Global Trends in Atherosclerotic Cardiovascular Disease.

PURPOSE: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality, affecting over 523 million people globally. Atherosclerotic diseases, particularly ischemic heart disease (IHD) and stroke, are the primary mediators of CVD burden and trends, with half of CVD deaths attributed to IHD, and another quarter to ischemic stroke. The aim of this review was to provide an overview of world-wide trends in the burden of atherosclerotic CVD. METHODS: A literature review of published studies reporting regional or global trends or burden of CVD was undertaken, with a specific focus on atherosclerotic-mediated CVDs. FINDINGS: While long-term trends in age-standardized rates of CVD mortality and incidence indicate substantial declines in disease burden, the impact of population growth and ageing has contributed to a continued increase in the absolute number of people living with CVD. Additionally, when data are restricted to the most recent decade, there are indications that even declines in age-standardized CVD rates may have attenuated. Trends are also heterogeneous across countries and regions, with a relative increase in CVD burden in developing countries and differing trends within countries. The impact of the COVID-19 pandemic resulted in substantial short-term reductions in hospitalization rates for major atherosclerotic CVDs including acute coronary syndromes and heart failure in some countries. IMPLICATIONS: Recent attenuation of declines in atherosclerotic CVDs with increasing absolute burden has significant implications for health systems and resource availability, with the impact of the COVID-19 pandemic on longer-term trends in CVD yet to be clearly established.

Effects of the COVID-19 pandemic on secondary care for cardiovascular disease in the UK: an electronic health record analysis across three countries.

BACKGROUND: Although morbidity and mortality from COVID-19 have been widely reported, the indirect effects of the pandemic beyond 2020 on other major diseases and health service activity have not been well described. METHODS AND RESULTS: Analyses used national administrative electronic hospital records in England, Scotland, and Wales for 2016-21. Admissions and procedures during the pandemic (2020-21) related to six major cardiovascular conditions [acute coronary syndrome (ACS), heart failure (HF), stroke/transient ischaemic attack (TIA), peripheral arterial disease (PAD), aortic aneurysm (AA), and venous thromboembolism(VTE)] were compared with the annual average in the pre-pandemic period (2016-19). Differences were assessed by time period and urgency of care.In 2020, there were 31 064 (-6%) fewer hospital admissions [14 506 (-4%) fewer emergencies, 16 560 (-23%) fewer elective admissions] compared with 2016-19 for the six major cardiovascular diseases (CVDs) combined. The proportional reduction in admissions was similar in all three countries. Overall, hospital admissions returned to pre-pandemic levels in 2021. Elective admissions remained substantially below expected levels for almost all conditions in all three countries [-10 996 (-15%) fewer admissions]. However, these reductions were offset by higher than expected total emergency admissions [+25 878 (+6%) higher admissions], notably for HF and stroke in England, and for VTE in all three countries. Analyses for procedures showed similar temporal variations to admissions. CONCLUSION: The present study highlights increasing emergency cardiovascular admissions during the pandemic, in the context of a substantial and sustained reduction in elective admissions and procedures. This is likely to increase further the demands on cardiovascular services over the coming years.

Relative contribution of trends in myocardial infarction event rates and case fatality to declines in mortality: an international comparative study of 1·95 million events in 80·4 million people in four countries.

BACKGROUND: Myocardial infarction mortality has declined since the 1970s, but contemporary drivers of this trend remain unexplained. The aim of this study was to compare the contribution of trends in event rates and case fatality to declines in myocardial infarction mortality in four high-income jurisdictions from 2002-15. METHODS: Linked hospitalisation and mortality data were obtained from New South Wales (NSW), Australia; Ontario, Canada; New Zealand; and England, UK. People aged between 30 years and 105 years were included in the study. Age-adjusted trends in myocardial infarction event rates and case fatality were estimated from Poisson and binomial regression models, and their relative contribution to trends in myocardial infarction mortality calculated. FINDINGS: 1 947 895 myocardial infarction events from a population of 80·4 million people were identified in people aged 30 years or older. There were significant declines in myocardial infarction mortality, event rates, and case fatality in all jurisdictions. Age-standardised myocardial infarction event rates were highest in New Zealand (men 893/100 000 person-years in 2002, 536/100 000 person-years in 2015; women 482/100 000 person-years in 2002, 271/100 000 person-years in 2015) and lowest in England (men 513/100 000 person-years in 2002, 382/100 000 person-years in 2015; women 238/100 000 person-years in 2002, 173/100 000 person-years in 2015). Annual age-adjusted reductions in event rates ranged from -2·6% (95% CI -3·0 to -2·3) in men in England to -4·3% (-4·4 to -4·1) in women in Ontario. Age-standardised case fatality was highest in England in 2002 (48%), but declined at a greater rate than in the other jurisdictions (men -4·1%/year, 95% CI -4·2 to -4·0%; women -4·4%/year, -4·5 to -4·3%). Declines in myocardial infarction mortality rates ranged from -6·1%/year to -7·6%/year. Event rate declines were the greater contributor to myocardial infarction mortality reductions in Ontario (69·4% for men and women), New Zealand (men 68·4%; women 67·5%), and NSW women (60·1%), whereas reductions in case fatality were the greater contributor in England (60% in men and women) and for NSW men (54%). There were greater contributions from case fatality than event rate reductions in people younger than 55 years in all jurisdictions, with contributions to mortality declines varying by country in those aged 55-74 years. Event rate declines had a greater impact than changes in case fatality in those aged 75 years and older. INTERPRETATION: While the mortality burden of myocardial infarction has continued to fall across these four populations, the relative contribution of trends in myocardial infarction event rates and case fatality to declining mortality varied between jurisdictions, including by age and sex. Understanding the causes of this variation will enable optimisation of prevention and treatment efforts. FUNDING: National Health and Medical Research Council, Australia; Australian Research Council; Health Research Council of New Zealand; Canadian Institutes of Health Research, Canada; National Institute for Health Research, UK.

