Inequalities in treatment among patients with colon and rectal cancer: a multistate survival model using data from England national cancer registry 2012-2016.

BACKGROUND: Individual and tumour factors only explain part of observed inequalities in colorectal cancer survival in England. This study aims to investigate inequalities in treatment in patients with colorectal cancer. METHODS: All patients diagnosed with colorectal cancer in England between 2012 and 2016 were followed up from the date of diagnosis (state 1), to treatment (state 2), death (state 3) or censored at 1 year after the diagnosis. A multistate approach with flexible parametric model was used to investigate the effect of income deprivation on the probability of remaining alive and treated in colorectal cancer. RESULTS: Compared to the least deprived quintile, the most deprived with stage I-IV colorectal cancer had a lower probability of being alive and treated at all the time during follow-up, and a higher probability of being untreated and of dying. The probability differences (most vs. least deprived) of being alive and treated at 6 months ranged between -2.4% (95% CI: -4.3, -1.1) and -7.4% (-9.4, -5.3) for colon; between -2.0% (-3.5, -0.4) and -6.2% (-8.9, -3.5) for rectal cancer. CONCLUSION: Persistent inequalities in treatment were observed in patients with colorectal cancer at every stage, due to delayed access to treatment and premature death.

Fe(III)/peroxymonosulfate oxidation system for the degradation of rhein, a toxic component abundance in rhubarb residue.

Rhubarb is widely used in health care, but causing a great amount of rhein-containing herbal residue. Rhein with several toxicities might pollute environment, damage ecology and even hazard human health if left untreated. In this study, the degradation effects of bisulfite- (BS) and peroxymonosulfate- (PMS) based oxidation systems on rhein in rhubarb residue were compared and investigated. The effects of BS and PMS with two valence states of ferric ion (Fe) on the degradation of rhein in rhubarb residue were optimized for the selection of optimal oxidation system. The influences of reaction temperature, reaction time and initial pH on the removal of rhein under the optimal oxidation system were evaluated. The chemical profiles of rhubarb residue with and without oxidation process were compared by UPLC-QTOF-MS/MS, and the degradation effects were investigated by PLS-DA and S plot/OPLS-DA analysis. The results manifested that PMS showed relative higher efficiency than BS on the degradation of rhein. Moreover, Fe(III) promoted the degradation effect of PMS, demonstrated that Fe(III)/PMS is the optimal oxidation system to degrade rhein in rhubarb residue. Further studies indicated that the degradation of rhein by the Fe(III)/PMS oxidation system was accelerated with the prolong of reaction time and the elevation of reaction temperature, and also affected by the initial pH. More importantly, Fe(III)/PMS oxidation system could degrade rhein in rhubarb residue completely under the optimal conditions. In conclusion, Fe(III)/PMS oxidation system is a feasible method to treat rhein in rhubarb residue.

Inequalities in cancer mortality trends in people with type 2 diabetes: 20 year population-based study in England.

AIMS/HYPOTHESIS: The aim of this study was to describe the long-term trends in cancer mortality rates in people with type 2 diabetes based on subgroups defined by sociodemographic characteristics and risk factors. METHODS: We defined a cohort of individuals aged ≥35 years who had newly diagnosed type 2 diabetes in the Clinical Practice Research Datalink between 1 January 1998 and 30 November 2018. We assessed trends in all-cause, all-cancer and cancer-specific mortality rates by age, gender, ethnicity, socioeconomic status, obesity and smoking status. We used Poisson regression to calculate age- and calendar year-specific mortality rates and Joinpoint regression to assess trends for each outcome. We estimated standardised mortality ratios comparing mortality rates in people with type 2 diabetes with those in the general population. RESULTS: Among 137,804 individuals, during a median follow-up of 8.4 years, all-cause mortality rates decreased at all ages between 1998 and 2018; cancer mortality rates also decreased for 55- and 65-year-olds but increased for 75- and 85-year-olds, with average annual percentage changes (AAPCs) of -1.4% (95% CI -1.5, -1.3), -0.2% (-0.3, -0.1), 1.2% (0.8, 1.6) and 1.6% (1.5, 1.7), respectively. Higher AAPCs were observed in women than men (1.5% vs 0.5%), in the least deprived than the most deprived (1.5% vs 1.0%) and in people with morbid obesity than those with normal body weight (5.8% vs 0.7%), although all these stratified subgroups showed upward trends in cancer mortality rates. Increasing cancer mortality rates were also observed in people of White ethnicity and former/current smokers, but downward trends were observed in other ethnic groups and non-smokers. These results have led to persistent inequalities by gender and deprivation but widening disparities by smoking status. Constant upward trends in mortality rates were also observed for pancreatic, liver and lung cancer at all ages, colorectal cancer at most ages, breast cancer at younger ages, and prostate and endometrial cancer at older ages. Compared with the general population, people with type 2 diabetes had a more than 1.5-fold increased risk of colorectal, pancreatic, liver and endometrial cancer mortality during the whole study period. CONCLUSIONS/INTERPRETATION: In contrast to the declines in all-cause mortality rates at all ages, the cancer burden has increased in older people with type 2 diabetes, especially for colorectal, pancreatic, liver and endometrial cancer. Tailored cancer prevention and early detection strategies are needed to address persistent inequalities in the older population, the most deprived and smokers.

