New guidelines have been published for cardiovascular-kidney-metabolic (CKM) syndrome, outlining the key aspects of its detection, classification, management, and prevention.

The American Heart Association and the American College of Cardiology have developed joint guidelines on CKM, published in Circulation, which highlight its classification, the detection of risk factors, and guidelines for prevention and treatment.

As Marta Cobo, cardiologist and president-elect of the Heart Failure Association of the Spanish Society of Cardiology, explained to El Médico Interactivo, part of the Medscape’s Professional network, CKM is common, although its prevalence depends on the definition used and whether its early stages are included. According to an analysis of the US National Health and Nutrition Examination Survey, nearly 90% of adults met criteria for some stage of the syndrome, and about 15% were classified as having advanced disease, stage 3 or 4.

These figures must be interpreted appropriately. The classification ranges from very early stages — such as excess body fat or prediabetes — to the presence of clinical cardiovascular or renal disease. In fact, stage 2, defined by metabolic factors such as hypertension, diabetes, hypertriglyceridemia, metabolic syndrome, or chronic kidney disease (CKD), is the most common.

In his opinion, Spain needs specific studies that apply this new classification consistently. However, given the high prevalence of obesity, hypertension, type 2 diabetes (T2D), and CKD, it is reasonable to assume that the burden on the healthcare system is also significant. Its relevance lies not only in its frequency but also in the fact that the coexistence of these conditions multiplies the risk for cardiovascular and renal events and mortality.

Along these lines, Emilio Sánchez Álvarez, president of the Spanish Society of Nephrology, noted that “in Spain, 40% of the population is overweight, 15% is obese, 14% has diabetes, 15% has CKD, one third of the population has high blood pressure, 1 in 4 Spanish adults smokes, and nearly half has hypercholesterolemia.”

Risk Factors

Regarding risk factors, specialists point out that the central factor is usually excess or dysfunction of adipose tissue, particularly visceral fat. This promotes inflammation, insulin resistance, and the progressive onset of high blood pressure, dyslipidemia, T2D, and kidney disease. Thus, Cobo noted that “among the main risk factors are being overweight and having abdominal obesity, high blood pressure, hyperglycemia and diabetes, hypertriglyceridemia, metabolic syndrome, albuminuria, and reduced glomerular filtration rate. Risk is also increased by a sedentary lifestyle, an unhealthy diet, smoking, sleep disorders — especially obstructive sleep apnea — and steatotic liver disease associated with metabolic dysfunction.”

In this context, the guidelines also note that there are risk factors for disease progression that are often not sufficiently assessed, such as chronic inflammatory diseases, a family history of diabetes or kidney failure, depression and anxiety, premature menopause, polycystic ovary syndrome, erectile dysfunction, and adverse obstetric history, such as gestational diabetes, preeclampsia, or preterm birth.

Social determinants of health must also be considered; factors such as economic hardship, food insecurity, an environment that hinders physical activity, low health literacy, or barriers to accessing care and treatments can contribute to both the onset and progression of the syndrome.

Stratification

For nephrologists, several aspects are of particular interest. On the one hand, the guideline stratifies CKM syndrome into four stages, ranging from the risk of developing the syndrome to having already experienced cardiovascular or renal events. On the other hand, it introduces risk assessment using a series of equations based on the patient’s individual data, plus the presence of risk factors, thereby establishing a numerical assessment of the risk of experiencing events over the next 10 or 30 years. Furthermore, it incorporates another highly innovative element: taking into account lifestyle factors — how patients live, under what conditions, how they eat, and their involvement in cardiovascular care — because these are aspects that must be addressed as measures to be implemented once the syndrome has been diagnosed.

For her part, the cardiologist maintains that the main advance is that it transforms the conceptual framework proposed by the American Heart Association in 2023 into a true clinical practice guideline. It is no longer limited to defining the syndrome but establishes how to detect, classify, treat, and monitor it. One of its essential points is staging from stage 0 to stage 4. Stage 0 corresponds to favorable cardiovascular, renal, and metabolic health; stage 1, to excess body fat or adiposity dysfunction; stage 2, to the onset of metabolic factors or kidney disease; stage 3, to subclinical cardiovascular disease, very high-risk kidney disease, or very high cardiovascular risk; and stage 4, to clinical cardiovascular disease.

In his opinion, another new feature is the incorporation of the PREVENT equations, which allow for the estimation not only of the risk for atherosclerotic cardiovascular disease but also of the risk for heart failure and total cardiovascular risk over 10 and 30 years. This is particularly important because heart failure is one of the main manifestations of the CKM syndrome.

Obesity

It should also be noted that the guidelines classify obesity as a chronic disease and as one of the underlying causes of the syndrome. Therefore, they recommend assessing both BMI and waist circumference and propose a stepwise treatment approach that includes intensive lifestyle intervention, anti-obesity pharmacotherapy, and metabolic surgery when indicated.

