key: cord-0309382-nrsgspf0
authors: De Rubeis, V.; Lee, J.; Anwer, M. S.; Yoshida-Montezumaa, Y.; Andreacchi, A. T.; Stone, E.; Iftikhar, S.; Morgenstern, J. D.; Rebinsky, R.; Neil-Sztramko, S. E.; Alvarez, E.; Apatu, E.; Anderson, L. N.
title: Impact of disasters, including pandemics, on cardiometabolic outcomes across the life-course: A systematic review
date: 2020-11-30
journal: nan
DOI: 10.1101/2020.11.27.20239830
sha: 9cfadc452c45bc08f62b80669058ee6ce12b28b8
doc_id: 309382
cord_uid: nrsgspf0

Objectives: Disasters, such as the current COVID-19 pandemic, disrupt daily life, increase uncertainty and stress, and may increase long term risk of adverse cardiometabolic outcomes, including heart disease, obesity and diabetes. The objective was to conduct a systematic review to determine the impact of disasters, including pandemics, on cardiometabolic outcomes across the life course. Design: A systematic search was conducted in May 2020 using two electronic databases, EMBASE and Medline. All studies were screened in duplicate at title and abstract, and full text level. Studies were eligible for inclusion if they assessed an association with population level or community disaster and cardiometabolic outcomes. There were no restrictions on year of publication, country or population. Non-English and earthquake related studies were excluded. Data were extracted on study characteristics, exposure (e.g., type of disaster, name of specific event, region, year), cardiometabolic outcomes, and measures of effect. Study quality was evaluated using the Joanna Briggs Institute critical appraisal tools. Results: A total of 58 studies were included, with 24 studies reporting the effects of exposure to disaster during pregnancy/childhood and 34 studies reporting the effects of exposure during adulthood. Studies included exposure to natural (60%) and human-made (40%) disasters, with only 3 (5%) of these studies evaluating previous pandemics. Most studies were conducted in North America (62%). Most studies reported increased cardiometabolic risk, including increased cardiovascular disease incidence or mortality, diabetes, and obesity. Few studies investigated potential mechanisms or identified high risk subgroups. Conclusions: Understanding the long-term consequences of disasters on cardiometabolic outcomes across the life-course may inform public health strategies for the current COVID-19 pandemic. This review found strong evidence of an increased association between disaster exposure and cardiometabolic outcomes across the life-course, although more research is needed to better understand the mechanisms and preventative efforts. PROSPERO registration: CRD 42020186074

Understanding the long-term consequences of disasters on cardiometabolic outcomes across the life-course may inform public health strategies for the current COVID-19 pandemic. This review found strong evidence of an increased association between disaster exposure and cardiometabolic outcomes across the life-course, although more research is needed to better understand the mechanisms and preventative efforts.

PROSPERO registration: CRD -42020186074 Strengths and limitations of this study:

• This systematic review is one of the first to review the literature on disasters, including pandemics, and subsequent cardiometabolic outcomes throughout the life-course. • A comprehensive search strategy was developed in consultation with Health Science Librarians at McMaster University, which resulted in 58 studies that were eligible for inclusion into the review. • Due to the heterogeneity of the included studies, a meta-analysis was not conducted.

• This review contributes a synthesis of the literature on the impact of disasters and cardiometabolic outcomes, that can help to inform public health strategies for the current COVID-19 pandemic.

understanding this can inform targeted interventions. The primary objective of this review was to determine the impact of disasters, including pandemics such as COVID-19, on risk of cardiometabolic outcomes across the life-course. The secondary objectives were to determine how to reduce the impact of chronic disease outcomes following a disaster and to identify populations at highest risk of cardiometabolic outcomes following a disaster.

A systematic review was conducted following the Preferred Reporting Items for Systematic

Reviews and Meta-Analyses (PRISMA) (14) . This review was registered on PROSPERO (CRD -42020186074).

