1,721,092 research outputs found
Long-term effects of hemostatic variables on fatal coronary heart disease: 30-year results from the first prospective Northwick Park Heart Study (NPHS-I)
Full text linkBackground: The long-term associations of established risk factors for coronary heart disease (CHD), for example cholesterol, are well known, but not for the less familiar hemostatic variables. Objectives: To establish whether associations between hemostatic variables and CHD first identified nearly three decades ago have persisted long-term. Methods: The first Northwick Park Heart Study (NPHS-I) recruited 2167 white men and 941 white women, average age at entry 48 years, on whom measures of factor (F) VII activity (VIIc) and plasma fibrinogen were carried out, both at entry and at follow-up approximately 6 years later. Results: During a median follow-up of 29 years, 231 male and 36 female CHD deaths were recorded from notifications by the Office for National Statistics. VIIc at recruitment was significantly related to CHD mortality, corrected rate ratio, RR, per 1 SD increase 1.56 (95% CI 1.29, 1.88) in men and RR 1.78 (95% CI 1.17, 2.72) in women. Recruitment fibrinogen was also strongly related to CHD mortality in men, RR 1.63 (95% CI 1.33, 1.99) but not in women, RR 0.75 (95% CI 0.40, 1.43). The associations persisted after controlling for confounders and were confirmed using 6-year follow-up measurements and in analyses omitting deaths within 10 years of recruitment. Conclusions: The hemostatic system contributes to CHD mortality, and its effect is stable over time. For VIIc, the effect was similar in men and women, while for fibrinogen it appeared to be present only in men
Circulating markers of arterial thrombosis and late-stage age-related macular degeneration: a case-control study.
No full textPURPOSE: The aim of this study was to examine the relation of late-stage age-related macular degeneration (AMD) with markers of systemic atherothrombosis. METHODS: A hospital-based case-control study of AMD was undertaken in London, UK. Cases of AMD (n=81) and controls (n=77) were group matched for age and sex. Standard protocols were used for colour fundus photography and to classify AMD; physical examination included height, weight, history of or treatment for vascular-related diseases and smoking status. Blood samples were taken for measurement of fibrinogen, factor VIIc (FVIIc), factor VIIIc, prothrombin fragment F1.2 (F1.2), tissue plasminogen activator, and von Willebrand factor. Odds ratios from logistic regression analyses of each atherothrombotic marker with AMD were adjusted for age, sex, and established cardiovascular disease risk factors, including smoking, blood pressure, body mass index, and total cholesterol. RESULTS: After adjustment FVIIc and possibly F1.2 were inversely associated with the risk of AMD; per 1 standard deviation increase in these markers the odds ratio were, respectively, 0.62 (95% confidence interval 0.40, 0.95) and 0.71 (0.46, 1.09). None of the other atherothrombotic risk factors appeared to be related to AMD status. There was weak evidence that aspirin is associated with a lower risk of AMD. CONCLUSIONS: This study does not provide strong evidence of associations between AMD and systematic markers of arterial thrombosis, but the potential effects of FVIIc, and F1.2 are worthy of further investigation
Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials
Full text linkBackground Low-dose aspirin is of definite and substantial net benefit for many people who already have occlusive vascular disease. We have assessed the benefits and risks in primary prevention. Methods We undertook meta-analyses of serious vascular events (myocardial infarction, stroke, or vascular death) and major bleeds in six primary prevention trials (95000 individuals at low average risk, 660000 person-years, 3554 serious vascular events) and 16 secondary prevention trials (17000 individuals at high average risk, 43 000 person-years, 3306 serious vascular events) that compared long-term aspirin versus control. We report intention-to-treat analyses of first events during the scheduled treatment period. Findings in the primary prevention trials, aspirin allocation yielded a 12% proportional reduction in serious vascular events (0.51% aspirin vs 0.57% control per year, p=0.0001), due mainly to a reduction of about a fifth in non-fatal myocardial infarction (0.18% vs 0.23% per year, p<0.0001). The net effect on stroke was not significant (0.20% vs 0.21% per year, p=0.4: haernorrhagic stroke 0.04% vs 0.03%, p=0.05; other stroke 0.16% vs 0.18% per year, p=0.08). Vascular mortality did not differ significantly (0.19% vs 0.19% per year, p=0.7). Aspirin allocation increased major gastrointestinal and extracranial bleeds (0.10% vs 0.07% per year, p<0.0001), and the main risk factors for coronary disease were also risk factors for bleeding. In the secondary prevention trials, aspirin allocation yielded a greater absolute reduction in serious vascular events (6.7% vs 8.2% per year, p<0.0001), with a non-significant increase in haernorrhagic stroke but reductions of about a fifth in total stroke (2.08% vs 2.54% per year, p=0.002) and in coronary events (4.3% vs 5.3% per year, p<0.0001). In both primary and secondary prevention trials, the proportional reductions in the aggregate of all serious vascular events seemed similar for men and women. Interpretation In primary prevention without previous disease, aspirin is of uncertain net value as the reduction in occlusive events needs to be weighed against any increase in major bleeds. Further trials are in progress. Funding UK Medical Research Council, British Heart Foundation, Cancer Research UK, and the European Community Biomed Programme
Recent respiratory infection and risk of venous thromboembolism: case-control study through a general practice database.
