Social Relationships and Mortality Risk: A Meta-analytic Review: e1000316

Abstract

Background

The quality and quantity of individuals' social relationships has been linked not only to mental health but also to both morbidity and mortality.

Objectives

This meta-analytic review was conducted to determine the extent to which social relationships influence risk for mortality, which aspects of social relationships are most highly predictive, and which factors may moderate the risk.

Data Extraction

Data were extracted on several participant characteristics, including cause of mortality, initial health status, and pre-existing health conditions, as well as on study characteristics, including length of follow-up and type of assessment of social relationships.

Results

Across 148 studies (308,849 participants), the random effects weighted average effect size was OR = 1.50 (95% CI 1.42 to 1.59), indicating a 50% increased likelihood of survival for participants with stronger social relationships. This finding remained consistent across age, sex, initial health status, cause of death, and follow-up period. Significant differences were found across the type of social measurement evaluated (p<0.001); the association was strongest for complex measures of social integration (OR = 1.91; 95% CI 1.63 to 2.23) and lowest for binary indicators of residential status (living alone versus with others) (OR = 1.19; 95% CI 0.99 to 1.44).

Conclusions

The influence of social relationships on risk for mortality is comparable with well-established risk factors for mortality.

Please see later in the article for the Editors' Summary

Abstract

Background

The quality and quantity of individuals' social relationships has been linked not only to mental health but also to both morbidity and mortality.

Objectives

This meta-analytic review was conducted to determine the extent to which social relationships influence risk for mortality, which aspects of social relationships are most highly predictive, and which factors may moderate the risk.

Data Extraction

Data were extracted on several participant characteristics, including cause of mortality, initial health status, and pre-existing health conditions, as well as on study characteristics, including length of follow-up and type of assessment of social relationships.

Results

Across 148 studies (308,849 participants), the random effects weighted average effect size was OR = 1.50 (95% CI 1.42 to 1.59), indicating a 50% increased likelihood of survival for participants with stronger social relationships. This finding remained consistent across age, sex, initial health status, cause of death, and follow-up period. Significant differences were found across the type of social measurement evaluated (p<0.001); the association was strongest for complex measures of social integration (OR = 1.91; 95% CI 1.63 to 2.23) and lowest for binary indicators of residential status (living alone versus with others) (OR = 1.19; 95% CI 0.99 to 1.44).

Conclusions

The influence of social relationships on risk for mortality is comparable with well-established risk factors for mortality.

Please see later in the article for the Editors' Summary

Citation: Holt-Lunstad J, Smith TB, Layton JB (2010) Social Relationships and Mortality Risk: A Meta-analytic Review. PLoS Med 7(7): e1000316. doi:10.1371/journal.pmed.1000316

Academic Editor: Carol Brayne, University of Cambridge, United Kingdom

Received: December 30, 2009; Accepted: June 17, 2010; Published: July 27, 2010

Copyright: © 2010 Holt-Lunstad et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This research was generously supported by grants from the Department of Gerontology at Brigham Young University awarded to JHL and TBS and from TP Industrial, Inc awarded to TBS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: CI, confidence interval; CVD, cardiovascular disease; OR, odds ratio

Editors' Summary

Background

Humans are naturally social. Yet, the modern way of life in industrialized countries is greatly reducing the quantity and quality of social relationships. Many people in these countries no longer live in extended families or even near each other. Instead, they often live on the other side of the country or even across the world from their relatives. Many also delay getting married and having children. Likwise, more and more people of all ages in developed countries are living alone, and loneliness is becoming increasingly common. In the UK, according to a recent survey by the Mental Health Foundation, 10% of people often feel lonely, a third have a close friend or relative who they think is very lonely, and half think that people are getting lonelier in general. Similarly, across the Atlantic, over the past two decades there has been a three-fold increase in the number of Americans who say they have no close confidants. There is reason to believe that people are becoming more socially isolated.

Why Was This Study Done?

