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Annamaria Del Franco, Fabio A. Division of Cardiology, School of Medicine, University of Perugia, Perugia, Italy. Institute of Neuroscience, National Research Council CNR , Pisa, Italy. Department of Developmental Neuroscience, IRCCS Stella Maris Foundation, Calambrone, PI, Italy.

Division of Cardiology and Cardiovascular Medicine, Fondazione Toscana Gabriele Monasterio, Pisa, Italy. Andrea Barison, Yu F.

Cardiomyopathy Unit, Azienda Ospedaliera Universitaria Careggi, Florence, Italy. Lewis Katz School of Medicine, Cardiovascular Research Center, Temple University, Philadelphia, PA, USA. Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University and Civil Hospital, Brescia, Italy.

You can also search for this author in PubMed Google Scholar. Correspondence to Michele Emdin. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4.

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Reprints and permissions. Del Franco, A. et al. Creatine deficiency and heart failure. Heart Fail Rev 27 , — Download citation. Accepted : 08 September Published : 07 October Issue Date : September Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Download PDF. Abstract Impaired cardiac energy metabolism has been proposed as a mechanism common to different heart failure aetiologies. The Myocardial Creatine Kinase System in the Normal, Ischaemic and Failing Heart Chapter © The Failing Heart: Is It an Inefficient Engine or an Engine Out of Fuel?

Chapter © Metabolic remodelling in heart failure Article 18 June Use our pre-submission checklist Avoid common mistakes on your manuscript. Biochemistry of creatine Creatine Cr is a guanidino compound that plays a vital role in the energy metabolism of cells.

Full size image. Physiology of creatine and phosphocreatine in cardiomyocytes Chemical energy in the form of ATP is produced from multiple substrates principally long-chain fatty acids, lactate, and glucose , predominantly in the mitochondria via oxidative phosphorylation.

Assessment of cardiac creatine metabolism Magnetic resonance spectroscopy MRS is the only technique capable to non-invasively measure the ratios and concentrations of endogenous cardiac high-energy phosphate metabolites and CK flux in human hearts.

Creatine deficiency in heart failure According to the energy starvation hypothesis, altered myocardial metabolism anticipates and sustains contractile dysfunction [ 23 ]. Exercise training and creatine kinase system Training increases exercise capacity, quality of life, and reduces morbidity and mortality in HF by improving endothelial function and coronary perfusion, decreasing peripheral resistance and ventricular remodelling, as well as neuro-endocrine and pro-inflammatory activation [ 43 ].

Pharmacological approaches to improve cardiac metabolism in heart failure Neurohormonal antagonists are the cornerstone of pharmacological therapy of HF.

Table 1 Clinical studies on supplementation of creatine Cr or phosphocreatine PCr in patients with acute or chronic heart failure HF. NYHA, New York Heart Association; RCT, randomized clinical trial.

References provided in Supplemental Material Full size table. Conclusions As a component of the energy buffer system, Cr is involved in cardiac metabolism to transfer energy from site of production to site of utilization.

Central illustration Failing heart shows a decreased creatine Cr content and creatine kinase CK activity, as well as a reduced expression of Cr transporter. Data availability Not applicable. Code availability Not applicable. Abbreviations ADP: Adenosine diphosphate ATP: Adenosine triphosphate AGAT: L-arginine:glycine amidinotransferase Cr: Creatine CK: Creatine kinase CrT: Creatine transporter GA: Guanidinoacetate GAMT: S-adenosyl-L-methionine:guanidinoacetate N-methyltransferase HF: Heart failure MRS: Magnetic resonance spectroscopy PCr: Phosphocreatine.

Hypertension treatment was defined as regularly taking antihypertensive drugs within two weeks before investigation. Smoking was defined as participants smoked one or more cigarettes per day during the 30 days prior to the survey Drinking was defined as having consumed alcohol in the 30 days before the survey and at least once a week The China-PAR risk score included sex, age, SBP, WC, smoking, diabetes, geographic region, urbanization, family history of CVD, and treatment for hypertension.

Continuous variables meeting the normal distribution were expressed using the mean ± standard deviation SD and use F-test. Categorical variables are expressed as counts and percentages and were compared using x 2 - test. Multivariate logistic regression analysis was used to determine the association of serum creatinine with cardiovascular risk factors.