Full text linkBACKGROUND: The association between respiratory infection and risk of heart attacks and strokes is well established. However, less evidence exists for an association between respiratory infection and venous thromboembolism (VTE). In this article, we describe the associations between respiratory infection and VTE. METHODS: All cases aged ≥18 years of first-time diagnosis of deep-vein thrombosis (DVT) or pulmonary embolism (PE) were identified together with single-matched controls from a primary care general practice database. In addition to the matching characteristics, information was collected on other potentially important confounding factors. RESULTS: There were 457/11,557 (4.0%) DVT cases with respiratory infection in the year before the index date (73 in the preceding month) compared with 262/11,557 (2.3%) controls (24 in the preceding month). There was an increased risk of DVT in the month following infection [adjusted odds ratio (OR) = 2.64, 95% confidence interval (95% CI) 1.62-4.29] which persisted up to a year. There were 180/5162 (3.5%) PE cases with respiratory infection in the year before the index date compared with 94/5162 (1.8%) controls excluding those in the preceding month to avoid the possible misdiagnosis of early PE. There was an increased risk of PE in the 3 months following infection (adjusted OR = 2.50, 95% CI 1.33-4.72) which may have persisted up to a year. CONCLUSIONS: There are strong associations between recent respiratory infection and VTE. There should be less distinction between venous and arterial events in decisions about preventing or aborting infections, especially in high-risk patients
Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials.
No full textBACKGROUND: High-dose aspirin (≥500 mg daily) reduces long-term incidence of colorectal cancer, but adverse effects might limit its potential for long-term prevention. The long-term effectiveness of lower doses (75-300 mg daily) is unknown. We assessed the effects of aspirin on incidence and mortality due to colorectal cancer in relation to dose, duration of treatment, and site of tumour. METHODS: We followed up four randomised trials of aspirin versus control in primary (Thrombosis Prevention Trial, British Doctors Aspirin Trial) and secondary (Swedish Aspirin Low Dose Trial, UK-TIA Aspirin Trial) prevention of vascular events and one trial of different doses of aspirin (Dutch TIA Aspirin Trial) and established the effect of aspirin on risk of colorectal cancer over 20 years during and after the trials by analysis of pooled individual patient data. RESULTS: In the four trials of aspirin versus control (mean duration of scheduled treatment 6·0 years), 391 (2·8%) of 14 033 patients had colorectal cancer during a median follow-up of 18·3 years. Allocation to aspirin reduced the 20-year risk of colon cancer (incidence hazard ratio [HR] 0·76, 0·60-0·96, p=0·02; mortality HR 0·65, 0·48-0·88, p=0·005), but not rectal cancer (0·90, 0·63-1·30, p=0·58; 0·80, 0·50-1·28, p=0·35). Where subsite data were available, aspirin reduced risk of cancer of the proximal colon (0·45, 0·28-0·74, p=0·001; 0·34, 0·18-0·66, p=0·001), but not the distal colon (1·10, 0·73-1·64, p=0·66; 1·21, 0·66-2·24, p=0·54; for incidence difference p=0·04, for mortality difference p=0·01). However, benefit increased with scheduled duration of treatment, such that allocation to aspirin of 5 years or longer reduced risk of proximal colon cancer by about 70% (0·35, 0·20-0·63; 0·24, 0·11-0·52; both p<0·0001) and also reduced risk of rectal cancer (0·58, 0·36-0·92, p=0·02; 0·47, 0·26-0·87, p=0·01). There was no increase in benefit at doses of aspirin greater than 75 mg daily, with an absolute reduction of 1·76% (0·61-2·91; p=0·001) in 20-year risk of any fatal colorectal cancer after 5-years scheduled treatment with 75-300 mg daily. However, risk of fatal colorectal cancer was higher on 30 mg versus 283 mg daily on long-term follow-up of the Dutch TIA trial (odds ratio 2·02, 0·70-6·05, p=0·15). INTERPRETATION: Aspirin taken for several years at doses of at least 75 mg daily reduced long-term incidence and mortality due to colorectal cancer. Benefit was greatest for cancers of the proximal colon, which are not otherwise prevented effectively by screening with sigmoidoscopy or colonoscopy. FUNDING: None
Long-term association of routine blood count (Coulter) variables on fatal coronary heart disease: 30-year results from the first prospective Northwick Park Heart Study (NPHS-I).