Some experts think that social isolation is bad for human health. They point to a 1988 review of five prospective studies (investigations in which the characteristics of a population are determined and then the population is followed to see whether any of these characteristics are associated with specific outcomes) that showed that people with fewer social relationships die earlier on average than those with more social relationships. But, even though many prospective studies of mortality (death) have included measures of social relationships since that first review, the idea that a lack of social relationships is a risk factor for death is still not widely recognized by health organizations and the public. In this study, therefore, the researchers undertake a systematic review and meta-analysis of the relevant literature to determine the extent to which social relationships influence mortality risk and which aspects of social relationships are most predictive of mortality. A systematic review uses predefined criteria to identify all the research on a given topic; a meta-analysis uses statistical methods to combine the results of several studies.

What Did the Researchers Do and Find?

The researchers identified 148 prospective studies that provided data on individuals' mortality as a function of social relationships and extracted an "effect size" from each study. An effect size quantifies the size of a difference between two groups--here, the difference in the likelihood of death between groups that differ in terms of their social relationships. The researchers then used a statistical method called "random effects modeling" to calculate the average effect size of the studies expressed as an odds ratio (OR)--the ratio of the chances of an event happening in one group to the chances of the same event happening in the second group. They report that the average OR was 1.5. That is, people with stronger social relationships had a 50% increased likelihood of survival than those with weaker social relationships. Put another way, an OR of 1.5 means that by the time half of a hypothetical sample of 100 people has died, there will be five more people alive with stronger social relationships than people with weaker social relationships. Importantly, the researchers also report that social relationships were more predictive of the risk of death in studies that considered complex measurements of social integration than in studies that considered simple evaluations such as marital status.

What Do These Findings Mean?

These findings indicate that the influence of social relationships on the risk of death are comparable with well-established risk factors for mortality such as smoking and alcohol consumption and exceed the influence of other risk factors such as physical inactivity and obesity. Furthermore, the overall effect of social relationships on mortality reported in this meta-analysis might be an underestimate, because many of the studies used simple single-item measures of social isolation rather than a complex measurement. Although further research is needed to determine exactly how social relationships can be used to reduce mortality risk, physicians, health professionals, educators, and the media should now acknowledge that social relationships influence the health outcomes of adults and should take social relationships as seriously as other risk factors that affect mortality, the researchers conclude.

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000316.

* The Mental Health America Live Your Life Well page includes information about how social relationships improve both mental and physical health

* The Mental Health Foundation, a UK charity, has information on loneliness and mental health; its report "The Lonely Society?" can be

[Figure omitted, see PDF]

Figure 1. Flow diagram.

Data Abstraction

To increase the accuracy of coding and data entry, each article was initially coded by two raters. Subsequently, the same article was independently coded by two additional raters. Coders extracted several objectively verifiable characteristics of the studies: (a) the number of participants and their composition by age, gender, marital status, distress level, health status, and pre-existing health conditions (if any), as well as the percentage of smokers and percentage of physically active individuals, and, of course, the cause of mortality; (b) the length of follow up; (c) the research design; and (d) the aspect of social relationships evaluated.

Data within studies were often reported in terms of odds ratios (ORs), the likelihood of mortality across distinct levels of social relationships. Because OR values cannot be meaningfully aggregated, all effect sizes reported within studies were transformed to the natural log OR (lnOR) for analyses and then transformed back to OR for interpretation. When effect size data were reported in any metric other than OR or lnOR, we transformed those values using statistical software programs and macros (e.g., Comprehensive Meta-Analysis [24]). In some cases when direct statistical transformation proved impossible, we calculated the corresponding effect sizes from frequency data in matrices of mortality status by social relationship status. When frequency data were not reported, we recovered the cell probabilities from the reported ratio and marginal probabilities. When survival analyses (i.e., hazard ratios) were reported, we calculated the effect size from the associated level of statistical significance, often derived from 95% confidence intervals (CIs). Across all studies we assigned OR values less than 1.00 to data indicative of increased mortality and OR values greater than 1.00 to data indicative of decreased mortality for individuals with relatively higher levels of social relationships.

