Abstract
Background
Patients hospitalized with coronavirus disease 2019 (COVID-19) frequently require mechanical ventilation and have high mortality rates. However, the impact of viral burden on ...these outcomes is unknown.
Methods
We conducted a retrospective cohort study of patients hospitalized with COVID-19 from 30 March 2020 to 30 April 2020 at 2 hospitals in New York City. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load was assessed using cycle threshold (Ct) values from a reverse transcription-polymerase chain reaction assay applied to nasopharyngeal swab samples. We compared characteristics and outcomes of patients with high, medium, and low admission viral loads and assessed whether viral load was independently associated with intubation and in-hospital mortality.
Results
We evaluated 678 patients with COVID-19. Higher viral load was associated with increased age, comorbidities, smoking status, and recent chemotherapy. In-hospital mortality was 35.0% (Ct <25; n = 220), 17.6% (Ct 25–30; n = 216), and 6.2% (Ct >30; n = 242) with high, medium, and low viral loads, respectively (P < .001). The risk of intubation was also higher in patients with a high viral load (29.1%) compared with those with a medium (20.8%) or low viral load (14.9%; P < .001). High viral load was independently associated with mortality (adjusted odds ratio aOR, 6.05; 95% confidence interval CI, 2.92–12.52) and intubation (aOR, 2.73; 95% CI, 1.68–4.44).
Conclusions
Admission SARS-CoV-2 viral load among hospitalized patients with COVID-19 independently correlates with the risk of intubation and in-hospital mortality. Providing this information to clinicians could potentially be used to guide patient care.
We evaluated 678 hospitalized patients with coronavirus disease 2019 and found that 35.0% of patients with a high severe acute respiratory syndrome coronavirus 2 viral load on admission died compared with 17.6% and 6.2% of patients with medium and low viral loads, respectively.
Despite potential harm that can result from polypharmacy, real-world data on polypharmacy in the setting of heart failure (HF) are limited. We sought to address this knowledge gap by studying older ...adults hospitalized for HF derived from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke).
We examined 558 older adults aged ≥65 years with adjudicated HF hospitalizations from 380 hospitals across the United States. We collected and examined data from the REGARDS baseline assessment, medical charts from HF-adjudicated hospitalizations, the American Hospital Association annual survey database, and Medicare's Hospital Compare website. We counted the number of medications taken at hospital admission and discharge; and classified each medication as HF-related, non-HF cardiovascular-related, or noncardiovascular-related.
The vast majority of participants (84% at admission and 95% at discharge) took ≥5 medications; and 42% at admission and 55% at discharge took ≥10 medications. The prevalence of taking ≥10 medications (polypharmacy) increased over the study period. As the number of total medications increased, the number of noncardiovascular medications increased more rapidly than the number of HF-related or non-HF cardiovascular medications.
Defining polypharmacy as taking ≥10 medications might be more ideal in the HF population as most patients already take ≥5 medications. Polypharmacy is common both at admission and hospital discharge, and its prevalence is rising over time. The majority of medications taken by older adults with HF are noncardiovascular medications. There is a need to develop strategies that can mitigate the negative effects of polypharmacy among older adults with HF.
The American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort risk equations were developed to estimate atherosclerotic cardiovascular disease (CVD) risk and guide statin ...initiation.
To assess calibration and discrimination of the Pooled Cohort risk equations in a contemporary US population.
Adults aged 45 to 79 years enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study between January 2003 and October 2007 and followed up through December 2010. We studied participants for whom atherosclerotic CVD risk may trigger a discussion of statin initiation (those without clinical atherosclerotic CVD or diabetes, low-density lipoprotein cholesterol level between 70 and 189 mg/dL, and not taking statins; n = 10,997).
Predicted risk and observed adjudicated atherosclerotic CVD incidence (nonfatal myocardial infarction, coronary heart disease CHD death, nonfatal or fatal stroke) at 5 years because REGARDS participants have not been followed up for 10 years. Additional analyses, limited to Medicare beneficiaries (n = 3333), added atherosclerotic CVD events identified in Medicare claims data.
