Summary This Review is intended to help clinicians, patients, and the public make informed decisions about statin therapy for the prevention of heart attacks and strokes. It explains how the evidence ...that is available from randomised controlled trials yields reliable information about both the efficacy and safety of statin therapy. In addition, it discusses how claims that statins commonly cause adverse effects reflect a failure to recognise the limitations of other sources of evidence about the effects of treatment. Large-scale evidence from randomised trials shows that statin therapy reduces the risk of major vascular events (ie, coronary deaths or myocardial infarctions, strokes, and coronary revascularisation procedures) by about one-quarter for each mmol/L reduction in LDL cholesterol during each year (after the first) that it continues to be taken. The absolute benefits of statin therapy depend on an individual's absolute risk of occlusive vascular events and the absolute reduction in LDL cholesterol that is achieved. For example, lowering LDL cholesterol by 2 mmol/L (77 mg/dL) with an effective low-cost statin regimen (eg, atorvastatin 40 mg daily, costing about £2 per month) for 5 years in 10 000 patients would typically prevent major vascular events from occurring in about 1000 patients (ie, 10% absolute benefit) with pre-existing occlusive vascular disease (secondary prevention) and in 500 patients (ie, 5% absolute benefit) who are at increased risk but have not yet had a vascular event (primary prevention). Statin therapy has been shown to reduce vascular disease risk during each year it continues to be taken, so larger absolute benefits would accrue with more prolonged therapy, and these benefits persist long term. The only serious adverse events that have been shown to be caused by long-term statin therapy—ie, adverse effects of the statin—are myopathy (defined as muscle pain or weakness combined with large increases in blood concentrations of creatine kinase), new-onset diabetes mellitus, and, probably, haemorrhagic stroke. Typically, treatment of 10 000 patients for 5 years with an effective regimen (eg, atorvastatin 40 mg daily) would cause about 5 cases of myopathy (one of which might progress, if the statin therapy is not stopped, to the more severe condition of rhabdomyolysis), 50–100 new cases of diabetes, and 5–10 haemorrhagic strokes. However, any adverse impact of these side-effects on major vascular events has already been taken into account in the estimates of the absolute benefits. Statin therapy may cause symptomatic adverse events (eg, muscle pain or weakness) in up to about 50–100 patients (ie, 0·5–1·0% absolute harm) per 10 000 treated for 5 years. However, placebo-controlled randomised trials have shown definitively that almost all of the symptomatic adverse events that are attributed to statin therapy in routine practice are not actually caused by it (ie, they represent misattribution). The large-scale evidence available from randomised trials also indicates that it is unlikely that large absolute excesses in other serious adverse events still await discovery. Consequently, any further findings that emerge about the effects of statin therapy would not be expected to alter materially the balance of benefits and harms. It is, therefore, of concern that exaggerated claims about side-effect rates with statin therapy may be responsible for its under-use among individuals at increased risk of cardiovascular events. For, whereas the rare cases of myopathy and any muscle-related symptoms that are attributed to statin therapy generally resolve rapidly when treatment is stopped, the heart attacks or strokes that may occur if statin therapy is stopped unnecessarily can be devastating.
