Short-term Absolute Risk Research Articles

1067-P: Short-Term Risk of Type 2 Diabetes Mellitus in Adults Treated with Corticosteroids: An Observational Study

Background: Exposure to corticosteroids is recognised to increase the risk of developing type 2 diabetes (T2DM). Our aim was to evaluate the short-term absolute risk of T2DM over the course of people’s first continuous exposure to corticosteroids. Methods: This was an observational study using UK data from the Clinical Practice Research Datalink. Adult patients were selected if exposed to systemic corticosteroids for any condition and had no prior T2DM. Non-exposed adults matched on age, sex, disease burden were selected from the general population. Patients were followed from their first exposure to corticosteroid to 90 days following the end of continuous prescribing. Absolute risk rates were calculated by age, sex and BMI category. Results: In total, 536,852 exposed patients were matched 1:1 to non-exposed controls. Mean age was 51 years; 59% were female. Obese males aged 43-67 years exposed to corticosteroids had the highest absolute risk of T2DM (41.8 per 1,000 patient years (PKPY)); in matched non-exposed controls this was 24.0 PKPY. Generally, patients taking steroids had greater risk of T2DM compared with those in the same age, sex and BMI category never exposed to steroids. Conclusions: Whilst it is understood that exposure to corticosteroids increases the risk of T2DM, there are large differences in risk in accordance with age, sex and BMI. Alternatives to corticosteroids are urgently needed. Disclosure E. Berni: Consultant; Self; AstraZeneca. S. Jenkins-jones: Consultant; Self; AstraZeneca. C. Astbury: Employee; Self; AstraZeneca. M. N. Brown: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. P. R. Hunt: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. C. J. Currie: Consultant; Self; AstraZeneca. S. Adamsson eryd: Employee; Self; AstraZeneca. P. Ambery: Employee; Self; AstraZeneca.

Risk of gastrointestinal bleeding associated with oral anticoagulation and non-steroidal anti-inflammatory drugs in patients with atrial fibrillation: a nationwide study.

Non-vitamin K antagonist oral anticoagulants (NOACs) are displacing vitamin K antagonists (VKAs) for stroke prophylaxis in patients with atrial fibrillation (AF). Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) could increase gastrointestinal bleeding (GIB) risks among these patients. The aim of this study was to examine the risk of GIB among Danish AF patients taking oral anticoagulants (OACs) and NSAIDs. Using nationwide administrative registries, we determined concomitant NSAID use among anticoagulant-naïve patients with AF initiating OACs between August 2011 and June 2017. We calculated short-term absolute risks differences and hazard ratios (HRs) for GIB based on multiple adjusted cause-specific Cox regressions with time-dependent NSAID treatment. Among 41183 patients [median age 70 years (interquartile range 64-78); 55% men], 21% of patients on NOACs and 18% on VKA were co-prescribed NSAIDs. The differences in absolute risk [95% confidence interval (CI)] of GIB within 14 days of commencing concomitant NSAID therapy (vs. no concomitant NSAID therapy) were 0.10% (0.04-0.18%) for NOACs and 0.13% (0.03-0.24%) for VKA. NOACs overall were associated with less GIB than VKA [HR 0.77 (95% CI 0.69-0.85)]. Compared with OACs alone, concomitant NSAIDs doubled the GIB risk associated with NOACs overall [HR 2.01 (95% CI 1.40-2.61)] and with VKA [HR 1.95 (95% CI 1.21-2.69)]. Among this nationwide AF population taking OACs, concomitant NSAID therapy increased the short-term absolute risk of GIB. Non-vitamin K antagonist oral anticoagulants alone were associated with lower GIB risks than VKA but concomitant NSAIDs abolished this advantage. The findings align with post hoc analyses from randomized studies. Physicians should exercise appropriate caution when prescribing NSAIDs for patients with AF taking NOACs or VKA.

Short-term risk of cervical intraepithelial neoplasia grades 2 and 3 for women with normal cytology and human papillomavirus infection

To assess the risk of cervical intraepithelial neoplasia grades 2, 3 or higher (CIN 2/3+) for women with normal cytology and concurrent high-risk human papillomavirus infection (HR-HPV). We examined 2 200 women every 6 months for an average of 9 years. Cervical smears and samples for HPV DNA were obtained at each visit. Absolute risk of subsequent CIN2/CIN3+ was estimated using the Kaplan-Meier method. The absolute risk of CIN2/CIN3+ among HR-HPV-positive women with normal Pap smear results was 1.06% (95%CI, 0.57-2.20), 5 times higher the risk among all women with normal Pap smears (0.20%; 95%CI, 0.12-0.32) but 7 times lower than that for women with HR-HPV infection and LSIL (7.24%; 95%CI, 3.78-15.2). Short-term absolute risk of CIN2/3+ after a normal Pap smear with concurrent HR-HPV infection is low (~1%), suggesting that the HR-HPV test has limited utility in short-term clinical decision-making for women with normal cytology.

Guidelines for Prevention of Cardiovascular Disease in Women: A Summary of Recommendations

Cardiovascular disease (CVD) is a major cause of mortality in women. The first evidence-based guidelines for the prevention of CVD in women were developed in 2004 and updated this year. The 2007 guidelines place more emphasis on women's overall lifetime coronary heart disease risk, as opposed to short-term absolute risk, than did the 2004 recommendations. Depending on the criteria met, women are classified as being at high risk, at risk, or at optimal risk. The authors provide an overview of the recommendations in the 3 different categories: lifestyle interventions, major risk factor interventions, and preventive drug interventions.

