Which patients should receive aspirin for primary prevention of cardiovascular disease? An economic evaluation

Low-dose aspirin is a standard care for secondary prevention of cardiovascular disease (CVD). Its use in primary prevention is less widely accepted, however, despite recent meta-analyses and US and European guidelines supporting its use in individuals at increased CVD risk. The aim of this study was to define which patients should receive aspirin for primary prevention of CVD using data from four European countries. Based on the clinical data from two meta-analyses, a state-transition model was developed to compare the costs and effects of no treatment and low-dose aspirin as primary prevention for CVD over 10 years. The model was applied to patients at different 10-year risks (2-5%) of fatal CVD according to the SCORE equation. Direct costs from the perspective of the healthcare payer were used (base year 2003). Country-specific discounting was applied. Treating patients with a 10-year risk of fatal CVD of 2% or higher with low-dose aspirin resulted in lower total costs and more quality-adjusted life-years gained in the UK, Germany and Spain. In Italy, savings started at a 10-year fatal CVD risk of 3%. This difference was due to the higher cost of gastrointestinal bleeding in Italy. Monte Carlo analysis showed that aspirin was dominant in more than 90% of patients at a 10-year risk of 4% and 5% in the four countries. In conclusion, low-dose aspirin treatment becomes cost-saving at a very low 10-year risk of fatal CVD. The cost of gastrointestinal bleeding defines the level at which low-dose aspirin becomes cost-saving.     

Risk factors associated with NSAID-induced upper gastrointestinal bleeding resulting in hospital admissions: A cross-sectional, retrospective, case series analysis in valencia, spain

Abstract

Background

NSAIDs are a significant cause of drug-related hospital admissions and deaths. The therapeutic effects of NSAIDs have been associated with the risk for developing adverse events, mainly in the gastrointestinal tract.

Objectives

The focus of this study was to identify the most common risk factors associated with NSAID-induced upper gastrointestinal bleeding (UGIB) resulting in hospital admissions. A secondary end point was the relationship between use of gastroprotective treatment and relevant risk factors to NSAID-induced UGIB in the selected population.

Methods

This study was a cross-sectional, retrospective, case-series analysis of NSAID-induced UGIB resulting in hospital admission to the Requena General Hospital, Valencia, Spain, occurring from 1997 to 2005. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify UGIB admissions associated with NSAIDs. To estimate the probability of association between UGIB and the use of NSAIDs, the Naranjo adverse drug reaction probability was used. Patients were categorized as high-risk to develop UGIB if they met ≥1 of the following risk criteria (relevant risk factors): aged ≥65 years (age risk factor); peptic ulcer disease or NSAID gastropathy occurring in the year before their hospital admission (history risk factor); and concomitant use of other NSAIDs, systemic corticoids, oral anticoagulants, or platelet aggregation inhibitors (concomitant medication risk factor). Patients were categorized as candidates to use gastroprotections if they met ≥1 of the relevant risk factors. Patients were categorized as users of gastroprotective treatment if they used proton pump inhibitors, histamine H₂-receptor antagonists, or misoprostol at hospital admission.

Results

This study comprised 209 cases of NSAID-induced UGIB (129 men, 80 women: mean [SD] age, 71.5 [13.8] years; 128 [61.2%] receiving acetyl salicylic acid [ASA], with 72 [34.4%] receiving low-dose [80–325 mg] ASA). Prevalence of relevant risk factors for UGIB were as follows: age, 158 (75.6%) patients; history, 37 (17.7%); and concomitant medication, 35 (16.7%). One hundred seventy-eight (85.2%) patients met ≥1 criterion for using a gastroprotective agent; 28 (15.6%) were actually using one. Only the history risk factor was significantly associated with the use of gastroprotective treatment (P = 0.007; odds ratio = 3.17).

