Abstract
Background/Aim: Transient ischaemic attack (TIA) is characterised by a temporary neurological dysfunction resulting from focal ischaemia in the brain, spinal cord or retina without acute infarction. These episodes typically last less than 24 hours and are significant predictors of subsequent ischaemic strokes. Hypertension is a major risk factor for cerebrovascular events, and primary aldosteronism (PA) is recognised as a common cause of secondary hypertension. This case report presents a male patient with secondary hypertension due to Conn Syndrome, a form of PA, who experienced a TIA manifesting as left leg weakness, underscoring the heightened stroke risk associated with secondary hypertension. Case Report: A 78-year-old male with secondary hypertension caused by Conn Syndrome presented with an episode of left leg weakness that resolved within 24 hours. After ruling out other potential causes such as metabolic disturbances, infections, and structural brain lesions, he was diagnosed with TIA and treated with dual antiplatelet therapy. A carotid ultrasound revealed significant stenosis, leading to a referral for carotid endarterectomy. Long-term management included clopidogrel monotherapy and optimising hypertension control. Conclusion: This case highlights the increased stroke risk in patients with Conn Syndrome-related hypertension, emphasising the importance of early recognition and optimising hypertension management in patients with secondary hypertension to prevent future cerebrovascular events.
- Transient ischaemic attack
- stroke
- cerebrovascular events
- aldosteronism
- Conn Syndrome
- secondary hypertension
- differential diagnosis
Secondary hypertension affects about 10% of individuals with hypertension (1, 2). Primary aldosteronism (PA), renal disease, obstructive sleep apnea, certain medications and substance abuse or recreational drugs are the main causes of secondary hypertension (3, 4). Diagnosing and addressing the underlying cause of secondary hypertension can lead to a significant improvement in blood pressure control, or even resolution of the condition (4), thereby lowering the associated cardiovascular and cerebrovascular risks (5).
A systematic review conducted to assess the prevalence of PA in patients with hypertension reported prevalence estimates ranging from 3.2% to 12.7% in general primary care settings and from 1% to 29.8% in specialised referral centers worldwide (6). PA is characterised by excessive aldosterone production, which enhances renal sodium reabsorption, leading to sodium and water retention, hypokalaemia due to increased potassium secretion, and subsequent plasma volume expansion and hypertension (7). Conn syndrome, a type of PA, is the lead cause of secondary hypertension and cerebrovascular events including stroke (5, 8) due to sustained hypertension and potential vascular damage (9). There is an expanding body of evidence indicating that PA contributes to inflammatory, fibrotic, and remodelling changes in cardiovascular and renal tissues, effects that seem to occur independently of hypertension induced by PA (10, 11). Multiple studies have demonstrated that patients with PA have increased morbidity and mortality (3), along with a significantly heightened risk for renal and cardiovascular complications, such as chronic kidney disease (CKD), myocardial infarction, arrhythmias and stroke (either hemorrhagic or ischaemic) (12-14).
In patients who experience an ischaemic stroke, transient ischaemic attacks (TIAs) typically occur in the hours and days before the event, with approximately 15% of ischaemic strokes being preceded by a TIA (15). A TIA is currently defined as a sudden onset of focal neurological symptoms that resolve quickly, typically within 24 hours, caused by disrupted blood flow to a specific area of the brain (16). Approximately 50 per 100,000 people in the United Kingdom (UK) experience their first TIA each year (17), and many of these patients face lasting physical and psychological effects (18). In the UK, there are approximately 100,000 strokes annually, leading to around 38,000 deaths each year. Stroke is also a major cause of disability, with over 30% of survivors struggling with activities of daily life and functional capacity four years later (17, 19). The average societal cost of stroke per person in the UK is £45,409 in the first 12 months and £24,778 in subsequent years (18). Patients who have had a TIA are at increased risk for ischaemic stroke and require secondary prevention medicines and lifestyle changes to reduce this risk (17, 20, 21). A large comprehensive analysis in Sweden (2010-2019) of 201,316 cases of ischemic stroke found that patients with recurrent ischemic strokes were more likely to have had a prior TIA than those with first-ever strokes, at 14.2% versus 7.4% (p<0.001) (22).
