What are the key takeaways from the symposium on cardiometabolic diseases at the Academy of Medicine?

“Cardio-metabolic diseases, everyone involved”: the symposium co-organized by the ICAN IHU at the French National Academy of Medicine, with the collaboration of Inserm ‘s Physiopathology, Metabolism and Nutrition Institute , brought together for the first time all those involved in the fight against cardio-metabolic diseases: researchers and clinicians from a wide range of disciplines, healthcare agencies, industry and patients.

What lessons can we learn?

Still little known to the general public, the term cardiometabolic refers to all cardiovascular and metabolic diseases (diabetes, hypercholesterolemia, obesity, steatohepatitis linked to metabolic dysfunction, cardiac, vascular or renal disease) that expose patients to the risk of cardiovascular morbidity or mortality.

These diseases are linked to aging, the Western lifestyle, diet, pollution and a sedentary lifestyle: we can speak of an epidemic. But there is no such thing as fatality, and new therapies are now making it possible to combat these diseases effectively. ” On the one hand, we have serious diseases, which are the second leading cause of death in France, and on the other, patients are somewhat unaware of, or minimize, the risks involved”.

The challenge is immense. Cardiovascular disease is the second leading cause of death in France, and over 15 million people are at high or very high cardiovascular^risk2. The prevalence of hypercholesterolemia in the general population is 29.^7%3, that of diabetes 9.^9%4 and the number of obese people more than doubled between 1997 and 2024, with 18% of the adult population now ^concerned5. What’s more, French people are unequally exposed to these risks, depending on their socio-economic ^category6. Above all, these diseases must be considered as a whole, as they are largely interlinked.

“A person with type 1 diabetes who develops a kidney complication will have a higher risk of cardiac death,” illustrates Prof. Christian Boitard, Permanent Secretary of the French National Academy of Medicine.

Prof. Vlad Ratziu, of the Gastroenterology and Hepatology Department at the Pitié-Salpêtrière Hospital, and a researcher at the ICAN IHU, even refers to the liver as a “constellation”. “It is at the heart of an interconnected system of organs. Insulin resistance favours the onset of metabolic steatohepatic disease (MASH), which in turn favours the development of diabetes, hypertension and atherosclerosis”, he describes. Improved knowledge is enabling us to take better account of these interconnections.

All those involved agree on the importance of primary prevention in curbing this epidemic. The modifiable risk factors are well known: smoking, fatty and sugary diets, excessive alcohol consumption and a sedentary lifestyle. The IHU ICAN barometer reveals that two-thirds of French people are aware of the importance of regular physical activity and a balanced diet. They owe this awareness, among other things, to the prevention campaigns run by health agencies.

Just like Santé Publique France. However, Anne-Sophie Joly, Founder of the Collectif National des Associations d’Obèses, points out that it’s not just a question of personal responsibility: ” Diet, a sedentary lifestyle, stress… We can’t blame the population for all these ills. Obesity is also the consequence of food processing, advertising, hidden sugars, pollution… We need to tackle these problems together”. Perhaps promoting health education from an early age, at school, would have a real impact on public health?

But above all, nothing can be achieved without a strong commitment from healthcare professionals. In the latest IHU ICAN barometer, 71% of those surveyed cited their doctor as a source of information on cardiometabolic diseases. In this respect, the prevention check-ups offered by the CNAM at different ages provide an opportunity to take stock of patients’ lifestyle habits and environment.

“ Risk factors need to be systematically identified in the population, and non-drug interventions such as sports and nutrition need to be mobilized. They are effective, devoid of undesirable effects, and inexpensive ,” insists Dr Catherine Grenier, Director of Insurance (CNAM).

Better screening for these diseases is also essential for earlier treatment. According to CNAM figures reported by Catherine Grenier, 28% of diabetics are diagnosed with a complication, 23% of heart failure patients are diagnosed with an acute exacerbation, and 30% of dialysis patients are started urgently each year due to insufficient screening for kidney failure.

If the figures presented at the symposium are anything to go by, many patients do not appear to be receiving optimal care. A number of levers have been identified that could change this situation.

The first lever is better compliance with recommendations for managing patients at cardiovascular risk. The term ” inertia ” has been used on several occasions to describe the lack of ambition shown by some healthcare professionals when faced with the failure of their patients to achieve their cardiometabolic targets. Pr Bertrand Cariou, Director of the Institut du Thorax, took the example of LDLc levels, whose target is set at 0.55g/L in subjects at high cardiovascular ^risk8.

In a European study published in ²⁰²³⁹, almost 22% of patients at high to very high cardiovascular risk were not receiving any lipid-lowering therapy, and 80% of patients were not meeting recommended LDLc targets. The Fédération Française des Diabétiques is also contributing to this assessment. Its latest study, ADHÈRECO, has not yet been published, and was designed to assess compliance with the latest HAS recommendations (2024) among people with type 2 diabetes. Among the 1,517 patients surveyed, 20% were unaware of their blood pressure and 40% were unaware of whether they had hypercholesterolemia. Among patients at high cardiovascular risk, three quarters were not taking a statin, and 66.5% were missing a GLP-1 agonist or SGLT-2 inhibitor. ” A majority of patients are under-treated in relation to the recommendations, even though compliance measured in this study is good”, clarifies Dr Jean-François Thébaut, cardiologist and Vice-President in charge of advocacy at the Fédération Française des Diabétiques.

