Prevalence of primary aldosteronism in acute stroke or transient ischemic attack: a systematic review and meta-analysis.

Background and purpose: Primary aldosteronism (PA) is the most common endocrine cause of secondary hypertension with a prevalence of 14% in patients with newly diagnosed hypertension. Patients with PA experience a higher rate of cardiovascular events including stroke when compared to those with blood pressure matched essential hypertension. This systematic review and meta-analysis summarize current evidence on the prevalence of PA in patients with acute stroke or transient ischemic attack (TIA). Methods: Two reviewers independently reviewed the literature for observational studies on the prevalence of PA in patients with acute stroke or TIA. MEDLINE and Embase were searched for studies up to December 13, 2023. Results: Three single center studies conducted in Japan, Singapore and China were found to meet the inclusion criteria. The reported prevalence of PA in two cohort studies of adults with stroke or TIA were 3.1% and 4.0% and a third cross-sectional study in adults under 45 years old revealed a prevalence rate of 12.9%. Following a meta-analysis, the pooled prevalence of PA in adults with stroke or TIA is 5.8% [95% CI 1.6%-12.3%]. Conclusions: A considerable proportion of patients with stroke or TIA may have PA as the underlying cause of their hypertension. Given the increased risk of stroke associated with PA, clinicians should consider screening for PA in hypertensive patients with stroke or TIA. Further research is needed to evaluate the effect of timing and interfering medications on test results, which will inform an evidence-based approach to testing for PA following TIA or stroke. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022328644.

Variants in ZFX are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt.

Pathogenic variants in multiple genes on the X chromosome have been implicated in syndromic and non-syndromic intellectual disability disorders. ZFX on Xp22.11 encodes a transcription factor that has been linked to diverse processes including oncogenesis and development, but germline variants have not been characterized in association with disease. Here, we present clinical and molecular characterization of 18 individuals with germline ZFX variants. Exome or genome sequencing revealed 11 variants in 18 subjects (14 males and 4 females) from 16 unrelated families. Four missense variants were identified in 11 subjects, with seven truncation variants in the remaining individuals. Clinical findings included developmental delay/intellectual disability, behavioral abnormalities, hypotonia, and congenital anomalies. Overlapping and recurrent facial features were identified in all subjects, including thickening and medial broadening of eyebrows, variations in the shape of the face, external eye abnormalities, smooth and/or long philtrum, and ear abnormalities. Hyperparathyroidism was found in four families with missense variants, and enrichment of different tumor types was observed. In molecular studies, DNA-binding domain variants elicited differential expression of a small set of target genes relative to wild-type ZFX in cultured cells, suggesting a gain or loss of transcriptional activity. Additionally, a zebrafish model of ZFX loss displayed an altered behavioral phenotype, providing additional evidence for the functional significance of ZFX. Our clinical and experimental data support that variants in ZFX are associated with an X-linked intellectual disability syndrome characterized by a recurrent facial gestalt, neurocognitive and behavioral abnormalities, and an increased risk for congenital anomalies and hyperparathyroidism.

Hypertension Management in Stroke Prevention: Time to Consider Primary Aldosteronism.

Primary aldosteronism confers a higher risk of stroke, atrial fibrillation, and cardiovascular disease than blood pressure matched essential hypertension. It is the most common endocrine cause of secondary hypertension with prevalence estimates of up to 13% in primary care and 30% in referral centers around the world. Unlike essential hypertension, primary aldosteronism has targeted medical treatment and potentially curative surgical solutions which can ameliorate the associated cardiovascular risks. This narrative review highlights an evidence gap in the optimal diagnosis and targeted treatment of primary aldosteronism in secondary stroke prevention. Over half of the patients suffering a stroke have blood pressure in the hypertensive range and less than a third achieve optimal blood pressure control. There are no guideline recommendations to test for primary aldosteronism in these patients, although up to 30% of patients with resistant hypertension may have this disease. The accurate diagnosis of primary aldosteronism could significantly improve blood pressure, simplify the medication regimen and reduce the overall cardiovascular risk in these patients. The challenges associated with screening for primary aldosteronism following stroke may be overcome by novel blood tests which are less affected by antihypertensive medications routinely used in stroke care. Approximately one-quarter of all strokes occur in patients who have previously had a stroke. Modifying hypertension, the leading modifiable risk factor, would, therefore, have significant public health implications. As clinicians, we must increase our awareness of primary aldosteronism in patients with stroke, particularly in those with resistant hypertension, to enable targeted therapy and reduce the risk of stroke recurrence.