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Here’s what you need to know about cardiovascular-kidney-metabolic syndrome, newly defined by the AHA | Nephrology | JAMA


Cardiovascular disease often occurs in cases of kidney disease and metabolic diseases, including obesity and type 2 diabetes. And having more than one of these conditions increases health and mortality risks, particularly from cardiovascular disease. A Presidential Advisory from the American Heart Association (AHA) recently published in Traffic recently defined the adverse interaction between these conditions as cardiovascular-kidney-metabolic (CKM) syndrome.

The advisory provides guidance on how to stage CKM syndrome in patients, predict its cardiovascular consequences, and effectively manage, prevent, and even reverse it in adults and children. The evidence is detailed in a separate scientific statement. Together, the publications provide a framework for holistically and equitably improving population CKM health, according to the advisory. They also lay the foundations for a new cardiovascular disease risk calculator that will incorporate the CKM health concept for the first time.

The advisory notes that harmful, mutually reinforcing relationships between metabolic diseases, chronic kidney disease, and cardiovascular disease are known. However, opinions vary on how these conditions together constitute a syndrome, suggesting a common underlying pathophysiology.

“There has been growing interest in the interaction between these conditions, but there has not been a clear definition,” said Chiadi E. Ndumele, MD, PhD, chair of the editorial advisory board, in an interview with JAMA. This has altered treatment that covers the entire risk spectrum of CKM syndrome, added Ndumele, associate professor and director of obesity and cardiometabolism research at Johns Hopkins University.

To address the high and growing prevalence of poor CKM health, the AHA developed a consensus statement to clarify the definition of CKM syndrome and tools to better detect, prevent, and manage it . They are integrated into the opinion and the scientific declaration, which are the result of a multidisciplinary committee composed of 28 experts in cardiology, nephrology, endocrinology, primary care and pediatrics.

The advisory attempts to bridge sometimes inconsistent specialty-specific recommendations, Ndumele said. “Great attention has been paid to harmonizing current guidelines. Where there were gaps or lack of clarity, we identified those areas and then tried to provide clarity as much as possible.

Metabolic diseases, such as obesity and type 2 diabetes, and chronic kidney disease can damage almost every major organ system. In particular, they increase the risk of cardiovascular diseases, including heart failure, atrial fibrillation, coronary heart disease, stroke and peripheral artery disease, as well as the risk of premature death. Collectively, heart disease, stroke, kidney disease, and diabetes directly accounted for more than 1 million deaths in the United States in 2021, or about 29%. Indeed, the increasing prevalence of CKM-related risks has slowed five decades of decline in cardiovascular disease mortality, the opinion notes. And overweight and its downstream comorbidities directly and indirectly cost an estimated $1.7 trillion per year.

“There was a lot of urgency to address this challenge and, at the same time, there was a growing range of therapeutic options to address it,” Ndumele said. “The obvious public health challenge and growing clinical options make this initiative very timely. »

Simply put, the advisory defines CKM syndrome as a health disorder caused by links between heart disease, kidney disease, diabetes and obesity, leading to poor health outcomes. The syndrome increases the risk of development and progression of cardiovascular disease and affects both those at risk and those with existing cardiovascular disease.

Adopting this definition helps clarify the understanding of these adverse interactions and supports specific concepts for staging, screening, risk stratification, as well as prevention and treatment, Ndumele said. It can also help communicate metabolic health factors and their risks to patients more effectively, without judgment, according to Ashish Sarraju, MD, a preventative cardiologist at the Cleveland Clinic, who was not involved in developing the advice.

The staging of CKM syndrome presented in the opinion reflects its pathophysiology, its risk factors and its opportunities for prevention and care:

  • Step 0: no CKM risk factors

  • Step 1: excessive or dysfunctional adiposity – a source of proinflammatory and prooxidative secretions that cause tissue damage and reduce insulin sensitivity

  • 2nd step : metabolic risk factors, particularly hypertriglyceridemia, hypertension, diabetes and metabolic syndrome; or moderate to high risk chronic kidney disease

  • Step 3: subclinical cardiovascular disease with CKM syndrome or risk equivalents – particularly high predicted cardiovascular disease risk or very high risk chronic kidney disease

  • Step 4: clinical cardiovascular disease with CKM syndrome

“The goal is to clarify how to use these therapeutic tools and better support lifelong prevention,” Ndumele said. “With substantial lifestyle changes and significant weight loss, we may even see stage regression. »

Screening and risk assessment

Screening for risk factors should begin early in life, the advisory notes, and should increase in frequency if the stages of CKM syndrome progress. A new risk calculator to be released soon will integrate CKM health to facilitate the assessment of cardiovascular risk and prediction of outcomes, which is expected to begin at age 30 for affected patients. Social determinants of health significantly affect risk and must be screened for and addressed.

Excess body fat and associated insulin resistance are the cause of many of the damages linked to CKM syndrome, according to the scientific statement. They should be resolved through lifestyle modification and weight loss, the recommendations say. Early use of medications, including sodium-glucose transport protein 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists, may also reduce the risk of cardiovascular disease. Education and support for healthy lifestyles can help improve the health of CKM patients and the population.

The advisory highlights that holistic care strategies, including value- and volume-based models that support interdisciplinary care, can help reduce care fragmentation and improve treatment and outcomes. These strategies should address the social determinants of health. The formation of multidisciplinary teams and community partnerships can help mobilize resources for an effective response.

Strengths and limitations

According to the scientific statement, there is strong evidence to support the idea that CKM syndrome increases health risks. But there are significant gaps in understanding.

The mechanisms linking CKM risk factors to cardiovascular disease and chronic kidney disease, both individually and in combination, are clearer in some cases than others. For example, the inflammation, dyslipidemia, hypertension, and insulin resistance of CKM syndrome appear to accelerate atherosclerotic cardiovascular disease. In contrast, the mechanisms linking CKM syndrome to heart failure and arrhythmias are less well described, although inflammation is increasingly understood as a cause of heart failure with preserved ejection fraction. Additionally, the relationship between cardiovascular disease and increased risk of subsequent kidney disease is poorly understood, the release notes.

Furthermore, the biological and chemical mechanisms underlying sex differences in presentation and progression are also not well understood. Neither are the influences of genetic risk factors. The risks of CKM syndrome also differ significantly among racial and ethnic groups, with much of the difference related to social determinants of health. Individual risk is likely influenced by environmental, lifestyle and epigenetic interconnections, the release said.

And while evidence supports approaches to prevention and management of CKM syndrome, there are also gaps in understanding. These gaps include information on optimal structures for interdisciplinary teams and coordinators; maternal and early life interventions; weight loss approaches; use of SGLT2 inhibitors, GLP-1 receptor agonists, and lipid-lowering therapies; and management of cardiovascular disease in patients with chronic kidney disease.

More research is needed to address these gaps, as is advocacy for promoting insurance coverage for high-cost medications and adopting delivery models that support integration of care, Ndumele said. “Implementation within and between health centers is key. »

According to Sarraju, the value of consulting lies in its comprehensive and understandable approach to a complex problem. “This statement unifies many individual concepts that doctors are already familiar with and provides an approach that is easier to implement and communicate with patients,” he said. “Hopefully this will allow preventive and therapeutic measures to be implemented earlier in life and in a more effective way. »

Published online: November 8, 2023. doi:10.1001/jama.2023.22276.

Conflict of Interest Disclosures: Dr. Ndumele said he received grant funding from the National Institutes of Health and the AHA. No further disclosures have been reported.

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