Pre-thrombolysis serum sodium concentration is associated with post-thrombolysis symptomatic intracranial hemorrhage in ischemic stroke patients

 Useless with no information on maintaining serum sodium concentrations to the right level!

Pre-thrombolysis serum sodium concentration is associated with post-thrombolysis symptomatic intracranial hemorrhage in ischemic stroke patients

Xiaolan WuZhuangzhuang Jiang^*Dongjuan XuRufang ZhangHongfei Li

• Department of Neurology, Dongyang People’s Hospital, Affiliated to Wenzhou Medical University, Dongyang, China

Background and aim: Symptomatic intracranial hemorrhage (sICH) was the most serious complication associated with alteplase intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients. However, the relationship between serum sodium levels and post-thrombolysis symptomatic intracranial hemorrhage has not been investigated. Therefore, the aim of this study was to investigate the relationship between pre-thrombolysis serum sodium levels and sICH after IVT, as well as to explore the optimal pre-thrombolysis serum sodium levels for lowering the risk of sICH following IVT.

Methods: From July 1, 2017 to April 30, 2023, out-of-hospital AIS patients who received IVT in the emergency department were enrolled in this study. Serum sodium levels were measured at admission prior to IVT, and National Institutes of Health Stroke Scale scores were continuously assessed during and after thrombolysis. Routine follow-up neuroimaging was performed between 22 to 36 h after IVT. Initially, three logistic regression models and restricted cubic splines (RCS) were established to investigate the relationship between serum sodium levels and post-thrombolysis sICH. Furthermore, to evaluate the predictive value of serum sodium for post-thrombolysis sICH, we compared area under the receiver operating characteristic curve (AUROC) and net reclassification improvement (NRI) before and after incorporating serum sodium into traditional models. Finally, subgroup analysis was conducted to explore interactions between serum sodium levels and other variables.

Results: A total of 784 AIS patients who underwent IVT were enrolled, among whom 47 (6.0%) experienced sICH. The median serum sodium concentration for all patients was 139.10 [interquartile ranges (IQR): 137.40–141.00] mmol/L. Patients who developed sICH had lower serum sodium levels than those without sICH [138.20(IQR:136.00–140.20) vs. 139.20(IQR:137.40–141.00), p = 0.031]. Logistic regression analysis (model 3) revealed a 14% reduction in the risk of post-thrombolysis sICH for every 1 mmol/L increase in serum sodium levels after adjusting for confounding variables (p < 0.001). The risk of post-thrombolysis sICH was minimized within the serum sodium range of 139.1–140.9 mmol/L compared to serum sodium concentration below 137.0 mmol/L [odds ratio (OR) = 0.33, 95% confidence interval (CI): 0.13–0.81] in model3. Furthermore, there was a significant trend of decreasing risk for sICH as serum sodium concentrations increased across the four quartiles (P for trend = 0.036). The RCS analysis indicated a statistically significant reduction in the risk of sICH as serum sodium levels increased when the concentration was below 139.1 mmol/L. Incorporating serum sodium into traditional models improved their predictive performance, resulting in higher AUROC and NRI values. Subgroup analysis suggested that early infarct signs (EIS) appeared to moderate the relationship between serum sodium and sICH (p < 0.05).

Conclusion: Lower serum sodium levels were identified as independent risk factors for post-thrombolysis sICH. Maintaining pre-thrombolysis serum sodium concentrations above 139.1 mmol/L may help reduce the risk of post-thrombolysis sICH.

Good hydration linked to healthy aging

Does your doctor have enough functioning brain cells to have a protocol to test your serum sodium levels? NO? Then you don't have a functioning stroke doctor. 

Good hydration linked to healthy aging

NIH findings may provide early clues about increased risks for advanced biological aging and premature death

Adults who stay well-hydrated appear to be healthier, develop fewer chronic conditions, such as heart and lung disease, and live longer than those who may not get sufficient fluids, according to a National Institutes of Health study published in eBioMedicine external link .    

