Burden of stroke in the Kingdom of Saudi Arabia: A soaring epidemic

BACKGROUND: Stroke mortality and related functional disability have been declining over the last two decades, but stroke continues to represent the second leading cause of cardiovascular death worldwide and the number one cause for acquired long-term disability. OBJECTIVES: Assess short- and long-term health outcomes after acute ischemic stroke and analyze factors associated with poor survival and functional outcomes. DESIGN: Retrospective and survival analysis SETTING: Inpatient unit at a tertiary care referral hospital. PATIENTS AND METHODS: All patients admitted with acute ischemic stroke from 1 January 2017 to 31 August 2018 were included in the study. Functional status was assessed using the modified Rankin Scale (mRS). Other demographic and clinical variables were obtained from medical records. Data were analyzed by multivariable logistic regression, Cox proportional hazards, and the Kaplan-Meier method. Long-term follow-up data, including mortality and mRS was collected by follow-up phone call. MAIN OUTCOME MEASURES: Functional dependency and factors associated with mortality. SAMPLE SIZE AND CHARACTERISTICS: 110 with mean age of 67.0 (14.7) years; 59 patients (53.6%) were males. RESULTS: Hypertension (75.5%), diabetes mellitus (54.6%), and dyslipidemia (29.1%) were common. Sixty-five patients (59.1%) had mRS >2 upon discharge including 18 patients (16.4%) who died during the hospital stay. The cumulative mortality rate was 25.4% (28/110) at 12 months and 30.0% (33/110) at 24 months. Twenty-nine stroke survivors (29/70, 41.4%) remained physically dependent (mRS >2) at the end of follow-up. Old age, atrial fibrillation, history of prior stroke, chronic kidney disease, and peripheral arterial disease were associated with increased mortality and functional dependence. CONCLUSIONS: Patients in Oman with acute ischemic stroke tend to have a high comorbidity burden, and their functional dependency and mortality are higher compared to patients from developed countries. Therefore, evidence-based measures such as establishing stroke units are essential to improve the health outcomes of patients with acute ischemic stroke. LIMITATIONS: Retrospective at single center. CONFLICT OF INTEREST: None.

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“…These findings are similar to findings of previous studies in the Middle East, including studies in Saudi Arabia. 14 - 18 …”

Section: Discussionmentioning

confidence: 99%

Health outcomes after acute ischemic stroke:retrospective and survival analysis from Oman

et al. 2022

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“…Developing countries such as the Kingdom of Saudi Arabia (KSA) and also the developed countries are now witnessing an escalation in the rate of metabolic disorders [ 51 , 52 , 53 , 54 ]. Diabetes, often accompanied by endothelial dysfunctions and a poor level of bioactive NO, is one such disorder that increases the risk of stroke by at least twofold [ 52 , 53 ] and is known to increase the risk and severity of stroke [ 10 , 55 ]. The low level of NO 2 − , the most common form of endogenous bioactive NO, correlated with the increased severity, mortality, and poor outcomes after stroke [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Inhibition of Class III Alcohol Dehydrogenase 5: Turning Remote Ischemic Conditioning Effective in a Diabetic Stroke Model

et al. 2022

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The restoration of cerebral blood flow (CBF) to achieve brain tissue oxygenation (PbtO2) is the primary treatment for ischemic stroke, a significant cause of adult mortality and disability worldwide. Nitric oxide (NO) and its bioactive s-nitrosylated (SNO) reservoirs, such as s-nitrosoglutathione (GSNO), induce hypoxic vasodilation to enhance CBF during ischemia. The endogenous pool of SNOs/GSNO is enhanced via the activation of endothelial NO synthase (eNOS/NOS3) and by the suppression of class III alcohol dehydrogenase 5 (ADH5), also known as GSNO reductase (GSNOR). Remote ischemic conditioning (RIC), which augments NOS3 activity and SNO, is an emerging therapy in acute stroke. However, RIC has so far shown neutral effects in stroke clinical trials. As the majority of stroke patients are presented with endothelial dysfunctions and comorbidities, we tested the hypothesis that NOS3 dysfunction and diabetes will abolish the protective effects of RIC therapy in stroke, and the prior inhibition of GSNOR will turn RIC protective. Our data demonstrate that RIC during thrombotic stroke failed to enhance the CBF and the benefits of thrombolysis in NOS3 mutant (NOS3+/−) mice, a genetic model of NOS3 dysfunction. Interestingly, thrombotic stroke in diabetic mice enhanced the activity of GSNOR as early as 3 h post-stroke without decreasing the plasma nitrite (NO2−). In thrombotic stroke, neither a pharmacological inhibitor of GSNOR (GRI) nor RIC therapy alone was protective in diabetic mice. However, prior treatment with GRI followed by RIC enhanced the CBF and improved recovery. In a reperfused stroke model, the GRI–RIC combination therapy in diabetic mice augmented PbtO2, a translatory signature of successful microvascular reflow. In addition, RIC therapy unexpectedly increased the inflammatory markers at 6 h post-stroke in diabetic stroke that were downregulated in combination with GRI while improving the outcomes. Thus, we conclude that preexisting NOS3 dysfunctions due to comorbidities may neutralize the benefits of RIC in stroke, which can be turned protective in combination with GRI. Our findings may support the future clinical trial of RIC in comorbid stroke. Further studies are warranted to test and develop SNO reservoirs as the blood-associated biomarker to monitor the response and efficacy of RIC therapy in stroke.