In people with T2D, treatment selection should be guided by organ protection and not exclusively by reducing glycated hemoglobin. “SGLT2 inhibitors and GLP-1-based therapies play a leading role due to their cardiovascular, renal, and metabolic benefits, and can be used in combination in selected patients,” noted the specialist, who added that “renal function should be assessed using two parameters: estimated glomerular filtration rate [estimated glomerular filtration rate] and the urine albumin-to-creatinine ratio. Measuring only creatinine or GFR may overlook patients with albuminuria and high cardiovascular and renal risk. In cases of kidney disease associated with diabetes or albuminuria, the guidelines recommend the use of renin-angiotensin system inhibitors, SGLT2 inhibitors, and — when albuminuria persists — finerenone or GLP-1-based therapies.”

Finally, the guidelines explicitly incorporate interdisciplinary care, social determinants, monitoring after treatment initiation, and the goal not only of preventing progression but also of achieving regression of the CKM stage whenever possible.

Clinical Application

To apply these guidelines in daily clinical practice, we must first stop evaluating the heart, kidneys, and metabolism separately. For any patient with obesity, hypertension, diabetes, dyslipidemia, kidney disease, or cardiovascular disease, we must ask ourselves which other components of the syndrome are present and at what stage they are. In fact, the nephrologist emphasized that the approach to these patients must be comprehensive. It is clear that this is not easy to accomplish in a single visit — initially in primary care — but it can subsequently be transferred to specialized care. “I believe that nurses must be involved in promoting lifestyle changes, smoking cessation, physical activity, and healthy diets.”

The cardiologist noted that “the frequency of follow-up can be adapted to the stage. For a person in stage 0, lipid, blood glucose, and kidney function tests can be performed at least every 5 years. In stage 1, these should be repeated every 2 or 3 years, in addition to annual monitoring of anthropometric measurements and blood pressure. Starting in stage 2, the assessment of metabolic and renal factors must be conducted at least annually and more frequently if the disease progresses or treatments are changed.”

She then explained that the next step is to calculate cardiovascular risk using the PREVENT equations, whenever applicable, and to use that risk to determine the intensity of treatment. We should not wait for a heart attack, heart failure, or advanced kidney disease to occur before intervening.

Multidisciplinary Management

As for treatment, it must be multifactorial. This includes a healthy diet, physical activity, smoking cessation, adequate sleep, and weight control, as well as the early use of treatments with proven cardiovascular and renal benefits. It is important to avoid therapeutic inertia and to systematically verify whether patients indicated for an SGLT2 inhibitor, a GLP-1-based therapy, a renin-angiotensin system inhibitor, or finerenone are actually receiving these medications at the appropriate dose.

After initiating or intensifying treatment, it is essential to schedule follow-up visits. Tolerance, adherence, blood pressure, renal function, potassium levels, blood glucose, weight, and albuminuria must be assessed based on the medication used and the patient’s characteristics. The guideline should not become a mere list of tests or medications, but rather a simple, standardized clinical pathway tailored to individual risk.

The two specialists agree that the approach must be coordinated. Álvarez noted that it involves various specialties, starting with primary care, but also including cardiology, endocrinology, nephrology, and likely internal medicine and neurology as well because these organs are affected by this syndrome. “All of us healthcare professionals must work together to do our very best to ensure a coordinated approach. I believe that primary care should be the cornerstone around which everything revolves, but specialists must be there to provide support in every situation.”

In fact, Cobo pointed out, “the new guidelines recommend interdisciplinary care models, especially when at least two of these three conditions coexist:T2D, CKD, and cardiovascular disease. Coordination is even more important when a patient is at high risk or in an advanced stage of the disease.”

In recent years, the Spanish societies of cardiology and nephrology have promoted an innovative care model based on so-called cardiorenal units.

These units bring together professionals from different specialties to provide a joint assessment and coordinated follow-up for highly complex patients, particularly those with heart failure, CKD, multiple comorbidities, high frailty, or treatments requiring close monitoring. “This model helps reduce fragmentation of care, facilitate therapeutic optimization, and improve continuity of care,” explained the specialists.

Coordination Point

However, there must be a clearly identified professional or coordination point. The key is for someone to oversee the joint care plan, reconcile medications, monitor safety, ensure follow-up, and facilitate communication among professionals and with the patient.

Coordinated care does not mean that all patients must be treated simultaneously by multiple specialists. Less complex cases can be managed using agreed-upon protocols, while higher-risk patients require a multidisciplinary assessment and targeted referrals. Cardiorenal units are a good example of how to organize this care for the most complex patients. The goal is to combine expertise without fragmenting care.

Cobo and Álvarez declared having no relevant financial relationships.

This story was translated from El Médico Interactivo, part of the Medscape Professional Network.