Disease incidence and not case fatality drives the rural disadvantage in myocardial-infarction-related mortality in Germany.

OBJECTIVE: Demographic and infrastructural developments might compromise medical care provision in rural regions, particularly for acute health conditions. Studying the case of myocardial infarction (MI), we investigated how MI-related mortality at ages 65+ varies between rural and urban regions in Germany and to what extent differences are driven by varying case fatality and disease incidence. METHODS: The study relies on data containing all hospitalizations, cause-specific deaths and population counts for the total German population between years 2012-2018 and ages 65+. MI-related mortality, MI incidence and case fatality are compared between urban and rural regions in a population-wide analysis. The impacts of changing incidence and case fatality on rural-urban MI-related mortality differences are assessed using a counterfactual approach. RESULTS: Rural regions in Germany show systematically higher MI-related death rates and MI incidence at ages 65+ compared to urban regions. Higher mortality is primarily the result of higher MI incidence in rural regions, while case fatality is largely similar. The rural excess in MI-related death rates would be nullified and 1 out of 6 MI-related deaths in rural regions could be prevented if rural regions in Germany would have at least the median MI incidence of urban regions. CONCLUSIONS: MI incidence and not case fatality drives the rural disadvantage in MI-related mortality in Germany. Higher MI incidence points towards potential regional variation in the effectiveness of disease prevention. The findings highlight that improving disease prevention at the patient level carries larger opportunities for reducing regional MI-related mortality inequalities in Germany.

Continued decline in the incidence of myocardial infarction beyond the COVID-19 pandemic: a nationwide study of the Swedish population aged 60 and older during 2015-2022.

The number of myocardial infarctions declined during the early COVID-19 pandemic but mechanisms behind these declines are poorly understood. COVID-19 infection is also associated with an increased risk of myocardial infarction which could lead to higher incidence rates in the population. This study aims to shed light on the seemingly paradoxical relationship between COVID-19 and myocardial infarction occurrence on the population level by exploring long-term trends in incidence rates, case fatality, and proportion of patients dying before reaching a hospital. Our work is based on a linkage of administrative registers covering the entire population aged 60 + in Sweden. Considering both long-term trends since 2015 and seasonal variability, we compared observed incidence, case fatality, and proportions of patients hospitalized to expected values during 2020-2022. Despite more than 200 laboratory-confirmed COVID-19 cases per 1000 inhabitants by the end of 2022, incidence rates of myocardial infarction continued to decline, thus following the long-term trend observed already before 2020. During the first pandemic wave there was an additional incidence decline corresponding to 13% fewer myocardial infarctions than expected. This decline was neither accompanied by increasing case fatality nor by lower shares of patients being hospitalized. We found no increase in the population-level incidence of myocardial infarction despite large-scale exposure to COVID-19, which suggests that the effect of COVID-19 on myocardial infarction risk is not substantial. Increased pressure on the Swedish health care system has not led to increased risks or poorer outcomes for patients presenting with acute myocardial infarction.

Frailty Among Breast Cancer Survivors: Evidence From Swedish Population Data.

Incidence and survival of breast cancer, the most common cancer among women, have been increasing, leaving survivors at risk of aging-related health conditions. In this matched cohort study, we examined frailty risk with the Hospital Frailty Risk Score among breast cancer survivors (n = 34,900) and age-matched comparison subjects (n = 290,063). Women born in 1935-1975, registered in the Swedish Total Population Register (1991-2015), were eligible for inclusion. Survivors had a first breast cancer diagnosis in 1991-2005 and survived ≥5 years after initial diagnosis. Death date was determined by linkage to the National Cause of Death Registry (through 2015). Cancer survivorship was weakly associated with frailty (subdistribution hazard ratio (SHR) = 1.04, 95% confidence interval (CI): 1.00, 1.07). In age-stratified models, those diagnosed at younger ages (<50 years) had higher risk of frailty (SHR = 1.12, 95% CI: 1.00, 1.24) than those diagnosed at ages 50-65 (SHR = 1.03, 95% CI: 0.98, 1.07) or >65 (SHR = 1.09, 95% CI: 1.02, 1.17) years. Additionally, there was increased risk of frailty for diagnoses in 2000 or later (SHR = 1.15, 95% CI: 1.09, 1.21) compared with before 2000 (SHR = 0.97, 95% CI: 0.93, 1.17). This supports work from smaller samples showing that breast cancer survivors have increased frailty risk, particularly when diagnosed at younger ages.