Using health data gathered from 11,255 adults over a 30-year period, researchers analyzed links between serum sodium levels – which go up when fluid intake goes down – and various indicators of health. They found that adults with serum sodium levels at the higher end of a normal range were more likely to develop chronic conditions and show signs of advanced biological aging than those with serum sodium levels in the medium ranges. Adults with higher levels were also more likely to die at a younger age. 

 “The results suggest that proper hydration may slow down aging and prolong a disease-free life,” said Natalia Dmitrieva, Ph.D., a study author and researcher in the Laboratory of Cardiovascular Regenerative Medicine at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH.  

 The study expands on research the scientists published in March 2022, which found links between higher ranges of normal serum sodium levels and increased risks for heart failure. Both findings came from the Atherosclerosis Risk in Communities (ARIC) study, which includes sub-studies involving thousands of Black and white adults from throughout the United States. The first ARIC sub-study started in 1987 and has helped researchers better understand risk factors for heart disease, while shaping clinical guidelines for its treatment and prevention. 

For this latest analysis, researchers assessed information study participants shared during five medical visits – the first two when they were in their 50s, and the last when they were between ages 70-90. To allow for a fair comparison between how hydration correlated with health outcomes, researchers excluded adults who had high levels of serum sodium at baseline check-ins or with underlying conditions, like obesity, that could affect serum sodium levels.  

They then evaluated how serum sodium levels correlated with biological aging, which was assessed through 15 health markers. This included factors, such as systolic blood pressure, cholesterol, and blood sugar, which provided insight about how well each person’s cardiovascular, respiratory, metabolic, renal, and immune system was functioning. They also adjusted for factors, like age, race, biological sex, smoking status, and hypertension.

They found that adults with higher levels of normal serum sodium – with normal ranges falling between 135-146 milliequivalents per liter (mEq/L) – were more likely to show signs of faster biological aging. This was based on indictors like metabolic and cardiovascular health, lung function, and inflammation. For example, adults with serum sodium levels above 142 mEq/L had a 10-15% associated increased odds of being biologically older than their chronological age compared to ranges between 137-142 mEq/L, while levels above 144 mEq/L correlated with a 50% increase. Likewise, levels of 144.5-146 mEq/L were associated with a 21% increased risk of premature death compared to ranges between 137-142 mEq/L. 

Similarly, adults with serum sodium levels above 142 mEq/L had up to a 64% increased associated risk for developing chronic diseases like heart failure, stroke, atrial fibrillation and peripheral artery disease, as well as chronic lung disease, diabetes, and dementia. Conversely, adults with serum sodium levels between 138-140 mEq/L had the lowest risk of developing chronic disease.  

The findings don’t prove a causal effect, the researchers noted. Randomized, controlled trials are necessary to determine if optimal hydration can promote healthy aging, prevent disease, and lead to a longer life. However, the associations can still inform clinical practice and guide personal health behavior.  

“People whose serum sodium is 142 mEq/L or higher would benefit from evaluation of their fluid intake,” Dmitrieva said. She noted that most people can safely increase their fluid intake to meet recommended levels, which can be done with water as well as other fluids, like juices, or vegetables and fruits with a high water content. The National Academies of Medicine external link , for example, suggest that most women consume around 6-9 cups (1.5-2.2 liters) of fluids daily and for men, 8-12 cups (2-3 liters). 

Others may need medical guidance due to underlying health conditions. “The goal is to ensure patients are taking in enough fluids, while assessing factors, like medications, that may lead to fluid loss,” said Manfred Boehm, M.D., a study author and director of the Laboratory of Cardiovascular Regenerative Medicine. “Doctors may also need to defer to a patient’s current treatment plan, such as limiting fluid intake for heart failure.”   

