Death Certificates Research Articles

Abstract 4136762: Association Between Circadian Rest/Activity Rhythms and Incident Dementia in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Alterations in circadian rest/activity rhythms (RARs) are common among older adults. RARs can be derived from accelerometry data and are routinely used as proxy measures. Evidence suggests that altered (e.g., fragmented, delayed) RARs may be risk factors for dementia. However, results have been mixed. Using data from the ARIC Study, a community-based cohort, we assessed the association between RARs and incident dementia. Methods: ARIC participants without dementia who wore the Zio XT ECG Patch in 2016-17 for > 3 days were included. RARs were obtained from an accelerometer within the Zio XT ECG Patch and measures of interdaily stability (IS; consistency), intradaily variability (IV; fragmentation), and relative amplitude (RA; strength) were derived. Dementia cases were identified through 2020 using in-person and phone-based cognitive assessments, hospitalization discharge codes, or death certificates. Cox proportional hazards models were used. Results: Of the 2,183 participants (mean [SD] age 79 [4.5] years, 58% female, 24% identified as Black), 176 (8%) developed dementia. Median follow-up time was 3 years and mean Zio XT ECG Patch wear time was 12 days. After multivariable adjustment, lower RA and higher IV were associated with incident dementia (HRs [95% CIs] per 1-SD increment: 0.65 [0.56-0.76], 1.19 [1.02-1.38]). No significant association between IS and dementia was noted; however, there was an interaction by race (p=0.03). Stratified results were not significant, but effect estimates were in opposite directions: (HRs [95% CIs] per 1-SD increment in IS: 0.78 [0.59-1.02] in Black participants and 1.17 [0.96-1.41] in white participants, respectively). No interactions by sex or APOEε4 were noted (p>0.10). Conclusion: In this community-based cohort of older adults, weaker circadian rhythm strength and fragmentation were associated with dementia risk. The association between IS and dementia may differ by race; however, this needs to be further examined in future research. Overall, measures of circadian RARs may be risk factors for dementia. Additional research is warranted to determine whether they can be novel targets for dementia prevention.

Abstract 4136776: Prognostic Value of Resting Heart Rate and Heart Rate Variability in the 12-lead Electrocardiogram: Mortality Data From the CODE Nationwide Database

Introduction: Resting Heart Rate (HR) and Heart Rate Variability (HRV) reflect autonomic control, and are implicated as prognostic factors. We aimed to evaluate the prognostic value of HR and HRV in a cohort from a nationwide telemedicine network. Methods: We assessed unique ECGs recorded from patients ≥16 years-old, from the tele-ECG database of the Telehealth Network of Minas Gerais, Brazil, between 2010 and 2017. Variables of interest were HR and standard deviation of normal RR intervals (SDNN). Self-informed data were collected: sex, age, risk factors (hypertension, dyslipidemia, diabetes, smoking) and comorbidities (myocardial infarction, Chronic Obstructive Pulmonary Disease, and Chagas disease). Outcomes of interest were all-cause and cardiovascular mortality, assessed by ICD codes reported in death certificates, through linkage with the Mortality Information System. Cox regression was applied to evaluate the association between HR and HRV and the outcomes, in 4 models: 1. Unadjusted; 2. Adjusted for sex and age; 3. Model 2 + risk factors + clinical comorbidities; 4. Model 3 + HRV or HR, respectively. Results: At total 992.611 individuals were included, median age of 55 years, 60% women. In 6 years, there were 33.292 deaths (3,37%), 21% due to cardiovascular causes. Patients who died had higher prevalence of all risk factors and comorbidities, as well as higher HR: 76 (IQR 66-87) vs. 74 (IQR 65-83) bpm, p<0.001 and lower HRV: 84 (IQR 51-127) vs. 114 (IQR 74-153), p<0.001. After adjustments (model 4), all HR quartiles were independently associated a progressively increased risk of all-cause mortality, being 88% higher for the 4 th quartile (HR=1.88 (95%CI 1.77–1.89). Similarly, the 1 st and 2 nd HRV quartiles remained associated with increased all-cause mortality (1 st quartile HR=1.42 (95%CI 1.37–1.47) in the final model. For cardiovascular mortality, HR was also an independent predictor, with a progressively higher risk, with a 77% increase (HR=1.77 95%CI 1.65–1.91) in the 4 th quartile. HRV was also an independent predictor of cardiovascular death, with a 33% risk increase (HR=1.33, 95%CI 1.23–1.44) for the 1 st quartile. Male gender, age, and all risk factors and comorbidities were also independent predictors of all-cause and cardiovascular mortality. Conclusions: In a large cohort of Brazilian adults, baseline HR and HRV were independent predictors of all-cause and cardiovascular mortality, after adjustment for clinical variables and autonomic indexes.

