Jawad H. Butt

Endothelial Function in Migraine With Aura – A Systematic Review

An increased risk of ischemic stroke is repeatedly reported in young subjects with migraine with aura (MA). Such may be caused by changes in endothelial function. The present review evaluates current evidence on endothelial function in MA patients.

Short- and long-term cause of death in patients undergoing isolated coronary artery bypass grafting: A nationwide cohort study

Objectives: Knowledge of the association between time and causes of death after coronary artery bypass grafting is sparse. We examined short‐ and long‐term mortality and cause of death in patients undergoing coronary artery bypass grafting. Methods: With the use of Danish nationwide registries, we identified all patients undergoing isolated coronary artery bypass grafting from 1998 to 2014. Cause of death was classified as cardiovascular or noncardiovascular according to death certificates. Landmark analyses of the cumulative incidences of cardiovascular and noncardiovascular mortality after 1, 3, and 5 years after coronary artery bypass grafting were performed. Multivariable cause‐specific Cox regression models were used to evaluate changes over time in the risk of all‐cause, cardiovascular, and noncardiovascular mortality after 1 and 7 years after coronary artery bypass grafting, respectively. Results: Among 37,495 included patients, 12,230 (32.6%) died during a median follow‐up of 7.4 years. Causes of death were classified as cardiovascular in 6459 patients (52.8%) and noncardiovascular in 5771 patients (47.2%). Within the first year, the incidence of cardiovascular death was higher compared with noncardiovascular death (3.9% vs 1.1%, P < .001). The cumulative incidences of cardiovascular and noncardiovascular were deaths similar in the periods 1 to 3 years (2.3% vs 2.6%, P = .004), 3 to 5 years (3.1% vs 3.2%, P = .75), and 5 to 7 years postsurgery (3.7% vs 4.0%, P = .07). The crude rates and adjusted risks of short‐ and long‐term all‐cause and cardiovascular mortality decreased during the study period despite an increase in age and burden of comorbidities. Conclusions: In patients undergoing coronary artery bypass grafting, cardiovascular causes were responsible for the majority of deaths within the first year. Deaths due to noncardiovascular causes gained importance over time elapsed since coronary artery bypass grafting.

Beta-Blockers for Exams Identify Students at High Risk of Psychiatric Morbidity

OBJECTIVES Beta-blockers relieve the autonomic symptoms of exam-related anxiety and may be beneficial in exam-related and performance anxiety, but knowledge on related psychiatric outcomes is unknown. We hypothesized that beta-blocker therapy for exam-related anxiety identifies young students at risk of later psychiatric events. METHODS Using Danish nationwide administrative registries, we studied healthy students aged 14-30 years (1996-2012) with a first-time claimed prescription for a beta-blocker during the exam period (May-June); students who were prescribed a beta-blocker for medical reasons were excluded. We matched these students on age, sex, and time of year to healthy and study active controls with no use of beta-blockers. Risk of incident use of antidepressants, incident use of other psychotropic medications, and suicide attempts was examined by cumulative incidence curves for unadjusted associations and multivariable cause-specific Cox proportional hazard analyses for adjusted hazard ratios (HRs). RESULTS We identified 12,147 healthy students with exam-related beta-blocker use and 12,147 matched healthy students with no current or prior use of beta-blockers (median age, 19 years; 80.3% women). Among all healthy students, 0.14% had a first-time prescription for a beta-blocker during the exam period with the highest proportion among students aged 19 years (0.39%). Eighty-one percent of the students filled only that single prescription for a beta-blocker during follow-up. During follow-up, 2225 (18.3%) beta-blocker users and 1400 (11.5%) nonbeta-blocker users were prescribed an antidepressant (p < 0.0001); 1225 (10.1%) beta-blocker users and 658 (5.4%) nonbeta-blocker users were prescribed a psychotropic drug (p < 0.0001); and 16 (0.13%) beta-blocker users and 6 (0.05%) nonbeta-blocker users attempted suicide (p = 0.03). Exam-related beta-blocker use was associated with an increased risk of antidepressant use (adjusted HRs, 1.68 [95% confidence intervals (CIs), 1.57-1.79], p < 0.0001), other psychotropic medication use (HR, 1.93 [95% CI, 1.76-2.12] p < 0.0001), and suicide attempts (HR, 2.67 [95% CI, 1.04-6.82] p = 0.04). CONCLUSION In healthy students, use of beta-blockers during the exam period was associated with an increased risk of psychiatric outcomes and might identify psychologically vulnerable students who need special attention.