Conclusions

In this study of NSAID-induced UGIB resulting in hospital admission, age was the most common risk factor. However, this criterion was not associated with the use of gastroprotective agents. A large number of cases were associated with the use of ASA, primarily in those receiving low doses. A significant lack of gastroprotective agent use was observed in patients who met the criteria to use them.Key Words: nonsteroidal anti-inflammatory drugs, upper gastrointestinal bleeding, hospital admissions, elderly, risk factors     

老年人上消化道出血与长期服用小剂量阿司匹林的关系

目的　观察长期服用小剂量阿司匹林老年人上消化道出血的发生情况及影响因素。方法　 5 6例服用小剂量阿司匹林老年人 ,根据胃镜检查前一周内有无上消化道出血将其分为出血组与非出血组 ,胃镜观察其胃、十二指肠黏膜损伤情况 ,快速尿素酶试验和改良Giesma染色方法检测幽门螺杆菌 ,分析其上消化道出血的有关影响因素。结果　 5 6例老年人中发生上消化道出血 17例 ,发生率 30 4 % ,出血组胃黏膜损伤积分、幽门螺杆菌 (Hp)感染率均明显高于非出血组 (P <0 0 1)。多因素分析表明 ,Hp感染、既往出血病史及年龄可增加上消化道出血的危险性 ,而用药时间与上消化道出血无相关性。结论　长期小剂量服用阿司匹林可增加老年人上消化道出血的危险性 ,其发生与Hp感染、既往出血病史及年龄有关     

Extensive phenotype data and machine learning in prediction of mortality in acute coronary syndrome – the MADDEC study

Objective: Investigation of the clinical potential of extensive phenotype data and machine learning (ML) in the prediction of mortality in acute coronary syndrome (ACS).Methods: The value of ML and extensive clinical data was analyzed in a retrospective registry study of 9066 consecutive ACS patients (January 2007 to October 2017). Main outcome was six-month mortality. Prediction models were developed using two ML methods, logistic regression and extreme gradient boosting (xgboost). The models were fitted in training set of patients treated in 2007–2014 and 2017 (81%, n = 7344) and validated in a separate validation set of patients treated in 2015–2016 with full GRACE score data available for comparison of model accuracy (19%, n = 1722).Results: Overall, six-month mortality was 7.3% (n = 660). Several variables were found to be significantly associated with six-month mortality by both ML methods. The xgboost scored the best performance: AUC 0.890 (0.864–0.916). The AUC values for logistic regression and GRACE score were 0.867(0.837–0.897) and 0.822 (0.785–0.859), respectively. The AUC value of xgboost was better when compared to logistic regression (p = .012) and GRACE score (p < .00001).Conclusions: The use of extensive phenotype data and novel machine learning improves prediction of mortality in ACS over traditional GRACE score.

KEY MESSAGES

• The collection of extensive cardiovascular phenotype data from electronic health records as well as from data recorded by physicians can be used highly effectively in prediction of mortality after acute coronary syndrome.
• Supervised machine learning methods such as logistic regression and extreme gradient boosting using extensive phenotype data significantly outperform conventional risk assessment by the current golden standard GRACE score.
• Integration of electronic health records and the use of supervised machine learning methods can be easily applied in a single centre level to model the risk of mortality.

     

Risk factors for rebleeding in patients with obscure gastrointestinal bleeding from southern China

BackgroundTo identify the risk factors associated with rebleeding in obscure gastrointestinal bleeding (OGIB) patients from southern China.MethodsThis retrospective study involved 229 patients who underwent small bowel endoscopy in our hospital between 1 January 2018 and 1 December 2020. The clinical characteristics and risk factors related to rebleeding were retrospectively evaluated.ResultsRebleeding patients were significantly older than non-rebleeding patients (53.0 ± 15.9 vs. 46.2 ± 17.8 years), had lower hemoglobin concentrations (89.2 ± 28.1 vs. 126.2 ± 25.1 g/L), and higher blood urea nitrogen concentrations (5.4 ± 2.6 vs. 4.5 ± 2.2 µmol/L), respectively. A higher percentage of rebleeding patients had diabetes mellitus (13.9% vs. 2.9%) and overt bleeding (70.4% vs. 38.6%), and required blood transfusions (43.1% vs. 8.0%), compared with non-rebleeding patients, respectively. Multivariate logistic analysis indicated that drinking alcohol (odds ratio (OR): 9.27; 95% confidence interval (CI) = 1.35–63.78), anemia (OR: 17.38; 95% CI = 5.48–55.10), and blood transfusion (OR: 3.76; 95% CI = 1.04–13.56) increased the risk of rebleeding in OGIB patients.ConclusionOur data suggested that OGIB patients who drink alcohol, have anemia, and require blood transfusion have an increased risk of rebleeding.     