The Impact of Hip Fracture on Geriatric Care and Mortality Among Older Swedes: Mapping Care Trajectories and Their Determinants.

In this study, we examined the impact of hip fractures on trajectories of home care, nursing home residence, and mortality among individuals aged 65 years or more and explored the impacts of living arrangements, cohabitation, frailty, and socioeconomic position on these trajectories. Based on a linkage of nationwide Swedish population registers, our study included 20,573 individuals with first hip fracture in 2014-2015. Care trajectories during the 2 years following the fracture were visualized and compared with those of 2 hip-fracture-free control groups drawn from the general population: age- and sex-matched controls and health-matched controls identified through propensity score matching. Multistate modeling was employed to identify sociodemographic and health-related factors associated with care trajectories among hip fracture patients. We found that hip fracture patients already had worse health than the general population before their fracture. However, when controlling for prefracture health, hip fractures still had a considerable impact on use of elder-care services and mortality. Comparisons with the health-matched controls suggest that hip fractures have an immediate, yet short-term, impact on care trajectories. Long-term care needs are largely attributable to poorer health profiles independent of the fracture itself. This emphasizes the importance of adequate comparison groups when examining the consequences of diseases which are often accompanied by other underlying health problems.

Variation in End-of-Life Trajectories in Persons Aged 70 Years and Older, Sweden, 2018‒2020.

Objectives. To analyze variation in end-of-life trajectories with regard to elder care and medical care and how they relate to age, gender, and causes of death. Methods. We analyzed all deaths of persons at age 70 years and older between the years 2018 and 2020 in Sweden, using a linkage of population registers. We applied latent class analysis to identify distinct types of end-of-life trajectories. Results. We identified 6 different types of end-of-life trajectories. The types differed substantially in the amount of utilized elder care and medical care before death. Deaths characterized by high levels of elder care and medical care utilization become more common with age. The trajectory types show distinct cause-of-death profiles. Conclusions. Most deaths today do not comply with what is often referred to as a "good" death (e.g., retaining control or requiring low levels of elder care). The results suggest that longer lifespans partly result from a prolonged dying process. Public Health Implications. The current modes of dying call for a discussion about how we want to die in an era of increasing lifespans and aging societies. (Am J Public Health. 2023;113(7):786-794. https://doi.org/10.2105/AJPH.2023.307281).

Centenarians: who are they? A description of the total Swedish centenarian population in terms of living arrangements, health, and care utilization.

BACKGROUND: The global centenarian population has doubled each decade and is expected to continue growing. However, information regarding how they live, their health status, and care needs is limited. AIMS: This study aims to describe the total Swedish centenarian population in terms of health status, living arrangements, and socio-demographic characteristics. METHODS: This nationwide register-based study included all Swedish people reaching age 100 between 2013 and 2018. We analyzed their socio-demographic characteristics, living arrangements, number of prescribed drugs, and health status. Moreover, their care transitions from age 100 and two years forward were described. RESULTS: Of 5,882 centenarians (80.7% women), only 15.0% lived at home without formal care and 24.5% cohabited on their 100th birthday. Men (22.7%) were more likely than women (13.2%) to live at home without care. Approximately half of the centenarians lived in care homes, with fewer men (41.0%) than women (54.0%). Around 66.6% had a child living within the 50 km range. Most (76.5%) had an income below the median for Swedish older adults. Almost none were free from drugs, and polypharmacy was common (65.3%). Over half had at least one morbidity. Two years later, only 4.3% lived at home without care, and 63.9% died. CONCLUSION: Sweden's centenarian population is highly dependent on home care and care homes. Among the ones still living at home, the vast majority live alone and have low incomes. Strategies to manage health and social care demands of this growing population group in the coming decade are important.

Years of life lost during the Covid-19 pandemic in Sweden considering variation in life expectancy by level of geriatric care.

The Covid-19 pandemic has not affected the population evenly. This must be acknowledged when it comes to understanding the Covid-19 death toll and answering the question of how many life years have been lost. We use level of geriatric care to account for variation in remaining life expectancy among individuals that died during 2020. Based on a linkage of administrative registers, we estimate remaining life expectancy stratified by age, sex, and care status using an incidence-based multistate model and analyze the number of years of life lost (YLL) during 2020 in Sweden. Our results show that remaining life expectancy between individuals with and without care differs substantially. More than half of all Covid-19 deaths had a remaining life expectancy lower than 4 years. Yet, in a 1-year perspective, Covid-19 did not seem to replace other causes of death. Not considering the differences in remaining life expectancy in the affected populations overestimated YLL by 40% for women and 30% for men, or around 2 years per death. While the unadjusted YLL from Covid-19 amounted to an average of 7.5 years for women and 8.6 years for men, the corresponding YLL adjusted for care status were 5.4 and 6.6, respectively. The total number of YLL to Covid-19 in 2020 is comparable to YLL from ischemic heart disease in 2019 and 2020. Our results urge the use of subgroup specific mortality when counting the burden of Covid-19. YLL are considerably reduced when the varying susceptibility for death is considered, but even if most lifespans were cut in the last years of life, the YLL are still substantial.

