Vitamin D serum level predicts stroke clinical severity, functional independence, and disability—A retrospective cohort study

But it seems nothing here even remotely suggests administering Vitamin D post stroke. So before you have your stroke make sure your vitamin D levels are up to snuff. 

Vitamin D serum level predicts stroke clinical severity, functional independence, and disability—A retrospective cohort study

Abdullah R. Alharbi^1,2†, Amer S. Alali^3†, Yahya Samman^1,4,5, Nouf A. Alghamdi^1,6, Omar Albaradie^1,4,5, Maan Almaghrabi^1,7, Seraj Makkawi^1,4,8, Saeed Alghamdi^1,4,8, Mohammad S. Alzahrani⁹, Mohammed Alsalmi^1,4,8, Vardan T. Karamyan^10,11, Khalid Al Sulaiman^12,13,14,15, Ohoud Aljuhani¹⁶ and Faisal F. Alamri^1,5,17*

• ¹King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
• ²College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
• ³Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
• ⁴College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
• ⁵Department of Basic Sciences, College of Science and Health Professions (KSAU-HS), King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
• ⁶Department of Medicine, College of Medicine, Al-Baha University, Al-Baha, Saudi Arabia
• ⁷College of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
• ⁸Department of Medicine, Ministry of the National Guard-Health Affairs, Jeddah, Saudi Arabia
• ⁹Department of Clinical Pharmacy, College of Pharmacy, Taif University, Taif, Saudi Arabia
• ¹⁰Department of Pharmaceutical Sciences, Jerry. H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, United States
• ¹¹Center for Blood Brain Barrier Research, Jerry. H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, United States
• ¹²Department of Pharmaceutical Care, King Abdulaziz Medical City, Riyadh, Saudi Arabia
• ¹³College of Pharmacy, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
• ¹⁴King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
• ¹⁵Saudi Critical Care Pharmacy Research (SCAPE) Platform, Riyadh, Saudi Arabia
• ¹⁶Department of Pharmacy Practice, King Abdulaziz University, Jeddah, Saudi Arabia
• ¹⁷King Salman Center for Disability Research, Riyadh, Saudi Arabia

Background: Stroke is a leading cause of mortality and disability and one of the most common neurological conditions globally. Many studies focused on vitamin D as a stroke risk factor, but only a few focused on its serum level as a predictor of stroke initial clinical severity and recovery with inconsistent results. The purpose of this study was to assess the relationship between serum vitamin D levels and stroke clinical severity at admission and functional independence and disability at discharge in Saudi Arabia.

Methodology: A retrospective cohort study of adult ischemic stroke patients who had their vitamin D tested and admitted within 7 days of exhibiting stroke symptoms at King Abdulaziz Medical City (KAMC) Jeddah, Saudi Arabia. Based on vitamin D level, the patients were categorized into normal [25(OH)D serum level ≥ 75 nmol/L], insufficient [25(OH)D serum level is 50–75 nmol/L], and deficient [25(OH)D serum level ≤ 50 nmol/L]. The primary outcome was to assess the vitamin D serum level of ischemic stroke patients’ clinical severity at admission and functional independence at discharge. The National Institute of Health Stroke Scale (NIHSS) was used to assess the clinical severity, whereas the modified Rankin scale (mRS) was used to assess functional independence and disability.

Results: The study included 294 stroke patients, out of 774, who were selected based on the inclusion and exclusion criteria. The mean age of the participants was 68.2 ± 13.4 years, and 49.3% were male. The patients’ distribution among the three groups based on their vitamin D levels is: normal (n = 35, 11.9%), insufficient (n = 66, 22.5%), and deficient (n = 196, 65.6%). After adjusting for potential covariates, regression analysis found a significant inverse relationship of NIHSS based on 25(OH)D serum level (beta coefficient: −0.04, SE: 0.01, p = 0.003). Patients with deficient serum vitamin D level also had significantly higher odds of worse functional independence in mRS score [OR: 2.41, 95%CI: (1.13–5.16), p = 0.023] when compared to participants with normal vitamin D level.

Conclusion: Low vitamin D levels were associated with higher severity of stroke at admission and poor functional independence and disability at discharge in patients with acute ischemic stroke. Further randomized clinical and interventional studies are required to confirm our findings.