Temporal changes in infective endocarditis guidelines during the last 12 years: High-level evidence needed

Background Infective endocarditis (IE) is a complex disease necessitating extensive clinical guidelines. The guidelines from the American Heart Association (AHA) and the European Society of Cardiology (ESC) have been markedly extended during the last 12 years. We examined the evidence base for these changes. Methods IE guidelines published by AHA and ESC were reviewed. We categorized and combined guidelines into 3 time periods: (1) 2004 (AHA) and 2005 (ESC), (2) 2007 (AHA) and 2009 (ESC), and (3) 2015 (AHA) and 2015 (ESC). Number of recommendations, classes of recommendations (I, II, or III), and levels of evidence (LOE) (A, B, or C) were assessed and the changes over time. Results From period 1 to period 3, we found a statistically significant increase in total number of IE recommendations from 37 to 253 (P < .01), a 6.8‐fold increase. There were a significant decrease in LOE A (from 7 [20.0%] in period 1 to 4 [1.6%] in period 3, P < .0001, a 57% decrease), a nonsignificant decrease in LOE B recommendations (from 17 [48.6%] in period 1 to 115 [45.9%] in period 3, P = .29, a 6.8‐fold increase), and a significant increase in LOE C recommendations (from 11 [31.4%] in period 1 to 134 [53.0%] in period 3, P = .02, a 12.2‐fold increase). Conclusions The number of IE guideline recommendations has increased 6‐ to 7‐fold during the last decade without a corresponding increase in evidence. These results highlight the strong need for more clinical studies to improve the level of evidence in IE guidelines.

Prestroke and Poststroke Antithrombotic Therapy in Patients With Atrial Fibrillation: Results From a Nationwide Cohort

Key Points Question Is oral anticoagulation therapy used and effective for secondary stroke prophylaxis in patients with atrial fibrillation? Findings In this cohort study of 30 626 intermediate- to high-risk patients with atrial fibrillation having an ischemic stroke, 36.3% received oral anticoagulation therapy before their stroke, and 52.5% received oral anticoagulation therapy after their stroke. Oral anticoagulation therapy was associated with a statistically significant reduction in thromboembolic risk. Meaning There exists a major potential for optimization of both primary and secondary stroke prophylaxis in patients with atrial fibrillation.

Long-term thromboembolic risk in patients with postoperative atrial fibrillation after coronary artery bypass graft surgery and patients with nonvalvular atrial fibrillation

Importance New-onset postoperative atrial fibrillation (POAF) is a common complication of coronary artery bypass graft (CABG) surgery. However, the long-term risk of thromboembolism in patients who develop POAF after CABG surgery remains unknown. In addition, information on stroke prophylaxis in this setting is lacking. Objective To examine stroke prophylaxis and the long-term risk of thromboembolism in patients with new-onset POAF after first-time isolated CABG surgery compared with patients with nonsurgical, nonvalvular atrial fibrillation (NVAF). Design, Setting, and Participants This cohort study used data from a clinical cardiac surgery database and Danish nationwide registries to identify patients undergoing first-time isolated CABG surgery who developed new-onset POAF from January 1, 2000, through June 30, 2015. These patients were matched by age, sex, CHA2DS2-VASc score, and year of diagnosis to patients with nonsurgical NVAF in a 1 to 4 ratio. Data analysis was completed from February 2017 to January 2018. Main Outcomes and Measures The proportion of patients initiating oral anticoagulation therapy within 30 days and the rates of thromboembolism. Results A total of 2108 patients who developed POAF after CABG surgery were matched with 8432 patients with NVAF. In the full population of 10 540 patients, the median (interquartile range) age was 69.2 (63.7-74.7) years; 8675 patients (82.3%) were men. Oral anticoagulation therapy was initiated within 30 days postdischarge in 175 patients with POAF (8.4%) and 3549 patients with NVAF (42.9%). The risk of thromboembolism was lower in the POAF group than in the NVAF group (18.3 vs 29.7 events per 1000 person-years; adjusted hazard ratio [HR], 0.67; 95% CI, 0.55-0.81; P < .001). Anticoagulation therapy during follow-up was associated with a lower risk of thromboembolic events in both patients with POAF (adjusted HR, 0.55; 95% CI, 0.32-0.95; P = .03) and NVAF (adjusted HR, 0.59; 95% CI, 0.51-0.68; P < .001) compared with patients who did not receive any anticoagulation therapy. Further, the risk of thromboembolism was not significantly higher in patients with POAF compared with those who did not develop POAF after CABG surgery (adjusted HR, 1.11; 95% CI, 0.94-1.32; P < .24). Conclusions and Relevance New-onset POAF in patients who had undergone CABG surgery was associated with a lower long-term thromboembolic risk than that of patients who had NVAF. These data do not support the notion that new-onset POAF should be regarded as equivalent to primary NVAF in terms of long-term thromboembolic risk.

