Christopher Song

Association of Vitamin D Receptor Gene Polymorphism and Parkinson's Disease in Koreans

1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), which is the biologically active form of vitamin D, has anti-inflammatory effects and can prevent experimental Parkinsons disease (PD). 1,25(OH)2D3 exerts most of its actions only after it binds to its specific nuclear receptors. Eighty-five Korean patients with PD and 231 unrelated healthy individuals were evaluated to determine if vitamin D receptor gene (VDRG) BsmI polymorphisms were markers for the susceptibility to PD in Korean patients. Each polymorphism was detected using polymerase chain reaction (PCR)-based restriction analysis. In addition, the relationship between the BsmI polymorphisms and the clinical manifestations of PD was evaluated. Overexpression of the b allele (91.2 vs. 85.7%; p=0.069) and homozygote bb (84.7 vs. 72.7%; p=0.043) was found in the PD patients compared with the controls. These results show for the first time an association between PD and a VDRG polymorphism, which might be involved in the pathogenesis of PD, or in the linkage disequilibrium of the VDRG to another pathogenic gene locus.

Left Atrial Appendage Function and Stroke Risk

About 30% to 40% of ischemic stroke is of unknown cause.1,2 Recently, biomarkers of atrial dysfunction, or atrial cardiopathy, have been associated with embolic stroke risk even in the absence of atrial fibrillation (AF), suggesting that the presence of AF is not required for left atrial thromboembolism to occur.3 Most left atrial thrombi occur in the left atrial appendage (LAA), but there is limited use of LAA dysfunction parameters, such as LAA flow velocity and morphology, to predict ischemic stroke risk. Here we review the literature on the association between LAA pathology and dysfunction and ischemic stroke, with a focus on patients with unexplained, or cryptogenic, stroke. Each year, at least 200000 people in the United States experience a cryptogenic stroke.1,2 The classification of cryptogenic stroke, a subgroup of stroke of undetermined cause, was conventionally made when the initial stroke evaluation was unrevealing, regardless of whether the evaluation was exhaustive, routine, or incomplete.4 More recently, investigators have used the term embolic stroke of undetermined source in reference to a nonlacunar infarction occurring in the absence of a specific identifiable high-risk stroke mechanism, such as AF, valvular heart disease, or large artery stenosis.5 The idea that such infarctions are caused by a distant source of embolus is supported by findings from the National Institute of Neurological Disorders and Stroke Databank, indicating that undocumented cardiac or aortic sources of embolism were found in about two thirds of patients with cryptogenic stroke on follow-up testing.2 One of the most common mechanisms often found in a delayed fashion after cryptogenic stroke is paroxysmal AF, which is detected in ≤30% of patients with cryptogenic stroke on outpatient heart-rhythm monitoring.6,7 However, more than half of cryptogenic strokes remain a mystery even after long-term …

Cardiac magnetic resonance imaging: a new tool to identify cardioaortic sources in ischaemic stroke

Stroke of undetermined aetiology or ‘cryptogenic’ stroke accounts for 30–40% of ischaemic strokes despite extensive diagnostic evaluation. The role and yield of cardiac imaging is controversial. Cardiac MRI (CMR) has been used for cardiac disorders, but its use in cryptogenic stroke is not well established. We reviewed the literature (randomised trials, exploratory comparative studies and case series) on the use of CMR in the diagnostic evaluation of patients with ischaemic stroke. The literature on the use of CMR in the diagnostic evaluation of ischaemic stroke is sparse. However, studies have demonstrated a potential role for CMR in the diagnostic evaluation of patients with cryptogenic stroke to identify potential aetiologies such as cardiac thrombi, cardiac tumours, aortic arch disease and other rare cardiac anomalies. CMR can also provide data on certain functional and structural parameters of the left atrium and the left atrial appendage which have been shown to be associated with ischaemic stroke risk. CMR is a non-invasive modality that can help identify potential mechanisms in cryptogenic stroke and patients who may be targeted for enrolment into clinical trials comparing anticoagulation to antiplatelet therapy in secondary stroke prevention. Prospective studies are needed to compare the value of CMR as compared to transthoracic and transesophageal echocardiography in the diagnostic evaluation of cryptogenic stroke.

