Summary Background The benefits of blood pressure lowering treatment for prevention of cardiovascular disease are well established. However, the extent to which these effects differ by baseline blood ...pressure, presence of comorbidities, or drug class is less clear. We therefore performed a systematic review and meta-analysis to clarify these differences. Method For this systematic review and meta-analysis, we searched MEDLINE for large-scale blood pressure lowering trials, published between Jan 1, 1966, and July 7, 2015, and we searched the medical literature to identify trials up to Nov 9, 2015. All randomised controlled trials of blood pressure lowering treatment were eligible for inclusion if they included a minimum of 1000 patient-years of follow-up in each study arm. No trials were excluded because of presence of baseline comorbidities, and trials of antihypertensive drugs for indications other than hypertension were eligible. We extracted summary-level data about study characteristics and the outcomes of major cardiovascular disease events, coronary heart disease, stroke, heart failure, renal failure, and all-cause mortality. We used inverse variance weighted fixed-effects meta-analyses to pool the estimates. Results We identified 123 studies with 613 815 participants for the tabular meta-analysis. Meta-regression analyses showed relative risk reductions proportional to the magnitude of the blood pressure reductions achieved. Every 10 mm Hg reduction in systolic blood pressure significantly reduced the risk of major cardiovascular disease events (relative risk RR 0·80, 95% CI 0·77–0·83), coronary heart disease (0·83, 0·78–0·88), stroke (0·73, 0·68–0·77), and heart failure (0·72, 0·67–0·78), which, in the populations studied, led to a significant 13% reduction in all-cause mortality (0·87, 0·84–0·91). However, the effect on renal failure was not significant (0·95, 0·84–1·07). Similar proportional risk reductions (per 10 mm Hg lower systolic blood pressure) were noted in trials with higher mean baseline systolic blood pressure and trials with lower mean baseline systolic blood pressure (all ptrend >0·05). There was no clear evidence that proportional risk reductions in major cardiovascular disease differed by baseline disease history, except for diabetes and chronic kidney disease, for which smaller, but significant, risk reductions were detected. β blockers were inferior to other drugs for the prevention of major cardiovascular disease events, stroke, and renal failure. Calcium channel blockers were superior to other drugs for the prevention of stroke. For the prevention of heart failure, calcium channel blockers were inferior and diuretics were superior to other drug classes. Risk of bias was judged to be low for 113 trials and unclear for 10 trials. Heterogeneity for outcomes was low to moderate; the I2 statistic for heterogeneity for major cardiovascular disease events was 41%, for coronary heart disease 25%, for stroke 26%, for heart failure 37%, for renal failure 28%, and for all-cause mortality 35%. Interpretation Blood pressure lowering significantly reduces vascular risk across various baseline blood pressure levels and comorbidities. Our results provide strong support for lowering blood pressure to systolic blood pressures less than 130 mm Hg and providing blood pressure lowering treatment to individuals with a history of cardiovascular disease, coronary heart disease, stroke, diabetes, heart failure, and chronic kidney disease. Funding National Institute for Health Research and Oxford Martin School.
Peripheral artery disease is a major cardiovascular disease that affected 202 million people worldwide in 2010. In the past decade, new epidemiological data on peripheral artery disease have emerged, ...enabling us to provide updated estimates of the prevalence and risk factors for peripheral artery disease globally and regionally and, for the first time, nationally.
For this systematic review and analysis, we did a comprehensive literature search for studies reporting on the prevalence of peripheral artery disease in the general population that were published between Jan 1, 2011, and April 30, 2019, in PubMed, MEDLINE, Embase, the Global Health database, CINAHL, the Global Health Library, the Allied and Complementary Medicine Database, and ProQuest Dissertations and Theses Global. We also included the Global Peripheral Artery Disease Study of 2013 and the China Peripheral Artery Disease Study as sources. Peripheral artery disease had to be defined as an ankle–brachial index lower than or equal to 0·90. With a purpose-built data collection form, data on study characteristics, sample characteristics, prevalence, and risk factors were abstracted from all the included studies identified from the sources. Age-specific and sex-specific prevalence of peripheral artery disease was estimated in both high-income countries (HICs) and low-income and middle-income countries (LMICs). We also did random-effects meta-analyses to pool the odds ratios of 30 risk factors for peripheral artery disease in HICs and LMICs. UN population data were used to generate the number of people affected by the disease in 2015. Finally, we derived the regional and national numbers of people with peripheral artery disease on the basis of a risk factor-based model.