There were 338 adjudicated events (192 CHD events, 146 strokes). The observed and predicted 5-year atherosclerotic CVD incidence per 1000 person-years for participants with a 10-year predicted atherosclerotic CVD risk of less than 5% was 1.9 (95% CI, 1.3-2.7) and 1.9, respectively, risk of 5% to less than 7.5% was 4.8 (95% CI, 3.4-6.7) and 4.8, risk of 7.5% to less than 10% was 6.1 (95% CI, 4.4-8.6) and 6.9, and risk of 10% or greater was 12.0 (95% CI, 10.6-13.6) and 15.1 (Hosmer-Lemeshow χ2 = 19.9, P = .01). The C index was 0.72 (95% CI, 0.70-0.75). There were 234 atherosclerotic CVD events (120 CHD events, 114 strokes) among Medicare-linked participants and the observed and predicted 5-year atherosclerotic CVD incidence per 1000 person-years for participants with a predicted risk of less than 7.5% was 5.3 (95% CI, 2.8-10.1) and 4.0, respectively, risk of 7.5% to less than 10% was 7.9 (95% CI, 4.6-13.5) and 6.4, and risk of 10% or greater was 17.4 (95% CI, 15.3-19.8) and 16.4 (Hosmer-Lemeshow χ2 = 5.4, P = .71). The C index was 0.67 (95% CI, 0.64-0.71).
In this cohort of US adults for whom statin initiation is considered based on the ACC/AHA Pooled Cohort risk equations, observed and predicted 5-year atherosclerotic CVD risks were similar, indicating that these risk equations were well calibrated in the population for which they were designed to be used, and demonstrated moderate to good discrimination.
Guidelines recommend lifestyle modification for patients with coronary heart disease (CHD). Few data demonstrate which lifestyle modifications, if sustained, reduce recurrent CHD and mortality risk ...in cardiac patients after the postacute rehabilitation phase. We determined the association between ideal lifestyle factors and recurrent CHD and all-cause mortality in REasons for Geographic and Racial Differences in Stroke study participants with CHD (n = 4,174). Ideal lifestyle factors (physical activity ≥4 times/week, nonsmoking, highest quartile of Mediterranean diet score, and waist circumference <88 cm for women and <102 cm for men) were assessed through questionnaires and an in-home study visit. There were 447 recurrent CHD events and 745 deaths over a median 4.3 and 4.5 years, respectively. After multivariable adjustment, physical activity ≥4 versus no times/week and non-smoking versus current smoking were associated with reduced hazard ratios (HRs; 95% confidence interval CI) for recurrent CHD (HR 0.69, 95% CI 0.54 to 0.89 and HR 0.50, 95% CI 0.39 to 0.64, respectively) and death (HR 0.71, 95% CI 0.59 to 0.86 and HR 0.53, 95% CI 0.44 to 0.65, respectively). The multivariable-adjusted HRs (and 95% CIs) for recurrent CHD and death comparing the highest versus lowest quartile of Mediterranean diet adherence were 0.77 (95% CI 0.55 to 1.06) and 0.84 (95% CI 0.67 to 1.07), respectively. Neither outcome was associated with waist circumference. Comparing participants with 1, 2, and 3 versus 0 ideal lifestyle factors (non-smoking, physical activity ≥4 times/week, and highest quartile of Mediterranean diet score), the HRs (and 95% CIs) were 0.60 (95% CI 0.44 to 0.81), 0.49 (95% CI 0.36 to 0.67), and 0.38 (95% CI 0.21 to 0.67), respectively, for recurrent CHD and 0.65 (95% CI 0.51 to 0.83), 0.57 (95% CI 0.43 to 0.74), and 0.41 (95% CI 0.26 to 0.64), respectively, for death. In conclusion, maintaining smoking cessation, physical activity, and Mediterranean diet adherence is important for secondary CHD prevention.
Excessive sedentary time is ubiquitous in Western societies. Previous studies have relied on self-reporting to evaluate the total volume of sedentary time as a prognostic risk factor for mortality ...and have not examined whether the manner in which sedentary time is accrued (in short or long bouts) carries prognostic relevance.
To examine the association between objectively measured sedentary behavior (its total volume and accrual in prolonged, uninterrupted bouts) and all-cause mortality.
Prospective cohort study.
Contiguous United States.
7985 black and white adults aged 45 years or older.