Summary Background In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different ...AEs have been reported than in blinded trials. Methods In the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial, patients aged 40–79 years with hypertension, at least three other cardiovascular risk factors, and fasting total cholesterol concentrations of 6·5 mmol/L or lower, and who were not taking a statin or fibrate, had no history of myocardial infarction, and were not being treated for angina were randomly assigned to atorvastatin 10 mg daily or matching placebo in a randomised double-blind placebo-controlled phase. In a subsequent non-randomised non-blind extension phase (initiated because of early termination of the trial because efficacy of atorvastatin was shown), all patients were offered atorvastatin 10 mg daily open label. We classified AEs using the Medical Dictionary for Regulatory Activities. We blindly adjudicated all reports of four prespecified AEs of interest—muscle-related, erectile dysfunction, sleep disturbance, and cognitive impairment—and analysed all remaining AEs grouped by system organ class. Rates of AEs are given as percentages per annum. Results The blinded randomised phase was done between February, 1998, and December, 2002; we included 101 80 patients in this analysis (5101 50% in the atorvastatin group and 5079 50% in the placebo group), with a median follow-up of 3·3 years (IQR 2·7–3·7). The non-blinded non-randomised phase was done between December, 2002, and June, 2005; we included 9899 patients in this analysis (6409 65% atorvastatin users and 3490 35% non-users), with a median follow-up of 2·3 years (2·2–2·4). During the blinded phase, muscle-related AEs (298 2·03% per annum vs 283 2·00% per annum; hazard ratio 1·03 95% CI 0·88–1·21; p=0·72) and erectile dysfunction (272 1·86% per annum vs 302 2·14% per annum; 0·88 0·75–1·04; p=0·13) were reported at a similar rate by participants randomly assigned to atorvastatin or placebo. The rate of reports of sleep disturbance was significantly lower among participants assigned atorvastatin than assigned placebo (149 1·00% per annum vs 210 1·46% per annum; 0·69 0·56–0·85; p=0·0005). Too few cases of cognitive impairment were reported for a statistically reliable analysis (31 0·20% per annum vs 32 0·22% per annum; 0·94 0·57–1·54; p=0·81). We observed no significant differences in the rates of all other reported AEs, with the exception of an excess of renal and urinary AEs among patients assigned atorvastatin (481 1·87% per annum vs 392 1·51% per annum; 1·23 1·08–1·41; p=0·002). By contrast, during the non-blinded non-randomised phase, muscle-related AEs were reported at a significantly higher rate by participants taking statins than by those who were not (161 1·26% per annum vs 124 1·00% per annum; 1·41 1·10–1·79; p=0·006). We noted no significant differences between statin users and non-users in the rates of other AEs, with the exception of musculoskeletal and connective tissue disorders (992 8·69% per annum vs 831 7·45% per annum; 1·17 1·06–1·29; p=0·001) and blood and lymphatic system disorders (114 0·88% per annum vs 80 0·64% per annum; 1·40 1·04–1·88; p=0·03), which were reported more commonly by statin users than by non-users. Interpretation These analyses illustrate the so-called nocebo effect, with an excess rate of muscle-related AE reports only when patients and their doctors were aware that statin therapy was being used and not when its use was blinded. these results will help assure both physicians and patients that most AEs associated with statins are not causally related to use of the drug and should help counter the adverse effect on public health of exaggerated claims about statin-related side-effects. Funding Pfizer, Servier Research Group, and Leo Laboratories.
Summary Background Chinese men now smoke more than a third of the world's cigarettes, following a large increase in urban then rural usage. Conversely, Chinese women now smoke far less than in ...previous generations. We assess the oppositely changing effects of tobacco on male and female mortality. Methods Two nationwide prospective studies 15 years apart recruited 220 000 men in about 1991 at ages 40–79 years (first study) and 210 000 men and 300 000 women in about 2006 at ages 35–74 years (second study), with follow-up during 1991–99 (mid-year 1995) and 2006–14 (mid-year 2010), respectively. Cox regression yielded sex-specific adjusted mortality rate ratios (RRs) comparing smokers (including any who had stopped because of illness, but not the other ex-smokers, who are described as having stopped by choice) versus never-smokers. Findings Two-thirds of the men smoked; there was little dependence of male smoking prevalence on age, but many smokers had not smoked cigarettes throughout adult life. Comparing men born before and since 1950, in the older generation, the age at which smoking had started was later and, particularly in rural areas, lifelong exclusive cigarette use was less common than in the younger generation. Comparing male mortality RRs in the first study (mid-year 1995) versus those in the second study (mid-year 2010), the proportional excess risk among smokers (RR-1) approximately doubled over this 15-year period (urban: RR 1·32 95% CI 1·24–1·41 vs 1·65 1·53–1·79; rural: RR 1·13 1·09–1·17 vs 1·22 1·16–1·29), as