[Show abstract][Hide abstract] ABSTRACT: Background:
In secondary cardiovascular prevention, discontinuation of acetylsalicylic acid (ASA) is associated with an increased risk of cardiovascular events. This study assessed the impact of ASA reinitiation on the risk of myocardial infarction and coronary heart disease death.
Patients prescribed ASA for secondary cardiovascular prevention and who had had a period of ASA discontinuation of ≥90 days in 2000-2007 were identified from The Health Improvement Network (N = 10,453). Incidence of myocardial infarction/coronary heart disease death was calculated. Survival analyses using adjusted Cox proportional hazard models were performed to calculate hazard ratios and 95% confidence intervals for the risk of myocardial infarction/coronary heart disease death associated with ASA use patterns after the initial period of discontinuation. Individuals who were prescribed ASA during follow-up were considered reinitiators.
The incidence of myocardial infarction/coronary heart disease death was 8.90 cases per 1000 person-years. Risk of myocardial infarction/coronary heart disease death was similar for current ASA users, who had been continuously exposed since reinitiation, and patients who had not reinitiated ASA (hazard ratio 1.27, 95% confidence interval 0.93-1.73). Among reinitiators, an additional period of ASA discontinuation was associated with increased risk of myocardial infarction/coronary heart disease death compared with no reinitiation (current users: hazard ratio 1.46, 95% confidence interval 1.13-1.90; noncurrent users: hazard ratio 1.70, 95% confidence interval 1.31-2.21).
ASA reinitiation was not associated with a decreased risk of myocardial infarction/coronary heart disease death. This may be explained by confounding by indication/comorbidity, whereby higher-risk patients are more likely to reinitiate therapy. An additional period of ASA discontinuation among reinitiators was associated with an increased risk of myocardial infarction/coronary heart disease death.
European Journal of Preventive Cardiology 11/2015; DOI:10.1177/2047487315618795 · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diabetes and chronic kidney disease (CKD) are independent predictors of death and cardiovascular events and their concomitant prevalence has increased in recent years. The aim of this study was to characterize the effect of the estimated glomerular filtration rate (eGFR) and other factors on the risk of death and cardiovascular events in patients with type 2 diabetes.
A cohort of 57,946 patients with type 2 diabetes who were aged 20–89 years in 2000–2005 was identified from The Health Improvement Network, a UK primary care database. Incidence rates of death, myocardial infarction (MI), and ischemic stroke or transient ischemic attack (IS/TIA) were calculated overall and by eGFR category at baseline. eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) study equation. Death, MI and IS/TIA cases were detected using an automatic computer search and IS/TIA cases were further ascertained by manual review of medical records. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) for death, MI, and IS/TIA associated with eGFR category and other factors were estimated using Cox regression models adjusted for potential confounders.
Overall incidence rates of death (mean follow-up time of 6.76 years), MI (6.64 years) and IS/TIA (6.56 years) were 43.65, 9.26 and 10.39 cases per 1000 person-years, respectively. A low eGFR (15–29 mL/min) was associated with an increased risk of death (HR: 2.79; 95% CI: 2.57–3.03), MI (HR: 2.33; 95% CI: 1.89–2.87) and IS/TIA (HR: 1.77; 95% CI: 1.43–2.18) relative to eGFR ≥ 60 mL/min. Other predictors of death, MI and IS/TIA included age, longer duration of diabetes, poor control of diabetes, hyperlipidemia, smoking and a history of cardiovascular events.
In patients with type 2 diabetes, management of cardiovascular risk factors and careful monitoring of eGFR may represent opportunities to reduce the risks of death, MI and IS/TIA.
[Show abstract][Hide abstract] ABSTRACT: Background:
Some research has suggested a potential link between prenatal exposure to proton pump inhibitors (PPIs) or H2 -receptor antagonists (H2 RAs) and the development of childhood asthma.
To quantify the relative risk of asthma in children who experienced pre-natal exposure to PPIs and/or H2 RAs, adjusting for potential confounders.
In this observational cohort study (NCT01787435), women aged 18-45 years with completed pregnancies between January 1996 and December 2010 were identified from The Health Improvement Network in the United Kingdom, and were linked to infants. Hazard ratios (HRs) were estimated using Cox proportional hazard models.
Our analysis identified 2371 prenatally exposed and 7745 unexposed infants. The incidence of asthma (per 1000 person-years) was 19.52 in the unexposed cohort, 23.88 in the PPI cohort and 32.16 in the H2 RA cohort. After adjusting for maternal healthcare utilisation during the year before pregnancy, the HR for asthma in infants whose mothers received prescriptions at any time during pregnancy was 1.12 (95% confidence interval: 0.88-1.44) for PPIs and 1.43 (1.20-1.70) for H2 RAs, when compared with unexposed infants. With further adjustment for maternal comorbidities and other medications, the HR for asthma was 1.03 (0.76-1.40) for PPIs and 1.32 (1.05-1.64) for H2 RAs.