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“…More than 13 million strokes per year occur worldwide, placing stroke among the leading causes of adult mortality and disability ( , accessed on 31 August 2021) [ 2 ]. The Kingdom of Saudi Arabia (KSA) is a high-income country yet has limited healthcare infrastructures [ 3 ]; hence, the escalating rate of stroke in the KSA is frightening, and now recognized as the second major contributor to adult mortality in the nation [ 3 ]. Advancements in stroke management made faster interventions feasible in remote settings, thereby reducing the mortality but the risk of increasing number of disabled survivors remains associated [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…The Kingdom of Saudi Arabia (KSA) is a high-income country yet has limited healthcare infrastructures [ 3 ]; hence, the escalating rate of stroke in the KSA is frightening, and now recognized as the second major contributor to adult mortality in the nation [ 3 ]. Advancements in stroke management made faster interventions feasible in remote settings, thereby reducing the mortality but the risk of increasing number of disabled survivors remains associated [ 3 ]. Since the microvascular reperfusion and restoration of PbtO2 remains the only proven therapeutic strategy in stroke, the development of field therapies, which can be conveniently administered to the stroke victims in the primary care centers, during transportation and in the emergency departments (EDs), is essentially needed for faster interventions.…”

Section: Introductionmentioning

confidence: 99%

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Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage

et al. 2021

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The COVID-19 pandemic has escalated the occurrence of hypoxia including thrombotic stroke worldwide, for which nitric oxide (NO) therapy seems very promising and translatable. Therefore, various modes/routes of NO-delivery are now being tested in different clinical trials for safer, faster, and more effective interventions against ischemic insults. Intravenous (IV) infusion of S-Nitrosoglutathione (GSNO), the major endogenous molecular pool of NO, has been reported to protect against mechanical cerebral ischemia-reperfusion (IR); however, it has been never tested in any kind of “clinically” relevant thromboembolic stroke models with or without comorbidities and in combination with the thrombolytic reperfusion therapy. Moreover, “IV-effects” of higher dose of GSNO following IR-injury have been contradicted to augment stroke injury. Herein, we tested the hypothesis that nebulization of low-dose GSNO will not alter blood pressure (BP) and will mitigate stroke injury in diabetic mice via enhanced cerebral blood flow (CBF) and brain tissue oxygenation (PbtO2). GSNO-nebulization (200 μg/kgbwt) did not alter BP, but augmented the restoration of CBF, improved behavioral outcomes and reduced stroke injury. Moreover, GSNO-nebulization increased early reoxygenation of brain tissue/PbtO2 as measured at 6.5 h post-stroke following thrombolytic reperfusion, and enervated unwanted effects of late thrombolysis in diabetic stroke. We conclude that the GSNO-nebulization is safe and effective for enhancing collateral microvascular perfusion in the early hours following stroke. Hence, nebulized-GSNO therapy has the potential to be developed and translated into an affordable field therapy against ischemic events including strokes, particularly in developing countries with limited healthcare infrastructure.

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Burden of stroke in the Kingdom of Saudi Arabia: A soaring epidemic

Cited by 21 publications

References 36 publications

Health outcomes after acute ischemic stroke:retrospective and survival analysis from Oman

Health outcomes after acute ischemic stroke:retrospective and survival analysis from Oman

Pharmacological Inhibition of Class III Alcohol Dehydrogenase 5: Turning Remote Ischemic Conditioning Effective in a Diabetic Stroke Model

Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage

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