We included 118 articles for systematic review and analysis. The prevalence of peripheral artery disease increased consistently with age. At younger ages, prevalence was slightly higher in LMICs than HICs (4·32%, 95% CI 3·01–6·29, vs 3·54%, 1·17–10·24, at 40–44 years), but the increase with age was greater in HICs than LMICs, leading to a higher prevalence in HICs than LMICs at older ages (21·24%, 15·22–28·90, vs 12·04%, 8·67–16·60, at 80–84 years). In HICs, prevalence was slightly higher in women than in men up to age 75 years (eg, 7·81%, 3·97–14·77, vs 6·60%, 3·74–11·38, at 55–59 years), whereas in LMICs little difference was found between women and men (eg, 6·40%, 5·06–8·05, vs 6·37%, 4·74–8·49, at 55–59 years). Overall, the global prevalence of peripheral artery disease in people aged 25 years and older was 5·56%, 3·79–8·55, and the prevalence estimate was higher in HICs than that in LMICs (7·37%, 4·35–13·66, vs 5·09%, 3·64–7·24). Smoking, diabetes, hypertension, and hypercholesterolaemia were major risk factors for peripheral artery disease. Globally, a total of 236·62 million people aged 25 years and older were living with peripheral artery disease in 2015, among whom 72·91% were in LMICs. The Western Pacific Region had the most peripheral artery disease cases (74·08 million), whereas the Eastern Mediterranean Region had the least (14·67 million). More than two thirds of the global peripheral artery disease cases were concentrated in 15 individual countries in 2015.
Peripheral artery disease continues to become an increasingly serious public health problem, especially in LMICs. With the demographic trend towards ageing and projected rise in important risk factors, a larger burden of peripheral artery disease is to be expected in the foreseeable future.
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A large study shows that irradiation of the chest in women with breast cancer delivers an average of about 5 Gy and that the risk of a subsequent coronary event increases at a rate of 7.4% per gray ...in a linear fashion, without a threshold and with no apparent decline over time.
Randomized trials have shown that radiotherapy for early-stage breast cancer can reduce the rates of recurrence and of death from breast cancer.
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However, long-term follow-up in some trials has shown that radiotherapy can also increase the risk of ischemic heart disease, presumably through incidental irradiation of the heart.
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Radiotherapy regimens for breast cancer have changed since the women in these trials were irradiated, and the doses of radiation to which the heart is exposed are now generally lower.
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Nevertheless, in most women, the heart still receives doses of 1 to 5 Gy.
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Several studies have suggested that . . .
Summary Background Recent hypertension guidelines have reversed previous recommendations for lower blood pressure targets in high-risk patients, such as those with cardiovascular disease, renal ...disease, or diabetes. This change represents uncertainty about whether more intensive blood pressure-lowering strategies are associated with greater reductions in risk of major cardiovascular and renal events. We aimed to assess the efficacy and safety of intensive blood pressure-lowering strategies. Methods For this updated systematic review and meta-analysis, we systematically searched MEDLINE, Embase, and the Cochrane Library for trials published between Jan 1, 1950, and Nov 3, 2015. We included randomised controlled trials with at least 6 months' follow-up that randomly assigned participants to more intensive versus less intensive blood pressure-lowering treatment, with different blood pressure targets or different blood pressure changes from baseline. We did not use any age or language restrictions. We did a meta-analysis of blood pressure reductions on relative risk (RR) of major cardiovascular events (myocardial infarction, stroke, heart failure, or cardiovascular death, separately and combined), and non-vascular and all-cause mortality, end-stage kidney disease, and adverse events, as well as albuminuria and progression of retinopathy in trials done in patients with diabetes. Findings We identified 19 trials including 44 989 participants, in whom 2496 major cardiovascular events were recorded during a mean 3·8 years of follow-up (range 1·0–8·4 years). Our meta-analysis showed that after randomisation, patients in the more intensive blood pressure-lowering