Original research••

Myocardial infarction and physical function: the REasons for Geographic And Racial Differences in Stroke prospective cohort study

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Abstract

Objective To examine associations between myocardial infarction (MI) and multiple physical function metrics.

Methods Among participants aged≥45 years in the REasons for Geographic And Racial Differences in Stroke prospective cohort study, instrumental activities of daily living (IADL), activities of daily living (ADL), gait speed, chair stands and Short Form-12 physical component summary (PCS) were assessed after approximately 10 years of follow-up. We examined associations between MI and physical function (no MI (n=9472), adjudicated MI during follow-up (n=288, median 4.7 years prior to function assessment), history of MI at baseline (n=745), history of MI at baseline and adjudicated MI during follow-up (n=70, median of 6.7 years prior to function assessment)). Models were adjusted for sociodemographic characteristics, health behaviours, depressive symptoms, cognitive impairment, body mass index, diabetes, hypertension and urinary albumin to creatinine ratio. We examined subgroups defined by age, gender and race.

Results The average age at baseline was 62 years old, 56% were women and 35% were black. MI was significantly associated with worse IADL and ADL scores, IADL dependency, chair stands and PCS, but not ADL dependency or gait speed. For example, compared with participants without MI, IADL scores (possible range 0–14, higher score represents worse function) were greater for participants with MI during follow-up (difference: 0.37 (95% CI 0.16 to 0.59)), MI at baseline (0.26 (95% CI 0.12 to 0.41)) and MI at baseline and follow-up (0.71 (95% CI 0.15 to 1.26)), p<0.001. Associations tended to be greater in magnitude among participants who were women and particularly black women.

Conclusion MI was associated with various measures of physical function. These decrements in function associated with MI may be preventable or treatable.

What is already known on this topic

Myocardial infarction (MI) has been associated with worse physical function, though most studies predate the current era, when large ST-segment elevation MIs are rare.

What this study adds

MI is associated with physical function assessed using both self-reported tools and measured performance in the current treatment era. The associations may be greater in magnitude among women, and particularly black women.

How this study might affect research, practice or policy

Increased screening for declines in physical function among MI survivors and increased use and greater equity in interventions to prevent or reverse declines in function associated with MI may be warranted.

Introduction

Physical function is a multidimensional construct including ability to move around the environment and conduct basic and more complex self-care activities.1 2 Diminished function is increasingly common with advancing age and is associated with low quality of life, disability, loss of independence and mortality.1 3–5 Prior studies found that prevalent coronary heart disease and incident myocardial infarction (MI) were associated with poor physical function.6–12 However, many of these studies were conducted prior to the current era of primary prevention and treatment for acute coronary syndrome, when ST-segment elevation MI were more common. Non-ST-segment elevation MI has smaller areas of ischaemic injury compared with ST-segment elevation MI and now represents the majority of MI in the USA.13–15 Additionally, acute treatments that limit ischaemic injury and long-term treatments that prevent recurrent events could reduce the direct cardiac contributions to poor physical function but side effects and complications of these treatments could increase risk of physical function impairment.

Because physical function is the result of a complex interaction between health conditions and contextual factors such as age, the role of MI in function may vary by age, gender and race and ethnicity.2 6 10 11 16 Improved understanding of which aspects of physical function are associated with MI in the contemporary era could lead to identification of individuals with the greatest need for approaches to mitigate and/or accommodate functional impairments. Therefore, the objective of this study was to examine associations between MI and physical function among REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants and evaluate potential differences in associations by age, gender and race.

Methods

Study population

The REGARDS study recruited 30 239 participants aged 45 years and older who identified as black or white race from across the continental USA in 2003–2007, with oversampling of black individuals and residents of the high-stroke mortality Stroke Belt and Stroke Buckle regions of the Southeastern USA.17 At baseline, participants completed a computer-assisted telephone interview that asked questions about sociodemographic characteristics, health behaviours and medical history followed by an in-home examination conducted by a trained health technician to measure anthropometrics, blood pressure and ECG, collect blood and urine samples and conduct a medication inventory. Participants have been contacted by telephone every 6 months for assessment of cardiovascular hospitalisations and cognitive function. In 2013–2016 after approximately 10 years of follow-up, surviving participants were invited to participate in a follow-up assessment including a computer-assisted telephone interview and in-home examination to update baseline measurements and to collect information on function. For this analysis, we included 10 575 participants who completed the baseline and follow-up assessments, had available information on the history of MI at baseline, did not have missing or erroneous data on physical function measures and did not have a self-reported history of stroke at baseline or an adjudicated stroke during follow-up (online supplemental figure 1).