All-cause and cardiorenal mortality in 6 million adults with and without type 2 diabetes: A comparative, trend analysis in Canada, Spain, and the UK.

AIMS: To understand geographical and temporal patterns in the diabetes gap, the excess mortality risk associated with type 2 diabetes (T2D), in three high-income countries. METHODS: Using databases from Canada (Ontario), Spain (Catalonia) and the UK (England), we harmonized the study design and the analytical strategy to extract information on subjects aged over 35 years with incident T2D between 1998 and 2018 matched to up to five subjects without diabetes. We used Poisson models to estimate age-specific mortality trends by diabetes status and rate ratios and rate differences associated with T2D. RESULTS: In more than 6 million people, 694 454 deaths occurred during a follow-up of 52 million person-years. Trends in all-cause mortality rates differed between Ontario and England; yet, the diabetes gaps were very similar in recent years: in 2018, we estimated 1.3 (95% confidence interval: 0.8, 1.8) and 0.8 (0.2, 1.5) more deaths per 1000 person-years in 50-year-old men with diabetes in Ontario and England, respectively, and 8.9 (6.1, 11.7) and 12.1 (9.1, 15.1) in 80-year-old men; between-country differences were small also in women. In Catalonia, rate ratios comparing T2D with no diabetes in men in 2018 were 1.53 (1.11, 2.11) at 50 years old, 0.88 (0.72, 1.06) at 60 years old, 0.74 (0.60, 0.90) at 70 years old and 0.81 (0.66, 1.00) at 80 years old, indicating lower mortality rates in men with T2D from the age of 60 years; rates were similar in women with and without diabetes at all ages. The diabetes gaps in cardiorenal mortality mirrored those of all-cause mortality: we observed consistent reductions in the proportions of cardiorenal deaths in subjects aged 80 years but variations in subjects aged ≤70 years, regardless of the presence of diabetes. CONCLUSIONS: By reducing the confounding impact of epidemiological and analytical differences, this study showed geographical similarities and differences in the diabetes gap: an excess risk of all-cause and cardiorenal mortality in subjects with T2D is still present in Ontario and England in recent years, particularly in elderly subjects. Conversely, there were very small gaps in young men with T2D or even lower mortality rates in older subjects with T2D in Catalonia.

Glycosylated haemoglobin and prognosis in 10,536 people with cancer and pre-existing diabetes: a meta-analysis with dose-response analysis.

