Michelle Schmiegelow

Valproate attenuates the risk of myocardial infarction in patients with epilepsy: a nationwide cohort study

Patients with epilepsy have increased risk of myocardial infarction (MI). Valproate can exert anti‐atherosclerotic effects. We therefore examined the risk of MI in patients with epilepsy receiving valproate.

Obesity is a risk factor for atrial fibrillation among fertile young women: a nationwide cohort study

AIMS Obesity has been associated with increased risk of atrial fibrillation (AF), but whether this risk is also prevalent in younger individuals is unknown. We therefore investigated the risk of AF in relation to body mass index (BMI) among young fertile women. METHODS AND RESULTS By cross-linkage of nationwide registers of childbirth and hospitalization, we identified 271 203 women without prior AF who gave birth in Denmark between 2004 and 2009. Body mass index (kg/m(2)) was examined as a risk factor for AF using proportional hazard models. Mean age was 30.6 years (4.7 SD) and median follow-up was 4.6 years (interquartile range 2.9-5.8). During the follow-up, 110 women were hospitalized with first-time AF; very few individuals had known risk factors for AF. Overall incidence rate of AF was 9.3 [95% confidence interval (CI): 7.7-11.2] per 100 000 person-years. According to BMI, the incidence rate of AF per 100 000 person-years was 7.4 (5.6-9.7) in normal weight (BMI: 18.5-24.9), 8.5 (5.5-13.1) in overweight (BMI: 25-29.9), 15.8 (9.3-26.7) in obese (BMI: 30-35), and 27.3 (15.5-48.1) in very obese (BMI >35) individuals. Multivariable regression analyses adjusted for age, hyperthyroidism, and previous use of beta-blockers revealed a hazard ratio of 2.04 (95% CI: 1.13-3.69) in the obese and 3.50 (1.86-6.58) in the very obese individuals compared with normal weight. CONCLUSION Obesity is a risk factor for AF among young and essentially healthy fertile women despite the low incidence of AF. These results may have implications for prevention of AF.

Risk of cancer in patients using glucose-lowering agents: a nationwide cohort study of 3.6 million people

Objectives To study the association between exposures to glucose-lowering therapy and risk of cancer using the nationwide administrative registers in Denmark. Design Nationwide cohort study. Setting All hospitals in Denmark. Participants All individuals aged ≥35 years in 1998–2009 who were naive to glucose-lowering treatment and had no history of cancer. Primary measures outcomes: first cancer diagnosis between 1998 and 2009. The RR of cancer as dependent on exposure to individual glucose-lowering agents was assessed by multivariable Poisson regression models. Results Of 159 894 patients that initiated treatment with glucose-lowering agents, 12 789 developed cancer, incidence rate 17.4/1000 person-years. Of the remaining 3 447 904 individuals not using glucose-lowering agents, 293 878 developed cancer, incidence rate 7.9/1000 person-years. Use of different types of glucose-lowering agents including human insulin, insulin analogues, as well as sulfonylureas were associated with a quantitatively similar and significantly increased RR of cancer of 1.2–1.3 compared with unexposed individuals after multivariable adjustment. For the majority of agents, the authors identified the highest RR of cancer during the first 30 treatment days with a subsequent decline of risk approaching the cancer risk of the background population only 6–12 months after initiation of treatments. Conclusions Use of most glucose-lowering agents including sulfonylureas was associated with a comparable increased risk of cancer shortly after initiation of treatment and subsequently a decline to the risk of the background population. This suggests that the relation is not causal.

Associations Between Body Mass Index and Development of Metabolic Disorders in Fertile Women—A Nationwide Cohort Study

