ArticlePDF Available

Loneliness and social isolation as risk factors for CVD: Implications for evidence-based patient care and scientific inquiry


Abstract and Figures

A recent meta-analysis has shown that loneliness and social isolation are risk factors for coronary heart disease and stroke.1 These latest findings, specific to cardiovascular outcomes, are consistent with substantial research indicating broad health risks (eg, immune functioning, cardiovascular functioning, cognitive decline) associated with the quantity and quality of social relationships—including several meta-analyses documenting mortality risk.2 ,3 In the most comprehensive of these,3 the overall odds for mortality was 1.50, similar to the risk from light smoking and exceeding the risks conferred by hypertension and obesity. Thus, the epidemiological data suggest that having more and better quality social relationships is linked to decreased health risks and having fewer and poorer quality relationships increased risk.2 ,3 Research has also documented the influence of social connections (including measures specific to loneliness and isolation) on multiple pathways involved in both the development and progression of coronary heart disease and stroke. As depicted in figure 1, these include lifestyle (eg, nutrition, physical activity, sleep),4 treatment adherence and cooperation,5 and direct effects on surrogate biological markers.6 ,7 Recent longitudinal data from four nationally representative US samples revealed a dose–response effect of social integration on several surrogate biomarkers of cardiovascular disease including hypertension, body mass index, waist circumference and inflammation (hs-CRP).6 Moreover, most epidemiological studies control for lifestyle factors (eg, smoking, physical activity), documenting an independent influence of social relationships on mortality. Taken together, these latest findings specific to loneliness and isolation1 bolster the already robust evidence documenting that social connections significantly predict morbidity and mortality, supporting the case for inclusion as a risk factor for cardiovascular disease (CVD). Figure 1 Simplified model of possible direct and indirect pathways by which social connections influence disease morbidity and mortality. How should these data inform clinical practice? …
Content may be subject to copyright.
Loneliness and social isolation as risk
factors for CVD: implications for
evidence-based patient care and
scientic inquiry
Julianne Holt-Lunstad,
Timothy B Smith
A recent meta-analysis has shown that
loneliness and social isolation are risk
factors for coronary heart disease and
These latest ndings, specicto
cardiovascular outcomes, are consistent
with substantial research indicating broad
health risks (eg, immune functioning, car-
diovascular functioning, cognitive decline)
associated with the quantity and quality of
social relationshipsincluding several
meta-analyses documenting mortality
In the most comprehensive of
the overall odds for mortality was
1.50, similar to the risk from light
smoking and exceeding the risks con-
ferred by hypertension and obesity. Thus,
the epidemiological data suggest that
having more and better quality social rela-
tionships is linked to decreased health
risks and having fewer and poorer quality
relationships increased risk.
Research has also documented the inu-
ence of social connections (including mea-
sures specic to loneliness and isolation)
on multiple pathways involved in both the
development and progression of coronary
heart disease and stroke. As depicted in
gure 1, these include lifestyle (eg, nutri-
tion, physical activity, sleep),
adherence and cooperation,
and direct
effects on surrogate biological markers.
Recent longitudinal data from four
nationally representative US samples
revealed a doseresponse effect of social
integration on several surrogate biomar-
kers of cardiovascular disease including
hypertension, body mass index, waist cir-
cumference and inammation (hs-CRP).
Moreover, most epidemiological studies
control for lifestyle factors (eg, smoking,
physical activity), documenting an inde-
pendent inuence of social relationships
on mortality. Taken together, these latest
ndings specic to loneliness and isola-
bolster the already robust evidence
documenting that social connections sig-
nicantly predict morbidity and mortality,
supporting the case for inclusion as a risk
factor for cardiovascular disease (CVD).
How should these data inform clinical
practice? To begin, the data suggest the
need for greater prioritisation and inclu-
sion of social variables (quantity and
quality) in medical education, individual
risk assessment and public health surveil-
lance, guidelines and policies applied to
populations and health service delivery.
Medical education
The cumulative evidence points to the
benet of including social factors in
medical training and continuing education
for healthcare professionals. Physicians
supervising students and residents can
assess patients social risk factors and then
discuss with patients the importance of
nurturing and maintaining positive social
connections as part of a healthy lifestyle.
Evidence-based training could include
social factors in medical case examples
and textbooks to provide realistic patient
descriptions with life circumstances rele-
vant to disease development, progression
and response to treatment. For instance, a
case description of a 55-year-old male
with hypertension and atrial brillation
who is responding poorly to treatment
could include relevant circumstances of
intense marital conict that have elevated
levels of distress and increased adiposity
due to increased consumption of low
quality foods away from home. Given the
multiple social factors associated with
health conditions and patients responses
to treatment, medical training that
requires consideration of patients social
circumstances could improve patients
Medical training can also make explicit
the processes for making effective
referrals to mental health and social
support services. In the hypothetical case
of the patient mentioned above, referral
for marital counselling and stress manage-
ment therapy would be indicated. Medical
training can encourage physicians to pro-
actively identify relevant social and psy-
chological conditions, rather than ignore
those conditions simply because they
would be treated by another specialist. In
the same way cardiologists refer and
follow-up with patients who have
comorbid renal disease, they should refer
and follow-up with patients experiencing
social isolation or distress. Social factors
must now be given attention in course-
work detailing the major ndings of
health psychology and neuroscience,
rather than relegating such information to
a side note (eg, a mini-lecture during stu-
dents exposure to psychiatry).