Myocardial infarction

Because we were interested in both incident and recurrent MI, we compared participants with a history of MI at baseline, adjudicated MI during follow-up, both or neither. The history of MI was defined as participant self-report of MI or heart attack diagnosis or evidence of prior MI on ECG at baseline. Medical records for potentially MI-related hospitalisations identified during the two times annual telephone follow-up calls were retrieved and adjudicated by a team of clinician-investigators based on signs and symptoms of ischaemia, ECG findings and rising and/or falling pattern of cardiac enzymes.18

Physical function assessment

The function assessment conducted 2013–2016 included both self-reported metrics (instrumental activities of daily living (IADL), activities of daily living (ADL) and Short-Form-12 physical component summary (PCS) score) and observed metrics (gait speed and chair stands). These metrics largely assess physical aspects of function, though they could also be influenced by cognitive function and mental health as well as environmental and other contextual characteristics. The set of metrics was chosen to be comparable to prior studies of physical function and ageing and because they could be administered through a computer-assisted telephone interview or an in-home examination conducted by a health technician.

IADL were household chores, purchasing items, planning and preparing meals, managing money, using a telephone, taking medications and travelling by vehicle. ADL were getting out of bed or chair, eating, dressing, bathing and using a toilet. For each activity, participants selected from the options ‘I could do it by myself with no difficulty’ (assigned a value of 0), ‘I could do it by myself with some difficulty’ (assigned a value of 1) and ‘I would need someone to help me do it’ (assigned a value of 2). We created IADL and ADL scores by summing across activities, as in prior studies.8 The possible IADL score range was 0–14 and the possible ADL score range was 0–10; higher scores indicate worse function. We also examined dichotomous outcomes of IADL dependency and ADL dependency, defined as needing help to do at least one activity.

The timed walk, used to calculate gait speed, and chair stands used procedures similar to prior studies.19 20 During the in-home visit, participants completed two 8-foot timed walks, using canes or walkers if needed, and the results were averaged. Participants were timed completing five chair stands (standing up and sitting down without using arms). For both the timed walk and chair stand, times>1 min or <1 s were considered erroneous and were not included in analyses. Gait speed was estimated in metres/second from the timed walk.

The PCS is a self-reported measure of health-related quality of life and function derived from the Medical Outcomes Study surveys, normed to have a mean of 50 and a SD of 10 in the general population of the USA, with higher scores indicating better function.21

Covariates

We selected covariates using the WHO International Classification of Function, which is a biopsychosocial model that describes functional decline as a result of interactions between health conditions and personal/environmental contextual factors, including age.2 Baseline contextual factors included age at baseline, gender, race, education, income, marital status, social isolation (not seeing close friends or family at least once per month), cigarette smoking and region of residence categorised as Stroke Buckle, Stroke Belt and non-Belt, consistent with the participant sampling strategy.17 Contextual factors assessed at follow-up were participant-reported frequency of receipt of social and emotional support and marital status. Health conditions at baseline included depressive symptoms (≥4 on the Center for Epidemiologic Studies Depression 4-item scale), cognitive impairment (≤4 on the Six-Item Screener), body mass index, diabetes (self-report of diabetes medication use, fasting blood glucose≥126 mg/dL or if the participant was not fasting, blood glucose≥200 mg/dL), hypertension (blood pressure≥140/90 mmHg or self-report of blood pressure lowering medication use) and elevated urinary albumin to creatinine ratio (>30 mg/g).22 Health conditions assessed during follow-up included percutaneous coronary intervention, coronary artery bypass grafting and heart failure hospitalisation which were detected and adjudicated using the same methods described above for MI. Health conditions assessed at the follow-up interview and in-home examination included new cognitive impairment (≤4 on the Six-Item Screener), change in body mass index, incident hypertension, incident diabetes, incident albumin to creatinine>30 mg/g, depressive symptoms (≥10 on the Center for Epidemiologic Studies Depression 10-item scale) and number of medications assessed on a medication inventory.