Correlation between dietary selenium intake and stroke in the National Health and Nutrition Examination Survey 2003–2018

BackgroundEpidemiologic evidence of the effect of dietary selenium intake on stroke risk remains controversial. This study aimed to examine the cross-sectional correlation between dietary selenium intake and the risk of stroke in adults.Materials and methodsWe retrospectively analysed 39,438 participants from the National Health and Nutrition Examination Survey 2003–2018, aged 20–85 years. Participants were divided into quartiles depending on daily dietary selenium intake: quartile 1 (0–77 μg), quartile 2 (77–108 μg), quartile 3 (108–148 μg), and quartile 4 (148–400 μg). The dose-response relationship was assessed using the restricted cubic spline function.ResultsThe adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of stroke were 0.70 (0.55, 0.88) for participants in quartile 2, 0.71 (0.53, 0.93) for quartile 3, and 0.61 (0.43, 0.85) for quartile 4 compared with that in quartile 1. p-Value for trend through quartiles was .007. A non-linear negative correlation between dietary selenium intake and stroke was observed in the threshold effect analysis and restricted cubic spline function (p-value for non-linearity < .001). An initial decrease in odds of stroke lower than 105 μg/day selenium intake (0.61 [0.44, 0.85], p = .004) was followed by a platform beyond 105 μg/day (0.97 [0.81, 1.16], p = .723). In the subgroup analysis, adjusted ORs (95% CIs) of stroke were 0.51 (0.36, 0.70) for female participants, 0.63 (0.40, 0.99) for participants with age <60 years, 0.63 (0.47, 0.85) for participants with poverty-income ratio < 2.14, 0.66 (0.50, 0.87) for participants with overweight and obesity, 0.66 (0.52, 0.84) for participants with hypertension, 0.72 (0.53, 0.97) for participants without diabetes, and 0.72 (0.56, 0.92) for non-anaemic participants.ConclusionsDietary selenium had a negative and non-linear correlation with the risk of stroke in adults. The correlation varied across different population subgroups.

KEY MESSAGES

• Dietary selenium had a negative and non-linear correlation with the risk of stroke in adults.
• Non-linear negative correlation trends were observed in subpopulations of females, age <60 years, poverty-income ratio <2.14, overweight and obesity, hypertension, non-diabetes, and non-anaemia.
• Dietary selenium intake of approximately 105 μg per day has an optimum effect on stroke.

     

Efficacy and safety of intravenous esmolol for cardiac protection in non-cardiac surgery. A systematic review and meta-analysis

Haemodynamic instability predisposes patients to cardiac complications in non-cardiac surgery. Esmolol, a short-acting cardioselective beta-adrenergic blocker might be efficient in perioperative cardiac protection, but could affect other vital organs, such as the kidneys, and post-discharge survival. We performed a systematic review on the use of esmolol for perioperative cardiac protection. We searched PubMed, Ovid Medline and Cochrane Central Register for Controlled trials. Eligible randomized controlled studies (RCTs) reported a perioperative esmolol intervention with at least one of the primary (major cardiac or renal complications during the first 30 postoperative days) or secondary (postoperative adverse effects and all-cause mortality) outcomes. We included 196 adult patients from three RCTs. Esmolol significantly reduced postoperative myocardial ischaemia, RR =0.43 [95% confidence interval, CI: 0.21–0.88], p = .02. No association with clinically significant bradycardia and hypotension compared to patients receiving control treatment could be confirmed (RR =7.4 [95% CI: 0.29–139.81], p = .18 and RR =2.21 [95% CI: 0.34–14.36], p = .41, respectively). No differences regarding other outcomes were observed. No study reported postoperative renal outcomes. Esmolol seems promising for the prevention of perioperative myocardial ischaemia. However, the association with bradycardia and hypotension remains unclear. Randomized trials investigating the effect of β1-selective blockade on clinically relevant outcomes and non-cardiac vital organs are warranted.

Key messages

• Short-acting cardioselective esmolol seems efficient in the prevention of perioperative myocardial ischaemia.
• The possibly increased risk of bradycardia and hypotension with short-acting intravenous beta blockade could not be confirmed or refuted by available data. Future adequately powered trials investigating the effect of β1-selective blockade on clinically relevant outcomes and non-cardiac vital organs are warranted.