Long-term trends in population-based hospitalisation rates for myocardial infarction in England: a national database study of 3.5 million admissions, 1968-2016.

AIM: To analyse the timing and scale of temporal changes in rates of hospitalised myocardial infarction (MI) in England by age and sex from 1968 to 2016. METHODS: MI admissions for adults aged 15-84 years were identified from electronic hospital data. We calculated age-standardised and age-specific rates, and examined trends using joinpoint. RESULTS: From 1968 to 2016, there were 3.5 million admissions for MI in England (68% men). Rates increased in the early years of the study in both men and women, peaked in the mid-1980s (355 per 100 000 population in men; 127 in women) and declined by 38.8% in men and 37.4% in women from 1990 to 2011. From 2012, however, modest increases were observed in both sexes. Long-term trends in rates over the study period varied by age and sex, with those aged 70 years and older having the greatest and most sustained increases in the early years (1968-1985). During subsequent years, rates decreased in most age groups until 2010-2011. The exception was younger women (35-49 years) and men (15-34 years) who experienced significant increases from the mid-1990s to 2007 (range +2.1%/year to 4.7%/year). From 2012 onwards, rates increased in all age groups except the oldest, with the most marked increases in men aged 15-34 years (7.2%/year) and women aged 40-49 (6.9%-7.3%/year) . CONCLUSION: Despite substantial declines in hospital admission rates for MI in England since 1990, the burden of annual admissions remains high. Continued surveillance of trends and coronary disease preventive strategies are warranted.

The impact of physical activity and an additional behavioural risk factor on cardiovascular disease, cancer and all-cause mortality: a systematic review.

BACKGROUND: Regular physical activity improves overall health, and has the capacity to reduce risk of chronic diseases and death. However, better understanding of the relationship between multiple lifestyle risk behaviours and disease outcomes is pertinent for prioritising public health messaging. The aim of this systematic review is to examine the association between physical inactivity in combination with additional lifestyle risk behaviours (smoking, alcohol, diet, or sedentary behaviour) for cardiovascular disease, cancer, and all-cause mortality. METHODS: We searched Ovid Medline, EMBASE, and the Cochrane Register from 1 January 2010 to 12 December 2017, for longitudinal observational studies of adults (18+ years) in the general population with a publication date of 2010 onwards and no language restriction. Main exposure variables had to include a physical activity measure plus at least one other lifestyle risk factor. In total, 25,639 studies were identified. Titles, abstracts and full-text articles of potentially relevant papers were screened for eligibility. Data was extracted and quality assessment was completed using a modified Newcastle-Ottawa Scale (NOS). RESULTS: Across the 25 eligible studies, those participants who reported being physically active combined with achieving other health behaviour goals compared to those who were categorised as physically inactive and did not achieve other positive lifestyle goals, were at least half as likely to experience an incident cardiovascular disease (CVD) event, die from CVD, or die from any cause. These findings were consistent across participant age, sex, and study length of follow-up, and even after excluding lower quality studies. We also observed a similar trend among the few studies which were restricted to cancer outcomes. Most studies did not consider epidemiological challenges that may bias findings, such as residual confounding, reverse causality by pre-existing disease, and measurement error from self-report data. CONCLUSIONS: High levels of physical activity in combination with other positive lifestyle choices is associated with better health outcomes. Applying new approaches to studying the complex relationships between multiple behavioural risk factors, including physical activity, should be a priority.

Determinants of the decline in mortality from acute stroke in England: linked national database study of 795 869 adults.