Our analysis showed no association between prenatal exposure to PPIs and asthma in childhood after adjusting for confounders. The association found for H2 RAs may be explained largely by underlying environmental or genetic factors, as suggested by reductions in hazard ratio estimates following adjustment for maternal comorbidities.
[Show abstract][Hide abstract] ABSTRACT: Background
The aim of this study was to analyse the risk of uncomplicated peptic ulcer disease (PUD) in a cohort of new users of low-dose acetylsalicylic acid (ASA) for secondary prevention of cardiovascular events in a UK primary care setting.Methods
New users of low-dose ASA for secondary prevention of cardiovascular events, aged 50-84 years in 2000-2007, were identified from The Health Improvement Network. Among those 38,975 individuals, 309 patients were considered to be incident cases of uncomplicated PUD. Incidence of uncomplicated PUD was calculated and a nested case¿control analysis adjusted for potential confounding factors was performed to calculate the odds ratios (ORs) for the association of potential risk factors with uncomplicated PUD.ResultsThe crude incidence of uncomplicated PUD was 1.41 per 1000 person-years (95% confidence interval [CI], 1.26-1.58). Individuals with a history of PUD were more likely to develop uncomplicated PUD than those without such a history (hazard ratio [HR], 2.22, 95% CI, 1.60-3.09). In nested case¿control analyses, the risk of uncomplicated PUD was associated with current use of non-steroidal anti-inflammatory drugs, oral steroids or acid suppressants. Other risk factors for developing uncomplicated PUD included smoking, stress, depression, anaemia and social deprivation.Conclusion
Our results indicate that several risk factors significantly increase the risk of development of uncomplicated PUD in new users of low-dose ASA. Therefore, physicians should monitor ASA users for gastrointestinal symptoms and signs of ulcer, particularly if they have additional risk factors.
[Show abstract][Hide abstract] ABSTRACT: Background Anticoagulants and/or antiplatelet agents such as acetylsalicylic acid (ASA) are important in prevention of cardiovascular (CV) events, but may be associated with upper gastrointestinal bleeding (UGIB). However, discontinuing these agents may leave patients at risk of CV events. Objectives This study aimed to assess patterns of therapy after UGIB in routine clinical practice. Methods The Health Improvement Network UK primary care database was used to identify a cohort of patients aged 40-84 years with a UGIB event between 2000 and 2007 (n = 2,036). Patients were followed up for 1 year from the recorded UGIB. Re-prescription rates for antithrombotics and drugs that can modify the risk of UGIB were estimated at 30, 90, 180, and 365 days. Results At 365 days, the re-prescription rate was 43 % for ASA, 66 % for warfarin, 69 % for clopidogrel, and 49 % for dipyridamole. The re-prescription rate of gastroprotective agents at 365 days for current users of histamine H2-receptor antagonists was 36 % and that of proton pump inhibitors (PPIs) was 97 %. In patients who were prescribed ASA before UGIB (n = 572), only 24 % were prescribed a PPI in the previous year. In patients who were prescribed ASA in the year after UGIB (n = 337), 92 % were prescribed a PPI. Conclusions Antiplatelet use fell after UGIB events. In patients who were prescribed a PPI after a UGIB event, there was increased re-prescription of antiplatelet agents and antithrombotics.
American Journal of Cardiovascular Drugs 08/2014; 14(6). DOI:10.1007/s40256-014-0088-x · 2.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this retrospective database study, carried out using The Health Improvement Network, a UK primary care database, we followed up patients who were prescribed low-dose acetylsalicylic acid (ASA) (75-300 mg/day) for the secondary prevention of cardiovascular disease in 2000-2007, and who discontinued therapy for a period of at least 90 days during that time (n = 11,565). We assessed the incidence of, and factors associated with, ASA represcription. Patients were followed up from the first day after their initial 90-day period of discontinuation (start date) until ASA represcription, death, or the end of the study period (31 December 2010). Hazard ratios for factors associated with represcription were calculated using Cox regression models. The cumulative incidence of ASA represcription was 85.2 % over the entire follow-up period, and 63.5 % of all represcriptions were received in the first 6 months after patients' start dates. Factors significantly associated with a reduced likelihood of ASA represcription included being aged 75-84 years, cardiovascular and gastrointestinal comorbidities (in particular, atrial fibrillation and high overall gastrointestinal risk), adverse drug reactions experienced during therapy, and use of gastroprotective or cardiovascular medications (most notably warfarin). Factors significantly associated with an increased likelihood of ASA represcription included obesity, diabetes mellitus, stable angina, depression, and use of non-steroidal anti-inflammatory drugs. In conclusion, approximately 85 % of patients who discontinued low-dose ASA therapy were subsequently represcribed ASA during the study period. Comorbidities and comedication use affected represcription rates.