Case Report
Case presentation. A 78-year-old male was referred to Same Day Emergency Care (SDEC) by his general practitioner after presenting with an episode of left leg weakness that occurred and resolved within the previous 24 hours. The patient and his partner reported a history of dragging his left leg and frequently catching his left foot on pavements while walking. These symptoms were particularly noticeable during a visit to his local bowls club. Feeling generally unwell, he subsequently returned home. The patient had been treated for a urinary tract infection (UTI) in the preceding two weeks. His significant past medical history included CKD, Conn Syndrome, hypertension, and a previous ablation for atrioventricular nodal reentrant tachycardia (AVNRT). There was no relevant family history of health conditions. The patient, who was retired and fully independent in mobility and activities of daily living, lived at home with his partner. He was an ex-smoker, having quit approximately 20 years ago. His current medications included atorvastatin 20 mg once daily, bisoprolol 5 mg once daily, and spironolactone 25 mg once daily. No recent changes in medication were reported.
Differential diagnoses/investigations. It can be challenging to differentiate TIA caused by thrombosis or embolism from other conditions that result in temporary neurological symptoms. Other conditions that can present similarly to TIA and stroke include metabolic disturbances, vasospasm, seizures, acute infections, migraines with aura, and space-occupying lesions such as tumours (17, 23). The patient’s history made migraine an unlikely cause, as he denied experiencing headaches or aura-like symptoms before the onset of limb weakness. Blood tests were conducted to rule out alternative causes of the patient’s symptoms. The possibility of an ongoing or recurrent UTI was excluded based on a C-reactive protein (CRP) level of 2 and a normal white blood cell count (24). The patient’s sodium, potassium, and urea levels were within normal ranges, ruling out metabolic disturbances as a cause for his symptoms. Blood glucose testing also excluded hypoglycaemia as a potential cause.
An electrocardiogram (ECG) was performed to investigate the presence of atrial fibrillation, a condition well-established as being associated with stroke, with 80% of ischaemic cardioembolic strokes in elderly patients linked to atrial fibrillation (25). The ECG showed sinus rhythm, reducing the likelihood of a cardioembolic stroke caused by atrial fibrillation. A computed tomography (CT) head scan was also performed to exclude haemorrhage or other space-occupying lesions such as tumours. The CT head scan revealed no acute intracranial pathology, effectively excluding haemorrhage or tumour as alternative causes for the patient’s symptoms. It should be noted that a non-contrast CT scan may not detect ischaemic changes, whereas MRI offers greater sensitivity for detecting such changes (26).
Management plan. The patient was referred to a specialist for further management advice. Having excluded haemorrhagic stroke, the recommended treatment included a single dose of aspirin 300 mg, initiation of clopidogrel 75 mg once daily until the patient could be reviewed in the TIA clinic, and advising the patient that he would be unable to drive for one month according to NICE guidelines (17). Additionally, clear safety netting advice was provided, instructing the patient to call an ambulance for urgent reassessment in the event of any further neurological symptoms.
The patient was reviewed in the TIA clinic the following day, where carotid ultrasound dopplers revealed a significant homogeneous plaque in the right carotid bulb, causing 70-79% stenosis. Consequently, he was referred to the vascular team for consideration of carotid endarterectomy. In the interim, the treatment regimen included aspirin 75 mg once daily, clopidogrel 75 mg once daily, and an increase in atorvastatin from 20 mg to 80 mg once daily. The vascular team reviewed the patient one week after his TIA clinic appointment, and he subsequently underwent a carotid endarterectomy. Dual antiplatelet therapy (DAPT) was recommended initially and continued for 90 days, followed by a transition to clopidogrel monotherapy (27). However, the patient was switched to clopidogrel monotherapy one-week post-carotid endarterectomy.
