e because this new approach can move us beyond a system arranged around traditional risk factors and organ systems. It can move us to a much more precise approach targeting the molecular biology that forms the basis of chronic diseases and accelerated aging.
Understanding the full potential of primary care redesign requires a very short trip into the basic science weeds. If you just understand the rest of this article and the links, you will understand what next-generation chronic disease management could be. It is not that hard.
For example, elevated LDL cholesterol levels are a traditional target for therapies to reduce the risk of cardiovascular events, such as heart attacks and stroke. However, about half of all heart attacks occur in people with normal levels of LDL cholesterol. This suggests that other factors may be contributing to the risk in those people. Several seminal studies have pointed at inflammation as a critical pathway in the pathogenesis of atherosclerosis.
The Jupiter Trial
Paul Ridker is a cardiologist at Harvard Medical School. He is the leading proponent of the “inflammatory hypothesis” of cardiovascular disease. The 2008 Jupiter trial made him famous in medical circles.
The trial enrolled 17,802 healthy patients with normal LDL cholesterol levels (according to guidelines at the time) but a high level of the inflammatory marker C-reactive protein (CRP). Half of the patients were randomly assigned to receive the statin and half did not.
Although many in the public think of statins as cholesterol-lowering drugs, they also have significant effects in reducing inflammation. The results were dramatic leading the cessation of the trial after a median of ~2 years. Rosuvastatin treatment cut the incidence of a first cardiovascular event in these individuals by half. LDL levels were reduced by 50% and CRP by 37%.
The CANTOS trial
Dr. Ridker expanded this concept in the 2017 CANTOS trial designed to determine the impact on cardiovascular events if inflammation was reduced but cholesterol levels were not impacted.
Patients with a history of heart attack and a high CRP received the injectable monoclonal antibody canakinumab that neutralizes the inflammatory mediator interleukin 1B (initiates inflammatory signaling cascade). That intervention reduced heart attacks by 15%.
This study provided compelling evidence that targeting inflammation instead or (or in addition to) lowering lipids is a viable approach to the prevention of cardiovascular disease.
In a follow-up review, Ridker and his colleague, Aaron Aday, wrote the following:
“Successfully addressing traditional CVD risk factors should not falsely reassure clinicians and patients that nothing more can be done to further reduce [CVD] risk…”
Dr. Ridker summarizes the implications like this: “CANTOS is what we call systems biology.
When I was a medical student, we taught heart, lung, kidney, brain. however, We don’t do that anymore. Instead, We teach inflammation, fibrosis, and metabolism.
The best scientists at Harvard are calling for a move away from a medical system designed around organ systems. Instead, they advocate moving toward a system based on genetics, epigenetics, and molecular biology. This is because the same molecular signaling that causes a heart attack also causes stroke and kidney failure.
It makes no sense to send these people to cardiologists, neurologists, and nephrologists. The best management will not come from partialists. It will come from generalists who are experts in molecular medical management. That, in a nutshell, is primary care 3.0.
Other articles in this series:
William H. Bestermann MD and Patricia Salber MD, MBA
William H. Bestermann Jr., MD is a board-certified internist who has practiced preventive cardiology for more than 20 years. His core expertise is consistently producing optimal medical therapy (OMT) for cardiovascular and related conditions. He does this by using evidence-based care processes consistent with best practices.
He looks at OMT as a product. He understands how health care organizations can combine new s