OBJECTIVES: To study trends in stroke mortality rates, event rates, and case fatality, and to explain the extent to which the reduction in stroke mortality rates was influenced by changes in stroke event rates or case fatality. DESIGN: Population based study. SETTING: Person linked routine hospital and mortality data, England. PARTICIPANTS: 795 869 adults aged 20 and older who were admitted to hospital with acute stroke or died from stroke. MAIN OUTCOME MEASURES: Stroke mortality rates, stroke event rates (stroke admission or stroke death without admission), and case fatality within 30 days after stroke. RESULTS: Between 2001 and 2010 stroke mortality rates decreased by 55%, stroke event rates by 20%, and case fatality by 40%. The study population included 358 599 (45%) men and 437 270 (55%) women. Average annual change in mortality rate was -6.0% (95% confidence interval -6.2% to -5.8%) in men and -6.1% (-6.3% to -6.0%) in women, in stroke event rate was -1.3% (-1.4% to -1.2%) in men and -2.1% (-2.2 to -2.0) in women, and in case fatality was -4.7% (-4.9% to -4.5%) in men and -4.4% (-4.5% to -4.2%) in women. Mortality and case fatality but not event rate declined in all age groups: the stroke event rate decreased in older people but increased by 2% each year in adults aged 35 to 54 years. Of the total decline in mortality rates, 71% was attributed to the decline in case fatality (78% in men and 66% in women) and the remainder to the reduction in stroke event rates. The contribution of the two factors varied between age groups. Whereas the reduction in mortality rates in people younger than 55 years was due to the reduction in case fatality, in the oldest age group (≥85 years) reductions in case fatality and event rates contributed nearly equally. CONCLUSIONS: Declines in case fatality, probably driven by improvements in stroke care, contributed more than declines in event rates to the overall reduction in stroke mortality. Mortality reduction in men and women younger than 55 was solely a result of a decrease in case fatality, whereas stroke event rates increased in the age group 35 to 54 years. The increase in stroke event rates in young adults is a concern. This suggests that stroke prevention needs to be strengthened to reduce the occurrence of stroke in people younger than 55 years.

Comparative trends in coronary heart disease subgroup hospitalisation rates in England and Australia.

BACKGROUND: Population-based coronary heart disease (CHD) studies have focused on myocardial infarction (MI) with limited data on trends across the spectrum of CHD. We investigated trends in hospitalisation rates for acute and chronic CHD subgroups in England and Australia from 1996 to 2013. METHODS: CHD hospitalisations for individuals aged 35-84 years were identified from electronic hospital data from 1996 to 2013 for England and Australia and from the Oxford Region and Western Australia. CHD subgroups identified were acute coronary syndromes (ACS) (MI and unstable angina) and chronic CHD (stable angina and 'other CHD'). We calculated age-standardised and age-specific rates and estimated annual changes (95% CI) from age-adjusted Poisson regression. RESULTS: From 1996 to 2013, there were 4.9 million CHD hospitalisations in England and 2.6 million in Australia (67% men). From 1996 to 2003, there was between-country variation in the direction of trends in ACS and chronic CHD hospitalisation rates (p<0.001). During 2004-2013, reductions in ACS hospitalisation rates were greater than for chronic CHD hospitalisation rates in both countries, with the largest subgroup declines in unstable angina (England: men: -7.1 %/year, 95% CI -7.2 to -7.0; women: -7.5 %/year, 95% CI -7.7 to -7.3; Australia: men: -8.5 %/year, 95% CI -8.6 to -8.4; women: -8.6 %/year, 95% CI -8.8 to -8.4). Other CHD rates increased in individuals aged 75-84 years in both countries. Chronic CHD comprised half of all CHD admissions, with the majority involving angiography or percutaneous coronary intervention. CONCLUSIONS: Since 2004, rates of all CHD subgroups have fallen, with greater declines in acute than chronic presentations. The slower declines and high proportion of chronic CHD admissions undergoing coronary procedures requires greater focus.

Epidemiology report: trends in sex-specific cerebrovascular disease mortality in Europe based on WHO mortality data.

AIMS: There have been substantial declines in cerebrovascular disease mortality across much of Europe, mirroring trends in deaths from cardiovascular disease as a whole. No study has investigated trends in cerebrovascular disease, and its subtypes within all European countries. This study aimed to examine sex-specific trends in cerebrovascular disease, and three of its sub-types: ischaemic stroke, haemorrhagic stroke, and subarachnoid haemorrhage (SAH), in Europe between 1980 and 2016. METHODS AND RESULTS: Sex-specific mortality data for each country of the World Health Organization (WHO) Europe region were extracted from the WHO global mortality database and analysed using Joinpoint software to examine trends. The number and location of significant joinpoints for each country by sex and subtype was determined using a log-linear model. The annual percentage change within each segment was calculated along with the average annual percentage change over the duration of all available data. The last 35 years have seen large overall declines in cerebrovascular disease mortality rates in the majority of European countries. While these declines have continued steadily in more than half of countries, this analysis has revealed evidence of recent plateauing and even increases in stroke mortality in a number of countries, in both sexes, and in all four geographical sub-regions of Europe. Analysis by stroke sub-type revealed that recent plateauing was most common for haemorraghic stroke and increases were most common for ischaemic stroke. CONCLUSION: These findings highlight the need for continued research into the inequalities in both current stroke mortality outcomes and trends across Europe, as well as the causes behind any recent plateauing of total cerebrovascular disease or its subtypes.

