In a recent Ground Truths podcast, Dr. Eric Topol interviewed Dr. Pradeep Natarajan, Director of Preventive Cardiology at Mass General Hospital, about the evolving landscape of cardiovascular disease prevention. Their discussion covered a range of topics from new biomarkers to innovative drugs and genetic insights that are reshaping our approach to heart health.
Expanding Beyond Traditional Lipid Markers
While LDL cholesterol remains a crucial target in cardiovascular prevention, Dr. Natarajan highlighted the importance of looking beyond this traditional marker. He emphasised the value of measuring ApoB, which provides a more accurate count of atherogenic particles and can be particularly useful in patients with features of insulin resistance.
Dr. Natarajan suggests aiming for an ApoB level about 10% lower than the LDL cholesterol target. He explained, “If we’re aiming for about 40 [mg/dL for LDL], that’s like 36 [mg/dL for ApoB], so relatively similar. If it’s not and it’s higher, then obviously increase the LDL cholesterol-lowering medicines because lower the ApoB and then follow the ApoB with the lipids going forward.”
The Role of Inflammation in Heart Disease
The conversation touched on the often-overlooked role of inflammation in cardiovascular disease. Dr. Natarajan discussed the CANTOS trial, which demonstrated that targeting inflammation with canakinumab, an IL-1β antibody, could reduce cardiovascular events. He also mentioned the potential of colchicine, an inexpensive anti-inflammatory drug, in secondary prevention of cardiovascular events.
Regarding colchicine, Dr. Natarajan stated, “I do really think about it particularly for patients who have had recurrent events. The people who market the medicine and do research do remind us that C-reactive protein was not required in the inclusion, but nobody has done that secondary assessment to see if measuring C-reactive protein would be helpful in identifying the beneficial patients.”
Clonal Hematopoiesis of Indeterminate Potential (CHIP)
Dr. Natarajan, a leader in CHIP research, explained how these acquired mutations in blood stem cells can significantly increase cardiovascular risk. Despite strong evidence linking CHIP to adverse cardiovascular outcomes, routine testing is not yet implemented due to cost and insurance considerations.
He noted the potential for future screening: “There are research tests that are kind of in the $10 to $20 range right now for CHIP. And if flipped over to the clinical side will also be reasonably low cost. And so, for the paradigm for clinical implementation, that cost part is necessary.”
The Promise of Polygenic Risk Scores
Both doctors expressed frustration at the slow adoption of polygenic risk scores (PRS) in clinical practice. These scores, derived from hundreds of genetic variants, can identify individuals at high risk for coronary artery disease much earlier than traditional risk factors.
Dr Natarajan emphasised the potential impact: “By polygenic risk score, you can find 1 in 5 individuals with that same risk [as familial hypercholesterolemia]. If you go higher than that, it’ll be even higher risk related to that. And that is noble information very early in life.”
Emerging Drug Classes: GLP-1 Agonists and SGLT2 Inhibitors
The podcast highlighted the expanding role of drugs originally developed for diabetes in cardiovascular prevention. GLP-1 receptor agonists have shown remarkable benefits in weight loss and cardiovascular outcomes, while SGLT2 inhibitors have proven effective in heart failure management, particularly in patients with preserved ejection fraction.
Dr Natarajan expressed enthusiasm about these developments: “I feel like every week I’m reading a new clinical trial about a new clinical outcome benefit as it relates to GLP-1 receptor agonists… The fact that we have medicines that are safe and effective for lowering weight that also have real strong effects on clinical outcomes is tremendous.”
Looking to the Future
Dr. Natarajan emphasised the need for continued innovation in cardiovascular prevention. He pointed out that as traditional risk factors are better managed, new factors like insulin resistance and obesity are becoming increasingly important.
Reflecting on the future, he said, “There is a dramatic potential for these kinds of therapies in reducing the residual risks that we see related to cardiovascular disease. So I’m enthusiastic and excited. I think a lot more biology needs to be understood of how much of this is being influenced specifically through this pathway versus a very effective weight loss medicine.”
In conclusion, the conversation between Dr. Topol and Dr. Natarajan painted a picture of a field on the cusp of significant advancements. The tools for preventing cardiovascular disease are expanding rapidly, from novel biomarkers and genetic risk assessment to innovative drug therapies. However, the challenge remains in translating these scientific advancements into widespread clinical practice, particularly in healthcare systems not optimised for preventive care.