AIMS: To assess whether glycaemic control is associated with prognosis in people with cancer and pre-existing diabetes. METHODS: In this pre-registered systematic review (PROSPERO: CRD42020223956), PubMed and Web of Science were searched on 25th Nov 2021 for studies investigating associations between glycosylated haemoglobin (HbA1c) and prognosis in people with diabetes and cancer. Summary relative risks (RRs) and 95% Confidence Intervals (CIs) for associations between poorly controlled HbA1c or per 1-unit HbA1c increment and cancer outcomes were estimated using a random-effects meta-analysis. We also investigated the impact of potential small-study effects using the trim-and-fill method and potential sources of heterogeneity using subgroup analyses. RESULTS: Fifteen eligible observational studies, reporting data on 10,536 patients with cancer and pre-existing diabetes, were included. Random-effects meta-analyses indicated that HbA1c ≥ 7% (53 mmol/mol) was associated with increased risks of: all-cause mortality (14 studies; RR: 1.14 [95% CI: 1.03-1.27]; p-value: 0.012), cancer-specific mortality (5; 1.68 [1.13-2.49]; p-value: 0.011) and cancer recurrence (8; 1.68 [1.18-2.38; p-value: 0.004]), with moderate to high heterogeneity. Dose-response meta-analyses indicated that 1-unit increment of HbA1c (%) was associated with increased risks of all-cause mortality (13 studies; 1.04 [1.01-1.08]; p-value: 0.016) and cancer-specific mortality (4; 1.11 [1.04-1.20]; p-value: 0.003). All RRs were attenuated in trim-and-fill analyses. CONCLUSIONS: Our findings suggested that glycaemic control might be a modifiable risk factor for mortality and cancer recurrence in people with cancer and pre-existing diabetes. High-quality studies with a larger sample size are warranted to confirm these findings due to heterogeneity and potential small-study effects. In the interim, it makes clinical sense to recommend continued optimal glycaemic control.

Risk of cancer incidence and mortality associated with diabetes: A systematic review with trend analysis of 203 cohorts.

AIM: Whether the relative risk of cancer incidence and mortality associated with diabetes has changed over time is unknown. DATA SYNTHESIS: On August 12th, 2020, we electronically searched for observational studies reporting on the association between diabetes and cancer. We estimated temporal trends in the relative risk of cancer incidence or mortality associated with diabetes and calculated the ratio of relative risk (RRR) comparing different periods. As many as 193 eligible articles, reporting data on 203 cohorts (56,852,381 participants; 3,735,564 incident cancer cases; 185,404 cancer deaths) and covering the period 1951-2013, were included. The relative risk of all-site cancer incidence increased between 1980 and 2000 [RRR 1990 vs.1980: (1.24; 95% CI: 1.16, 1.34); 2000 vs.1990: (1.23; 1.15, 1.31)] and stabilised thereafter at a relative risk of 1.2; the relative risk of all-site cancer mortality was constant at about 1.2 from 1980 to 2010. Both magnitudes and trends in relative risk varied across cancer sites: the relative risk of colorectal, female breast, and endometrial cancer incidence and pancreatic cancer mortality was constant during the observed years; it increased for bladder, stomach, kidney, and pancreatic cancer incidence until 2000; and decreased for liver while increased for prostate, colon and gallbladder cancer incidence after 2000. CONCLUSIONS: Alongside the increasing prevalence of diabetes, the temporal patterns of the relative risk of cancer associated with diabetes may have contributed to the current burden of cancer in people with diabetes.

Severe hypoglycaemia and absolute risk of cause-specific mortality in individuals with type 2 diabetes: a UK primary care observational study.

