AHA 23 Spotlight: The Evolving Landscape of Modifiable Cardiovascular Risk Factors, with Deepak Bhatt, MD, MPH

The core concepts that define cardiovascular risk management have been undergoing a once quiet, but now undeniable evolution in recent decades.

Although lifestyle management, including diet, exercise, and smoking cessation, still hold fast to their roles as the foundation of risk management, cardiologists and other members of the care team have begun to recognize additional drivers of risk, such as inflammation and lipoprotein(a). This evolving landscape was on display at the American Heart Association Scientific Sessions 2023.

Adding to the evidence base for inflammation as a driver of cardiovascular risk from the meeting was an analysis of the CLEAR Outcomes trial presented by Paul Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital. Results of this study suggested baseline hsCRP (highest vs lowest quartiles) was significantly associated with an increased risk of the incident composite endpoint (Hazard Ratio [HR], 1.43; 95% Confidence Interval [CI], 1.24-1.65), cardiovascular mortality (HR, 2.00; 95% CI, 1.53-2.61), and all-cause mortality (HR, 2.21; 95% CI, 1.79-2.73).¹

This study comes less than a year after Ridker presented similar results in patients using statin therapy at the American College of Cardiology 2023 annual meeting, which concluded elevated hsCRP was associated with a 30% increase in risk of cardiovascular events and a more than doubling in risk of cardiovascular and all-cause mortality in fully adjusted analyses accounting for LDL-C and residual cholesterol risk.¹

Outside of this data, the evidence of the growing recognition is apparent in the US Food and Drug Administration’s’ approval of low-dose colchicine tablets (Lodoco) for reducing the risk of myocardial infarction, stroke, coronary revascularization, and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular disease. Announced in June 2023, the approval marked the first instance in the agency’s history where an agent was awarded an indication as an anti-inflammatory atheroprotective cardiovascular treatment.²

Data surrounding Lp(a) and novel treatments for management took centerstage at AHA 2023. Data presented at the meeting not only highlighted the association of Lp(a) with increased risk of cardiovascular events, but also the lack of testing and management options for these patients. One example of the numerous studies calling attention to increased risk was an analysis of data from the Mass General Brigham Lp(a) Registry presented by Adam Berman, MD, senior fellow at Brigham and Women’s Hospital. Results of this study indicated elevated Lp(a) was independently associated with long-term MACE among individuals with and without baseline ASCVD, with further analysis suggested a reduced Lp(a) threshold may be more appropriate in secondary prevention when compared with primary prevention.³

In a late breaking session, Steve Nissen, MD, chief academic officer of the Heart Vascular and Thoracic Institute at Cleveland Clinic, presented results of a phase 1 trial examining safety and efficacy of 6 dosages of lepodisiran relative to placebo therapy for lowering Lp(a) in adults without cardiovascular disease and with lipoprotein(a) serum concentrations of 75 nmol/L or greater. Results of the trial suggested use of the agent in any of the 4 dosage formulations of 32 mg or more was associated with a median reduction of 76% or greater in Lp(a), with the 304 mg and 608 mg doses associated with median changes of 96% and 97%, respectively.⁴

In addition to inflammation and Lp(a), data from the SELECT trial presented at AHA 2023 has cast aside any remaining doubt about obesity as a modifiable risk factor. Results of the trial, which compared semaglutide 2.4 mg against placebo for effect on 3-point MACE, concluded use was associated with a 20% relative risk reduction, with results also pointing to nonsignificant signals of benefit for heart failure outcomes, cardiovascular mortality, and type 2 diabetes.⁵

To learn more about the evolving landscape of cardiovascular risk management, check out our interview with Deepak Bhatt, MD, MPH, director of Mount Sinai Heart and the Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai, from AHA 2023.

Relevant disclosures for Bhatt include Amarin, AstraZeneca, Sanofi, Pfizer, Roche, Amgen, and Eli Lilly and Company, among others.

References:

1. Campbell P. Inflammation could be better predictor of cardiovascular events than LDL-C, study finds. HCP Live. November 10, 2023. Accessed November 14, 2023. https://www.hcplive.com/view/new-aha-23-data-further-highlights-role-of-inflammation-in-cardiovascular-risk.
2. Campbell P. FDA approves colchicine tablets for reducing cardiovascular risk. HCP Live. June 20, 2023. Accessed November 14, 2023. https://www.hcplive.com/view/fda-approves-colchicine-tablets-for-reducing-cardiovascular-risk.
3. German AN, Biery D, Besser S, et al. The Association of Lipoprotein(a) With Major Adverse Cardiovascular Events Among Individuals with and Without Baseline Atherosclerotic Cardiovascular Disease: The Mass General Brigham Lp(a) Registry. Paper presented at: American Heart Association Scientific Sessions 2023; November 10 – 13; Philadelphia, PA. Accessed November 10, 2023.
4. Campbell P. Lepodisiran, a small interfering RNA, could lower lp(a) by more than 95%. HCP Live. November 12, 2023. Accessed November 14, 2023. https://www.hcplive.com/view/lepodisiran-a-small-intefering-rna-could-lower-lp-a-more-than-90-.
5. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes [published online ahead of print, 2023 Nov 11]. N Engl J Med. 2023;10.1056/NEJMoa2307563. doi:10.1056/NEJMoa2307563