The association between serum klotho protein and stroke: a cross-sectional study from NHANES 2007–2016

 

You probably want to ask your incompetent? doctor for the protocols that create proper levels in humans. Since they won't exist yet, your incompetent doctors can sit with heads up asses doing nothing OR get research done! I'm guessing head up ass is the preferred position! Why is your doctor not fired yet?

I'm sure your incompetent? doctor DID NOTHING WITH THIS RESEARCH!

Klotho protein levels linked to Alzheimer's, cognitive decline, amyloid and tau burden November 2022 

The latest here for your doctor to DO NOTHING!

The association between serum klotho protein and stroke: a cross-sectional study from NHANES 2007–2016

Hongjia Xu^1†Yiming Ding^2,3†Ye Zhang¹Jianwen Li¹Shiyue Zhou¹Dewei Wang¹Xinyue Xing¹Xiaoyu Ma¹Cunfu Wang^1*Shunliang Xu^1,4*

• ¹Department of Neurology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
• ²Department of Pediatric Surgery, Qilu Hospital of Shandong University, Jinan, China
• ³Cheeloo College of Medicine, Shandong University, Jinan, China
• ⁴Department of Human Genetics, School of Medicine, Emory University, Atlanta, GA, United States

Objective: Serum klotho protein is a protein with anti-aging effects. Since the relationship between serum klotho and Stroke remains rather ambiguous, this research probed into the potential correlation between serum klotho concentration and Stroke.

Methods: This study employed a cross-sectional design and incorporated population data from the NHANES from 2007 to 2016. Weighted univariate and multivariate logistic regression models were utilized to inspect the relationship between klotho and Stroke. Stratified analyses and interaction tests were carried out to explore the latent correlation between klotho and Stroke. Finally, a fitted smooth curve was adopted to depict the non-linear relationship.

Results: In this study, after excluding all the missing data, a total of 12,414 participants were encompassed, including 450 Stroke individuals. After adjusting for all covariates, higher klotho was associated with a lower prevalence of Stroke. According to the subgroup analyses and interaction tests, age, gender, race, BMI, hypertension, diabetes mellitus, family members, drinker and smoker were not significantly correlated with the influence of klotho and Stroke. After adjusting for all covariates, higher klotho was associated with a lower prevalence of stroke [OR: 0.68, 95% CI: 0.47–0.99].

Conclusion: This study disclosed the negative correlation between serum klotho protein levels and the prevalence of Stroke. Further prospective studies are requisite to investigate the impact of serum klotho protein levels on Stroke and determine the causal relationship.

1 Introduction

Stroke represents the second leading global cause of mortality, surpassed only by acute ischemic heart disease (1). This severe acute cerebrovascular disease not only threatens survival but frequently induces debilitating sequelae including motor deficits, cognitive impairment, and affective disorders, imposing substantial socioeconomic burdens and quality-of-life deterioration (2). With the current development of an aging population, the prevalence rate of stroke is continuously rising (3). Furthermore, stroke is currently emerging gradually among the young population (attributed to factors including patent foramen ovale, dyslipidemia, hormonal therapies, and genetic predisposition) (4, 5). Since stroke is a global public health problem, researchers have never stopped their research on the specific etiology, pathogenesis, predictive means and treatment measures of stroke. And they have been endeavoring to prevent the occurrence of stroke and handle it in a timely manner through some laboratory test indicators and other approaches.

The klotho gene, first identified through longevity studies in murine models (1997), has emerged as a pleiotropic regulator of aging processes. In mice, the overexpression of the klotho gene prolongs lifespan, while its mutation reduces it (6). The human klotho gene is situated at chromosome 13q12. It demonstrates effects such as anti-aging and anti-inflammation and is correlated with numerous age-related diseases (7, 8). The klotho protein encoded by the klotho gene is predominantly a single-channel transmembrane protein, and its soluble component can be cleaved to form α-klotho and dissolve in the blood, featuring three distinct functional types: membrane-bound α-klotho, truncated soluble α-klotho, and secreted α-klotho (6). Unless otherwise specified, the term “klotho” specifically refers to α-klotho. In previous studies, it has been found to be associated with kidney diseases (9), cardiovascular diseases (10, 11), and diabetes mellitus (12). Additionally, in the field of neurology, it has also been discovered that its reduction might be related to Alzheimer’s disease and other degenerative disorders (13). In 2014, Dubal and colleagues discovered that mice with higher serum klotho levels exhibited stronger cognitive function across all age groups, independent of the aging process (14). Subsequently, the team of Castner demonstrated through experiments in rodents and primates that klotho enhances synaptic plasticity and cognitive capacity. Notably, their research revealed that a single low-dose (but not high-dose) administration of klotho could improve memory function in aged non-human primates (15). Emerging evidence from animal studies has demonstrated that beyond its well-documented cardiovascular effects, klotho protein plays a significant role in mediating ischemic preconditioning mechanisms. This endogenous neuroprotective function not only reduces stroke prevalence but also exhibits therapeutic potential through multifaceted cerebroprotective actions, including attenuation of oxidative stress and modulation of apoptotic pathways (16, 17).

Despite these advances, critical knowledge gaps persist regarding klotho’s clinical relevance in cerebrovascular disease. Whether serum klotho levels demonstrate an independent association with stroke risk beyond traditional cardiovascular risk factors. The number of related clinical studies is limited, and the sample sizes therein are relatively small. We hypothesize that: Serum klotho concentration inversely correlates with stroke prevalence in adults. This association remains significant after comprehensive adjustment for confounders including lipid profiles and metabolic comorbidities. Hence, we carried out this research, conducting a large-sample study in the NHANES, which is representative of the national population, in the hope of testing these hypotheses between serum klotho and the prevalence of Stroke in the clinical setting.

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