Validation of Repeated Endothelial Function Measurements Using EndoPAT in Stroke

Background Decreased endothelial function (EF) may be a prognostic marker for stroke. Measuring pharmacological effects on EF may be of interest in the development of personalized medicine for stroke prevention. In this study, we assessed the reliability of repeated EF measurements using a pulse amplitude tonometry technology in acute stroke patients. Similarly, reliability was tested in healthy subjects devoid of vascular disease to estimate reactivity and reliability in a younger non-stroke population. Materials and methods EF was assessed using the EndoPAT2000 in 20 healthy volunteers (men 50%, mean age 35.85 ± 3.47 years) and 21 stroke patients (men 52%, mean age 66.38 ± 2.85 years, and mean NIHSS 4.09 ± 0.53) under standardized conditions. EF was measured as the reactive hyperemia index (RHI), logarithm of RHI (lnRHI), and Framingham RHI (fRHI). Measurements were separated by 1.5 and 24 h to assess same-day and day-to-day reliability, respectively. Results Fair to moderate correlations of measurements [intraclass correlation coefficient (ICC)same-day 0.29 and ICCday-to-day 0.52] were detected in healthy subjects. In stroke patients, we found moderate to substantial correlation of both same-day and day-to-day repeated measurements (ICCsame-day 0.40 and ICCday-to-day 0.62). fRHI compared with RHI and lnRHI showed best reliability. Conclusion Repeated measurements of fRHI in stroke patients show moderate reliability on same-day and substantial on day-to-day measurements. Likewise, in healthy subjects there was substantial reliability on day-to-day measurement, but only moderate on same-day measurements. In general, day-to-day correlation of repeated EF measurements was far better than that of same-day measurements, which ranged from poor to moderate depending on the specific outcome measure of EF. A possible carryover effect should be considered if same-day repeated testing of drug effects is applied in future studies.

Return to the workforce following coronary artery bypass grafting: A Danish nationwide cohort study

BACKGROUND Returning to the workforce after coronary artery bypass grafting (CABG) holds important socioeconomic consequences not only for patients, but the society as well. Yet data on this issue are limited. We examined return to the workforce and associated factors in patients of working age undergoing CABG. METHODS AND RESULTS Using Danish nationwide administrative registries, we identified 6031 patients of working age (18-60years) undergoing isolated CABG (1998-2011) who were part of the workforce 30days prior to admission and alive at discharge. One year after discharge for CABG, 4827 (80.0%) patients had returned to the workforce, 614 (10.2%) were on paid sick leave, 267 (4.4%) received disability pension, 250 (4.1%) were on early retirement, 57 (0.9%) had died, and 16 (0.3%) had emigrated. Factors associated with return to the workforce were identified using multivariable logistic regression. Younger age (18-45 versus 56-60years; odds ratio, 1.89; 95% confidence interval, 1.48-2.42), male sex (1.51, 1.24-1.84), and higher level of education (higher educational level versus basic school; 1.53, 1.05-2.23) and income (highest quartile versus lowest; 3.01, 2.42-3.75) were associated with return to the workforce. Urgency of surgery (emergency versus elective; 0.65, 0.49-0.88), cardiovascular comorbidity, a history of chronic kidney disease (0.49, 0.29-0.84) and liver disease (0.47, 0.28-0.80), as well as additional hospital admissions within the first year post-discharge (>2 versus none; 0.25, 0.19-0.32) were associated with a lower likelihood of returning to the workforce. CONCLUSION One year after discharge for CABG, four out of five patients were part of the workforce and mortality was low. Younger age, male sex, higher socioeconomic status, and absence of major comorbidities were associated with return to the workforce.