     

Association between IL1B −511C/T polymorphism and Behçet’s disease: a meta-analysis

BackgroundMany studies have investigated the relationship between the interleukin-1β gene (IL1B) −511C/T polymorphism and the risk of Behçet’s disease (BD); however, the conclusions remain controversial.MethodsIn this study, we systemically retrieved relevant studies from the Chinese Biomedicine Database, China National Knowledge Infrastructure, Embase, Cochrane Library, and PubMed databases. We then calculated the odds ratios (ORs) and 95% confidence intervals (CIs) using the meta-package Stata version 12.0.ResultsThe IL1B −511C/T polymorphism was not related to BD susceptibility using any of the tested models (C vs T: OR = 1.20, 95% CI = 0.97–1.49; CC vs TT: OR = 1.27, 95% CI = 0.95–1.70; CT vs TT: OR = 1.03, 95% CI = 0.781.36; dominant model: OR = 1.12, 95% CI = 0.87–1.46; recessive model: OR = 1.27, 95% CI = 0.89–1.82). Similarly, subgroup analysis including studies consistent with the Hardy–Weinberg equilibrium revealed no association between the IL1B polymorphism and BD susceptibility.ConclusionThis meta-analysis indicates that the IL1B −511C/T polymorphism is unlikely to affect the risk of BD; however, further large-scale, carefully designed studies are needed to verify these results.     

Prognostic significance of CDKN2A/B deletions in acute lymphoblastic leukaemia: a meta-analysis

Background: Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) genes are frequently altered in acute lymphoblastic leukaemia (ALL) patients. The aim of this meta-analysis was to comprehensively assess the prognostic value of CDKN2A/B deletions in ALL patients.Methods: Systematic literature review was conducted in PubMed, Embase and Cochrane databases up to July 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models.Results: A total of thirteen studies including 2857 patients were eligible for this meta-analysis. Combined HRs suggested that CDKN2A/B deletions were poor prognostic factors for both overall survival (OS) (HR = 2.15, 95% CI 1.82–2.54) and event-free survival (EFS)/disease-free survival (DFS)/relapse-free survival (RFS) (HR = 2.16, 95% CI 1.73–2.69). The adverse impact remained significant in both adult and paediatric ALL patients, and also in subgroups by ethnicity, ALL type, detection method of CDKN2A/B deletions, statistical method and endpoint.Conclusions: Our findings suggested that CDKN2A/B deletions were associated with poor prognosis independently in both adult and childhood ALL patients. Inclusion of CDKN2A/B status may further improve the risk stratification of ALL patients.

Key Messages

• Although numerous studies have explored the prognostic significance of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions in acute lymphoblastic leukaemia (ALL) patients, the results remain conflicting.
• In this meta-analysis, we found that CDKN2A/B deletions were independent poor prognostic markers for both adult and paediatric ALL patients.
• Our findings justify the inclusion of CDKN2A/B status in the risk stratification of ALL patients.

     

Scoring systems used to predict mortality in patients with acute upper gastrointestinal bleeding in the ED

Objective

Acute upper gastrointestinal bleeding (UGIB) is a potentially life-threatening condition that requires rapid assessment in the emergency department (ED). We aimed to compare the performance of the AIMS65, Glasgow-Blatchford (Blatchford), preendoscopic Rockall (pre-Rockall), and preendoscopic Baylor bleeding (pre-Baylor) scores in predicting 30-day mortality in patients with acute UGIB in the ED setting.

Prophylactic tracheal intubation for upper GI bleeding: A meta-analysis

AIM: To evaluate usefulness of prophylactically intubating upper gastrointestinal bleeding (UGIB) patients. METHODS: UGIB results in a significant number of hospital admissions annually with endoscopy being the key intervention. In these patients, risks are associated with the bleeding and the procedure, including pulmonary aspiration. However, very little literature is available assessing the use of prophylactic endotracheal intubation on aspiration in these patients. A comprehensive search was performed in May 2014 in Scopus, CINAHL, Cochrane databases, PubMed/Medline, Embase, and published abstracts from national gastroenterology meetings in the United States (2004-2014). Included studies examined UGIB patients and compared prophylactic intubation to no intubation before endoscopy. Meta-analysis was conducted using RevMan 5.2 by Mantel-Haenszel and DerSimonian and Laird models with results presented as odds ratio for aspiration, pneumonia (within 48 h), and mortality. Funnel plots were utilized for publication bias and I² measure of inconsistency for heterogeneity assessments. RESULTS: Initial search identified 571 articles. Of these articles, 10 relevant peer-reviewed articles in English and two relevant abstracts were selected to review by two independent authors (Almashhrawi AA and Bechtold ML). Of these studies, eight were excluded: Five did not have a control arm, one was a letter the editor, one was a survey study, and one was focused on prevention of UGIB. Therefore, four studies (N = 367) were included. Of the UGIB patients prophylactically intubated before endoscopy, pneumonia (within 48 h) was identified in 20 of 134 (14.9%) patients as compared to 5 of 95 (5.3%) patients that were not intubated prophylactically (P = 0.02). Despite observed trends, no significant differences were found for mortality (P = 0.18) or aspiration (P = 0.11). CONCLUSION: Pneumonia within 48 h is more likely in UGIB patients who received prophylactic endotracheal intubation prior to endoscopy.     