AIMS/HYPOTHESIS: Several pathophysiological mechanisms would suggest a causal link between hypoglycaemia and cardiovascular death; conversely, current knowledge would not support a causal relationship with other causes of death. To clarify the nature and the magnitude of the association between hypoglycaemia and death, we investigated the 5 year mortality risks for cardiovascular disease, cancer and other causes in individuals with type 2 diabetes admitted to hospital for a severe hypoglycaemic episode. METHODS: We defined in the UK Clinical Practice Research Datalink database a prevalent cohort of adults with type 2 diabetes diagnosed between 1 January 1998 and 1 January 2011 (index date), with available linkage to the Office for National Statistics (ONS) and the Hospital Episode Statistics (HES). A hospital admission reporting hypoglycaemia as the underlying cause was identified before the index date in the HES; date and underlying cause of death were obtained from the ONS. We quantified the 5 year risk of cause-specific death in people with and without admission to hospital for severe hypoglycaemia, adjusting for potential confounders and accounting for competing risk. RESULTS: Of the 74,610 subjects included in the cohort, 388 (0.5%) were admitted at least once for a severe hypoglycaemic episode; subjects admitted were older, with higher HbA1c and a greater prevalence of multimorbidity. During a median follow-up of 7.1 years, 236 (60.8%) and 18,539 (25.0%) deaths occurred in subjects with and without a previous severe hypoglycaemia, respectively. Non-cardiovascular causes accounted for 71% of all deaths in both subjects with and without hypoglycaemia. In a 60-year-old person with severe hypoglycaemia, the 5 year absolute risk of death, adjusted for age, sex, ethnicity, systolic blood pressure, total cholesterol, HbA1c, BMI, eGFR, smoking status, alcohol consumption and deprivation (Townsend score), was 6.6%, 1.1% and 13.1% for cardiovascular, cancer and other causes, respectively, while the 5 year absolute risk difference compared with a subject without severe hypoglycaemia was 4.7% (95% CI 1.0, 8.3) for cardiovascular, -1.4% (-4.1, 1.4) for cancer and 11.1% (6.1, 16.1) for other causes of death. Results were consistent in models further adjusted for medications and comorbidities (myocardial infarction, stroke, peripheral artery disease, heart failure, atrial fibrillation, cancer), with sulfonylurea and insulin associated with increased mortality rates (from cause-specific hazard ratio of 1.06 [95% CI 0.99, 1.14] for cancer death with use of sulfonylurea to 1.42 [1.29, 1.56] for cardiovascular death with use of insulin). Results were robust to missing data. CONCLUSIONS/INTERPRETATION: The results of this study indicate severe hypoglycaemia as a marker of, rather than causally linked to, an increased risk of long-term mortality. Regardless of the nature of the association, a severe hypoglycaemic episode represents a strong negative prognostic factor in patients with type 2 diabetes. Graphical abstract.

Durability of glycaemic control in patients with type 2 diabetes after metformin failure: Prognostic model derivation and validation using the DISCOVER study.

AIM: To develop and internally validate prognostic models on the long-term durability of glycaemic control in patients with type 2 diabetes after metformin failure. MATERIALS AND METHODS: DISCOVER is a 3-year, prospective observational study across six continents investigating second-line glucose-lowering therapies. In this analysis from 35 countries, we included patients on metformin initiating second-line glucose-lowering medication(s) because of physician-defined lack of efficacy. The outcome was durability of glycaemic control, defined as three consecutive levels of HbA1c at 6-, 12- and 24-month follow-up at target (HbA1c equal to or lower than the level when the physician initiated the second-line therapy in patients with baseline HbA1c ≤7% [53 mmol/mol]; and equal to or lower than 7% in those with baseline HbA1c >7%). We developed and internally validated two prognostic models: a base model, which included age, sex, ethnicity, country income group, baseline HbA1c and second-line therapy, and an advanced model, established through statistical variable selections from a model including base variables and 13 additional predictors selected from a literature review. We used logistic regression to develop and 500 bootstrapping samples to internally validate the models; discrimination and calibration were used to assess model performance. RESULTS: Overall, 896 out of 2995 participants (29.9%) had sustained glycaemic control. The base model performed well: Nagelkerke R2 was 0.13, C-index 0.70 (95% CI: 0.68, 0.71) and bias-corrected C-index 0.69 after internal validation. Diabetes duration, insurance type, estimated glomerular filtration rate and glucose self-monitoring were additionally selected in the advanced model, which had only a slightly better performance compared with the base model: Nagelkerke R2 0.20, C-index 0.71 (95% CI: 0.69, 0.73) and bias-corrected C-index 0.70. Calibration plots showed good calibrations of both validated models. CONCLUSION: These prognostic models, which include simple demographic and routinely collected clinical information, enabled the estimation of the probability of 2-year sustained glycaemic control in patients after metformin failure. The models have been implemented into a web-based tool to support healthcare professionals in their decisions.

Duration of Type 2 Diabetes and Incidence of Cancer: An Observational Study in England.

