AHA Advisory Focuses on Cardiovascular-Kidney-Metabolic Syndrome – Renal and Urology News

In its new presidential advisory, the American Heart Association (AHA) has shined a spotlight on cardiovascular-kidney-metabolic (CKM) syndrome – a newly described multisystem syndrome highlighting the interactions among risk factors linked to poor health, organ damage, cardiovascular events, and early death, including obesity, type 2 diabetes and other metabolic abnormalities, chronic kidney disease (CKD), and cardiovascular disease risk.

According to the advisory, “rather than simply considering cardiorenal syndrome and cardiometabolic disease as separate entities, it is increasingly clear that we need to consider their overlap as a broader construct of CKM syndrome.

“Nearly every major organ system is affected as a consequence of CKM syndrome, with associated clinical challenges including kidney failure, premature cognitive decline, metabolic dysfunction-associated steatotic liver disease (previously nonalcoholic fatty liver disease), obstructive sleep apnea, and increased risk for cancer. However, the greatest clinical impact of CKM syndrome with regard to morbidity and premature mortality is through the disproportionate burden of [cardiovascular disease].”

More than 90 million adults, or 1 in 3 individuals, in the US have at least 3 risk factors for CKM syndrome, according to Chiadi Ndumele, MD, PhD, MHS, a cardiologist and member of the advisory writing committee. Social determinants of health and risk enhancers also play a role in who is prone to developing these risk factors and who receives adequate care, Dr Ndumele, an associate professor at Johns Hopkins University in Baltimore, Maryland, pointed out. Prevention efforts and early life screening for risk factors are major goals of this initiative, he said.

The advisory, published in Circulation, takes an interdisciplinary approach to preventing and managing CKM syndrome throughout a patient’s lifetime from youth to adulthood. It provides guidance on CKM syndrome prevention, staging, prediction, and approaches to holistic and equitable care.

CKM Syndrome Staging

The advisory details a CKM syndrome staging framework designed to help clinicians slow progression by considering the totality of patients’ individual risk exposures. The frequency and intensity of screening should increase with the CKM syndrome stage. The framework outlines how and when to use specific therapies.

• Stage 0 describes healthy adults with no risk factors whom clinicians can encourage to preserve cardiovascular health through AHA’s life’s essential 8: eating healthy, staying active, maintaining healthy weight, avoiding smoking, and maintaining normal range blood pressure, blood sugar, and lipids. Clinicians should screen these adults every 3-5 years to assess blood pressure, triglycerides, HDL cholesterol, and blood sugar. At every stage, clinicians should perform yearly measurement of waist circumference and body mass index and encourage healthy lifestyle behaviors.
• Stage 1 describes adults with excess or dysfunctional adipose tissue from overweight, obesity, abdominal obesity, and/or impaired glucose tolerance. (Women with gestational diabetes fall into this category.) Clinicians should screen every 2-3 years for blood pressure, triglycerides, cholesterol, and blood sugar. The goal is at least 5% weight loss, with treatment for glucose intolerance if needed.
• Stage 2 describes adults with metabolic risk factors or CKD. These individuals have type 2 diabetes, hypertension, hypertriglyceridemia, metabolic syndrome, and/or metabolic or nonmetabolic etiologies of CKD. Yearly assessment of blood pressure, triglycerides, cholesterol, and blood sugar is warranted. Kidney function should be assessed at least yearly and more frequently in those at risk for kidney failure. CKD screening should include blood and urine testing for estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR).

Stage 2 warrants intensified lifestyle medication and targeted therapies to control blood pressure, blood sugar, and cholesterol, protect kidney function, and reduce the risk of heart failure. Medications may include glucagon-like peptide 1 (GLP-1) receptor agonists or sodium glucose contransporter 2 inhibitors (SGLT2i).

• Stage 3 describes adults with subclinical atherosclerotic cardiovascular disease or subclinical heart failure. It also includes those with risk equivalents including patients with stage 4-5 CKD and those with high predicted cardiovascular risk.