Statistical analysis

We first calculated descriptive statistics (means and SD for continuous variables, n and percent for categorical variables) by MI category (no MI, MI during follow-up, MI at baseline, MI at baseline and during follow-up) and tested for differences between groups using analysis of variance or χ² tests. We compared IADL score, ADL score, timed walk, chair stand and PCS across MI categories using a series of linear regression models with each metric considered separately. Model 1 was unadjusted, model 2 adjusted for age at baseline, race and gender and model 3 further adjusted for baseline contextual factors and health conditions. Because some outcomes had skewed distributions, particularly IADL and ADL scores, we used empirical variance estimators to calculate CIs and p values. We tested for differences in physical function by MI category using three degree of freedom type III tests. Additionally, we tested for differences between groups with MI using two degree of freedom tests. To examine differences in proportions of participants with dependency in IADL and ADL across MI categories, we used logistic regression models, adjusted as described above.

To explore potential selection bias from non-participation in the follow-up, which may be due to the competing risk of mortality or to poor health and impaired function, we conducted sensitivity analyses using inverse probability of attrition weighting.23 The model to calculate the weights included the same covariates as model 3 above. Inverse probability of attrition weighting uses measured information on the whole cohort at baseline to estimate what the associations might have been if there was complete participation at follow-up. We conducted a sensitivity analysis adjusting for contextual factors and health conditions assessed during follow-up. We could not determine whether these characteristics preceded or followed MI for participants who experienced incident or recurrent MI during the study period. Therefore, this model included characteristics that may be confounders or may be on the causal pathway between MI and physical function. Among participants who had incident MI during the study period, we examined the association of the time between MI and the physical function assessment and physical function metrics using linear regression. We conducted an additional sensitivity analysis excluding participants with an MI in the year prior to the second in-home visit (n=37) because our focus was on longer-term associations of MI with physical function and the effects of MI may be greatest immediately following MI.7 Finally, we conducted a sensitivity analysis excluding individuals with heart failure hospitalisation during follow-up because heart failure can cause declines in function independent of MI.7 We tested for interaction by age (<75 vs ≥75 years at baseline, approximately 85 years at function assessment), gender, race and race–gender groups. We conducted stratified analyses when p values for interaction were <0.10. Multiple imputation by chained equations was used to account for missing values for the covariates.24 We simulated 30 complete datasets and combined point estimates and variances across datasets using Rubin’s rules. Analyses were conducted using StataMP V.14 (College Station, Texas, USA). P values<0.05 were considered statistically significant for main effects and <0.10 for interactions.

Results

At baseline, 9760 of 10 575 participants did not have a history of MI; of these participants, 288 had an adjudicated MI during approximately 10 years of follow-up (median 4.7 years prior to physical function assessment, 25th percentile 2.2 years, 75th percentile 6.7 years). Among the 815 participants with a history of MI at baseline; 70 had an adjudicated MI during follow-up (median 6.7 years prior to physical function assessment, 25th percentile 3.9 years, 75th percentile 7.7 years). Compared with participants without MI, participants with MI at baseline or during follow-up were on average older, a smaller proportion were black and a greater proportion were male and had lower income (table 1).

Table 1

Characteristics of REasons for Geographic And Racial Differences in Stroke study participants by history of myocardial infarction (MI) at baseline and 10-year follow-up

IADL and ADL

IADL scores were significantly different across groups, with higher scores among participants with MI, when adjusted for baseline covariates (table 2 and figure 1). Participants with a history of MI at baseline and during follow-up had IADL scores that were numerically greater than those with MI at baseline only or MI during follow-up only, but these differences were not statistically significant. Among participants without MI, 10.5% had at least one IADL dependency compared with 19.1% who had MI during follow-up, 15.7% who had a history of MI at baseline and 21.4% who had a history of MI at baseline and recurrent MI during follow-up (online supplemental table 1). The odds of having at least one IADL dependency were significantly different across groups defined by MI in adjusted models. Differences in ADL scores remained significant after adjusting for covariates measured at baseline. Among participants without MI, 0.7% had at least one ADL dependency compared with 1.7% who had MI during follow-up, 1.6% who had a history of MI at baseline and 2.9% who had a history of MI at baseline and recurrent MI during follow-up. However, the prevalence of ADL dependency was not statistically significantly different across groups when adjusted for baseline characteristics.

