Cardiovascular disease attacked on all fronts

The rate of mortality from cardiovascular disease has fallen in the last 50 years, despite an increase in life expectancy. This achievement is associated with the identification of risk factors, the development of incredible drugs and surgical treatments, and improved organisation of care, enabling an effective response to emergencies. Alain Tedgui, an author of important publications on atherosclerosis, reflects on these different advances.

“Remarkable” is the term employed by Alain Tedgui* to describe the progress made in the cardiovascular field in the last fifty years: In the 1950s, deaths from cardiovascular disease represented half of all mortality in developed countries. Today they represent only 30%, despite an increase in life expectancy. This progress is associated with the identification of risk factors involved in the occurrence of these diseases, as well as the development of drugs and the improvement of management procedures—emergency departments, cardiac intensive care units, coronary angioplasty, heart surgery, etc. French teams, especially at Inserm, have been and continue to be heavily involved in these advances.

Fusion d'images multimodales pour l'optimisation de la thérapie de resynchronisation cardiaque. Equipe : Images et Modèles pour la Planification et l'Assistance Chirurgicale et Thérapeutique (IMPACT) campus de Beaulieu Rennes. © Inserm-LTSI-IMPACT/LTSI

Fusion d'images multimodales pour l'optimisation de la thérapie de resynchronisation cardiaque. Equipe : Images et Modèles pour la Planification et l'Assistance Chirurgicale et Thérapeutique (IMPACT) campus de Beaulieu Rennes.

What is cardiovascular disease?
Cardiovascular disease is a class of diseases that affect the cardiac activity and blood circulation: coronary heart disease, which affects the arteries to the heart, cerebrovascular disease, which affects the blood vessels to the brain, peripheral arterial disease, which affects the blood vessels to the arms and legs, and cardiopathies affecting the cardiac muscle and valves.
Coronary heart disease, usually caused by narrowing of an artery by atheromatous plaques, is the most common cardiovascular disease in developed countries.

“Epidemiological data from the Framingham cohort really marked a turning point in favour of prevention,” begins Alain Tedgui. “Begun in 1948, this is the largest study on cardiovascular risks ever carried out. It is always cited.” At the time, confronted by the extent of mortality from cardiovascular disease in the USA, the American NIH Heart, Lung and Blood Institute (NHLBI) launched a vast study to identify factors contributing to the onset of this disease. A huge cohort of adults from the town of Framingham, Massachusetts, with no history of cardiovascular disease, was established. Data collected soon showed how a high cholesterol level, hypertension or tobacco consumption exposes individuals to cardiovascular disease and an increased risk of death. As a result, primary prevention became a pet subject, and health professionals became involved in a war against these risk factors, urging patients to change certain behaviours and using new treatments.

Confronting hyperlipidaemia and hypertension

Lipoprotéines de basse densité, LDL, en microscopie électronique à transmission. © Inserm/U321

Lipoprotéines de basse densité, LDL, en microscopie électronique à transmission.

During that time, lipid metabolism came under scrutiny. The main mechanisms were deciphered, particularly the mechanism involving LDL lipoproteins and their receptors. The first molecule of the statin family, which is active against this mechanism, came into being in 1987. By helping to reduce the level of LDL cholesterol by approximately 30%, regardless of initial level, statins were to effect a profound change in the management of hypercholesterolaemia. Studies have shown it: these drugs reduce mortality from cardiovascular disease.

Observation en lumière polarisée de cristaux de rénine humaine. © Inserm/Mornon, Jean-Paul

Observation en lumière polarisée de cristaux de rénine humaine.