The goal of care in stage 3 is increasing or changing medications or lifestyle efforts to prevent progression to symptomatic cardiovascular disease (eg, heart failure) and kidney failure. Regression may be possible. Clinicians should use coronary artery calcium screening to guide decisions about cholesterol-lowering statin therapy if necessary.

• Stage 4 describes patients with clinical cardiovascular disease including coronary heart disease, heart failure, atrial fibrillation, stroke, or peripheral arterial disease. People may have already had a heart attack or stroke. Stage 4b patients also have end-stage kidney disease (ESKD) and are therefore at the highest risk for cardiovascular events, hospitalizations, and premature death. The goal of management in stage 4 is individualized treatment to optimize care and secondary prevention.

Enhancing Risk Prediction With a New Tool

The AHA will be unveiling a new risk calculator that includes CKM components such as cardiovascular disease, CKD, and metabolic disorders. It will gauge an individual’s risk for heart failure in addition to heart attack and stroke.

The new tool – to be presented at AHA’s Scientific Sessions in Philadelphia, Pennsylvania on November 11-13, 2023 – goes beyond the current pooled cohort equation. It starts younger (at age 30 years) and reflects risk in various ethnicities. The calculator will include blood sugar measurement results, eGFR, UACR, and social determinants of health.

The risk calculator will calculate both 10-year and 30-year cardiovascular disease risk.

Risk-Enhancing Factors

The advisory noted specific factors and medical history that can increase the likelihood that CKM syndrome progresses to a more advanced stage. These factors might adversely affect predisposition, lifestyle behaviors, medication exposures, and more.

• Family history of diabetes or kidney failure
• High-sensitivity C-reactive protein of 2.0 mg/L or higher
• Chronic inflammatory conditions such as lupus and HIV/AIDS
• High-risk demographic groups such as South Asians and individuals of low socioeconomic status
• Adverse social determinants of health (eg, economic instability, low education, poor health care access, under-resourced neighborhoods, and low social/community context due to racism, etc)
• Mental health disorders
• Sleep disorders
• Sex-specific factors (eg, erectile dysfunction, premature menopause, hypertensive disorders of pregnancy, preterm birth, polycystic ovarian syndrome)

Major goals are to find optimal strategies to support lifestyle change and weight loss at every stage, tailored approaches to selecting cardioprotective anti-hyperglycemic therapies in at-risk patients and those with existing cardiovascular disease, the use of lipid-lowering therapies beyond statins in those with diabetes and/or high risk for CKM syndrome, and management of cardiovascular disease in patients with CKD.

The call to action centers on addressing research gaps and improving patients’ social determinants of health, access to pharmacotherapies, CKM syndrome education, interdisciplinary care, obesity management, and community support.

“We actually now have therapies that converge together and meaningfully improve outcomes, whether from a metabolic, cardiovascular, or kidney perspective,” said Janani Rangaswamy, MD, a nephrologist and coauthor of the paper. She is also professor of medicine at the George Washington University School of Medicine in Washington, DC. Dr Rangaswamy mentioned, for example, that high-level evidence supports SGLT2i for cardio-kidney protection in patients who have CKD with and without diabetes across albuminuria categories and patients who have heart failure with preserved or reduced ejection fraction. Combined use of SGLT2i and GLP-1 RA may be considered for those with multiple CKM syndrome risk factors in the setting of high predicted cardiovascular risk. In patients with CKD and diabetes, finerenone, a nonsteroidal mineralocorticoid receptor antagonist, data shows benefit on top of renin angiotensin aldosterone system inhibitors.

The advisory proposed value-based care whereby patients with at least 2 criteria for CKM syndrome see a multidisciplinary care team that includes representation from primary care, cardiology, nephrology, and endocrinology with oversight from a care coordinator. The goal is upfront, guideline-recommended treatment.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References

Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular-kidney-metabolic health: A presidential advisory rom the American Heart Association. Published online October 9, 2023. Circulation. doi:10.1161/CIR.0000000000001184

Cardiovascular kidney metabolic health: Presidential advisory. Accessed on October 13, 2023 at https://www.youtube.com/watch?v=HfN3GzuY1dI

Heart disease risk, prevention and management redefined. News release. American Heart Association; October 9, 2023.