Background Metabolic disorders are relatively uncommon in young women, but may increase with obesity. The associations between body mass index (BMI) and risks of diabetes, hypertension, and dyslipidemia in apparently healthy, young women have been insufficiently investigated, and are the aims of this study. Methods and Results Women giving birth during the years 2004–2009, with no history of cardiovascular disease, renal insufficiency, pregnancy‐associated metabolic disorders, diabetes, hypertension, or dyslipidemia were identified in nationwide registers. Women were categorized as underweight (BMI<18.5 kg/m2), normal weight (BMI=18.5 to <25 kg/m2), overweight (BMI=25 to <30 kg/m2), obese‐I (BMI=30 to <35 kg/m2), obese‐II (BMI=35 to <40 kg/m2), and obese‐III (BMI≥40 kg/m2). We assessed risks by Poisson regression models (adjusted for age, calendar year; reference=normal weight). The cohort comprised 252 472 women with a median age of 30.4 years (IQR=27.2;33.7) and a median follow‐up of 5.5 years (IQR=3.9;6.8). In total, 2029 women developed diabetes, 3133 women developed hypertension, and 1549 women developed dyslipidemia. Rate ratios (RRs) of diabetes were: 0.84 (95% confidence interval [CI]=0.62 to 1.14) for underweight, 2.63 (CI=2.36 to 2.93) for overweight, 4.83 (CI=4.27 to 5.47) for obese grade‐I, 7.17 (CI=6.10 to 8.48) for obese grade‐II, and 6.93 (CI=5.47 to 8.79) for obese grade‐III women. For hypertension, corresponding RRs were 0.86 (CI=0.69 to 1.09), 1.82 (CI=1.67 to 1.98), 2.81 (CI=2.52 to 3.13), 3.92 (CI=3.36 to 4.56), and 5.69 (CI=4.71 to 6.89), and for dyslipidemia, RRs were 1.18 (CI=0.85 to 1.65), 2.01 (CI=1.75 to 2.31), 3.11 (CI=2.61 to 3.70), 4.64 (CI=3.66 to 5.87), and 3.72 (CI=2.53 to 5.48). Conclusions In this nationwide study of fertile, apparently healthy women, pre‐pregnancy BMI was strongly associated with an increased risk of diabetes, hypertension, and dyslipidemia within 5.5 years following childbirth.

Prepregnancy Obesity and Associations With Stroke and Myocardial Infarction in Women in the Years After Childbirth A Nationwide Cohort Study

Background— Cardiovascular events (stroke or myocardial infarction) are often associated with poorer prognosis in younger, compared with older individuals. We examined the associations between prepregnancy obesity and the risks of myocardial infarction and stroke in young, healthy women. Methods and Results— All Danish women giving birth during 2004–2009 without a history of renal disease or cardiovascular disease were identified from national registers and followed for a median time of 4.5 years (interquartile range, 2.8–5.8). They were grouped according to prepregnancy body mass index (BMI) in underweight (BMI<18.5 kg/m2), normal weight (BMI=18.5–<25 kg/m2), overweight (BMI=25–<30 kg/m2), and obese (BMI≥30 kg/m2). The hazard ratios of myocardial infarction, ischemic stroke, and a composite outcome (myocardial infarction, stroke, cardiovascular death) were assessed using multivariable Cox regression models. We included 273 101 women with a median age of 30.4 years (interquartile range, 27.2–33.8). A total of 68 women experienced a myocardial infarction, and 175 women experienced an ischemic stroke. The adjusted hazard ratios of myocardial infarction compared with normal weight were 2.50 (95% confidence interval [95% CI], 0.97–6.50) in underweight, 1.68 (95% CI, 0.92–3.06) in overweight, and 2.63 (95% CI, 1.41–4.91) in obese women. For ischemic stroke the adjusted hazard ratios were 1.06 (95% CI, 0.44–2.28) in underweight, 1.27 (95% CI, 0.87–1.85) in overweight, and 1.89 (95% CI, 1.25–2.84) in obese women, respectively. For the composite outcome, hazard ratios were 1.34 (95% CI, 0.81–2.20), 1.43 (95% CI, 1.11–1.84), and 1.76 (95% CI, 1.31–2.34) for underweight, overweight, and obese women. Conclusions— In apparently healthy women of fertile age, prepregnancy obesity was associated with increased risks of ischemic stroke and myocardial infarction in the years after childbirth.

Risk factors for venous thromboembolism during pregnancy

Pregnant women are at an increased risk of venous thromboembolism (VTE). Risk factors for VTE among pregnant women are not sufficiently investigated.

Relation of body mass index to risk of stent thrombosis after percutaneous coronary intervention.

Stent thrombosis is a devastating complication after percutaneous coronary intervention (PCI), but the influence of obesity on risk of stent thrombosis is unclear, and it is unknown if this relation is dependent on stent type. The objective of this study was to examine the relation between body mass index (BMI) and stent thrombosis after PCI with bare-metal stent (BMS) or drug-eluting stent (DES). We followed 5,515 patients who underwent PCI with implantation of ≥1 BMS or DES at a high-volume tertiary invasive cardiology center from 2000 through 2006. Only patients with a single type of stent (BMS or DES) implanted at the index PCI were included. Median follow-up period was 26 months (interquartile range 12 to 44) and definite stent thrombosis occurred in 78 patients. Hazard ratio of definite stent thrombosis adjusted for number of stents at the index PCI was 0.92 (95% confidence interval [CI] 0.86 to 0.97) for each increase in kilograms per square meter of BMI. There was no significant interaction between stent type and BMI (p = 0.48). Hazard ratios for probable stent thrombosis and possible stent thrombosis adjusted for numbers of stents at the index PCI were 1.01 (CI 0.99 to 1.03) and 0.99 (CI 0.98 to 1.01) for each increase in kilograms per square meter of BMI, respectively. In conclusion, BMI was inversely correlated with risk of definite stent thrombosis after PCI irrespective of stent type.