Abstract 4120332: RISING TRENDS IN ISCHEMIC HEART DISEASE RELATED MORTALITY AMONG OLDER ADULTS WITH SLEEP APNEA IN THE UNITED STATES FROM 1999 TO 2021

Introduction: Sleep apnea (SA) is often underrecognized and undertreated despite its high prevalence in the adult population and its association with adverse cardiovascular outcomes. There are limited estimates of national trends on cardiovascular mortality in older patients with sleep apnea. We aimed to assess the sex and race-related trends of ischemic heart disease (IHD) mortality in the older adults with SA using a large population-based database. Methods: We utilized the Centers for Disease Control and Prevention Wide-Ranging, Online Data for Epidemiologic Research (CDC WONDER) database which provides information from death certificates of all US residents according to the International Classification of Diseases, Tenth Revision (ICD-10). The demographic and mortality data were obtained for the United States population >65 years from 1999 to 2021. Ischemic heart disease (ICD-10 codes I20-I25) was listed as the underlying cause of death, and SA (G47.3) as a contributing cause of death. Age adjusted mortality rates (AAMRs) per 1,000,000 population were calculated by standardizing deaths to the year 2000 US population. We used Jointpoint Regression Program to analyze temporal trends in mortality from 2000 to 2021. Average annual percentage change (AAPC) with 95% CI were calculated to examine trends in AAMR over time. Results: Overall, AAMR of IHD mortality for patients with SA increased from 7.9 per 1,000,000 (95% CI, 6.9-8.8) in 1999 to 53.4 per 1,000,000 (95% CI, 51.4-55.4) in 2021 with an AAPC of 9.1% per year (95% CI, 8.8-9.5). Men had consistently higher AAMR than women throughout the study period (overall AAMR men: 45.51 (95% CI, 44.8-46.2); women: 12.5 (95% CI, 12.2-12.8). Both the groups had a similar increasing trend in AAMR, with men having a steeper increase. [AAPC men: 9.3% (95% CI, 8.5-10.8) versus AAPC women: 8.6%, 95% CI, 8.1-9.7]. Non Hispanic (NH) White population had the greatest AAMR throughout the study period, followed by NH Black and Hispanic or Latino. The NH White population had the largest increase in AAMR from 1999 to 2021 (AAPC 9.4%, 95% CI:8.9-10.1). Conclusion: In the United States, there has been a general increase in IHD mortality related to sleep apnea over the last two decades. This rising trend as noted in our analysis is concerning and underscores the need for more robust cardiovascular surveillance in these patients.

Abstract 4112716: The Trend In Racial Differences In Mortality Attributed To Congenital Heart Diseases In Infants In The United States From 2005 To 2019

Background: Deaths from congenital heart disease (CHD) in children have been decreasing in the United States. We examined the differences in mortality trends between Non-Hispanic Black (NHB) and Non-Hispanic White (NHW) infants. Methods: We retrospectively analyzed publicly available data from the Centers for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (CDC WONDER). The data was obtained from the linked birth/infant deaths from 2005 to 2019. We evaluated all infant deaths up to 1 year of age with the cause of death listed as CHD (International classification of diseases, 10 th revision (ICD-10) codes Q20-Q26 (except atrial septal defect, Q21.1 and patent ductus arteriosus, Q25. CHD infant mortality rate (IMR) was calculated per 100,000 live births. Race was ascertained based on death certificate reporting. Joinpoint regression was used to examine CHD-IMR by year, including stratification by NHB vs NHW, and neonatal vs postneonatal. The difference between NHB and NHW CHD-IMR was ascertained via the Mann-Whitney U test. P<0.05 was considered statistically significant. Results: Out of 60,243,988 live births, there were 19,004 CHD-related infant deaths. The characteristics of the study population are displayed in Table 1. The overall CHD-IMR declined from 36.1 to 27.0 per 100,000 live births (25.2%) with an average annual percentage change (AAPC) of -2.1 [95% CI -2.6, -1.572] (Figure 1). The CHD-IMR was significantly higher in NHB than in NHW (40 vs 29.3; P<0.0001) and this difference remained when the mortality rate was stratified by neonatal and post-neonatal periods. The CHD-IMR decreased significantly in NHW [AAPC: -2%; 95% CI: -2.5, -1.5%], but not in NHB [AAPC of -1.4%, 95% CI, -3.0, 0.3%]. The NHB-to-NHW CHD-IMR ratio, a measure of CHD-IMR disparity averaged 1.4 over the study period [AAPC: 0.8%; 95% CI: -0.2, 1.8%] (Figure 2). Conclusions: The CHD-IMR declined significantly for NHW, but not in NHB in the US from 2005 to 2019. The CHD-IMR was higher in NHB than in NHW. There was no significant change in the NHB-to-NHW CHD-IMR ratio, signifying no change in the disparity that exists between NHB and NHW IMR. These findings may have implications for patient care and public health policymaking. They lay the groundwork for additional studies to determine and understand the drivers behind these findings such as in prenatal diagnosis.