A Simple Score That Predicts Paroxysmal Atrial Fibrillation on Outpatient Cardiac Monitoring after Embolic Stroke of Unknown Source

BACKGROUND Occult paroxysmal atrial fibrillation (AF) is detected in 16%-30% of patients with embolic stroke of unknown source (ESUS). The identification of AF predictors on outpatient cardiac monitoring can help guide clinicians decide on a duration or method of cardiac monitoring after ESUS. METHODS We included all patients with ESUS who underwent an inpatient diagnostic evaluation and outpatient cardiac monitoring between January 1, 2013, and December 31, 2016. Patients were divided into 2 groups based on detection of AF or atrial flutter during monitoring. We compared demographic data, clinical risk factors, and cardiac biomarkers between the 2 groups. Multivariable logistic regression was used to determine predictors of AF. RESULTS We identified 296 consecutive patients during the study period; 38 (12.8%) patients had AF detected on outpatient cardiac monitoring. In a multivariable regression analysis, advanced age (ages 65-74: odds ratio [OR] 2.36, 95% confidence interval [CI] .85-6.52; ages 75 or older: OR 4.08, 95% CI 1.58-10.52) and moderate-to-severe left atrial enlargement (OR 4.66, 95% CI 1.79-12.12) were predictors of AF on outpatient monitoring. We developed the Brown ESUS-AF score: age (65-74 years: 1 point, 75 years or older: 2 points) and left atrial enlargement (moderate or severe: 2 points) with good prediction of AF (area under the curve .725) and was internally validated using bootstrapping. The percentage of patients with AF detected in each score category were as follows: 0: 4.2%; 1: 14.8%; 2: 20.8%; 3: 22.2%; 4: 55.6%. CONCLUSIONS The Brown ESUS-AF score predicts AF on prolonged outpatient monitoring after ESUS. More studies are needed to externally validate our findings.

Ischemic Stroke Risk After Acute Coronary Syndrome.

Background Prior studies show an increased risk of ischemic stroke (IS) after myocardial infarction; however, there is limited evidence on long‐term risk and whether it is directly related to cardiac injury. We hypothesized that the risk of IS after acute coronary syndrome is significantly higher if there is evidence of cardiac injury, such as ST‐segment elevation myocardial infarction (STEMI) or non‐STEMI, than when there is no evidence of cardiac injury, such as in unstable angina. Methods and Results Administrative claims data were obtained from all emergency department encounters and hospitalizations at Californias nonfederal acute care hospitals between 2008 and 2011. Patients with STEMI, non‐STEMI, and unstable angina were identified using appropriate International Classification of Diseases, Ninth Revision, Clinical Modification codes. The primary outcome was IS during 2 years of follow‐up. Unadjusted and adjusted Cox proportional hazards models were used to determine the association between acute coronary syndrome subtype and IS risk. We identified 73 059 patients with a diagnosis of STEMI (n=26 427), non‐STEMI (n=39 833), or unstable angina (n=6819) during the study period. In the fully adjusted models that included potential confounders such as atrial fibrillation and congestive heart failure, the risk of IS was higher with STEMI (hazard ratio 4.17, 95% CI 3.00–5.83; P<0.001) and non‐STEMI (hazard ratio 3.73, 95% CI 2.68–5.19, P<0.001) compared with unstable angina. Conclusions Non‐STEMI and STEMI confer an equally increased risk of IS. Studies exploring IS mechanisms in cardiac patients are needed to improve and tailor stroke prevention strategies.

Early Elevated Troponin Levels After Ischemic Stroke Suggests a Cardioembolic Source