A systematic search was conducted in May 2020 using the electronic databases EMBASE and MEDLINE. The health research librarians at McMaster University assisted in developing the search strategy. The search broadly captured two concepts: disasters and cardiometabolic outcomes (e.g., diabetes, obesity, hypertension). The complete search strategy for EMBASE can be found in Table 1 . The search strategy for MEDLINE can be found in the Appendix (Table A1 ). Reference lists of eligible studies and relevant systematic reviews were hand searched to identify additional articles.

Studies were eligible for inclusion if they assessed the relationship between a populationlevel or community disaster and the risk of future cardiometabolic outcomes including CVD, diabetes or obesity or cardiometabolic risk scores (15) . CVD included myocardial infarction, stroke, hypertension and angina. There were no restrictions on year of publication, country of disaster, or population. Only studies evaluating the impact of real-world disasters in humans were included. Due to the research team's capacity, only studies published in English were included. Observational and quasi-experimental study designs, including case-control, cohort and other longitudinal study designs or natural experiments were included. Outcomes that were not cardiometabolic-related or acute cardiometabolic events, such as an immediate complication (defined as <1 month after disaster), were excluded. Studies that assessed the exposure to a chemical as a result of the disaster, were excluded, as we were not interested in outcomes resulting from chemical exposure. Earthquake studies were also excluded since a . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101/2020.11.27.20239830 doi: medRxiv preprint systematic review was published in 2018 that assessed the impact of earthquakes on cardiometabolic outcomes (16).

After running the search, all identified studies were imported into Covidence and duplicates were removed (17) . Studies were screened at title and abstract-level, and then at full-text by two independent reviewers (VD, JL, MSA, YYM, ATA, ES, SI, JDM, RR LNA). Conflicts were resolved by a third reviewer who made the final decision regarding eligibility for inclusion.

A data extraction template was created, and pilot tested prior to data extraction. Data were then extracted from all studies by two independent abstractors (VD, JL, SMA, YYM, ATA, RR) and conflicts were resolved by a third independent abstractor. Study characteristics including year of publication, study design, country of disaster, sample size, and length of study were extracted where reported. Specific information on the exposure and outcome in each study were extracted including the type and name of the disaster, country and year of the disaster, the outcome of interest, and how the exposure and outcome were measured. Finally, any information on subgroups including age, population, sex and disaster type were also extracted, if applicable.

Critical appraisal was conducted using the Joanna Briggs Institute (JBI) Critical Appraisal Tools (18) . This tool was chosen due to the availability of checklists for a wide range of study designs, including cohort, cross-sectional and quasi-experimental designs (18) . The quasi-experimental study design checklist was used for natural experiments including time-series studies and pre/post designs, as it was decided this was the most appropriate tool. All studies were critically appraised independently by two individuals (VD, JL, MA, YYM, ATA, ES, SI) and a third individual was consulted for any discrepancies.

Data from the included studies were narratively synthesized. Results are presented by exposure period (perinatal/childhood versus adulthood) and by cardiometabolic outcome (obesity, CVD, and diabetes). Characteristics of studies are presented as frequencies and percentages. Due to the heterogeneity of studies, a meta-analysis was not conducted.

A total of 4830 studies were identified through the electronic database search. An additional 12 studies were identified through manual searching of the reference lists of relevant studies. After removing duplicates (n=439), 4403 studies were screened at title and abstract level. After applying inclusion and exclusion criteria, 4068 studies were excluded, leaving 335 studies screened for full-text eligibility. A total of 58 studies were eligible for inclusion into the review. The complete screening process is described in Figure 1 . (25, 26) and seven studies assessed outcomes during childhood and adolescence (13, [19] [20] [21] [22] [23] [24] . The length of studies, including prospective follow-up and retrospective assessment, ranged from 1 month to 95 years. Most studies (n=36) focused on disasters that occurred in North America (12, [19] [20] [21] [22] [23] [24] [25] [26] 36, 37, 40, [43] [44] [45] [46] [47] 49, 50, 52, 53, [55] [56] [57] [58] [61] [62] [63] [65] [66] [67] [68] [69] [70] 73, 74) , followed by Europe (n=13) (27) (28) (29) (30) (31) (32) (33) 39, 41, 51, 60, 71, 72) . The remaining disasters occurred in Asia (n=7) (13, 35, 38, 42, 48, 54, 59) and Africa (n=2) (34, 64) . The characteristics of included studies and key findings are provided in Table 3 for disaster exposure during   the perinatal period and childhood, and Table 4 for exposure during adulthood.