Differences in risk factors for 3 types of stroke: UK prospective study and meta-analyses.

OBJECTIVE: To compare associations of behavioral and related factors for incident subarachnoid hemorrhage and intracerebral hemorrhage and ischemic stroke. METHODS: A total of 712,433 Million Women Study participants without prior stroke, heart disease, or cancer reported behavioral and related factors at baseline (1999-2007) and were followed up by record linkage to national hospital admission and death databases. Cox regression yielded adjusted relative risks (RRs) by type of stroke. Heterogeneity was assessed with χ2 tests. When appropriate, meta-analyses were done of published prospective studies. RESULTS: After 12.9 (SD 2.6) years of follow-up, 8,128 women had an incident ischemic stroke, 2,032 had intracerebral hemorrhage, and 1,536 had subarachnoid hemorrhage. In women with diabetes mellitus, the risk of ischemic stroke was substantially increased (RR 2.01, 95% confidence interval [CI] 1.84-2.20), risk of intracerebral hemorrhage was increased slightly (RR 1.31, 95% CI 1.04-1.65), but risk of subarachnoid hemorrhage was reduced (RR 0.43, 95% CI 0.26-0.69) (heterogeneity by stroke type, p < 0.0001). Stroke incidence was greater in women who rated their health as poor/fair compared to those who rated their health as excellent/good (RR 1.36, 95% CI 1.30-1.42). Among 565,850 women who rated their heath as excellent/good, current smokers were at an increased risk of all 3 stroke types, (although greater for subarachnoid hemorrhage [≥15 cigarettes/d vs never smoker, RR 4.75, 95% CI 4.12-5.47] than for intracerebral hemorrhage [RR 2.30, 95% CI 1.94-2.72] or ischemic stroke [RR 2.50, 95% CI 2.29-2.72]; heterogeneity p < 0.0001). Obesity was associated with an increased risk of ischemic stroke and a decreased risk of hemorrhagic stroke (heterogeneity p < 0.0001). Meta-analyses confirmed the associations and the heterogeneity across the 3 types of stroke. CONCLUSION: Classic risk factors for stroke have considerably different effects on the 3 main pathologic types of stroke.

Identification of myocardial infarction type from electronic hospital data in England and Australia: a comparative data linkage study.

OBJECTIVE: To determine the utility of International Classification of Diseases (ICD) codes in investigating trends in ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) using person-linked electronic hospitalisation data in England and Western Australia (WA). METHODS: All hospital admissions with myocardial infarction (MI) as the principal diagnosis were identified from 2000 to 2013 from both jurisdictions. Fourth-digit ICD-10 codes were used to delineate all MI types-STEMI, NSTEMI, unspecified and subsequent MI. The annual frequency of each MI type was calculated as a proportion of all MI admissions. For all MI and each MI type, age-standardised rates were calculated and age-adjusted Poisson regression models used to estimate annual percentage changes in rates. RESULTS: In 2000, STEMI accounted for 49% of all MI admissions in England and 59% in WA, decreasing to 35% and 25% respectively by 2013. Less than 10% of admissions were recorded as NSTEMI in England throughout the study period, whereas by 2013, 70% of admissions were NSTEMI in WA. Unspecified MI comprised 60% of all MI admissions in England by 2013, compared with <1% in WA. Trends in age-standardised rates differed for all MI (England, -2.7%/year; WA, +1.7%/year), underpinned by differing age-adjusted trends in NSTEMI (England, -6.1%/year; WA, +10.2%/year). CONCLUSION: Differences between the proportion and trends for MI types in English and WA data were observed. These were consistent with the coding standards in each country. This has important implications for using electronic hospital data for monitoring MI and identifying MI types for outcome studies.

Hypertension in pregnancy and risk of coronary heart disease and stroke: A prospective study in a large UK cohort.

