Serum Klotho: a predictor of prognosis in cardiovascular events

Highlights Serum Klotho levels are linked to cardiovascular disease progression. Elevated Klotho levels may indicate poor prognosis in acute cardiac events. Klotho shows antioxidative, anti-inflammatory, and cardioprotective effects. Klotho could serve as a biomarker for risk assessment in cardiovascular events. Future research should explore Klotho's therapeutic potential in heart disease. Klotho protein has emerged as a significant player in cardiovascular health, showing potential protective effects against cardiovascular diseases. Klotho is primarily expressed in the kidneys and exerts various biological effects, including antioxidative, anti-inflammatory, and anti-apoptotic properties[1,2]. Numerous studies have identified a relationship between Klotho levels and cardiac health, indicating that this protein may play a vital role in cardiovascular disease progression and outcomes[3,4]. Despite its importance, the specific expression and function of Klotho in acute cardiovascular conditions, such as acute coronary syndrome (ACS) and myocardial infarction (MI), have not been extensively studied until recently. A recent study by Pei et al investigated serum Klotho levels in patients with ACS, focusing on its correlation with cardiac and renal function and potential as a prognostic indicator for in-hospital outcomes[5]. This observational cohort study involving 349 ACS patients revealed that serum Klotho levels were significantly elevated in acute myocardial infarction (AMI) patients compared to those with unstable angina. Importantly, higher serum Klotho levels were associated with a poorer in-hospital prognosis, suggesting its potential role as an independent risk factor for adverse outcomes. The α-Klotho protein, a member of the Klotho family, exhibits cardioprotective effects, especially in conditions involving oxidative stress, inflammation, and myocardial remodeling[6,7]. Animal studies have demonstrated that Klotho deficiency can lead to cardiomyopathy, arteriosclerosis, and accelerated aging, whereas supplementation of Klotho has been found to reduce myocardial ischemia/reperfusion injury[6,8,9]. These cardioprotective properties highlight Klotho’s potential significance in cardiovascular diseases. Human studies further support this notion, showing that low Klotho levels are linked to an increased risk of cardiovascular events such as heart failure and atherosclerosis. For example, Klotho concentrations were found to be associated with a heightened risk of cardiovascular death[10]. These findings suggest that Klotho may serve as a protective factor; however, the dynamics of its expression in acute cardiac events require further exploration. Recent investigations have revealed that serum Klotho levels tend to rise during acute cardiac events such as AMI[4]. This elevation might indicate a compensatory response to acute cardiac stress, where Klotho is mobilized to protect the myocardium. The consistent observation of elevated Klotho levels in acute cardiac conditions supports the hypothesis that this protein plays a crucial role in modulating the body’s response to cardiovascular stress. This elevation could be a sign of the body’s attempt to counteract damage caused by acute myocardial injury. The interaction of Klotho with cardiac function is multifaceted. Research indicates that Klotho exerts protective effects on cardiac tissues by reducing oxidative stress, apoptosis, and inflammation[6,11]. It has been shown to modulate myocardial remodeling, thereby potentially reducing the severity of cardiac damage[12]. However, the exact mechanisms through which Klotho interacts with cardiac function are still under investigation. Klotho can influence the activity of cardiac-specific markers, such as brain natriuretic peptide (BNP), suggesting its involvement in regulating cardiac function[13]. Additionally, the protein’s antioxidative properties, achieved through activating the Nrf2-GR pathway, are believed to contribute to its protective effects on the heart[14]. The emerging role of Klotho as a prognostic biomarker for cardiovascular events is gaining attention. Elevated serum Klotho levels, particularly in acute cardiac conditions, may provide valuable insights into the prognosis of patients with ACS or AMI. Given its correlation with cardiac function and outcomes, Klotho may serve as an additional tool for clinicians to identify high-risk patients, thereby allowing for more tailored and aggressive treatment strategies. Klotho possesses a predictive capability for adverse outcomes in cardiovascular disease that is comparable to or even better than established markers such as serum creatinine and BNP[15]. The ability of Klotho to enhance the predictive accuracy of traditional risk factors makes it a promising candidate for future cardiovascular risk assessment protocols. Future research should explore the therapeutic potential of modulating Klotho levels, focusing on how its supplementation or inhibition might improve outcomes in ACS or chronic heart failure. Understanding the precise mechanisms by which Klotho interacts with cardiac function, oxidative stress, and inflammation is crucial for designing targeted therapies. As research progresses, Klotho may prove invaluable in predicting and preventing adverse cardiovascular outcomes, ultimately leading to improved management of MI and related conditions.