Periodontal disease as a predictor of chronic kidney disease (CKD) stage in older adults

ObjectiveThe aim of this study was to evaluate periodontal disease as a predictor of chronic kidney disease (CKD) stage in older adults.MethodsA total of 1159 adults aged 65 to 80 years and diagnosed with periodontal disease and CKD (stages 1, 2, and 3) were randomly selected for a cross-sectional study. Periodontal status was assessed using the Community Periodontal Index of Treatment Needs (CPITN) and CKD was staged using the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) guidelines.ResultsIn patients with stage 1 CKD, the odds ratios (ORs) (95% confidence intervals [CIs]) for CPITN-1, CPITN-2, CPITN-3, and CPITN-4 were 1.13 (0.83–1.55), 1.47 (1.13–1.81), 1, and 1, respectively. In patients with stage 2 CKD, the ORs (95% CIs) for CPITN-1, CPITN-2, CPITN-3, and CPITN-4 were 1.49 (1.14–1.93), 1.37 (1.02–1.78), 3.07 (2.81–3.25), and 3.65 (3.49–3.71), respectively. In patients with stage 3 CKD, the ORs (95% CIs) for CPITN-1, CPITN-2, CPITN-3, and CPITN-4 were 1, 1, 4.61 (4.47–5.21), and 5.23 (5.14–5.47), respectively.ConclusionThe highest CPITN values (CPITN-3 and CPITN-4) were associated with CKD stages 2 and 3. Thus, periodontal disease may be associated with progression of CKD.     

Risk of preterm birth in primiparous women with exposure to antidepressant medication before pregnancy and/or during pregnancy – impact of body mass index

Introduction: Preterm birth is a major cause of infant mortality. It is unknown whether body mass index (BMI) influences the risk of preterm birth in women, who prenatally use antidepressants.Materials and methods: The study cohort (N = 6920) consists of all primiparous European born women without previously diagnosed diabetes from the city of Vantaa, Finland, who delivered a singleton child between 2009 and 2015. Data on births, pre-pregnancy BMI and purchases of antidepressants from 12 months before conception until delivery were obtained from Finnish National Registers.Results: Of the primiparous women, 9.9% used antidepressants. The overall prevalence of preterm birth was 5.2%. In women with a pre-pregnancy BMI <18.5 kg/m², the Odds Ratio (OR) for preterm birth among antidepressant users compared with those who were non-users was 1.91 (95% confidence intervals [CI] 0.40 to 9.15, adjusted for age, smoking, education, use of fertility treatments and number of previous pregnancies) while in women with a pre-pregnancy BMI ≥30 kg/m², the OR was 0.53 (95% CI 0.21–1.36), respectively.Discussion: Primiparous women using antidepressants, who were underweight before conception should be closely monitored and provided tailored care in a maternity clinic to minimize the risk of preterm birth.

Key messages

• In primiparous women, one in ten used antidepressant medications before pregnancy and/or during pregnancy.
• In primiparous women, the prevalence of preterm birth was 5%.
• Underweight primiparous women using antidepressants should be closely monitored and provided tailored care in a maternity clinic.

     

A randomized trial of low-dose aspirin in the prevention of clinical type 2 diabetes in women