treatment group had mean blood pressure levels of 133/76 mm Hg, compared with 140/81 mm Hg in the less intensive treatment group. Intensive blood pressure-lowering treatment achieved RR reductions for major cardiovascular events (14% 95% CI 4–22), myocardial infarction (13% 0–24), stroke (22% 10–32), albuminuria (10% 3–16), and retinopathy progression (19% 0–34). However, more intensive treatment had no clear effects on heart failure (15% 95% CI −11 to 34), cardiovascular death (9% –11 to 26), total mortality (9% –3 to 19), or end-stage kidney disease (10% –6 to 23). The reduction in major cardiovascular events was consistent across patient groups, and additional blood pressure lowering had a clear benefit even in patients with systolic blood pressure lower than 140 mm Hg. The absolute benefits were greatest in trials in which all enrolled patients had vascular disease, renal disease, or diabetes. Serious adverse events associated with blood pressure lowering were only reported by six trials and had an event rate of 1·2% per year in intensive blood pressure-lowering group participants, compared with 0·9% in the less intensive treatment group (RR 1·35 95% CI 0·93–1·97). Severe hypotension was more frequent in the more intensive treatment regimen (RR 2·68 1·21–5·89, p=0·015), but the absolute excess was small (0·3% vs 0·1% per person-year for the duration of follow-up). Interpretation Intensive blood pressure lowering provided greater vascular protection than standard regimens. In high-risk patients, there are additional benefits from more intensive blood pressure lowering, including for those with systolic blood pressure below 140 mmHg. The net absolute benefits of intensive blood pressure lowering in high-risk individuals are large. Funding National Health and Medical Research Council of Australia.
Large-scale and contemporary population-based studies of heart failure incidence are needed to inform resource planning and research prioritisation but current evidence is scarce. We aimed to assess ...temporal trends in incidence and prevalence of heart failure in a large general population cohort from the UK, between 2002 and 2014.
For this population-based study, we used linked primary and secondary electronic health records of 4 million individuals from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex. Eligible patients were aged 16 years and older, had contributed data between Jan 1, 2002, and Dec 31, 2014, had an acceptable record according to CPRD quality control, were approved for CPRD and Hospital Episodes Statistics linkage, and were registered with their general practice for at least 12 months. For patients with incident heart failure, we extracted the most recent measurement of baseline characteristics (within 2 years of diagnosis) from electronic health records, as well as information about comorbidities, socioeconomic status, ethnicity, and region. We calculated standardised rates by applying direct age and sex standardisation to the 2013 European Standard Population, and we inferred crude rates by applying year-specific, age-specific, and sex-specific incidence to UK census mid-year population estimates. We assumed no heart failure for patients aged 15 years or younger and report total incidence and prevalence for all ages (>0 years).
From 2002 to 2014, heart failure incidence (standardised by age and sex) decreased, similarly for men and women, by 7% (from 358 to 332 per 100 000 person-years; adjusted incidence ratio 0·93, 95% CI 0·91–0·94). However, the estimated absolute number of individuals with newly diagnosed heart failure in the UK increased by 12% (from 170 727 in 2002 to 190 798 in 2014), largely due to an increase in population size and age. The estimated absolute number of prevalent heart failure cases in the UK increased even more, by 23% (from 750 127 to 920 616). Over the study period, patient age and multi-morbidity at first presentation of heart failure increased (mean age 76·5 years SD 12·0 to 77·0 years 12·9, adjusted difference 0·79 years, 95% CI 0·37–1·20; mean number of comorbidities 3·4 SD 1·9 vs 5·4 2·5; adjusted difference 2·0, 95% CI 1·9–2·1). Socioeconomically deprived individuals were more likely to develop heart failure than were affluent individuals (incidence rate ratio 1·61, 95% CI 1·58–1·64), and did so earlier in life than those from the most affluent group (adjusted difference −3·51 years, 95% CI −3·77 to −3·25). From 2002 to 2014, the socioeconomic gradient in age at first presentation with heart failure widened. Socioeconomically deprived individuals also had more comorbidities, despite their younger age.