Sedentary time was measured using a hip-mounted accelerometer. Prolonged, uninterrupted sedentariness was expressed as mean sedentary bout length. Hazard ratios (HRs) were calculated comparing quartiles 2 through 4 to quartile 1 for each exposure (quartile cut points: 689.7, 746.5, and 799.4 min/d for total sedentary time; 7.7, 9.6, and 12.4 min/bout for sedentary bout duration) in models that included moderate to vigorous physical activity.
Over a median follow-up of 4.0 years, 340 participants died. In multivariable-adjusted models, greater total sedentary time (HR, 1.22 95% CI, 0.74 to 2.02; HR, 1.61 CI, 0.99 to 2.63; and HR, 2.63 CI, 1.60 to 4.30; P for trend < 0.001) and longer sedentary bout duration (HR, 1.03 CI, 0.67 to 1.60; HR, 1.22 CI, 0.80 to 1.85; and HR, 1.96 CI, 1.31 to 2.93; P for trend < 0.001) were both associated with a higher risk for all-cause mortality. Evaluation of their joint association showed that participants classified as high for both sedentary characteristics (high sedentary time ≥12.5 h/d and high bout duration ≥10 min/bout) had the greatest risk for death.
Participants may not be representative of the general U.S. population.
Both the total volume of sedentary time and its accrual in prolonged, uninterrupted bouts are associated with all-cause mortality, suggesting that physical activity guidelines should target reducing and interrupting sedentary time to reduce risk for death.
National Institutes of Health.
Myocardial infarction (MI) is an established risk factor for atrial fibrillation (AF). However, the extent to which AF is a risk factor for MI has not been investigated.
To examine the risk of ...incident MI associated with AF.
A prospective cohort of 23,928 participants residing in the continental United States and without coronary heart disease at baseline were enrolled from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort between 2003 and 2007, with follow-up through December 2009.
Expert-adjudicated total MI events (fatal and nonfatal).
Over 6.9 years of follow-up (median 4.5 years), 648 incident MI events occurred. In a sociodemographic-adjusted model, AF was associated with about 2-fold increased risk of MI (hazard ratio HR, 1.96 95% CI, 1.52-2.52). This association remained significant (HR, 1.70 95% CI, 1.26-2.30) after further adjustment for total cholesterol, high-density lipoprotein cholesterol, smoking status, systolic blood pressure, blood pressure-lowering drugs, body mass index, diabetes, warfarin use, aspirin use, statin use, history of stroke and vascular disease, estimated glomerular filtration rate, albumin to creatinine ratio, and C-reactive protein level. In subgroup analysis, the risk of MI associated with AF was significantly higher in women (HR, 2.16 95% CI, 1.41-3.31) than in men (HR, 1.39 95% CI, 0.91-2.10) and in blacks (HR, 2.53 95% CI, 1.67-3.86) than in whites (HR, 1.26 95% CI, 0.83-1.93); for interactions, P = .03 and P = .02, respectively. On the other hand, there were no significant differences in the risk of MI associated with AF in older (≥75 years) vs younger (<75 years) participants (HR, 2.00 95% CI, 1.16-3.35 and HR, 1.60 95% CI, 1.11-2.30, respectively); for interaction, P = .44.
AF is independently associated with an increased risk of incident MI, especially in women and blacks. These findings add to the growing concerns of the seriousness of AF as a public health burden: in addition to being a well-known risk factor for stroke, AF is also associated with increased risk of MI.
We sought to determine the associations between baseline chronic medical conditions and future risk of sepsis.
Longitudinal cohort study using the 30,239 community-dwelling participants of the ...REGARDS cohort. We determined associations between baseline chronic medical conditions and incident sepsis episodes, defined as hospitalization for an infection with the presence of infection plus two or more systemic inflammatory response syndrome criteria.
Over the mean observation time of 4.6 years (February 5, 2003 through October 14, 2011), there were 975 incident cases of sepsis. Incident sepsis episodes were associated with older age (p<0.001), white race (HR 1.39; 95% CI: 1.22-1.59), lower education (p<0.001) and income (p<0.001), tobacco use (p<0.001), and alcohol use (p = 0.02). Incident sepsis episodes were associated with baseline chronic lung disease (adjusted HR 2.43; 95% CI: 2.05-2.86), peripheral artery disease (2.16; 1.58-2.95), chronic kidney disease (1.99; 1.73-2.29), myocardial infarction 1.79 (1.49-2.15), diabetes 1.78 (1.53-2.07), stroke 1.67 (1.34-2.07), deep vein thrombosis 1.63 (1.29-2.06), coronary artery disease 1.61 (1.38-1.87), hypertension 1.49 (1.29-1.74), atrial fibrillation 1.48 (1.21-1.81) and dyslipidemia 1.16 (1.01-1.34). Sepsis risk increased with the number of chronic medical conditions (p<0.001).