OBJECTIVE—Subclinical inflammation is linked with the development of type 2 diabetes, and epidemiologic data suggest that this association may be stronger in women. Although small clinical studies have shown a prominent hypoglycemic effect of short-term high-dose aspirin, no randomized trials have directly evaluated the efficacy of aspirin in diabetes prevention at doses acceptable for use in routine clinical practice. We evaluated whether chronic low-dose aspirin prevents the development of clinical diabetes among initially healthy American women.RESEARCH DESIGN AND METHODS—Subjects were enrolled in the Women''s Health Study, a 10-year randomized double-blind, placebo-controlled trial of aspirin and vitamin E for primary prevention of cardiovascular disease and cancer. Between 1992 and 1995, 38,716 women aged ≥45 years and free of clinical diabetes were randomly assigned to either low-dose aspirin or placebo (median follow-up 10.2 years). Documented clinical type 2 diabetes was prospectively evaluated throughout the trial.RESULTS—Among women randomly assigned to receive aspirin (n = 19,326) or placebo (n = 19,390), there was no statistically significant difference in the incidence of type 2 diabetes. There were 849 cases of diabetes in the aspirin group and 847 in the placebo group (rate ratio 1.01 [95% CI 0.91–1.11]). Stratification by diabetes risk factors including age, BMI, family history of diabetes, physical activity, A1C, and high-sensitivity C-reactive protein did not support a modulating effect of these variables. Analyses accounting for treatment duration and adherence similarly found no beneficial effects.CONCLUSIONS—These data suggest that long-term low-dose aspirin does not prevent the development of clinical type 2 diabetes in initially healthy women.The ability of salicylates, such as aspirin, to reduce glucose levels was described >125 years ago (1). This effect was largely forgotten until the emergence of recent data linking inflammation with the development of type 2 diabetes. A wealth of experimental and epidemiological evidence now indicates that insulin resistance and type 2 diabetes are, in part, obesity-linked inflammatory disorders (2), and the presence of subclinical inflammation is now known to be a potent indicator of risk for this disease. This relationship may be of particular importance in the pathogenesis of diabetes in women among whom obesity-triggered inflammation may be heightened compared with that in men (3). These findings have spurred interest in the use of anti-inflammatory drugs in diabetes prevention and treatment (4). However, data pertaining to this novel approach are sparse with no large-scale randomized studies available to date.Aspirin is an anti-inflammatory agent with pleiotropic actions, many of which remain poorly understood. The cellular and molecular mechanisms of the hypoglycemic response to aspirin are an area of active investigation but likely involve anti-inflammatory pathways distinct from effects on prostaglandin synthesis (5,6). Several small clinical studies (7–10) have reported that short-term high-dose aspirin (3–10 g/day for 3 days–3 weeks) improves glucose handling and may ameliorate insulin resistance in diabetic patients, albeit with a high rate of side effects. Although data are not available on the hypoglycemic action of low-dose aspirin, several short-term clinical trials demonstrated that aspirin triggers the production of anti-inflammatory mediators (11) and lowers systemic levels of inflammatory biomarkers at doses as low as 30 mg/day (12). Whether chronic low-dose aspirin therapy has favorable clinical effects is unknown.We assessed whether long-term low-dose aspirin therapy reduces the incidence of clinical type 2 diabetes in the randomized treatment arms of the Women''s Health Study (WHS). The WHS tested the efficacy of low-dose aspirin in the primary prevention of cardiovascular disease and cancer over a 10-year period in a large group of initially healthy women. The occurrence of clinical diabetes was ascertained prospectively throughout the trial.     

Glycemic Control and Cardiovascular Disease in 7,454 Patients With Type 1 Diabetes: An observational study from the Swedish National Diabetes Register (NDR)

OBJECTIVE

We assessed the association between A1C and cardiovascular diseases (CVDs) in an observational study of patients with type 1 diabetes followed for 5 years.

RESEARCH DESIGN AND METHODS

A total of 7,454 patients were studied from the Swedish National Diabetes Register (aged 20–65 years, diabetes duration 1–35 years, followed from 2002 to 2007).

RESULTS

Hazard ratios (HRs) for fatal/nonfatal coronary heart disease (CHD) per 1% unit increase in baseline or updated mean A1C at Cox regression analysis were 1.31 and 1.34 and 1.26 and 1.32, respectively, for fatal/nonfatal CVD (all P < 0.001 after adjustment for age, sex, diabetes duration, blood pressure, total and LDL cholesterol, triglycerides, BMI, smoking, and history of CVD). HRs were only slightly lower for CHD (P = 0.002) and CVD (P = 0.002–0.007) after also adjusting for albuminuria. Adjusted 5-year event rates of CHD and CVD increased progressively with higher A1C, ranging from 5 to 12%, as well as when subgrouped by shorter (1–20 years) or longer (21–35 years) duration of diabetes. A group of 4,186 patients with A1C 5–7.9% (mean 7.2) at baseline showed risk reductions of 41% (95% confidence intervals: 15–60) (P = 0.005) for fatal/nonfatal CHD and 37% (12–55) (P = 0.008) for CVD, compared with 3,268 patients with A1C 8–11.9% (mean 9.0), fully adjusted also for albuminuria.