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Figure 1

Association between myocardial infarction (MI) and instrumental activities of daily living (IADL) score (A), activities of daily living (ADL) score (B), gait speed (C), chair stands (D) and physical component summary (PCS) score (E) at approximately 10 years of follow-up among REasons for Geographic And Racial Differences in Stroke study participants. Adjusted for baseline age, race, gender, education, income, marital status, social isolation, cigarette smoking, region, depressive symptoms, cognitive impairment, body mass index, diabetes, hypertension and albumin-to-creatinine ratio>30 (ie, model 3 in table 2).

Table 2

Association between myocardial infarction and physical function at approximately 10 years of follow-up among REasons for Geographic And Racial Differences in Stroke study participants

Gait speed and chair stand

Gait speed did not differ significantly across groups. Differences between groups in mean time to complete five chair stands were statistically significant when adjusted for baseline covariates. The chair stand times were numerically greater when comparing participants with MI during follow-up to those with MI at baseline only, but this did not reach statistical significance.

Physical component summary

Differences in PCS scores between groups remained significant after adjustment. When comparing between groups with MI, participants with MI at baseline and follow-up had the lowest PCS scores and participants with MI at baseline only had the highest PCS scores (p<0.001).

Sensitivity analyses

After weighting for inverse probability of attrition, associations between MI and functional status were similar to unweighted analyses; however, associations with ADL score and chair stand were not statistically significant (online supplemental table 2). When adjusting for characteristics assessed during follow-up, results were largely similar, though the prevalence of IADL dependency was not statistically significantly different across groups (online supplemental table 3). Among the 288 participants with incident MI during study follow-up, time between MI event and physical function assessment was not significantly associated with IADL score, ADL score, gait speed or chair stand (online supplemental table 4). Each 1-year longer interval between MI and physical function assessment was associated with 0.58 (95% CI 0.15 to 1.01) points greater mean PCS score. When excluding participants with MI in the year prior to function assessment, results were similar to the primary analyses (online supplemental table 5). Excluding participants with heart failure hospitalisations attenuated the associations of MI with IADL score and PCS (online supplemental table 6).

Interactions with age, gender and race

The magnitude of the association of MI at baseline and follow-up with IADL dependency was stronger for participants≥75 years of age at baseline (adjusted OR compared with no MI=5.77, 95% CI 1.58 to 21.13) compared with younger participants (adjusted OR 1.19, 95% CI 0.55 to 2.57) (p interaction=0.02) (online supplemental table 7). In contrast, the associations of MI with chair stands and PCS score were greater in magnitude for participants<75 years of age at baseline (p interaction=0.008 and 0.10, respectively).

The association of MI with IADL score was greater in magnitude among women than among men (p interaction=0.007) (online supplemental table 8) and figure 2). When considering gender and race jointly, black women appeared to have stronger associations between MI and IADL scores (p interaction=0.01) and ADL scores (p interaction=0.06) than other race–gender groups (online supplemental table 9 and figure 3). Other tests of interaction between MI and age, gender, race and race–gender groups were not statistically significant (p interaction>0.10).

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Figure 2

Association between myocardial infarction and instrumental activities of daily living (IADL) score at approximately 10 years of follow-up among REasons for Geographic And Racial Differences in Stroke study participants, stratified by gender. Adjusted for baseline age, race, gender, education, income, marital status, social isolation, cigarette smoking, region, depressive symptoms, cognitive impairment, body mass index, diabetes, hypertension and albumin-to-creatinine ratio>30 (ie, model 3 in table 2).

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Figure 3

Association between myocardial infarction and instrumental activities of daily living (IADL) score (A) and activities of daily living (ADL) score (B) at approximately 10 years of follow-up among REasons for Geographic And Racial Differences in Stroke study participants, stratified by race and gender. Adjusted for baseline age, race, gender, education, income, marital status, social isolation, cigarette smoking, region, depressive symptoms, cognitive impairment, body mass index, diabetes, hypertension and albumin-to-creatinine ratio>30 (ie, model 3 in table 2).