Risk assessment
Patient information should be used to
inform treatment. Hospitals and clinics
should include assessments of social inte-
gration and/or loneliness in electronic
medical records. This important step can
identify individuals at riskwhich may
also have multiple implications for health
service delivery. Further, at a broader
level, population-wide surveillance will
aid public health efforts.
Such efforts will require multifactorial
risk assessment. While short and simple
assessments are desirable, single-item
assessments would be insufcient and
problematic. According to meta-analytic
multivariate measures of social rela-
tionships yield data much more predictive
of death (OR=1.91) than simplistic mea-
sures (OR=1.19). Further, although lone-
liness and social isolation entail equivalent
levels of risk, they are not interchange-
able. Social isolation denotes few social
connections or interactions, whereas lone-
liness involves the subjective perception of
isolationthe discrepancy between ones
desired and actual level of social connec-
tion. Although social isolation and loneli-
ness may co-occur, individuals can be
isolated without feeling lonely or feel
lonely despite having others present. Thus
assessments should include objective/
quantitative aspects of relationships (eg,
network size, marital status), as well as
more subjective/qualitative aspects (eg,
loneliness, social support, perceived rela-
tionship quality). Each signi cantly pre-
dicts risk for mortality,
and may
potential tap into different mechanistic
pathways; thus, multifactorial assessments
may best capture overall risk. A key chal-
lenge will be how to develop a
Department of Psychology and Neuroscience, Brigham
Young University, Provo, Utah, USA;
Department of
Counseling Psychology, Brigham Young University,
Provo, Utah, USA
Correspondence to Dr Julianne Holt-Lunstad,
Department of Psychology and Neuroscience, Brigham
Young University, Provo UT 84602, USA;
Holt-Lunstad J, Smith TB. Heart Month 2016 Vol 0 No 0 1
Heart Online First, published on April 18, 2016 as 10.1136/heartjnl-2015-309242
Copyright Article author (or their employer) 2016. Produced by BMJ Publishing Group Ltd (& BCS) under licence. on April 19, 2016 - Published by from
point-of-care assessment that is multifa-
ceted, has predictive validity, and easily
incorporated into day-to-day clinical
Population-based recommendations
and policies
The WHO now lists Social Support
Networks as a determinant of health
Major health organisations specictocar-
diovascular disease (eg, American Heart
Association, British Heart Foundation)
should also include social connections in
their lists of major risk factors, similar to
comparable lifestyle factors that currently
receive sustained attention. Government
and pr ofessional health organisations will
need to establish recommendations for
social relationship quantity and quality for
the broader population and specicrisk
groups. These recommendations should be
based on empirical evidence, subject to
periodic revision and annual public health
Among other European nations, the UK
has already undertaken several public
health initiatives intended to reduce social
isolation and decrease risk for premature
mortality. Current efforts are focused pri-
marily on older adults or individuals
reporting high levels of loneliness;
however, recommendations and cautions
can be broadly applied. A broad approach
is supported by evidence indicating (a)
remarkable consistency of effect across
different countries and across multiple
individual characteristics (eg, gender,
health status), with data suggesting greater
relative risk prior to retirement age;
(b) a
gradient effect of social connection rather
than a threshold effect
and (c) social
relationships affect cardiovascular health
by altering biomarkers and shaping health
behaviours across the lifespanincluding
adolescence, young adulthood, middle age
and old age.
Thus, efforts to promote
public health via social connection need
not be limited to specic groups but can
be applied across the risk trajectory.
Health service delivery: prevention
Attention to social connection needs to be
incorporated into existing preventative
efforts. Chronic illnesses, including car-
diovascular diseases, develop slowly over
decades. Because social relations inuence
multiple mechanistic pathways in both the
development and progression of disease,
they warrant attention in primary, second-
ary and tertiary prevention efforts. Given
efforts aimed at primary prevention result
in lower economic costs to the individual,
family, employers and the broader health-
care systemwe urge healthcare and
health policy professionals to prioritise
social connections in prevention efforts.
Despite robust literature of epidemio-
logical evidence, several important ques-
tions remain.
Causal mechanisms
Social isola tion and loneliness are clearly
risk factors for cardio vascular disease
How ev er, the term risk fact or can
imply prediction and causality, and causality
is not easily established. Similar to other risk
factors for CVD (eg, hypertension, obesity,
smoking, choles terol levels) the inuence of
social rela tionships is complex and multifac-
torial (no single putative mechanism).
Furthermore, we must take a multilevel
approach considering microlevel (eg, genetic
markers of susceptibility, geneenvironment
intera ctions) to macrolev el (eg, cultural
norms, neighbourhood chara cteristics) pro-
cesses to better understand additional path-
wa ys by which social r ela tionships inuence
which we ma y interv ene to r educe risk and
improve health.
Perhaps the biggest challenge and oppor-
tunity for the future is to design effective
interventions to increase social connec-
tions. Previous interventions involving
social support have had mixed results.