Long-Term Ozone Exposure, COPD, and Asthma Mortality: A Retrospective Cohort Study in the Republic of Korea

Ozone concentrations have increased in recent decades, and several studies have reported that long-term exposure to ozone increases the mortality risk induced by respiratory conditions. However, research on cause-specific mortality related to ozone exposure and respiratory diseases remains scarce. We constructed a retrospective cohort of 5,360,032 adults aged ≥ 65 years from the National Health Insurance Service of Republic of Korea, and death certificates were obtained from Statistics Republic of Korea to determine the cause of death between 2010 and 2019. The daily maximum 8 h average levels of ozone during the warm season annually (May–September) and other air pollutants were determined for the residential district. We analyzed the data using a time-varying Cox proportional hazards model with individual- and district-level covariates, incorporating a competing risk framework to address deaths from causes other than chronic obstructive pulmonary disease (COPD) and asthma. In our single-pollutant model with a 3-year moving average, a 1 ppb increase in ozone exposure was associated with a hazard ratio (HR) of 1.011 (95% confidence interval [CI]: 1.008–1.013) for COPD mortality and an HR of 1.016 (95% CI: 1.011–1.022) for asthma mortality. In our model adjusted for the presence of underlying diseases and district-level variables, the HRs were 1.009 (95% CI: 1.008–1.014) for COPD and 1.017 (95% CI: 1.011–1.023) for asthma, respectively. These associations remained robust in our two-pollutant model, except for NO2 and COPD. A linear concentration–response relationship was identified between ozone concentration, COPD, and asthma mortality. In this large nationwide cohort study, long-term exposure to ozone was associated with an increased risk of death from COPD and asthma in older Korean adults.

Decedents Found in Bathtubs.

We investigated deaths in bathtubs for criteria to assist in death certification. We reviewed 252 deaths in which the person was found dead in a bathtub/shower at home. We extracted cause, manner, age, clad or unclad, water in the bathtub, water running, and face submersion. Of the 252 deaths, heart disease was the leading cause of death (129), followed by intoxication (47), trauma (22), drowning (28), and other diseases (26). The manners of death were 155 natural, 64 accident, 30 suicide, and 3 homicides. All drowning fatalities involved the decedent having their face submerged. Intoxication and natural deaths had submersion of the face in 15% and 12% of deaths, respectively. For nondrowning causes of death, the majority were without face submersion. For natural deaths, the predominant circumstance was the individual discovered unclad with water in the bathtub and the face not submerged. Conversely, for suicides, the majority were found clad without water. A comprehensive investigation incorporating a scene examination, gathering of the medical and psychosocial history, and typically an autopsy is needed to certify the cause and manner of death. Face submersion alone is not diagnostic of a drowning and must be interpreted with the medical history and autopsy findings.

The burden of all-cause mortality following influenza-associated hospitalizations, FluSurv-NET, 2010-2019.

While the estimated number of U.S. influenza-associated deaths is reported annually, detailed data on the epidemiology of influenza-associated deaths, including the burden of in-hospital versus post-hospital discharge deaths are limited. Using data from the 2010-11 through 2018-19 seasons from the Influenza Hospitalization Surveillance Network, we linked cases to death certificates to identify patients who died from any cause during their influenza hospital stay or within 30 days post discharge. We described demographic and clinical characteristics of patients who died in hospital versus post discharge and characterized locations and causes of death (COD). Among 121,390 cases hospitalized with laboratory-confirmed influenza over 9 seasons, 5.5% died; 76% of deaths were in patients ≥65 years, 71% were non-Hispanic White, and 34% had ≥4 underlying medical conditions. Among all patients with an influenza-associated hospitalization who died, 48% of deaths occurred after hospital discharge; the median days from discharge to death was 9 days (IQR 3-19 days). Post-discharge deaths more often occurred in older patients and among those with underlying medical conditions. Only 37% of patients who died had "influenza" as a COD on their death certificate. Influenza was more frequently listed as a COD among persons who died in-hospital compared with cardiovascular disease among those who died after discharge. All-cause mortality burden is substantial among patients hospitalized with influenza, with almost 50% of deaths occurring within 30 days after hospital discharge. Surveillance systems should consider capture of post-discharge outcomes to better characterize the impact of influenza on all-cause mortality.

Characteristics of Children Ages 1-17 Who Died of COVID-19 in 2020-2022 in the United States.

This study describes characteristics of children ages 1 to 17 years who died of coronavirus disease 2019 (COVID-19) in 2020 to 2022 and whose deaths were reviewed by child death review (CDR) teams across the United States. We used data in the National Fatality Review-Case Reporting System to examine children who died of COVID-19. Deaths were determined because of COVID-19 from death certificates or CDR determinations. A total of 183 children 1 to 17 years old who died of COVID-19 were reported in the National Fatality Review-Case Reporting System. One-third (33%) were 15- to 17-year-olds, and 26% were 1- to 4-year-olds. Fifty-six percent were reported as male, 54% white, 24% Black, and 18% Hispanic ethnicity. Physicians declared cause of death in at least 82% of deaths. More than two-thirds (68%) had a medical condition (excluding COVID-19) at time of death. The most common conditions were nervous system disorders (19%), congenital disorders (14%), obesity (12%), respiratory disorders (12%), and neurodevelopmental disorders (10%). Of children with an underlying condition, 35% had 3 or more conditions. Less than half (42%) had contact with a health care provider within a month of their death; and three-fourths died within 14 days of exposure. This study describes the demographics, death investigation findings, and medical conditions of children who died of COVID-19. The results highlight the short timeline between COVID-19 exposure and death. Pandemic planning that prioritizes prevention efforts and timely access to effective medical care may result in saving children's lives.