Despite a moderate decline in standardised incidence of heart failure, the burden of heart failure in the UK is increasing, and is now similar to the four most common causes of cancer combined. The observed socioeconomic disparities in disease incidence and age at onset within the same nation point to a potentially preventable nature of heart failure that still needs to be tackled.
British Heart Foundation and National Institute for Health Research.
Despite the vast amount of evidence on the benefits of blood pressure lowering accumulated to date, elevated blood pressure is still the leading risk factor for disease and disability worldwide. The ...purpose of this review is to summarize the epidemiological evidence underpinning the association between blood pressure and a range of conditions. This review focuses on the association between systolic and diastolic blood pressures and the risk of cardiovascular and renal disease. Evidence for and against the existence of a J-shaped curve association between blood pressure and cardiovascular risk, and differences in the predictive power of systolic, diastolic, and pulse pressure, are described. In addition, global and regional trends in blood pressure levels and management of hypertension are reviewed.
Today, despite decades of developments in medicine and the growing interest in precision healthcare, vast majority of diagnoses happen once patients begin to show noticeable signs of illness. Early ...indication and detection of diseases, however, can provide patients and carers with the chance of early intervention, better disease management, and efficient allocation of healthcare resources. The latest developments in machine learning (including deep learning) provides a great opportunity to address this unmet need. In this study, we introduce BEHRT: A deep neural sequence transduction model for electronic health records (EHR), capable of simultaneously predicting the likelihood of 301 conditions in one's future visits. When trained and evaluated on the data from nearly 1.6 million individuals, BEHRT shows a striking improvement of 8.0-13.2% (in terms of average precision scores for different tasks), over the existing state-of-the-art deep EHR models. In addition to its scalability and superior accuracy, BEHRT enables personalised interpretation of its predictions; its flexible architecture enables it to incorporate multiple heterogeneous concepts (e.g., diagnosis, medication, measurements, and more) to further improve the accuracy of its predictions; its (pre-)training results in disease and patient representations can be useful for future studies (i.e., transfer learning).
Multimorbidity in people with cardiovascular disease (CVD) is common, but large-scale contemporary reports of patterns and trends in patients with incident CVD are limited. We investigated the burden ...of comorbidities in patients with incident CVD, how it changed between 2000 and 2014, and how it varied by age, sex, and socioeconomic status (SES).
We used the UK Clinical Practice Research Datalink with linkage to Hospital Episode Statistics, a population-based dataset from 674 UK general practices covering approximately 7% of the current UK population. We estimated crude and age/sex-standardised (to the 2013 European Standard Population) prevalence and 95% confidence intervals for 56 major comorbidities in individuals with incident non-fatal CVD. We further assessed temporal trends and patterns by age, sex, and SES groups, between 2000 and 2014. Among a total of 4,198,039 people aged 16 to 113 years, 229,205 incident cases of non-fatal CVD, defined as first diagnosis of ischaemic heart disease, stroke, or transient ischaemic attack, were identified. Although the age/sex-standardised incidence of CVD decreased by 34% between 2000 to 2014, the proportion of CVD patients with higher numbers of comorbidities increased. The prevalence of having 5 or more comorbidities increased 4-fold, rising from 6.3% (95% CI 5.6%-17.0%) in 2000 to 24.3% (22.1%-34.8%) in 2014 in age/sex-standardised models. The most common comorbidities in age/sex-standardised models were hypertension (28.9% 95% CI 27.7%-31.4%), depression (23.0% 21.3%-26.0%), arthritis (20.9% 19.5%-23.5%), asthma (17.7% 15.8%-20.8%), and anxiety (15.0% 13.7%-17.6%). Cardiometabolic conditions and arthritis were highly prevalent among patients aged over 40 years, and mental illnesses were highly prevalent in patients aged 30-59 years. The age-standardised prevalence of having 5 or more comorbidities was 19.1% (95% CI 17.2%-22.7%) in women and 12.5% (12.0%-13.9%) in men, and women had twice the age-standardised prevalence of depression (31.1% 28.3%-35.5% versus 15.0% 14.3%-16.5%) and anxiety (19.6% 17.6%-23.3% versus 10.4% 9.8%-11.8%). The prevalence of depression was 46% higher in the most deprived fifth of SES compared with the least deprived fifth (age/sex-standardised prevalence of 38.4% 31.2%-62.0% versus 26.3% 23.1%-34.5%, respectively). This is a descriptive study of routine electronic health records in the UK, which might underestimate the true prevalence of diseases.