The discharge summary recommended that the general practitioner review and consider initiating an angiotensin-converting enzyme inhibitor for hypertension management. The patient was scheduled for regular follow-ups to monitor BP, renal function, and adherence to antiplatelet therapy. Tailored lifestyle modifications with a focus on goal setting, including dietary changes to reduce salt intake and moderate regular physical activity were strongly encouraged to optimise cardiovascular health.
Discussion
Patients with secondary hypertension are at significantly heightened risk of morbidity and mortality (5, 13, 14), making early identification and treatment essential to prevent the progression to serious cardiovascular and cerebrovascular events. Secondary hypertension should therefore be a key consideration in newly diagnosed hypertensive patients, especially as undiagnosed secondary causes, such as PA, can significantly increase the risk of cardiovascular and cerebrovascular events, including stroke (5, 14). Failure to identify and manage underlying causes can lead to delayed treatment and an increased risk of stroke.
Although it can be argued that hypertension management should always include an assessment for secondary causes, it is neither practical nor cost-effective to screen all hypertensive patients (3). In clinical practice, it is therefore essential to recognise certain red flags that may suggest secondary hypertension, such as early onset of grade 2 or 3 hypertension (before the age of 40), sudden or worsening hypertension, grade 3 or resistant hypertension (requiring three or more antihypertensive medications), history of repetitive UTIs, and paroxysmal hypertension indicative of catecholamine excess (e.g., episodes of anxiety, palpitations, sweating, and headache suggestive of phaeochromocytoma). Other indicators include diuretic-provoked hypokalaemia, elevated creatinine after starting ACE inhibitors, a family history of early-onset hypertension or stroke, and hypokalaemia (suggestive of PA) (4, 12). However, PA is frequently indicated solely by the presence of hypertension, as the majority of patients do not exhibit other typical symptoms such as hypokalaemia (4). The evaluation of patients with suspected PA includes a thorough history and physical examination (3) to identify potential clinical indicators, prior to initiating antihypertensive medications that may interfere with the laboratory results such as the aldosterone-to-renin ratio. Other tests such as urea and electrolytes (U&Es), creatinine, and the urine albumin-to-creatinine ratio (uACR) can help make the diagnosis.
A multicenter study demonstrated that individuals with PA have a higher incidence of cardiovascular and cerebrovascular events compared to age, sex, and blood pressure-matched patients with essential hypertension (8). This multicenter study was however carried out in Japan, where factors such as genetics, comorbidities, and lifestyle may differ from those in other populations, potentially limiting the generalisability of the findings (8). Moreover, renal diseases are the most common cause of secondary hypertension (28), which accounts for 10% of all hypertension cases (28). In individuals with CKD, cardiovascular disease is the leading cause of morbidity and mortality (29), with the risk of cardiovascular disease mortality tripling once an estimated glomerular filtration rate of 15 ml/min/1.73 m² is reached (30). In this case report, the patient’s CKD and hypertension, which are attributed to both Conn Syndrome and CKD, are significant risk factors for cerebrovascular events including TIA/stroke (31).
Approximately two-thirds of all ischaemic cerebrovascular events are either TIAs or minor strokes (32). The pathophysiology of TIA varies depending on the subtype (33), but all involve a transient interruption in the arterial blood supply to a part of the brain (34). Causes of TIA include large artery atherothrombosis, small vessel arteriosclerosis, cardiac emboli, arterial dissection, hypercoagulable states, or, in some cases, unknown (cryptogenic) origins (34). It has been reported that the risk of stroke within 90 days following a TIA is up to 23%, which underscores the importance of initiating secondary preventive measures as early as possible (35).