The authors also cited research that finds about half of people worldwide don’t meet recommendations for daily total water external link intake, which often starts at 6 cups (1.5 liters).  

“On the global level, this can have a big impact,” Dmitrieva said. “Decreased body water content is the most common factor that increases serum sodium, which is why the results suggest that staying well hydrated may slow down the aging process and prevent or delay chronic disease.” 

This research was supported by the Division of Intramural Research at NHLBI. The ARIC study has been supported by research contracts from NHLBI, NIH, and the Department of Health and Human Services.        

STUDY: Dmitrieva NI, Gagarin A, Liu D, et al. Middle-age high normal serum sodium as a risk factor for accelerated biological aging, chronic diseases, and premature mortality. eBioMedicine. 2023. doi: 10.1016/j.ebiom.2022.104404 external link .  

Adequate hydration may slow biological aging, reduce disease risk

 Another protocol for your doctor to have in place to make sure you leave the hospital better than you came in. 

Which means you probably need to be catheterized or diapered immediately in the hospital. There aren't enough nurses to get all their patients safely to the bathroom in time. When I'm traveling, especially on airplanes and buses, I purposely stay dehydrated in order not to need to use the bathroom.

Is there a way to test sodium levels at home?

Due to the nature of sodium's chemistry, it cannot be tested by a simple test kit method.

Your doctor's responsibility to test this on you. 

On coffee:

The caffeine in coffee gives it diuretic effects, meaning it causes your body to pass more urine. But these effects are too mild to cause dehydration, especially if you're a regular coffee drinker. Coffee may even be hydrating for some people, because it contains a lot of water.

On alcohol:

Which alcohol is most dehydrating?

How much does 1 glass of wine dehydrate you?

For reference, a standard drink—12 ounces of beer, 5 ounces of wine, 1.5 ounces of liquor—has 14 grams of alcohol, according to the National Institute on Alcohol Abuse and Alcoholism [3]. In other words, the alcohol alone in one standard drink can make your body produce a little less than half a cup of pee

So to calculate; a standard 5 ounce glass of wine produces less than 4 ounces of pee. That doesn't sound like dehydration.  Beer would make even better sense.

 The latest here:

Adequate hydration may slow biological aging, reduce disease risk

Adults with elevated serum sodium in middle age, a marker of inadequate fluid intake, were more likely to be biologically older than their chronological age and develop chronic diseases compared with adequately hydrated adults, data show.

“There has been a shift in thinking about the roles of good hydration,” Natalia Dmitrieva, PhD, senior research scientist in the Laboratory of Cardiovascular Regenerative Medicine at the NHLBI, told Healio. “Traditionally, the focus has been on short-term effects of big water losses that occur, for example, during prolonged exercise or exposure to heat. In recent years, a growing number of epidemiological studies show links between poor hydration and adverse long-term health outcomes such as HF, diabetes and kidney function decline, and now also with chronic diseases in general and premature mortality.”

Source: Adobe Stock

Dmitrieva and colleagues analyzed data from 15,752 middle-aged adults aged 45 to 66 years at baseline who participated in the ongoing Atherosclerosis Risk in Communities study and were followed for 25 years. Researchers assessed serum sodium as a proxy for hydration habits and estimated the relative speed of aging by calculating biological age, using age-dependent biomarkers and assessing risk for chronic diseases and premature mortality.

Researchers found that a serum sodium of more than 142 mmol/L in middle age was associated with a 39% increased risk for developing chronic diseases (HR = 1.39; 95% CI, 1.18-1.63), whereas a serum sodium of more than 144 mmol/L was associated with a 21% elevated risk for premature mortality (HR = 1.21; 95% CI, 1.02-1.45).

Participants with serum sodium of more than 142 mmol/L were up to twice as likely to be biologically older than their chronological age (OR = 1.5; 95% CI, 1.14-1.96). A higher biological age was associated with an increased risk for chronic diseases, including HF, dementia, chronic lung disease, stroke, diabetes, peripheral vascular disease and atrial fibrillation (HR = 1.7; 95% CI, 1.5-1.93), as well as premature mortality (HR = 1.59; 95% CI, 1.39-1.83), according to the researchers.