Sensitivity analysis excluded the participants receiving hypertension treatment and diabetes, and multiple linear regression analysis was used to study the relationship between serum creatinine level and year cardiovascular risk.

Statistical analyses were performed using SPSS version The general characteristics of the participants enrolled in this study by serum creatinine levels are presented in Table 1.

Among all participants, the average age was Multivariable logistic regression was performed to study the relationship between serum creatinine and cardiovascular risk factors, as shown in Table 2 , in total participants, the odds ratio OR for age, overweight and obesity, drinking, physical exercise, and intake of vegetables and fruits and so on, were 1.

Results further analyzed according to gender stratification was shown in Figure 2 , the OR for age, drinking and physical exercise was 1. Figure 2 Association between serum creatinine and cardiovascular risk factors according to gender stratification.

CI, confidence interval. As for women, the OR for age, hypertension treatment, physical exercise and intake of vegetables and fruits was 1. The results showed that serum creatinine was positively associated with age, while negatively associated with physical activity in both genders. The year predicted cardiovascular risk according to quartiles of serum creatinine is shown in Figure 3.

In the total participants, the average risk of CVD in Q1 and Q4 groups were The mean risk of CVD in Q1 and Q4 groups were Figure 3 Cardiovascular risk according to quartiles of serum creatinine.

the Q1 group. The distribution of cardiovascular risk classes according to quartiles of serum creatinine is shown in Figure 4.

In the total participants, the proportions of participants with high predicted risk in Q1 and Q4 groups were After grouping by gender, the proportions of individuals at high risk in Q1 and Q4 groups were Figure 4 Distribution of cardiovascular risk classes according to quartiles of serum creatinine.

The results of the multiple linear regression are shown in Table 3. In order to exclude the confounding effects of hypertension treatment and diabetes on serum creatinine, we conducted sensitivity analysis and excluded hypertension patients with hypertension treatment or diabetes, as shown in Table 4.

Table 4 Association between serum creatinine level and cardiovascular risk sensitivity analysis. The morbidity and mortality of CVD have been increasing gradually in China, partly attributed to the increased exposure and aggregation of multiple cardiovascular risk factors Previous studies have shown that prevention and control measures based on risk factors can effectively reduce cardiovascular risk Elevated creatinine levels have been reported to play a role in the increased risk of a variety of CVD, in addition, some clinical studies have found that increased serum creatinine levels, which often indicate a decrease in glomerular filtration rate, may be used as a predictive marker for CVD 22 , 23 , similarly, our study showed that the average risk in serum creatinine levels Q1 and Q4 groups were Hypertension is an important risk factor in the development of CVD.

The relationship between creatinine and multiple cardiovascular risk factors and cardiovascular risk in patients with hypertension needs to be fully elucidated. In our study, serum creatinine levels were found to be strongly associated with cardiovascular risk factors in hypertensive patients.

The results have important clinical significance. Firstly, we used a relatively novel risk prediction model to evaluate individual cardiovascular risk and provided reference for the control of hypertensive patients with high creatinine level to reduce cardiovascular risk.

Secondly, serum creatinine is a relatively convenient biochemical index, and serum creatinine in addition to traditional CVD risk factors should be taken into account when evaluating risk for development of CVD in hypertensive patients, especially in male.

Based on the China-PAR project, the China-PAR risk score has good internal consistency and has been proved to be a suitable method for predicting year cardiovascular risk in Chinese population The year cardiovascular risk for each individual was calculated using the China-PAR risk calculation equation.

Hypertension patients are at high risk of CVD, at the same time, the pathogenesis of hypertension is closely related to the kidney, which is not only an important organ for blood pressure regulation, but also one of the target organs of hypertension, studies have shown that hypertensive patients with renal impairment have an increased risk of overall CVD, and even mild renal dysfunction can lead to increased mortality and morbidity of CVD In our study, it was also shown that hypertensive individuals with higher creatinine levels had a higher cardiovascular risk.