Risk of second primary cancers in nodal non-Hodgkin lymphoma patients by primary lymph node location: a retrospective cohort population-based study.

Non-Hodgkin lymphoma (NHL) is a diverse group of blood cancers with increasing incidence and survival rates due to advancements in treatment and early detection. However, NHL survivors are at significant risk of developing second primary cancers, which can adversely impact their long-term survival. This retrospective population-based cohort study utilized data from the Surveillance, Epidemiology, and End Results database, covering 17 geographic areas in the United States from 2000 to 2021. The authors included patients diagnosed with nodal NHL as a first primary cancer and excluded those diagnosed at autopsy or via death certificate only. Standardized Incidence Ratios, Absolute Excess Risks, and Person-Years at Risk were calculated to evaluate the risk of developing SPCs according to the primary lymph node site and stratified by latency periods following the initial NHL diagnosis. The cohort included 54012 NHL patients. The authors' results showed that for most SPCs, the risk of development was different for different primary NHL lymph node locations. The highest risks were observed for thyroid cancer, acute myeloid leukemia, and Hodgkin lymphoma. Notably, the risk for thyroid cancer was highest in the first year post-diagnosis, while hematological malignancies such as acute myeloid leukemia and Hodgkin lymphoma showed elevated risks in the intermediate and late latency periods. NHL survivors are at an increased risk of developing SPCs, influenced by the primary lymph node site and latency period. These findings highlight the need for tailored surveillance strategies and preventive measures to mitigate the long-term risks of SPCs in NHL survivors. Further research is necessary to elucidate the underlying mechanisms and to develop targeted interventions for this high-risk population.

Analysis of Mortality Causes and Locations in Veterans with ALS: A Decade Review.

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that leads to rapid degeneration of nerves in the brain and spinal cord, with eventual loss of voluntary movements, including breathing. This retrospective study of medical record data from 105 US veterans diagnosed with ALS at the Oklahoma City VA Medical Center between 2010 and 2021 aimed to identify patient demographics, and the causes and places of death for these veterans. MATERIAL AND METHODS Data from 105 US veterans diagnosed with ALS by the El Escorial criteria and supported by neurophysiology testing was reviewed. The information about the place and cause of death was obtained from each patient's care provider and death certificate. Crude mortality rates (per 100 person-years) and standardized mortality ratios (SMRs) were calculated for the causes of death, by sex, age group, and location of death. RESULTS During the 11-year follow-up period, 80 (76.2%) veterans with ALS died. The mean (SD) follow-up time was 4.53 (4.55) years. Most of the deaths were due to respiratory failure and pneumonia (n=43, mortality rate=9.21 per 100 person-years). Most patients died at home (n=71, 88.7%). The annual crude mortality rate was 16.7 and the all-cause death SMR was 25.63 (95% CI, 20.32-31.55). CONCLUSIONS This study's findings are that in veterans with ALS, the main cause of death is respiratory disease (failure). The main location of death was the home, with their family members. The all-cause mortality rate among veterans with ALS was 26 times greater than for the general Oklahoma population.

Reactive surveillance of deaths involving a fall among the elderly in France, 2015 to March 2023

Abstract In 2022, France launched an elderly anti-fall plan with a goal to reduce fatal falls by 20% within 5 years. In a reactive monitoring approach ensuring comparability over the period, our study aims to develop an algorithm to identify deaths involving a fall using free-text medical causes in death certificates. This will enable proactive surveillance and evaluate plan effectiveness upon completion. We devised an algorithm based on textual search of fall-related expressions in death certificates. Performance metrics were assessed by contrasting algorithm-identified deaths with those flagged by ICD-10 fall-related codes. We compared also temporal dynamics between the algorithms from 2015 to 2021. Analysis was performed by age group, gender and place of death. Additionally, our algorithm enabled estimation of fall-related death trends from 2015 to 2023. The free-text algorithm exhibited robust performance, with a sensitivity and PPV of 95% when compared to deaths coded with an ICD-10 fall-related underlying or associated cause. Temporal trends between both were highly correlated (correlation coefficient=0.99). Instead of the usual 10000 deaths for fall, we revealed about 13000 deaths linked to falls considering both primary and associated causes. Among these, approximately three-quarters were coded as the underlying cause of death in ICD-10 coding. Regarding trends, the results are preliminary and suggested an increase in mortality rates related to falls detected by the algorithm between 2015 and 2022. Our approach distinguishes falls from other competing causes that often relegate them to secondary status in the chain of morbid events leading to death. With free-text medical causes accessible within 3 to 4 months, monitoring deaths involving falls can be done at a detailed geographic level and in a more reactive way. Looking ahead, we must also consider incorporating the impact of epidemics and/or heat waves to accurately evaluate the effectiveness of the anti-fall plan. Key messages • Algorithm using free-text of death certificates identify deaths involving falls. • Our innovative approach isolates falls from other competing causes, elevating their significance in death processes.