did the smoking-attributed fraction of deaths at ages 40–79 years (urban: 17% vs 26%; rural: 9% vs 14%). In the second study, urban male smokers who had started before age 20 years (which is now typical among both urban and rural young men) had twice the never-smoker mortality rate (RR 1·98, 1·79–2·19, approaching Western RRs), with substantial excess mortality from chronic obstructive pulmonary disease (COPD RR 9·09, 5·11–16·15), lung cancer (RR 3·78, 2·78–5·14), and ischaemic stroke or ischaemic heart disease (combined RR 2·03, 1·66–2·47). Ex-smokers who had stopped by choice (only 3% of ever-smokers in 1991, but 9% in 2006) had little smoking-attributed risk more than 10 years after stopping. Among Chinese women, however, there has been a tenfold intergenerational reduction in smoking uptake rates. In the second study, among women born in the 1930s, 1940s, 1950s, and since 1960 the proportions who had smoked were, respectively, 10%, 5%, 2%, and 1% (3097/30 943, 3265/62 246, 2339/97 344, and 1068/111 933). The smoker versus non-smoker RR of 1·51 (1·40–1·63) for all female mortality at ages 40–79 years accounted for 5%, 3%, 1%, and <1%, respectively, of all the female deaths in these four successive birth cohorts. In 2010, smoking caused about 1 million (840 000 male, 130 000 female) deaths in China. Interpretation Smoking will cause about 20% of all adult male deaths in China during the 2010s. The tobacco-attributed proportion is increasing in men, but low, and decreasing, in women. Although overall adult mortality rates are falling, as the adult population of China grows and the proportion of male deaths due to smoking increases, the annual number of deaths in China that are caused by tobacco will rise from about 1 million in 2010 to 2 million in 2030 and 3 million in 2050, unless there is widespread cessation. Funding Wellcome Trust, MRC, BHF, CR-UK, Kadoorie Charitable Foundation, Chinese MoST and NSFC
What makes UK Biobank special? Collins, Rory
The Lancet (British edition),
03/2012, Letnik:
379, Številka:
9822
Journal Article
Recenzirano
... conditions are typically caused by many diff erent exposures that might each have moderate eff ects and interact with each other in complex ways.3,4 To investigate a wide range of exposures, ...extensive information needs to be collected through questionnaires and physical measurements, as well as by storing biological samples that allow many diff erent types of assay (eg, genetic, proteomic, metabonomic, or biochemical). ... to study reliably the sort of eff ects of diff erent exposures that it is plausible to expect, many thousands of cases of a specifi c disease may be required.4 Prospective cohorts have a number of advantages for the comprehensive and reliable quantifi cation of the combined eff ects of lifestyle, environment, genes, and other exposures on health outcomes.3,5 In particular, exposures can be assessed before they are aff ected by disease or its treatment, or by a person's response to developing disease.
Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of ...middle and old age.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several countries affected by the COVID-19 pandemic have reported a substantial drop in the number of patients attending the emergency department with acute coronary syndromes and a reduced number of ...cardiac procedures. We aimed to understand the scale, nature, and duration of changes to admissions for different types of acute coronary syndrome in England and to evaluate whether in-hospital management of patients has been affected as a result of the COVID-19 pandemic.
We analysed data on hospital admissions in England for types of acute coronary syndrome from Jan 1, 2019, to May 24, 2020, that were recorded in the Secondary Uses Service Admitted Patient Care database. Admissions were classified as ST-elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), myocardial infarction of unknown type, or other acute coronary syndromes (including unstable angina). We identified revascularisation procedures undertaken during these admissions (ie, coronary angiography without percutaneous coronary intervention PCI, PCI, and coronary artery bypass graft surgery). We calculated the numbers of weekly admissions and procedures undertaken; percentage reductions in weekly admissions and across subgroups were also calculated, with 95% CIs.
Hospital admissions for acute coronary syndrome declined from mid-February, 2020, falling from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020, a reduction of 40% (95% CI 37–43). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% (95% CI 13–20) reduction from baseline. During the period of declining admissions, there were reductions in the numbers of admissions for all types of acute coronary syndrome, including both STEMI and NSTEMI, but relative and absolute reductions were larger for NSTEMI, with 1267 admissions per week in 2019 and 733 per week by the end of March, 2020, a percent reduction of 42% (95% CI 38–46). In parallel, reductions were recorded in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%, 95% CI 12–29) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%, 29–45). The median length of stay among patients with acute coronary syndrome fell from 4 days (IQR 2–9) in 2019 to 3 days (1–5) by the end of March, 2020.