CONCLUSIONS

This observational study of patients in modern everyday clinical practice demonstrates progressively increasing risks for CHD and CVD with higher A1C, independently of traditional risk factors, with no J-shaped risk curves. A baseline mean A1C of 7.2% showed considerably reduced risks of CHD and CVD compared with A1C 9.0%, emphasizing A1C as a strong independent risk factor in type 1 diabetes.Patients with type 1 diabetes have long been considered to have increased risks of cardiovascular disease (CVD) and mortality (1,2), and this has recently been confirmed in two studies (3,4) from the General Practice Research Database in the U.K. Based on data from 1992 to 1999, risks of CVD and mortality were four to eight times higher in men and women with type 1 diabetes than nondiabetic individuals (3,4).While the association between glycemia and microvascular complications is established (5,6), there have been no long-term randomized clinical studies satisfactorily examining the relationship with macrovascular complications in type 1 diabetes, and epidemiological studies have shown conflicting results (7–14). The Epidemiology of Diabetes Interventions and Complications (EDIC) Study showed that patients who had previously been subjected to intensive glucose control during the Diabetes Control and Complications Trial (DCCT) had a considerably lower risk of CVD than patients receiving standard treatment (1983–1993) (7). A small study from Finland on late-onset type 1 diabetic patients without albuminuria showed increased risk of coronary heart disease (CHD) with poor glycemic control (9), but the EURODIAB Prospective Complications Study (PCS), the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study, and the Wisconsin Epidemiologic Study of Diabetic Retinopathy did not demonstrate a significant relationship between glycemia and CHD after controlling for other cardiovascular risk factors (10–13). However, a recent study (14) from the Pittsburgh EDC showed that change in A1C was related to coronary artery disease, whereas baseline A1C was not.With this background, we assessed the association between A1C and CHD, stroke, and CVD in a large cohort of patients with type 1 diabetes, aged 20–65 years, treated in everyday clinical practice from 2002 to 2007. Data were used from the Swedish National Diabetes register (NDR), a quality-assurance tool in diabetes care with nationwide coverage with recently published reports regarding type 1 and type 2 diabetes (15–17).     

Risk for ischemic stroke and coronary heart disease associated with migraine and migraine medication among older adults

BackgroundMigraine has been associated with cardiovascular disease (CVD) events among middle-aged adults. The objective of this study was to determine the risk for ischemic stroke and coronary heart disease (CHD) events among older adults with versus without migraine.MethodsThis retrospective cohort study was conducted using data from US adults ≥66 years of age with Medicare health insurance between 2008 and 2017. After stratification by history of CVD, patients with a history of migraine were matched 1:4 to those without a history of migraine, based on calendar year, age, and sex. Patients were followed through December 31, 2017 for ischemic stroke and CHD events including myocardial infarction or coronary revascularization. All analyses were done separately for patients with and without a history of CVD.ResultsAmong patients without a history of CVD (n = 109,950 including n = 21,990 with migraine and n = 87,960 without migraine), 1789 had an ischemic stroke and 3552 had a CHD event. The adjusted hazard ratio (HR) among patients with versus without migraine was 1.20 (95% confidence interval [95%CI], 1.07–1.35) for ischemic stroke and 1.02 (95%CI, 0.93–1.11) for CHD events. Compared to patients without migraine, those with migraine who were taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.43 [95%CI, 1.20–1.69]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.79 [95%CI, 0.67–0.93]). Among patients with a history of CVD (n = 79,515 including n = 15,903 with migraine and n = 63,612 without migraine), 2960 had an ischemic stroke and 7981 had a CHD event. The adjusted HRs (95%CI) for ischemic stroke and CHD events associated with migraine were 1.27 (1.17–1.39) and 0.99 (0.93–1.05), respectively. Patients with migraine taking an opioid medication had a higher risk for ischemic stroke (adjusted HR 1.21 [95%CI, 1.07–1.36]), while those taking a triptan had a lower risk for CHD events (adjusted HR 0.83 [95%CI, 0.72–0.95]), each versus those without migraine.ConclusionsOlder adults with migraine are at increased risk for ischemic stroke. The risk for ischemic stroke among older adults with migraine may differ by migraine medication classes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01338-z.