Of the 24 studies that evaluated perinatal and childhood exposure to disaster, 12 studies evaluated human-made disasters (27) (28) (29) (30) (31) (32) (33) (34) (35) 38, 39, 45) and the remaining 12 evaluated natural disasters (13, [19] [20] [21] [22] [23] [24] [25] [26] 36, 37, 40) of which two were pandemics (36, 37) . Most studies (n=15) assessed the disaster as the main exposure of interest (22, (26) (27) (28) (29) (30) (31) (33) (34) (35) (36) (37) (37) (38) (39) (40) . The remaining studies evaluated stress (e.g., maternal stress, disaster-related PTSD, subjective stress, objective hardship) (19) (20) (21) (22) (23) 25, 45) , maternal weight and maternal nutrition status (13,79), cognitive appraisal (24) , and coping strategies (25) that . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101/2020.11. 27.20239830 doi: medRxiv preprint were the result of the disaster as the exposure variable. The age when cardiometabolic outcomes were assessed varied across studies, with 7 studies evaluating outcomes during childhood and adolescence (≤18 years of age) (13, [19] [20] [21] [22] [23] [24] , 4 studies during young to mid adulthood (>18-40 years of age) (25, 34, 80, 83) , and 10 during later adulthood (≥50 years of age) (28, (30) (31) (32) (33) (36) (37) (38) (39) (40) . Ekamper et al. (2015) , evaluated outcomes throughout the life-course, with age at outcome ranging from 18-63 years (29) .

Two studies (26, 45) did not specifically identify the age at which outcomes were assessed. Detailed characteristics and findings of all studies that assessed perinatal and childhood exposures to disasters can be found in Table 3 .

Studies that assessed human-made disasters found an increased association or increased change in obesity, metabolic syndrome, CVD related-outcomes and diabetes, however not all were statistically significant (OR range 1.15-3.11; hazard ratio (HR) range: 1.26-1.91) (27, (29) (30) (31) (32) (33) (34) (35) 38, 45) . Some studies also reported no association or a decreased association following exposure to human-made disasters and cardiometabolic outcomes (OR range: 0.94-1.02) (29, 34) . Among the studies that evaluated natural disasters, maternal stress, including objective hardship and objective prenatal maternal stress, were found to increase the odds of obesity using different adiposity measures during childhood and adolescence (19) (20) (21) . However, weak correlations were found between subjective distress/stress and body mass index (BMI) (r=0.39; p=0.03), zBMI (r=0.40; p=0.02), and body fat percentage (r=0.33; p=0.09) in offspring at age 13 (22) . The prevalence of heart disease, ischemic heart disease, emergency department visits for gestational hypertension, myocardial infarction, diabetes diagnoses and diabetes-related emergency department visits increased after exposure to Hurricanes Sandy, San Felipe and Ciprian, and the 1918 Influenza Pandemic (26, 36, 40) . In addition, exposure to hurricanes and stress-related to hurricanes was noted to increase pregnancy induced hypertension and gestational diabetes (odds ratio (OR) range: 1.13-1.22) (25) .

Thirty-four studies investigated the effects of exposure to disasters during adulthood on cardiometabolic outcomes. The length of follow-up ranged from 1 month to 13 years. There were 23 studies that examined natural disasters (12, [42] [43] [44] 46, 49, 50, [52] [53] [54] [56] [57] [58] [59] 62, 63, 65, [71] [72] [73] [74] , and 11 studies that examined human-made disasters (41, 47, 48, 51, 55, 60, 61, (66) (67) (68) (69) (70) . Of these studies, only one evaluated the impact of an infectious disease epidemic (64) . Most studies (12, 41-44,46,48,50,52-54,56- . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101/2020.11.27.20239830 doi: medRxiv preprint 64,66,69-74) considered the disaster as the main exposure of interest (n=27). The remaining 7 studies assessed disaster-related stress (51, 55, 65, 67) , including post-traumatic stress disorder (PTSD) and

psychological strain, unemployment rates as a result of the disaster (49) and exposure to damaged or collapsed buildings during the World Trade Center disaster (68) . Detailed characteristics and findings of all studies that assessed adult exposures to disasters are included in Table 4 .