The burden of multimorbidity and comorbidity in patients with incident non-fatal CVD increased between 2000 and 2014. On average, older patients, women, and socioeconomically deprived groups had higher numbers of comorbidities, but the type of comorbidities varied by age and sex. Cardiometabolic conditions contributed substantially to the burden, but 4 out of the 10 top comorbidities were non-cardiometabolic. The current single-disease paradigm in CVD management needs to broaden and incorporate the large and increasing burden of comorbidities.
Hypertension is a common comorbidity in patients with heart failure and most drugs that have demonstrated to improve prognosis in this population have the potential to reduce blood pressure. ...Nonetheless, the relationship between blood pressure and clinical outcomes and the relevance of blood pressure reduction in heart failure remains unclear. This narrative review summarises the evidence currently available to guide blood pressure treatment in this patient group and highlights key questions for further research. In patients with heart failure with reduced ejection fraction, guidelines consensually recommend treating hypertension with drugs that have compelling indications in heart failure, with a target blood pressure of 130/80 mmHg. In patients with heart failure with preserved ejection fraction, guidelines acknowledge that the optimal treatment strategy remains unclear and thus recommend adopting a similar treatment strategy to patients with reduced ejection fraction. In any case, low blood pressure should not deter uptitration of drugs otherwise indicated to improve prognosis in heart failure, provided that patients tolerate drugs without adverse events. In the absence of evidence for modification of treatment efficacy and safety by baseline blood pressure, it is likely that treatment may actually lead to higher absolute risk reduction in patients with the lowest blood pressure. Special considerations and treatment adjustments are needed in the elderly as well as in patients with diabetes, chronic kidney disease and atrial fibrillation. More evidence is needed on blood pressure management in patients with heart failure in general, in whom the increasing burden of multimorbidity adds further complexity to treatment.
Higher levels of physical activity (PA) are associated with a lower risk of cardiovascular disease (CVD). However, uncertainty exists on whether the inverse relationship between PA and incidence of ...CVD is greater at the highest levels of PA. Past studies have mostly relied on self-reported evidence from questionnaire-based PA, which is crude and cannot capture all PA undertaken. We investigated the association between accelerometer-measured moderate, vigorous, and total PA and incident CVD.
We obtained accelerometer-measured moderate-intensity and vigorous-intensity physical activities and total volume of PA, over a 7-day period in 2013-2015, for 90,211 participants without prior or concurrent CVD in the UK Biobank cohort. Participants in the lowest category of total PA smoked more, had higher body mass index and C-reactive protein, and were diagnosed with hypertension. PA was associated with 3,617 incident CVD cases during 440,004 person-years of follow-up (median (interquartile range IQR): 5.2 (1.2) years) using Cox regression models. We found a linear dose-response relationship for PA, whether measured as moderate-intensity, vigorous-intensity, or as total volume, with risk of incident of CVD. Hazard ratios (HRs) and 95% confidence intervals for increasing quarters of the PA distribution relative to the lowest fourth were for moderate-intensity PA: 0.71 (0.65, 0.77), 0.59 (0.54, 0.65), and 0.46 (0.41, 0.51); for vigorous-intensity PA: 0.70 (0.64, 0.77), 0.54 (0.49,0.59), and 0.41 (0.37,0.46); and for total volume of PA: 0.73 (0.67, 0.79), 0.63 (0.57, 0.69), and 0.47 (0.43, 0.52). We took account of potential confounders but unmeasured confounding remains a possibility, and while removal of early deaths did not affect the estimated HRs, we cannot completely dismiss the likelihood that reverse causality has contributed to the findings. Another possible limitation of this work is the quantification of PA intensity-levels based on methods validated in relatively small studies.
In this study, we found no evidence of a threshold for the inverse association between objectively measured moderate, vigorous, and total PA with CVD. Our findings suggest that PA is not only associated with lower risk for of CVD, but the greatest benefit is seen for those who are active at the highest level.
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