by José Luis Cárdenas Tomažič / Dr. Guillermo E. Maligne

Adapted from the Spanish column originally published in El Economista on June 10th, 2026 (Eje Cardio-Reno-Metabólico: la oportunidad que los sistemas de salud no pueden seguir postergando)

For decades, health systems in Latin America and around the world have been organized under a logic that is now beginning to show its limits. We built hospitals, specialties, budgets, and coverage programs as if chronic diseases followed separate paths. The endocrinologist treats glucose, the nephrologist monitors declining kidney function, the cardiologist focuses on the heart, and the psychiatrist addresses mental health.

Those who have worked in hospitals, payers, or public agencies know that reality rarely respects these boundaries. The same patient appears again and again in different clinics, different budgets, and different administrative records. What are separate problems for the system are, for the individual, a single medical story.

The scientific evidence accumulated in recent years is confirming something many clinicians had long observed: a large proportion of chronic diseases share biological mechanisms, risk factors, and disease trajectories. Fragmentation is no longer just an organizational issue. It is a clinical limitation and, increasingly, an economic one.

When Organs Stop Being Islands

In October 2023, the American Heart Association published a consensus that marked a turning point: the formal definition of Cardiovascular-Kidney-Metabolic syndrome, or CKM (Circulation, Ndumele et al., 2023), also referred to as cardio-renal-metabolic syndrome.

This was not an academic reclassification. It was the official recognition of what everyday clinical practice had already been signaling: the accumulation of visceral fat, insulin resistance, systemic inflammation, and vascular damage do not affect isolated organs. They are part of a single process that simultaneously compromises arteries, kidneys, heart, and metabolism. In other words, many diseases we still manage separately are different expressions of the same trajectory of deterioration.

However, even this perspective may be incomplete if it leaves out the brain. The relationship between cardio-renal-metabolic syndrome and mental health is becoming increasingly difficult to ignore. Patients with major depression have a significantly higher risk of developing cardiovascular disease and type 2 diabetes — with relative risk increases that various studies, using different methodologies, place between 40% and 60% (Firth et al., Lancet Psychiatry, 2019; Zeng et al., Molecular Psychiatry, 2025).

This is not merely about unhealthy habits. There are concrete biological bridges: inflammation generated by adipose tissue affects the brain, chronic stress alters hormonal processes capable of accelerating cardiovascular deterioration, and small cerebral arteries progressively sustain silent damage. The relationship also works in the opposite direction: living for years with complex chronic diseases affects mental health. That said, it is important to be precise: the evidence linking metabolic deterioration to neuropsychiatric alterations is more robust than the causal demonstration in the reverse direction. Research is advancing, but there are still questions without definitive answers.

For health management, the key point is simpler: patients do not experience these conditions as independent compartments. Consider a specific case — a 58-year-old man with obesity, type 2 diabetes, hypertension, and depression. Four clinics, multiple administrative pathways, and treatment recommendations that do not always align. From a biological perspective, in many such cases we are observing different manifestations of a single disease process. Yet the system records them as four separate problems and finances them as if they were unrelated. That is precisely the gap we need to close.

The Cost of Looking the Other Way

Fragmentation has clinical consequences. But it also has economic ones, and these are often what ultimately drive decision-makers. Advanced complications of chronic diseases represent one of the main sources of financial pressure on health systems. Complications of diabetes account for a substantial proportion of total disease-related spending, and the coexistence of diabetes, chronic kidney disease, and heart failure can consume, in some regions, more than half of the budget allocated to non-communicable diseases (Lancet Diabetes & Endocrinology, 2024).

The problem is that these costs rarely appear in a single account. They are distributed across hospitalizations, outpatient services, disability, rehabilitation, and productivity losses. This makes them less visible than the price of a new medication, even though they are far higher.

When intervention occurs at an advanced stage — when the patient already requires dialysis, experiences a hospitalization due to heart failure, or suffers a major cardiovascular event — the margin to alter prognosis becomes much narrower, and the cost much higher.

To this must be added the impact of mental health, which economic analyses frequently overlook. Depression in patients with heart failure is associated with a 30% to 50% increase in hospitalization risk and a 30% to 40% reduction in adherence to pharmacological treatment (Chouairi et al., J Card Fail, 2021; Berimavandi et al., Health Sci Rep, 2025).

In other words, the best medication in the world loses effectiveness if the patient does not take it — and often they do not, because no one is paying attention to their mental health.

Therapies That Protect More Than One Organ — and a System That Still Struggles to Evaluate Them

Here lies one of the most compelling dilemmas of our time. In recent years, medications initially developed for diabetes have demonstrated, in Phase III clinical trials, the ability to reduce major cardiovascular events and slow the progression of kidney disease — with effect sizes that in several studies reach or exceed 20% for the composite outcomes evaluated (New England Journal of Medicine, Lincoff et al., 2023).

Some of these compounds are also being studied for their potential effects on cognition and brain health; available results are promising, though not yet conclusive.

The challenge is that when benefits are distributed across different organs, specialties, and budgets, traditional cost-effectiveness analyses — designed to evaluate a drug for a single indication — correctly capture costs but often underestimate the real benefit. What appears expensive from a nephrology perspective may be highly efficient from the standpoint of the health system as a whole.

Health economics is beginning to address this issue seriously, proposing evaluation frameworks capable of measuring the systemic value of such interventions (Soares et al., Value in Health, 2025). However, academic discussion is advancing faster than changes in coverage systems.

The fundamental question is not how much it costs to incorporate these innovations, but how much it costs to continue without them.

What Needs to Change — and What Depends on Decisions, Not Evidence

Evidence has already transformed the way we understand these diseases. What has not changed at the same pace are the structures we use to manage them. Clinical guidelines continue to operate in silos. Budgets remain compartmentalized. Payment mechanisms still incentivize individual services rather than integrated outcomes.

None of these barriers today stem from a lack of scientific knowledge. To a large extent, they reflect institutional inertia accumulated over decades.

Changing that inertia requires concrete decisions: aligning clinical guidelines across specialties, designing financial incentives that reward patient outcomes rather than isolated activities, and revising evaluation models to reflect the real value of interventions whose benefits are distributed over time and across multiple organs.

The cardio-renal-metabolic concept is not an academic refinement for medical conferences. It is a tangible opportunity to rethink how we allocate scarce resources in the face of a growing burden of chronic disease.

Medicine has already understood that the patient is more than the sum of their organs. The remaining challenge is for regulation, financing, and health system organization to begin acting accordingly.

Because if the available data show anything, it is that the cost of integration can be measured. The cost of fragmentation, by contrast, continues to be paid every day — in installments, and spread across so many different budgets that no one ever fully sees the whole picture.

How much longer can we afford to wait before making the change?

References:

References:

• Berimavandi M, et al. Relationship between depression and medication adherence in cardiovascular disease. Health Sci Rep. 2025.
• Chouairi F, et al. The impact of depression on outcomes in patients with heart failure. J Card Fail. 2021.
• Firth J, Siddiqi N, Koyanagi A, et al. The Lancet Psychiatry Commission: a blueprint for protecting physical health in people with mental illness.
  Lancet Psychiatry. 2019;6(8):675–712.
• Lincoff AM, Brown‑Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389:2221–2232. doi:10.1056/NEJMoa2307563.
• Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular–Kidney–Metabolic Health: A Scientific Statement From the American Heart Association.
  Circulation. 2023;148(20):1606–1635.
• Soares M, Glynn D, Layne R, Palmer S. A policy framework for multi-indication evidence synthesis in health technology assessment (HTA).
  Value Health. 2025;28(Suppl 1):S18–S19.