From Heart to Vessels to System: The Evolution of Cardiovascular Prevention Into the CKM syndrome Era

For decades, the story of cardiovascular disease prevention was told through the lens of the heart. Coronary artery disease, myocardial infarction, and heart failure dominated the narrative. But science has steadily widened the aperture- first to the vasculature, then to the kidneys and metabolism, revealing that what was once considered a cardiac problem is, in fact, a systemic syndrome. This evolution has culminated in the American Heart Association's formal recognition of Cardiovascular-Kidney-Metabolic (CKM) syndrome, a paradigm that is reshaping how clinicians think about risk, prevention, and treatment.

Act I: The Cardiac Era -Treating the End-Stage Event

Through much of the 20th century, cardiovascular medicine was reactive. The focus was on managing acute coronary events -thrombolytics for myocardial infarction, coronary artery bypass grafting, and later, stents. Prevention, when it existed, centered on individual risk factors: lower the cholesterol, treat the blood pressure, stop the smoking. Each risk factor was addressed in isolation, and the heart was the organ of interest.

This approach saved millions of lives. Cardiovascular death rates declined dramatically from the 1960s through the 2000s, driven by advances in acute care and secondary prevention. But the model had a fundamental limitation: it waited for disease to declare itself at the organ level before intervening.

Act II: The Cardiovascular Continuum -Connecting Risk Factors to End-Organ Damage

The Cardiovascular Continuum: A Game-Changer in Heart Health

In 1991, Drs. Victor Dzau and Eugene Braunwald revolutionized our understanding of heart disease with the concept of the cardiovascular continuum, published in the American Heart Journal. This framework illustrates how cardiovascular risk factors, such as dyslipidemia, hypertension, diabetes, and smoking, trigger a chain reaction leading to atherosclerosis, coronary artery disease, and ultimately heart failure.

The brilliance of this idea lies in its simplicity: cardiovascular disease is a continuous process, not a series of isolated events. By intervening early in this continuum, we can halt the progression toward serious health issues. In 2006, Dzau expanded this model to include obesity and oxidative stress as critical factors, emphasizing their role in tissue damage.

This shift transformed clinical practice, moving the focus from merely treating heart attacks to preventing them and from managing heart failure to preventing its underlying causes. It also recognized atherosclerosis as a systemic vascular disease, affecting multiple arteries throughout the body.

Act III: The Vascular Expansion- Atherosclerosis as a Systemic Disease

As the continuum concept evolved, clinicians began to understand that atherosclerosis transcends anatomical boundaries. Coronary artery disease often coexists with carotid stenosis, peripheral artery disease (PAD), aortic disease, and renal artery stenosis more frequently than chance would suggest. This led to the emergence of polyvascular disease, which refers to atherosclerosis affecting two or more arterial areas. This condition is a significant risk marker, impacting 15-30% of patients with atherosclerosis and leading to much higher rates of major cardiovascular events compared to those with isolated disease.

This insight prompted key changes in risk assessment, expanding it beyond coronary arteries to include ankle-brachial index screening, carotid imaging, and coronary artery calcium scoring.

However, even with this broader view, important factors remained overlooked. The focus primarily on arterial disease often neglected the metabolic and renal contributors to atherosclerosis, as well as the non-atherosclerotic cardiovascular issues, particularly heart failure, which increasingly contribute to cardiovascular morbidity and mortality.

Act IV: The CKM Revolution - A Multisystem Paradigm

In 2023, the AHA officially defined CKM syndrome as a systemic disorder driven by the interplay of metabolic risk factors, chronic kidney disease (CKD), and cardiovascular issues, leading to multi-organ dysfunction and increased cardiovascular risks. This was more than just a rebranding; it reshaped our understanding of cardiovascular disease as a result of intertwined metabolic and renal problems.

CKM Staging System

The CKM framework introduces a novel staging system that starts with adiposity:

• Stage 0: No CKM risk factors

• Stage 1: Excess or dysfunctional adiposity

• Stage 2: Metabolic risk factors (hypertension, diabetes, dyslipidemia, metabolic syndrome) or moderate-to-high-risk CKD

• Stage 3: Subclinical cardiovascular disease (CVD) with CKM risk factors or equivalents (very high-risk CKD, high predicted CVD risk)

• Stage 4: Clinical CVD with coexisting metabolic risk factors or CKD

Key Features of the CKM Framework

Several aspects of this framework stand out:

• It identifies dysfunctional adiposity as the primary trigger, rather than cholesterol or blood pressure. Visceral fat releases harmful substances that damage the heart, arteries, and kidneys.

• The staging is bidirectional, allowing patients to move back to lower stages with effective interventions, even reaching Stage 0.

• CKD is now a central element of the syndrome, emphasizing its role in both accelerating and being accelerated by metabolic and cardiovascular diseases.

The Scale of CKM Syndrome

Population data reveals the extent of CKM syndrome, affecting about 90% of US adults at various stages, with Stage 2 being the most common, impacting nearly half of all adults. Transitioning from Stage 1 to higher stages occurs in about one-third of individuals, with each progression significantly increasing cardiovascular mortality risk—Stage 4 carries over a fivefold increase compared to Stage 0.

Why the Shift Matters: Therapeutics That Cross Organ Boundaries

Perhaps the most compelling reason for the CKM paradigm is therapeutic. A new generation of medications (SGLT 2 inhibitors, GLP-1 agonists), that does not respect the traditional organ-based silos of cardiology, nephrology, and endocrinology and neither should the framework used to deploy them.

