of socially isolated patients with coronary artery disease who are at elevated risk for mortality Self-reported life satisfaction and 20-year mortality in healthy Finnish adults Why do men get more heart disease than women? An international perspective Depressive symptoms and lack of social integration in relation to prognosis of CHD in middleaged women. The Stockholm Female Coronary Risk Study Social Networks and Health Outcomes: Importance for Racial and Socioeconomic Disparities in Cardiovascular Outcomes A conceptual model of social networks and mechanisms of cancer mortality, and potential strategies to improve survival The role of social relationships in the link between olfactory dysfunction and mortality Loneliness, Social Isolation, and Cardiovascular Health Loneliness and Health in Older Adults: A Mini-Review and Synthesis Breast cancer and social environment: getting by with a little help from our friends. Personal Networks and Mortality Risk in Older Adults: A Twenty-Year Longitudinal Study Social relationships and health: The toxic effects of perceived social isolation Vitamin D and the social aspects of disease Social Isolation Loneliness and pathways to disease Social relationships and mortality in patients with congestive heart failure Segregation and mortality: The deadly effects of racism? Social relationships and health Myocardial infarction and coronary death among women: psychosocial predictors from a 20-year follow-up of women in the Framingham Study. Disability, psychosocial factors and mortality among the elderly in a rural French population Social ties and survival among the elderly in Tampere, Finland. International Journal of Epidemiology Relationship between respiratory mortality and self-perceptions of aging Psychological predictors of mortality in old age Social networks and longevity. A 14 year follow-up study among elderly in Denmark. Effects of social support and personal coping resources on mortality in older age: the Longitudinal Aging Study Amsterdam Positive life orientation as a predictor of 10-year outcome in an aged population. Loneliness in older persons: a predictor of functional decline and death. Loneliness, health, and longevity Social isolation, social activity and loneliness as survival indicators in old age; a nationwide survey with a 7-year follow-up Mortality and depressive symptoms in inhabitants of residential homes. Psychosocial factors and breast cancer: a 6-year Italian follow-up study. Psychotherapy and psychosomatics Health and social networks as predictors of survival in old age. A longitudinal analysis of factors related to survival in old age Social networks, social support, and mortality among older people in Japan

Research exploring biological links between loneliness/social isolation and mortality
Social isolation and adult mortality: the role of chronic inflammation and sex differences Social isolation, C-reactive protein, and coronary heart disease mortality among communitydwelling adults Social isolation and cardiovascular disease: an atherosclerotic pathway? Loneliness in older adults is associated with diminished cortisol output Sleep disturbance and longitudinal risk of inflammation: Moderating influences of social integration and social isolation in the Coronary Artery Risk Development in Young Adults (CARDIA) study Social isolation and health, with an emphasis on underlying mechanisms Frequency of Leaving the House and Mortality from Age 70 to 95 Prevalence of orthostatic hypertension in the very elderly and its relationship to all-cause mortality One is the deadliest number: the detrimental effects of social isolation on cerebrovascular diseases and cognition. The neuroendocrinology of social isolation Toward a neurology of loneliness Social network ties and inflammation in U.S. Adults with cancer Loneliness matters: A theoretical and empirical review of consequences and mechanisms Neural pathways link social support to attenuated neuroendocrine stress responses Peritoneal dialysis-related peritonitis: Can we predict it? Social integration is associated with fibrinogen concentration in elderly men

Research exploring behavioural links between loneliness/social isolation and mortality
Loneliness and mortality among older adults in China Loneliness and risk of mortality: a longitudinal investigation in Alameda County, California Consequences of loneliness on physical activity and mortality in older adults and the power of positive emotions The Pathophysiology of Perceived Social Isolation: Effects on Health and Mortality. Sleep disturbance and longitudinal risk of inflammation: Moderating influences of social integration and social isolation in the Coronary Artery Risk Development in Young Adults (CARDIA) study Social isolation and health, with an emphasis on underlying mechanisms Does current smoking predict future frailty? The English longitudinal study of ageing The association between social support and physical activity in older adults: a systematic review Gender differences in the roles for social support in ensuring adequate fruit and vegetable consumption among older adult Canadians Unobtrusive in-home detection of time spent out-of-home with applications to loneliness and physical activity Nutritional risk and body mass index predict hospitalization, nursing home admissions, and mortality in community-dwelling older adults: results from the UAB Study of Aging with 8.5 years of follow-up Using multi-level data to estimate the effect of social capital on hazardous alcohol consumption in the former Soviet Union Living alone and alcohol-related mortality: a population-based cohort study from Finland Eating habits and appetite control in the elderly: the anorexia of aging. Effects of depression and social integration on the relationship between alcohol consumption and all-cause mortality The anatomy of loneliness Contribution of risk factors to excess mortality in isolated and lonely individuals: an analysis of data from the UK Biobank cohort study.

Research exploring psychological links between loneliness/social isolation and mortality
Loneliness and risk of mortality: a longitudinal investigation in Alameda County, California The Pathophysiology of Perceived Social Isolation: Effects on Health and Mortality. Loneliness and cardiovascular disease and the role of late-life depression Longitudinal study of suicide after traumatic injury Is depression in old age fatal only when people feel lonely? Suicide and suicidal behavior Psychosocial influences on the development and course of coronary heart disease: Current status and implications for research and practice Papers exploring potential interventions Effects of psychosocial group rehabilitation on health, use of health care services, and mortality of older persons suffering from loneliness: a randomized, controlled trial to decrease loneliness and social isolation The personal and community impact of a Scottish Men's Shed Psychosocial interventions for patients with coronary heart disease and depression: A systematic review and meta-analysis Pet ownership protects against the risks and consequences of coronary heart disease An exploration of the value and mechanisms of befriending for older adults in England The role of social relations in health promotion Exploring interactive surface designs for eliciting social activity from elderly adults