Induction of migraine-like headache, but not aura, by cilostazol in patients with migraine with aura

Whether migraine headache and migraine aura share common pathophysiological mechanisms remains to be understood. Cilostazol causes cAMP accumulation and provokes migraine-like headache in migraine patients without aura. We investigated if cilostazol induces aura and migraine-like headache in patients with migraine with aura and alters peripheral endothelial function and levels of endothelial markers. In a randomized, double-blinded, placebo-controlled crossover study, 16 patients with migraine with aura (of whom 12 patients exclusively had attacks of migraine with aura) received 200 mg cilostazol (Pletal®) or placebo on two separate days. The development, duration, and characteristics of aura and headache were recorded using a questionnaire. Peripheral endothelial function was assessed by digital pulse amplitude tonometry using EndoPAT2000, and endothelial markers (VCAM1, E-selectin, and VEGFA) were measured. After administration of cilostazol, 14 patients (88%) experienced headache compared with six patients (38%) after placebo (P = 0.009). The headache in 12 patients (75%) after cilostazol and one patient (6%) after placebo fulfilled the criteria for migraine-like attacks (P = 0.0002). Patients reported that the attack mimicked the headache phase during their usual migraine attacks. However, aura symptoms were elicited in one patient after cilostazol and one patient after placebo. Further, endothelial function, as assessed by peripheral arterial tonometry, and endothelial markers were not significantly altered by cilostazol. Accumulation of cAMP by cilostazol induces migraine-like headache, but not aura, in patients with migraine with aura, even in those who exclusively reported attacks of migraine with aura in their spontaneous attacks. These findings further support dissociation between the aura and the headache phase with a yet unknown trigger for the aura and link between aura and headache. In addition, cilostazol administration did not significantly alter endothelial function, as assessed by peripheral arterial tonometry, or the endothelial markers, VCAM1, E-selectin, and VEGFA. However, post hoc analyses showed that our study was statistically underpowered for these outcomes.

Return to the workforce following infective endocarditis—A nationwide cohort study

Background The ability to return to work after infective endocarditis (IE) holds important socioeconomic consequences for both patients and society, yet data on this issue are sparse. We examined return to the workforce and associated factors in IE patients of working age. Methods Using Danish nationwide registries, we identified 1,065 patients aged 18–60 years with a first‐time diagnosis of IE (1996–2013) who were part of the workforce prior to admission and alive at discharge. Results One year after discharge, 765 (71.8%) patients had returned to the workforce, 130 (12.2%) were on paid sick leave, 76 (7.1%) received disability pension, 23 (2.2%) were on early retirement, 65 (6.1%) had died, and 6 (0.6%) had emigrated. Factors associated with return to the workforce were identified using multivariable logistic regression. Younger age (18–40 vs 56–60 years; odds ratio, 2.85; 95% CI, 1.71–4.76) and higher level of education (higher educational level vs basic school; 5.47, 2.05–14.6) and income (highest quartile vs lowest; 3.17, 1.85–5.46) were associated with return to the workforce. Longer length of hospital stay (>90 vs 14–30 days; 0.16, 0.07–0.38); stroke during IE admission (0.38, 0.21–0.71); and a history of chronic kidney disease (0.29, 0.11–0.75), chronic obstructive pulmonary disease (0.31, 0.13–0.71), and malignancy (0.39, 0.22–0.69) were associated with a lower likelihood of returning to the workforce. Conclusions Seven of 10 patients who were part of the workforce prior to IE and alive at discharge were part of the workforce 1 year later. Younger age, higher socioeconomic status, and absence of major comorbidities were associated with return to the workforce.