The rate by which mortality increase with age is the same for those who experienced chronic disease as for the general population.

BACKGROUND: Mortality doubles approximately every 6-7 years during adulthood. This exponential increase in death risk with chronological age is the population-level manifestation of ageing, and often referred to as the rate-of-ageing. OBJECTIVE: We explore whether the onset of severe chronic disease alters the rate-of-ageing. METHODS: Using Swedish register data covering the entire population of the birth cohorts 1927-30, we analyse whether being diagnosed with myocardial infarction, diabetes or cancer results in a deviation of the rate-of-ageing from those of the total population. We also quantify the long-term mortality effects of these diseases, using ages with equivalent mortality levels for those with disease and the total population. RESULTS: None of the diseases revealed a sustained effect on the rate-of-ageing. After an initial switch upwards in the level of mortality, the rate-of-ageing returned to the same pace as for the total population. The time it takes for the rate to return depends on the disease. The long-term effects of diabetes and myocardial infarction amount to mortality levels that are equivalent to those aged 5-7 years older in the total population. For cancer, the level of mortality returns to that of the total population. CONCLUSION: Our results suggest an underlying process of ageing that causes mortality to increase at a set pace, with every year older we become. This process is not affected by disease history. The persistence of the rate-of-ageing motivates a critical discussion of what role disease prevention can play in altering the progression of ageing.

Excess mortality from COVID-19: weekly excess death rates by age and sex for Sweden and its most affected region.

BACKGROUND: Sweden has one of the highest numbers of COVID-19 deaths per inhabitant globally. However, absolute death counts can be misleading. Estimating age- and sex-specific mortality rates is necessary in order to account for the underlying population structure. Furthermore, given the difficulty of assigning causes of death, excess all-cause mortality should be estimated to assess the overall burden of the pandemic. METHODS: By estimating weekly age- and sex-specific death rates during 2020 and during the preceding 5 years, our aim is to get more accurate estimates of the excess mortality attributed to COVID-19 in Sweden, and in the most affected region Stockholm. RESULTS: Eight weeks after Sweden's first confirmed case, the death rates at all ages above 60 were higher than for previous years. Persons above age 80 were disproportionally more affected, and men suffered greater excess mortality than women in ages up to 75 years. At older ages, the excess mortality was similar for men and women, with up to 1.5 times higher death rates for Sweden and up to 3 times higher for Stockholm. Life expectancy at age 50 declined by <1 year for Sweden and 1.5 years for Stockholm compared to 2019. CONCLUSIONS: The excess mortality has been high in older ages during the pandemic, but it remains to be answered if this is because of age itself being a prognostic factor or a proxy for comorbidity. Only monitoring deaths at a national level may hide the effect of the pandemic on the regional level.

The rise in the number of long-term survivors from different diseases can slow the increase in life expectancy of the total population.

BACKGROUND: Recent improvements in life expectancy in many countries stem from reduced mortality from cardiovascular disease and cancer above the age of 60. This is the combined result of decreased incidence and improved survival among those with disease. The latter has led to a higher proportion in the population of people with a past history of disease. This is a group with higher mortality than the general population. How growing shares of persons with past history of disease and improved survival with disease have affected changes in life expectancy of the total population is the objective of this paper. METHODS: Using register data for the total Swedish population, we stratified the population based on whether individuals have been diagnosed with myocardial infarction, stroke, hip fracture, colon cancer, or breast cancer. Using a novel decomposition approach, we decomposed the changes in life expectancy at age 60 between 1994 and 2016 into contributions from improved survival with disease and from changes in proportion of people with past history of disease. RESULTS: Improvements in survival from disease resulted in gains of life expectancy for the total population. However, while the contributions to life expectancy improvements from myocardial infarction, stroke and breast cancer were substantial, the contributions from the other diseases were minor. These gains were counteracted, to various degrees, by the increasing proportion of people with raised mortality due to a past history of disease. For instance, the impact on life expectancy by improved survival from breast cancer was almost halved by the increasing share of females with a past history of breast cancer. CONCLUSION: Rising numbers of survivors of different diseases can slow the increase in life expectancy. This dynamic may represent the costs associated with successful treatment of diseases, and thus, a potential "failure of success." This dynamic should be considered when assessing mortality and life expectancy trends. As populations are aging and disease survival continues to improve, this issue is likely to become even more important in the future.