No full textBACKGROUND: Since evidence of a long-term association between routine blood count (Coulter) variables and coronary heart disease (CHD) is inconsistent, the authors analysed white blood cell count (WBC), red blood cell count (RBC), haemoglobin (Hgb), packed cell volume (PCV) and platelet count for their long-term associations with CHD mortality in the first Northwick Park Heart Study (NPHS-I). NPHS-I has follow-up information for >30 years on 2167 White men and 941 White women and holds entry and follow-up data on haematological variables and other known CHD risk factors. METHODS: Proportional hazards Cox models were fitted to estimate rate ratios (RRs) for the separate and joint effects of entry and follow-up Coulter variables. RESULTS: Entry RBC, PCV and Hgb were significant risk factors for CHD mortality after adjustment for gender but only PCV remained significant after adjustment for potential confounders [RR per 1 standard deviation (SD) increase = 1.17, 95% confidence interval (CI) 1.00-1.37]. This effect was partly reduced when the values of 6 years were analysed (RR per 1 SD increase = 1.10, 95% CI 0.93-1.30). No significant gender, smoking or age/time interactions were identified. PCV was the only significant predictor when all Coulter variables were studied jointly. CONCLUSION: PCV was found to predict CHD mortality even after controlling for classical risk factors. This may give some insight into possible mechanisms, such as an influence on thrombin production
The primary and secondary prevention of coronary artery disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).
No full textThe following chapter devoted to antithrombotic therapy for chronic coronary artery disease (CAD) is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggests that individual patient values may lead to different choices (for a full understanding of the grading see the "Grades of Recommendation" chapter by Guyatt et al in this supplement, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following: for patients with non-ST-segment elevation (NSTE)-acute coronary syndrome (ACS) we recommend daily oral aspirin (75-100 mg) [Grade 1A]. For patients with an aspirin allergy, we recommend clopidogrel, 75 mg/d (Grade 1A). For patients who have received clopidogrel and are scheduled for coronary bypass surgery, we suggest discontinuing clopidogrel for 5 days prior to the scheduled surgery (Grade 2A). For patients after myocardial infarction, after ACS, and those with stable CAD and patients after percutaneous coronary intervention (PCI), we recommend daily aspirin (75-100 mg) as indefinite therapy (Grade 1A). We recommend clopidogrel in combination with aspirin for patients experiencing ST-segment elevation (STE) and NSTE-ACS (Grade 1A). For patients with contraindications to aspirin, we recommend clopidogrel as monotherapy (Grade 1A). For long-term treatment after PCI in patients who receive antithrombotic agents such as clopidogrel or warfarin, we recommend aspirin (75 to 100 mg/d) [Grade 1B]. For patients who undergo bare metal stent placement, we recommend the combination of aspirin and clopidogrel for at least 4 weeks (Grade 1A). We recommend that patients receiving drug-eluting stents (DES) receive aspirin (325 mg/d for 3 months followed by 75-100 mg/d) and clopidogrel 75 mg/d for a minimum of 12 months (Grade 2B). For primary prevention in patients with moderate risk for a coronary event, we recommend aspirin, 75-100 mg/d, over either no antithrombotic therapy or vitamin K antagonist (Grade 1A)
Health related quality of life after combined hormone replacement therapy: randomised controlled trial
Full text linkObjective: To assess the effect of combined hormone replacement therapy (HRT) on health related quality of life. Design: Randomised placebo controlled double blind trial. Setting: General practices in United Kingdom (384), Australia (94), and New Zealand (24). Participants Postmenopausal women aged 50-69 at randomisation; 3721 women with a uterus were randomised to combined oestrogen and progestogen (n=1862) or placebo (n=1859). Data on health related quality of life at one year were available from 1043 and 1087women, respectively. Interventions: Conjugated equine oestrogen 0.625 mg plus medroxyprogesterone acetate 2.5/5.0 mg or matched placebo orally daily for one year. Main outcome measures: Health related quality of life and psychological wellbeing as measured by the women’s health questionnaire. Changes in emotional and physical menopausal symptoms as measured by a symptoms questionnaire and depression by the Centre for Epidemiologic Studies depression scale (CES-D). Overall health related quality of life and overall quality of life as measured by the European quality of life instrument (EuroQol) and visual analogue scale, respectively. Results: After one year small but significant improvements were observed in three of nine components of the women’s health questionnaire for those taking combined HRT compared with those taking placebo: vasomotor symptoms (P<0.001), sexual functioning (P<0.001), and sleep problems (P<0.001). Significantly fewer women in the combined HRT group reported hot flushes (P<0.001), night sweats (P<0.001), aching joints and muscles (P=0.001), insomnia (P<0.001), and vaginal dryness (P<0.001) than in the placebo group, but greater proportions reported breast tenderness (P<0.001) or vaginal discharge (P<0.001). Hot flushes were experienced in the combined HRT and placebo groups by 30% and 29% at trial entry and 9% and 25% at one year, respectively. No significant differences in other menopausal symptoms, depression, or overall quality of life were observed at one year. Conclusions: Combined HRT started many years after the menopause can improve health related quality of life.Amanda J Welton, Madge R Vickers, Joseph Kim, Deborah Ford, Beverley A Lawton, Alastair H MacLennan, Sarah K Meredith, Jeannett Martin and Tom W Meade for the WISDOM tea
Design and intermediate results of the Lower Extremity Arterial Disease Event Reduction (LEADER)* trial of bezafibrate in men with lower extremity arterial disease [ISRCTN4119421].