Additional research is needed to deter-
mine what works best for whom, in what
conditions. Notably, the major effects
established via epidemiological data are
based on existing social relationships (eg,
family, friends), yet many clinical inter-
ventions use hired personnel to deliver
support to patients. This discrepancy may
be problematic because support from the
patients family and broader social net-
works may differ from that provided by
hired personnel in several important ways
(eg, trust built over decades, regular social
contact, importance of the relationship,
degree of social control, sense of obliga-
tion in the relationship). Thus, efforts to
strengthen existing family relationships
may prove more effective than interven-
tions by hired personnel.
Figure 1 Simplied model of possible direct and indirect pathways by which social connections inuence disease morbidity and mortality.
2 Holt-Lunstad J, Smith TB. Heart Month 2016 Vol 0 No 0
Editorial on April 19, 2016 - Published by from
On a related note, policies that for essen-
tial reasons restrict access to patients
medical records and information may have
indirectly contributed to a practice climate
not conducive to family involvement, even
when the patient authorises family involve-
ment. Hospitals and clinics should make
efforts to enhance family involvement
when authorised by the patient.
Social technology
Social technology has rapidly become a
dominant form of communication and
social interaction. While existing and
developing technology has the potential
to combat loneliness and isolation (facili-
tating social connection), it may also con-
tribute to problems exacerbating risk.
With such rapid changes in the way
people are interacting socially, empirical
research is needed to address several
important questions. Does interacting
socially via technology reduce or replace
face-to-face social interaction and/or alter
social skills? Due to the rapid and instant
access afforded, does technology acceler-
ate relationship processes (both positive
and negative) leading to accentuation of
sociality or lack thereof? Do social rela-
tionships/interactions via technology have
a similar inuence health and well-being?
Decades of research have documented an
unequivocal inuence of social connec-
tions on longevity,
with a recent
meta-analysis conrming the association
between social isolation and CVD.
projected increases in levels of social
isolation and loneliness in Europe and
North America, medical science needs to
squarely address the ramications for
physical health. Similar to how cardiolo-
gists and other healthcare professionals
have taken strong public stances regarding
other factors exacerbating CVD (eg,
smoking, diets high in saturated fats),
further attention to social connections is
needed in research and public health sur-
veillance, prevention and intervention
efforts. Those efforts will necessarily inte-
grate methods and ndings from related
disciplines and expand the complexity of
research questions and analyses.
Twitter Follow Julianne Holt-Lunstad at @jholtlunstad
Contributors JHL and TBS participated in the drafting
of this editorial and take full responsibility for its
Competing interests None declared.
Provenance and peer review Commissioned;
internally peer reviewed.
Open Access This is an Open Access article
distributed in accordance with the Creative Commons
Attribution Non Commercial (CC BY-NC 4.0) license,
which permits others to distribute, remix, adapt, build
upon this work non-commercially, and license their
derivative works on different terms, provided the
original work is properly cited and the use is non-
commercial. See:
To cite Holt-Lunstad J, Smith TB. Heart Published
Online First: [please include Day Month Year]
Heart 2016;0:13. doi:10.1136/heartjnl-2015-309242
1 Valtorta NK, Kanaan M, Gilbody S, et al. Loneliness
and social isolation as risk factors for coronary heart
disease and stroke: systematic review and
meta-analysis of longitudinal observational studies.
Heart Published Online First 2016 (heartjnl-2015-
2 Holt-Lunstad J, Smith TB, Baker M, et al. Loneliness
and social isolation as risk factors for mortality:
a meta-analytic review. Perspect Psychol Sci
3 Holt-Lunstad J, Smith TB, Layton JB. Social
relationships and mortality risk: a meta-analytic
review. PLoS Med 2010;7:e1000316.
4 Umberson D, Crosnoe R, Reczek C. Social
relationships and health behavior across life course.
Annu Rev Sociol 2010;36:13957.
5 DiMatteo MR. Social support and patient adherence to
medical treatment: a meta-analysis. Health Psychol
6 Yang YC, Boen C, Gerken K, et al. Social relationships
and physiological determinants of longevity across the
human life span. Proc Natl Acad Sci USA 2016.
7 Uchino BN. Social support and health: a review of
physiological processes potentially underlying links to
disease outcomes. J Behav Med 2006;29:37787.
8 Stampfer MJ, Ridker PM, Dzau VJ. Risk factor criteria.
Circulation 2004;109:IV-35.
Holt-Lunstad J, Smith TB. Heart Month 2016 Vol 0 No 0 3
Editorial on April 19, 2016 - Published by from
evidence-based patient care and scientific
factors for CVD: implications for
Loneliness and social isolation as risk
Julianne Holt-Lunstad and Timothy B Smith
published online April 18, 2016Heart
Updated information and services can be found at:
These include:
This article cites 6 articles, 2 of which you can access for free at:
Open Access See:
provided the original work is properly cited and the use is
non-commercially, and license their derivative works on different terms,
permits others to distribute, remix, adapt, build upon this work
Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
This is an Open Access article distributed in accordance with the Creative
Email alerting
box at the top right corner of the online article.