BACKGROUND: Many studies investigating long-term vascular disease risk associated with hypertensive pregnancies examined risks in relatively young women among whom vascular disease is uncommon. We examined the prospective relation between a history of hypertension during pregnancy and coronary heart disease (CHD) and stroke in middle-aged UK women. METHODS: In 1996-2001, 1.1 million parous women (mean age=56years) without vascular disease at baseline reported their history of hypertension during pregnancy and other factors. They were followed for incident CHD and stroke (hospitalisation or death). Adjusted relative risks (RRs) were calculated using Cox regression. RESULTS: Twenty-six percent (290,008/1.1 million) reported having had a hypertensive pregnancy; 27% (79,163/290,008) of women with hypertensive pregnancy, but only 10% (82,145/815,560) of those without hypertensive pregnancy, reported being treated for hypertension at baseline. Mean follow-up was 11.6years (mean ages at diagnosis/N of events: CHD=65years/N=68,161, ischaemic stroke=67years/N=8365, haemorrhagic stroke=64years/N=5702). Overall, the RRs (95% confidence interval [CI]) of incident disease in women with hypertensive pregnancy versus those without such history were: CHD=1.29 (1.27-1.31), ischaemic stroke=1.29 (1.23-1.35), and haemorrhagic stroke=1.14 (1.07-1.21). However, among women with hypertensive pregnancy who were not taking hypertension treatment at baseline, their RRs (95% CI) were only modestly increased: CHD=1.17 (1.14-1.19), ischaemic stroke=1.18 (1.11-1.25), and haemorrhagic stroke=1.09 (1.02-1.18). CONCLUSION: Hypertension during pregnancy was associated with increased CHD and stroke incidence in middle age, largely because such women also had hypertension in their 50s and 60s, which has a substantially greater effect on vascular disease risk than hypertension during pregnancy without hypertension later in life.

B-type natriuretic peptide-guided treatment for heart failure.

BACKGROUND: Heart failure is a condition in which the heart does not pump enough blood to meet all the needs of the body. Symptoms of heart failure include breathlessness, fatigue and fluid retention. Outcomes for patients with heart failure are highly variable; however on average, these patients have a poor prognosis. Prognosis can be improved with early diagnosis and appropriate use of medical treatment, use of devices and transplantation. Patients with heart failure are high users of healthcare resources, not only due to drug and device treatments, but due to high costs of hospitalisation care. B-type natriuretic peptide levels are already used as biomarkers for diagnosis and prognosis of heart failure, but could offer to clinicians a possible tool to guide drug treatment. This could optimise drug management in heart failure patients whilst allaying concerns over potential side effects due to drug intolerance. OBJECTIVES: To assess whether treatment guided by serial BNP or NT-proBNP (collectively referred to as NP) monitoring improves outcomes compared with treatment guided by clinical assessment alone. SEARCH METHODS: Searches were conducted up to 15 March 2016 in the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (OVID), Embase (OVID), the Database of Abstracts of Reviews of Effects (DARE) and the NHS Economic Evaluation Database in the Cochrane Library. Searches were also conducted in the Science Citation Index Expanded, the Conference Proceedings Citation Index on Web of Science (Thomson Reuters), World Health Organization International Clinical Trials Registry and ClinicalTrials.gov. We applied no date or language restrictions. SELECTION CRITERIA: We included randomised controlled trials of NP-guided treatment of heart failure versus treatment guided by clinical assessment alone with no restriction on follow-up. Adults treated for heart failure, in both in-hospital and out-of-hospital settings, and trials reporting a clinical outcome were included. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data and evaluated risk of bias. Risk ratios (RR) were calculated for dichotomous data, and pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated for continuous data. We contacted trial authors to obtain missing data. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, we assessed the quality of the evidence and GRADE profiler (GRADEPRO) was used to import data from Review Manager to create a 'Summary of findings' table. MAIN RESULTS: We included 18 randomised controlled trials with 3660 participants (range of mean age: 57 to 80 years) comparing NP-guided treatment with clinical assessment alone. The evidence for all-cause mortality using NP-guided treatment showed uncertainty (RR 0.87, 95% CI 0.76 to 1.01; patients = 3169; studies = 15; low quality of the evidence), and for heart failure mortality (RR 0.84, 95% CI 0.54 to 1.30; patients = 853; studies = 6; low quality of evidence).The evidence suggested heart failure admission was reduced by NP-guided treatment (38% versus 26%, RR 0.70, 95% CI 0.61 to 0.80; patients = 1928; studies = 10; low quality of evidence), but the evidence showed uncertainty for all-cause admission (57% versus 53%, RR 0.93, 95% CI 0.84 to 1.03; patients = 1142; studies = 6; low quality of evidence).Six studies reported on adverse events, however the results could not be pooled (patients = 1144; low quality of evidence). Only four studies provided cost of treatment results, three of these studies reported a lower cost for NP-guided treatment, whilst one reported a higher cost (results were not pooled; patients = 931, low quality of evidence). The evidence showed uncertainty for quality of life data (MD -0.03, 95% CI -1.18 to 1.13; patients = 1812; studies = 8; very low quality of evidence).We completed a 'Risk of bias' assessment for all studies. The impact of risk of bias from lack of blinding of outcome assessment and high attrition levels was examined by restricting analyses to only low 'Risk of bias' studies. AUTHORS' CONCLUSIONS: In patients with heart failure low-quality evidence showed a reduction in heart failure admission with NP-guided treatment while low-quality evidence showed uncertainty in the effect of NP-guided treatment for all-cause mortality, heart failure mortality, and all-cause admission. Uncertainty in the effect was further shown by very low-quality evidence for patient's quality of life. The evidence for adverse events and cost of treatment was low quality and we were unable to pool results.

