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This Review presents data describing the health burden of cardiovascular disease (CVD) within and across the WHO European Region. CVD remains the most common cause of death in the region. Deaths from CVD in those aged 60 million potential years of life lost to CVD in Europe annually. Although more women than men die from CVD, age-standardized rates of both morbidity and death are higher in men, and these differences in rates are greatest in individuals aged

AimTo 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.MethodsMI 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.ResultsFrom 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) .ConclusionDespite 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.

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. Electronic supplementary material The online version of this article (10.1186/s12889-019-7030-8) contains supplementary material, which is available to authorized users.

Background: Myocardial infarction (MI) mortality has declined since the 1970s, but contemporary drivers of this trend remain unexplained. The aim was to compare the contribution of trends in event rates and case fatality to declines in MI mortality in four high-income jurisdictions from 2002-2015. Methods: Linked hospitalisation and mortality data were obtained from New South Wales (NSW), Ontario, New Zealand and England. Age-adjusted trends in MI event rates and case fatality were estimated from Poisson and binomial regression models, and their relative contribution to trends in MI mortality calculated. Findings: A total of 1,947,895 MI events were identified in ≥30 year olds. There were significant declines in MI mortality, event rates and case fatality in all jurisdictions. Age-standardised MI event rates were highest in New Zealand (men: 893/100,000 in 2002, 536/100,000 in 2015; women: 482/100,000 in 2002, 271/100,000 in 2015) and lowest in England (men: 513/100,000 in 2002, 382/100,000 in 2015; women: 238/100,000 in 2002, 173/100,000 in 2015). Annual age-adjusted reductions in event rates ranged from -2·6% (95% CI -2·7, -2·6) in men in England to -4·3% (95% CI -4·4, -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, -4·0%); women: -4·4%/year, (95% CI: -4·5, -4·3%)). Declines in MI mortality rates ranged from -6.1%/year to -7.6%/year. Event rate declines were the greater contributor to MI mortality reductions in Ontario (69·4%), New Zealand (men 68·4%; women 67·5%) and NSW women (60·1%), while reductions in case fatality were the greater contributor in England (60% in men and women). There were greater contributions from case fatality reductions in younger age groups and event rate declines in older age groups. Interpretation: The contribution of trends in MI event rates and case fatality varied between jurisdictions, including by age and sex. Understanding the causes of this variation will enable optimisation of prevention and treatment efforts. Funding Information: NHMRC (Australia); Health Research Council New Zealand; Canadian Institutes for Health Research; National Institute for Health Research, Oxford. Declaration of Interests: None to declare. Ethics Approval Statement: This study was approved by the University of Toronto Health Sciences Research Ethics Board, NSW Population & Health Services Research Ethics Committee (reference 2016/09/654), the New Zealand Health and Disability Ethics Committees (reference number H13/049) and the Central and South Bristol Multi-Centre Research Ethics Committee (04/Q2006/176).

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.

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 (

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. B-type natriuretic peptide-guided treatment for heart failure patients Review question We aimed to discover whether using B-type natriuretic-guided treatment or a health plan alone is more effective for managing patients with heart failure. Background Heart failure is a complex condition that occurs when the heart does not pump blood effectively enough to meet the needs of the body. It is caused by a range of diseases that impair the structure and function of the heart and may result in breathlessness, fatigue and fluid retention. People with heart failure are frequently users of general practice and hospitals, particularly as inpatients. Furthermore, they have reduced life expectancy, although medicines and other treatments can improve the chance of survival. B-type natriuretic peptide (NP) is a substance produced in the heart. The measurement of NP can be used to indicate the condition of the heart. For some time, NP has been used for diagnosing heart failure and predicting what is likely to happen. We wanted to discover if NP may also offer a way to manage and make the best use of medicines. Study selection and characteristics We carried out a review of all studies and the evidence is current to 15 March 2016. We found 18 studies of NP-guided treatment in which 3660 patients with heart failure took part. Patients were between 62 to 80 years old at the start of the studies. The duration of each study ranged from one to 54 months. Eight out of the 18 studies were part or fully funded by pharmaceutical companies, one was funded by a national research body, five were partially funded either by national research grants, lotteries, hospital funds and/or pharmaceutical companies and four studies did not report the funding source. Key results The evidence was unclear as to whether number of deaths from any cause varied between patients with heart failure using NP-guided treatment compared with those using a health plan alone. Nor was it clear as to whether there were less deaths when the results were separated into patients older or younger than 75 years old (age results only included three studies). Furthermore, we found that the evidence was unclear whether the number of deaths from heart failure alone varied between the NP-guided treatment or health plan alone groups. We found that hospital admission due to heart failure may be reduced in the patients using NP-guided treatment compared with a health plan alone. Based on these results we would expect that out of 1000 patients with heart failure who are guided by a health plan alone, 377 would experience an admission to hospital due to heart failure. Whereas, between 230 and 301 patients would experience an admission to hospital due to heart failure if they received NP-guided treatment. However, the evidence was unclear as to whether the numbers of hospital admission from any cause were affected. There was limited information about either harms to patients, or the cost of the treatment. It was not possible to combine the results from these studies for these outcomes. However, four of the six studies commented that they found no difference in harms or less difference in harms between the patients using NP-guided treatment compared with a health plan alone, the other two studies did not comment. Four studies reported results on costs, three of these reported there may be lower costs in the NP-guided treatment groups compared with health plan groups. Lower costs appeared to be due to less cost for hospital stays. However, one study reported that NP-guided treatment was unlikely to be cost-effective. The evidence was unclear as to if a benefit was shown in the replies to quality-of-life surveys when comparing between NP-guided treatment and health plan only groups. Quality of evidence Overall evidence for death from all causes, from heart failure alone and for hospital admission was of low quality. For harm to patients and cost outcomes the quality of evidence was low, whilst evidence for patients' quality of life surveys was very low. For all outcomes there was little evidence due to the way the studies were conducted. In addition, for harm to patients and cost of treatment there were differences in the type of information available.