Polygenic prediction of coronary artery disease among 130,000 Mexican adults

Abstract Background Coronary artery disease (CAD) is a leading cause of premature mortality globally. Polygenic risk scores (PRSs) have been reported to enhance CAD prediction in populations of European ancestry but evidence from other populations is limited. We assessed the transferability and relevance of eight different external PRSs to the odds of premature CAD in a Mexican population with high levels of relatedness and ancestry admixture. Methods 128,388 genotyped participants aged 35-74 years who were recruited between 1998 and 2004 into the Mexico City Prospective Study (MCPS) were included. We selected and recreated eight previously-reported CAD PRSs. The number of single nucleotide polymorphism variants included in the PRSs varied from 44 to 6,472,620. Premature CAD was defined as either self-reported history of heart attack or angina at recruitment or death before age 75 with CAD recorded on the death certificate. Age and sex-adjusted logistic regression was used to estimate the ability of each PRS to predict CAD, both overall and separately by age, sex and estimated proportion of Indigenous American ancestry. Analyses were repeated after further adjustment for conventional risk factors (blood pressure, adiposity, smoking, diabetes and highest education achieved). Risk discrimination was assessed using C-statistic. Results Of the 128,388 participants, 68% were women, mean (SD) age was 50.2±10.9 years and the average proportion of Indigenous American ancestry was 67%. CAD was identified for 3,871 (3.0%) participants; prior CAD was reported by 1,669 (1.3%) participants while 2,360 (1.8%) participants died before age 75 years with CAD mentioned on the death certificate. All eight PRSs were positively and approximately log-linearly associated with the odds of CAD, but the strength of association varied between the PRSs, ranging from a 7% increase per 1SD higher PRS (odds ratio [OR] 1.07, 95% CI 1.04-1.11) to a 33% increase (OR 1.33, 95% CI 1.29-1.37). Collectively, age, sex and (any) PRS resulted in a C-statistic of 0.70-0.71. C-statistics were slightly lower among those with a higher proportion of indigenous American ancestry. For four of the eight PRSs (including three of the four multi-ancestry PRSs) the increase in odds of CAD per 1SD higher PRS was significantly greater for men than women (eg, for the PRS with the strongest overall association with CAD the OR per 1SD higher PRS was 1.43 [95% CI 1.36-1.49] in men and 1.25 [1.20-1.31] in women). Further inclusion of conventional vascular risk factors reduced the strengths of associations of each PRS with CAD only slightly but increased the model C statistic to 0.74 in all cases. Conclusions In this population of admixed Mexican adults, existing PRSs predicted CAD reasonably well and independently of conventional vascular risk factors. Ancestry-specific instruments that more closely represent genetic variation in Mexico may further enhance polygenic prediction of CAD risk.Table 1.Baseline characteristicsFigure 1.Main analysis results

Left atrial function for predicting atrial fibrillation: a machine learning approach

Abstract Background Common risk scores for atrial fibrillation (AF) are based on clinical risk factors, and little is known about the contribution of left atrial (LA) function parameters to risk assessment. Purpose To determine whether a machine learning-based model that includes LA function parameters outperforms a commonly used risk scores, the CHARGE-AF, in predicting AF. Methods Participants in the Atherosclerosis Risk in Communities (ARIC) Study (a community-based cohort study in the USA) who attended visit 5 (2011-2013) and without a history of AF were included in this analysis. Incident AF was ascertained from ECG during study visits, hospitalization discharge codes, and death certificates. Random survival forest methodology was used to build a prediction model for AF; candidate variables included traditional clinical risk factors and measures of LA structure and function. Dataset was randomly split into a training (75%) and testing (25%) cohort. For each variable, importance was measured based on the reduction in Harrell’s c-statistic if the variable was randomly permuted prior to obtaining predicted values. Variables significantly associated with AF were included in the final model. Model calibration was tested using the Greenwood-Nam-D'Agostino (GND) test. Discrimination ability of our model was assessed in the testing cohort using Harrell’s c-statistic and compared with that of the CHARGE-AF model. Results 4,909 participants (59% female, 22% Black, mean age 75 years) were included. During a median follow-up of 7.0 years (1st-3rd quartile: 5.4-7.8), 650 participants developed AF. Variables significantly associated with incident AF were race, triglycerides, systolic blood pressure, coronary heart disease, age, LA maximal volume index, NT-proBNP, and LA reservoir strain (Figure 1). LA reservoir strain was the variable most strongly associated with AF. The final model showed good discrimination (c-statistic (95% CI): 0.734 (0.698-0.768)). The GND test did not detect statistically significant miscalibration (GND p=0.08). Compared with our model, CHARGE-AF had lower discrimination ability (c-statistic (95% CI): 0.635 (0.594-0.677)) and the difference was statistically significant (difference in c-statistic (95% CI): 0.099 (0.043-0.152)). Conclusion A machine learning-based model with few variables including LA function outperforms a commonly used risk model in predicting AF. Incorporation of LA functional assessment may help inform clinicians regarding individual risk of AF.

