Notice of Special Interest (NOSI): Advancing Research in Lipoprotein(a) and Cardiovascular Disease (R01 Clinical Trials Allowed) and (R01 No Clinical Trials Allowed)
Notice Number:

Key Dates

Release Date:

November 10, 2022

First Available Due Date:
February 05, 2023
Expiration Date:
January 08, 2026

Related Announcements

PA-20-183 Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-185 NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

NOT-HL-19-690 NHLBI Limitations on Clinical Trial Applications Submitted to the NIH Parent (R01 Clinical Trial Required) Funding Opportunity Announcement (FOA)

Issued by

National Heart, Lung, and Blood Institute (NHLBI)


The purpose of this NOSI is to stimulate research on lipoprotein(a) [Lp(a)] and its role in cardiovascular disease (CVD). We encourage multidisciplinary collaborations to conduct basic, preclinical, and mechanistic clinical studies on Lp(a) and CVD.

Lp(a) is composed of a low-density lipoprotein (LDL)-like particle, linked to apolipoprotein(a) [apo(a)]. Apo(a) has many different isoforms and makes Lp(a) a complex lipoprotein. Lp(a) is subject to tight genetic control mostly in the LPA gene encoding apo(a). Patients with elevated Lp(a) levels have an increased risk of CVD, including heart attack, stroke and peripheral arterial disease as well as calcific aortic stenosis (AS). Recent genetic studies indicate that Lp(a) is a causal and independent risk factor for CVD. It is well established that Lp(a) levels differ across different racial and ethnic groups.

Although much progress has been made in Lp(a) field, there are still many unanswered questions such as fundamentally understanding Lp(a) biology and pathophysiology, globally standardized Lp(a) assays, risk and therapy thresholds of Lp(a) in different racial/ethnic groups, Lp(a) in clinical risk prediction, and identification of novel therapeutic targets.

There are several challenges and barriers that have hindered the progress in Lp(a) and CVD field. These may include: 1) the lack of awareness on the large global impact of Lp(a) in CVD. It was only recently that strong evidence for a causal relationship of Lp(a) levels to CVD was emerging from epidemiological, genome-wide association studies, and Mendelian randomization studies; 2) the lack of reliable in vitro cell lines and in vivo animal models. Lp(a) is not present in commonly studied laboratory animals and the structure of Lp(a) is complex and thus makes it difficult to generate appropriate animal models to study Lp(a); 3) the lack of standardized Lp(a) assays. Lp(a) assays have been significantly improved through the years. However, global standardization of Lp(a) assays is still in development; and 4) the lack of specific therapies to lower Lp(a) levels. The recent therapeutic development that targets apo(a) is promising but these are still in different phases of clinical trials.

Thus, this NOSI is intended to facilitate collaborative research on Lp(a) and investigate its role in CVD development.

Selected Research Examples

Research areas of interest include, but are not limited to the following:

    • Study the biosynthesis of apo(a), endogenous Lp(a) particle assembly, secretion, and clearance
    • Elucidate the relationship between Lp(a) structure and function
    • Investigate the route of Lp(a) catabolism in both physiological and altered conditions and identify relevant receptors
    • Develop new model systems such as in vitro cell lines and in vivo animal models that are suited for Lp(a) research
    • Examine the mechanism(s) of Lp(a) in CVD development e.g., Lp(a) may contribute to oxidation, inflammation, fibrinolysis, and atherogenesis
    • Identify new targets and novel mechanisms of Lp(a)-lowering for the development of therapeutic agents
    • Understand the mechanistic links between apo(a) isoforms and SNPs and risk for CVD
    • Evaluate risk and therapy thresholds of Lp(a) and genetic contribution to differences in Lp(a) levels in different racial/ethnic groups
    • Determine the clinical utility of Lp(a) to predict risk in diverse population-based studies using optimal laboratory assays
    • Explore the potential of improving Lp(a) standardization by the harmonization of different Lp(a) assays

Application and Submission Information

This notice applies to due dates on or after February 5, 2023 and subsequent receipt dates through January 7, 2026. 

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.

  • PA-20-183 - NIH Research Project Grant (Parent R01 Clinical Trial Required)
  • PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)


Note: NHLBI will accept only mechanistic studies that meet the NIH definition of a clinical trial (see NOT-HL-18-662 and NOT-NS-18-011) in response to PA-20-183 NIH Research Project Grant (Parent R01 Clinical Trial Required) and its reissues. For additional information, please see the NHLBI Policy Regarding Submission of Clinical Trial Applications Notice for help in identifying the most appropriate FOA (see NOT-HL-18-611).

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

  • For funding consideration, applicants must include “NOT-HL-22-052” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.


Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

Lijuan Liu, PhD
National Heart, Lung, and Blood Institute
Division of Cardiovascular Sciences
Telephone: 301-435-0582

Peer Review Contact(s)
Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Jasmine Johnson
National Heart, Lung, and Blood Institute
Telephone: 301-827-8177