Timing and risk factors for clinical fractures among postmenopausal women: a 5-year prospective study

BackgroundMany risk factors for fractures have been documented, including low bone-mineral density (BMD) and a history of fractures. However, little is known about the short-term absolute risk (AR) of fractures and the timing of clinical fractures. Therefore, we assessed the risk and timing of incident clinical fractures, expressed as 5-year AR, in postmenopausal women.MethodsIn total, 10 general practice centres participated in this population-based prospective study. Five years after a baseline assessment, which included clinical risk factor evaluation and BMD measurement, 759 postmenopausal women aged between 50 and 80 years, were re-examined, including undergoing an evaluation of clinical fractures after menopause. Risk factors for incident fractures at baseline that were significant in univariate analyses were included in a multivariate Cox survival regression analysis. The significant determinants were used to construct algorithms.ResultsIn the total group, 12.5% (95% confidence interval (CI) 10.1–14.9) of the women experienced a new clinical fracture. A previous clinical fracture after menopause and a low BMD (T-score <-1.0) were retained as significant predictors with significant interaction. Women with a recent previous fracture (during the past 5 years) had an AR of 50.1% (95% CI 42.0–58.1) versus 21.2% (95% CI 20.7–21.6) if the previous fracture had occurred earlier. In women without a fracture history, the AR was 13.8% (95% CI 10.9–16.6) if BMD was low and 7.0% (95% CI 5.5–8.5) if BMD was normal.ConclusionIn postmenopausal women, clinical fractures cluster in time. One in two women with a recent clinical fracture had a new clinical fracture within 5 years, regardless of BMD. The 5-year AR for a first clinical fracture was much lower and depended on BMD.

Age and Time Need Not and Should Not Be Eliminated From the Coronary Risk Prediction Models

Risk assessment, risk communication, and risk management are 3 fundamental steps in the primary and secondary prevention of coronary heart disease (CHD). Consequently, national and international guidelines1–4 have been formulated to assist clinicians in providing standardized care for treating coronary risk factors. These guidelines are consistent with the best available scientific evidence on risks of developing CHD and potential strategies to reduce those risks via nonpharmacological and pharmacological interventions. One of the critical concepts on which contemporary guidelines are founded is the notion that the choice and intensity of an intervention strategy should in part be based on the underlying risk—ie, the absolute risk of experiencing a CHD event during a short-term period. This is typically estimated as the 10-year risk of CHD for a man or a woman of a specific age.1,3,4 In this issue of Circulation , Ridker and Cook5 present an argument to eliminate both the age and the time dependency of CHD risk prediction algorithms. On the basis of the objectives of current guidelines and risk prediction algorithms, we disagree with the suggestion made by Ridker and Cook. We submit that not only is removal of age and time from the risk prediction equations not necessary, but, to the contrary, such removal may be inappropriate. Furthermore, as we demonstrate below, the objectives desired by Ridker and Cook are already available with the existing prediction algorithms and often have been incorporated into the standard use of the current guidelines. See p 657 Before we proceed, it would be useful to summarize the observations made by Ridker and Cook. First, they point out the possibility that young individuals with multiple risk factors and very low short-term CHD risk but a much higher lifetime CHD risk (patient example 1 in their article) may not be targeted …

Treatment of high blood pressure and gain in event-free life expectancy

Consideration of absolute risk has been recommended for making decisions concerning preventive treatment in hypertension. We performed simulations to estimate the benefit of antihypertensive therapy over a life-time. The rate of nonfatal and fatal events of untreated hypertensives in the US population were estimated using data from Individual Data ANalysis of Antihypertensive drug intervention trials (INDANA; a meta-analysis on individual data in hypertension) and specific cause of death from national statistics. Disease-free survival curves until all patients have died were built using the "life-table" method. The treatment effect estimated from INDANA was applied to this curve to obtain the disease-free survival curve of the life-long treated population. Gains in event-free life expectancy (GLE) were estimated from survival curves. A sensitivity analysis was performed to assess the impact of possible death misclassifications. For a 40-year-old man, the gain in life expectancy without stroke and major cardiovascular events were 27 and 32 months, respectively, and were more substantial than those without coronary disease (19 months). The GLE decreased slowly with increasing age at the beginning of treatment, whereas short-term absolute risk reductions increase sharply with age. Policies based on the selection of patients to treat according to absolute benefit do not maximize the GLE compared with strategies that treat low-risk patients.

Low bone mineral density in premenopausal women.

With the proliferation of bone densitometers, an increasing number of premenopausal women are having their bone density tested. Approximately 15% of premenopausal women have bone mineral density that is more than 1 standard deviation less than the young-adult mean, and approximately 0.6% are more than 2.5 standard deviation below young-adult mean bone density. Most premenopausal women with low bone density have low peak bone mass, stable bone density, and low short-term absolute risk of fracture. The management of these patients involves nonpharmacologic lifestyle measures and reassurances that fracture risk is low. A minority of premenopausal women with low bone density have increased short-term absolute fracture risk with contributing diseases, conditions, or medications that should be identified and treated. Premenopausal women with fractures are at increased risk for fractures later in life. Methods for evaluating these patients and selecting those who require additional care are reviewed.

Global risk of cardiovascular disease

UK death rates from coronary heart disease are among the highest in the world. This is because the UK has high levels of standard risk factors and a low level...