From Siloed Care to Integrated Prevention

The CKM construct also demands a rethinking of how care is delivered. Historically, a patient with obesity, prediabetes, early CKD, and borderline hypertension might see a primary care physician for blood pressure, an endocrinologist for glucose, and a nephrologist only after significant kidney function decline with no single clinician owning the integrated risk picture. The CKM framework calls for interdisciplinary care models that assess and address the full spectrum of metabolic, renal, and cardiovascular risk at every encounter.

The AHA's PREVENT equations, developed alongside the CKM construct, operationalize this vision by incorporating kidney function and BMI as a predictor of cardiovascular risk and enabling 10- and 30-year risk estimates for total CVD (not just atherosclerotic heart disease but also heart failure) .

The AHA's Life's Essential 8 -diet, physical activity, nicotine exposure, sleep, BMI, blood lipids, blood glucose, and blood pressure - provides the behavioral foundation, while CKM staging provides the clinical scaffolding for escalating pharmacological intervention as risk accumulates.

Looking Forward

The shift from a focus on cardiac and vascular diseases to the CKM framework signifies more than just a change in disease classification. It highlights a growing awareness that heart attacks, strokes, heart failure, and kidney failure all stem from shared metabolic dysfunctions. To effectively prevent these conditions, we must tackle their root causes comprehensively and early.

While the CKM framework is still in its infancy, there are gaps in our understanding, such as the mechanisms of organ crosstalk, the impact of hepatic issues (like MASLD/MASH) as a potential fourth axis, and sex-specific differences in CKM progression. However, one thing is clear: the future of cardiovascular prevention lies not just in targeting the heart or blood vessels, but in a holistic, systemic approach, with the CKM continuum serving as our guiding map.

Lifestyle Is the First Prescription

At Preventiononly, lifestyle modification isn’t a pamphlet- it’s the clinical intervention. Targeted nutrition, structured movement, sleep optimization, and stress physiology management address CKM syndrome at its root in ways no medication can fully replicate. We use your real data - labs, imaging, Apple Watch HRV, activity logs, to build a precision lifestyle strategy that moves your biology in the right direction.

Where lifestyle alone isn’t enough, a new generation of medications - SGLT2 inhibitors, GLP-1 receptor agonists works across cardiovascular, kidney, and metabolic axes simultaneously, because that’s how the disease actually works. We deploy them strategically, as precision tools layered onto a lifestyle foundation.

The Question That Changes Everything

The old model asked: do you have heart disease?

We ask a better one: where are you on the continuum, and what can we do right now to reverse it?

Early. When the biology is still pliable. When the interventions are least invasive. When the outcomes are most transformable.

Your heart was never the whole story. We read the whole picture and then we do something about it.

Ready to find out where you stand? Your prevention evaluation starts here.

References

1. Cardiovascular Science, Medicine, and Society: The Brave New World: The ACC Braunwald Lecture 2025. Regan JA, Laitner MH, Dzau VJ. Journal of the American College of Cardiology. 2026;:S0735-1097(26)00073-2. doi:10.1016/j.jacc.2025.12.085.

2. Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association. Ndumele CE, Rangaswami J, Chow SL, et al. Circulation. 2023;148(20):1606-1635. doi:10.1161/CIR.0000000000001184.

3. A Synopsis of the Evidence for the Science and Clinical Management of Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Scientific Statement From the American Heart Association. Ndumele CE, Neeland IJ, Tuttle KR, et al. Circulation. 2023;148(20):1636-1664. doi:10.1161/CIR.0000000000001186.

4. Novel Prediction Equations for Absolute Risk Assessment of Total Cardiovascular Disease Incorporating Cardiovascular-Kidney-Metabolic Health: A Scientific Statement From the American Heart Association. Khan SS, Coresh J, Pencina MJ, et al. Circulation. 2023;148(24):1982-2004. doi:10.1161/CIR.0000000000001191.

5. Cardiovascular-Kidney-Metabolic (CKM) Syndrome: Prevalence, Risks, Disease Trajectories, and Early-Stage Management. Gunnarsson S, Vito O, Unwin RJ. American Journal of Physiology. Cell Physiology. 2025;. doi:10.1152/ajpcell.00499.2025.

6. Prevalence and Mortality Association of Different Stages of Cardiovascular-Kidney-Metabolic Syndrome. Chen Y, Wu X, Long T, et al. JACC. Advances. 2025;4(6 Pt 2):101843. doi:10.1016/j.jacadv.2025.101843.

7. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2026. American Diabetes Association Professional Practice Committee for Diabetes*. Diabetes Care. 2026;49(Supplement_1):S216-S245. doi:10.2337/dc26-S010.

8. Cardiovascular, Kidney, and Safety Outcomes With GLP-1 Receptor Agonists Alone and in Combination With SGLT2 Inhibitors in Type 2 Diabetes: A Systematic Review and Meta-Analysis. Neuen BL, Fletcher RA, Heath L, et al. Circulation. 2024;150(22):1781-1790. doi:10.1161/CIRCULATIONAHA.124.071689.

9. The "Cardiovascular-Kidney-Metabolic" Era in CKD Management: Integrated Risk Factor Control and Prognostic Benefits. Peng Z, Liang X, Su L, et al. American Journal of Nephrology. 2026;:1-16. doi:10.1159/000552163.

10. 2025 ACC/AHA Clinical Practice Guidelines Core Principles and Development Process: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Writing Committee Members, Otto CM, Abdullah AR, et al. Circulation. 2025;152(18):e359-e370. doi:10.1161/CIR.0000000000001383.