The studies that assessed exposure to human-made disasters during adulthood reported mixed results in terms of associations with outcomes and statistical significance. Most studies reported an increased association with outcomes, including heart disease-related mortality, CVD hospitalization, complaints of CVD, vascular problems, stroke, and incidence of hypertension (OR range: 1.21-3.30; HR range: 1.63-1.82) (41, 43, 47, 51, 55, 60, 61, 67, 68, 70) . No association or a decreased association with CVD hospitalizations was noted following exposure to the World Trade Centre attacks (47, 66) . In addition, time of evaluation from damaged buildings resulting from the World Trade Centre also had a decreased association with cardiometabolic outcomes (OR range: 0.7-0.9) (68) . Among studies that evaluated the impact of exposure to natural disasters on subsequent cardiometabolic outcomes, nearly all studies reported an increased association (OR range: 1.08-5.65; relative risk (RR) range: 2.01-2.62; HR range:

1.72-3.29) (43, 44, 49, 56, 62, 70) . However, five studies reported no association or a decreased association after exposure to hurricanes among specific groups or at different timepoints following a disaster (47, 56, 58, 62, 70) . Several studies evaluated the mean difference in outcomes including cardiovascular, diabetes and obesity-related outcomes, however, these results were very inconsistent, with some studies noting an increase, some a decrease and other reporting no change in outcomes following a disaster (12, 46, [52] [53] [54] 57, 59, 63, 65, 73, 74) .

Across all studies, few evaluated effect modification or subgroups of a population that may be at a greater risk of negative health outcomes following disasters. Some studies stratified by sex (28, 32, 34, 39, 43, 48, 55, 62) , gestational timing of exposure (20, 27, (29) (30) (31) 33, 36) , year of birth or age at outcome (40, 62, 67) , urban or rural area (35) , race (43, 46) and socioeconomic status (65), however, results varied greatly due to the differences in exposure period, disaster type, cardiometabolic outcome and age at outcome. One study explored the possible mediators between cognitive appraisal following the Quebec Ice Storm and obesity. It was noted that negative cognitive appraisal was found to predict . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101/2020.11.27.20239830 doi: medRxiv preprint obesity via DNA methylation of diabetes-related genes (24) . No studies evaluated or discussed possible interventions to mitigate risk of cardiometabolic disease following a disaster.

The critical appraisal assessment for all study designs are found in Tables A2-A4 . Among the cohort studies, most studies met all criteria included in the checklist indicating high study quality. For instance, almost all cohort studies had comparable populations that were recruited in a similar way and exposures that were assessed in the same way across populations. However, across almost all cohort studies, information on follow-up or strategies to address incomplete follow-up were unclear or not addressed. The critical appraisal results for cross-sectional studies were inconsistent with a small number of studies meeting only some checklist requirements. For quasi-experimental studies, the checklist requirement for within person comparisons were not applicable for all studies, however, all studies clearly defined the cause and effect within the study.

Exposure to both natural and human-made disasters, including famine, war, terrorism, natural disasters, and infectious disease epidemics, during both the perinatal/childhood and adult periods were associated with increased cardiometabolic outcomes including obesity, hypertension, myocardial infarction, diabetes, and cardiac mortality in most studies. These findings emphasize that the burden of disasters extends beyond the known direct harm they cause, and attention is needed on the detrimental indirect long-term effects on cardiometabolic health and chronic disease. Meta-analysis was not possible due to the very heterogeneous study designs, measures of effect, outcomes, and timing of exposures. The included studies also reported varied follow-up periods and length of retrospective assessment. From an epidemiological standpoint, the difference in the follow-up periods, timing of exposure, year of disaster and geographic location may help to explain the variation in the reported results. It is important for future studies to explore these differences and how they may influence cardiometabolic outcomes.

