AF and stroke are related and ZNF566, PDZK1IP1, ZFHX3, and PITX2 genes are significantly associated with novel biomarkers involved in AF-related stroke.
Participants included patients after stroke (N=1560) hospitalized between January 3, 2006, and December 26, 2012, satisfying the following criteria: (1) data on age, sex, duration from stroke to hospital admission, length of stay, FIM score, modified Rankin Scale (mRS) score, Glasgow Coma Scale score, Japan Stroke Scale score, and self-exercise program participation were available; and (2) admitted within 7 days after stroke onset, length of stay was between 7 and 60 days, prestroke mRS score was ≤2, and not discharged because of FIM or mRS exacerbation.
The multiple linear regression analysis showed that sarcopenia was independently associated with FIM motor score at discharge in patients with all disease types (β = -0.189 [stroke], -0.240 [musculoskeletal disorders], -0.230 [hospital-associated deconditioning]; all P < 0.05), with FILS score at discharge only in patients with musculoskeletal disorders (β = -0.271, P < 0.001), but not in patients with stroke (β = -0.061, P = 0.375) or those with hospital-associated deconditioning (β = -0.131, P = 0.070).
GLP-1 agonists did not affect the risk of MI (RR: 0.917; CI: 0.830-1.014; p = 0.092) as well as the risk of stroke (RR: 0.882; CI: 0.759-1.023; p = 0.097), HF (RR: 0.967; CI: 0.803-1.165; p = 0.725), retinopathy (RR: 1.000; CI: 0.807-1.238; p = 0.997) and nephropathy (RR: 0.866; CI: 0.625-1.199; p = 0.385).
In comparison, GLP-1 RA appear to preferentially reduce ischemic events (stroke or myocardial infarction) over hospitalization for heart failure, and demonstrated renoprotection in several of the CVOTs.
GLP-1 agonists on the other hand, showed significant reduction in MACE (RR 0.92; 95% CI 0.87-0.97), death from CV causes (RR=0.88; 95% CI 0.80-0.97), and death from any cause (RR=0.89; 95% CI 0.82-0.96).
SGLT2i and GLP-1 RA may have a synergic effect on glucose reduction, weight reduction, renal impairment (both an independent lethal disease and a CVD risk factor) improvement, and cardiac event reduction, because the first reduces HF and related events and the second decreases CVD risk (mainly MI and stroke).
Shortly thereafter, the injectable glucagon-like peptide agonists (GLP-1) liraglutide and semaglutide found a significant reduction in composite major cardiovascular events (CV death, non-fatal MI, or stroke).
Previous research has demonstrated that GLP-1 analogs are neuroprotective in several neurological disease models including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke.
AF and stroke are related and ZNF566, PDZK1IP1, ZFHX3, and PITX2 genes are significantly associated with novel biomarkers involved in AF-related stroke.
In our study we are focusing on a possible correlation between detection of atrial fibrillation by an implantable ECG recorder, and PITX2 and/or ZFHX3 gene mutations in cryptogenic stroke/TIA patients.
We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10(-16)) and ZFHX3 (p=2·28×10(-8)), and for large-vessel stroke at a 9p21 locus (p=3·32×10(-5)) and HDAC9 (p=2·03×10(-12)).
Each of these underlying pathologies may have a specific genetic architecture.Previous genome-wide association studies (GWAS) showed association of variants near PITX2 and ZFHX3 with atrial fibrillation and stroke.
Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26 × 10<sup>-19</sup>; joint OR 1·37, 1·30-1·45, p=2·79 × 10<sup>-32</sup>) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93 × 10<sup>-7</sup>; joint OR 1·17, 1·11-1·23, p=2·29 × 10<sup>-10</sup>) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50 × 10<sup>-8</sup>; joint OR 1·24, 1·15-1·33, p=4·52 × 10<sup>-9</sup>) for large artery atherosclerosis stroke.
Replication of protein-coding variants in candidate genes was observed for 2 previously reported GWAS associations: ZFHX3 (cardioembolic stroke) and ABCA1 (large-vessel stroke).