OBJECTIVE: To investigate the association between duration of type 2 diabetes and cancer incidence. RESEARCH DESIGN AND METHODS: In the Clinical Practice Research Datalink database, we identified 130,764 individuals with type 2 diabetes aged ≥35 years at diagnosis who were linked to hospital and mortality records. We used sex-stratified Royston-Parmar models with two timescales to estimate incidence rates of all cancers, the four commonest cancers in the U.K. (colorectal, lung, prostate, breast), and the obesity-related cancers (e.g., liver, ovary) between 1 January 1998 and 14 January 2019, by age and diabetes duration. RESULTS: During 1,089,923 person-years, 18,977 incident cancers occurred. At the same age, rates of all cancers in men and women did not vary across durations ranging from diagnosis to 20 years; conversely, for any duration, there was a strong, positive association between age and cancer rates. In men, the rate ratio (95% CI) comparing 20 with 5 years of duration was 1.18 (0.82-1.69) at 60 years of age and 0.90 (0.75-1.08) at 80 years; corresponding ratios in women were 1.07 (0.71-1.63) and 0.84 (0.66-1.05). This pattern was observed also for the four commonest cancers. For obesity-related cancers, although rates were generally higher in individuals with a higher BMI, there was no association with duration at any level of BMI. CONCLUSIONS: In this study, we did not find evidence of an association between duration of type 2 diabetes and risk of cancer, with the higher risk observed for longer durations related to ageing.

Kidney Function and Long-Term Risk of End-Stage Kidney Disease and Mortality in a Multiethnic Population.

Introduction: Contemporary differences between South Asian and White ethnicities in the incidence of end-stage kidney disease (ESKD) and mortality are poorly described. Methods: Data for all South Asian patients who had an estimated glomerular filtration rate (eGFR) measure after January 1, 2006, and 1 million randomly selected participants of other ethnicities were extracted from the Clinical Practice Research Datalink (CPRD). All participants were followed-up with from index date until ESKD, all-cause mortality, or end of study. All-cause mortality rate and ESKD incidence rate by age were described among Whites and South Asians, and adjusted hazard ratios (HRs) of these 2 outcomes by baseline eGFR estimated using Cox proportional hazard model. Results: A total of 40,888 South Asians and 236,634 Whites were followed for a median of 5.3 and 9.4 years for ESKD incidence and mortality outcomes, respectively. All-cause mortality rates were higher among Whites than South Asians; South Asian women aged between 70 and 85 years had a slightly higher ESKD incidence rate compared to their White counterparts. Compared to Whites with a baseline eGFR of 90 ml/min per 1.73 m2, adjusted HRs for all-cause mortality were significantly lower among South Asians than Whites; however, adjusted HRs for ESKD incidence by baseline eGFR were similar in both ethnicities. Calculating South Asian eGFRs using an ethnicity-specific equation had no impact on the results. Conclusions: South Asians experience lower mortality than Whites but not substantially higher rates of ESKD. Further research is warranted to better understand the reasons for these ethnic differences and possible impacts on chronic kidney disease (CKD) service delivery and patient outcomes.

Glucose Control, Sulfonylureas, and Insulin Treatment in Elderly People With Type 2 Diabetes and Risk of Severe Hypoglycemia and Death: An Observational Study.

OBJECTIVE: To estimate the relative and absolute risk of severe hypoglycemia and mortality associated with glucose control, sulfonylureas, and insulin treatment in elderly people with type 2 diabetes. RESEARCH DESIGN AND METHODS: We identified elderly subjects (≥70 years old) with type 2 diabetes between 2000 and 2017 in the U.K. Clinical Practice Research Datalink primary care database with linkage to hospitalization and death data. Subjects with three consecutive HbA1c values <7% (53 mmol/mol) while on insulin and/or sulfonylureas within 60 days prior to the third HbA1c value (exposed) were matched with subjects not exposed. Hazard ratios (HRs) and absolute risks were estimated for hospitalizations for severe hypoglycemia and cardiovascular and noncardiovascular-related mortality. RESULTS: Among 22,857 included subjects (6,288 [27.5%] exposed, of whom 5,659 [90.0%] were on a sulfonylurea), 10,878 (47.6%) deaths and 1,392 (6.1%) severe hypoglycemic episodes occurred during the follow-up. In comparison with nonexposed subjects, the adjusted HR in exposed subjects was 2.52 (95% CI 2.23, 2.84) for severe hypoglycemia, 0.98 (0.91, 1.06) for cardiovascular mortality, and 1.05 (0.99, 1.11) for noncardiovascular mortality. In a 70-, 75-, 80-, and 85-year-old subject, the 10-year risk of severe hypoglycemia was 7.7%, 8.1%, 8.6%, and 8.4% higher than in nonexposed subjects, while differences for noncardiovascular mortality ranged from 1.2% (95% CI -0.1, 2.5) in a 70-year-old to 1.6% (-0.2, 3.4) in an 85-year-old subject. Sulfonylurea and insulin use were more relevant predictors of severe hypoglycemia and death than were glucose levels. CONCLUSIONS: Elderly subjects with type 2 diabetes and low HbA1c on sulfonylurea or insulin treatment experienced a substantially higher risk of hospitalization for severe hypoglycemia but had no clear evidence of increased risks of mortality.