Full text linkBACKGROUND: Raised levels of both triglycerides and fibrinogen, each of which are reduced by bezafibrate, may contribute to lower extremity arterial disease (LEAD). This condition is characterized by a particularly high incidence of coronary heart disease (CHD) and stroke, but is little studied thus far in randomised controlled trials. METHOD: Patients were recruited through 85 practices in the British Medical Research Council General Practice Research Framework and through nine hospital vascular clinics. The treatment regimen, which is double-blind and placebo-controlled, is bezafibrate 400 mg/day. The 1568 patients recruited represent 86% of those eligible at screening. RESULTS: None of the anticipated side effects (mainly gastrointestinal) differed between the two groups. Nearly 80% of the total person-years accrued at 3 years were spent on trial treatment. Bezafibrate significantly reduced total cholesterol by approximately 8.0% and low-density lipoprotein (LDL)-cholesterol by approximately 9.0%, and increased high-density lipoprotein (HDL)-cholesterol by approximately 11.0% initially, falling to about 6.0% at 3 years. Triglycerides were significantly reduced by about 23.0% and fibrinogen by about 14.0%. Plasma creatinine rose by approximately 11% in those on active treatment. All of these effects were highly significant (P < 0.0001). Bezafibrate had no effect on the level of C-reactive protein (CRP). CONCLUSION: The trial recruited an unusually high proportion of eligible patients, ensuring the general applicability of its results. The fibrinogen-lowering and lipid-modifying effects of bezafibrate were confirmed. Although bezafibrate lowers fibrinogen, it has no effect on CRP; this suggests that the reduction in fibrinogen is due to an effect on its metabolism rather than suppression of an inflammatory response
Circulating levels of coagulation and inflammation markers and cancer risks: individual participant analysis of data from three long-term cohorts.
No full textBACKGROUND: Basic and clinical research support the hypothesis that activation of the coagulation and inflammation pathways may affect cancer onset, but there is limited epidemiological data to support this. METHODS: We examined a large range of haemostatic and inflammation markers, including fibrinogen, in 19 303 male participants from three English cohorts followed for up to 30 years. After excluding the first 3 years of follow-up, 2908 incident cancers were accrued. Competing risk models were fitted to estimate rate ratios (RRs) for cancer incidence, adjusting for age and other confounders. RESULTS: Baseline white blood cell (WBC) count and circulating levels of fibrinogen, C-reactive protein (CRP), factor VII antigen (VIIa) and prothrombin fragment F1.2 were positively associated with risk of smoking-related cancers, particularly lung cancer. The magnitude of these associations was highest for persistently raised fibrinogen levels. There was, however, substantial confounding by smoking with risk being fully (WBC, CRP and VIIa) or partially (fibrinogen) removed after adjustment. The pooled RRs (95% confidence interval) per one standard deviation increase in fibrinogen levels before and after adjustment for smoking habits were 1.23 (1.12, 1.36) and 1.12 (1.05, 1.20), respectively. The fibrinogen associations were present only among current smokers at entry. The effect of smoking on smoking-related cancers was partly mediated by fibrinogen levels. CONCLUSIONS: Our results are consistent with elevated circulating levels of fibrinogen and F1.2 being predictors of risk of smoking-related cancers. Further research is necessary to clarify whether elevated levels of fibrinogen and F1.2 are causally relevant or simply correlates of the smoking-cancer association
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