When multiple effect sizes were reported within a study at the same point in time (e.g., across different measures of social relationships), we averaged the several values (weighted by standard error) to avoid violating the assumption of independent samples. In such cases, the aggregate standard error value for the lnOR were estimated on the basis of the total frequency data without adjustment for possible correlation among the averaged values. Although this method was imprecise, the manuscripts included in the meta-analysis did not report the information necessary to make the statistical adjustments, and we decided not to impute values given the wide range possible. In analyzing the data we used the shifting units of analysis approach [25] which minimizes the threat of nonindependence in the data while at the same time allowing more detailed follow-up analyses to be conducted (i.e., examination of effect size heterogeneity).

When multiple reports contained data from the same participants (publications of the same database), we selected the report containing the whole sample and eliminated reports of subsamples. When multiple reports contained the same whole sample, we selected the one with the longest follow-up duration. When multiple reports with the same whole sample were of the same duration, we selected the one reporting the greatest number of measures of social relationships.

In cases where multiple effect sizes were reported across different levels of social relationships (i.e., high versus medium, medium versus low), we extracted the value with the greatest contrast (i.e., high versus low). When a study contained multiple effect sizes across time, we extracted the data from the longest follow-up period. If a study used statistical controls in calculating an effect size, we extracted the data from the model utilizing the fewest statistical controls so as to remain as consistent as possible across studies (and we recorded the type and number of covariates used within each study to run post hoc comparative analyses). We coded the research design used rather than estimate risk of individual study bias. The coding protocol is available from the authors.

The majority of information obtained from the studies was extracted verbatim from the reports. As a result, the inter-rater agreement was quite high for categorical variables (mean Cohen's kappa = 0.73, SD = 0.13) and for continuous variables (mean intraclass correlation [26] = 0.80, SD = .14). Discrepancies across coding pairs were resolved through further scrutiny of the manuscript until consensus was obtained.

Aggregate effect sizes were calculated using random effects models following confirmation of heterogeneity. A random effects approach produces results that generalize beyond the sample of studies actually reviewed [27]. The assumptions made in this meta-analysis clearly warrant this method: The belief that certain variables serve as moderators of the observed association between social relationships and mortality implies that the studies reviewed will estimate different population effect sizes. Random effects models take such between-studies variation into account, whereas fixed effects models do not [28]. In each analysis conducted, we examined the remaining variance to confirm that random effects models were appropriate.

Results

Statistically nonredundant effect sizes were extracted from 148 studies ([29]-[176]; see Table 1). Data were reported from 308,849 participants, with 51% from North America, 37% from Europe, 11% from Asia, and 1% from Australia. Across all studies, the average age of participants at initial evaluation was 63.9 years, and participants were evenly represented across sex (49% female, 51% male). Of the studies examined, 60% involved community samples, but 24% examined individuals receiving outpatient medical treatment, and 16% utilized patients in inpatient medical settings. Of studies involving patients with a pre-existing diagnosis, 44% were specific to cardiovascular disease (CVD), 36% to cancer, 9% to renal disease, and the remaining 11% had a variety of conditions including neurological disease. Research reports most often (81%) considered all-cause mortality, but some restricted evaluations to mortality associated with cancer (9%), CVD (8%), or other causes (2%). Participants were followed for an average of 7.5 years (SD = 7.1, range = 3 months to 58 years), with an average of 29% of the participants dying within each study's follow-up period.

Table 1. Overview of the 148 studies included in the meta-analysis.

Omnibus Analysis

Across 148 studies, the random effects weighted average effect size was OR = 1.50 (95% confidence interval [CI] = 1.42 to 1.59), which indicated a 50% increased likelihood of survival as a function of stronger social relations. Odds ratios ranged from 0.77 to 6.50, with substantial heterogeneity across studies (I2 = 81% [95% CI = 78% to 84%]; Q(147) = 790, p<0.001; τ2 = 0.07), suggesting that systematic effect size variability was unaccounted for. Thus factors associated with the studies themselves (e.g., publication status), participant characteristics (e.g., age, health status), and the type of evaluation of social relationships (e.g., structural social networks versus perceptions of functional social support) may have moderated the overall results. We therefore conducted additional analyses to determine the extent to which these variables moderated the overall results.