Cardiovascular events and mortality in people with and without type 2 diabetes: An observational study in a contemporary multi-ethnic population.

AIMS/INTRODUCTION: The aim of this study was to examine ethnicity-specific associations between type 2 diabetes mellitus and the risk of a cardiovascular disease (CVD) event as well as risk of specific CVD phenotypes in England. METHODS: We obtained data from the Clinical Practice Research Datalink for adults with and without type 2 diabetes mellitus diagnosed 2000-2006. The outcome was the first CVD event during 2007-2017 and the following components: aortic aneurysm, cerebrovascular accidents, heart failure, myocardial infarction, peripheral vascular disease and other CVD-related conditions. Flexible parametric survival models were used to estimate ethnicity-specific adjusted hazard ratios. RESULTS: A total of 734,543 people with and without type 2 diabetes mellitus (29,847; 4.1%) were included; most were of white ethnicity (93.0% with and 92.3% without type 2 diabetes mellitus) followed by South Asian (3.2 and 4.6%). During a median follow-up period of 11.0 years, 67,218 events occurred (6,156 in individuals with type 2 diabetes mellitus). Type 2 diabetes mellitus was associated with a small increase in CVD events (adjusted hazard ratio 1.06, 95% confidence interval 1.02-1.09) in individuals of white ethnicity; whereas the adjusted hazard ratios were considerably higher in individuals of South Asian ethnicity (1.28, 95% confidence interval 1.09-1.51), primarily due to an increased risk of myocardial infarction (1.53, 95% confidence interval 1.08-2.18). CONCLUSIONS: Despite universal access to healthcare, there are large disparities in CVD outcomes in people with and without type 2 diabetes mellitus. Other non-traditional risk factors might play a role in the higher CVD risk associated with type 2 diabetes mellitus in individuals of South Asian ethnicity.

Association of Type 2 Diabetes With Cancer: A Meta-analysis With Bias Analysis for Unmeasured Confounding in 151 Cohorts Comprising 32 Million People.

BACKGROUND AND PURPOSE: Whether the association between type 2 diabetes (T2D) and cancer is causal remains controversial. The goal of this work is to assess the robustness of the observational associations between T2D and cancer to unmeasured confounding. DATA SOURCES AND STUDY SELECTION: PubMed, Web of Science, and the Cochrane library were systematically searched on 10 January 2019 for observational studies investigating associations between T2D and cancer incidence or mortality. DATA EXTRACTION AND DATA SYNTHESIS: Cohort-level relative risk (RR) was extracted. RRs were combined in random-effects meta-analyses and pooled estimates used in bias analyses. A total of 151 cohorts (over 32 million people, 1.1 million cancer cases, and 150,000 cancer deaths) were included. In meta-analyses, T2D was associated with incidence of several cancers, from prostate (RR 0.83; 95% CI 0.79, 0.88) to liver (2.23; 1.99, 2.49), and with mortality from pancreatic cancer (1.67; 1.30, 2.14). In bias analyses, assuming an unmeasured confounding associated with both T2D and cancer with a RR of 1.5, the proportion of studies with a true effect size larger than a RR of 1.1 (i.e., 10% increased risk in individuals with T2D) was nearly 100% for liver, pancreatic, and endometrial, 86% for gallbladder, 67% for kidney, 64% for colon, 62% for colorectal, and <50% for other cancer incidences, and 92% for pancreatic cancer mortality. LIMITATIONS: Biases other than unmeasured confounding were not analytically assessed. CONCLUSIONS: Our findings strongly suggest a causal association between T2D and liver, pancreatic, and endometrial cancer incidence, and pancreatic cancer mortality. Conversely, associations with other cancers were less robust to unmeasured confounding.

