CKM syndrome leads to elevated cardiovascular disease risk earlier in life

People with chronic kidney disease, Type 2 diabetes or both were predicted to have elevated cardiovascular disease (CVD) risk 8 to 28 years sooner than someone without those conditions, according to a preliminary study to be presented at the American Heart Association's Scientific Sessions 2024. The meeting, Nov. 16-18, 2024, in Chicago, is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science.

Current guidelines on CVD prevention define CVD risk as elevated if the chance of having a heart attack or stroke in the next 10 years is 7.5% or higher. Chronic kidney disease and Type 2 diabetes increase risk and are two of the four components of cardiovascular-kidney-metabolic (CKM) syndrome, which the American Heart Association defines as the interplay of cardiovascular disease, kidney disease and the metabolic disorders Type 2 diabetes and obesity. This study aimed to better understand the effects of (CKM) syndrome on CVD risk.

Researchers created risk profiles to simulate men and women with and without chronic kidney disease and/or Type 2 diabetes at each age from 30 to 79 years. They used the American Heart Association Predicting Risk of cardiovascular disease EVENTs (PREVENT™) calculator to determine at what age someone with each risk profile would be expected to have elevated CVD risk.

The risk profiles were based on data from the National Health and Nutrition Examination Survey 2011-2020. Chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) of 44.5, which indicates stage 3 kidney disease. Type 2 diabetes was indicated as a "yes" response to the PREVENT calculator prompt, "Any history of diabetes." Profiles without CKM syndrome were derived from average blood pressure, cholesterol and eGFR levels representing survey participants who did not have diabetes, were not taking medicines to lower blood pressure or cholesterol and were non-smokers.

According to the American Heart Association, nearly half of all U.S. adults are living with some form of CVD, and one in three has at least three risk factors that contribute to CKM syndrome. Identifying who is at greatest risk earlier can improve primary prevention and reduce the risk of premature death from CVD.

Our findings help to interpret the combination of risk factors that will lead to a high predicted CVD risk and at what age they have an impact on risk. For example, if someone has borderline-elevated levels of blood pressure, glucose and/or impaired kidney function, but they don't yet have hypertension or diabetes or chronic kidney disease, their risk may not be recognized. Understanding how age interacts with risk factor levels is important to optimize CKM health."

Vaishnavi Krishnan, B.S., lead study author, researcher at Northwestern University in Chicago and medical student, Boston University School of Medicine, Boston

Without CKM syndrome, the expected age to reach elevated CVD risk was 68 years for women and 63 for men. However, with CKM components added to the simulated patient profile, the same risk level was predicted to occur at a much younger age:

• For adults with stage 3 chronic kidney disease, predicted 10-year CVD risk was elevated at age 60 for women and 55 for men. This is 8 years younger than expected for men and women without CKM syndrome.
• For adults with Type 2 diabetes, predicted 10-year risk of CVD was elevated at age 59 for women and 52 for men. This is 9 years younger for women and 11 years younger for men compared to those without CKM syndrome.
• For adults who had both Type 2 diabetes and stage 3 chronic kidney disease, predicted 10-year risk of CVD was elevated at age 42 for women and 35 for men. This is 26 years younger for women and 28 years younger for men compared to those without CKM syndrome.

"A strength of this study is that it spans nearly the full adult life course and examines how risk factor levels due to CKM conditions of chronic kidney disease and Type 2 diabetes may impact predicted CVD risk," Krishnan said. "However, a limitation of this study is that these are predicted risk calculations based on a simulated population."

"This is an early step in the process of understanding how a risk model works," said Sadiya S. Khan, M.D., M.Sc., co-author of the study, the Magerstadt Professor of Cardiovascular Epidemiology and an associate professor of cardiology, medical social sciences and preventive medicine (epidemiology) at Northwestern School of Medicine in Chicago, and chair of the writing group for the PREVENT equations. "Future work and guidelines are needed to determine how to use the PREVENT equations and what risk thresholds should be used in a clinical setting."

To address the complex health threat of CKM syndrome, the American Heart Association, celebrating 100 years of lifesaving service as a global force for healthier lives for all, has launched a four-year Cardiovascular-Kidney-Metabolic (CKM) Health Initiative, supported by Novo Nordisk and Boehringer Ingelheim. The initiative will track CKM measures in the Association's Get With The Guidelines® and outpatient data registries; improve coordination among CVD, kidney and diabetes specialists; and promote best practices, including guideline-directed treatment. This work will help assess gaps in clinical care, identify areas for future research, and implement guidelines and screening recommendations to provide clear and definitive advice for CKM syndrome treatment.