Following a review by the vascular team and a carotid endarterectomy, the patient was prescribed antiplatelet monotherapy with clopidogrel 75 mg daily. According to NICE guidelines (27), dual antiplatelet therapy is recommended for up to 90 days, followed by monotherapy with clopidogrel 75 mg daily as standard treatment. A meta-analysis comparing aspirin monotherapy with P2Y12 inhibitors, such as clopidogrel, for secondary prevention of cardiovascular events demonstrated a significant reduction in major adverse cardiovascular events (MACE) by 11% with P2Y12 inhibitors without increasing the risk of major bleeding or mortality (36). The consistency of these results across different P2Y12 inhibitors (clopidogrel and ticagrelor) is a notable strength. However, limitations include variability in the definition of MACE, the wide-ranging prevalence of CKD, smoking status, and diabetes among studies, and a higher loss to follow-up in the P2Y12 group. The short follow-up duration in most trials may also explain the lack of significant difference in all-cause mortality (36). In terms of safety, evidence from an analysis of real-world prescribing data, combined with adverse drug event reports, indicates that Clopidogrel and Aspirin are associated with a lower incidence of serious and fatal adverse effects compared to other agents, such as Ticagrelor and Prasugrel (37).
NICE also recommends high-intensity statin therapy, unless contraindicated, following a TIA diagnosis (27). Statins have proven benefits in both the primary and secondary prevention of cardiovascular disease (38, 39). However, the safety and effectiveness of statins in the primary and secondary prevention of cardiovascular disease are questioned by some investigators (40). Statin-associated muscle symptoms are the most common reason for discontinuation, with 65% of individuals citing muscle-related side effects as the primary cause of non-adherence or stopping statin use (41, 42). The prevalence of statin intolerance is debated, with concerns that it is overestimated and overdiagnosed, as most symptoms attributed to statins are believed to be driven by the nocebo effect (43). While some studies report statin discontinuation rates as high as 50% (44), a meta-analysis of 176 studies found an overall statin intolerance prevalence of 9.1%, with lower rates when assessed using specific criteria, suggesting possible overestimation (45). Limitations of the meta-analysis include insufficient reporting of statin intolerance risk factors and the potential influence of the nocebo effect.
Secondary prevention also involves lifestyle modifications aimed at optimising cardiovascular health and reducing the risk of a stroke event, with interventions focused on reducing modifiable risk factors, such as hypertension and physical inactivity (20). However, addressing the rehabilitative needs of patients with TIA, particularly in elderly individuals with high cardiovascular risk like our patient, can be challenging, leading to uncertainty regarding the most effective strategies for implementation (46). Therefore, it was crucial to tailor lifestyle modifications for our patient with an emphasis on simplifying the target and individualising goal-setting.
Conclusion
Conn Syndrome and renal disease commonly cause secondary hypertension, which is a major risk factor for TIA/stroke. This case underscores the critical need for careful management of secondary hypertension in Conn Syndrome, as it markedly increases the risk of stroke. Early diagnosis and optimising hypertension management can reduce the likelihood of future cerebrovascular events. This case also highlights the importance of a comprehensive diagnostic approach and early and targeted interventions, including timely surgical interventions, dual antiplatelet therapy, and individualised antihypertensive strategies, which are critical in preventing recurrent cerebrovascular events.
Acknowledgements
This publication was supported by the University of Exeter. For the purpose of open access, the Authors have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.
Footnotes
Authors’ Contributions
DL: Patient management, assessment, data collection and manuscript contribution. KM: Manuscript drafting, study supervision and assurance of scientific rigour. DL, KM, KE, RD, TJK: Critical discussion and clinical review. MA: Reviewed the manuscript and provided general feedback.
Data Availability
All data relevant to the study are included in the article.
Conflicts of Interest
The Authors have no conflicts of interest to declare in relation to this case report.
- Received October 11, 2024.
- Revision received October 16, 2024.
- Accepted October 17, 2024.
- Copyright © 2025 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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