Receive free email alerts when new articles cite this article. Sign up in the
Articles on similar topics can be found in the following collections
(614)Tobacco use
(8633)Drugs: cardiovascular system
(44)Press releases
(165)Open access
To request permissions go to:
To order reprints go to:
To subscribe to BMJ go to: on April 19, 2016 - Published by from
... More recent evidence has identified a key role of non-traditional risk factors such as psychosocial stressors as critical elements of hypertension etiology [5]. Among these psychosocial factors, work stress and social isolation have received special attention [6][7][8][9][10][11]. Job strain, a well-established operationalization of work stress, has reliably been associated with hypertension in systematic reviews and meta-analyses [6,7]. ...
... Among these psychosocial factors, work stress and social isolation have received special attention [6][7][8][9][10][11]. Job strain, a well-established operationalization of work stress, has reliably been associated with hypertension in systematic reviews and meta-analyses [6,7]. Social isolation, defined as a lack of social contacts and shortage of social relationships, has been evidenced as a severe psychosocial stressor in adulthood that demonstrates robust associations with CVD and consistently predicts increased hypertension risk [8][9][10][11]. ...
... These results are consistent with the literature on job strain and social isolation-the individual constituents of exposure to APDs-which has demonstrated robust and stable associations with cardiovascular diseases and hypertension [5][6][7][8][9][10][11]40]. Indeed, social isolation in adulthood has been linked to drastically increased CVD mortality risk, as well as hypertension [8,9,11]. ...
Full-text available
Hypertension is a key driver of cardiovascular diseases. However, how stressors contribute to the development of hypertension remains unclear. The objective of this study was to examine prospective associations of adverse childhood experiences (ACEs) and adulthood psychosocial disadvantages (APDs) with incident hypertension. Data were from the Mid-life in the United States (MIDUS) study, a national, population-based, prospective cohort study. ACEs were examined via retrospective reports, and APDs including work stress and social isolation were assessed using survey measures. Incident hypertension was defined based on self-reported physician diagnosis. Baseline data were collected in 1995, with follow-up in 2004–2006 and 2013–2014. Cox proportional hazards regression was applied to assess prospective associations of ACEs and APDs with incident hypertension in 2568 workers free from hypertension at baseline. After adjustment for covariates, baseline APDs were associated with increased incident hypertension (aHR and 95% CI = 1.48 [1.09, 2.01]) during a 20-year follow-up, whereas ACEs showed null associations. Moreover, a moderating effect by ACEs was observed—the effect of APDs on risk of hypertension was stronger when ACEs were present (aHR and 95% CI = 1.83 [1.17, 2.86]). These findings underscore the importance of psychosocial stressors as nontraditional risk factors of cardiometabolic disorders.
... Despite the organometrics and oxidative status of spleen in 3xTg-AD females did not reach statistical significance, their correlation with frailty score and HPA axis suggests that even a short isolation in 3xTg-AD female survivors may increase their risk of morbidity and mortality. In fact, various meta-analyses have described that social isolation is associated with an increased risk of cardiovascular disease and stroke (Holt-Lunstad and Smith, 2016;Valtorta et al., 2016), and it is considered a risk factor for all-cause mortality (Holt-Lunstad et al., 2015). ...
Full-text available
Coping with emotional stressors strongly impacts older people due to their age-related impaired neuroendocrine and immune systems. Elevated cortisol levels seem to be associated with an increased risk of cognitive decline and dementia. In Alzheimer’s disease (AD), alterations in the innate immune system result in crosstalk between immune mediators and neuronal and endocrine functions. Besides, neuropsychiatric symptoms such as depression, anxiety, or agitation are observed in most patients. Here, we studied the psychophysiological response to intrinsic (AD-phenotype) and extrinsic (anxiogenic tests) stress factors and their relation to liver, kidneys, heart, and spleen oxidative status in 18-months-old female gold-standard C57BL/6 mice and 3xTg-AD mice model for AD. The emotional, cognitive, and motor phenotypes were assessed under three different anxiogenic conditions. Survival, frailty index, and immunoendocrine status (corticosterone levels and oxidative stress of peripheral organs) were evaluated. Genotype differences in neuropsychiatric-like profiles and cognitive disfunction in 3xTg-AD females that survived beyond advanced stages of the disease persisted despite losing other behavioral and hypothalamic–pituitary–adrenal (HPA) physiological differences. A secondary analysis studied the impact of social isolation, naturally occurring in 3xTg-AD mice due to the death of cage mates. One month of isolation modified hyperactivity and neophobia patterns and disrupt the obsessive-compulsive disorder-like digging ethogram. Frailty index correlated with spleen organometrics in all groups, whereas two AD-specific salient functional correlations were identified: (1) Levels of corticosterone with worse performance in the T-maze, (2) and with a lower splenic GPx antioxidant enzymatic activity, which may suppose a potent risk of morbidity and mortality in AD.
... Interestingly, individuals belonging to this cluster were more frequently the sole users of the connected scales in their household, a proxy for living alone. It is well known that social isolation (individual or within the community) is associated with increased cardiovascular risk 26 and is increasingly recognized as an emerging cardiovascular risk factor to take into account in risk stratification. 27 Furthermore, living alone is related to adverse carotid stiffness, independently of potential confounders; and in addition vascular stiffness is related to residing in socially deprived neighbourhoods, but only in men. ...