Background and Purpose— Elevated cardiac troponin is a marker of cardiac disease and has been recently shown to be associated with embolic stroke risk. We hypothesize that early elevated troponin levels in the acute stroke setting are more prevalent in patients with embolic stroke subtypes (cardioembolic and embolic stroke of unknown source) as opposed to noncardioembolic subtypes (large-vessel disease, small-vessel disease, and other). Methods— We abstracted data from our prospective ischemic stroke database and included all patients with ischemic stroke during an 18-month period. Per our laboratory, we defined positive troponin as ≥0.1 ng/mL and intermediate as ≥0.06 ng/mL and <0.1 ng/mL. Unadjusted and adjusted regression models were built to determine the association between stroke subtype (embolic stroke of unknown source and cardioembolic subtypes) and positive and intermediate troponin levels, adjusting for key confounders, including demographics (age and sex), clinical characteristics (hypertension, hyperlipidemia, diabetes mellitus, renal function, coronary heart disease, congestive heart failure, current smoking, and National Institutes of Health Stroke Scale score), cardiac variables (left atrial diameter, wall-motion abnormalities, ejection fraction, and PR interval on ECG), and insular involvement of infarct. Results— We identified 1234 patients, of whom 1129 had admission troponin levels available; 10.0% (113/1129) of these had a positive troponin. In fully adjusted models, there was an association between troponin positivity and embolic stroke of unknown source subtype (adjusted odds ratio, 4.46; 95% confidence interval, 1.03–7.97; P=0.003) and cardioembolic stroke subtype (odds ratio, 5.00; 95% confidence interval, 1.83–13.63; P=0.002). Conclusions— We found that early positive troponin after ischemic stroke may be independently associated with a cardiac embolic source. Future studies are needed to confirm our findings using high-sensitivity troponin assays and to test optimal secondary prevention strategies in patients with embolic stroke of unknown source and positive troponin.

Left Atrial Appendage Morphology and Embolic Stroke of Undetermined Source: A Cross-Sectional Multicenter Pilot Study

BACKGROUND The left atrial appendage (LAA) is the main source of thrombus in atrial fibrillation, and there is an association between non-chicken wing (NCW) LAA morphology and stroke. We hypothesized that the prevalence of NCW LAA morphology would be higher among patients with cardioembolic (CE) stroke and embolic stroke of undetermined source (ESUS) than among those with noncardioembolic stroke (NCS). METHODS This multicenter retrospective pilot study included consecutive patients with ischemic stroke from 3 comprehensive stroke centers who previously underwent a qualifying chest computed tomography (CT) to assess LAA morphology. Patients underwent inpatient diagnostic evaluation for ischemic stroke, and stroke subtype was determined based on ESUS criteria. LAA morphology was determined using clinically performed contrast enhanced thin-slice chest CT by investigators blinded to stroke subtype. The primary predictor was NCW LAA morphology and the outcome was stroke subtype (CE, ESUS, NCS). RESULTS We identified 172 patients with ischemic stroke who had a clinical chest CT performed. Mean age was 70.1 ± 14.3 years and 51.7% were male. Compared with patients with NCS, the prevalence of NCW LAA morphology was higher in patients with CE stroke (58.7% versus 46.3%, P = .1) and ESUS (58.8% versus 46.3%, P = .2), but this difference did not achieve statistical significance. CONCLUSION The prevalence of NCW LAA morphology may be similar in patients with ESUS and CE, and may be higher than that in those with NCS. Larger studies are needed to confirm these associations.

Left Atrial Enlargement and Anticoagulation Status in Patients with Acute Ischemic Stroke and Atrial Fibrillation

BACKGROUND Despite anticoagulation therapy, ischemic stroke risk in atrial fibrillation (AF) remains substantial. We hypothesize that left atrial enlargement (LAE) is more prevalent in AF patients admitted with ischemic stroke who are therapeutic, as opposed to nontherapeutic, on anticoagulation. METHODS We included consecutive patients with AF admitted with ischemic stroke between April 1, 2015, and December 31, 2016. Patients were divided into two groups based on whether they were therapeutic (warfarin with an international normalized ratio ≥ 2.0 or non-vitamin K oral anticoagulant with uninterrupted use in the prior 2 weeks) versus nontherapeutic on anticoagulation. Univariable and multivariable models were used to estimate associations between therapeutic anticoagulation and clinical factors, including CHADS2 score and LAE (none/mild versus moderate/severe). RESULTS We identified 225 patients during the study period; 52 (23.1%) were therapeutic on anticoagulation. Patients therapeutic on anticoagulation were more likely to have a larger left atrial diameter in millimeters (45.6 ± 9.2 versus 42.3 ± 8.6, P = .032) and a higher CHADS2 score (2.9 ± 1.1 versus 2.4 ± 1.1, P = .03). After adjusting for the CHADS2 score, patients who had a stroke despite therapeutic anticoagulation were more likely to have moderate to severe LAE (odds ratio, 2.05; 95% confidence interval, 1.01-4.16). CONCLUSION LAE is associated with anticoagulation failure in AF patients admitted with an ischemic stroke. This provides indirect evidence that LAE may portend failure of anticoagulation therapy in patients with AF; further studies are needed to delineate the significance of this association and improve stroke prevention strategies.