[Show abstract][Hide abstract] ABSTRACT: 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.
American journal of cardiovascular drugs : drugs, devices, and other interventions. 08/2014;
[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 : drugs, devices, and other interventions. 06/2014;
[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; · 2.75 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: 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: 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; · 6.18 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). · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Some pharmacokinetic studies have reported that proton pump inhibitors (PPIs) reduce the activity of clopidogrel, but the results of studies assessing clinical outcomes in patients receiving both drugs are inconsistent. We have therefore carried out a population-based cohort study with nested case-control analysis, in order to evaluate changes in the risk of cardiovascular and peptic ulcer bleeding (PUB) events associated with PPI use in patients receiving clopidogrel. A total of 42,542 patients aged 50-84 years in 2000-2007 who survived an acute coronary event were identified in two UK-based primary care databases (The Health Improvement Network and the General Practice Research Database). Individuals were followed up to identify incident cases of non-fatal myocardial infarction/coronary death (n = 2,546) and PUB (n = 194). Controls were frequency matched to cases by age, sex and calendar year. Compared with PPI non-use, current continuous PPI use was not associated with a significant change in risk of non-fatal myocardial infarction/coronary death among current continuous users of clopidogrel monotherapy (relative risk [RR], 1.06; 95% confidence interval [95% CI], 0.47 to 2.36) or dual antiplatelet therapy (DAT; RR, 0.80; 95% CI, 0.47 to 1.37) who initiated their antiplatelet therapy shortly after their coronary event. Among patients prescribed DAT at the start date, the RR of PUB events associated with current PPI use initiated at the start date was 0.66 (95% CI, 0.27 to 1.60).
Thrombosis and Haemostasis 07/2013; 110(4). · 5.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: For patients at high cardiovascular and high gastrointestinal (GI) risk, coprescription of a proton pump inhibitor (PPI) with low-dose aspirin is recommended. We aimed to quantify the extent to which low-dose aspirin discontinuation in patients at high cardiovascular risk is affected by PPI use and baseline GI risk. Patients aged 50 to 84 years who had evidence of ischemic heart disease or cardiovascular disease and who were new users of low-dose aspirin in 2000 to 2007 were identified using The Health Improvement Network (n = 35,604). Aspirin discontinuation was defined as a period of at least 90 days after completion of the last prescribed course during which no repeat prescription was issued. The incidence of low-dose aspirin discontinuation was 26.8 per 100 person-years (95% confidence interval [CI] 26.2 to 27.4). The age-, gender-, and indication-adjusted risk of aspirin discontinuation was 15% less among continuous PPI users than among PPI nonusers (hazard ratio [HR] 0.85, 95% CI 0.78 to 0.92); after further adjusting for number of coprescribed medications, the HR was 0.95 (95% CI 0.87 to 1.03). Continuous PPI use was associated with a reduced risk of aspirin discontinuation among patients at high GI risk (HR 0.83; 95% CI 0.74 to 0.93) but not among those at low GI risk (HR 1.08; 95% CI 0.96 to 1.21). In conclusion, among patients at high GI risk, concomitant users of aspirin and PPI showed a greater aspirin adherence than aspirin users not on PPI. Further studies need to confirm factors with the potential to increase adherence to long-term aspirin.
The American journal of cardiology 07/2013; · 3.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:: Some recent reports suggest an increased risk of fractures with use of proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs), although results are inconsistent and a causal relationship has yet to be proven. As these acid-suppressive drugs may have uncommon adverse effects on the central nervous system (CNS), such as dizziness, we investigated whether their use is associated with falls as a possible mechanism for increasing fracture risk. METHODS:: A cohort study with nested case-control analysis and two validation strategies was performed using data from UK patients (aged 40-89 years) included in The Health Improvement Network database (2000-2008). Due to the large number of falls, a random sample of 20,000 cases was used for the analysis. RESULTS:: The overall incidence of falls per 1000 person-years was 13.0 (95% confidence interval [CI] = 12.9-13.1). After adjustment for potential confounders, there was no relationship between falls and current use of single PPIs (odds ratio [OR] = 0.95; 95% CI = 0.89-1.02) or H2RAs (OR = 1.01; 95% CI = 0.90-1.14); there was no relationship with dose or duration of treatment. Falls were associated with CNS disorders and treatment with various pharmacological agents including antiparkinson drugs (OR = 2.7; 95% CI = 2.2-3.3) and antiepileptics (OR = 2.1; 95% CI = 1.8-2.3). CONCLUSIONS:: There was no association between falls and use of PPIs or H2RAs. Any potential increase in the risk of fractures proposed to be associated with the use of acid-suppressive drugs is not via an increased risk of falls.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Simple global self-ratings of health (SRH) have become increasingly used in national and international public health monitoring, and in recent decades recommended as a standard part of health surveys. Monitoring developments in population health requires identification and use of health measures, valid in relation to targets for population health. The aim of the present study was to investigate associations between SRH and sick leave, disability pension, hospital admissions, and mortality, adjusted for effects of significant covariates, in a large population-based cohort. METHODS: The analyses were based on screening data from eight population-based cohorts in southern and central Sweden, and on official register data regarding sick-leave, disability pension, hospital admissions, and death, with little or no data loss. Sampling was performed 1973--2003. The study population consisted of 11,880 women and men, age 25--99 years, providing 14,470 observations. Information on SRH, socio-demographic data, lifestyle variables and somatic and psychological symptoms were obtained from questionnaires. RESULTS: There was a significant negative association between SRH and sick leave (Beta -13.2, p<0.0001, and -9.5, p<0.01, in women and men, respectively), disability pension (Hazard ratio 0.77, p<0.0001 and 0.76, p<0.0001, in women and men, respectively), and mortality, adjusted for covariates. SRH was also significantly associated with hospital admissions in men (Hazard ratio 0.87, p<0.0001), but not in women (Hazard ratio 0.96, p0.20). Associations between SRH on the one hand, and sick leave, disability pension, hospital admission, and mortality, on the other, were robust during the follow-up period. CONCLUSIONS: SRH had strong predictive validity in relation to use of social insurance facilities and health care services, and to mortality. Associations were strong and robust during follow-up.
