European Journal of Cardiovascular Medicine

Cerebrovascular accidents (CVA), or strokes, are the second leading cause of death globally and the third leading cause of disability, with 70% of strokes and 87% of both stroke related deaths and disability-adjusted life years occurring in low- and middle-income countries. [1] Acute ischemic stroke leads to significant metabolic changes in the brain, including rapid loss of potassium and magnesium from the brain parenchyma and uptake of sodium and calcium. This ionic imbalance exacerbates cerebral arterial constriction, ischemic depolarization, and cell death due to adenosine triphosphate (ATP) depletion and calcium overload.

Magnesium plays a pivotal role in cerebrovascular health by promoting cerebral arteriolar vasodilation and enhancing cerebral blood flow. Its functions include inhibiting the presynaptic release of excitatory neurotransmitters, blocking the N-methyl-D-aspartate (NMDA) receptor, antagonizing vasoconstrictors like endothelin-1, and suppressing anoxic depolarization. Magnesium deficiency is associated with vasoconstriction, endothelial injury, and atherosclerosis progression. Studies suggest magnesium's neuroprotective effects in lacunar stroke, hemorrhagic stroke, and early treatment within three hours of onset. [2]

Similarly, potassium has demonstrated protective effects in ischemic stroke. Hypokalemia is linked to an increased risk of ischemic and hemorrhagic strokes, particularly in hypertensive patients. Elevated potassium levels have cardioprotective effects by inhibiting processes such as free radical formation, vascular smooth muscle cell proliferation, platelet aggregation, and arterial thrombosis. Potassium-rich diets, primarily from fruits and vegetables, are inversely associated with stroke risk and mortality. [3, 4].

Potassium influences endothelial function through vasodilation, increased nitric oxide synthesis, and reduced intracellular calcium. It also minimizes free radical generation, thrombosis, and neointimal formation, thereby improving vascular health. Dietary potassium. intake is inversely associated with stroke risk, with an optimal intake of approximately 90 mmol/day being linked to the lowest stroke incidence. [4]

Electrolyte imbalances, such as hypomagnesemia and hypokalemia, can exacerbate the severity of ischemic strokes by enhancing vascular dysfunction, oxidative stress, and thrombosis. Identifying their prognostic impact in stroke patients may offer insights into personalized treatment strategies. Serum potassium regulation is intricately linked to aldosterone secretion and the renin-angiotensin-aldosterone system (RAAS), which can also influence stroke outcomes. Magnesium and potassium levels are influenced by comorbidities like hypertension, diabetes mellitus (DM), dyslipidemia, and coronary artery disease (CAD), which are known risk factors for strokes.[5-6]

Given the aging global population and the increasing burden of stroke, understanding prognostic markers like magnesium and potassium is crucial. Research is expanding on the role of these electrolytes in diseases like CVA, CAD, DM, and hypertension.This study aims to evaluate the prognostic significance of serum magnesium and potassium levels in acute ischemic stroke.

This hospital-based, observational, and prospective study was conducted in the medical wards and outpatient department (OPD) of Government Multispecialty Hospital, Sector 16, Chandigarh, over seven months from July 2020 to January 2021. Pretesting, questionnaire modification, and groundwork for data collection were completed by June 2020. Data collection utilized convenient sampling, targeting a calculated sample size of 90 patients based on an estimated stroke prevalence of 2.5% in India.

The study included patients diagnosed with acute ischemic stroke within 72 hours, aged above 25 years, from both sexes, and radiologically confirmed using CT or MRI. Exclusion. criteria were patients with symptoms onset beyond 72 hours, end-stage renal disease, chronic diarrhea, regular alcohol consumption, or medication-induced electrolyte imbalances. Critically ill patients, those with hypoglycemia, seizures, or migraines were also excluded. Consecutive eligible patients fulfilling the criteria were recruited until the sample size was achieved.

On admission, detailed sociodemographic and clinical histories were recorded. Serum magnesium and potassium levels were measured using venous samples processed within two hours on an automated biochemistry analyzer (XL-1000). Magnesium levels were determined via the xylidyl blue method, while potassium levels employed the ISE indirect method. Proper protocols ensured sample integrity. Additional biochemical parameters, including random blood sugar, lipid profiles, and blood pressure, were measured. Neurological assessments were conducted using the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS).Data were checked for completeness, cleaned, and entered into Microsoft Excel, with random verification for accuracy. Statistical analysis was performed using SPSS version 21.0. Descriptive statistics were used for categorical and continuous variables. Associations between clinical, sociodemographic, and laboratory parameters were analyzed using the chi-square test.Ethical approval was obtained from the Institutional Ethical Committee of GMCH. Written informed consent was acquired from participants or their relatives

Table 1 summarizes the baseline characteristics of the 90 study participants. The mean age was 60.9 years, with a range of 32 to 82 years. The mean serum magnesium and potassium levels were 1.98 mg/dl and 4.02 mg/dl, respectively. Blood pressure measurements revealed a mean systolic blood pressure (SBP) of 151.8 mmHg and a diastolic blood pressure (DBP) of .7 mmHg. The mean random blood sugar (RBS) level was 140.5 mg/dl, indicating variability in glycemic status among participants.

Table 2 provides the distribution of participants based on age, gender, and comorbidities. Over half (56.7%) of participants were above 60 years, and 58.9% were male. Regarding comorbidities, 23.3% had diabetes mellitus (DM), 40% had hypertension, and 6.7% had coronary artery disease (CAD), highlighting the prevalence of cardiovascular risk factors in the study group.