Full-text available
Aims To investigate the impact of coronavirus disease 2019 lockdown on trajectories of arterial pulse-wave velocity in a large population of users of connected smart scales that provide reliable measurements of pulse-wave velocity. Methods and results Pulse-wave velocity recordings obtained by Withings Heart Health & Body Composition Wi-Fi Smart Scale users before and during lockdown were analysed. We compared two demonstrative countries: France, where strict lockdown rules were enforced (n = 26 196) and Germany, where lockdown was partial (n = 26 847). Subgroup analysis was conducted in users of activity trackers and home blood pressure monitors. Linear growth curve modelling and trajectory clustering analyses were performed. During lockdown, a significant reduction in vascular stiffness, weight, blood pressure, and physical activity was observed in the overall population. Pulse-wave velocity reduction was greater in France than in Germany, corresponding to 5.2 month reduction in vascular age. In the French population, three clusters of stiffness trajectories were identified: decreasing (21.1%), stable (60.6%), and increasing pulse-wave velocity clusters (18.2%). Decreasing and increasing clusters both had higher pulse-wave velocity and vascular age before lockdown compared with the stable cluster. Only the decreasing cluster showed a significant weight reduction (−400 g), whereas living alone was associated with increasing pulse-wave velocity cluster. No clusters were identified in the German population. Conclusions During total lockdown in France, a reduction in pulse-wave velocity in a significant proportion of French users of connected smart bathroom scales occurred. The impact on long-term cardiovascular health remains to be established.-Lay Summary Pulse-wave velocity (PWV) measurements from users of connected smart bathroom scales showed that during the first COVID-19 imposed lockdown in France and Germany, arterial stiffness decreased, with greater improvement in France, where three distinct patterns of PWV progression could be identified.
... Social isolation and loneliness have been increasingly recognized as a public health priority due to their effects on mental and physical health (92) and have been a significant concern during the Covid-19 pandemic. Although social isolation and loneliness are sometimes correlated, social scientists make conceptual and empirical distinctions between the two constructs (93). Social isolation is a lack of (or infrequent) social contact that may occur when an individual lives alone or has few social ties, whereas loneliness is a subjective feeling of social disconnection that results from a discrepancy between an individual's actual and desired social relationships (94). ...
Full-text available
A growing body of literature has emphasized the importance of biobehavioral processes – defined as the interaction of behavior, psychology, socioenvironmental factors, and biological processes – for clinical outcomes among transplantation and cellular therapy (TCT) patients. TCT recipients are especially vulnerable to distress associated with pandemic conditions and represent a notably immunocompromised group at greater risk for SARS-CoV-2 infection with substantially worse outcomes. The summation of both the immunologic and psychologic vulnerability of TCT patients renders them particularly susceptible to adverse biobehavioral sequelae associated with the Covid-19 pandemic. Stress and adverse psychosocial factors alter neural and endocrine pathways through sympathetic nervous system and hypothalamic-pituitary-adrenal axis signaling that ultimately affect gene regulation in immune cells. Reciprocally, global inflammation and immune dysregulation related to TCT contribute to dysregulation of neuroendocrine and central nervous system function, resulting in the symptom profile of depression, fatigue, sleep disturbance, and cognitive dysfunction. In this article, we draw upon literature on immunology, psychology, neuroscience, hematology and oncology, Covid-19 pathophysiology, and TCT processes to discuss how they may intersect to influence TCT outcomes, with the goal of providing an overview of the significance of biobehavioral factors in understanding the relationship between Covid-19 and TCT, now and for the future. We discuss the roles of depression, anxiety, fatigue, sleep, social isolation and loneliness, and neurocognitive impairment, as well as specific implications for sub-populations of interest, including pediatrics, caregivers, and TCT donors. Finally, we address protective psychological processes that may optimize biobehavioral outcomes affected by Covid-19.
... However, in this latter study, data were collected from the general population where people were encouraged to answer a questionnaire and/or perform cognitive online, a recruitment procedure vulnerable to selection bias. The psychological stress caused by quarantine, fear, and loneliness will activate stress responses that in turn may influence cognitive capabilities (16,(47)(48)(49)(50). It is therefore crucial to compare COVID-19 cases to a matching control population who experienced the same level of social restrictions and other stressors during the pandemic. ...
Full-text available
Introduction: Coronavirus disease 2019 (COVID-19) is prevalent among young people, and neurological involvement has been reported. We investigated neurological symptoms, cognitive test results, and biomarkers of brain injury, as well as associations between these variables in non-hospitalized adolescents and young adults with COVID-19. Methods: This study reports baseline findings from an ongoing observational cohort study of COVID-19 cases and non-COVID controls aged 12-25 years (Clinical Trials ID: NCT04686734). Symptoms were charted using a standardized questionnaire. Cognitive performance was evaluated by applying tests of working memory, verbal learning, delayed recall, and recognition. The brain injury biomarkers, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp), were assayed in serum samples using ultrasensitive immunoassays. Results: A total of 405 COVID-19 cases and 111 non-COVID cases were prospectively included. Serum Nfl and GFAp concentrations were significantly elevated in COVID-19 cases as compared with non-COVID controls (p = 0.050 and p = 0.014, respectively). The COVID-19 cases reported more fatigue (p < 0.001) and post-exertional malaise (PEM) (p = 0.001) compared to non-COVID-19 controls. Cognitive test performance and clinical neurological examination did not differ across the two groups. Within the COVID-19 group, there were no associations between symptoms, cognitive test results, and NfL or GFAp levels. However, fatigue and PEM were strongly associated with older age and female sex. Conclusions: Non-hospitalized adolescents and young adults with COVID-19 reported more fatigue and PEM and had slightly elevated levels of brain injury markers, but showed normal cognitive performance. No associations were found between symptoms, brain injury markers, and cognitive test results, but fatigue and PEM were strongly related to female sex and older age.
