Loneliness and Risk for Cardiovascular Disease: Mechanisms and Future Directions

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Abstract

Purpose of review

In this review, we synthesise recent research on the association between loneliness and cardiovascular disease (CVD). We present evidence for mechanisms underlying this association and propose directions for future research.

Recent findings

Loneliness is related to increased risk of early mortality and CVD comparable to other well-established risk factors such as obesity or smoking.

Summary

Loneliness has been linked to higher rates of incident CVD, poorer CVD patient outcomes, and early mortality from CVD. Loneliness likely affects risk for these outcomes via health-related behaviours (e.g. physical inactivity and smoking), biological mechanisms (e.g. inflammation, stress reactivity), and psychological factors (e.g. depression) to indirectly damage health.

Related collections

Most cited references 76

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Loneliness and social isolation as risk factors for mortality: a meta-analytic review.

Julianne Holt-Lunstad, Timothy B Smith, Mark Baker … (2015)

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.

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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

Luigi Ferrucci, Elisa Fabbri (2018)

Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.

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An overview of systematic reviews on the public health consequences of social isolation and loneliness

N. Leigh-Hunt, D. Bagguley, K. Bash … (2017)

Social isolation and loneliness have been associated with ill health and are common in the developed world. A clear understanding of their implications for morbidity and mortality is needed to gauge the extent of the associated public health challenge and the potential benefit of intervention.