To assess the possibility of publication bias [177], we conducted several analyses. First, we calculated the fail-safe N [177] to be 4,274, which is the theoretical number of unpublished studies with effect sizes averaging zero (no effect) that would be needed to render negligible the omnibus results. Second, we employed the "trim and fill" methodology described by Duval and Tweedie [178],[179] to estimate the number of studies missing due to publication bias, but this analysis failed to reveal any studies that would need to be created on the opposite side of the distribution, meaning that adjustment to the omnibus effect size was unnecessary. Third, we calculated both Egger's regression test and the alternative to that test recommended by Peters and colleagues [180] that is better suited to data in lnOR format. The results of both analyses failed to reach statistical significance (p>0.05). Finally, we plotted a contour-enhanced funnel plot (Figure 2) [181]. The data obtained from this meta-analysis were fairly symmetrical with respect to their own mean; fewer than ten studies were "missing" on the left side of the distribution that would have made the plot symmetrical. Based on these several analyses, publication bias is unlikely to threaten the results.

[Figure omitted, see PDF]

Figure 2. Contour enhanced funnel plot.

Moderation by Social Relationship Assessment, and by Participant and Study Characteristics

Given that structural versus functional components of social relationships may influence health in different ways [11],[12], the high degree of heterogeneity observed in the omnibus results may have been due in part to differences between the components of social relationships evaluated within and across studies. Hence the remaining analyses separately evaluate effect sizes obtained from structural, functional, and combined (structural and functional) measures of social relationships. Table 2 provides definitions of the types and subtypes of social relationships evaluated.

Table 2. Descriptive coding of the measures used to assess social relationships.

Structural aspects of social relationships.

Sixty-three studies had data exclusive to structural measures of social relationships (see Figure 3). Across these studies, the random effects weighted average effect size was OR = 1.57 (95% CI = 1.46 to 1.70), which value fell within the CI of the omnibus results reported previously. The heterogeneity across studies was still quite large (I2 = 84% [95% CI = 80% to 87%]; Q(62) = 390, p<0.001; τ2 = 0.07), so we undertook metaregression with prespecified participant and study characteristics.

[Figure omitted, see PDF]

Figure 3. Forest plot of structural measures.

Metaregression is an analogue to multiple regression analysis for effect sizes. Its primary purpose is to ascertain which continuous and categorical (dummy coded) variables predict variation in effect size estimates. Using random effects weighted metaregression, we examined the simultaneous association (with all variables entered into the model) between effect sizes and prespecified participant and study characteristics (Table 3). To examine the most precise effect size estimates available and to increase the statistical power associated with this analysis, we shifted the unit of analysis [24] and extracted effect sizes within studies that were specific to measures of structural aspects of social relationships. That is, if a study contained effect sizes from both structural and functional types of social relationships, we extracted the structural types for this analysis (with identical subtypes aggregated), which resulted in a total of 230 unique effect sizes across 116 studies. A total of 18% of the variance in these effect sizes was explained in the metaregression (p<0.001). As can be seen in Table 3, effect sizes based on data controlling for other variables were lower in magnitude than those based on raw data. Moreover, effect sizes differed in magnitude across the subtype of structural social relationships measured. Complex measures of social integration were associated with larger effect size values than measures of social participation. Binary measures of whether participants lived alone (yes/no) were associated with smaller effect size values. Average random effects weighted odds ratios for the various subtypes of social relationships are reported in Table 4.

Table 3. Random effects metaregression for effect size estimates of structural social relationships.

Table 4. Weighted average effect sizes across different measures of social relationships.

Functional aspects of social relationships.

Twenty-four studies had data exclusive to functional measures of social relationships (see Figure 4). Across these studies, the random effects weighted average effect size was OR = 1.46 (95% CI = 1.28 to 1.66), which value fell within the CI of the omnibus results reported previously. There was moderate heterogeneity across studies (I2 = 47% [95% CI = 16% to 68%]; Q(23) = 44, p<0.01; τ2 = 0.04), so we conducted a random effects metaregression using the same variables and analytic procedures described previously. We extracted 87 unique effect sizes that were specific to measures of functional social relationships within 72 studies. A total of 16.5% of the variance in these effect sizes was explained in the metaregression, but the model did not reach statistical significance (p = 0.46). The results were not moderated by any of the specified participant characteristics (age, sex, initial health status, cause of mortality) or study characteristics (length of follow-up, geographic region, statistical controls).