Validity over time of self-reported anthropometric variables during follow-up of a large cohort of UK women.

BACKGROUND: In prospective epidemiological studies, anthropometry is often self-reported and may be subject to reporting errors. Self-reported anthropometric data are reasonably accurate when compared with measurements made at the same time, but reporting errors and changes over time in anthropometric characteristics could potentially generate time-dependent biases in disease-exposure associations. METHODS: In a sample of about 4000 middle-aged UK women from a large prospective cohort study, we compared repeated self-reports of weight, height, derived body mass index, and waist and hip circumferences, obtained between 1999 and 2008, with clinical measurements taken in 2008. For self-reported and measured values of each variable, mean differences, correlation coefficients, and regression dilution ratios (which measure relative bias in estimates of linear association) were compared over time. RESULTS: For most variables, the differences between self-reported and measured values were small. On average, reported values tended to be lower than measured values (i.e. under-reported) for all variables except height; under-reporting was greatest for waist circumference. As expected, the greater the elapsed time between self-report and measurement, the larger the mean differences between them (each P < 0.001 for trend), and the weaker their correlations (each P < 0.004 for trend). Regression dilution ratios were in general close to 1.0 and did not vary greatly over time. CONCLUSION: Reporting errors in anthropometric variables may result in small biases to estimates of associations with disease outcomes. Weaker correlations between self-reported and measured values would result in some loss of study power over time. Overall, however, our results provide new evidence that self-reported anthropometric variables remain suitable for use in analyses of associations with disease outcomes in cohort studies over at least a decade of follow-up.

Age at menarche and risks of coronary heart and other vascular diseases in a large UK cohort.

BACKGROUND: Early menarche has been associated with increased risk of coronary heart disease (CHD), but most studies were relatively small and could not assess risk across a wide range of menarcheal ages; few have examined associations with other vascular diseases. We examined CHD, cerebrovascular disease, and hypertensive disease risks by age at menarche in a large prospective study of UK women. METHODS AND RESULTS: In 1.2 million women (mean±SD age, 56±5 years) without previous heart disease, stroke, or cancer, menarcheal age was reported to be 13 years by 25%, ≤10 years by 4%, and ≥17 years by 1%. After 11.6 years of follow-up, 73 378 women had first hospitalization for or death from CHD, 25 426 from cerebrovascular disease, and 249 426 from hypertensive disease. Using Cox regression, we calculated relative risks for each vascular outcome by single year of menarcheal age. The relationship was U-shaped for CHD. Compared with women with menarche at 13 years, the adjusted relative risk for CHD for menarche at ≤10 years of age was 1.27 (95% confidence interval, 1.22-1.31; P<0.0001) and for menarche at ≥17 years of age was 1.23 (95% confidence interval, 1.16-1.30; P<0.0001). U-shaped relationships were also seen for cerebrovascular and hypertensive disease, although the magnitudes of these risks for early and late menarche were smaller than those for CHD. CONCLUSIONS: In this cohort, the relation of age at menarche to vascular disease risk was U shaped, with both early and late menarche being associated with increased risk. Associations were weaker for cerebrovascular and hypertensive disease than for CHD.

Marital status and ischemic heart disease incidence and mortality in women: a large prospective study.

BACKGROUND: Being married has been associated with a lower mortality from ischemic heart disease (IHD) in men, but there is less evidence of an association for women, and it is unclear whether the associations with being married are similar for incident and for fatal IHD. We examined the relation between marital status and IHD incidence and mortality in the Million Women Study. METHODS: A total of 734,626 women (mean age 60 years) without previous heart disease, stroke or cancer, were followed prospectively for hospital admissions and deaths. Adjusted relative risks (RRs) for IHD were calculated using Cox regression in women who were married or living with a partner versus women who were not. The role of 14 socio-economic, lifestyle and other potential confounding factors was investigated. RESULTS: 81% of women reported being married or living with a partner and they were less likely to live in deprived areas, to smoke or be physically inactive, but had a higher alcohol intake than women who were not married or living with a partner. During 8.8 years of follow-up, 30,747 women had a first IHD event (hospital admission or death) and 2,148 died from IHD. Women who were married or living with a partner had a similar risk of a first IHD event as women who were not (RR = 0.99, 95% confidence interval (CI) 0.96 to 1.02), but a significantly lower risk of IHD mortality (RR = 0.72, 95% CI 0.66 to 0.80, P <0.0001). This lower risk of IHD death was evident both in women with and without a prior IHD hospital admission (respectively: RR = 0.72, 95% CI 0.60 to 0.85, P <0.0001, n = 683; and 0.70, 95% CI 0.62 to 0.78, P <0.0001, n = 1,465). These findings did not vary appreciably between women of different socio-economic groups or by lifestyle and other factors. CONCLUSIONS: After adjustment for socioeconomic, lifestyle and other factors, women who were married or living with a partner had a similar risk of developing IHD but a substantially lower IHD mortality compared to women who were not married or living with a partner.