A novel electrocardiogram-based model for prediction of dementia: the Atherosclerosis Risk in Communities (ARIC) study

Abstract Background Current dementia prediction models, such as the UK Biobank Dementia Risk Score (UKBDRS, 12 variables), are limited by having variables that are difficult to obtain, subjectively measured, and self-reported. Although individual ECG parameters are linked to higher dementia risk, no study has combined multiple ECG parameters to create an ECG model for dementia prediction. Purpose Using data from the ARIC study, a prospective community-based cohort of Black and White participants in the USA that started in 1987-89, we created an ECG model (based on 7 pre-defined ECG parameters linked to dementia) and compared its model discrimination with the UKBDRS. Methods Participants without prevalent dementia from 2 baselines were included: Visit 4 (V4, 1996-98) and V5 (2011-13). Seven ECG parameters were examined: heart rate, abnormal P-wave terminal force in lead V1 (PTFV1), prolonged P wave duration, abnormal P wave axis, advanced interatrial block, left ventricular hypertrophy (LVH, Cornell voltage criteria), and corrected QT interval (QTc). Dementia cases were identified through 2019 using in-person and phone cognitive assessments, hospitalisation codes, and death certificates. Using a backward selection method (keeping variables with P<0.10 and age, since it is an important dementia risk factor), parsimonious Cox regression models were constructed for prediction of dementia over the longest available follow-up (V4: 23 years, V5: 8 years). Model discrimination of the ECG models and UKBDRS variables was evaluated by the Harrell’s C-statistic (95% CI). Results At V4, 11,520 participants (mean age, 62.8 ± 5.7 years; 56% women; 22% Black) were included; 2,427 developed dementia. At V5, 5,667 participants (mean age, 75.4 ± 5.1 years; 59% women; 22% Black) were included; 830 developed dementia. Figures 1 and 2 show the C-statistic (95%) and area under the ROC curve for the ECG model and UKBDRS variables at V4 and V5, respectively. The C-statistic (95% CI) for both ECG models were >0.70 and comparable with the corresponding UKBDRS models. Conclusion For middle-aged and older adults, a dementia prediction model comprising age and 4 ECG variables has good discrimination for dementia that is comparable with the 12-variable UKBDRS model. Since ECG variables are easily obtainable and objectively measured, these ECG models will be easier to adopt than the UKBDRS model. Further work to validate this model in an external cohort and develop a risk score will facilitate clinical translation.

Mortality related to different circulatory diseases: a multiple causes of death analysis, 2008-2022

Abstract Background Mortality from circulatory diseases significantly increased in 2020 compared to pre-pandemic years in many countries. However, data were mostly limited to the underlying cause of death and to the first phases of the pandemic. Analyses of any mention of a disease in death certificates (multiple causes of death approach, MCOD) are more robust to changes in coding rules/practices and to the role of COVID-19 as a competing cause of death. Methods Mortality records were extracted from 2008 to 2022 among residents of the Veneto Region (Northeastern Italy, 4.9 million population). Based on MCOD, age-standardized mortality rates (2013 European standard) were computed for ischemic heart diseases (IHD), cerebrovascular diseases (CVD), atrial fibrillation (AF), and hypertensive diseases (HD). The annual percent change (APC) was estimated through the pre-pandemic period (2008-2019), and change in rates during pandemic years were computed compared to 2019. Results Before the pandemic, rates were steeply declining for IHD (APC -5.1%; 95%CI -5.5, -4.6) and CVD (-4.0%; -4.4, -3.5); mortality related to HD reduced at a slower pace (-1.9%; -2.3, -1.4), whereas AF-related mortality was increasing (+1.0%; 0.1, 1.8). During the first year of the pandemic, the growth in mortality compared to 2019 was +26% for HD, +18% for AF, +13% for CVD and +12% for IHD. In 2021-2022, rates for CVD and IHD returned to pre-pandemic levels; rates for HD reduced with respect to 2020 but remained above the baseline; AF-related mortality was still increasing. Conclusions The pandemic differentially impacted mortality associated to different circulatory diseases, depending on pre-existing long-term trends (increasing for AF) and on susceptibility to severe COVID-19 disease (higher for HD). Continuous surveillance based on MCOD is warranted to properly assess changes in mortality associated to specific circulatory diseases after the end of the pandemic. Key messages • Multiple causes of death analyses are warranted to assess how the pandemic affected pre-existing long term trends in cause-specific mortality. • Mortality related to different circulatory diseases increased in 2020, but pre-pandemic trends, the extent of the increase in 2020, and further changes observed in 2021-2022 largely diverged.