BMC Public Health 12/2012; 12(1):1103. · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Up to one-third of patients with gastroesophageal reflux disease (GERD) in primary care have residual symptoms despite proton pump inhibitor (PPI) therapy. We aimed to characterize partial response to PPIs among adult patients in UK primary care.
Newly diagnosed GERD patients aged 20-79 years who were prescribed PPI for treatment of GERD were identified in The Health Improvement Network. Those with a treatment change suggesting partial response to PPIs (new treatment added to PPI, increased PPI dose, or switching PPI) during the subsequent 6 months were identified as potential cases and confirmed after manual review of each patient's complete computer medical record including free-text comments. Patients without these treatment changes were study controls. A nested case-control analysis was conducted using logistic regression.
The proportion of newly diagnosed GERD patients with partial response to PPI therapy was 18.6% (1201/6453). Partial response was associated with female gender (odds ratio [OR]: 1.20; 95% confidence interval [CI]: 1.05-1.37), anxiety or depression (OR: 1.15; 95% CI: 1.00-1.31), and prescription of ≥ 6 drugs in the month before GERD diagnosis (OR: 1.42; 95% CI: 1.14-1.78). Among new PPI users (n = 2907), partial response was associated with esophageal ulcer or Barrett's esophagus at initial diagnosis (OR: 3.14; 95% CI: 1.60-6.17).
Approximately one in five newly diagnosed patients with GERD appear to have a partial response to PPI therapy. Female gender, polymedication, and a severe initial diagnosis may be associated with partial response.
Scandinavian Journal of Gastroenterology 04/2012; 47(7):751-61. · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine trends and predictors of clopidogrel and proton pump inhibitor (PPI) coprescription with low-dose acetylsalicylic acid (ASA) prescribed for secondary cardiovascular or cerebrovascular disease (CVD) prevention in UK primary care.
Patients aged 50-84 years who received a first prescription for low-dose ASA for secondary CVD prevention in 2000-2001 (n = 10,330) or 2006-2007 (n = 8154) were identified in The Health Improvement Network UK primary care database. Clopidogrel or PPI coprescriptions received within 15 days after the first low-dose ASA prescription were ascertained.
Clopidogrel coprescription with low-dose ASA increased from 1.6% to 25.2% between the two study periods; PPI coprescription increased from 11.6% to 28.3%. Low-dose ASA indications of myocardial infarction [odds ratio (OR) 11.7, 95% confidence interval (CI) 10.2 to 13.4] and unstable angina (OR 1.73, 95%CI 1.09 to 2.75) were positive predictors of clopidogrel coprescription in 2006-2007, relative to chronic ischaemic heart disease. Patients at high risk of upper gastrointestinal bleeding were more likely to receive a PPI than those at lower risk in 2006-2007 (OR 4.36, 95%CI 3.93 to 4.84). In this period, 65.5% of patients who required a clopidogrel coprescription according to guideline recommendations received one, and 44.3% of patients at high risk of upper gastrointestinal bleeding received a PPI.
Clopidogrel and PPI coprescription with low-dose ASA increased markedly between 2000-2001 and 2006-2007; however, many patients on low-dose ASA did not receive the recommended coprescriptions at the end of the study period.
Pharmacoepidemiology and Drug Safety 02/2012; 21(5):463-9. · 2.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Global self-rated health (SRH) has become extensively used as an outcome measure in population health surveillance. The aim of this study was to analyse the effects of age and secular trend (year of investigation) on SRH.