The rationale for the positive association between serum creatinine and cardiovascular risk remains to be fully clarified. Serum creatinine refers to endogenous serum creatinine, which is the product of human muscle metabolism and the surrogate of renal function Serum creatinine behaves as a marker of pro-inflammatory state, and inflammation-mediated endothelial dysfunction has been shown to be associated with the occurrence of cardiovascular events in women with reduced renal function, in addition, high serum creatinine is often accompanied by a decrease in glomerular filtration rate, which is prone to water-sodium retention and increases the burden on the heart as well as cardiovascular risk 9 , Although this study highlights the association between serum creatinine levels and cardiovascular risk factors and year risk of CVD in patients with hypertension in Jiangsu province of China, there are several limitations.

The participants with hypertension were recruited from a single province in China, so extrapolation to other populations should be cautious. In addition, our study is a cross-sectional study, and prospective studies are needed for further verification.

Finally, other factors that may affect creatinine levels and cardiovascular risk factors such as urea nitrogen and uric acid were missing in this study, and the number and type of antihypertensive drugs were not considered in the study, but we conducted a sensitivity analysis to reduce part of the confounding effect.

In conclusion, serum creatinine was associated with several cardiovascular risk factors in a hypertensive population in Jiangsu province. The year cardiovascular risk was higher in hypertensive patients with higher serum creatinine levels, especially in men. Creatinine-reduction and kidney-sparing therapy is essential for patients with hypertension to optimize control of cardiovascular risk factors and reduce cardiovascular risk.

The studies involving human participants were reviewed and approved by the Ethics Review Board of Jiangsu Center for Disease Control and Prevention SLB Study concept and design: QX, YuZ, YoZ, YQ, XC; Acquisition of data: XC, DW, HJ, JL, YQ, QX; Analysis and interpretation of data: XC, DW, HJ, JL, YQ, YoZ, QX; Drafting of the manuscript: XC, DW, JL, YQ, QX; Critical revision of the manuscript for important intellectual content: QX, YQ, YuZ; Statistical analysis: XC, DW, JL, YQ, QX; Obtained funding: QX; Technical, or material support: YQ, YoZ, YuZ, QX; Study supervision: QX.

All authors contributed to the article and approved the submitted version. This study was supported by the Projects in the Chinese National Science and Technology Pillar Program during the 12th Five-year Plan Period BAI11B01 , and Jiangsu Province Health Research Project H We thank Wang Zenwu and Wang Xin Division of Prevention and Community Health, National Center for Cardiovascular Disease, Fuwai Hospital for their constructive suggestions and the technical support.

We thank all the colleagues involving in this survey from Pizhou, Haian, Peixian, Sihong County and Jiangye District Center for Disease Control and Prevention. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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Creatine is an amino acid compound found in muscle cells where it aids in the regeneration of ATP, or energy production. Creatine monohydrate the most popular and researched form is a creatine molecule with one additional water molecule which helps your cells absorb and retain water for hydration.

To put it simply, creatine is an energy source for muscle cells and helps in performance and recovery. Creatine monohydrate supplementation safely increases the stores of the compound in muscle cells to the maximum amount. How much should I take?. A study done in used 16 clinical trials from over a decade to conclude that in participants, creatine supplementation undoubtedly out-performed placebo in muscle growth and strength.

There are also new studies being conducted to show that creatine might be an essential part of healthy heart function. Another study theorized that because failing hearts typically show a decrease in creatine transportation, it could be beneficial to supplement. Even though the findings were not conclusive, they were deemed to be encouraging and warrant future research.

How much should I take? Most research has been conducted using an average of grams per day, this is a safe amount. Keep in mind that a small percentage of the population actually produces creatine to the maximum extent — these people will see little to no benefit from supplementation. Is it possible to take too much creatine?

Generally speaking, yes. You might experience some stomach discomfort but any excess will exit your body through the urinary tract. If this occurs, reduce your dosage. Taking above the recommended amount for too long can result in kidney damage. Are creatine monohydrate and steroids similar?

Once a divisive topic, creatine is now one of the most effective and safe dietary supplements that gives proven results. When taken in approved dosages, creatine has been shown to increase muscle mass, strength, brain function, and potentially heart function as well.

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Thank you for subscribing! Sorry something went wrong with your subscription Please, try again in a couple of minutes Retry. Show references Kreider RB, et al. International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine.

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