METHODS: Patients with cryptogenic stroke referred between August 2014 and February 2017 had ILRs implanted. Episodes of AF >2 minutes duration were recorded using proprietary algorithms within the ILRs, whereupon clinicians and patients were alerted via remote monitoring. All AF episodes were adjudicated using recorded electrograms. Once AF was detected, patients were counseled for anticoagulation.
RESULTS: Seventy-one patients with cryptogenic stroke, (age 61.9 ± 13.5 years, 77.5% male, mean CHA2DS2VASc score of 4.2 ± 1.3) had ILRs implanted. Time from stroke to the ILR implant was a median of 66 days. Duration of ILR monitoring was 345 ± 229 days. The primary endpoint of AF detection at 6 months was 12.9%; and at 12 months it was 15.2%. Median time to detection of AF was 50 days. The AF episodes were all asymptomatic and lasted a mean of 77 minutes (± 118.9). Anticoagulation was initiated in all but 1 patient found to have AF.
CONCLUSIONS: The incidence of occult AF is high in Asian patients with cryptogenic stroke and comparable to western cohorts. The combination of ILR and remote monitoring is a highly automated, technologically driven, and clinically effective technique to screen for AF.
METHODS: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls.
RESULTS: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2.
CONCLUSIONS: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.
METHODS: Male Sprague Dawley rats were subjected to permanent bilateral occlusion of common carotid arteries (PBOCCA) or sham surgery. Then, PBOCCA rats received ip injections with, either vehicle (control group), the muscarinic receptor agonist oxotremorine (0.1 mg/kg), or the acetylcholinesterase inhibitor physostigmine (0.1 mg/kg). Cognitive functions were evaluated using a passive avoidance task and the Morris water maze test. In addition, hippocampal LTP was recorded in vivo under anaesthesia.
RESULTS: The PBOCCA rats exhibited significant deficits in passive avoidance retention and spatial learning and memory tests. They also showed a suppression of LTP formation in the hippocampus. Oxotremorine and physostigmine significantly improved the learning and memory deficits as well as the suppression of LTP in PBOCCA rats.
CONCLUSIONS: The present data suggest that the cholinergic system plays an important role in CCH-induced cognitive deficits and could be an effective therapeutic target for the treatment of VaD.