... Social isolation is defined as a state of little to no interaction with family and friends and non-participation in social activities [7]. Social isolation is a high-risk factor for all-cause mortality [8][9][10][11] and coronary vascular disease [12][13][14][15][16][17]. Moreover, social isolation has been associated with depression [18], dementia, and declining cognitive functioning [19][20][21]. ...
Full-text available
Background: The coronavirus disease 2019 (COVID-19) has adversely affected social contact and physical activity. This study investigated the correlation between physical activity, social contact, and sedentary time among adults aged 65 years and above during the COVID-19 pandemic. Methods: This study was conducted in N City, H Prefecture, Japan. The authors randomly selected 4,996 adults, aged 65 years and above (mean age 74.1 ± 6.1 years), living in N City, and survey forms were distributed by mail in mid-August 2020. Altogether, 1,925 participants were included in this study. The survey comprised questions concerning the participants' sex, height, weight, age, smoking and drinking habits, living arrangements, social contact assessments, physical activity levels, and sedentary time. Moreover, linear regression analysis was utilized to investigate the associations between the variables. Results: The reported median physical activity was 1272 metabolic equivalent of task-min/week (interquartile range 528-2628), and the reported median sedentary time was 360 min/week (interquartile range 240-600). COVID-19 "somewhat," "quite a lot," or "completely" hindered the frequency of in-person contact with friends among 75.5% of the respondents and hampered the frequency of virtual contact with friends among 38.8% of the respondents. Physical activity was associated significantly with in-person contact indicators: "interaction with friends" (B = -0.111; 95%CI: -0.187, -0.035; p = 0.004) and "social participation" (B = -0.163; 95%CI: -0.248, -0.079; p < 0.001). These associations remained significant for both multivariate analysis Models 1 (sex and age) and 2 (addition of body mass index [BMI], alcohol use, smoking, living alone, and the number of illnesses to Model 1). Additionally, sedentary time was significantly associated with the social contact variable of "interaction with friends" (B = 0.04; 95%CI: 0.016, 0.064; p = 0.001). This association remained significant in both multivariate analysis models. Conclusions: Significant associations were confirmed between reduced social contact, decreased physical activity, and more sedentary behavior among older adults due to COVID-19. Hence, continuous monitoring and support for social activities among susceptible older adults in extraordinary circumstances are essential.
To address the gap of lacking research on the association between coping self-efficacy and loneliness, this study examined this relationship to inform future research and intervention on loneliness. Using data from 151 community-dwelling older adults ages 65 and older, we estimated multivariate logistic regression models with age, race/ethnicity, sex, body mass index, chronic disease composite score, social support, coping self-efficacy, and depression symptoms. Loneliness was reported in 32.1% of participants and negatively associated with coping self-efficacy (OR = 0.68, 95% CI: 0.50–0.93) while controlling for age, race, sex, chronic disease composite score, and body mass index. Our findings suggest that coping self-efficacy may be a target for intervention involving loneliness in future research; however, the causal relationship between coping self-efficacy and loneliness should be explored further.