American Journal of Cardiovascular Drugs 06/2014; 14(4). DOI:10.1007/s40256-014-0079-y · 2.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
We aimed to clarify the nature of the association between hip fracture risk and use of proton pump inhibitors (PPIs) or histamine2-receptor antagonists (H2RAs).Methods
We identified patients 40–89 years of age with a recorded hip fracture diagnosis in 2000–2008 using The Health Improvement Network, a UK primary care research database. Computerized records were reviewed and questionnaires sent to primary care physicians to validate hip fracture cases. A cohort study with a nested case-control analysis was performed to estimate the association between the use of acid-suppressive drugs and hip fracture.ResultsOverall incidence of hip fracture per 1000 person-years was 1.31 (95% confidence interval [CI] 1.28–1.33). There was a modest increased risk of hip fracture after adjustment for potential confounders (odds ratios [OR] during current use of PPIs and H2RAs: 1.09 [95% CI 1.01–1.17] and 1.04 [95% CI 0.90–1.19], respectively). Relative to nonuse, an increased risk of fracture was observed with medium and high doses of PPIs (OR 1.11 [95% CI 1.01–1.22] and OR 1.31 [95% CI 1.06–1.61], respectively) and high doses of H2RAs (OR 2.77, 95% CI 1.21–6.37). No duration response was observed (ORs for current PPI use less than 1 month and 5 years or longer: 1.16 [95% CI 0.94–1.43] and 1.02 [95% CI 0.87–1.20], respectively).Conclusions
Patients treated with PPIs showed a modest increased risk of hip fracture after adjustment for potential cofounders. Any remaining association between PPI use and hip fracture risk may be attributable to residual confounding.
[Show abstract][Hide abstract] ABSTRACT: Hip fractures represent a major public health challenge worldwide. Multinational studies using a common methodology are scarce. We aimed to estimate the incidence rates (IRs) and trends of hip/femur fractures over the period 2003-2009 in five European countries. The study was performed using seven electronic health-care records databases (DBs) from Denmark, The Netherlands, Germany, Spain, and the United Kingdom, based on the same protocol. Yearly IRs of hip/femur fractures were calculated for the general population and for those aged ≥50 years. Trends over time were evaluated using linear regression analysis for both crude and standardized IRs. Sex- and age-standardized IRs for the UK, Netherlands, and Spanish DBs varied from 9 to 11 per 10,000 person-years for the general population and from 22 to 26 for those ≥50 years old; the German DB showed slightly higher IRs (about 13 and 30, respectively), whereas the Danish DB yielded IRs twofold higher (19 and 52, respectively). IRs increased exponentially with age in both sexes. The ratio of females to males was ≥2 for patients aged ≥70-79 years in most DBs. Statistically significant trends over time were only shown for the UK DB (CPRD) (+0.7 % per year, P < 0.01) and the Danish DB (-1.4 % per year, P < 0.01). IRs of hip/femur fractures varied greatly across European countries. With the exception of Denmark, no decreasing trend was observed over the study period.
Calcified Tissue International 04/2014; 94(6). DOI:10.1007/s00223-014-9850-y · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: From the mid-1980s to mid-1990s, the WHO MONICA Project monitored coronary events and classic risk factors for coronary heart disease (CHD) in 38 populations from 21 countries. We assessed the extent to which changes in these risk factors explain the variation in the trends in coronary-event rates across the populations.
Methods: In men and women aged 35—64 years, non-fatal myocardial infarction and coronary deaths were registered continuously to assess trends in rates of coronary events. We carried out population surveys to estimate trends in risk factors. Trends in event rates were regressed on trends in risk score and in individual risk factors.
Findings: Smoking rates decreased in most male populations but trends were mixed in women; mean blood pressures and cholesterol concentrations decreased, bodymass index increased, and overall risk scores and coronary-event rates decreased. The model of trends in 10-year coronary-event rates against risk scores and single risk factors showed a poor fit, but this was improved with a 4-year time lag for coronary events. The explanatory power of the analyses was limited by imprecision of the estimates and homogeneity of trends in the study populations.
Interpretation: Changes in the classic risk factors seem to partly explain the variation in population trends in CHD. Residual variance is attributable to difficulties in measurement and analysis, including time lag, and to factors that were not included, such as medical interventions. The results support prevention policies based on the classic risk factors but suggest potential for prevention beyond these.
