PROJECT SUMMARY The aging vasculature and associated inflammation converge as a powerful force to cause two of the most common cardiovascular conditions in older adults aged at least 75 years—heart failure with preserved ejection fraction (HFpEF) and acute myocardial infarction (AMI). Despite the negative impact of HFpEF and AMI on morbidity and mortality among older adults, there are no evidence-based strategies to prevent HFpEF and AMI among older adults. There is a strong biologic rationale that statins could prevent HFpEF and/or AMI events, given their capacity to mitigate endothelial dysfunction, suppress inflammation, and prevent ischemia. However, no randomized controlled trial (RCT) to date has examined whether statins can prevent incident HFpEF and/or AMI events in adults aged at least 75 years—the subpopulation at greatest risk for these events. The objectives of this proposal are: (1) To determine whether statins prevent incident HFpEF hospitalizations in older adults; (2) To determine whether statins prevent AMI events in older adults; (3) To determine the impact of relying on diagnosis codes to identify HFpEF and AMI. This project is an ancillary study to the ongoing NIH-funded Pragmatic Evaluation of Events And Benefits of Lipid-lowering in Older Adults (PREVENTABLE) RCT, which is examining the risks and benefits of statins in adults aged at least 75 years. Given its size (N~20,000), duration (~4 years follow-up), and study design (double-blinded, placebo-controlled, randomized trial), PREVENTABLE offers an unprecedented opportunity to examine whether statins prevent incident HFpEF and/or AMI events. However, the parent RCT’s reliance on diagnosis codes to ascertain cardiovascular events will not allow detailed insights into HFpEF or AMI given the inherent limitations of diagnosis codes to detect these events. This ancillary study will directly overcome this limitation by adding expert-adjudicated outcomes through medical record review. This study will address a huge unmet clinical need with high likelihood of informing clinical practice, and extend the impact of PREVENTABLE with minimal additional burden on study sites or participants. Our team is uniquely qualified to carry out this proposed study given our extensive experience with medical record retrieval on a national scale and with cardiovascular event adjudication; and expertise in cardiovascular epidemiology, HFpEF, AMI, geriatric cardiology, and clinical trial biostatistics. The long-term goal of this research is to identify prevention strategies for two of the most common cardiovascular events among older adults. The expected outcomes of the proposed research are 1) potential guideline-altering evidence on the effect of statins on incident HFpEF and AMI in older adults; and 2) foundational data for optimizing the use of diagnosis codes for clinical, administrative, and research purposes for studies of HF and AMI. This research directly addresses NHLBI Strategic Vision Objective 5 to “develop and optimize novel… therapeutic strategies to prevent… diseases.”

PROJECT NARRATIVE The proposed ancillary study will leverage an ongoing randomized controlled trial to address whether statins prevent two of the most common cardiovascular conditions experienced by older adults—heart failure with preserved ejection fraction (HFpEF) and acute myocardial infarction (AMI). This proposal will also determine the negative impact of relying on diagnosis codes to identify HFpEF and AMI events in the modern era. The proposed research is consistent with the broader public health goals of disease prevention, and addresses NHLBI Strategic Vision Objective 5 to “develop and optimize novel… therapeutic strategies to prevent… diseases.”