[Figure omitted, see PDF]

Figure 4. Forest plot of functional measures.

Combined assessments of social relationships.

Sixty-one studies had combined data of both structural and functional measures of social relationships (see Figure 5). Across these studies, the random effects weighted average effect size was OR = 1.44 (95% CI = 1.32 to 1.58). A large degree of heterogeneity characterized studies (I2 = 82% [95% CI = 78% to 86%]; Q(60) = 337, p<0.001; τ2 = 0.09), and we conducted a random effects metaregression using the same variables and analytic procedures described previously. We extracted 64 unique effect sizes that evaluated combined structural and functional measures of social relationships within 61 studies. The metaregression explained only 6.8% of the variance in these effect sizes, and the model failed to reach statistical significance (p = 0.95). None of the variables in the metaregression moderated the results.

[Figure omitted, see PDF]

Figure 5. Forest plot of combined measures.

Discussion

Cumulative empirical evidence across 148 independent studies indicates that individuals' experiences within social relationships significantly predict mortality. The overall effect size corresponds with a 50% increase in odds of survival as a function of social relationships. Multidimensional assessments of social integration yielded an even stronger association: a 91% increase in odds of survival. Thus, the magnitude of these findings may be considered quite large, rivaling that of well-established risk factors (Figure 6). Results also remained consistent across a number of factors, including age, sex, initial health status, follow-up period, and cause of death, suggesting that the association between social relationships and mortality may be generalized.

[Figure omitted, see PDF]

Figure 6. Comparison of odds (lnOR) of decreased mortality across several conditions associated with mortality.

Note: Effect size of zero indicates no effect. The effect sizes were estimated from meta analyses: ; A = Shavelle, Paculdo, Strauss, and Kush, 2008 [205]; B = Critchley and Capewell, 2003 [206]; C = Holman, English, Milne, and Winter, 1996 [207]; D = Fine, Smith, Carson, Meffe, Sankey, Weissfeld, Detsky, and Kapoor, 1994 [208]; E = Taylor, Brown, Ebrahim, Jollife, Noorani, Rees et al., 2004 [209]; F, G = Katzmarzyk, Janssen, and Ardern, 2003 [210]; H = Insua, Sacks, Lau, Lau, Reitman, Pagano, and Chalmers, 1994 [211]; I = Schwartz, 1994 [212].

The magnitude of risk reduction varied depending on the type of measurement of social relationships (see Table 4). Social relationships were most highly predictive of reduced risk of mortality in studies that included multidimensional assessments of social integration. Because these studies included more than one type of social relationship measurement (e.g., network based inventories, marital status, etc.), such a measurement approach may better represent the multiple pathways (described earlier) by which social relationships influence health and mortality [182]. Conversely, binary evaluations of living alone (yes/no) were the least predictive of mortality status. The reliability and validity of measurement likely explains this finding, and researchers are encouraged to use psychometrically sound measures of social relationships (e.g., Table 2). For instance, while researchers may be tempted to use a simple single-item such as "living alone" as a proxy for social isolation, it is possible for one to live alone but have a large supportive social network and thus not adequately capture social isolation. We also found that social isolation had a similar influence on likelihood of mortality compared with other measures of social relationships. This evidence qualifies the notion of a threshold effect (lack of social relationships is the only detrimental condition); rather, the association appears robust across a variety of types of measures of social relationships.

This meta-analysis also provides evidence to support the directional influence of social relationships on mortality. Most of the studies (60%) involved community cohorts, most of whom would not be experiencing life-threatening conditions at the point of initial evaluation. Moreover, initial health status did not moderate the effect of social relationships on mortality. Although illness may result in poorer or more restricted social relationships (social isolation resulting from physical confinement), such that individuals closer to death may have decreased social support compared to healthy individuals, the findings from these studies indicate that general community samples with strong social relationships are likely to remain alive longer than similar individuals with poor social relations. However, causality is not easily established. One cannot randomly assign human participants to be socially isolated, married, or in a poor-quality relationship. A similar dilemma characterizes virtually all lifestyle risk factors for mortality: for instance, one cannot randomly assign individuals to be smokers or nonsmokers. Despite such challenges, "smoking represents the most extensively documented cause of disease ever investigated in the history of biomedical research" [183]. The link between social relationships and mortality is currently much less understood than other risk factors; nonetheless there is substantial experimental, cross-sectional, and prospective evidence linking social relationships with multiple pathways associated with mortality (see [182] for review). Existing models for reducing risk of mortality may be substantially strengthened by including social relationship factors.