Background: Epidemiological studies have shown that taller people are at increased risk of cancer, but it is unclear if height-associated risks vary by cancer site, or by other factors such as smoking and socioeconomic status. Our aim was to investigate these associations in a large UK prospective cohort with sufficient information on incident cancer to allow direct comparison of height-associated risk across cancer sites and in relation to major potential confounding and modifying factors. Methods: Information on height and other factors relevant for cancer was obtained in 1996-2001 for middle-aged women without previous cancer who were followed up for cancer incidence. We used Cox regression models to calculate adjusted relative risks (RRs) per 10 cm increase in measured height for total incident cancer and for 17 specific cancer sites, taking attained age as the underlying time variable. We also did a meta-analysis of published results from prospective studies of total cancer risk in relation to height. Findings: 1 297 124 women included in our analysis were followed up for a total of 11·7 million person-years (median 9·4 years per woman, IQR 8·4-10·2), during which time 97 376 incident cancers occurred. The RR for total cancer was of 1·16 (95% CI 1·14-1·17; p

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 P 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.

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

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 [greater than or equal to]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.

Introduction Many studies investigating long-term vascular disease risk associated with hypertensive pregnancies examined risks in relatively young women among whom coronary heart disease (CHD) is uncommon. Objective We examined the prospective relation between a history of hypertension during pregnancy and CHD in middle-aged women. Methods At study baseline of the UK Million Women study (1996–2001), 1.1 million parous women (mean age = 56 years) without vascular disease reported their medical history including, including information on having had high blood pressure during pregnancy, as well as other factors relating to health and lifestyle. They were followed for incident CHD (hospitalisation or death), and adjusted relative risks were calculated using Cox regression. Results Of the 1.1 million women in the cohort study, 26% reported having had a hypertensive pregnancy. Among these women who reported having had hypertension during pregnancy, 27% also reported being treated for hypertension at baseline; in contrast, among women without a hypertensive pregnancy, only 10% reported being treated for hypertension at baseline. After a mean follow-up of 12 years, over 68,000 women subsequently had a first coronary disease event. Overall, a hypertensive pregnancy compared to those without such history was associated with an increased risk of CHD (relative risk = 1.29, P Conclusion Hypertension during pregnancy was associated with increased risk of incident CHD, mainly because many of these women will have had hypertension in their 50s and 60s, which has a substantially greater effect on coronary disease than hypertension during pregnancy. The high proportion of those who reported having had hypertension during pregnancy in this cohort may suggest that this group included women who experienced hypertensive pregnancy that did not meet clinical criteria for specific disorders such as preeclampsia, the prevalence of which is usually relatively low.

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.

Hip fracture risk is known to increase with physical inactivity and decrease with obesity, but there is little information on their combined effects. We report on the separate and combined effects of body mass index (BMI) and physical activity on hospital admissions for hip fracture among postmenopausal women in a large prospective UK study. Baseline information on body size, physical activity, and other relevant factors was collected in 1996-2001, and participants were followed for incident hip fractures by record linkage to National Health Service (NHS) hospital admission data. Cox regression was used to calculate adjusted relative risks of hip fracture. Among 925,345 postmenopausal women followed for an average of 6.2 years, 2582 were admitted to hospital with an incident hip fracture. Hip fracture risk increased with decreasing BMI: Compared with obese women (BMI of 30+ kg/m2), relative risks were 1.71 [95% confidence interval (CI) 1.47-1.97)] for BMI of 25.0 to 29.9 kg/m2 and 2.55 (95% CI 2.22-2.94) for BMI of 20.0 to 24.9 kg/m2. The increase in fracture risk per unit decrease in BMI was significantly greater among lean women than among overweight women (pa