Coronary heart disease incidence in women by waist circumference within categories of body mass index.

High body mass index (BMI) and large waist circumference are separately associated with increased coronary heart disease (CHD) risk but these measures are highly correlated. Their separate associations with incident CHD, cross-classifying one variable by the other, are less investigated in large-scale studies. We examined these associations in a large UK cohort (the Million Women Study), which is a prospective population-based study. We followed 496,225 women (mean age 60 years) with both waist circumference and BMI measurements who had no vascular disease or cancer. Adjusted relative risk and 20-year cumulative CHD incidence (first coronary hospitalization or death) from age 55 to 74 years were calculated using Cox regression. Plasma apolipoproteins were assayed in 6295 randomly selected participants. There were 10,998 incident coronary events after mean follow up of 5.1 years. Within each BMI category (<25, 25-29.9, ≥30 kg/m(2)), CHD risk increased with increasing waist circumference; within each waist circumference category (<70, 70-79.9, ≥79 cm), CHD risk increased with increasing BMI. The cumulative CHD incidence was lowest in women with BMI <25 kg/m(2) and waist circumference <70 cm, with 1 in 14 (95% confidence interval 1 in 12 to 16) women developing CHD in the 20 years from age 55 to 74 years, and highest in women with BMI ≥30 kg/m(2) and waist circumference ≥80 cm, with 1 in 8 (95% confidence interval 1 in 7 to 9) women developing CHD over the same period. Similar associations for apolipoprotein B to A1 ratio across adiposity categories were observed, particularly in non-obese women. Our conclusions were that both waist circumference and BMI are independently associated with incident CHD.

Body mass index and incident coronary heart disease in women: a population-based prospective study.

BACKGROUND: A high body mass index (BMI) is associated with an increased risk of mortality from coronary heart disease (CHD); however, a low BMI may also be associated with an increased mortality risk. There is limited information on the relation of incident CHD risk across a wide range of BMI, particularly in women. We examined the relation between BMI and incident CHD overall and across different risk factors of the disease in the Million Women Study. METHODS: 1.2 million women (mean age=56 years) participants without heart disease, stroke, or cancer (except non-melanoma skin cancer) at baseline (1996 to 2001) were followed prospectively for 9 years on average. Adjusted relative risks and 20-year cumulative incidence from age 55 to 74 years were calculated for CHD using Cox regression. RESULTS: After excluding the first 4 years of follow-up, we found that 32,465 women had a first coronary event (hospitalization or death) during follow-up. The adjusted relative risk for incident CHD per 5 kg/m2 increase in BMI was 1.23 (95% confidence interval (CI) 1.22 to 1.25). The cumulative incidence of CHD from age 55 to 74 years increased progressively with BMI, from 1 in 11 (95% CI 1 in 10 to 12) for BMI of 20 kg/m2, to 1 in 6(95% CI 1 in 5 to 7) for BMI of 34 kg/m2. A 10 kg/m2 increase in BMI conferred a similar risk to a 5-year increment in chronological age. The 20 year cumulative incidence increased with BMI in smokers and non-smokers, alcohol drinkers and non-drinkers, physically active and inactive, and in the upper and lower socioeconomic classes. In contrast to incident disease, the relation between BMI and CHD mortality (n=2,431) was J-shaped. For the less than 20 kg/m2 and ≥35 kg/m2 BMI categories, the respective relative risks were 1.27 (95% CI 1.06 to 1.53) and 2.84 (95% CI 2.51 to 3.21) for CHD deaths, and 0.89 (95% CI 0.83 to 0.94) and 1.85 (95% CI 1.78 to 1.92) for incident CHD. CONCLUSIONS: CHD incidence in women increases progressively with BMI, an association consistently seen in different subgroups. The shape of the relation with BMI differs for incident and fatal disease.

Vascular disease in women: comparison of diagnoses in hospital episode statistics and general practice records in England.