Table 3 highlights the association between serum magnesium and potassium levels and stroke severity, as assessed by the National Institutes of Health Stroke Scale (NIHSS). Patients with serum magnesium levels <1.7 mg/dl had significantly higher NIHSS scores at all time points, indicating worse stroke outcomes. Similarly, patients with serum potassium levels <3.5 mg/dl had higher NIHSS scores at all time points, with a significant difference at the 1-month mark. These findings suggest a strong association between electrolyte imbalances and stroke severity and recovery.

Table 4 examines the relationship between serum magnesium levels and comorbidities. Participants with DM and CAD had significantly lower mean magnesium levels (1.83 mg/dl and 1.62 mg/dl, respectively) compared to those without these conditions. However, the difference in magnesium levels between hypertensive and non-hypertensive participants was not statistically significant.

Table 5 shows the relationship between serum potassium levels and comorbidities. Diabetic participants had a significantly higher mean potassium level (4.24 mg/dl) compared to non- diabetics (3.96 mg/dl). Participants with CAD also had higher mean potassium levels (4.43 mg/dl) compared to those without CAD, although this difference was not statistically

significant. Potassium levels did not differ significantly between hypertensive and non- hypertensive participants.

Table 1: Demographic and Clinical Characteristics of Study Participants

Table 2: Distribution of Participants by Demographics

Table 3: NIHSS Score by Serum Magnesium and Potassium Levels

Table 4: Serum Magnesium Levels and Associated Factors

Table 5: Serum Potassium Levels and Associated Factors

Stroke is the third leading cause of mortality globally, with trace element imbalances, including magnesium and potassium, implicated in its pathophysiology. Magnesium, in particular, has been identified as a potential predictor for stroke outcomes. Mechanisms by which low magnesium levels exacerbate stroke severity include promoting inflammation, oxidative modification, thrombus formation, and vascular constriction. Magnesium also plays a role in reducing ischemic injury through vasodilation, energy preservation, and catecholamine reuptake. Conversely, potassium intake is associated with lower blood. pressure and stroke risk, although the relationship between serum potassium levels and stroke outcomes is complex due to confounding factors like drug therapy [7-9].

In this study, 90 participants were analyzed, with a mean age of 60.9 years. The majority (56.7%) were older than 60 years. Similar trends were observed in studies by Feng et al., where stroke incidence was predominantly seen in older populations, and the mean age in NIHSS ≥10/death group was 64.43 ± 11.87 years [10]. Gender distribution showed a male predominance (58.9%), aligning with findings from Feng et al. and Samavarch et al., where 60.34% and 50.3% of stroke participants were male, respectively [10-11].

The mean serum magnesium level among participants was 1.98 mg/dl. Magnesium levels were inversely associated with age, with the highest levels observed in younger participants. However, these differences were not statistically significant. Comparatively, Samavarch et al. reported lower magnesium levels in ischemic stroke patients (1.63 ± 0.42 mg/dl) [11], while Feng et al. found an inverse relationship between magnesium levels and NIHSS scores [10]. The study by Ohira et al. highlighted the increased risk of ischemic stroke with low serum magnesium levels, although the association was not significant after adjusting for hypertension and diabetes [12].

In diabetic patients, the mean serum magnesium level was significantly lower (1.83 mg/dl) than in non-diabetics (2.03 mg/dl). Nearly half (47.6%) of diabetic participants had magnesium levels below 1.7 mg/dl. Studies by Arpaci et al. and Parlapally reported similar findings, where decreased magnesium levels were linked to poor glycemic control and increased HbA1c levels [13-14]. Hypomagnesemia in hypertensive patients was also prevalent, with significantly more hypertensive participants having magnesium levels below

1.7 mg/dl compared to non-hypertensive individuals. Guerrero et al. reported similar findings, associating hypomagnesemia with prehypertension and hypertension in children [15]. CAD patients in this study exhibited significantly lower magnesium levels (1.62 mg/dl), consistent with findings from Amighi et al. and Ma et al. [16-17].

Participants with serum magnesium levels below 1.7 mg/dl had significantly higher NIHSS scores at all intervals, indicating worse stroke outcomes. Feng et al. similarly reported that patients in the highest quartile of serum magnesium levels had a reduced risk of NIHSS

≥10/death compared to those in the lowest quartile (RR 0.47, p < 0.05) [10].

The mean serum potassium level was 4.02 mg/dl, with no significant differences across age groups. Diabetic participants had significantly higher potassium levels (4.2 mg/dl) compared to non-diabetics (3.96 mg/dl). However, hypokalemia (<3.5 mg/dl) was more prevalent among non-diabetic participants, echoing findings by Chatterjee et al., who reported an inverse association between potassium levels and diabetes risk [18].

In hypertensive participants, mean potassium levels were slightly higher but not significantly different from non-hypertensive individuals. Johnson et al. found that increased serum potassium levels were associated with stroke risk in normotensive and hypertensive populations [19]. CAD patients exhibited higher mean potassium levels (4.43 mg/dl) than non-CAD patients, though this difference was not statistically significant.

Patients with serum potassium levels below 3.5 mg/dl had higher NIHSS scores at all intervals, with the difference being significant at the 1-month mark. This suggests that hypokalemia may be linked to poorer recovery, as highlighted by Smith et al., who reported increased stroke risk with hypokalemia among hypertensive patients [20].

This study concluded that serum magnesium levels were significantly lower in patients with ischemic stroke who presented with higher NIHSS scores. Additionally, reduced magnesium levels were observed in patients with acute ischemic stroke who also had comorbid conditions such as diabetes mellitus, hypertension, and coronary artery disease, compared to those without these conditions. On the other hand, low serum potassium levels in patients with acute ischemic stroke were significantly associated only with higher NIHSS scores at one month, with no other significant correlations identified in our study. These findings suggest that serum magnesium levels at the time of admission may serve as a valuable prognostic marker in patients with acute ischemic stroke.

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