Discussion

In the REGARDS study population, we found that history of MI was associated with worse function as measured by IADL scores, IADL dependency, ADL scores, chair stands and PCS. These metrics differed in the type of assessment (self-reported or observed) and in the types of activities targeted. However, the results of the current study were largely consistent across metrics, suggesting that MI could lead to impairment in various aspects of physical function. The exceptions were ADL dependency, which was uncommon in this study of community dwelling individuals (<1%), and gait speed, measured using an 8-foot timed walk, which was practical for in-home assessment but is a shorter distance than is recommended for use in clinical practice.25 There was some evidence for stronger associations among women, and particularly black women. In this study, we examined individuals with both incident and recurrent MI. The population with a history of MI includes people with recurrent events and with distant history of MI, but these individuals have not previously been well-represented in the literature on MI and physical function. Although associations tended to be numerically greater for participants with MI during follow-up compared with MI at baseline only, most of these differences did not reach statistical significance. These findings in a contemporary population complement prior studies examining the association of MI with function conducted with ST-segment elevation MI was more common and extend prior work suggesting that black individuals and women, particularly black women, are especially vulnerable to worse physical function associated with MI.

Methods for assessing physical function are variable in clinical practice and in research. Several studies of MI and physical function have examined the ability to conduct ADL and IADL.7 8 Other studies have assessed observed physical performance measures like gait speed and chair stands; self-reported measures of physical health-related quality of life and function like PCS; and other measures of physical function and disability.9–12 A unique aspect of the current study among REGARDS participants was the multicomponent assessment of physical function covering many of the domains examined in prior studies, with small-to-moderate differences observed between participants with and without MI. For the IADL and ADL scores used in this study, a 1-unit difference is interpretable as one additional limitation (having difficulty completing the task) or dependency (requiring another assistance from another person). Although the mean differences in IADL and ADL scores between individuals with and without MI were relatively modest (<1), the odds of IADL dependency was 56% higher among individuals with incident MI compared with individuals without MI and the odds of ADL dependency was 84% higher, though not statistically significant. The clinically meaningful change in time to complete five chair stands has been reported to range from 0.5 to 4.7 s, depending on estimation method.26 In this study population, the adjusted difference between participants with incident MI and those without MI was 1.2 s. The clinically meaningful difference in PCS has been reported to range from 0.6 to 12.127; in this study population, individuals with incident MI had PCS scores that were 4.2 points lower than participants without MI.

Mechanisms that may link MI with physical function include pathologic and psychosocial changes caused by MI, limitations in function increasing risk of MI, effects of hospitalisation and acute and postacute therapies for MI and shared risk factors between MI and worse function.28 While this study and most prior studies have found that MI and other coronary heart diseases are associated with worse function, the Medical Outcomes Study found that there was substantial variation in function within groups of individuals with chronic conditions, including heart disease.12 In the biopsychosocial model of function and disability, physical function results from the interplay between health conditions (including mental health and cognitive conditions), contextual characteristics and personal characteristics.2 Supporting the concept that physical health conditions alone do not determine physical function, clinical measures of heart disease severity are not strongly associated with physical function.8 28

Importantly, declines in physical function due to MI may be prevented or ameliorated through individual and system interventions.9 29–34 For example, structured cardiac rehabilitation is effective at preventing or reducing declines in function following an MI.34 The CAPABLE intervention, which incorporates home visits by nurses, occupational therapists and handy workers who can modify the home environment, has shown success in reversing function limitations and slowing decline while also being cost-effective.33 Tailored geriatric care pathways for hospitalised older adults may also prevent or reverse MI-associated declines in function; however, the evidence for these hospital system interventions is mixed and may depend on other aspects of care delivery.32 The prior literature supporting these interventions suggests that the differences in physical function by MI status we observed are not inevitable.