Hospital congestion, delayed discharge, and bypassing primary care facilities are challenges facing the Iranian health‐care sector. We conducted a case study at the Sheikh al‐Rais Specialty Clinic, Tabriz, Iran, to find plausible, practical policy options for designing and implementing a referral system to reduce and regulate referral volumes to this clinic. We first reviewed the evidence on existing options of hospital congestion and unnecessary referral reduction by conducting a scoping literature review and then supplemented the findings with 18 semistructured interviews. We examined the perspectives of service users and experts in the field. Six practical policy options were identified: institutionalization of the referral system and family physician program, reinforcing gatekeeping system, use of telemedicine, utilization of educational algorithms, implementation of electronic health records, and establishing specialized clinics in different city areas. Local context adaptation, ensuring the availability of resources, political support, and feasibility are critical factors for successful policy implementation. 伊朗医疗部门面临的挑战包括医院拥挤、出院延迟和绕过初级保健设施。我们在伊朗大不里士的Sheikh al‐Rais专科诊所进行了一项案例研究,以寻找合理且实用的政策选项,用于设计和实施转诊系统,进而减少和调节该诊所的转诊量。我们首先使用范围综述,审视了关于医院拥挤和减少不必要转诊的现有选项,随后通过18次半结构化访谈补充了研究结果。我们分析了该领域的服务用户和专家的观点。确定了六个实用的政策选项:转诊系统和家庭医生计划的制度化、加强把关系统、使用远程医疗、使用教育算法、实施电子医疗记录、以及在不同城市地区建立专科诊所。适应地方情境、确保资源的可用性、政治支持、以及可行性是政策实施取得成功的关键因素。 La congestión hospitalaria, el retraso en el alta y eludir los centros de atención primaria son desafíos que enfrenta el sector de la atención médica iraní. Realizamos un estudio de caso en la Clínica de Especialidades Sheikh al‐Rais, Tabriz, Irán, para encontrar opciones de políticas prácticas y plausibles sobre el diseño e implementación de un sistema de derivación para reducir y regular los volúmenes de derivación a esta clínica. Primero revisamos la evidencia sobre las opciones existentes de congestión hospitalaria y reducción de referencias innecesarias mediante la realización de una revisión de la literatura de alcance y luego complementamos los hallazgos con 18 entrevistas semiestructuradas. Examinamos las perspectivas de los usuarios del servicio y los expertos en el campo. Se identificaron seis opciones prácticas de política: institucionalización del sistema de referencia y el programa de médicos de familia, refuerzo del sistema de vigilancia, uso de telemedicina, utilización de algoritmos educativos, implementación de registros de salud electrónicos y establecimiento de clínicas especializadas en diferentes áreas de la ciudad. La adaptación al contexto local, asegurando la disponibilidad de recursos, el apoyo político y la viabilidad son factores críticos para la implementación exitosa de políticas. Improving documentation using electronic health records, integrating electronic ‎health records with referral systems, controlling and reducing the demand for unnecessary ‎referrals through screening mechanisms, and the ability to refer patients to the most appropriate ‎level of referral are crucial. The workload in (sub‐) specialized university clinics can be reduced by ‎implementing the proposed policy options. Establishing an electronic health record system is pivotal in providing advanced and qualified health‐care services. Improving documentation using electronic health records, integrating electronic ‎health records with referral systems, controlling and reducing the demand for unnecessary ‎referrals through screening mechanisms, and the ability to refer patients to the most appropriate ‎level of referral are crucial. The workload in (sub‐) specialized university clinics can be reduced by ‎implementing the proposed policy options. Establishing an electronic health record system is pivotal in providing advanced and qualified health‐care services.
Globally, vascular diseases are a leading cause of morbidity and mortality. Many of the most significant risk factors for vascular disease have a gendered dimension, and sex differences in vascular diseases incidence are apparent, worldwide. In this narrative review, we provide a contemporary picture of sex and gender-related determinants of vascular disease. We illustrate key factors underlying sex-specific risk stratification, consider similarities and sex differences in vascular disease risk and outcomes comparing data from the global North (i.e., developed high income countries in the Northern hemisphere and Australia) and the global South (i.e., regions outside Europe and North America), and explore the relationship between country-level gendered inequities in vascular disease risk and the United Nation’s gender inequality index. Review findings suggest that the rising incidence of vascular disease in women is partly explained by an increase in the prevalence of traditional risk factors linked to gender-related determinants such as shifting roles and relations related to the double burden of employment and caregiving responsibilities, lower educational attainment, lower socioeconomic status, and higher psychosocial stress. Social isolation partly explained the higher incidence of vascular disease in men. These patterns were found to be apparent across the global North and South. Study findings emphasize the necessity of taking into account sex differences and gender-related factors in the determination of the vascular disease risk profiles and management strategies. As we move towards the era of precision medicine, future research is needed that identifies, validates and measures gender-related determinants and risk factors in the global South.
Full-text available
Background The influence of social relationships on morbidity is widely accepted, but the size of the risk to cardiovascular health is unclear. Objective We undertook a systematic review and meta-analysis to investigate the association between loneliness or social isolation and incident coronary heart disease (CHD) and stroke. Methods Sixteen electronic databases were systematically searched for longitudinal studies set in high-income countries and published up until May 2015. Two independent reviewers screened studies for inclusion and extracted data. We assessed quality using a component approach and pooled data for analysis using random effects models. Results Of the 35 925 records retrieved, 23 papers met inclusion criteria for the narrative review. They reported data from 16 longitudinal datasets, for a total of 4628 CHD and 3002 stroke events recorded over follow-up periods ranging from 3 to 21 years. Reports of 11 CHD studies and 8 stroke studies provided data suitable for meta-analysis. Poor social relationships were associated with a 29% increase in risk of incident CHD (pooled relative risk: 1.29, 95% CI 1.04 to 1.59) and a 32% increase in risk of stroke (pooled relative risk: 1.32, 95% CI 1.04 to 1.68). Subgroup analyses did not identify any differences by gender. Conclusions Our findings suggest that deficiencies in social relationships are associated with an increased risk of developing CHD and stroke. Future studies are needed to investigate whether interventions targeting loneliness and social isolation can help to prevent two of the leading causes of death and disability in high-income countries. Study registration number CRD42014010225.