Compared with the weekly average in 2019, there was a substantial reduction in the weekly numbers of patients with acute coronary syndrome who were admitted to hospital in England by the end of March, 2020, which had been partly reversed by the end of May, 2020. The reduced number of admissions during this period is likely to have resulted in increases in out-of-hospital deaths and long-term complications of myocardial infarction and missed opportunities to offer secondary prevention treatment for patients with coronary heart disease. The full extent of the effect of COVID-19 on the management of patients with acute coronary syndrome will continue to be assessed by updating these analyses.
UK Medical Research Council, British Heart Foundation, Public Health England, Health Data Research UK, and the National Institute for Health Research Oxford Biomedical Research Centre.
UK Biobank is a population-based cohort of half a million participants aged 40-69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world's largest multi-modal imaging study, ...with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future directions.
IMPORTANCE: In China, diabetes prevalence has increased substantially in recent decades, but there are no reliable estimates of the excess mortality currently associated with diabetes. OBJECTIVES: To ...assess the proportional excess mortality associated with diabetes and estimate the diabetes-related absolute excess mortality in rural and urban areas of China. DESIGN, SETTING, AND PARTICIPANTS: A 7-year nationwide prospective study of 512 869 adults aged 30 to 79 years from 10 (5 rural and 5 urban) regions in China, who were recruited between June 2004 and July 2008 and were followed up until January 2014. EXPOSURES: Diabetes (previously diagnosed or detected by screening) recorded at baseline. MAIN OUTCOMES AND MEASURES: All-cause and cause-specific mortality, collected through established death registries. Cox regression was used to estimate adjusted mortality rate ratio (RR) comparing individuals with diabetes vs those without diabetes at baseline. RESULTS: Among the 512 869 participants, the mean (SD) age was 51.5 (10.7) years, 59% (n = 302 618) were women, and 5.9% (n = 30 280) had diabetes (4.1% in rural areas, 8.1% in urban areas, 5.8% of men, 6.1% of women, 3.1% had been previously diagnosed, and 2.8% were detected by screening). During 3.64 million person-years of follow-up, there were 24 909 deaths, including 3384 among individuals with diabetes. Compared with adults without diabetes, individuals with diabetes had a significantly increased risk of all-cause mortality (1373 vs 646 deaths per 100 000; adjusted RR, 2.00 95% CI, 1.93-2.08), which was higher in rural areas than in urban areas (rural RR, 2.17 95% CI, 2.07-2.29; urban RR, 1.83 95% CI, 1.73-1.94). Presence of diabetes was associated with increased mortality from ischemic heart disease (3287 deaths; RR, 2.40 95% CI, 2.19-2.63), stroke (4444 deaths; RR, 1.98 95% CI, 1.81-2.17), chronic liver disease (481 deaths; RR, 2.32 95% CI, 1.76-3.06), infections (425 deaths; RR, 2.29 95% CI, 1.76-2.99), and cancer of the liver (1325 deaths; RR, 1.54 95% CI, 1.28-1.86), pancreas (357 deaths; RR, 1.84 95% CI, 1.35-2.51), female breast (217 deaths; RR, 1.84 95% CI, 1.24-2.74), and female reproductive system (210 deaths; RR, 1.81 95% CI, 1.20-2.74). For chronic kidney disease (365 deaths), the RR was higher in rural areas (18.69 95% CI, 14.22-24.57) than in urban areas (6.83 95% CI, 4.73-9.88). Among those with diabetes, 10% of all deaths (16% rural; 4% urban) were due to definite or probable diabetic ketoacidosis or coma (408 deaths). CONCLUSIONS AND RELEVANCE: Among adults in China, diabetes was associated with increased mortality from a range of cardiovascular and noncardiovascular diseases. Although diabetes was more common in urban areas, it was associated with greater excess mortality in rural areas.
PDF