Time and cause of death in patients after acute coronary syndrome

Abstract Background Acute coronary syndrome (ACS) remains a substantial mortality burden despite enormous progress achieved in treatment and prevention in recent decades, yet systematic investigation of detailed causes of death among ACS patients remains limited. Objective This study aimed to describe the association between time and cause of death in patients after ACS using data from a large, multicenter, contemporary cohort. Methods Patients’ data from the China Chest Pain Database between 2015 and 2021 were linked to the China National Death Registration System Database using unique national IDs to obtain accurate vital status. Patients with documented death records were extracted into a merged database, which encompassed all deaths that occurred in the hospital and post-discharge out-of-hospital. Patients were enrolled with a discharge diagnosis of ACS. Cardiovascular (CV) mortality was defined as a death certificate with a CV diagnosis using the ICD-10 classification listed as the primary cause of death. A trend chi-square test was performed to assess the causes of death at different times after ACS. Results Among the 126,704 eligible patients, the mean age at baseline was 74 (66, 81) years old, 39.3% were women. Of these patients, 16,546 (13.1%) died during hospitalisation, 53,980 (42.6%) within the first six months after discharge, 19,664 (15.5%) from 6 to12 months after discharge, and 36,514 (28.8%) beyond 12 months after discharge. The most common cause of CV death was ischemic heart disease (70.1%), followed by ischemic stroke (7.1%) and hemorrhagic stroke (6.8%). The main causes of non-CV death were malignant tumours (37.1%) and respiratory disease (21.5%). For death in-hospital, within the first six months, from 6 to 12 months post-discharge, and beyond 12 months, the proportion of CV causes was 86.3%, 78.3%, 70.7%, and 67.9%, respectively (P<0.001). The proportion of deaths due to haemorrhagic stroke and aortic aneurysm/dissection increased progressively with time to death increasing (P<0.001). Meanwhile, the proportion of non-CV deaths continuously increased, reaching 13.7%, 21.7%, 29.3%, and 32.1%, respectively. Conclusion Despite cardiovascular diseases being the primary cause of death in patients after ACS, the causes of death vary among patients with different times of death, highlighting the importance of categorising patients into distinct population groups according to time after ACS for targeted cause-specific preventive strategies.

Long-term exposure to PM2.5 and mortality among Japanese community-dwelling adults

Abstract Background Long-term exposure to PM2.5 (particulate matter with a diameter of 2.5 μm or smaller) is a risk factor for mortality and cardiovascular disease including stroke. However, there was limited evidence for the association between PM2.5 exposure and stroke in Asia where the major cardiovascular disease is stroke. Additionally, the causal association between PM2.5 and respiratory disease is still unresolved. The aim of this study was to investigate the association between long-term exposure to PM2.5 and all-cause, cardiovascular, and respiratory disease mortality in a Japanese community-based prospective cohort. Methods This study included 46,974 participants (19,707 men; 27,267 women) from the second cohort of the Ibaraki Prefectural Health Study. The participants were followed up from baseline survey (in 2009) to 31 December 2019. We confirmed underlying causes by death certificates. Using the PM2.5 concentrations estimated by the inverse distance weighting methods based on ambient air monitoring data, administrative area level concentrations were assigned to each participant. The hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality using a Cox proportional hazard model were presented. Results We identified 2,789 all-cause deaths during the 470,178 person-years of follow-up. PM2.5 exposure had no significant association with all-cause and cause-specific mortality. The multivariable-adjusted HRs per 1 μg/m3 increase in the PM2.5 concentration were 0.94 (95% CI = 0.80-1.12) for coronary heart disease, 0.92 (95% CI = 0.81-1.04) for stroke and 1.09 (95% CI = 0.97-1.23) for non-malignant respiratory disease. Conclusions We observed little evidence of increased risk of all-cause and cause-specific mortality by long-term exposure to PM2.5 whose concentrations ranged from 8.3 to 13.1 μg/m3. A somewhat increased trend for non-malignant respiratory disease mortality may not be negligible. Key messages • We found little evidence of increased risk of all-cause and cause-specific mortality by long-term exposure to PM2.5. • Somewhat increased tendency for non-malignant respiratory disease mortality associated with PM2.5 exposure was observed.

Mortality and causes of death in Serbia: redistribution of garbage codes to ischemic heart disease

Abstract Background Cardiovascular diseases are ranked as the number one cause of death in Serbia, and one-fifth of them present ischemic heart disease (IHD). However, the physicians certifying the cause of death have either not been adequately involved in how to complete a death certificate according to the current International Statistical Classification of Diseases (ICD-10) or due to a high level of administrative tasks sometimes fail to complete the process of death certification. That is why we aimed to investigate the garbage codes (GCs) and the effects of their redistribution on underlying cause of death (CoD) estimates for IHD for 2015 and 2020. Methods Data from Belgrade mortality statistics in 2015 and 2020 were used to describe the occurrence and redistribution of garbage codes (GCs), defined as unspecified or impossible causes of death. In order to redistribute GCs we observed the underlying, antecedent, immediate causes and other conditions that contributed to deaths. Redistribution was done by consulting GBD methodology for GC proportional redistribution. The ICD-10 code range for IHD is I20-I25. Results In Belgrade, 17% (4022/23663) and 20.9% (5818/27775) of the deaths were coded with a garbage code in 2015 and 2020, respectively. In 2015, 2102 deaths (10.7% of all well-defined CoD) were attributed to IHD, while in 2020, 1806 (8,2% of all well-defined CoD) deaths were attributed to IHD. Finally, we redistributed a total of 452 deaths (GC type 1 203.9, GC type 2 122.1 and GC type 3 126.2 deaths) and 572 deaths (GC type 1 250.1, GC type 2 110.9, GC type 3 210.7 and GC type 4 22) due to IHD in 2015 and 2020, respectively. These calculations indicate a total number of 2554 and 2378 deaths due to IHD in 2015 and 2020, respectively. Conclusions A more detailed analysis of local practices, as well as continuing medical education in the field of death certification, could be a step forward in the future process of decreasing the number of GCs. Key messages • Since the huge number of deaths was added to ischemic heart disease in 2015 and 2020, it is crucial to focus on a more reliable disease surveillance system including better coding practices. • A deep understanding of the garbage codes and their redistribution could significantly shape future decisions on factors contributing to ischemic heart diseases.

