A recent article published in the Circulation journal investigated the interplay among chronic kidney disease, metabolic risk factors, and the cardiovascular system on morbidity and mortality.

It focused on providing guidance to care for patients with cardiovascular-kidney-metabolic syndrome.

Study: Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. Image Credit: SewCreamStudio/Shutterstock.com

What is cardiovascular-kidney-metabolic syndrome?

Cardiovascular-kidney-metabolic (CKM) health is associated with pathophysiological interactions among metabolic risk factors (e.g., diabetes and obesity), cardiovascular system, and chronic kidney disease (CKD).

Several studies have indicated poor CKM health leads to multiorgan disease, excess morbidity, and premature death. It must be noted that the maximum healthcare expenditure is driven by cardiovascular disease (CVD).

The prevalence of poor CKM heath is extremely high worldwide. Although the increased majority of CKM has raised significant concerns, advancing science and technology has provided significant opportunities to alleviate the disease burden.

For instance, several therapies have been formulated that benefit kidney and metabolic disease. It also provides a protective effect against adverse CVD events and mortality. However, there is a need for better guidance to protect the global population from CKM syndrome.

Cardiorenal syndrome has been defined as a bidirectional relationship between heart and kidney dysfunctions. Here, dysfunction of one organ leads to malfunction of another.

Cardiometabolic disease occurs due to excess and dysfunction of adipose tissue that induces insulin resistance and inflammation and triggers the incidence of several metabolic risk factors that ultimately enhance the possibility of CVD events. 

Kidney dysfunctions have recently been identified as a crucial factor mediating the association between CVD events, particularly heart failure, and metabolic risk factors. Previous studies have shown that albuminuria is a robust predictor of adverse CVD events.

However, in general practice, the rates of albuminuria testing are significantly low, even among high-risk populations. This observation indicates the urgent need to increase awareness among clinicians that can effectively reduce the morbidity and mortality rates due to CKM syndrome. 

CKM syndrome affects all major organ systems through premature cognitive decline, kidney failure, obstructive sleep apnea, metabolic dysfunction–associated steatotic liver disease, atherogenesis, coronary heart disease, peripheral artery disease, stroke, atrial fibrillation, and myocardial function. 

There is a need for a clear definition of CKM syndrome. Furthermore, an effective risk prediction tool and strategies to reduce CKM manifestations are urgently needed. Optimal CKM prevention and management will significantly reduce morbidity and mortality rates.

Effective therapies for CKM syndrome

Several therapies benefit renal functions and metabolic risk factors and prevent CVD events.

An antidiabetic agent, namely, sodium-glucose cotransporter-2 (SGLT2) inhibitors, exhibited preventive effects on renal, cardiac, and metabolic systems. This drug reduced hospitalization rates, particularly due to heart failure.

Another therapy linked to glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) also improved insulin resistance and glycemia. It also enabled weight reduction that significantly reduced CVD events. Renin-angiotensin-aldosterone system (RAAS) inhibitors have also positively affected CKM syndrome.

Major highlights of presidential advisory from the American Heart Association to manage CKM

CKM syndrome has been defined as a health disorder that is associated with obesity, CKD, diabetes, and CVD that includes atrial fibrillation, heart failure, stroke, peripheral artery disease, and coronary heart disease. Individuals at risk of CVD or with existing CVD are included in CKM syndrome.

A CKM staging that reflects on the pathophysiology, risk factors, and preventive and treatment opportunities for CKM syndrome has been developed. Stage zero indicates the absence of CKM risk factors, and stage one represents excess or dysfunctional adiposity.

Stage two indicates the presence of metabolic risk factors, such as hypertension, metabolic syndrome, hypertriglyceridemia, and diabetes, along with moderate-to-high-risk CKD. Stage three includes subclinical CVD in CKM syndrome, high CVD risk, or very high predicted CKD risks. Stage four represents clinical CVD in CKM syndrome. The presence of high-risk factors increases the progression of CKM stages.

It is imperative to screen for CKM risk factors throughout life and categorize them into respective stages. This will help manage CKM syndrome better across all age groups. Using a CKM risk calculator starting at 30 years of age would also help manage CKM syndrome.

Value- and volume-based strategies could improve interdisciplinary care for patients with many comorbidities within CKM syndrome. Since CKM syndrome is more prevalent in individuals with adverse social determinants of health (SDOH), it is important to screen SDOH systematically. These factors must be incorporated into the clinical care model to identify individuals at a high risk of CKM syndrome.

Suitable lifestyle-based interventions must be developed to address weight loss, which could prevent progression or promote regression along CKM stages. Suitable use of cardioprotective antihyperglycemic agents in diabetic patients could alleviate CKM syndrome.

Also, kidney-protective therapies that include angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers must be used appropriately.

It is important to increase awareness of CKM syndrome through education to optimize CKM health in the global population. More research is required to understand CKM syndrome better and formulate optimal strategies to reduce associated mortality and morbidity rates.

Journal reference:

• Ndumele, E.C. et al. (2023) Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory from the American Heart Association. Circulation. doi: https://doi.org/10.1161/CIR.0000000000001184. https://www.ahajournals.org/doi/10.1161/CIR.0000000000001184