Full-text available
Two decades of research indicate causal associations between social relationships and mortality, but important questions remain as to how social relationships affect health, when effects emerge, and how long they last. Drawing on data from four nationally representative longitudinal samples of the US population, we implemented an innovative life course design to assess the prospective association of both structural and functional dimensions of social relationships (social integration, social support, and social strain) with objectively measured biomarkers of physical health (C-reactive protein, systolic and diastolic blood pressure, waist circumference, and body mass index) within each life stage, including adolescence and young, middle, and late adulthood, and compare such associations across life stages. We found that a higher degree of social integration was associated with lower risk of physiological dysregulation in a dose-response manner in both early and later life. Conversely, lack of social connections was associated with vastly elevated risk in specific life stages. For example, social isolation increased the risk of inflammation by the same magnitude as physical inactivity in adolescence, and the effect of social isolation on hypertension exceeded that of clinical risk factors such as diabetes in old age. Analyses of multiple dimensions of social relationships within multiple samples across the life course produced consistent and robust associations with health. Physiological impacts of structural and functional dimensions of social relationships emerge uniquely in adolescence and midlife and persist into old age.
Full-text available
Actual and perceived social isolation are both associated with increased risk for early mortality. In this meta-analytic review, our objective is to establish the overall and relative magnitude of social isolation and loneliness and to examine possible moderators. We conducted a literature search of studies (January 1980 to February 2014) using MEDLINE, CINAHL, PsycINFO, Social Work Abstracts, and Google Scholar. The included studies provided quantitative data on mortality as affected by loneliness, social isolation, or living alone. Across studies in which several possible confounds were statistically controlled for, the weighted average effect sizes were as follows: social isolation odds ratio (OR) = 1.29, loneliness OR = 1.26, and living alone OR = 1.32, corresponding to an average of 29%, 26%, and 32% increased likelihood of mortality, respectively. We found no differences between measures of objective and subjective social isolation. Results remain consistent across gender, length of follow-up, and world region, but initial health status has an influence on the findings. Results also differ across participant age, with social deficits being more predictive of death in samples with an average age younger than 65 years. Overall, the influence of both objective and subjective social isolation on risk for mortality is comparable with well-established risk factors for mortality. © The Author(s) 2015.
Full-text available
Sociological theory and research point to the importance of social relationships in affecting health behavior. This work tends to focus on specific stages of the life course, with a division between research on childhood/adolescent and adult populations. Yet recent advances demonstrate that early life course experiences shape health outcomes well into adulthood. We synthesize disparate bodies of research on social ties and health behavior throughout the life course, with attention to explaining how various social ties influence health behaviors at different life stages and how these processes accumulate and reverberate throughout the life course.
Full-text available
The quality and quantity of individuals' social relationships has been linked not only to mental health but also to both morbidity and mortality. 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 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. 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). 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.
Full-text available
Social support has been reliably related to lower rates of morbidity and mortality. An important issue concerns the physiological mechanisms by which support influences such health endpoints. In this review, I examine evidence linking social support to changes in cardiovascular, neuroendocrine, and immune function. Consistent with epidemiological evidence, social support appears to be related to more positive "biological profiles" across these disease-relevant systems. Recent research on immune-mediated inflammatory processes is also starting to provide data on more integrative physiological mechanisms potentially linking social support to health. The implications of these links, along with future research directions are discussed.
The concept of the risk factor for chronic diseases, such as cardiovascular disorders, is derived from the application of epidemiological methods initially developed for infectious and nutritional deficiency diseases to chronic conditions to identify the factor(s) linked to the development of the chronic disease. Typically in infectious or nutritional deficiency conditions, a single causative agent or primary cause is identified. Thus, the cause of tuberculosis is the tubercle bacillus, and the cause of pellagra is niacin deficiency. However, for cardiovascular diseases, in which causes are usually complex and multifactorial, new concepts were required. For example, individuals with hypertension have a far greater risk for cardiovascular disease than those without hypertension, but many individuals with hypertension never have clinical sequelae, and many individuals with diagnosed cardiovascular diseases have no hypertension. One can also argue that many individuals who are exposed to the tubercle bacillus do not develop clinical tuberculosis, but the converse is not true; no one has tuberculosis without the tubercle bacillus. This provides a clear distinction between multifactorial diseases, such as coronary disease where the risk factor concept is paramount, and other health conditions. The initial application of the risk factor concept was well developed long before the term was coined. Early in the previous century, insurance companies noted that individuals with high blood pressure were at higher risk for premature mortality1 and therefore would be accepted for life insurance only on payment of an additional premium. Insurance companies also recognized the related risk factor of obesity, and imposed higher premiums on overweight clients. In this context, risk factors are used as predictors of disease and mortality. Surprisingly, insurance companies failed to recognize the enormous contribution of smoking to cardiovascular risk until later. Although the underlying concept had been widely discussed and applied, the term “risk factor” was …
In a review of the literature from 1948 to 2001, 122 studies were found that correlated structural or functional social support with patient adherence to medical regimens. Meta-analyses establish significant average r-effect sizes between adherence and practical, emotional, and unidimensional social support; family cohesiveness and conflict; marital status; and living arrangement of adults. Substantive and methodological variables moderate these effects. Practical support bears the highest correlation with adherence. Adherence is 1.74 times higher in patients from cohesive families and 1.53 times lower in patients from families in conflict. Marital status and living with another person (for adults) increase adherence modestly. A research agenda is recommended to further examine mediators of the relationship between social support and health.
  • J Holt-Lunstad
  • T B Smith
Holt-Lunstad J, Smith TB. Heart Month 2016 Vol 0 No 0