Evaluating perinatal health in Europe: a comparison of routine population birth data sources

Abstract Background International comparisons provide essential benchmarks for evaluating perinatal health policies, but these rely on the availability of routine national birth data. This study aimed to describe population birth data sources in Europe by their ability to provide core perinatal health indicators. Methods The Euro-Peristat Network collected routine national data on a recommended set of core indicators from 2015 to 2021 using a federated protocol based on a common data model with 17 data items. Data providers filled in an on-line questionnaire to describe the sources used in each country. We classified countries by the number of data items they provided (all 16, 15-14, <14). Results 28 out of the 31 countries that provided data responded to the survey. Routine data sources included birth certificates (14 countries), electronic medical records (EMR) from delivery hospitalizations (14 countries), direct entry by health providers (9 countries), EMR from other care providers (6 countries) and Hospital Discharge Summaries (7 countries). Completeness of population coverage was at least 98%, with 15 countries reporting 100%. These databases most often included mothers giving birth on the national territory, regardless of nationality or place of residence (19 countries). In 20 countries, routine sources were linked, including linkage between birth and death certificates (15 countries). Countries providing all 16 items (N = 8) were more likely to use EMRs from delivery hospitalizations, 88%, compared to 50% and 13% in countries with 15-14 items (N = 13) and <14 items (N = 8). Linkage was also more common in these countries, 100%, versus 75% and 50% respectively. Other data source characteristics did not differ by the ability to provide data for the common data model. Conclusions There is high diversity in the data sources used to construct perinatal health indicators in Europe. Countries using EMR with linkage to other sources had the best data availability. Key messages • There is high diversity in the data sources used to construct perinatal health indicators in Europe. • Countries using Electronic Medical Records with linkage to other sources had the best data availability.

Circulating secretoneurin concentrations predict cardiovascular death in ambulatory patients with heart failure

Abstract Background Secretoneurin (SN) is a novel biomarker, which predicts cardiovascular (CV)-related mortality in patients with acute dyspnea and sepsis. Higher SN concentrations have also been found associated with all-cause death in outpatients with heart failure (HF), but whether SN primarily reflects cardiovascular (CV)-related mortality in HF outpatients is not known. Objectives To evaluate the relation between SN concentrations and CV- & non-CV death in ambulatory patients with HF. Methods We studied 184 consecutive patients who attended our HF clinic for routine follow up and had stored blood samples available for SN analysis. SN concentrations were measured with a CE-marked SN ELISA assay. We assessed the associations between SN concentrations and CV & non-CV death. Mortality was ascertained using medical records, autopsy reports and death certificates, and CV deaths included sudden cardiac deaths or mortality due to myocardial infarction, HF or stroke. We assessed association with CV & non-CV death by Kaplan-Meier curves and by Cox proportional hazard regression analysis. Results Median age was 76 years (range: 38-94 years) and two thirds were male. Sixty-three percent had HF with reduced ejection fraction, 22% had NYHA III/IV symptoms and median NT-proBNP was 1079 (interquartile range: 462-2347) ng/L. Median SN level was 60 (range: 21-134) pmol/L. In multivariable linear regression analysis, impaired renal function and lower body-mass index were significantly associated with increasing (log)SN concentration. During median follow up of 540 days, there were 18 CV deaths, including 15 HF deaths, and 7 non-CV deaths. A higher SN concentration was associated with higher risk of CV death, while we did not find statistically significant association between SN concentrations and non-CV deaths (Figure). Patients with SN concentration in the top tertile had 15-fold increased risk of CV death compared to patients with SN concentration in the lowest tertile. In multivariable Cox regression analysis that adjusted for age, NYHA functional class, frailty status, increasing SN concentrations were independently associated with CV death: hazard ratio per logSN (95% CI): 3.01 (1.02-8.90), p=0.04. Conclusion In ambulatory patients with HF, circulating SN concentrations were predictive of CV death. Higher SN concentrations in ambulatory HF patients seemed to be linked to impaired renal function and lower body-mass index. Figure: Kaplan Meier curves illustrating the relation between SN tertiles and (A) CV mortality (B) Non-CV mortality.