BACKGROUND: Electronic linkage to routine administrative datasets, such as the Hospital Episode Statistics (HES) in England, is increasingly used in medical research. Relatively little is known about the reliability of HES diagnostic information for epidemiological studies. In the United Kingdom (UK), general practitioners hold comprehensive records for individuals relating to their primary, secondary and tertiary care. For a random sample of participants in a large UK cohort, we compared vascular disease diagnoses in HES and general practice records to assess agreement between the two sources. METHODS: Million Women Study participants with a HES record of hospital admission with vascular disease (ischaemic heart disease [ICD-10 codes I20-I25], cerebrovascular disease [G45, I60-I69] or venous thromboembolism [I26, I80-I82]) between April 1st 1997 and March 31st 2005 were identified. In each broad diagnostic group and in women with no such HES diagnoses, a random sample of about a thousand women was selected for study. We asked each woman's general practitioner to provide information on her history of vascular disease and this information was compared with the HES diagnosis record. RESULTS: Over 90% of study forms sent to general practitioners were returned and 88% of these contained analysable data. For the vast majority of study participants for whom information was available, diagnostic information from general practice and HES records was consistent. Overall, for 93% of women with a HES diagnosis of vascular disease, general practice records agreed with the HES diagnosis; and for 97% of women with no HES diagnosis of vascular disease, the general practitioner had no record of a diagnosis of vascular disease. For severe vascular disease, including myocardial infarction (I21-22), stroke, both overall (I60-64) and by subtype, and pulmonary embolism (I26), HES records appeared to be both reliable and complete. CONCLUSION: Hospital admission data in England provide diagnostic information for vascular disease of sufficient reliability for epidemiological analyses.

Long-term survival and recurrence after acute myocardial infarction in England, 2004 to 2010.

BACKGROUND: There are limited population-based national data on prognosis in survivors of acute myocardial infarction (AMI), particularly on long-term survival and the risk of recurrence. METHODS AND RESULTS: Record linkage of hospital and mortality data identified 387 452 individuals in England who were admitted to hospital with a main diagnosis of AMI between 2004 and 2010 and who survived for at least 30 days. Seven years after an AMI, the risk of death from any cause in survivors of first or recurrent AMI was, respectively, 2 and 3 times higher than that in the English general population of equivalent age. For all survivors of a first AMI, the risk of a second AMI was highest during the first year and the cumulative risk increased more gradually thereafter. For men, 1- and 7-year cumulative risks were 5.6% (95% confidence interval [CI], 5.5-5.7) and 13.9% (95% CI, 13.7-14.1); for women, they were 7.2% (95% CI, 7.1-7.4) and 16.2% (95% CI, 16.0-16.5). Older age, higher deprivation, no revascularization procedures, and presence of comorbidities were associated with higher recurrence risk. CONCLUSIONS: Survivors of both first and recurrent AMI remained at a significantly higher risk of death compared with the general population for at least 7 years after the event. For survivors of first AMI, the influence of predisposing factors for second AMI lessened with time after the initial event. The results reinforce the importance of acute clinical care and secondary prevention in improving long-term prognosis of hospitalized AMI patients.

Determinants of the decline in mortality from acute myocardial infarction in England between 2002 and 2010: linked national database study.

OBJECTIVE: To report trends in event and case fatality rates for acute myocardial infarction and examine the relative contributions of changes in these rates to changes in total mortality from acute myocardial infarction by sex, age, and geographical region between 2002 and 2010. DESIGN: Population based study using person linked routine hospital and mortality data. SETTING: England. PARTICIPANTS: 840,175 people of all ages who were admitted to hospital for acute myocardial infarction or died suddenly from acute myocardial infarction. MAIN OUTCOME MEASURES: Acute myocardial infarction event, 30 day case fatality, and total mortality rates. RESULTS: From 2002 to 2010 in England, the age standardised total mortality rate fell by about half, whereas the age standardised event and case fatality rates both declined by about one third. In men, the acute myocardial infarction event, case fatality, and total mortality rates declined at an average annual rate of, respectively, 4.8% (95% confidence interval 3.0% to 6.5%), 3.6% (3.4% to 3.7%), and 8.6% (5.4% to 11.6%). In women, the corresponding figures were 4.5% (1.7% to 7.1%), 4.2% (4.0% to 4.3%), and 9.1% (4.5% to 13.6%). Overall, the relative contributions of the reductions in event and case fatality rates to the decline in acute myocardial infarction mortality rate were, respectively, 57% and 43% in men and 52% and 48% in women; however, the relative contributions differed by age, sex, and geographical region. CONCLUSIONS: Just over half of the decline in deaths from acute myocardial infarction during the 2000s in England can be attributed to a decline in event rate and just less than half to improved survival at 30 days. Both prevention of acute myocardial infarction and acute medical treatment have contributed to the decline in deaths from acute myocardial infarction over the past decade.