Dmitrieva said people whose serum sodium is 142 mEq/L or higher would benefit from evaluation of their fluid intake..

“The links from the observational epidemiological studies need to be confirmed in interventional trials,” Dmitrieva told Healio. “The next step for this research would be to test whether improved hydration can indeed slow down the aging process and improve health outcomes.”

“On the global level, this can have a big impact,” Dmitrieva said in a press release. “Decreased body water content is the most common factor that increases serum sodium, which is why the results suggest that staying well hydrated may slow down the aging process and prevent or delay chronic disease.”

Perspective

Back to Top

Deepak L. Bhatt, MD, MPH

These findings are in line with advice many people around the world received when they were young — drink six to eight glasses of water every day. For many years, that advice went in and out of vogue. This study does pass the common-sense test that staying well hydrated is probably a good idea. Whether doing that or simply drinking whenever you are thirsty makes a real difference is unclear. Where this can fall apart is with older adults or those with clinical or subclinical dementia, when a person can lose their sense of thirst. There, it is important to make the extra effort to make sure vulnerable people stay hydrated.

This analysis included middle-aged people aged 45 to 66 years, so dementia is likely not a major factor. The only way to prove this observational analysis is to conduct a proper randomized trial comparing different degrees of water intake. That would be inexpensive because water is inexpensive; however, dietary trials are notoriously difficult and the cohort would need to be large to see any measurable effect size.

As a standard part of a lab draw, clinicians always get a sodium level, so if someone’s sodium level is off, a clinician would act on it. If the sodium level is only in the high-normal range, I don’t know if a clinician would necessarily act on that and try to include water intake as part of an already busy clinic visit. From a lay person’s practical perspective, it makes sense to stay well hydrated in life. Should you force yourself to drink even if you are not thirsty? I’m not sure I endorse that; however, in this peripandemic era where many people may work from home and live a more sedentary lifestyle, it is important not to lose track of staying well hydrated.

Deepak L. Bhatt, MD, MPH

Cardiology Today Intervention Section Editor

Director, Mount Sinai Heart

Dr. Valentin Fuster Professor of Cardiovascular Medicine

The Icahn School of Medicine at Mount Sinai

Disclosures: Bhatt reports various financial ties with various pharmaceutical and device companies.

Good hydration may slow down aging and prolong disease-free life

Which means you probably need to be catheterized or diapered immediately in the hospital. There aren't enough nurses to get all their patients safely to the bathroom in time. When I'm traveling, especially on airplanes and buses, I purposely stay dehydrated in order not to need to use the bathroom.

Is there a way to test sodium levels at home?

Due to the nature of sodium's chemistry, it cannot be tested by a simple test kit method.

Your doctor's responsibility to test this on you.

Good hydration may slow down aging and prolong disease-free life

Adults who stay well-hydrated appear to be healthier, develop fewer chronic conditions, such as heart and lung disease, and live longer than those who may not get sufficient fluids, according to a National Institutes of Health study published in eBioMedicine.

Using health data gathered from 11,255 adults over a 30-year period, researchers analyzed links between serum sodium levels – which go up when fluid intake goes down – and various indicators of health. They found that adults with serum sodium levels at the higher end of a normal range were more likely to develop chronic conditions and show signs of advanced biological aging than those with serum sodium levels in the medium ranges. Adults with higher levels were also more likely to die at a younger age. 

"The results suggest that proper hydration may slow down aging and prolong a disease-free life," said Natalia Dmitrieva, Ph.D., a study author and researcher in the Laboratory of Cardiovascular Regenerative Medicine at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH.  