Incidence of Atrial Fibrillation in Patients with either Heart Failure or Acute Myocardial Infarction and Left Ventricular Dysfunction: A Cohort Study

BackgroundWe examined the incidence of new-onset atrial fibrillation in patients with left ventricular dysfunction. Patients either had a recent myocardial infarction (with or without clinical heart failure) or symptomatic heart failure (without a recent MI). Patients were with and without treatment with the class III antiarrhythmic drug dofetilide over 36 months.MethodsThe Danish Investigations of Arrhythmia and Mortality ON Dofetilide (DIAMOND) studies included 2627 patients without atrial fibrillation at baseline, who were randomised to treatment with either dofetilide or placebo.ResultsThe competing risk analyses estimated the cumulative incidences of atrial fibrillation during the 42 months of follow-up to be 9.6% in the placebo-treated heart failure-group, and 2.9% in the placebo-treated myocardial infarction-group.Cox proportional hazard regression found a 42% significant reduction in the incidence of new-onset AF when assigned to dofetilide compared to placebo (hazard ratio 0.58, 95% confidence interval 0.40-0.82) and there was no interaction with study (p = 0.89).In the heart failure-group, the incidence of atrial fibrillation was significantly reduced to 5.6% in the dofetilide-treated patients (hazard ratio 0.57, 95% confidence interval 0.38-0.86).In the myocardial infarction-group the incidence of atrial fibrillation was reduced to 1.7% with the administration of dofetilide. This reduction was however not significant (hazard ratio 0.61, 95% confidence interval 0.30-1.24).ConclusionIn patients with left ventricular dysfunction the incidence of AF in 42 months was 9.6% in patients with heart failure and 2.9% in patients with a recent MI. Dofetilide significantly reduced the risk of developing atrial fibrillation compared to placebo in the entire study group and in the subgroup of patients with heart failure. The reduction in the subgroup with recent MI was not statistically significant, but the hazard ratio was similar to the hazard ratio for the heart failure patients, and there was no difference between the effect in the two studies (p = 0.89 for interaction).

Associations between metabolic disorders and risk of cancer in Danish men and women - a nationwide cohort study

BackgroundThe prevalence of metabolic disorders is increasing and has been suggested to increase cancer risk, but the relation between metabolic disorders and risk of cancer is unclear, especially in young adults. We investigated the associations between diabetes, hypertension, and hypercholesterolemia on risk of all-site as well as site-specific cancers.MethodsWe consecutively included men and women from nationwide Danish registries 1996–2011, if age 20–89 and without cancer prior to date of entry. We followed them throughout 2012. Metabolic disorders were defined using discharge diagnosis codes and claimed prescriptions. We used time-dependent sex-stratified Poisson regression models adjusted for age and calendar year to assess associations between metabolic disorders, and risk of all-site and site-specific cancer (no metabolic disorders as reference).ResultsOver a mean follow-up of 12.6 (±5.7 standard deviations [SD]) years, 4,826,142 individuals (50.2 % women) with a mean age of 41.4 (±18.9 SD) years had 423,942 incident cancers. Incidence rate ratios (IRRs) of all-site cancer in patients with diabetes or hypertension were highest immediately following diagnosis of metabolic disorder. In women, cancer risk associated with diabetes continued to decline albeit remained significant (IRRs of 1.18–1.22 in years 1–8 following diagnosis). For diabetes in men, and hypertension, IRRs stabilized and remained significantly increased after about one year with IRRs of 1.10-1.13 in men for diabetes, and 1.07–1.14 for hypertension in both sexes. Conversely, no association was observed between hypercholesterolemia (treatment with statins) and cancer risk. The association between hypertension and cancer risk was strongest in young adults aged 20–34 and decreased with advancing age.ConclusionsDiabetes and hypertension were associated with increased risk of all-site cancer.

Impact of metabolic disorders on the relation between overweight/obesity and incident myocardial infarction and ischaemic stroke in fertile women: a nationwide cohort study.

Whether overweight is a risk factor for cardiovascular disease in the absence of metabolic disorders remains under debate and is largely unexamined in young women. We evaluated the risk of myocardial infarction and ischaemic stroke in fertile women conditional on time‐dependent presence of metabolic disorders.