Prospective cohort study, using population-based data from eight ongoing cohort studies, with sampling performed between 1973 and 2003.
11 880 women and men, aged 25-99 years, providing 14 470 observations.
In multiple ordinal logistic regression analyses, adjusted for the effects of covariates, there were independent effects of age (p<0.0001) and of year of investigation (p<0.0001) on SRH. In women the association was linear, showing lower levels of SRH with increased age, and more recent year of investigation. In men the association was curvilinear, and thus more complex. The final model explained 76.2% of the SRH variance in women and 74.5% of the variance in men.
SRH was strongly and inversely associated with age in both sexes, after adjustment for other outcome-affecting variables. There was a strongly significant effect of year of investigation indicating a change in SRH, in women towards lower levels over calendar time, in men with fluctuations across time.
[Show abstract][Hide abstract] ABSTRACT: Androgen deprivation therapy (ADT) is used to delay tumour development and improve survival in patients with prostate cancer. However, several randomized controlled trials and observational studies have suggested that ADT may increase the risk of cardiovascular events.
The aim of the study was to evaluate the risk of coronary heart disease (CHD) and heart failure (HF) in patients with prostate cancer receiving ADT in UK primary care, and to evaluate the risks associated with individual ADT and combination ADT.
The UK General Practice Research Database was used to identify a cohort of patients with a first prostate cancer diagnosis during 1999-2005. These patients were followed up to assess the occurrence of acute myocardial infarction (AMI), death from CHD, incident HF and hospitalization due to acute decompensated HF. Nested case-control analyses were performed to assess the risk of these outcomes associated with anti-androgen therapy, as well as different types of ADT and combinations of ADT.
Current anti-androgen use was associated with a significant increase in the risk of hospitalization due to HF (odds ratio [OR] 2.15; 95% CI 1.08, 4.29), but not of incident HF, CHD or AMI. When assessed individually, there was no significant association of bicalutamide or cyproterone use with the risk of AMI or CHD. Current use of bicalutamide 50 mg/day was associated with a significant increase in the risk of HF (OR 3.28; 95% CI 1.31, 8.18); however, this increased risk of HF was only found in patients taking bicalutamide 50 mg/day in combination with luteinizing hormone-releasing hormone (LHRH) receptor agonists. There were no cases of hospitalized HF in patients taking bicalutamide 50 mg/day as monotherapy and there was no significant association between current use of bicalutamide 150 mg/day and the risk of hospitalized HF. Combination therapy with LHRH agonists and anti-androgens was associated with a significant increase in the risk of CHD (OR 4.35; 95% CI 1.94, 9.75), AMI (OR 3.57; 95% CI 1.44, 8.86), incident HF (OR 3.19; 95% CI 1.10, 9.27) and hospitalized HF (OR 3.39; 95% CI 1.07, 10.70) compared with non-use of these drugs.
In men with prostate cancer, combination therapy with LHRH agonists and anti-androgens is associated with significant increases in the risk of CHD, AMI, incident HF and hospitalized HF. Individual therapies do not appear to increase the risk of these outcomes.
Drug Safety 11/2011; 34(11):1061-77. · 2.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ischaemic cerebrovascular accident (ICVA) is a common cause of morbidity and mortality. Identification of risk factors can reduce its incidence. We aim to estimate the incidence rate (IR) of hospitalised ICVA in the general population by sex and quantify its risk associated with several factors.
We followed up 907, 001 individuals aged 40-84 years during a mean of 3.63 years to ascertain the first episode of hospitalised ICVA between 2000 and 2004 using a UK primary care database. We evaluated the risk factors for ICVA through unconditional logistic regression (OR) with a nested case-control analysis, using 2953 incident cases and 10, 000 random controls frequency-matched by age, sex and year.
The IR of hospitalised ICVA was 1.94 (95%CI: 1.87-2.01) per 1000 person-years in men and 1.59 (95%CI: 1.53-1.65) in women. The IR ratio adjusted by age was 1.35 (95%CI: 1.28-1.43). Major risk factors for the first ICVA were atrial fibrillation (AF) (OR of 1.96 (95%CI: 1.59-2.42) for men and 3.54 (95%CI: 2.85-4.39) for women), smoking, epilepsy and hypertension. AF patients on anticoagulant therapy presented a reduced risk of ICVA (OR: 0.39; 95%CI: 0.27-0.56) in both sexes. Hypertensive women that discontinued the treatment had an increased risk (OR: 2.53; 95%CI: 1.63-3.91).
Men had higher incidence of hospitalised ICVA than women. AF was the major risk factor for ICVA (more in women than men), followed by smoking. Among AF patients, those under anticoagulant therapy showed a significant reduced risk of first ICVA. Antihypertensive drug discontinuation increased the risk of ICVA among women.
Pharmacoepidemiology and Drug Safety 08/2011; 20(10):1050-6. · 2.90 Impact Factor