Individuals with chronic medical conditions are at increased risk of future sepsis events.
Background
Social determinants of health (SDOHs) cluster together and can have deleterious impacts on health outcomes. Individually, SDOHs increase the risk of cancer mortality, but their cumulative ...burden is not well understood. The authors sought to determine the combined effect of SDOH on cancer mortality.
Methods
Using the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, the authors studied 29,766 participants aged 45+ years and followed them 10+ years. Eight potential SDOHs were considered, and retained SDOHs that were associated with cancer mortality (P < .10) were retained to create a count (0, 1, 2, 3+). Cox proportional hazard models estimated associations between the SDOH count and cancer mortality through December 31, 2017, adjusting for confounders. Models were age‐stratified (45‐64 vs 65+ years).
Results
Participants were followed for a median of 10.6 years (interquartile range IQR, 6.5, 12.7 years). Low education, low income, zip code poverty, poor public health infrastructure, lack of health insurance, and social isolation were significantly associated with cancer mortality. In adjusted models, among those <65 years, compared to no SDOHs, having 1 SDOH (adjusted hazard ratio aHR, 1.39; 95% CI, 1.11‐1.75), 2 SDOHs (aHR, 1.61; 95% CI, 1.26‐2.07), and 3+ SDOHs (aHR, 2.09; 95% CI, 1.58‐2.75) were associated with cancer mortality (P for trend <.0001). Among individuals 65+ years, compared to no SDOH, having 1 SDOH (aHR, 1.16; 95% CI, 1.00‐1.35) and 3+ SDOHs (aHR, 1.26; 95% CI, 1.04‐1.52) was associated with cancer mortality (P for trend = .032).
Conclusions
A greater number of SDOHs were significantly associated with an increased risk of cancer mortality, which persisted after adjustment for confounders.
Individually, social determinants of health increase the risk of cancer mortality, but their cumulative burden is not well understood. A greater number of social determinants of health in the same individual are found to be significantly associated with an increased risk of cancer mortality, even after adjustment for a variety of confounders.
Individuals infected with SARS-CoV-2 who also display hyperglycemia suffer from longer hospital stays, higher risk of developing acute respiratory distress syndrome (ARDS), and increased mortality. ...Nevertheless, the pathophysiological mechanism of hyperglycemia in COVID-19 remains poorly characterized. Here, we show that hyperglycemia is similarly prevalent among patients with ARDS independent of COVID-19 status. Yet among patients with ARDS and COVID-19, insulin resistance is the prevalent cause of hyperglycemia, independent of glucocorticoid treatment, which is unlike patients with ARDS but without COVID-19, where pancreatic beta cell failure predominates. A screen of glucoregulatory hormones revealed lower levels of adiponectin in patients with COVID-19. Hamsters infected with SARS-CoV-2 demonstrated a strong antiviral gene expression program in the adipose tissue and diminished expression of adiponectin. Moreover, we show that SARS-CoV-2 can infect adipocytes. Together these data suggest that SARS-CoV-2 may trigger adipose tissue dysfunction to drive insulin resistance and adverse outcomes in acute COVID-19.
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•Hyperglycemia is highly prevalent in acute respiratory distress syndrome ± COVID-19•Insulin resistance is the main cause for hyperglycemia in patients with severe COVID-19•Patients with COVID-19 and hamsters infected with SARS-CoV-2 have decreased adiponectin•SARS-CoV-2 can directly infect human and mouse adipocytes
Here, Reiterer et al. report that hyperglycemia in critically ill patients with COVID-19 is caused mainly by insulin resistance and is associated with decreased circulating adiponectin. SARS-CoV-2 is shown to directly infect human adipocytes, trigger an inflammatory antiviral response in the adipose tissue, and cause its dysfunction.
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