The study expands on research the scientists published in March 2022, which found links between higher ranges of normal serum sodium levels and increased risks for heart failure. Both findings came from the Atherosclerosis Risk in Communities (ARIC) study, which includes sub-studies involving thousands of Black and white adults from throughout the United States. The first ARIC sub-study started in 1987 and has helped researchers better understand risk factors for heart disease, while shaping clinical guidelines for its treatment and prevention. 

For this latest analysis, researchers assessed information study participants shared during five medical visits – the first two when they were in their 50s, and the last when they were between ages 70-90. To allow for a fair comparison between how hydration correlated with health outcomes, researchers excluded adults who had high levels of serum sodium at baseline check-ins or with underlying conditions, like obesity, that could affect serum sodium levels.

They then evaluated how serum sodium levels correlated with biological aging, which was assessed through 15 health markers. This included factors, such as systolic blood pressure, cholesterol, and blood sugar, which provided insight about how well each person's cardiovascular, respiratory, metabolic, renal, and immune system was functioning. They also adjusted for factors, like age, race, biological sex, smoking status, and hypertension.

They found that adults with higher levels of normal serum sodium – with normal ranges falling between 135-146 milliequivalents per liter (mEq/L) – were more likely to show signs of faster biological aging. This was based on indictors like metabolic and cardiovascular health, lung function, and inflammation. For example, adults with serum sodium levels above 142 mEq/L had a 10-15% associated increased odds of being biologically older than their chronological age compared to ranges between 137-142 mEq/L, while levels above 144 mEq/L correlated with a 50% increase. Likewise, levels of 144.5-146 mEq/L were associated with a 21% increased risk of premature death compared to ranges between 137-142 mEq/L.

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Similarly, adults with serum sodium levels above 142 mEq/L had up to a 64% increased associated risk for developing chronic diseases like heart failure, stroke, atrial fibrillation and peripheral artery disease, as well as chronic lung disease, diabetes, and dementia. Conversely, adults with serum sodium levels between 138-140 mEq/L had the lowest risk of developing chronic disease.

The findings don't prove a causal effect, the researchers noted. Randomized, controlled trials are necessary to determine if optimal hydration can promote healthy aging, prevent disease, and lead to a longer life. However, the associations can still inform clinical practice and guide personal health behavior.  

People whose serum sodium is 142 mEq/L or higher would benefit from evaluation of their fluid intake."

Natalia Dmitrieva, Ph.D., Study Author

She noted that most people can safely increase their fluid intake to meet recommended levels, which can be done with water as well as other fluids, like juices, or vegetables and fruits with a high water content. The National Academies of Medicine, for example, suggest that most women consume around 6-9 cups (1.5-2.2 liters) of fluids daily and for men, 8-12 cups (2-3 liters). 

Others may need medical guidance due to underlying health conditions. "The goal is to ensure patients are taking in enough fluids, while assessing factors, like medications, that may lead to fluid loss," said Manfred Boehm, M.D., a study author and director of the Laboratory of Cardiovascular Regenerative Medicine. "Doctors may also need to defer to a patient's current treatment plan, such as limiting fluid intake for heart failure."

The authors also cited research that finds about half of people worldwide don't meet recommendations for daily total water intake, which often starts at 6 cups (1.5 liters).  

"On the global level, this can have a big impact," Dmitrieva said. "Decreased body water content is the most common factor that increases serum sodium, which is why the results suggest that staying well hydrated may slow down the aging process and prevent or delay chronic disease."

This research was supported by the Division of Intramural Research at NHLBI. The ARIC study has been supported by research contracts from NHLBI, NIH, and the Department of Health and Human Services.   

Source:

NIH/National Heart, Lung and Blood Institute

Journal reference:

Dmitrieva, N.I., et al. (2023) Middle-age high normal serum sodium as a risk factor for accelerated biological aging, chronic diseases, and premature mortality. eBioMedicine. doi.org/10.1016/j.ebiom.2022.104404.