How Has the Lower Boundary of Human Mortality Evolved, and Has It Already Stopped Decreasing?

In contrast to the upper boundary of mortality, the lower boundary has so far largely been neglected. Based on the three key features-location, sex-specific difference, and level-I analyze past and present trends in the lower boundary of human mortality. The analysis is based on cohort mortality data for 38 countries, covering all the cohorts born between 1900 and 1993. Minimum mortality is analyzed using observed as well as smoothed estimates. The results show that the ages at which minimum mortality is reached have shifted to lower ages. Although the differences have become almost negligible over time, males are showing higher levels of minimum mortality than females. The level of minimum mortality was halved more than five times over the analyzed time horizon. The results also suggest that even after more than 150 years of mortality improvements, minimum mortality has not yet reached a lowest limit and is likely to decrease further in the near future. Trends in the three key features also raise questions about the importance of evolutionary, social, and biological determinants for the recent and future development of minimum mortality.

Rectangularization of the survival curve reconsidered: The maximum inner rectangle approach.

Rectangularization of the survival curve-a key analytical framework in mortality research-relies on assumptions that have become partially obsolete in high-income countries due to mortality reductions among the oldest old. We propose refining the concept to adjust for recent and potential future mortality changes. Our framework, the 'maximum inner rectangle approach' (MIRA) considers two types of rectangularization. Outer rectangularization captures progress in mean lifespan relative to progress in maximum lifespan. Inner rectangularization captures progress in lifespan equality relative to progress in mean lifespan. Empirical applications show that both processes have generally increased since 1850. However, inner rectangularization has displayed country-specific patterns since the onset of sustained old-age mortality declines. Results from separating premature and old-age mortality, using the MIRA, suggest there has been a switch from reducing premature deaths to extending the premature age range; a shift potentially signalling a looming limit to the share of premature deaths.

Lifespan Disparity as an Additional Indicator for Evaluating Mortality Forecasts.

Evaluating the predictive ability of mortality forecasts is important yet difficult. Death rates and mean lifespan are basic life table functions typically used to analyze to what extent the forecasts deviate from their realized values. Although these parameters are useful for specifying precisely how mortality has been forecasted, they cannot be used to assess whether the underlying mortality developments are plausible. We therefore propose that in addition to looking at average lifespan, we should examine whether the forecasted variability of the age at death is a plausible continuation of past trends. The validation of mortality forecasts for Italy, Japan, and Denmark demonstrates that their predictive performance can be evaluated more comprehensively by analyzing both the average lifespan and lifespan disparity-that is, by jointly analyzing the mean and the dispersion of mortality. Approaches that account for dynamic age shifts in survival improvements appear to perform better than others that enforce relatively invariant patterns. However, because forecasting approaches are designed to capture trends in average mortality, we argue that studying lifespan disparity may also help to improve the methodology and thus the predictive ability of mortality forecasts.

Trajectories of Long-term Care after Stroke in Sweden: Nationwide Study Exploring Patterns and Determinants.

OBJECTIVES: Stroke is a leading cause of mortality and disability worldwide. Although studies have primarily focused on health and functioning among stroke survivors, there is limited research on longitudinal patterns of long-term care use among older adults with stroke. This study explores long-term care trajectories among older men and women with stroke in the Swedish population. DESIGN: Nationwide prospective cohort study. SETTING AND PARTICIPANTS: All individuals aged ≥70 years hospitalized with a first stroke in 2015-2017 followed in the Swedish population registers for 3 years. METHODS: Care trajectories among patients with strokes were visualized and compared to trajectories in 2 control groups: (1) same-aged peers randomly drawn from the general population and (2) older adults with health and sociodemographic characteristics similar to patients with strokes but without stroke identified through propensity score matching. Multivariable Cox regression and multistate models were used to identify determinants of mortality and care trajectories among patients with strokes. RESULTS: We identified 31,560 individuals with stroke (mean age 82.9 years). Already before the stroke, these individuals had a higher comorbidity burden and received more long-term care than their same-aged peers. Compared with both control groups, patients with strokes were also more likely to enter long-term care. However, 38% of patients with strokes survived for 3 years without taking up long-term care. Sex, income, cohabitation, and comorbidities were associated with care trajectories. Care status was a more robust predictor of mortality after stroke than the established Charlson comorbidity index. CONCLUSIONS AND IMPLICATIONS: Experiencing a stroke increases both mortality and long-term care utilization, and once formal long-term care is provided, exceedingly few patients with strokes return to living without care. However, a considerable part of care utilization and mortality after stroke is concentrated among those with preexisting care needs. Prestroke care utilization should thus be considered in future studies exploring stroke prognosis.