The second lever is the reorganization of care paths to take account of medical and therapeutic advances. Anne-Marie Armantéras, Chairman of the Board of Directors of the ICAN HCI, proposes a paradigm shift towards a genuine healthcare offering, no longer focused solely on care.

In fact, management must be comprehensive, taking into account all risk factors and co-morbidities. Take liver disease, for example. “For a patient, consulting a hepatologist alone would be a waste of time. The liver is a hyper-connected organ, and it is necessary to recognize this, provided that other organ diseases remain undiagnosed and primary and secondary prevention is inadequate”, explains Pr Vlad Ratziu. This is why, since 2019, the ICAN IHU and the AP-HP have been developing a specific, multidisciplinary pathway for patients with MASH, at the Pitié-Salpêtrière hospital. Hepatologists, radiologists, cardiologists, dieticians and diabetologists are mobilized for a comprehensive assessment of hepatic and cardiometabolic risk.

Obesity has also benefited from multidisciplinary care since the creation of Specialized Obesity Centers in 2012. And the benefits for patients are real, according to Pr Judith Aron-Wisnewsky, Nutrition Department – Cardiometabolism Pole, Pitié-Salpêtrière Hospital/IHU ICAN. “Obesity affects several organs and tissues, and is accompanied by metabolic complications (cardiovascular risk, type 2 diabetes, steatopathy, chronic kidney disease, infertility, etc.), mechanical complications (respiratory and osteoarticular problems, gastrointestinal reflux), as well as oral and dental problems, psychological problems, etc. The care offered by these centers takes into account the medical impact of obesity and quality of life, taking into account the etiology of the disease and the patient’s life trajectory. And this care must be long-term, given the risk of weight regain later on”, she sums up.

Clearly, there is still room for improvement. Anne Sophie Joly points the finger at the lack of recognition of obesity as a chronic disease, in the absence of ALD, and the lack of reimbursement for GLP-1 analogues available in France, which, at around €300 a month, represents a loss of opportunity for many patients, particularly the less well-off who pay the heaviest price for obesity.

The last few years have seen the arrival of therapeutic solutions offering effective protection against cardiovascular risk. And research is in full swing.

Indeed, technological advances have made it possible to generate data like never before. Transcriptomics, proteomics, metabolomics, imaging, artificial intelligence, etc. are accelerating our understanding of the links between cardiometabolic diseases, promoting the discovery of diagnostic or prognostic biomarkers, and therapeutic targets. The close collaboration between public and private research teams and clinicians, notably within the IHI ICAN, is a real driving force behind these advances.

Philip Janiak, Chairman and CEO of Corteria Pharmaceuticals, has calculated that some 70 phase 1-3 clinical trials are underway in obesity, to lose weight but also combat the complications of obesity. Among the molecules being evaluated are double or even triple agonists. They target the GLP-1 and glucagon pathways (mazdutide, survodutide), or GLP-1 and amylin (cagrisema), or GLP1-glucagon-GIP (retatrutide). ” Developments involve both new molecules and improved dosage forms, with treatments to be taken orally, or prolonged release on a once-a-month basis,” explains Philip Janiak.

In obesity, the efficacy of new treatments is approaching that of bariatric surgery. Retatrutide 12mg, for example, leads to a -24% reduction in body weight at 48 ^weeks10. Above all, these treatments reduce the risk of cardiovascular events and cardiovascular ^mortality11. Recently, GLP-1 analogues have also proved beneficial in cases of heart failure and ^preserved ejection fraction12 , or against sleep ^apnea13…

Effective treatments are also being developed for MASH to reduce inflammation and prevent the onset of fibrosis. Several avenues are being explored, with two molecules in phase 3: semaglutide, a GLP-1 agonist, and resmetirom, a THR-β agonist. ” These drugs have similar efficacy but very different modes of action,” notes Prof. Vlad Ratziu. The former acts indirectly on hepatic steatosis via weight loss and metabolic regulation, while the latter directly targets a receptor involved in hepatic lipid metabolism. What remains to be done is to improve our knowledge of MASH in order to personalize these treatments.

To carry out this work, Prof. Stéphane Hatem emphasizes the importance of patient participation in cohorts and clinical trials, with varied, high-resolution, long-term data collection. This is a major challenge if we are to have sufficiently large databases to use artificial intelligence. This will enable us to identify sub-groups of patients who do not respond to treatment, or to identify new therapeutic targets. There are, however, legal hurdles to be overcome to facilitate the secondary reuse of health data generated in these various studies,” he warns. It’s a question of attracting French research into partnerships and consortiums. IHU ICAN is working on this with AP-HP . There has also been talk of integrating new types of data into the SNDS: biological reports from hospitals or laboratories, data from hospital health warehouses on certain indicators, etc. Similarly, the French health insurance scheme is working on the legal possibility of using the information in “Mon espace santé” in an anonymous way.

On the strength of these observations and outlooks, all the players present at the event expressed the wish to work together in the interests of patients. An incentive to make cardiometabolic diseases a major national cause?