Concurrently, management of hypertension also progressed. In the 1970s, Pierre Corvol, a physician and researcher at Inserm, contributed to describing the system that controls the arterial blood pressure from the kidneys: the renin-angiotensin system. The first protein, known as angiotensin I, is transformed into angiotensin II through the action of angiotensin-converting enzyme (ACE). This cascade contributes to increasing the blood pressure. The discovery resulted in the development of two types of very effective hypotensive drugs: ACE inhibitors and angiotensin II receptor antagonists (ARA2), in about 1990. By adding to the existing therapeutic arsenal of beta-blockers and diuretics, these two new classes of drugs have considerably improved the control of hypertension.

Infarctions are less and less fatal

Apart from primary prevention, major advances have enabled a reduction in morbidity and mortality associated with infarction. Emergency thrombolysis (to dissolve the clot obstructing an artery) and restoration of blood flow to blocked arteries by angioplasty (a surgical technique) have indeed reversed the prognosis for victims. These successes were made possible by improved organisation of care, enabling the intervention of the emergency ambulance service (SAMU) in record time, and management in specialised care units.

After an infarction, the placement of a stent (a device inserted into the artery to keep it dilated) and initiation of medical treatment also considerably reduce complications and the risk of recurrence. And let us not forget: the placement of the first stent in a coronary artery was performed in 1986 in Toulouse, by Jacques Puel, a physician and researcher at Inserm.

Other treatment approaches, such as cell therapy, are currently being tested for the repair of lesions caused by these episodes. At Inserm, Philippe Menasché uses embryonic stem cells: he induces their differentiation into cardiac cells in order to improve myocardial contraction. These cells most often secrete biological factors that contribute more to regeneration than the differentiated cells themselves.

A better understanding of sudden death

Knowledge relating to adult sudden death has also benefited from research. Although prevention and management remain difficult, epidemiology and knowledge of the mechanisms involved have advanced, especially thanks to the work of Pierre Ducimetière and Xavier Jouven at Inserm.

Adult sudden death is the result of an abnormal ventricular rhythm (fibrillation or tachycardia) in 80% of cases. In the 1990s, investigators discovered that it involved a genetic problem in about 20-30% of cases, and mutations were identified in genes coding for proteins controlling the electrical activity of the heart. Automatic defibrillators are therefore now regularly implanted in patients at increased risk of sudden death.

Other studies carried out at Inserm by Michel Haïssaguerre have shown that some cases of atrial fibrillation are linked to a problem at the junction between the pulmonary veins and the left atrium of the heart, leading to electrical overstimulation. It is possible to correct this risk of fibrillation by cauterising the fibres in this area.

Advantages of surgery

Finally, surgery has made enormous progress: since the 1960s, bypass operations have allowed the circumvention of stenotic areas (excessive narrowing of the arteries), and, especially thanks to the work of Alain Carpentier, a heart valve can be repaired. At the time, we were far from thinking that the first artificial hearts would be implanted 50 years later in the same units...

Inauguration du centre de recherche de l'hôpital européen Georges Pompidou le 8 septembre 2009. Présentation du coeur artificiel, Carmat, mis au point par le professeur Alain Carpentier. © Inserm/Begouen, Etienne

Inauguration du centre de recherche de l'hôpital européen Georges Pompidou le 8 septembre 2009. Présentation du coeur artificiel, Carmat, mis au point par le professeur Alain Carpentier.

Organe artificiel. Pacemaker, stimulateur cardiaque en place. © Inserm/Thomas, Daniel

Organe artificiel. Pacemaker, stimulateur cardiaque en place.

Présentation d'une endoprothèse aortique devant un écran de modélisation. Plateforme informatique CIC-IT. Unité Mixte de recherche Inserm UMR 1099 CHU de Rennes Pontchaillou. © Inserm/Patrice Latron

Présentation d'une endoprothèse aortique devant un écran de modélisation. Plateforme informatique CIC-IT. Unité Mixte de recherche Inserm UMR 1099 CHU de Rennes Pontchaillou.

 

Note
*Director, Paris-Cardiovascular Research Centre (PARCC) at the Georges-Pompidou European Hospital (HEGP), and Inserm Unit 970/Paris Descartes University

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