Blood biomarker profiles and exceptional longevity: comparison of centenarians and non-centenarians in a 35-year follow-up of the Swedish AMORIS cohort.

Comparing biomarker profiles measured at similar ages, but earlier in life, among exceptionally long-lived individuals and their shorter-lived peers can improve our understanding of aging processes. This study aimed to (i) describe and compare biomarker profiles at similar ages between 64 and 99 among individuals eventually becoming centenarians and their shorter-lived peers, (ii) investigate the association between specific biomarker values and the chance of reaching age 100, and (iii) examine to what extent centenarians have homogenous biomarker profiles earlier in life. Participants in the population-based AMORIS cohort with information on blood-based biomarkers measured during 1985-1996 were followed in Swedish register data for up to 35 years. We examined biomarkers of metabolism, inflammation, liver, renal, anemia, and nutritional status using descriptive statistics, logistic regression, and cluster analysis. In total, 1224 participants (84.6% females) lived to their 100th birthday. Higher levels of total cholesterol and iron and lower levels of glucose, creatinine, uric acid, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, lactate dehydrogenase, and total iron-binding capacity were associated with reaching 100 years. Centenarians overall displayed rather homogenous biomarker profiles. Already from age 65 and onwards, centenarians displayed more favorable biomarker values in commonly available biomarkers than individuals dying before age 100. The differences in biomarker values between centenarians and non-centenarians more than one decade prior death suggest that genetic and/or possibly modifiable lifestyle factors reflected in these biomarker levels may play an important role for exceptional longevity.

Time trends in atrial fibrillation-related stroke during 2001-2020 in Sweden: a nationwide, observational study.

Background: Great efforts have been made to improve stroke prevention in atrial fibrillation (AF) patients. Meanwhile, incidence of AF is increasing, which may affect the share of AF-related stroke on all strokes. We aimed to examine the temporal trends in the incidence of AF-related ischemic stroke between 2001 and 2020, if it varied by use of novel oral anticoagulant drugs (NOAC), and if the relative risk of ischemic stroke associated with AF changed over time. Methods: Data from the total Swedish population aged ≥70 years during the period 2001-2020 were used. Annual incidence rate (IR) was calculated for overall and AF-related ischemic stroke which was defined as first-ever ischemic stroke with AF diagnosed up to 5 years before, on the same day, or within 2 months after the stroke event. Cox regression models were performed to examine if the hazard ratio (HR) between AF and stroke changed over time. Findings: While IR of ischemic strokes declined during 2001-2020, IR of AF-related ischemic stroke remained stable between 2001 and 2010 but showed a consistent decline between 2010 and 2020. The HR of ischemic stroke within 3 years from an AF diagnosis came down from 2.39 (95% confidence interval: 2.31-2.48) to 1.54 (1.48-1.61) over the study period, which was largely explained by a substantial increase in the use of NOAC among AF patients after 2012. Yet, by the end of 2020, 24% of all ischemic strokes had a preceding or concurrent AF diagnosis, which is slightly higher than in 2001. Interpretation: Even though both the absolute and relative risk of AF-related ischemic stroke declined over the past 20 years, every fourth ischemic stroke in 2020 still had a preceding or concurrent AF diagnosis. This represents a great potential for future gains in stroke prevention among AF patients. Funding: Swedish Research Council and Loo and Hans Osterman Foundation for Medical Research.

Trends in Frailty Between 1990 and 2020 in Sweden Among 75-, 85-, and 95-Year-Old Women and Men: A Nationwide Study from Sweden.