[Show abstract][Hide abstract] ABSTRACT: SUMMARY: The WHO MONICA Project is designed to measure the trends in mortality and morbidity from coronary heart disease (CHD) and stroke, and to assess the extent to which they are related to changes in known risk factors in different populations in 27 countries. Risk-factor data are collected from population samples examined in at least two population surveys (one at the beginning of the study and the other at the end). The results of the baseline population surveys are presented. In populations studied, the proportion of smokers varied between 34-62% among men and 3-52% among women. The population median of systolic blood pressure varied between 121-146 mmHg in men. In women the figures were 118 mmHg and 141 mmHg respectively. In diastolic blood pressure, the variation of median was from 74 mmHg to over 91 mmHg among men and from 72-89 mmHg among women. The third major risk factor considered was total cholesterol, with the population median ranging between 4.1-6.4 mmol/l among men and 4.2-6.3 mmol/l among women. Caution is required when making cross-sectional comparisons between the risk-factor levels as the MONICA Project was not designed for this purpose. Nevertheless, these data demonstrate clearly the large variety of baseline risk-factor patterns in populations studied in the MONICA Project.
MeSH Terms: Adult; Australia; Blood Pressure; Body Weight; China; Cholesterol/blood; Coronary Disease/etiology*; Data Interpretation, Statistical; Europe; Female; Humans; Male; Middle Aged; Population Surveillance*; Quality Control; Risk Factors; Smoking/statistics & numerical data; USSR; World Health Organization;
[Show abstract][Hide abstract] ABSTRACT: Atrial fibrillation is one of the most common arrhythmias in clinical practice and it is often diagnosed after a complication occurs. The study aimed to evaluate the predictive value of atrial natriuretic peptide (ANP) for atrial fibrillation in a male population-based study.
This study is a part of the "Study of Men Born in 1913 and 1923", a longitudinal prospective cohort study of men, living in the city of Gothenburg in Sweden. A population-based sample of 528 men was investigated in 1988 when they were aged 65years (n=134) and 75years (n=394), and they were followed up for 16years. Blood samples were collected from all 528 men at baseline and plasma ANP levels were analyzed by radioimmunoassay. Hazard ratios were estimated by competing-risk regression analysis. One hundred five participants were excluded because of a prior diagnosis of atrial fibrillation, congestive heart failure, severe hypertension, or severe chronic renal insufficiency. Of the remaining 423 participants, 90 men were diagnosed with atrial fibrillation over the 16-year follow-up. In multivariable analysis, men in the two highest quartiles of ANP levels had a significantly higher risk for atrial fibrillation compared with men in the lowest ANP quartile. The adjusted ratio was 3.14 (95% CI 1.59-6.20) for the third ANP quartile and 3.36 (95% CI 1.72-6.54) for the highest quartile of ANP level.
In this population-based longitudinal study, we found that elevated ANP levels at baseline predicted atrial fibrillation during a follow-up time of 16years.
International journal of cardiology 11/2013; 171(1). DOI:10.1016/j.ijcard.2013.11.042 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study evaluated the risk of cardiovascular events associated with the use of proton pump inhibitors (PPIs) in new users of acetylsalicylic acid (ASA) for the secondary prevention of cardiovascular events. Two cohorts of patients aged 50-84 years were identified from UK primary care databases: individuals with a first prescription for ASA (75-300 mg/day) for secondary prevention of cardiovascular events (n = 39,513; CVD cohort) or with a record of hospitalisation for an acute coronary event (n = 42,542; ACS cohort) in 2000-2007. Cases of non-fatal myocardial infarction (MI) and coronary death were identified: 1,222 in the CVD cohort and 604 among new users of ASA in the ACS cohort. A nested case-control analysis estimated the relative risk (RR) of non-fatal MI or coronary death associated with use vs non-use of PPI therapy. Current continuous use of PPI therapy was not associated with a significant increase in RR overall: in the CVD cohort (RR = 1.14 [95% confidence interval = 0.91-1.43]); in the ACS cohort (0.88 [0.66-1.18]); or among current continuous users of ASA as antiplatelet monotherapy (CVD cohort: 1.15 [0.80-1.66]; ACS cohort: 0.73 [0.43-1.23]; pooled analysis of both cohorts: 0.96 [0.62-1.48]). Among first-time users of ASA for the secondary prevention of cardiovascular events, PPI use was not shown to be associated with an increased risk of non-fatal MI or coronary death.
Thrombosis and Haemostasis 10/2013; 111(1). DOI:10.1160/TH13-07-0542 · 4.98 Impact Factor