Introduction

Stroke continues to be the world’s leading cause of long-term impairment of physical, cognitive, psychosocial, and other functions (Al Shoyaib et al., 2021a; Alamri et al., 2021). Nearly 85% of stroke survivors suffer paresis after stroke, and 50% of them continue living with motor impairments through the rest of their lives (Syeara et al., 2020). Several risk factors were found to be linked to stroke, including unmodifiable risk factors such as genetics, gender, and age, and modifiable risk factors such as hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation, cigarette smoking, and sedentary lifestyle (Kuriakose and Xiao, 2020; Sayed et al., 2022). Given the limited therapeutic time window for improving stroke outcomes, identifying novel risk variables and severity predictors in ischemic stroke patients can aid in identification of patients that are at higher or lower risk of poor outcomes and allow stratification of patients for more personalized care and therapy (Kwakkel et al., 1996; Vijayan et al., 2019; Al Shoyaib et al., 2021b). Therefore, the discovery and validation of new predictive prognostic biomarkers is an active area of research, and some blood biomarkers and circulating molecules such as uric acid, interleukin 6, and vitamin D have already been introduced as predictors of stroke outcomes (Tu et al., 2013; Huang et al., 2016; Ng et al., 2017; Kamtchum-Tatuene and Jickling, 2019).

The physiological roles of vitamin D include calcium absorption from the gut, bone mineralization and growth, muscle function, and modulation of immunity (Lips, 2006; Bikle, 2009). In addition, recent studies indicate the role of vitamin D in cardiovascular disease prevention (Pilz et al., 2008). Low levels of 25-hydroxyvitamin D [25(OH)D, a vitamin D biomarker], have been linked to an elevated risk of coronary artery disease, ischemic heart disease, heart failure (HF), and stroke (Saponaro et al., 2019). Low vitamin D levels have also been linked to hypertension, dyslipidemia, and diabetes, all of which have an impact on cardiovascular and cerebrovascular events (Forman et al., 2007; Song et al., 2013; Lupton et al., 2016). Based on these studies, vitamin D deficiency is deemed to be a public health concern, especially for stroke patients.

In addition, several studies have investigated the role of vitamin D in stroke pathophysiology (Takeda et al., 2010; Wong et al., 2010; Balden et al., 2012). Vitamin D deficiency has been linked to increased post-stroke inflammatory activity by dysregulating the inflammatory response (Takeda et al., 2010; Wong et al., 2010; Balden et al., 2012). Vitamin D deficiency was associated with increased levels of interleukin-6 and high-sensitivity C-reactive protein in acute stroke patients (Wang et al., 2018). Also, vitamin D was shown to induce the expression of insulin-like growth factor 1 (IGF-1), a neuroprotective hormone that prevents axon and dendritic degeneration, and has antithrombotic properties (Turetsky et al., 2015; Yalbuzdag et al., 2015; Huang et al., 2016). Furthermore, vitamin D may also improve post-ischemic stroke vasodilation and neuronal survival by stimulating nitric oxide synthase (Turetsky et al., 2015; Yalbuzdag et al., 2015). These studies indicate a possible interaction between the level of vitamin D and stroke pathophysiology.

Previous experimental and observational studies have suggested that low vitamin D levels are independently associated with larger infarct volumes (Balden et al., 2012; Wang et al., 2014; Turetsky et al., 2015; Huang et al., 2016; Nie et al., 2017). Low levels of vitamin D have been identified in several epidemiological studies as a predictor of increased risk of stroke (Poole et al., 2006; Pilz et al., 2008; Chowdhury et al., 2012; Shi et al., 2020). Furthermore, decreased serum 25(OH)D levels in ischemic stroke patients were shown to independently predict stroke recurrence and mortality at 24 months (Qiu et al., 2017).

To date, limited studies have been done to investigate the impact of vitamin D level on stroke clinical severity and functional recovery with conflicting results (Bolland et al., 2010; Kuhn et al., 2013; Gupta et al., 2014; Wang et al., 2014; Park et al., 2015; Turetsky et al., 2015). Moreover, given the high prevalence (60%) of the Saudi Arabian population with vitamin D deficiency according to a recent meta-analysis (Al-Alyani et al., 2018). This study was conducted to assess the correlation between serum 25(OH)D levels and the clinical severity of ischemic stroke at admission and functional recovery at discharge in a cohort of patients in Saudi Arabia.

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