20-year trends in cause-specific heart failure outcomes by sex, socioeconomic status, and place of diagnosis: a population-based study.

BACKGROUND: Heart failure is an important public health issue affecting about 1 million people in the UK, but contemporary trends in cause-specific outcomes among different population groups are unknown. METHODS: In this retrospective, population-based study, we used the UK Clinical Practice Research Datalink and Hospital Episodes Statistics databases to identify a cohort of patients who had a diagnosis of incident heart failure between Jan 1, 1998, and July 31, 2017. Patients were eligible for inclusion if they were aged 30 years or older with a first code for heart failure in their primary care or hospital record during the study period. We assessed cause-specific admission to hospital (ie, hospitalisation) and mortality, by age, sex, socioeconomic status, and place of diagnosis (ie, hospital vs community diagnosis). We calculated outcome rates separately for the first year (first-year rates) and for the second-year onwards (subsequent-year rates). Patients were followed up until death or study end. This study is registered with Clinical Practice Research Datalink Independent Scientific Advisory Committee, protocol number 18_037R. FINDINGS: We identified 88 416 individuals with incident heart failure over the study period, of whom 43 461 (49%) were female. The mean age was 77·8 years (SD 11·3) and median follow-up was 2·4 years (IQR 0·5 to 5·7). Age-adjusted first-year rates of hospitalisation increased by 28% for all-cause admissions, from 97·1 (95% CI 94·3 to 99·9) to 124·2 (120·9 to 127·5) per 100 person-years; by 28% for heart failure-specific admissions, from 17·2 (16·2 to 18·2) to 22·1 (20·9 to 23·2) per 100 person-years; and by 42% for non-cardiovascular admissions, from 59·2 (57·2 to 61·2) to 83·9 (81·3 to 86·5) per 100 person-years. 167 641 (73%) of 228 113 hospitalisations were for non-cardiovascular causes and annual rate increases were higher for women (3·9%, 95% CI 2·8 to 4·9) than for men (1·4%, 0·6 to 2·1; p<0·0001); and for patients diagnosed with heart failure in hospital (2·4%, 1·4 to 3·3) than those diagnosed in the community (1·2%, 0·3 to 2·2). Annual increases in hospitalisation due to heart failure were 2·6% (1·9 to 3·4) for women compared with stable rates in men (0·6%, -0·9 to 2·1), and 1·6% (0·6 to 2·6) for the most deprived group compared with stable rates for the most affluent group (1·2%, -0·3 to 2·8). A significantly higher risk of all-cause hospitalisation was found for the most deprived than for the most affluent (incident rate ratio 1·34, 95% CI 1·32 to 1·35) and for the hospital-diagnosed group than for the community-diagnosed group (1·76, 1·73 to 1·80). Age-adjusted first-year rates of all-cause mortality decreased by 6% from 24·5 (95% CI 23·4 to 39·2) to 23·0 (22·0 to 24·1) per 100 person-years. Annual change in mortality was -1·4% (95% CI -2·3 to -0·5) in men but was stable for women (0·3%, -0·5 to 1·1), and -2·7% (-3·2 to -2·2) for the community-diagnosed group compared with -1·1% (-1·8 to -0·4) in the hospital-diagnosed group (p<0·0001). A significantly higher risk of all-cause mortality was seen in the most deprived group than in the most affluent group (hazard ratio 1·08, 95% CI 1·05 to 1·11) and in the hospital-diagnosed group than in the community-diagnosed group (1·55, 1·53 to 1·58). INTERPRETATION: Tailored management strategies and specialist care for patients with heart failure are needed to address persisting and increasing inequalities for men, the most deprived, and for those who are diagnosed with heart failure in hospital, and to address the worrying trends in women. FUNDING: Wellcome Trust.