BACKGROUND: Aging is the primary risk factor for frailty, which is defined as an inability to respond to acute or chronic stressors. Individuals are living longer with greater multimorbidity, but there is a paucity of evidence examining frailty across birth cohorts and ages. METHODS: We investigated frailty prevalence and its association with mortality at ages 75, 85, and 95 in the 1895-1945 birth cohorts in Sweden with data from population registries. Frailty was assessed with the Hospital Frailty Risk Score (HFRS). RESULTS: We observed that frailty increased with increasing age and that it has become more common in more recent birth cohorts. At age 75, the percent frail in the Total Population Register increased from 1.1% to 4.6% from birth cohorts 1915-1945, corresponding to calendar years 1990-2020. At age 85, the percentage of frail increased from 3.5% to 11.5% from birth cohorts 1905-1935, and at age 95 from birth cohorts 1895-1925, from 4.7% to 18.7%. Our results show that the increase was primarily driven by an increase in the distribution of individuals with scores in the highest quartile of HFRS, while the bottom 3 quartiles remained relatively stable across birth cohorts. Women accounted for a greater distribution of the overall population and frail population, though these disparities decreased over time. Despite increasing levels of frailty, the relationship between frailty and mortality did not change over time, nor did it differ by sex. CONCLUSION: Increased frailty with improved survival points to a chronic condition that could be intervened upon.

Cardiovascular Mortality Gap Between the United States and Other High Life Expectancy Countries in 2000-2016.

OBJECTIVES: Reductions in U.S. cardiovascular disease (CVD) mortality have stagnated. While other high life expectancy countries (HLCs) have also recently experienced a stall, the stagnation in CVD mortality in the United States appeared earlier and has been more pronounced. The reasons for the stall are unknown. We analyze cross-national variations in mortality trends to quantify the U.S. exceptionality and provide insight into its underlying causes. METHODS: Data are from the World Health Organization (2000-2016). We quantified differences in levels and trends of CVD mortality between the United States and 17 other HLCs. We decomposed differences to identify the individual contributions of major CVD subclassifications (ischemic heart disease [IHD], stroke, other heart diseases). To identify potential behavioral explanations, we compared trends in CVD mortality with trends in other causes of death related to obesity, smoking, alcohol, and drugs. RESULTS: Our study has four central findings: (a) U.S. CVD mortality is consistently higher than the average of other HLCs; (b) the U.S.-HLC gap declined until around 2008 and increased thereafter; (c) the shift from convergence to divergence was mainly driven by slowing IHD and stroke mortality reductions and increasing mortality from other CVD causes; (d) among the potential risk factors, only obesity- and alcohol-related mortality showed age-specific temporal changes that are similar to those observed for cardiovascular mortality. DISCUSSION: The exceptional changes in U.S. CVD mortality are driven by a distinct pattern of slowing reductions in IHD and stroke mortality and deteriorating mortality from other CVD causes. Obesity and alcohol abuse appear to be interrelated factors.

Blood-Based Biomarkers and Long-term Risk of Frailty-Experience From the Swedish AMORIS Cohort.

BACKGROUND: Frailty is associated with reduced quality of life, poor health outcomes, and death. Past studies have investigated how specific biomarkers are associated with frailty but understanding biomarkers in concert with each other and the associated risk of frailty is critical for clinical application. METHODS: Using a sample aged ≥59 years at baseline from the Swedish AMORIS (Apolipoprotein MOrtality RISk) cohort (n = 19 341), with biomarkers measured at baseline (1985-1996), we conducted latent class analysis with 18 biomarkers and used Cox models to determine the association between class and frailty and all-cause mortality. RESULTS: Four classes were identified. Compared to the largest class, the Reference class (81.7%), all other classes were associated with increased risk of both frailty and mortality. The Anemia class (5.8%), characterized by comparatively lower iron markers and higher inflammatory markers, had hazard ratio (HR) = 1.54, 95% confidence interval (CI) 1.38, 1.73 for frailty and HR = 1.76, 95% CI 1.65, 1.87 for mortality. The Diabetes class (6.5%) was characterized by higher glucose and fructosamine, and had HR = 1.59, 95% CI 1.43, 1.77 for frailty and HR = 1.74, 95% CI 1.64, 1.85 for mortality. Finally, the Liver class (6.0%), characterized by higher liver enzyme levels, had HR = 1.15, 95% CI 1.01, 1.30 for frailty and HR = 1.40, 95% CI 1.31, 1.50 for mortality. Sex-stratified analyses did not show any substantial differences between men and women. CONCLUSIONS: Distinct sets of commonly available biomarkers were associated with development of frailty and monitoring these biomarkers in patients may allow for earlier detection and possible prevention of frailty, with the potential for improved quality of life.