Notably, the overall effect for social relationships on mortality reported here may be a conservative estimate. Many studies included in the meta-analysis utilized single item measures of social relations, yet the magnitude of the association was greatest among those studies utilizing complex assessments. Moreover, because many studies statistically adjusted for standard risk factors, the effect may be underestimated, since some of the impact of social relationships on mortality may be mediated through such factors (e.g., behavior, diet, exercise). Additionally, most measures of social relations did not take into account the quality of the social relationships, thereby assuming that all relationships are positive. However, research suggests this is not the case, with negative social relationships linked to greater risk of mortality [184],[185]. For instance, marital status is widely used as a measure of social integration; however, a growing literature documents its divergent effects based on level of marital quality [186],[187]. Thus the effect of positive social relationships on risk of mortality may actually be much larger than reported in this meta-analysis, given the failure to account for negative or detrimental social relationships within the measures utilized across studies.

Other possible limitations of this review should be acknowledged. Statistical controls (e.g., age, sex, physical condition, etc.) employed by many of the studies rule out a number of potentially confounding variables that might account for the association between social relationships and mortality. However, studies used an inconsistent variety of controlling variables, and some reports involved raw data (Table 1). Although effect size magnitude was diminished by the inclusion of statistical controls only within the data obtained by measures of structural social relationships (but not functional or combined measures), future research can better specify which variables are most likely to impact the overall association. It must also be acknowledged that existing data primarily represent research conducted in North America and Western Europe. Although we found no differences across world region, future reviews inclusive of research written in all languages (not only English) with participants better representing other world regions may yield better estimates across populations.

Approximately two decades after the review by House and colleagues [1], a generation of empirical research validates their initial premise: Social relationships exert an independent influence on risk for mortality comparable with well established risk factors for mortality (Figure 6). Although limited by the state of current investigations and possible omission of pertinent reports, this meta-analysis provides empirical evidence (nearly 30 times the number of studies previously reported) to support the criteria for considering insufficient social relationships a risk factor of mortality (i.e., strength and consistency of association across a wide range of studies, temporal ordering, and gradient of response) [188]. The magnitude of the association between social relationships and mortality has now been established, and this meta-analysis provides much-needed clarification regarding the social relationship factor(s) most predictive of mortality. Future research can shift to more nuanced questions aimed at (a) understanding the causal pathways by which social participation promotes health, (b) refining conceptual models, and (c) developing effective intervention and prevention models that explicitly account for social relations.

Some steps have already been taken identifying the psychological, behavioral, and physiological pathways linking social relationships to health [5],[182],[189]. Social relationships are linked to better health practices and to psychological processes, such as stress and depression, that influence health outcomes in their own right [190]; however, the influence of social relationships on health cannot be completely explained by these processes, as social relationships exert an independent effect. Reviews of such findings suggest that there are multiple biologic pathways involved (physiologic regulatory mechanisms, themselves intertwined) that in turn influence a number of disease endpoints [182],[191]-[193]. For instance, a number of studies indicate that social support is linked to better immune functioning [194]-[197] and to immune-mediated inflammatory processes [198]. Thus interdisciplinary work and perspective will be important in future studies given the complexity of the phenomenon.

