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In their laudable analysis of the Prospective Urban and Rural Epidemiology study, Naito and colleagues(1) used multivariable Cox regression to examine social isolation in relation to all-cause mortality, cardiovascular disease (CVD) mortality, and cause-specific incidence and mortality. Drawing upon the latest evidence in the field, the purpose of this letter is to highlight three strengths of this study and propose an alternative explanation for the observed association between social isolation and CVD incidence.
Naito and colleagues’ study contributes novel insights into potential risk factors for social isolation across high, middle and low income settings. Further, their findings in relation to all-cause and CVD mortality strengthen the literature suggesting that greater isolation is associated with increased mortality.(2) While it is unclear that the assumptions required to calculate population attributable fraction(3) are reasonably met when examining social isolation and mortality, the authors' analysis also contribute to growing evidence(4) that raises questions about the validity of the popular claim that social isolation is as bad for health as smoking.(5–8)
Compared to less isolated participants, Naito and colleagues observed 15% increased CVD incidence among the most isolated participants (HR=1.15, 95% CI: 1.05 – 1.25).(1) The CVD incidence outcome they measured “…included fatal or non-fatal myocardial infarction, stroke, heart failure and ot...
Compared to less isolated participants, Naito and colleagues observed 15% increased CVD incidence among the most isolated participants (HR=1.15, 95% CI: 1.05 – 1.25).(1) The CVD incidence outcome they measured “…included fatal or non-fatal myocardial infarction, stroke, heart failure and other fatal CVD events.”(1) The authors suggest that inconsistencies between this finding and previous research may be explained by variation in their social isolation indices and the studied population’s characteristics. Indeed, this remains possible given that the authors use a mix of more and less subjective measures of social relationships and social support to construct their social isolation index. However, the observed association may also be a product of how CVD incidence was measured.
Recent evidence examining social isolation and incident CVD outcomes suggests that social isolation may play a greater role impacting one’s likelihood of surviving their first CVD event rather than one’s risk of developing CVD in the first place.(9) Earlier this month, a prospective analysis of about 940,000 UK adults found that after adjustment potential confounders, social isolation was not associated with non-fatal coronary heart disease (CHD) incidence (HR= 1.01, 95% CI: 0.98-1.04), weakly associated with non-fatal stroke incidence (HR=1.13, 95% CI: 1.08-1.18), and strongly associated with fatal incident CHD (HR= 1.86, 95% CI: 1.63-2.21) and fatal incident stroke events (HR= 1.91, 95% CI: 1.48-2.46).(9) These findings were supported by other recent and large prospective studies from the USA and UK.(10–13) Therefore, the association observed by Naito and colleagues may also be driven by increased risk of fatal incident CVD events among the most isolated participants as opposed to non-fatal events.
Careful outcome measurement is one tool for helping tease-out potential explanatory pathways linking social isolation and health. The latest evidence suggests that timely access to help with seeking healthcare in response to a life threatening event may be a key pathway linking social isolation and CVD mortality outcomes.(9) Perhaps due in part to the timing of publication, Naito and colleagues present several potential explanations for their findings with exception of this “delays in seeking care” hypothesis. Future research examining CVD and non-CVD incidence outcomes should continue explicitly defining the theoretical and conceptual models underpinning the hypothesized relationships between social isolation and specific disease outcomes under investigation.
1. Naito R, Leong DP, Bangdiwala SI, et al. Impact of social isolation on mortality and morbidity in 20 high-income, middle-income and low-income countries in five continents. BMJ Glob Heal. 2021;6(3):e004124. doi:10.1136/bmjgh-2020-004124
2. Holt-Lunstad J, Smith TB, Baker M, Harris T, Stephenson D. Loneliness and Social Isolation as Risk Factors for Mortality: a Meta-Analytic Review. Perspect Psychol Sci. 2015;10(2):227-237. doi:10.1177/1745691614568352
3. Mansournia MA, Altman DG. Population attributable fraction. BMJ. 2018;360:k757. doi:10.1136/bmj.k757
4. Smith RW, Barnes I, Reeves G, Green J, Beral V, Floud S. P84 Is social isolation as bad for health as smoking 15 cigarettes per day? Findings from two large prospective UK cohorts. J Epidemiol Community Health. 2019;73(Suppl 1):A108 LP-A109. doi:10.1136/jech-2019-SSMabstracts.234
5. Kristof N. Let’s Wage a War on Loneliness. The New York Times. https://www.nytimes.com/2019/11/09/opinion/sunday/britain-loneliness-epi.... Published November 9, 2019. Accessed February 22, 2020.
6. Graham J. Loneliness as a health threat: New campaign raises awareness. STAT News. https://www.statnews.com/2016/11/16/loneliness-health/. Published 2016. Accessed June 28, 2019.
7. Yang YC, Boen C, Gerken K, Li T, Schorpp K, Harris KM. Social relationships and physiological determinants of longevity across the human life span. Proc Natl Acad Sci. 2016;113(3):578-583. doi:10.1073/PNAS.1511085112
8. Courtin E, Knapp M. Social isolation, loneliness and health in old age: a scoping review. Health Soc Care Community. 2017;25(3):799-812. doi:10.1111/hsc.12311
9. Smith RW, Barnes I, Green J, Reeves GK, Beral V, Floud S. Social isolation and risk of heart disease and stroke: analysis of two large UK prospective studies. Lancet Public Heal. 2021. doi:10.1016/S2468-2667(20)30291-7
10. Chang S-C, Glymour M, Cornelis M, et al. Social Integration and Reduced Risk of Coronary Heart Disease in Women: The Role of Lifestyle Behaviors. Circ Res. 2017;120(12):1927-1937. http://circres.ahajournals.org/content/early/2017/03/30/CIRCRESAHA.116.3....
11. Valtorta NK, Kanaan M, Gilbody S, Hanratty B. Loneliness, social isolation and risk of cardiovascular disease in the English Longitudinal Study of Ageing. Eur J Prev Cardiol. 2018;25(13):1387-1396. doi:10.1177/2047487318792696
12. Elovainio M, Hakulinen C, Pulkki-Råback L, et al. Contribution of risk factors to excess mortality in isolated and lonely individuals: an analysis of data from the UK Biobank cohort study. Lancet Public Heal. 2017;2(6):e260-e266. doi:10.1016/S2468-2667(17)30075-0
13. Hakulinen C, Pulkki-Råback L, Virtanen M, Jokela M, Kivimäki M, Elovainio M. Social isolation and loneliness as risk factors for myocardial infarction, stroke and mortality: UK Biobank cohort study of 479 054 men and women. Heart. March 2018. http://heart.bmj.com/content/early/2018/03/16/heartjnl-2017-312663.abstract.