The current study among REGARDS participants and other studies have found that MI was more strongly associated with some measures of function among women, and particularly black women.16 Some prior studies have found stronger associations of MI with function among older compared with younger adults16; among REGARDS participants, we found conflicting evidence across physical function measures. Differences in associations of MI with physical function may result from disparities in receipt of interventions that can prevent or reverse function declines. For example, in the USA, few of those eligible complete cardiac rehabilitation programmes; older individuals, women and black individuals are less likely to receive cardiac rehabilitation, due in part to differential referral.35 Racial disparities in use and quality of home healthcare, which may mitigate function limitations, have also been observed in some but not all studies.36 37

The large geographically diverse study population of black and white American adults in the REGARDS study, multidimensional assessment of physical function and examination of distant and more recent MI are major strengths of this study. However, this population included relatively high-functioning, community-dwelling individuals who agreed to participate in a telephone interview and in-home study visit and completed the function assessments. Non-participation in the second in-home visit or in the gait speed and chair stand assessments because of death or physical function limitations related to MI may have biased results; this concern is somewhat mitigated by sensitivity analyses using inverse probability of attrition weighting that were consistent with the primary analyses. The results may not be generalisable to individuals who are living in residential care settings, those who identify as race other than black or white and to those receiving care outside of the USA. Gait speed measured using an 8-foot timed walk is systematically lower than gait speed measured from longer walking distances.25 The assessment of physical function occurred at varying time points relative to MI events, which could increase heterogeneity within the groups with MI. Among participants with incident MI, the time between the MI event and follow-up assessment had modest associations with PCS but not the other measures of function assessed. Most individuals with MI had a remote history of MI (ie, at least 10 years for those with a history of MI at baseline and no MI event during follow-up; median of 4.7 years for those with MI during follow-up), and results were similar when excluding individuals with MI in the year prior to the function assessment. We adjusted for a number of comorbidities and health behaviours that may increase risk for both MI and physical function limitations, but not all potential shared risk factors were available in this study. We lacked information on MI severity. However, prior literature indicates that measures of cardiac pathology, angina and laboratory exercise capacity are not strongly associated with function among people with coronary heart disease.8 28 38 39 We have limited information on care provided for the MI; therefore, we could not evaluate the role of MI care and disparities in care in our associations, though adjusting for revascularisation did not substantially change our findings. Additionally, it is possible that physical function limitations increase the risk of MI (ie, reverse causation).3

In summary, history of MI was associated with worse physical function across multiple measures, and these associations may be stronger among women, and particularly black women.

Twitter: @EmilyLevitan
Contributors: EBL, PG, JB, OS, MRS, RWD, TMB and MMS conceptualised the research question. RWD, TMB and MMS contributed to data collection. CBB provided expertise in ageing and ageing research. EBL and JB designed the statistical approach and JB conducted statistical analyses. All authors contributed to interpretation of the results. EBL drafted the manuscript, and all authors revised the manuscript for important intellectual content and approved the final version. EBL is responsible for the overall content as guarantor.
Funding: The REGARDS study is supported by cooperative agreement U01 NS041588, cofunded by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA), National Institutes of Health, Department of Health and Human Services. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NINDS or the NIA. Representatives of the NINDS were involved in the review of the manuscript but were not directly involved in the collection, management, analysis or interpretation of the data. Additional funding was provided by R01 HL80477 and R01 HL165452 from the National Heart Lung and Blood Institute (NHLBI). Representatives from NHLBI did not have any role in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, or the preparation or approval of the manuscript.
Competing interests: EBL reports research funding from Amgen, unrelated to the current work. The other authors do not have conflicts to report.
Patient and public involvement: Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review: Not commissioned; externally peer reviewed.
Supplemental material: This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Data availability statement

Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available. The REGARDS study shares data with investigators through formal data use agreements. Requests for information on this process and data access may be sent to the REGARDS study at regardsadmin@uab.edu.

Ethics statements

Patient consent for publication:

Ethics approval:

This study involves human participants. The REGARDS study was approved by the institutional review boards at participating institutions, and REGARDS participants provided written informed consent. This analysis was approved by the University of Alabama at Birmingham Institutional Review Board (IRB-060217017). Participants gave informed consent to participate in the study before taking part.

Acknowledgements

The authors thank the other investigators, the staff and the participants of the REGARDS study for their valuable contributions. A full list of participating REGARDS investigators and institutions can be found at: https://www.uab.edu/soph/regardsstudy/.

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