Perhaps the most important challenge posed by these findings is how to effectively utilize social relationships to reduce mortality risk. Preliminary investigations have demonstrated some risk reduction through formalized social interventions [199]. While the evidence is mixed [2],[6], it should be noted that most social support interventions evaluated in the literature thus far are based on support provided from strangers; in contrast, evidence provided in this meta-analysis is based almost entirely on naturally occurring social relationships. Moreover, our analyses suggest that received support is less predictive of mortality than social integration (Table 4). Therefore, facilitating patient use of naturally occurring social relations and community-based interventions may be more successful than providing social support through hired personnel, except in cases in which patient social relations appear to be detrimental or absent. Multifaceted community-based interventions may have a number of advantages because such interventions are socially grounded and include a broad cross-section of the public. Public policy initiatives need not be limited to those deemed "high risk" or those who have already developed a health condition but could potentially include low- and moderate-risk individuals earlier in the risk trajectory [200]. Overall, given the significant increase in rate of survival (not to mention quality of life factors), the results of this meta-analysis are sufficiently compelling to promote further research aimed at designing and evaluating interventions that explicitly account for social relationship factors across levels of health care (prevention, evaluation, treatment compliance, rehabilitation, etc.).

Conclusion

Data across 308,849 individuals, followed for an average of 7.5 years, indicate that individuals with adequate social relationships have a 50% greater likelihood of survival compared to those with poor or insufficient social relationships. The magnitude of this effect is comparable with quitting smoking and it exceeds many well-known risk factors for mortality (e.g., obesity, physical inactivity). These findings also reveal significant variability in the predictive utility of social relationship variables, with multidimensional assessments of social integration being optimal when assessing an individual's risk for mortality and evidence that social isolation has a similar influence on mortality to other measures of social relationships. The overall effect remained consistent across a number of factors, including age, sex, initial health status, follow-up period, and cause of death, suggesting that the association between social relationships and mortality may be general, and efforts to reduce risk should not be isolated to subgroups such as the elderly.

To draw a parallel, many decades ago high mortality rates were observed among infants in custodial care (i.e., orphanages), even when controlling for pre-existing health conditions and medical treatment [201]-[204]. Lack of human contact predicted mortality. The medical profession was stunned to learn that infants would die without social interaction. This single finding, so simplistic in hindsight, was responsible for changes in practice and policy that markedly decreased mortality rates in custodial care settings. Contemporary medicine could similarly benefit from acknowledging the data: Social relationships influence the health outcomes of adults.

Physicians, health professionals, educators, and the public media take risk factors such as smoking, diet, and exercise seriously; the data presented here make a compelling case for social relationship factors to be added to that list. With such recognition, medical evaluations and screenings could routinely include variables of social well-being; medical care could recommend if not outright promote enhanced social connections; hospitals and clinics could involve patient support networks in implementing and monitoring treatment regimens and compliance, etc. Health care policies and public health initiatives could likewise benefit from explicitly accounting for social factors in efforts aimed at reducing mortality risk. Individuals do not exist in isolation; social factors influence individuals' health though cognitive, affective, and behavioral pathways. Efforts to reduce mortality via social relationship factors will require innovation, yet innovation already characterizes many medical interventions that extend life at the expense of quality of life. Social relationship-based interventions represent a major opportunity to enhance not only the quality of life but also survival.

Supporting Information

Alternative Language Abstract S1.

Abstract translated into Japanese by Hideko Cannell.

(0.02 MB DOC)

Alternative Language Abstract S2.

Abstract translated into Spanish by Rod Veas.

(0.03 MB DOC)

Text S1.

PRISMA checklist.

(0.06 MB DOC)

Text S2.

Review protocol.

(0.05 MB DOC)

Acknowledgments

We would like to thank Jennie Bingham, Wendy Birmingham, Anne Brown, Hoku Conklin, Shawna Rae Cope, Kaitie Dyson, Stacie Fraire, Jeffrey Gale, Karen Gochnour, Angela Salas Hamaker, Adam Howard, Brian Mead, Esther Rawlings, Keely Smith, Effie Thacker, and Hiroko Umeda for their assistance with coding. We would also like to thank Bert Uchino, University of Utah, and Teresa Seeman, UCLA, for their helpful feedback on an earlier version of this paper.

Author Contributions

ICMJE criteria for authorship read and met: JHL TS JBL. Agree with the manuscript's results and conclusions: JHL TS JBL. Designed the experiments/the study: TS. Analyzed the data: JHL TS JBL. Collected data/did experiments for the study: JHL TS JBL. Wrote the first draft of the paper: JHL TS. Contributed to the writing of the paper: JHL TS JBL.

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