Studies also reported insufficient data on subgroups that were at increased risk of worse cardiometabolic health outcomes and interventions that were implemented to mitigate risk of cardiometabolic outcomes. There were also few results that investigated sex and gender differences, or . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101/2020.11.27.20239830 doi: medRxiv preprint that applied an equity lens. It has been noted that those of different levels of socioeconomic status experience differential cardiometabolic outcomes (84, 85) . This signifies the importance of exploring associations between exposure to disasters and cardiometabolic outcomes stratified by these factors.

Understanding how these associations differ will also help to identify groups of people who will experience worse outcomes following a disaster.

The potential mechanisms discussed whereby exposure to disaster could increase cardiometabolic outcomes include maternal objective hardship, subjective stress and various coping mechanisms, psychological strains including PTSD, anxiety and fear, and reduced health care service access. One study that explored mediators in the association between stress and obesity measures identified the role of DNA methylation in this association (24) . The findings from this study are important to better understand a possible pathway of obesity development following exposure to a disaster. More studies are needed that evaluate other mechanisms, such as disruptions to healthcare or medication access, and changes in dietary intake or physical activity. Understanding the mechanistic pathway following exposure to disaster will allow for targeted public health strategies, contributing to a mitigation of risk. pandemic, which is affecting millions of people worldwide. While only a small proportion of the identified studies focused on pandemics and epidemics, the findings may serve to guide our understanding of expected outcomes and to develop future research to study the effects of COVID-19 on cardiometabolic outcomes. The results from this study can also be used to better understand the trade-off between the implementation of public health measures, such as physical distancing to reduce transmission of a virus, and the implications with access to healthcare, as the review found access to healthcare was limited following a disaster (12). The findings from this review can help to inform future decisions by policy makers regarding the implementation of various public health measures.

The overall findings of this review indicate exposure to any type of disaster may increase the risk of cardiometabolic outcomes including obesity, diabetes and CVD. Further, our results suggest that increased risk is observed for disaster exposure at any period over the life-course from the perinatal . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted November 30, 2020. child and adult periods. However, more studies are needed to understand the mechanisms which may explain these associations and to identify subgroups of the population at highest risk of long-term cardiometabolic outcomes post-disaster. Findings from this review may inform research that should be conducted in the context of the current COVID-19 pandemic and may inform public health mitigation measures that should be considered post-pandemic to prevent long term cardiometabolic outcomes in the population. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101/2020.11.27.20239830 doi: medRxiv preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101/2020.11.27.20239830 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101/2020.11.27.20239830 doi: medRxiv preprint Does not equal to 100% as studies report multiple cardiometabolic outcomes 4. Includes hypertension, coronary artery disease/heart disease, angina, heart attack/myocardial infarction, metabolic syndrome, cardiac disease related blood markers, stroke 5. Diabetes, blood glucose, metabolic syndrome 6. Gestational diabetes, gestational hypertension, pre-eclampsia . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted November 30, 2020. ; Table 3 . Characteristics of included studies investigating the association between exposure to a disaster during the perinatal and childhood periods and cardiometabolic outcomes across the life-course, by disaster type (n=24) Infants who were exposed to famine in utero whose mother had a daily ration <1000 calories during any 13-week period of gestion compared to infants who were born before or conceived after the famine period (before November 1943 or after February 1947) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint

The copyright holder for this this version posted November 30, 2020. ; https://doi.org/10.1101/2020.11.27.20239830 doi: medRxiv preprint

Abbreviations: AMI: Acute myocardial infarction; BMI: Body mass index; BP: Blood pressure; CI: Confidence Interval; CHD: Coronary heart disease; Chol: Cholesterol; CVD: Cardiovascular disease; HDL: High-density lipoproteins; HR: Hazard ratio; LDL: Low-density lipoproteins OR: Odds Ratio; PMNS: Prenatal Maternal Stress

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